Objective: Colorectal cancer(CRC) is one of the most common types of human cancers. As a tumor suppressor, SMAD4 plays a key role in colorectal carcinogenesis and invasiveness. Copy number variations(CNVs) of the...Objective: Colorectal cancer(CRC) is one of the most common types of human cancers. As a tumor suppressor, SMAD4 plays a key role in colorectal carcinogenesis and invasiveness. Copy number variations(CNVs) of the SMAD4 gene have been reported to be associated with cancer pathogenesis in array-based studies in different populations. Here we aimed to investigate the CNVs of the SMAD4 gene in a relatively large number of CRC patients from China. Methods: In the present study, we collected 147 Chinese CRC tumors as well as self-paired normal control tissues. Quantitative PCR was carried out to examine the copy number as well as the m RNA expression of the SMAD4 gene. Results: Our results showed that the copy number deletions of SMAD4 were frequent in a relatively high percentage of CRC samples(34.7%, 51 out of 147). There was a positive correlation between the copy number decrease of SMAD4 and tumor progression in CRCs. Furthermore, copy number loss of SMAD4 was correlated with decreased m RNA expression.Conclusions: These findings suggested that the copy number deletions of SMAD4 were frequent in CRC patients from China and had the potential to serve as a diagnostic indicator, alone or in combination with other markers, for CRC.展开更多
Autophagy plays an important role in the interaction between viruses and host cells.SARS-CoV-2 infection can disrupt the autophagy process in target cells.However,the precise molecular mechanism is still unknown.In th...Autophagy plays an important role in the interaction between viruses and host cells.SARS-CoV-2 infection can disrupt the autophagy process in target cells.However,the precise molecular mechanism is still unknown.In this study,we discovered that the Nsp8 of SARS-CoV-2 could cause an increasing accumulation of autophagosomes by preventing the fusion of autophagosomes and lysosomes.From further investigation,we found that Nsp8 was present on mitochondria and can damage mitochondria to initiate mitophagy.The results of experiments with immunofluorescence revealed that Nsp8 induced incomplete mitophagy.Moreover,both domains of Nsp8 orchestrated their function during Nsp8-induced mitophagy,in which the N-terminal domain colocalized with mitochondria and the C-terminal domain induced auto/mitophagy.This novel finding expands our understanding of the function of Nsp8 in promoting mitochondrial damage and inducing incomplete mitophagy,which helps us to understand the etiology of COVID-19 as well as open up new pathways for creating SARS-CoV-2 treatment methods.展开更多
Human microorganisms,including bacteria,fungi,and viruses,play key roles in several physiological and pathological processes.Some studies discovered that tumour tissues once considered sterile actually host a variety ...Human microorganisms,including bacteria,fungi,and viruses,play key roles in several physiological and pathological processes.Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms,which have been confirmed to be closely related to oncogenesis.The concept of intratumoural microbiota was subsequently proposed.Microbiota could colonise tumour tissues through mucosal destruction,adjacent tissue migration,and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment.Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations,affecting epigenetic modifications,promoting inflammation response,avoiding immune destruction,regulating metabolism,and activating invasion and metastasis.Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging,new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination.In addition,interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy,especially immunotherapy,although there are some inevitable challenges.Here,we aim to provide an extensive review of the concept,development history,potential sources,heterogeneity,and carcinogenic mechanisms of intratumoural microorganisms,explore the potential role of microorganisms in tumour prognosis,and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.展开更多
Summary What is already known about this topic?Research evidence is insufficient to suggest whether routine human immunodeficiency virus(HIV)screening in healthcare settings is effective in promoting greater awareness...Summary What is already known about this topic?Research evidence is insufficient to suggest whether routine human immunodeficiency virus(HIV)screening in healthcare settings is effective in promoting greater awareness of HIV-positive status.What is added by this report?This study found that,following the implementation of routine HIV screening in hospitals in Xishuangbanna Prefecture,Yunnan Province,there was a significant increase in the number of HIV screenings,positive results,and the positive rate of HIV screening in primary-level hospitals.What are the implications for public health practice?Routine hospital-based HIV screening is effective in identifying HIV infections in areas with concentrated epidemics.展开更多
基金supported by grants from Scientific Research Foundation of Hubei Health Department (JX3B88)
文摘Objective: Colorectal cancer(CRC) is one of the most common types of human cancers. As a tumor suppressor, SMAD4 plays a key role in colorectal carcinogenesis and invasiveness. Copy number variations(CNVs) of the SMAD4 gene have been reported to be associated with cancer pathogenesis in array-based studies in different populations. Here we aimed to investigate the CNVs of the SMAD4 gene in a relatively large number of CRC patients from China. Methods: In the present study, we collected 147 Chinese CRC tumors as well as self-paired normal control tissues. Quantitative PCR was carried out to examine the copy number as well as the m RNA expression of the SMAD4 gene. Results: Our results showed that the copy number deletions of SMAD4 were frequent in a relatively high percentage of CRC samples(34.7%, 51 out of 147). There was a positive correlation between the copy number decrease of SMAD4 and tumor progression in CRCs. Furthermore, copy number loss of SMAD4 was correlated with decreased m RNA expression.Conclusions: These findings suggested that the copy number deletions of SMAD4 were frequent in CRC patients from China and had the potential to serve as a diagnostic indicator, alone or in combination with other markers, for CRC.
