In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking ...In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.展开更多
Objective:Intimate partner violence(IPV)among people living with the human immune deficiency virus(PLHIV)poses a significant threat to efforts to reduce the spread of human immune deficiency virus(HIV)and achieve the ...Objective:Intimate partner violence(IPV)among people living with the human immune deficiency virus(PLHIV)poses a significant threat to efforts to reduce the spread of human immune deficiency virus(HIV)and achieve the sustainable development goals.In Ghana,scholarly research on the forms and prevalence of IPV is available,however knowledge of the prevalence of IPV among PLHIV is limited.To understand the prevalence of IPV among PLHIV and the intersectional factors that contribute to it,this study examined the overall prevalence of IPV among PLHIV and the associated sociodemographic factors across ten regions of Ghana.Methods:We administered face-to-face survey questionnaires to 661 randomly selected antiretroviral therapy(ART)clients using Research Electronic Data Capture tools.We used descriptive statistics(mean,standard deviation,minimum,and maximum),pairwise correlation,and multivariate regression analysis to look at the data.Results:The clients of ART experienced various forms of IPV,including sexual,physical,emotional,and economic violence and controlling behaviour.The overall prevalence of IPV among PLHIV was 27.5%.This result,although on par with the global IPV average(27%),is 1.5%higher than the national rate(26%).The Upper West Region had the highest prevalence in all the categories of IPV analysed,followed by Oti Region in second place and the Upper East Region in third,except for the prevalence of sexual violence,where Greater Accra Region ranks second.In specific regions of Ghana,sociodemographic factors shaped by patriarchal and economic considerations contribute to a higher prevalence of IPV among people living with HIV.Conclusion:The findings have implications for developing policies and interventions that address the specific factors associated with HIV-induced IPV in different regions of Ghana.These interventions should also include screening PLHIV receiving ART for their IPV status regardless of gender and deploying culturally appropriate education at the community level to foster empathy towards intimate partners living with HIV.展开更多
Thichosanthin(Tk), a polypeptide with 249 amino acid residues isolated and purified from a Chinese medicinal herb, showed the capability of inducing abortion and was able to inhibit tumor growth and HIV replication. O...Thichosanthin(Tk), a polypeptide with 249 amino acid residues isolated and purified from a Chinese medicinal herb, showed the capability of inducing abortion and was able to inhibit tumor growth and HIV replication. Owing to sequence homology of the peptide with a ribosomeinactivating protein, the downward activity of Tk was suggested to be related to its cytotoxic property. We report here, however, that Tk could exert potent inhibitory effects on human lymphoproliferative responses in vitro to allogeneic, mitogenic and soluble antigens with 50% inhibition doses ranged between 0.05 and 0.5 μg/ml. The lowresponsiveness caused by Tk was not due to toxic cytolysis. Rather, evidences suggested that, in the dose range adopted, the Tk-induced inhibition was attributable, at least in part, to immune suppression, in view of (1) Tk was more effective in the early stage of alloreactivity; (2)Suppression also occurred if responder cells were pulsetreated with Tk rather than cocultured; (3) Irradiated Tk-pulsed cells were capable of inducing suppression in a Tk-free culture; (4) Suppression could also be transferred by the supernatants of Tk-pulsed cultured cells; (5) Tkinduced immune suppression was diminished by depletion of CD8+ cells from the culture, and, finally; (6) Adding CD8+ cells back to the culture could restore the suppres Trichosanthin-induced humall immune suppression sion. Thus the possibility that Tk might function as a down-regulator by immunological mechanisms in human immune responses is discussed.展开更多
Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase(IN) protein. IN catalyzes two distinct che...Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase(IN) protein. IN catalyzes two distinct chemical reactions: 3'-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3'-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980 s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus(PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus(RSV) and β-retrovirus mouse mammary tumor virus(MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.展开更多
The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimen...The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental animals.However,it is undeniable that interspecies differences between humans and mice can lead to experimental errors.The differences in the immune system have become an impor-tant factor limiting current immunological research.The application of immunodefi-cient mice provides a possible solution to these problems.By transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune responses.Researchers have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune reconstitution.Through genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts.From initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related studies.In this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches.展开更多
