MedComm - Future medicine最新文献

{"title":"Ferredoxin 1, the key regulator of cuproptosis, was associated with prognosis and immune cell infiltration in clear cell renal cell carcinoma","authors":"Dian Xia,&nbsp;Kun Liu,&nbsp;Wen Jiao,&nbsp;Longfei Peng,&nbsp;Qi Liu,&nbsp;Chang Liu,&nbsp;Liangkuan Bi","doi":"10.1002/mef2.36","DOIUrl":"10.1002/mef2.36","url":null,"abstract":"<p>According to a number of studies, the occurrence and progression clear cell renal cell carcinoma (ccRCC), among the most prevalent cancerous tumors of the urinary bladder, may be inextricable from metabolism and immunology. The recent discovery of cuproptosis revealed a novel cell death mechanism based on mitochondrial respiration and the tricarboxylic acid cycle, and cuproptosis is strongly linked to the metabolic process. The cuproptosis process is different from the previously revealed cell death processes such as pyroptosis, apoptosis and ferroptosis, which is expected to provide a new perspective in the study of tumor mechanism. Here we aim to explore the important role of key regulators of cuproptosis in renal cancer using a combination of bioinformatics and experimental validation. We found that Ferredoxin 1 (FDX1) was related to the infiltration of various immune cells in the tumor microenvironment and the response to immunotherapy in ccRCC. At the same time, the experiment confirmed that FDX1 was significantly lower in ccRCC, which was consistent with the previous analysis results. In conclusions, FDX1 was expected to be an important marker of immune infiltration, immunotherapy, and tumor prognosis in ccRCC.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48284816","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":"Direct cellular targets and anticancer mechanisms of the natural product oridonin","authors":"Jialin Yao,&nbsp;Lu Liu,&nbsp;Qingxiang Sun,&nbsp;Xiaofei Shen","doi":"10.1002/mef2.35","DOIUrl":"https://doi.org/10.1002/mef2.35","url":null,"abstract":"<p>Cancer is one of the leading causes of death worldwide. The proliferation, survival, and metastasis of cancer cells are governed by a complex series of intracellular and extracellular signaling pathways. Therefore, efficient cancer therapy often requires the modulation of multiple targets. Besides, the modulation of several biological targets with a single drug can lead to synergistic therapeutic effects and avoid side effects associated with combination therapy. Oridonin, an ent-kaurane type diterpenoid isolated from <i>Rabdosia rubescens</i>, has been reported to possess potent anti-inflammatory, antioxidant, anticancer, and neuroprotective activities. Among its many benefits, the anticancer effects have attracted the most attention because of its effectiveness in many tumor cells and its potential to overcome therapeutic resistance. Recently, several proteins involved in oncogenic signaling, including CRM1, PHGDH, HSP70, AML1-ETO, and STAT3, were identified as functional targets of oridonin and its analogs. The binding mechanism and the consequence of oridonin binding to these oncogenic proteins are summarized and discussed. These advances suggest that oridonin exhibits broad spectrum anticancer effects by targeting multiple oncogenic proteins mainly via Michael addition between its unsaturated ketone and the cysteines in the target proteins. Therefore, oridonin and its derivatives hold the potential to be developed as multitargeting anticancer drugs.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.35","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50118717","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":"Direct cellular targets and anticancer mechanisms of the natural product oridonin","authors":"Jialin Yao, Lu Liu, Qingxiang Sun, Xiaofei Shen","doi":"10.1002/mef2.35","DOIUrl":"https://doi.org/10.1002/mef2.35","url":null,"abstract":"","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51382192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of genome and epigenome on intratumor heterogeneity in colorectal cancer","authors":"Jia-qian Huang,&nbsp;Hui-yan Luo","doi":"10.1002/mef2.34","DOIUrl":"10.1002/mef2.34","url":null,"abstract":"<p>Recently, two companion papers published in <i>Nature</i> by Timon Heide et al.<span>¹</span> and Jacob Househam et al.