{"title":"Evaluation and Modulation of Gut Microbiome Dysfunction in Chronically Critically Ill Patients: A Prospective Pilot Study.","authors":"Ekaterina Chernevskaya, Ekaterina Sorokina, Petr Polyakov, Kirill Gorshkov, Nadezda Kovaleva, Vladislav Zakharchenko, Natalia Beloborodova","doi":"10.3390/ijms26199778","DOIUrl":"10.3390/ijms26199778","url":null,"abstract":"<p><p>Assessing gut microbiota disturbances for subsequent modulation remains a challenge. This study aims to evaluate the safety and efficacy of a microbiota-oriented strategy in treating patients with chronic critical illness (CCI). This single-center prospective study included chronically critically ill patients, stratified into three groups by severity of microbiota dysfunction. Three different microbiota modulation regimens including metabiotics, enteral, and anaerobic-safe systemic antibiotics were applied subsequently. Forty-three patients with chronic critical illness were included. Mild microbiota dysfunction was present in 49% patients, moderate in 19% and severe in 32%. Monitoring of biomarkers for 14 days confirmed the safety of reducing the pharmacological load in mild to moderate microbiota dysfunction. The microbiota-oriented strategy demonstrated improvements in neurological condition, a decrease in inflammation, and normalization of several hematological and biochemical parameters, without contributing to the activation of opportunistic microorganisms in the intestinal microbiota. The incidence of pneumonia in patients with CCI was reduced significantly during the 28-day observation period. The results of the pilot study suggest the potential benefits of a microbiota-oriented strategy in preventing nosocomial pneumonia in CCI patients.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seok-Hoon Han, Ji-Hwan Kim, Yewon Han, Sangjin Kim, Hyowon Jin, Won-Yung Lee
{"title":"Multiscale Interactome-Guided Discovery Candidate Herbs and Active Ingredients Against Hyperthyroidism by Biased Random Walk Algorithm.","authors":"Seok-Hoon Han, Ji-Hwan Kim, Yewon Han, Sangjin Kim, Hyowon Jin, Won-Yung Lee","doi":"10.3390/ijms26199789","DOIUrl":"10.3390/ijms26199789","url":null,"abstract":"<p><p>Hyperthyroidism features excess thyroid hormone and a hypermetabolic state; although drugs and definitive therapies exist, mechanism-anchored options are still needed. We built a multiscale interactome and applied a biased random-walk diffusion model to prioritize herbal candidates, active ingredients, and mechanisms. Herb-compound records came from OASIS; targets from DrugBank, TTD, and STITCH; and disease genes from DisGeNET. For each herb and compound, we simulated diffusion profiles, computed the correlation with the hyperthyroidism profile, and assessed target overlap ratio. Herbs were ranked by correlation and <i>p</i> < 0.05 overlap, retaining those with ≥5 active compounds linked to disease targets. Top signals included <i>Geranii Herba</i> (0.021), Gastrodiae Rhizoma (0.012), and <i>Veratri Rhizoma Et Radix</i> (0.011), plus seven herbs at 0.010. Herb-disease relationships were strongly enriched. Enrichment analyses highlighted MAPK, PI3K-AKT, p53, HIF-1, and thyroid hormone signaling, with Gene Ontology terms for apoptosis/anoikis, inflammation, and RNA polymerase II-dependent transcription. Compound-level analysis recovered evidence-supported ellagic acid and diosgenin and proposed resveratrol, cardamomin, 20-hydroxyecdysone, and (Z)-anethole as novel candidates. Subnetwork mapping linked these compounds to phosphorylation, GPCR-cAMP/TSH signaling, and transcriptional control. This framework recapitulates known thyroid-modulating herbs and elevates underappreciated leads with testable mechanisms, supporting the discovery of multi-target therapeutics for hyperthyroidism.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucia Iavarone, Renato Franco, Federica Zito Marino, Giuseppe D'Abbronzo, Giuseppe Argenziano, Camila Scharf, Grazia Nucci, Andrea Ronchi, Gerardo Cazzato
