Background: Chest wall tumors are rare and mostly malignant. More than half of the malignancies are primary and the remainder are metastatic. Many studies have reported that metastatic lesions occur with about the sam...Background: Chest wall tumors are rare and mostly malignant. More than half of the malignancies are primary and the remainder are metastatic. Many studies have reported that metastatic lesions occur with about the same frequency as primary tumor. We evaluate common histological types of chest wall tumors in a tertiary center for respiratory and thoracic diseases (National Research Institute of Tuberculosis and Lung Disease). Method: We performed a retrospective study of chest wall tumors at National Research Institute of Tuberculosis and Lung Disease (NRITLD) from April 2001 to March 2010. The pathology slides of patients were retrieved from the pathology archive of NRITLD and reviewed by two pathologists. The lesions were classified as primary or metastatic according to the relevant clinical data and imaging findings. Result: A total of 124 chest wall tumors were identified in patients with a mean age of 47.7 years (range 4-90 years). The male/female ratio was 2:1. The most commonly affected side was the right (42.7%). There were 105 malignant tumors (84.7%), out of which 49 (46.2%) were primary and 57 (53.8%) were metastatic in origin. The majority of the metastatic lesions were epithelial tumors (36/57) (63.1%). The metastatic origin was clear in 51 cases, mostly arising from the lungs (35.7%). The most common types of primary chest wall tumors were primitive neuroectodermal tumor (15/49, 30.6%), chondrosarcoma (7/49, 14.3%), and malignant fibrous histiocytoma, undifferentiated pleomorphic sarcoma (5/49, 10.2%). The most common benign tumor was lipoma (5/18, 35.7%). Conclusion: Most common tumors of chest wall in this study were malignant, mostly metastatic epithelial neoplasms.展开更多
A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosam...A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1ⅢB into target cell. which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosamine were important moities to prepare gossypol derivatives as HIV- 1 entry inhibitors besides certain amino acids.展开更多
RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G...RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules(SG) and GW182/DCP-specific RNA processing bodies(PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude m RNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. Virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.展开更多
Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvan...Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are alw needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine ays for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly （I：C）, was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly （I：C） derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.展开更多
Dengue virus(DENV) and Zika virus(ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there...Dengue virus(DENV) and Zika virus(ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there are few effective vaccines and therapies available against these viruses. Therefore, the discovery of new antiviral agents is critical.Herein, a scorpion venom peptide(Smp76) characterized from Scorpio maurus palmatus was successfully expressed and purified in Escherichia coli BL21(DE3). The recombinant Smp76(rSmp76) was found to effectively inhibit DENV and ZIKV infections in a dose-dependent manner in both cultured cell lines and primary mouse macrophages. Interestingly,rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection, similar to the effect of interferon(IFN)-b. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN-b by activating interferon regulatory transcription factor 3(IRF3) phosphorylation, enhancing the type-Ⅰ IFN response and inhibiting viral infection.This mechanism is significantly different from traditional virucidal antimicrobial peptides(AMPs). Overall, the scorpion venom peptide Smp76 is a potential new antiviral agent with a unique mechanism involving type-Ⅰ IFN responses,demonstrating that natural AMPs can enhance immunity by functioning as immunomodulators.展开更多
Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China. In contrast, this review provides a comprehensive update on the prevalence of multiple HIV- 1 subtyp...Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China. In contrast, this review provides a comprehensive update on the prevalence of multiple HIV- 1 subtypes, consequent emergence of recombinant and novel forms of HIV- 1 in China, and the implications this may have on HIV diversity and the development of effective vaccines. In addition it also examines the dissemination of primary drug resistance in therapy naive patients, as well as co-infections with two other important viruses-hepatitis B and C. The main purpose of this review is to provide a current snapshot of HIV-1 pathogenesis in China and possibly shed some light on the future of HIV evolution, and potential challenges for future vaccine and anti-retroviral therapeutics against HIV strains in this area.展开更多
Human parainfluenza virus type 3(HPIV3),a member of the Paramyxoviridae family,can cause lower respiratory disease in infants and young children.The phosphoprotein(P)of HPIV3 is an essential cofactor of the viral RNA-...Human parainfluenza virus type 3(HPIV3),a member of the Paramyxoviridae family,can cause lower respiratory disease in infants and young children.The phosphoprotein(P)of HPIV3 is an essential cofactor of the viral RNA-dependent RNA polymerase large protein(L).P connects nucleocapsid protein(N)with L to initiate genome transcription and replication.Sumoylation influences many important pathways of the target proteins,and many viral proteins are also themselves sumoylated.In this study,we found that the P of HPIV3 could be sumoylated,and mutation of K492 and K532 to arginine(PK492 R/K532 R)failed to be sumoylated within P,which enhances HPIV3 minigenome activity.Biochemical studies showed that PK492 R/K532 Rhad no effect on its interactions with N,formation of homo-tetramers and formation of inclusion bodies.Finally,we found that incorporation of K492 R/K532 R into a recombinant HPIV3(rHPIV3-PK492 R/K532 R)increased viral production in culture cells,suggesting that sumoylation attenuates functions of P and down-regulates viral replication.展开更多
