Elevated expression of periostin in diabetic cardiomyopathy and the effect of valsartan.

BACKGROUND: Periostin, an extracellular matrix protein, plays a significant role in adverse cardiac remodeling. However, no report has documented the function of periostin in left ventricular remodeling of streptozototin (STZ)-induced diabetic rats. The aim of the present study was to observe the expression of periostin in Wistar rat's myocardium of diabetic cardiomyopathy (DCM) and the effect of valsartan on it. METHODS: Immunohistochemistry, real-time polymerase chain reaction, and Western blot analysis were used to determine the degree of expression and location of periostin, transforming growth factor (TGF)-ß1, TGF-ß1 type II receptor (TGF-ß1 R II), and Type I and III collagens in the myocardium of STZ-induced diabetic rats. RESULTS: Periostin, TGF-ß1, TGF-ß1 R II, and Type I and III collagens were significantly increased in the myocardium of diabetic rats compared with control group on both messenger ribonucleic acid and protein levels. In addition, diabetic rats treated with valsartan could have reduced expression of periostin and improved cardiac remodeling of DCM. CONCLUSIONS: Periostin may play a crucial role in cardiac remodeling and myocardial interstitial fibrosis process of DCM and it could be one of the important mechanisms for valsartan to improve the ventricular remodeling of DCM.

Geographic differences in psychological symptoms, sleep quality, and quality of life in patients with inflammatory bowel disease: A multicenter study in China.

OBJECTIVE: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). METHODS: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. RESULTS: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). CONCLUSION: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice.

[Anatomical evaluation and clinical significance of lateral ankle ligament].

OBJECTIVE: To measure anatomy of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) and their relationship to adjacent osseous structures, in order to provide anatomical reference to surgical procedures. METHODS: Twenty-six human ankle cadavers were used in this study. The mean value of length, insertion width, insertion angle and distance to adjacent osseous structures were measured. RESULTS: The lengths of ATFL and CFL were (20.08 ± 2.16) mm and (32.72 ± 9.17) mm. The width of ATFL were (8.75 ± 1.8) mm (proximal) and (9.26 ± 1.34) mm (distal) respectively. The distance of distal ATFL footprint to the upper-surface of talus neck were (12.92 ± 0.93) mm, the distance of proximal ATFL footprint to fibular tip were (11.44±0.61) mm. The width of CFL were (4.76 ± 0.62) mm (proximal) and (5.08 ± 0.77) mm (distal) respectively. The distance of proximal CFL footprint to fibular tip were (3.74 ± 0.55) mm, The distance of distal CFL footprint to the surface of subtalar joint were (12.62 ± 2.08) mm. The insertion angle with fibular axis in lateral view of ATFL and CFL were 81° ± 11°and 47° ± 16° respectively. ATFL in anterioposterior view had 67° ± 7° angle with fibular axis. CONCLUSION: The length and width of ATFL and CFL were relatively constant. The lateral insertion angle was relatively with large variation. These data may provide reference for reconstructing lateral ankle ligaments.

Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes.

BACKGROUND: Patients with diabetes mellitus are at higher risk of myocardial ischemia/ reperfusion injury (MI/RI). Shuxin decoction (SXT) is a proven recipe modi-fication from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" according to the traditional Chinese medicine theory. It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting. However, the underlying mechanism is still unclear. AIM: To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes. METHODS: This paper presents an ensemble model combining network pharmacology and biology. The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT. In parallel, therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB. The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery. The major results of bioinformatics analysis were subsequently validated by animal experiments. RESULTS: According to the hypothesis derived from bioinformatics analysis, SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein (LDL) and inhibiting the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway. Subsequent animal experiments confirmed the hypothesis. The treatment with a dose of SXT (2.8 g/kg/d) resulted in a reduction in oxidized LDL, AGEs, and RAGE, and regulated the level of blood lipids. Besides, the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated, whereas Bcl-2 expression was up-regulated. The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats. CONCLUSION: This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes. Moreover, animal experiments verified that SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.

Polydatin induces apoptosis and autophagy via STAT3 signaling in human osteosarcoma MG-63 cells.

