Selenium (Se) is an essential trace element. Autoimmune thyroid diseases (AITD) are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the ...Selenium (Se) is an essential trace element. Autoimmune thyroid diseases (AITD) are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium (Se) and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases (AITD).展开更多
In our previous study,we found that Shoutai pills could improve the embryo implantation rate as well as the levels of estrogen,progesterone and estrogen receptor in rats with stimulated ovulation.However,the mechanism...In our previous study,we found that Shoutai pills could improve the embryo implantation rate as well as the levels of estrogen,progesterone and estrogen receptor in rats with stimulated ovulation.However,the mechanism is not clear.This study was designed to investigate the effect of Shoutai pills on the levels of Th1 and Th2 cytokines in rats with stimulated ovulation and the mechanism.The rat model of stimulated ovulation was established by combined injection of pregnant mare serum gonadotropin(PMSG)and human chorionic gonadotropin(HCG).Then the rats were randomly divided into model group(M),Shoutai pills group(S),progesterone group(P)and normal group(N).All the pregnant rats were treated from the first day.The S and P groups were administrated with gavage of Shoutai pills and injection of progesterone respectively,and N and M groups were given the same volume of normal saline and distilled water respectively.After treatment for 7 days,the animals were executed for serum and uterine tissues.The ELISA method was adopted to detect the contents of Thl cytokines[interferon-γ(INF-γ),interleukin-2(IL-2)]and Th2 cytokines(IL-4,IL-6,IL-10).The expression of leukemia inhibitory factor(L1F)and leukemia inhibitory factor receptor(LIFR)was detected by Western blotting and real-time PCR.As compared with N group,the expression levels of IFN-y and IL-2 in M group were significantly increased,and those of IL-4,IL-6,IL-10.LIF and LIFR were significantly decreased(P<0.05).As compared with M group,the levels of IL-4,IL-6,IL-10,LIF and LIFR in S group were significantly increased(P<0.05),and those of IFN-γand IL-2 were significantly decreased(P<0.05).It was suggested that Shoutai pills can increase the levels of IL-4.1L-6,IL-10,LIF and LIFR as well as reduce the levels of INF-γand IL-2 in rats with stimulated ovulation.The Shoutai pills may improve endometrial receptivity and promote embryo implantation by maintaining the balanee of Th1/Th2 cytokines.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
Bisphenol A (BPA) is used in huge amounts for many plastic products and is a hormone (estrogen) disrupting agent. BPA as well as FFAs may be deleterious for the immune system. The aim was to identify Th2 cytokines and...Bisphenol A (BPA) is used in huge amounts for many plastic products and is a hormone (estrogen) disrupting agent. BPA as well as FFAs may be deleterious for the immune system. The aim was to identify Th2 cytokines and some of their signal transduction mechanisms in INS-1 cells, an insulin secreting cell line. Screening using a proteome profile indicated an increase of IL-1, IL-2, IL-4, IL-6, IL-10, IL-13 and IL-17 by BPA. Also FFAs (in combination with LPS) were positive. In detailed quantitative measurements, these results were confirmedly indicating a complex array of pro-and anti-inflammatory potential. The interaction of BPA with 17β-estradiol was non-additive with respect to IL-4 and IL-6 release and additive with respect to FFA interaction indicating same and different mechanisms of action, respecttively. As signal transduction PI3K (Wortmannin-sensitive) and STAT-3/6 (Tofacitinib-sensitive) are involved in various effects, INS-1 cells release several cytokines due to BPA and FFA attack which may be involved in disturbance of glucose homoeostasis and type 1 diabetes.展开更多
Objective: To investigate the effect of dexmedetomidine on Th1/Th2 cytokines and immune function in patients with breast cancer after radical mastectomy. Methods: In our hospital from July 2016 to July 2017 undergoing...Objective: To investigate the effect of dexmedetomidine on Th1/Th2 cytokines and immune function in patients with breast cancer after radical mastectomy. Methods: In our hospital from July 2016 to July 2017 undergoing radical mastectomy for breast cancer were studied in 79 patients, were randomly divided into observation group and control group. Two groups of patients with routine preoperative preparation, monitoring blood pressure, electrocardiogram, heart rate, pulse, oxygen saturation, establish vein channel, using propofol, remifentanil, vecuronium induced anesthesia, observation group before induction of anesthesia, dexmedetomidine 1 μg/kg, 10 min after