Background. Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods. The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S‐O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2′,7′‐dichlorofluorescin diacetate (DCFH‐DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG. Results. Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 vs. 11.9 ± 0.7; P < 0.05). The expression of RANKL, TNF‐α, IL‐1β, and IL‐6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both P < 0.05). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (P < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM. Conclusions. DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.

To observe the expression of uncoupling protein (UCP2) and its effect on modulation of mitochondrial function and apoptosis of cardiomyocytes exposed to high-glucose. AC16 cardiomyoctyes were randomly divided into normal-glucose group (NG), high-glucose group (HG), HG+ UCP2 siRNA group and HG+ negative control siRNA group.The expression of UCP2, succinodehydrogenase(SDH) activity, ATP content, reactive oxygen species (ROS) generation, cell apoptotic rate, caspase-3 activity and cell viability were detected. Compared with the cardiomyocytes in NG group, the ROS production, apoptotic rate and caspase-3 activity were significantly increased in HG group, accompanying with the decreases in SDH activity, ATP content and cell viability.The expression of UCP2 was increased in HG group. Furthermore, UCP2 siRNA inhibited the expression of UCP2 and aggravated high-glucose induced the ROS production (37.96±1.08 vs 27.68±0.60, P<0.05), cell apoptosis ((25.68±0.78)% vs (17.80±0.99)%, P<0.05), caspase-3 activity ((2.71±0.13)% vs (2.14±0.28)%, P<0.05) and cell inactivation (0.74±0.04 vs 0.62±0.03, P<0.05), but had no impact on SDH activity and ATP content in cardiomyocytes. The up-regulation of UCP2 expression in cardiomyocytes, induced by high-glucose, maybe a protective mechanism for the mitochondrial damage, and UCP2 may inhibit high-glucose induced cardiomyocytes apoptosis.

Atherosclerosis is a severe cardiovascular disease characterized by narrowing of the lumen, plaque formation, and blood flow turbulence as a result of cholesterol and lipid accumulation in the inner lining of arteries. Bishkhapra (Trianthema portulacastrum Linn.) is a well-known common weed belonging to the family Aizoaceae. Several bioactive compounds have been isolated from this weed and widely used against several diseases. The present study evaluated the protective and therapeutic efficacies of T. portulacastrum against atherosclerosis in a rat model. The animals were divided into the sham, control (diabetes- + atherosclerosis-inducing diet), 100 mg/kg T. portulacastrum treatment, 200 mg/kg T. portulacastrum treatment, and positive control groups. Blood glucose, cholesterol, triglyceride, and other lipid parameters, as well as the expression of G-protein-coupled receptor 124 (GPR124), were measured. Glucose, cholesterol, and triglycerides were significantly reduced to near normal levels. The serum levels of fibrinogen, sVCAM-1, and oxidized low density lipoproteins were substantially increased in control rats. Treatment with the T. portulacastrum extract reversed these levels to near normal levels. The mRNA expression of GPR124 was increased by 150% in the control group. However, treatment with T. portulacastrum extract decreased the mRNA expression up to 40% compared with the control group. Rats treated with 100 and 200 mg/kg T. portulacastrum extract showed a decrease in GPR124 protein expression by 9.5% and 33.3%, respectively. Taken together, the results suggest that an extract of T. portulacastrum is effective against atherosclerosis in streptozotocin-induced diabetic rats.