Lan Lin, Zhiyi Qiang, Kaiao Chen, Ying Huo, Wei Liu, Jian Yang
{"title":"DEC1 deficiency protects against bone loss induced by ovariectomy through inhibiting inflammation.","authors":"Lan Lin, Zhiyi Qiang, Kaiao Chen, Ying Huo, Wei Liu, Jian Yang","doi":"10.7555/JBR.38.20240069","DOIUrl":"10.7555/JBR.38.20240069","url":null,"abstract":"<p><p>Previous studies have shown that differentiated embryo-chondrocyte expressed gene 1 (DEC1) promotes osteoblast osteogenesis. To investigate the role of DEC1 in postmenopausal osteoporosis (PMOP), we utilized the two types (DEC1 <sup>+/+</sup>, DEC1 <sup>-/-</sup>) mice to establish an ovariectomy (OVX) model and found that the bone loss in DEC1 <sup>-/-</sup> OVX mice were much less than that in DEC1 <sup>+/+</sup> OVX mice. The expression levels of RUNX2 and OSX significantly increased in DEC1 <sup>-/-</sup> OVX mice compared with those in DEC1 <sup>+/+</sup> OVX mice. Whereas, NFATc1, c-Fos, CTSK and RANKL/OPG significantly decreased in DEC1 <sup>-/-</sup> OVX mice compared with those in DEC1 <sup>+/+</sup> OVX mice. Likewise, DEC1 deficiency suppressed IL-6 and IL-1β. Further study showed <i>Runx2</i>, <i>Osx,</i> <i>Alp</i>, and <i>Ocn</i> significantly increased in DEC1 <sup>-/-</sup> OVX BMSCs compared with those in DEC1 <sup>+/+</sup> OVX BMSCs. And the mRNA levels of <i>IL-1β, IL-6</i>, <i>Tnf-α</i> and <i>Ifn-γ</i> increased significantly in DEC1 <sup>+/+</sup> OVX BMMs compared with those in DEC1 <sup>+/+</sup> sham BMMs, but not in DEC1 <sup>-/-</sup> OVX BMMs compared with those in DEC1 <sup>-/-</sup> sham BMMs. Furthermore, the p-IκBα and p-P65 significantly increased in DEC1 <sup>+/+</sup> OVX BMMs compared with those in DEC1 <sup>+/+</sup> sham BMMs, but did not increase in DEC1 <sup>-/-</sup> OVX BMMs compared with those in DEC1 <sup>-/-</sup> sham BMMs. Taken together, DEC1 deficiency inhibits the NF-κB pathway induced by OVX, thereby decreasing cytokines, and subsequently, inhibits the decrease of osteogenesis and the increase of osteoclastogenesis caused by OVX. The findings provide a novel understanding of postmenopausal osteoporosis development, which offers potential avenues for the intervention strategies.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-16"},"PeriodicalIF":2.2,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161374","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":"Post-transcriptional dysregulation in autism, schizophrenia, and bipolar disorder.","authors":"Yuanyuan Wang, Yitong Yan, Bin Zhou, Mingyan Lin","doi":"10.7555/JBR.38.20240114","DOIUrl":"https://doi.org/10.7555/JBR.38.20240114","url":null,"abstract":"<p><p>The alteration of gene expression is not restricted to transcriptional regulation but includes a variety of post-transcriptional mechanisms, however, the role of the latter underlying many diseases remains relatively unknown. By utilizing an RNA-Seq dataset of 1510 brain samples from individuals with autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ), and controls, we assessed the contribution of post-transcriptional dysregulation and identified top perturbators accountable for transcriptomic changes of expression in neuropsychiatric disorders. Around 30% of the variability in expression can be attributed to post-transcriptional dysregulation. Interestingly, RNA stability tended to decrease in SCZ and BD, leading to the inhibition of neurogenesis and neural differentiation, while the increase in ASD, resulted in enhanced activity of apoptosis. This finding implicated contrasting pathologies involving RNA stability among neuropsychiatric disorders. An RNA binding protein (RBP)-ELAVL3 - is predicted to be significantly involved in the disruption of RNA stability in all three disorders. To validate, we knocked down its expression in cerebral organoids. Not only differentially expressed genes in <i>ELAVL3</i>-knockdown covered a considerable proportion of predicted targets in three disorders, we also found neurogenesis was significantly affected, given the diminished proliferation and consequently the reduced size of the organoids. Our study extends the current understanding of the link between post-transcriptional regulation and neuropsychiatric disorders and provides new therapeutic targets for early intervention.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-14"},"PeriodicalIF":2.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161684","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}
