Biomolecules最新文献

{"title":"Electrostatic Effects on Tau Nanocondensates.","authors":"Phoebe S Tsoi, Lathan Lucas, Derek Rhoades, Josephine C Ferreon, Allan Chris M Ferreon","doi":"10.3390/biom15030406","DOIUrl":"10.3390/biom15030406","url":null,"abstract":"<p><p>Biomolecular condensates (BMCs) are membrane-less protein compartments with physiological and pathological relevance. The formation of BMCs is driven by a process known as liquid-liquid phase separation (LLPS), a field that has largely focused on the study of micron-sized condensates. However, there have been recent studies showing that proteins that undergo LLPS also form nanometer-sized condensates. These nanometer-sized condensates, or nanocondensates, are distinct from microcondensates and potentially exhibit more relevance in cell biology. The field of nanocondensate research is in its infancy, with limited biophysical studies of these structures. Here, we studied condensate formation and dissolution of wild-type and disease-linked (hyperphosphorylated and missense mutated) Tau. We investigated the effects of solution condition modulation on nanocondensate formation and dissolution, and observed that Tau condensation is strongly regulated by electrostatic forces and less affected by hydrophobic disruption. We observed that all three Tau variants studied shared condensate formation properties when in solution conditions with the same ionic strength. However, hyperphosphorylated and missense-mutated Tau exhibited higher resistance to dissolution compared to wild-type Tau. This study uncovers additional distinctions between different types of condensates, which provides further insight into the distinctions between physiological and pathological condensates.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological and Inflammatory Consequences of Aging.","authors":"Mario García-Domínguez","doi":"10.3390/biom15030404","DOIUrl":"10.3390/biom15030404","url":null,"abstract":"<p><p>Aging is a complex, progressive, and irreversible biological process that entails numerous structural and functional changes in the organism. These changes affect all bodily systems, reducing their ability to respond and adapt to the environment. Chronic inflammation is one of the key factors driving the development of age-related diseases, ultimately causing a substantial decline in the functional abilities of older individuals. This persistent inflammatory state (commonly known as \"inflammaging\") is characterized by elevated levels of pro-inflammatory cytokines, an increase in oxidative stress, and a perturbation of immune homeostasis. Several factors, including cellular senescence, contribute to this inflammatory milieu, thereby amplifying conditions such as cardiovascular disease, neurodegeneration, and metabolic disorders. Exploring the mechanisms of chronic inflammation in aging is essential for developing targeted interventions aimed at promoting healthy aging. This review explains the strong connection between aging and chronic inflammation, highlighting potential therapeutic approaches like pharmacological treatments, dietary strategies, and lifestyle changes.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Design and In Vitro and In Vivo Characterization of an ApoE-Based Synthetic High-Density Lipoprotein for Sepsis Therapy.","authors":"Ling Guo, Yaxia Yuan, Fang Zheng, Changguo Zhan, Xiangan Li","doi":"10.3390/biom15030397","DOIUrl":"10.3390/biom15030397","url":null,"abstract":"<p><p><b>Introduction:</b> Septic patients have low levels of high-density lipoproteins (HDLs), which is a risk factor. Replenishing HDLs with synthetic HDLs (sHDLs) has shown promise as a therapy for sepsis. This study aimed to develop a computational approach to design and test new types of sHDLs for sepsis treatment. <b>Methods:</b> We used a three-step computational approach to design sHDL nanoparticles based on the structure of HDLs and their binding to endotoxins. We tested the efficacy of these sHDLs in two sepsis mouse models-cecal ligation and puncture (CLP)-induced and <i>P. aeruginosa</i>-induced sepsis models-and assessed their impact on inflammatory signaling in cells. <b>Results:</b> We designed four sHDL nanoparticles: two based on the ApoA-I sequence (YGZL1 and YGZL2) and two based on the ApoE sequence (YGZL3 and YGZL4). We demonstrated that an ApoE-based sHDL nanoparticle, YGZL3, provides effective protection against CLP- and <i>P. aeruginosa</i>-induced sepsis. The sHDLs effectively suppressed inflammatory signaling in HEK-blue or RAW264 cells. <b>Conclusions:</b> Unlike earlier approaches, we developed a new approach that employs computational simulations to design a new type of sHDL based on HDL's structure and function. We found that YGZL3, an ApoE sequence-based sHDL, provides effective protection against sepsis in two mouse models.