Ochratoxin A(OTA),one of the most dangerous mycotoxins for human health,has been subjected to numerous studies for separation and detection in minimal amounts.Aptamers as novel recognition elements have been employed ...Ochratoxin A(OTA),one of the most dangerous mycotoxins for human health,has been subjected to numerous studies for separation and detection in minimal amounts.Aptamers as novel recognition elements have been employed to fabricate ultrasensitive biosensors for the detection of OTA and designing delicate analytical tools.This review attempted to comprehensively examine all reported aptamer-based detection and separation platforms for ochratoxin.The most relevant databases were considered to discover all specific aptamers for dealing with OTA.Aptamer-based detection and separation devices specified for OTA were searched for,analyzed,discussed,and classified based on their specifications.The optical aptasensors have gathered a higher interest than electrochemical aptasensors,which can achieve a lower limit of detections.Moreover,some extraction platforms based on these aptamers were also found.However,aptamer-based devices seem to have some challenges in their application.展开更多
Crimean-Congo hemorrhagic fever virus(CCHFV) is responsible for widespread tick-borne zoonotic viral disease CCHF in African, Middle Eastern, Asian, and European countries. CCHFV can be spread to humans through tick b...Crimean-Congo hemorrhagic fever virus(CCHFV) is responsible for widespread tick-borne zoonotic viral disease CCHF in African, Middle Eastern, Asian, and European countries. CCHFV can be spread to humans through tick bites or contact with infected animals or humans, and it often progresses from asymptomatic to severe/lethal illness, with fatality rates ranging from 10% to 40% in humans. Today, CCHF is growing into a significant public health concern due to its very high prevalence, severity of the condition, and lack of available vaccines and specific treatments. Recent research has been drawn towards a more accurate study of CCHFV characteristics, including the structure, genetic diversity, mechanisms involved in pathogenesis and immunopathogenesis, and clinical features. In addition, the use of animal models(mouse and non-human primates) and advanced diagnostic tools in recent years has resulted in a significant advance in CCHF related studies. In this context, we summarized the latest findings about CCHF research, its health complications, animal models, current diagnosis, vaccination, and CCHF treatments, and therapeutic strategies. Furthermore, we discussed existing deficiencies and problems in CCHFV analysis, as well as areas that still need to yield conclusive answers.展开更多
After its initial outbreak in 2019,the 2019 novel coronavirus disease(COVID-19)remains a global health concern.COVID-19 is well known for causing severe respiratory pathology,but it can also cause a variety of extra-p...After its initial outbreak in 2019,the 2019 novel coronavirus disease(COVID-19)remains a global health concern.COVID-19 is well known for causing severe respiratory pathology,but it can also cause a variety of extra-pulmonary manifestations.Among them,myocardial injury has received substantial attention because it is usually associated with poor prognosis and mortality,thus emphasizing the importance of monitoring and managing myocardial injury in patients with COVID-19.Myocarditis has received attention as a complication of myocardial injury during and after the onset of COVID-19.Here,to aid in clinical decision-making,we present a narrative review on COVID-19-associated myocardial injury and myocarditis,discussing clinical evidence,pathogenesis,diagnostic tools,and thera-peutic strategies.展开更多
Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules”(IBAGs),where anti-termination factor M2-1 and ...Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules”(IBAGs),where anti-termination factor M2-1 and viral mRNAs are concentrated.However,the mechanism of IBAG formation and the physiological function of IBAGs are unclear.Here,we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein(mRNP)condensates formed by secondary LLPS.Mechanistically,the RSV nucleoprotein(N)and M2-1 interact with and recruit PABP to IBs,promoting PABP to bind viral mRNAs transcribed in IBs by RNArecognition motif and drive secondary phase separation.Furthermore,PABP-eIF4G1 interaction regulates viral mRNP condensate composition,thereby recruiting specific translation initiation factors(eIF4G1,eIF4E,eIF4A,eIF4B and eIF4H)into the secondary condensed phase to activate viral mRNAs for ribosomal recruitment.Our study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.展开更多
Summary： Over-expression of APP and Swedish mutation could cause some familial early onset AD. In this study, a primary screening was conducted of effective small interference RNAs （siRNAs） targeted wild type APP ...Summary： Over-expression of APP and Swedish mutation could cause some familial early onset AD. In this study, a primary screening was conducted of effective small interference RNAs （siRNAs） targeted wild type APP （APPwt） and Swedish mutant APP （APPswe）. One siRNA targeting APPwt and the other siRNA targeting APPswe were designed, All these siRNAs were endogenously expressed by siRNAs expressing plasmids, COS-7 cells were transiently co-transfected with APP-GFP recombinant plasmids and siRNA expression vector, The silencing effect of each siRNA was quantitatively assessed by the level of expression of green fluorescent protein （GFP）. It was found that the siRNAs silenced APPwt and APPswe to different degrees, siRNA directed against APPswe was more effective in suppressing the expression of fusion gene of APPswe than that of APPwt. The silencing effect of siRNA directed against APPswe indicating allele-specific silencing property of the siRNAs. Therefore, siRNAs directed against APP play an important role both in the therapeutic study of Alzheimer disease and functional exploration ofAPP gene.展开更多
