The 2023 MDPI Annual Report has
been released!
 
22 pages, 5418 KiB  
Review
Mastering Death: The Roles of Viral Bcl-2 in dsDNA Viruses
by Chathura D. Suraweera, Benjamin Espinoza, Mark G. Hinds and Marc Kvansakul
Viruses 2024, 16(6), 879; https://doi.org/10.3390/v16060879 (registering DOI) - 30 May 2024
Abstract
Proteins of the Bcl-2 family regulate cellular fate via multiple mechanisms including apoptosis, autophagy, senescence, metabolism, inflammation, redox homeostasis, and calcium flux. There are several regulated cell death (RCD) pathways, including apoptosis and autophagy, that use distinct molecular mechanisms to elicit the death [...] Read more.
Proteins of the Bcl-2 family regulate cellular fate via multiple mechanisms including apoptosis, autophagy, senescence, metabolism, inflammation, redox homeostasis, and calcium flux. There are several regulated cell death (RCD) pathways, including apoptosis and autophagy, that use distinct molecular mechanisms to elicit the death response. However, the same proteins/genes may be deployed in multiple biochemical pathways. In apoptosis, Bcl-2 proteins control the integrity of the mitochondrial outer membrane (MOM) by regulating the formation of pores in the MOM and apoptotic cell death. A number of prosurvival genes populate the genomes of viruses including those of the pro-survival Bcl-2 family. Viral Bcl-2 proteins are sequence and structural homologs of their cellular counterparts and interact with cellular proteins in apoptotic and autophagic pathways, potentially allowing them to modulate these pathways and determine cellular fate. Full article
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14 pages, 5898 KiB  
Article
Theoretical and Experimental Verification of the Physical–Mechanical Properties of Organic Bone Meal Granular Fertilizers
by Eglė Jotautienė, Vaidas Bivainis, Davut Karayel and Ramūnas Mieldažys
Agronomy 2024, 14(6), 1171; https://doi.org/10.3390/agronomy14061171 (registering DOI) - 30 May 2024
Abstract
Continuous efforts are being made to improve fertilizer efficiency by improving fertilizer technology, quality, and application rates. Granular organic fertilizers are more difficult to achieve uniform application because their physical–mechanical properties differ significantly from mineral fertilizers. The properties of granular organic fertilizers can [...] Read more.
Continuous efforts are being made to improve fertilizer efficiency by improving fertilizer technology, quality, and application rates. Granular organic fertilizers are more difficult to achieve uniform application because their physical–mechanical properties differ significantly from mineral fertilizers. The properties of granular organic fertilizers can best be determined experimentally. However, these studies are often quite complex. Modern engineering modeling software makes it possible to model the properties of granular fertilizers and their dispersion. This study deals with the theoretical and experimental verification of the physical–mechanical properties of organic bone meal granular fertilizer. For the verification of selected properties of bone meal granules, the following studies were carried out on the granules: determination of poured bulk density, static and dynamic angles of repose, static and dynamic friction coefficients of granule surface, etc. The results showed that for modeling fertilizer properties, it is sufficient to carry out a static compression test to determine the modulus of elasticity and a friction test between granules and the contacting surface to determine the static and dynamic friction coefficients. The remaining properties of the granules can be modeled and calibrated with the DEM software Altair EDEM 2023. Full article
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18 pages, 3090 KiB  
Article
Adipo-Epithelial Transdifferentiation in In Vitro Models of the Mammary Gland
by Jessica Perugini, Arianna Smorlesi, Samantha Acciarini, Eleonora Mondini, Georgia Colleluori, Chiara Pirazzini, Katarzyna Malgorzata Kwiatkowska, Paolo Garagnani, Claudio Franceschi, Maria Cristina Zingaretti, Christian Dani, Antonio Giordano and Saverio Cinti
Cells 2024, 13(11), 943; https://doi.org/10.3390/cells13110943 (registering DOI) - 30 May 2024
Abstract
Subcutaneous adipocytes are crucial for mammary gland epithelial development during pregnancy. Our and others’ previous data have suggested that adipo-epithelial transdifferentiation could play a key role in the mammary gland alveolar development. In this study, we tested whether adipo-epithelial transdifferentiation occurs in vitro. [...] Read more.
Subcutaneous adipocytes are crucial for mammary gland epithelial development during pregnancy. Our and others’ previous data have suggested that adipo-epithelial transdifferentiation could play a key role in the mammary gland alveolar development. In this study, we tested whether adipo-epithelial transdifferentiation occurs in vitro. Data show that, under appropriate co-culture conditions with mammary epithelial organoids (MEOs), mature adipocytes lose their phenotype and acquire an epithelial one. Interestingly, even in the absence of MEOs, extracellular matrix and diffusible growth factors are able to promote adipo-epithelial transdifferentiation. Gene and protein expression studies indicate that transdifferentiating adipocytes exhibit some characteristics of milk-secreting alveolar glands, including significantly higher expression of milk proteins such as whey acidic protein and β-casein. Similar data were also obtained in cultured human multipotent adipose-derived stem cell adipocytes. A miRNA sequencing experiment on the supernatant highlighted mir200c, which has a well-established role in the mesenchymal–epithelial transition, as a potential player in this phenomenon. Collectively, our data show that adipo-epithelial transdifferentiation can be reproduced in in vitro models where this phenomenon can be investigated at the molecular level. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Adipose Organ Remodelling)
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27 pages, 2510 KiB  
Review
Diaphragm Ultrasound in Different Clinical Scenarios: A Review with a Focus on Older Patients
by Carmine Siniscalchi, Antonio Nouvenne, Nicoletta Cerundolo, Tiziana Meschi, Andrea Ticinesi and on behalf of the Parma Post-Graduate Specialization School in Emergency-Urgency Medicine Interest Group on Thoracic Ultrasound
Geriatrics 2024, 9(3), 70; https://doi.org/10.3390/geriatrics9030070 (registering DOI) - 30 May 2024
Abstract
Diaphragm muscle dysfunction is increasingly recognized as a fundamental marker of several age-related diseases and conditions including chronic obstructive pulmonary disease, heart failure and critical illness with respiratory failure. In older individuals with physical frailty and sarcopenia, the loss of muscle mass and [...] Read more.