infusion, followed by 0.5 μg/kg/h continuous infusion to the end of the operation, the control group with normal saline continuous infusion till the end of the operation. Two groups of patients before induction of anesthesia (T0), at the end of operation (T1), 6 h after operation (T2), 24 h after operation (T3), 72 h after operation (T4) from peripheral venous blood determination of interleukin-2 by ELISA method (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon gamma (IFN-γ), calculated IFN-γ/IL-4 in T0, T2, T3, T4from peripheral blood. CD3+, CD4+, CD8+, NK cells were determined by flow cytometry and CD4+/CD8+ were calculated. Results: Two groups of IL-2 and IFN- in T1, T2, T3gamma, T4is higher than T0, IL-10 less than T0, and the observation group IFN-γ/IL-4 is higher than T0, the control group was lower than that of T0when compared with T0significant difference, 2 in group IL-4 had no obvious changes were observed in group IL-2;IFN-γ, IFN-γ/IL-4 in T1, T2, T3, T4higher than the control group, IL-10 was lower than the control group, significant difference between the 2 groups. CD3+, CD4+, CD4+/CD8+, NK cells in T2group was lower than that of T0, T3, and CD8+ had no obvious change, compared with T0significant difference;the observation group CD3+, CD4+, CD4+/CD8+, T2, T3in NK cells was higher than the control group, significant difference between the 2 groups. Conclusion: Dexmedetomidine can inhibit the stress response during the perioperative period of radical mastectomy, correct the balance disorder of Th1/Th2, improve the level of T lymphocyte subsets, and exert better immune protection function.展开更多
As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis(EP) is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-l...As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis(EP) is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in peripheral blood mononuclear cells(PBMCs) derived from EP patients, and gene expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2 reaction pattern played in the pathogenesis of EP was also discussed. Serum levels of IFN-γ, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP patients, 20 psoriasis vulgaris(PV) patients and 15 healthy controls. The expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels of IFN-γ, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy controls. The levels of IL-4 and IL-10 were 69.44±11.45 and 12.62±4.57 pg/mL, respectively, in EP patients, significantly higher than those in PV patients and healthy controls(P〈0.05). Flow cytometry revealed the levels of both Th1 and Th2 in PBMCs from EP patients were higher than those in healthy controls, and the Th1/Th2 ratio was dramatically lower than in PV patients(P〈0.01). The ratios of IFN-γ/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0, suggesting a reversal when compared with the other two groups. Our study indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern, and the balance of Th cell subsets inclines to Th2, which might be one of the important mechanisms of EP pathogenesis.展开更多
The ongoing outbreak of novel coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused an unprecedented global health crisis.Development of a cure for this de...The ongoing outbreak of novel coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused an unprecedented global health crisis.Development of a cure for this devastating disease is currently at full speed,with several vaccines against COVID-19 already authorized and administered.Currently,demand for these vaccines far exceeds supply.As such,boosting immunity represents a viable route to halt the rapid spread of SARS-CoV-2 and limit fatalities until vaccines become more readily and widely available.The use of phytochemicals appears to be a promising panacea.Sesamin,a lignan isolated from Sesamum indicum seeds,is known for its potent pharmacological properties,and is therefore hypothesized as a potential candidate in the therapeutic regimen against COVID-19.Herein,we highlight the confirmed therapeutic anti-inflammatory and immune-modulatory potential of sesamin against myriads of respiratory disorders,and tentatively suggest that sesamin may exert similar potent effects against COVID-19.Precisely,we speculate that sesamin may help alleviate COVID-19 via restoring Th1/Th2 balance and preventing inflammation and cytokine storm development.Additionally,we further support the promising role of sesamin against COVID-19 by underscoring the direct evidence,which suggests that sesamin may demonstrate promising inhibitory potential against three important SARS-CoV-2 targets,namely main protease,spike protein,and angiotensin-converting enzyme 2 receptor.Although preliminary,there is ample evidence to propose sesamin as a potential phytotherapeutic and prophylactic candidate against COVID-19.Further in vitro,in vivo,and preclinical studies are required to further substantiate the role of sesamin in the prevention and/or treatment of COVID-19.展开更多
