American journal of clinical and experimental immunology最新文献

{"title":"Association of early-pregnancy platelet-to-high-density lipoprotein cholesterol ratio with preeclampsia: a retrospective cohort study.","authors":"Feifei Wang, Andi Wang, Dong Jiang, Chunhua Lin, Wenyu Fu, Longwei Qiao, Jian Sun","doi":"10.62347/IHVE5947","DOIUrl":"10.62347/IHVE5947","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia (PE) is a major cause of poor maternal and perinatal outcomes. While a number of biophysical and biochemical markers have been explored for early prediction, there is a need for low-cost accessible markers. The platelet-to-high-density lipoprotein cholesterol ratio (PHR) might reflect the combined effects of impaired platelet function, inflammatory thrombosis and reduced protection against vascular injury.</p><p><strong>Methods: </strong>This retrospective cohort included 11,618 pregnancies assessed in early pregnancy. PHR, calculated from platelet count and high-density lipoprotein cholesterol, was analyzed per 10-unit increment. Logistic regression assessed associations with PE, subgroup analyses examined major phenotypes, and receiver operating characteristic analyses compared individual discrimination with mean arterial pressure multiples of the median (MAP MoM) and placental growth factor multiples of the median (PlGF MoM) values.</p><p><strong>Results: </strong>Among 11,618 pregnancies, 468 women (4.03%) developed PE. Median PHR per 10 was lower among women who developed PE than among those who did not (15.07 [IQR, 11.93-18.24] vs. 19.05 [IQR, 16.82-21.75]; P<0.001). In multivariable analyses controlling for maternal age, body mass index before pregnancy, parity, type of gestation, and conception by in vitro fertilization, every 10-point rise in PHR was linked to a reduced likelihood of PE (adjusted odds ratio, 0.69; 95% CI, 0.67-0.72; P<0.001). PHR values were significantly decreased in early-onset, preterm, and late-onset PE compared with pregnancies without PE (all P<0.01), but did not differ significantly across these three subtypes. Among participants with available Fetal Medicine Foundation (FMF) screening data, the AUCs were 0.732 (95% CI, 0.693-0.771) for PHR, 0.702 (95% CI, 0.669-0.738) for MAP MoM, and 0.606 (95% CI, 0.570-0.638) for PlGF MoM.</p><p><strong>Conclusion: </strong>Lower early-pregnancy PHR was independently associated with subsequent PE. PHR had the highest AUC point estimate among the three individual biomarkers evaluated.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 4","pages":"269-276"},"PeriodicalIF":1.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042180","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":"Immune cell interactions and lung damage in SARS-CoV-2 special attention on monocytes/macrophages, T and B lymphocytes, dendritic cells and Toll-like receptors in SARS-CoV-2.","authors":"Maya Vladova Gulubova, Maria-Magdalena Krasimirova Ignatova, Dobromira Nikolaeva Dimitrova, Julian Rumenov Ananiev","doi":"10.62347/EXEK6507","DOIUrl":"10.62347/EXEK6507","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is caused by a novel human virus - SARS-CoV-2, is characterized in severe cases by dysregulated innate and adaptive immune responses leading to lung injury and systemic hyperinflammation. This review summarizes the roles of monocyte/macrophages, T and B lymphocytes, dendritic cells, and Toll-like receptor signaling in the immunopathogenesis of severe COVID-19. Severe COVID-19 is characterized by light neutrophilia, reduced numbers of transitional and non-classical monocytes, lymphopenia and diminished conventional and plasmacytoid dendritic cells (DCs). Inflammatory monocytes/macrophage activation and excessive cytokine production contribute to alveolar damage and cytokine storm. Alveolar macrophages (AMs) are abortively infected by the virus in an ACE2-dependent manner, but still no virus replication has been detected. AMs produce high quantities of IL-6 TNF-α, and IL-1β promoting cytokine storm. T lymphocytes dysregulation is associated with lymphopenia, impaired antiviral responses, and T-cell exhaustion. Severe COVID-19 infection causes a disproportionate decrease of CD4⁺ T cells, reduced CD8⁺ T cells and alteration of T cell subsets i.e. Tregs decrease and stimulation of Th1, Th2 and Th17. TLR3 and TLR7 are broadly expressed on human immune cells and recognize dsRNA and ssRNA in the endosome. Since TLR7 duplicated genes are localized on the X-chromosome, the disease is more expressed in men. B cell responses are characterized by impaired germinal center