Background: Lung cancer is among the most common cancers. Search is ongoing to find biomarkers to improve the diagnosis lung cancer techniques in early stages. In this study we evaluate the sensitivity and specificity...Background: Lung cancer is among the most common cancers. Search is ongoing to find biomarkers to improve the diagnosis lung cancer techniques in early stages. In this study we evaluate the sensitivity and specificity of the MUC1 and CEA gene expressions in the peripheral blood of non-small cell lung cancer (NSCLC). Material and Methods: This study was done in Masih Daneshvari Hospital, Tehran, Iran and was case/control study that conducted on 30 NSCLC patients and 30 healthy controls. Peripheral blood was collected and total RNA was extracted then cDNA was synthesized. Sample was separately assessed by real time PCR. Results: The expression of CEA gen was positive in 24 patients indicating 80% sensitivity for this marker. The expression of CEA gen was positive in 9 controls out of 30 each. A statistically significant difference was detected between patients and healthy controls with regard to CEA mRNA expression (P 0.001). The MUC1 gen expressed in 20 out of 30 patients, while it expressed in 3 controls. The difference in MUC1 mRNA expression was statistically significant between NSCLC patients and healthy controls (P 0.001). Conclusion: MUC1 and CEA are molecular biomarkers with relatively favorable sensitivity for primary diagnosis of NSCLC.展开更多
Background and Objectives: Breast cancer is among the most common causes of cancer related mortality in women worldwide. Early detection and prompt diagnosis of tumor is the first step to prevent cancer-related morbid...Background and Objectives: Breast cancer is among the most common causes of cancer related mortality in women worldwide. Early detection and prompt diagnosis of tumor is the first step to prevent cancer-related morbidity and mortality, and a comprehensive understanding of the involved molecular mechanisms can greatly help in this respect. Breast cancer, like many other types of cancer, is caused by a combination of genetic and epigenetic changes such as inactivation of tumor suppressor genes. Materials and Methods: This study was performed on 40 breast cancer patients and 40 healthy controls. Quantitative real time reverse transcription polymerase chain reaction (real time qRT-PCR) was used to assess the expression of carcinoembryonic antigen (CEA) and mammaglobin mRNA in the peripheral blood of patients and healthy controls. The two groups were compared using t-test. Results: The two groups were not significantly different in terms of the mean age. Twenty-nine out of 40 cancer patients were positive for CEA mRNA and its sensitivity was calculated to be 72.5%. Twelve out of 40 healthy controls were positive for CEA mRNA. Twenty-six out of 40 patients were positive for mammaglobin mRNA indicative of 65% sensitivity while only five out of 40 healthy controls were positive for mammaglobin mRNA. Conclusion: Both CEA and mammaglobin mRNA had high sensitivity in cancer patients;thus, they can be used for screening and early detection of breast cancer patients. Further studies with larger sample sizes are required to confirm the current findings.展开更多
Introduction: Ovarian cancer is one of the most common malignancies in women and the fifth cause of cancer-related deaths in women worldwide. Contrary to the challenges in developing new clinical markers using the con...Introduction: Ovarian cancer is one of the most common malignancies in women and the fifth cause of cancer-related deaths in women worldwide. Contrary to the challenges in developing new clinical markers using the conventional methods, recent advances in genomics and proteomics have led to identification of candidate and promising biomarkers for the diagnosis of ovarian cancer. Human epididymis protein 4 (HE4) is such a marker that has recently been reported to correlate with recurrence or progression of epithelial ovarian cancer. The purpose of this study was to measure the expression level of HE4 gene in women with ovarian cancer. Methodology: We evaluated and compared paraffin-embedded tissue samples of 20 ovarian cancer patients with 10 samples from healthy individuals. RNA was initially extracted from the samples and cDNA was synthetized. Gene expression level was then measured using real-time polymerase chain reaction (PCR). Results: Our results demonstrated that HE4 gene expression level was significantly higher in samples of patients with ovarian cancer compared with samples from healthy individuals. Moreover, higher levels of HE4 gene expression were associated with more advanced disease and larger tumor size. Conclusion: HE4 gene over-expression has the potential to be used as a biomarker for detecting early-stage ovarian cancer in women. Future more comprehensive studies are needed to confirm our findings.展开更多
