International Journal of Molecular Sciences最新文献

{"title":"Morphinan Alkaloids and Their Transformations: A Historical Perspective of a Century of Opioid Research in Hungary.","authors":"János Marton, Paul Cumming, Kenner C Rice, Joannes T M Linders","doi":"10.3390/ijms26062736","DOIUrl":"10.3390/ijms26062736","url":null,"abstract":"<p><p>The word opium derives from the ancient Greek word ὄπιον (ópion) for the juice of any plant, but today means the air-dried seed capsule latex of <i>Papaver somniferum</i>. Alkaloid chemistry began with the isolation of morphine from crude opium by Friedrich Wilhelm Adam Sertürner in 1804. More than a century later, Hungarian pharmacist János Kabay opened new perspectives for the direct isolation of morphine from dry poppy heads and straw without the labor-intensive harvesting of opium. In 2015, Kabay's life and achievements obtained official recognition as constituting a «Hungarikum», thereby entering the national repository of matters of unique cultural value. To this day, the study of <i>Papaver</i> alkaloids is a focus of medicinal chemistry, the (perhaps unstated) aspiration of which is to obtain an opioid with lesser abuse potential and side effects, while retaining good analgesic properties. We begin this review with a brief account of opiate biosynthesis, followed by a detailed presentation of semisynthetic opioids, emphasizing the efforts of the Alkaloida Chemical Company, founded in 1927 by János Kabay, and the morphine alkaloid group of the University of Debrecen.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719087","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":"Neuroprotection vs. Neurotoxicity: The Dual Impact of Brain Lipids in Depression.","authors":"Yuting Yan, Yan Zhang, Mengting Liu, Lingjie Li, Yanrong Zheng","doi":"10.3390/ijms26062722","DOIUrl":"10.3390/ijms26062722","url":null,"abstract":"<p><p>Growing neurochemical evidence highlights cerebral lipid dysregulation as a key factor in the pathophysiology of major depressive disorder (MDD). This review systematically explores the dual roles of lipid species in both normal behavioral regulation and MDD development. By critically examining the recent literature, we classify these lipid species into two functional categories based on their functional neuroactivity: (1) neuroprotective lipids (sphingomyelin, cholesterol, cardiolipin, sphingosine, phosphatidic acid, and phosphatidylserine), which exert neuroprotective effects by modulating membrane fluidity and supporting synaptic vesicle trafficking; and (2) neurotoxic lipids (ceramides, phosphatidylinositol, phosphocholine, and phosphatidylethanolamine), which promote apoptotic signaling cascades and disrupt mitochondrial bioenergetics. An unresolved but critical question pertains to the maintenance of homeostatic equilibrium between these opposing lipid classes. This balance is essential, given their significant impact on membrane protein localization and function, monoaminergic neurotransmitter metabolism, energy homeostasis, and redox balance in neural circuits involved in mood regulation. This emerging framework positions cerebral lipidomics as a promising avenue for identifying novel therapeutic targets and developing biomarker-based diagnostic approaches for MDD treatment.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719090","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 Combination of Physiological and Transcriptomic Approaches Reveals New Insights into the Molecular Mechanisms of <i>Leymus chinensis</i> Growth Under Different Shading Intensities.","authors":"Xinru Li, Qianqian Yu, Zhongxu Yao, Shuo Li, Lichao Ma, Kunlong Su, Guofeng Yang","doi":"10.3390/ijms26062730","DOIUrl":"10.3390/ijms26062730","url":null,"abstract":"<p><p><i>Leymus chinensis</i> is a grass species in the family Triticeae that is found in the Eurasian grassland region and is known for its outstanding ecological advantages and economic value. However, the increasing adoption of photovoltaic agriculture has modified the light environment for the grass, markedly inhibiting its photosynthesis, growth, and yield. This study used physiological and transcriptomic analyses to investigate the complex response mechanisms of two <i>L. chinensis</i> genotypes (Zhongke No. 3 [<i>Lc3</i>] and Zhongke No. 5 [<i>Lc5</i>]) under shading stress. Growth phenotype analysis revealed the superior growth performance of <i>Lc3</i> under shading stress, evidenced by enhanced plant height and photosynthetic parameters. Additionally, differentially expressed genes (DEGs) were predominantly enriched