Clinical And Experimental Medicine[JOURNAL]
Sun
200 papers
LncRNA CCAT2 role in female-related cancer progression and diagnosis: a comprehensive review.
Vanan AG, Hassanzadeh F, Ghorbaninezhad F … +8 more , Taheri F, Bahrami O, Heidari P, Baharvand Z, Raissi S, Eini P, Tahmasebi S, Safarzadeh E
Clin Exp Med · 2026 Feb · PMID 41655184 · Full text
Female-related cancers, including breast, ovarian, endometrial, and cervical malignancies, are among the most prevalent and clinically significant health challenges worldwide. Their development involves a complex interpl...
Female-related cancers, including breast, ovarian, endometrial, and cervical malignancies, are among the most prevalent and clinically significant health challenges worldwide. Their development involves a complex interplay of genetic mutations, environmental factors, lifestyle influences, and therapeutic interventions. Long non-coding RNAs (lncRNAs) have emerged as critical regulators in these cancers, modulating epigenetic mechanisms, transcriptional programs, and post-transcriptional processes. Aberrant lncRNA expression promotes tumor initiation, drives progression and metastasis, and facilitates epithelial-mesenchymal transition (EMT) and angiogenesis. Among these, colon cancer-associated transcript 2 (CCAT2) has been identified as an oncogenic lncRNA across multiple tumor types. CCAT2 primarily activates the Wnt/β-catenin signaling pathway, enhancing β-catenin transcriptional activity and upregulating downstream targets such as MYC and cyclin D1, which are essential for cancer cell proliferation and survival. Despite growing evidence of its oncogenic role, the specific contribution of CCAT2 to female-related cancers remains incompletely understood. This study systematically reviews recent findings on CCAT2's role in the development and progression of breast, ovarian, endometrial, and cervical cancers, elucidates the underlying molecular mechanisms, and evaluates its potential as a diagnostic and prognostic biomarker. Furthermore, the translational potential of CCAT2 as a therapeutic target is discussed, highlighting opportunities for improving clinical outcomes in these malignancies.
Monitoring cancer-related fatigue and quality of life in breast and prostate cancer patients after primary treatment: a study protocol for the REBECCA trials in Norway.
Stensland M, Bru KF, Austdal M … +25 more , Dahl IH, Jonsdottir K, Lende TH, Heimvik C, Elve I, Omdal R, van der Giezen M, Kvivik I, Tangeland B, Davidsen L, Hashemi M, Cais A, van Dijk KJ, Seyoum Y, Blåfjelldal V, Sola ST, Papadopoulos A, Kiriakidou N, Ioakeimidis I, Diou C, Sarafis I, Delopoulos A, Janssen EAM, Gilje B, Tjensvoll K
Clin Exp Med · 2026 Feb · PMID 41655181 · Full text
The REBECCA project taps into the potential of using real-world data (RWD) for supporting groundbreaking clinical research on complex chronic conditions as a complement to Randomised Controlled Trials. REBECCA moves beyo...
The REBECCA project taps into the potential of using real-world data (RWD) for supporting groundbreaking clinical research on complex chronic conditions as a complement to Randomised Controlled Trials. REBECCA moves beyond the analysis of clinical data from Electronic health records, by combining it with detailed monitoring data from multiple wearables, online behaviour and self-reported data to monitor patients's quality of life in terms of their functional and emotional status. The project focuses on the detection of cancer-related fatigue, developed during breast cancer recovery, using digital biomarker profiles for early detection of the disease and assessing the value of detailed and longitudinal patient monitoring as a means of improving patient care. The project also demonstrates the extensibility of REBECCA monitoring to other forms of cancer, such as prostate cancer. We describe the three clinical trials being conducted in Norway and the use of the REBECCA platform, capable of detailed monitoring and privacy preserving federated cross-country data analysis. The RWD will be analyzed in the context of data from questionnaires (Patient Reported Outcome Measures) and results from analysis of biological samples. Through this approach we expect that the REBECCA project will produce new knowledge on clinical management of cancer patients and contribute to new biological knowledge on cancer-related fatigue. Status and perspectives: The REBECCA project is ongoing, and patient follow-up will be completed during February 2026. The initial analyses of RWD, PROMs and biological samples have started together with the partners in the REBECCA consortium. The REBECCA trials are approved by the Regional Ethics Committee of the Western Health Authority (REK Vest) under the IDs 225,855 (REBECCA-1), 242,088 (REBECCA-2) and 619,903 (REBECCA-3). All trials have also been registered at clinicaltrials.gov (NCT05587777, NCT06120595 and NCT06435091). Trial registration: NCT05587777, Retrospectively registered 19th of October 2022, https://clinicaltrials.gov/study/ NCT05587777; NCT05587777, Retrospectively registered 6th of November 2023, https://clinicaltrials.gov/study/ NCT06120595; NCT05587777, Retrospectively registered 23rd of May 2024, https://clinicaltrials.gov/study/ NCT06435091.