Diaphragm muscle dysfunction is increasingly recognized as a fundamental marker of several age-related diseases and conditions including chronic obstructive pulmonary disease, heart failure and critical illness with respiratory failure. In older individuals with physical frailty and sarcopenia, the loss of muscle mass and function may also involve the diaphragm, contributing to respiratory dysfunction. Ultrasound has recently emerged as a feasible and reliable strategy to visualize diaphragm structure and function. In particular, it can help to predict the timing of extubation in patients undergoing mechanical ventilation in intensive care units (ICUs). Ultrasonographic evaluation of diaphragmatic function is relatively cheap, safe and quick and can provide useful information for real-time monitoring of respiratory function. In this review, we aim to present the current state of scientific evidence on the usefulness of ultrasound in the assessment of diaphragm dysfunction in different clinical settings, with a particular focus on older patients. We highlight the importance of the qualitative information gathered by ultrasound to assess the integrity, excursion, thickness and thickening of the diaphragm. The implementation of bedside diaphragm ultrasound could be useful for improving the quality and appropriateness of care, especially in older subjects with sarcopenia who experience acute respiratory failure, not only in the ICU setting. Full article
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22 pages, 4111 KiB  
Article
Exploring Cannabinoids as Potential Inhibitors of SARS-CoV-2 Papain-like Protease: Insights from Computational Analysis and Molecular Dynamics Simulations
by Jamie Holmes, Shahidul M. Islam and Kimberly A. Milligan
Viruses 2024, 16(6), 878; https://doi.org/10.3390/v16060878 (registering DOI) - 30 May 2024
Abstract
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches. The present research investigates the potential [...] Read more.
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global COVID-19 pandemic, challenging healthcare systems worldwide. Effective therapeutic strategies against this novel coronavirus remain limited, underscoring the urgent need for innovative approaches. The present research investigates the potential of cannabis compounds as therapeutic agents against SARS-CoV-2 through their interaction with the virus’s papain-like protease (PLpro) protein, a crucial element in viral replication and immune evasion. Computational methods, including molecular docking and molecular dynamics (MD) simulations, were employed to screen cannabis compounds against PLpro and analyze their binding mechanisms and interaction patterns. The results showed cannabinoids with binding affinities ranging from −6.1 kcal/mol to −4.6 kcal/mol, forming interactions with PLpro. Notably, Cannabigerolic and Cannabidiolic acids exhibited strong binding contacts with critical residues in PLpro’s active region, indicating their potential as viral replication inhibitors. MD simulations revealed the dynamic behavior of cannabinoid–PLpro complexes, highlighting stable binding conformations and conformational changes over time. These findings shed light on the mechanisms underlying cannabis interaction with SARS-CoV-2 PLpro, aiding in the rational design of antiviral therapies. Future research will focus on experimental validation, optimizing binding affinity and selectivity, and preclinical assessments to develop effective treatments against COVID-19. Full article
(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)
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22 pages, 3418 KiB  
Article
Metabolomic Profiling and In Vivo Antiepileptic Effect of Zygophyllum album Aerial Parts and Roots Crude Extracts against Pentylenetetrazole-Induced Kindling in Mice
by Asmaa R. Abdel-Hamed, Alaa S. Wahba, Dina M. Khodeer, Maged S. Abdel-Kader, Jihan M. Badr, Sebaey Mahgoub and Dina M. Hal
Metabolites 2024, 14(6), 316; https://doi.org/10.3390/metabo14060316 (registering DOI) - 30 May 2024
Abstract
The chemical profiles of both Zygophyllum album (Z. album) aerial parts and roots extracts were evaluated with LC-ESI-TOF-MS/MS analysis. Twenty-four compounds were detected. Among them, some are detected in both the aerial parts and the roots extracts, and others were detected [...] Read more.
The chemical profiles of both Zygophyllum album (Z. album) aerial parts and roots extracts were evaluated with LC-ESI-TOF-MS/MS analysis. Twenty-four compounds were detected. Among them, some are detected in both the aerial parts and the roots extracts, and others were detected in the aerial parts only. The detected compounds were mainly flavonoids, phenolic compounds, triterpenes and other miscellaneous compounds. Such compounds contribute to the diverse pharmacological activities elicited by the Z. album species. This study aimed to elucidate the antiepileptic effect of Z. album aerial parts and roots crude extracts against pentylenetetrazole (PTZ)-induced kindling in mice. Male albino mice were divided into four groups, eight animals each. All groups, except the control group, were kindled with PTZ (35 mg/kg i.p.), once every alternate day for a total of 15 injections. One group was left untreated (PTZ group). The remaining two groups were treated prior to PTZ injection with either Z. album aerial parts or roots crude extract (400 mg/kg, orally). Pretreatment with either extract significantly reduced the seizure scores, partially reversed the histological changes in the cerebral cortex and exerted antioxidant/anti-inflammatory efficacy evinced by elevated hippocampal total antioxidant capacity and SOD and catalase activities, parallel to the decrement in MDA content, iNOS activity and the TXNIB/NLRP3 axis with a subsequent decrease in caspase 1 activation and a release of IL-1β and IL-18. Moreover, both Z. album extracts suppressed neuronal apoptosis via upregulating Bcl-2 expression and downregulating that of Bax, indicating their neuroprotective and antiepileptic potential. Importantly, the aerial parts extract elicited much more antiepileptic potential than the roots extract did. Full article
(This article belongs to the Section Plant Metabolism)
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14 pages, 2354 KiB  
Article
Intercropping as a Strategy for Weed Management in Faba Bean (Vicia faba L.)
by Ángel M. Villegas-Fernández, Ahmed A. Amarna, Juan Moral and Diego Rubiales
Agronomy 2024, 14(6), 1170; https://doi.org/10.3390/agronomy14061170 (registering DOI) - 30 May 2024
Abstract
Faba bean is an important legume crop worldwide, which is grown both for food and feed. As for many legume crops, postemergence weed control is difficult. The aim of this work was to assess the potential of intercropping in weed management by assessing [...] Read more.
