BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylatio...BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed.AIM To elucidate the autophagy-related genes of m6A with a diagnostic value for UC.METHODS The correlation between m6A-related genes and autophagy-related genes(ARGs)was analyzed.Finally,gene set enrichment analysis(GSEA)was performed on the characteristic genes.Additionally,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in mice.RESULTS GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor kappa-B.Furthermore,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group.CONCLUSION This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC.展开更多
Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the g...Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the growth and migration of cancers.However,the mechanisms and targets mediating M2 macrophage infiltration in pancreatic cancer remain elusive.Methods:The M2 macrophage infiltration score of patients was assessed using the xCell algorithm.Using weighted gene co-expression network analysis(WGCNA),module genes associated with M2 macrophages were identified,and a predictive model was designed.The variations in immunological cell patterns,cancer mutations,and enrichment pathways between the cohorts with the high-and low-risk were examined.Additionally,the expression of FCGR3A and RNASE2,as well as their association with M2 macrophages were evaluated using the HPA,TNMplot,and GEPIA2 databases and verified by tissue immunofluorescence staining.Moreover,in vitro cell experiments were conducted,where FCGR3A was knocked down in pancreatic cancer cells using siRNA to analyze its effects on M2 macrophage infiltration,tumor proliferation,and metastasis.Results:The prognosis of patients in high-risk and low-risk groups was successfully distinguished using a prognostic risk score model of M2 macrophage-related genes(p=0.024).Between the high-and low-risk cohorts,there have been notable variations in immune cell infiltration patterns,tumor mutations,and biological functions.The risk score was linked to the manifestation of prevalent immunological checkpoints,immunological scores,and stroma values(all p<0.05).In vitro experiments and tissue immunofluorescence staining revealed that FCGR3A can promote the infiltration or polarization of M2 macrophages and enhance tumor proliferation and migration.Conclusions:In this study,an M2 macrophage-related pancreatic cancer risk score model was established,and found that FCGR3A was correlated with tumor formation,metastasis,and M2 macrophage infiltration.展开更多
Myzus persicae(M.persicae)is now considered a threat to agricultural crops due to economic losses.Numerous synthetic insecticides applied every year against M.persicae,are reported to be unsafe for environment,humans,...Myzus persicae(M.persicae)is now considered a threat to agricultural crops due to economic losses.Numerous synthetic insecticides applied every year against M.persicae,are reported to be unsafe for environment,humans,and beneficial insects.Furthermore,several species of Myzus have been found to develop resistance due to over application of these insecticides.Therefore,it is required to find some novel insecticide that would be safe for the environment as well as for humans.In the current study,two major pure constituentsα-pinene andβ-caryophyllene were evaluated for their insecticidal potential against M.persicae using a fumigant toxicity assay.Furthermore,impact ofα-pinene andβ-caryophyllene on expression of five different genes,e.g.,HSP 60,FPPS I,OSD,TOL and ANT responsible for reproduction,dispersion,and growth of M.persicae has also been investigated.To perform fumigant toxicity assay,five different concentrations(3.5,4,4.5,5 and 6μL L−1)ofα-pinene andβ-caryophyllene were prepared.Lethal concentration(LC)was calculated,and gene expression studies were executed through qRT PCR at LC30 ofα-pinene andβ-caryophyllene.Both constituents demonstrated excellent fumigant toxicity effects against M.persicae at all five concentrations.However,α-pinene shows significantly better results(98%)as compared toβ-caryophyllene(80%)after 72 h at 6μL L−1 of dose.The highest upregulation in expression was demonstrated at LC30 dose ofα-pinene in five in three out of five genes understudy(TOL,ANT,and FPPS I).Conversely,two genes HSP 60 and OSD demonstrated downregulation at LC30 dose ofβ-caryophyllene.Conclusively,our results highlighted the promising insecticidal potential of both compoundsα-pinene andβ-caryophylleneby interfering with the reproduction and development related processes in M.persicae,allowing us to recommend the phytoconstituents under investigation as an ecofriendly alternative to synthetic insecticides.展开更多
Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guine...Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guinea pigs were used, of which: 12 were surgically inoculated with Ad-Hath1-EGFP in the bony groove of round window niche, and 8 with artificial perilymph. Auditory brainstem response(ABR) thresholds were determined in all animals before and 5 days after surgery. On post-surgery day 5 and day 14, animals were sacrificed and whole mounts of cochlea and frozen sections were examined. Results ABR tests showed no significant change of hearing after the surgery. Strong fluorescence staining in the cochleae was seen in Ad-Hath1-EGFP groups. The highest levels of gene expression were seen in the post-surgery day 5 group with little decrease on post-surgery day 14.The contralateral cochlea and those in the control groups were free of fluorescence staining. Conclusion The transgenic Hath1-EGFP can be effectively delivered into the inner ear through intact RWM, in an atraumatic manner.展开更多
BACKGROUND: The development of a harmless and effi- cient nonviral gene delivery system that can facilitate the penetration of nucleic acids through the plasma membrane is a key to successful gene therapy. The aim of ...BACKGROUND: The development of a harmless and effi- cient nonviral gene delivery system that can facilitate the penetration of nucleic acids through the plasma membrane is a key to successful gene therapy. The aim of this study was to test a nonviral gene transferring vector's function of delivering DNA into liver cells to provide an important clue for gene transfer in liver gene therapy. METHODS: The complex of DNA and DNA delivering protein was injected into mice through their tail veins. Then the mice were killed and their liver tissue was sec- tioned. The gene transferring results were detected using a confocal laser scanning microscope. RESULTS: Fluorescence analysis indicated that both DNA- membrane penetrating peptide (MPP) complex and DNA- hepatocyte specific receptor binding domain ( HSRBD) - MPP complex could go into liver cells. The fluorescence value of liver cells in the DNA-HSRBD-MPP group was higher than that in the DNA-MPP group. CONCLUSIONS; MPP can successfully deliver DNA and protein into cells, and MPP with a HSRBD can specifically deliver DNA into liver cells. These have laid a foundation for further study on the nonviral liver cell gene delivering system.展开更多
Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles ...Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles of Michigan Cancer Foundation-7(MCF-7)cells treated with or without 4 cholic acid derivatives were detected by gene chip technology.Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map(CMap)database.The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking.The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database,and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231(MDA-MB-231)cells.Results:Compared with the reference genome in the CMap database,the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic,anticancer,anti-inflammatory,and antiinfective drugs.Among them,4 derivatives were associated with antianxiety drugs,and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gammaaminobutyric acid(GABA)receptors.Moreover,the cytoskeletal pathway is one of the pathways enriched in the derivatives.Of them,ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.Conclusion:The gene expression detection method,combined with CMap and pathway enrichment analysis,could be used to study the mechanism of the active ingredients of TCM.In addition,our research showed that cholic acid derivatives have a potential affinity for membrane receptors,where they can exert anxiolytic activity by modulating opioid receptor,GABA receptor,and dopamine receptor.Moreover,ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation,probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.展开更多