"Cytokine-Mediated tumor sensitization: mechanistic frameworks and therapeutic opportunities in cancer Immunotherapy".
Aghaei M, Bahreiny SS, Mahdizade AH … +3 more , Abbasi A, Magharati A, Yousefi-Avarvand A
Clin Exp Med · 2026 Feb · PMID 41655180 · Full text
Cytokines are pivotal regulators of immune responses and inflammation, and their dysregulation is implicated in cancer initiation and progression. A deeper understanding of cytokine-mediated modulation of tumor cell beha...
Cytokines are pivotal regulators of immune responses and inflammation, and their dysregulation is implicated in cancer initiation and progression. A deeper understanding of cytokine-mediated modulation of tumor cell behavior may uncover novel therapeutic targets for cancer treatment.A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases using keywords such as "cytokines," "tumor sensitization," "immune regulation," and "cancer therapy." Peer-reviewed articles published between 2002 and 2025 were evaluated and synthesized to provide an updated overview of cytokine-related therapeutic strategies.This review highlights the complex roles of key cytokines-including interleukins (IL-1, IL-6, IL-8, IL-10, IL-17), interferons (types I and II), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β)-in modulating tumor cell susceptibility to therapeutic interventions. While cytokines exhibit both tumor-promoting and tumor-suppressive properties, recent advances in cytokine engineering, targeted delivery systems, and combination immunotherapies have enhanced their clinical potential.Integrating cytokine modulation into oncology may improve personalized immunotherapy outcomes.
PRKD1/EIF5A/β-catenin axis inhibits tumorigenesis and metastasis in non-small-cell lung cancer.
Wang Y, Zhang M, Fang L … +5 more , Qu J, Huo C, Li R, Yao J, Qu Y
Clin Exp Med · 2026 Feb · PMID 41655151 · Full text
PRKD1 is downregulated in non-small-cell lung cancer (NSCLC). Whether and how PRKD1 regulates tumorigenesis and metastasis is previously unknown. Here, we report that PRKD1 negatively regulates β-catenin protein abundanc...
PRKD1 is downregulated in non-small-cell lung cancer (NSCLC). Whether and how PRKD1 regulates tumorigenesis and metastasis is previously unknown. Here, we report that PRKD1 negatively regulates β-catenin protein abundance. PRKD1 promotes ubiquitination and degradation of EIF5A. EIF5A upregulates β-catenin and activates the Wnt signaling pathway. Thus, the PRKD1/EIF5A/β-catenin axis modulates the Wnt signaling pathway in NSCLC. Functionally, PRKD1 inhibits cell proliferation and metastasis both in vitro and in vivo. PRKD1 is downregulated and EIF5A is upregulated in NSCLC. Lower PRKD1 and higher EIF5A predict a worse patient survival. Our study suggests that the PRKD1/EIF5A/β-catenin axis is involved in the carcinogenesis of NSCLC and may serve as a new therapeutic target for NSCLC.
Joint association of systemic inflammatory response index and thromboelastography maximum amplitude with the risk of early atherosclerosis in patients with rheumatoid arthritis.
Zhang Q, Xu Q, Huang R … +5 more , Yin R, Sun M, Jiang D, Tao H, Jin H
Clin Exp Med · 2026 Feb · PMID 41655141 · Full text
Systemic inflammation and hypercoagulability are two major characteristics of rheumatoid arthritis (RA), both contributing to atherosclerosis development. This study aims to evaluate their joint and mutual associations w...
Systemic inflammation and hypercoagulability are two major characteristics of rheumatoid arthritis (RA), both contributing to atherosclerosis development. This study aims to evaluate their joint and mutual associations with early atherosclerosis risk in RA patients via the systemic inflammation response index (SIRI) and thromboelastography maximum amplitude (TEG-MA). The study encompassed 335 RA patients who fulfilled the specified inclusion criteria. Logistic regression assessed SIRI, TEG-MA, and their combined link to early atherosclerosis risk. Both multiplicative and additive interactions were evaluated, and a bidirectional mediation model explored their reciprocal impacts on early atherosclerosis. After full confounder adjustment, SIRI and TEG-MA both showed significant positive links to early atherosclerosis risk, whether analyzed as continuous or categorical variables (P < 0.05). In joint analyses, RA patients with both high SIRI and TEG-MA had a 10.06-fold higher risk than those with low levels of both (odds ratio [OR]: 10.06, 95% confidence interval [CI]: 3.75-25.90). SIRI and TEG-MA showed notable additive interaction in affecting atherosclerosis risk, with relative excess risk of interaction (RERI) at 4.03 (95% CI: 1.25-9.36), attributable proportion of interaction (API) at 0.42 (95% CI: 0.03-0.79), and synergy index (SI) at 1.73 (95% CI: 1.03-2.96). No significant multiplicative interaction was detected (P > 0.05). Mutual mediation analysis showed SIRI mediated 40.6% of TEG-MA's effect, while TEG-MA mediated 27.6% of SIRI's effect on atherosclerosis risk. These results suggest that there is an intertwined and mutually reinforcing relationship between inflammation and hypercoagulability in the occurrence and progression of atherosclerosis in RA.