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Adventitious Matches of Non-Donors Related to True Contributors.","authors":"Kaitlin Huffman, Lilliana Moreno","doi":"10.3390/biom15030398","DOIUrl":"10.3390/biom15030398","url":null,"abstract":"<p><p>Relatives share more DNA with one another than unrelated individuals. Therefore, there is an increased risk of close relatives (e.g., siblings or parents and children of true donors) adventitiously 'matching' DNA mixtures to which they are not a true contributor. One such method of addressing relatives is to utilize alternative propositions within probabilistic genotyping software (e.g., STRmix^TM). As the number of related individuals within a mixture increases, so does the potential for adventitious matches of related non-donors to the mixture due to increased allele sharing. The extent to which siblings and parents/children of true donors result in adventitious matches to mixtures in which they are non-donors is presented as well as the impact of overestimating the number of contributors (NOC) when related donors are in question.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absolute Quantitative Metagenomic Analysis Provides More Accurate Insights for the Anti-Colitis Effect of Berberine via Modulation of Gut Microbiota.","authors":"Jiaguo Zhan, Jiale Cheng, Wenhui Chang, Yuying Su, Xixin Yue, Chongming Wu","doi":"10.3390/biom15030400","DOIUrl":"10.3390/biom15030400","url":null,"abstract":"<p><p>Current gut microbiota studies often rely on relative quantitative sequencing. However, under certain circumstances, while the relative quantitative abundance of these bacteria may remain stable, the absolute quantities of specific bacteria can vary considerably. Since the function of bacteria is directly linked to their total numbers, absolute quantification is crucial. This study aims to identify the optimal method for microbiome analysis by comparing relative and absolute quantitative sequencing. Using ulcerative colitis, which is closely associated with gut microbiota, as a disease model and berberine (which affects microbiota) versus sodium butyrate (which does not) as drugs, relative and absolute quantitative methods were used to evaluate the varying effects of the different drugs on the regulation of gut microbiota in UC-affected animals. The regulatory effects of BBR on gut microbiota were further synthesized as identified in earlier studies using an individual-based meta-analysis, and we compared these findings with our absolute sequencing results. The results from absolute sequencing were more consistent with the actual microbial community, suggesting that relative abundance measurements might not accurately reflect the true abundance of microbial species. Moreover, meta-analysis results were only partially consistent with absolute quantitative sequencing and sometimes directly opposed, suggesting that relative quantitative sequencing analyses are prone to misinterpretation and incorrect correlation of results. This study underscores the importance of absolute quantitative analysis in accurately representing the true microbial counts in a sample and evaluating the modulatory effects of drugs on the microbiome, which plays a vital role in the study of the microbiome.