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OBJECTIVE：To study the effects of Purple frute scens leaves polysaccharides （PPLPs）on oxidative stress and PI3K/AKT/GLUT4 signaling pathway of pancreatic tissues in diabetes mellitus （DM）model mice. METHODS ：Totally 60 mice were given intraperitoneal injection of STZ （60 mg/kg）to induce DM model. The 40 successful modeling mice were randomly divided into model group ，metformin group （positive control ，200 mg/kg），PPLPs high-dose and low-dose groups （400，200 mg/kg），with 10 mice in each group. Another 10 healthy mice were selected as the normal group （normal saline ）. They were given relevant medicine intragastrically ，once a day ，for consecutive 28 days. During the experiment ，general information and body weight of mice were observed ；oral glucose tolerance （OGTT）test（determining FBG at 0，30，60，120 min after giving 40％ glucose solution ）was conducted. After last medication ，the changes of related blood glucose indexes （FBG，FINS，ISI，IRI）， blood lipid indexes （HDL-C，LDL-C，TC，TG）and oxidant stress indexes （MDA content and the activities of SOD ，CAT， GSH-Px）as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were determined. RESULTS ：During the experiment ，compared with normal group ，the mice were slow in action ，the feed consumption and water consumption increased，and body weight significantly increased in model group （P＜0.05）. 0，30，60，120 min after giving glucose ，the FBG content of mice were all increased significantly （P＜0.05）. After last medication ，the contents of FINS and HDL-C in serum as well as ISI ，the activities of SOD ，CAT and GSH-Px as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were all decreased significantly （P＜0.05）；the contents of FBG and LDL-C ，TC and TG in serum as well as IRI ， 疗。E-mail：sunguangping83@163.com MDA content in pancreatic tissue were all increased significantly（P＜0.05）. Compared with model group ，the general condition and OGTT of mice in each administration group was improved；the contents of FINS and HDL-C in serum as well as ISI ，the activities of SOD ，CAT and GSH-Px as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were all increased significantly （P＜0.05）；the contents of FBG，LDL-C，TC and TG in serum as well as IRI ，MDA content of pancreatic tissue were decreased significantly （P＜0.05）. CONCLUSIONS：PPLPs has anti-diabetic effects ，which are related to reducting oxidative stress level and promoting the activation of PI 3K/AKT/GLUT4 signaling pathway.
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Objective To observe the change of T helper 17 (Th17),regulatory T cell (Treg) as a percentage of lymphocytes and the Th17/Treg ratio in peripheral blood of patients with coal-burning-borne arsenic poisoning,and to explore the role of Th17 cells and Treg cells balance in arsenic-induced immune injury.Methods A case-control study was conducted to investigate 149 cases of arsenic poisoning in Yuzhang arsenic poisoning area in the southwestern Gnizhou Province,and the age was (50.69 ± 6.14) years old,including 94 males and 55 females.The diagnosis was based on the "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015),and the cases were divided into mild arsenic poisoning group (39 cases),moderate arsenic poisoning group (54 cases) and severe arsenic poisoning group (56 cases);forty--one residents of non-arsenic exposed villages about 12 km away from the diseased area were collected as control group,the age was (45.76 ± 7.88) years old,including 12 males and 29 females.Hair samples and peripheral blood were collected from the subjects.The content of hair arsenic was detected by inductively coupled plasma mass spectrometry (ICP-MS).The percentages of Th17 cells and Treg cells in peripheral blood lymphocytes were detected by flow cytometry,and changes in the ratio of Th17/Treg in each group were analyzed.Results The hair arsenic contents in control,mild,moderate,and severe arsenic poisoning groups [median (quartile)] were 0.12 (0.08-0.18),0.20 (0.16-0.33),0.25 (0.18-0.41),0.28 (0.21-0.50) μg/g,and the differences were statistically significant between groups (H =52.22,P ＜ 0.01),and the hair arsenic content in each arsenic poisoning group was higher than that of the control group (P ＜ 0.05).The percentages of Th17 cells in peripheral blood lymphocytes of moderate and severe arsenic poisoning groups [(0.42 ± 0.21)％,(0.41 ± 0.23)％] were higher than that of the control group [(0.29 ± 0.16)％,P ＜ 