Ruxolitinib reduces macrophage pyroptosis in aplastic anaemia.
Xu X, Zhong C, Meng X … +2 more , Song N, Fu R
Clin Exp Med · 2026 Feb · PMID 41653353 · Full text
Aplastic anaemia (AA) is a disease that shows complex pathogenesis involving multiple immune factors. While immunosuppressive therapies such as cyclosporine can effectively control AA, they may be ineffective in certain...
Aplastic anaemia (AA) is a disease that shows complex pathogenesis involving multiple immune factors. While immunosuppressive therapies such as cyclosporine can effectively control AA, they may be ineffective in certain patients or those with relapse. Therefore, new treatments are needed. Among the targets for these treatments, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway regulates inflammatory cytokines and immune activation. Ruxolitinib, a JAK1/2 inhibitor, reduces T-cell activation and the associated inflammatory response and improves AA disease status in mice. However, its mechanism of action is unclear; thus, further research is needed before its clinical use. We previously showed increased pyroptosis in patients with severe AA (SAA) and that macrophage pyroptosis is an important factor in immune activation. The current study investigated the interaction of ruxolitinib with macrophages and whether the drug could treat SAA by improving pyroptosis levels. We induced differentiation of the THP-1 human monocyte cell line into macrophages in vitro and then induced pyroptosis. After constructing a macrophage pyroptosis model, treatment with different concentrations of ruxolitinib was administered. The results showed that ruxolitinib reduced the levels of pyroptosis and inflammatory-related factors. We then used the SAA mouse model to validate this conclusion. In conclusion, ruxolitinib may affect SAA by reducing the level of macrophage pyroptosis.
Sex and menopause-based differences in presentation of early Lyme disease: A prospective cohort study.
Rebman AW, Yang T, Aucott JN
Clin Exp Med · 2026 Feb · PMID 41653328 · Full text
Although prior research has established sex and menopausal status-based differences in immune response, susceptibility, and severity to a variety of pathogens, their relevance in early Lyme disease is understudied. We ex...
Although prior research has established sex and menopausal status-based differences in immune response, susceptibility, and severity to a variety of pathogens, their relevance in early Lyme disease is understudied. We examined the clinical and serologic presentation of patients with early Lyme disease, stratified first by sex then by menopausal status. We also explored the hypothesis that males would present with more severe early Lyme disease. In this prospective cohort study from the Mid-Atlantic US, 243 adult, antibiotic-naïve patients were enrolled with a diagnostic erythema migrans rash present. Demographic, physical exam, symptom, laboratory, and two-tier serology data were collected at a baseline, and a post-treatment visit 3 weeks later. Lyme disease severity was operationalized through six indicators: rash size, number of acute symptoms, dermatologic dissemination, positive serology, liver function elevation, and elevated neutrophil-lymphocyte ratio. Unadjusted group comparisons and multivariate regression adjusting for potential confounders were used to assess difference. In logistic models adjusted for age, Lyme disease duration, systemic steroid use, and co-morbid thyroid disease, males had higher odds of testing two-tier positive (OR = 1.77 [1.03, 3.04], p = 0.039). This difference was more pronounced between males and pre-menopausal females (OR = 2.93 [1.26-6.79], p = 0.012) and no significant difference was found comparing males to post-menopausal females. In ordinal logistic models with Lyme disease severity as the outcome adjusted for age and Lyme disease duration, males had higher odds of being in a higher disease severity score category (OR = 1.94 [1.20,3.15], p = 0.028); again, particularly in comparison to pre-menopausal females (OR = 2.26 [1.13,4.58], p = 0.044). Heart palpitations (p = 0.023), vomiting (p = 0.007), and photophobia (p = 0.057) trended towards higher reporting among females, while sleep difficulty (p = 0.010) was higher among males. No differences were found on non-dermatologic components of the physical exam. We found sex and menopausal status to be relevant in accounting for variability in two-tier serologic status and severity of early Lyme disease in a well-characterized group of patients. Lower rates of seroreactivity among females is unexpected but may be consistent with lower acute severity of disease. Our clinical findings underscore the need for additional research to understand possible contributing biologic and/or social behavioral factors, as well as their impact on timely diagnosis and post-treatment conditions.
Integrating multi-source data and machine learning to Decipher the psoriasis-COPD comorbidity.
He Y, Xiang L, He Y … +4 more , Wang G, Jiang H, Li Y, Qi X
Clin Exp Med · 2026 Feb · PMID 41653319 · Full text
The epidemiological and molecular associations between psoriasis and chronic obstructive pulmonary disease (COPD) remain incompletely elucidated. To explore this association and shared mechanisms, this study integrated d...
