Biological Procedures Online最新文献

{"title":"Identification of Kaempferol for Skeletal Muscle Wasting in Cancer Cachexia Through Bibliometric Analysis and Network Pharmacology: Metabolomic and Experimental Evaluation.","authors":"Chenhong Zhu, Sheng Chen, Ying Qu, Mingyu He, Ren Nie, Zhengyi Liu, Yuxiang Hu, Jiangnan Huang, Chun Shen, Ziyi Chen, Jing Wen, Lihuai Wang, Yinhui Sun","doi":"10.1186/s12575-026-00361-1","DOIUrl":"10.1186/s12575-026-00361-1","url":null,"abstract":"<p><strong>Background: </strong>Cancer cachexia (CC) is a multifactorial syndrome characterized by progressive skeletal muscle wasting, systemic inflammation, and metabolic dysregulation. Traditional Chinese medicine (TCM) contains numerous bioactive compounds with potential multitarget effects, but systematic strategies for identifying and experimentally evaluating candidate compounds for CC remain limited. This study aimed to identify and evaluate a TCM-derived candidate compound for CC-associated skeletal muscle wasting.</p><p><strong>Methods: </strong>Bibliometric analysis was used to identify frequently studied TCM formulas and core herbs in cachexia-related research, followed by network pharmacology analysis of candidate compounds and associated pathways. Kaempferol (KA) was then evaluated in A549 tumor-bearing mice by assessing tumor burden, cachexia-related phenotypes, skeletal muscle histology, untargeted metabolomics, inflammatory mediators, muscle degradation-related markers, autophagy-associated endpoints, and ultrastructure. A549-conditioned medium (A549-CM)-treated C2C12 myotubes were used for complementary in vitro evaluation under conditions with or without supplemental prostaglandin E2 (PGE2).</p><p><strong>Results: </strong>KA was selected as a representative candidate based on its distribution among the core herbs, network associations, and reported pharmacological activities. In A549 tumor-bearing mice, high-dose KA (100 mg/kg/day) significantly reduced tumor weight and was accompanied by improvements in food intake, estimated tumor-free body weight, gastrocnemius weight, myofiber cross-sectional area, and forelimb grip strength compared with the model group (all P < 0.05). KA treatment was also associated with lower serum TNF-α, IL-6, and PGE2 concentrations; reduced skeletal muscle COX-2, Atrogin-1, and MuRF1 expression; lower LC3B-II/LC3B-I ratio and p62 protein level; and fewer autophagic vacuole-like structures (all P < 0.05). Untargeted metabolomics revealed KA-associated alterations in arachidonic acid metabolism, glycerophospholipids, amino acids, and energy-related metabolites. In A549-CM-treated C2C12 myotubes, KA modulated atrophy-related gene expression, autophagy-associated endpoints, and cytoplasmic vacuolation in both the absence and presence of supplemental PGE2 (P < 0.05).</p><p><strong>Conclusions: </strong>KA reduced tumor burden and was accompanied by improvements in cachexia-related phenotypes and skeletal muscle outcomes. The molecular, metabolic, and cell-based findings further associated KA treatment with lower systemic inflammatory mediator levels, reduced muscle protein degradation-related markers, and alterations in inflammatory lipid metabolism and autophagy-associated endpoints. These findings support further investigation of KA as a TCM-derived candidate for CC-associated skeletal muscle wasting. Future studies should distinguish its direct muscle-related effects from the systemic benefits associa","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential Mechanism of Zhizhu Decoction in the Treatment of Constipation-Predominant Irritable Bowel Syndrome Through Network Pharmacology and Experimental Validation.","authors":"Zhibin Zhang, Rong Wu, Fang Liu, Simin Chen, Lina Guan, Yu Zhan, Yong Wen, Xuegui Tang","doi":"10.1186/s12575-026-00353-1","DOIUrl":"10.1186/s12575-026-00353-1","url":null,"abstract":"<p><strong>Aim of the study: </strong>Zhizhu Decoction (ZZD), a classical traditional Chinese herbal formula composed of Atractylodis Macrocephalae Rhizoma and Aurantii Fructus Immaturus, has long been used to treat gastrointestinal disorders resembling constipation-predominant irritable bowel syndrome (IBS-C). This study aimed to elucidate the potential therapeutic mechanisms of ZZD in IBS-C by integrating network pharmacology, molecular docking, and in vivo experimental validation.