Objective:To explore the influence of fermented red ginseng extract (FRGE) in the proliferation of rat glomerular mesangial cells (GMCs) and the degradation of extracellular matrix(ECM)under high sugar stimulation, and to clarify the prevention and treatment effects of FRGE on diabetic nephropathy (DN) and the possible mechanism.Methods:The rat GMCs were cultured and divided into normal concentration of D-glucose (NG) group, high concentration of D-glucose (HG) group and high concentration of D-glucose plus different concentrations (3.75, 7.50, 15.00 mg·L-1) of FRGE groups. The proliferation rates of rat GMCs were detected with MTT,and the type Ⅳcollagen(Col Ⅳ) levels in supernatants of the GMCs were detected by ELISA. The protein expressions levels of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) were detected with Western blotting m ethod.Results:Compared with NG group, the proliferation rate of GMCs in HG group was increased(P<0.01), the Col Ⅳ level was increased(P<0.01),the MMP-2 expression level was decreased, and the TIMP-2 expression level was up-regulated(P<0.01).Compared with HG group, the proliferation rates of GMCs in various FRGE groups were decreased(P<0.01), the Col Ⅳ levels were decreased(P<0.01),the expression levels of TIMP-2 were reduced(P<0.01),and the expression levels of MMP-2 were increased(P<0.01).Conclusion:FRGE can inhibit the proliferation of rat GMCs induced by high sugar and promote the ECM degradation to delay the occurrence and development of DN.

OBJECTIVETo assess complement-mediated myocardial injury on isolated guinea pig working hearts and cardioprotective effects of CD59.

METHODSUsing a modified Langendorff apparatus, isolated guinea-pig working hearts were perfused with a modified Krebs Henseleit buffer containing 3% heat-inactivated human plasma and zymosan (IPZ) (control) (n = 10), 3% normal human plasma and zymosan (NPZ) (n = 10), or 3% normal human plasma and zymosan and 1.5 microg/ml CD59 (NPZC) (n = 10), respectively. Epicardial electrocardiogram (ECG), cardiac output (CO), coronary arterial flow (CF), maximum left ventricular developed pressure (LVP(max)), maximum left ventricular developed pressure increase rate (+ dp/dt(max)), maximum left ventricular developed pressure decrease rate (- dp/dt(max)) and heart rate (HR) were recorded at 0, 15, 30, 45 and 60 min of treatment. After the experiment, immunohistochemical examination was performed to detect the presence of C3a or C5b-9 in the myocardium of the isolated hearts.

RESULTSCompared the IPZ group, hearts treated with NPZ showed a slight depression on ST segments of epicardial ECG at 15 min, a significant elevation between 30 min to 60 min, a decrease in CF, CO, LVP(max), + dp/dt(max) and - dp/dt(max), and an increase in HR at 15 min. The observed alterations in CF, CO, LVP(max), + dp/dt(max) and - dp/dt(max) remained decreased, while the HR remained increased until the end of the protocol. The all above parameters of hearts treated with NPZC were similar to the control group (IPZ) at any given time. Immunohistochemical examination showed positive signals of C3a and C5b-9 in the myocardium of hearts treated with NPZ. C3a was positive in NPZC, and C3a and C5b-9 were negative in IPZ.

CONCLUSIONSActivated human complements directly damage isolated guinea pig working hearts, and CD59 offers a significant protection against the injuries.

Animals ; CD59 Antigens ; pharmacology ; Complement C3a ; antagonists & inhibitors ; metabolism ; Complement Inactivator Proteins ; pharmacology ; Electrocardiography ; Guinea Pigs ; Heart ; drug effects ; physiology ; Immunohistochemistry ; In Vitro Techniques ; Male ; Myocardium ; metabolism ; pathology ; Time Factors

The tumor microenvironment,particularly the hypoxic property and glutathione(GSH)overexpression,substantially inhibits the efficacy of cancer therapy.In this article,we present the design of a magnetic nanoplatform(MNPT)comprised of a photosensitizer(Ce6)and an iron oxide(Fe3O4)/manganese oxide(MnO2)composite nanozyme.Reactive oxygen species(ROS),such as singlet oxygen(1O2)radicals produced by light irradiation and hydroxyl radicals(·OH)produced by catalysis,are therapeutic species.These therapeutic substances stimulate cell apoptosis by increasing oxidative stress.This apoptosis then triggers the immunological response,which combines photodynamic therapy and T-cell-mediated immunotherapy to treat cancer.Furthermore,MNPT can be utilized as a contrast agent in magnetic resonance and fluorescence dual-modality imaging to give real-time tracking and feedback on treatment.

