To explore the mechanisms underlying ocular infection by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),we conducted a comprehensive review of current literature,focusing on viral entry pathways,receptor ...To explore the mechanisms underlying ocular infection by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),we conducted a comprehensive review of current literature,focusing on viral entry pathways,receptor expression in ocular tissues,and associated clinical manifestations.This review encompasses studies published within the last five years with a focus on original research and systematic reviews that provide molecular,histological,or clinical evidence.The findings show that SARS-CoV-2 can infect ocular tissues through multiple receptors beyond angiotensin-converting enzyme 2(ACE2),including transmembrane serine protease 2(TMPRSS2),CD147,alanyl aminopeptidase N(ANPEP),dipeptidyl peptidase 4(DPP4),angiotensin II receptor type 2(AGTR2),and polymeric immunoglobulin receptor(PIGR),which are expressed in retinal,conjunctival,corneal,limbal,and photoreceptor cells.The virus may also reach ocular structures via neurovascular invasion.Clinically,patients with coronavirus disease 2019(COVID-19)may present with a broad spectrum of ophthalmic manifestations,including conjunctivitis,hyperreflective lesions in the inner retinal layers,flame-shaped hemorrhages,cottonwool spots,retinal pallor,hard exudates,and various forms of maculopathy,such as paracentral acute middle maculopathy and acute macular neuroretinopathy(AMN).These signs reflect both direct viral damage and secondary effects of systemic inflammation and microvascular injury.Understanding the molecular and clinical spectrum of ocular involvement is essential for early diagnosis,appropriate ophthalmologic care,and the prevention of long-term visual sequelae in patients affected by COVID-19.展开更多
AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in vario...AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.展开更多
Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompr...Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompromised patients,particularly people with HIV(PWH).Whether PWH are more vulnerable to COVID with more adverse outcomes has been extensively studied,but the findings are inconsistent.Many cohort studies and meta-analyses support that PWH have a higher risk of SARSCoV-2 infection and more severe COVID-19 outcomes(Bertagnolio et al.,2022;Ssentongo et al.,2021).展开更多
Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas,making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells.However,little is know...Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas,making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells.However,little is known about the mechanisms underlying the glioma-induced tropism of stem cells.Soluble factors including chemokines or growth factors released and expressed by glioma cells at least mediate the tropism of stem cells for gliomas.Here we review the possible mechanisms of stem cells tropism for malignant gliomas.展开更多
AIM： To investigate the selective tropism of liver stem cells to hepatocellular carcinoma （HCC） in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS： ...AIM： To investigate the selective tropism of liver stem cells to hepatocellular carcinoma （HCC） in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS： WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein （EGFP）. An animal model of HCC in Wistar rats was established by implanting HCC cells （CBRH7919） combined with an immunosuppressive drug. EGFP labeled liver stern cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stern cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stern cells within the tumor tissue were observed and analyzed.RESULTS： Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue.CONCLUSION： Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.展开更多
OBJECTIVE: To study the meridian tropism(MT) for three Chinese medicines: Tinglizi(Semen Lepidii Apetali, TLZ), Yiyiren(Semen Coicis, YYR), Cheqianzi(Semen Plantaginis, CQZ) in vivo experiments.METHODS: The extracts o...OBJECTIVE: To study the meridian tropism(MT) for three Chinese medicines: Tinglizi(Semen Lepidii Apetali, TLZ), Yiyiren(Semen Coicis, YYR), Cheqianzi(Semen Plantaginis, CQZ) in vivo experiments.METHODS: The extracts of TLZ,YYR, CQZ were orally administered to rats at a dose 234, 700 and 350 mg/kg, respectively. The urinary excretion rate, loss in weight of rats and the electrolyte levels in the plasma were measured, in order to assess the mechanisms of the three traditional Chinese diuretic medicines.RESULTS: TLZ, YYR and CQZ exhibited obvious diuretic effect and reduced the weight of saline-loaded animals. All the three diuretic medicines differentially reduced various serum, urinary, lung, stomach, kidney and hormonal markers, thus indicating the different mechanisms of action and a close resemblance with their different meridian as per the MT theory.CONCLUSION: Our findings suggest that the three Traditional Chinese Medicine(TCM) medicines-TLZ,YYR and CQZ-possess different Shamisen meridian.This can support the regimen of treating the same disease with different therapies in TCM theory.展开更多
Objective:To evaluate parasite distribution and tissue tropism of Toxoplasma gondii tachyzoites in experimentally infected mice using real time QPCR.Methods:In this survey 16 Balb/c mice were inoculated with 1×10...Objective:To evaluate parasite distribution and tissue tropism of Toxoplasma gondii tachyzoites in experimentally infected mice using real time QPCR.Methods:In this survey 16 Balb/c mice were inoculated with 1×10~4 alive tachyzoites of Toxoplasma gondii RH strain.After 1,2,3 days post infection and the last day(before death),different tissues of mice including blood,brain,eye,liver,spleen,kidney,heart and muscle were harvested.Following tissues DNA extraction,the parasite burden was quantified using real time QPCR targeting the B1 gene(451 bp).Results:It showed that Toxoplasma after intraperitoneal injection was able to movement to various tissues in24 hours.Parasite burden was high in all tissues but the most number of parasites were observed in kidney,heart and liver,respectively.Conclusions:These data provide significant baseline information about Toxoplasma pathogenesis,vaccine monitoring and drug efficiency.展开更多