Clinicians involved in HIV/AIDS （Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome） prevention of mother to child transmission （PMTCT） programme and research activities can benefit from the advantag...Clinicians involved in HIV/AIDS （Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome） prevention of mother to child transmission （PMTCT） programme and research activities can benefit from the advantages that computerized systems add to medical practice even in resource constrained sub-Saharan clinic settings. Their continued use of paper based systems presents clinical data management and patient care challenges. A portable point of care data capture electronic system and a computerized clinic patient management system （CCPMS） were implemented to remedy these challenges. PMTCT report compilation was easier with the portable data collection system whose data were found to be more complete and accurate with a 0.83% error rate compared to a 4.1% error rate in the paper registers. A resounding majority of clinicians preferred using the new CCPMS with many of the view that it improved drug inventory and general clinic management with a positive effect on patient care.展开更多
Over the past decade, we have seen an alarming number of high-profile outbreaks of newly emerging and re-emerging viruses.Recent outbreaks of avian influenza viruses, Middle East respiratory syndrome coronaviruses, Zi...Over the past decade, we have seen an alarming number of high-profile outbreaks of newly emerging and re-emerging viruses.Recent outbreaks of avian influenza viruses, Middle East respiratory syndrome coronaviruses, Zika virus and Ebola virus present great threats to global health. Considering the pivotal role of host T-cell immunity in the alleviation of symptoms and the clearance of viruses in patients, there are three issues to be primarily concerned about T-cell immunity when a new virus emerges: first, does the population possess pre-existing T-cells against the new virus through previous infections of genetically relevant viruses; second, does a proper immune response arise in the patients to provide protection through an immunopathogenic effect; lastly, how long can the virus-specific immune memory persist. Herein, we summarize the current updates on the characteristics of human T-cell immunological responses against recently emerged or re-emerged viruses, and emphasize the necessity for timely investigation on the T-cell features of these viral diseases, which may provide beneficial recommendations for clinical diagnosis and vaccine development.展开更多
In a recent study,Yong-Guang Yang and colleagues developed a severely immunodeficient pig model that supports long-term engraftment and multilineage differentiation of human hematopoietic stem/progenitor cells(HSPCs)....In a recent study,Yong-Guang Yang and colleagues developed a severely immunodeficient pig model that supports long-term engraftment and multilineage differentiation of human hematopoietic stem/progenitor cells(HSPCs).1 This breakthrough addresses key limitations of current humanized mouse models,including their small size and limited lifespan,and offers a promising platform for the large-scale production of human immune cells,potentially functioning as an in vivo bioreactor.展开更多
Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria.Nasal or oral administratio...Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria.Nasal or oral administration has the advantage of being needle free and self-administered,thereby improving compliance and coverage of large populations.In China,the experience of COVID-19 has promoted substantial efforts in the development of nasal vaccinations in the general health protection strategy.The hurdles we are facing in the development of mucosal vaccines,however,come from the still limited knowledge of the mechanisms controlling mucosal immunity in different anatomical locations and in response to different pathogens/vaccines.Identifying and filling the knowledge gaps in order to develop effective and safe mucosal immunization strategies requires global collaboration,not only at the scientific level but,most importantly,by engaging public and private health organizations,governments,and regulatory authorities.We have highlighted here some of the crucial issues in mucosal immunization and provided suggestions for the way forward toward a global preparedness effort to prevent infectious diseases and ensure vaccine equity.展开更多
Animal models have been extensively used as a gold standard in various biological research,including immu-nological studies.Despite high availability and ease of handling procedure,they inadequately represent complex ...Animal models have been extensively used as a gold standard in various biological research,including immu-nological studies.Despite high availability and ease of handling procedure,they inadequately represent complex interactions and unique cellular properties in humans due to inter-species genetic and microenvironmental differences which have resulted in clinical-stage failures.Organoid technology has gained enormous attention as they provide sophisticated insights about tissue architecture and functionality in miniaturized organs.In this review,we describe the use of organoid system to overcome limitations in animal-based investigations,such as physiological mismatch with humans,costly,time-consuming,and low throughput screening.Immune organoids are one of the specific advancements in organogenesis ex vivo,which can reflect human adaptive immunity with more physiologically relevant aspects.We discuss how immune organoids are established from patient-derived lymphoid tissues,as well as their characteristics and functional features to understand immune mechanisms and responses.Also,some bioengineering perspectives are considered for any potential progress of immuno-engineered organoids.展开更多
