Molecular Medicine最新文献

{"title":"Impact of intermittent fasting versus vitamin D on high fat fructose-induced pancreatic steatosis: possible role of aquaporins.","authors":"Basma Adel Khattab, Maha Osman Hammad, Zienab Helmy Eldken, Doaa Hellal, Sherin Zohdy Mohamed, Noha Hammad Sakr","doi":"10.1186/s10020-025-01239-w","DOIUrl":"10.1186/s10020-025-01239-w","url":null,"abstract":"<p><strong>Background: </strong>The molecular basis of pancreatic steatosis is not entirely known. Aquaporins (AQPs) are integral membrane proteins involved in a variety of pancreatic functions. Given the little data regarding the potential role of aquaporins in the pathogenesis of pancreatic steatosis, this study was designed to assess the role of aquaporins and the NLRP3-inflammasome in the rat model of high-fat fructose diet (HFFD) and to investigate the impact of vitamin D supplementation and alternate day fasting (ADF) in ameliorating HFFD-induced pancreatic steatosis.</p><p><strong>Method: </strong>Twenty-four Sprague-Dawley male rats were divided equally into 4 groups. Group I (control group), Group II (HFFD group), Group III (HFFD + ADF group), and Group IV (HFFD + vitamin D group). By the end of the experiment, fasting blood samples were collected for determination of blood glucose, serum insulin, lipid profile, and insulin resistance. Oxidative stress biomarkers (malondialdehyde and reduced glutathione), inflammatory markers (interleukin-1β and TNF-α), and expression of aquaporins (AQP-1, AQP-3, and AQP-7) genes were evaluated in pancreatic tissues. Histopathological examination of the pancreas and immunohistochemistry of the NLRP3-infammasome and AQP-7 were performed.</p><p><strong>Results: </strong>The HFFD group exhibited pancreatic steatosis with a significant elevation in the levels of blood sugar, serum insulin, insulin resistance, lipid profile, oxidative stress, inflammatory markers, and AQP-3 and AQP-7 mRNA expressions. Regarding histopathology, there were pale vacuolated-stained cytoplasm in acinar pancreatic cells and increased immunoreactivity for AQP-7 and NLRP3-inflammasome. All these parameters improved with ADF and vitamin D supplementation, with more favorable effects for ADF.</p><p><strong>Conclusion: </strong>ADF and vitamin D treatment ameliorated the effect of the high-fat fructose diet at both levels of the biochemical and histopathological examinations.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"207"},"PeriodicalIF":6.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL9 mediated N1-Histidine methylation of SLC39A7 confers ferroptosis resistance and inhibits adipogenic differentiation in mesenchymal stem cells.","authors":"Jiahao Jin, Quanfeng Li, Yunhui Zhang, Pengfei Ji, Xinlang Wang, Yibin Zhang, Zihao Yuan, Jianan Jiang, Guangqi Tian, Mingxi Cai, Pei Feng, Yanfeng Wu, Peng Wang, Wenjie Liu","doi":"10.1186/s10020-025-01271-w","DOIUrl":"10.1186/s10020-025-01271-w","url":null,"abstract":"<p><p>Osteoporosis is a prevalent systemic metabolic disease, and an imbalance in the adipogenic and osteogenic differentiation of mesenchymal stem cells (MSCs) plays a crucial role in its pathogenesis. Thus, elucidating the mechanisms that regulate MSC lineage allocation is urgently needed. METTL9 was recently characterized as a novel N1-histidine methyltransferase that performs a wide range of functions. however, the role of METTL9 in the imbalance of MSC differentiation in osteoporosis remains unclear. In this study, we found that METTL9 expression was downregulated in osteoporosis, and further adipogenic functional experiments revealed that METTL9 negatively regulated the adipogenic differentiation of MSCs both in vitro and in vivo. Mechanistically, METTL9 mediated methylation of SLC39A7 at the His45 and His49 residues suppressed ferroptosis through the endoplasmic reticulum (ER) stress regulatory protein kinase R-like endoplasmic reticulum kinase (PERK)/ATF4 signaling pathway and the downstream protein SLC7A11. Moreover, SLC7A11 transported cystine for intracellular glutathione synthesis, eliminating intracellular reactive oxygen species (ROS) and inhibiting MSC adipogenic differentiation. Additionally, METTL9 overexpression significantly alleviated bone loss in ovariectomy (OVX) model mice. In summary, our results suggest that the METTL9/SLC39A7 axis may be a promising diagnostic and therapeutic target for osteoporosis.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"206"},"PeriodicalIF":6.