<span>²</span> suggested that phenotypic characteristics can vary without heritable (epi)genetic alteration to drive gene expression change, namely phenotypic plastic, which could take part in intratumor heterogeneity in colorectal cancer (CRC) evolution.</p><p>As in other cancer types, intratumor heterogeneity represents a challenge in the facets of tumorigenesis, evolution, and therapy response in CRC.<span>³</span> However, the information on how genomes and epigenomes contribute to intratumor heterogeneity is limited. What's more, although consensus molecular subtypes (CMS) and CRC intrinsic subtypes (CRIS) are approaches used to classify CRC cases by gene expression patterns,<span>⁴</span> Househam et al.<span>²</span> found that very few tumors with sufficient samples could be homogeneously classified by these classifiers, indicating intratumor heterogeneity of molecular subtypes in CRC and the discrepancy between CMS and CRIS classifications. Therefore, the researchers collected a large number of samples from a multiregion of carcinoma, concomitant adenoma if present, and a distant region of the normal epithelium to integrate their spatially resolved mutiomics analysis with single gland profiling data set, and combine with computational modeling to understand the cancer cell biology and assess the functional impact of altered gene expression on the evolution of CRC, due to intratumor heterogeneity is a significant confounding factor in bulk-tumor profiling (Figure 1). As for spatially resolved multiomics analysis, it presents a new avenue to reveal tumors and microenvironments co-evolution, which could be used to clarify heterogeneity.<span>⁵</span> In detail, it contains a strategy for the spatial sampling of tumor tissue to implement a series of new spatial genomic, transcriptomic, and proteomic technologies.<span>⁵</span></p><p>Heide et al.<span>¹</span> first looked forward to measuring genome–epigenome co-evaluation in a quantitative manner and gained some evidence. First of all, it was confirmed that there were recurrent cancer driver mutation events in CRC. After examining somatic mutations in chromatin modifier genes and assessing the evolutionary selection by the ratio of nonsynonymous to synonymous substitutions (<i>dN</i>/<i>dS</i>), they identified clear evidence of clonal truncating mutations of chromatin modifiers genes, which indicated that somatic mutations affect the epigenome. Besides, somatic chromatin accessibility alterations (SCAAs), which were found in known driver genes without accompanying mutations, were a substitute pattern for driver gene (in)activation. Subsequently, Heide et al. found that most SCAAs occurred at the onset of the adenoma-carcinoma transition. And SCAAs were indeed changes that originated ","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42934811","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":"Antiangiogenic therapy for ocular diseases: Current status and challenges","authors":"Rongyuan Chen,&nbsp;Juanhua Zhu,&nbsp;Jiaxin Hu,&nbsp;Xuri Li","doi":"10.1002/mef2.33","DOIUrl":"10.1002/mef2.33","url":null,"abstract":"<p>Angiogenesis is the process of new blood vessel growth from pre-existing ones involving vascular endothelial cell activation, proliferation, migration, and tube formation. The vascular endothelial growth factor A (VEGF-A) is known to be a key factor that promotes angiogenesis. Pathological angiogenesis is a key and common feature of numerous ocular neovascular diseases, such as wet age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, and corneal neovascularization. Although anti-VEGF treatment has been a great success for the treatment of such ocular neovascular diseases, many challenges exist, such as limited efficacy, unresponsiveness in many patients, drug resistance, treatment burden due to repeated intravitreous injection, all of which incent much effort and enthusiasm to find new and better treatment for ocular neovascular diseases. In recent years, new antiangiogenic drug, targets and drug delivery methods have been developed. This perspective discusses the status of currently available therapies, challenges, opportunities, and potential new directions toward better therapies for ocular neovascular diseases.