ALBERT

Description: Successful cases of treatment of Bevacizumab for preventing scar after trabeculectomy in glaucoma patients encourage us to explore its mechanism. In this study, we primarily isolated conjunctival fibroblast from rat. RT-PCR analysis for the cells implicated that conjunctival fibroblast expressed vascular endothelial growth factor (VEGF) and its receptors. Immunofluorescence staining also showed positive staining for VEGFR-1. Furthermore, growth of fibroblast was significantly inhibited by Bevacizumab at dose of 2.5 mg/ml. Real time PCR results showed after 48 h intervention of 2.5 mg/ml Bevacizumab, the mRNA expressions of VEGF and its receptors decreased compared to the control group ( P  〈 0.05) and Bevacizumab also decreased expression of TGFβ1 and TGFβ2 ( P  〈 0.05). In summary, our finding demonstrated that Bevacizumab could directly act on fibroblast and inhibit VEGF, TGFβ1, and TGFβ2 expression.

Description: Like any other unusual state of consciousness, the condition of anesthesia remains a mystery, especially regarding the information processing events of the brain. Evoked potentials are the only known way to understand the neurophysiological events of brain in this condition. Auditory evoked potentials (AEPs) have been used as a measure of the depth of anesthesia during the intra-operative process. AEPs have been classically divided, on the basis of their latency, into first, fast, middle, slow, and late components. Auditory evoked potential has been advocated for the assessment of intra-operative awareness (IOA) but has not been considered seriously enough to be universalized. It is because we have not explored enough the impact of auditory perception and auditory information processing on the IOA phenomena as well as on the subsequent psychological impact of IOA on the patient. This limitation is because we have poor understanding of the subconscious auditory processing itself. This perspective is especially important because more of the IOA phenomena exist in the subconscious domain than they do in the conscious domain of explicit recall. Two important forms of these subconscious manifestations of IOA are the implicit recall phenomena and post-operative dreams related to the operation. Here we present a review of the neurophysiological and neuropsychological correlates of auditory processing during anesthesia. We start with a brief description of auditory awareness and the factors affecting it. Further, we proceed to the evaluation of conscious and subconscious information processing by auditory modality and how they interact during and after intra-operative period. Further, we show that both conscious and subconscious auditory processing affect the IOA experience and both have serious psychological implications on the patient subsequently. These effects could be prevented using auditory evoked potential during monitoring of anesthesia, especially the midlatency auditory evoked potentials. To conclude, we propose that the use of Auditory evoked potential should be universal with general anesthesia use in order to prevent the occurrences of distressing outcomes resulting from both conscious and subconscious auditory processing during anesthesia.

Description: Within the field of mental health, the concept of predisposition or that of being “at risk” has been properly addressed by Mrazek and Haggarty. This period prior to clear diagnosis of psychosis has been referred by several names like ‘premorbid’ phase, at-risk individuals, predisposed individuals, prodromal phase, etc. The premorbid phase is perhaps the most debated term in this list because this term suggests that the morbidity arises only in the overt illness phase. However, evidences arising from several different lines of observations suggest that this may not be the case. In spite of the fact that it has been generally accepted that the prodromal phase precedes the clinical phase, identification of this phase remains a challenge. The real challenge in identifying the onset of the prepsychotic phase is the differentiation of ‘normal’ experiences from these ‘abnormal’ experiences. Much fewer studies have been conducted for the assessment of cognitive functions in prodromal phase or predisposed phases of schizophrenia. Cognitive deficits, particularly in memory and attentional functions, are among the most extensively documented aspects of psychosis. Regarding the somatosensory abnormalities in the high-risk individuals, so far there has been only one study conducted which involved somatosensory evoked potentials in these patients.

Description: Dihydroartemisinin (DHA) is a promising anti-cancer compound capable of inhibiting proliferation and inducing apoptosis of various cancer cells, including colorectal cancer. However, the molecular mechanisms have not been well understood. This study aimed to explore the underlying mechanism of DHA-induced apoptosis in HCT-116 cells. Cell counting kit-8 assay and flow cytometry analysis confirmed that DHA inhibited proliferation, arrested cell cycle at G0/G1 phase, and enhanced apoptosis in HCT-116 cells. Fluo-3/AM-stained flow cytometry assay revealed that the intracellular Ca 2+ concentration of HCT-116 cells was increased significantly after DHA treatment. Meanwhile, the activity of sarco/endoplasmic reticulum calcium ATPase (SERCA) was appeared to be reduced in a dose-dependent manner. We further detected the upregulated expression of CAAT/enhancer binding protein homologous protein (CHOP) in DHA-treated HCT-116 cells. Conversely, silencing CHOP resulted in a decrease of DHA-induced apoptosis. In addition, the expression of Bax in cytoplasm was elevated significantly along with the sharply decline of Bcl-2 expression in DHA-treated HCT-116 cells. Moreover, the distributions of Bid on mitochondria were increased, accompanied by the activation of caspase-3 in the presence of DHA. Overall, our data indicated that DHA triggered endoplasmic reticulum (ER) stress through inhibiting SERCA activity to release intracellular Ca 2+ from ER, the upregulated expression of CHOP activated mitochondrial apoptosis pathway to induce apoptosis of HCT-116 cells. Therefore, our findings provide a theoretical foundation for DHA as a potential candidate in treatment of colorectal cancer.

Description: The present study elucidated the prospective of Azadirachta indica supplementation, if any, in affording chemoprevention by modulating the altered cancer markers and ultrastructural changes in DMH-induced colorectal carcinogenesis in rats. The rats were segregated into four groups viz., normal control, DMH treated, A . indica treated, and DMH+AI treated. Initiation and induction of colon carcinogenesis were achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for both 10 and 20 weeks. A . indica extract was supplemented to rats at a dose rate of 100 mg/kg body weight of animals thrice a week on alternative days, ad libitum for two different time durations of 10 and 20 weeks. The study observed a significant increase in the number of aberrant crypt foci in colons of DMH-treated rats at both the time intervals which were decreased significantly upon AI supplementation. Also, a significant increase was seen in the enzyme activity of alkaline phosphatase, which, however, was moderated upon AI administration to DMH-treated rats. Changes in the ultrastructural architecture of colonic cells were apparent following both the treatment schedules of DMH; however, the changes were prominent following 20 weeks of DMH treatment. The most obvious changes were seen in the form of altered nuclear shape and disruption of cellular integrity, which were appreciably improved upon AI supplementation. In conclusion, the study shows the chemopreventive abilities of AI against DMH-induced colorectal carcinogenesis in rats.

Description: We wished to evaluate the effects of Pseudomonas aeruginosa (mannose-sensitive hemagglutination pilus strain, PA-MSHA) as an immunostimulating and anti-tumor agent for treatment of bladder cancer. Immunostimulating effects were assessed by the in vitro proliferation assay of murine splenic lymphocytes. Anti-tumor effects were studied in a subcutaneous tumor model established in female C57BL/6 mice using the MB49 bladder cell line. These mice received subcutaneous injections of normal saline (control group) or PA-MSHA (high, medium, or low dose, respectively, 1.6–2.0 × 10 9 , 3.2– .0 × 10 8 , 6.4–8.0 × 10 7 CFU/ml) twice a week for 3 weeks. Mice survival, tumor volume, vascular endothelial growth factor (VEGF) expression, microvessel density (MVD), serum levels of TNF-α and IFN-γ, and blood CD4 + /CD8 + counts were the study outcomes. We observed that PA-MSHA promoted the growth of splenic lymphocytes in vitro. In the murine tumor model, PA-MSHA prolonged mice survival and reduced tumor growth. Furthermore, VEGF and MVD were also diminished by PA-MSHA. Mice that received high and medium dose of PA-MSHA had significantly higher serum levels of IFN-γ and TNF-α (days 21 and 28), and higher levels of CD4 + /CD8 + cells (days 21 and 28). In conclusion, PA-MSHA exerts beneficial effects on increasing proliferation of murine splenic lymphocytes in vitro and inhibits the growth of bladder tumor in a murine model. Therefore, PA-MSHA may be useful an immunostimulating and anti-tumor agent for bladder cancer therapy.

Description: Currently, as there is no systematic norm or standard for drug safety and inspection, it cannot be judged whether the regulatory authority or regulators have fulfilled their administrative responsibilities entirely or not, when a drug safety-related incident occurs. And there is a probability that some may even be wrongly punished. In this study, we have analyzed the risk of not having appropriate norms in place and also put forward recommendations for the government or the regulatory authorities to set up norms to be fulfilled for drug safety and inspection issues. This, on one hand, could provide a basic guideline for the regulatory authorities and regulators to improve their professional levels and administrative acumen and on the other hand, it could also provide a baseline for society to judge whether the regulatory authorities and regulators have fulfilled their responsibilities correctly and thereby also help prevent regulators from being mistakenly punished. This study proposes that a systematic and functional norm for drug safety and inspection could be set up relating to the determination of the responsibilities of regulatory authorities and scope of various inspections, number and frequency of inspections, number and qualifications of regulators, handling of inspection results, inspection records, and disciplinary codes for inspectors. This study also puts forward suggestions on who should be responsible for drafting the norms and what are the factors that need to be considered while formulating the norms.

Description: Serum uric acid (SUA) elevation has been previously related to impaired fasting glucose and type 2 diabetes. The present study was comprehensive to examine the associations between SUA and impaired glucose tolerance (IGT) in Chinese adults. For this purpose, data were collected from a community-based health examination survey conducted in Central China; 2-h glucose (OGTT) and SUA were measured in 1956 men and women. In multivariate models, SUA levels were significantly associated with an increasing trend of 2-h glucose (OGTT) ( P for trend 〈 0.0001). The odds ratios (OR; 95 % CI) of IGT across increasing quartiles of SUA were 1.0, 1.354 (0.948–2.087), 1.337 (0.959–2.251), and 2.192 (1.407–3.416), after adjusting for age, sex, body mass index, waist circumference, fasting insulin, blood pressure, serum lipids, serum creatinine, and estimated glomerular filtration rate. ( P for trend = 0.001). In addition, we found an additive pattern between SUA and triglyceride (TG; P  = 0.038) or between SUA and low-density lipoprotein cholesterol (LDL-C; P  = 0.041) in relation to IGT. SUA was related to IGT in the Chinese adults, independent of other conventional metabolic risk factors. TG and LDL-C might modify the associations.