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a disease-specific accessible transcriptional signature as a biomarker for ataxia with oculomotor apraxia type 2.","authors":"Kathie J Ngo, Darice Y Wong, Alden Y Huang, Hane Lee, Stanley F Nelson, Brent L Fogel","doi":"10.1186/s10020-025-01257-8","DOIUrl":"10.1186/s10020-025-01257-8","url":null,"abstract":"<p><strong>Background: </strong>Genetic ataxias are clinically heterogenous neurodegenerative conditions often involving rare or private mutations and it is often difficult to assign pathogenicity to rare gene variants solely based on DNA sequencing. An effective functional assay from an easy-to-obtain biospecimen would aid this assessment and be of high clinical value. SETX encodes a ubiquitous DNA/RNA helicase crucial for resolving R-loops and maintaining genome stability. Loss-of-function mutations cause a recessive disorder, Ataxia with Oculomotor Apraxia Type 2 (AOA2).</p><p><strong>Methods: </strong>Here we utilize Weighted Gene Co-expression Network Analysis (WGCNA) from patient blood to construct an AOA2-specific transcriptomic signature as a biomarker to evaluate SETX variants in patients clinically suspected of having AOA2.</p><p><strong>Results: </strong>WGCNA from peripheral blood RNA of 11 AOA2 patients from 7 families initially identified a single gene module that was modestly effective in distinguishing individuals with AOA2 from controls (sensitivity 73%, specificity 97%) and was able to robustly differentiate AOA2 patients from those with genetically distinct, yet phenotypically similar, neurological disorders (sensitivity 100%, specificity 100%). An independent derivation of the transcriptional biomarker identified a dual module model that was able to better distinguish individuals with AOA2 from controls (sensitivity 100%, specificity 97%). As validation, we examined a second cohort of 21 patients from 13 families and demonstrate that this dual module transcriptional biomarker could discriminate patients clinically suspected of AOA2 from controls (57%, 95%CI: 34%-78%). Overall, the transcriptional biomarker was able to separate AOA2 subjects (n = 32) from controls (n = 35) with 72% sensitivity and 97% specificity. Notably, this transcriptomic biomarker enabled verification of the first pathogenic SETX mutation found in a non-canonical transcript, expanding the spectrum of mutations that contribute to AOA2.</p><p><strong>Conclusions: </strong>Our study identified a transcriptional biomarker that was able to differentiate AOA2 from controls and from other related neurological disorders, consequently expanding the spectrum of known pathogenic mutations. This proof-of-concept study illustrates that transcriptional biomarkers may be used to validate variants of uncertain significance in known genetic diseases.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"205"},"PeriodicalIF":6.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of placental development and function by ubiquitination.","authors":"Xue Wang, Xiaoqing Li, Shanshan Yuan, Zhiju Gu, Zihao An, Qiang Xu, Bin Cao, Yanhua Song, Chao Tang","doi":"10.1186/s10020-025-01268-5","DOIUrl":"10.1186/s10020-025-01268-5","url":null,"abstract":"<p><p>The proper distribution of nutrients and metabolites between the mother and fetus is one important factor for successful pregnancy. As a bridge, the placenta plays a key role in sensing the nutritional needs of the fetus, coordinating the maternal nutrition supply, and enhancing its nutritional transport capabilities. Imperfect placental development can lead to pregnancy-related disorders such as preeclampsia, recurrent miscarriage, and/or fetal growth restriction, posing risks to both mother and child in the short and long term. However, current understanding of the human placenta remains as a \"black box\", and its developmental control mechanisms for adaptive pregnant regulation still needs to be elucidated. As one form of post-translational modification (PTM), ubiquitination plays an important role in regulating cellular functions and is regarded as a valuable drug target. Particularly, ubiquitination related to placenta development has been discovered in recent years. Placental development processes closely associated with pregnant complications, such as blastocyst implantation, syncytiotrophoblast cell differentiation, and immune barrier maintenance, have been reported to be affected by ubiquitination. However, the diagnosis and intervention of pregnancy diseases also urgently need to be improved. Thus, aiming to comprehensive summarize and further exploring the molecular mechanism, target and regulatory mechanism of pregnancy complications, we have herein reviewed genes and pathways regulating pregnancy progress and diseases and focusing on ubiquitin-related physiological process in placenta.