The epidemiological and molecular associations between psoriasis and chronic obstructive pulmonary disease (COPD) remain incompletely elucidated. To explore this association and shared mechanisms, this study integrated data of the National Health and Nutrition Examination Survey (NHANES) 2003–2014 (n = 17,416), assessing this association via multivariable logistic regression and subgroup analysis. Transcriptomic data of psoriasis (skin tissue) and COPD (alveolar macrophages) were retrieved from the Gene Expression Omnibus (GEO) database. Candidate biomarkers were identified via differentially expressed gene (DEG) analysis, weighted gene coexpression network analysis (WGCNA), and machine learning [Random Forest (RF) and least absolute shrinkage and selection operator (LASSO)], followed by validation of their diagnostic efficacy. In the fully weighted and adjusted model, no statistically significant association was found between psoriasis and COPD (OR = 1.25, 95% CI: 0.93–1.68, p = 0.14), although trend-level associations were observed among smokers, individuals with hypertension, and those with unstable marital status. We identified 85 shared differentially expressed genes (DEGs), enriched in inflammatory pathways such as the chemokine signaling pathway, and screened three candidate genes (UCK2, P4HA1, and HIBADH). A RF diagnostic model based on these genes achieved Area Under the Curves (AUCs) of 0.935 for psoriasis and 0.962 for COPD in external validation sets. These findings suggest that the comorbidity between psoriasis and COPD may be influenced by risk factors such as smoking and hypertension, as well as shared inflammatory pathways and differentially expressed genes (DEGs) regulation. Psoriasis could serve as a potential window for early COPD screening and provide novel cross-disease therapeutic targets.
Extracellular matrix remodeling in the pathogenesis and therapeutic strategies of rheumatoid arthritis.
Yang Q, Xu Y, Xu J … +10 more , Zhang J, Yan H, Xiao N, Lu H, Mu J, Quan S, Luo R, Mao J, Xie Z, Li Z
Clin Exp Med · 2026 Feb · PMID 41653212 · Full text
The pathological process of rheumatoid arthritis is not only driven by immune inflammation but is more profoundly shaped by abnormal remodeling of the extracellular matrix. This study systematically reviews the core mani...
The pathological process of rheumatoid arthritis is not only driven by immune inflammation but is more profoundly shaped by abnormal remodeling of the extracellular matrix. This study systematically reviews the core manifestations of abnormal extracellular matrix remodeling in RA: matrix sclerosis, excessive degradation mediated by matrix metalloproteinase/a disintegrin and metalloproteinase with thrombospondin motifs, and degradation fragments as damage-associated molecular patterns activating the TLR4/RAGE pathway, thereby forming a self-perpetuating vicious cycle of "sclerosis-degradation-inflammation amplification-resclerosis," significantly exacerbating inflammatory reactions and joint damage. It proposes a dual framework of "mechanism loop-clinical loop," emphasizing the integration of the biomarkers C1M, C3M, COMP, HA, and other ECM-degradation fragments for dynamic disease monitoring, progression prediction, and precise efficacy evaluation. By combining biomarker panels with imaging data, it is expected to optimize the stratification of high-risk populations and individualized treatment adjustments, which may enhance the precision of diagnostic and therapeutic strategies and provide a new direction for RA to progress from inflammation control to structural protection.
SIRT1-mediated FABP4 destabilization attenuates fibrosis and ferroptosis in non-alcoholic fatty liver disease.
Qiu H, Chen K, Qiu Y … +4 more , Yang Y, Wang T, Wang W, Jiang L
Clin Exp Med · 2026 Feb · PMID 41649608 · Full text
OBJECTIVE: This study aims to unveil the role and mechanism of histone deacetylase SIRT1 in modulating fatty acid binding protein 4 (FABP4) stability and its impact on hepatic fibrosis and ferroptosis in non-alcoholic fa...
OBJECTIVE: This study aims to unveil the role and mechanism of histone deacetylase SIRT1 in modulating fatty acid binding protein 4 (FABP4) stability and its impact on hepatic fibrosis and ferroptosis in non-alcoholic fatty liver disease (NAFLD). METHODS: A murine NAFLD fibrosis model was induced by a Western diet combined with CCl4 injection. Mice received adenoviruses carrying oe-SIRT1 or sh-FABP4 three days before modeling. In vitro, NCTC 1469 hepatocytes were exposed to palmitic acid (PA) and transfected with oe-SIRT1 or oe-FABP4. Histopathology was assessed by HE, Masson, and Sirius red staining, and α-SMA by immunohistochemistry. Biochemical assays and molecular analyses measured liver injury markers, ferroptosis-related proteins, oxidative stress indices, and SIRT1/FABP4 expression. Cell viability, death, and lipid deposition were evaluated by CCK-8, LDH release, and Oil Red O staining. Co-IP and CHX chase assays examined SIRT1–FABP4 interaction, acetylation, and protein stability. RESULTS: NAFLD mice showed decreased SIRT1 and increased FABP4, with lipid degeneration, collagen deposition, α-SMA upregulation, and aggravated ferroptosis. Either SIRT1 overexpression or FABP4 knockdown alleviated inflammation, fibrosis, and ferroptosis in vivo. In PA-treated hepatocytes, cell viability declined, LDH release and lipid deposition increased, AST/ALT rose, ferroptosis intensified, SIRT1 was suppressed, and FABP4 was upregulated. Enhancing SIRT1 reduced FABP4 expression, attenuated lipid accumulation, and limited ferroptosis. Mechanistically, SIRT1 interacted with FABP4 to decrease its acetylation, thereby lowering FABP4 stability. FABP4 overexpression partially reversed the protective effect of SIRT1, promoting ferroptosis and lipid deposition. CONCLUSION: SIRT1 reduces FABP4 acetylation and stability, thereby suppressing ferroptosis and hepatic fibrosis in NAFLD.