基金supported by the National Natural Science Foundation of China (grant numbers 32100131 and 31670716)Wuhan Science and Technology Bureau[grant numbers 2020020601012318]+1 种基金Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine) (grant numbers WDCM2022008)Jianghan University (grant numbers 08190006,06210035,2021yb138 and 2019037).
文摘Autophagy plays an important role in the interaction between viruses and host cells.SARS-CoV-2 infection can disrupt the autophagy process in target cells.However,the precise molecular mechanism is still unknown.In this study,we discovered that the Nsp8 of SARS-CoV-2 could cause an increasing accumulation of autophagosomes by preventing the fusion of autophagosomes and lysosomes.From further investigation,we found that Nsp8 was present on mitochondria and can damage mitochondria to initiate mitophagy.The results of experiments with immunofluorescence revealed that Nsp8 induced incomplete mitophagy.Moreover,both domains of Nsp8 orchestrated their function during Nsp8-induced mitophagy,in which the N-terminal domain colocalized with mitochondria and the C-terminal domain induced auto/mitophagy.This novel finding expands our understanding of the function of Nsp8 in promoting mitochondrial damage and inducing incomplete mitophagy,which helps us to understand the etiology of COVID-19 as well as open up new pathways for creating SARS-CoV-2 treatment methods.
基金supported by the National Natural Science Foundation of China(No.82330003,No.82070099,No.82102496,No.82001988)National Science and Technology Major Project of the Ministry of Science and Technology of China(2022YFF1203300)+1 种基金Major Project of the Department of Science and Technology of Hubei(2022BCA016)Hubei Key Laboratory of Biological Targeted Therapy(2022swbx009).
文摘Human microorganisms,including bacteria,fungi,and viruses,play key roles in several physiological and pathological processes.Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms,which have been confirmed to be closely related to oncogenesis.The concept of intratumoural microbiota was subsequently proposed.Microbiota could colonise tumour tissues through mucosal destruction,adjacent tissue migration,and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment.Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations,affecting epigenetic modifications,promoting inflammation response,avoiding immune destruction,regulating metabolism,and activating invasion and metastasis.Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging,new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination.In addition,interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy,especially immunotherapy,although there are some inevitable challenges.Here,we aim to provide an extensive review of the concept,development history,potential sources,heterogeneity,and carcinogenic mechanisms of intratumoural microorganisms,explore the potential role of microorganisms in tumour prognosis,and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.
基金Supported by the China National Science and Technology Major Projects in Infectious Disease from the Ministry of Science and Technology[Grant no.2017ZX10201101-002-003].
文摘Summary What is already known about this topic?Research evidence is insufficient to suggest whether routine human immunodeficiency virus(HIV)screening in healthcare settings is effective in promoting greater awareness of HIV-positive status.What is added by this report?This study found that,following the implementation of routine HIV screening in hospitals in Xishuangbanna Prefecture,Yunnan Province,there was a significant increase in the number of HIV screenings,positive results,and the positive rate of HIV screening in primary-level hospitals.What are the implications for public health practice?Routine hospital-based HIV screening is effective in identifying HIV infections in areas with concentrated epidemics.