Biomolecules & biomedicine最新文献

{"title":"Small cell lung cancer (SCLC): At the door of targeted therapies.","authors":"Krešimir Tomić, Semir Vranić","doi":"10.17305/bb.2025.13195","DOIUrl":"10.17305/bb.2025.13195","url":null,"abstract":"<p><p>Small-cell lung cancer (SCLC) is a tobacco-associated neuroendocrine tumor comprising ~15% of lung cancers (~150,000 cases/year). For decades, outcomes stagnated: most patients present with extensive-stage disease, screening rarely detects early tumors, surgery is seldom feasible, and platinum-etoposide remained the first-line standard with median overall survival (OS) <12 months. Radiotherapy (including consolidative thoracic RT) and prophylactic cranial irradiation or MRI surveillance offered incremental gains. Two shifts have begun to change the field. First, four transcriptional subtypes (SCLC-A, -N, -P, and inflammatory SCLC-I) support a more personalized approach, with SCLC-I appearing more responsive to immune checkpoint inhibitors (ICI). Second, adding atezolizumab or durvalumab to chemotherapy in extensive-stage SCLC produced a modest median OS gain but, crucially, a tail of long-term survivors. Subsequent trials extended these advances: IMforte suggested benefit from lurbinectedin maintenance with atezolizumab in ES-SCLC, and ADRIATIC demonstrated a landmark OS improvement (~22 months) with durvalumab consolidation after concurrent chemoradiotherapy in limited-stage SCLC. Targeted strategies are now emerging. Delta-like ligand 3 (DLL3), overexpressed in >80% of SCLC, enables T-cell-redirecting therapy: the bispecific T-cell engager tarlatamab improved OS to 13.6 vs 8.3 months over standard second-line chemotherapy, with manageable cytokine release syndrome and occasional ICANS. B7 homolog 3 (B7-H3, CD276), uniformly expressed across SCLC subtypes and linked to poor prognosis, is another compelling target: the antibody-drug conjugate ifinatamab deruxtecan achieved a 54.8% response rate and meaningful survival in heavily pretreated patients, earning FDA Breakthrough designation. Together, DLL3- and B7-H3-directed therapies (with additional ADCs against Trop-2 and SEZ6 in development) are redefining second-line and later care. Key next steps include optimizing sequencing/combination strategies, managing BiTE-specific toxicities, and developing predictive biomarkers. After decades of futility, SCLC is transitioning from uniform chemotherapy to a precision-medicine paradigm with cautious optimism.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12499548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remimazolam vs propofol for postoperative delirium in adults undergoing general anesthesia: A meta-analysis.","authors":"Huijin Zhou, Jing Zhang, Chunyan Du","doi":"10.17305/bb.2025.12826","DOIUrl":"https://doi.org/10.17305/bb.2025.12826","url":null,"abstract":"<p><p>Postoperative delirium (POD) is a prevalent and serious complication in adults undergoing surgery with general anesthesia. Remimazolam, an innovative ultra-short-acting benzodiazepine, has been identified as a potential alternative to propofol due to its advantageous pharmacological properties. However, its impact on POD remains uncertain. This study conducted a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of the PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang databases was performed up to March 29, 2025. Randomized controlled trials (RCTs) comparing remimazolam and propofol in adult surgical patients under general anesthesia, specifically reporting on POD incidence, were included. A random-effects model was utilized to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs), accounting for heterogeneity. The analysis included seventeen RCTs encompassing 3,133 patients. Overall, remimazolam significantly decreased the risk of POD compared to propofol (OR: 0.71, 95% CI: 0.52-0.97, p = 0.03; I² = 36%). Sensitivity analyses, which involved excluding one study at a time, yielded consistent results, reinforcing the robustness of the findings. Subgroup analyses revealed uniform effects across different study designs (single-blind vs. double-blind; OR: 0.73 vs. 0.64; p = 0.71) and age groups (adults vs. elderly; OR: 0.64 vs. 0.72; p = 0.79). A trend toward greater benefit was observed in studies with longer follow-up periods (7 days: OR: 0.42) and in those employing the CAM or CAM-ICU for POD diagnosis, although subgroup differences were not statistically significant. In conclusion, remimazolam is associated with a significantly reduced risk of POD compared to propofol in adults undergoing general anesthesia.