</p><p><strong>Materials and methods: </strong>Active compounds and targets of ZZD were identified using network pharmacology, followed by molecular docking to evaluate compound-target interactions. An IBS-C rat model was established to assess the therapeutic effects of ZZD. H&E and AB-PAS staining were used to observe histological lesions in colonic tissues. TUNEL staining was performed to detect apoptotic epithelial cells in colon sections. Immunohistochemistry (IHC) was used to assess the spatial distribution of TPH1 and tight junction proteins ZO-1 and Claudin-1 in colon tissues. RT-qPCR combined with western blotting was used to quantify the expression of ZO-1 and Claudin-1. Serum 5-HT concentrations were determined by ELISA, and liquid chromatography-mass spectrometry (LC-MS) was used to measure fecal short-chain fatty acid (SCFA) levels.</p><p><strong>Results: </strong>Network pharmacology analysis: ZZD contains 23 bioactive compounds. This herbal formula mainly acts on core targets including AKT1, BCL-2, Caspase-3, and EGFR, with prominent enrichment of PI3K/AKT, apoptosis, TNF and NF-κB signaling. Molecular docking results further confirmed the favorable binding affinity of its main active ingredients (luteolin, naringenin, 3β-acetoxyatractylone, and 8β-ethoxyatractylenolide III) to these targets. In vivo experiments: In IBS-C model rats, ZZD intervention alleviated weight loss, elevated 24-h fecal output, fecal water content and Bristol stool scale scores, accelerated small intestinal carbon powder transit, and lowered visceral hypersensitivity as indicated by reduced AWR scores (P < 0.05), and it recovered goblet cell abundance, improved crypt architecture and thickened colonic mucus and muscular layers. ZZD markedly alleviated colonic injury and maintained intestinal barrier and tight junction integrity, as evidenced by upregulation of mRNA and protein levels of tight junction proteins ZO-1 and Claudin-1 (P < 0.05), as well as restoration of their continuous distribution in rat colonic tissues. ZZD suppressed epithelial apoptosis by downregulating Caspase-3 and upregulating BCL-2 and c-JUN (P < 0.05). In addition, IHC staining for TPH1, a specific marker of EC cells, revealed that ZZD treatment significantly increased the number of TPH1‑positive cells in the colonic epithelium (P < 0.0001), accompanied by elevated serum 5‑HT levels (P < 0.0001), suggesting recovery of the EC cell population and intestinal 5‑HT synthetic capacity. Moreover, ZZD increased th","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Chang-Wei-Qing Combined with PD-1 Inhibitor Alleviates Colitis-Associated Colorectal Tumorigenesis by Modulating the Gut Microbiota and Restoring Intestinal Barrier.","authors":"Junkai Wen, Shunyun Wang, Kexiang Sun, Haoyue Wang, Zeting Yuan, Wanli Deng","doi":"10.1186/s12575-026-00352-2","DOIUrl":"10.1186/s12575-026-00352-2","url":null,"abstract":"","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Validation of Genes Involved in Immune and Ferroptosis in Polycystic Ovarian Syndrome Using Bioinformatics and Experimental Approach.","authors":"Yang Chen, Liwei Xing, Zhe He, Xiaoqi Wang, Yujing Chen, Xiaowei Yuan, Rong Zhao","doi":"10.1186/s12575-026-00355-z","DOIUrl":"10.1186/s12575-026-00355-z","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disease. This study aimed to investigate the synergistic role of immune dysregulation and ferroptosis during the pathogenesis of PCOS.