Faba bean is an important legume crop worldwide, which is grown both for food and feed. As for many legume crops, postemergence weed control is difficult. The aim of this work was to assess the potential of intercropping in weed management by assessing the effect of mixing faba bean with different crops (wheat, barley, and pea) on weeds in the South of Spain. Four field trials were conducted over four consecutive seasons, and the results found that the addition of alternate intercropping of faba bean and barley achieved high levels of weed control, both for coverage and biomass (92.7% and 76.6%, respectively). Intercropping with wheat did not reduce weed coverage but did decrease weed biomass by 46.1% as compared with the faba bean monocrop. Intercropping with pea did not provide significant reductions in weed coverage or weed biomass. The diversity of the weed community was not altered by the different crop combinations tested. Additional experiments under controlled conditions were carried out to determine the possible role of barley allelopathy in weed suppression. A strong allelopathic effect entailing a reduction in the number of plants and biomass was detected for four weeds including Sinapis arvensis, Polypogon monspeliensis, Matricaria camomilla, and Medicago truncatula. It can be concluded that intercropping faba bean with barley is an excellent strategy for weed control in Southern Spain. Full article
(This article belongs to the Section Weed Science and Weed Management)
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11 pages, 3046 KiB  
Article
Degradation of Toxins Derived from Foodborne Pathogens by Atmospheric-Pressure Dielectric-Barrier Discharge
by Akikazu Sakudo and Yoshihito Yagyu
Int. J. Mol. Sci. 2024, 25(11), 5986; https://doi.org/10.3390/ijms25115986 (registering DOI) - 30 May 2024
Abstract
Foodborne diseases can be attributed not only to contamination with bacterial or fungal pathogens but also their associated toxins. Thus, to maintain food safety, innovative decontamination techniques for toxins are required. We previously demonstrated that an atmospheric-pressure dielectric-barrier discharge (APDBD) plasma generated by [...] Read more.
Foodborne diseases can be attributed not only to contamination with bacterial or fungal pathogens but also their associated toxins. Thus, to maintain food safety, innovative decontamination techniques for toxins are required. We previously demonstrated that an atmospheric-pressure dielectric-barrier discharge (APDBD) plasma generated by a roller conveyer plasma device is effective at inactivating bacteria and fungi in foods. Here, we have further examined whether the roller conveyer plasma device can be used to degrade toxins produced by foodborne bacterial pathogens, including aflatoxin, Shiga toxins (Stx1 and Stx2), enterotoxin B and cereulide. Each toxin was spotted onto an aluminum plate, allowed to dry, and then treated with APDBD plasma applied by the roller conveyer plasma device for different time periods. Assessments were conducted using a competitive enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS). The results demonstrate a significant time-dependent decrease in the levels of these toxins. ELISA showed that aflatoxin B1 concentrations were reduced from 308.6 µg/mL to 74.4 µg/mL within 1 min. For Shiga toxins, Stx1 decreased from 913.8 µg/mL to 65.1 µg/mL, and Stx2 from 2309.0 µg/mL to 187.6 µg/mL within the same time frame (1 min). Enterotoxin B levels dropped from 62.67 µg/mL to 1.74 µg/mL at 15 min, and 1.43 µg/mL at 30 min, but did not display a significant decrease within 5 min. LC-MS/MS analysis verified that cereulide was reduced to below the detection limit following 30 min of APDBD plasma treatment. Taken together, these findings highlight that a range of foodborne toxins can be degraded by a relatively short exposure to plasma generated by an APDBD using a roller conveyer device. This technology offers promising advancements in food safety, providing a novel method to alleviate toxin contamination in the food processing industry. Full article
(This article belongs to the Collection Feature Papers in Materials Science)
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16 pages, 480 KiB  
Article
Laboratory Investigations on the Potential Efficacy of Biological Control Agents on Two Thrips Species, Onion Thrips (Thrips tabaci Lindeman) and Western Flower Thrips (Frankliniella occidentalis (Pergande))
by Ashley Summerfield, Rosemarije Buitenhuis, Sarah Jandricic and Cynthia D. Scott-Dupree
Insects 2024, 15(6), 400; https://doi.org/10.3390/insects15060400 (registering DOI) - 30 May 2024
Abstract
Thrips biocontrol research in greenhouse crops has focused primarily on western flower thrips (WFT; Frankliniella occidentalis). However, recent outbreaks of onion thrips (OT; Thrips tabaci) in Ontario, Canada, demonstrate that biocontrol-based IPM programs for WFT do not control OT sufficiently to [...] Read more.