The study of security in computer networks is a key issue, which is a rapidlygrowing area of interest because of its importance. Main network security problems are analyzed inthis paper above all, which currently are ...The study of security in computer networks is a key issue, which is a rapidlygrowing area of interest because of its importance. Main network security problems are analyzed inthis paper above all, which currently are confronted with network systems and existing works inintrusion detection. And then an intrusion detection system model based on Immune Principle (IPIDS)is presented. Meanwhile, it expatiates detailed implementation of the methods how to reduce the highfalse positive and negative alarms of the traditional Intrusion Detection System (IDS). At last asimple simulation is performed on this model just using string match algorithm as binding mechanism.The simulation results indicate that the model can detect malicious activity effectively, andconsequently the security and steadiness of the whole network system are improved also.展开更多
Background:There is sufficient epidemiological and biological evidence of increased human susceptibility to viral pathogens such as Middle East respiratory syndrome coronavirus,respiratory syncytial virus,human metapn...Background:There is sufficient epidemiological and biological evidence of increased human susceptibility to viral pathogens such as Middle East respiratory syndrome coronavirus,respiratory syncytial virus,human metapneumovirus and influenza virus,in cold weather.The pattern of outbreak of the coronavirus disease 2019(COVID-19)in China during the flu season is further proof that meteorological conditions may potentially influence the susceptibility of human populations to coronaviruses,a situation that may become increasingly evident as the current global pandemic of COVID-19 unfolds.Main body:A very rapid spread and high mortality rates have characterized the COVID-19 pandemic in countries north of the equator where air temperatures have been seasonally low.It is unclear if the currently high rates of COVID-19 infections in countries of the northern hemisphere will wane during the summer months,or if fewer people overall will become infected with COVID-19 in countries south of the equator where warmer weather conditions prevail through most of the year.However,apart from the influence of seasons,evidence based on the structural biology and biochemical properties of many enveloped viruses similar to the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2(aetiology of COVID-19),support the higher likelihood of the latter of the two outcomes.Other factors that may potentially impact the rate of virus spread include the effectiveness of infection control practices,individual and herd immunity,and emergency preparedness levels of countries.Conclusion:This report highlights the potential influence of weather conditions,seasons and non-climatological factors on the geographical spread of cases of COVID-19 across the globe.展开更多
Diarrhea can occur at an early or advanced stage of acquired immunodeficiency syndrome(AIDS)as a usual symptom in people with human immunodeficiency virus(HIV)infection.While it is usually not fatal,it can influence p...Diarrhea can occur at an early or advanced stage of acquired immunodeficiency syndrome(AIDS)as a usual symptom in people with human immunodeficiency virus(HIV)infection.While it is usually not fatal,it can influence patients’quality of life seriously.It has shown to be efficacious and improves people’s immune status to a certain extent to treat HIV/AIDS-related diarrhea on the basis of syndrome differentiation and treatment or Chinese herbs plus conventional treatment.Therefore,it may have a good application potential.Here,we outline a protocol for the systematic review of this health-care intervention,with the aim to evaluate the beneficial effects and safety of Traditional Chinese Medicine(TCM)for patients who suffer from HIV/AIDS-associated diarrhea.Randomized controlled trials that compare Chinese herbs with placebo or other effective treatments will be searched and included,in spite of publication status or language.The primary outcomes include diarrhea frequency and fecal character.The databases we will search as follows:China Science and Technology Journal Database(VIP),Chinese Biomedical Literature Database(Sino Med),Wanfang Data,China National Knowledge Infrastructure,Pub Med and the CENTRAL in Cochrane Library.Two authors will respectively conduct the screening of trials,data extraction,and use the Cochrane risk of bias tool to assess the methodological quality.We will analyze the data and perform a meta-analysis if possible.We intend to identify potential therapeutic modalities that may be of benefit to inform clinical practice by supplying existing evidence of the helpful effects and safety of TCM to treat patients suffering from HIV/AIDS-associated diarrhea.展开更多