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"202"},"PeriodicalIF":6.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucosal implications of oral Jak3-targeted drugs in COVID patients.","authors":"Narendra Kumar, Daniel Segovia, Priyam Kumar, Hima Bindu Atti, Soaham Kumar, Jayshree Mishra","doi":"10.1186/s10020-025-01260-z","DOIUrl":"10.1186/s10020-025-01260-z","url":null,"abstract":"<p><p>The JAK family, particularly JAK3, plays a crucial role in immune signaling and inflammatory responses. Dysregulated JAK3 activation in SARS-CoV-2 infections has been associated with severe inflammation and respiratory complications, making JAK inhibitors a viable therapeutic option. However, their use raises concerns regarding immunosuppression, which could increase susceptibility to secondary infections. While long-term adverse effects are less of a concern in acute COVID-19 treatment, patient selection and monitoring remain critical. Furthermore, adverse effects associated with oral JAK3 inhibitors necessitate the exploration of alternative strategies to optimize therapeutic efficacy while minimizing risks. This review highlights the role of JAK3 in immune and epithelial cells, examines the adverse effects of oral JAK3 inhibitors in COVID-19 and other treatments, and discusses alternative therapeutic strategies for improving patient outcomes.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"203"},"PeriodicalIF":6.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ITIH4 alleviates OVA-induced asthma by regulating lung-gut microbiota.","authors":"Yi-Hsuan Liu, Yueh-Lun Lee, Chia-Li Han, Yu-Chun Lo, Zih-An Liao, Yu-Syuan Shih, Yi-Wen Lin, Syue-Wei Peng, Kang-Yun Lee, Shu-Chuan Ho, Sheng-Ming Wu, Cheng-Wei Lin, Kian Fan Chung, Jer-Hwa Chang, Hsiao-Chi Chuang","doi":"10.1186/s10020-025-01270-x","DOIUrl":"10.1186/s10020-025-01270-x","url":null,"abstract":"<p><strong>Background: </strong>Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), a Type 2 acute phase protein, is critical for resolving inflammation and promoting tissue repair. While its role in chronic respiratory diseases is recognized, its effects on asthma remain unclear. This study investigated the effects of ITIH4 on the modulation of lung and gut microbiota, the attenuation of allergic inflammation, and the improvement of respiratory outcomes in an asthma mouse model.</p><p><strong>Methods: </strong>Six-week-old male Balb/c mice were divided into five groups: control, ITIH4, ovalbumin (OVA), and two OVA + ITIH4 treatment groups at different doses. Lung function and oxygen saturation were measured, and bronchoalveolar lavage fluid (BALF) was analyzed for white blood cell counts and cytokines. Lung and gut microbiota were profiled using 16 S rRNA gene sequencing, and short-chain fatty acids (SCFAs) were measured using gas chromatography-mass spectrometry (GC-MS). Proteomic profiling of intestinal tissues was conducted to identify ITIH4-associated signaling pathways.</p><p><strong>Results: </strong>ITIH4 administration significantly mitigated OVA-induced asthma symptoms by reducing weight loss, airway resistance, and tissue damping (p < 0.05). Histological analysis showed decreased airway wall thickening and lung injury scores (p < 0.05). ITIH4 also lowered BALF eosinophils and lymphocytes, IgE, and Th2 cytokines (IL-4, IL-5, and IL-13) (p < 0.05). ITIH4 treatment modulated microbiome composition, enriching Gram-positive taxa (Nocardioidaceae and Acholeplasmataceae) and depleting Gram-negative Helicobacteraceae (p < 0.05). SCFAs correlated with microbiome alterations, notably reduced 4-methylpentanoic acid levels (p < 0.05). Proteomic analysis revealed a dose-dependent activation of granzyme A signaling and suppression of metabolic and solute transport pathways.</p><p><strong>Conclusions: </strong>ITIH4 ameliorates asthma symptoms by modulating lung and gut microbiota, dampening Th2-driven inflammation, and restoring mucosal immune balance. These findings support ITIH4 as a potential candidate for microbiome-targeted asthma therapy.