BACKGROUND Danon disease(DD),in which mutations in the X-linked lysosome-associated membrane protein-2(LAMP-2)gene result in hypertrophic cardiomyopathy,is a rare disease,reported primarily in small samples or cases.H...BACKGROUND Danon disease(DD),in which mutations in the X-linked lysosome-associated membrane protein-2(LAMP-2)gene result in hypertrophic cardiomyopathy,is a rare disease,reported primarily in small samples or cases.However,with the development of cardiac magnetic resonance imaging and genetic technology in recent years,the number of reports has increased.CASE SUMMARY We report a case of DD in an adolescent male patient,confirmed by genetic testing.The patient was admitted to our hospital with complaints of a three-year history of chest tightness and shortness of breath.His preliminary clinical diagnosis is hypertrophic cardiomyopathy.Our report includes the patient’s clinical course from hospital admission to death,step-by-step diagnosis,treatment course,and noninvasive imaging features.We highlight how a noninvasive diagnostic approach,based solely on clinical and imaging“red flags”for DD,can be used to achieve a diagnosis of DD with a high degree of confidence.CONCLUSION DD is a very dangerous cardiomyopathy,and it is necessary to achieve early diagnosis and treatment.展开更多
Pathophysiological explanations for metamorphopsia associated with retinal pathologies generally focus on photoreceptor organization disruption. However, the retinal microarchitecture is complicated, and we hypothesiz...Pathophysiological explanations for metamorphopsia associated with retinal pathologies generally focus on photoreceptor organization disruption. However, the retinal microarchitecture is complicated, and we hypothesize that other retinal cells may also be involved. Metamorphopsia has been widely studied in eyes with epiretinal membranes and we revisit the idea that Müller cell displacement causes retinal macropsia. A Pub Med query and related article search for the macula ultrastructure under normal and pathological conditions revealed an enormous amount of information, particularly ultrahigh definition optical coherence tomography and other retinal imaging modality studies. Findings of these imaging studies support our hypothesis that Müller cells, and not cone photoreceptors, are primarily responsible for macropsia in eyes with epiretinal membranes. More specifically, we conclude that displacement of Müller cell endfeet, and not photoreceptor cones, is a more likely the explanation for retinal macropsia associated with epiretinal membranes.展开更多
AIM: To document with spectral-domain optical coherence tomography the morphological regeneration of the fovea after resolution of cystoid macular edema(CME) without and with internal limiting membrane(ILM) detachment...AIM: To document with spectral-domain optical coherence tomography the morphological regeneration of the fovea after resolution of cystoid macular edema(CME) without and with internal limiting membrane(ILM) detachment and to discuss the presumed role of the glial scaffold for foveal structure stabilization. METHODS: A retrospective case series of 38 eyes of 35 patients is described. Of these, 17 eyes of 16 patients displayed foveal regeneration after resolution of CME, and 6 eyes of 6 patients displayed CME with ILM detachment. Eleven eyes of 9 patients displayed other kinds of foveal and retinal disorders associated with ILM detachment. RESULTS: The pattern of edematous cyst distribution, with or without a large cyst in the foveola and preferred location of cysts in the inner nuclear layer or Henle fiber layer(HFL), may vary between different eyes with CME or in one eye during different CME episodes. Large cysts in the foveola may be associated with a tractional elevation of the inner foveal layers and the formation of a foveoschisis in the HFL. Edematous cysts are usually not formed in the ganglion cell layer. Eyes with CME and ILM detachment display a schisis between the detached ILM and nerve fiber layer(NFL) which is traversed by Müller cell trunks. ILM detachment was also found in single eyes with myopic traction maculopathy, macular pucker, full-thickness macular holes, outer lamellar holes, and glaucomatous parapapillary retinoschisis, and in 3 eyes with Müller cell sheen dystrophy(MCSD). As observed in eyes with MCSD, cellophane maculopathy, and macular pucker, respectively, fundus light reflections can be caused by different highly reflective membranes or layers: the thickened and tightened ILM which may or may not be detached from the NFL, the NFL, or idiopathic epiretinal membranes. In eyes with short single or multiple CME episodes, the central fovea regenerated either completely, which included the disappearance of irregularities of the photoreceptor layer lines and the reformation of a fovea externa, or with remaining irregularities of the photoreceptor layer lines. CONCLUSION: The examples of a complete regeneration of the foveal morphology after transient CME show that the fovea may withstand even large tractional deformations and has a conspicuous capacity of structural regeneration as long as no cell degeneration occurs. It is suggested that the regenerative capacity depends on the integrity of the threedimensional glial scaffold for foveal structure stabilization composed of Müller cell and astrocyte processes. The glial scaffold may also maintain the retinal structure after loss of most retinal neurons as in late-stage MCSD.展开更多