{"title":"Ocular Melanoma: A Comprehensive Review with a Focus on Molecular Biology.","authors":"Lucia Iavarone, Renato Franco, Federica Zito Marino, Giuseppe D'Abbronzo, Giuseppe Argenziano, Camila Scharf, Grazia Nucci, Andrea Ronchi, Gerardo Cazzato","doi":"10.3390/ijms26199799","DOIUrl":"10.3390/ijms26199799","url":null,"abstract":"<p><p>Ocular melanoma is a rare but clinically significant malignancy, primarily comprising uveal and conjunctival subtypes. Although sharing some histopathological features with cutaneous melanoma, these tumours are characterized by distinct molecular and biological profiles with direct implications for prognosis and treatment. Uveal melanoma is predominantly driven by mutations in <i>GNAQ</i> and <i>GNA11</i>, along with alterations in <i>BAP1</i>, <i>SF3B1</i>, and <i>EIF1AX</i>, which are key prognostic determinants. Conversely, conjunctival and eyelid melanoma exhibits greater molecular similarity to cutaneous melanoma, commonly involving <i>BRAF</i>, <i>NRAS</i>, <i>NF1</i>, and <i>TERT</i> promoter mutations. Despite progress in the molecular characterization of these entities, metastatic disease continues to confer a poor prognosis, particularly in uveal melanoma. Ongoing research into the molecular basis of ocular melanoma is essential to advance targeted therapies and improve clinical outcomes. The aim of this review is to provide a comprehensive overview of ocular melanoma, with a particular focus on the molecular biology underlying its clinical behaviour and emerging therapeutic opportunities.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Szu-Nian Yang, Yi-Ping Chang, Oscar C Y Yang, Chi-Sheng Wu, Chiu-Chen Huang, Jia-Feng Chang, Chia-Ming Liang, Shun-Tai Dai, Lung Chen, Chih-Ping Hsu
{"title":"Lychee Seed Extract Targets Proliferation, Differentiation, and Cell Cycle Proteins to Suppress Human Colorectal Tumor Growth in Xenograft Models.","authors":"Szu-Nian Yang, Yi-Ping Chang, Oscar C Y Yang, Chi-Sheng Wu, Chiu-Chen Huang, Jia-Feng Chang, Chia-Ming Liang, Shun-Tai Dai, Lung Chen, Chih-Ping Hsu","doi":"10.3390/ijms26199786","DOIUrl":"10.3390/ijms26199786","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading global health challenge, and natural products are increasingly explored for their multi-targeted therapeutic potential. <i>Litchi chinensis</i> seed extract (LCSE) has shown promising anti-cancer activity in vitro, though its in vivo effects remain underexplored. LCSE was analyzed by colorimetric assays and HPLC to quantify the phytochemical composition. Nude mice bearing HT-29 or SW480 xenografts were orally administered LCSE (0.1 or 0.6 g/kg) daily for 14 days. Tumor volume was measured, and immunohistochemistry was used to assess EGFR, p21, p53, Ki-67, CEA, CK20, CDX2, and Bax expression. Phytochemical profiling demonstrated LCSE contains abundant phenolics and flavonoids, with gallic acid as a predominant constituent, underscoring the potential bioactive properties. LCSE significantly inhibited tumor growth in HT-29 xenografts and dose-dependently reduced EGFR, p21, p53, cell cycle proteins and proliferation/differentiation markers. In SW480 tumors, inhibitory effects were evident primarily at the higher dose, with limited reduction in p53 expression. Bax levels remained unchanged in both models, indicating a non-apoptotic mechanism. No systemic toxicity was observed in treated mice. LCSE exhibits dose-dependent anti-tumor activity in CRC xenografts, likely mediated through suppression of proliferation and modulation of key regulatory proteins rather than apoptosis. These findings support LCSE as a safe, multi-target botanical candidate for CRC intervention and justify further mechanistic and translational studies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Combinatorial ERK Inhibition Enhances MAPK Pathway Suppression in BRAF-Mutant Melanoma.","authors":"Corinna Kosnopfel, Tobias Sinnberg, Shrunal Mane, Michelle Dongo, Claus Garbe, Heike Niessner","doi":"10.3390/ijms26199794","DOIUrl":"10.3390/ijms26199794","url":null,"abstract":"<p><p>Small molecule inhibitors targeting BRAF mutations at V600 and downstream MEK represent a significant advancement in treating BRAF-mutant melanoma. However, resistance mechanisms, often involving reactivation of the MAPK pathway via ERK1/2, limit their efficacy. The ERK1/2 inhibitor ravoxertinib (GDC0994) was tested on melanoma cell lines with and without resistance to BRAFi or BRAFi + MEKi. Short-term assays evaluated cell viability, apoptosis induction, and pathway modulation via Western Blot, while long-term effects were assessed using a colony formation assay. Resistant and parental melanoma cells responded to long-term ERKi treatment with reduced growth, independent of sensitivity to BRAF or MEK inhibitors. Adding ERKi to BRAFi/MEKi significantly enhanced apoptosis and growth inhibition, particularly in resistant lines. Although ravoxertinib alone showed limited antitumor activity, its combination with BRAFi/MEKi yielded substantial benefits, especially in chronic settings. These findings suggest that combinatorial regimens incorporating ERK inhibitors represent a promising therapeutic strategy for BRAF-mutant melanoma.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rocío Olivera-Salazar, Pedro Villarejo Campos, Rocío Barrueco Gutiérrez, Luz Vega-Clemente, Luis Javier Serrano, Soledad García Gómez-Heras, Damián García-Olmo, Mariano García-Arranz