Description: The objective of the study is to investigate the CXCR5 and MMP-13 expression in colorectal cancer and explore its correlation between the clinicopathological characteristics and prognosis. The expressions of CXCR5 and MMP-13 proteins in 236 paired specimens of colorectal cancer and incisal edge normal tissues as well as 62 samples of colorectal adenoma tissues were analyzed by immunohistochemistry. The CXCR5 and MMP-13 positive expression rate in colorectal cancer tissues was 43.6 and 80.5 %, respectively. Both rates were higher than those in the incisal edge healthy intestinal mucosal tissues (4.2 and 13.1 %) and colorectal adenoma tissues (24.2 and 64.5 %), P  〈 0. 05 in both cases. The expressions of the CXCR5 and MMP-13 proteins were positively related to the lymph node and distal metastasis, tumor stage and relapse, P  〈 0. 05. The expression of the CXCR5 protein was positively related to MMP-13, P  〈 0. 05. The median and overall survival in the patients with positive CXCR5 and MMP-13 expression were significantly shorter than those with negative expression: median survival, 20.5 months (CXCR5 +) versus 30.8 months (CXCR5 −), 20.3 months (MMP-13 +) versus 24.6 months; overall survival, 26.5 months (CXCR5 +) versus 47.5 months (CXCR5 −), 22.7 months (MMP-13 +) versus 29.3 months. The expression of CXCR5 and MMP-13 could promote the pathogenesis, development, metastasis, and relapse of colorectal cancer. It could also serve as a valuable indicator for the prediction of metastasis and relapse of colorectal cancer.

Description: To compare the degree and distribution of mineralization in femoral neck cortex from 23 women with hip fractures (age 65–96 years) and 17 female controls (age 72–103 years), we obtained 3D data by synchrotron radiation microtomography (SRμCT). Variables were degree of mineralization of bone (DMB) in total cortex (cDMB SR MEAN), osteons (oDMB SR MEAN), and pure interstitial tissue (intDMB SR MEAN). The cortex on SRμCT images was divided into nine to twelve 50-μm zones from the periosteum to the endosteum; cDMB SR MEAN, oDMB SR MEAN, and intDMB SR MEAN were measured in each zone. We used descriptive statistics and t tests, general linear model analyses to compare DMB SR values across zones and individuals, one-way analysis of variance for within-group comparisons of zones. In patients, the variance of mineral content value was not different than in controls, but mean values of degree of mineralization varied across zones. These cross-sectional data suggest that bone fragility may be related to a greater heterogeneity of the distribution of mineralization in femoral neck cortex.

Description: SOX9 gene encodes a transcription factor essential for a central role in the development and differentiation of multiple cell lineages, such as in neurogenesis, neural crest development, etc. Recent study reported that overexpression of SOX9 mRNA is closely associated with poor clinical outcome of patients with malignant gliomas. In the present study, we have explored the regulatory role of SOX9 in glioma metastasis. To investigate the role of SOX9 in glioma metastasis, SOX9 overexpressed in human glioma cell line U251 on cell migration and invasion was evaluated via wound scratch, Transwell assay without or with Matrigel. SOX9-induced changes in EMT process were evaluated by Western blot. Furthermore, the role of β-catenin in the regulatory effect of SOX9 on cell migration and invasion, and EMT process was explored by suppressing β-catenin expression in SOX9-overexpressed U251 cells. SOX9 overexpression in U251 cells resulted in a significant increase in cell migration and invasion. SOX9 overexpression also markedly promoted the EMT process. More importantly, our results revealed that SOX9 stimulated metastasis through activating Wnt/β-catenin signaling. In summary, this study indicated that the promoting effect of SOX9 on glioma metastasis was, at least in part, through Wnt/β-catenin signaling. The findings in this study highlight the effectiveness and therapeutic potential to utilize SOX9 targeted strategies in the treatment of glioma.

Description: In this study, we develop a fast and convenient method for the detection of 18 types of free amino acids in the serum of ischemic stroke patients. We use high performance liquid chromatography-diode array detector and thermo C18 column to separate 6-aminoquinolyl- N -hydroxysuccinimidyl carbamate-derivatized amino acids. We find that Gln, His, Gly, Arg, and Cys levels are significantly lower in the serum of ischemic stroke patients comparing with normal persons. Our data indicate that this simple method can be used to detect free amino acids in serum with accurate and reliable results. This study provides a basis for the clinical treatment of ischemic stroke patients and suggests that amino acids can be supplemented to the patients during clinical treatment, which may improve patient prognosis.

Description: The purpose of the study was to analyze the computed tomography (CT) findings of primitive neuroectodermal tumor (PNET) of the kidney and correlate them pathologically. Ten cases of pathologically confirmed renal PNET were collected and retrospectively reviewed. The CT features that were analyzed include tumor size, shape, margins, density, nature of enhancement, presence of thrombosis, and metastasis, etc. These parameters were correlated with pathological findings and combined with literature review. The median age of the patients was 30 years. CT images showed solitary, large, ill-defined, irregular, or lobulated heterogeneous mass. Invasive growth toward the renal cortex and pelvis with renal cortical interruptions were seen in eight cases with one case exhibiting invasion that extended beyond the renal capsule with soft tissue seen in the perirenal fat pace. The tumors were confined to the kidney contour with enlargement of kidney in six of the cases. Cystic changes with mural nodules were detected in three cases. Eight cases showed persistent moderate enhancement during the nephrographic phase. Irregular septum-like structures were seen in four cases. Thrombosis was detected in eight cases. Lymph node metastasis was detected in eight cases with bilateral lung metastasis in two and bone metastasis in one. Renal PNET is a rare highly aggressive disease affecting younger people. It should be considered as a strong differential when well confined, yet large tumors that cause enlargement of the kidney are seen and also when tumors expressing cystic changes along with mural nodules are seen. Although renal PNET has certain other characteristic CT features, pathological and immunohistochemistry report must also be sought for definitive diagnosis.

Description: Viral myocarditis (VMC) is a common clinical condition; however, no specific treatment has been available from the perspective of modern western medicine, and typically only symptomatic treatment is provided in clinical settings. The traditional Chinese medicine (TCM) has shown certain advantages in treating VMC. Last few years have witnessed certain advances in the TCM-based research on the etiology and pathogenesis of VMC and its clinical management. This article reviews the clinical advances made in the TCM-based management of VMC in the last 5 years.

Description: Severe acute pancreatitis (SAP) is a common acute abdominal disease. This study was designed to investigate the preventive effects of curcumin on SAP and its possible mechanism of action. We observed increased volume of ascites, serum AMY, IL-6, and TNF-α levels, and expression of TLR-4 and NF-κB mRNA and protein in a rat model of SAP. Application of curcumin resulted in lower ascites volume and serum AMY. The levels of serum cytokines IL-10 and TNF-α were also significantly reduced after curcumin treatment, as evident from ELISA analysis. RT-PCR analysis showed down-regulation of TLR4 and NF-κB expressions as a function of curcumin treatment. Our results demonstrate the protective effect of curcumin in a rat model of SAP via the involvement of TLR-4/NF-κB signaling pathway.

Description: The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder cancer need further research.

Description: Chronic myeloid leukemia (CML) is a clonal disorder characterized by excessive accumulation of myeloid cells in the peripheral blood. In the present study, to investigate the role of Hiwi in leukemogenesis, lentivirus-mediated Hiwi overexpression was performed in a CML cell line, K562 cells. Our data revealed that Hiwi protein expression was undetectable in K562 cells, and its overexpression suppressed cell proliferation, induced cell cycle arrest at G0/G1 and G2/M phases, and promoted apoptosis in K562 cells in vitro. Expression of anti-apoptotic protein, Bcl-2, was decreased in cells expressing Hiwi, whereas that of pro-apoptotic proteins, Bax, activated caspase-3, -9, and cleaved poly (ADP-ribose) polymerase were increased. Additionally, Hiwi upregulation enhanced the chemosensitivity of CML cells to daunomycin. Our study illustrates that expression deletion of Hiwi may be involved in the pathogenesis of human CML and suggests a possible role of Hiwi in regulating the cell growth, cell cycle, and apoptosis of CML cells in vitro.

Description: Molecular dynamics simulations, binding free energy calculations, principle component analysis (PCA), and residue interaction network analysis were employed in order to investigate the molecular mechanism of M184I single mutation which played pivotal role in making the HIV-1 reverse transcriptase (RT) totally resistant to lamivudine. Results showed that single mutations at residue 184 of RT caused (1) distortion of the orientation of lamivudine in the active site due to the steric conflict between the oxathiolane ring of lamivudine and the side chain of beta-branched amino acids Ile at position 184 which, in turn, perturbs inhibitor binding, (2) decrease in the binding affinity by (~8 kcal/mol) when compared to the wild-type, (3) variation in the overall enzyme motion as evident from the PCA for both systems, and (4) distortion of the hydrogen bonding network and atomic interactions with the inhibitor. The comprehensive analysis presented in this report can provide useful information for understanding the drug resistance mechanism against lamivudine. The results can also provide some potential clues for further design of novel inhibitors that are less susceptible to drug resistance.

Description: The aim of this study was to analyze the placental expression and allele status of promoter region of Klotho in association with preeclampsia, which represents the most common hypertensive disease of pregnancy. Klotho mRNA and protein levels were determined using real-time PCR and Western blot, respectively, in placental tissue samples obtained from 34 patients affected with preeclampsia and 34 controls. A PCR-based genotyping analysis was carried out in the promoter region of Klotho gene. Moreover, expression levels of pluripotency markers, Nanog and Oct4, and telomere length were assessed using real-time PCR. Klotho mRNA and protein levels were reduced in preeclamptic placentas compared with controls. −744delA single-nucleotide polymorphism was significantly associated with preeclampsia. In pathological placentas, there was a downregulation of pluripotency markers and a reduced telomere length. This study is the first to evaluate the placental expression level of Klotho in association with preeclampsia. Further analyses will clarify its role in the pathogenesis of this pregnancy hypertensive disorder.

Description: Patients with hyperhomocysteinemia (HHcy), or elevated plasma homocysteine (Hcy), are at higher risk of developing arrhythmias and sudden cardiac death; however, the mechanisms are unknown. In this study, the effects of HHcy on sinus node function, atrioventricular conduction, and ventricular vulnerability were investigated by electrophysiological (EP) analysis, and the role of magnesium (Mg 2+ ), an endogenous N -methyl- d -aspartate (NMDA) receptor antagonist, in attenuating EP changes due to HHcy was explored. Wild-type mice ( WT ) and mice receiving Hcy in the drinking water for 12 weeks ( DW ) were subjected to electrocardiographic and EP studies. DW compared to WT had significantly shorter RR, PR, QT, and HV intervals, corrected sinus node recovery times (CSNRT), Wenckebach periodicity (WP), atrioventricular nodal effective refractory periods (AVNERP), and right ventricular effective refractory periods (RVERP). To examine the role of Mg 2+ in mitigating conduction changes in HHcy, WT , DW , and heterozygous cystathionine-β-synthase knockout mice ( CBS + /− ) were subjected to repeat EP studies before and after administration of low-dose magnesium sulfate (20 mg/kg). Mg 2+ had no effect on EP variables in WT, but significantly slowed CSNRT, WP, and AVNERP in DW , as well as WP and AVNERP in CBS + /− . These findings suggest that ionic channels modulated by Mg 2+ may contribute to HHcy-induced conduction abnormalities.

