Biomolecules & biomedicine最新文献

{"title":"Targeting TXNIP for neuroprotection: A novel approach to reducing inflammation and promoting recovery in ischemic stroke.","authors":"Chongxin He, Yong Bao, Yong Xu, Jingjing Cheng, Xinxin Hu","doi":"10.17305/bb.2024.11366","DOIUrl":"https://doi.org/10.17305/bb.2024.11366","url":null,"abstract":"<p><p>Ischemic stroke often results in high mortality and significant disability. Current research primarily focuses on understanding neuroinflammation and cell death following a stroke to identify novel therapeutic targets. This study investigates the endothelial cell-specific role of Thioredoxin interacting protein (TXNIP) in ischemic stroke and its underlying molecular mechanisms both in vitro and in vivo. By targeting endothelial cells, we aim to determine how TXNIP knockdown promotes neuroprotection, enhances angiogenesis, and reduces inflammation post-stroke. In vitro, an oxygen-glucose deprivation (OGD) model using bEnd.3 cells simulated ischemic conditions. Cellular injury was evaluated through cell proliferation and angiogenesis assays, while dual immunofluorescence staining assessed ZO-1 and CD31 expression. Western blotting measured protein levels of TXNIP, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), ASC, pro-caspase-1, and interleukin-1β (IL-1β). In vivo, a middle cerebral artery occlusion (MCAO) mouse model was employed to mimic ischemic stroke. Brain injury was evaluated using triphenyl tetrazolium chloride (TTC) and Nissl staining, and molecular changes in injury markers were assessed via Western blot analysis. In vitro, TXNIP knockdown promoted cell proliferation and angiogenesis, reduced inflammation, and decreased ZO-1 and CD31 fluorescence intensity. TXNIP knockdown also reversed OGD-induced upregulation of TXNIP, NLRP3, ASC, pro-caspase-1, and IL-1β. In vivo, TXNIP knockdown improved neurological recovery, reflected by lower Longa scores, increased Nissl body presence, and reduced infarct size. These findings suggest that TXNIP knockdown mitigates inflammation, enhances angiogenesis, and reduces cerebral damage following ischemic stroke. This provides valuable insights into potential endothelial cell-specific therapeutic strategies for stroke treatment.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association of rs25487 of the XRCC1 gene and rs13181 of the ERCC2 gene polymorphisms with the ovarian cancer risk.","authors":"Tatiana Zavarykina, Maria Kapralova, Polina Lomskova, Aleksandra Asaturova, Grigory Khabas, Lyailya Kayumova, Dmitry Khodyrev, Irina Pronina, Maya Sannikova, Svetlana Khokhlova","doi":"10.17305/bb.2024.11314","DOIUrl":"https://doi.org/10.17305/bb.2024.11314","url":null,"abstract":"<p><p>Ovarian cancer (OC) is the most lethal gynecological cancer worldwide. DNA damage plays an important role in cancer development, and the proteins encoded by XRCC1 and ERCC2 are important components of the DNA repair system. This study aimed to examine the relationship between the rs25487 XRCC1 and rs13181 ERCC2 polymorphisms and the risk of OC development in women from the Moscow region. DNA was isolated from the blood of 129 healthy donors and tissues and blood samples from 125 patients with OC and studied using real-time PCR. An increase in odds ratios (OR) was obtained for OC tissue and blood for both T (OR = 1.46, 95% confidence interval [CI] = 1.22-1.76, P = 0.00005), and for T/T of rs25487 XRCC1. The most significant OR values were found for the T/T genotype using the codominant model (OR = 2.11, 95% CI = 1.44-3.07, P = 0.00006) and dominant model (OR = 3.13, 95% CI = 1.44-6.79, P = 0.0025) for the pooled blood and tissue groups. For rs13181 ERCC2, differences were observed for the T/G genotype in OC tissues (OR = 0.69, 95% CI = 0.51-0.92, P = 0.011) in the codominant model. In this study, the association of allele T and genotypes of rs25487 XRCC1 and T/G of rs13181 ERCC2 with OC was shown. Our results indicate that these polymorphisms may be involved in the pathogenesis of OC and are promising for further studies on therapeutic applications in OC.