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decitabine suppresses tumor growth by activating mouse mammary tumor virus and interferon-β pathways.","authors":"Ryan Johnson, Andrew Brola, Cade Wycoff, William Wycoff, Seth Neumeyer, Richard Tuttle, Sarah Light, Jiayi Li, Stephen Christensen, Yingguang Liu","doi":"10.17305/bb.2025.12852","DOIUrl":"https://doi.org/10.17305/bb.2025.12852","url":null,"abstract":"<p><p>Decitabine (DAC), a DNA methyltransferase inhibitor (DNMTi), is clinically effective in hematological malignancies such as myelodysplastic syndrome and acute myeloid leukemia, but its precise antineoplastic mechanisms remain incompletely understood. Beyond promoter demethylation, DAC is known to activate endogenous retroviruses (ERVs) and trigger type I interferon (IFN-I) responses, a phenomenon known as viral mimicry. The aim of this study was to investigate the roles of the mouse mammary tumor virus (MMTV) and interferon-β (IFN-β) in DAC-mediated tumor suppression. We employed two murine tumor models-4T1 mammary carcinoma and MC38 colon adenocarcinoma-in syngeneic immunocompetent mice, immunodeficient nude mice, and in vitro cultures. RNA and protein expression were assessed by quantitative PCR and immunoblotting, while functional contributions of MMTV and IFN-β were tested using short hairpin RNA (shRNA) knockdowns. DAC treatment suppressed tumor growth and pulmonary metastasis in vivo and inhibited cancer cell proliferation in vitro. It induced transcription of MMTV and expression of IFN-β, with a strong negative correlation between MMTV Env protein levels and tumor mass. Knockdown of either MMTV or IFN-β conferred resistance to DAC, confirming their functional roles. Reciprocal regulation was observed: MMTV knockdown reduced IFN-β expression, while IFN-β knockdown increased MMTV Env accumulation. Furthermore, DAC upregulated interferon regulatory factor 7 (IRF7), but this effect declined during prolonged treatment, suggesting a temporally restricted therapeutic window. In conclusion, our findings provide in vivo support for the viral mimicry hypothesis and demonstrate that MMTV and IFN-β contribute to DAC-mediated tumor suppression. The observed IRF7 downregulation and potential induction of immune checkpoints highlight the importance of therapeutic strategies combining DNMTis with immune checkpoint blockade to sustain antineoplastic efficacy.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of topical nitroglycerin on neoangiogenesis and pedicle-independent viability in a rat dorsal skin flap model.","authors":"Oğuzhan Karakoç, Selman Hakkı Altuntaş, İlkay Armağan","doi":"10.17305/bb.2025.12781","DOIUrl":"10.17305/bb.2025.12781","url":null,"abstract":"<p><p>Interpolated flaps are frequently used in reconstructive surgery when free tissue transfer is not feasible, but they require staged procedures due to pedicle dependence. Flap autonomization, the process by which transferred tissue develops new vascular connections and survives independently of its pedicle, is essential before division. Although methods such as delay techniques, hyperbaric oxygen (HBO), vascular endothelial growth factor (VEGF), and stem cell therapies have been tested to enhance angiogenesis, the effect of topical nitroglycerin (NTG), a nitric oxide (NO) donor with vasodilatory, anti-inflammatory, and angiogenic properties, has not been investigated. This study aimed to evaluate the effect of topical NTG on neoangiogenesis and flap autonomization in a rat dorsal skin flap model. Sixty Wistar-Albino rats were divided into five groups (n = 12). A 3×3 cm dorsal flap with a caudal pedicle was elevated in all animals. In Groups 1-3, pedicles were transected on day 5: Group 1 received vaseline, Group 2 received NTG for 5 days then vaseline, and Group 3 received NTG continuously. Groups 4 and 5 were sacrificed on day 5 to assess early angiogenesis after vaseline or NTG. Flap survival was analyzed with ImageJ, angiogenesis with VEGF, CD34, and CD105 staining, and histology with Hematoxylin and Eosin (H&E) and Masson's Trichrome. Flap survival was significantly greater in Groups 2 (485.5 mm²) and 3 (757.3 mm²) than in Group 1 (273.5 mm²), with Group 3 highest (p < 0.01). NTG-treated groups showed increased VEGF, CD34, and CD105 expression, with the strongest angiogenesis in Group 3. Group 5 also had higher vascular proliferation than Group 4 (p < 0.001). Histology showed that NTG reduced epithelial disruption, hemorrhage, collagen degradation, and leukocytic infiltration while enhancing vascular proliferation. In conclusion, continuous topical NTG enhanced angiogenesis and accelerated flap autonomization, leading to greater viability after pedicle division. NTG may help shorten pedicle division intervals and improve outcomes in reconstructive surgery, but further molecular and clinical studies are needed.