People′s environmental tropism has an effect on their understanding of tourism-nature relationship,and also influences their attitudes to natural resources utilization and environmental protection.Taking Jiuzhaigou N...People′s environmental tropism has an effect on their understanding of tourism-nature relationship,and also influences their attitudes to natural resources utilization and environmental protection.Taking Jiuzhaigou National Park of China as a study case,the authors conducted some quantitative analyses with the tools of SPSS 16.0 and LISREL 8.7,to explore the influence of tourists′ environmental tropism on their attitudes to tourism and nature conservation in the natural tourist destination.Three hypotheses and the theoretic model of influences of tourists′ environmental tropism on their attitudes to tourism and nature conservation have been tested and accepted based on the Structural Equation Model analysis on survey data collected in Jiuzhaigou National Park of China.Some conclusions were drawn as follows: 1) tourists′ human-prioritized concept influences their cognition to tourism-nature relationship.This concept has a positive influence on their supportive attitudes to tourism,but a negative influence on their attitudes to nature conservation;2) tourists′ human-nature coordination concept has a positive influence on their supportive attitudes to both tourism and nature conservation,especially to the latter.This paper generally proves that human′s environmental tropism does have an influence on their attitudes to tourism and nature conservation in natural tourist destinations.展开更多
OBJECTIVE:To investigate whether Fuzi(Radix Aconiti Praeparata) has fewer "hot" characteristics when administered without Ganjiang(Rhizoma Zingiberis).METHODS:Differences in the thermotropism behaviors of mi...OBJECTIVE:To investigate whether Fuzi(Radix Aconiti Praeparata) has fewer "hot" characteristics when administered without Ganjiang(Rhizoma Zingiberis).METHODS:Differences in the thermotropism behaviors of mice treated either with Fuzi(Radix Aconiti Praeparata),Ganjiang(Rhizoma Zingiberis) or the combination of the two given intragastrically were investigated using the Animal Thermotropism Behavior Surveillance System.The water intake volume,oxygen consumption volume,adenosine triphosphatase(ATPase) activity,total antioxidant capacity(T-AOC) and total superoxide dismutase(T-SOD) activity were determined during the investigation.RESULTS:When Fuzi and Ganjiang were administered together,the rate at which mice remained on a warm plate("remaining rate") and the times and distances of their movement were all significantly reduced(P<0.05).Compared with the Normal group,the reduction was 55.1%,48.3% and 44.8%,while compared with the Fuzi group,the reduction was 57.6%,34.3% and 36.0%,indicating that "cold" tropism was significantly increased.Compared with the Normal and Fuzi groups,the ATPase activity and the respiratory oxygen consumption volume of the Fuzi + Ganjiang group were significantly increased(P<0.05),suggesting an improvement in energy metabolism and showing a "hot" characteristic when Fuzi and Ganjiang are present together.Additionally,the T-AOC and T-SOD activity were significantly enhanced(P<0.05).CONCLUSION:The behavior of mice tending toward "cold" tropism can be regarded as a quantitative reflection of Fuzi having fewer characteristics consistent w ith a "hot" nature when not used with Ganjiang,the functional mechanism of which may be a change in the ATPase activity in liver tissue.展开更多
Natural clays have been used by man in infections of bacterial etiology, since the first historical registers. Our attention turned to a red-colored clay, known in the northeast of Brazil as “barro de louça”...Natural clays have been used by man in infections of bacterial etiology, since the first historical registers. Our attention turned to a red-colored clay, known in the northeast of Brazil as “barro de louça” (dish clay). These clays and other natural earth materials seem interesting to us, as the blockage of the liberation of toxins or inactivation, may be related to the interruption of infection cycles in the skin and mucous membranes. The adsorptive and absorptive properties of the mineral clays are well documented in the cure process of skin and gastrointestinal diseases. Susceptibility and bacterial tropism tests were carried out. The results were analyzed and interpreted according to the conventional microbiological protocol. The bacterial strains, Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa, did not present a susceptibility profile to an isotonic solution of clay, but there was an increase of the bacterial tropism as the concentration of the isotonic solution was increased, being the minimal observed concentration of 100 mg/mL. Our aim is to document a type of red clay from the northeast of Brazil with possible attraction properties (Tropism) to bacteria and their toxins.展开更多
The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has significantly burdened global public health.However,the tropism of SARS-CoV-2 within the human b...The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has significantly burdened global public health.However,the tropism of SARS-CoV-2 within the human body remains not fully understood.In this review,we overview the literature on SARS-CoV-2 infection across various human organs and tissues.We summarize the relevant specimen types,techniques for examining SARS-CoV-2 tropism,and findings at both organ/tissue and cellular levels.To systematically evaluate the evidence supporting SARS-CoV-2 tissue tropism,we establish a hierarchical classification system based on two key criteria:(1)specimen origin and(2)detection methodology.Clinical specimens obtained directly from COvID-19 patients provide the most definitive evidence,whereas organoid-derived specimens and animal models indicate potential infectivity under artificial conditions.In terms of detection methods,we