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"204"},"PeriodicalIF":6.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paris saponin VII attenuates psoriasiform inflammation by regulating STAT3/NFκB signaling pathway and Caspase-1-induced pyroptosis.","authors":"Xiangnan Zhou, Jingyuan Ning, Doudou Wu, Qingwu Liu, Wenbo Jiang, Jiayi Liu, Rui Cai, Diangang Liu, Yanping Bai","doi":"10.1186/s10020-025-01253-y","DOIUrl":"10.1186/s10020-025-01253-y","url":null,"abstract":"<p><p>Psoriasis is a significant global health challenge due to limited treatment efficacy. Paris saponin VII (PSVII) shows anti-inflammatory and anti-proliferative potential but its role in psoriasis is unclear. In this study, PSVII was identified from a library of natural compounds as a therapeutic candidate for psoriasis. In a murine model, PSVII reduced skin lesion severity, epidermal thickness, and inflammatory factor expression, preliminaryly indicating its anti-inflammatory properties. In vitro, PSVII inhibited HaCaT cell hyperproliferation, regulated the cell cycle, induced apoptosis, and modulated reactive oxygen species (ROS). Bioinformatics analyses suggested that signal transducer and activator of transcription 3 (STAT3), cysteine aspartate specific protease 1 (Caspase-1), and the process of pyroptosis are likely targets and mechanisms of PSVII action. PSVII could reduce cell mortality in psoriatic cells and lowered expression levels of NLR Family Pyrin Domain Containing 3 (NLRP3), Caspase-1, Gasdermin D (GSDMD), Interleukins (IL)-18, and IL-1β, underscoring its potential role in modulating pyroptosis within these cells. Mechanistically, PSVII may suppress the STAT3/nuclear factor kappa B (NFκB) signaling pathway. Consequently, PSVII plays a significant role in psoriasis management. PSVII could modulate pyroptotic cell death in psoriatic cells by targeting the STAT3/NFκB signaling cascade, leading to anti-inflammatory and anti-proliferative effects, and thereby ameliorating psoriasis symptoms.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"200"},"PeriodicalIF":6.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired wound healing in Parkinson's disease: a hypothesis on altered epidermal growth factor (EGF) and N-methyl-D-aspartate (NMDA) signaling in keratinocytes.","authors":"Caroline Liu, Johanna Ghebrehiwet-Kuflom, Roslyn Rivkah Isseroff, Sara Dahle, Vera Morhenn","doi":"10.1186/s10020-025-01247-w","DOIUrl":"10.1186/s10020-025-01247-w","url":null,"abstract":"<p><p>Parkinson's Disease (PD) is a neurodegenerative disorder characterized by the depletion of dopaminergic neurons in the substantia nigra, leading to hallmark motor symptoms such as bradykinesia, tremor, and rigidity. While the focus of PD has been on motor changes, dermatological changes are also commonly seen and may even precede the neurological symptoms. Individuals with PD may exhibit impaired wound healing, potentially due to dysregulated mechanisms involving epidermal growth factor (EGF) and N-methyl-D-aspartate (NMDA) in keratinocytes. This paper hypothesizes that the potential for impaired wound healing in PD patients is linked to reduced EGFR activity and altered NMDAR subunit expression in keratinocytes, in contrast to the upregulated wound healing seen in conditions like psoriasis, which demonstrates elevated EGFR and changes in NMDAR subunit activity. Furthermore, a potential co-interaction between EGF and NMDA in keratinocytes may further contribute to impaired wound healing. Investigating these signaling mechanisms can improve understanding and management of associated dermatological symptoms. We propose additional studies to quantify differences in rates of wound healing between PD patients and age-matched controls in effort to explore therapeutic targets for enhancing wounding healing in the context of PD.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"201"},"PeriodicalIF":6.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin reverses 5-FU resistance induced by radiotherapy through mediating folate metabolism in colorectal cancer.","authors":"Shuxuan Wang, Yanyan Lin, Qianqian Zhao, Huanliang Chen, Shisuo Du, Zhaochong Zeng","doi":"10.1186/s10020-025-01206-5","DOIUrl":"10.1186/s10020-025-01206-5","url":null,"abstract":"<p><strong>Purpose: </strong>Radiation therapy has revolutionized the treatment of primary or liver metastases in colorectal cancer (CRC). In colorectal cancer, conventional fractionation (1.8 ~ 2.0 Gy daily) is typically used for treatment. Nevertheless, there is a paucity of research investigating the potential implications of radiation therapy-induced alterations in the expression levels of regulatory genes on resistance to chemotherapy agents. Herein, we explored the mechanism by which conventional fractionation drives 5-fluorouracil (5-FU) resistance and metformin (Met) rescued 5-FU resistance in CRC.