Polydatin, a natural product, is detected in many daily diets, such as grape juices and peanut. Autophagy regulation is recognized as a new potential strategy for cancer therapy, and previous studies demonstrated that polydatin showed remarkable anti-cancer ability. Nevertheless, the capability of polydatin to induce autophagy and its role in anti-osteosarcoma remains obscure. In this study, we investigated the anticancer effect of polydatin on human osteosarcoma cell line MG-63 and its underlying mechanism. Our results indicated that polydatin significantly inhibited proliferation of MG-63 cells in a dose- and time-dependent manner, and increased their apoptosis and autophagic flux. Further experiments showed that polydatin reduced the expression and phosphorylation (Y705) level of STAT3 (Signal transducer and activator of transcription 3), increased the expression of autophagy-related genes (Atg12, Atg14, BECN1, PIC3K3), and therewith triggered autophagic cell death in MG-63 cells. Of note, the cytotoxicity effect of polydatin was rescued by co-treatment with Colivelin (STAT3 activator), suggesting the dependency of MG-63 cells on STAT3 for survival in this process. Moreover, polydatin-triggered autophagy and apoptosis were remarkably reduced following exposure to autophagy inhibitor 3-methyladenine, while cell viability was increased. In conclusion, these data demonstrated that polydatin induced MG-63 cell death through inducing apoptosis, and autophagy which was mediated via the STAT3 signaling. Therefore, polydatin might be a potential clinical drug in the remedy of osteosarcoma.

Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in Rats.

Stem cell therapies for intervertebral disc degeneration have been demonstrated as a promising strategy. Previous studies have shown that human nucleus pulposus cell- (NPC-) derived exosomes can induce the differentiation of mesenchymal stem cells (MSCs) into NP-like cells in vitro. However, the mechanism of MSC differentiation into NP-like cells with the induction of NPC exosomes is still unclear. Here, we verified the induction effects of NPC exosomes on the differentiation of MSCs into NP-like cells. In addition, the Notch1 pathway was downregulated in this process. Then, DAPT and soluble Jagged1 (SJAG) were applied to inhibit or enhance the expression of the Notch1 pathway, respectively, resulting in the upregulation or downregulation of collagen II, aggrecan, and Sox9 in MSCs. Knocking down of Notch1 protein facilitated the effects of NPC exosomes on the differentiation of MSCs into NP-like cells. NPC exosomes were more effective than an indirect coculture system in terms of the differentiation of MSCs into NP-like cells. Inhibition of NPC exosome secretion with Rab27a siRNA prevented the induction effects of an indirect coculture system on the differentiation of MSCs into NP-like cells. Transwell migration assays revealed that NPC exosomes could promote the migration of MSCs. Taken together, the Notch1 pathway was negatively associated with the differentiation of MSCs into NP-like cells with the treatments of NPC exosomes. Inhibition of the Notch1 pathway facilitates NPC exosome-induced differentiation of MSCs into NP-like cells in vitro. NPC exosomes play a key role in the differentiation of MSCs into NP-like cells in an indirect coculture system of NPCs and MSCs.

miR-146a promotes growth of osteosarcoma cells by targeting ZNRF3/GSK-3ß/ß-catenin signaling pathway.

MicroRNA-146a-5p (miR-146a) functions as a tumor suppressor or oncogene involved in multiple biological processes. But, the underlying molecular mechanisms by which miR-146a contributes to osteosarcoma (OS) remain unclear. The correlation of miR-146a expression with clinicopathologic characteristics and prognosis of OS patients was analyzed by Kaplan-Meier and Cox regression analysis. Cell growth in vitro and in vivo was assessed by MTT, cell colony formation and animal models. The target of miR-146a was identified by bioinformatics software and gene luciferase reporter. As a result, miR-146a expression was substantially elevated in OS tissues and was positively associated with the tumor size (P=0.001) and recurrence (P=0.027) of OS patients. Moreover, knockdown of miR-146a suppressed cell proliferation and colony formation in vitro and in vivo. In addition, zinc and ring finger 3 (ZNRF3) was identified as a direct target of miR-146a in OS cells, and was negatively correlated with miR-146a expression in OS tissues. Overexpression of ZNRF3 inhibited cell growth and rescued the tumor-promoting role of miR-146a via inhibition of GSK-3ß/ß-catenin signaling pathway. Taken together, miR-146a may function as an oncogene in OS cells by targeting ZNRF3/GSK-3ß/ß-catenin signaling pathway, and represent a promising biomarker for OS patients.

Tissue-engineered rhesus monkey nerve grafts for the repair of long ulnar nerve defects: similar outcomes to autologous nerve grafts.

Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomorphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve graft.

Chitosan-Coated Diatom Silica as Hemostatic Agent for Hemorrhage Control.