prioritize viral particle identification over viral protein or RNA detection,as the latter requires further confirmation to establish productive infection.Our findings indicate that SARS-CoV-2 potentially targets multiple human organ systems,including the respiratory tract,lungs,kidneys,heart,blood vessels,pancreas,small intestine,liver,and salivary glands.By contrast,viral tropism for the central nervous system and the reproductive system remains uncertain and requires further validation.At the cellular level,we identify specific target cell types vulnerable to infection,including ciliated epithelial cells,alveolar type II pneumocytes,enterocytes,cardiomyocytes,vascular endothelial cells,renal tubular epithelial cells,and pancreatic acinar cells.Furthermore,we analyze the correlation between angiotensin-converting enzyme 2 receptor distribution patterns and viral tropism,as well as potential variations in tissue specificity among different viral variants.We expect this review to provide a comprehensive landscape of SARS-CoV-2 tropism and enhance our understanding of the life cycle and consequences of SARS-CoV-2 infection within the human body.展开更多
The coronavirus disease 2019(COVID-19)pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is spread primary via respiratory droplets and infects the lungs.Current...The coronavirus disease 2019(COVID-19)pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is spread primary via respiratory droplets and infects the lungs.Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines(transformed or cancer cells)and species differences between animals and humans.Organoids are stem cell-derived selforganized three-dimensional culture in vitro and model the physiological conditions of natural organs.Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells(hESCs)-derived lung organoids,including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs.The infected ceils were ciliated,club,and alveolar type 2(AT2)cells,which were sequentially located from the proximal to the distal airway and terminal alveoli,respectively.Additionally,RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes,especially lipid metabolism,in addition to the well-known upregulation of immune response.Further,Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids.Therefore,human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.展开更多
The description and differentiation of the so-called"Cold"and"Hot"natures,the primary"Drug Naure"of Chinese medicine,is the focus of theoretical research.In this study,the divergency betw...The description and differentiation of the so-called"Cold"and"Hot"natures,the primary"Drug Naure"of Chinese medicine,is the focus of theoretical research.In this study,the divergency between the"Cold"and the"Hot"natures was investigated through examining the temperature tropism of mice affected by Coptis chinensis Franch and its processed materials by using a cold/hot plate differentiating technology.After exposure to C.chinensis Franch,the macroscopic behavioral index of the remaining rate(RR)on a warm pad(40℃)significantly increased(P<0.05),suggesting the enhancement of Hot tropism.The internal indexes of adenosine triphosphatase(ATPase)activity and oxygen consuming volume decreased significantly(P<0.05),suggesting the decapability of energy metabolism.This external behavior of Hot tropism might reflect the internal Cold nature of C.chinensis Franch.However,the processed materials of C.chinensis Franch exhibited a different Cold nature in temperature tropism compared with crude C.chinensis Franch(CC):the Cold nature of bile-processed C.chinensis Franch(BC)enhanced while the ginger-processed C.chinensis Franch(GC)changed inversely.The changing sequence was consistent with the theoretical prognostication.It is indicated that the external Cold&Hot natures of Chinese medicine may possibly reflect in an ethological way for the changes of animal’s temperature tropism which might be internally regulated by the body’s energy metabolism.展开更多
HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtyp...HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtypes B and C. The results showed that R5 and X4 variants experienced differential evolutionary patterns and different HIV-1 genes encountered various positive selection pressures, suggesting that complex selection pressures are driving HIV-1 evolution. Compared with other hypervariable regions of Gp120, significantly more positively selected sites were detected in the V3 region of subtype B X4 variants, V2 region of subtype B R5 variants, and V1 and V4 regions of subtype C X4 variants, indicating an association of positive selection with co-receptor recognition/binding. Intriguingly, a significantly higher proportion (33.3% and 55.6%, P【0.05) of positively selected sites were identified in the C3 region than other conserved regions of Gp120 in all the analyzed HIV-1 variants, indicating that the C3 region might be more important to HIV-1 adaptation than previously thought. Approximately half of the positively selected sites identified in the env gene were identical between R5 and X4 variants. There were three common positively selected sites (96, 113 and 281) identified in Gp41 of all X4 and R5 variants from subtypes B and C. These sites might not only suggest a functional importance in viral survival and adaptation, but also imply a potential cross-immunogenicity between HIV-1 R5 and X4 variants, which has important implications for AIDS vaccine development.展开更多