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48718750","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":"VDDB: A comprehensive resource and machine learning tool for antiviral drug discovery","authors":"Shunming Tao,&nbsp;Yihao Chen,&nbsp;Jingxing Wu,&nbsp;Duancheng Zhao,&nbsp;Hanxuan Cai,&nbsp;Ling Wang","doi":"10.1002/mef2.32","DOIUrl":"10.1002/mef2.32","url":null,"abstract":"<p>Virus infection is one of the major diseases that seriously threaten human health. To meet the growing demand for mining and sharing data resources related to antiviral drugs and to accelerate the design and discovery of new antiviral drugs, we presented an open-access antiviral drug resource and machine learning platform (VDDB), which, to the best of our knowledge, is the first comprehensive dedicated resource for experimentally verified potential drugs/molecules based on manually curated data. Currently, VDDB highlights 848 clinical vaccines and 199 clinical antibodies, as well as over 710,000 small molecules targeting 39 medically important viruses including severe acute respiratory syndrome coronavirus 2. Furthermore, VDDB stores approximately three million records of pharmacological data for these collected potential antiviral drugs/molecules, involving 314 cell infection-based phenotypic and 234 target-based genotypic assays. Based on these annotated pharmacological data, VDDB allows users to browse, search, and download reliable information about these collects for various viruses of interest. In particular, VDDB also integrates 57 cell infection- and 117 target-based associated high-accuracy machine learning models to support various antivirals identification-related tasks, such as compound activity prediction, virtual screening, drug repositioning, and target fishing. VDDB is freely accessible at https://vddb.idruglab.cn.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44418384","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":"Reconsidering the role of receptors for SARS-CoV-2 in clear cell renal cell carcinoma: Friends or foes","authors":"Aimin Jiang,&nbsp;Le Qu,&nbsp;Bing Liu,&nbsp;Anbang Wang,&nbsp;Linhui Wang","doi":"10.1002/mef2.31","DOIUrl":"10.1002/mef2.31","url":null,"abstract":"<p>At the end of 2019, the new coronavirus began to spread around the world. World Health Organization named this virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which caused coronavirus disease (COVID-19). In most people without underlying medical conditions, symptoms of SARS-CoV-2 infection are often mild and nonlethal. However, patients with cancer have significantly higher rates of severe SARS-CoV-2 infection and disease-related mortality than normal individuals.<span>¹</span> Numerous studies have shown that progressive malignancy is an independent risk factor for severe SARS-CoV-2 infection and related death. The incidence of long-term sequelae of SARS-CoV-2 infection in cancer patients is estimated at 15%–30%.<span>²</span> Although the use of vaccines has reduced the chance of severe SARS-CoV-2 infection incidence, large-scale trials often exclude cancer patients. It remains to be seen how effective and safe the vaccine is in cancer patients and how long it is durable. Multiorgan single-cell sequencing analysis confirmed that key receptors for SARS-CoV-2 infection in humans include ACE2 (angiotensin-converting enzyme 2), TMPRSS2 (transmembrane serine protease 2), NRP1 (neuropilin-1), AXL (AXL receptor tyrosine kinase), FURIN, and CTSL1 (cathepsin L1).<span>³</span> SARS-CoV-2 infection may directly or indirectly lead to acute kidney injury, which may be related to the cytophilic effects of the virus and cytokine-induced systemic inflammatory responses. These receptors may play a key role in SARS-CoV-2 infection-induced acute kidney injury and even death. These key receptors provide crucial evidence for the development of antiviral drugs for SARS-CoV-2. However, further research on these receptors in cancer patients is warranted.</p><p>First, the expression profiling of prognosis prediction was investigated in multicancers. We found that except TMPRSS2, the remaining five receptors (ACE2, NRP1, AXL, FURIN, and CTSL1) were upregulated in various cancers, especially in kidney renal clear cell carcinoma (KIRC) (Figure 1A). The relationship between these receptors and the prognosis of cancer patients was analyzed. The results suggested that these four receptors, ACE2, NRP1, FURIN, and CTSL1, were prognostic risk factors in various cancers such as glioma, while in KIRC, they are protective factors for overall survival (Figure 1B). Similarly, ACE2, NRP1, and CTSL1 receptors were prognostic risk