</p><p><strong>Methods and materials: </strong>RNA sequencing, differential genes expression analysis was performed to identify the 5-FU resistance genes after irradiation (according to the convention of cell irradiation, 2 Gy × 8 scheme was selected). Drug sensitivity assay, immunofluorescence staining, folate analogs concentration measurement was used to explore the biological function of histocompatibility minor 13 (HM13) and γ-Glutamyl Hydrolase (GGH). Combined chemosensitivity test and xenograft mouse model has been used to gain insights into the underlying clinical value of the combination of 5-FU and Met.</p><p><strong>Results: </strong>The conventional fractionation scheme (2 Gy × 8) induced resistance to 5-FU in the CRC cell line HCT-15, accompanied by an elevated RNA expression level of peptidase HM13. Mechanistically, the increased expression of HM13 caused an abnormal shearing of the N-terminal signal peptide of γ-Glutamyl Hydrolase (GGH), which resulted in decreased intracellular content of 5, 10-methylenetetrahydrofolate (5,10-CH₂-THF).</p><p><strong>Conclusion: </strong>We revealed a new mechanism of 5-FU resistance induced by irradiated with 2 Gy × 8 through the HM13-GGH-5,10-CH₂-THF axis. The synergistic effect of Met and 5-FU can rescue 5-FU resistance after conventional fractionated irradiation. In summary, this work will help to reveal the mechanisms of IR-induced 5-FU resistance, which is important for finding new therapeutic targets and improving the efficacy of chemotherapy regimens after radiotherapy.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"199"},"PeriodicalIF":6.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating autism spectrum disorder pathophysiology using a trace amine-focused approach: targeting the gut.","authors":"L Pretorius, J A Coetzee, A P Dos Santos, C Smith","doi":"10.1186/s10020-025-01232-3","DOIUrl":"10.1186/s10020-025-01232-3","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) affects approximately 1% of the population directly, but also a much higher proportion (family and caregivers) indirectly. Although ASD is characterized by high prevalence of anxiety and poor gastrointestinal health, current treatment strategies are mainly focused on neurological symptomatic treatment, with little to no attention to gut health. Furthermore, many psychiatric drugs used for management of secondary neurological symptoms, are known to exacerbate gut health issues and neurological dysregulation across the gut-brain axis.Trace amines are neurotransmitter-like substances synthesized endogenously in the human brain - in trace amounts - but also in high abundance by the microbiome. Emerging evidence suggests dysregulation of the trace amine system in ASD. Since trace aminergic signalling is central to regulatory system homeostasis, we hypothesize targeting this system in the ASD context. Given the various sources of trace amines, we suggest that normalization of functional dysbiosis in terms of trace aminergic signalling - rather than microbial compositional dysbiosis - should be a focus in medicines development. In addition, a holistic consideration including also other factors at play in determining trace aminergic signalling outcome - such as receptor binding, enzymatic role players, etc. - is required to fully elucidate and therapeutically modify the pathophysiology of regulatory systems implicated in ASD.This review firstly provides a brief overview of trace amine dysregulation in ASD for context. Secondly, we formulate our hypothesis on how this may therapeutically address symptomology, with consideration of cellular and molecular mechanism interplay across the gut-brain axis. Finally, we provide a critical assessment of advances in therapeutics development and drug re-purposing, gaps in knowledge and priorities for medicines development going forward.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"198"},"PeriodicalIF":6.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}