It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/glycolipids containing sialic acids inα2,6-linkage;while avian and equine influenza viruses preferentially bind ...It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/glycolipids containing sialic acids inα2,6-linkage;while avian and equine influenza viruses preferentially bind to those containing sialic acids inα2,3-linkage.Even though this generalized view is accurate for H3 subtype isolates,it may not be accurate and absolute for all subtypes of influenza A viruses and,therefore,needs to be reevaluated carefully and realistically.Some of the studies published in major scientific journals on the subject of tissue tropism of influenza viruses are inconsistent and caused confusion in the scientific community.One of the reasons for the inconsistency is that most studies were quantitative descriptions of sialic acid receptor distributions based on lectin or influenza virus immunohistochemistry results with limited numbers of stained cells.In addition,recent studies indicate thatα2,3-andα2,6-linked sialic acids are not the sole receptors determining tissue and host tropism of influenza viruses.In fact,determinants for tissue and host tropism of human,avian and animal influenza viruses are more complex than what has been generally accepted.Other factors,such as glycan topology,concentration of invading viruses,local density of receptors,lipid raft microdomains,coreceptors or sialic acid-independent receptors,may also be important.To more efficiently control the global spread of pandemic influenza such as the current circulating influenza A H1N1,it is crucial to clarify the determinants for tissue and host tropism of influenza viruses through quantitative analysis of experimental results.In this review,I will comment on some conflicting issues related to tissue and host tropism of influenza viruses,discuss the importance of quantitative analysis of lectin and influenza virus immunohistochemistry results and point out directions for future studies in this area,which should lead to a better understanding of tissue and host tropism of influenza viruses.展开更多
Channel tropism is investigated and developed through long-term clinical practice.In recent years,the development of channel tropism theory has attracted increasing attention.This study analyzed channel tropism theory...Channel tropism is investigated and developed through long-term clinical practice.In recent years,the development of channel tropism theory has attracted increasing attention.This study analyzed channel tropism theory and the problems associated with it.Results showed that this theory and systems biology have a similar holistic viewpoint.Systems biology could provide novel insights and platform in the study of channel tropism.Some problems in channel tropism theory,including pharmacology and action mechanism,were investigated.展开更多
Objective To observe the meridian tropism of Polygoni Avicularis Herba by tissue distribution of avicularin in rats. Methods Tissue distribution of avicularin in rat following a single iv administration was appointed ...Objective To observe the meridian tropism of Polygoni Avicularis Herba by tissue distribution of avicularin in rats. Methods Tissue distribution of avicularin in rat following a single iv administration was appointed and observed. HPLC method was established and validated for the determination of avicularin in rat tissues. Results Kidney and bladder were the most important target tissue of avicularin. Conclusion HPLC method is successfully applied to tissues distribution study of avicularin after iv administration to rats, and the results explain Polygoni Avicularis Herba on bladder tropism reasonably.展开更多
Objective： To investigate the relationship between tissue distributions of modified Wuzi Yanzong prescription（加味五子衍宗方, MWP） in rats and meridian tropism theory. Methods： A high-performance liquid chromatogr...Objective： To investigate the relationship between tissue distributions of modified Wuzi Yanzong prescription（加味五子衍宗方, MWP） in rats and meridian tropism theory. Methods： A high-performance liquid chromatography with Fourier transform-mass spectrometry（HPLC-FT） method was used to identify the metabolites of MWP in different tissues of rats after continued oral administration of MWP for 7 days. The relationship between MWP and meridian tropism theory was studied according to the tissue distributions of the metabolites of MWP in rats and the relevant literature. Results： Nineteen metabolites, mainly flavanoid compounds, were detected in the different rat tissues and classified to each herb in MWP. Further, it was able to establish that the tissue distributions of the metabolites of MWP were consistent with the descriptions of meridian tropism of MWP available in literature, this result might be useful in clarifying the mechanism of MWP on meridian tropism. In the long run, these data might provide scientific evidence of the meridian tropism theory to further promote the reasonable, effective utilization, and modernization of Chinese medicine. Conclusion： The tissue distributions of MWP in vivo were consistent with the descriptions of meridian tropism of MWP.展开更多
文摘To explore the mechanisms underlying ocular infection by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),we conducted a comprehensive review of current literature,focusing on viral entry pathways,receptor expression in ocular tissues,and associated clinical manifestations.This review encompasses studies published within the last five years with a focus on original research and systematic reviews that provide molecular,histological,or clinical evidence.The findings show that SARS-CoV-2 can infect ocular tissues through multiple receptors beyond angiotensin-converting enzyme 2(ACE2),including transmembrane serine protease 2(TMPRSS2),CD147,alanyl aminopeptidase N(ANPEP),dipeptidyl peptidase 4(DPP4),angiotensin II receptor type 2(AGTR2),and polymeric immunoglobulin receptor(PIGR),which are expressed in retinal,conjunctival,corneal,limbal,and photoreceptor cells.The virus may also reach ocular structures via neurovascular invasion.Clinically,patients with coronavirus disease 2019(COVID-19)may present with a broad spectrum of ophthalmic manifestations,including conjunctivitis,hyperreflective lesions in the inner retinal layers,flame-shaped hemorrhages,cottonwool spots,retinal pallor,hard exudates,and various forms of maculopathy,such as paracentral acute middle maculopathy and acute macular neuroretinopathy(AMN).These signs reflect both direct viral damage and secondary effects of systemic inflammation and microvascular injury.Understanding the molecular and clinical spectrum of ocular involvement is essential for early diagnosis,appropriate ophthalmologic care,and the prevention of long-term visual sequelae in patients affected by COVID-19.
