Journal of Biomedical Science最新文献

{"title":"Targeting NLRP3 signaling reduces myocarditis-induced arrhythmogenesis and cardiac remodeling","authors":"Chye-Gen Chin, Yao-Chang Chen, Fong-Jhih Lin, Yung-Kuo Lin, Yen-Yu Lu, Tzu-Yu Cheng, Shih-Ann Chen, Yi-Jen Chen","doi":"10.1186/s12929-024-01032-7","DOIUrl":"https://doi.org/10.1186/s12929-024-01032-7","url":null,"abstract":"Myocarditis substantially increases the risk of ventricular arrhythmia. Approximately 30% of all ventricular arrhythmia cases in patients with myocarditis originate from the right ventricular outflow tract (RVOT). However, the role of NLRP3 signaling in RVOT arrhythmogenesis remains unclear. Rats with myosin peptide–induced myocarditis (experimental group) were treated with an NLRP3 inhibitor (MCC950; 10 mg/kg, daily for 14 days) or left untreated. Then, they were subjected to electrocardiography and echocardiography. Ventricular tissue samples were collected from each rat’s RVOT, right ventricular apex (RVA), and left ventricle (LV) and examined through conventional microelectrode and histopathologic analyses. In addition, whole-cell patch-clamp recording, confocal fluorescence microscopy, and Western blotting were performed to evaluate ionic currents, intracellular Ca2+ transients, and Ca2+-modulated protein expression in individual myocytes isolated from the RVOTs. The LV ejection fraction was lower and premature ventricular contraction frequency was higher in the experimental group than in the control group (rats not exposed to myosin peptide). Myocarditis increased the infiltration of inflammatory cells into cardiac tissue and upregulated the expression of NLRP3; these observations were more prominent in the RVOT and RVA than in the LV. Furthermore, experimental rats treated with MCC950 (treatment group) improved their LV ejection fraction and reduced the frequency of premature ventricular contraction. Histopathological analysis revealed higher incidence of abnormal automaticity and pacing-induced ventricular tachycardia in the RVOTs of the experimental group than in those of the control and treatment groups. However, the incidences of these conditions in the RVA and LV were similar across the groups. The RVOT myocytes of the experimental group exhibited lower Ca2+ levels in the sarcoplasmic reticulum, smaller intracellular Ca2+ transients, lower L-type Ca2+ currents, larger late Na+ currents, larger Na+–Ca2+ exchanger currents, higher reactive oxygen species levels, and higher Ca2+/calmodulin-dependent protein kinase II levels than did those of the control and treatment groups. Myocarditis may increase the rate of RVOT arrhythmogenesis, possibly through electrical and structural remodeling. These changes may be mitigated by inhibiting NLRP3 signaling.","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"49 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dengue virus pathogenesis and host molecular machineries","authors":"Saumya Sinha, Kinjal Singh, Y. S. Ravi Kumar, Riya Roy, Sushant Phadnis, Varsha Meena, Sankar Bhattacharyya, Bhupendra Verma","doi":"10.1186/s12929-024-01030-9","DOIUrl":"https://doi.org/10.1186/s12929-024-01030-9","url":null,"abstract":"Dengue viruses (DENV) are positive-stranded RNA viruses belonging to the Flaviviridae family. DENV is the causative agent of dengue, the most rapidly spreading viral disease transmitted by mosquitoes. Each year, millions of people contract the virus through bites from infected female mosquitoes of the Aedes species. In the majority of individuals, the infection is asymptomatic, and the immune system successfully manages to control virus replication within a few days. Symptomatic individuals may present with a mild fever (Dengue fever or DF) that may or may not progress to a more critical disease termed Dengue hemorrhagic fever (DHF) or the fatal Dengue shock syndrome (DSS). In the absence of a universally accepted prophylactic vaccine or therapeutic drug, treatment is mostly restricted to supportive measures. Similar to many other viruses that induce acute illness, DENV has developed several ways to modulate host metabolism to create an environment conducive to genome replication and the dissemination of viral progeny. To search for new therapeutic options, understanding the underlying host-virus regulatory system involved in various biological processes of the viral life cycle is essential. This