Microblog is a new Internet featured product, which has seen a rapid development in recent years. Researchers from different countries are making various technical analyses on microblogging applications. In this study...Microblog is a new Internet featured product, which has seen a rapid development in recent years. Researchers from different countries are making various technical analyses on microblogging applications. In this study, through using the natural language processing(NLP) and data mining, we analyzed the information content transmitted via a microblog, users' social networks and their interactions, and carried out an empirical analysis on the dissemination process of one particular piece of information via Sina Weibo.Based on the result of these analyses, we attempt to develop a better understanding about the rule and mechanism of the informal information flow in microblogging.展开更多
Phosphatase and tensin homolog deleted on chromosome ten(PTEN)is a well-known tumor suppressor that acts as a dual-specificity phosphatase and is frequently mutated in human cancer.Our previous work has demonstrated t...Phosphatase and tensin homolog deleted on chromosome ten(PTEN)is a well-known tumor suppressor that acts as a dual-specificity phosphatase and is frequently mutated in human cancer.Our previous work has demonstrated that PTEN also plays a vital role in type I interferon responses and antiviral innate immunity.Recently,a translational variant of PTEN with a long N-terminal extension(PTEN-L)has been discovered that is secreted into the extracellular environment and enters recipient cells,where it exerts a phosphatase function antagonistic to PI3K/Akt signaling and tumorigenesis.In this study,we demonstrate that PTEN-L promotes type I interferon responses and antiviral innate immunity during viral infection in a phosphatase activity-dependent manner.Compared with canonical PTEN,PTEN-L also exerts its antiviral function when it is applied exogenously in protein form.This finding was confirmed in cell cultures and mouse infection models.Furthermore,PTEN-L enhances the responses of both type I interferon and proinflammatory cytokines,thus suggesting that PTEN-L might possess additional functions compared with those of PTEN.Thus,the antiviral function of PTEN-L may open an avenue for the use of PTEN-L in antiviral therapy,particularly in patients with PTEN-deficient tumors.展开更多
Dear Editor,The outbreak of SARS-CoV-2 leads global epidemic with high morbidity and mortality.However,the pathophysiology of this deadly virus is complex and largely unknown.Autophagy is a highly conserved homeostati...Dear Editor,The outbreak of SARS-CoV-2 leads global epidemic with high morbidity and mortality.However,the pathophysiology of this deadly virus is complex and largely unknown.Autophagy is a highly conserved homeostatic process that allows cells to recycle their components.Several studies provided evidence that human coronavirus infections are closely related to various cellular aspects associated with autophagy.1 Autophagy may play a crucial role in the SARS-CoV-2 viral lifecycle.展开更多
Dear Editor,The serine-threonine kinase Akt plays a central role in regulating cell proliferation,migration,angiogenesis,transformation,energy metabolism,and death.1 The stimulation of growth factors recruits the PI3K...Dear Editor,The serine-threonine kinase Akt plays a central role in regulating cell proliferation,migration,angiogenesis,transformation,energy metabolism,and death.1 The stimulation of growth factors recruits the PI3K to the plasma membrane and phosphatidylinositol-3A5-trisphosphate(PIP3),which in turn recruits Akt to the plasma membrane through PH domain of Akt.展开更多
In a study published in cellular and molecular immunology,Wan et al.demonstrate a new mechanism of viral immune evasion.1 It was observed that Rubicon,the RUN domain Beclin-1-interacting and cysteine-rich domain-conta...In a study published in cellular and molecular immunology,Wan et al.demonstrate a new mechanism of viral immune evasion.1 It was observed that Rubicon,the RUN domain Beclin-1-interacting and cysteine-rich domain-containing protein,is induced by viral infection and antagonizes interferon(IFN)production,thereby facilitating viral replication.This study not only demonstrates a direct link between Rubicon and NF-κB essential modulator(NEMO),but also demonstrates how the interaction between Rubicon and NEMO inhibits the production of type I interferon.This study shows a previously unrecognized function of Rubicon as an important negative regulator of the innate immune response.展开更多
文摘Background: Chest wall tumors are rare and mostly malignant. More than half of the malignancies are primary and the remainder are metastatic. Many studies have reported that metastatic lesions occur with about the same frequency as primary tumor. We evaluate common histological types of chest wall tumors in a tertiary center for respiratory and thoracic diseases (National Research Institute of Tuberculosis and Lung Disease). Method: We performed a retrospective study of chest wall tumors at National Research Institute of Tuberculosis and Lung Disease (NRITLD) from April 2001 to March 2010. The pathology slides of patients were retrieved from the pathology archive of NRITLD and reviewed by two pathologists. The lesions were classified as primary or metastatic according to the relevant clinical data and imaging findings. Result: A total of 124 chest wall tumors were identified in patients with a mean age of 47.7 years (range 4-90 years). The male/female ratio was 2:1. The most commonly affected side was the right (42.7%). There were 105 malignant tumors (84.7%), out of which 49 (46.2%) were primary and 57 (53.8%) were metastatic in origin. The majority of the metastatic lesions were epithelial tumors (36/57) (63.1%). The metastatic origin was clear in 51 cases, mostly arising from the lungs (35.7%). The most common types of primary chest wall tumors were primitive neuroectodermal tumor (15/49, 30.6%), chondrosarcoma (7/49, 14.3%), and malignant fibrous histiocytoma, undifferentiated pleomorphic sarcoma (5/49, 10.2%). The most common benign tumor was lipoma (5/18, 35.7%). Conclusion: Most common tumors of chest wall in this study were malignant, mostly metastatic epithelial neoplasms.