基金supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)+1 种基金Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
文摘AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
基金National Key Research and Development Project of China(2023YFC2306600)Key Program of the National Natural Science Foundation of China(82430070)+6 种基金Shanghai Pujiang Program(No.23PJ1410800)National Natural Science Foundation of China(82072260,32370168)Eastern Talent Plan Leading Project,Shanghai Hospital Development Center Foundation(SHDC12022121)Shanghai 2020“Science and Technology Innovation Action Plan”Medical Innovation Research Special(20Z11900900)Three-year Action Plan(2023-2025)Key Discipline Program on Public Health System Construction of Shanghai(GWVI-11.1-15)Construction of the Major Infectious Disease Medical Treatment System(GWVI-2.2).
文摘Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompromised patients,particularly people with HIV(PWH).Whether PWH are more vulnerable to COVID with more adverse outcomes has been extensively studied,but the findings are inconsistent.Many cohort studies and meta-analyses support that PWH have a higher risk of SARSCoV-2 infection and more severe COVID-19 outcomes(Bertagnolio et al.,2022;Ssentongo et al.,2021).
文摘Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas,making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells.However,little is known about the mechanisms underlying the glioma-induced tropism of stem cells.Soluble factors including chemokines or growth factors released and expressed by glioma cells at least mediate the tropism of stem cells for gliomas.Here we review the possible mechanisms of stem cells tropism for malignant gliomas.
文摘AIM： To investigate the selective tropism of liver stem cells to hepatocellular carcinoma （HCC） in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS： WB-F344, a kind of rat liver stem cell, was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein （EGFP）. An animal model of HCC in Wistar rats was established by implanting HCC cells （CBRH7919） combined with an immunosuppressive drug. EGFP labeled liver stern cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells. Furthermore, hepatic stern cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stern cells within the tumor tissue were observed and analyzed.RESULTS： Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line, named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo. According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration, localization, and proliferation of the hepatic stem cells within the tumor tissue.CONCLUSION： Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted gene therapy of HCC.
基金Supported by the National Basic Research Program of China(973 Program)Study on the Medicinal Properties of Xuanxie Lishui Traditional Chinese Medicine(No.2013CB531802)
文摘OBJECTIVE: To study the meridian tropism(MT) for three Chinese medicines: Tinglizi(Semen Lepidii Apetali, TLZ), Yiyiren(Semen Coicis, YYR), Cheqianzi(Semen Plantaginis, CQZ) in vivo experiments.METHODS: The extracts of TLZ,YYR, CQZ were orally administered to rats at a dose 234, 700 and 350 mg/kg, respectively. The urinary excretion rate, loss in weight of rats and the electrolyte levels in the plasma were measured, in order to assess the mechanisms of the three traditional Chinese diuretic medicines.RESULTS: TLZ, YYR and CQZ exhibited obvious diuretic effect and reduced the weight of saline-loaded animals. All the three diuretic medicines differentially reduced various serum, urinary, lung, stomach, kidney and hormonal markers, thus indicating the different mechanisms of action and a close resemblance with their different meridian as per the MT theory.CONCLUSION: Our findings suggest that the three Traditional Chinese Medicine(TCM) medicines-TLZ,YYR and CQZ-possess different Shamisen meridian.This can support the regimen of treating the same disease with different therapies in TCM theory.
基金prepared from Yousef Dadimoghaddam's MScthesis and supported by grant(no.90-31) from Deputy of Research,Mazandaran University of Medical Sciences.Sari,IranThe spousor or Junding organization had norole in the design or conduct of this research
文摘Objective:To evaluate parasite distribution and tissue tropism of Toxoplasma gondii tachyzoites in experimentally infected mice using real time QPCR.Methods:In this survey 16 Balb/c mice were inoculated with 1×10~4 alive tachyzoites of Toxoplasma gondii RH strain.After 1,2,3 days post infection and the last day(before death),different tissues of mice including blood,brain,eye,liver,spleen,kidney,heart and muscle were harvested.Following tissues DNA extraction,the parasite burden was quantified using real time QPCR targeting the B1 gene(451 bp).Results:It showed that Toxoplasma after intraperitoneal injection was able to movement to various tissues in24 hours.Parasite burden was high in all tissues but the most number of parasites were observed in kidney,heart and liver,respectively.Conclusions:These data provide significant baseline information about Toxoplasma pathogenesis,vaccine monitoring and drug efficiency.