Background Human urate anion exchanger (hURAT1) as a major urate transporter expressed on renal tubular epithelial cells regulates blood urate level by reabsorbing uric acid. Antibody is an important tool to study h...Background Human urate anion exchanger (hURAT1) as a major urate transporter expressed on renal tubular epithelial cells regulates blood urate level by reabsorbing uric acid. Antibody is an important tool to study hURAT1. This study aimed, by genetic immunization, to produce mouse anti-hURAT1 polyclonal antibody with high throughput and high specificity and to detect the location of hURAT1 in human kidney.Methods Human renal total RNA was isolated and the entire cDNA of hURAT1 was amplified by RT-PCR. The sequence of intracellular high antigenicity fragment (A280 to R349) was chosen by prediction software of protein antigenicity, and its cDNA was amplified from cDNA of hURAT1, and then cloned into pBQAP-TT vector to construct recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization. Mice were inoculated with this recombinant plasmid and two other adjuvant plasmids, pCMVi-GMCSF and pCMVi-Flt3L, which helped to enhance the antibody’s generation. After four weeks, the mice were sacrificed to obtain the anti-hURAT1 antibody from serum. The antibody was identified by western blot analysis and immunohistochemistry. At the same time, rabbit anti-hURAT1 antibody was produced by protein immunization. The specificity and efficiency between the rabbit and mouse anti-hURAT1 antibody were compared by western blot analysis and immunohistochemistry. Results The entire cDNA of hURAT1 and cDNA of its intracellular high immunogenic fragment were amplified successfully. Recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization was confirmed by restriction digestion and sequencing. Both!the mouse anti-hURAT1 antibody and rabbit anti-hURAT1 antibody recognized 58kD hURAT1 and 64kD glycosylated hURAT1 protein bands in western blot. Immunohistochemically, hURAT1 was located at the brush border membrane of renal proximal tubular cells. In addition, the throughput and specificity of the mouse anti-hURAT1 antibody were higher than those of the rabbit anti-hURAT1 antibody.Conclusion Genetic immunization can generate anti-hURAT1 polyclonal antibody of high throughput and specificity.展开更多
Humanized immune system(HIS)mice have been developed and used as a small surrogate model to study human immune function under normal or disease conditions.Although variations are found between models,most HIS mice sho...Humanized immune system(HIS)mice have been developed and used as a small surrogate model to study human immune function under normal or disease conditions.Although variations are found between models,most HIS mice show robust human T cell responses.However,there has been unsuccessful in constructing HIS mice that produce high-affinity human antibodies,primarily due to defects in terminal B cell differentiation,antibody affinity maturation,and development of primary follicles and germinal centers.In this review,we elaborate on the current knowledge about and previous attempts to improve human B cell development in HIS mice,and propose a potential strategy for constructing HIS mice with improved humoral immunity by transplantation of human follicular dendritic cells(FDCs)to facilitate the development of secondary follicles.展开更多
Chemokines are small protein molecules associated with various physiological events precisely in immune modulation via dhemokine receptors.The chemokine receptors are G-protein coupled receptors express mainly on the ...Chemokines are small protein molecules associated with various physiological events precisely in immune modulation via dhemokine receptors.The chemokine receptors are G-protein coupled receptors express mainly on the cell surface of immune cells.Retrovi-ruses,including HIV in the early stage of infection,primarily target chemokines receptors and get intemalized easily into immune cells;T cell and escape from immune surveillance.HIV glycoprotein selectively develops an affinity for the extracellular domain of chemokines recep-tors and allows the pathogen to intemalize via CCR-5.Now,CCR-5 remains a crucial signaling pathway that can be translated into the therapeutic target by changing the receptor protein environment.Many populations have a mutation in coding and promoter regions of CCR-5,tun-ing a resistance for HIV infection.Natively,there are several mechanisms where the human genome remains in the dynamic state by changing its composition and acquiring variations.Sin-gle nucleotide polymorphism is spontaneous phenomenon responsible for precise and point mutation at the genome.Several studies have demonstrated that European and African Amer-ican populations are enriched in significant CCR5 promoter SNP(CCR5432)in the coding and promoter region as well.Now,such SNP can be an early-stage biomarker in studying HIV and other similar infections.Here,in this study,we have elucidated the role of SNP(both the pro-moter and coding region)and the fate of HIV infections.We also empathized with the genetics of such SNPs,mostly frequency and its immunological impact.展开更多
Cancer is a major public health problem in the world.There is still a long way to go before we can manage cancer as a chronic disease or cure cancer.And now,cancer immunotherapy,a strategy that harnesses the human imm...Cancer is a major public health problem in the world.There is still a long way to go before we can manage cancer as a chronic disease or cure cancer.And now,cancer immunotherapy,a strategy that harnesses the human immune system to fight against cancer is paving the path to curing it.Activating the immune system for therapeutic benefit in cancer has become a goal in immunology and oncology.展开更多
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035National Key Research and Development Project,Grant/Award Number:2022YFA1103803。
文摘In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.