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting cell types and densities in the tumor microenvironment improves prognostic risk assessment for breast cancer.","authors":"Pu Liu, Xueli Zhang, Wenwen Wang, Yunping Zhu, Yongfang Xie, Yanhong Tai, Jie Ma","doi":"10.17305/bb.2024.10974","DOIUrl":"10.17305/bb.2024.10974","url":null,"abstract":"<p><p>A comprehensive evaluation of the relationship between the densities of various cell types in the breast cancer tumor microenvironment and patient prognosis is currently lacking. Additionally, the absence of a large patch-level whole slide imaging (WSI) dataset of breast cancer with annotated cell types hinders the ability of artificial intelligence to evaluate cell density in breast cancer WSI. We first employed Lasso-Cox regression to build a breast cancer prognosis assessment model based on cell density in a population study. Pathology experts manually annotated a dataset containing over 70,000 patches and used transfer learning based on ResNet152 to develop an artificial intelligence model for identifying different cell types in these patches. The results showed that significant prognostic differences were observed among breast cancer patients stratified by cell density score (P = 0.0018), with the cell density score identified as an independent prognostic factor for breast cancer patients (P < 0.05). In the validation cohort, the predictive performance for overall survival (OS) was satisfactory, with area under the curve (AUC) values of 0.893 (OS) at 1-year, 0.823 (OS) at 3-year, and 0.861 (OS) at 5-year intervals. We trained a robust model based on ResNet152, achieving over 99% classification accuracy for different cell types in patches. These achievements offer new public resources and tools for personalized treatment and prognosis assessment.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"106-114"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of the prognostic nomogram and treatment recommendation in patients with mixed endometrial carcinoma treated with hysterectomy.","authors":"Luyao Kang, Gaili Ji, Nan Zhang, Jie Meng, Duan Liu, Hongyu Li","doi":"10.17305/bb.2024.10754","DOIUrl":"10.17305/bb.2024.10754","url":null,"abstract":"<p><p>Mixed endometrial carcinomas (MECs) account for approximately 3%-10% of all endometrial carcinomas (ECs). These are defined as a combination of two or more distinct histologic subtypes, with at least one being a type II tumor that constitutes at least 5% of the overall tumor. However, the associated prognostic factors and treatment of MECs remain unclear. The study aimed to identify the independent prognostic factors of MEC patients treated with hysterectomy and to explore the optimal treatment modalities for overall survival (OS) and cancer-specific survival (CSS). Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 12,848 MEC patients treated with hysterectomy were screened. Independent prognostic factors were identified by Cox regression analysis and used to construct the nomogram. The concordance indices (C-indices) of OS and CSS were 0.807 and 0.834 in the training set. Validation of the nomogram revealed that the receiver operating curve (ROC) maintained good discrimination, the decision curve analysis (DCA) had a high net benefit rate, and the calibration curves showed high consistency. Patients were grouped by the nomogram formula and the number of positive regional lymph nodes (NPR-Lymph node) to evaluate the therapeutic outcomes of chemotherapy, radiotherapy, neoadjuvant treatment, and lymph node operation. Survival analysis revealed that chemotherapy could improve the prognosis for OS and CSS in the high-risk group and in the group with NPR-Lymph node counts above 1 (P < 0.05). Radiotherapy was associated with better OS and CSS in the intermediate-risk and high-risk groups, and in the group with NPR-Lymph node counts above 0 (P < 0.05). Lymphadenectomy was found to prolong OS and CSS in the high-risk group (P < 0.05), while neoadjuvant treatment did not prolong OS and CSS in any group. Thus, in this study, the nomogram for MEC patients treated with hysterectomy was successfully built and validated which could effectively predict the prognosis and identify at-risk population to guide clinical decision making. The NPR-Lymph node was identified as a potentially strong prognostic indicator with good clinical value.