To investigate the expression of vaginal Th1 and Th2 cytokines in rats with experimental vaginal candidiasis under different immune conditions, ICR murine vaginal candidiasis model was established and immno-suppressed...To investigate the expression of vaginal Th1 and Th2 cytokines in rats with experimental vaginal candidiasis under different immune conditions, ICR murine vaginal candidiasis model was established and immno-suppressed murine models of vaginal cadidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls. The mRNA level of Th1 （IL-2）/Th2 （IL-4, IL-10, TGF-β1） cytokines in murine vaginal tissues was determined by RT-PCR. The cykotine in local tissues was increased to different extent under normal immune condition. IL-2 mRNA was increased during early stage of infection, while IL-10 was increased transiently during late stage of infection. TGF-β1 production was found to be increased persistently. At same time, the expression of IL-2 mRNA was suppressed in immno-suppressed group, and the level of IL-4, IL-10, and TGF-β1 were higher than the normal immunity group to different degree during infection. The high level of IL-2 mRNA during early stage of infection was associated with clearance of mucosal Candidia albicans （C. albicans）, and its expression suppressed leading to decreased clearance of mucosal C. albican in immuno-suppression. The over-expression of IL-4 and IL-10 could significantly enhance the susceptibility to C. albicans infection in mice.展开更多
In order to investigate the expression of Th1 and Th2 cytokines in the vaginal candidiasis caused by Candida, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of ...In order to investigate the expression of Th1 and Th2 cytokines in the vaginal candidiasis caused by Candida, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animals were pretreated with estradiol. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-2, IL-4, IL-10 and TGF-β1 in the vagina in the mice of different groups at different time points after the beginning of the experiment. The average expression level of IL-2 mRNA in group D （estrogen-treated mice） was significantly higher than that in groups H （estrogen-untreated mice） and I （control group） on the day 2. The average expression level of IL-4 mRNA in group D was significantly higher than that in groups I and H on the day 5. The average expression level of IL-10 mRNA in group D was significantly higher than that in groups H and I from day 7 to 11. The average expression level of TGF-β1 mRNA in group D was significantly higher than that in groups H and I at all time points. It was concludes that the high-level expression of IL-2 mRNA during early infection was associated with clearance of mucosal C. albicans, and the high-level expression of IL-10 mRNA during late stage of the infection was related to susceptibility to infection. TGF-β1 may play a predominant role when the virtual absence of changes in other Th-type cytokines during infection.展开更多
AIM: To explore the role of CDX2 in the multi-drug resistance (MDR) process of gastric cancer in vitro and in vivo . METHODS: A cisplatin-resistant gastric cancer cell line with stable downregulation of CDX2 was estab...AIM: To explore the role of CDX2 in the multi-drug resistance (MDR) process of gastric cancer in vitro and in vivo . METHODS: A cisplatin-resistant gastric cancer cell line with stable downregulation of CDX2 was established. mRNA and protein expression levels of CDX2, survivin, cyclin D1, and c-Myc were detected by western blotting and semi-quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The influence of downregulation of CDX2 on MDR was assessed by measuring IC50 of SGC7901/DDP cells to cisplatin, doxorubicin, and 5-fluorouracil, rate of doxorubicin efflux, apoptosis, and cell cycle progression detected by flow cytometry. In addition, we determined the in vivo effects of CDX2 small interfering RNA (siRNA) on tumor size, and apoptotic cells in tumor tissues were detected by deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and hematoxylin and eosin staining. RESULTS: CDX2 siRNA led to downregulation of endogenous CDX2 mRNA (0.31 ± 0.05 vs 1.10 ± 0.51, 0.31 ± 0.05 vs 1.05 ± 0.21, P = 0.003) and protein (0.12 ± 0.08 vs 0.51 ± 0.07, 0.12 ± 0.08 vs 0.55 ± 0.16, P = 2.57 × 10 -4) expression. It significantly promoted the sensitivity of SGC7901/DDP cells to cisplatin (0.12 ± 0.05 vs 0.33 ± 0.08, 0.12 ± 0.05 vs 0.39 ± 0.15, P = 0.001), doxorubicin (0.52 ± 0.13 vs 4.11 ± 1.25, 0.52 ± 0.13 vs 4.05 ± 1.44, P = 2.81 × 10-4), and 5-fluorouracil (0.82 ± 0.13 vs 2.81 ± 0.51, 0.82 ± 0.13 vs 3.28 ± 1.03, P = 1.71 × 10-4). Flow cytometry confirmed that the percentage of apoptotic cells increased after CDX2 downregulation (32.15% ± 2.15% vs 17.63% ± 3.16%, 32.15% ± 2.15% vs 19.3% ± 2.25%, P = 1.73 × 10-6). This notion was further supported by the observation that downregulation of CDX2 blocked entry into the S-phase of the cell cycle (31.53% ± 3.78% vs 65.05% ± 7.25%, 31.53% ± 3.78% vs 62.27% ± 5.02%, P = 7.55 × 10-7). Furthermore, downregulation of CDX2 significantly increased intracellular accumulation of doxorubicin (0.21 ± 0.06 vs 0.41 ± 0.11, 0.21 ± 0.06 vs 0.40 ± 0.08, P = 0.003). In molecular studies, semiquantitative RT-PCR and western blotting revealed that CDX2 downregulation could inhibit expression of c-Myc, survivin and cyclin D1. CONCLUSION: CDX2 may be involved in regulating multiple signaling pathways in reversing MDR, suggesting that CDX2 may represent a novel target for gastric cancer therapy.展开更多