Uncontrolled hemorrhage leads to high death risk both in military and civilian trauma. Current hemostatic agents still have various limitations and side effects. In this study, natural diatom silica obtained from diatomite and diatom culture was purified and developed for hemorrhage control. To improve the biocompatibility and hemostatic performance of diatom silica, a series of chitosan-coated diatom (CS-diatom) was developed. The composition of CS-diatom prepared was optimized by in vitro hemocompatibility and blood coagulation evaluation for that prepared with 0.5%, 1%, 3%, and 5% chitosan. The results demonstrated that the CS-diatom prepared with 1% chitosan exhibited favorable biocompatibility (hemolysis ratio < 5%, no cytotoxicity to MEFs), great fluid absorbility (24.39 ± 1.53 times the weight of liquid), and desirable hemostasis effect (351 ± 14.73 s at 5 mg/mL, 248 ± 32.42s at 10 mg/mL). Further blood coagulation mechanism study indicated that CS-diatom could provide an ideal interface to induce erythrocyte absorption and aggregation, along with activating the intrinsic coagulation pathway and thus accelerated blood coagulation. Benefitting from the multiple hemostatic performances, CS-diatom showed the shortest clotting time (98.34 ± 26.54 s) and lowest blood loss (0.31 ± 0.11 g) in rat-tail amputation model compare to diatomite and diatom as well as gauze and commercial QuikClot zeolite. The results evidenced that the CS-diatom was a safe and effective hemostatic agent and provided a new understanding of nonsynthetic mesoporous materials for hemorrhage control.

Arthroscopic treatment of bony loose bodies in the subacromial space.

INTRODUCTION: Multiple bony loose bodies in the subacromial space caused form cartilage or bone cells and continue to grow. PRESENTATION OF CASE: A 58-year-old man with two-year history of swelling and pain of the right shoulder. He had no history of tuberculosis and rheumatoid arthritis. Magnetic resonance (MR) images showed some bony loose bodies in the subacromial space. The removal of loose bodies and bursa debridement were performed arthroscopically. Histological diagnosis of them was synovitis with fibrous bodies. DISCUSSION: Extra-articular loose bodies is extremely rare, especially in the subacromial space, which maybe originated in the proliferative synovial bursa. Most authors recommend open removal to relive the pain, but there were choice to apply arthroscopy to remove them. CONCLUSION: The mechanism of formation of bony loose bodies is not clear, may be associated with synovial cartilage metaplasia. Arthroscopic removal of loose bodies and bursa debridement is a good option for treatment of the loose body in the subacromial space, which can receive good function.

Lifestyle intervention in non-alcoholic fatty liver disease in Chengyang District, Qingdao, China.

AIM: To evaluate the effect of a 6 and 12 mo lifestyle modification intervention in nonalcoholic fatty liver diseases (NAFLD) in Chengyang District of Qingdao. METHODS: Participants with NAFLD who had resided in Chengyang District for more than 5 years were enrolled in this study. After the 6 and 12 mo lifestyle modification intervention based on physical activity, nutrition and behavior therapy, parameters such as body weight, body mass index (BMI), waist circumference, serum alanine aminotransferase (ALT), aspartate aminotransferase values, serum cholesterol, triglycerides, fasting glucose, fasting insulin and visceral fat area (VFA), the liver-spleen ratio and the homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated and compared between participants with and without the intervention. RESULTS: Seven hundred and twenty-four participants were assigned to the lifestyle intervention group (LS) and 363 participants were assigned to the control group (CON). After the intervention, body weights in the LS group were significantly decreased compared to those in the CON group at 6 mo (11.59% ± 4.7% vs 0.4% ± 0.2%, P = 0.001) and at 12 mo (12.73% ± 5.6% vs 0.9% ± 0.3%, P = 0.001). Compared with the CON group, BMI was more decreased in the LS group after 6 and 12 mo (P = 0.043 and P = 0.032). Waist circumference was more reduced in the LS group than in CON (P = 0.031 and P = 0.017). After the 6 and 12 mo intervention, ALT decreased significantly in the LS group (P = 0.003 and P = 0.002). After 6 and 12 mo, the metabolic syndrome rate had decreased more in the LS group compared with the CON group (P = 0.026 and P = 0.017). After 12 mo, the HOMA-IR score decreased more obviously in the LS group (P = 0.041); this result also appeared in the VFA after 12 mo in the LS group (P = 0.035). CONCLUSION: Lifestyle intervention was effective in improving NAFLD in both 6 and 12 mo interventions. This intervention offered a practical approach for treating a large number of NAFLD patients in the Chengyang District of Qingdao.