Thrips biocontrol research in greenhouse crops has focused primarily on western flower thrips (WFT; Frankliniella occidentalis). However, recent outbreaks of onion thrips (OT; Thrips tabaci) in Ontario, Canada, demonstrate that biocontrol-based IPM programs for WFT do not control OT sufficiently to prevent crop losses. A lack of comparative studies makes it difficult to determine which program components for WFT are failing for OT. We conducted several laboratory trials examining the extent to which commercial biocontrol products kill OT compared to WFT. These included phytoseiid mites (Amblyseius swirskii, Neoseiulus cucumeris, Amblydromalus limonicus, Iphiseius degenerans), a large generalist predator (Orius insidiosus), an entomopathogenic fungus (Beauveria bassiana strain GHA), and entomopathogenic nematodes (Steinernema feltiae, S. carpocapsae, Heterorhabditis bacteriophora). In no-choice trials, A. swirskii and O. insidiosus consumed more OT than WFT (first instars and adults, respectively). In choice trials, A. swirskii, N. cucumeris, and O. insidiosus consumed more OT than WFT. Steinernema feltiae caused higher mortality in OT than WFT. There was no difference in mortality between thrips species exposed to other biocontrol agents. This suggests available tools have the potential to manage OT as well as WFT. Possible explanations why this potential is not realized in commercial settings are explored. Full article
(This article belongs to the Special Issue Diversity and Abundance of Predators and Parasitoids of Insect Pests)
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18 pages, 5042 KiB  
Article
Astragalus Polysaccharide Modulates the Gut Microbiota and Metabolites of Patients with Type 2 Diabetes in an In Vitro Fermentation Model
by Xin Zhang, Lina Jia, Qian Ma, Xiaoyuan Zhang, Mian Chen, Fei Liu, Tongcun Zhang, Weiguo Jia, Liying Zhu, Wei Qi and Nan Wang
Nutrients 2024, 16(11), 1698; https://doi.org/10.3390/nu16111698 (registering DOI) - 30 May 2024
Abstract
This study investigated the effect of astragalus polysaccharide (APS, an ingredient with hypoglycemic function in a traditional Chinese herbal medicine) on gut microbiota and metabolites of type 2 diabetes mellitus (T2DM) patients using a simulated fermentation model in vitro. The main components of [...] Read more.
This study investigated the effect of astragalus polysaccharide (APS, an ingredient with hypoglycemic function in a traditional Chinese herbal medicine) on gut microbiota and metabolites of type 2 diabetes mellitus (T2DM) patients using a simulated fermentation model in vitro. The main components of APS were isolated, purified, and structure characterized. APS fermentation was found to increase the abundance of Lactobacillus and Bifidobacterium and decrease the Escherichia-Shigella level in the fecal microbiota of T2DM patients. Apart from increasing propionic acid, APS also caused an increase in all-trans-retinoic acid and thiamine (both have antioxidant properties), with their enrichment in the KEGG pathway associated with thiamine metabolism, etc. Notably, APS could also enhance fecal antioxidant properties. Correlation analysis confirmed a significant positive correlation of Lactobacillus with thiamine and DPPH-clearance rate, suggesting the antioxidant activity of APS was related to its ability to enrich some specific bacteria and upregulate their metabolites. Full article
(This article belongs to the Section Nutrition and Diabetes)
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22 pages, 2263 KiB  
Article
The Effect of Ambient Illumination and Text Color on Visual Fatigue under Negative Polarity
by Qiangqiang Fan, Jinhan Xie, Zhaoyang Dong and Yang Wang
Sensors 2024, 24(11), 3516; https://doi.org/10.3390/s24113516 (registering DOI) - 30 May 2024
Abstract
This study investigates the effects of ambient illumination and negatively polarized text color on visual fatigue, exploring the issue of visual fatigue when using visual display terminals in low-illumination environments. The research methodology utilizes an experimental design to collect data on changes in [...] Read more.
This study investigates the effects of ambient illumination and negatively polarized text color on visual fatigue, exploring the issue of visual fatigue when using visual display terminals in low-illumination environments. The research methodology utilizes an experimental design to collect data on changes in pupil accommodation and blink rate through an eye tracker. Participants completed a reading task while exposed to various text colors and ambient light conditions to evaluate visual fatigue and cognitive performance. The study’s findings suggest that text color significantly affects visual fatigue, with red text causing the highest level of visual fatigue and yellow text causing the lowest level of visual fatigue. Improvements in ambient lighting reduce visual fatigue, but the degree of improvement varies depending on the text color. Additionally, cognitive performance is better when using yellow and white text but worse when using red text. Yellow text is the most effective choice for reducing visual fatigue under negative polarity. Increasing ambient lighting can also improve visual fatigue in low-illumination conditions. These findings will offer valuable guidance for designing visual terminal device interfaces, especially for low-illumination or night environments, to minimize visual fatigue and improve user experience. Full article
(This article belongs to the Special Issue Vision Science and Technology in Human Computer Interaction Systems)
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16 pages, 3598 KiB  
Article
Bone Metabolism and Dental Implant Insertion as a Correlation Affecting on Marginal Bone Remodeling: Texture Analysis and the New Corticalization Index, Predictor of Marginal Bone Loss—3 Months of Follow-Up
by Tomasz Wach, Piotr Szymor, Grzegorz Trybek, Maciej Sikora, Adam Michcik and Marcin Kozakiewicz
J. Clin. Med. 2024, 13(11), 3212; https://doi.org/10.3390/jcm13113212 (registering DOI) - 30 May 2024
Abstract
Background/Objectives: The general condition of implantology patients is crucial when considering the long- and short-term survival of dental implants. The aim of the research was to evaluate the correlation between the new corticalization index (CI) and patients’ condition, and its impact on marginal [...] Read more.
