Biomolecules最新文献

{"title":"ACAA2 Protects Against Cardiac Dysfunction and Lipid Peroxidation in Renal Insufficiency with the Treatment of S-Nitroso-L-Cysteine.","authors":"Zhengqi Xu, Feng Jiang, Xiaofan Wu, Bowen Ren, Cuntai Zhang, Li Lin, Sheng Li","doi":"10.3390/biom15030364","DOIUrl":"10.3390/biom15030364","url":null,"abstract":"<p><p>The key fatty acid β-oxidation protein acetyl-CoA acyltransferase 2 (ACAA2) plays a significant role in myocardial lipid peroxidation and cardiac dysfunction induced by renal insufficiency. However, the mechanisms of lipid metabolism related to renal insufficiency-associated cardiac dysfunction remain poorly understood, and current clinical treatments have been largely ineffective. Through analysis of the Gene Expression Omnibus (GEO) database, we identified that the cardiac functional changes caused by renal insufficiency were primarily centered around the fatty acid β-oxidation signaling pathway, where ACAA2 plays a pivotal role in fatty acid β-oxidation, the tricarboxylic acid cycle, and ketone body metabolism. In an adenine-induced renal insufficiency mouse model, further examination with hematoxylin-eosin staining, Masson staining, and Oil Red O staining revealed alterations in the heart and kidney as well as the accumulation of lipid. Non-invasive blood pressure measurements and ultrasound images demonstrated improvements of peripheral vascular and right ventricular hemodynamic parameters with S-nitroso-L-cysteine (CSNO) inhalation therapy. In cell experiments, knocking down ACAA2 led to accumulation of lipid droplets and exacerbation of oxidative stress in cardiomyocytes, while overexpression of ACAA2 reversed these effects. The transcription factor FOXO4 was found to regulate lipid peroxidation by modulating ACAA2, and knocking down FOXO4 partially restored the expression of ACAA2, reducing oxidative stress in cardiomyocytes. Furthermore, exogenous CSNO effectively restored the expression of ACAA2 and reduced the level of FOXO4, thereby mitigating lipid peroxidation and improving cardiac function. Therefore, in the context of renal insufficiency, regulating the FOXO4-ACAA2 axis through CSNO inhalation therapy may provide a novel therapeutic strategy for alleviating myocardial lipid peroxidation and improving cardiac function.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728228","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":"On-Tissue Chemical Derivatization for Mass Spectrometry Imaging of Fatty Acids with Enhanced Detection Sensitivity.","authors":"Malik Ebbini, Zicong Wang, Hua Zhang, Kelly H Lu, Penghsuan Huang, Cameron J Kaminsky, Luigi Puglielli, Lingjun Li","doi":"10.3390/biom15030366","DOIUrl":"10.3390/biom15030366","url":null,"abstract":"<p><p>The dysregulation of fatty acid (FA) metabolism is linked to various brain diseases, including Alzheimer's disease (AD). Mass spectrometry imaging (MSI) allows for the visualization of FA distribution in brain tissues but is often limited by low detection sensitivity and high background interference. In this work, we introduce a novel on-tissue chemical derivatization method for FAs using Girard's Reagent T (GT) as a derivatization reagent combined with 2-chloro-1-methylpyridinium iodide (CMPI) as a coupling reagent and triethylamine (TEA) to provide a basic environment for the reaction. This method significantly enhances the detection sensitivity of FAs, achieving a 1000-fold improvement over traditional negative ion mode analysis. Our method enabled us to observe a notable depletion of oleic acid in the corpus callosum of AD mouse model brain tissue sections compared to wild-type control brain tissue sections. The reliability of our method was validated using LC-MS/MS, which confirmed the presence of eight distinct GT-labeled FAs across various tissue locations. This approach not only improves FA detection in brain tissues but also has the potential to provide a deeper understanding of FA dynamics associated with AD pathogenesis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728266","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":"Formation of a Neuronal Membrane Model: A Quartz Crystal Microbalance with Dissipation Monitoring Study.","authors":"Elaheh Kamaloo, Terri A Camesano, Ramanathan Nagarajan","doi":"10.3390/biom15030362","DOIUrl":"10.3390/biom15030362","url":null,"abstract":"<p><p>Supported lipid bilayers (SLBs) that model neuronal membranes are needed to explore the role of membrane lipids in the misfolding and aggregation of amyloid proteins associated with neurodegenerative diseases, including Parkinson's and Alzheimer's disease. The neuronal membranes include not only phospholipids, but