review aims to summarize the complex interaction between DENV and the host cellular machinery, comprising regulatory mechanisms at various molecular levels such as epigenetic modulation of the host genome, transcription of host genes, translation of viral and host mRNAs, post-transcriptional regulation of the host transcriptome, post-translational regulation of viral proteins, and pathways involved in protein degradation.","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"51 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of peptides in nanosystems for diagnosing and managing bacterial sepsis","authors":"Mohammed A. Gafar, Calvin A. Omolo, Eman Elhassan, Usri H. Ibrahim, Thirumala Govender","doi":"10.1186/s12929-024-01029-2","DOIUrl":"https://doi.org/10.1186/s12929-024-01029-2","url":null,"abstract":"Sepsis represents a critical medical condition stemming from an imbalanced host immune response to infections, which is linked to a significant burden of disease. Despite substantial efforts in laboratory and clinical research, sepsis remains a prominent contributor to mortality worldwide. Nanotechnology presents innovative opportunities for the advancement of sepsis diagnosis and treatment. Due to their unique properties, including diversity, ease of synthesis, biocompatibility, high specificity, and excellent pharmacological efficacy, peptides hold great potential as part of nanotechnology approaches against sepsis. Herein, we present a comprehensive and up-to-date review of the applications of peptides in nanosystems for combating sepsis, with the potential to expedite diagnosis and enhance management outcomes. Firstly, sepsis pathophysiology, antisepsis drug targets, current modalities in management and diagnosis with their limitations, and the potential of peptides to advance the diagnosis and management of sepsis have been adequately addressed. The applications have been organized into diagnostic or managing applications, with the last one being further sub-organized into nano-delivered bioactive peptides with antimicrobial or anti-inflammatory activity, peptides as targeting moieties on the surface of nanosystems against sepsis, and peptides as nanocarriers for antisepsis agents. The studies have been grouped thematically and discussed, emphasizing the constructed nanosystem, physicochemical properties, and peptide-imparted enhancement in diagnostic and therapeutic efficacy. The strengths, limitations, and research gaps in each section have been elaborated. Finally, current challenges and potential future paths to enhance the use of peptides in nanosystems for combating sepsis have been deliberately spotlighted. This review reaffirms peptides' potential as promising biomaterials within nanotechnology strategies aimed at improving sepsis diagnosis and management. • Due to their unique characteristics, Peptides hold significant promise as part of nanotechnology approaches for diagnosing and treating sepsis, a current leading global killer. • Various diagnostic nanotools utilizing peptides as pathogen recognition moieties can improve the pathogen capturing efficiency for sepsis diagnosis. • Nano-delivery can overcome the limitations of bioactive peptides and enhance their antibacterial and anti-inflammatory efficacy in sepsis management. • Peptides offer significant capabilities as targeting moieties and nanocarriers to augment the effectiveness of antisepsis agents. • Future research identified can potentiate the applications of peptides for the diagnosis and treatment of sepsis.","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"28 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of NETosis by ACE2-cross-reactive anti-SARS-CoV-2 RBD antibodies in patients with COVID-19","authors":"Kun-Han Hsieh, Chiao-Hsuan Chao, Yi-Ling Cheng, Yen-Chung Lai, Yung-Chun Chuang, Jen-Ren Wang, Sui-Yuan Chang, Yuan-Pin Hung, Yi-Ming Arthur Chen, Wei-Lun Liu, Woei-Jer Chuang, Trai-Ming Yeh","doi":"10.1186/s12929-024-01026-5","DOIUrl":"https://doi.org/10.1186/s12929-024-01026-5","url":null,"abstract":"High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown. In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied. An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection. Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients.","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"64 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice","authors":"Vicki Wang, Kuan-Yin Tseng, Tung-Tai Kuo, Eagle Yi-Kung Huang, Kuo-Lun Lan, Zi-Rong Chen, Kuo-Hsing Ma, Nigel H. Greig, Jin Jung, Ho-II Choi, Lars Olson, Barry J. Hoffer, Yuan-Hao Chen","doi":"10.1186/s12929-024-01025-6","DOIUrl":"https://doi.org/10.1186/s12929-024-01025-6","url":null,"abstract":"Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood. In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse. Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae. Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD. ","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"48 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington’s disease","authors":"Tamara Vasilkovska, Somaie Salajeghe, Verdi Vanreusel, Johan Van Audekerke, Marlies Verschuuren, Lydiane Hirschler, Jan Warnking, Isabel Pintelon, Dorian Pustina, Roger Cachope, Ladislav Mrzljak, Ignacio Muñoz-Sanjuan, Emmanuel L. Barbier, Winnok H. De Vos, Annemie Van der Linden, Marleen Verhoye","doi":"10.1186/s12929-024-01028-3","DOIUrl":"https://doi.org/10.1186/s12929-024-01028-3","url":null,"abstract":"Huntington’s disease (HD) is marked by a CAG-repeat expansion in the huntingtin gene that causes neuronal dysfunction and loss, affecting mainly the striatum and the cortex. Alterations in the neurovascular coupling system have been shown to lead to dysregulated energy supply to brain regions in several neurological diseases, including HD, which could potentially trigger the process of neurodegeneration. In particular, it has been observed in cross-sectional human HD studies that vascular alterations are associated to impaired cerebral blood flow (CBF). To assess whether whole-brain changes in CBF are present and follow a pattern of progression, we investigated both resting-state brain perfusion and vascular reactivity longitudinally in the zQ175DN mouse model of HD. Using pseudo-continuous arterial spin labelling (pCASL) MRI in the zQ175DN model of HD and age-matched wild-type (WT) mice, we assessed whole-brain, resting-state perfusion at 3, 6 and 9 and 13 months of age, and assessed hypercapnia-induced cerebrovascular reactivity (CVR), at 4.5, 6, 9 and 15 months of age. We found increased perfusion in cortical regions of zQ175DN HET mice at 3 months of age, and a reduction of this anomaly at 6 and 9 months, ages at which behavioural deficits have been reported. On the other hand, under hypercapnia, CBF was reduced in zQ175DN HET mice as compared to the WT: for multiple brain regions at 6 months of age, for only somatosensory and retrosplenial cortices at 9 months of age, and brain-wide by 15 months. CVR impairments in cortical regions, the thalamus and globus pallidus were observed in zQ175DN HET mice at 9 months, with whole brain reactivity diminished at 15 months of age. Interestingly, blood vessel density was increased in the motor cortex at 3 months, while average vessel length was reduced in the lateral portion of the caudate putamen at 6 months of age. Our findings reveal early cortical resting-state hyperperfusion and impaired CVR at ages that present motor anomalies in this HD model, suggesting that further characterization of brain perfusion alterations in animal models is warranted as a potential therapeutic target in HD.","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"29 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial peptide thanatin fused endolysin PA90 (Tha-PA90) for the control of Acinetobacter baumannii infection in mouse model","authors":"Jeonghyun Lim, Heejoon Myung, Daejin Lim, Miryoung Song","doi":"10.1186/s12929-024-01027-4","DOIUrl":"https://doi.org/10.1186/s12929-024-01027-4","url":null,"abstract":"This study addresses the urgent need for infection control agents driven by the rise of drug-resistant pathogens such as Acinetobacter baumannii. Our primary aim was to develop and assess a novel endolysin, Tha-PA90, designed to combat these challenges. Tha-PA90 incorporates an antimicrobial peptide (AMP) called thanatin at its N-terminus, enhancing bacterial outer membrane permeability and reducing host immune responses. PA90 was selected as the endolysin component. The antibacterial activity of the purified Tha-PA90 was evaluated using an in vitro colony-forming unit (CFU) reduction assay and a membrane permeability test. A549 cells were utilized to measure the penetration into the