Journal of Biomedical Research最新文献

{"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 a pattern of iron-mediated regulatory cell death characterized by oxidative damage. The molecular regulatory mechanisms are related to iron metabolism, lipid peroxidation, and glutathione metabolism. Additionally, some immunological signaling pathways, such as the cyclic GMP-AMP synthase-stimulator of the interferon gene axis, the Janus kinase-signal transducer and activator of transcription 1 axis, and the transforming growth factor beta 1-Smad3 axis, may also participate in the regulation of ferroptosis. Studies have shown that ferroptosis is significantly associated with 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 aforementioned conditions.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"413-435"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","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":"Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis.","authors":"Shiya Xie, Yanjie Yang, Zhen Jin, Xiaocong Liu, Shuping Zhang, Ning Su, Jiaqi Liu, Congrong Li, Dong Zhang, Leilei Gao, Zhixia 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, their roles in mammalian female meiosis, which accounts for over 80% of gamete-originated human reproductive diseases, remain unexplored. 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 the chromosome-based increase in the microtubule (MT) polymer, increased aberrant kinetochore-MT (K-MT) attachment, delayed meiosis, and severely affected normal fertility. We demonstrated that the inhibition of aurora B, a key kinase for correcting aberrant K-MT attachment, significantly eliminated KL2 expression from chromosomes. Additionally, KL2 interacted with phosphorylated eukaryotic elongation factor-2 kinase, and they competed for chromosome binding. Phosphorylated KL2 was also localized at spindle poles, with its phosphorylation regulated by extracellular signal-regulated kinase 1/2. In summary, the current 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":"485-499"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","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}

{"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":"10.7555/JBR.38.20240054","url":null,"abstract":"<p><p>Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes, notably the chromatin configuration transition from a non-surrounding nucleolus (NSN) to surrounding nucleolus (SN) in germinal vesicle oocytes. In the current study, we found that nuclear speckles (NSs), a subnuclear structure mainly composed of serine-arginine (SR) proteins, changed from a diffuse spotted distribution in mouse NSN oocytes to an aggregated pattern in SN oocytes. We also found that the SR protein-specific kinase 1 (SRPK1), an enzyme that phosphorylates SR proteins, co-localized with NSs at the SN stage, and that NSN oocytes failed to transition to SN oocytes after the inhibition of SRPK1 activity. Furthermore, the typical structure of the chromatin ring around the nucleolus in SN oocytes collapsed after treatment with an SRPK1 inhibitor. Mechanistically, phosphorylated SR proteins were found to be related to chromatin as shown by a salt extraction experiment, and <i>in situ</i> DNase I assay showed that the accessibility of chromatin was enhanced in SN oocytes when SRPK1 was inhibited, accompanied by a decreased repressive modification on histone and the abnormal recurrence of a transcriptional signal. In conclusion, our results indicated that SRPK1-regulated phosphorylation of SR proteins was involved in the NSN-SN transition and played an important role in maintaining the condensed nucleus of SN oocytes <i>via</i> interacting with chromatin.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"198-208"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982682/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEC1 deficiency protects against bone loss induced by ovariectomy by 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>Studies have shown that differentiated embryo-chondrocyte expressed gene 1 (DEC1) promotes osteoblast osteogenesis. To investigate the role of DEC1 in postmenopausal osteoporosis, we used the two genotypes of mice ( <i>Dec1</i> ^+/+ and <i>Dec1</i> ^-/-) to establish an ovariectomy model and found that the bone loss was significantly lower in <i>Dec1</i> ^-/- ovariectomy mice than in <i>Dec1</i> ^+/+ ovariectomy mice. The expression levels of RUNX2 and OSX were significantly increased in <i>Dec1</i> ^-/- ovariectomy mice, compared with <i>Dec1</i> ^+/+ ovariectomy mice; however, the expression levels of NFATc1, c-Fos, CTSK, and RANKL/OPG ratio were significantly decreased in <i>Dec1</i> ^-/- ovariectomy mice, compared with those in <i>Dec1</i> ^+/+ ovariectomy mice. Likewise, DEC1 deficiency also suppressed the expression levels of IL-6 and IL-1β. Further results showed that the mRNA expression levels of <i>Runx2</i>, <i>Osx</i>, and <i>Alp</i> were significantly increased in bone marrow mesenchymal stem cells of <i>Dec1</i> ^-/- ovariectomy mice, compared with those of <i>Dec1</i> ^+/+ ovariectomy mice. Moreover, the mRNA levels of <i>Il1b</i>, <i>Il6</i>, <i>Tnfa</i>, and <i>Ifng</i> were significantly increased in bone marrow-derived macrophages (BMMs) of <i>Dec1</i> ^+/+ovariectomy mice, compared with those of <i>Dec1</i> ^+/+ sham mice, but not in <i>Dec1</i> ^-/- ovariectomy BMMs, when compared with those in <i>Dec1</i> ^-/- sham BMMs. Additionally, the expression levels of p-IκBα and p-P65 were significantly increased in <i>Dec1</i> ^+/+ ovariectomy BMMs, compared with those in <i>Dec1</i> ^+/+ sham BMMs, but did not increase in <i>Dec1</i> ^-/- ovariectomy BMMs, compared with those in <i>Dec1</i> ^-/- sham BMMs. Taken together, DEC1 deficiency inhibited the NF-κB pathway induced by ovariectomy, thereby decreasing cytokines and subsequently inhibiting the decrease of osteogenesis and the increase of osteoclastogenesis caused by ovariectomy. The findings may provide a novel understanding of postmenopausal osteoporosis development, and offer potential avenues for the disease intervention.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"613-627"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","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":"WITHDRAWN: Coronary atherosclerotic plaque regression strategies.","authors":"Anastasia V Poznyak, Alexey A Yakovlev, Mikhail А Popov, Alexander D Zhuravlev, Vasily N Sukhorukov, Alexander N Orekhov","doi":"10.7555/JBR.37.20230223","DOIUrl":"10.7555/JBR.37.20230223","url":null,"abstract":"<p><p>Ahead of Print article withdrawn by publisher.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-21"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","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}