Description: The objective of this study was to explore the early diagnosis methods of severe pediatric pneumonia. A total of 65 cases hospitalized in pediatric departments and ICU of our hospital because of severe pneumonia were divided into two groups according to pathogen detection. The groups were as follows: 34 cases of bacterial pneumonia, 32 cases of a non-bacterial pneumonia, and 37 cases of healthy children after physical examination in our hospital as the control group. The peripheral blood was sampled from each of the three groups for procalcitonin (PCT). The pediatric PCT level in peripheral blood of the bacterial pneumonia group was significantly higher than that of non-bacterial pneumonia group and the control group. The statistical differences (each at p  〈 0.01) and the level of pediatric serum PCT in the bacterial pneumonia group before treatment were statistically different from that in the same group after treatment ( p  〈 0.01), while the level of pediatric serum PCT in non-bacterial pneumonia group before treatment was statistical indifferent from that in the same group after treatment ( p  〉 0.01). PCT level in pediatric peripheral blood is an important diagnostic indicator of bacterial infection and a sensitive indicator of distinction between bacterial pneumonia and the non-bacterial pneumonia, thus being of great significance for clinical and differential diagnosis.

Description: The prognostic role of phosphatase and tensin homolog (PTEN) in non-small cell lung cancer (NSCLC) has been controversial. In this study, levels of PTEN expression were investigated in NSCLC patients and their prognostic value in NSCLC was assessed. PTEN expression in tumor tissues from 68 NSCLC patients was analyzed using immunohistochemistry and confocal microscopy. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. NSCLC patients classified as expressers of high levels of PTEN ( n  = 46) had better prognoses than those classified as expressers of low levels (mean survival 17.1 vs. 12.9 months, log rank P  = 0.038). In patients with adenocarcinoma (AC), high PTEN expression ( n  = 9) was associated with significantly longer survival than low PTEN expression (mean survival 23.50 vs. 15.54 months, log rank P  = 0.043). High levels of PTEN expression resulted in 43 % reduction in risk for all NSCLC patients (HR 0.57, 95 % CI 0.33–0.98, P  = 0.041). PTEN expression and clinical stage remained significantly associated with survival after adjustment for age, sex, and tumor type (HR 0.56, 95 % CI 0.32–0.99; P  = 0.048; HR 0.54, 95 % CI 0.36–0.97; P  = 0.045). No significant difference in continuous PTEN expression levels was observed among groups with different clinical or pathological characteristics ( P  〉 0.17). When levels of PTEN expression were binarized using the optimal cut-point, higher levels of PTEN expression were observed in patients with T1/T2 than in those with T3/T4 (80 and 58 %, respectively, P  = 0.049) and in patients with AC than in those with squamous-cell carcinoma (78 and 58 %, respectively, P  = 0.08). No significant difference in binarized PTEN expression levels was found among groups with any other clinical/pathologic characteristic ( P  〉 0.28). Our results suggest that high levels of PTEN expression may be favorable prognostic markers in NSCLC patients.

Description: Our objective is to explore the tumor-specific mutated genes by transcriptome sequencing of patients with acute myeloblastic leukemia. 96 patients with subtype M2 acute myeloid leukemia (AML), admitted during January 2007 to January 2012, were selected. Bone marrow and peripheral blood samples from the patients after the first visit and the patients who were improved or alleviated, were subjected to high-throughput sequencing to compare the gene expression. The single nucleotide mutation related to subtype M2 AML was detected. Meanwhile, real-time fluorescent quantitation RT-PCR was used to detect the AML1/ETO fusion gene and its correlation with prognosis after treatment. Among 96 patients, AML1 – ETO fusion gene was positive in 52 cases, the positive rate was 54.17 %. The complete relief (CR) rate of AML1 – ETO fusion gene positive patients was 84.62 %, and the CR rate of AML1/ETO fusion gene negative patients was 77.27 %; the CR rate of AML1 – ETO positive patients was higher than that of patients without the fusion gene, however there was no statistical difference. In the analysis of recurrent gene mutation in AML-M2 patients, IDH2 , ASXL1 , TET2 , JAK1 and JAK2 gene expressions were not significantly different before treatment and after CR, however, IDHI , JAK3 , ABL1 and BCR gene expressions were significantly different. In the study of transcriptome in AML-M2 patients, high-throughput sequencing could effectively detect the difference of the gene expression before treatment and after CR. Furthermore, positive expression of AML1 – ETO fusion gene had effect on the prognosis of patients.

Description: The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. RT-PCR was used to detect the mRNA expression of IL-6, IL-10, Cox-2, iNOS, and TNF-α4h following reperfusion. Infarct volume at different time points after I/R was analyzed using 2,3,5-triphenyl tetrazolium staining, and neurological damage score (neurological severity scores, NSS) was used to evaluate the effect of PSD-93 gene knockout on the MCAO-induced neurological injury. In WT mice, early I/R injury led to the increase in the mRNA expression of proinflammatory cytokines IL-6, Cox-2, iNOS, and TNF-α that coincided with the decrease in the expression of anti-inflammatory cytokine IL-10, as compared to the sham group ( P  〈 0.05). This effect was markedly attenuated by depleting PSD-93 levels by gene knockout. As compared to sham group, in PSD-93 KO mice I/R4h led to downregulation of Cox-2 and iNOS expression, and increase in the mRNA levels of IL-10 ( P  〈 0.05). In addition, following MCAO, PSD-93 KO mice exhibited improved NSS and reduced infarct volumes, as compared with WT animals. PSD-93 knockout may play a neuroprotective role by mediating the early release of inflammatory cytokines induced by cerebral ischemia.

Description: The purpose of this article is to study the effect of ephedrine and phenylephrine on placental vascular resistance during cesarean section under epidural anesthesia via Doppler ultrasonography. Sixty female subjects, scheduled for elective cesarean section and had an intrathecal injection of bupivacaine, were randomly divided into two groups to receive phenylephrine (50 μg/min) or ephedrine (4 mg/min) via titration to maintain systolic blood pressure at baseline. Doppler ultrasonography was used to measure baseline vascular resistance values prior to administration of anesthesia, and resistance index (RI) and systolic peak velocity/diastolic velocity (S/D) values of umbilical artery and uterine artery were measured at each time point within first 20 min following intrathecal injection. Blood samples were collected from umbilical artery and umbilical vein during delivery to assess the blood gas values. No significant differences in RI and S/D values of umbilical artery and uterine artery after intrathecal injection were found between two groups. RI and S/D values of uterine artery slightly increased in both groups at each time point after anesthesia, but remained within the normal range. No significant differences were observed in blood gas values and the total amount of vasoconstriction drugs between two groups. In contrast to previous reports that used animal models, our study did not show increased placental vascular resistance in patients following phenylephrine (50 μg/min) or ephedrine (4 mg/min) infusion, as well as no significant differences in the effect of either of these two. The discrepancy between the results of human and animal studies may be related to species differences and the mechanism of human placental vascular remodeling.

Description: Recent years, we has witnessed a sharp increase in the complications of Type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Here we aimed to determine the risk factors for T2DM patients with NAFLD and the relationship of serum uric acid (SUA) in these complications. We performed retrospective analysis of 300 T2DM patients admitted into our hospital from April 2010 to January 2014. We divided the T2DM patients into two groups based on whether the patients also had NAFLD or not, Group A (without NAFLD, 155 cases) and Group B (with NAFLD, 145 cases). General information of the patients was collected and analyzed statistically. Meanwhile, we detected and compared the blood biochemistry, glucose, and fasting insulin (FINS), and further performed Logistic regression analysis and determined the risk factors in T2DM patients with NAFLD. Significantly higher BMI, waist circumference, hip circumference, WHR, systolic, and diastolic blood pressure were observed in T2DM patients with NAFLD than the patients without NAFLD, which were statistically different ( P  〈 0.05). There were also significant higher levels of TC, TG, ALT, AST, GGT, and SUA in T2DM patients with NAFLD than those in patients without NAFLD, which were statistically different ( P  〈 0.05). Significantly higher levels of FPG, FINS, and HOMA-IR were observed in the T2DM patients with NAFLD than those without, which were statistically significant ( P  〈 0.05). Logistic regression analysis also showed high BMI, WHR, TG, and SUA were independent risk factors in T2DM patients with NAFLD ( P  〈 0.05). Meanwhile, SUA levels were positively correlated with BMI, W, H, WHR, hip circumference, waist circumference, TG, ALT, AST, GGT, FPG, FINS, and HOMA-IR, which were statistically significant ( P  〈 0.05). The risk factors for T2DM patients with NAFLD are mainly BMI, WHR, TG, and SUA. Our findings provide clinical implications for the prevention and early diagnosis of T2DM patients with NAFLD.

Description: Our objective is to investigate the promoting effect of hypoxic preconditioning combined with microbubble (MB)-mediated ultrasound (US) on the SDF-1/CXCR4 expression and the migration ability of mesenchymal stem cells (MSCs). Based on the uniform design, the parameters of MB-mediated US, such as the total treatment time (T), acoustic intensity (Q), and the dosage of MBs, were optimized firstly. The results were assessed by regression analysis. Using the optimum irradiation parameters, the concentration of SDF-1 in the supernatant, the expression levels of membrane CXCR4, and the cell viability of hypoxic MSCs or normoxic MSCs were compared. The in vitro transwell migration assay was performed as well. The best combination of parameters for more SDF-1 secretion and less MSCs death was T  = 30 s, A  = 0.6 W/cm 2 , and MB  = 10 6 /ml. After 24 h of hypoxic preconditioning, the expression of SDF-1 and surface CXCR4 was increased in the hypoxic MSC group as compared to the normoxic MSC group ( P  〈 0.05). On the basis of that, MB-mediated US could further upregulate the expression of SDF-1/CXCR4 with the optimum parameters ( P  〈 0.05), while the cell viability was only decreased by about 9–10 % compared to the untreated groups. The number of successfully migrated cells was also the largest in the hypoxic preconditioning combined with MB-mediated US group than all the other groups. The results obtained indicate the combination of hypoxic preconditioning, and MB-mediated US can upregulate the SDF-1/CXCR4 expression and improve the migration ability in MSCs.

