{"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}
Jiang Cao, Jie Chang, Chaoqin Wu, Sheng Zhang, Binyu Wang, Kaixiang Yang, Xiaojian Cao, Tao Sui
{"title":"Extradural contralateral S1 nerve root transfer for spastic lower limb paralysis.","authors":"Jiang Cao, Jie Chang, Chaoqin Wu, Sheng Zhang, Binyu Wang, Kaixiang Yang, Xiaojian Cao, Tao Sui","doi":"10.7555/JBR.37.20230068","DOIUrl":"10.7555/JBR.37.20230068","url":null,"abstract":"<p><p>The current study aims to ascertain the anatomical feasibility of transferring the contralateral S1 ventral root (VR) to the ipsilateral L5 VR for treating unilateral spastic lower limb paralysis. Six formalin-fixed (three males and three females) cadavers were used. The VR of the contralateral S1 was transferred to the VR of the ipsilateral L5. The sural nerve was selected as a bridge between the donor and recipient nerve. The number of axons, the cross-sectional areas and the pertinent distances between the donor and recipient nerves were measured. The extradural S1 VR and L5 VR could be separated based on anatomical markers of the dorsal root ganglion. The gross distance between the S1 nerve root and L5 nerve root was 31.31 (± 3.23) mm in the six cadavers, while that on the diffusion tensor imaging was 47.51 (± 3.23) mm in 60 patients without spinal diseases, and both distances were seperately greater than that between the outlet of S1 from the spinal cord and the ganglion. The numbers of axons in the S1 VRs and L5 VRs were 13414.20 (± 2890.30) and 10613.20 (± 2135.58), respectively. The cross-sectional areas of the S1 VR and L5 VR were 1.68 (± 0.26) mm <sup>2</sup> and 1.08 (± 0.26) mm <sup>2</sup>, respectively. In conclusion, transfer of the contralateral S1 VR to the ipsilateral L5 VR may be an anatomically feasible treatment option for unilateral spastic lower limb paralysis.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"394-400"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41177563","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}
Xinlu Chai, Yuting Meng, Wei Ge, Juan Wang, Fei Li, Xue Jun Wang, Xuerong Wang
{"title":"A novel synthesized prodrug of gemcitabine based on oxygen-free radical sensitivity inhibited the growth of lung cancer cells.","authors":"Xinlu Chai, Yuting Meng, Wei Ge, Juan Wang, Fei Li, Xue Jun Wang, Xuerong Wang","doi":"10.7555/JBR.37.20230022","DOIUrl":"10.7555/JBR.37.20230022","url":null,"abstract":"<p><p>In the present study, we introduced the H <sub>2</sub>O <sub>2</sub>-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine (GEM) to synthesize a new target compound named GEM-ZZQ, and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy. We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions <i>in vitro</i> and that it could be activated by H <sub>2</sub>O <sub>2</sub> to release GEM. Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM. For the lung cancer cell lines that are resistant to the epidermal growth factor receptor (EGFR)-targeting inhibitor osimertinib, GEM-ZZQ showed less growth inhibition than GEM; however, GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups. In summary, we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"355-366"},"PeriodicalIF":2.3,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234957","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":"HSP90B1-mediated plasma membrane localization of GLUT1 promotes radioresistance of glioblastomas.","authors":"Yanhui Li, Yuqian Ge, Mengjie Zhao, Fangshu Ding, Xiuxing Wang, Zhumei Shi, Xin Ge, Xiefeng Wang, Xu Qian","doi":"10.7555/JBR.37.20220234","DOIUrl":"10.7555/JBR.37.20220234","url":null,"abstract":"<p><p>Ionizing radiation is a popular and effective treatment option for glioblastoma (GBM). However, resistance to radiation therapy inevitably occurs during treatment. It is urgent to investigate the mechanisms of radioresistance in GBM and to find ways to improve radiosensitivity. Here, we found that heat shock protein 90 beta family member 1 (HSP90B1) was significantly upregulated in radioresistant GBM cell lines. More importantly, HSP90B1 promoted the localization of glucose transporter type 1, a key rate-limiting factor of glycolysis, on the plasma membrane, which in turn enhanced glycolytic activity and subsequently tumor growth and radioresistance of GBM cells. These findings imply that targeting HSP90B1 may effectively improve the efficacy of radiotherapy for GBM patients, a potential new approach to the treatment of glioblastoma.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"326-339"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175606","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}