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"159-171"},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12499550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presepsin as a diagnostic biomarker for sepsis across neonates, children, and adults: A meta-analysis.","authors":"Kaicheng Peng, Xiangmin Zhang, Qinyuan Li, Zhengxiu Luo","doi":"10.17305/bb.2025.12909","DOIUrl":"10.17305/bb.2025.12909","url":null,"abstract":"<p><p>Sepsis remains a leading global health challenge, with delayed recognition and limited diagnostic accuracy of current tools contributing to high morbidity and mortality. Conventional clinical scores (SOFA/qSOFA), standard biomarkers (CRP, PCT), and blood cultures suffer from delayed responsiveness, insufficient specificity, or slow turnaround, underscoring the urgent need for more reliable early diagnostic strategies. Presepsin, a soluble CD14 subtype generated during pathogen recognition by innate immune cells, has emerged as a promising biomarker with potential to reflect infection status earlier and more specifically than traditional markers. This systematic review and meta-analysis quantitatively evaluated the diagnostic accuracy of presepsin across diverse populations. PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies published between 2015 and 2025. Forty-seven studies involving 7,087 participants were included. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC), and likelihood ratios (PLR/NLR) with 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity was assessed with I² statistics, meta-regression, and subgroup analyses. Study quality was evaluated using QUADAS-2. Presepsin demonstrated excellent overall diagnostic performance: pooled sensitivity 0.84 (95% CI: 0.81-0.88), specificity 0.86 (95% CI: 0.80-0.90), DOR 32.23 (95% CI: 20.11-51.66), and AUC 0.91 (95% CI: 0.88-0.93). Subgroup analyses confirmed robust performance across settings and populations, with particularly high accuracy in neonates (sensitivity 0.90, specificity 0.92, AUC 0.96), followed by children (sensitivity 0.84, specificity 0.81, AUC 0.88, NLR 0.20) and adults (sensitivity 0.81, specificity 0.82, AUC 0.87). Meta-regression identified year of publication, geographic region, specimen type, population, and diagnostic criteria as key contributors to heterogeneity, but sensitivity analyses confirmed result stability. No significant publication bias was observed (p = 0.33). In conclusion, presepsin is a valuable and highly promising biomarker for sepsis diagnosis, showing favorable diagnostic accuracy across populations, with strongest utility in neonates. Its application in pediatric and adult patients warrants further validation through large, prospective, multi-center studies.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"307-319"},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extraovarian fibrothecomas: Two case reports and comprehensive review of ovarian sex cord-stromal fibroma-thecoma tumors.","authors":"Nejra Selak, Ivana Čerkez, Ermina Iljazović, Azra Sadiković, Maja Konrad Čustović, Jasminka Mustedanagić Mujanović, Edina Ahmetović Karić","doi":"10.17305/bb.2025.12816","DOIUrl":"10.17305/bb.2025.12816","url":null,"abstract":"<p><p>Sex cord-stromal tumors are rare ovarian neoplasms, with fibromas comprising approximately 4% and thecomas accounting for 0.5-1% of all ovarian tumors. The occurrence of these tumors outside the ovaries is exceptionally rare and diagnostically challenging, often mimicking malignancy when associated with ascites, elevated CA-125 levels, or Meigs-like syndrome. This review aims to synthesize current knowledge on the histopathological, immunohistochemical, radiological, and molecular features of ovarian fibroma-thecoma group tumors and highlight their clinical relevance. We report two postmenopausal women with large abdominal masses located extraovarian: one in the broad ligament and the other adherent to the omentum and intestines. In the first case, markedly elevated CA-125, ascites, and pleural effusion initially suggested Meigs syndrome. The second case presented with an abdominal mass and ascites. Imaging studies indicated the possibility of malignant ovarian tumors in both patients, leading to surgical excision. Histopathological examination revealed spindle-to-oval tumor cells arranged in fascicular or storiform patterns, with focal lipid-rich theca-like cells. Immunohistochemical analysis showed that the tumors were positive for vimentin, WT1, progesterone receptor (PR), and variably for estrogen receptor (ER), CD56, inhibin, and calretinin, while being negative for markers of epithelial, melanocytic, and gastrointestinal stromal tumors. A review of the literature identified only 11 well-documented cases of extraovarian fibroma-thecoma group tumors, which most commonly arise in the broad ligament or pelvic cavity. These cases are frequently associated with ascites and elevated CA-125 levels and are often misdiagnosed preoperatively as malignant disease. Our cases underscore the importance of considering extraovarian fibromas and thecomas in the differential diagnosis of pelvic and abdominal masses presenting with similar features. Accurate pathological assessment can prevent unnecessary radical surgeries and promote more favorable patient outcomes.