Objective: To study the clinical effects of Prescription Zhuyun-Ⅲ (助孕3号方, ZYⅢ) on early pregnant women diagnosed as threatened abortion, and its mechanism in immunity and endocrine by determining serum Th1- a...Objective: To study the clinical effects of Prescription Zhuyun-Ⅲ (助孕3号方, ZYⅢ) on early pregnant women diagnosed as threatened abortion, and its mechanism in immunity and endocrine by determining serum Th1- and Th2-type cytokines, progesterone, and β-human chorionic gonadotropin (β-HCG). Methods: The treatment group comprised 30 early pregnant women diagnosed as threatened abortion of deficiency syndrome of Pi (脾), Shen (肾), or both. The control group consisted of 20 normal early pregnant women of similar gestational age. Patients in the treatment group were administered with ZYⅢ for 4 weeks. Peripheral blood samples were collected pre- and post-treatment from both the treatment and the control groups. Serum Thl-type cytokine [interleukin-2 (IL-2)] and Th2-type cytokine [interleukin-10 (IL-10)] were determined by flow cytometry, and serum progesterone and 13-HCG were determined by ELISA. Results: (1) The treatment was effective in 26 and ineffective in 4 patients of the treatment group. Therefore, the cure percentage was 86.67%. (2) In the treatment group before the treatment, IL-2 was significantly higher, IL-10 tended to be less, and the Th1/Th2 balance shifted toward Thl compared with those in the control group. (3) After the treatment, IL-2 was decreased, IL-10 was increased, and IL-2/IL-10 was decreased. Both progesterone and β-HCG were increased. Changes of progesterone were positively correlated with changes of IL-10, whereas changes of β-HCG were negatively correlated with changes of IL-2. Conclusions: Our study suggests that ZYⅢ has an evident function of protecting the fetus, and one of its mechanisms is inhibiting the secretion of Thl cytokines, promoting the secretion of Th2 cytokines, and recovering the pathological shift of the Th1/Th2 balance. The other possible mechanism is increasing serum progesterone and β-HCG concentrations. Moreover, there are some correlations between the above two effects.展开更多
Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination ...Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A (CsA) on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation.Methods The model of rat orthotopic liver transplantation was established by modified Kamada's technique. Recipients were divided into group A (control group): SD→SD; group B (group of rejection): SD→Wistar without any treatment; group C: SD→Wistar with CsA monotherapy from day 1 to day 5; and group D: SD→Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7.Results The survival period of recipients in groups A (〉60 days) and D (〉60 days) was significantly longer than that in group B (13.8±2.4 days). The serum levels of interleukin 2 (IL-2) and interferon y in group B were significantly higher than those in other groups; the level of tumor necrosis factor a was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B (P〈0.05).Conclusions Combined immune therapy can prolong the survival of al log rafts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.展开更多
Obejctive To investigate the imbalance of Th1/Th2 type cytokines in patients with systemic lupus erythematosus (SLE) and its relation to disease activity Methods Intracellular cytokines were determined by flow cy...Obejctive To investigate the imbalance of Th1/Th2 type cytokines in patients with systemic lupus erythematosus (SLE) and its relation to disease activity Methods Intracellular cytokines were determined by flow cytometry following whole blood culture Results Patients with systemic lupus erythematosus disease activity index (SLEDAI) >10 had statistically significantly fewer CD4 + or CD8 + T cells producing IFN γ than patients with SLEDAI =0, SLEDAI 1-10 or healthy controls ( P <0 01, P <0 01 or P <0 05, respectively) Patients with SLEDAI>10 also had decreased ratio of IFN γ/IL 4 positive CD4 + or CD8 + T cells, compared with patients with SLEDAI =0, SLEDAI 1-10 or healthy controls ( P <0 05) The decreased Th1 or Tc1 cells and the ratios of IFN γ: IL 4 positive CD4 + T cells were significantly correlated with disease activity ( P <0 05) Conclusion SLE is characterized by an imbalance of Th1/Th2 and Tc1/Tc2 cytokines The decreased Th1 or Tc1 cells and the Th1/Th2 ratio are related to disease activity展开更多