Deciphering whipple's disease complexity.
Korybski J, Zelig J, Narayanan S … +6 more , Blonski W, Kazimierski KM, Dierkes JH, Popiela HL, Gabriel AP, Neubauer K
Clin Exp Med · 2026 Feb · PMID 41649590 · Full text
Whipple's disease is a sporadic infectious condition, with an incidence rate of approximately 1 per million individuals. The causative agent is the gram-positive bacterium Tropheryma whipplei. The disease manifests with...
Whipple's disease is a sporadic infectious condition, with an incidence rate of approximately 1 per million individuals. The causative agent is the gram-positive bacterium Tropheryma whipplei. The disease manifests with a wide range of clinical symptoms, including non-specific presentations such as diarrhea, arthralgia, and fever, as well as the more pathognomonic lipodystrophy. This diversity in presentation poses a significant diagnostic challenge even for experienced clinicians. Our review aims to provide an updated overview encompassing the latest insights into Whipple's disease, focusing on epidemiology, pathophysiology, genetic predisposition, clinical manifestations, diagnosis, immune reconstitution inflammatory syndrome, and treatment. Herein, we have additionally explored many of the confounding factors in the diagnosis and management of Whipple's disease, including the variable presentations among patients colonized by Trophyrema whipplei as well as the limitations of current treatment options, and underscore the need for further research and guidelines related to this complex disease process.
In vitro assays as a tool to personalize treatment in central nervous system tumors: a systematic literature review.
Offi M, Buccarelli M, Chiesa S … +12 more , Mazzarella C, Falchetti ML, Ceccarelli GM, Di Monaco G, Cocilovo FM, Taglialatela M, Shetty S, Olivi A, Lauretti L, Pallini R, Ricci-Vitiani L, D'Alessandris QG
Clin Exp Med · 2026 Feb · PMID 41649584 · Full text
Personalized therapy in neuro-oncology has traditionally relied on molecular profiling. However, clinical benefit has been scarce to date. Recently, in vitro drug sensitivity testing using patient-derived models-such as...
Personalized therapy in neuro-oncology has traditionally relied on molecular profiling. However, clinical benefit has been scarce to date. Recently, in vitro drug sensitivity testing using patient-derived models-such as organoids and cell lines-has emerged as a promising strategy. We systematically reviewed evidence on the efficacy of in vitro drug screening in predicting treatment outcome for brain tumors, including but not limited to glioblastoma. PRISMA guidelines were followed. Fifteen studies were included, comprising 300 patients overall. Cohort studies built the largest group; only one randomized clinical trial was found. In vitro assays, using patient-derived stem cells, standardized assays ad the ChemoID, or tumor-derived organoids, were able to reliably predict treatment outcome. However, the overall quality of evidence was limited. These models may overcome limitations of molecular profiling, especially in glioblastoma, where driver mutations are often lacking and the molecular profile evolves at recurrence. Although initial results are promising, further validation is needed before clinical implementation.
USP36 inhibits ferroptosis of melanoma cells by stabilizing APEX1.
Zhang L, Zhang Y, Yin H
Clin Exp Med · 2026 Feb · PMID 41649582 · Full text
Cutaneous melanoma is an aggressive skin cancer characterized by high rates of recurrence and mortality, especially in its advanced stages. Ferroptosis, a distinct form of programmed cell death, has emerged as a promisin...
Cutaneous melanoma is an aggressive skin cancer characterized by high rates of recurrence and mortality, especially in its advanced stages. Ferroptosis, a distinct form of programmed cell death, has emerged as a promising therapeutic strategy for cancer. Nevertheless, the regulatory mechanisms underlying ferroptosis in melanoma remain poorly defined. In this study, we aimed to elucidate the role of USP36, a deubiquitinating enzyme that removes ubiquitin from substrate proteins, in the ferroptosis of melanoma cells. Using A375 and SK-MEL-28 melanoma cells treated with the ferroptosis inducer erastin, we analyzed USP36 expression and evaluated its functional role through both overexpression and knockdown experiments. Co-immunoprecipitation and ubiquitination assays demonstrated that USP36 stabilizes APEX1 through the cleavage of its K48-linked ubiquitin chains. We further employed USP36-deficient xenograft models to assess tumor growth and ferroptosis sensitivity. Our results indicate that erastin downregulates USP36, whereas overexpression of USP36 suppresses ferroptosis. Importantly, knockdown of APEX1 abolished the anti-ferroptotic effect of USP36. In addition, USP36-deficient tumors exhibited reduced proliferation and enhanced ferroptosis. Collectively, these findings establish USP36 as an oncogene in melanoma that inhibits ferroptosis through stabilization of APEX1. Therefore, targeting the USP36-APEX1 axis may represent a novel therapeutic approach for melanoma treatment.