</p><p><strong>Methods: </strong>Through integrating multiple Gene Expression Omnibus (GEO) datasets, differentially expressed genes (DEGs) were screened and subjected to functional enrichment analysis; weighted gene co‑expression network analysis combined with LASSO, RandomForest, and support vector machine‑recursive feature elimination algorithms were employed to identify key candidate genes; in vitro, human ovarian granulosa cells (KGN) were treated with dihydrotestosterone (DHT), NNMT expression was regulated via lentiviral vectors together with ferroptosis inhibitor intervention, and cell viability, cytotoxicity, and ferroptosis‑related indicators were examined; in vivo, a PCOS mouse model was established using dehydroepiandrosterone, and ovarian pathology, hormone levels, as well as molecular expression of the ferroptosis pathway were analyzed.</p><p><strong>Results: </strong>DEGs in PCOS were significantly enriched in immune response and ferroptosis pathways. Twelve candidate genes were identified through screening multiple GEO datasets and demonstrated diagnostic potential. DHT induced ferroptosis in KGN cells by upregulating NNMT, manifesting as reduced cell viability, increased LDH release, accompanied by Fe²⁺ accumulation, enhanced lipid peroxidation, downregulation of SLC7A11/GPX4, and upregulation of ACSL4. This process could be partially reversed by ferroptosis inhibitors. Knockdown of NNMT effectively alleviated the DHT‑induced ferroptosis phenotype. Ovaries from PCOS mice exhibited typical pathological alterations, concurrent with elevated NNMT expression and abnormal activation of the ferroptosis pathway.</p><p><strong>Conclusion: </strong>This study has uncovered novel mechanisms underlying the development and progression of PCOS, offering potential targets for its diagnosis and treatment.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huangjing Jiangzhi Granules Ameliorate Nonalcoholic Fatty Liver Disease by Activating the FOXA1-DERL1 Regulatory Axis to Suppress Lipid Accumulation, Endoplasmic Reticulum Stress, and Apoptosis.","authors":"Dongyu Xie, Yunqing Wu, Jiawei Jiang, Lu Xu, Xueqin Sun, Jun Ouyang, Biao Xi, Dongliang Zhang, Haina Xie","doi":"10.1186/s12575-026-00356-y","DOIUrl":"10.1186/s12575-026-00356-y","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is an emerging health issue worldwide. It involves intrahepatic lipid accumulation that is potentially deleterious. Traditional Chinese Medicine called Huangjing Jiangzhi (HJJZ) granules holds promise for NAFLD treatment. This study explored the mechanism by which HJJZ granules improve NAFLD in male C57BL/6 mice and oleic acid-induced HepG2 cells.H&E staining, Oil Red O staining, the TUNEL assay, and Western blotting were employed. Chromatin immunoprecipitation and dual-luciferase reporter assays were used to examine transcriptional regulation.HJJZ granules alleviated hepatic steatosis, reduced serum ALT/AST levels, improved lipid profiles, suppressed hepatocyte apoptosis, and inhibited the PERK-eIF2α-CHOP pathway in high-fat diet-fed mice and oleic acid-treated cells. These granules specifically upregulated the expression of the transcription factor FOXA1. FOXA1 knockdown abolished all protective effects of HJJZ granules. Mechanistically, FOXA1 was shown to transcriptionally activate DERL1 expression. DERL1 overexpression rescued the steatotic, apoptotic, and endoplasmic reticulum (ER) stress phenotypes in FOXA1-deficient cells.HJJZ granules ameliorate NAFLD by attenuating lipid accumulation, apoptosis, and ER stress. This protective effect is mediated through FOXA1 upregulation, which, in turn, transcriptionally enhances DERL1 expression, thereby mitigating ER stress. The FOXA1/DERL1 axis is a critical mechanistic pathway for HJJZ granule action.