Background/Objectives: The general condition of implantology patients is crucial when considering the long- and short-term survival of dental implants. The aim of the research was to evaluate the correlation between the new corticalization index (CI) and patients’ condition, and its impact on marginal bone loss (MBL) leading to implant failure, using only radiographic (RTG) images on a pixel level. Method: Bone near the dental implant neck was examined, and texture features were analyzed. Statistical analysis includes analysis of simple regression where the correlation coefficient (CC) and R2 were calculated. Detected relationships were assumed to be statistically significant when p < 0.05. Statgraphics Centurion version 18.1.12 (Stat Point Technologies, Warrenton, VA, USA) was used to conduct the statistical analyses. Results: The research revealed a correlation between MBL after 3 months and BMI, PTH, TSH, Ca2+ level in blood serum, phosphates in blood serum, and vitamin D. A correlation was also observed between CI and PTH, Ca2+ level in blood serum, vitamin D, LDL, HDL, and triglycerides on the day of surgery. After 3 months of the observation period, CI was correlated with PTH, TSH, Ca2+ level in blood serum, and triglycerides. Conclusion: The results of the research confirm that the general condition of patients corresponds with CI and MBL. A patient’s general condition has an impact on bone metabolism around dental implants. Implant insertion should be considered if the general condition of the patient is not stable. However, CI has not yet been fully investigated. Further studies are necessary to check and categorize the impact of corticalization on marginal bone loss near dental implants. Full article
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14 pages, 1194 KiB  
Review
ARID1A Mutations in Gastric Cancer: A Review with Focus on Clinicopathological Features, Molecular Background and Diagnostic Interpretation
by Giuseppe Angelico, Giulio Attanasio, Lorenzo Colarossi, Cristina Colarossi, Matteo Montalbano, Eleonora Aiello, Federica Di Vendra, Marzia Mare, Nicolas Orsi and Lorenzo Memeo
Cancers 2024, 16(11), 2062; https://doi.org/10.3390/cancers16112062 (registering DOI) - 30 May 2024
Abstract
AT-rich interaction domain 1 (ARID1A) is a pivotal gene with a significant role in gastrointestinal tumors which encodes a protein referred to as BAF250a or SMARCF1, an integral component of the SWI/SNF (SWItch/sucrose non-fermentable) chromatin remodeling complex. This complex is instrumental [...] Read more.
AT-rich interaction domain 1 (ARID1A) is a pivotal gene with a significant role in gastrointestinal tumors which encodes a protein referred to as BAF250a or SMARCF1, an integral component of the SWI/SNF (SWItch/sucrose non-fermentable) chromatin remodeling complex. This complex is instrumental in regulating gene expression by modifying the structure of chromatin to affect the accessibility of DNA. Mutations in ARID1A have been identified in various gastrointestinal cancers, including colorectal, gastric, and pancreatic cancers. These mutations have the potential to disrupt normal SWI/SNF complex function, resulting in aberrant gene expression and potentially contributing to the initiation and progression of these malignancies. ARID1A mutations are relatively common in gastric cancer, particularly in specific adenocarcinoma subtypes. Moreover, such mutations are more frequently observed in specific molecular subtypes, such as microsatellite stable (MSS) cancers and those with a diffuse histological subtype. Understanding the presence and implications of ARID1A mutations in GC is of paramount importance for tailoring personalized treatment strategies and assessing prognosis, particularly given their potential in predicting patient response to novel treatment strategies including immunotherapy, poly(ADP) ribose polymerase (PARP) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors. Full article
(This article belongs to the Special Issue Relevant Prognostic Factors in Gastric Cancer)
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25 pages, 5791 KiB  
Article
Applying Physiologically Based Pharmacokinetic Modeling to Interpret Carbamazepine’s Nonlinear Pharmacokinetics and Its Induction Potential on Cytochrome P450 3A4 and Cytochrome P450 2C9 Enzymes
by Xuefen Yin, Brian Cicali, Leyanis Rodriguez-Vera, Viera Lukacova, Rodrigo Cristofoletti and Stephan Schmidt
Pharmaceutics 2024, 16(6), 737; https://doi.org/10.3390/pharmaceutics16060737 (registering DOI) - 30 May 2024
Abstract
Carbamazepine (CBZ) is commonly prescribed for epilepsy and frequently used in polypharmacy. However, concerns arise regarding its ability to induce the metabolism of other drugs, including itself, potentially leading to the undertreatment of co-administered drugs. Additionally, CBZ exhibits nonlinear pharmacokinetics (PK), but the [...] Read more.
Carbamazepine (CBZ) is commonly prescribed for epilepsy and frequently used in polypharmacy. However, concerns arise regarding its ability to induce the metabolism of other drugs, including itself, potentially leading to the undertreatment of co-administered drugs. Additionally, CBZ exhibits nonlinear pharmacokinetics (PK), but the root causes have not been fully studied. This study aims to investigate the mechanisms behind CBZ’s nonlinear PK and its induction potential on CYP3A4 and CYP2C9 enzymes. To achieve this, we developed and validated a physiologically based pharmacokinetic (PBPK) parent–metabolite model of CBZ and its active metabolite Carbamazepine-10,11-epoxide in GastroPlus®. The model was utilized for Drug–Drug Interaction (DDI) prediction with CYP3A4 and CYP2C9 victim drugs and to further explore the underlying mechanisms behind CBZ’s nonlinear PK. The model accurately recapitulated CBZ plasma PK. Good DDI performance was demonstrated by the prediction of CBZ DDIs with quinidine, dolutegravir, phenytoin, and tolbutamide; however, with midazolam, the predicted/observed DDI AUClast ratio was 0.49 (slightly outside of the two-fold range). CBZ’s nonlinear PK can be attributed to its nonlinear metabolism caused by autoinduction, as well as nonlinear absorption due to poor solubility. In further applications, the model can help understand DDI potential when CBZ serves as a CYP3A4 and CYP2C9 inducer. Full article
(This article belongs to the Special Issue Advances in Pharmacokinetics and Drug Interactions)
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16 pages, 5676 KiB  
Article
Imbalance in Unc80 RNA Editing Disrupts Dynamic Neuronal Activity and Olfactory Perception
by Hui-Wen Chen, Chung-Pei Ma, En Chin, Yi-Tung Chen, Teh-Cheng Wang, Yu-Ping Kuo, Chia-Hao Su, Po-Jung Huang and Bertrand Chin-Ming Tan
Int. J. Mol. Sci. 2024, 25(11), 5985; https://doi.org/10.3390/ijms25115985 (registering DOI) - 30 May 2024
Abstract
A-to-I RNA editing, catalyzed by the ADAR protein family, significantly contributes to the diversity and adaptability of mammalian RNA signatures, aligning with developmental and physiological needs. Yet, the functions of many editing sites are still to be defined. The Unc80 gene stands out [...] Read more.