{"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 injuries. Hematoma, as the primary pathology of ICH, undergoes metabolism and triggers biochemical and biomechanical alterations in the brain, leading to the secondary injury. Past endeavors mainly aimed at biochemical-initiated mechanisms for causing secondary injury, which have made limited progress in recent years, although ICH itself is also highly biomechanics-related. The discovery of the mechanically-activated cation channel Piezo1 provides a new avenue to further explore the mechanisms underlying the 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":"436-447"},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","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}

{"title":"Acrolein-triggered atherosclerosis <i>via</i> AMPK/SIRT1-CLOCK/BMAL1 pathway and a protection from intermittent fasting.","authors":"Qianfeng Chen, Yuxia Zhong, Bohan Li, Yucong Feng, Yuandie Zhang, Tao Wei, Margaret Zaitoun, Shuang Rong, Hua Wan, Qing Feng","doi":"10.7555/JBR.38.20240025","DOIUrl":"https://doi.org/10.7555/JBR.38.20240025","url":null,"abstract":"<p><p>Circadian clock plays a vital role in the pathological progression of cardiovascular disease (CVD). Our previous studies showed that acrolein, an environmental pollutant, promoted atherosclerosis by reducing CLOCK/BMAL1 and disturbing circadian rhythm. Whereas, intermittent fasting (IF), a diet pattern, was able to ameliorate acrolein-induced atherosclerosis. <i>In vivo</i>, mice were fed acrolein 3 mg/kg/day <i>via</i> drinking water and IF for 18h (0:00-18:00). We observed that IF decreased acrolein-accelerated the formation of aortic lesion in <i>ApoE</i> ^-/- mice. Up-regulation of <i>NF-κB, IL-1β</i> and <i>TNF-α</i> levels were found in liver and heart tissue upon acrolein exposure, while was down-regulated by IF. Interestingly, IF treatment exhibited higher AMPK, p-AMPK and SIRT1and lower MAPK expression which was caused by acrolein. Besides, circadian genes <i>Clock/ Bmal1</i> expression were suppressed and disturbed treated with acrolein, while were reversed by IF. Furthermore, consistent with that <i>in vivo</i>, short-term starvation as a fasting cell model <i>in vitro</i> could improve the disorders of CLOCK/BMAL1 and raised SIRT1 <i>via</i> regulating AMPK, as well as ROS-MAPK induced by acrolein. In conclusion, we demonstrated that IF repressed ROS-MAPK while activated AMPK to elevate the expression of circadian clock genes to ameliorate acrolein-induced atherogenesis, which shed a novel light to prevent cardiovascular diseases.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-15"},"PeriodicalIF":2.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161434","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":"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}

{"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}

{"title":"Evaluating short-term and long-term liver fibrosis improvement in hepatitis C patients after 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 the 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. By the fibrosis-4 (FIB-4) index, patients were categorized based on their baseline fibrosis levels, and the improvement in fibrosis was analyzed in both 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 63.0% and 67.6% of the patients during the short-term and long-term follow-up, respectively. Short-term improvement was associated with factors including ribavirin usage, blood cholinesterase levels, alanine transaminase levels, albumin levels, and the baseline FIB-4 index, while 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, which will provide crucial insights for enhancing patient care in hepatitis C management.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"464-472"},"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}