also significant amounts of cholesterol, sphingomyelin, and gangliosides, which are critical to its biological function. In this study, we explored the conditions for the formation of an SLB, for the five-component lipid mixture composed of zwitterionic 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), anionic 1,2-dioleoyl- sn-glycero-3-phospho-L-serine (DOPS), nonionic cholesterol (Chol), zwitterionic sphingomyelin (SM), and anionic ganglioside (GM), using the quartz crystal microbalance with dissipation monitoring (QCM-D) technique, by varying experimental parameters such as pH, buffer type, temperature, vesicle size, and osmotic stress. SLB formation from this multicomponent lipid system was found challenging because the vesicles adsorbed intact on the quartz crystal and failed to rupture. For most of the variables tested, other than osmotic stress, we found no or only partial vesicle rupture leading to either a supported layer of vesicles or a partial SLB that included unruptured vesicles. When osmotic stress was applied to the vesicles already adsorbed on the surface, by having a different salt concentration in the rinse buffer that follows vesicle flow compared to that of the dilution buffer during vesicle flow and adsorption, vesicle rupture increased, but it remained incomplete. In contrast, when osmotic stress was applied during vesicle flow and adsorption on the surface, by having different salt concentrations in the dilution buffer in which vesicles flowed compared to the hydration buffer in which vesicles were prepared, complete vesicle rupture and successful formation of a rigid SLB was demonstrated. The robustness of this approach to form SLBs by applying osmotic stress during vesicle adsorption was found to be independent of the number of lipid components, as shown by SLB formation from the 1-, 2-, 3-, 4-, and 5-component lipid systems.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728219","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":"Thyroid Hormones and Metabolism Regulation: Which Role on Brown Adipose Tissue and Browning Process?","authors":"Laura Sabatino, Cristina Vassalle","doi":"10.3390/biom15030361","DOIUrl":"10.3390/biom15030361","url":null,"abstract":"<p><p>Thyroid hormones (THs) are important modulators of many metabolic processes, being strictly associated with the control of energy balance, mainly through activities on the brain, white and brown adipose tissue, skeletal muscle, liver, and pancreas. In this review, the principal mechanisms of TH regulation on metabolic processes will be discussed and THs' relevance in metabolic disease progression will be evaluated, especially in the cardiovascular context and correlated diseases. Moreover, we will discuss THs' regulatory role on metabolic events in white and brown adipose tissue, with a special focus on the process of \"browning\", which consists of the gradual acquisition by white adipocytes of the physical and functional characteristics of brown adipocytes. The advancements in research on molecular mechanisms and proposed physiopathological relevance of this process will be discussed.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728334","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":"Identification of a Possible Endocannabinoid-Mediated Mechanism of Action of Cetylated Fatty Acids.","authors":"Giulia Bononi, Carlotta Granchi, Tiziano Tuccinardi, Filippo Minutolo","doi":"10.3390/biom15030363","DOIUrl":"10.3390/biom15030363","url":null,"abstract":"<p><p>Some musculoskeletal disorders, including osteoarthritis; arthrosis; post-traumatic injuries; and other inflammatory tendon, joint and muscular afflictions, still represent unmet medical needs. Cetylated fatty acids (CFAs) are key components of widely distributed over-the-counter products, especially for topical use, which are intended to reduce symptoms associated with these conditions. Nevertheless, the mechanism of action of CFAs' analgesic and anti-inflammatory properties has not yet been clearly established. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG) and anandamide (AEA), are known to produce analgesic and anti-inflammatory effects. These compounds undergo physiological inactivation operated by several enzymes, including monoacylglycerol lipase (MAGL). We herein demonstrate for the first time that the therapeutic effects of CFAs may be attributable, at least in part, to their MAGL inhibition activities, which induce a local increase in analgesic/anti-inflammatory endocannabinoids in close proximity to the site of administration. These findings pave the way for the development of new potent local analgesic agents, whose action is based on an indirect cannabinoid effect.