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Mechanisms of Ruangan Huayu Formula in Liver Cirrhosis: Network Pharmacology, Molecular Docking and Experimental Validation.","authors":"Haina Xie, Yujie Wang, Mengqian Zhu, Luming Hou, Xin Sun, Xiaodi Gao, Sicheng Gao, Junfeng Zhu","doi":"10.1186/s12575-026-00354-0","DOIUrl":"10.1186/s12575-026-00354-0","url":null,"abstract":"<p><strong>Background: </strong>Liver cirrhosis remains a challenging global health issue for which current treatment options are largely limited to managing acute liver failure, with no definitive curative therapies available. The Ruangan Huayu Formula (RGHY) has shown promising clinical effects in recent years; however, its comprehensive chemical profile and the specific mechanisms underlying its anti-cirrhotic activity remain to be fully elucidated.</p><p><strong>Methods: </strong>Ultra-high-performance liquid chromatography-Orbitrap-explorative mass spectrometry (UHPLC-OE-MS) was performed to characterize the chemical profile of the RGHY. Network pharmacology and molecular docking were leveraged to identify potential targets and pathways. Antifibrotic efficacy and underlying mechanisms of RGHY were evaluated using a thioacetamide (TAA)-induced liver fibrosis model in male Sprague-Dawley rats, along with transforming growth factor-beta (TGF-β)-stimulated human hepatic stellate cells (LX-2) in vitro.</p><p><strong>Results: </strong>UHPLC-OE-MS study showed various chemical components of RGHY. Network pharmacology analysis revealed 57 intersecting targets, with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway standing out. Molecular docking studies returned strong binding scores for AKT1, SRC, PIK3CA, and STAT3 as core targets key to RGHY compounds. RGHY was shown to significantly alleviate TAA-induced liver injury and fibrosis by down-regulating the PI3K/AKT pathway. In vitro, RGHY-containing serum and its key bioactive compounds (7,3',4'-trihydroxyflavone and sulfuretin) disrupted TGF-β-induced LX-2 cell activation, migration, and fibrogenesis. The PI3K/AKT signaling pathway was confirmed to involve in mediating the antifibrotic effects of RGHY.</p><p><strong>Conclusion: </strong>RGHY and its bioactive compounds 7,3',4'-trihydroxyflavone and effectively attenuated liver fibrosis and hepatic stellate cell activation through multicomponent, multitarget actions, primarily by modulating the PI3K/AKT pathway. These findings provide mechanistic evidence supporting its traditional use and its potential as a therapeutic candidate for liver cirrhosis.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148496999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Expression of SAMM50 Indicates Poor Clinical Prognosis in Hepatocellular Carcinoma and Represents a Potential Novel Biomarker.","authors":"Huawei Zhai, Banglian Cai, Zihao Zheng, Fujing Cai, Zhenmiao Wan, Yuchen Pan, Guangzheng Sun, Haifeng Zhang, Jinhai Li","doi":"10.1186/s12575-026-00351-3","DOIUrl":"10.1186/s12575-026-00351-3","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Identifying diagnostic and prognostic biomarkers and therapeutic targets for hepatocellular carcinoma (HCC) is essential to improve risk stratification, guide individualized treatment, and enhance therapeutic efficacy.The expression of SAMM50 (Sorting and Assembly Machinery Component 50) was initially analyzed in publicly accessible curated genomic and proteomic databases, such as the Cancer Cell Line Encyclopedia, the Human Protein Atlas, and other HCC-specific repositories. This analysis revealed differential expression patterns between HCC and non-neoplastic liver tissue. Subsequently, clinicopathological data and tissue specimens were collected from 200 HCC patients who underwent treatment at our institution. The protein and transcript levels of SAMM50 were experimentally measured in paired HCC and adjacent non-tumorous tissues using immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The association between SAMM50 expression and key clinicopathological features was further evaluated. Univariate and multivariate Cox proportional hazards analyses were performed to determine the independent prognostic value of SAMM50 expression in HCC. Based on