SHED-derived exosomes ameliorate hyposalivation caused by Sjögren's syndrome via Akt/GSK-3β/Slug-mediated ZO-1 expression / 中华医学杂志(英文版)

BACKGROUND@#Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The treatment is still challenging. This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth (SHED-exos) in sialadenitis caused by SS.@*METHODS@#SHED-exos were administered to the submandibular glands (SMGs) of 14-week-old non-obese diabetic (NOD) mice, an animal model of the clinical phase of SS, by local injection or intraductal infusion. The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice. Protein expression was examined by western blot analysis. Exosomal microRNA (miRNAs) were identified by microarray analysis. Paracellular permeability was evaluated by transepithelial electrical resistance measurement.@*RESULTS@#SHED-exos were injected into the SMG of NOD mice and increased saliva secretion. The injected SHED-exos were taken up by glandular epithelial cells, and further increased paracellular permeability mediated by zonula occluden-1 (ZO-1). A total of 180 exosomal miRNAs were identified from SHED-exos, and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway might play an important role. SHED-exos treatment down-regulated phospho-Akt (p-Akt)/Akt, phospho-glycogen synthase kinase 3β (p-GSK-3β)/GSK-3β, and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells. Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1, a PI3K agonist. Slug bound to the ZO-1 promoter and suppressed its expression. For safer and more effective clinical application, SHED-exos were intraductally infused into the SMGs of NOD mice, and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and Slug and increased ZO-1 expression.@*CONCLUSION@#Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3β/Slug pathway-mediated ZO-1 expression.

Effects of Weichang'an Pill on contraction of isolated ileum smooth muscles in rats / 中国药理学通报

Aim To investigate the impact and mechanism of Weichang'an Pill(WCA),its ethanol extract(EE),water extract(WE),and active ingredients on the contraction of isolated rat ileum smooth muscles induced by acetylcholine(ACh). Methods In vitro tissue bath experiment,WCA,EE,WE,or their active ingredients were added under the action of ACh,and then the contraction tension of isolated ileum smooth muscle from rats was recorded. The binding affinity ofthe active ingredients to the muscarinic acetylcholine M3 receptor was explored by molecular docking. Results WCA,EE,and WE were able to considerably inhibit the excitatory contraction of the ileal smooth muscles induced by ACh. Costunolide,dehydrocostus lactone,santalol,muscone,emodin,chrysophanol,physcion,crotonoside,magnolol,and honokiol were also significantly effective against ACh-induced ileal smooth muscle contraction. Conclusions WCA,EE,WE,and their active ingredients may help to promote intestinal smooth muscle relaxation by blocking the binding of the M3 receptor on the membrane of ileal smooth muscle with ACh.

Rapamycin and Paclitaxel Affect Human Aortic Smooth Muscle Cells-Derived Foam Cells Viability and Proliferation