{"title":"Combined Treatment of Sodium Butyrate and Bromelain Enhanced Anticancer Effects in Colorectal Cancer Cell Lines: A Promising Therapeutic Approach.","authors":"Rocío Olivera-Salazar, Pedro Villarejo Campos, Rocío Barrueco Gutiérrez, Luz Vega-Clemente, Luis Javier Serrano, Soledad García Gómez-Heras, Damián García-Olmo, Mariano García-Arranz","doi":"10.3390/ijms26199803","DOIUrl":"10.3390/ijms26199803","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most prevalent and lethal cancers worldwide, with few effective treatment options and substantial associated side effects. As a result, there is growing interest in therapeutic alternatives that reduce toxicity. Natural compounds such as sodium butyrate (NaB), a microbial metabolite of dietary fiber, and bromelain, a proteolytic enzyme from pineapple, have shown individual anticancer properties. However, their combined effect in CRC remains underexplored. This study investigates the synergistic potential of NaB and bromelain in colorectal cancer cell lines, focusing on their ability to inhibit proliferation, induce apoptosis, and modulate key molecular pathways. Findings reveal that co-treatment enhances antitumor activity <i>in vitro</i>, suggesting a promising and safer therapeutic strategy for CRC.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgios Malis, Christina N Banti, Alexia Tialiou, Michael R Reithofer, Antonios G Hatzidimitriou, Sotiris K Hadjikakou, Konstantina C Fylaktakidou, George Psomas
{"title":"Cobalt(II) Complexes of 4'-Bromo-Fenamic Acid: Antioxidant Properties, Antibacterial Activity, and Interaction with DNA and Albumins.","authors":"Georgios Malis, Christina N Banti, Alexia Tialiou, Michael R Reithofer, Antonios G Hatzidimitriou, Sotiris K Hadjikakou, Konstantina C Fylaktakidou, George Psomas","doi":"10.3390/ijms26199787","DOIUrl":"10.3390/ijms26199787","url":null,"abstract":"<p><p>The reaction of 4'-bromo-fenamic acid, a bromo-derivative of fenamic acid (the scaffold of the fenamate non-steroidal anti-inflammatory drugs), with Co(II) in the absence or presence of various nitrogen-donor ligands yielded nine novel, neutral mononuclear Co(II) complexes. These complexes were characterized by physicochemical and spectroscopic techniques and single-crystal X-ray crystallography. The biological evaluation of the compounds focused on their antioxidant and antimicrobial efficacy, as well as their interaction with calf-thymus DNA, pBR322 plasmid DNA (in the absence or presence of diverse irradiations) and serum albumins. The complexes have shown significant antioxidant activity since they can scavenge 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals (up to 96.48 ± 0.07%) and reduce H<sub>2</sub>O<sub>2</sub> (up to 96.93 ± 0.53%). Antimicrobial testing revealed that the complexes were more active than free 4'-bromo-fenamic acid with four of them classified as bactericidal agents against selected bacterial strains. The compounds can interact with calf-thymus DNA via intercalation, and the calculated DNA-binding constants are on the 10<sup>6</sup> M<sup>-1</sup> order. The plasmid DNA-cleavage ability of the compounds is strongly enhanced under UVA irradiation (photocleavage > 90%). In addition, the compounds can bind tightly and reversibly to serum albumins with binding constants in the 10<sup>5</sup> M<sup>-1</sup> range.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preexisting Genetic Background Primes the Responses of Human Neurons to Amyloid β.","authors":"Adedamola Saidi Soladogun, Li Zhang","doi":"10.3390/ijms26199804","DOIUrl":"10.3390/ijms26199804","url":null,"abstract":"<p><p>The deposition of amyloid beta (Aβ) in the human brain is a hallmark of Alzheimer's disease (AD). Aβ has been shown to exert a wide range of effects on neurons in cell and animal models. Here, we take advantage of differentiated neurons from iPSC-derived neural stem cells of human donors to examine its effects on human neurons. Specifically, we employed two types of neurons from genetically distinct donors: one male carrying APO E2/E2 (M E2/E2) and one female carrying APO E3/E3 (F E3/E3). Genome-wide RNA-sequencing analysis identified 64 and 44 genes that were induced by Aβ in M E2/E2 and F E3/E3 neurons, respectively. GO and pathway analyses showed that Aβ-induced genes in F E3/E3 neurons do not constitute any statistically significant pathways whereas Aβ-induced genes in M E2/E2 neurons constitute a complex network of activated pathways. These pathways include those promoting inflammatory responses, such as IL1β, IL4, and TNF, and those promoting cell migration and movement, such as chemotaxis, migration of cells, and cell movement. These results strongly suggest that the effects of Aβ on neurons are highly dependent on their genetic background and that Aβ can promote strong responses in inflammation and cell migration in some, but not all, neurons.