Objective:Idiopathic pulmonary fibrosis(IPF)is a progressive and lethal interstitial lung disease with high mortality.The pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has bee...Objective:Idiopathic pulmonary fibrosis(IPF)is a progressive and lethal interstitial lung disease with high mortality.The pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has been demonstrated previously.This study aimed to evaluate the effect of Jinbei Oral Liquid(JBOL)on IPF and its relationship with Th1/Th2 shift.Methods:Rats were divided into six groups:control group,model group(bleomycin),pirfenidone group(positive group,54 mg/kg,i.g.)and JBOL(5.4,10.8 and 21.6 mL/kg,i.g.)groups.The rat model was established by an intratracheal instillation of bleomycin(BLM,5 mg/kg).One day after injection of BLM,pirfenidone or JBOL was given to rats once daily within 28 consecutive days,respectively.Positron emission tomography/computed tomography(PET/CT)was performed on the treated rats.The extent of alveolitis and fibrosis was observed by H&E and Masson trichrome staining.The contents of TGF-β1,TNF-α,IL-4 and IFN-γwere further quantified by ELISA assay.Results:PET/CT and histopathological evidence showed the ability of JBOL to attenuate bleomycininduced alveolitis and fibrosis extent,and the alveolitis lesion score was markedly decreased compared with the model group.The increased expression of inflammatory cytokines TGF-β1 and TNF-αinduced by bleomycin was also suppressed by JBOL.The Th1 response was limited by the reduced IFN-γafter BLM administration,and the Th2 response predominated significantly marked by the increased IL-4.JBOL could increase the level of IFN-γand markedly increased the ratio of IFN-γ/IL-4.Conclusion:These findings suggested that JBOL may attenuate BLM-induced idiopathic pulmonary fibrosis via reducing inflammatory cell infiltration,pro-inflammatory cytokine release and excessive collagen deposition in rats.One of the mechanisms is the reversion of Th1/Th2 shift caused by BLM.展开更多
Objective: To evaluate the effect of short-term and long-term immunization of recombinant disorganized muscle protein-1(r DIM-1) in rodents against human filarial parasite Brugia malayi.Methods: Recombinant Brugia mal...Objective: To evaluate the effect of short-term and long-term immunization of recombinant disorganized muscle protein-1(r DIM-1) in rodents against human filarial parasite Brugia malayi.Methods: Recombinant Brugia malayi DIM-1(rDIM-1 bm) protein was cloned, expressed and purified using a Ni-NTA affinity column. Mastomys coucha were immunized with rDIM-1 bm in three immunization schedules: short-term(3-dose of rDIM-1 bm), and long-term(booster doses till 3-and 6-week) and subsequently challenged with infective third-stage larvae of filarial parasite Brugia malayi(L3). Microfilaraemia was monitored in L3 exposed groups on day 90 post larval inoculation(p.l.i.) and continued till day 205 p.l.i. On day 205 p.l.i. all the infected animals were killed and total worm burden was estimated. Cellular proliferative response, macrophage activity, nitric oxide(NO) release, specific IgG and its subtypes, IgE, IgA and Th1(IFN-γ, TNF-ααand IL-2) and Th2(IL-4, IL-5, IL-6, IL-10 and IL-13) cytokine release were determined. Results: Of the 3 different immunization schedules, shortterm immunization(3-dose schedule) showed better reduction in microfilarial burden(36%-63%) in the peripheral circulation, adult worm load(52%), whereas long-term immunization(3-and 6-week schedule) exerted less effect on peripheral microfilariae count(9%-58%), and adult worm burden(9%-12.5%). Short-term immunization resulted in upregulation of cellular proliferation, macrophages activity, NO release, specific IgG, IgG1, IgG2 a, Ig G2 b, IgE and IgA levels and both Th1(IFN-γ, TNF-α and IL-2) and Th2(IL-4, IL-5, IL-6, IL-10 and IL-13) cytokine release whereas long-term immunization(3-and 6-week schedule) exerted less effect on parasite burden and showed mixed immunological responses. None of the rDIM-1 bm administration schedules induced any pathology in lymphoid tissues, or alteration in mast cell number and granularity. Conclusions: The short-term immunization with rDIM-1 bm(3-dose schedule) induces robust immune responses and protects the host from filarial parasite infection.展开更多
基金supported by three programs from the National Natural Science Foundation of China (NSFC) (The experimental study on the effect of trace elements iodine and selenium on the autoimmune thyroid disease (No.30571564)The cross-sectional investigation on hypothyroidism induced by excess iodine intake and the experimental research on pathogenesy (No.30972465)The change of thyroid pathology and the levels of T3,T4 in SePP1,GPX3 knock out mice (No.30810103004)
文摘Selenium (Se) is an essential trace element. Autoimmune thyroid diseases (AITD) are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium (Se) and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases (AITD).