Objective To analyze the characteristics of nerve damage in diabetic peripheral neuropathy by ultrasound and neuroelectrophysiological techniques and provide a basis for early diagnosis and treatment of diabetic peripheral neuropathy. Methods From January 2016 to May 2018, 225 patients with type 2 diabetes admitted to the hospital were divided into DPN group (110 cases) and non-diabetic peripheral neuropathy (NDPN) group (115 cases),and 120 healthy volunteers were as controls. Ultrasound and nerve conduction velocity(NCV) were used to analyze the characteristics of nerve damage in diabetic peripheral neuropathy(DPN). Results Among the three study groups, the sensory nerves conduction velocity and motor nerves conduction velocity of the ulnar nerve, median nerve, and common peroneal nerve were significantly reduced in the DPN group. But in the same group,the ulnar nerve, median nerve, and common peroneal nerve cross-sectional area (CSA) was significantly increased [(8.68 ± 1.89) mm2 vs. (6.79 ± 1.69) and (5.82 ± 1.57) mm2, (10.59 ± 1.82) mm2 vs. (7.98 ± 1.97) and (7.25 ± 1.71) mm2, (21.24 ± 2.53 )mm2 vs. (16.54 ± 2.49) and (15.40 ± 2.20) mm2]. In the measurement of sensory nerve conduction velocity, the abnormalities of ulnar nerve, median nerve and common peroneal nerve were significantly higher than thoseof motor nerve [34.54%(38/110) vs. 18.18%(20/110), 36.36% (40/110)vs. 20.90% (23/110), 52.72% (58/110) vs. 20.00% (22/110)]. In ultrasound and SCV, the proportion of ulnar nerve and median nerve injury was higher in patients aged 45 years or older or patients over 10 years of course (P<0.05). The proportion of median nerve injury was higher in patients with larger MAGE (P < 0.05). In the abnormal performance of ultrasound: the proportion of abnormal ulnar nerve, median nerve and common peroneal nerve in patients with large MAGE was significantly higher than that in patients with small MAGE (P<0.05); the results of ultrasound measurement of CSA showed that the ulnar nerve, median nerve and common peroneal nerve thickening were more obvious in patients with MAGE>4 mmol/L. Conclusions DPN affects sensory nerves first, and the proportion of injury is significantly higher than that of motor nerves; lower limb nerves are more susceptible to damage, compared with upper limb nerves; patients aged 45 years or older or patients with course over 10 years have a higher proportion of ulnar nerve and median nerve damage; patients with larger MAGE (>4 mmol/L) have a higher proportion of median nerve damage. The characteristics above can provide an effective basis for the prevention, diagnosis and treatment of DPN.

Objective To establish the finite element model of upper cervical vertebrae C0-3 with Jefferson fracture, and to analyze the influence of posterior atlantoaxial fusion (PSF) and occipitocervical fusion (OCF) on biomechanical properties of the vertebral body and mechanical conduction of the screw-rod system. Methods Based on CT images, the C0-3 segment Jefferson fracture model of human upper cervical spine was established. PSF, OCF1 and OCF2 internal fixation were performed according to surgical plan in clinic, and 50 N concentrated force and 1.5 N·m torque were applied to bottom of the occipital bone. The stress distribution and range of motion (ROM) of the cervical vertebral body, the maximum stress of the screw-rod system and the stress distribution of the intervertebral disc for C0-3 segment during flexion, extension, bending and rotation of the upper cervical spine were studied. Results Compared with PSF, the ROM of OCF1 and OCF2 vertebral bodies increased, and the stress of the nail rod decreased. OCF had a better fixation effect. Conclusions PSF, OCF1 and OCF2 fixation method can reduce the upper cervical ROM and restore stability of the upper cervical spine, which make stress distributions of the vertebral body and intervertebral disc tend to be at normal level. The research result can provide a theoretical basis for clinical surgery plan.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.