in starch and sucrose metabolism and glycolysis/gluconeogenesis pathways, which were the most consistently enriched in both <i>L. chinensis</i> genotypes. However, the flavonoid biosynthesis and galactose metabolism pathways were more enriched in <i>Lc3</i>. Weighted gene co-expression network analysis identified the <i>LcGolS2</i> gene, which encodes galactinol synthase, as a potential hub gene for resistance to shade stress in comparisons across different cultivars and shading treatments. The use of qRT-PCR analysis further validated the genes involved in these pathways, suggesting that they may play critical roles in regulating the growth and development of <i>L. chinensis</i> under shading conditions. These findings provide new insights into the molecular mechanisms underlying the growth and development of <i>L. chinensis</i> under different shading stress conditions.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719123","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 Novel Antagonist of BRS-3 from Natural Products and Its Protective Effects Against H₂O₂-Induced Cardiomyocyte Injury.","authors":"Jihong Lu, Lehao Wu, Jianzheng Zhu, Han Zhou, Mingzhu Fang, Hongshuo Liang, Miao Guo, Mo Chen, Yuhang Zhu, Jixia Wang, Hua Xiao, Yan Zhang","doi":"10.3390/ijms26062745","DOIUrl":"10.3390/ijms26062745","url":null,"abstract":"<p><p>The identification of exogenous ligands from natural products is an alternative strategy to explore the unrevealed physiological functions of orphan G-protein-coupled receptors (GPCRs). In this study, we have successfully identified and pharmacologically characterized licoisoflavone A (LIA) as a novel selective antagonist of BRS-3, an orphan GPCR. Functional studies showed that pretreatment with LIA ameliorated hydrogen peroxide (H₂O₂)-induced cardiomyocyte injury. Furthermore, LIA pretreatment significantly restored the activities of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), as well as lactate dehydrogenase (LDH) levels, in H9c2 cells following H₂O₂ exposure. The protective effect of LIA was also evident in primary cardiomyocytes from rats and mice against H₂O₂-induced cell injury but was absent in primary cardiomyocytes derived from bombesin receptor subtype-3 knockout (<i>Brs3</i>^-/y) mice, strongly confirming the mechanism of LIA's action through BRS-3 antagonism. Proteomics studies further revealed that LIA exerted its protective effects via activating the integrin/ILK/AKT and ERK/MAPK signaling pathways. Complementary findings from Bantag-1, a well-recognized antagonist of BRS-3, in human embryonic kidney 293 mBRS-3 (HEK293-mBRS-3) stable cells and B16 cell lines, which demonstrated resistance to H₂O₂-induced damage, further supported the pivotal role of BRS-3 in oxidative stress-induced cell injury. Our study contributes to expanding our understanding of the potential pharmacological functions of BRS-3, unveiling previously unknown pharmacological functionality of this orphan receptor.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718761","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":"Molecular Mechanisms of Plant Abiotic Stress Tolerance.","authors":"Michael Moustakas","doi":"10.3390/ijms26062731","DOIUrl":"10.3390/ijms26062731","url":null,"abstract":"<p><p>Global climate change compromises sufficient food production, and it is estimated that it may be reduced by 11-25% at the end of this century [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719086","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":"Chronic Antibody-Mediated Rejection and Plasma Cell ER Stress: Opportunities and Challenges with Calcineurin Inhibitors.","authors":"Ching-Yi Tsai, Chih-Yuan Lee, Jia-Huang Chen, Chih-Kang Chiang","doi":"10.3390/ijms26062711","DOIUrl":"10.3390/ijms26062711","url":null,"abstract":"<p><p>Chronic alloantibody-mediated rejection (cAMR) remains a major challenge in transplant immunology, with no FDA-approved targeted therapies currently available. Despite advancements in cellular immunosuppression, effective strategies to mitigate alloantibody-mediated rejection are still lacking. This review provides a comprehensive overview of transplant rejection with a particular focus on the pathophysiology and therapeutic landscape of cAMR. We highlight the role of plasma cell-driven alloantibody production and its susceptibility to endoplasmic reticulum (ER) stress, a pathway with potential for therapeutic intervention. Special attention is given to calcineurin inhibitors (CNIs), which, beyond their well-established T-cell inhibitory effects, exhibit differential impacts on ER stress and plasma cell viability. By delineating the mechanistic differences between cyclosporine and tacrolimus in regulating ER stress responses, we propose potential therapeutic implications for optimizing cAMR management. This review underscores the need for innovative strategies targeting plasma cell biology to improve long-term transplant outcomes.