Abstract Introduction: Drug-eluting stents (DES) coated with rapamycin or paclitaxel as antiproliferative substances significantly reduced the incidence of clinical restenosis and had fewer side effects after percutaneous coronary intervention. However, DES coated with rapamycin or paclitaxel still cause restenosis due to abnormal tissue growth which remained a therapeutic problem, particularly in certain subgroups, possibly due to drug concentrations. This study examined the impact of different concentrations of rapamycin and paclitaxel on cytokine, cell viability and proliferation in human aortic smooth muscle cells (HASMC)-derived foam cells. Methods: The foam cell model was established in vitro by incubating HASMC with 20 µg/mL oxidized low-density lipoprotein (ox-LDL) for 48 hours. Subsequently, foam cells were treated with different concentrations (0.01 µg/mL, 0.1 µg/mL, 0.5 µg/mL, 1 µg/mL, 5 µg/mL and 10 µg/mL) of rapamycin or paclitaxel for 48 hours, to measure cytokine, cell viability and proliferation by ELISA and MTT, respectively. Finally, viability and proliferation were measured by MTT after the foam cells were treated with 1 µg/mL rapamycin or paclitaxel combined with cytokine antibody for 48 hours. Results: After incubation of HASMC with ox-LDL, the ratios of cholesterol ester and total cholesterol increased significantly (55.29%) (P<0.01). Lipid staining with Oil Red O showed many lipid vacuoles and red dye particles in the cells. Meanwhile, cell viability and proliferation significantly increased compared with the control. This indicated that HASMC had been transformed into foam cells (P<0.01) while rapamycin or paclitaxel concentrations ≥0.1 µg/mL can significantly decrease the foam cell proliferation (P<0.05 or P<0.01), and 1 µg/mL of rapamycin or paclitaxel appeared the most effective concentration. As for cytokines, rapamycin or paclitaxel concentrations ≥1 ug/mL could significantly increase the level of inflammatory cytokines IL-6 (P<0.05 or P<0.01), which was enhanced with the increase of drug concentration. However, rapamycin or paclitaxel concentrations ≥1 µg/mL could significantly reduce the levels of anti-inflammatory cytokines IL-35 and transforming growth factor beta (TGF-β) (P<0.05 or P<0.01), which decreased with the increase of drug concentration. In addition, rapamycin or paclitaxel combined with anti-IL-1β, anti-IL-6, anti- TNF-α or anti-IL-35 had no significant effect on foam cell proliferation compared to the drug alone. However, rapamycin or paclitaxel combined with anti-IL-10 or anti-TGF-β can significantly enhance foam cell proliferation (P<0.01). In addition, there was no difference in the effects of the same concentrations of rapamycin and paclitaxel on foam cells. Conclusion: Although rapamycin or paclitaxel can reduce foam cell proliferation, too high or too low concentrations could decrease effectiveness. In particular, a high dose can induce foam cells to increase inflammatory cytokines secretion, reduce anti-inflammatory cytokines secretion, and thus affect the inhibiting proliferation. For rapamycin- and paclitaxel-eluting stents, this conclusion may explain the clinical observation of in-stent restenosis after percutaneous coronary intervention. DES coated with an appropriate concentration of rapamycin or paclitaxel may, at least to some extent, contribute significantly to reducing incidence of late in-stent restenosis.

Efficacy and safety of Nocardia rubra cell wall skeleton for the treatment of erosive oral lichen planus / 北京大学学报(医学版)

OBJECTIVE@#To observe the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) for the treatment of erosive oral lichen planus (EOLP).@*METHODS@#Sixty patients with clinically and pathologically diagnosed EOLP were randomly divided into the experimental group and control group according to the random number. Patients in the experimental group were treated with lyophilized powder containing Nr-CWS combined with normal saline. Patients in the control group received topical placebo without Nr-CWS combined with normal saline. Changes in the EOLP lesion area and the patient's pain level were recorded at the timepoints of weeks 1, 2, and 4 after the two different treatments, respectively. The changes of the patient's REU scoring system (reticulation, erythema, ulceration), the visual analogue scale and the oral health impact score (OHIP-14) were compared between the experimental group and control group after treatment, and the safety indicators of the two groups at the initial diagnosis and after 4 weeks' treatment were also observed, respectively.@*RESULTS@#Totally, 62 patients with clinically and pathologically diagnosed EOLP were enrolled, 2 of whom were lost to the follow-up, with 31 in the experimental group, and 29 in the control group. The mean age of the experimental group and control group were (52.9±12.4) years and (54.07±12.40) years, respectively. There was no significant difference in the oral periodontal index between the experimental group and control group. In the experimental group, the erosive area of oral lichen planus was significantly reduced 1, 2, and 4 weeks after the Nr-CWS's treatment (P < 0.05), the reduction rate was 81.75%, the patient's pain index was also decreased (P < 0.05), and in addition, the OHIP-14 was reduced (P < 0.05). The changes of the REU scoring system, the visual analogue scale and the OHIP-14 were significantly different between the experimental group and control group after treatment. There was no significant difference in the safety index between the two groups.@*CONCLUSION@#The priliminary data show that the Nr-CWS is effective and safe to treat EOLP.

