Journal of Biomedical Research最新文献

{"title":"Hepatic SIRT6 protects against cholestatic liver disease primarily <i>via</i> inhibiting bile acid synthesis.","authors":"Wen Zhang, Jiahui Wang, Luyao Yang, Yuyun Shao, Hongjun Peng, Longfeng Jiang, Liang Sheng","doi":"10.7555/JBR.38.20240172","DOIUrl":"https://doi.org/10.7555/JBR.38.20240172","url":null,"abstract":"<p><p>Cholestatic liver disease, caused by the accumulation of hazardous bile acids in the liver, may result in cirrhosis, fibrosis, or liver failure. Activation of SIRT6 prevents cholestasis-associated pathological events, such as oxidative stress and mitochondrial biogenesis disorders, and inhibits bile acid synthesis to alleviate cholestatic liver injury. However, it is still uncertain which pathway is responsible for the therapeutic effect of SIRT6 in reducing cholestasis. Therefore, we treated liver-specific <i>Sirt6</i> knockout mice with N-Acetylcysteine, Keap1-Nrf2-IN-1, or acadesine to remove oxidative stress and/or trigger mitochondrial biogenesis after cholestatic liver disease modeling, but these measures did not significantly improve cholestatic symptoms. However, MDL801, a SIRT6 agonist that downregulating CYP7A1, the key enzyme in bile acid synthesis, exhibited favorable therapeutic effects. In addition, the hepatic knockdown of <i>Cyp7A1</i> further confirmed that inhibition of hepatic bile acid synthesis might be the main pathway by which SIRT6 alleviates cholestatic liver disease. These findings provide a solid basis for the potential application of SIRT6 agonists in the treatment of cholestatic liver disease.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-17"},"PeriodicalIF":2.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anlotinib reverses osimertinib resistance <i>via</i> inhibiting epithelial-to-mesenchymal transition and angiogenesis in non-small cell lung cancer.","authors":"Liting Lv, Xin Hua, Jiaxin Liu, Sutong Zhan, Qianqian Zhang, Xiao Liang, Jian Feng, Yong Song","doi":"10.7555/JBR.38.20240045","DOIUrl":"https://doi.org/10.7555/JBR.38.20240045","url":null,"abstract":"<p><p>In the present, we aimed to investigate the effect of anlotinib on the potential reversal of osimertinib resistance by inhibiting the formation of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In a clinical case, anlotinib reversed osimertinib resistance in Non-small cell lung cancer (NSCLC). We performed an immunohistochemical experiment on tumor tissues from three non-small cell lung cancer patients exhibiting osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A (VEGFA) before and after osimertinib resistance. The results revealed the downregulation of E-cadherin, coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance, compared with the expression in tissues of patients before taking osimertinib. Subsequently, we established osimertinib-resistant cell lines and found that the osimertinib-resistant cells acquired the EMT features. Then, we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT. The expression levels of VEGFA and micro-vessels were analyzed in the combination group <i>in vitro</i>. Finally, we explored the reversal of osimertinib resistance in combination with anlotinib <i>in vivo</i> with 20 nude mice. The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of resistant cells, which also inhibited tumor growth, exerted anti-tumor activity, and ultimately reversed osimertinib resistance in mice. The co-administration of osimertinib and anlotinib demonstrated their synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients, ultimately reversing osimertinib resistance.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-15"},"PeriodicalIF":2.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold nanorods as biocompatible nano-agents for the enhanced photothermal therapy in skin disorders.","authors":"Yamei Gao, Shaohu Huo, Chao Chen, Shiyu Du, Ruiyuan Xia, Jian Liu, Dandan Chen, Ziyue Diao, Xin Han, Zhiqiang Yin","doi":"10.7555/JBR.38.20240119","DOIUrl":"https://doi.org/10.7555/JBR.38.20240119","url":null,"abstract":"<p><p>Rod-shaped gold nanomaterials, known as gold nanorods (GNRs), may undergo specific surface alterations, because of their straightforward surface chemistry. This feature makes them appropriate for use as functional and biocompatible nano-formulations. By optimizing the absorption of longitudinally localized surface plasmon resonance (LSPR) in the near-infrared (NIR) region, which corresponds to the NIR bio-tissue window, GNRs with appropriate modifications may improve the results of photothermal treatment (PTT). In dermatology, potential noninvasive uses of GNRs to enhance wound healing, manage infections, combat cutaneous malignancies, and remodel skin tissues <i>via</i> PTT have attracted research attention in recent years. In this review, the basic properties of GNRs, such as shape, size, optical performance, photothermal efficiency, and metabolism, are discussed firstly. Then, the disadvantages of using these particles in photodynamic therapy (PDT) are proposed. Next, biological applications of GNRs-based PTT are summarized in detail. Finally, the limitations and future perspectives of this research are summarized, providing a comprehensive outlook for prospective GNRs with PTT.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-17"},"PeriodicalIF":2.