MicroRNAs as novel therapeutic targets against inflammatory bowel disease through modulation of ferroptosis.
Bu S, Chen M, Li J … +2 more , Zhang T, Yu Y
Clin Exp Med · 2026 Feb · PMID 41642459 · Full text
Inflammatory Bowel Disease (IBD), driven by mucosal barrier dysfunction and immune regulation disruption, is characterized by chronic gastrointestinal inflammation and frequent disease relapse. While traditional therapie...
Inflammatory Bowel Disease (IBD), driven by mucosal barrier dysfunction and immune regulation disruption, is characterized by chronic gastrointestinal inflammation and frequent disease relapse. While traditional therapies focus on immune suppression, recent evidence identifies ferroptosis-an iron-dependent form of regulated cell death-as a critical driver of intestinal epithelial injury. Central to this process are microRNAs (miRNAs), which act as post-transcriptional "switches" regulating the three metabolic axes of ferroptosis: antioxidant defense (GPX4, System Xc-), iron trafficking, and lipid peroxidation. This review synthesizes emerging evidence on the miRNA-ferroptosis network in IBD. We highlight how specific dysregulated miRNAs, such as miR-129-5p and the IRF7/miR-375 axis, strip the epithelium of its defenses, promoting lethal lipid peroxidation. Furthermore, we examine the clinical transformation of these insights into novel therapies, including the oral small molecule ABX464 (obefazimod) and bioengineered exosome delivery systems. By moving beyond broad immunosuppression to targeted metabolic reprogramming, miRNA-based interventions offer a promising frontier for overcoming resistance to current biologic therapies and achieving deep mucosal healing in IBD.
Alternative splicing events show high prognostic values and indicate potential core genes in acute myeloid leukemia.
Li S, An L, Shao S … +3 more , Wei T, Tong Y, Tong Y
Clin Exp Med · 2026 Feb · PMID 41636901 · Full text
Alternative splicing (AS) plays critical roles in acute myeloid leukemia (AML), but the prognostic values of AS events are rarely studied. In this study, we performed comprehensive analysis in AS events of 126 AML patien...
Alternative splicing (AS) plays critical roles in acute myeloid leukemia (AML), but the prognostic values of AS events are rarely studied. In this study, we performed comprehensive analysis in AS events of 126 AML patients from the Cancer Genome Altas (TCGA) database by using the TCGA Splice Seqdataset. Univariate Cox analysis was performed to identify prognosis-associated (PA) AS events. Then LASSO regression analysis was conducted to obtain appropriate PAAS events and multivariate Cox analysis was used to build the risk models of all PAAS events and seven individual PAAS events, which were verified by Kaplan-Meier plot and AUC curve. Later, the correlation between PAAS and splicing factors (SFs) was analyzed by Spearman's correlation analysis. Gene function analysis was used to explore the role of SFs in AML development. A total of 1,847 AS events were related to overall survival of AML patients. All risk score models that were constructed based on prognosis-associated (PA) AS events of different AS types showed superior accuracy in predicting 5-year survival, especially the model of alternative acceptor (one subtype of AS) with an area under the receiver operating characteristic (ROC) curve of 0.953. And the risk score turned out to be an independent prognostic factor in AML. Fifty-five differentially expressed splicing factors (SFs) were found and four (JUN, YBX3, HSPA1B and RNU5A-1) were correlated with PAASs as regulators. And YBX3 was considered the core SF as its prognostic value in patients with AML. Function prediction suggested YBX3 played key roles in AML differentiation. Notably, 75.7% of prognostic AS events showed differential splicing between AML and normal controls, supporting their biological relevance. Our findings revealed that AS events were excellent outcome predictors for AML patients and they provided clues of potential mechanisms and therapeutic targets of AML.
Novel antagonist APG-115 targets MDM2-p53 to induce p53-mediated apoptosis and radiosensitization in colorectal cancer.
Yi H, Han Y, Wang X … +3 more , Li Q, Xiong L, Li S
Clin Exp Med · 2026 Feb · PMID 41629729 · Full text
Colorectal cancer remains a major global health burden, and treatment outcomes for advanced disease are still unsatisfactory. APG-115 is a next-generation small-molecule MDM2 inhibitor developed in China that restores wi...