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Eye Lens Protein, γS Crystallin, Undergoes Glutathionylation-Induced Disulfide Bonding Between Cysteines 22 and 26.","authors":"Kate Halverson-Kolkind, David C Thorn, Martin Tovar-Ramirez, Eugene Shakhnovich, Larry David, Kirsten Lampi","doi":"10.3390/biom15030402","DOIUrl":"10.3390/biom15030402","url":null,"abstract":"<p><p>The oxidation of cysteines in crystallins is a major age-related modification associated with cataract formation. The purpose of this research was to determine the susceptibility of γS-crystallin to glutathionylation-induced oxidation and disulfide bond formation. Recombinantly expressed wild-type human γS-crystallin and four cysteine-to-serine mutants were reduced and incubated for up to 2 days with oxidized glutathione. Following incubation and alkylation, the overall degree of glutathionylation and disulfide bond formation were determined by whole-mass measurement. Tryptic digests were also analyzed by LC-MS/MS to identify specific sites of S-glutathionylation and disulfide linkages. We determined that C22, C24, and C26 undergo glutathione-mediated disulfide interchange with each other, with C24 being most susceptible to oxidation and mixed disulfide formation. Our data suggest C24 is S-glutathionylated sequentially with C22 and C26 participating in disulfide exchange reactions, yielding a major species with a single glutathionylation at C24 and a disulfide between C22 and C26. The results imply that as glutathione levels are depleted in aged lenses, γS-crystallin undergoes stepwise oxidation reactions and disulfide shuffling, which may contribute towards its aggregation and cataract formation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between hsTnT and NT-proBNP and Peripheral Artery Disease in People with HIV: A Multicentre Danish Cohort Study.","authors":"Thomas R Holtveg, Anne Marie Reimer Jensen, Ask Bock, Moises Alberto Suarez-Zdunek, Andreas D Knudsen, Børge G Nordestgaard, Shoaib Afzal, Thomas Benfield, Sisse R Ostrowski, Tor Biering-Sørensen, Ruth Frikke-Schmidt, Susanne D Nielsen","doi":"10.3390/biom15030401","DOIUrl":"10.3390/biom15030401","url":null,"abstract":"<p><p>People with HIV (PWH) have a high risk of peripheral artery disease (PAD), and high-sensitivity troponin (hsTnT) and NT-pro B-type natriuretic peptide (NT-proBNP) may be useful biomarkers for PAD in PWH. We assessed associations between hsTnT and NT-proBNP and both prevalent PAD and de novo PAD. Adult PWH were examined at baseline and after 2 years. Inclusion criteria were (1) measurements of hsTnT and NT-proBNP at baseline and (2) ankle brachial index (ABI) at baseline for prevalent PAD and both visits for de novo PAD. PAD was defined as ABI ≤ 0.9. We included 1011 PWH, and 88 (8.7%) had PAD at baseline. Among 802 PWH, 29 (3.6%) had de novo PAD at follow-up. A doubling in hsTnT concentration was associated with prevalent PAD with an OR 1.41 (95% CI: 1.02-1.96, <i>p</i> = 0.04) and 1.40 (95% CI: 0.99-1.98, <i>p</i> = 0.055) in a base model and an adjusted model, respectively. High hsTnT was associated with a risk ratio of 3.39 (95% CI: 1.24-9.27, <i>p</i> = 0.02) for de novo PAD in an unadjusted model and 3.44 (95% CI: 0.98-12.10, <i>p</i> = 0.05) after adjustments. NT-proBNP was not associated with PAD. Thus, hsTnT was associated with higher odds of prevalent PAD and increased risk of de novo PAD.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the CNOT1(800-999) HEAT Domain and Its Interactions with Tristetraprolin (TTP) as Revealed by Hydrogen/Deuterium Exchange Mass Spectrometry.","authors":"Maja K Cieplak-Rotowska, Michał Dadlez, Anna Niedzwiecka","doi":"10.3390/biom15030403","DOIUrl":"10.3390/biom15030403","url":null,"abstract":"<p><p>CNOT1, a key scaffold in the CCR4-NOT complex, plays a critical role in mRNA decay, particularly in the regulation of inflammatory responses through its interaction with tristetraprolin. A fragment of the middle part of CNOT1 (residues 800-999) is an example of an α-helical HEAT-like repeat domain. The HEAT motif is an evolutionarily conserved motif present in scaffolding and transport proteins across a wide range of organisms. Using hydrogen/deuterium exchange mass spectrometry (HDX MS), a method that has not been widely explored in the context of HEAT repeats, we analysed the structural dynamics of wild-type CNOT1(800-999) and its two double point mutants (E893A/Y900A, E893Q/Y900H) to find the individual contributions of these CNOT1 residues to the molecular recognition of tristetraprolin (TTP). Our results show that the differences in the interactions of CNOT1(800-999) variants with the TTP peptide fragment are due to the absence of the critical residues resulting from point mutations and not due to the perturbation of the protein structure. Nevertheless, the HDX MS was able to detect slight local changes in structural dynamics induced by protein point mutations, which are usually neglected in studies of intermolecular interactions.