Opioid-induced fragile regulatory T cells contribute to NAc synaptic plasticity and withdrawal symptoms / 西安交通大学学报(医学版)

Decline of immunity is an epidemiological feature of opioid addicts. Recent work reveals a landscape of peripheral immune microenvironment in opioid addicts. Opioid addicts exhibit a significant expansion of fragile-like regulatory T cells (Tregs) and enhanced Treg-derived interferon-γ (IFN-γ) expression. IFN-γ signaling reshapes synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent withdrawal symptoms. Treg fragility transformation from WT Tregs is primarily due to opioid-induced global hypoxia during acute withdrawal period. Opioids increase the expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disrupt blood-brain barrier (BBB) integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7 (Fabp7), both of which trigger peripheral Treg infiltration into NAc. Recent studies suggest that subtle homeostatic changes in the peripheralimmune milieu may also contribute to modulating synapses that are responsible for addictive behaviors, which may lead to the development of new therapeutic strategies.

Effect of acupuncture on the expressions of TNF-α and IFN-γ in patients with premature ovarian failure / 中国针灸

OBJECTIVE@#To explore the clinical effect of acupuncture and the potential effect mechanism in patients with premature ovarian failure.@*METHODS@#A total of 104 patients with premature ovarian failure were randomized into an acupuncture group and a western medication group, 52 cases in each one. In the western medication group, the conjugated estrogens tablets were prescribed for oral administration, 0.625 mg each time, once a day, consecutively for 21 days. On the 16th day of medication with conjugated estrogens tablets, the oral administration of medroxyprogesterone acetate tablets were supplemented, 10 mg each time, once a day, consecutively for 5 days, and then, these two kinds of western medication were discontinued for 1 week. A total of 3 cycles were required in treatment with 28 days as an artificial cycle. In the acupuncture group, acupuncture was applied. Two groups of acupoints were selected. The first group of acupoints were stimulated before ovulation and the acupoints were Guanyuan (CV 4), Guilai (ST 29), Taichong (LR 3), Taixi (KI 3), Xuehai (SP 10), Sanyinjiao (SP 6), Zigong (EX-CA 1), Yinlingquan (SP 9), Zusanli (ST 36), Shuidao (ST 28), Dahe (KI 12) and Tianshu (ST 25). The second group of acupoints were stimulated after ovulation and the acupoints included Ciliao (BL 32), Shiqizhui (EX-B 8), Ganshu (BL 18), Shenshu (BL 23), Geshu (BL 17) and Pishu (BL 20). The therapeutic effect was observed and compared in the patients between the two groups, as well as the expressions of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) and the levels of serum luteinizing hormone (LH), follicule stimulating hormone (FSH) and estradiol (E) before and after treatment.@*RESULTS@#The total effective rate was 90.4% (47/52) in the acupuncture group, higher than 67.3% (35/62) in the western medication group (<0.05). After treatment, the expressions of IFN-γ and TNF-α in the acupuncture group were obviously lower than the western medication group (<0.05). Except for serum LH after treatment, at the end of treatment and in 30 days and 90 days after treatment, the levels of serum E in the acupuncture group were higher obviously than the western medication group and the levels of serum LH and FSH were lower obviously than the western medication group (all <0.05).@*CONCLUSION@#Acupuncture promotes the regular menstruation, effectively regulates the levels of serum LH, FSH and E and improves the pituitary gland and the ovary endocrine in the patients with premature ovarian failure. Such effect may be related to the the improvements in the expressions of IFN-γ and TNF-α, the inhibition of the apoptosis of ovarian granulosa cells, the recovery of ovarian function and the enhancement of reserve capacity.

Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.

Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.

Influence of isoniazid on immune function of rat / 药物评价研究

Objective To study the influence of isoniazid on lymphocyte factor expression and macrophage function of rats.Methods Healthy male SD rats were randomly divided into three groups,which was treated for one month,three months and withdrawal for one month after treated for three months,and each group was randomly divided into isoniazid group and control group.The isoniazid groups were ig with isoniazid at dose of 120 mg/kg every other day and control groups were fed on normal saline.At the corresponding time points,the level of interleukin-12 (IL-12) and interferon-γ (IFN-γ) was detected with ELISA method,detected serum lysozyme content by agar plate method,and Comori method was used for the detection of acid phosphatase levels in peritoneal fluid.Results At all the time points,levels of IL-12,IFN-γ and lysozyme in isoniazid group were not significantly different compared with control group.There were statistically significant differences in acid phosphatase between isoniazid group and control group after treated for one month (P ＜ 0.05),but the significant differences disappeared at the next two time points.Conclusion Isoniazid of 120 mg/kg may have no obvious influence on the immune function of rat.We don't detect the immune injury.