Description: The aim of the study was to explore the expression of three genes, HSPD1, SCUBE3, and CXCL14, in osteosarcoma cells and tissue, as well as their association with the prognosis of patients with osteosarcoma. The expression of HSPD1, SCUBE3, and CXCL14 in osteosarcoma cells was detected by using Western blotting method. siRNA was used to knockdown the expression of the three genes. CCK8 cell proliferation assay was used to observe the effect of siRNA interference on U2OS cell proliferation. The expression of the three genes in osteosarcoma tissue was detected employing immunohistochemical method. Kaplan–Meier survival analysis was used to compare the relations between the expression of the three genes and prognosis. The Western blotting results showed that the expression of Hsp70, SCUBE3 protein, and CXCL14 chemotactic factor in osteosarcoma cells was significantly higher than that in normal osteocytes ( p  〈 0.05). After the three genes were interfered by siRNA, the mRNA and protein expression levels of these genes in osteosarcoma cells were significantly decreased ( p  〈 0.05). The growth rate of U2OS cell after the siRNA interference was significantly lower than that before interference and that in the control group transfected with negative control siRNA ( p  〈 0.05). The result of immunohistochemistry demonstrated that the expression of Hsp70, SCUBE3 protein, and CXCL14 chemotactic factor in osteosarcoma tissues was significantly higher than that in adjacent muscle tissue ( p  〈 0.05). Kaplan–Meier survival analysis indicated that the survival rate of the patients with high expression of those three kinds of genes was obviously lower than that of other patients ( p  〈 0.05). There was no significant difference between the survival rates of patients with high or low expression of two genes ( p  〉 0.05). The expression of HSPD1, SCUBE3, and CXCL14 was all high in osteosarcoma tissues and cells; moreover, the three kinds of genes had close correlations with the prognosis of the patients. Targeted inhibition of these three genes could inhibit the proliferation of the tumor, which may become a new therapeutic target.

Description: The aim of the study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy of personalized nutrition guidance on birth rate of fetal macrosomia in the pooled studies. A comprehensive search was conducted to identify all eligible studies using the databases of PubMed, MEDLINE, Embase, Wanfang, Chongqing Weipu Database for Chinese Technical Periodicals and China National Knowledge Infrastructure and reference lists of relevant articles. The methodological quality of the included trials was assessed based on the Jadad scale. We used risk ratios (RRs) to assess the strength of the association, and 95 % confidence intervals (CIs) to evaluate the precision of the estimate. Heterogeneity, publication bias, and sensitivity analysis were also explored. A total of nine RCT studies, including 7,458 pregnant women, were included in the present meta-analysis. The overall results showed that personalized nutrition guidance significantly reduced the birth rate of fetal macrosomia (RR 0.289, 95 % CI 0.184–0.453, P  〈 0.01) in Chinese population. Simultaneously, publication bias was detected in this meta-analysis. The personalized nutrition guidance can significantly reduce the birth rate of fetal macrosomia. However, due to the limited number of RCTs, especially those with large sample size and multicenter that were quantitatively insufficient, further studies of high quality are required.

Description: Several monomers isolated from Tripterygium wilfordii Hook f. ( Celastraceae ) have attracted worldwide interest. In this study, we established a simple and reliable kidney transplantation model in beagle dog to evaluate the immunosuppressive activity of demethylzeylasteral (T-96), an immunosuppressive monomer isolated from the root xylem of T. wilfordii . Recipient and donor male beagle dogs were obtained from two different breeders to ensure MHC mismatching. All dogs were randomly divided into six groups following kidney transplantation, and different doses of T-96 or cyclosporine A (CsA) were administered to each group during 14 days of observation. The results showed that T-96 alone at a dosage of 10 or 20 mg/kg/day prolonged graft survival up to 10.83 ± 1.47 or 11.17 ± 1.47 days. A combination of T-96 and CsA significantly prolonged the survival time to 13.33 ± 1.75 days. The results demonstrated that T-96 can inhibit acute rejection in kidney transplantation, and the inhibitory effect of T-96 was enhanced when combined with CsA, which suggests the possible use in organ transplantation to prevent immune rejection.

Description: Curcumin possesses anti-cancer effects. In the current study, we tested the effect of curcumin on cell proliferation, viability, apoptosis, cell cycle phases, and activation of the PI3K/Akt pathway in the renal cell carcinoma (RCC) cell line RCC-949. We observed that cell proliferation and viability were markedly inhibited by curcumin, while cell apoptosis was promoted. The latter effect was associated with increased expression of Bcl-2 and diminished expression of Bax (both: mRNA and protein). The cells treated with curcumin increasingly went into cell cycle arrest, which was likely mediated by diminished expression of cyclin B1, as seen in curcumin-treated cells. In addition, curcumin decreased activation of the PI3K/AKT signaling pathway. In conclusion, our results demonstrate that curcumin exerts anti-cancer effects by negative modulation of the PI3K/AKT signaling pathway and may represent a promising new drug to treat RCC.

Description: The present study intends to explore the influence of intensity-modulated radiation therapy on the quality of life for patients with nasopharyngeal carcinoma, which provides a theoretical basis and practical foundation for clinical practice. The present study randomly enrolled 130 cases of patients with nasopharyngeal carcinoma (NPC) in different stages who were admitted in The Second Affiliated Hospital of Fujian Medical University and the First Affiliated Hospital of Chongqing Medical University from September 2007 to August 2012, including 65 cases in IMRT group who received intensity-modulated radiation therapy and 65 cases in CRT group who received conventional radiation therapy. The prescribed dose in the target region of radical radiation therapy was 72 Gy/36 f; the prescribed dose in the target region at high risk was 60–64 Gy/30–32 f; the prescribed dose in the target region at low risk was 50–54 Gy/25–27 f and 2 Gy/f, with conventional fractionated irradiation of 1 f/d and 5 f/w. The data of the quality of life for patients with NPC who received intensity-modulated radiation therapy and conventional radiation therapy were collected and analyzed by filling in the questionnaire survey, including the Quality of Life Questionnaire of Head and Neck 35 (QLQ-H&N35) and Shot Form 36 Health Survey Questionnaire (SF-36). RP, VT, BP, SF, and RE scores in eight fields in SF-36 Scale were declined during the radiation therapy and risen again after radiation therapy, and those measured at 6 months after radiation therapy were higher than those before radiation therapy (all P  〈 0.05). The scores in IMRT group measured at two and six months after radiation therapy were all higher than those in CRT group (all P  〈 0.05). The scores of head and neck pain, pararthria, dysphagia, social difficulty, sensory difficulty, difficulty in feeding, xerostomia, cough, sticky saliva, and sensory discomfort during the radiation therapy were lower than those before radiation therapy (all P  〈 0.05). Except for the scores of sticky saliva and xerostomia, the other scores measured at 6 months after radiation therapy were all lower than those before radiation therapy, and the scores of dysphagia, sticky saliva, and xerostomia in MRT group were lower than those in CRT group (all P  〈 0.05). Conventional radiation therapy and intensity-modulated radiation therapy can cause a decline the quality of life for the patient with head and neck cancer, but intensity-modulated radiation therapy can improve local tumor control rate and significantly reduce the incidence of adverse reactions.

Description: A research on Jinyulian Oral Solution was conducted and the objectives were to discover its possible acute toxicity and antibacterial effects when used in vitro and in vivo. Regarding the acute toxicity test, Kunming mice were fed a maximum amount of the solution as their stomachs could hold, i.e., 40 mL kg −1 . To ascertain the minimum inhibitory concentration (MIC) of the solution, two types of germs, i.e., Staphylococcus aureus and Escherichia coli , were selected and tube dilution method was adopted. An antibacterial experimental model relying on animals’ body was developed for the researchers to observe the solution’s antibacterial effects. Test results showed that no abnormalities were discovered within 14 days after the initial date of testing and the mice grew as normal when fed with an amount of the solution 250 times of a normal clinical doze (In this case a man was assumed to weigh 60 kg.) and that the solution demonstrated obvious antibacterial effects on the two types of selected germs. The respective measured MIC 50 and MIC 90 values of the two germs were 3.2, 12.8, 6.4, and 25.6 mg L −1 . Therefore, it is reasonable to conclude that Jinyulian Oral Solution possesses no acute toxicity but obvious antibacterial effects on the two before-mentioned germs.

Description: The aim of this study is to explore the expression and significance of urokinase-type plasminogen activator (u-PA) and vascular endothelial growth factor (VEGF) in gastric cancer, providing a novel insight for the diagnosis and treatment of gastric cancer. The gastric cancer specimens, which were excised from 87 patients and confirmed during July, 2012–July, 2014, were selected as observation group, and the normal tissue next to the tumor (more than 5 cm from the edge of the tumor) from 45 patients were randomly selected as control. u-PA and VEGF were detected by immunohistochemistry for the analysis of the correlation of u-PA and VEGF in two groups. The positive rates of u-PA and VEGF in gastric cancer tissue were 81.61 and 79.31 %, respectively, which were 6.67 and 8.89 % in the control group, respectively. The positive rates in the observation group were obviously higher than those in the control group, and the difference was statistically significant ( P  〈 0.05). Among the 87 gastric cancer tissue samples from the observation group, the positive rates of u-PA and VEGF in the gastric cancer with poor differentiation, lymphatic metastasis, invasion up to serosal layer, and TNM stage III + IV were obviously higher than those in the gastric cancer with high differentiation, non-lymphatic metastasis, invasion not up to the serosal layer, and TNM stage I + II, and the difference was statistically significant ( P  〈 0.05). Among the 87 gastric cancer tissue samples from the observation group, u-PA and VEGF were found to be positive in 60 cases and negative in 7 cases. By comparing the two groups, u-PA and VEGF were positively correlated in gastric cancer tissue ( P  〈 0.05). u-PA and VEGF were highly expressed in gastric cancer tissue, which could be used as the molecular biological indicators to predict the invasion and metastasis potential of gastric cancer. The combination of two factors plays a guiding role in early diagnosis and treatment of gastric cancer.