基金supported by the Christian Health Association of Ghana under Global Fund New Funding Model 3(NFM 3)HIV/TB Community Systems Strengthening programme(CSS)。
文摘Objective:Intimate partner violence(IPV)among people living with the human immune deficiency virus(PLHIV)poses a significant threat to efforts to reduce the spread of human immune deficiency virus(HIV)and achieve the sustainable development goals.In Ghana,scholarly research on the forms and prevalence of IPV is available,however knowledge of the prevalence of IPV among PLHIV is limited.To understand the prevalence of IPV among PLHIV and the intersectional factors that contribute to it,this study examined the overall prevalence of IPV among PLHIV and the associated sociodemographic factors across ten regions of Ghana.Methods:We administered face-to-face survey questionnaires to 661 randomly selected antiretroviral therapy(ART)clients using Research Electronic Data Capture tools.We used descriptive statistics(mean,standard deviation,minimum,and maximum),pairwise correlation,and multivariate regression analysis to look at the data.Results:The clients of ART experienced various forms of IPV,including sexual,physical,emotional,and economic violence and controlling behaviour.The overall prevalence of IPV among PLHIV was 27.5%.This result,although on par with the global IPV average(27%),is 1.5%higher than the national rate(26%).The Upper West Region had the highest prevalence in all the categories of IPV analysed,followed by Oti Region in second place and the Upper East Region in third,except for the prevalence of sexual violence,where Greater Accra Region ranks second.In specific regions of Ghana,sociodemographic factors shaped by patriarchal and economic considerations contribute to a higher prevalence of IPV among people living with HIV.Conclusion:The findings have implications for developing policies and interventions that address the specific factors associated with HIV-induced IPV in different regions of Ghana.These interventions should also include screening PLHIV receiving ART for their IPV status regardless of gender and deploying culturally appropriate education at the community level to foster empathy towards intimate partners living with HIV.
文摘Thichosanthin(Tk), a polypeptide with 249 amino acid residues isolated and purified from a Chinese medicinal herb, showed the capability of inducing abortion and was able to inhibit tumor growth and HIV replication. Owing to sequence homology of the peptide with a ribosomeinactivating protein, the downward activity of Tk was suggested to be related to its cytotoxic property. We report here, however, that Tk could exert potent inhibitory effects on human lymphoproliferative responses in vitro to allogeneic, mitogenic and soluble antigens with 50% inhibition doses ranged between 0.05 and 0.5 μg/ml. The lowresponsiveness caused by Tk was not due to toxic cytolysis. Rather, evidences suggested that, in the dose range adopted, the Tk-induced inhibition was attributable, at least in part, to immune suppression, in view of (1) Tk was more effective in the early stage of alloreactivity; (2)Suppression also occurred if responder cells were pulsetreated with Tk rather than cocultured; (3) Irradiated Tk-pulsed cells were capable of inducing suppression in a Tk-free culture; (4) Suppression could also be transferred by the supernatants of Tk-pulsed cultured cells; (5) Tkinduced immune suppression was diminished by depletion of CD8+ cells from the culture, and, finally; (6) Adding CD8+ cells back to the culture could restore the suppres Trichosanthin-induced humall immune suppression sion. Thus the possibility that Tk might function as a down-regulator by immunological mechanisms in human immune responses is discussed.
基金Supported by United States National Institutes of Health grant,No.R01AI070042
文摘Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase(IN) protein. IN catalyzes two distinct chemical reactions: 3'-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3'-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980 s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus(PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus(RSV) and β-retrovirus mouse mammary tumor virus(MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.
基金Scientific and Technological Resources Coordination Project of Shaanxi Province,Grant/Award Number:2020PT-002,2022PT-43 and CX-PT-18Special Fund for Military Laboratory Animals,Grant/Award Number:SYDW_KY(2021)13State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Grant/Award Number:CBSKL2022ZZ28。
文摘The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental animals.However,it is undeniable that interspecies differences between humans and mice can lead to experimental errors.The differences in the immune system have become an impor-tant factor limiting current immunological research.The application of immunodefi-cient mice provides a possible solution to these problems.By transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune responses.Researchers have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune reconstitution.Through genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts.From initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related studies.In this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches.
