Low-intensity pulsed ultrasound combined with ST36 modulate gastric smooth muscle contractile marker expression via RhoA/Rock and MALAT1/miR-449a/DLL1 signaling in diabetic rats.

BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) combined with acupoint can promote gastric motility of diabetic rats. The switch of gastric smooth muscle cell (GSMCs) phenotype was related to the diabetes-induced gastric dysfunction, but the mechanism is not clearly elucidated. This study was aimed at exploring the underlying mechanism of LIPUS stimulation application in diabetic gastroparesis rats. METHODS: In this study, Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DGP), and LIPUS-treated group (LIPUS). LIPUS irradiation was performed bilaterally at ST36 for 20 min per day for 4 weeks. The gastric emptying rate was measured by ultrasound examination. Contraction ability of GSMCs was assessed by muscle strip experiment. The expression of related proteins or mRNAs including α-SMA, SM22α, MHC, RhoA, Rock2, p-MYPT1, MYPT1, p-MLC, MLC, MALAT1, miR-449a, and DLL1 was detected by different methods such as western blotting, RT-qPCR, immunohistochemistry, and immunofluorescence staining, as appropriate. KEY RESULTS: (a) LIPUS stimulation at ST36 could improve the gastric motility dysfunction of diabetic rats. (b) LIPUS increased RhoA, Rock2, p-MYPT1, and p-MLC expression level. (c) MALAT1 and DLL1 contents were decreased, but the level of miR-449a was increased in the LIPUS group. CONCLUSIONS & INFERENCES: LIPUS may affect the contractile marker expression of gastric smooth muscle through the RhoA/Rock and MALAT1/miR-449a/DLL1 pathway to ameliorate DGP.

Low-intensity pulsed ultrasound at ST36 improves the gastric motility by TNF-α/IKKß/NF-κB signaling pathway in diabetic rats.

BACKGROUND AND AIM: Low-intensity pulsed ultrasound (LIPUS) can effectively regulate the central and peripheral nervous system. However, whether LIPUS could act on acupuncture points to modulate the activity of peripheral nervous has rarely been studied. Our study aimed to investigate whether LIPUS at ST36 could improve gastric emptying in diabetic gastroparesis rats. METHODS: Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DM), and diabetic gastroparesis LIPUS treated group (LIPUS). The body weight and blood glucose were recorded every week. Glucose tolerance, gastric emptying rate, and gastric motility were measured before and after treatment. Gastric motility was assessed by ultrasonic examination and Muscle strip experiment. The expression level of c-Kit was assessed by immunohistochemistry staining. Levels of TNF-α, p-NF-κB p-65, NF-κB p-65, and p-IKKß, IKKß were measured by western blot. RESULTS: We reported LIPUS at an intensity of 0.88 W/cm2 exhibited significant differences in functional recovery of gastric delayed emptying in diabetic rats. Through ultrasound gastric motility functional testing and analysis of gastric antral smooth muscle strips indirectly and directly proved the effectiveness of LIPUS for the recovery of gastric delayed emptying. Pathological analysis and western blot indicated that the mechanism by which LIPUS applied to ST36 improved gastric motility may be partially attributed to the inhibition of the TNF-α/IKKß/NF-κB signaling pathway, thereby rescuing the damaged interstitial cells of Cajal network. CONCLUSION: LIPUS at ST36 improved the gastric motility and rescued the damaged networks of interstitial cells of Cajal. LIPUS may have a promising therapeutic potential for diabetic gastroparesis.

The Influence of Diabetes, Hypertension, and Hyperlipidemia on the Onset of Age-Related Macular Degeneration in North China: The Kailuan Eye Study / 生物医学与环境科学（英文）

Objective@#To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD.@*Methods@#A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD.@*Results@#The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD.@*Conclusion@#There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.