基金Under the auspices of Sino-British Fellowship Trust by British Academy (No.SG-47266)National Natural Science Foundation of China (No.49571031)Foundation of China Scholarship Council (No.2008619067)
文摘People′s environmental tropism has an effect on their understanding of tourism-nature relationship,and also influences their attitudes to natural resources utilization and environmental protection.Taking Jiuzhaigou National Park of China as a study case,the authors conducted some quantitative analyses with the tools of SPSS 16.0 and LISREL 8.7,to explore the influence of tourists′ environmental tropism on their attitudes to tourism and nature conservation in the natural tourist destination.Three hypotheses and the theoretic model of influences of tourists′ environmental tropism on their attitudes to tourism and nature conservation have been tested and accepted based on the Structural Equation Model analysis on survey data collected in Jiuzhaigou National Park of China.Some conclusions were drawn as follows: 1) tourists′ human-prioritized concept influences their cognition to tourism-nature relationship.This concept has a positive influence on their supportive attitudes to tourism,but a negative influence on their attitudes to nature conservation;2) tourists′ human-nature coordination concept has a positive influence on their supportive attitudes to both tourism and nature conservation,especially to the latter.This paper generally proves that human′s environmental tropism does have an influence on their attitudes to tourism and nature conservation in natural tourist destinations.
基金Supported by National Natural Sciences Foundation(No. 81173571)National Basic Research Program of China (No.2007CB512607)
文摘OBJECTIVE:To investigate whether Fuzi(Radix Aconiti Praeparata) has fewer "hot" characteristics when administered without Ganjiang(Rhizoma Zingiberis).METHODS:Differences in the thermotropism behaviors of mice treated either with Fuzi(Radix Aconiti Praeparata),Ganjiang(Rhizoma Zingiberis) or the combination of the two given intragastrically were investigated using the Animal Thermotropism Behavior Surveillance System.The water intake volume,oxygen consumption volume,adenosine triphosphatase(ATPase) activity,total antioxidant capacity(T-AOC) and total superoxide dismutase(T-SOD) activity were determined during the investigation.RESULTS:When Fuzi and Ganjiang were administered together,the rate at which mice remained on a warm plate("remaining rate") and the times and distances of their movement were all significantly reduced(P<0.05).Compared with the Normal group,the reduction was 55.1%,48.3% and 44.8%,while compared with the Fuzi group,the reduction was 57.6%,34.3% and 36.0%,indicating that "cold" tropism was significantly increased.Compared with the Normal and Fuzi groups,the ATPase activity and the respiratory oxygen consumption volume of the Fuzi + Ganjiang group were significantly increased(P<0.05),suggesting an improvement in energy metabolism and showing a "hot" characteristic when Fuzi and Ganjiang are present together.Additionally,the T-AOC and T-SOD activity were significantly enhanced(P<0.05).CONCLUSION:The behavior of mice tending toward "cold" tropism can be regarded as a quantitative reflection of Fuzi having fewer characteristics consistent w ith a "hot" nature when not used with Ganjiang,the functional mechanism of which may be a change in the ATPase activity in liver tissue.
文摘Natural clays have been used by man in infections of bacterial etiology, since the first historical registers. Our attention turned to a red-colored clay, known in the northeast of Brazil as “barro de louça” (dish clay). These clays and other natural earth materials seem interesting to us, as the blockage of the liberation of toxins or inactivation, may be related to the interruption of infection cycles in the skin and mucous membranes. The adsorptive and absorptive properties of the mineral clays are well documented in the cure process of skin and gastrointestinal diseases. Susceptibility and bacterial tropism tests were carried out. The results were analyzed and interpreted according to the conventional microbiological protocol. The bacterial strains, Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa, did not present a susceptibility profile to an isotonic solution of clay, but there was an increase of the bacterial tropism as the concentration of the isotonic solution was increased, being the minimal observed concentration of 100 mg/mL. Our aim is to document a type of red clay from the northeast of Brazil with possible attraction properties (Tropism) to bacteria and their toxins.
基金funded by Science Fund for Creative Research Groups of the National Natural Science Foundation of China(82221004),the National Natural Science Foundation(81930063)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-038)and Changping Laboratory research fund.