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718931","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":"Impact of Glucagon-like Peptide-1 Receptor Agonists on Mental Illness: Evidence from a Mendelian Randomization Study.","authors":"Longgang Xiang, Ying Peng","doi":"10.3390/ijms26062741","DOIUrl":"10.3390/ijms26062741","url":null,"abstract":"<p><p>Emerging evidence suggests that glucagon-like peptide-1 receptor (GLP1R) agonists may have potential benefits for mental illnesses. However, their exact effects remain unclear. This study investigated the causal relationship between glucagon-like peptide-1 receptor agonist (GLP1RA) and the risk of 10 common mental illnesses, including attention deficit and hyperactivity disorder, anorexia nervosa, anxiety disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, post-traumatic stress disorder, schizophrenia, cannabis use disorder, and alcohol use disorder. We selected GLP1RA as the exposure and conducted a Mendelian randomization (MR) analysis. The cis-eQTLs of the drug target gene <i>GLP1R</i>, provided by eQTLGen, were used to simulate the pharmacological effects of GLP1RA. Type 2 diabetes and BMI were included as positive controls. Using data from both the Psychiatric Genomic Consortium and FinnGen, we conducted separate MR analyses for the same disease across these two independent databases. Meta-analysis was used to pool the results. We found genetic evidence suggesting a causal relationship between GLP1RA and a reduced risk of schizophrenia [OR (95% CI) = 0.84 (0.71-0.98), <i>I</i>² = 0.0%, common effects model]. Further mediation analysis indicated that this effect might be unrelated to improvements in glycemic control but rather mediated by BMI. However, the findings of this study provide insufficient evidence to support a causal relationship between GLP1RA and other mental illnesses. Sensitivity analyses did not reveal any potential bias due to horizontal pleiotropy or heterogeneity in the above results (<i>p</i> > 0.05). This study suggests that genetically proxied activation of glucagon-like peptide-1 receptor is associated with a lower risk of schizophrenia. GLP1R is implicated in schizophrenia pathogenesis, and its agonists may exert potential benefits through weight management. Our study provides useful information for understanding the neuropsychiatric effects of GLP1RA, which may contribute to refining future research designs and guiding clinical management. Moreover, our findings could have significant implications for overweight individuals at high risk of schizophrenia when selecting weight-loss medications. Future research should further investigate the potential mechanisms underlying the relationship between GLP1RA and schizophrenia.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718937","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":"Uncovering Key Genes Associated with the Short-Winged Trait in Faba Bean (<i>Vicia faba</i> L.) Through Re-Sequencing and Genome-Wide Association Studies (GWASs).","authors":"Haitian Yu, Chaoqin Hu, Xin Yang, Qiong Li, Yubao Wang, Zhengming Dai, Jie Cun, Aiqing Zheng, Yanhua Jiang, Qinfang Wang, Meiyuan Lv, Feng Yang, Yuhua He","doi":"10.3390/ijms26062733","DOIUrl":"10.3390/ijms26062733","url":null,"abstract":"<p><p>Faba bean (<i>Vicia faba</i> L.) is a globally significant legume valued for its applications in food, vegetables, and green manure, yet its high outcrossing rate (30-80%) poses challenges for production development. A rare short-winged trait identified in Yunnan, China, offers promise for developing low-outcrossing varieties, reducing outcrossing rates to below 5%. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses revealed that the epidermal cells of normal wing petals are conical, while those of short-wing petals are tubular. This study examined 200 F₂ lines from crosses between 'K0692' (short-winged) and 'Yundou 1183', as well as 'Yundoulvxin 1' (short-winged) and 'Yundou 1183'. The GWASs identified 10 SNP loci across chromosomes 2, 3, 4, and 5, with SNP_chr4::1013887633 explaining 22.20% of the wing trait variation. Key candidate genes were identified, such as VFH_III145120, which influences floral identity; and VFH_III149200, associated with epidermal differentiation. GO enrichment analysis demonstrated significant gene involvement in RNA localization, ribosome biogenesis, and preribosome metabolism, while KEGG analysis linked these genes to pathways in amino acid, nucleotide, and purine metabolism; ubiquitin-mediated proteolysis; and protein processing in the endoplasmic reticulum. These findings lay a foundation for breeding low-outcrossing faba bean varieties and enhancing sustainable faba bean cultivation.