Description: We sought to evaluate the prognosis of different treatment strategies on patients with multivessel coronary disease and high SYNTAX score. 171 patients with multivessel coronary disease and SYNTAX score ε33, who underwent coronary angiography between July 2009 and July 2010 at our hospital were retrospectively selected and divided into incomplete and complete revascularization intervention groups (IR), a coronary artery bypass surgery group (CABG), a conservative drug therapy group according to treatment strategies chosen and agreed by the patients. These patients were followed up for 19.44 ± 5.73 months by telephone or outpatient service. We found the medical treatment group has a lower overall survival than the IR, CR group, and CABG group ( P log-rank values are 0.03, 0.03, and 0.02, respectively). The medical treatment group also has a lower survival than the IR group, CR group, and CABG group in cerebral stroke and recurrent myocardial infarction (MI) ( P log-rank values are 0.004, 0.03, and 0.001, respectively) and MACE events ( P log-rank values are 0.003, 0.001 and P  〈 0.001, respectively). The medical treatment group and IR group have lower survival in recurrent angina pectoris than the CR group and CABG group ( P log-rank values are 0.02, 0.02 and 0.03, 0.008, respectively). There are no significant differences between the CR group and the CABG group in number of deaths, strokes and recurrent MIs, MACE events, angina pectoris ( P log-rank values are 0.69, 0.53, and 0.86, respectively). The IR group shows a lower survival than the CR group and CABG group only in angina pectoris ( P log-rank values are 0.03 and 0.008, respectively). For the patients with a high SYNTAX score, medical treatment is still inferior to revascularization therapy (interventional therapy or coronary artery bypass surgery). It appears that the CABG is not obviously superior to the coronary intervention therapy. Complete revascularization and coronary artery bypass grafting treatments simply have better survival in angina pectoris compared to the incomplete revascularization. Therefore, individual treatment strategies are recommended and more trials are required to study these effects.

Description: We tried to determine the risk factors for the long-term efficacy, recurrence, and metastasis of small hepatocellular carcinoma (HCC, diameter 〈5 cm). One hundred sixty-eight small liver cancer patients received percutaneous cryoablation therapy by argon–helium superconducting surgery system under the ultrasound guidance. Clinical parameter and the efficacy were analyzed after follow-up. After cryoablation treatment, the median follow-up time for the 168 patients was 36 (7–41) months. Liver functions were impaired as indicated by increased alanine aminotransferase, total bilirubin, total protein, albumin, and prothrombin activity. The difference of VEGF expression in liver cancer and the surrounding tissue is significant. 1-, 2-, and 3-year overall survival were 92.9, 83.9, and 65.5 %, respectively. Relapse-free survival was 76.8, 53.0, and 41.1 %. Less tumor number, higher tumor differentiation, and low VEGF expression predict higher metastasis-free and relapse-free survival rate. Lower Child-Pugh classification is correlated with the higher overall survival after cryoablation. There was no statistical significance in in situ intrahepatic recurrence patients, but VEGF changes were statistically significant for metastasis in other parts of liver or extrahepatic metastasis. Tumor number, differentiation, VEGF expression, large vessel invasion, lymph node, and extrahepatic metastasis all affect the overall and relapse-free survival. VEGF expression can be a predictable factor for liver cancer recurrence and metastasis.

Description: Human salivary aldehyde dehydrogenase (hsALDH) enzyme appears to be the first line of defense in the body against exogenous toxic aldehydes. However till date much work has not been done on this important member of the ALDH family. In this study, we have purified hsALDH to homogeneity by diethylaminoethyl-cellulose (DEAE-cellulose) ion-exchange chromatography in a single step. The molecular mass of the homodimeric enzyme was determined to be approximately 108 kDa. Four aromatic substrates; benzaldehyde, cinnamaldehyde, 2-naphthaldehyde and 6-methoxy-2-naphthaldehyde were used for determining the activity of pure hsALDH. K m values for these substrates were calculated to be 147.7, 5.31, 0.71 and 3.31 μM, respectively. The best substrates were found to be cinnamaldehyde and 2-naphthaldehyde since they exhibited high V max /K m values. 6-methoxy-2-naphthaldehyde substrate was used for further kinetic characterization of pure hsALDH. The pH and temperature optima of hsALDH were measured to be pH 8 and 45 °C, respectively. The pure enzyme is highly unstable at high temperatures. Ethanol, hydrogen peroxide and SDS activate hsALDH, therefore it is safe and beneficial to include them in mouthwashes and toothpastes in low concentrations.

Description: Gnaphalium affine is an annual herbaceous plant that is used as a traditional medicine in some Latin American and Asian countries. However, systematic studies on its anti-inflammatory activity and signaling pathways have not yet been reported. In this study, we investigated the anti-inflammatory effect of G. affine methanol extract in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells and fractioned the methanol extract into hexane, chloroform, ethyl acetate (EtOAc), butyl alcohol (BuOH), and distilled water (DW) by measuring the generation of nitric oxide (NO). G. affine inhibited the generation of NO and prostaglandin E 2 . The chloroform-soluble fraction most effectively inhibited LPS-stimulated NO production. We also examined the cytotoxicity of G. affine in three normal cell lines: RAW264.7, HEK293, and HaCaT. Cell viability assays showed that the methanol extract and chloroform-soluble fraction of G. affine had no cytotoxic effect on normal cell lines. The expression of pro-inflammatory mediators was also investigated. Western blotting and immunofluorescence showed that G. affine reduces the expression of iNOS, COX-2, and MAPKs, as well as activation of NF-κB in LPS-stimulated RAW264.7 cells. RT-PCR showed that G. affine also negatively regulates inflammatory cytokines at the gene expression level. Taken together, G. affine exerts its anti-inflammatory activity through inhibition of NO generation as a result of inhibiting NF-κB and MAPKs-related inflammatory signaling pathways. In addition, the result of GC–MS analysis revealed the presence of nineteen different types of constituents including guaiacol in the chloroform-soluble fraction of G. affine .

Description: Eight-hydroxyquinolines (8HQs) are a class of compounds that have been identified as potential therapeutics for a number of neurodegenerative diseases. Understanding the influence of structural modifications to the 8HQ scaffold on cellular behaviour will aid the identification of compounds that might be effective in treating dementias. In this study, we describe the action of 2-[(dimethylamino)methyl]-8-hydroxyquinoline (DMAMQ) on adult murine neural stem cells (NSCs) cultured in vitro. Treatment of NSCs with DMAMQ resulted in enhanced self-renewal and increased neurite outgrowth. Concurrent with the positive growth effects was an increase in intracellular reactive oxygen species, with the growth being inhibited by inactivation of the NADPH oxidase (Nox) enzyme family. Our results indicate that DMAMQ can stimulate neurogenesis via the Nox signalling pathway, which may provide therapeutic benefit in treating dementias of various types by replenishing neurones using the brain’s own reserves. The narrow concentration range over which these effects were observed, however, suggests that there may exist only a small therapeutic window for neuro-regenerative applications.

Description: Nanodiamond (ND) is an attractive class of nanomaterial for fluorescent labeling, magnetic sensing of biological molecules, and targeted drug delivery. Many of those applications require tethering of target biological molecules on the ND surface. Even though many approaches have been developed to attach macromolecules to the ND surface, it remains challenging to characterize dynamics of tethered molecule. Here, we show high-frequency electron paramagnetic resonance (HF EPR) spectroscopy of nitroxide-functionalized NDs. Nitroxide radical is a commonly used spin label to investigate dynamics of biological molecules. In the investigation, we developed a sample holder to overcome water absorption of HF microwave. Then, we demonstrated HF EPR spectroscopy of nitroxide-functionalized NDs in aqueous solution and showed clear spectral distinction of ND and nitroxide EPR signals. Moreover, through EPR spectral analysis, we investigate dynamics of nitroxide radicals on the ND surface. The demonstration sheds light on the use of HF EPR spectroscopy to investigate biological molecule-functionalized nanoparticles.

Description: Around 50 % of the world’s population is at the risk of dengue, a viral infection. Presently, there are not many drugs and prophylactic measures available to control dengue viral infection, and hence, there is an urgent need to develop effective antidengue compound from natural sources. In the current study, we explored the antiviral properties of the medicinal plant Vetiveria zizanioides against dengue virus. Initially, the antiviral properties of active compounds were examined using docking analysis along with reference ligand. The enzyme–ligand complex which showed higher binding affinity than the reference ligand was employed for subsequent analysis. The stability of the top scoring enzyme–ligand complex was further validated using molecular simulation studies. On the whole, the study reveals that the compound Ethyl 4-(4-methylphenyl)-4-pentenoate has an effective antiviral property, which can serve as a potential lead molecule in drug discovery process.

Description: Metalloporphyrins are an important group of sensitizers with a porphyrin skeleton. Their photophysical properties are significantly affected by the nature of the central ion. In this work, we focus on the mechanical properties of a cervix carcinoma cell line which underwent photodynamic treatment (PDT) with MgTPPS 4 photosensitzer. Atomic force microscopy alongside confocal microscopy was used to quantify and qualify the structural characteristics before and after PDT. Cells before PDT showed a fine actin network and higher elasticity with the median of Young modulus 12.2 kPa. After PDT, the median of Young modulus was 13.4 kPa and a large redistribution in the actin network was observed.

Description: Ribosomal S6 kinases (RSKs) are the major functional components in mitogen-activated protein kinase (MAPK) pathway, and these are activated by upstream Extracellular signal-regulated kinase. Upon activation, RSKs activate a number of substrate molecules involved in transcription, translation and cell-cycle regulation. But how cellular binding partners are engaged in the MAPK pathways and regulate the molecular mechanisms have not been explored. Considering the importance of protein–protein interactions in cell signalling and folding pattern of native protein, functional C-terminal kinase domain of RSK3 has been characterized using in vitro, in silico and biophysical approaches. RSKs discharge different functions by binding to downstream kinase partners. Hence, depending upon cellular binding partners, RSKs translocate between cytoplasm and nucleus. In our study, it has been observed that the refolded C-terminal Kinase domain (CTKD) of RSK 3 has a compact domain structure which is predominantly α-helical in nature by burying the tryptophans deep into the core, which was confirmed by CD, Fluorescence spectroscopy and limited proteolysis assay. Our study also revealed that RSK 3 CTKD was found to be a homotrimer from DLS experiments. A model was also built for RSK 3 CTKD and was further validated using PROCHECK and ProSA webservers.

Description: Cytokine interleukin-11 (IL-11) is a multifunctional protein with diverse roles in the normal cell signaling and in various pathologies. The structure of IL-11 is characterized by a four-helix bundle motif comprising two pairs of antiparallel α-helices arranged in an up–up–down–down configuration. Evaluation of the intrinsic disorder predisposition of human IL-11 by several computational tools clearly shows that this protein is predicted to have functional disordered regions potentially involved in interaction with natural binding partners. Signaling by IL-11 proceeds via an interaction of the protein with its membrane-specific receptor IL-11Rα and a subsequent interaction of the complex with the transmembrane signal-transducing receptor GP130. Cytoplasmic domain of IL-11Rα is predicted to be very disordered, and noticeable amount of disorder is present even in the large extracellular domain of the protein. GP130 is also predicted to have long disordered region that is located at the C-terminal of the protein and is expected to have several disorder-based binding sites. It shows that intrinsic disorder might play an important role in functioning of this signaling machine. A specific subset of the calcium sensor proteins (calmodulin, S100P, S100B, NCS-1, GCAP-1/2) exhibits metal-dependent binding of IL-11 with dissociation constants in a range of 1–19 μM, and the structural features of their hinge regions likely ensure selectivity and calcium sensitivity of IL-11 binding to the EF-hand proteins studied. IL-11 exhibits multiple effects on hematopoietic and non-hematopoietic systems. It plays a major role in orchestrating complex processes of tumor development and progression.