cytosol and the cytotoxicity of Tha-PA90. Finally, infection control was monitored in A. baumannii infected mice following the intraperitoneal administration of Tha-PA90. Tha-PA90 demonstrated remarkable in vitro efficacy, completely eradicating A. baumannii strains, even drug-resistant variants, at a low concentration of 0.5 μM. Notably, it outperformed thanatin, achieving only a < 3-log reduction at 4 μM. Tha-PA90 exhibited 2–3 times higher membrane permeability than a PA90 and thanatin mixture or PA90 alone. Tha-PA90 was found within A549 cells' cytosol with no discernible cytotoxic effects. Furthermore, Tha-PA90 administration extended the lifespan of A. baumannii-infected mice, reducing bacterial loads in major organs by up to 3 logs. Additionally, it decreased proinflammatory cytokine levels (TNF-α and IL-6), reducing the risk of sepsis from rapid bacterial lysis. Our findings indicate that Tha-PA90 is a promising solution for combating drug-resistant A. baumannii. Its enhanced efficacy, low cytotoxicity, and reduction of proinflammatory responses render it a potential candidate for infection control. This study underscores the significance of engineered endolysins in addressing the pressing challenge of drug-resistant pathogens and offers insights into improved infection management strategies.","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"18 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: A novel HIF1α-STIL-FOXM1 axis regulates tumor metastasis","authors":"Yi-Wei Wang, Shu-Chuan Chen, De-Leung Gu, Yi-Chen Yeh, Jhih-Jie Tsai, Kuo-Tai Yang, Yuh-Shan Jou, Teh-Ying Chou, Tang K. Tang","doi":"10.1186/s12929-024-01021-w","DOIUrl":"https://doi.org/10.1186/s12929-024-01021-w","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction&lt;/b&gt;&lt;b&gt;: &lt;/b&gt;&lt;b&gt;J Biomed Sci 29, 24 (2022)&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/s12929-022-00807-0&lt;/b&gt;&lt;/p&gt;&lt;br/&gt;&lt;p&gt;After publication of this article [1], it was brought to our attention that the figure 6, supplementary figure s5, Supplementary Figure S8 need to be corrected.&lt;/p&gt;&lt;p&gt;The Incorrect figure 6 is:&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Figa_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure a\" aria-describedby=\"Figa\" height=\"859\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Figa_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;p&gt;The correct figure 6 is:&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Figb_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure b\" aria-describedby=\"Figb\" height=\"861\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Figb_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;p&gt;The Incorrect supplementary figure s5 is:&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Figc_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure c\" aria-describedby=\"Figc\" height=\"636\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Figc_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;p&gt;The correct supplementary figure s5 is:&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Figd_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure d\" aria-describedby=\"Figd\" height=\"636\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Figd_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;p&gt;The Incorrect Supplementary Figure S8 is:&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Fige_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure e\" aria-describedby=\"Fige\" height=\"1091\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Fige_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;p&gt;The correct Supplementary Figure S8 is:&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12929-024-01021-w/MediaObjects/12929_2024_1021_Figf_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure f\" aria-describedby=\"Figf\" height=\"1346\" loading=\"lazy\" s","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"243 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significance of hepatitis B virus capsid dephosphorylation via polymerase.","authors":"Chih-Hsu Chang, Chiaho Shih","doi":"10.1186/s12929-024-01022-9","DOIUrl":"10.1186/s12929-024-01022-9","url":null,"abstract":"<p><strong>Background: </strong>It is generally believed that hepatitis B virus (HBV) core protein (HBc) dephosphorylation (de-P) is important for viral DNA synthesis and virion secretion. HBV polymerase contains four domains for terminal protein, spacer, reverse transcriptase, and RNase H activities.