A-to-I RNA editing, catalyzed by the ADAR protein family, significantly contributes to the diversity and adaptability of mammalian RNA signatures, aligning with developmental and physiological needs. Yet, the functions of many editing sites are still to be defined. The Unc80 gene stands out in this context due to its brain-specific expression and the evolutionary conservation of its codon-altering editing event. The precise biological functions of Unc80 and its editing, however, are still largely undefined. In this study, we first demonstrated that Unc80 editing occurs in an ADAR2-dependent manner and is exclusive to the brain. By employing the CRISPR/Cas9 system to generate Unc80 knock-in mouse models that replicate the natural editing variations, our findings revealed that mice with the “gain-of-editing” variant (Unc80G/G) exhibit heightened basal neuronal activity in critical olfactory regions, compared to the “loss-of-editing” (Unc80S/S) counterparts. Moreover, an increase in glutamate levels was observed in the olfactory bulbs of Unc80G/G mice, indicating altered neurotransmitter dynamics. Behavioral analysis of odor detection revealed distinctive responses to novel odors—both Unc80 deficient (Unc80+/) and Unc80S/S mice demonstrated prolonged exploration times and heightened dishabituation responses. Further elucidating the olfactory connection of Unc80 editing, transcriptomic analysis of the olfactory bulb identified significant alterations in gene expression that corroborate the behavioral and physiological findings. Collectively, our research advances the understanding of Unc80’s neurophysiological functions and the impact of its editing on the olfactory sensory system, shedding light on the intricate molecular underpinnings of olfactory perception and neuronal activity. Full article
(This article belongs to the Section Molecular Neurobiology)
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10 pages, 524 KiB  
Article
The Association between Family History of Lung Cancer and Development of Lung Cancer: Analysis from the KoGES Data in Korea
by Sang Hyuk Kim, Hyun Lee, Bo-Guen Kim, Sang-Heon Kim, Jang Won Sohn, Ho Joo Yoon, Seung Hun Jang and Dong Won Park
Cancers 2024, 16(11), 2063; https://doi.org/10.3390/cancers16112063 (registering DOI) - 30 May 2024
Abstract
Comprehensive analyses of the association between a family history of lung cancer and lung cancer risk are limited, especially in the Korean population. We used baseline data from the Korean Genome and Epidemiology Study, conducted between 2001 and 2013. This study enrolled 198,980 [...] Read more.
Comprehensive analyses of the association between a family history of lung cancer and lung cancer risk are limited, especially in the Korean population. We used baseline data from the Korean Genome and Epidemiology Study, conducted between 2001 and 2013. This study enrolled 198,980 individuals. Lung cancer diagnoses and family histories were determined using questionnaires. Multivariable logistic regression analysis was performed to evaluate the effect of family history on the risk of lung cancer. Of 198,980 individuals, 6296 (3.2%) and 140 (0.1%) had a family history of lung cancer and lung cancer, respectively. Individuals with a family history of lung cancer in first-degree relatives (FDRs) had a higher risk of lung cancer development than those without (adjusted odds ratio [aOR] = 2.28, 95% confidence interval [CI] = 1.11–4.66). This was more pronounced in young individuals (<60 years) who had affected relatives diagnosed with lung cancer before the age of 60 years (aOR = 3.77, 95% CI = 1.19–11.88). In subgroup analyses, this association was more evident in women, never smokers, and young individuals. A family history of lung cancer, especially in FDRs, is a significant risk factor for lung cancer development in Korea. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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9 pages, 194 KiB  
Article
“Wasn’t in Our Game Plan”: Reflections of Older Grandparents Navigating Child Welfare Systems
by Tina L. Peterson
Societies 2024, 14(6), 79; https://doi.org/10.3390/soc14060079 (registering DOI) - 30 May 2024
Abstract
Kinship caregivers encounter complex issues when interfacing with the child welfare system. Most kinship care families are not connected to child welfare. The experiences and extent of child welfare connection among older grandparents raising adolescent grandchildren are understudied. This study describes in-depth reflections [...] Read more.
Kinship caregivers encounter complex issues when interfacing with the child welfare system. Most kinship care families are not connected to child welfare. The experiences and extent of child welfare connection among older grandparents raising adolescent grandchildren are understudied. This study describes in-depth reflections from older grandparents raising adolescent grandchildren about circumstances leading to kinship care and the extent of child welfare involvement. Nineteen older grandparents raising adolescent grandchildren participated in qualitative phenomenological interviews. Eligibility criteria included identifying as a primary caregiver aged 40 or older for a grandchild 12 years or older who lived with them at least three days during the week. Respondents were primarily married (58%), white/non-Hispanic (53%), and grandmothers (84%) and had some college education or were college graduates (79%). Older grandparent caregivers described three themes: the intensive child welfare path, the influence of indirect child welfare professionals, and guardians with influence. The onset of kinship care, with or without intensive child welfare involvement, stemmed primarily from child abuse and neglect linked primarily to adolescent pregnancies and parental substance use. Child welfare and other helping professionals must recognize and problem-solve with older grandparent caregivers to meet complex stage-of-life needs in and outside of traditional child welfare settings. Full article
11 pages, 3401 KiB  
Article
Sensitive Detection of Oral Leukoplakia: Analyzing P90 Biomarkers in Saliva and Tissue
by Hsiao-Hsuan Wan, Haochen Zhu, Chao-Ching Chiang, Jian-Sian Li, Fan Ren, Cheng-Tse Tsai, Yu-Te Liao, Dan Neal, Joseph Katz and Josephine F. Esquivel-Upshaw
Biosensors 2024, 14(6), 281; https://doi.org/10.3390/bios14060281 (registering DOI) - 30 May 2024
Abstract
Oral cancer represents a significant global public health challenge, contributing substantially to the incidence and mortality of cancer. Despite established risk factors such as tobacco use and alcohol consumption, early detection remains crucial for effective treatment. This study introduces a novel approach using [...] Read more.