Advances on treatment of allergic disease by isoflavonic phytoestrogens / 中国药理学通报

Isoflavone phytoestrogen,which is one of the biologi-cal flavonoids, has effect on immune system. Previous research has demonstrated that isoflavone phytoestrogens improve allergic symptom via sustaining Th1/Th2 balance, regulating immune cells and increasing the host on the food of the trigger tolerance effects. This review provides information for the effect of isofla-vone phytoestrogens on allergic disease and its mechanism, ho-ping to promote its research and utilization.

Advances on epithelial mesenchymal transformation and airway remodeling of asthma / 中国药理学通报

Bronchial asthma is a respiratory system disease char-acterized by airway remodeling as a pathological basis. Repeated inflammatory infiltration and tissue damage repair can lead to airway remodeling. At present,the mechanism of airway remod-eling is not comprehensive. Studies have shown that epithelial-mesenchymal transition (EMT) plays an important role in the genesis and development of airway remodeling. Airway epithelial cells can be induced to mesenchymal transition through a variety of secretion factors and signaling pathways,leading to airway re-modeling in asthma. This review summarizes the study of EMT and airway remodeling in asthma,providing a reference for clini-cal follow-up treatment and research.

Transperitoneal versus extraperitoneal robot-assisted radical prostatectomy for localized prostate cancer / 中华男科学杂志

Objective@#To compare the clinical effects of transperitoneal (Tp) versus extraperitoneal (Ep) robot-assisted radical prostatectomy (RARP) in the treatment of localized prostate cancer.@*METHODS@#We searched PubMed, EMBASE, Web of Science, EBSCO, Cochrane Library, Wanfang, CNKI, and CBM for the articles comparing the clinical effect Tp-RARP with that of Ep-RARP in the treatment of localized prostate cancer published from January 2000 to November 2016. All the articles must meet the inclusion criteria, that is, dealing with at least one of the following aspects: operation time, intraoperative blood loss, postoperative catheterization time, length of bed confinement, perioperative complications, positive surgical margins, bowel-related complications, postoperative anastomotic leakage, and postoperative urinary continence. We subjected the data obtained to statistical analysis using the RevMan5.3 software.@*RESULTS@#Two randomized controlled trials and six case-control studies were included in this meta-analysis, involving 451 cases of Tp-RARP and 676 cases of Ep-RARP. Compared with Tp-RARP, Ep-RARP showed significantly shorter operation time (WMD = 21.39, 95% CI: 7.54－35.24, P = 0.002), shorter length of bed confinement (WMD = 0.85, 95% CI: 0.61－1.09, P <0.001), and lower rate of bowel-related complications (RR = 9.74, 95% CI: 3.26－29.07, P <0.001). However, no statistically significant differences were found between the two strategies in intraoperative blood loss (WMD = －8.12, 95% CI: －27.86－11.63, P = 0.42), postoperative catheterization time (WMD = 0.17, 95% CI: －0.55－0.21, P = 0.38), or the rates of perioperative complications (RR = 1.34, 95% CI: －0.97－1.87, P = 0.08), positive surgical margins (RR = 1.24, 95% CI: 0.95－1.61, P = 0.12), anastomotic leakage (RR = 0.98, 95% CI: 0.46－2.10, P = 0.95), urinary continence at 3 months (RR = 0.96, 95% CI: 0.91－1.00, P = 0.05) and urinary continence at 6 months (RR = 1.00, 95% CI: 0.97－1.02, P = 0.82).@*CONCLUSIONS@#Ep-RARP has the advantages of shorter operation time, shorter length of bed confinement and lower rate of bowel-related complications over Tp-RARP, and therefore may be a better option for the treatment of localized prostate cancer. However, more multi-centered randomized controlled clinical trials are needed for further evaluation of these two approaches.