With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluo-rescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyn...With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluo-rescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyngeal carcinoma (NPC) patients and 315 controls (normal and patients with other tumors). MA-IgA antibody was positive in 96.8% of the pretreatment NPC patients with a GMT of 1:36.3. MA-IgA detection by this method was more sensitive than EA-IgA detection by IE. In contrast, patients with tumors other than NPC were negative for MA-IgA antibody. 9.1% of VCA-IgA positive persons were MA-IgA positive with a GMT of less than 1:5. No MA-IgA positive was found in VCA-IgA negatives. The results indicated that this method was relatively specific. In the treatment group, the positive rate and GMT of MA-IgA antibody declined with increase in survival time and the decline was faster than VCA-IgA. When recurrence or distant metastasis developed, similar to VCA-IgA and EA-IgA antibodies, the positive rate and GMT of MA-IgA antibody increased to its pretreatment level. Therefore, MA-IgA detection might be valuable in the early diagnosis and monitor of NPC.展开更多
为探究外膜蛋白A(outer membrane protein A,OmpA)对米尔伊丽莎白菌致病作用的影响,以蛙源米尔伊丽莎白菌FL160902为研究对象,通过同源重组法构建OmpA缺失株△ompA,比较缺失株和野生株的生长特性、生物膜形成能力、抗血清杀伤能力、对...为探究外膜蛋白A(outer membrane protein A,OmpA)对米尔伊丽莎白菌致病作用的影响,以蛙源米尔伊丽莎白菌FL160902为研究对象,通过同源重组法构建OmpA缺失株△ompA,比较缺失株和野生株的生长特性、生物膜形成能力、抗血清杀伤能力、对细胞的黏附能力以及对蛙的致病性差异。结果显示:△ompA的生长能力和抗血清杀伤能力与野生株无显著差异;但与野生株相比,△ompA的生物膜形成能力增加了66%,△ompA对bEnd.3细胞的黏附能力降低了61%;黑斑蛙感染试验显示,△ompA在黑斑蛙血液、脾和脑组织中的载菌量分别为(3.15×10^(8)±0.09×10^(8))、(2.11×10^(8)±0.07×10^(8))和(6.61×10^(8)±0.16×10^(8))copies/g,均显著低于野生株,且△ompA对黑斑蛙的致死率为37%,显著低于野生株的致死率(75%)。上述结果表明,ompA基因缺失不改变米尔伊丽莎白菌的抗血清杀伤能力,但增加了菌株的生物膜形成能力,减弱了菌株的黏附能力,从而降低了该菌对蛙的致病性。展开更多
文摘BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed.AIM To elucidate the autophagy-related genes of m6A with a diagnostic value for UC.METHODS The correlation between m6A-related genes and autophagy-related genes(ARGs)was analyzed.Finally,gene set enrichment analysis(GSEA)was performed on the characteristic genes.Additionally,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in mice.RESULTS GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor kappa-B.Furthermore,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group.CONCLUSION This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC.
文摘Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the growth and migration of cancers.However,the mechanisms and targets mediating M2 macrophage infiltration in pancreatic cancer remain elusive.Methods:The M2 macrophage infiltration score of patients was assessed using the xCell algorithm.Using weighted gene co-expression network analysis(WGCNA),module genes associated with M2 macrophages were identified,and a predictive model was designed.The variations in immunological cell patterns,cancer mutations,and enrichment pathways between the cohorts with the high-and low-risk were examined.Additionally,the expression of FCGR3A and RNASE2,as well as their association with M2 macrophages were evaluated using the HPA,TNMplot,and GEPIA2 databases and verified by tissue immunofluorescence staining.Moreover,in vitro cell experiments were conducted,where FCGR3A was knocked down in pancreatic cancer cells using siRNA to analyze its effects on M2 macrophage infiltration,tumor proliferation,and metastasis.Results:The prognosis of patients in high-risk and low-risk groups was successfully distinguished using a prognostic risk score model of M2 macrophage-related genes(p=0.024).Between the high-and low-risk cohorts,there have been notable variations in immune cell infiltration patterns,tumor mutations,and biological functions.The risk score was linked to the manifestation of prevalent immunological checkpoints,immunological scores,and stroma values(all p<0.05).In vitro experiments and tissue immunofluorescence staining revealed that FCGR3A can promote the infiltration or polarization of M2 macrophages and enhance tumor proliferation and migration.Conclusions:In this study,an M2 macrophage-related pancreatic cancer risk score model was established,and found that FCGR3A was correlated with tumor formation,metastasis,and M2 macrophage infiltration.