基金the National Natural Science Foundation of China(No.30770228)for financial support
文摘A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV- 1I activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1ⅢB into target cell. which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosamine were important moities to prepare gossypol derivatives as HIV- 1 entry inhibitors besides certain amino acids.
基金supported by grants from the China Natural Science Foundation (81825015 and 31630086)the Natural Science Foundation of Hubei Province Innovation Group (2017CFA022)Intramural Research Program of NCI/NIH (1ZIASC010357 to ZMZ)
文摘RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules(SG) and GW182/DCP-specific RNA processing bodies(PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude m RNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. Virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.
基金supported by the National Natural Science Foundation of China (30670097)National Basic Research Program of China (973 Program) (2005CB522903)+1 种基金National Key R&D Program (2007BAI28B04)National S&T Major Project on Major Infectious Diseases (2008ZX10001-010)from the Ministry of Science and Technology of the People’s Republic of China
文摘Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are alw needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine ays for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly （I：C）, was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly （I：C） derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.
基金supported by grants from National Science Fund of China (Nos. 31572289, 31872239 and 81630091)International S&T Cooperation Program of China (No. S2016G3110)+3 种基金Hubei Science Fund (Nos. 2015CFA042 and 2016CFA018)China-Kazakhstan Cooperation Program (No. CK-07-09)Fundamental Research Funds for the Central Universities in China (Nos. 2042017kf0242 and 2042017kf0199)financial support from Higher Education Commission (HEC) of Pakistan
文摘Dengue virus(DENV) and Zika virus(ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there are few effective vaccines and therapies available against these viruses. Therefore, the discovery of new antiviral agents is critical.Herein, a scorpion venom peptide(Smp76) characterized from Scorpio maurus palmatus was successfully expressed and purified in Escherichia coli BL21(DE3). The recombinant Smp76(rSmp76) was found to effectively inhibit DENV and ZIKV infections in a dose-dependent manner in both cultured cell lines and primary mouse macrophages. Interestingly,rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection, similar to the effect of interferon(IFN)-b. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN-b by activating interferon regulatory transcription factor 3(IRF3) phosphorylation, enhancing the type-Ⅰ IFN response and inhibiting viral infection.This mechanism is significantly different from traditional virucidal antimicrobial peptides(AMPs). Overall, the scorpion venom peptide Smp76 is a potential new antiviral agent with a unique mechanism involving type-Ⅰ IFN responses,demonstrating that natural AMPs can enhance immunity by functioning as immunomodulators.
文摘Several reviews have focused on the nature of HIV infection and its spread in various geographical regions of China. In contrast, this review provides a comprehensive update on the prevalence of multiple HIV- 1 subtypes, consequent emergence of recombinant and novel forms of HIV- 1 in China, and the implications this may have on HIV diversity and the development of effective vaccines. In addition it also examines the dissemination of primary drug resistance in therapy naive patients, as well as co-infections with two other important viruses-hepatitis B and C. The main purpose of this review is to provide a current snapshot of HIV-1 pathogenesis in China and possibly shed some light on the future of HIV evolution, and potential challenges for future vaccine and anti-retroviral therapeutics against HIV strains in this area.