0.05].The percentages of Treg cells in peripheral blood lymphocytes of mild,moderate and severe arsenic poisoning groups [(0.37 ± 0.18)％,(0.31 ± 0.19)％,(0.27 ± 0.18)％] were lower than that of the control group [(0.71 ± 0.20)％,P ＜ 0.05];with respect to the mild arsenic poisoning group,the percentage of Treg cells in severe arsenic poisoning group was reduced (P ＜ 0.05).The ratios of Th17/Treg in mild,moderate and severe arsenic poisoning groups (1.17 ± 0.63,1.56 ± 0.69,1.83 ± 0.85) were higher than that of the control group (0.43 ± 0.22,P ＜ 0.05);compared with mild arsenic poisoning group,the ratio of Th17/Treg in severe arsenic poisoning group was elevated (P ＜ 0.05).Correlation analysis showed that the hair arsenic content was positively correlated with the percentage of Th17 cells in peripheral blood lymphocytes and the ratio of Th17/Treg (r =0.323,0.608,P ＜ 0.05),and negatively correlated with the percentage of Treg cells in peripheral blood lymphocytes (r =-0.486,P ＜ 0.05).Conclusion Coal-burning-borne arsenic poisoning can cause the proportion of Th17 cells in the peripheral blood of patients to increase in lymphocytes,and the proportion of Treg cells in lymphocytes to decrease,which in turn changes the balance of Th17/Treg,resulting in weakened immune tolerance and disorder the regulation of inflammatory response,thus participates in the occurrence and development of arsenic-induced immune damage.
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Objective To investigate the expression of transcription factor forkhead/winged helix transcription factor 3 (Foxp3),immune factor transforming growth factor-beta 1 (TGF-β1),and T-lymphocyte activation related factor interleukin-2 (IL-2) in peripheral blood of patients with coal-burning arsenic poisoning,and to analyze the effects of arsenic exposure on immune function.Methods A case-control study was conducted to investigate 149 cases [94 males and 55 females,(50.69 ± 6.14) years old] of arsenic poisoning in Yuzhang coalburning arsenic poisoning area,southwestern Guizhou Province,and the cases were diagnosed based on the "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015) and confirmed by clinical review.According to skin damage,the patients were divided into mild arsenic poisoning group (39 cases),moderate arsenic poisoning group (54 cases) and severe arsenic poisoning group (56 cases);and 41 cases [12 males and 29 females,(45.76 ± 7.88) years old] of non-arsenic exposed residents from 12 km of Yuzhang coal-burning area were selected as control group.Morning urine and peripheral blood samples were collected with informed consent.Urine arsenic content was measured by inductively coupled plasma mass spectrometry (ICP-MS).Urine arsenic was corrected by creatinine (Cr).Detection of regulatory T cell (Treg)-specific transcription factor Foxp3 gene expression in human peripheral blood was done by real-time fluorescence quantitative PCR,and the levels of Treg-related immune factor TGF-β1 and IL-2 in serum were detected by enzyme linked immunosorbent assay (ELISA).Results The urinary arsenic contents [median (quartile):29.13 (19.75-54.50),31.81 (17.52-53.31),30.51 (18.35-45.76) μg/g Cr] in each arsenic poisoning group were higher than that in the control group [21.62 (17.65-28.44) μg/g Cr,P ＜ 0.05].The expression levels of Foxp3 mRNA in peripheral blood of each arsenic poisoning group [median (quartile):0.58 (0.17-1.27),0.32 (0.17-0.61),0.33 (0.13-0.62)] were significantly lower than that in the control group [0.87 (0.64-1.50),P ＜ 0.05];compared with mild arsenic poisoning group,the expression of Foxp3 mRNA in peripheral blood of moderate and severe arsenic poisoning groups decreased (P ＜ 0.05).The contents of serum TGF-β1 [(13.14 ± 5.19),(12.85 ± 5.51),(12.78 ± 4.95) μg/L] in each arsenic poisoning group were significantly higher than that in the control group [(3.90 ± 1.53) μg/L,P ＜ 0.05].The levels of IL-2 in serum of each arsenic poisoning group [(9.85 ± 5.38),(11.64 ± 6.40),(12.27 ± 6.19) ng/L] were lower than that in the control group [(34.30 ± 4.84) ng/L,P ＜ 0.05];the serum level of IL-2 in severe arsenic poisoning group was higher than that in mild arsenic poisoning group (P ＜ 0.05).Conclusions Arsenic exposure can cause abnormal changes of Treg-specific transcription factor Foxp3 and related immune factors TGF-β1 and IL-2 in peripheral blood of patients.It is suggested that Treg dysfunction may be related to arsenic poisoning.