基金funded by the Researchers Supporting Project Number(RSP2023R123),King Saud University,Riyadh,Saudi Arabia.
文摘Myzus persicae(M.persicae)is now considered a threat to agricultural crops due to economic losses.Numerous synthetic insecticides applied every year against M.persicae,are reported to be unsafe for environment,humans,and beneficial insects.Furthermore,several species of Myzus have been found to develop resistance due to over application of these insecticides.Therefore,it is required to find some novel insecticide that would be safe for the environment as well as for humans.In the current study,two major pure constituentsα-pinene andβ-caryophyllene were evaluated for their insecticidal potential against M.persicae using a fumigant toxicity assay.Furthermore,impact ofα-pinene andβ-caryophyllene on expression of five different genes,e.g.,HSP 60,FPPS I,OSD,TOL and ANT responsible for reproduction,dispersion,and growth of M.persicae has also been investigated.To perform fumigant toxicity assay,five different concentrations(3.5,4,4.5,5 and 6μL L−1)ofα-pinene andβ-caryophyllene were prepared.Lethal concentration(LC)was calculated,and gene expression studies were executed through qRT PCR at LC30 ofα-pinene andβ-caryophyllene.Both constituents demonstrated excellent fumigant toxicity effects against M.persicae at all five concentrations.However,α-pinene shows significantly better results(98%)as compared toβ-caryophyllene(80%)after 72 h at 6μL L−1 of dose.The highest upregulation in expression was demonstrated at LC30 dose ofα-pinene in five in three out of five genes understudy(TOL,ANT,and FPPS I).Conversely,two genes HSP 60 and OSD demonstrated downregulation at LC30 dose ofβ-caryophyllene.Conclusively,our results highlighted the promising insecticidal potential of both compoundsα-pinene andβ-caryophylleneby interfering with the reproduction and development related processes in M.persicae,allowing us to recommend the phytoconstituents under investigation as an ecofriendly alternative to synthetic insecticides.
基金National NaturalScience Foundation grants No.30730040 and No.30628030.
文摘Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guinea pigs were used, of which: 12 were surgically inoculated with Ad-Hath1-EGFP in the bony groove of round window niche, and 8 with artificial perilymph. Auditory brainstem response(ABR) thresholds were determined in all animals before and 5 days after surgery. On post-surgery day 5 and day 14, animals were sacrificed and whole mounts of cochlea and frozen sections were examined. Results ABR tests showed no significant change of hearing after the surgery. Strong fluorescence staining in the cochleae was seen in Ad-Hath1-EGFP groups. The highest levels of gene expression were seen in the post-surgery day 5 group with little decrease on post-surgery day 14.The contralateral cochlea and those in the control groups were free of fluorescence staining. Conclusion The transgenic Hath1-EGFP can be effectively delivered into the inner ear through intact RWM, in an atraumatic manner.
基金This study was supported by grants from the National Natural Science Foun-dation of China( No:30472251 )and the Shanxi Youth Science Fund ( No.020011028).
文摘BACKGROUND: The development of a harmless and effi- cient nonviral gene delivery system that can facilitate the penetration of nucleic acids through the plasma membrane is a key to successful gene therapy. The aim of this study was to test a nonviral gene transferring vector's function of delivering DNA into liver cells to provide an important clue for gene transfer in liver gene therapy. METHODS: The complex of DNA and DNA delivering protein was injected into mice through their tail veins. Then the mice were killed and their liver tissue was sec- tioned. The gene transferring results were detected using a confocal laser scanning microscope. RESULTS: Fluorescence analysis indicated that both DNA- membrane penetrating peptide (MPP) complex and DNA- hepatocyte specific receptor binding domain ( HSRBD) - MPP complex could go into liver cells. The fluorescence value of liver cells in the DNA-HSRBD-MPP group was higher than that in the DNA-MPP group. CONCLUSIONS; MPP can successfully deliver DNA and protein into cells, and MPP with a HSRBD can specifically deliver DNA into liver cells. These have laid a foundation for further study on the nonviral liver cell gene delivering system.
