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BACKGROUND: Porcine pancreatic islet transplantation is a common treatment for diabetes mellitus, but inflammatory reaction and oxidative stress can lead to poor long-term effect. It has been confirmed that transplantation of porcine bone marrow mesenchymal stem cells with islets can improve graft function. However, it has not been reported that porcine bone marrow mesenchymal stem cells regulate the expression of miR-299-5p in islet cells to regulate the function and survival rate of islet β cells. OBJECTIVE: To investigate the effects of bone marrow mesenchymal stem cells in pigs on functional impairment of islet in pig by regulating the JNK/C-Jun pathway through the miR-299-5p/SIAH1 molecular axis. METHODS: Lipopolysaccharide was used to induce functional impairment of porcine islet cells, which were co-cultured with bone marrow mesenchymal stem cells for 24 hours. Interleukin-6, interleukin-1β, tumor necrosis factor-α, reactive oxygen species, superoxide dismutase and insulin levels in islet cells were detected by ELISA. Hoechst 33258 staining was used to observe apoptosis. Annexin V-FITC/PI was used to detect the apoptosis rate of porcine islet cells. Western blotting was used to detect the expression of SIAH1 and proteins associated with JNK/C-Jun pathway. The expression of miRNAs in porcine islet cells was detected by qPCR. The dual-luciferase reporter gene assay verified the targeting relationship between miR-299-5p and SIAH1. RESULTS AND CONCLUSION: (1) Bone marrow mesenchymal stem cells in pigs inhibited the up-regulation of interleukin-6, interleukin-1β, tumor necrosis factor-α, reactive oxygen species and pro-apoptotic effects, and also inhibited the down-regulation of superoxide dismutase and insulin secretion induced by lipopolysaccharide. (2) Bone marrow mesenchymal stem cells of pigs significantly upregulated miR-299-5p expression. miR-299-5p inhibited activation of the JNK/C-Jun pathway by down-regulating SIAH1 expression. (3) Results indicate that bone marrow mesenchymal stem cells of pigs inhibit the activation of the JNK/C-Jun pathway, inhibit the inflammatory response, oxidative stress and apoptosis of islet cells in pigs, and promote the secretion of insulin by regulating the miR-299-5p/SIAH1 axis, hereby improving the functional damage of porcine islet cells.
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Objective To investigate the role of perioperative antiviral therapy with Entecavir for patients with hepatitis B virus related hepatocellular carcinoma (HBV-HCC) with low serum HBV DNA levels.Methods The HVB-HCC patients were randomly divided into 2 groups.Patients in the antiviral group received Entecavir 4 days before hepatic resection while patients in the control group received no antiviral treatment.The serum HBV DNA,liver function,morbidity and length of hospital stay were compared between the two groups.Results Sixteen patients in the control group (n =44) developed HBV reactivation.On the other hand,only 1 patient in the antiviral group (n =44) developed HBV reactivation.Recovery in liver function in the antiviral group was much faster than the control group,especially for glutamic-pyruvic transaminase level.The antiviral group had significantly lower morbidity and shorter total or postoperative hospitalization (all P ＜ 0.05).Conclusions Patients with HBV-HCC with low levels of HBV DNA have a high risk of developing HBV reactivation in the perioperative period.Perioperative antiviral therapy was safe and efficacious in preventing HBV reactivation,improved liver function,reduced postoperative complications and shortened hospitalization.
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Aim To study the effect of astragaloside (AS-Ⅳ) in CLP-induced septic mice.Methods C57BL/6 mice were randomly divided into the sham group, CLP group and CLP+ AS-Ⅳ group.Two days before operation, AS-Ⅳ (10 mg·kg-1) solution was intragastrically administered into CLP +AS-Ⅳ group, and the other groups were treated with normal saline.A sepsis model was established by cecal ligation and puncture (CLP).Blood, peritoneal fluid and tissue organs were collected at 6 h and 24 h.Neutrophils of blood were purified by Percoll density gradient.Transwell was used to detect the chemotaxis function of neutrophils.The killing activity of neutrophils was detected by coculture with E.coli.Results The survival rate of AS-Ⅳ-pretreated septic mice significantly increased.The number of neutrophils in peritoneal fluid was enhanced markedly.The number of bacteria in the peritoneal fluid, blood and tissue organs such as liver, lung and kidney significantly decreased after AS-Ⅳ pretreatment.The chemotaxis and killing activity of neutrophils increased significantly in AS-Ⅳ-treated mice (P<0.05).Conclusion Astragaloside displays an immunoprotective effect in CLP-induced septic mice, which is related to the upregulation of CXCR2 expression on neutrophils and the increase of neutrophil antibacterial activity.