文摘Clinicians involved in HIV/AIDS （Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome） prevention of mother to child transmission （PMTCT） programme and research activities can benefit from the advantages that computerized systems add to medical practice even in resource constrained sub-Saharan clinic settings. Their continued use of paper based systems presents clinical data management and patient care challenges. A portable point of care data capture electronic system and a computerized clinic patient management system （CCPMS） were implemented to remedy these challenges. PMTCT report compilation was easier with the portable data collection system whose data were found to be more complete and accurate with a 0.83% error rate compared to a 4.1% error rate in the paper registers. A resounding majority of clinicians preferred using the new CCPMS with many of the view that it improved drug inventory and general clinic management with a positive effect on patient care.
基金supported by the National Key Research and Development Program of China(2017YFC1200202)the China Mega-Project on Infectious Disease Prevention(2016ZX10004222-003)+1 种基金the National Natural Science Foundation of China(81401312,81373141)the National Natural Science Foundation of China Innovative Research Group(81621091)
文摘Over the past decade, we have seen an alarming number of high-profile outbreaks of newly emerging and re-emerging viruses.Recent outbreaks of avian influenza viruses, Middle East respiratory syndrome coronaviruses, Zika virus and Ebola virus present great threats to global health. Considering the pivotal role of host T-cell immunity in the alleviation of symptoms and the clearance of viruses in patients, there are three issues to be primarily concerned about T-cell immunity when a new virus emerges: first, does the population possess pre-existing T-cells against the new virus through previous infections of genetically relevant viruses; second, does a proper immune response arise in the patients to provide protection through an immunopathogenic effect; lastly, how long can the virus-specific immune memory persist. Herein, we summarize the current updates on the characteristics of human T-cell immunological responses against recently emerged or re-emerged viruses, and emphasize the necessity for timely investigation on the T-cell features of these viral diseases, which may provide beneficial recommendations for clinical diagnosis and vaccine development.
基金supported the Natural Science Foundation of Jilin Province(YDZJ202201ZYTS101).
文摘In a recent study,Yong-Guang Yang and colleagues developed a severely immunodeficient pig model that supports long-term engraftment and multilineage differentiation of human hematopoietic stem/progenitor cells(HSPCs).1 This breakthrough addresses key limitations of current humanized mouse models,including their small size and limited lifespan,and offers a promising platform for the large-scale production of human immune cells,potentially functioning as an in vivo bioreactor.
基金supported by the Gates Foundation(INV-059115)the Alliance of International Science Organizations(ANSO-CR-KP-2022-01)partly supported by the National Natural Science Foundation of China(92469301).
文摘Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria.Nasal or oral administration has the advantage of being needle free and self-administered,thereby improving compliance and coverage of large populations.In China,the experience of COVID-19 has promoted substantial efforts in the development of nasal vaccinations in the general health protection strategy.The hurdles we are facing in the development of mucosal vaccines,however,come from the still limited knowledge of the mechanisms controlling mucosal immunity in different anatomical locations and in response to different pathogens/vaccines.Identifying and filling the knowledge gaps in order to develop effective and safe mucosal immunization strategies requires global collaboration,not only at the scientific level but,most importantly,by engaging public and private health organizations,governments,and regulatory authorities.We have highlighted here some of the crucial issues in mucosal immunization and provided suggestions for the way forward toward a global preparedness effort to prevent infectious diseases and ensure vaccine equity.
基金supported by the NUS Presidential Young Professor-ship,Ministry of Education Tier 1,National Medical Research Council Open Fund Young Investigator Research Grant,Manufacturing,Trade and Connectivity Young Investigator Research Grant,iHT OOE award,NUS Healthy Longevity TRP Aged Mice Funding,Joint NCIS Centre Grant and NUS Centre for Cancer Research(N2CR)Seed Funding Programme,TREX Grant,PCM Seed Grant,and PREPARE Strategic Open Grant Call(Vaccines&Therapeutics Co-Operative Programme).
文摘Animal models have been extensively used as a gold standard in various biological research,including immu-nological studies.Despite high availability and ease of handling procedure,they inadequately represent complex interactions and unique cellular properties in humans due to inter-species genetic and microenvironmental differences which have resulted in clinical-stage failures.Organoid technology has gained enormous attention as they provide sophisticated insights about tissue architecture and functionality in miniaturized organs.In this review,we describe the use of organoid system to overcome limitations in animal-based investigations,such as physiological mismatch with humans,costly,time-consuming,and low throughput screening.Immune organoids are one of the specific advancements in organogenesis ex vivo,which can reflect human adaptive immunity with more physiologically relevant aspects.We discuss how immune organoids are established from patient-derived lymphoid tissues,as well as their characteristics and functional features to understand immune mechanisms and responses.Also,some bioengineering perspectives are considered for any potential progress of immuno-engineered organoids.