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"94-105"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0023179 modulated the processes of proliferation, apoptosis, and EMT in non-small cell lung cancer cells via the miR-615-5p/CDH3 axis.","authors":"Qingkui Guo, Min Zheng, Chen Zhu, Bin Wu","doi":"10.17305/bb.2024.10944","DOIUrl":"10.17305/bb.2024.10944","url":null,"abstract":"<p><p>Circular RNA (circRNA) has been widely studied as a competitive endogenous RNA targeting microRNA (miRNA)/messenger RNA to regulate cancer progression. However, the regulatory mechanism of circ_0023179 in non-small cell lung cancer (NSCLC) remains unclear. The expression levels of circ_0023179, miR-615-5p and Cadherin 3 (CDH3) in NSCLC were detected using quantitative real-time polymerase chain reaction. The stability of circ_0023179 was verified using ribonuclease R enzyme, actinomycin D and agarose gel electrophoresis. Colony formation and thymidine analog 5-ethynyl-2'-deoxyuridine assays were performed to examine proliferation changes in NSCLC cells. Western blot was used to assess the levels of CDH3 and epithelial-mesenchymal transition (EMT)-related marker proteins to evaluate EMT. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to explore the potential mechanisms of circ_0023179 in regulating NSCLC progression. Finally, the effects of circ_0023179 on NSCLC tumour growth in vivo were explored using a nude mouse subcutaneous tumour model. The results showed that the expression of circ_0023179 was remarkably higher in NSCLC tissues and cells, and it had a significant effect on NSCLC cell proliferation. Additionally, the knockdown of circ_0023179 significantly inhibited tumour growth in NSCLC mice. Mechanistically, circ_0023179 alleviated its inhibition of downstream CDH3 through the sponge-like adsorption of miR-615-5p. The downregulation of miR-615-5p and the upregulation of CDH3 mitigated the inhibitory effect of silencing circ_0023179 on NSCLC cell proliferation. In conclusion, silencing circ_0023179 inhibited NSCLC cell proliferation by targeting the miR-615-5p/CDH3 axis involved in NSCLC progression.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"155-164"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-149-3p targeting <i>TMPRSS4</i> regulates the sensitivity to cisplatin to inhibit the progression of lung cancer.","authors":"Beibei Qin, Dongfang Tang, Mingzhi Zhang","doi":"10.17305/bb.2024.11163","DOIUrl":"10.17305/bb.2024.11163","url":null,"abstract":"<p><p>Lung cancer cells tend to develop resistance to cisplatin (DDP) during continuous chemotherapy, making it crucial to improve DDP sensitivity to enhance therapeutic outcomes. The levels of miR-149-3p in lung tissues and cells, as well as the biological behaviors of lung cancer cells, were analyzed. H446/DDP and A549/DDP cell lines were established to investigate how miR-149-3p affects lung cancer cells' sensitivity to DDP. Bioinformatics analysis predicted transmembrane serine protease 4 (TMPRSS4) as a downstream target of miR-149-3p, which was subsequently confirmed. Western blot analysis was used to examine proteins related to migration, invasion, apoptosis, and TMPRSS4 expression. Additionally, a subcutaneous graft tumor model in nude mice was created to assess the impact of miR-149-3p on tumor growth. In lung cancer tissues and cells, miR-149-3p expression was reduced, while TMPRSS4 expression was elevated. Overexpression of miR-149-3p inhibited cancer progression, promoted apoptosis, and enhanced the chemosensitivity of lung cancer cells to DDP. Moreover, miR-149-3p negatively regulated TMPRSS4, reducing malignancy-associated characteristics of lung cancer cells and further improving their DDP sensitivity. In vivo, high miR-149-3p expression increased the chemosensitivity of cancer cells. In conclusion, miR-149-3p suppresses the aggressive progression of lung cancer by directly downregulating TMPRSS4 and enhances the responsiveness of lung cancer cells to DDP.