{"title":"Drug resistance mechanisms in cancers: Execution of pro-survival strategies.","authors":"Pavan Kumar Dhanyamraju","doi":"10.7555/JBR.37.20230248","DOIUrl":"10.7555/JBR.37.20230248","url":null,"abstract":"<p><p>One of the quintessential challenges in cancer treatment is drug resistance. Several mechanisms of drug resistance have been described to date, and new modes of drug resistance continue to be discovered. The phenomenon of cancer drug resistance is now widespread, with approximately 90% of cancer-related deaths associated with drug resistance. Despite significant advances in the drug discovery process, the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy. Therefore, understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities. In the present review, I discuss the different mechanisms of drug resistance in cancer cells, including DNA damage repair, epithelial to mesenchymal transition, inhibition of cell death, alteration of drug targets, inactivation of drugs, deregulation of cellular energetics, immune evasion, tumor-promoting inflammation, genome instability, and other contributing epigenetic factors. Furthermore, I highlight available treatment options and conclude with future directions.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"95-121"},"PeriodicalIF":2.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11001593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983000","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}
Tianle Jin, Maoxing Fei, Shiqiao Luo, Handong Wang
{"title":"Piezo1 as a potential player in intracranial hemorrhage: from perspectives on biomechanics and hematoma metabolism.","authors":"Tianle Jin, Maoxing Fei, Shiqiao Luo, Handong Wang","doi":"10.7555/JBR.37.20230241","DOIUrl":"10.7555/JBR.37.20230241","url":null,"abstract":"<p><p>Intracranial hemorrhage (ICH) causes numerous neurological deficits and deaths worldwide each year, leaving a significant health burden on the public. The pathophysiology of ICH is complicated, and involves both primary and secondary injury. Hematoma, as the prime pathology of ICH, undergoes metabolism and triggers biochemical and biomechanical alterations in the brain, leading to secondary injury. Past endeavors mainly aimed at biochemical-initiated mechanisms for causing secondary injury have made limited progress in recent years, although ICH itself is also highly biomechanics-related. The discovery of the mechanical-activated cation channel Piezo1 provides a new avenue to further explore underlying mechanisms of secondary injury. The current article reviews the structure and gating mechanisms of Piezo1, its roles in the physiology/pathophysiology of neurons, astrocytes, microglia, and bone-marrow-derived macrophages, and especially its roles in erythrocytic turnover and iron metabolism, revealing a potential interplay between the biomechanics and biochemistry of hematoma in ICH. Collectively, these advances provide deeper insights into the secondary injury of ICH and lay the foundations for future research.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161653","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}
Jing Xue, Linwei Zhang, Jingxian Tao, Xuexue Xie, Xi Wang, Linlin Wu, Shuhu Du, Ninghua Tan, Yang Jin, Jianming Ju, Junting Fan, Jun Wang, Fei Huan, Rong Gao
{"title":"A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F.","authors":"Jing Xue, Linwei Zhang, Jingxian Tao, Xuexue Xie, Xi Wang, Linlin Wu, Shuhu Du, Ninghua Tan, Yang Jin, Jianming Ju, Junting Fan, Jun Wang, Fei Huan, Rong Gao","doi":"10.7555/JBR.37.20230169","DOIUrl":"10.7555/JBR.37.20230169","url":null,"abstract":"<p><p>As a potential endocrine-disrupting chemical, bisphenol F (BPF) may cause nonalcoholic fatty liver disease (NAFLD)-like changes, but the mechanisms underpinning its pathogenesis as well as the intervention strategies remain poorly understood. Using the electron microscopy technology, along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays, we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells, accompanied by an increased total level of triglycerides. At the molecular level, the lipogenesis-associated mRNAs and proteins, including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase-1, peroxisome proliferator-activated receptor gamma, and CCAAT-enhancer-binding proteins, increased significantly <i>via</i> the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling regulation in both <i>in vitro</i> and <i>in vivo</i> studies. Furthermore, the immunofluorescence results also showed the robust lipogenesis induced by BPF, evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei. To investigate the intervention strategies for BPF-induced NAFLD-like changes, we demonstrated that bellidifolin, isolated and purified from <i>Swertia chirayita</i>, significantly attenuated BPF-induced lipid droplet deposition in HepG2 cell and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins. Therefore, the present study elucidates the mechanisms underlying BPF-induced lipid accumulation in HepG2 cells, while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-14"},"PeriodicalIF":2.2,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161432","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":"Phase separation and transcriptional regulation in cancer development.","authors":"Yan Gu, Ke Wei, Jun Wang","doi":"10.7555/JBR.38.20230214","DOIUrl":"https://doi.org/10.7555/JBR.38.20230214","url":null,"abstract":"<p><p>Liquid-liquid phase separation, a novel biochemical phenomenon, has been increasingly studied for its medical applications. It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes. During transcriptional regulation, dynamic condensates are formed through interactions between transcriptional elements, such as transcription factors, coactivators, and mediators. Cancer is a disease characterized by uncontrolled cell proliferation, but the precise mechanisms underlying tumorigenesis often remain to be elucidated. Emerging evidence has linked abnormal transcriptional condensates to several diseases, especially cancer, implying that phase separation plays an important role in tumorigenesis. Condensates formed by phase separation may have an effect on gene transcription in tumors. In the present review, we focus on the correlation between phase separation and transcriptional regulation, as well as how this phenomenon contributes to cancer development.