formation and extrafollicular antibody production. B cells produce neutralizing antibodies having little somatic hypermutations (SHM) that block the virus in the extra-follicular space. The activation of B cells via contact with Tfh cells antigen and BCR antigen is described. The reduction of germinal centers in thoracic lymph nodes and spleen is discussed. DCs depletion and dysfunction reduce antigen-presentation and interferon responses. A significant reduction of conventional DCs1 and DCs2 and of pDCs in blood is detected. Simultaneously, CD1c⁺ DCs are recruited and increased in the lung in severe COVID-19. Toll-like receptor pathways further amplify inflammatory signaling and immune imbalance. Collectively, these immune alterations contribute to defective viral clearance and progressive lung injury. Understanding the interactions between innate and adaptive immune responses in COVID-19 may support the development of targeted immunomodulatory therapies and provide broader insights into viral immunopathology.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 4","pages":"290-306"},"PeriodicalIF":1.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042220","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":"Association of miR-10a expression and its rs3809783 polymorphism with postoperative incisional pain via Bcl-6/Tfh targeting in patients undergoing laparoscopic cholecystectomy.","authors":"Yue Sun, Lan Zhao, Zengzhen Zhang, Huiqing Li, Xiaobo Fu","doi":"10.62347/QNRH4270","DOIUrl":"10.62347/QNRH4270","url":null,"abstract":"<p><p>This study aimed to investigate the role of miR-10a and its rs3809783 polymorphism in postoperative incisional pain among patients undergoing laparoscopic cholecystectomy for acute cholecystitis (ACC-LC). Levels of miR-10a and immune markers (CD68, CD19, CD3, T-bet, GATA-3, IL-17A, Bcl-6) were measured in gallstone mucosal tissue, and genotyping was performed via PCR and sequencing. An incisional pain mouse model was used for mechanistic exploration. The results showed that miR-10a expression was decreased in ACC-LC patients compared with controls and was negatively correlated with pain intensity. Patients carrying the rs3809783 AT genotype exhibited lower miR-10a levels and higher pain scores than AA carriers. Among the elevated immune markers, only Bcl-6/Tfh was associated with pain severity. Further analysis confirmed Bcl-6 as a direct target of miR-10a, with the A→T substitution at rs3809783 enhancing Bcl-6-mediated Tfh polarization. This genotype was also correlated with longer anal exhaust time, higher inflammatory markers, and more complications. In conclusion, miR-10a and its rs3809783 polymorphism may serve as biomarkers for postoperative pain in ACC-LC by regulating the Bcl-6/Tfh pathway.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 4","pages":"322-332"},"PeriodicalIF":1.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042235","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":"Meta-analysis of the changes in clinical features and characteristics of lung cancer under bronchoscopy.","authors":"Lile Wang, Jianyi Zhou, Ruicheng Hu","doi":"10.62347/GJTJ5573","DOIUrl":"10.62347/GJTJ5573","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to summarize the clinical features and evolutionary changes of lung cancer under bronchoscopy.</p><p><strong>Methods: </strong>Relevant literature on the \"clinical characteristics and evolving features of lung cancer observed under bronchoscopy\" was retrieved from Chinese and English databases, including CNKI, Wanfang, VIP, PubMed, and Web of Science.</p><p><strong>Results: </strong>A total of 21 studies published between 2005 and 2023 were included, involving 8,892 patients, with 10 studies in English and 11 in Chinese. All studies were analyzed using a random-effects model with the Freeman-Tukey double arcsine transformation for meta-analysis of single proportions. The pooled estimate for the diagnostic accuracy of bronchoscopy in lung cancer was 2.22 (95% CI: 2.10-2.34; Q=42.21, P<0.01). Regarding pathological types, the pooled estimates were 1.20 for lung squamous cell carcinoma (95% CI: 0.90-1.50; Q=328.08, P<0.01), 0.77 for small cell lung cancer (95% CI: 0.62-0.93; Q=219.43, P<0.01), 0.67 for non-small cell lung cancer (95% CI: 0.49-0.86; Q=66.84, P<0.01), and 1.53 for lung adenocarcinoma (95% CI: 1.06-2.01; Q=2096.93, P<0.01). For age distribution, the pooled estimate was 1.45 for patients aged ≥60 years (95% CI: 0.91-1.99; Q=886.54, P<0.01) and 1.69 for patients aged <60 years (95% CI: 1.15-2.23; Q=886.54, P<0.01). The pooled estimates for male and female patients were 1.59 (95% CI: 1.17-2.02; Q=983.83, P<0.01) and 1.55 (95% CI: 1.12-1.97; Q=983.83, P<0.01), respectively. Regarding bronchoscopic morphological patterns, the pooled estimates were 1.50 for proliferative-type lung cancer (95% CI: 1.25-1.74; Q=180.64, P<0.01), 1.14 for infiltrative-type lung cancer (95% CI: 0.94-1.35; Q=225.58, P<0.01), and 0.83 for lung cancer with non-specific bronchoscopic changes (95% CI: 0.60-1.06; Q=498.02, P<0.01). Meta-regression analysis of lung adenocarcinoma indicated that publication year and study design were significant sources of heterogeneity among the included studies (P<0.01).