hLife最新文献

{"title":"Current perspectives on neuroendocrine tumors","authors":"Sunil Kumar Verma ,&nbsp;Renu Khare ,&nbsp;Devendra Singh","doi":"10.1016/j.hlife.2024.07.006","DOIUrl":"10.1016/j.hlife.2024.07.006","url":null,"abstract":"<div><div>Neoplasms arising from neuroendocrine cells form a heterogeneous group known as neuroendocrine tumors (NETs), which possess both endocrine and neural characteristics. These tumors can occur in various organs throughout the body, with the most prominent sites being the gastrointestinal tract, pancreas, and lungs. Despite their relatively low incidence, NETs have gained significant attention due to their unique biology and clinical behavior. This review intends to provide a widespread gestalt of the present perception of NETs, including their epidemiology, etiology, pathogenesis, classification, clinical presentation, diagnostic modalities, treatment options, and prognosis. Treatment strategies for NETs depend on tumor grade, stage, location, and functional status. Surgical resection remains the pillar of curative treatment for localized disease; on the other hand, systemic therapies take account of targeted therapies like tyrosine kinase inhibitors (TKIs), peptide receptor radionuclide therapy (PRRT), somatostatin analogs, and immunotherapy have shown promising results in advanced cases. In conclusion, this review provides an up-to-date summary of our current knowledge regarding neuroendocrine tumors. Further research is needed to better understand the underlying molecular mechanisms driving tumor development and progression. This will aid in developing novel therapeutic strategies targeting specific pathways involved in NET pathogenesis to improve patient outcomes.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 11","pages":"Pages 563-575"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted protein editing technique in living mammalian cells by peptide-fused PNGase","authors":"Min Wu ,&nbsp;Guijie Bai ,&nbsp;Ziyi Zhang ,&nbsp;Haixia Xiao ,&nbsp;Wenliang Sun ,&nbsp;Chaoguang Tian","doi":"10.1016/j.hlife.2024.07.003","DOIUrl":"10.1016/j.hlife.2024.07.003","url":null,"abstract":"<div><div>Various precise gene editing techniques at the DNA/RNA level, driven by clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology, have gained significant prominence. Yet, research on targeted protein editing techniques remains limited. Only a few attempts have been made, including the use of specific proteases and de-O-glycosylating enzymes as editing enzymes. Here, we propose direct editing of N-glycosylated proteins using de-N-glycosylating enzymes to modify N-glycosylation and simultaneously alter the relevant asparagine residue to aspartate in living cells. Selective protein deglycosylation editors were developed by fusing high-affinity protein-targeting peptides with active peptide:N-glycanases (PNGases). Three crucial cell membrane proteins, programmed cell death protein-1 (PD-1), programmed cell death-1 ligand 1 (PD-L1), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein, were chosen to be tested as a proof of concept. N-linked glycans were removed, and the relevant sites were converted from Asn to Asp in living mammalian cells, destabilizing target proteins and accelerating their degradation. Further investigation focused on SARS-CoV-2 spike protein deglycosylation editing. The collaboration of LCB1-PNGase F (PNGF) effectively reduced syncytia formation, inhibited pseudovirus packaging, and significantly hindered virus entry into host cells, which provides insights for coronavirus disease 2019 (COVID-19) treatment. This tool enables editing protein sequences post-de-N-glycosylation in living human cells, shedding light on protein N-glycosylation functions, and Asn to Asp editing in organisms. It also offers the potential for developing protein degradation technologies.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 11","pages":"Pages 576-591"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141692481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory functions and mechanisms of human microbiota in infectious diseases","authors":"","doi":"10.1016/j.hlife.2024.03.004","DOIUrl":"10.1016/j.hlife.2024.03.004","url":null,"abstract":"<div><div>The human microbiota, a diverse community of microorganisms living on or within their hosts, play an irreplaceable role in maintaining human health. Dysbiosis of the microbiota is associated with the pathogenesis of diverse human diseases. In recent years, growing evidence has been presented to support the substantial effect of human microbiota on the progression of infectious diseases. In this review, we describe the functional role of human microbiota in infectious diseases by highlighting their Janus-faced effects in the regulation of acute and chronic infections as well as their related co-morbidities. Thereafter, we review the latest advances elucidating the mechanisms underlying tri-directional interactions between the microbiota, hosts, and invading pathogens, with a further discussion on external environmental factors that shape this interconnected regulatory network. A better understanding of the regulatory functions and mechanisms of human microbiota in infectious diseases will facilitate the development of new diagnostic, preventive, and therapeutic approaches for infectious diseases.