文摘In our previous study,we found that Shoutai pills could improve the embryo implantation rate as well as the levels of estrogen,progesterone and estrogen receptor in rats with stimulated ovulation.However,the mechanism is not clear.This study was designed to investigate the effect of Shoutai pills on the levels of Th1 and Th2 cytokines in rats with stimulated ovulation and the mechanism.The rat model of stimulated ovulation was established by combined injection of pregnant mare serum gonadotropin(PMSG)and human chorionic gonadotropin(HCG).Then the rats were randomly divided into model group(M),Shoutai pills group(S),progesterone group(P)and normal group(N).All the pregnant rats were treated from the first day.The S and P groups were administrated with gavage of Shoutai pills and injection of progesterone respectively,and N and M groups were given the same volume of normal saline and distilled water respectively.After treatment for 7 days,the animals were executed for serum and uterine tissues.The ELISA method was adopted to detect the contents of Thl cytokines[interferon-γ(INF-γ),interleukin-2(IL-2)]and Th2 cytokines(IL-4,IL-6,IL-10).The expression of leukemia inhibitory factor(L1F)and leukemia inhibitory factor receptor(LIFR)was detected by Western blotting and real-time PCR.As compared with N group,the expression levels of IFN-y and IL-2 in M group were significantly increased,and those of IL-4,IL-6,IL-10.LIF and LIFR were significantly decreased(P<0.05).As compared with M group,the levels of IL-4,IL-6,IL-10,LIF and LIFR in S group were significantly increased(P<0.05),and those of IFN-γand IL-2 were significantly decreased(P<0.05).It was suggested that Shoutai pills can increase the levels of IL-4.1L-6,IL-10,LIF and LIFR as well as reduce the levels of INF-γand IL-2 in rats with stimulated ovulation.The Shoutai pills may improve endometrial receptivity and promote embryo implantation by maintaining the balanee of Th1/Th2 cytokines.
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.
文摘Bisphenol A (BPA) is used in huge amounts for many plastic products and is a hormone (estrogen) disrupting agent. BPA as well as FFAs may be deleterious for the immune system. The aim was to identify Th2 cytokines and some of their signal transduction mechanisms in INS-1 cells, an insulin secreting cell line. Screening using a proteome profile indicated an increase of IL-1, IL-2, IL-4, IL-6, IL-10, IL-13 and IL-17 by BPA. Also FFAs (in combination with LPS) were positive. In detailed quantitative measurements, these results were confirmedly indicating a complex array of pro-and anti-inflammatory potential. The interaction of BPA with 17β-estradiol was non-additive with respect to IL-4 and IL-6 release and additive with respect to FFA interaction indicating same and different mechanisms of action, respecttively. As signal transduction PI3K (Wortmannin-sensitive) and STAT-3/6 (Tofacitinib-sensitive) are involved in various effects, INS-1 cells release several cytokines due to BPA and FFA attack which may be involved in disturbance of glucose homoeostasis and type 1 diabetes.