</p><p><strong>Conclusion: </strong>Among lung cancers diagnosed by bronchoscopy, lung adenocarcinoma was the predominant pathological type, and the proliferative type was the most common bronchoscopic morphological pattern. Most patients were younger than 60 years, and the proportion of male patients was slightly higher than that of female patients.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 4","pages":"307-321"},"PeriodicalIF":1.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042286","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":"Morphine-induced dysbiosis and metabolic remodeling of the gut microbiota is transmissible via fecal microbiota transplantation in mice.","authors":"Yi Zhu, Jin-Yi Wan, Richard Sawadogo, Jia-Min Zhong, Hai-Qiang Yao, Qi-Hui Zhang, Chong-Zhi Wang, Ming Xu, Chun-Su Yuan","doi":"10.62347/KPLF6948","DOIUrl":"10.62347/KPLF6948","url":null,"abstract":"<p><strong>Objective: </strong>Opioids such as morphine are widely used analgesics but are highly addictive. Emerging evidence implicates the gut microbiota in modulating opioid-associated pathophysiology. However, the global metabolic impact of morphine on gut microbial function and the causal transmissibility of morphine-induced dysbiosis remain to be fully elucidated.</p><p><strong>Methods: </strong>Adult C57BL/6 mice received repeated morphine administration for four consecutive days. Fecal metabolomic profiling was performed using integrated gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) platforms. Gut microbial composition was analyzed by 16S rRNA gene sequencing and terminal restriction fragment length polymorphism (T-RFLP) profiling. To determine causality and transmissibility, fecal microbiota transplantation (FMT) was conducted from morphine-treated donor mice into antibiotic-depleted recipient mice.</p><p><strong>Results: </strong>Repeated morphine administration induced a profound global reprogramming of fecal metabolic profiles, with clear separation between morphine-treated and control mice. A total of 179 fecal metabolites were annotated. Morphine significantly increased diethylene glycol, N-acetyl-L-glutamic acid, and urea, while decreasing 3-aminoisobutyric acid, 2-aminobutyric acid, and pseudouridine. Pathway enrichment analysis revealed that amino acid-centered metabolic pathways, including branched-chain amino acid biosynthesis, arginine biosynthesis, and aminoacyl-tRNA biosynthesis, were the most prominently disrupted. Morphine exposure also induced a distinct dysbiotic microbial signature characterized by expansion of <i>Enterococcus faecalis</i> and <i>Alistipes indistinctus</i>, and depletion of <i>Prevotella melaninogenica</i>. Importantly, FMT from morphine-treated donors into microbiota-depleted recipients successfully transferred both the dysbiotic microbial structure and metabolic phenotype. Post-transplant recipient mice exhibited microbial profiles closely resembling morphine-treated donors, demonstrating that the morphine-induced dysbiosis is transmissible in the short term in the absence of direct drug exposure.</p><p><strong>Conclusion: </strong>Repeated acute morphine exposure alters fecal amino acid and nitrogen metabolism and drives a transmissible dysbiotic state in the short term. These findings highlight a potential association between morphine exposure, metabolic remodeling, and gut dysbiosis, suggesting the gut microbiota may be a relevant factor in opioid-associated intestinal interactions.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 4","pages":"277-289"},"PeriodicalIF":1.