基金supported by the National Natural Science Foundation of China(22067016).
文摘Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles of Michigan Cancer Foundation-7(MCF-7)cells treated with or without 4 cholic acid derivatives were detected by gene chip technology.Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map(CMap)database.The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking.The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database,and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231(MDA-MB-231)cells.Results:Compared with the reference genome in the CMap database,the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic,anticancer,anti-inflammatory,and antiinfective drugs.Among them,4 derivatives were associated with antianxiety drugs,and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gammaaminobutyric acid(GABA)receptors.Moreover,the cytoskeletal pathway is one of the pathways enriched in the derivatives.Of them,ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.Conclusion:The gene expression detection method,combined with CMap and pathway enrichment analysis,could be used to study the mechanism of the active ingredients of TCM.In addition,our research showed that cholic acid derivatives have a potential affinity for membrane receptors,where they can exert anxiolytic activity by modulating opioid receptor,GABA receptor,and dopamine receptor.Moreover,ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation,probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.
文摘BACKGROUND Danon disease(DD),in which mutations in the X-linked lysosome-associated membrane protein-2(LAMP-2)gene result in hypertrophic cardiomyopathy,is a rare disease,reported primarily in small samples or cases.However,with the development of cardiac magnetic resonance imaging and genetic technology in recent years,the number of reports has increased.CASE SUMMARY We report a case of DD in an adolescent male patient,confirmed by genetic testing.The patient was admitted to our hospital with complaints of a three-year history of chest tightness and shortness of breath.His preliminary clinical diagnosis is hypertrophic cardiomyopathy.Our report includes the patient’s clinical course from hospital admission to death,step-by-step diagnosis,treatment course,and noninvasive imaging features.We highlight how a noninvasive diagnostic approach,based solely on clinical and imaging“red flags”for DD,can be used to achieve a diagnosis of DD with a high degree of confidence.CONCLUSION DD is a very dangerous cardiomyopathy,and it is necessary to achieve early diagnosis and treatment.
文摘Pathophysiological explanations for metamorphopsia associated with retinal pathologies generally focus on photoreceptor organization disruption. However, the retinal microarchitecture is complicated, and we hypothesize that other retinal cells may also be involved. Metamorphopsia has been widely studied in eyes with epiretinal membranes and we revisit the idea that Müller cell displacement causes retinal macropsia. A Pub Med query and related article search for the macula ultrastructure under normal and pathological conditions revealed an enormous amount of information, particularly ultrahigh definition optical coherence tomography and other retinal imaging modality studies. Findings of these imaging studies support our hypothesis that Müller cells, and not cone photoreceptors, are primarily responsible for macropsia in eyes with epiretinal membranes. More specifically, we conclude that displacement of Müller cell endfeet, and not photoreceptor cones, is a more likely the explanation for retinal macropsia associated with epiretinal membranes.