Oral cancer represents a significant global public health challenge, contributing substantially to the incidence and mortality of cancer. Despite established risk factors such as tobacco use and alcohol consumption, early detection remains crucial for effective treatment. This study introduces a novel approach using a transistor-based biosensor system for detecting the P90 (CIP2A) protein. We tested the presence of CIP2A in human leukoplakia samples, which can undergo malignant conversion into aggressive oral squamous cell carcinoma. The method used commercially available glucose test strips functionalized with P90 antibodies, providing high sensitivity and a low limit of detection which was five orders lower than that of commercial ELISA kits. A specially designed printed circuit board (PCB) facilitated accurate measurements, and the device’s performance was optimized through characteristic tests. Human sample testing validated the biosensor’s effectiveness in distinguishing samples after cell lysis. This study contributes to advancing accurate and cost-effective diagnostic approaches for oral pre-cancer and cancer tissues. Full article
(This article belongs to the Section Biosensors and Healthcare)
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16 pages, 4471 KiB  
Review
Covalent Organic Frameworks Based Electrocatalysts for Two-Electron Oxygen Reduction Reaction: Design Principles, Recent Advances, and Perspective
by Rui Qiao, Jinyan Wang, Hongyin Hu and Shuanglong Lu
Molecules 2024, 29(11), 2563; https://doi.org/10.3390/molecules29112563 (registering DOI) - 30 May 2024
Abstract
Hydrogen peroxide (H2O2) is an environmentally friendly oxidant with a wide range of applications, and the two-electron pathway (2e) of the oxygen reduction reaction (ORR) for H2O2 production has attracted much attention due to [...] Read more.
Hydrogen peroxide (H2O2) is an environmentally friendly oxidant with a wide range of applications, and the two-electron pathway (2e) of the oxygen reduction reaction (ORR) for H2O2 production has attracted much attention due to its eco-friendly nature and operational simplicity in contrast to the conventional anthraquinone process. The challenge is to design electrocatalysts with high activity and selectivity and to understand their structure–activity relationship and catalytic mechanism in the ORR process. Covalent organic frameworks (COFs) provide an efficient template for the construction of highly efficient electrocatalysts due to their designable structure, excellent stability, and controllable porosity. This review firstly outlines the design principles of COFs, including the selection of metallic and nonmetallic active sites, the modulation of the electronic structure of the active sites, and the dimensionality modulation of the COFs, to provide guidance for improving the production performance of H2O2. Subsequently, representative results are summarized in terms of both metallic and metal-free sites to follow the latest progress. Moreover, the challenges and perspectives of 2e ORR electrocatalysts based on COFs are discussed. Full article
(This article belongs to the Section Electrochemistry)
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21 pages, 668 KiB  
Review
Hemodialysis Procedures for Stable Incident and Prevalent Patients Optimize Hemodynamic Stability, Dialysis Dose, Electrolytes, and Fluid Balance
by Stefano Stuard, Christophe Ridel, Mario Cioffi, Alijana Trost-Rupnik, Konstantin Gurevich, Marija Bojic, Yerkebulan Karibayev, Nilufar Mohebbi, Wojciech Marcinkowski, Vlasta Kupres, Jelena Maslovaric, Alon Antebi, Pedro Ponce, Mamdouh Nada, Maria Eva Baro Salvador, Jaroslav Rosenberger, Tomas Jirka, Kira Enden, Volodymyr Novakivskyy, Daniela Voiculescu, Martin Pachmann and Otto Arkossyadd Show full author list remove Hide full author list
J. Clin. Med. 2024, 13(11), 3211; https://doi.org/10.3390/jcm13113211 (registering DOI) - 30 May 2024
Abstract
The demographic profile of patients transitioning from chronic kidney disease to kidney replacement therapy is changing, with a higher prevalence of aging patients with multiple comorbidities such as diabetes mellitus and heart failure. Cardiovascular disease remains the leading cause of mortality in this [...] Read more.
The demographic profile of patients transitioning from chronic kidney disease to kidney replacement therapy is changing, with a higher prevalence of aging patients with multiple comorbidities such as diabetes mellitus and heart failure. Cardiovascular disease remains the leading cause of mortality in this population, exacerbated by the cardiovascular stress imposed by the HD procedure. The first year after transitioning to hemodialysis is associated with increased risks of hospitalization and mortality, particularly within the first 90–120 days, with greater vulnerability observed among the elderly. Based on data from clinics in Fresenius Medical Care Europe, Middle East, and Africa NephroCare, this review aims to optimize hemodialysis procedures to reduce mortality risk in stable incident and prevalent patients. It addresses critical aspects such as treatment duration, frequency, choice of dialysis membrane, dialysate composition, blood and dialysate flow rates, electrolyte composition, temperature control, target weight management, dialysis adequacy, and additional protocols, with a focus on mitigating prevalent intradialytic complications, particularly intradialytic hypotension prevention. Full article
(This article belongs to the Special Issue Novelty in the Management of Progression and Complications of CKD)
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21 pages, 621 KiB  
Article
Glycoprotein Acetyls Is a Novel Biomarker Predicting Cardiovascular Complications in Rheumatoid Arthritis
by Melody Kasher, Maxim B. Freidin, Frances M. K. Williams, Stacey S. Cherny, Shai Ashkenazi and Gregory Livshits
Int. J. Mol. Sci. 2024, 25(11), 5981; https://doi.org/10.3390/ijms25115981 (registering DOI) - 30 May 2024
Abstract
The relationship between rheumatoid arthritis (RA) and early onset atherosclerosis is well depicted, each with an important inflammatory component. Glycoprotein acetyls (GlycA), a novel biomarker of inflammation, may play a role in the manifestation of these two inflammatory conditions. The present study examined [...] Read more.