基金supported by grants from National Key R&D Program of China(2017YFA0505801)the National Natural Science Foundation of China(81825015,81871650 and 31630086)+2 种基金National Science and Technology Major Project(2018ZX10101004)the Natural Science Foundation of Hubei Province Innovation Group(2017CFA022)Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory(2019ACCP-MS06)。
文摘Human parainfluenza virus type 3(HPIV3),a member of the Paramyxoviridae family,can cause lower respiratory disease in infants and young children.The phosphoprotein(P)of HPIV3 is an essential cofactor of the viral RNA-dependent RNA polymerase large protein(L).P connects nucleocapsid protein(N)with L to initiate genome transcription and replication.Sumoylation influences many important pathways of the target proteins,and many viral proteins are also themselves sumoylated.In this study,we found that the P of HPIV3 could be sumoylated,and mutation of K492 and K532 to arginine(PK492 R/K532 R)failed to be sumoylated within P,which enhances HPIV3 minigenome activity.Biochemical studies showed that PK492 R/K532 Rhad no effect on its interactions with N,formation of homo-tetramers and formation of inclusion bodies.Finally,we found that incorporation of K492 R/K532 R into a recombinant HPIV3(rHPIV3-PK492 R/K532 R)increased viral production in culture cells,suggesting that sumoylation attenuates functions of P and down-regulates viral replication.
文摘Ochratoxin A(OTA),one of the most dangerous mycotoxins for human health,has been subjected to numerous studies for separation and detection in minimal amounts.Aptamers as novel recognition elements have been employed to fabricate ultrasensitive biosensors for the detection of OTA and designing delicate analytical tools.This review attempted to comprehensively examine all reported aptamer-based detection and separation platforms for ochratoxin.The most relevant databases were considered to discover all specific aptamers for dealing with OTA.Aptamer-based detection and separation devices specified for OTA were searched for,analyzed,discussed,and classified based on their specifications.The optical aptasensors have gathered a higher interest than electrochemical aptasensors,which can achieve a lower limit of detections.Moreover,some extraction platforms based on these aptamers were also found.However,aptamer-based devices seem to have some challenges in their application.
文摘Crimean-Congo hemorrhagic fever virus(CCHFV) is responsible for widespread tick-borne zoonotic viral disease CCHF in African, Middle Eastern, Asian, and European countries. CCHFV can be spread to humans through tick bites or contact with infected animals or humans, and it often progresses from asymptomatic to severe/lethal illness, with fatality rates ranging from 10% to 40% in humans. Today, CCHF is growing into a significant public health concern due to its very high prevalence, severity of the condition, and lack of available vaccines and specific treatments. Recent research has been drawn towards a more accurate study of CCHFV characteristics, including the structure, genetic diversity, mechanisms involved in pathogenesis and immunopathogenesis, and clinical features. In addition, the use of animal models(mouse and non-human primates) and advanced diagnostic tools in recent years has resulted in a significant advance in CCHF related studies. In this context, we summarized the latest findings about CCHF research, its health complications, animal models, current diagnosis, vaccination, and CCHF treatments, and therapeutic strategies. Furthermore, we discussed existing deficiencies and problems in CCHFV analysis, as well as areas that still need to yield conclusive answers.
基金This work was supported by the National Natural Science Foundation of China(No.82070425,Zhibing Lu)the Program of Excellent Doctoral(Postdoctoral)of Zhongnan Hospital,Wuhan University(No.ZNYB2020027,Huanhuan Cai).
文摘After its initial outbreak in 2019,the 2019 novel coronavirus disease(COVID-19)remains a global health concern.COVID-19 is well known for causing severe respiratory pathology,but it can also cause a variety of extra-pulmonary manifestations.Among them,myocardial injury has received substantial attention because it is usually associated with poor prognosis and mortality,thus emphasizing the importance of monitoring and managing myocardial injury in patients with COVID-19.Myocarditis has received attention as a complication of myocardial injury during and after the onset of COVID-19.Here,to aid in clinical decision-making,we present a narrative review on COVID-19-associated myocardial injury and myocarditis,discussing clinical evidence,pathogenesis,diagnostic tools,and thera-peutic strategies.
基金supported by the grants from National Key R&D Program of China(2021YFC2300702 and 2021YFC2300200)the Hubei Provincial Natural Science Foundation of China(2021CFB364)+1 种基金the National Natural Science Foundation of China(82130064,81825015,U22A20337 and 32000119)the Key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory(JXBS001).
文摘Inclusion bodies(IBs)of respiratory syncytial virus(RSV)are formed by liquid-liquid phase separation(LLPS)and contain internal structures termed“IB-associated granules”(IBAGs),where anti-termination factor M2-1 and viral mRNAs are concentrated.However,the mechanism of IBAG formation and the physiological function of IBAGs are unclear.Here,we found that the internal structures of RSV IBs are actual M2-1-free viral messenger ribonucleoprotein(mRNP)condensates formed by secondary LLPS.Mechanistically,the RSV nucleoprotein(N)and M2-1 interact with and recruit PABP to IBs,promoting PABP to bind viral mRNAs transcribed in IBs by RNArecognition motif and drive secondary phase separation.Furthermore,PABP-eIF4G1 interaction regulates viral mRNP condensate composition,thereby recruiting specific translation initiation factors(eIF4G1,eIF4E,eIF4A,eIF4B and eIF4H)into the secondary condensed phase to activate viral mRNAs for ribosomal recruitment.Our study proposes a novel LLPS-regulated translation mechanism during viral infection and a novel antiviral strategy via targeting on secondary condensed phase.