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718379","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":"Data-Driven Modeling and Design of Sustainable High Tg Polymers.","authors":"Qinrui Liu, Michael F Forrester, Dhananjay Dileep, Aadhi Subbiah, Vivek Garg, Demetrius Finley, Eric W Cochran, George A Kraus, Scott R Broderick","doi":"10.3390/ijms26062743","DOIUrl":"10.3390/ijms26062743","url":null,"abstract":"<p><p>This paper develops a machine learning methodology for the rapid and robust prediction of the glass transition temperature (Tg) for polymers for the targeted application of sustainable high-temperature polymers. The machine learning framework combines multiple techniques to develop a feature set encompassing all relative aspects of polymer chemistry, to extract and explain correlations between features and Tg, and to develop and apply a high-throughput predictive model. In this work, we identify aspects of the chemistry that most impact Tg, including a parameter related to rotational degrees of freedom and a backbone index based on a steric hindrance parameter. Building on this scientific understanding, models are developed on different types of data to ensure robustness, and experimental validation is obtained through the testing of new polymer chemistry with remarkable Tg. The ability of our model to predict Tg shows that the relevant information is contained within the topological descriptors, while the requirement of non-linear manifold transformation of the data also shows that the relationships are complex and cannot be captured through traditional regression approaches. Building on the scientific understanding obtained from the correlation analyses, coupled with the model performance, it is shown that the rigidity and interaction dynamics of the polymer structure are key to tuning for achieving targeted performance. This work has implications for future rapid optimization of chemistries.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718729","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":"Clonal Hematopoiesis of Indeterminate Potential and Atrial Fibrillation: Insights into Pathophysiology and Clinical Implications.","authors":"Paschalis Karakasis, Panagiotis Theofilis, Eleftheria Lefkou, Antonios P Antoniadis, Dimitrios Patoulias, Panagiotis Korantzopoulos, Nikolaos Fragakis","doi":"10.3390/ijms26062739","DOIUrl":"10.3390/ijms26062739","url":null,"abstract":"<p><p>Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a novel risk factor for cardiovascular diseases. CHIP is characterized by the expansion of hematopoietic stem cell clones harboring somatic mutations in genes such as TET2, DNMT3A, and ASXL1, which are implicated in inflammation, atrial remodeling, and hypercoagulability. These mutations foster a pro-inflammatory and pro-thrombotic environment conducive to arrhythmogenesis, thereby linking CHIP to the development and progression of atrial fibrillation (AF). Mechanistic insights indicate that CHIP contributes to atrial fibrosis, disrupts calcium signaling, and exacerbates oxidative stress, all of which heighten susceptibility to AF. Clinical studies, including epidemiological and Mendelian randomization analyses, further support the association between CHIP and an increased risk of both incident and progressive AF, with specific mutations such as TET2 and ASXL1 identified as significant contributors. Additionally, CHIP has been linked to adverse outcomes in AF, including elevated rates of heart failure, thromboembolism, and mortality. Understanding CHIP's role in AF pathophysiology offers opportunities for the development of precision medicine approaches, providing novel avenues for early intervention and targeted AF treatment. This review synthesizes current mechanistic and clinical evidence on the role of CHIP in AF, emphasizes its potential as a biomarker for risk stratification, and explores emerging therapeutic strategies targeting CHIP-associated pathways.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718951","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}