文摘Objective: To investigate the effect of dexmedetomidine on Th1/Th2 cytokines and immune function in patients with breast cancer after radical mastectomy. Methods: In our hospital from July 2016 to July 2017 undergoing radical mastectomy for breast cancer were studied in 79 patients, were randomly divided into observation group and control group. Two groups of patients with routine preoperative preparation, monitoring blood pressure, electrocardiogram, heart rate, pulse, oxygen saturation, establish vein channel, using propofol, remifentanil, vecuronium induced anesthesia, observation group before induction of anesthesia, dexmedetomidine 1 μg/kg, 10 min after infusion, followed by 0.5 μg/kg/h continuous infusion to the end of the operation, the control group with normal saline continuous infusion till the end of the operation. Two groups of patients before induction of anesthesia (T0), at the end of operation (T1), 6 h after operation (T2), 24 h after operation (T3), 72 h after operation (T4) from peripheral venous blood determination of interleukin-2 by ELISA method (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon gamma (IFN-γ), calculated IFN-γ/IL-4 in T0, T2, T3, T4from peripheral blood. CD3+, CD4+, CD8+, NK cells were determined by flow cytometry and CD4+/CD8+ were calculated. Results: Two groups of IL-2 and IFN- in T1, T2, T3gamma, T4is higher than T0, IL-10 less than T0, and the observation group IFN-γ/IL-4 is higher than T0, the control group was lower than that of T0when compared with T0significant difference, 2 in group IL-4 had no obvious changes were observed in group IL-2;IFN-γ, IFN-γ/IL-4 in T1, T2, T3, T4higher than the control group, IL-10 was lower than the control group, significant difference between the 2 groups. CD3+, CD4+, CD4+/CD8+, NK cells in T2group was lower than that of T0, T3, and CD8+ had no obvious change, compared with T0significant difference;the observation group CD3+, CD4+, CD4+/CD8+, T2, T3in NK cells was higher than the control group, significant difference between the 2 groups. Conclusion: Dexmedetomidine can inhibit the stress response during the perioperative period of radical mastectomy, correct the balance disorder of Th1/Th2, improve the level of T lymphocyte subsets, and exert better immune protection function.
基金supported by grants from the National Natural Science Foundation of China(Nos.81171495 and 81271765)
文摘As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis(EP) is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in peripheral blood mononuclear cells(PBMCs) derived from EP patients, and gene expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2 reaction pattern played in the pathogenesis of EP was also discussed. Serum levels of IFN-γ, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP patients, 20 psoriasis vulgaris(PV) patients and 15 healthy controls. The expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels of IFN-γ, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy controls. The levels of IL-4 and IL-10 were 69.44±11.45 and 12.62±4.57 pg/mL, respectively, in EP patients, significantly higher than those in PV patients and healthy controls(P〈0.05). Flow cytometry revealed the levels of both Th1 and Th2 in PBMCs from EP patients were higher than those in healthy controls, and the Th1/Th2 ratio was dramatically lower than in PV patients(P〈0.01). The ratios of IFN-γ/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0, suggesting a reversal when compared with the other two groups. Our study indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern, and the balance of Th cell subsets inclines to Th2, which might be one of the important mechanisms of EP pathogenesis.
文摘The ongoing outbreak of novel coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused an unprecedented global health crisis.Development of a cure for this devastating disease is currently at full speed,with several vaccines against COVID-19 already authorized and administered.Currently,demand for these vaccines far exceeds supply.As such,boosting immunity represents a viable route to halt the rapid spread of SARS-CoV-2 and limit fatalities until vaccines become more readily and widely available.The use of phytochemicals appears to be a promising panacea.Sesamin,a lignan isolated from Sesamum indicum seeds,is known for its potent pharmacological properties,and is therefore hypothesized as a potential candidate in the therapeutic regimen against COVID-19.Herein,we highlight the confirmed therapeutic anti-inflammatory and immune-modulatory potential of sesamin against myriads of respiratory disorders,and tentatively suggest that sesamin may exert similar potent effects against COVID-19.Precisely,we speculate that sesamin may help alleviate COVID-19 via restoring Th1/Th2 balance and preventing inflammation and cytokine storm development.Additionally,we further support the promising role of sesamin against COVID-19 by underscoring the direct evidence,which suggests that sesamin may demonstrate promising inhibitory potential against three important SARS-CoV-2 targets,namely main protease,spike protein,and angiotensin-converting enzyme 2 receptor.Although preliminary,there is ample evidence to propose sesamin as a potential phytotherapeutic and prophylactic candidate against COVID-19.Further in vitro,in vivo,and preclinical studies are required to further substantiate the role of sesamin in the prevention and/or treatment of COVID-19.