Colorectal cancer remains a major global health burden, and treatment outcomes for advanced disease are still unsatisfactory. APG-115 is a next-generation small-molecule MDM2 inhibitor developed in China that restores wild-type p53 activity. However, its therapeutic potential in colorectal cancer has not been fully explored. APG-115's impact on colorectal cancer cells was evaluated through CCK-8 assays and AnnexinV-FITC/PI staining. The dependence of APG-115 activity on p53 status was assessed in p53-knockdown cell lines. In vivo, the antitumor efficacy and radiosensitizing effects of APG-115 were evaluated in nude-mouse xenograft models. APG-115 exerted a potent inhibitory effect on the proliferation of p53 wild-type colorectal cancer cell lines LOVO, RKO, and HCT116, while showed no significant impact on p53-mutant lines. In wild-type cells, APG-115 induced apoptosis in a dose-dependent manner and caused G0/G1 cell-cycle arrest. APG-115 significantly upregulated p53 and its downstream targets (MDM2, p21, PUMA), whereas these effects were absent in p53-mutant or p53-knockdown cells. In vivo, APG-115 suppressed RKO tumor growth in a dose-dependent manner, accompanied by increased p53, MDM2 and p21 expression and reduced Ki-67. Immunofluorescence further confirmed enhanced apoptosis following treatment. Importantly, the combination of APG-115 with radiotherapy significantly promoted apoptosis, decreased the S-phase proportion, and increased G2-phase arrest in p53 wild-type cells. Radiosensitization was abolished in p53-knockout RKO xenografts, confirming the requirement of an intact MDM2-p53 pathway. APG-115 effectively inhibits proliferation, induces apoptosis, and enhances radiosensitivity in p53 wild-type colorectal cancer. These findings support APG-115 as a promising therapeutic candidate for colorectal cancers retaining functional p53.
Comprehensive analysis of COLGALT1 in tumor microenvironment regulation and prognosis of clear cell renal cell carcinoma.
Guo Y, Wang B, Ding G … +4 more , Zhang Y, Wang Y, Ma X, Wu J
Clin Exp Med · 2026 Feb · PMID 41627587 · Full text
Collagen galactosyltransferase 1 (COLGALT1), a key enzyme involved in collagen post-translational modification, has been implicated in extracellular matrix remodeling across multiple cancer types, yet its prognostic sign...
Collagen galactosyltransferase 1 (COLGALT1), a key enzyme involved in collagen post-translational modification, has been implicated in extracellular matrix remodeling across multiple cancer types, yet its prognostic significance and relationship with the tumor immune microenvironment in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, we analyzed multi-omics datasets from public repositories to assess COLGALT1 expression patterns, clinical relevance, and prognostic value in ccRCC. Quantitative real-time PCR was performed to validate its expression in renal cancer cell lines and normal renal tubular epithelial cells. Immune infiltration profiles were characterized using multiple computational algorithms, and a competing endogenous RNA network was constructed to explore regulatory mechanisms. Our results demonstrated that COLGALT1 expression was significantly upregulated in ccRCC at both mRNA and protein levels and was positively associated with the infiltration of monocytes, T helper 2 cells, macrophages, regulatory T cells, and natural killer cells. Notably, COLGALT1 expression correlated strongly with markers of M2 macrophages, suggesting a role in promoting an immunosuppressive tumor microenvironment. These findings identify COLGALT1 as a novel prognostic biomarker and potential therapeutic target in ccRCC, highlighting its contribution to extracellular matrix remodeling and immune regulation.
Artificial Intelligence-based detection of neuropsychiatric lupus: an exploratory meta-analysis of neuroimaging and multimodal biomarker models.
Nouroozi F, Kazemi HS, Alinezhad A … +16 more , Goudarzi N, Khosravi MK, Narimani Z, Asouri ZA, Ahari SG, Mehrjerdi RS, Saeidi R, Mavi MM, Ahmadifard H, Khosravi F, Alipour M, Abdollahi Z, Shemshad R, Ganjipour P, Anar MA, Rostami E
Clin Exp Med · 2026 Feb · PMID 41627551 · Full text
Neuropsychiatric systemic lupus erythematosus (NPSLE) remains challenging to diagnose because of heterogeneous clinical presentations, nonspecific findings, and the absence of definitive biomarkers. Artificial intelligen...