Description: Copper is one of the most abundant biological metals, and its chemical properties mean that organisms need sophisticated and multilayer mechanisms in place to maintain homoeostasis and avoid deleterious effects. Studying copper proteins requires multiple techniques, but electron paramagnetic resonance (EPR) plays a key role in understanding Cu(II) sites in proteins. When spin-labels such as aminoxyl radicals (commonly referred to as nitroxides) are introduced, then EPR becomes a powerful technique to monitor not only the coordination environment, but also to obtain structural information that is often not readily available from other techniques. This information can contribute to explaining how cuproproteins fold and misfold. The theory and practice of EPR can be daunting to the non-expert; therefore, in this mini review, we explore how nitroxide spin-labelling can be used to help the inorganic biochemist gain greater understanding of cuproprotein structure and function in vitro and how EPR imaging may help improve understanding of copper homoeostasis in vivo.

Description: Microorganisms have a large number of tools to withstand different, and sometimes strong, environmental stresses, including irradiation, but this ability should be further evaluated for certain applications. Growth inhibition and morphological alterations of Escherichia coli M-17 and Pseudomonas aeruginosa GRP3 wild-type cells caused by UV-A irradiation have been detected in the present study. Comparative analysis was carried out using well-established microbiological methods (determination of specific growth rate, growth lag phase duration, and colony-forming unit number—CFU) and computational approaches, employing light microscopy and digital image analysis to evaluate bacterial cell morphology. Decreases in the specific growth rate, prolonged lag-phases, and lowered CFUs were observed after 5 and 10 min of UV irradiation (approx. 40 Gy) compared to the control (nonirradiated) cells. Accordingly, two computational parameters—the average bacterial cell surface area and the bacterial cell perimeter (i.e., of the 2D projection of bacterial cells in microscopy image)—were reduced. The ratio of bacterial cell surface area ( S ) to the square of the perimeter ( p 2 ) was reduced after 5 min of irradiation, but after 10 min of irradiation the studied bacterial cells became flat cylinders. The revealed findings are concluded to be highly useful in developing new, rapid analysis methods to monitor environmental and UV irradiation effects on bacteria and to detect bacterial cell morphology alterations.

Description: Pseudomonas aeruginosa ( P. aeruginosa) is an opportunistic bacterium that frequently causes nosocomial infections. New generation cephalosporins and β-lactams along with inhibitors are used for the treatment of opportunistic bacterial infections. The indiscriminate use of antibiotics has led to the emergence of bacterial resistance. Carbapenem class of antibiotics like imipenem and meropenem are currently the final line of antibiotics for the treatment of infections caused by multidrug-resistant P. aeruginosa . Recent reports indicate that P. aeruginosa has acquired resistance to imipenem through a class D oxacillinase—OXA-10 extended spectrum β-lactamase (ESBL). OXA-10 ESBL is encoded by the gene bla OXA-10 . There is an urgent need to develop OXA-10 ESBL non-hydrolysing inhibitors. We have attempted to locate OXA-10 ESBL inhibitors by performing molecular docking and molecular dynamics studies on OXA-10 ESBL with imipenem analogues from ZINC database as well as employing imipenem to understand the mechanism of resistance at the structural level. Our in-silico analysis of imipenem analogues reveals that ZINC44672480 has ideal characteristics for a potent OXA-10 ESBL non-hydrolysing inhibitor. We believe that the results from our study will provide valuable insights into the mechanism of drug resistance and aid in designing potent inhibitors against OXA-10 ESBL producing P. aeruginosa .

Description: Patients with peripheral nerve injuries, especially severe injury, often face poor nerve regeneration and incompletely functional recovery, even after surgical nerve repair. Current researches have extensively focused on the new approaches for the treatment of peripheral nerve injuries. This review summarizes treatments of peripheral nerve injures, from conventional suturing method, to conduit coaptation with stem cell and growth factor, and review the developments of research and clinical application of these therapies.

Description: Fatty acid delta 6-desaturase (D6DES) and elongases are key enzymes in the synthesis of polyunsaturated fatty acids (PUFAs) including arachidonic acid (ARA) and eicosapentaenoic acid (EPA) from microorganisms to higher animals. To identify the genes encoding D6DES and elongases for PUFAs, we isolated each cDNA with a high similarity to the D6DES and ELOVL5-like elongases of mammals and fishes via degenerate PCR and RACE-PCR from Acanthopagrus schlegelii . A recombinant vector expressing AsD6DES was subsequently constructed and transformed into Saccharomyces cerevisiae to test the enzymatic activity toward n -6 and n -3 fatty acids in the PUFA biosynthesis. The heterologously expressed AsD6DES produced γ-linolenic acid (GLA, C 18:3 n -6) and stearidonic acid (STA, C 18:4 n -3) at conversion rates of 26.3–35.6 % from exogenous linoleic acid (LA, C 18:2 n -6) and α-linolenic acid (ALA, C 18:3 n -3) substrates, respectively. When AsELOVL5 was expressed in yeast, it conferred an ability to elongate GLA to di-homo-γ-linolenic acid (DGLA, C 20:3 n -6). In addition, AsELOVL5 showed an ability to convert ARA (C 20:4 n -6) and EPA (C 20:5 n -3) to dodecylthioacetic acid (DTA, C 22:4 n -6) and docosapentaenoic acid (DPA, C 22:5 n -3), respectively. In these results, the AsD6DES encodes a delta 6-fatty acid desaturase and the AsELOVL5 encoding a long-chain fatty acid elongase shows activity to enlongate C 18 Δ6/C 20 Δ5, but not C 22 .

Description: Currently, autologous bone marrow-derived stem cell is one of the most innovative areas of stem cells research. Previous studies on animal models of nervous system diseases have shown that these cells have a good effect on nervous system disorders. The alternative treatment with stem cells for the nervous system diseases has also gradually reached to clinical application stage. The prospect is captivating, but the safety and efficacy of this procedure need further research. To observe the clinical efficacy and side effects of the treatment for autologous mesenchymal stem cells and neural stem/progenitor cells which are in differentiated form by inducing with cerebrospinal fluid in the patients with nervous system diseases, thirty patients were selected from our hospital (2009-10 to 2012-07) and were followed at 1 month, 3 months, 6 months, 1 year and 2 years after the treatment with autologous mesenchymal stem cells and neural stem/progenitor cells in differentiated form was introduced. In this paper, we will introduce the process to make cells accessible for the clinical application by the description of the changes observed in 7 cases were followed for 2 years. The time for bone marrow mesenchymal stem cells could be available for clinical needs is as early as 5 days, not later than 10 days, and the median time is 8 days, while neural stem/progenitor cells in differentiated form can be available for clinical needs in as early as 12 days, not later than 15 days, and the median time is 13.5 days (statistical explanation: Case 5 only uses autologous mesenchymal stem cells, and Case 7 has two times bone marrow punctures). The neurological function of the patients was improved in 1-month follow-up, and the patients have a better discontinuous trend (statistical explanation: sometimes the neurological function of the patients between two adjacent follow-ups does not change significantly). After transplantation, four patients appeared to have transient fever, but it was easily controlled by symptomatic treatment. Seven patients did not appear to show secondary tumor induced by transplantation of stem cells in 2-year follow-up. Thus, it suggests that the use of autologous bone marrow-derived stem cells transplantation in patients with nervous system diseases is a feasible, convenient, safe, and effective method.

Description: The purpose of this study was to examine the relationship between the genetic polymorphism in the promoter of the SLC6A4 gene encoding the serotonin transporter (5-HTT) and the sensitivity to noxious stimulation from a clinical perspective. The genotyping of the 217 outpatients with mild epidermal abrasion in lateral crural region was performed by a combination of polymerase chain reaction and digestion. The intensity of pain to medical alcohol treatment was rated on a visual analog scale (VAS). The results suggest that the human triallelic 5-HTT genotypes are related to individual differences in sensitivity to alcoholic sting. According to the VAS ratings, the subjects with the 5-HTT low-expression genotype reported more pain than those with 5-HTT medium- and high-expression genotypes following test stimuli. There is no significant difference between sexes in the same SLC6A4 genotype and between medium and high expressions of 5-HTT subjects. Taken together, our study supports the hypothesis that the transcription rate of the 5-HTT transporter may play an important role in the pain sensitivity and central sensitization.

Description: Gastric cancer is one of the most outgoing human cancers in the world. Two main functional types were described: Intestinal adenocarcinoma and diffuse one. The most important purpose of this review is to analyze and investigate the main genetic factors involved in tumorogenesis of stomach and the molecular mechanism of their expression regulation alongside with the importance of cancer stem cells and their relationship with gastric cancer. It is evident that proper diagnosis of molecular case of cancer may lead to absolute treatment and at least reduction in the disease severity. However, stemness factors such as Sox2, Oct3/4, and Nanog were related with induced pluripotent stem cells, proposing a correlation between these stemness factors and cancer stem cells. Moreover, aberrant induction by Helicobacter pylori of the intestinal-specific homeobox transcription factors, CDX1 and CDX2, also plays an important role in this modification. There are some genes which are directly activated by CDX1 in gastric cancer and distinguished stemness-related reprogramming factors like SALL4 and KLF5. Correspondingly, we also aimed to present the main important epigenetic changes such as DNA methylation, histone modification, and chromatin modeling of stemness genes in disease development. Remarkably, a better understanding of molecular bases of cancer may lead to novel diagnostic, therapeutic, and preventive approaches by some genetic and epigenetic changes such as gene amplifications, gene silencing by DNA methylation, losses of imprinting, LOH, and mutations. Consequently, genome-wide searches of gene expression are widely important for surveying the proper mechanisms of cancer emergence and development. Conspicuously, this review explains an outline of the molecular mechanism and new approaches in gastric cancer.

Description: Breast cancer during lactation is very rare, accounting for 〈3 % of all breast cancers. Its diagnosis and treatment is often delayed during pregnancy. We report a case of female lactating breast carcinoma in a 29-year old patient. The disease was stage IIIB (T4N1M0). The patient received preoperative induction chemotherapy and high-dose chemotherapy with peripheral blood stem cell support, followed by adjuvant chemotherapy and endocrine therapy. The metastases were detected 17 months after operation, palliative treatment including different chemotherapy for 60 cycles, locoregional radiotherapy and endocrine therapy. The total number of cycles of chemotherapy was 67, and the survival time was 118 months. We discuss the diagnosis and treatment options for breast cancer during lactation, based on a literature review.