基金Supported by Guangdong Province Key Scientific and Technological Project(No.C30103)
文摘Objective: To study the clinical effects of Prescription Zhuyun-Ⅲ (助孕3号方, ZYⅢ) on early pregnant women diagnosed as threatened abortion, and its mechanism in immunity and endocrine by determining serum Th1- and Th2-type cytokines, progesterone, and β-human chorionic gonadotropin (β-HCG). Methods: The treatment group comprised 30 early pregnant women diagnosed as threatened abortion of deficiency syndrome of Pi (脾), Shen (肾), or both. The control group consisted of 20 normal early pregnant women of similar gestational age. Patients in the treatment group were administered with ZYⅢ for 4 weeks. Peripheral blood samples were collected pre- and post-treatment from both the treatment and the control groups. Serum Thl-type cytokine [interleukin-2 (IL-2)] and Th2-type cytokine [interleukin-10 (IL-10)] were determined by flow cytometry, and serum progesterone and 13-HCG were determined by ELISA. Results: (1) The treatment was effective in 26 and ineffective in 4 patients of the treatment group. Therefore, the cure percentage was 86.67%. (2) In the treatment group before the treatment, IL-2 was significantly higher, IL-10 tended to be less, and the Th1/Th2 balance shifted toward Thl compared with those in the control group. (3) After the treatment, IL-2 was decreased, IL-10 was increased, and IL-2/IL-10 was decreased. Both progesterone and β-HCG were increased. Changes of progesterone were positively correlated with changes of IL-10, whereas changes of β-HCG were negatively correlated with changes of IL-2. Conclusions: Our study suggests that ZYⅢ has an evident function of protecting the fetus, and one of its mechanisms is inhibiting the secretion of Thl cytokines, promoting the secretion of Th2 cytokines, and recovering the pathological shift of the Th1/Th2 balance. The other possible mechanism is increasing serum progesterone and β-HCG concentrations. Moreover, there are some correlations between the above two effects.
文摘Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A (CsA) on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation.Methods The model of rat orthotopic liver transplantation was established by modified Kamada's technique. Recipients were divided into group A (control group): SD→SD; group B (group of rejection): SD→Wistar without any treatment; group C: SD→Wistar with CsA monotherapy from day 1 to day 5; and group D: SD→Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7.Results The survival period of recipients in groups A (〉60 days) and D (〉60 days) was significantly longer than that in group B (13.8±2.4 days). The serum levels of interleukin 2 (IL-2) and interferon y in group B were significantly higher than those in other groups; the level of tumor necrosis factor a was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B (P〈0.05).Conclusions Combined immune therapy can prolong the survival of al log rafts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.
文摘Obejctive To investigate the imbalance of Th1/Th2 type cytokines in patients with systemic lupus erythematosus (SLE) and its relation to disease activity Methods Intracellular cytokines were determined by flow cytometry following whole blood culture Results Patients with systemic lupus erythematosus disease activity index (SLEDAI) >10 had statistically significantly fewer CD4 + or CD8 + T cells producing IFN γ than patients with SLEDAI =0, SLEDAI 1-10 or healthy controls ( P <0 01, P <0 01 or P <0 05, respectively) Patients with SLEDAI>10 also had decreased ratio of IFN γ/IL 4 positive CD4 + or CD8 + T cells, compared with patients with SLEDAI =0, SLEDAI 1-10 or healthy controls ( P <0 05) The decreased Th1 or Tc1 cells and the ratios of IFN γ: IL 4 positive CD4 + T cells were significantly correlated with disease activity ( P <0 05) Conclusion SLE is characterized by an imbalance of Th1/Th2 and Tc1/Tc2 cytokines The decreased Th1 or Tc1 cells and the Th1/Th2 ratio are related to disease activity
基金The National Science and Technology Major Project for'Significant New Drugs Development'(2018ZX09721004-010)provides financial support during the literature searching and experimental materialsthe Major Program of the National Natural Science Foundation of China(No.81891012)provides financial support during the data analysisthe CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2017-I2M-1-013)provide financial support during the language revising and publication.