文摘Summary： Over-expression of APP and Swedish mutation could cause some familial early onset AD. In this study, a primary screening was conducted of effective small interference RNAs （siRNAs） targeted wild type APP （APPwt） and Swedish mutant APP （APPswe）. One siRNA targeting APPwt and the other siRNA targeting APPswe were designed, All these siRNAs were endogenously expressed by siRNAs expressing plasmids, COS-7 cells were transiently co-transfected with APP-GFP recombinant plasmids and siRNA expression vector, The silencing effect of each siRNA was quantitatively assessed by the level of expression of green fluorescent protein （GFP）. It was found that the siRNAs silenced APPwt and APPswe to different degrees, siRNA directed against APPswe was more effective in suppressing the expression of fusion gene of APPswe than that of APPwt. The silencing effect of siRNA directed against APPswe indicating allele-specific silencing property of the siRNAs. Therefore, siRNAs directed against APP play an important role both in the therapeutic study of Alzheimer disease and functional exploration ofAPP gene.
文摘Background: Lung cancer is among the most common cancers. Search is ongoing to find biomarkers to improve the diagnosis lung cancer techniques in early stages. In this study we evaluate the sensitivity and specificity of the MUC1 and CEA gene expressions in the peripheral blood of non-small cell lung cancer (NSCLC). Material and Methods: This study was done in Masih Daneshvari Hospital, Tehran, Iran and was case/control study that conducted on 30 NSCLC patients and 30 healthy controls. Peripheral blood was collected and total RNA was extracted then cDNA was synthesized. Sample was separately assessed by real time PCR. Results: The expression of CEA gen was positive in 24 patients indicating 80% sensitivity for this marker. The expression of CEA gen was positive in 9 controls out of 30 each. A statistically significant difference was detected between patients and healthy controls with regard to CEA mRNA expression (P 0.001). The MUC1 gen expressed in 20 out of 30 patients, while it expressed in 3 controls. The difference in MUC1 mRNA expression was statistically significant between NSCLC patients and healthy controls (P 0.001). Conclusion: MUC1 and CEA are molecular biomarkers with relatively favorable sensitivity for primary diagnosis of NSCLC.
文摘Background and Objectives: Breast cancer is among the most common causes of cancer related mortality in women worldwide. Early detection and prompt diagnosis of tumor is the first step to prevent cancer-related morbidity and mortality, and a comprehensive understanding of the involved molecular mechanisms can greatly help in this respect. Breast cancer, like many other types of cancer, is caused by a combination of genetic and epigenetic changes such as inactivation of tumor suppressor genes. Materials and Methods: This study was performed on 40 breast cancer patients and 40 healthy controls. Quantitative real time reverse transcription polymerase chain reaction (real time qRT-PCR) was used to assess the expression of carcinoembryonic antigen (CEA) and mammaglobin mRNA in the peripheral blood of patients and healthy controls. The two groups were compared using t-test. Results: The two groups were not significantly different in terms of the mean age. Twenty-nine out of 40 cancer patients were positive for CEA mRNA and its sensitivity was calculated to be 72.5%. Twelve out of 40 healthy controls were positive for CEA mRNA. Twenty-six out of 40 patients were positive for mammaglobin mRNA indicative of 65% sensitivity while only five out of 40 healthy controls were positive for mammaglobin mRNA. Conclusion: Both CEA and mammaglobin mRNA had high sensitivity in cancer patients;thus, they can be used for screening and early detection of breast cancer patients. Further studies with larger sample sizes are required to confirm the current findings.
文摘Introduction: Ovarian cancer is one of the most common malignancies in women and the fifth cause of cancer-related deaths in women worldwide. Contrary to the challenges in developing new clinical markers using the conventional methods, recent advances in genomics and proteomics have led to identification of candidate and promising biomarkers for the diagnosis of ovarian cancer. Human epididymis protein 4 (HE4) is such a marker that has recently been reported to correlate with recurrence or progression of epithelial ovarian cancer. The purpose of this study was to measure the expression level of HE4 gene in women with ovarian cancer. Methodology: We evaluated and compared paraffin-embedded tissue samples of 20 ovarian cancer patients with 10 samples from healthy individuals. RNA was initially extracted from the samples and cDNA was synthetized. Gene expression level was then measured using real-time polymerase chain reaction (PCR). Results: Our results demonstrated that HE4 gene expression level was significantly higher in samples of patients with ovarian cancer compared with samples from healthy individuals. Moreover, higher levels of HE4 gene expression were associated with more advanced disease and larger tumor size. Conclusion: HE4 gene over-expression has the potential to be used as a biomarker for detecting early-stage ovarian cancer in women. Future more comprehensive studies are needed to confirm our findings.