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Objective To evaluate the effect of spinal cord stimulation (SCS) on the expression of spinal substance P (SP) and calcitonin gene-related peptide (CGRP) in rats with neuropathic pain.Methods Forty-eight male Sprague-Dawley rats, aged 8 weeks, weighing 250-300 g, were randomly divided into 4 groups (n =12 each) using a random number table: sham operation group (S group) , n europathic pain group (group NP), sham electrical stimulation group (N-SCS group) , and SCS group.Neuropathic pain was induced by chronic constriction injury (CCI) in anesthetized rats.The sciatic nerve was exposed, and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 chromic catgut.Electrodes were placed into the epidural space at 5 days after CCI in N-SCS and SCS groups, and in addition, SCS was performed at 12-14 days after CCI in SCS group.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before CCI, and 1, 4, 7 and 14 days after CCI.After measurement of pain threshold at day 14 after CCI, the animals were sacrificed, and the lumbar segments (L4-6) of the spinal cord were obtained for determination of the expression of SP and CGRP in the spinal cord by immunohistochemistry.Results Compared with group S, the MWT was significantly decreased, and the expression of SP and CGRP protein and mRNA was up-regulated in NP, N-SCS and SCS groups (P＜0.05).Compared with group NP, the MWT was significantly increased, and the expression of SP and CGRP protein and mRNA was down-regulated in group SCS (P＜0.05).Conclusion The mechanism by which SCS mitigates neuropathic pain may be related to down-regulated expression of SP and CGRP in the spinal cord of rats.
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Objective To investigate the relationship between the mechanism of mitigation of neuropathic pain by spinal cord stimulation (SCS) and high mobility group protein box-1 (HMGB1)/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway in the spinal cord of rats.Methods Forty-eight male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 4 groups (n =12 each) using a random number table:sham operation group (S group),chronic constrictive injury (CCI) group,sham SCS group (S-SCS group),and SCS group.Neuropathic pain was induced by CCI in the animals anesthetized with intraperitoneal chloral hydrate.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.Electrodes were placed into the epidural space at 5 days after CCI in S-SCS and SCS groups,and in addition SCS was performed at 12-14 days after CCI in SCS group.Paw withdrawal threshold to mechanical stimulation (MWT) were measured at 1 day before operation and 1,4,7,14 days after CCI.After measurement of pain threshold at day 14 after CCI,the animals were sacrificed and the lumbar segments (L4-6) of the spinal cord were obtained for determination of mRNA expression of HMGB1,TLR4,and NF-κB p65 (in the nuclear protein,by real-time fluorescent quantitative PCR),protein expression of TLR4 and NF-κBp65 (by Western blot),and protein expression of HMGB1 (by immunohistochemistry).Results Compared with S group,MWT was significantly decreased after CCI,the mRNA and protein expression of HMGB1 and TLR4 was up-regulated,and the expression of NF-κB p65in the nuclear protein and mRNA was up-regulated in CCI,S-SCS and SCS groups.Compared with CCI group,MWT was significantly increased after spinal cord stimulation,the mRNA and protein expression of HMGB1 and TLR4 was down-regulated,and the expression of NF-κB p65 in the nuclear protein and mRNA was down-regulated in SCS group.Conclusion The mechanism by which SCS mitigates neuropathic pain may be related to inhibition of HMGB1/TLR4/NF-κB signaling pathway in the spinal cord of rats.
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Objective To investigate effects of depression on C-reactive protein ( CRP) and low density lipoprotein ( LDL) levels in patients with coronary artery disease .Methods Eighty coronary heart disease patients with and without depression and 20 coronary heart disease-free cases were selected , CRP and LDL levels were measured and compared among three groups .The correlation of depression scores with CRP and LDL were analyzed .Results Depression self rating scale ( SDS) , and Hamilton Depression Scale ( HAMD) scores of patients with coronary heart disease ( CHD)+depression were 46.22 ±3.90 , and 24.39 ±3.08 ,which were sig-nificantly higher than control group (22.46 ±6.22,10.36 ±4.22) and non-depressed CHD patients (29.36 ±5.34, and 10.30 ± 4.11 ) ( P 0.05 ) .CRP and LDL levels of patients with CHD +depression were ( 24.36 ±3.25 ) mg/L, ( 2.85 ± 1.42 ) mmol/L, which were significantly higher than control group and non-depressed CHD patients ( P <0.05 ) .CRP and LDL lev-els of non-depressed CHD patients were higher than control group ( P <0.05 ) .SDS, and HAMD scores had a positive correlation with CRP, LDL, and heart rate ( P <0.05).Conclusions CHD patients should remain optimistic relaxed state of mind to improve the treatment of coronary heart disease .