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-15"},"PeriodicalIF":2.3,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161651","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":"Alternative polyadenylation-related genetic variants contribute to bladder cancer risk.","authors":"Ting Liu, Jingjing Gu, Chuning Li, Mengfan Guo, Lin Yuan, Qiang Lv, Chao Qin, Mulong Du, Haiyan Chu, Hanting Liu, Zhengdong Zhang","doi":"10.7555/JBR.37.20230063","DOIUrl":"10.7555/JBR.37.20230063","url":null,"abstract":"<p><p>Aberrant alternative polyadenylation (APA) events play an important role in cancers, but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer. Previous genome-wide association study performed APA quantitative trait loci (apaQTL) analyses in bladder cancer, and identified 17 955 single nucleotide polymorphisms (SNPs). We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways, high mutational burden, and immune infiltration. Association analysis showed that apaQTL-associated SNPs rs34402449 C>A, rs2683524 C>T, and rs11540872 C>G were significantly associated with susceptibility to bladder cancer (rs34402449: OR = 1.355, 95% confidence interval [CI]: 1.159-1.583, <i>P</i> = 1.33 × 10 <sup>-4</sup>; rs2683524: OR = 1.378, 95% CI: 1.164-1.632, <i>P</i> = 2.03 × 10 <sup>-4</sup>; rs11540872: OR = 1.472, 95% CI: 1.193-1.815, <i>P</i> = 3.06 × 10 <sup>-4</sup>). Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer ( <i>P</i> <sub>trend</sub> = 2.87 × 10 <sup>-12</sup>). We found that <i>PRR13</i>, being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines, was more highly expressed in bladder cancer tissues than in adjacent normal tissues. Moreover, the rs2683524 T allele was correlated with shorter 3' untranslated regions of <i>PRR13</i> and increased <i>PRR13</i> expression levels. Collectively, our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"405-417"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489516","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":"Effect of remimazolam <i>vs.</i> propofol on hemodynamics during general anesthesia induction in elderly patients: Single-center, randomized controlled trial.","authors":"Mingfeng He, Chanjuan Gong, Yinan Chen, Rongting Chen, Yanning Qian","doi":"10.7555/JBR.37.20230110","DOIUrl":"10.7555/JBR.37.20230110","url":null,"abstract":"<p><p>The current study aimed to compare the effects between remimazolam and propofol on hemodynamic stability during the induction of general anesthesia in elderly patients. We used propofol at a rate of 60 mg/(kg·h) in the propofol group (group P) or remimazolam at a rate of 6 mg/(kg·h) in the remimazolam group (group R) for the induction. A processed electroencephalogram was used to determine whether the induction was successful and when to stop the infusion of the study drug. We measured when patients entered the operating room (T <sub>0</sub>), when the induction was successful (T <sub>1</sub>), and when before (T <sub>2</sub>) and 5 min after successful endotracheal intubation (T <sub>3</sub>). We found that mean arterial pressure (MAP) was lower at T <sub>1-3</sub>, compared with T <sub>0</sub> in both groups, but higher at T <sub>2</sub> in the group R, while ΔMAP <sub>T0-T2</sub> and ΔMAP <sub>max</sub> were smaller in the group R (ΔMAP <sub>T0-T2</sub>: the difference between MAP at time point T <sub>0</sub> and T <sub>2</sub>, ΔMAP <sub>max</sub>: the difference between MAP at time point T <sub>0</sub> and the lowest value from T <sub>0</sub> to T <sub>3</sub>). Cardiac index and stroke volume index did not differ between groups, whereas systemic vascular resistance index was higher at T <sub>1-3</sub> in the group R. These findings show that remimazolam, compared with propofol, better maintains hemodynamic stability during the induction, which may be attributed to its ability to better maintain systemic vascular resistance levels.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"66-75"},"PeriodicalIF":2.2,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10818176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71423754","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":"Histone lactylation promotes cell proliferation, migration and invasion through targeting HMGB1 in endometriosis.","authors":"Jie Chen, Pengfei Qin, Yanli Sun, Suping Han","doi":"10.7555/JBR.37.20230095","DOIUrl":"10.7555/JBR.37.20230095","url":null,"abstract":"<p><p>Endometriosis is defined as a condition with endometrium-like tissues migrating outside of the pelvic cavity. However, the mechanism of endometriosis is still unclear. Lactate can be covalently modified to lysine residues of histones and other proteins, which is called lactylation. The results showed that the higher level of lactate and lactate dehydrogenase A enhanced the histone H3 lysine 18 lactylation (H3K18lac) in ectopic endometrial tissues and ectopic endometrial stromal cells than that in normal endometrial tissues and normal endometrial stromal cells. Lactate promoted cell proliferation, migration, and invasion in endometriosis. Mechanistically, lactate induced H3K18lac to promote the expression of high-mobility group box 1 (HMGB1) in endometriosis, and HMGB1 knockdown significantly reduced the cell proliferation, migration, and invasion of the lactate-treated cells through the phosphorylation of AKT. In conclusion, lactate could induce histone lactylation to promote endometriosis progression by upregulating the expression of HMGB1, which may provide a novel target for the prevention and treatment of endometriosis.