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of γ-Aminobutyric Acid (GABA) as an Inhibitory Neurotransmitter in Diabetes Management: Mechanisms and Therapeutic Implications.","authors":"Hassan Barakat, Thamer Aljutaily","doi":"10.3390/biom15030399","DOIUrl":"10.3390/biom15030399","url":null,"abstract":"<p><p>GABA (γ-Aminobutyric Acid), a well-established inhibitory neurotransmitter in the central nervous system, has garnered considerable interest for its potential role in diabetes management, particularly due to its presence in pancreatic islets. This review aims to explore the therapeutic role of GABA in diabetes management and its potential mechanisms for antidiabetic effects. Relevant studies were searched across databases such as PubMed and ScienceDirect, applying strict eligibility criteria focused on GABA administration methods and diabetic models. The collective results showed that the administration of GABA in diabetic models resulted in remarkable enhancements in glucose and insulin homeostasis, favorable modifications in lipid profiles, and amelioration of dysfunctions across neural, hepatic, renal, and cardiac systems. The findings from the literature demonstrated that GABAergic signaling within pancreatic tissues can significantly contribute to the stimulation of β cell proliferation through the facilitation of a sustained <i>trans</i>-differentiation process, wherein glucagon-secreting α cells are converted into insulin-secreting β-like cells. In addition, activated GABAergic signaling can trigger the initiation of the PI3K/AKT signaling pathway within pancreatic tissues, leading to improved insulin signaling and maintained glucose homeostasis. GABAergic signaling can further function within hepatic tissues, promoting inhibitory effects on the expression of genes related to gluconeogenesis and lipogenesis. Moreover, GABA may enhance gut microbiota diversity by attenuating gut inflammation, attributable to its anti-inflammatory and immunomodulatory properties. Furthermore, the neuroprotective effects of GABA play a significant role in ameliorating neural disorders associated with diabetes by facilitating a substantial reduction in neuronal apoptosis. In conclusion, GABA emerges as a promising candidate for an antidiabetic agent; however, further research is highly encouraged to develop a rigorously designed framework that comprehensively identifies and optimizes the appropriate dosages and intervention methods for effectively managing and combating diabetes.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevation of Plasma IL-15 and RANTES as Potential Biomarkers of Healing in Chronic Venous Ulcerations: A Pilot Study.","authors":"Amanda Beneat, Vikki Rueda, Hardik Patel, Zarina Brune, Barbara Sherry, Andrew Shih, Sally Kaplan, Amit Rao, Annette Lee, Asha Varghese, Alisha Oropallo, Betsy J Barnes","doi":"10.3390/biom15030395","DOIUrl":"10.3390/biom15030395","url":null,"abstract":"<p><p>Chronic wounds present a large burden to our healthcare system and are typically marked by a failure to transition out of the inflammatory phase of wound healing. Venous leg ulcers (VLUs) represent the largest portion of chronic wounds. A pilot study of eleven (11) patients with VLUs seen over a 12-week period was undertaken utilizing RNA sequencing of wound biopsies and plasma cytokine levels to determine if biomarkers could be identified that would distinguish between wounds which heal versus those that do not. Chronic wounds were found to have increased expression of genes relating to epithelial-to-mesenchymal transition (EMT), cartilage and bone formation, and regulation of apical junction. Plasma cytokine levels showed predictive potential for IL-15 and RANTES, which were found to increase over time in patients with healed wounds. Further research is needed to validate these biomarkers as well as additional study of other chronic wound models, such as diabetic foot ulcers (DFUs).</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}