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Glioblastoma induces CAF-like astrocyte activation via the AKT/mTOR-SERPINH1/COL5A1 axis.","authors":"Jingxian Zhang, Yajia Chen, Hongwu Xu","doi":"10.17305/bb.2025.13134","DOIUrl":"10.17305/bb.2025.13134","url":null,"abstract":"<p><p>Correction to: Glioblastoma induces CAF-like astrocyte activation via the AKT/mTOR-SERPINH1/COL5A1 axis This corrigendum corrects the authors' affiliations to: Jingxian Zhang¹,²#, Yajia Chen¹,²#, and Hongwu Xu¹,²*. ¹Department of Neurosurgery, Tenth Affiliated Hospital, Southern Medical University, Dongguan, Guangdong, China. ²Department of Human Anatomy, Shantou University Medical College, Jinping District, Shantou, Guangdong, China. The authors sincerely apologize for this error and confirm that this correction does not affect the scientific content or conclusions of the article.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"172"},"PeriodicalIF":0.0,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12499543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive biomarkers for post-neonatal necrotizing enterocolitis intestinal stenosis: Role of JMJD3, CRP, and PCT.","authors":"Tao Qin, Chenxia Rao, Yunsen Deng","doi":"10.17305/bb.2025.12766","DOIUrl":"10.17305/bb.2025.12766","url":null,"abstract":"<p><p>Necrotizing enterocolitis (NEC) is a severe, often life-threatening gastrointestinal disease in neonates, predominantly affecting preterm infants, and is frequently complicated by intestinal stenosis-a condition whose nonspecific clinical manifestations make early diagnosis and timely intervention particularly challenging. We aimed to investigate the clinical characteristics of NEC intestinal stenosis and its correlation with the histone demethylase Jumonji domain-containing protein 3 (JMJD3). A total of 310 children with NEC treated between February 2021 and June 2024 were retrospectively enrolled, categorizing them into an NEC group (n=265) and a post-NEC intestinal stenosis group (n=45). General data and laboratory indicators were collected, and analyses were performed to identify factors influencing the development of post-NEC intestinal stenosis. Spearman correlation analysis was utilized to assess relationships between JMJD3 and clinical parameters. Results indicated that the post-NEC intestinal stenosis group exhibited significantly lower platelet counts (PLT) and elevated levels of serum C-reactive protein (CRP), procalcitonin (PCT), and JMJD3 in intestinal tissues (p<0.05). JMJD3 was significantly associated with the development of post-NEC intestinal stenosis (p<0.001), presenting a 3.114-fold increased risk. Furthermore, JMJD3 levels were negatively correlated with PLT levels and positively correlated with CRP and PCT levels (p<0.001). Receiver operating characteristic curve analysis demonstrated that the combination of CRP, PCT, and JMJD3 provided the highest predictive efficiency, with an area under the curve of 0.918, sensitivity of 86.67%, specificity of 86.42%, and a Youden index of 0.731 (p<0.05), all surpassing the performance of individual markers. In conclusion, levels of CRP, PCT, and JMJD3 were significantly elevated in NEC children with intestinal stenosis. Their combined assessment presents a highly effective approach for the early diagnosis of post-NEC intestinal stenosis.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"2810-2818"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of <i>TUBB</i>, <i>CLTA</i>, and <i>FBXL5 </i>as potential diagnostic markers of postmenopausal osteoporosis.","authors":"Yue Tan, Yujing Wang, Qin Zhu, Yan Xue, Xuhao Ji, Zhenkun Li, Jiawen Shen, Chengming Sun, Shiqi Ren, Chenlin Zhang, Jianfeng Chen","doi":"10.17305/bb.2025.12019","DOIUrl":"10.17305/bb.2025.12019","url":null,"abstract":"<p><p>Postmenopausal osteoporosis (PMOP) is recognized as the most prevalent bone disease worldwide. N6-methyladenosine (m6A) is one of the most common RNA modifications influencing the progression of various disorders; however, its specific role in PMOP remains unexplored. This study aims to investigate the expression profiles of m6A-related genes and their impact on the prognosis of PMOP patients. We utilized the GSE56815 expression analysis dataset obtained from the Gene Expression Omnibus (GEO) database and extracted m6A-related genes for further examination. Our analysis revealed that m6A-related genes exhibited differential expression between PMOP patients and healthy controls. We employed consensus clustering to identify subgroups within the PMOP cohort and conducted immunological analyses on these clusters. Additionally, we intersected the clusters to identify differentially expressed genes (DEGs) and analyzed potential diagnostic markers for PMOP using support vector machine recursive feature elimination (SVM-RFE), LASSO, and random forest (RF) algorithms, which were subsequently validated in the GSE56116 dataset. The receiver operating characteristic (ROC) curve was employed to assess the diagnostic significance of these markers. Furthermore, quantitative PCR (qPCR) was performed to validate the expression of the identified genes. In the GSE56815 dataset, we identified three subtypes associated with m6A modifications, leading to the identification of 302 shared DEGs among these subtypes. Gene ontology (GO) analysis indicated that the DEGs were predominantly enriched in nuclear specks, the nuclear envelope, and nucleocytoplasmic transport processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis further revealed that DEGs were primarily associated with endocytosis and nucleocytoplasmic transport pathways. Through the application of SVM, LASSO, and RF algorithms, we identified three potential diagnostic markers: TUBB, CLTA, and FBXL5, which demonstrated promising diagnostic capabilities when tested against an independent dataset. qPCR validation confirmed significant expression differences of these genes between the control and PMOP groups. The genetic markers identified in this study hold potential for accurately predicting the risk of PMOP in patients. The findings contribute to understanding the underlying molecular mechanisms of CLTA, TUBB, and FBXL5 in PMOP and may facilitate the development of novel therapeutic strategies and improved monitoring of the disease.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"354-367"},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbial metabolites and the brain-gut axis in Alzheimer's disease: A review.","authors":"Xinchen Ji, Jian Wang, Tianye Lan, Dexi Zhao, Peng Xu","doi":"10.17305/bb.2025.12921","DOIUrl":"10.17305/bb.2025.12921","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is increasingly recognised as a disorder that extends beyond the brain, with accumulating evidence implicating gut microbiota-derived metabolites in its onset and progression. This narrative review synthesises 92 peer-reviewed animal, human and meta-analytic studies published between 2010 and 2025 that investigated short-chain fatty acids (SCFAs), tryptophan-derived indoles and kynurenines, trimethylamine N-oxide (TMAO) and secondary bile acids in the context of AD. Collectively, the literature shows that SCFAs support blood-brain-barrier integrity, dampen microglial reactivity and enhance synaptic plasticity, yet can paradoxically amplify β-amyloid (Aβ) deposition under germ-free or supraphysiological conditions, highlighting the importance of host status and dosing. Beneficial indole metabolites such as indole-3-propionic acid counter oxidative stress, strengthen intestinal and cerebral barriers and suppress pro-inflammatory cascades, whereas a shift toward neurotoxic kynurenines correlates with cognitive decline. TMAO emerges as a consistently deleterious metabolite that aggravates endothelial dysfunction, neuroinflammation and Aβ aggregation; dietary precursor restriction and microbial enzyme inhibitors are therefore being explored as mitigation strategies. Secondary bile acids and polyphenol derivatives further modulate mitochondrial bioenergetics and NF-κB signalling, broadening the therapeutic landscape. Multi-omics profiling reveals that AD patients typically exhibit reduced SCFAs and indoles but elevated TMAO, changes that scale with Mini-Mental State Examination scores, brain atrophy and cerebrospinal Aβ₄₂ levels. Early probiotic and faecal-microbiota-transplant trials have begun to normalise these metabolite profiles and yield modest cognitive benefits, underscoring translational potential. Altogether, gut-derived metabolites are not passive by-products but active modulators of neural, immune and metabolic circuits along the microbiota-gut-brain axis; their targeted manipulation and standardised metabolomic assessment could enable earlier diagnosis and precision microbiome-based interventions for AD, a promise that now warrants validation in large, longitudinal and mechanistically informed clinical studies.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"240-250"},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}