Precision Clinical Medicine最新文献

{"title":"Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases","authors":"Huimin Chen, Xiaohan Wu, Chunjin Xu, Jian Lin, Zhanju Liu","doi":"10.1093/pcmedi/pbab025","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab025","url":null,"abstract":"Abstract Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation, hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"29 1","pages":"246 - 257"},"PeriodicalIF":5.3,"publicationDate":"2021-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81886816","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":"Inhibitory activity of medicinal mushroom Ganoderma lucidum on colorectal cancer by attenuating inflammation","authors":"Mandy M Liu, Tiantian Liu, S. Yeung, Zhijun Wang, B. Andresen, C. Parsa, R. Orlando, Bingsen Zhou, Wei Wu, Xia Li, Yilong Zhang, Charles Wang, Ying Huang","doi":"10.1093/pcmedi/pbab023","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab023","url":null,"abstract":"Abstract The medicinal mushroom Ganoderma lucidum (GL, Reishi or Lingzhi) exhibits an inhibitory effect on cancers. However, the underlying mechanism of the antitumor activity of GL is not fully understood. In this study, we characterized the gene networks regulated by a commercial product of GL containing a mixture of spores and fruiting bodies namely “GLSF”, in colorectal carcinoma. We found that in vitro co-administration of GLSF extract at non-toxic concentrations significantly potentiated growth inhibition and apoptosis induced by paclitaxel in CT26 and HCT-15 cells. GLSF inhibited NF-κB promoter activity in HEK-293 cells but did not affect the function of P-glycoprotein in K562/DOX cells. Furthermore, we found that when mice were fed a modified diet containing GLSF for 1 month prior to the CT26 tumor cell inoculation, GLSF alone or combined with Nab-paclitaxel markedly suppressed tumor growth and induced apoptosis. RNA-seq analysis of tumor tissues derived from GLSF-treated mice identified 53 differentially expressed genes compared to normal tissues. Many of the GLSF-down-regulated genes were involved in NF-κB-regulated inflammation pathways, such as IL-1β, IL-11 and Cox-2. Pathway enrichment analysis suggested that several inflammatory pathways involving leukocyte migration and adhesion were most affected by the treatment. Upstream analysis predicted activation of multiple tumor suppressors such as α-catenin and TP53 and inhibition of critical inflammatory mediators. “Cancer” was the major significantly inhibited biological effect of GLSF treatment. These results demonstrate that GLSF can improve the therapeutic outcome for colorectal cancer through a mechanism involving suppression of NF-κB-regulated inflammation and carcinogenesis.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"139 1","pages":"231 - 245"},"PeriodicalIF":5.3,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73265350","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":"CRISPR/Cas9 mediated somatic gene therapy for insertional mutations: the vibrator mouse model","authors":"Xin Fu, Jie Zhu, Yaou Duan, P. Lu, Kang Zhang","doi":"10.1093/pcmedi/pbab021","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab021","url":null,"abstract":"Abstract Somatic gene therapy remains technically challenging, especially in the central nervous system (CNS). Efficiency of gene delivery, efficacy in recipient cells, and proportion of cells required for overall benefit are the key points needed to be considered in any therapeutic approach. Recent efforts have demonstrated the efficacy of RNA-guided nucleases such as CRISPR/Cas9 in correcting point mutations or removing dominant mutations. Here we used viral delivered Cas9 plasmid and two guide RNAs to remove a recessive insertional mutation, vibrator (vb), in the mouse brain. The vb mice expressed ∼20% of normal levels of phosphatidylinositol transfer protein, α (PITPα) RNA and protein due to an endogenous retrovirus inserted in intron 4, resulting in early-onset tremor, degeneration of brainstem and spinal cord neurons, and juvenile death. The in situ CRISPR/Cas9 viral treatment effectively delayed neurodegeneration, attenuated tremor, and bypassed juvenile death. Our studies demonstrate the potential of CRISPR/Cas9-mediated gene therapy for insertional mutations in the postnatal brain.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"34 1","pages":"168 - 175"},"PeriodicalIF":5.3,"publicationDate":"2021-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89723565","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":"Improving T cell therapy: in vivo CRISPR-Cas9 screens tell us how to do","authors":"Tao Yin","doi":"10.1093/pcmedi/pbab015","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab015","url":null,"abstract":"Editor’s note A commentary on “In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer”.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"89 1","pages":"176 - 178"},"PeriodicalIF":5.3,"publicationDate":"2021-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75198038","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":"Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics.","authors":"Wenyi Liu, Luoxi Li, Jianxin Jiang, Min Wu, Ping Lin","doi":"10.1093/pcmedi/pbab014","DOIUrl":"10.1093/pcmedi/pbab014","url":null,"abstract":"<p><p>Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems (Cas) are efficient tools for targeting specific genes for laboratory research, agricultural engineering, biotechnology, and human disease treatment. Cas9, by far the most extensively used gene-editing nuclease, has shown great promise for the treatment of hereditary diseases, viral infection, cancers, and so on. Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications. Despite the rapid progress in basic research and clinical tests, some underlying problems present continuous, significant challenges, such as editing efficiency, relative difficulty in delivery, off-target effects, immunogenicity, etc. This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing toolkits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development. CRISPR-Cas systems, as a powerful gene-editing approach, will offer great hopes in clinical treatments for many individuals with currently incurable diseases.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 3","pages":"179-191"},"PeriodicalIF":5.1,"publicationDate":"2021-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39431646","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":"COVID-19 has triggered a new century of vaccination and infection control for the benefit of all mankind","authors":"B. Marshall","doi":"10.1093/pcmedi/pbab010","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab010","url":null,"abstract":"Modern safe vaccinations were pioneered in 1796 by Edward Jenner in England, when he noticed that milkmaids had beautiful complexions, clear of the blemishes from smallpox scars. This was attributed to their exposure to ‘cowpox’ in localised blisters, which seemed to protect them from the more severe and often fatal ‘smallpox’. In the twentieth century, the importance of immunity was emphasised by the very first Nobel Prize in Medicine, awarded to Emil Adolf von Bering who recognised the therapeutic role of antibodies in blood,1 using plasma from a recovered human (or horse) to protect and treat diphtheria, and eventually inventing the diphtheria vaccine in 1907. The first vaccines were simply made, being denatured protein extracts of live cultured bacteria, so there was no danger of causing the disease from the vaccination. Diphtheria-Pertussis-Tetanus (DPT) vaccine has long been available and is given to infants, making these three dreaded diseases of children uncommon in Western countries. My first personal experience with vaccination was as a 6-year-old (school grade 1) with my mother and 3-yearold brother attending the town hall in Kalgoorlie, Western Australia, for a mass polio vaccination administering the Salk vaccine. I remember that the vaccine was in a 50 ml multiple use bottle containing an estimated 25 dosages of 2 ml. The hall was pandemonium, with lines of people and numerous crying children. Hygiene in the stuffy, packed hall was less than ideal, the multiuse needles simply being soaked in alcohol for sterilisation between patients, becoming blunt and unsafe for use. But there had been at least a 12-month delay before the Salk vaccine could be used in Australia, as one of the early batches from Cutter Labs USA was withdrawn. The virus antigen made from cultured polio virus had not been sterilised adequately in 1955, resulting in more than 250 cases of actual polio in the USA. This caused the FDA to go on high alert, insisting on more stringent manufacturing and quality control procedures, followed by large-scale phase 1, 2 and 3 testing for all new vaccines. The concept is that, because vaccines are given to healthy people, a one-in-a-million incidence of severe side effects (or death) may be too much, even when preventing a dangerous disease such as polio or more recently COVID-19. Attenuated live polio vaccine replaced the Salk injected vaccine after 1960. Under the umbrella of the school vaccination programme, I received the new format whereby a drop of the pink vaccine was placed on a sugar cube and then eaten. The success of the new Sabin vaccine was its simplicity and oral format. After all, polio is an enterovirus, and I suppose family members could be infected with the live vaccine strain if schoolchildren experienced a very mild gastrointestinal illness at home. The live vaccination trivalent Sabin strain could cause overt polio in very few cases so that, as the actual wild-strain polio became extremely rare, vaccinations","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"23 1","pages":"77 - 79"},"PeriodicalIF":5.3,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87347898","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":"AI based colorectal disease detection using real-time screening colonoscopy","authors":"Jia-Ling Jiang, Qianrong Xie, Zhuo Cheng, Jianqiang Cai, Tian Xia, Hang Yang, Bo Yang, Hui-min Peng, Xue-song Bai, Mingque Yan, Xue Li, Jun Zhou, Xuan Huang, Liang Wang, Haiyan Long, Pingxi Wang, Yanpeng Chu, Fanwei Zeng, Xiu-wei Zhang, Guangyu Wang, Fanxin Zeng","doi":"10.1093/pcmedi/pbab013","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab013","url":null,"abstract":"Abstract Colonoscopy is an effective tool for early screening of colorectal diseases. However, the application of colonoscopy in distinguishing different intestinal diseases still faces great challenges of efficiency and accuracy. Here we constructed and evaluated a deep convolution neural network (CNN) model based on 117 055 images from 16 004 individuals, which achieved a high accuracy of 0.933 in the validation dataset in identifying patients with polyp, colitis, colorectal cancer (CRC) from normal. The proposed approach was further validated on multi-center real-time colonoscopy videos and images, which achieved accurate diagnostic performance on detecting colorectal diseases with high accuracy and precision to generalize across external validation datasets. The diagnostic performance of the model was further compared to the skilled endoscopists and the novices. In addition, our model has potential in diagnosis of adenomatous polyp and hyperplastic polyp with an area under the receiver operating characteristic curve of 0.975. Our proposed CNN models have potential in assisting clinicians in making clinical decisions with efficiency during application.