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728240","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":"Inhibitory Effect of <i>Lactiplantibacillus plantarun</i> HFY11 on Compound Diphenoxylate-Induced Constipation in Mice.","authors":"Fang Tan, Chang-Suk Kong","doi":"10.3390/biom15030358","DOIUrl":"10.3390/biom15030358","url":null,"abstract":"<p><p><i>Lactiplantibacillus plantarun</i> HFY11 (LP-HFY11) is a newly discovered microbial strain. This study was the first to investigate the preventive effect of LP-HFY11 on compound diphenoxylate induced constipation in mice by measuring intestinal contents, serum, and small intestinal tissue indexes. In mice suffering from constipation, LP-HFY11 could prevent the reduction in fecal weight, particle count, and water content. The constipated mice that ingested a high LP-HFY11 dose (LP-HFY11H) expelled the first black stool faster than the model group and the drug lactulose-treated group, but they were slower than the normal group. Furthermore, the small intestine in the LP-HFY11H group had a greater propulsion rate of activated charcoal than that in the model and lactulose groups, but the propulsion rate was still lower than that in the normal group. According to hematoxylin-eosin (H&E) staining, LP-HFY11H was more effective than lactulose at reducing intestinal villi breaking and constipation-induced harm to the small intestine. Simultaneously, compared with the model group, the LP-HFY11H group had markedly increased serum levels of motilin (MTL), endothelin-1 (ET-1), vasoactive intestinal peptide (VIP), and acetylcholinesterase (AchE). Transient receptor potential vanilloid 1 (TRPV1) expression was only higher than in the normal group, but the mRNA expression of c-Kit, stem cell factor (SCF), and glial cell line-derived neurotrophic factor (GDNF) was all higher in the small intestine in the LP-HFY11H group than in the model and lactulose groups, according to the results of quantitative polymerase chain reaction (qPCR) experiments. Analysis of microbial mRNA in the small intestinal contents of the constipated mice further validated the capacity of LP-HFY11 to decrease the abundance of <i>Firmicutes</i> and increase the abundance of <i>Bacteroidetes</i>, <i>Bifidobacteria</i>, and <i>Lactobacillus</i>. This revealed that LP-HFY11, which produced better results than the drug lactulose, can control the gut microbiota of constipated mice and successfully cure constipation. LP-HFY11 has the potential to be used as a probiotic in the treatment of constipation. It has good application prospects in the food industry and biopharma.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728259","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":"Mechanical Forces, Nucleus, Chromosomes, and Chromatin.","authors":"Malgorzata Kloc, Jarek Wosik","doi":"10.3390/biom15030354","DOIUrl":"10.3390/biom15030354","url":null,"abstract":"<p><p>Individual cells and cells within the tissues and organs constantly face mechanical challenges, such as tension, compression, strain, shear stress, and the rigidity of cellular and extracellular surroundings. Besides the external mechanical forces, cells and their components are also subjected to intracellular mechanical forces, such as pulling, pushing, and stretching, created by the sophisticated force-generation machinery of the cytoskeleton and molecular motors. All these mechanical stressors switch on the mechanotransduction pathways, allowing cells and their components to respond and adapt. Mechanical force-induced changes at the cell membrane and cytoskeleton are also transmitted to the nucleus and its nucleoskeleton, affecting nucleocytoplasmic transport, chromatin conformation, transcriptional activity, replication, and genome, which, in turn, orchestrate cellular mechanical behavior. The memory of mechanoresponses is stored as epigenetic and chromatin structure modifications. The mechanical state of the cell in response to the acellular and cellular environment also determines cell identity, fate, and immune response to invading pathogens. Here, we give a short overview of the latest developments in understanding these processes, emphasizing their effects on cell nuclei, chromosomes, and chromatin.