Description: The objective of this work was to study the effect of epidermal growth factor (EGF) induced secretions of angiogenesis factors in adipose-derived stem cells (ADSCs) and the involvement of mitogen-activated protein kinases (MAPK). ADSCs were cultured and ELISA assays were performed to quantify the vascular endothelial growth factor, the hepatocyte growth factor, and the stromal derived factor-1 in ADSC-conditioned medium before and after EGF treatments and after pharmacological inhibition of MAPKs with PD98059, SB203580, and SP600125. The tube formation assay was used to test the effects of EGF treated and inhibitor treated ADSCs on the human umbilical vein endothelial cells (HUVECs) tube formation. Liposuction was applied and ADSCs were cultured successfully. The ADSCs released a variety of angiogenic factors, with the EGF treatments enhancing secretions and promoting the HUVEC tube formation. The MAPK inhibitors PD98059 and SP600125 increased the paracrine to promote tubular formation, while the SB203580 played an opposite role. In conclusion, (1) the in vitro cultured ADSCs secrete various angiogenic factors and the EGF amplifies the secretion and can enhance the ADSCs on the HUVEC tube formation. (2) ERK1/2 and JNK pathway may be involved in the enhanced secretion capacity of ADSCs while the p38 pathway may exert an opposite effect.

Description: Calmodulin (CaM) binds to the FERM domain of 80 kDa erythrocyte protein 4.1R (R30) independently of Ca 2+ but, paradoxically, regulates R30 binding to transmembrane proteins in a Ca 2+ -dependent manner. We have previously mapped a Ca 2+ -independent CaM-binding site, pep11 (A 264 KKLWKVCVEHHTFFR), in 4.1R FERM domain and demonstrated that CaM, when saturated by Ca 2+ (Ca 2+ /CaM), interacts simultaneously with pep11 and with Ser 185 in A 181 KKLSMYGVDLHKAKD (pep9), the binding affinity of Ca 2+ /CaM for pep9 increasing dramatically in the presence of pep11. Based on these findings, we hypothesized that pep11 induced key conformational changes in the Ca 2+ /CaM complex. By differential scanning calorimetry analysis, we established that the C-lobe of CaM was more stable when bound to pep11 either in the presence or absence of Ca 2+ . Using nuclear magnetic resonance spectroscopy, we identified 8 residues in the N-lobe and 14 residues in the C-lobe of pep11 involved in interaction with CaM in both of presence and absence of Ca 2+ . Lastly, Kratky plots, generated by small-angle X-ray scattering analysis, indicated that the pep11/Ca 2+ /CaM complex adopted a relaxed globular shape. We propose that these unique properties may account in part for the previously described Ca 2+ /CaM-dependent regulation of R30 binding to membrane proteins.

Description: Isolation of peripheral blood mononuclear cells (PBMCs) is fraught with challenges including, but not limited to, the cost of limited gradients available for the isolation of PBMCs. Glycerol gradient (1.077 g/ml) was used to isolate PBMCs from adult peripheral blood. The differentiation potential of the isolated cells was assessed by culturing the cells in MEM at 37 °C in 5 % CO 2 . The results demonstrated that the isolated cells could differentiate into committed linages of the erythroid progeny. LDH assay revealed that glycerol was not cytotoxic to the cells. The use of glycerol density as an alternative could be significant in cell culture experiments.

Description: The divergence of protein (Hedgehog) in different organisms remains an unresolved issue to comprehend how the pathway in Hh signaling evolves. Insights into this question can help one identify the key molecules in Hh signaling. This work proposes a protein-associated factor in cells. The development of a non-reductionist theory of cellular functions in medicine is not sufficient. It is necessary to find the parameters with regards to molecules/genes that can elicit functions. This work shows that molecular interactions of gene products can be accomplished by biophysics logic. Defining the protein-associated factors in molecular activities and identifying its roles in molecular transduction are important. A misregulation in molecular switch can account for complex biomolecular consequences. This work shows the potential of the factor on homo-sapiens and unlocks its implications to gene multi-tasking functionality. The associated factor notion should facilitate the medical development in cancer therapeutics.

Description: IgA nephropathy (IgAN) or Berger’s disease is a slowly progressing disease that leads to end-stage renal disease in 50 % of the patients within 25 years of the disease. However, several factors are associated with the accelerated progression of this disease causing early development of end-stage disease. Persistent proteinuria or hematuria, poorly controlled hypertension, elevated serum creatinine and prevalent glomerulosclerosis are some of the risk factors that expedite the deteriorative effects of IgAN. Thus, the progression of the disease can be delayed if the associated risk factors are handled and addressed in the nick of time.

Description: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC–CC) is a rare form of primary liver cancer (PLC). It is difficult to make a correct preoperative diagnosis of cHCC–CC because of the lack of special features of the disease. We here present a case of a 68-year-old man who presented with fluctuant fever, chills, and sweating and was eventually diagnosed as cHCC–CC after surgery. The tumor was 6.0 cm in diameter with distinct borders and no satellite lesions or lymph nodes were observed during macroscopic examination of the resection specimen. The fever resolved in the postoperative period till the 28th day after surgery, when the patient developed extensive abdominal metastases and died shortly after. More attention should be paid to the patient with PLC showing abnormal features such as FUO, normal range of tumor markers, atypical imaging, and less cirrhosis. Hepatic resection is the treatment of choice although with short-term outcomes.

Description: To analyze the levels of oxidized low density lipoprotein (ox-LDL) and inflammatory cytokines in the plasma of gout patients. The levels of ox-LDL, hypersensitive C-reactive protein (hs-CRP), interleukin-1β, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured in the plasma of 41 gout patients [28 in acute phase episode, 13 in intermittent phase (IP)], and in 40 healthy controls. The relationship between ox-LDL and inflammation was also explored by measuring the levels of several pro-inflammatory cytokines in the plasma. The plasma levels of ox-LDL, hs-CRP, IL-6 and TNF-α were significantly increased in patients with gout in the acute phase compared to those in the IP group and healthy controls ( P  〈 0.05), but the levels of TGF-β were significantly lower in the acute phase group than in the IP group and healthy controls ( P  〈 0.01). The levels of ox-LDL in the gout patients in the IP were significantly higher than those in healthy controls ( P  〈 0.05). Correlation analysis indicated that the levels of ox-LDL were positively correlated with hs-CRP, IL-6 and TNF-α ( r  = 0.343, r  = 0.386, r  = 0.659, P  〈 0.01, respectively), but negatively correlated with TGF-β levels in patients in the acute phase ( r  = −0.240, P  〈 0.05). The levels of ox-LDL in gout patients were significantly higher than those in healthy controls. The changes in ox-LDL levels may be associated with enhanced inflammation in gout patients.

Description: Hispidulin is a flavonoid compound which is an active ingredient in a number of traditional Chinese medicinal herbs. However, it’s therapeutic activity remains poorly understood. The present study investigated the pro-apoptotic effects and mechanism by which Hispidulin induces apoptosis in human hepatoblastoma cancer (HepG2) cells. The results showed that Hispidulin induced cell death in a dose- and time-dependent manner in HepG2 cells whereas no toxic reaction was observed in normal human liver cells at indicated concentration. This study also demonstrated that Hispidulin induces apoptosis through mitochondrial dysfunction, which is characterized by decreased Bcl-2/Bax ratio, disrupted mitochondrial membrane potential and increased release of cytochrome C and activated capase-3. Our results also showed that mitochondrial dysfunction was triggered by Hispidulin-induced excessive ROS generation. Hispidulin also significantly inhibited Akt activation. ROS inhibitor NAC abrogated the inhibitory effect of Hispidulin on P13k/Akt signalling pathway and the proapoptotic effect in HepG2 cells. Our results demonstrate for the first time that Hispidulin induces apoptosis in HepG2 cells and suggested that the pro-apoptotic effect of Hispidulin was mediated through mitochondrial dysfunction and inhibition of P13k/Akt signalling pathway. Since no toxic effect was observed when normal liver cells were treated with Hispidulin, Hispidulin may have the potential to be used as therapeutic for liver cancer.

Description: Atherosclerosis, the leading cause of most cardiovascular disease, is a progressive multifaceted inflammatory disease characterized by extracellular matrix degradation and extensive remodeling of artery wall. However, its mechanism has not been completely understood, and animal models are useful to study its pathogenetic process. An analysis of literature on the nature of atherosclerosis indicates that focal accumulation of smooth muscle cells (SMCs) into the intima by plasma factors is fundamental to the entire process of plaque growth. In our previous study, vascular SMCs proliferation was obvious in elastase-induced aorta by day 15, which led to intimal hyperplasia and regression of rabbit aneurysm. Model induced by combination of balloon injury and an atherogenic diet in rabbits is the conventional, but most largely used experimental model of atherosclerosis. Since proliferation and accumulation of intimal SMCs are found in elastase-induced aorta, and hypercholesterolemia is usually induced by cholesterol-rich diets in rabbits, a novel atherosclerosis model may be induced by combination periaortic elastase incubation and cholesterol-rich diet.

Description: The heterocyclic trioxirane compound [1,3,5-tris((oxiran-2-yl)methyl)-1,3,5-triazinane-2,4,6-trione (TATT)] is a synthetic compound which has been used as an experimental anticancer agent in human clinical trials. Curcumin, an active natural compound in turmeric and curry, is an ingredient commonly used in the traditional diet of many Asian countries. In the present study, we observed that TATT exhibited a better anticancer effect on chemoresistant human colorectal cancer HT-29 cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with FDA-approved anticancer drugs (cisplatin, carboplatin, or oxaliplatin) using MTT assay. TATT also induced a stronger apoptotic effect than that seen with the three studied anticancer drugs, as characterized by externalization of phosphatidylserine using flow cytometry. Administration of caspase 8-specific inhibitor (z-IETD-fmk) and mitochondrial permeability transition pore inhibitor (cyclosporin A) demonstrated that TATT-induced apoptosis proceeded via both extrinsic and intrinsic signaling pathways. It is noteworthy that coadministration of curcumin further significantly increased TATT-induced cytotoxicity, externalization of phosphatidylserine (representing early apoptosis), and the percentages of cells at the sub-G1 phase (representing late apoptosis), producing an additivity and/or synergistic effect, and vice versa. Suppression of nuclear NF-κB was involved in curcumin-enhanced chemosensitivity of TATT. Overall, our data indicate that TATT exerts a chemotherapeutic effect on colorectal cancer cells and coadministration of curcumin enhances the treatment effect of TATT.