文摘Objective:Idiopathic pulmonary fibrosis(IPF)is a progressive and lethal interstitial lung disease with high mortality.The pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has been demonstrated previously.This study aimed to evaluate the effect of Jinbei Oral Liquid(JBOL)on IPF and its relationship with Th1/Th2 shift.Methods:Rats were divided into six groups:control group,model group(bleomycin),pirfenidone group(positive group,54 mg/kg,i.g.)and JBOL(5.4,10.8 and 21.6 mL/kg,i.g.)groups.The rat model was established by an intratracheal instillation of bleomycin(BLM,5 mg/kg).One day after injection of BLM,pirfenidone or JBOL was given to rats once daily within 28 consecutive days,respectively.Positron emission tomography/computed tomography(PET/CT)was performed on the treated rats.The extent of alveolitis and fibrosis was observed by H&E and Masson trichrome staining.The contents of TGF-β1,TNF-α,IL-4 and IFN-γwere further quantified by ELISA assay.Results:PET/CT and histopathological evidence showed the ability of JBOL to attenuate bleomycininduced alveolitis and fibrosis extent,and the alveolitis lesion score was markedly decreased compared with the model group.The increased expression of inflammatory cytokines TGF-β1 and TNF-αinduced by bleomycin was also suppressed by JBOL.The Th1 response was limited by the reduced IFN-γafter BLM administration,and the Th2 response predominated significantly marked by the increased IL-4.JBOL could increase the level of IFN-γand markedly increased the ratio of IFN-γ/IL-4.Conclusion:These findings suggested that JBOL may attenuate BLM-induced idiopathic pulmonary fibrosis via reducing inflammatory cell infiltration,pro-inflammatory cytokine release and excessive collagen deposition in rats.One of the mechanisms is the reversion of Th1/Th2 shift caused by BLM.
基金supported by Indian council of Medical Research,New Delhi,India(ICMR approval no.F/802/2010-ECD-11)CSIR,New Delhi,India,for award of Emeritus Scientist(scheme No.21(0963)/13/EMRII grant,29-10-2014)to P.K.M.
文摘Objective: To evaluate the effect of short-term and long-term immunization of recombinant disorganized muscle protein-1(r DIM-1) in rodents against human filarial parasite Brugia malayi.Methods: Recombinant Brugia malayi DIM-1(rDIM-1 bm) protein was cloned, expressed and purified using a Ni-NTA affinity column. Mastomys coucha were immunized with rDIM-1 bm in three immunization schedules: short-term(3-dose of rDIM-1 bm), and long-term(booster doses till 3-and 6-week) and subsequently challenged with infective third-stage larvae of filarial parasite Brugia malayi(L3). Microfilaraemia was monitored in L3 exposed groups on day 90 post larval inoculation(p.l.i.) and continued till day 205 p.l.i. On day 205 p.l.i. all the infected animals were killed and total worm burden was estimated. Cellular proliferative response, macrophage activity, nitric oxide(NO) release, specific IgG and its subtypes, IgE, IgA and Th1(IFN-γ, TNF-ααand IL-2) and Th2(IL-4, IL-5, IL-6, IL-10 and IL-13) cytokine release were determined. Results: Of the 3 different immunization schedules, shortterm immunization(3-dose schedule) showed better reduction in microfilarial burden(36%-63%) in the peripheral circulation, adult worm load(52%), whereas long-term immunization(3-and 6-week schedule) exerted less effect on peripheral microfilariae count(9%-58%), and adult worm burden(9%-12.5%). Short-term immunization resulted in upregulation of cellular proliferation, macrophages activity, NO release, specific IgG, IgG1, IgG2 a, Ig G2 b, IgE and IgA levels and both Th1(IFN-γ, TNF-α and IL-2) and Th2(IL-4, IL-5, IL-6, IL-10 and IL-13) cytokine release whereas long-term immunization(3-and 6-week schedule) exerted less effect on parasite burden and showed mixed immunological responses. None of the rDIM-1 bm administration schedules induced any pathology in lymphoid tissues, or alteration in mast cell number and granularity. Conclusions: The short-term immunization with rDIM-1 bm(3-dose schedule) induces robust immune responses and protects the host from filarial parasite infection.