Expression of stromal cell-derived factor 1 in the acute ischemia-reperfusion injury and its relationship with macrophages / 中华肾脏病杂志

Objective To observe the expression of stromal cell-derived factor 1 (SDF-1) in the kidney after ischemic reperfusion injury (IRI),and explore its relationship with macrophage during the IRI kidney.Methods A total of 28 healthy C57BL/6 male mice were used to establish renal IRI model by clamping both pedicles for 35 min followed by reperfusion.Kidney tissue samples were collected at indicated time points.Renal histological changes were estimated.The expression of SDF-1 was determined by immunohistochemistry,ELISA and real-time PCR.After the liposomal clodronate was injected intraperitoneally,the location of CD68 was observed by immunofluorescence.Renal histology and protein expression of SDF-1 were also detected.Results Compared with sham-operated group,classical tubular damage was found in IRI group,accompanied by a large number of inflammatory cells.The expression of total renal SDF-1 peaked on day 1 and decreased to control levels in the following days.SDF-1 in healthy kidney was localized at cortex,but spread to the corticomedullary area of the kidney during IRI.Compared with IRI groups,elimination of macrophage by injection of liposomal clodronate alleviated renal IRI and down-regulated the expressions of CD68 while up-regulating SDF-1.Conclusions SDF-1 expression is up-regulated in IRI kidney and is associated with macrophage.SDF-1 may play a role in the early phase of acute kidney injury and it may be a new marker in diagnosis of AKI.

Effect of ethylenediaminetetraacetic Acid (EDTA) gel on removing smear layer of root canal in vitro / 中国医学科学杂志(英文版)

FOR smear layer removal from root canal walls, ethylenediaminetetraacetic acid (EDTA) is an effective chelating agent and its efficiency depends upon a lot of factors such as concentration, pH, duration of application, the type of the solution, the root canal length, penetration depth of the material, and hardness of the dentin.The aim of this scanning electron microscopic study was to evaluate the effectiveness of 19% EDTA gel on smear layer removal at different time periods when used as a final step in the irrigation regime.

Systematic review of soy isoflavone supplements on osteoporosis in women

OBJECTIVE@#To clarify the effect of soy isoflavones on prevention of osteoporosis, and the effective dosage of soy isoflavones and its duration.@*METHODS@#Random control trials that investigated the association of soy isoflavones and osteoporosis were included in the meta-analysis by researching MEDLINE, EMBASE and the Chinese Biomedical Database up to October 2011. The Rev Man software was used for all of the statistical analysis.@*RESULTS@#The present meta-analysis found that soy isoflavones significantly increased the bone mineral density by 54% and decreased the bone resorption marker urinary deoxypyridinoline (DPD) by 23% compared to baseline in women. Using random effects model, the effect of isoflavones on bone mineral density (BMD) regarding menopausal status and isoflavone dose revealed higher weighted mean difference changes were found in postmenopausal women and isoflavone dose above 75 mg/d. Subgroup analysis of trials with menopausal status, supplement type, isoflavone dose and intervention duration that used soy isoflavone extracts resulted in significant different overall effect of DPD using by random effects model. Sensitivity analysis indicated that the effect of soy isoflavones on BMD and DPD was robust.@*CONCLUSIONS@#The present meta-analysis reveals that soy isoflavone supplements significantly increase bone mineral density and decrease the bone resorption marker urinary DPD. It shows no significant effect on bone formation markers serum bone alkaline phosphatase. The significant effect of soy isoflavones on BMD and urinary DPD is relative to menopausal status, supplement type, isoflavone dose and intervention duration.