文摘The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has significantly burdened global public health.However,the tropism of SARS-CoV-2 within the human body remains not fully understood.In this review,we overview the literature on SARS-CoV-2 infection across various human organs and tissues.We summarize the relevant specimen types,techniques for examining SARS-CoV-2 tropism,and findings at both organ/tissue and cellular levels.To systematically evaluate the evidence supporting SARS-CoV-2 tissue tropism,we establish a hierarchical classification system based on two key criteria:(1)specimen origin and(2)detection methodology.Clinical specimens obtained directly from COvID-19 patients provide the most definitive evidence,whereas organoid-derived specimens and animal models indicate potential infectivity under artificial conditions.In terms of detection methods,we prioritize viral particle identification over viral protein or RNA detection,as the latter requires further confirmation to establish productive infection.Our findings indicate that SARS-CoV-2 potentially targets multiple human organ systems,including the respiratory tract,lungs,kidneys,heart,blood vessels,pancreas,small intestine,liver,and salivary glands.By contrast,viral tropism for the central nervous system and the reproductive system remains uncertain and requires further validation.At the cellular level,we identify specific target cell types vulnerable to infection,including ciliated epithelial cells,alveolar type II pneumocytes,enterocytes,cardiomyocytes,vascular endothelial cells,renal tubular epithelial cells,and pancreatic acinar cells.Furthermore,we analyze the correlation between angiotensin-converting enzyme 2 receptor distribution patterns and viral tropism,as well as potential variations in tissue specificity among different viral variants.We expect this review to provide a comprehensive landscape of SARS-CoV-2 tropism and enhance our understanding of the life cycle and consequences of SARS-CoV-2 infection within the human body.
基金This work was supported by grants from National Natural Science Foundation of China(Grant Nos.82070002,82072329,81872511,and 81670093)Frontier Research Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)(2018GZR110105005)+6 种基金National Science and Technology Major Project(2018ZX10301101)the Natural Science Foundation of Guangdong Province(2018A030313455)the Program of Department of Science and Technology of Guangdong Province(2014B020212018)National Key Research and Development Project(2018YFA0507201)the special project for COVID-19 of Guangzhou Regenerative Medicine and Health Guangdong Labo・ratory(2020GZR110106006)the emergency grants for prevention and control of SARS-CoV-2 of Guangdong province(2020B111108001)National Postdoctoral Program for Innovative Talent(BX20190089).
文摘The coronavirus disease 2019(COVID-19)pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is spread primary via respiratory droplets and infects the lungs.Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines(transformed or cancer cells)and species differences between animals and humans.Organoids are stem cell-derived selforganized three-dimensional culture in vitro and model the physiological conditions of natural organs.Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells(hESCs)-derived lung organoids,including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs.The infected ceils were ciliated,club,and alveolar type 2(AT2)cells,which were sequentially located from the proximal to the distal airway and terminal alveoli,respectively.Additionally,RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes,especially lipid metabolism,in addition to the well-known upregulation of immune response.Further,Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids.Therefore,human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
基金Supported by the National Key Basic Research and Development Program of China(Grant Nos 2007CB512607 and 2006CB504703)the National Science Fund for Distinguished Young Scholars(Grant No 30625042)
文摘The description and differentiation of the so-called"Cold"and"Hot"natures,the primary"Drug Naure"of Chinese medicine,is the focus of theoretical research.In this study,the divergency between the"Cold"and the"Hot"natures was investigated through examining the temperature tropism of mice affected by Coptis chinensis Franch and its processed materials by using a cold/hot plate differentiating technology.After exposure to C.chinensis Franch,the macroscopic behavioral index of the remaining rate(RR)on a warm pad(40℃)significantly increased(P<0.05),suggesting the enhancement of Hot tropism.The internal indexes of adenosine triphosphatase(ATPase)activity and oxygen consuming volume decreased significantly(P<0.05),suggesting the decapability of energy metabolism.This external behavior of Hot tropism might reflect the internal Cold nature of C.chinensis Franch.However,the processed materials of C.chinensis Franch exhibited a different Cold nature in temperature tropism compared with crude C.chinensis Franch(CC):the Cold nature of bile-processed C.chinensis Franch(BC)enhanced while the ginger-processed C.chinensis Franch(GC)changed inversely.The changing sequence was consistent with the theoretical prognostication.It is indicated that the external Cold&Hot natures of Chinese medicine may possibly reflect in an ethological way for the changes of animal’s temperature tropism which might be internally regulated by the body’s energy metabolism.