</p><p><strong>Methods: </strong>HBV Polymerase mutants were transfected into HuH-7 cells and assayed for replication and HBc de-P by the Phos-tag gel analysis. Infection assay was performed by using a HepG2-NTCP-AS2 cell line.</p><p><strong>Results: </strong>Here, we show that a novel phosphatase activity responsible for HBc de-P can be mapped to the C-terminal domain of the polymerase overlapping with the RNase H domain. Surprisingly, while HBc de-P is crucial for viral infectivity, it is essential for neither viral DNA synthesis nor virion secretion. The potential origin, significance, and mechanism of this polymerase-associated phosphatase activity are discussed in the context of an electrostatic homeostasis model. The Phos-tag gel analysis revealed an intriguing pattern of \"bipolar distribution\" of phosphorylated HBc and a de-P HBc doublet.</p><p><strong>Conclusions: </strong>It remains unknown if such a polymerase-associated phosphatase activity can be found in other related biosystems. This polymerase-associated phosphatase activity could be a druggable target in clinical therapy for hepatitis B.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"34"},"PeriodicalIF":11.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of TRAIL receptor with phosphatase SHP-1 enables repressing T cell receptor signaling and T cell activation through inactivating Lck.","authors":"I-Tsu Chyuan, Hsiu-Jung Liao, Tse-Hua Tan, Huai-Chia Chuang, Yu-Chuan Chu, Meng-Hsun Pan, Chien-Sheng Wu, Ching-Liang Chu, Bor-Ching Sheu, Ping-Ning Hsu","doi":"10.1186/s12929-024-01023-8","DOIUrl":"10.1186/s12929-024-01023-8","url":null,"abstract":"<p><strong>Background: </strong>T cell receptor (TCR) signaling and T cell activation are tightly regulated by gatekeepers to maintain immune tolerance and avoid autoimmunity. The TRAIL receptor (TRAIL-R) is a TNF-family death receptor that transduces apoptotic signals to induce cell death. Recent studies have indicated that TRAIL-R regulates T cell-mediated immune responses by directly inhibiting T cell activation without inducing apoptosis; however, the distinct signaling pathway that regulates T cell activation remains unclear. In this study, we screened for intracellular TRAIL-R-binding proteins within T cells to explore the novel signaling pathway transduced by TRAIL-R that directly inhibits T cell activation.</p><p><strong>Methods: </strong>Whole-transcriptome RNA sequencing was used to identify gene expression signatures associated with TRAIL-R signaling during T cell activation. High-throughput screening with mass spectrometry was used to identify the novel TRAIL-R binding proteins within T cells. Co-immunoprecipitation, lipid raft isolation, and confocal microscopic analyses were conducted to verify the association between TRAIL-R and the identified binding proteins within T cells.</p><p><strong>Results: </strong>TRAIL engagement downregulated gene signatures in TCR signaling pathways and profoundly suppressed phosphorylation of TCR proximal tyrosine kinases without inducing cell death. The tyrosine phosphatase SHP-1 was identified as the major TRAIL-R binding protein within T cells, using high throughput mass spectrometry-based proteomics analysis. Furthermore, Lck was co-immunoprecipitated with the TRAIL-R/SHP-1 complex in the activated T cells. TRAIL engagement profoundly inhibited phosphorylation of Lck (Y394) and suppressed the recruitment of Lck into lipid rafts in the activated T cells, leading to the interruption of proximal TCR signaling and subsequent T cell activation.</p><p><strong>Conclusions: </strong>TRAIL-R associates with phosphatase SHP-1 and transduces a unique and distinct immune gatekeeper signal to repress TCR signaling and T cell activation via inactivating Lck. Thus, our results define TRAIL-R as a new class of immune checkpoint receptors for restraining T cell activation, and TRAIL-R/SHP-1 axis can serve as a potential therapeutic target for immune-mediated diseases.</p>","PeriodicalId":15365,"journal":{"name":"Journal of Biomedical Science","volume":"31 1","pages":"33"},"PeriodicalIF":11.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10967194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}