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<p><b>OBJECTIVE</b>To explore the enhanced sensitivity of leukemia cell line KG-1a to activated immune cell-mediated cytolysis after treated with resveratrol.</p><p><b>METHODS</b>The value of 50% inhibition concentration (IC₅₀) for KG-1a by resveratrol was analyzed using trypan blue staining. Peripheral blood mononuclear cells were separated, and then activated by interleukin (IL)-2 and IL-15. The sensitivity of KG-1a treated with and without resveratrol to activated immune cell-mediated cytolysis was assayed by lactate dehydrogenase (LDH) -releasing assay. The expression of tumor necrosis factor related apoptosis inducing ligand (TRAIL) on the surface of activated immune cells and its receptors (DR4/5 and DcR1/2) on the surface of KG-1a were detected by flow cytometry.</p><p><b>RESULTS</b>Resveratrol could inhibit the proliferation of KG-1a and IC50 at 24 h was 25 mmol/L. At a ratio of 10:1 or 20:1 between effect and target, the cytolytic rates of treated KG-1a by activated immune cells were (55.80 ± 10.88)% and (72.31 ± 13.06)%, significantly higher than (24.96 ± 9.25)% and (37.93 ± 5.21)% of untreated KG-1a (P<0.05). The expression of DR5 on the surface of KG-1a treated with resveratrol was (9.05 ± 3.57)%, significantly higher than (3.11 ± 0.54)% of untreated KG-1a (P<0.05). Conversely, the expression of DcR1 on the surface of treated KG-1a was (13.23 ± 3.56)%, lower than (53.75 ± 10.51)% of KG-1a (P<0.05). When TRAIL pathway on the surface of activated immune cells was blocked, the cytolytic rates of treated KG-1a were (35.97 ± 6.36)% and (49.80 ± 10.68)%, significantly lower than (52.92 ± 6.98)% and (70.73 ± 9.79)% of untreated KG-1a (P<0.05) at the same ratio of effector and target.</p><p><b>CONCLUSION</b>Resveratrol could enhance cytolytic sensitivity of KG-1a by activated immune cells through TRAIL pathway.</p>
Subject(s)
Humans , Male , Cell Line, Tumor , Cell Proliferation , Leukemia , Metabolism , Pathology , Leukocytes, Mononuclear , Allergy and Immunology , Metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand , Metabolism , Receptors, Tumor Necrosis Factor, Member 10c , Metabolism , Stilbenes , Pharmacology , TNF-Related Apoptosis-Inducing Ligand , MetabolismABSTRACT
Object To observe the protective effect of total isoflavones of pueraria DC (TIP) on osteoporosis induced by estrogen deficient rat Methods 42 10 month old female SD rats were bilaterally ovariectomized and 10 animals were made sham operation (Sham) under anesthesia. After 7 d, the ovariectomized rats were divided into 4 groups: untreated control (OVX) group (n=12); 2 treated groups (n= 10 each), one with 100 mg/kg TIP ig and the other with 20 mg/kg TIP ig, and a niylestrol group (E 3) (n= 10) The total body bone mineral content (BMC), and bone mineral density (BMD) and bone biodynamics were detected at 4th and 7th month Results 1 Compared with OVX group, BMC and BMD in TIP 100 mg/kg group were increased by 14 6% and 12.1% at 4th month, by 6 8% and 14 2% at 7th month, while in TIP 20 mg/kg group by 7 8% and 6 9% at 4th month, by 8 6% and 14 9% at 7th month 2 The densities of femur in TIP 100 and 20 mg/kg groups were respectively increased by 3 8% and 3 4%, while those of tibia by 6 8% and 6 3% than that of OVX control group The Ca contents were increased by more than 15% in the TIP treated groups 3 The maximum load and structural strength of femur were increased by 16 1% and 19 4% in TIP 100 mg/kg group and 9 1% and 12 5% in TIP 20 mg/kg group than OVX control group These parameters in tibia were also improved 4 Uterine weights both in TIP 100 and 20 mg/kg groups were almost increased by one fold than OVX group Conclusion TIP can protect osteoporosis induced by ovariectomized rats and these effect may be attributable to its week estrogen like action