Neuropsychiatric systemic lupus erythematosus (NPSLE) remains challenging to diagnose because of heterogeneous clinical presentations, nonspecific findings, and the absence of definitive biomarkers. Artificial intelligence (AI) methods have been increasingly explored using neuroimaging and other biologically informative data to support identification of neuropsychiatric involvement in systemic lupus erythematosus (SLE). However, the reported performance and methodological robustness of these approaches have not been systematically characterized. To perform an exploratory meta-analysis describing reported diagnostic performance, heterogeneity, and methodological characteristics of AI-based models using neuroimaging and multimodal biomarkers for detecting neuropsychiatric involvement in SLE. We conducted a PRISMA-compliant systematic review of studies applying machine learning or deep learning models to neuroimaging or biologically informative modalities relevant to central nervous system involvement, including structural or functional MRI, magnetic resonance spectroscopy, spectroscopy-based molecular fingerprints, and CSF or serum biomarkers. PubMed, Scopus, and Web of Science were searched through August 2025. Given substantial heterogeneity in study design, model objectives, input modalities, and validation strategies, analyses were undertaken within an exploratory framework. Random-effects models were used to summarize reported area under the curve (AUC), accuracy, sensitivity, and specificity. Subgroup and leave-one-out sensitivity analyses were performed. Fourteen studies involving more than 800 participants were included. Most studies used neuroimaging, particularly resting-state functional MRI, while others incorporated non-imaging biomarkers. Reported performance metrics were generally high (pooled AUC 0.86; accuracy 0.87), but between-study heterogeneity was substantial. Sensitivity analyses demonstrated that pooled estimates were unstable and influenced by individual studies. No clear performance differences were observed between classical machine learning and deep learning approaches. External validation and formal explainable AI methods were uncommon. This exploratory synthesis indicates that AI-based models applied to neuroimaging and multimodal biomarkers have shown promising reported performance in NPSLE. However, marked heterogeneity, limited robustness, and poor interpretability currently preclude firm conclusions regarding clinical applicability. More standardized, externally validated, and interpretable studies are needed before translation into clinical practice.
Gene mutation in metabolism syndrome with hematologic tumor: A retrospective cohort study.
Zhang Y, Yang L, Luo Y … +2 more , Deng J, Lou S
Clin Exp Med · 2026 Jan · PMID 41609917 · Full text
Metabolism Syndrome (MS) is strongly linked to tumorigenesis, yet its impact on gene mutations in hematologic tumors (HT) remains underexplored. This study aims to elucidate the effect of MS on HT gene mutations. Between...
Metabolism Syndrome (MS) is strongly linked to tumorigenesis, yet its impact on gene mutations in hematologic tumors (HT) remains underexplored. This study aims to elucidate the effect of MS on HT gene mutations. Between 2021 and 2024, 229 HT patients were enrolled, including 113 with MS and 116 without. All patients underwent thorough clinical assessments and gene mutation analyses. Univariate and multivariate logistic regression were used to identify factors associated with HT gene mutations, while Spearman's correlation evaluated the ordinal relationship between HT and MS. HT patients with MS exhibited significantly higher gene mutation rates than those without MS (79.65% vs. 68.10%, p = 0.047). Multivariate logistic regression analysis revealed associations between HT gene mutations and age (OR = 1.058, 95%CI, 1.030-1.088, p < 0.001) and clinical stage (OR = 0.371, 95%CI, 0.145-0.949, p < 0.001). Subgroup analysis indicated that MS-comorbid HT patients under 60 years exhibited a notably higher mutation rate than their non-MS counterparts (72.22% vs. 50.00%, p = 0.036). Spearman's correlation analysis further confirmed a link between HT gene mutations and MS (R = - 0.131, p = 0.047). This real-world retrospective study suggests that MS may elevate gene mutation rates in HT patients, especially those under 60 years old. However, tumor gene mutations are likely influenced by multiple factors, warranting further research with a broader range of variables for a more comprehensive understanding.
Metastatic organotropism in peritoneal metastasis: Paget's hypothesis revisited.
Kim D, Kaushal D, Wilson RB
Clin Exp Med · 2026 Jan · PMID 41609906 · Full text
Peritoneal metastasis (PM) of solid tumours is a major contributor to cancer-associated mortality and morbidity. The mechanism of PM development encapsulates Paget's hypothesis of seed and soil, whereby cancer cells remo...
Peritoneal metastasis (PM) of solid tumours is a major contributor to cancer-associated mortality and morbidity. The mechanism of PM development encapsulates Paget's hypothesis of seed and soil, whereby cancer cells remotely prepare a pre-metastatic niche in the peritoneal microenvironment to facilitate transcoelomic cancer progression. The bidirectional communication between cancer cells and host mesothelial cells, endothelial cells, leukocytes, adipocytes, and fibroblasts occurs via exosomes. Exosomes are nano-sized extracellular vesicles that carry cargos of proteins, cytokines, and microRNA. Cancer-derived exosomes enable exfoliated tumour cells to resist anoikis, disseminate, adhere, and implant in the peritoneum. This process involves the degradation of the peritoneal glycocalyx, the transformation of peritoneal mesothelial cells into cancer-associated fibroblasts via mesothelial-mesenchymal transition, and metabolic coupling with omental and subperitoneal adipocytes. Exosomes also enhance ascites and peritoneal immunosuppression. Exosomes promote PM development from mesenchymal subtypes of epithelial cancers, which have a predilection for transcoelomic metastasis compared to other molecular subtypes. Mesenchymal subtypes include diffuse gastric cancer, CMS4 colorectal cancer, and high-grade serous ovarian carcinoma. Understanding the oncogenic roles of exosomal cargo offers potential for future research and therapy in PM.
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