Influence of isoniazid on immune function of rat / 药物评价研究

Objective To study the influence of isoniazid on lymphocyte factor expression and macrophage function of rats.Methods Healthy male SD rats were randomly divided into three groups,which was treated for one month,three months and withdrawal for one month after treated for three months,and each group was randomly divided into isoniazid group and control group.The isoniazid groups were ig with isoniazid at dose of 120 mg/kg every other day and control groups were fed on normal saline.At the corresponding time points,the level of interleukin-12 (IL-12) and interferon-γ (IFN-γ) was detected with ELISA method,detected serum lysozyme content by agar plate method,and Comori method was used for the detection of acid phosphatase levels in peritoneal fluid.Results At all the time points,levels of IL-12,IFN-γ and lysozyme in isoniazid group were not significantly different compared with control group.There were statistically significant differences in acid phosphatase between isoniazid group and control group after treated for one month (P ＜ 0.05),but the significant differences disappeared at the next two time points.Conclusion Isoniazid of 120 mg/kg may have no obvious influence on the immune function of rat.We don't detect the immune injury.

Effect of moxibustion combined with autohemotherapy of acupoint injection for life quality of allergic rhinitis withdeficiency of lung and spleen:a randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects of moxibustion combined with autohemotherapy of acupoint injection and simple moxibustion for allergic rhinitis(AR) withdeficiency of lung and spleen and to explore its mechanism.</p><p><b>METHODS</b>By random number table,75 patients who matched the criteria were assigned into a moxibustion combined with autohemotherapy of acupoint injection group(a combination group,37 cases) and a moxibustion group(38 cases). In the combination group,moxibustion was used at bilateral Yingxiang(LI 20) and injection bila-teral Feishu(BL 13),Pishu(BL 20) and Zusanli(ST 36). In the moxibustion group,moxibustion was applied bilaterally at all the above acupoints. Acupoint injection was given twice a week,and moxibustion once a day,seven days as a course. The patients were observed for four courses and followed up half a year after treatment. Rhinoconjunctivitis quality of life questionnaire(RQLQ) was compared before and after treatment and at follow-up. The short-term and long-term effects as well as the changes of interferon-(IFN-),interleukin-4(IL-4) and immunoglobulin E(IgE) were observed in the two group.</p><p><b>RESULTS</b>After treatment,the obviously effective rate of the combination group was 75.68%(28/37),which was higher than 52.63%(20/38) of the moxibustion group(<0.05). But at follow-up, the obviously effective rate of the moxibustion group was 47.37%(18/38),which was better than 24.32%(9/37) of the combination group(<0.05). Life quality of the two group in all aspects after treatment and at follow-up were apparently improved compared with the baseline(<0.01,<0.05). After treatment,the life quality,sleep condition,non nasal-eye symptoms,behavior issue of the combination group were superior to those of the moxibustion group(all<0.05),and at follow-up,the above outcomes,the eye and nasal symptoms as well as emotional response of the mo-xibustion group were better(all<0.05). There was statistical significance in the two group about serum IFN-,IgE,IL-4 before and after treatment(<0.01,<0.05),and significance existed between the two groups(<0.05).</p><p><b>CONCLUSIONS</b>Moxibustion combined with autohemotherapy of acupoint injection can effectively improve the short-term quality of life of AR withdeficiency of lung and spleen. The mechanism may be related to balancing the immune response of Th1 and Th2.</p>

Changes of IL-18, TNF-α and IFN-γ levels in rats with experimental cirrhosis and their significance / 西安交通大学学报(医学版)

Objective To investigate the changes of interleukin-18 (IL-18), tumor necrosis factor-α(TNF-α) and interferon-γ (IFN-γ) levels of liver cirrhosis induced by the composite factors of carbon tetrachloride (CCl_4) in SD rats and their significance. Methods Totally 80 male SD rats of clean class were randomly divided into normal control group (20 rats) and model groups, the latter of which were further divided into three groups according to the length of administration time, namely, 2-week group (2 wk group), 4-week group (4 wk group) and 6-week group (6 wk group), with 20 rats in each. Six rats were killed after 2 wk, 4 wk and 6 wk administration time, respectively. The rat serum levels of IL-18, TNF-α and IFN-γ and the hepatic homogenate supernatant of IL-18 were detected by ELISA; pathological changes of liver tissues were observed by HE staining. Results ① Pathological observation revealed that in the model groups hepatic cells degenerated and swelled at week 2 while large amounts of fibrosis and pseudolobules of some liver tissues occurred at week 6. ② The serum levels of IL-18, TNF-α and IFN-γ were gradually increased with the modeling time, and they were significantly higher in 6-week group than in normal control group (P<0.01). ③ The levels of hepatic homogenate supernatant of IL-18 in the model groups were elevated with liver damage, and they were significantly higher in 6-week group than in normal control group (P<0.01). Conclusion During the formation of liver cirrhosis induced by composite factors of CCl_4 in rats, IL-18, TNF-α and IFN-γ levels gradually increase, suggesting that the three cytokines play a certain role during the occurrence of liver cirrhosis in rats.