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042247","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":"Multimodal AI in precision medicine: linking omics, imaging and clinical decisions.","authors":"Rong Wei, Qiping Zheng","doi":"10.62347/URCI9453","DOIUrl":"10.62347/URCI9453","url":null,"abstract":"<p><p>Precision medicine is shifting from a single-biomarker paradigm toward multimodal integration of molecular, imaging, and clinical data, with artificial intelligence (AI) serving as a key enabling technology. Multimodal imaging, computational pathology, spatial omics and liquid biopsy have all become more adept at capturing disease and biological variation, and foundation models, especially vision-language models, are now creating a common language between histology, molecular and biomedical text. AI-powered pipelines are also improving data quality upstream, which ultimately means that multimodal inference can be applied to tasks of real clinical importance: biomarker screening, modelling treatment outcomes, even autonomous coordination among diagnostic systems, rather than just retrospective prediction. But none of this means more modalities necessarily translate into more value. Additional data may introduce redundancy, technical artefacts, institutional bias, and missingness. The future of multimodal AI should therefore emphasize sufficiency rather than maximalism, with systems designed to accommodate incomplete or asynchronous inputs, quantify uncertainty, and demonstrate added value over established clinical standards. Ultimately, clinical utility will depend on external and prospective validation showing improvements in calibration, efficiency, net clinical benefit, and patient outcomes. The promise of AI-enabled multimodal precision medicine lies not in combining every available data stream, but in determining which molecular, morphological, and clinical information is necessary, complementary, and actionable for an individual patient at a specific decision point.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 4","pages":"333-339"},"PeriodicalIF":1.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042271","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":"Cancer-associated mutational patterns reshape miRNA regulatory regions and potentially disrupt miRNA-gene interactions.","authors":"Julia Ran, Xiwen Zhang, Joyce Tang, Yongsheng Bai","doi":"10.62347/FGPO8785","DOIUrl":"10.62347/FGPO8785","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are key post-transcriptional regulators frequently dysregulated in cancer, yet how somatic mutational patterns influence miRNA regulatory regions remains unclear. In this study, we integrated mutation profiles, transition-transversion (Ti/Tv) ratios, and miRNA-gene interaction analyses across multiple TCGA cancer subtypes to investigate how mutation patterns may affect miRNA binding regions. miRNA interactions were strongly enriched in 3' untranslated regions (3'UTRs), with fewer interactions observed in coding sequences (CDS). Across cancers, miRNA regions exhibited moderate GC content (~51%), which typically predicts elevated Ti/Tv ratios; however, most cancer cohorts showed markedly reduced Ti/Tv ratios, indicating a shift toward transversion-heavy mutational processes. Because transversions generally produce greater nucleotide class changes than transitions, this shift may increase the likelihood of disrupting sequence-specific miRNA binding. Supporting this, we identified missense mutations overlapping predicted miRNA binding sites within coding regions, highlighting a potential intersection between somatic mutations and post-transcriptional regulation. Together, these findings suggest that cancer-associated mutational patterns may reshape miRNA regulatory regions and alter miRNA-gene interactions, providing insight into how somatic mutations impact gene regulation beyond protein-coding changes.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 3","pages":"244-254"},"PeriodicalIF":1.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563561","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":"Cardiovascular toxicity induced by immune checkpoint inhibitors: mechanisms linking immune dysregulation and myocardial fibrosis.","authors":"Di Wang, Bin-Kui Jia, Zhao-Yu Li, Qian Qiao, Lu Cheng, Li-Hong Zhang, Xue-Rui Ye, Hao-Ling Zhang, Jing-Jing Zhang","doi":"10.62347/MTAX7470","DOIUrl":"10.62347/MTAX7470","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) play a key role in cancer immunotherapy, enhancing outcomes for patients with multiple malignancies by blocking the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways. Nevertheless, their application is limited due to immune-related adverse events (irAEs), which comprise various manifestations, among which cardiovascular toxicities - primarily myocarditis, arrhythmias, pericarditis, and heart failure - are a major