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727842","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":"Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.","authors":"Jente Van Campenhout, Yanthe Buntinx, Huan-Yu Xiong, Arne Wyns, Andrea Polli, Jo Nijs, Joeri L Aerts, Thessa Laeremans, Jolien Hendrix","doi":"10.3390/biom15030357","DOIUrl":"10.3390/biom15030357","url":null,"abstract":"<p><p>Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease, characterized by a diverse array of symptoms including post-exertional malaise (PEM), severe fatigue, and cognitive impairments, all of which drastically diminish the patients' quality of life. Despite its impact, no curative treatments exist, largely due to the limited understanding of the disease's underlying pathophysiology. Mitochondrial dysfunction, leading to impaired energy production and utilization, is believed to play a key role in the onset of fatigue and PEM, positioning it as a potential key pathophysiological mechanism underlying ME/CFS. Additionally, the disorder shows similarities to chronic viral infections, with frequent reports of immune system alterations, suggesting a critical role for immune (dys)functioning. In particular, the roles of immune senescence and immune exhaustion-two fundamental immune states-remain poorly understood in ME/CFS. This state-of-the-art review explores how metabolic dysfunction and immune dysfunction may be interconnected in ME/CFS, proposing that energy deficits may directly impair immune function. By examining this metabolic-immune interplay, this review highlights potential pathways for developing innovative therapeutic strategies that target both energy metabolism and immune regulation, offering hope for improving patient outcomes.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728340","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":"Scrutinizing Stator Rotation in the Bacterial Flagellum: Reconciling Experiments and Switching Models.","authors":"Ayush Joshi, Pushkar P Lele","doi":"10.3390/biom15030355","DOIUrl":"10.3390/biom15030355","url":null,"abstract":"<p><p>The bacterial flagellar motor is one of the few known rotary motors, powering motility and chemotaxis. The mechanisms underlying its rotation and the switching of its rotational direction are fundamental problems in biology that are of significant interest. Recent high-resolution studies of the flagellar motor have transformed our understanding of the motor, revealing a novel gear mechanism where a membranous pentamer of MotA proteins rotates around a cell wall-anchored dimer of MotB proteins to turn the contacting flagellar rotor. A derivative model suggests that significant changes in rotor diameter occur during switching, enabling each MotA₅MotB₂ stator unit to shift between internal and external gear configurations, causing clockwise (CW) and counterclockwise (CCW) motor rotation, respectively. However, recent structural work favors a mechanism where the stator units dynamically swing back and forth between the two gear configurations without significant changes in rotor diameter. Given the intricate link between the switching model and the gear mechanism for flagellar rotation, a critical evaluation of the underlying assumptions is crucial for refining switching models. This review scrutinizes key assumptions within prevailing models of flagellar rotation and switching, identifies knowledge gaps, and proposes avenues for future biophysical tests.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728305","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":"Application of Digital Polymerase Chain Reaction (dPCR) in Non-Invasive Prenatal Testing (NIPT).","authors":"Ying Guo, Pimlak Charoenkwan, Kuntharee Traisrisilp, Wirawit Piyamongkol, Fuanglada Tongprasert","doi":"10.3390/biom15030360","DOIUrl":"10.3390/biom15030360","url":null,"abstract":"<p><p>This article reviews the current applications of the digital polymerase chain reaction (dPCR) in non-invasive prenatal testing (NIPT) and explores its potential to complement or surpass the capabilities of Next-Generation Sequencing (NGS) in prenatal testing. The growing incidence of genetic disorders in maternal-fetal medicine has intensified the demand for precise and accessible NIPT options, which aim to minimize the need for invasive prenatal diagnostic procedures. Cell-free fetal DNA (cffDNA), the core analyte in NIPT, is influenced by numerous factors such as maternal DNA contamination, placental health, and fragment degradation. dPCR, with its inherent precision and ability to detect low-abundance targets, demonstrates robustness against these interferences. Although NGS remains the gold standard due to its comprehensive diagnostic capabilities, its high costs limit widespread use, particularly in resource-limited settings. In contrast, dPCR provides comparable accuracy with lower complexity and expense, making it a promising alternative for prenatal testing.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728231","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}