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"165-176"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the mechanism of liver cancer immune escape mediated by MINDY1 through regulation of PD-L1 ubiquitination level.","authors":"Xingchao Song, Wenjin Li, Chunyan Tian, Xiao Ma, Weibin Yang, Jiahua Zhou","doi":"10.17305/bb.2024.10962","DOIUrl":"10.17305/bb.2024.10962","url":null,"abstract":"<p><p>The novel deubiquitinase enzyme, motif interacting with ubiquitin-containing novel DUB family-1 (MINDY1), is highly expressed in liver cancer tissues and plays a crucial role in maintaining the stemness of liver cancer cells. Programmed death ligand-1 (PD-L1) is an immunosuppressive molecule overexpressed by tumour cells. The potential role of MINDY1 in inhibiting the stemness of liver cancer cells by deubiquitinating PD-L1 has not yet been reported. To investigate the mechanism by which MINDY1 mediates immune escape in liver cancer through the regulation of PD-L1 ubiquitination, we examined the expression levels of MINDY1 and PD-L1 in liver cancer and adjacent tissues from 50 hepatocellular carcinoma (HCC) patients using protein imprinting and immunohistochemistry. We analyzed the relationship between the expression levels of MINDY1 and PD-L1 in liver cancer tissues and their correlation with the 5-year tumor-free survival rates of patients. Subsequently, MINDY1 expression was knocked down in Huh7 cells using small interfering RNA (siRNA) interference or upregulated through transfection with a MINDY1 overexpression plasmid. The effects of MINDY1 knockdown or overexpression on the proliferation, apoptosis, migration, and invasion of HCC cells, as well as the regulation of PD-L1 binding and ubiquitination, were assessed. The 5-year tumor-free survival rates were significantly lower in both the high MINDY1 expression group and the high PD-L1 expression group (χ2 = 4.919 and 13.158, respectively). A significant difference in survival was observed between the high and low MINDY1 expression groups (χ2= 27.415). MINDY1 was found to directly interact with PD-L1, with MINDY1 gene knockdown promoting PD-L1 ubiquitination and MINDY1 overexpression inhibiting PD-L1 ubiquitination. All comparisons yielded statistically significant results (P < 0.05). In conclusion, MINDY1 inhibits the malignant progression of liver cancer by inhibiting PD-L1 ubiquitination and mediating immune escape.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"144-154"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CTHRC1 is associated with <i>BRAF</i>(V600E) mutation and correlates with prognosis, immune cell infiltration, and drug resistance in colon cancer, thyroid cancer, and melanoma.","authors":"Rumeng Zhang, Zhihao Wang, Huan Wang, Lin Li, Lin Dong, Lin Ding, Qiushuang Li, Linyan Zhu, Tiantian Zhang, Yong Zhu, Keshuo Ding","doi":"10.17305/bb.2024.10397","DOIUrl":"10.17305/bb.2024.10397","url":null,"abstract":"<p><p>Colon cancer, thyroid cancer, and melanoma are common malignant tumors that seriously threaten human health globally. The B-Raf proto-oncogene, serine/threonine kinase (BRAF)(V600E) mutation is an important driver gene mutation in these cancer types. In this study, we identified that collagen triple helix repeat containing 1 (CTHRC1) expression was associated with the BRAF(V600E) mutation in colon cancer, thyroid cancer, and melanoma. Based on database analysis and clinical tissue studies, CTHRC1 was verified to correlate with poor prognosis and worse clinicopathological features in colon cancer and thyroid cancer patients, but not in patients with melanoma. Several signaling pathways, immune cell infiltration, and immunotherapy markers were associated with CTHRC1 expression. Additionally, a high level of CTHRC1 was correlated with decreased sensitivity to antitumor drugs (vemurafenib, PLX-4720, dabrafenib, and SB-590885) targeting the BRAF(V600E) mutation. This study provides evidence of a significant correlation between CTHRC1 and the BRAF(V600E) mutation, suggesting its potential utility as a diagnostic and prognostic biomarker in human colon cancer, thyroid cancer, and melanoma.