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"470-478"},"PeriodicalIF":2.3,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72014341","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}
Xiaoqing Yuan, Yawei Liu, Xule Yang, Yun Huang, Xuan Shen, Hui Liang, Hongwen Zhou, Qian Wang, Xu Zhang, John Zhong Li
{"title":"Long noncoding RNA <i>lnc_217</i> regulates hepatic lipid metabolism by modulating lipogenesis and fatty acid oxidation.","authors":"Xiaoqing Yuan, Yawei Liu, Xule Yang, Yun Huang, Xuan Shen, Hui Liang, Hongwen Zhou, Qian Wang, Xu Zhang, John Zhong Li","doi":"10.7555/JBR.37.20230075","DOIUrl":"10.7555/JBR.37.20230075","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is considered a major health epidemic with an estimated 32.4% worldwide prevalence. No drugs have yet been approved and therapeutic nodes remain a major unmet need. Long noncoding RNAs are emerging as an important class of novel regulators influencing multiple biological processes and the pathogenesis of NAFLD. Herein, we described a novel long noncoding RNA, <i>lnc_217</i>, which was liver enriched and upregulated in high-fat diet-fed mice, and a genetic animal model of NAFLD. We found that liver specific knockdown of <i>lnc_217</i> was resistant to high-fat diet-induced hepatic lipid accumulation and decreased serum lipid in mice. Mechanistically, we demonstrated that knockdown of <i>lnc_217</i> not only decreased <i>de novo</i> lipogenesis by inhibiting sterol regulatory element binding protein-1c cleavage but also increased fatty acid β-oxidation through activation of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α. Taken together, we conclude that <i>lnc_217</i> may be a novel regulator of hepatic lipid metabolism and a potential therapeutic target for the treatment of hepatic steatosis and NAFLD-related metabolic disorders.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"448-459"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415530","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}
Qing Chen, Meiheng Sun, Xu Han, Hongfei Xu, Yongjian Liu
{"title":"Structural determinants specific for retromer protein sorting nexin 5 in regulating subcellular retrograde membrane trafficking.","authors":"Qing Chen, Meiheng Sun, Xu Han, Hongfei Xu, Yongjian Liu","doi":"10.7555/JBR.37.20230112","DOIUrl":"10.7555/JBR.37.20230112","url":null,"abstract":"<p><p>The endosomal trafficking of signaling membrane proteins, such as receptors, transporters and channels, is mediated by the retromer-mediated sorting machinery, composed of a cargo-selective vacuolar protein sorting trimer and a membrane-deforming subunit of sorting nexin proteins. Recent studies have shown that the isoforms, sorting nexin 5 (SNX5) and SNX6, have played distinctive regulatory roles in retrograde membrane trafficking. However, the molecular insight determined functional differences within the proteins remains unclear. We reported that SNX5 and SNX6 had distinct binding affinity to the cargo protein vesicular monoamine transporter 2 (VMAT2). SNX5, but not SNX6, specifically interacted with VMAT2 through the Phox domain, which contains an alpha-helix binding motif. Using chimeric mutagenesis, we identified that several key residues within this domain were unique in SNX5, but not SNX6, and played an auxiliary role in its binding to VMAT2. Importantly, we generated a set of mutant SNX6, in which the corresponding key residues were mutated to those in SNX5. In addition to the gain in binding affinity to VMAT2, their overexpression functionally rescued the altered retrograde trafficking of VMAT2 induced by siRNA-mediated depletion of <i>SNX5</i>. These data strongly suggest that SNX5 and SNX6 have different functions in retrograde membrane trafficking, which is determined by the different structural elements within the Phox domain of two proteins. Our work provides a new information on the role of SNX5 and SNX6 in the molecular regulation of retrograde membrane trafficking and vesicular membrane targeting in monoamine neurotransmission and neurological diseases.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":"37 6","pages":"492-506"},"PeriodicalIF":2.3,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591266","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":"Tofacitinib combined with local low-dose ixekizumab injection benefits those with peripheral psoriatic arthritis.","authors":"Ruiyuan Xia, Weixin Zhang, Jing Hang, Zhiqiang Yin","doi":"10.7555/JBR.37.20220253","DOIUrl":"10.7555/JBR.37.20220253","url":null,"abstract":"","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"92-94"},"PeriodicalIF":2.3,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10818174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54229194","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}