基金supported by the National Natural Science Foundation of China (Grant No. 30600352)the "Top-notch Personnel" Project of Ji-angsu University, the National Basic Research Program of China (Grant No. 2006CB504200)the Open Research Fund Program of the State Key Laboratory of Virology of China (Grant No. 2009008)
文摘HIV-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIV-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIV-1 subtypes B and C. The results showed that R5 and X4 variants experienced differential evolutionary patterns and different HIV-1 genes encountered various positive selection pressures, suggesting that complex selection pressures are driving HIV-1 evolution. Compared with other hypervariable regions of Gp120, significantly more positively selected sites were detected in the V3 region of subtype B X4 variants, V2 region of subtype B R5 variants, and V1 and V4 regions of subtype C X4 variants, indicating an association of positive selection with co-receptor recognition/binding. Intriguingly, a significantly higher proportion (33.3% and 55.6%, P【0.05) of positively selected sites were identified in the C3 region than other conserved regions of Gp120 in all the analyzed HIV-1 variants, indicating that the C3 region might be more important to HIV-1 adaptation than previously thought. Approximately half of the positively selected sites identified in the env gene were identical between R5 and X4 variants. There were three common positively selected sites (96, 113 and 281) identified in Gp41 of all X4 and R5 variants from subtypes B and C. These sites might not only suggest a functional importance in viral survival and adaptation, but also imply a potential cross-immunogenicity between HIV-1 R5 and X4 variants, which has important implications for AIDS vaccine development.
文摘It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/glycolipids containing sialic acids inα2,6-linkage;while avian and equine influenza viruses preferentially bind to those containing sialic acids inα2,3-linkage.Even though this generalized view is accurate for H3 subtype isolates,it may not be accurate and absolute for all subtypes of influenza A viruses and,therefore,needs to be reevaluated carefully and realistically.Some of the studies published in major scientific journals on the subject of tissue tropism of influenza viruses are inconsistent and caused confusion in the scientific community.One of the reasons for the inconsistency is that most studies were quantitative descriptions of sialic acid receptor distributions based on lectin or influenza virus immunohistochemistry results with limited numbers of stained cells.In addition,recent studies indicate thatα2,3-andα2,6-linked sialic acids are not the sole receptors determining tissue and host tropism of influenza viruses.In fact,determinants for tissue and host tropism of human,avian and animal influenza viruses are more complex than what has been generally accepted.Other factors,such as glycan topology,concentration of invading viruses,local density of receptors,lipid raft microdomains,coreceptors or sialic acid-independent receptors,may also be important.To more efficiently control the global spread of pandemic influenza such as the current circulating influenza A H1N1,it is crucial to clarify the determinants for tissue and host tropism of influenza viruses through quantitative analysis of experimental results.In this review,I will comment on some conflicting issues related to tissue and host tropism of influenza viruses,discuss the importance of quantitative analysis of lectin and influenza virus immunohistochemistry results and point out directions for future studies in this area,which should lead to a better understanding of tissue and host tropism of influenza viruses.
基金This study is supported by the National Basic Research Program(Grant No.2009CB522707)the Science Fund for Distinguished Young Scholars of Wuhan City(Grant No.D201050231081)the Project of Hubei Provincial Department of Education(Grant No.Q20101081).
文摘Channel tropism is investigated and developed through long-term clinical practice.In recent years,the development of channel tropism theory has attracted increasing attention.This study analyzed channel tropism theory and the problems associated with it.Results showed that this theory and systems biology have a similar holistic viewpoint.Systems biology could provide novel insights and platform in the study of channel tropism.Some problems in channel tropism theory,including pharmacology and action mechanism,were investigated.
基金Natural Science Foundation of Huaihai Institute of Technology (2010HS09, KX10051)
文摘Objective To observe the meridian tropism of Polygoni Avicularis Herba by tissue distribution of avicularin in rats. Methods Tissue distribution of avicularin in rat following a single iv administration was appointed and observed. HPLC method was established and validated for the determination of avicularin in rat tissues. Results Kidney and bladder were the most important target tissue of avicularin. Conclusion HPLC method is successfully applied to tissues distribution study of avicularin after iv administration to rats, and the results explain Polygoni Avicularis Herba on bladder tropism reasonably.
基金Supported by the National Natural Science Foundation of China(Nos.81102683,30973813 and 81173369)the Doctoral Fund of the Ministry of Education of China(Nos.20110001120055 and 20120001110105)the Natural Science Foundation of Beijing City(No.7132210)
文摘Objective： To investigate the relationship between tissue distributions of modified Wuzi Yanzong prescription（加味五子衍宗方, MWP） in rats and meridian tropism theory. Methods： A high-performance liquid chromatography with Fourier transform-mass spectrometry（HPLC-FT） method was used to identify the metabolites of MWP in different tissues of rats after continued oral administration of MWP for 7 days. The relationship between MWP and meridian tropism theory was studied according to the tissue distributions of the metabolites of MWP in rats and the relevant literature. Results： Nineteen metabolites, mainly flavanoid compounds, were detected in the different rat tissues and classified to each herb in MWP. Further, it was able to establish that the tissue distributions of the metabolites of MWP were consistent with the descriptions of meridian tropism of MWP available in literature, this result might be useful in clarifying the mechanism of MWP on meridian tropism. In the long run, these data might provide scientific evidence of the meridian tropism theory to further promote the reasonable, effective utilization, and modernization of Chinese medicine. Conclusion： The tissue distributions of MWP in vivo were consistent with the descriptions of meridian tropism of MWP.