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 10","pages":"Pages 496-513"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140283515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural insights into the distinct protective mechanisms of human antibodies targeting ZIKV NS1","authors":"Qi Pan ,&nbsp;Xiaomin Xing ,&nbsp;Jianhai Yu ,&nbsp;Qiang Chen ,&nbsp;Haizhan Jiao ,&nbsp;Wanqin Zhang ,&nbsp;Yingfen Wen ,&nbsp;Ming Gao ,&nbsp;Wei Zhao ,&nbsp;Lei Yu ,&nbsp;Hongli Hu","doi":"10.1016/j.hlife.2024.05.003","DOIUrl":"10.1016/j.hlife.2024.05.003","url":null,"abstract":"<div><div>Antibodies targeting non-structural protein 1 (NS1) confer protection against Zika virus (ZIKV). Although monoclonal antibodies (MAbs) 3G2 and 4B8 are more potent than MAb 4F10 in suppressing ZIKV infection in neonatal mice models, the epitopes are unclear. Herein, we determined the Cryo-electron microscopy (Cryo-EM) structures of ZIKV NS1 in complex with five human antibodies at 2.6–2.9 Å resolution. Group I antibodies (3G2 and 4B8) recognize the previously unreported epitopes on the outer surface of the NS1 dimer. The unique binding mode of Group I antibodies led to a stronger recognition of the cell surface form of NS1 and completely inhibited secreted form non-structural protein 1 (sNS1)-induced endothelial permeability <em>via</em> their immunoglobulin G (IgG) and Fab. Group II antibodies (4F10, 2E11, and 14G5) recognize common epitopes in the distal end of the β-ladder domain, with a blockade efficiency that may be related to their affinity for the sNS1 protein and the presence of full-length IgG. These findings elucidate the correlation between epitope recognition and protective efficacy of anti-NS1 antibodies and highlight the diagnostic and therapeutic potential of 3G2 and 4B8.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 10","pages":"Pages 527-541"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142533679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements for microbiome research in human health and disease: From composition to functionality","authors":"Nan Qin ,&nbsp;Stanislav Dusko Ehrlich","doi":"10.1016/j.hlife.2024.08.002","DOIUrl":"10.1016/j.hlife.2024.08.002","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 10","pages":"Pages 542-545"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142533680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kha-Ti Lim: Mother of ten thousand infants","authors":"","doi":"10.1016/j.hlife.2024.04.004","DOIUrl":"10.1016/j.hlife.2024.04.004","url":null,"abstract":"","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 10","pages":"Pages 493-495"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140787816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and investigation of all-in-one microneedles complexed with functionalized polydiacetylene liposomes for improved in situ detection sensitivity","authors":"Jiarui Wang ,&nbsp;Weimiao Li ,&nbsp;Yan Chen ,&nbsp;Meng Wu ,&nbsp;Yan Shi ,&nbsp;Jumin Lee ,&nbsp;Ming Kong","doi":"10.1016/j.hlife.2024.07.005","DOIUrl":"10.1016/j.hlife.2024.07.005","url":null,"abstract":"<div><div>Polydiacetylene (PDA) liposomes have been widely applied for detection due to their distinctive optical properties. However, the liquid phase in which PDA liposomes are dispersed generates several drawbacks, for instance, instability, compromise of detection sensitivity induced by dilution, and separation of target sampling and detection, making it inconvenient for application. In this paper, various functionalized PDA liposomes for detecting target were prepared, which were also immobilized into swelling microneedles to construct a solid-phase detection system. The PDA liposomes-complexed microneedles (PDA/MNs) enable the integration of target sampling and detection in one platform. The effects of the dispersing matrix phase on the detection sensitivity of PDA liposomes were systematically investigated from both environmental and chemical perspectives. PDA/MNs exhibited higher sensitivity than their counterparts in liquid phase. PDA/MNs were optimized and validated for lead ion (Pb²⁺) and sialic acid (SA) detections. For Pb²⁺ detection, the limit of detection (LOD) of the PDA/MNs was 13.7 μM and 2.5 times lower than the liquid phase. For SA detection, the LOD of the PDA/MNs was 0.83 μM and 1.7 times lower than the liquid phase. The results suggested that such PDA/MNs were validated to provide a label-free, stable, sensitive, and convenient tool in an all-in-one manner for physiologic target detection.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 10","pages":"Pages 514-526"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surpassing the natural limits of serological diagnostic tests","authors":"","doi":"10.1016/j.hlife.2024.06.001","DOIUrl":"10.1016/j.hlife.2024.06.001","url":null,"abstract":"<div><div>Serological tests have an important and irreplaceable role in the diagnosis of infectious diseases, both for individual patients and society. They indirectly identify the causative pathogen through the capture of antibodies, which contrasts with the direct detection by antigen and molecular biology tests that are also limited to active infections. Within point-of-care platforms, serodiagnostic assays can support immediate decisions in patient care and contain the spread of disease as they do not require highly trained personnel or dedicated infrastructure. By employing serodiagnosis, health officials can proactively respond and eliminate emerging health risks. Larger sample numbers can be screened in other formats for surveillance as well as securing donated blood supplies. Furthermore, an assay can be designed to detect any immunoglobulin from IgM to IgG and its subclasses, to IgA and IgE. However, most serological assays employ natural proteins as the defining antibody-capturing reagent, which compromises their performance by limiting the two critical parameters of a serodiagnostic test: specificity and sensitivity. To surpass this natural limitation, we have repurposed the β-barrel of fluorescent proteins to receive epitope sequences that dependably produce high-performing designer immunological reagents. Consequently, serodiagnosis can be conducted more accurately at a lower cost.