Description: The objective of this study was to evaluate the clinical efficacy and safety of nitroprusside injection for preventing the slow-flow/no-reflow phenomenon after percutaneous coronary intervention (PCI). We searched the Cochrane Central Register of Controlled Trials (Issue 2, 2011), PubMed, EMbase, and Google Scholar for data. Two reviewers independently evaluated the quality of the included studies and extracted the data. A meta-analysis was performed using RevMan 5.0 software. Four randomized controlled trials (RCTs) involving 319 patients were included. The results of the meta-analyses showed that intracoronary nitroprusside is beneficial in preventing no-reflow/slow-flow, in reducing corrected TIMI frame count, and in improving left ventricular ejection fraction. It also likely reduces adverse reactions in patients after PCI and rehospitalization due to cardiovascular events. However, we must caution that in this review, there is a moderate possibility of bias with regard to patient selection, performance, and publication because of the small number of included studies. A larger sample size and high-quality RCTs are needed for a more reassuring analysis.

Description: Cadmium (Cd) is a potent toxic element used in several industries and in the process contaminates air, soil, and water. Exposure of Saccharomyces cerevisiae to Cd increases the major phospholipids, and profound increase was observed in phosphatidylethanolamine (PE). In yeast, there are four different pathways contributing to the biosynthesis of PE, and contribution to PE pool through phosphatidylserine decarboxylase2 (psd2) is not significant in normal conditions. Upon Cd exposure, psd2Δ strain showed a significant decrease in major phospholipids including PE. When exposed to Cd, wild-type (WT) cells depicted an increase in ER stress and autophagy, whereas in psd2, ER stress was noted but autophagy process was impaired. The supplementation of ethanolamine did not overcome the Cd stress and also the autophagy process, whereas overexpression of PSD2 in psd2Δ increased the cellular tolerance, PE levels, and the autophagy process against Cd stress. From our studies, we can suggest that PSD2 of S. cerevisiae has an important role in PE synthesis and in autophagy process under Cd stress.

Description: Despite efforts in peripheral nerve injury and regeneration, it is difficult to achieve a functional recovery following extended peripheral nerve lesions. Even if artificial nerve conduit, cell components and growth factors can enhance nerve regeneration, integration in peripheral nerve repair and regeneration remains yet to be explored. For this study, we used chitosan/gelatin nerve graft constructed with collagenous matrices as a vehicle for Schwann cells and transforming growth factor-β1 to bridge a 10-mm gap of the sciatic nerve and explored the feasibility of improving regeneration and reinnervation in rats. The nerve regeneration was assessed with functional recovery, electrophysiological test, retrograde labeling, and immunohistochemistry analysis during the post-operative period of 16 weeks. The results showed that the internal sides of the conduits were compact enough to prevent the connective tissues from ingrowth. Nerve conduction velocity, average regenerated myelin area, and myelinated axon count were similar to those treated with autograft ( p  〉 0.05) but significantly higher than those bridged with chitosan/gelatin nerve graft alone ( p  〈 0.05). Evidences from retrograde labeling and immunohistochemistry analysis are further provided in support of improving axonal regeneration and remyelination. A designed graft incorporating all of the tissue-engineering strategies for peripheral nerve regeneration may provide great progress in tissue engineering for nerve repair.

Description: The aim of this study was to analyze the drug resistance of Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) in female reproductive track from 2007 to 2011 in Hangzhou. Antibiotics sensitivity test in Mycoplasma, which was isolated in clinics from 2007 to 2011 were analyzed retrospectively. The detection of Mycoplasma during 2007–2011 was 20,146 (54.37 %), of which the single infection rate of Uu was 42.08 %, of Mh 1.26 %, and of Uu+Mh was 11.02 %. The drug resistance rate of Uu was increased significantly in ofloxacin in 2007 (41.80 %), 2008 (45.94 %), 2009 (46.07 %), 2010 (50.36 %), and 2011 (53.22 %) ( P  〈 0.05). The resistance rate to ciprofloxacin was significantly increased in 2007 (67.15 %), 2008 (67.44 %), 2009 (73.00 %), 2010 (75.28 %), and 2011 (75.28 %) ( P  〈 0.05). Exceptionally, the resistance rates of the other antibiotics were low. The drug resistance rate of Uu was significantly increased with quinolones at increasing tendency. It is necessary to monitor the local drug resistance rate of Uu regularly to provide reasonable guidelines in clinics.

Description: Photoactivated (“caged”) fluorescent dyes are modern tools for structure and function studies of cell membranes and subcellular organelles. Recently synthesized precursors of rhodamine fluorescent dyes (abbreviations PFD813 and PFD814) important for microscopic probing of biological objects have been studied in solution. In order to characterize the behavior at interfaces, monolayers of PFD813 and PFD814 on water have been formed and investigated. The interactions of these precursors with the biomembrane component dimyristoylphosphatidylethanolamine in monolayers at the air–water interface and after transfer to glass plates have been studied by measuring monolayer parameters and spectroscopic properties before and after photo-chemical formation of the fluorescent rhodamine dyes Rho813 and Rho814, respectively.

Description: Computational prediction of disease-associated non-synonymous polymorphism (nsSNP) has provided a significant platform to filter out the pathological mutations from large pool of SNP datasets at a very low cost input. Several methodologies and complementary protocols have been previously implemented and has provided significant prediction results. Although the previously implicated prediction methods were capable of investigating the most likely deleterious nsSNPs, but due to the lack of genotype–phenotype association analysis, the prediction results lacked in accuracy level. In this work we implemented the computational compilation of protein conformational changes as well as the probable disease-associated phenotypic outcomes. Our result suggested E403K mutation in mitotic centromere-associated kinesin protein as highly damaging and showed strong concordance to the previously observed colorectal cancer mutations aggregation tendency and energy value changes. Moreover, the molecular dynamics simulation results showed major loss in conformation and stability of mutant N-terminal kinesin-like domain structure. The result obtained in this study will provide future prospect of computational approaches in determining the SNPs that may affect the native conformation of protein structure and lead to cancer-associated disorders.

Description: Infrared lasers are widely used in medicine, industry, and other fields. While science, medicine, and the society in general have benefited from the many practical uses of lasers, they also have inherent safety issues. Although several procedures have been put forward to protect the skin from non-specific laser-induced damage, individuals receiving laser therapy or researchers who use laser are still at risk for skin damage. This study aims to understand the interaction between laser and the skin, and to investigate the differences between the skin damage caused by 1,064-nm laser and common thermal burns. Skin lesions on Wistar rats were induced by a 1,064-nm CW laser at a maximum output of 40 W and by a copper brass bar attached to an HQ soldering iron. Histological sections of the lesions and the process of wound healing were evaluated. The widths of the epidermal necrosis and dermal denaturalization of each lesion were measured. To observe wound healing, the epithelial gap and wound gap were measured. Masson’s trichrome and picrosirius red staining were also used to assess lesions and wound healing. The thermal damage induced by laser intensified significantly in both horizontal dimension and in vertical depth with increased duration of irradiation. Ten days after wounding, the dermal injuries induced by laser were more severe. Compared with the laser-induced skin damage, the skin burn induced by an HQ soldering iron did not show a similar development or increased in severity with the passage of time. The results of this study showed the pattern of skin damage induced by laser irradiation and a heated brass bar. This study also highlighted the difference between laser irradiation and thermal burn in terms of skin damage and wound healing, and offers insight for further treatment.

Description: The present study examined kinetics of apoptosis and expression of apoptosis-related proteins Bcl-2, Bax, and caspase-3 in the CA3 hippocampus cells after diffuse brain injury (DBI) induced experimentally in rats. Percentage of apoptotic cells and expressions of above proteins were examined by flow cytometry and immunohistochemistry. Substantial neuronal apoptosis was documented in the CA3 hippocampus cells after DBI (22.26 ± 2.97 % at 72 h after DBI vs. 2.92 ± 0.88 % in sham-operated animals). Expression of Bc1-2 decreased, while expression of Bax and caspase-3 increased after DBI, with caspase-3 expression peaking after that of Bax (72 vs. 48 h, respectively). Further, the Bc1-2/Bax expression ratio decreased prior to increase of caspase-3 expression. In conclusion, cell apoptosis and altered expressions of Bcl-2, Bax, and caspase-3 are present in the CA3 region of hippocampus after experimental DBI. Changes in the Bc1-2/Bax expression ratio may facilitate activation of caspase-3 and aggravate neuronal apoptosis after brain injury.

Description: The aim of the present work is to evaluate the effect of caffeine, the world’s most popular psychoactive drug, on the electric activity of the rat’s brain that exposed to extremely low-frequency magnetic field (ELF-MF), during 15 days. The obtained results showed that administration of caffeine in a group of rats by dose of 10 mg/kg (equivalent to human daily consumption) caused a reduction in the mean power amplitude of electroencephalogram (EEG) trace for almost all frequency bands especially α (8–12 Hz). It was observed that the influence of caffeine was more evident in motor cortex than in visual cortex. While the exposure of another group to ELF-MF of intensity 0.2 mT during the same period caused an enhancement in the mean power amplitude of most EEG frequency bands; this was more observed in the right hemisphere of the brain than that of the left hemisphere. The administration of caffeine while rats were exposed to ELF-MF, led, after 5 days of exposure, to a great increase in the mean power amplitude of α band at all places of recording electrodes. It may be concluded that caffeine administration was more effective in reducing the hazardous of ELF-MF in motor cortex than in visual cortex.

Description: The present study evaluated the efficacy of intracoronary administration of verapamil to attenuate the no-reflow phenomenon following the primary percutaneous coronary intervention (PCI) in patients with the ST-segment elevation acute myocardial infarction (STEMI). A total of 201 patients with STEMI who underwent primary PCI within 12 h from the beginning of the heart attack were included. The no-reflow phenomenon was defined as substantial coronary anterograde flow of TIMI ≤2. Verapamil (100–200 μg) was injected into coronary artery immediately after no-reflow; the coronary arteriography was repeated later. Hundred and ninety-eight patients with STEMI successfully underwent primary PCI, and 246 stents were implanted with the average of 1.2 stents per patient. No-reflow occurred in 25 out of 198 patients (12.6 %). Twenty-one (84 %) patients developed the flow of TIMI ≥3 after intracoronary administration of verapamil, as revealed by repeated coronary angiography. Two patients developed transient hypotension which normalized without treatment within 3–5 min. Three patients showed sinus bradycardia, in one patient there was transient II sinoatrial block, and one patient developed type 1 atrioventricular block. All adverse effects were alleviated after intravenous injection of atropine (0.5–1 mg). In conclusion, the no-reflow phenomenon following primary PCI in patients with STEMI is significantly improved by intracoronary administration of verapamil which is useful to reduce cardiovascular events during operation.