these results, a reproducible and clinically applicable nomogram, supported by a forest plot, was constructed to facilitate prognostic prediction and support individualized therapeutic decision-making. Finally, in vitro and in vivo experiments were conducted to characterize the phenotypic alterations in HCC cells after SAMM50 knockdown, thereby confirming its involvement in critical oncogenic behaviors.This research demonstrated that the mRNA and protein levels of SAMM50 in HCC tissues were elevated compared to those in normal liver and adjacent tissues. Immunohistochemistry findings confirmed that SAMM50 protein levels were persistently higher in HCC tissues than in paired adjacent tissues. High expression of SAMM50 was correlated with unfavorable clinicopathological factors, encompassing pretreatment alpha-fetoprotein (AFP) levels, tumor size, T stage, American Joint Committee on Cancer (AJCC) stage, histological grade, and worse overall survival.Specifically, high expression of SAMM50 was linked to shorter overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Moreover, univariate and multivariate Cox analyses were conducted to investigate the association between SAMM50 expression and clinicopathological features in HCC patients and to identify independent prognostic factors. The area under the receiver operating characteristic (ROC) curve (AUC) for SAMM50 was 0.863, suggesting its potential as a diagnostic marker for HCC, though further validation in independent cohorts is needed. Silencing of SAMM50 inhibited HCC cell proliferation, migration, and invasion, promoted apoptosis in vitro, and suppressed HCC growth in vivo.This research demonstrates that SAMM50 shows potential diagnostic value for HCC, though this","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MKRN1 suppresses cuproptosis in colorectal cancer through ubiquitin-dependent regulation of SLC31A1.","authors":"Huali Luo, Jiaxin Hu, Xiaojing Lin, Shu Zhao, Mengxing Li, Qinshan Li","doi":"10.1186/s12575-026-00349-x","DOIUrl":"10.1186/s12575-026-00349-x","url":null,"abstract":"<p><strong>Background: </strong>Despite the emerging role of cuproptosis in cancer biology, the regulatory mechanism by which ubiquitination modulates this process through MKRN1 and SLC31A1 in colorectal cancer (CRC) progression remains unclear. This study aimed to elucidate the functional relationship between MKRN1, SLC31A1, and cuproptosis in CRC.</p><p><strong>Methods: </strong>Stable MKRN1-knockdown and MKRN1-overexpressing colorectal cancer (CRC) cell lines were established. Cuproptosis was induced using elesclomol and copper sulfate, and assessed by cell viability assays,, measurement of intracellular copper levels, and western blot analysis of hallmark proteins (HSP70 and DLAT). The MKRN1-SLC31A1 interaction was examined by co-immunofluorescence, ubiquitination assays (employing MG132, CHX, and linkage-specific ubiquitin mutants), and quantitative real-time PCR (q-PCR). Mitochondrial function was evaluated via JC-1 staining and transmission electron microscopy. Rescue experiments were conducted using dual genetic manipulation of MKRN1 and SLC31A1. Finally, in vivo validation was performed using a xenograft model in NOD-SCID mice.</p><p><strong>Results: </strong>MKRN1 overexpression significantly attenuated cuproptosis agonist-induced cytotoxicity and reduced intracellular copper accumulation. Mechanistically, MKRN1 directly interacts with SLC31A1 and promotes its polyubiquitination and subsequent proteasomal degradation. This degradation prevents copper overload, helping to maintain mitochondrial integrity.(as evidenced by maintained mitochondrial membrane potential and Tomm20 expression) and suppressing key cuproptosis hallmarks, including HSP70 induction and DLAT oligomerization. Genetic rescue experiments confirmed that SLC31A1 knockdown reversed the cuproptosis sensitivity conferred by MKRN1 depletion. Consistently, MKRN1 overexpression promoted tumor growth in vivo while concurrently suppressing cuproptosis.