Influence of hepatocyte growth factor-transfected bone marrow-derived mesenchymal stem cells towards renal fibrosis in rats

Background & objectives: Hepatocyte growth factor (HGF) produced by endothelial cells, fibroblasts, fat cells and other interstitial cells, can promote angiogenesis, repair damaged tissues and resist fibrosis. Mesenchymal stem cells (MSCs) are located in bone marrow and secrete a variety of cytokines and are often used in the repair and regeneration of damaged tissues. This study was aimed to investigate the influence of HGF-transfected bone marrow-derived MSCs towards renal fibrosis in rats. Methods: The HGF gene-carrying adenoviral vector (Ad-HGF) was transfected into MSCs, and the Ad-HGF-modified MSCs were transplanted into rats with unilateral ureteral obstruction (UUO). The localization of renal transplanted cells in the frozen section was observed with fluorescence microscope. The Masson's trichrome staining was performed to observe the renal collagen deposition, and the immunohistochemistry was performed to detect the expressions of ?-smooth muscle actin (?-SMA) and HGF in renal tissues. Reverse transcription (RT)-PCR was used to detect the mRNA expressions of ?-SMA, HGF and fibronectin (FN). Results: Ad-HGF-modified MSCs could highly express HGF in vitro. On the post-transplantation 3rd, 7th and 14th day, the 4',6-diamidino-2-phenylindole (DAP)-labelled transplanted cells were seen inside renal tissues. Compared with UUO group, the renal collagen deposition in transplantation group was significantly reduced, and the expressions of ?-SMA mRNA and protein were significantly decreased, while the expressions of HGF mRNA and protein were significantly increased, and the expression of FN mRNA was significantly decreased (P<0.001). Interpretation & conclusions: Trans-renal artery injection of HGF-modified MSCs can effectively reduce the renal interstitial fibrosis in UUO rat model.

Correlation of interleukin-33 with Th cytokines and clinical severity of dry eye disease

Purpose: The purpose of this study is to determine the tear and serum protein levels of interleukin-33 (IL-33) and its correlation with Th cytokines and disease severity in dry eye (DE) syndrome. Methods: Tear and serum samples were collected from 30 healthy volunteers, 30 DE patients with non-Sjogren's syndrome DE (NSSDE) and 30 DE patients with primary SSDE. The eight most frequent symptoms of DE were scored. All patients underwent corneal and conjunctival staining, tear film breakup time (TBUT), and Schirmer I test. The serum and tear levels of IL-33 were measured by enzyme-linked immunosorbent assay. The levels of IL-33 expression and its correlation with Th cytokines and disease severity were also analyzed. Results: We found that symptom scores and corneal staining grade were significantly higher in SSDE group compared with NSSDE and control group, whereas the results of TBUT and Schirmer I test were significantly lower in SSDE group compared with NSSDE and control group. The tear levels of IL-33 were significantly increased in tears of SSDE patients compared with those of controls and NSSDE patients (P < 0.05). Moreover, the elevated tear levels of IL-33 were positively correlated with symptom scores but negatively correlated with tear film breakup time and Schirmer I test in both NSSDE and SSDE patients (P < 0.05). The tear levels of IL-33 of both NSSDE and SSDE patients were also positively correlated with tear levels of IL-4 and IL-5 (P < 0.05). Correlation between the serum levels of IL-33 with Th1/17/Treg cytokines was not found. Conclusion: Elevated tear levels of IL-33 were associated with the Th2 cytokines and disease severity of DE. Therefore, IL-33 may have important roles in the immunopathogenesis of the DE.

Effects of herbal medicine Sijunzi decoction on rabbits after relieving intestinal obstruction

Intestinal obstruction leads to blockage of the movement of intestinal contents. After relieving the obstruction, patients might still suffer with compromised immune function and nutritional deficiency. This study aimed to evaluate the effects of Sijunzi decoction on restoring the immune function and nutritional status after relieving the obstruction. Experimental rabbits (2.5±0.2 kg) were randomly divided into normal control group, 2-day intestinal obstruction group, 2-day natural recovery group, 4-day natural recovery group, 2-day treated group, and 4-day treated group. Sijunzi decoction was given twice a day to the treated groups. The concentration of markers was analyzed to evaluate the immune function and nutritional status. The concentration of interleukin-2, immunoglobulins and complement components of the treated groups were significantly higher than the natural recovery group (P<0.05). The levels of CD4+ and CD4+/CD8+ increased then decreased in the treated groups. The levels of tumor necrosis factor-α and CD8+ were significantly lower than the natural recovery group. The level of total protein in the treated groups also increased then decreased after relieving the obstruction. The levels of albumin, prealbumin and insulin-like growth factor-1 were significantly higher in the treated groups than in the natural recovery group (P<0.05). Transferrin level in the treated groups was significantly higher than the obstruction group (P<0.05). Sijunzi decoction can lessen the inflammatory response and improve the nutrition absorption after relieving the obstruction.

Exercise improved lipid metabolism and insulin sensitivity in rats fed a high-fat diet by regulating glucose transporter 4 (GLUT4) and musclin expression

This study aimed to evaluate the effects of exercise training on triglyceride deposition and the expression of musclin and glucose transporter 4 (GLUT4) in a rat model of insulin resistance. Thirty male Sprague-Dawley rats (8 weeks old, weight 160±10 g) were fed a high-fat diet (40% calories from fat) and randomly divided into high-fat control group and swimming intervention group. Rats fed with standard food served as normal control. We found that 8-week swimming intervention significantly decreased body weight (from 516.23±46.27 to 455.43±32.55 g) and visceral fat content (from 39.36±2.50 to 33.02±2.24 g) but increased insulin sensitivity index of the rats fed with a high-fat diet. Moreover, swimming intervention improved serum levels of TG (from 1.40±0.83 to 0.58±0.26 mmol/L) and free fatty acids (from 837.80±164.25 to 556.38±144.77 μEq/L) as well as muscle triglycerides deposition (from 0.55±0.06 to 0.45±0.02 mmol/g) in rats fed a high-fat diet. Compared with rats fed a standard food, musclin expression was significantly elevated, while GLUT4 expression was decreased in the muscles of rats fed a high-fat diet. In sharp contrast, swimming intervention significantly reduced the expression of musclin and increased the expression of GLUT4 in the muscles of rats fed a high-fat diet. In conclusion, increased musclin expression may be associated with insulin resistance in skeletal muscle, and exercise training improves lipid metabolism and insulin sensitivity probably by upregulating GLUT4 and downregulating musclin.