Xia Wang, Shuai Zhou, Haojie Yin, Jian Han, Yue Hu, Siqi Wang, Congjing Wang, Jie Huang, Junqiang Zhang, Xiufeng Ling, Ran Huo
{"title":"The role of SRPK1-mediated phosphorylation of SR proteins in the chromatin configuration transition of mouse germinal vesicle oocytes.","authors":"Xia Wang, Shuai Zhou, Haojie Yin, Jian Han, Yue Hu, Siqi Wang, Congjing Wang, Jie Huang, Junqiang Zhang, Xiufeng Ling, Ran Huo","doi":"10.7555/JBR.38.20240054","DOIUrl":"https://doi.org/10.7555/JBR.38.20240054","url":null,"abstract":"<p><p>Meiotic resumption in mammalian oocytes involves nucleus and organelle structural changes, notably chromatin configuration transitioning from non-surrounding nucleolus (NSN) to surrounding nucleolus (SN) in germinal vesicle (GV) oocytes. Our study found that nuclear speckles, a subnuclear structure mainly composed of serine-arginine (SR) proteins, changed from a diffuse spotted distribution in mouse NSN oocytes to an aggregation pattern in SN oocytes. We further discovered that SRPK1, an enzyme phosphorylating SR proteins, co-localized with NS at SN stage and NSN oocytes failed to convert into SN oocytes after inhibiting the activity of SRPK1. Furthermore, the typical structure of chromatin ring around the nucleolus in SN oocytes collapsed after inhibitor treatment. To explore the underlying mechanism, phosphorylated SR proteins were confirmed to be associated with chromatin by salt extraction experiment, and <i>in situ</i> DNase I assay showed that the accessibility of chromatin enhanced in SN oocytes with SRPK1 inhibited, accompanied by decreased repressive modification on histone and abnormal recurrence of transcriptional signal. In conclusion, our results indicated that SRPK1-regulated phosphorylation on SR proteins was involved in the NSN to SN transition and played an important role in maintaining the condensation nucleus of SN oocytes via interacting with chromatin.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-11"},"PeriodicalIF":2.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161696","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}
Anastasia V Poznyak, Alexey A Yakovlev, Mikhail А Popov, Elena B Zhigmitova, Vasily N Sukhorukov, Alexander N Orekhov
{"title":"Atherosclerosis originating from childhood: Specific features.","authors":"Anastasia V Poznyak, Alexey A Yakovlev, Mikhail А Popov, Elena B Zhigmitova, Vasily N Sukhorukov, Alexander N Orekhov","doi":"10.7555/JBR.37.20230198","DOIUrl":"10.7555/JBR.37.20230198","url":null,"abstract":"<p><p>Atherosclerosis is extremely widespread. Traditionally, it is considered a disease of older people, who most often experience problems with the heart and blood vessels. While much attention from the scientific community has been paid to studying the association between aging and atherosclerosis, as well as its consequences, there is evidence that atherosclerosis occurs at an early age. Atherosclerosis may form both during intrauterine development and in childhood. Nutrition plays an important role in childhood atherosclerosis, along with previous infectious diseases and excess weight of both the child and the mother. In the present review, we examined the development of atherosclerosis and the prerequisites in childhood.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"233-240"},"PeriodicalIF":2.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11144930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081574","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}
Miao Xu, Yan Gao, Wenjie Yin, Qinghuai Liu, Songtao Yuan
{"title":"RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration.","authors":"Miao Xu, Yan Gao, Wenjie Yin, Qinghuai Liu, Songtao Yuan","doi":"10.7555/JBR.37.20230320","DOIUrl":"10.7555/JBR.37.20230320","url":null,"abstract":"<p><p>The retinal pigment epithelium (RPE) is fundamental to sustaining retinal homeostasis. RPE abnormality leads to visual defects and blindness, including age-related macular degeneration (AMD). Although breakthroughs have been made in the treatment of neovascular AMD, effective intervention for atrophic AMD is largely absent. The inadequate knowledge of RPE pathology is hindered by a lack of patient RPE datasets, especially at the single-cell resolution. In this study, we delved into a large-scale single-cell resource of AMD donors in which RPE cells were occupied in a substantial proportion. Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD. Both <i>in vivo</i> and <i>in vitro</i> models revealed that carboxypeptidase X, M14 family member 2 (CPXM2) was specifically expressed in the RPE cells of atrophic AMD, which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells. Additionally, silencing of <i>CPXM2</i> inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model. Thus, our results demonstrate that CPXM2 plays a crucial role in regulating atrophic AMD and may serve as a potential therapeutic target for atrophic AMD.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161688","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}
Lian Jun Shi, HuiMin Ge, Fan Ye, Xiumiao Li, Qin Jiang
{"title":"The role of pericyte in ocular vascular diseases.","authors":"Lian Jun Shi, HuiMin Ge, Fan Ye, Xiumiao Li, Qin Jiang","doi":"10.7555/JBR.37.20230314","DOIUrl":"10.7555/JBR.37.20230314","url":null,"abstract":"<p><p>Pericytes are located in the stromal membrane of the capillary outer wall and contain endothelial cells (ECs). They are pivotal in regulating blood flow, enhancing vascular stability, and maintaining the integrity of the blood-retina barrier (BRB)/blood-brain barrier (BBB). The pluripotency of pericytes allows them to differentiate into various cell types, highlighting their significance in vascular disease pathogenesis, as demonstrated by previous studies. This potential enables pericytes to be a potential biomarker for the diagnosis and a target for treatment of vascular disorders. The retina, an essential part of the eyeball, is an extension of cerebral tissue with a transparent refractive medium. It offers a unique window for assessing systemic microvascular lesions. Routine fundus examination is necessary for patients with diabetes and hypertension. Manifestations, such as retinal artery tortuosity, dilation, stenosis, and abnormal arteriovenous anastomosis, serve as typical hallmarks of retinal vasculopathy. Therefore, studies of ocular vascular diseases significantly facilitate the exploration of systemic vascular diseases.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161691","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}
Shi-Ya Xie, Yan-Jie Yang, Zhen Jin, Xiao-Cong Liu, Shu-Ping Zhang, Ning Su, Jia-Qi Liu, Cong-Rong Li, Dong Zhang, Lei-Lei Gao, Zhi-Xia Yang
{"title":"Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis.","authors":"Shi-Ya Xie, Yan-Jie Yang, Zhen Jin, Xiao-Cong Liu, Shu-Ping Zhang, Ning Su, Jia-Qi Liu, Cong-Rong Li, Dong Zhang, Lei-Lei Gao, Zhi-Xia Yang","doi":"10.7555/JBR.37.20230290","DOIUrl":"10.7555/JBR.37.20230290","url":null,"abstract":"<p><p>Microtubule-severing enzymes (MTSEs) play important roles in mitosis and meiosis of the primitive organisms. However, no studies have assessed their roles in mammalian meiosis of females, whose abnormality accounts for over 80% of the cases of gamete-originated human reproductive disease. In the current study, we reported that katanin-like 2 (KL2) was the only MTSE concentrating at chromosomes. Furthermore, the knockdown of <i>KL2</i> significantly reduced chromosome-based increase in the microtubule (MT) polymer, increased aberrant kinetochore-MT (K-MT) attachment, delayed meiosis, and severely affected normal fertility. Importantly, we demonstrated that the inhibition of aurora B, a key kinase for correcting aberrant K-MT attachment, eliminated KL2 from chromosomes completely. KL2 also interacted with phosphorylated eukaryotic elongation factor-2 kinase; they competed for chromosome binding. We also observed that the phosphorylated KL2 was localized at spindle poles, and that KL2 phosphorylation was regulated by extracellular signal-regulated kinase 1/2. In summary, our study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-15"},"PeriodicalIF":2.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161645","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}
Anastasia V Poznyak, Alexey Aleksandrovich Yakovlev, Mikhail А Popov, Alexander D Zhuravlev, Vasily N Sukhorukov, Alexander N Orekhov