The relationship between rheumatoid arthritis (RA) and early onset atherosclerosis is well depicted, each with an important inflammatory component. Glycoprotein acetyls (GlycA), a novel biomarker of inflammation, may play a role in the manifestation of these two inflammatory conditions. The present study examined a potential mediating role of GlycA within the RA–atherosclerosis relationship to determine whether it accounts for the excess risk of cardiovascular disease over that posed by lipid risk factors. The UK Biobank dataset was acquired to establish associations among RA, atherosclerosis, GlycA, and major lipid factors: total cholesterol (TC), high- and low-density lipoprotein (HDL, LDL) cholesterol, and triglycerides (TGs). Genome-wide association study summary statistics were collected from various resources to perform genetic analyses. Causality among variables was tested using Mendelian Randomization (MR) analysis. Genes of interest were identified using colocalization analysis and gene enrichment analysis. MR results appeared to indicate that the genetic relationship between GlycA and RA and also between RA and atherosclerosis was explained by horizontal pleiotropy (p-value = 0.001 and <0.001, respectively), while GlycA may causally predict atherosclerosis (p-value = 0.017). Colocalization analysis revealed several functionally relevant genes shared between GlycA and all the variables assessed. Two loci were apparent in all relationships tested and included the HLA region as well as SLC22A1. GlycA appears to mediate the RA–atherosclerosis relationship through several possible pathways. GlycA, although pleiotropically related to RA, appears to causally predict atherosclerosis. Thus, GlycA is suggested as a significant factor in the etiology of atherosclerosis development in RA. Full article
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14 pages, 578 KiB  
Article
High-Protein Processed Foods: Impact on Diet, Nutritional Status, and Possible Effects on Health
by Rosa M. Ortega, Nerea Arribas-López, María Dolores Salas-González, Aránzazu Aparicio, Liliana Guadalupe González-Rodríguez, Laura M. Bermejo, María Del Carmen Lozano-Estevan, Esther Cuadrado-Soto, Ana M. López-Sobaler and Viviana Loria-Kohen
Nutrients 2024, 16(11), 1697; https://doi.org/10.3390/nu16111697 (registering DOI) - 30 May 2024
Abstract
Proteins are macronutrients with multiple health benefits, but excessive consumption can negatively affect health. This study aimed to evaluate the characteristics of a sample of high-protein processed foods (HPPFs), describe how their consumption affects dietary balance, and acquire knowledge of the consumption patterns [...] Read more.
Proteins are macronutrients with multiple health benefits, but excessive consumption can negatively affect health. This study aimed to evaluate the characteristics of a sample of high-protein processed foods (HPPFs), describe how their consumption affects dietary balance, and acquire knowledge of the consumption patterns of these products in a Spanish population. A sample of HPPFs available in supermarkets and on websites was collected. The contribution to recommended protein intakes was calculated using national and international references and considering the single consumption of the HPPFs and the product plus 150 g of meat. Furthermore, an online survey was conducted among a convenience sample. A total of 36 enriched protein products were evaluated. The percentage of proteins in these products ranges from 10 to 88%. The contribution of the protein recommended intake was within a range of 87.4–306.6% and 66.4–232.8% (women and men, respectively), only considering the additional proteins from 150 g of meat. One hundred thirty-nine participants completed the survey; 67.6% affirmed that they had consumed HPPFs, and half consumed them without following any consumption control. Since these products are accessible to everyone in supermarkets and protein intake is generally higher than the recommended limits, regulating the mass sale of HPPFs is essential to ensure they do not lead to protein overconsumption. Full article
(This article belongs to the Special Issue Nutritional Screening and Assessment of Different Populations)
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12 pages, 1306 KiB  
Article
Nutritional Support in Malnourished Outpatients with Chronic Obstructive Pulmonary Disease (COPD): A Randomized Controlled Pilot Study
by Valerie Conway, Craig Hukins, Stacey Sharp and Peter F. Collins
Nutrients 2024, 16(11), 1696; https://doi.org/10.3390/nu16111696 (registering DOI) - 30 May 2024
Abstract
(1) Background: The evidence for nutritional support in COPD is almost entirely based on ready-to-drink oral nutritional supplements (ONSs). This study aimed to explore the effectiveness of powdered ONSs alongside individualized dietary counseling in the management of malnutrition. (2) Methods: Malnourished outpatients with [...] Read more.
(1) Background: The evidence for nutritional support in COPD is almost entirely based on ready-to-drink oral nutritional supplements (ONSs). This study aimed to explore the effectiveness of powdered ONSs alongside individualized dietary counseling in the management of malnutrition. (2) Methods: Malnourished outpatients with COPD were randomized to receive either routine care (Group A: counseling + recommended to purchase powdered ONSs) or an enhanced intervention (Group B: counseling + provision of powdered ONSs at no cost to the patient) for 12 weeks. Outcomes of interest were nutritional intake, weight status, and quality of life. (3) Results: A total of 33 outpatients were included, categorized as follows: Group A (n = 21); Group B (n = 12); severely malnourished (n = 9), moderately malnourished (n = 24), mean BMI 18.0 SD 2.5 kg/m2. No differences were observed between groups at baseline or at week 12; however, analysis of the whole cohort (Group A + B) revealed nutrition intervention resulted in significant improvements in protein intake (+25.4 SD 53.4 g/d; p = 0.040), weight (+1.1 SD 2.6 kg; p = 0.032) and quality of life (−4.4 SD 10.0; p = 0.040). Only 41.2% of Group A and 58.3% of Group B reported consuming ONSs at week 12. Adherence to ONSs was associated with weight gain (+1.9 SD 2.5 kg vs. +0.4 SD 2.5 kg; p = 0.098). (4) Conclusions: Nutritional support results in significant improvements in nutrition status and quality of life in malnourished outpatients with COPD. However, improvements are associated with adherence to ONSs, suggesting the type of ONSs and how they are provided are important considerations in clinical practice and future studies. Full article
(This article belongs to the Special Issue Nutrition and Lung Disease)
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