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helminth-derived molecules: pathogenic and pharmacopeial roles.","authors":"Yu Zhang, Chunxiang Shen, Xinyi Zhu, Chiuan Yee Leow, Minjun Ji, Zhipeng Xu","doi":"10.7555/JBR.38.20240177","DOIUrl":"10.7555/JBR.38.20240177","url":null,"abstract":"<p><p>Parasitic helminths, taxonomically comprising trematodes, cestodes, and nematodes, are multicellular invertebrates widely disseminated in nature and have afflicted people continuously for a long time. Helminths play potent roles in the host through generating a variety of novel molecules, including some excretory/secretory products and others that are involved in intracellular material exchange and information transfer as well as the initiation or stimulation of immune and metabolic activation. The helminth-derived molecules have developed powerful and diverse immunosuppressive effects to achieve immune evasion for parasite survival and establish chronic infections. However, they also improve autoimmune and allergic inflammatory responses and promote metabolic homeostasis by promoting metabolic reprogramming of various immune functions, and then inducing alternatively activated macrophages, T helper 2 cells, and regulatory T cells-mediated immune responses. Therefore, a deeper exploration of the immunopathogenic mechanism and immune regulatory mechanisms of helminth-derived molecules exerted in the host is crucial for understanding host-helminth interactions as well as the development of therapeutic drugs for infectious or non-infectious diseases. In this review, we focus on the properties of helminth-derived molecules to give an overview of the most recent scientific knowledge about their pathogenic and pharmacopeial roles in immune-metabolic homeostasis.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-22"},"PeriodicalIF":2.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of perioperative factors in the prognosis of cancer patients: A coin has two sides.","authors":"Yingzhou Tu, Sen Wang, Haoran Wang, Peiyao Zhang, Mengyu Wang, Cunming Liu, Chun Yang, Riyue Jiang","doi":"10.7555/JBR.38.20240164","DOIUrl":"https://doi.org/10.7555/JBR.38.20240164","url":null,"abstract":"<p><p>Cancer, the second leading cause of mortality globally, poses a significant health challenge. The conventional treatment for solid tumors involves surgical intervention, followed by chemo- and radio-therapies as well as target therapies, but the recurrence and metastasis of cancers remain a major issue. Anesthesia is essential for ensuring patient comfort and safety during surgical procedures. Despite its crucial role during the surgery, the precise effect of anesthesia on cancer patient outcomes is not clearly understood. This comprehensive review aims to elucidate the various anesthesia strategies used in the perioperative care of cancer patients and their potential effects on patients' prognosis, but understanding the complex relationship between anesthesia and cancer outcomes is crucial, given the complexity in cancer treaments. Examining potential implications of anesthesia strategies on cancer patient prognosis may help better understand treatment efficacy and risk factors of cancer recurrence and metastasis. Through a detailed analysis of anesthesia practices in cancer surgery, this review aims to provide insights that may lead to improving the existing anesthesia protocols and ultimately reduce risk factors for patient outcomes in the field of oncology.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of the mass balance, biotransformation, and safety of [ ¹⁴C]IBI351 in healthy Chinese subjects.","authors":"Shuaishuai Wang, Wen Lin, Bilal Ahmed, Tianqi Zhong, Jun Zhao, Lijun Xie, Hao Feng, Juan Chen, Chen Zhang, Peng Yan, Shirui Zheng, Lingge Cheng, Yipeng Cheng, Bei Zhu, Feng Han, Lulu Zhang, Chen Zhou","doi":"10.7555/JBR.38.20240254","DOIUrl":"https://doi.org/10.7555/JBR.38.20240254","url":null,"abstract":"<p><p>IBI351, a synthetic compound, exerts its anti-tumor effects by specifically, covalently, and irreversibly modifying the 12th cysteine residue of KRAS G12C. However, the pharmacokinetic characteristics of IBI351 in the human body have not been reported. The current study aimed to investigate the pharmacokinetics and safety of IBI351 in healthy Chinese male subjects. A single oral dose of 600 mg/150 μCi [ ¹⁴C]IBI351 was administered to six healthy male subjects. Blood, urine, and fecal samples were collected at continuous time points to analyze the levels of IBI351 parent drug and its metabolites. We found that IBI351 showed favorable pharmacokinetic characteristics, and was well tolerated in all the six participants. In addition, 17 major metabolites of IBI351 were analyzed and identified in the blood, urine, and feces. The main metabolic pathways included oxidation, hydrogenation, sulfonate conjugation, glucuronide conjugation, and cysteine conjugation. IBI351 and its metabolites were primarily excreted through feces. Taken together, this is the first study on the metabolism and safety of IBI351 in Chinese subjects, and these findings may guide future clinical development of IBI351 as a novel anti-tumor drug.