基金This work is sponsored by the National Natural Science Foundation of P. R. China (No.60173037 &70271050) National 863 High Technology Research Program ofP. R. China (No.2004AA775053) the Natural Science Foundation of Jiangsu Province (No.BK20031
文摘The study of security in computer networks is a key issue, which is a rapidlygrowing area of interest because of its importance. Main network security problems are analyzed inthis paper above all, which currently are confronted with network systems and existing works inintrusion detection. And then an intrusion detection system model based on Immune Principle (IPIDS)is presented. Meanwhile, it expatiates detailed implementation of the methods how to reduce the highfalse positive and negative alarms of the traditional Intrusion Detection System (IDS). At last asimple simulation is performed on this model just using string match algorithm as binding mechanism.The simulation results indicate that the model can detect malicious activity effectively, andconsequently the security and steadiness of the whole network system are improved also.
文摘Background:There is sufficient epidemiological and biological evidence of increased human susceptibility to viral pathogens such as Middle East respiratory syndrome coronavirus,respiratory syncytial virus,human metapneumovirus and influenza virus,in cold weather.The pattern of outbreak of the coronavirus disease 2019(COVID-19)in China during the flu season is further proof that meteorological conditions may potentially influence the susceptibility of human populations to coronaviruses,a situation that may become increasingly evident as the current global pandemic of COVID-19 unfolds.Main body:A very rapid spread and high mortality rates have characterized the COVID-19 pandemic in countries north of the equator where air temperatures have been seasonally low.It is unclear if the currently high rates of COVID-19 infections in countries of the northern hemisphere will wane during the summer months,or if fewer people overall will become infected with COVID-19 in countries south of the equator where warmer weather conditions prevail through most of the year.However,apart from the influence of seasons,evidence based on the structural biology and biochemical properties of many enveloped viruses similar to the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2(aetiology of COVID-19),support the higher likelihood of the latter of the two outcomes.Other factors that may potentially impact the rate of virus spread include the effectiveness of infection control practices,individual and herd immunity,and emergency preparedness levels of countries.Conclusion:This report highlights the potential influence of weather conditions,seasons and non-climatological factors on the geographical spread of cases of COVID-19 across the globe.
基金supported by the National Natural Science Foundation of China(Grant No.81673828)
文摘Diarrhea can occur at an early or advanced stage of acquired immunodeficiency syndrome(AIDS)as a usual symptom in people with human immunodeficiency virus(HIV)infection.While it is usually not fatal,it can influence patients’quality of life seriously.It has shown to be efficacious and improves people’s immune status to a certain extent to treat HIV/AIDS-related diarrhea on the basis of syndrome differentiation and treatment or Chinese herbs plus conventional treatment.Therefore,it may have a good application potential.Here,we outline a protocol for the systematic review of this health-care intervention,with the aim to evaluate the beneficial effects and safety of Traditional Chinese Medicine(TCM)for patients who suffer from HIV/AIDS-associated diarrhea.Randomized controlled trials that compare Chinese herbs with placebo or other effective treatments will be searched and included,in spite of publication status or language.The primary outcomes include diarrhea frequency and fecal character.The databases we will search as follows:China Science and Technology Journal Database(VIP),Chinese Biomedical Literature Database(Sino Med),Wanfang Data,China National Knowledge Infrastructure,Pub Med and the CENTRAL in Cochrane Library.Two authors will respectively conduct the screening of trials,data extraction,and use the Cochrane risk of bias tool to assess the methodological quality.We will analyze the data and perform a meta-analysis if possible.We intend to identify potential therapeutic modalities that may be of benefit to inform clinical practice by supplying existing evidence of the helpful effects and safety of TCM to treat patients suffering from HIV/AIDS-associated diarrhea.