</p><p><strong>Conclusion: </strong>In summary, MKRN1 suppresses copper-induced cell death in colorectal cancer by promoting the ubiquitination and proteasomal degradation of the copper transporter SLC31A1, thus limiting copper accumulation and mitochondrial toxicity. This mechanism confers resistance to copper-induced cell death and facilitates tumor progression, establishing the MKRN1/SLC31A1 axis as a promising therapeutic target.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Comparison of Two Rabbit Tibiofemoral Joint Replacement Models.","authors":"Bailey V Fearing, Sarah M Romereim, Matthew R Smykowski, K Eddie Afetse, Aatif A Jabbar, Elizabeth W Sloop, Kerry A Danelson, Jesse E Otero","doi":"10.1186/s12575-026-00350-4","DOIUrl":"10.1186/s12575-026-00350-4","url":null,"abstract":"<p><strong>Background: </strong>Joint arthroplasty, replacement of damaged articular surfaces with a prosthetic component, is an increasingly common orthopaedic procedure. Despite the overall success of arthroplasty, complications such as periprosthetic joint infection remain a persistent problem with severe consequences. With increasing clinical demands, the need for a reliable, reproducible model for testing therapeutic strategies for arthroplasty complications is fundamental.</p><p><strong>Results: </strong>In this study, a novel small animal model was designed and evaluated for downstream investigations. Two different implant designs (tibial vs. femoral) and surgical approaches were compared. The femoral implant resulted in fewer complications such as knee joint destabilization, severe swelling, and erosion of articular cartilage and subchondral bone. Rabbit care methodology was also optimized during model development, and both the process and results are presented to promote ethical and reproducible preclinical model research.</p><p><strong>Conclusions: </strong>The custom porous coated unicondylar femoral implant with a polished condylar surface demonstrated far fewer complications and adverse events than the tibial implant, as well as robust osseointegration. This will serve as a model for future investigations in preventing and treating joint arthroplasty complications.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethacrynic Oxadiazole 6u Induces Apoptosis by Targeting mTOR/c-Flip Axis and Noxa in Lymphoma Cells.","authors":"Yafei Kuang, Shuoyan Feng, Jinxiao Sun, Zhuomin Tan, Xuan Bao, Yongmi Huang, Yuetong Wang, Ping Gong, Samuel Waxman, Guisen Zhao, Jingyi Zhang, Yongkui Jing","doi":"10.1186/s12575-026-00348-y","DOIUrl":"10.1186/s12575-026-00348-y","url":null,"abstract":"<p><strong>Background: </strong>Evasion of apoptosis is a major cause of therapy failure in lymphoma. We studied a covalent compound 6u with an α, β-saturated carbonyl group derived from the diuretic drug ethacrynic acid to induce apoptosis of lymphoma cells by targeting antiapoptotic proteins.</p><p><strong>Results: </strong>We found that 6u induces apoptosis in 4 lymphoma cell lines, Daudi, Romas, Jeko-1 and Jurkat, accompanied by down-regulation of c-Flip and Mcl-1, as well as upregulation of Noxa. The down-regulation of Mcl-1 relies on Noxa induction and that the down-regulation of c-Flip is mediated by inhibiting protein synthesis pathway through covalent binding to mTOR complexes. Overexpression of c-Flip and silencing Noxa attenuate 6u-induced apoptosis. 6u modified with the saturated carbonyl structure loses the mTOR inhibition and apoptosis induction abilities. 6u exhibits potent anti-lymphoma effects in mantle cell lymphoma Jeko-1 xenografts without causing toxicity.</p><p><strong>Conclusion: </strong>6u functions as an apoptosis inducer through the α, β-saturated carbonyl group to decrease c-Flip and to induce Noxa. 6u represents a new type of covalent agent for targeting lymphoma by inducing apoptosis.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}