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valeria Lysakova, Aleksey Streletskiy, Olga Sineva, Elena Isakova, Larissa Krasnopolskaya
{"title":"Screening of Basidiomycete Strains Capable of Synthesizing Antibacterial and Antifungal Metabolites.","authors":"Valeria Lysakova, Aleksey Streletskiy, Olga Sineva, Elena Isakova, Larissa Krasnopolskaya","doi":"10.3390/ijms26199802","DOIUrl":"10.3390/ijms26199802","url":null,"abstract":"<p><p>Recently, the search for new antimicrobial compounds, including the secondary metabolites of basidiomycetes, has become increasingly important. Representatives of this division of higher fungi have high biosynthetic abilities, which contributes to their use as producers. In this work, extracts of culture liquids and submerged mycelia from 18 strains representing three different orders of basidiomycetes were studied. For this purpose, the submerged cultivation of strains, extraction of biological material, and evaluation of the extract's antimicrobial activity using the agar well diffusion method were carried out. The minimum inhibitory concentration was determined for extracts with strong activity. The most promising ones were analyzed using HPLC-MS. As a result, it was found that 16 strains contained antimicrobial metabolites. Thus, the strains selected for further work were <i>Hericium corraloides</i> 4, which showed not only the antibacterial but also antifungal activity of cultural liquid and submerged mycelia extracts, and <i>Fomitopsis betulina</i> 3, <i>Fomitopsis pinicola</i> 2, <i>Hericium erinaceus</i> 1, and <i>Laetiporus sulphureus</i> 4, whose cultural liquid extracts exhibited high antibacterial activity against Gram-positive and Gram-negative test cultures. For these strains, metabolic profiles were obtained using the method HPLC-MS. Using this method, two metabolites were preliminary identified: hericerin in <i>H. erinaceus</i> 1 and sulfureuine H in <i>L. sulphureus</i> 4.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Venous Thrombogenesis and Cervical Cancer: Plasma MicroRNAs as Prognostic Indicators of Tumor Behavior.","authors":"Mariana Teixeira Costa, Beatriz Vieira Neto, José Brito da Silva, Luísa Carvalho, Lurdes Salgado, Deolinda Pereira, Filomena Adega, Valéria Tavares, Rui Medeiros","doi":"10.3390/ijms26199796","DOIUrl":"10.3390/ijms26199796","url":null,"abstract":"<p><p>Cervical cancer (CC) is the fourth most common cancer among women globally, with venous thromboembolism (VTE) representing a life-threatening complication. Cancer-associated thrombosis (CAT) arises from tumor-driven activation of hemostasis, worsening prognosis. Recently, circulating microRNAs (miRNAs) have emerged as potential biomarkers for both CAT and cervical tumorigenesis. Thus, this study aimed to assess the implications of five miRNAs-miR-20a-5p, -23a-3p, -125b-5p, -145-5p, and -616-3p-in CC-related VTE context. These miRNAs were quantified by RT-qPCR in plasma from 69 CC patients before treatment. Briefly, VTE occurred in nine patients, decreasing overall survival (OS) [log-rank test, <i>p</i> = 0.005; hazard ratio (HR) = 4.78; 95% confidence interval (CI), 1.42-16.05]. Lower miR-20a-5p levels predicted VTE (ꭓ<sup>2</sup> test, <i>p</i> = 0.027) and, in subgroup analyses, they were linked to cervical squamous cell carcinoma (CSCC) and older age (ꭓ<sup>2</sup> test, <i>p</i> = 0.003 and <i>p</i> = 0.043, respectively). In VTE patients, miR-145-5p downregulation was associated with improved OS (log-rank test, <i>p</i> = 0.018), an effect also observed in the adenocarcinoma (ADC) subgroup (log-rank test, <i>p</i> = 0.039). The remaining miRNAs showed subtype-specific links to clinicopathological features and survival. These findings highlight the potential value of circulating miRNAs in thrombotic risk and prognosis assessment in CC.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}