Renal protective effects of sulodexide in diabetic rats and its anti-oxidative mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the renal protective effects of sulodexide and its anti-oxidative stress mechanism in diabetic rats.</p><p><b>METHOD</b>Thirty male SD rats were randomized into 3 equal groups, namely the control group, diabetic group, and sulodexide treatment group. Twelve weeks after establishment of rat diabetic models and administration of sulodexide, the rats were sacrificed for measurement of the urine volume, body mass, kidney mass/body weight ratio, plasma glucose, and glycosylated hemoglobin (HbA1c). Malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) activities in the renal tissue or serum were tested. Electron microscopy was performed to observe the pathological changes in the kidneys.</p><p><b>RESULTS</b>The urine volume, renal mass/body mass ratio, serum glucose, HbA1C, and serum and renal MDA levels all significantly increased in the diabetic rats in comparison with the normal controls (P<0.05). But the body weight and activities of SOD, CAT, and GSH-PX in the renal tissue in the normal control group were significantly higher than those in the diabetic and sulodexide group. After 12 weeks of sulodexide treatment, SOD, CAT, and GSH-PX activities in the renal tissue of rats were significantly increased in comparison with those in the diabetic rats (P<0.05). Electron microscopy showed obvious irregular thickening of the glomerular capillary basement membrane in the diabetic group with vacuolization in the mitochondria in the epithelial cells, and such pathological changes were significantly alleviated in the sulodexide treatment group.</p><p><b>CONCLUSIONS</b>Sulodexide can effectively lower the urinary albumin excretion rate, improve the ultrastructural renal pathologies and prevent glomerular basement membrane thickening in diabetic rats, probably in association with the reduction of the MDA levels and enhancement of SOD, CAT, and GSH-PX activities.</p>

Estrogen receptor alpha gene polymorphism associated with type 2 diabetes mellitus and the serum lipid concentration in Chinese women in Guangzhou / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha (ERalpha) gene (also named ESR1), including the XbaI and PvuII restriction enzyme polymorphisms of ESR1, which may be involved in disease pathogenesis. The aim of this study was to determine whether ERX gene polymorphisms are associated with type 2 diabetes mellitus and serum lipid level.</p><p><b>METHODS</b>Two hundred and ninety-nine patients with type 2 diabetes mellitus were compared with three hundred and forty-one health controls of Guangzhou in China, both were male and postmenopausal female residents at 51 - 70 years. ESR1 genotyping was performed using polymerase chain reaction (PCR) and PvuII and XbaI restriction fragment length polymorphism (PCR-RFLP) analysis.</p><p><b>RESULTS</b>ESR1 allelic frequencies of P, p and X, x alleles were 0.408, 0.592; 0.360, 0.640 in the type 2 diabetes mellitus group and 0.318, 0.682; 0.328, 0.672 in the control group, respectively. In case-control study, there was significant difference in PvuII, but not XbaI, allele frequency between the type 2 diabetes mellitus and control groups (P = 0.001 and P = 0.122). When the group was separated into men and women, the difference was significant in women (P < 0.001) but not in men (P = 0.854) with the PvuII genotype, and the effect of PvuII variant on the development of type 2 diabetes mellitus was improved with aging. In addition, PvuII genotype was associated with blood glucose [fasting blood glucose (FBG), postprandial blood glucose (PBG)] and serum lipid [total cholesterol (TC) and low density lipoprotein (LDL)-c] concentration in healthy women.</p><p><b>CONCLUSIONS</b>PvuII polymorphism of ESR1 increases susceptibility to type 2 diabetes mellitus in Chinese Guangzhou women. ESR1 variants may also impact serum lipid metabolism, which might provide a mechanism connecting ESR1 to type 2 diabetes.</p>

Comparison of once daily and twice daily administration of glimepiride with same total dosage in type 2 diabetes / 中华内分泌代谢杂志

A total of 126 patients with type 2 diabetes mellitus were randomized into two groups:one received glimepiride 1 mg twice daily and the other 2 mg once daily.Fasing blood glucose(BG),BG 2 h after meals(breakfast,lunch and dinner)and HbA_(IC)were tested,△and standard deviation of the 4 point BG were calculated.It was found that two kinds of administration of glimepiride were equally effective in decreasing BG and once daily aministration could ease better the fluctuation of BG.