Objective To investigate the effects of morroniside on the expression of vascular endothelial growth factor (VEGF) and fi-broblast growth factor-2 (FGF-2) in rat cortex after focal cerebral ischemia-reperfusion. Methods 30 male Sprague-Dawley rats were ran-domly divided into sham group, model group, morroniside-low group (30 mg/kg), morroniside-middle group (90 mg/kg) and morroni-side-high group (270 mg/kg). Middle cerebral arteries of rats were occluded for 30 minutes with Longa's method and re-perfused. The ex-pression of VEGF and FGF-2 in the ischemic ipsilateral cortex was detected with Western blotting 7 days after reperfusion. Results The ex-pression of both VEGF and FGF-2 increased in the ischemic ipsilateral cortexin in all the ischemic groups compared with the sham group (P<0.05). The expression of VEGF further increased in a dose-dependent manner in all the morroniside groups compared with that of model group (P<0.05), and the expression of FGF-2 increased in the morroniside-high group (P<0.001). Conclusion Morroniside could increase the expression of VEGF and FGF-2 after ischemia-reperfusion, which might promote angiogenesis.

Objective To explore the effects of morroniside on the expression of CD34 in ipsilateral cortex of rats after focal cerebral isch-emia-reperfusion. Methods 45 male Sprague-Dawley rats were divided into sham group (n=9), ischemia group (n=9), and morroniside groups (low, medium and high dosage groups, n=9). The middle cerebral artery were occluded for 30 minutes, and reperfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg, 270 mg/kg after operation. The expression of CD34 in the isch-emic ipsilateral cortex were detected with immunohistochemistry (n=6) and Western blotting (n=3) 7 days after operation. Results The ex-pression of CD34 increased in the ischemia group compared with the sham group, and further increased in the morroniside groups of high dos-age compared with the ischemia group (F>14.865, P<0.001). Conclusion Morroniside could increase the expression of CD34 in the ischemic ipsilateral cortex after ischemia-reperfusion in rats, which may promote the angiogenesis and neurogenesis after ischemia.

Objective:To investigate the effect of natural hyperoxic environment on liver lipid metabolism and liver function based on the bile acid-farnesoid X receptor pathway in sub-healthy rats.Methods:Forty adult male Wistar rats were randomly divided into control group ( n = 10) and sub-healthy model group ( n = 30). The control group was fed a normal diet, and the model group was fed a high-fat-sugar diet with limited daily activities for 5 weeks. The sub-healthy model was successfully established and the feeding conditions were restored. The hyperoxic intervention group (healthy group) were placed in a natural hyperoxic environment for 7 days. The rats feeding status in the spontaneous recovery group were unchanged. The appearance and exhaustive swimming time were compared before and after in healthy rats. Peripheral blood was collected for biochemical measurement. The fluorescence intensity of FXR and peroxisome proliferator activated receptor α (PPAR α) in liver tissue was detected by fluorescence double staining. Real-time fluorescent semi-quantitative PCR and Western blot were used to detect the RNA and protein expression condition of bile acid-FXR signaling pathway related indicators (FXR, PPARα, and SREBP-1c) in liver tissues. Results:Compared with the control group, the model group had gained body weight, and the vitality was decreased, while triglycerides [TG, (1.18 ± 0.20) mmol/L vs. (0.65 ± 0.12) mmol/L] and total cholesterol [TC, (1.23 ± 0.29) mmol/L vs. (1.00 ± 0.25) mmol/L] level was increased, ( P < 0.05), which suggests the presence of hepatic steatosis. TG and TC level in the healthy group and spontaneous recovery group were lower than the model group, and the differences between the healthy group and the model group were statistically significant ( P < 0.05). Compared with the model group, the expression of FXR and PPARα in the liver of the healthy and the spontaneous recovery group was enhanced, while the expression of the sterol regulatory element binding protein 1c (SREBP-1c) was decreased. FXR and PPARα mRNA levels in the healthy group and the model group were (9.27 ± 0.26 vs. 6.77 ± 0.20), and (9.71 ± 0.21 vs. 7.09 ± 0.24), P < 0.01, respectively. Compared with the model group, spontaneous recovery group mRNA levels were 7.99 ± 0.30 and 8.44 ± 0.28, P < 0.05, respectively. FXR and SREBP-1c protein levels between the healthy group and the model group were (1.30 ± 0.19 vs.0.43 ± 0.28), and (1.56 ± 0.22 vs. 2.43 ± 0.19), P < 0.01, respectively. Compared with the model group, the FXR and SREBP-1c protein levels of the spontaneous recovery group were 0.81 ± 0.33 vs. 2.10 ± 0.38, P < 0.05, respectively. In addition, natural hyperoxic environment had enhanced liver lipid metabolism and improved lipid disorders. Conclusion:The natural hyperoxic environment have the ability to regulate liver lipid metabolism and can improve mild hyperlipidemia to a certain extent.

Objective:To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury.Methods:Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ2 test or t-test was used for statistical analysis. Results:Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference ( χ2 ?=?9.975 0, P ?=?0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference ( χ2 ?= 0.593 5, P ?=?0.441 1). Conclusion:Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.