In allergies, an unbalanced immune response towards a T helper (Th) 2 profile with high levels of Immunoglobulin (Ig) E is produced. We have demonstrated that the pre-administration of Enterococcus faecalis CECT7121 p...In allergies, an unbalanced immune response towards a T helper (Th) 2 profile with high levels of Immunoglobulin (Ig) E is produced. We have demonstrated that the pre-administration of Enterococcus faecalis CECT7121 prevents the development of allergy in ovalbumin-immunized mice. In this work, we evaluated whether this bacterium can also revert an established allergic status. Mice were immunized with ovalbumin (OVA) and after that, were inoculated with an E. faecalis CECT7121 suspension. In immunized animals, serum specific immune response, proliferative activity of memory splenocytes, and levels of Th2 cytokines were assessed. The in vivo active cutaneous anaphylaxis test was also performed. The treatment with E. faecalis CECT7121 only increased anti-OVA IgG2a levels. No differences were observed in other specific immunological parameters. Probiotic-treatment did not prove to have any desensitizing effect on mice. These results, together with those recently published, can be concluded that this bacterium would not be appropriate for the treatment of allergic symptoms.展开更多
The pandemic of coronavirus disease 2019(COVID-19),a respiratory disease caused by a novel severe acute respiratory syndrome coronavirus-2,is causing substantial morbidity and mortality.Along with the respiratory symp...The pandemic of coronavirus disease 2019(COVID-19),a respiratory disease caused by a novel severe acute respiratory syndrome coronavirus-2,is causing substantial morbidity and mortality.Along with the respiratory symptoms,underlying diseases in senior patients,such as diabetes,hypertension,and coronary heart disease,are the most common comorbidities,which cause more severe outcomes and even death.During cellular attachment and entry of severe acute respiratory syndrome coronavirus-2,the key protein involved is the angiotensin I converting enzyme 2(ACE2),which is located on the membrane of host cells.Here,we aim to curate an expression profile of Ace2 and other COVID-19 related genes across the available diabetes murine strains.Based on strictly manual curation and bioinformatics analysis of the publicly deposited expression datasets,Ace2 and other potentially involved genes such as Furin,Tmprss2,Ang,and Ang2 were examined.We found that Ace2 expression is rather ubiquitous in three selected diabetes prone strains(db/db,ob/ob and diet-induced obese).With the most abundant datasets present,the liver shows a medium Ace2 expression level compared with the lungs,pancreatic islets,brain and even T cells.Age is a more critical factor for Ace2 expression in db/db compared with the other two strains.Besides Ace2,the other four host genes showed varied levels of correlation to each other.To accelerate research on the interaction between COVID-19 and underlying diseases,the Murine4Covid transcriptomics database(www.geneureka.org/Murine4Covid)will facilitate the design of research on COVID-19 and comorbidities.展开更多
基金the Science Research Foundation of Health Department of Hubei Prov-ince (No. JXIB048)Janssen Research Foundation
文摘To investigate the expression of vaginal Th1 and Th2 cytokines in rats with experimental vaginal candidiasis under different immune conditions, ICR murine vaginal candidiasis model was established and immno-suppressed murine models of vaginal cadidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls. The mRNA level of Th1 （IL-2）/Th2 （IL-4, IL-10, TGF-β1） cytokines in murine vaginal tissues was determined by RT-PCR. The cykotine in local tissues was increased to different extent under normal immune condition. IL-2 mRNA was increased during early stage of infection, while IL-10 was increased transiently during late stage of infection. TGF-β1 production was found to be increased persistently. At same time, the expression of IL-2 mRNA was suppressed in immno-suppressed group, and the level of IL-4, IL-10, and TGF-β1 were higher than the normal immunity group to different degree during infection. The high level of IL-2 mRNA during early stage of infection was associated with clearance of mucosal Candidia albicans （C. albicans）, and its expression suppressed leading to decreased clearance of mucosal C. albican in immuno-suppression. The over-expression of IL-4 and IL-10 could significantly enhance the susceptibility to C. albicans infection in mice.