文摘AIM: To document with spectral-domain optical coherence tomography the morphological regeneration of the fovea after resolution of cystoid macular edema(CME) without and with internal limiting membrane(ILM) detachment and to discuss the presumed role of the glial scaffold for foveal structure stabilization. METHODS: A retrospective case series of 38 eyes of 35 patients is described. Of these, 17 eyes of 16 patients displayed foveal regeneration after resolution of CME, and 6 eyes of 6 patients displayed CME with ILM detachment. Eleven eyes of 9 patients displayed other kinds of foveal and retinal disorders associated with ILM detachment. RESULTS: The pattern of edematous cyst distribution, with or without a large cyst in the foveola and preferred location of cysts in the inner nuclear layer or Henle fiber layer(HFL), may vary between different eyes with CME or in one eye during different CME episodes. Large cysts in the foveola may be associated with a tractional elevation of the inner foveal layers and the formation of a foveoschisis in the HFL. Edematous cysts are usually not formed in the ganglion cell layer. Eyes with CME and ILM detachment display a schisis between the detached ILM and nerve fiber layer(NFL) which is traversed by Müller cell trunks. ILM detachment was also found in single eyes with myopic traction maculopathy, macular pucker, full-thickness macular holes, outer lamellar holes, and glaucomatous parapapillary retinoschisis, and in 3 eyes with Müller cell sheen dystrophy(MCSD). As observed in eyes with MCSD, cellophane maculopathy, and macular pucker, respectively, fundus light reflections can be caused by different highly reflective membranes or layers: the thickened and tightened ILM which may or may not be detached from the NFL, the NFL, or idiopathic epiretinal membranes. In eyes with short single or multiple CME episodes, the central fovea regenerated either completely, which included the disappearance of irregularities of the photoreceptor layer lines and the reformation of a fovea externa, or with remaining irregularities of the photoreceptor layer lines. CONCLUSION: The examples of a complete regeneration of the foveal morphology after transient CME show that the fovea may withstand even large tractional deformations and has a conspicuous capacity of structural regeneration as long as no cell degeneration occurs. It is suggested that the regenerative capacity depends on the integrity of the threedimensional glial scaffold for foveal structure stabilization composed of Müller cell and astrocyte processes. The glial scaffold may also maintain the retinal structure after loss of most retinal neurons as in late-stage MCSD.
文摘With gene engineering EB virus membrane antigen as the diagnostic antigen, indirect immunofluo-rescence (IF) assay was used to detect IgA antibody against EB virus membrane antigen (MA-IgA) in sera from 202 nasopharyngeal carcinoma (NPC) patients and 315 controls (normal and patients with other tumors). MA-IgA antibody was positive in 96.8% of the pretreatment NPC patients with a GMT of 1:36.3. MA-IgA detection by this method was more sensitive than EA-IgA detection by IE. In contrast, patients with tumors other than NPC were negative for MA-IgA antibody. 9.1% of VCA-IgA positive persons were MA-IgA positive with a GMT of less than 1:5. No MA-IgA positive was found in VCA-IgA negatives. The results indicated that this method was relatively specific. In the treatment group, the positive rate and GMT of MA-IgA antibody declined with increase in survival time and the decline was faster than VCA-IgA. When recurrence or distant metastasis developed, similar to VCA-IgA and EA-IgA antibodies, the positive rate and GMT of MA-IgA antibody increased to its pretreatment level. Therefore, MA-IgA detection might be valuable in the early diagnosis and monitor of NPC.
文摘为探究外膜蛋白A(outer membrane protein A,OmpA)对米尔伊丽莎白菌致病作用的影响,以蛙源米尔伊丽莎白菌FL160902为研究对象,通过同源重组法构建OmpA缺失株△ompA,比较缺失株和野生株的生长特性、生物膜形成能力、抗血清杀伤能力、对细胞的黏附能力以及对蛙的致病性差异。结果显示:△ompA的生长能力和抗血清杀伤能力与野生株无显著差异;但与野生株相比,△ompA的生物膜形成能力增加了66%,△ompA对bEnd.3细胞的黏附能力降低了61%;黑斑蛙感染试验显示,△ompA在黑斑蛙血液、脾和脑组织中的载菌量分别为(3.15×10^(8)±0.09×10^(8))、(2.11×10^(8)±0.07×10^(8))和(6.61×10^(8)±0.16×10^(8))copies/g,均显著低于野生株,且△ompA对黑斑蛙的致死率为37%,显著低于野生株的致死率(75%)。上述结果表明,ompA基因缺失不改变米尔伊丽莎白菌的抗血清杀伤能力,但增加了菌株的生物膜形成能力,减弱了菌株的黏附能力,从而降低了该菌对蛙的致病性。