文摘Microblog is a new Internet featured product, which has seen a rapid development in recent years. Researchers from different countries are making various technical analyses on microblogging applications. In this study, through using the natural language processing(NLP) and data mining, we analyzed the information content transmitted via a microblog, users' social networks and their interactions, and carried out an empirical analysis on the dissemination process of one particular piece of information via Sina Weibo.Based on the result of these analyses, we attempt to develop a better understanding about the rule and mechanism of the informal information flow in microblogging.
基金We thank Dr Hong Wu for providing Pten−/−MEFs and Dr Hongliang Li for Ptenflox/flox mice and Dr Mingzhou Chen for providing VSV as a gift.This work was supported by the National Nature Science Foundation of China(grant 81620108020)the China‘973’Basic Research Program(#2013CB911101)Hubei Provincial Science&Technology Innovation Team grant(#2015CFA009).
文摘Phosphatase and tensin homolog deleted on chromosome ten(PTEN)is a well-known tumor suppressor that acts as a dual-specificity phosphatase and is frequently mutated in human cancer.Our previous work has demonstrated that PTEN also plays a vital role in type I interferon responses and antiviral innate immunity.Recently,a translational variant of PTEN with a long N-terminal extension(PTEN-L)has been discovered that is secreted into the extracellular environment and enters recipient cells,where it exerts a phosphatase function antagonistic to PI3K/Akt signaling and tumorigenesis.In this study,we demonstrate that PTEN-L promotes type I interferon responses and antiviral innate immunity during viral infection in a phosphatase activity-dependent manner.Compared with canonical PTEN,PTEN-L also exerts its antiviral function when it is applied exogenously in protein form.This finding was confirmed in cell cultures and mouse infection models.Furthermore,PTEN-L enhances the responses of both type I interferon and proinflammatory cytokines,thus suggesting that PTEN-L might possess additional functions compared with those of PTEN.Thus,the antiviral function of PTEN-L may open an avenue for the use of PTEN-L in antiviral therapy,particularly in patients with PTEN-deficient tumors.
基金Emergency Science and Technology Project of China's Ministry of Science and Technology(2020YFC0845600)Emergency Science and Technology Project of Hubei Province(2020FCA046)+4 种基金the Fundamental Research Funds for the Central University(2042021 kf0049)the Special Fund for COVID-19 Research of Wuhan University,National Key R&D Program of China(2017YFA0505801)the National Natural Science Foundation of China(81825015,81871650,and 31630086)National Science and Technology Major Project(2018ZX10101004)the Natural Science Foundation of Hubei Province Innovation Group(2017CFA022).
文摘Dear Editor,The outbreak of SARS-CoV-2 leads global epidemic with high morbidity and mortality.However,the pathophysiology of this deadly virus is complex and largely unknown.Autophagy is a highly conserved homeostatic process that allows cells to recycle their components.Several studies provided evidence that human coronavirus infections are closely related to various cellular aspects associated with autophagy.1 Autophagy may play a crucial role in the SARS-CoV-2 viral lifecycle.
基金This work is supported by the National Natural Science Foundation of China(#81620108020)Guangdong Zhujiang Talents Program,Shenzhen Science and Technology Program(#KQTD20180411143323605)National Ten-thousand Talents Program(all to D.G.).
文摘Dear Editor,The serine-threonine kinase Akt plays a central role in regulating cell proliferation,migration,angiogenesis,transformation,energy metabolism,and death.1 The stimulation of growth factors recruits the PI3K to the plasma membrane and phosphatidylinositol-3A5-trisphosphate(PIP3),which in turn recruits Akt to the plasma membrane through PH domain of Akt.
文摘In a study published in cellular and molecular immunology,Wan et al.demonstrate a new mechanism of viral immune evasion.1 It was observed that Rubicon,the RUN domain Beclin-1-interacting and cysteine-rich domain-containing protein,is induced by viral infection and antagonizes interferon(IFN)production,thereby facilitating viral replication.This study not only demonstrates a direct link between Rubicon and NF-κB essential modulator(NEMO),but also demonstrates how the interaction between Rubicon and NEMO inhibits the production of type I interferon.This study shows a previously unrecognized function of Rubicon as an important negative regulator of the innate immune response.