基金grants from the science Research Foundation of Health Department of Hubei Province,China (No. JXIB048)the Janssen Research Foundation
文摘In order to investigate the expression of Th1 and Th2 cytokines in the vaginal candidiasis caused by Candida, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animals were pretreated with estradiol. Reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-2, IL-4, IL-10 and TGF-β1 in the vagina in the mice of different groups at different time points after the beginning of the experiment. The average expression level of IL-2 mRNA in group D （estrogen-treated mice） was significantly higher than that in groups H （estrogen-untreated mice） and I （control group） on the day 2. The average expression level of IL-4 mRNA in group D was significantly higher than that in groups I and H on the day 5. The average expression level of IL-10 mRNA in group D was significantly higher than that in groups H and I from day 7 to 11. The average expression level of TGF-β1 mRNA in group D was significantly higher than that in groups H and I at all time points. It was concludes that the high-level expression of IL-2 mRNA during early infection was associated with clearance of mucosal C. albicans, and the high-level expression of IL-10 mRNA during late stage of the infection was related to susceptibility to infection. TGF-β1 may play a predominant role when the virtual absence of changes in other Th-type cytokines during infection.
基金Supported by Grants from the Natural Science Foundation of China, No. 81060201Natural Science Foundation of Guangxi,No. 2011GXNSFA018273 and No. 2013GXNSFAA019163the Key Health Science Foundation of Guangxi, No. 1298003-2-6
文摘AIM: To explore the role of CDX2 in the multi-drug resistance (MDR) process of gastric cancer in vitro and in vivo . METHODS: A cisplatin-resistant gastric cancer cell line with stable downregulation of CDX2 was established. mRNA and protein expression levels of CDX2, survivin, cyclin D1, and c-Myc were detected by western blotting and semi-quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The influence of downregulation of CDX2 on MDR was assessed by measuring IC50 of SGC7901/DDP cells to cisplatin, doxorubicin, and 5-fluorouracil, rate of doxorubicin efflux, apoptosis, and cell cycle progression detected by flow cytometry. In addition, we determined the in vivo effects of CDX2 small interfering RNA (siRNA) on tumor size, and apoptotic cells in tumor tissues were detected by deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and hematoxylin and eosin staining. RESULTS: CDX2 siRNA led to downregulation of endogenous CDX2 mRNA (0.31 ± 0.05 vs 1.10 ± 0.51, 0.31 ± 0.05 vs 1.05 ± 0.21, P = 0.003) and protein (0.12 ± 0.08 vs 0.51 ± 0.07, 0.12 ± 0.08 vs 0.55 ± 0.16, P = 2.57 × 10 -4) expression. It significantly promoted the sensitivity of SGC7901/DDP cells to cisplatin (0.12 ± 0.05 vs 0.33 ± 0.08, 0.12 ± 0.05 vs 0.39 ± 0.15, P = 0.001), doxorubicin (0.52 ± 0.13 vs 4.11 ± 1.25, 0.52 ± 0.13 vs 4.05 ± 1.44, P = 2.81 × 10-4), and 5-fluorouracil (0.82 ± 0.13 vs 2.81 ± 0.51, 0.82 ± 0.13 vs 3.28 ± 1.03, P = 1.71 × 10-4). Flow cytometry confirmed that the percentage of apoptotic cells increased after CDX2 downregulation (32.15% ± 2.15% vs 17.63% ± 3.16%, 32.15% ± 2.15% vs 19.3% ± 2.25%, P = 1.73 × 10-6). This notion was further supported by the observation that downregulation of CDX2 blocked entry into the S-phase of the cell cycle (31.53% ± 3.78% vs 65.05% ± 7.25%, 31.53% ± 3.78% vs 62.27% ± 5.02%, P = 7.55 × 10-7). Furthermore, downregulation of CDX2 significantly increased intracellular accumulation of doxorubicin (0.21 ± 0.06 vs 0.41 ± 0.11, 0.21 ± 0.06 vs 0.40 ± 0.08, P = 0.003). In molecular studies, semiquantitative RT-PCR and western blotting revealed that CDX2 downregulation could inhibit expression of c-Myc, survivin and cyclin D1. CONCLUSION: CDX2 may be involved in regulating multiple signaling pathways in reversing MDR, suggesting that CDX2 may represent a novel target for gastric cancer therapy.