文摘Background Human urate anion exchanger (hURAT1) as a major urate transporter expressed on renal tubular epithelial cells regulates blood urate level by reabsorbing uric acid. Antibody is an important tool to study hURAT1. This study aimed, by genetic immunization, to produce mouse anti-hURAT1 polyclonal antibody with high throughput and high specificity and to detect the location of hURAT1 in human kidney.Methods Human renal total RNA was isolated and the entire cDNA of hURAT1 was amplified by RT-PCR. The sequence of intracellular high antigenicity fragment (A280 to R349) was chosen by prediction software of protein antigenicity, and its cDNA was amplified from cDNA of hURAT1, and then cloned into pBQAP-TT vector to construct recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization. Mice were inoculated with this recombinant plasmid and two other adjuvant plasmids, pCMVi-GMCSF and pCMVi-Flt3L, which helped to enhance the antibody’s generation. After four weeks, the mice were sacrificed to obtain the anti-hURAT1 antibody from serum. The antibody was identified by western blot analysis and immunohistochemistry. At the same time, rabbit anti-hURAT1 antibody was produced by protein immunization. The specificity and efficiency between the rabbit and mouse anti-hURAT1 antibody were compared by western blot analysis and immunohistochemistry. Results The entire cDNA of hURAT1 and cDNA of its intracellular high immunogenic fragment were amplified successfully. Recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization was confirmed by restriction digestion and sequencing. Both!the mouse anti-hURAT1 antibody and rabbit anti-hURAT1 antibody recognized 58kD hURAT1 and 64kD glycosylated hURAT1 protein bands in western blot. Immunohistochemically, hURAT1 was located at the brush border membrane of renal proximal tubular cells. In addition, the throughput and specificity of the mouse anti-hURAT1 antibody were higher than those of the rabbit anti-hURAT1 antibody.Conclusion Genetic immunization can generate anti-hURAT1 polyclonal antibody of high throughput and specificity.
基金supported by the National Key Research and Development Program of China(2021YFA1100700)the National Natural Science Foundation of China(81941008)+3 种基金the Natural Science Foundation of Jilin Province,China(20200201191JC)the Department of Human Resource and Social Security of Jilin Province(2022DJ02)the Science Development of Jilin Province,China(20230505029ZP)the Bethune Medical Department of Jilin University(2022JBGS01)。
文摘Humanized immune system(HIS)mice have been developed and used as a small surrogate model to study human immune function under normal or disease conditions.Although variations are found between models,most HIS mice show robust human T cell responses.However,there has been unsuccessful in constructing HIS mice that produce high-affinity human antibodies,primarily due to defects in terminal B cell differentiation,antibody affinity maturation,and development of primary follicles and germinal centers.In this review,we elaborate on the current knowledge about and previous attempts to improve human B cell development in HIS mice,and propose a potential strategy for constructing HIS mice with improved humoral immunity by transplantation of human follicular dendritic cells(FDCs)to facilitate the development of secondary follicles.
文摘Chemokines are small protein molecules associated with various physiological events precisely in immune modulation via dhemokine receptors.The chemokine receptors are G-protein coupled receptors express mainly on the cell surface of immune cells.Retrovi-ruses,including HIV in the early stage of infection,primarily target chemokines receptors and get intemalized easily into immune cells;T cell and escape from immune surveillance.HIV glycoprotein selectively develops an affinity for the extracellular domain of chemokines recep-tors and allows the pathogen to intemalize via CCR-5.Now,CCR-5 remains a crucial signaling pathway that can be translated into the therapeutic target by changing the receptor protein environment.Many populations have a mutation in coding and promoter regions of CCR-5,tun-ing a resistance for HIV infection.Natively,there are several mechanisms where the human genome remains in the dynamic state by changing its composition and acquiring variations.Sin-gle nucleotide polymorphism is spontaneous phenomenon responsible for precise and point mutation at the genome.Several studies have demonstrated that European and African Amer-ican populations are enriched in significant CCR5 promoter SNP(CCR5432)in the coding and promoter region as well.Now,such SNP can be an early-stage biomarker in studying HIV and other similar infections.Here,in this study,we have elucidated the role of SNP(both the pro-moter and coding region)and the fate of HIV infections.We also empathized with the genetics of such SNPs,mostly frequency and its immunological impact.
文摘Cancer is a major public health problem in the world.There is still a long way to go before we can manage cancer as a chronic disease or cure cancer.And now,cancer immunotherapy,a strategy that harnesses the human immune system to fight against cancer is paving the path to curing it.Activating the immune system for therapeutic benefit in cancer has become a goal in immunology and oncology.