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 9","pages":"Pages 467-470"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000476/pdfft?md5=482905bb00c9e9befc43de6b36a959fb&pid=1-s2.0-S2949928324000476-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141410133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discoidin domain receptor 1 as a potent therapeutic target in solid tumors","authors":"","doi":"10.1016/j.hlife.2024.01.003","DOIUrl":"10.1016/j.hlife.2024.01.003","url":null,"abstract":"<div><div>Despite significant discoveries in basic cancer research and improvements in treatment options and clinical outcomes, cancer remains a major public health concern worldwide. Today, the main focus of cancer research is the signaling pathways that are crucial for cell survival, cell proliferation, and cell migration. The aberrant expression of proteins involved in these signaling pathways often leads to abnormal cell growth, cell metastasis, and invasion of healthy tissues. One such protein is discoidin domain receptor 1 (DDR1) which belongs to the family of receptor tyrosine kinases (RTKs) and is activated upon collagen binding, as a result, downstream signaling pathways are stimulated which are responsible for cell survival, cell growth, adhesion, extracellular matrix remodeling, and cell migration. DDR1 is found to have abnormally elevated expression in various solid tumors, implying a critical role in cancer progression. Traditional cancer treatment involves the use of cytotoxic drugs, chemotherapy, radiotherapy, and surgery, which do not provide long-term survival and often result in cancer recurrence. Numerous small-molecule kinase inhibitors have been synthesized against RTKs including DDR1 and have been highly efficacious in tumor reduction. More recently, targeting the DDR1 extracellular domain (ECD) has garnered much attention from researchers, as inhibiting the DDR1-collagen binding has been attributed to maximizing the likelihood of the combined cytotoxic effect of both immune cells and targeted drugs. This review focuses on the structure, function, activation, and signaling partners of DDR1, its role in different solid tumors, and finally discusses about designing more DDR1 non-kinase inhibitors as promising therapeutic strategies against DDR1-driven tumors.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 9","pages":"Pages 454-466"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000051/pdfft?md5=bc82c56122dee5f47002d68a90172204&pid=1-s2.0-S2949928324000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139639594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HiTIP-seq profiles epigenomic reprogramming of patient-derived diffuse midline glioma stem cells to epigenetic therapy","authors":"Zhongyao Chen ,&nbsp;Qiang Gao ,&nbsp;Yukui Shang ,&nbsp;Behzad Nasiri Ahmadabadi ,&nbsp;Yawei Hu ,&nbsp;Wei Zhang ,&nbsp;Peng Liu","doi":"10.1016/j.hlife.2024.07.004","DOIUrl":"10.1016/j.hlife.2024.07.004","url":null,"abstract":"<div><div>Diffuse midline glioma (DMG), H3K27-altered, is lethal pediatric-type, high-grade, localized to the midline region of the central nervous system. Effective treatment guidelines are absent, and clinical trials are preferred for primary or recurrent DMG patients. Recently, epigenetic agent-based immunotherapy has exhibited promising therapeutic effects in the clinical setting. However, the underlying mechanisms remain a mystery. The rare DMG tumor samples from biopsy or resection largely impede basic research, by using patient-derived tumor cells which better recapitulate the parental tumor's heterogeneity compared to established cell lines. As an epigenetic reprogramming disease, DMG exhibits a global loss of H3K27 trimethylation (H3K27me3) and a gain of H3K27 acetylation (H3K27ac). Analysis of multiple epigenetic marks is fundamentally necessary. However, traditional techniques cannot allow ultra-low input and high-throughput. Herein we have developed a new method called high-throughput <em>in situ</em> tagged immunoprecipitation sequencing (HiTIP-seq), which uses an integrated superhydrophobic microwell array technology (InSMART). We were able to perform 100 parallel assays from as few as 100 cells per microwell on a single chip. We applied the technology to profile epigenetic alterations of three-dimensional (3D) cell cultures derived from DMG patients. Our HiTIP-seq integrated with RNA sequencing (RNA-seq) analysis revealed that the combination of epigenetic agents (panobinostat and tazemetostat), reprogrammed histone modifications and drove transcriptome changes. Among them, Wnt inhibitory factor 1 (<em>WIF1</em>) has a gain of H3K27ac and a loss of H3K27me3, which leads to the upregulated expression. Altogether, HiTIP-seq is a versatile method for high-throughput analysis of histone modifications, suitable for both DMG research and studying rare 3D models.</div></div>","PeriodicalId":100609,"journal":{"name":"hLife","volume":"2 9","pages":"Pages 471-487"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949928324000622/pdfft?md5=1644a1fd4587672755b878818279935d&pid=1-s2.0-S2949928324000622-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141698860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}