基金supported by grants from Universidad de Buenos Aires(Argentina)and Fundación Alberto J.Roemmers.
文摘In allergies, an unbalanced immune response towards a T helper (Th) 2 profile with high levels of Immunoglobulin (Ig) E is produced. We have demonstrated that the pre-administration of Enterococcus faecalis CECT7121 prevents the development of allergy in ovalbumin-immunized mice. In this work, we evaluated whether this bacterium can also revert an established allergic status. Mice were immunized with ovalbumin (OVA) and after that, were inoculated with an E. faecalis CECT7121 suspension. In immunized animals, serum specific immune response, proliferative activity of memory splenocytes, and levels of Th2 cytokines were assessed. The in vivo active cutaneous anaphylaxis test was also performed. The treatment with E. faecalis CECT7121 only increased anti-OVA IgG2a levels. No differences were observed in other specific immunological parameters. Probiotic-treatment did not prove to have any desensitizing effect on mice. These results, together with those recently published, can be concluded that this bacterium would not be appropriate for the treatment of allergic symptoms.
基金This work was supported by the National Key Research and Development Program of China No.2017YFC1200206 and 2019YFC0840609(to KS)special fund of State Key Laboratory for Diagnosis and Treatment of Infectious Diseases No.SKLID2019KF05(to XH)the National Science and Technology Major Project of China No.2017ZX10105001(to KX)and 2017ZX10204401001002(to MY).
文摘The pandemic of coronavirus disease 2019(COVID-19),a respiratory disease caused by a novel severe acute respiratory syndrome coronavirus-2,is causing substantial morbidity and mortality.Along with the respiratory symptoms,underlying diseases in senior patients,such as diabetes,hypertension,and coronary heart disease,are the most common comorbidities,which cause more severe outcomes and even death.During cellular attachment and entry of severe acute respiratory syndrome coronavirus-2,the key protein involved is the angiotensin I converting enzyme 2(ACE2),which is located on the membrane of host cells.Here,we aim to curate an expression profile of Ace2 and other COVID-19 related genes across the available diabetes murine strains.Based on strictly manual curation and bioinformatics analysis of the publicly deposited expression datasets,Ace2 and other potentially involved genes such as Furin,Tmprss2,Ang,and Ang2 were examined.We found that Ace2 expression is rather ubiquitous in three selected diabetes prone strains(db/db,ob/ob and diet-induced obese).With the most abundant datasets present,the liver shows a medium Ace2 expression level compared with the lungs,pancreatic islets,brain and even T cells.Age is a more critical factor for Ace2 expression in db/db compared with the other two strains.Besides Ace2,the other four host genes showed varied levels of correlation to each other.To accelerate research on the interaction between COVID-19 and underlying diseases,the Murine4Covid transcriptomics database(www.geneureka.org/Murine4Covid)will facilitate the design of research on COVID-19 and comorbidities.