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"42-61"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epiplakin expression dynamics during colon carcinogenesis: Correlation with proliferation.","authors":"Damla Gül Fındık, Erhan Şahin, Özlem Türelik, Gürkan Güneri","doi":"10.17305/bb.2024.10981","DOIUrl":"10.17305/bb.2024.10981","url":null,"abstract":"<p><p>Colorectal cancer poses a significant global health challenge, with a considerable proportion arising from colon adenomas. Understanding the molecules involved in the carcinogenesis process is crucial for improving colon cancer diagnosis and prognosis. While research on the role of epiplakin in cancer remains limited compared to other plakin group proteins, comprehending its expression patterns and correlations can offer valuable insights into colon carcinogenesis. In this study, we analyzed 60 tissue samples, including colon adenocarcinomas, tubular adenomas (low malignancy risk group), tubulovillous adenomas (high malignancy risk group), and adjacent normal colon tissues. Classification and grading were reevaluated by histological examination. Immunohistochemistry was performed to assess epiplakin and Ki67 expression. Epiplakin optical density and the Ki67 proliferation index were calculated using ImageJ. Statistical analyses were conducted to evaluate correlations and significance. Epiplakin expression was significantly decreased in colon adenocarcinomas [optical density median 4.04 (95% CI, 3.98 to 4.24)] and tubulovillous adenomas [4.32 (95% CI, 4.08 to 4.32)] compared to normal colon tissues [4.61 (95% CI, 4.50 to 4.67)] and tubular adenomas [4.87 (95% CI, 4.67 to 4.88)] (P < 0.05). Moreover, adenoma groups exhibited higher proliferation indices (P < 0.05), and a positive correlation was found between epiplakin expression and the Ki67 proliferation index (r = 0.317, P < 0.05). Our study highlights the potential significance of epiplakin in colorectal cancer. Decreased epiplakin expression is associated with colon malignancy progression, suggesting its role as a potential marker.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"62-70"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Botulinum toxin type A inhibits the formation of hypertrophic scar through the JAK2/STAT3 pathway.","authors":"Yan Fan, Xuesong Guo, Yu Tian, Jie Li, Hongwei Xi","doi":"10.17305/bb.2024.10906","DOIUrl":"10.17305/bb.2024.10906","url":null,"abstract":"<p><p>Hypertrophic scar (HS) is a fibrous proliferative disorder that occurs in the dermis after skin injury. Studies have confirmed that Botulinum toxin type A (BTA) is effective in scar prevention and treatment. However, the specific mechanism remains uncertain. Hypertrophic scar fibroblasts (HSFs) and normal skin fibroblasts (NSFs) from the skin tissues of HS patients were isolated and cultured. Western blot analysis was conducted to measure the expression of JAK2/STAT3 pathway-related proteins. HSFs were treated with the JAK2 inhibitor (AG490) or agonist (C-A1). The CCK-8 assay, EdU staining, scratch-wound assay and transwell assay were used to examine the biological properties of HSFs. Western blot, immunofluorescence, and Sirius red staining were used to assess the fibrosis of HSFs. Additionally, a mouse full-thickness wound model was constructed to investigate the role of BTA in wound healing. The results showed that the JAK2 and STAT3 phosphorylation levels were markedly increased in HS tissues and HSFs. AG490 treatment reduced cell viability, proliferation and migration capacity, and inhibited the fibrosis of HSFs, whereas C-A1 treatment had the opposite effect. BTA treatment inhibited the JAK2/STAT3 pathway. BTA reduced cell viability, proliferation and migration ability, and inhibited the fibrosis of HSFs, while C-A1 intervention weakened the impact of BTA. Meanwhile, BTA promoted wound healing and reduced collagen deposition in vivo. In conclusion, BTA inhibited the JAK2/STAT3 pathway, which in turn hindered the proliferation, migration and fibrosis of HSFs, and promoted wound healing in mice.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":"249-258"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}