clinical challenge. While relatively rare, myocarditis has a fatality rate as high as 50%. The mechanisms underlying ICI-induced cardiovascular toxicity remain not fully understood, especially regarding how immune dysregulation translates into myocardial fibrosis. Herein, the immune dysregulation-inflammation-fibrosis axis is reviewed, and the mechanisms by which immune checkpoint blockade breaks cardiac immune tolerance, inducing T-cell activation, cytokine storms, and the subsequent production of anti-cardiac antibodies, are discussed. Moreover, the important function of non-coding RNAs (ncRNAs) in immunomodulatory and fibrotic pathways is then revealed as a key player in ICI-associated cardiac injury. It also discusses therapeutic strategies involving immune modulation and anti-fibrotic mechanisms, which may be suitable to reduce cardiovascular toxicity as well as improve the overall prognosis of patients. An improved mechanistic understanding underlying these processes will offer new theoretical insights into how to most effectively utilize ICIs safely.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 3","pages":"203-227"},"PeriodicalIF":1.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563557","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":"Expression and prognostic significance of CRKL in clear cell renal cell carcinoma.","authors":"Jinxia Wang, Ye Yang, Xiao Yuan, Weichen Wang","doi":"10.62347/BRIW9536","DOIUrl":"10.62347/BRIW9536","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney malignancy with limited prognostic biomarkers. CRKL has been implicated in cancer progression, but its prognostic value and immune associations in ccRCC remain unclear. Using TCGA, GEO, and UALCAN databases, we analyzed CRKL expression. Kaplan-Meier and multivariate Cox regression assessed survival; TIMER and TISIDB evaluated immune infiltration; LinkedOmics databases and GSEA identified enriched pathways. CRKL was significantly overexpressed in ccRCC tissues at both mRNA and protein levels. Surprisingly, high CRKL expression was associated with better overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), and disease free survival (DFS). Multivariate Cox analysis identified CRKL as an independent favorable prognostic factor (OS: HR = 0.469, 95% CI: 0.302-0.729, P < 0.001). CRKL positively correlated with immune cell infiltration and immune-related pathways. In conclusion, CRKL is overexpressed in ccRCC, paradoxically, higher expression predicts better prognosis and is associated with immune-active tumor microenvironment features. These findings suggest that the favorable prognosis associated with CRKL may be attributable to its immunomodulatory role within the tumor microenvironment, highlighting its potential as a novel prognostic biomarker for ccRCC.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 3","pages":"228-243"},"PeriodicalIF":1.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563688","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":"Targeting cannabinoid receptor 1 for multiple sclerosis: molecular docking and dynamic insights of berberine and curcumin as potential therapeutic agents.","authors":"Jehan Alrahimi","doi":"10.62347/BNNL4902","DOIUrl":"10.62347/BNNL4902","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by demyelination, inflammation, and progressive neurodegeneration. Cannabinoid receptor 1 (CB1) plays a role in neuroprotection and modulation of inflammatory responses, making it a potential therapeutic target in MS. This study evaluated selected natural compounds as CB1 modulators using an integrated computational approach. Compounds were screened based on ADMET properties, followed by molecular docking and 100 ns molecular dynamics simulations. Berberine and curcumin demonstrated binding affinities of -7.9 kcal/mol and -9.4 kcal/mol, respectively. Key binding interactions involved residues VAL137, LEU404, PHE408, ARG405, and ARG409 for berberine, and MET363, LEU193, LEU359, TRP356, PHE189, PHE177, HIS178, PHE174, PHE379, ALA380, and SER383 for curcumin. Stability analyzes including RMSD, RMSF, secondary structure elements, and protein-ligand contacts, indicated stable complex formation. These findings suggest that berberine and curcumin may serve as potential lead candidates targeting CB1 and warrant further experimental validation in multiple sclerosis research.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 3","pages":"193-202"},"PeriodicalIF":1.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563848","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}