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular evolution of intestinal-type early gastric cancer according to Correa cascade.","authors":"Fangyuan Li, Yaohui Wang, Xiaochun Ping, Jiani C Yin, Fufeng Wang, Xian Zhang, Xiang Li, Jing Zhai, Lizong Shen","doi":"10.7555/JBR.38.20240118","DOIUrl":"https://doi.org/10.7555/JBR.38.20240118","url":null,"abstract":"<p><p>Early screening is crucial for the prevention of intestinal-type gastric cancer. The objective of the current study was to ascertain molecular evolution of intestinal-type gastric cancer according to the Correa cascade for the precise gastric cancer screening. We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection-resected specimens from 14 Chinese patients by microdissection, and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using the whole exome sequencing, identifying multiple variants at different Correa stages. The results showed that <i>TP53</i>, <i>PCLO</i>, and <i>PRKDC</i> were the most frequently mutated genes in the early gastric cancer (EGC). A high frequency of <i>TP53</i> alterations was found in low-grade intraepithelial neoplasia (LGIN), which further increased in high-grade intraepithelial neoplasia (HGIN) and EGC. Intestinal metaplasia (IM) had no significant correlation with EGC in terms of mutational spectra, whereas both LGIN and HGIN showed higher genomic similarities to EGC, compared with IM. Based on Jaccard similarity coefficients, three evolutionary models were further constructed, and most patients showed linear progression from LGIN to HGIN, ultimately resulting in EGC. The ECM-receptor interaction pathway was revealed to be involved in the linear evolution. Additionally, the retrospective validation study of 39 patients diagnosed with LGIN indicated that <i>PRKDC</i> mutations, in addition to <i>TP53</i> mutations, may drive LGIN progression to HGIN or EGC. In conclusion, the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer, elucidates the underlying molecular mechanisms of gastric carcinogenesis, and provides some evidence for potential personalized gastric cancer surveillance.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-16"},"PeriodicalIF":2.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted therapy outcomes in acrodermatitis continua of Hallopeau: a systematic review.","authors":"ChaoJing Zhou, YiYun Hou, YuFei Wang, JiLiang Lu, YaMei Gao, ZhiQiang Yin","doi":"10.7555/JBR.38.20240090","DOIUrl":"10.7555/JBR.38.20240090","url":null,"abstract":"","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-3"},"PeriodicalIF":2.2,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variants and mRNA expression of <i>KLF4</i> and <i>KLF5</i> with hypertension: A combination of case-control study and cohort study.","authors":"Xu Han, Wen Li, Changying Chen, Jiahui Liu, Junxiang Sun, Feifan Wang, Chao Wang, Jialing Mu, Xincheng Gu, Fangyuan Liu, Hankun Xie, Song Yang, Chong Shen","doi":"10.7555/JBR.38.20240208","DOIUrl":"https://doi.org/10.7555/JBR.38.20240208","url":null,"abstract":"<p><p>Hypertension (HT) is a major risk factor for cardiovascular diseases. Krüppel-like factors (KLFs) are important transcription factors in eukaryotes. Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases, whereas population studies for associations between HT and KLF4 or KLF5 have been rarely reported. Thus, the current study aimed to examines the association of genetic variants and mRNA expression levels of <i>KLF4</i> and <i>KLF5</i> with HT, as well as the effect of antihypertensive drugs on the expression levels. The associations of one single-nucleotide polymorphism (SNP) in <i>KLF4</i> and three SNPs in <i>KLF5</i> with HT were investigated using a combination of case-control and cohort studies. The study population were selected from a community-based population cohort in four different regions of Jiangsu Province. Risks of HT were estimated through logistic and Cox regression analyses, respectively. In addition, mRNA expression levels of <i>KLF4</i> and <i>KLF5</i> were measured in 246 controls and 385 HT cases selected from the cohort study as mentioned above. Among the HT cases, 263 were not taking antihypertensive drugs [AHD(-)] and 122 were taking antihypertensive drugs [AHD(+)]. In the case-control study, SNP rs9573096 (C>T) in <i>KLF5</i> was significantly associated with an increased risk of HT in the additive model (adjusted odds ratio [OR], 1.106; 95% confidence interval [CI], 1.009 to 1.212). In the cohort study of the normotensive population, rs9573096 in <i>KLF5</i> was also significantly associated with an increased risk of HT in the additive model (adjusted hazards ratio [HR], 1.199; 95% CI, 1.070 to 1.344). <i>KLF4</i> and <i>KLF5</i> mRNA expression levels were significantly higher in the AHD(-) group than in the control group ( <i>P</i> < 0.05), but lower in the AHD(+) group than in the AHD(-) group ( <i>P</i> < 0.05). The current study demonstrated the associations of <i>KLF4</i> and <i>KLF5</i> genetic variants with hypertension, and the indicative discriminations of mRNA expression levels of <i>KLF4</i> and <i>KLF5</i> for risk of hypertension and antihypertensive treatment.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial commentary on the special issue of cancer research.","authors":"Editorial Board","doi":"10.7555/JBR.38.20240800","DOIUrl":"10.7555/JBR.38.20240800","url":null,"abstract":"","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":"38 4","pages":"287-288"},"PeriodicalIF":2.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}