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"42 1","pages":"109 - 118"},"PeriodicalIF":5.3,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75287183","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":"Spaceflight decelerates the epigenetic clock orchestrated with a global alteration in DNA methylome and transcriptome in the mouse retina.","authors":"Zhong Chen,&nbsp;Seta Stanbouly,&nbsp;Nina C Nishiyama,&nbsp;Xin Chen,&nbsp;Michael D Delp,&nbsp;Hongyu Qiu,&nbsp;Xiao W Mao,&nbsp;Charles Wang","doi":"10.1093/pcmedi/pbab012","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab012","url":null,"abstract":"<p><p>Astronauts exhibit an assortment of clinical abnormalities in their eyes during long-duration spaceflight. The purpose of this study was to determine whether spaceflight induces epigenomic and transcriptomic reprogramming in the retina or alters the epigenetic clock. The mice were flown for 37 days in animal enclosure modules on the International Space Station; ground-based control animals were maintained under similar housing conditions. Mouse retinas were isolated and both DNA methylome and transcriptome were determined by deep sequencing. We found that a large number of genes were differentially methylated with spaceflight, whereas there were fewer differentially expressed genes at the transcriptome level. Several biological pathways involved in retinal diseases such as macular degeneration were significantly altered. Our results indicated that spaceflight decelerated the retinal epigenetic clock. This study demonstrates that spaceflight impacts the retina at the epigenomic and transcriptomic levels, and such changes could be involved in the etiology of eye-related disorders among astronauts.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 2","pages":"93-108"},"PeriodicalIF":5.3,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbab012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39115369","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":"EyeHealer: A large-scale anterior eye segment dataset with eye structure and lesion annotations","authors":"Wenjia Cai, Jie Xu, Ke Wang, Xiaohong Liu, Wenqin Xu, Huimin Cai, Yuanxu Gao, Yuandong Su, Meixia Zhang, Jie Zhu, Charlotte L. Zhang, Edward Zhang, Fangfei Wang, Yun Yin, I. Lai, Guangyu Wang, Kang Zhang, Yingfeng Zheng","doi":"10.1093/pcmedi/pbab009","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab009","url":null,"abstract":"ABSTRACT Anterior segment eye diseases account for a significant proportion of presentations to eye clinics worldwide, including diseases associated with corneal pathologies, anterior chamber abnormalities (e.g. blood or inflammation), and lens diseases. The construction of an automatic tool for segmentation of anterior segment eye lesions would greatly improve the efficiency of clinical care. With research on artificial intelligence progressing in recent years, deep learning models have shown their superiority in image classification and segmentation. The training and evaluation of deep learning models should be based on a large amount of data annotated with expertise; however, such data are relatively scarce in the domain of medicine. Herein, the authors developed a new medical image annotation system, called EyeHealer. It is a large-scale anterior eye segment dataset with both eye structures and lesions annotated at the pixel level. Comprehensive experiments were conducted to verify its performance in disease classification and eye lesion segmentation. The results showed that semantic segmentation models outperformed medical segmentation models. This paper describes the establishment of the system for automated classification and segmentation tasks. The dataset will be made publicly available to encourage future research in this area.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"42 1","pages":"85 - 92"},"PeriodicalIF":5.3,"publicationDate":"2021-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82508690","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":"The mechanism by which noncoding RNAs regulate muscle wasting in cancer cachexia.","authors":"Xueer Zhou, Shoushan Hu, Yunan Zhang, Guan-Tao Du, Yi Li","doi":"10.1093/PCMEDI/PBAB008","DOIUrl":"https://doi.org/10.1093/PCMEDI/PBAB008","url":null,"abstract":"Cancer cachexia (CC) is a complex metabolic syndrome that accelerates muscle wasting and affects up to 80% of patients with cancer; however, timely diagnostic methods and effective cures are lacking. Although a considerable number of studies have focused on the mechanism of CC-induced muscle atrophy, few novel therapies have been applied in the last decade. In recent years, noncoding RNAs (ncRNAs) have attracted great attention as many differentially expressed ncRNAs in cancer cachectic muscles have been reported to participate in the inhibition of myogenesis and activation of proteolysis. In addition, extracellular vesicles (EVs), which function as ncRNA carriers in intercellular communication, are closely involved in changing ncRNA expression profiles in muscle and promoting the development of muscle wasting; thus, EV-related ncRNAs may represent potential therapeutic targets. This review comprehensively describes the process of ncRNA transmission through EVs and summarizes the pathways and targets of ncRNAs that lead to CC-induced muscle atrophy.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"93 1","pages":"136-147"},"PeriodicalIF":5.3,"publicationDate":"2021-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86976780","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}