{"title":"Coronary atherosclerotic plaque regression strategies.","authors":"Anastasia V Poznyak, Alexey Aleksandrovich Yakovlev, Mikhail А Popov, Alexander D Zhuravlev, Vasily N Sukhorukov, Alexander N Orekhov","doi":"10.7555/JBR.37.20230223","DOIUrl":"https://doi.org/10.7555/JBR.37.20230223","url":null,"abstract":"<p><p>Atherosclerosis poses a significant and widespread problem at the population level. Consequently, there is a pressing need to develop effective methods to reduce the risk associated with this condition, which holds a prominent position in cardiology research. The primary manifestation of atherosclerosis involves plaque formation on the walls of coronary arteries. These plaques not only disrupt blood flow but also raise the likelihood of thrombosis and subsequent cardiovascular events. Unfortunately, atherosclerosis itself is usually asymptomatic, resulting in challenges with diagnosis and a delayed initiation of treatment. Hence, strategies focusing on the regression of existing plaques within blood vessels play a crucial role. The present review encompasses comprehensive data on the regression of coronary atherosclerotic plaques, examining both the underlying mechanisms and a range of regression strategies, encompassing lifestyle modifications to medical interventions.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-14"},"PeriodicalIF":2.3,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161440","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}
Xiangyu Zhang, Yingchao Hu, Bingwei Wang, Shuo Yang
{"title":"Ferroptosis: Iron-mediated cell death linked to disease pathogenesis.","authors":"Xiangyu Zhang, Yingchao Hu, Bingwei Wang, Shuo Yang","doi":"10.7555/JBR.37.20230224","DOIUrl":"10.7555/JBR.37.20230224","url":null,"abstract":"<p><p>Ferroptosis is an iron-mediated regulatory cell death pattern characterized by oxidative damage. The molecular regulating mechanisms are related to iron metabolism, lipid peroxidation, and glutathione metabolism. Additionally, some immunological signaling pathways, such as the cyclic GMP-AMP synthase-stimulator ofinterferon genes axis, Janus kinase-signal transducer and activator of transcription 1 axis, and transforming growth factor beta 1-Smad3 axis may also participate in the regulation of ferroptosis. Studies have shown that ferroptosis is closely related to many diseases such as cancer, neurodegenerative diseases, inflammatory diseases, and autoimmune diseases. Considering the pivotal role of ferroptosis-regulating signaling in the pathogenesis of diverse diseases, the development of ferroptosis inducers or inhibitors may have significant clinical potential for the treatment of the aforementioned conditions.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-23"},"PeriodicalIF":2.2,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161410","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":"Evaluating short-term and long-term liver fibrosis improvement in hepatitis C patients post-DAA treatment.","authors":"Yifan Wang, Xinyan Ma, Yanzheng Zou, Ming Yue, Meiling Zhang, Rongbin Yu, Hongbo Chen, Peng Huang","doi":"10.7555/JBR.37.20230284","DOIUrl":"10.7555/JBR.37.20230284","url":null,"abstract":"<p><p>Despite achieving a high cure rate with direct-acting antivirals (DAAs) in hepatitis C treatment, further research is needed to identify additional benefits of the DAA therapy. The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs, who also achieved sustained virologic response (SVR). Using the fibrosis-4 (FIB-4) index, patients were categorized based on their baseline fibrosis level, and improvements in fibrosis were analyzed in both the short-term (9-26 weeks) and long-term (≥ 36 weeks) follow-up. The results showed a significant decrease in the FIB-4 index, indicating an improvement in liver fibrosis, in 63.00% of the patients during the short-term follow-up and 67.56% during the long-term follow-up. Short-term improvement was associated with factors including ribavirin (RBV) usage, blood cholinesterase levels, alanine transaminase levels, albumin levels, and the baseline FIB-4 index. Additionally, long-term improvement was associated with factors such as aspartate transaminase levels, total protein level, and the baseline FIB-4 index. The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis, providing crucial insights for enhancing patient care in hepatitis C management.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161455","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}