factors in gliomas and other tumors, and protective factors for disease progression-free survival in KIRC (Figure 1B). The protective induction of these three receptors on KIRC was also confirmed in the GSE29609 data set and the Japan-KIRC database (Figure 1C). The expression pattern of SARS-CoV-2 infection-related receptors in KIRC is different from other malignancies. ACE2, NRP1, and CTSL1 were highly expressed in KIRC tissues, but they were prognostic protective factors for patients. This may be rela","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.31","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42120305","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":"RNA modification pattern-based subtypes reveal heterogenous clinical outcomes and tumor immunity of clear cell renal cell carcinoma","authors":"Aimin Jiang,&nbsp;Zijun Xu,&nbsp;Xiao Fang,&nbsp;Di Gu,&nbsp;Kai Dong,&nbsp;Zhenjie Wu,&nbsp;Xinxin Gan,&nbsp;Bing Liu,&nbsp;Silun Ge,&nbsp;Le Qu,&nbsp;Peng Luo,&nbsp;Anbang Wang,&nbsp;Linhui Wang","doi":"10.1002/mef2.30","DOIUrl":"10.1002/mef2.30","url":null,"abstract":"<p>RNA methylation plays a key role across biological processes, which could be utilized as new weapons for cancer management. However, the implication of RNA methylation regulators in cancers, especially in clear cell renal cell cancer (ccRCC), remains largely unknown. We investigated the multiomics profile of RNA methylation regulators at the pan-cancer level. We found most RNA methylation regulators were dysregulated in cancers, which might be explained by genomic mutation and copy number variation. A novel subtype of ccRCC, RNA modification cancer subtype 2 (RMCS2), was identified and verified among different ccRCC cohorts. RMCS2 led to a shortened overall survival and had an activated state of PI3K-AKT-mTOR, KRAS, and retinoic acid metabolism signals, which resulted in an immune exhausted phenotype. In summary, our findings demonstrated that the aberrance of RNA methylation regulators was a common biological phenomenon pan-cancer. Dysregulated RNA methylation patterns could reshape tumor immunity thus impacting patients' prognosis and therapeutic response, and could function as a promising tool for ccRCC patients.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.30","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42039057","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":"Mesenchymal stem cell culture in aligned porous hydroxyapatite scaffolds using a multiwell plate bioreactor for bone tissue engineering","authors":"Gayathry G.,&nbsp;Athira R. K.,&nbsp;Anju M. S.,&nbsp;Anil Kumar P. R.,&nbsp;Harikrishna Varma P. R.,&nbsp;Naresh Kasoju,&nbsp;Manoj Komath","doi":"10.1002/mef2.17","DOIUrl":"10.1002/mef2.17","url":null,"abstract":"<p>Regeneration of bone lost by trauma, diseases and aging, and restoration of its load-bearing function are major clinical challenges. Hydroxyapatite (HA) is a clinically proven scaffold material for bone grafting, but the random-pore structure limits the homing of the cells inside the graft and the bone regeneration progresses with the resorption of the graft material. This work is based on the hypothesis that aligned through pores in the graft will lead to a faster healing by homing the local cells inside and provide a better environment for new bone formation through the graft structure. The investigation was done using aligned porous HA scaffolds seeded with human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) and cultured in a multiwell format bioreactor setup. The cell adhesion was studied by microscopy, cell proliferation was evaluated by Alamar blue assay and osteogenic differentiation was confirmed by biochemical and molecular assays. The results indicate that the hWJ-MSCs infiltrated through the aligned porous network of the scaffold, proliferated well when cultured in the expansion medium, and differentiated into osteogenic lineage when cultured in the differentiation medium.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46924692","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":"Artificial intelligence revolution in structure prediction for entire proteomes","authors":"Jun Zou","doi":"10.1002/mef2.19","DOIUrl":"https://doi.org/10.1002/mef2.19","url":null,"abstract":"","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42729635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}