Research Progress in Cell-Culture Models of Blood-Brain Barrier / 中国药学杂志

Studies of blood-brain barrier (BBB) play an important role in the R&D of new drugs for neurological disorders. Cellculture models of blood-brain barrier are helpful to study the functions and biological properties of the major BBB components, including brain microvascular endothelial cells, astrocytes, and pericytes, observe and analyze different components' reactions during the drug treatment, optimize the dosing progress, and reduce toxicity. According to the properties of individual BBB components, we summarized several widely used in vitro models of BBB, including monolayer models, co-culture models and the newly developed microfluidic-based models. By comparing their advantages and disadvantages, we provided suggestions on the selection of BBB models according to different research purposes.

Effect of artesunate on expressions of Toll-like receptor 4 and interleukin-8 in renal tissues of diabetic nephropathy rats / 天津医药

Objective To investigate effect of artesunate on expressions of Toll-like receotor-4 (TLR4) and interleu?kin-8 (IL-8) in renal tissue of diabetic nephropathy rats. Methods Male SD rats of over 200 g in body weight (n=45) were injected with low dosage streptozotocin and fed with high fat and sucrose diets to establish diabetes nephropathy (DN) model. Among all rats of successful model, thirty-two were randomly selected and divided into four groups (n=8 in each group), Mod?el group (Group B), Artesunate at high dose treatment group [30 mg/(kg · d)] (Group C), Artesunate at low dose treatment group [10 mg/(kg·d)] (Group D), Enalapril treatment group [10 mg/(kg·d)] (Group E). Another eight rats without STZ injec?tion whose body weight is under 200 g were assigned as Normal group (Group A). Then, rats in Group A and B were given the same volume of normal saline [10 mg/(kg·d)] while rats in Group C, D and E were given 30 mg/(kg·d) Artesunate, 10 mg/(kg·d) Artesunate and 10 mg/(kg · d) Enalapril respectively intragastrically for consecutive 12 weeks. Fasting blood glucose, body weight, kidney index, 24-hours proteinuria, serum creatinine (Cr) and blood urea nitrogen (BUN) were measured. Expression level of TLR4 in renal tissue of rats were examined by Western blot;ELISA was used to quantify the concentration of IL-8 in serum and renal tissue of rats. Results Compared with rats in Group A, the levels of Fasting blood glucose, kidney index , 24-hours proteinuria, Cr and BUN as well as the level of TLR4 in kidney, levels of IL-8 in serum and kidney all significant?ly increased in rats in Group B, C, D and E(P<0.05). On the other hand, body weight were decreased in rats of Group B, C, D and E compared to rats in Group A(P<0.05). The level of TLR4 in kidney, levels of IL-8 in serum and kidney, 24-hours proteinuria, Cr and BUN in rats of Group C, D and E were significantly lower than those in rats of Group B(P<0.05). Furthermore, compared with rats in Group D, the levels of TLR4 in kidney, IL-8 in serum and kidney, 24-hours proteinuria, Cr and BUN were decreased in rats in Group C and E(P<0.05). Pearson correlation analysis showed that the expression lev?el of TLR4 positively correlated with IL-8 level in serum (r=0.969, P<0.05), IL-8 level in kidney (r=0.972, P<0.05), 24-hours proteinuria(r=0.965, P<0.05), Cr(r=0.944, P<0.05)and BUN(r=0.903, P<0.05). IL-8 level in kidney positively correlated with 24-hours proteinuria(r=0.962, P<0.05), Cr(r=0.929, P<0.05)and BUN(r=0.940, P<0.05). Conclu?sion Artesunate decreases expression of TLR4 and IL-8, reduce 24-hours proteinuria, inhibits the inflammation of the DN,relives the pathological lesions of nephron rats with diabetic nephropathy.

Effects of artesunate on high glucose-induced cell apoptosis, TNF-αand IL-8 expression in renal tubular epithelial cells / 天津医药

Objective To investigate the effects of artesunate (Art) on cell apoptosis, tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) expression induced by high glucose in rat renal tubular epithelial cells (NRK-52E). Methods NRK-52E cells were cultured and divided into normal control group, high glucose group, high glucose with different concen?trations of Art (10 mg/L, 20 mg/L and 30 mg/L) groups, and high glucose with Ena (5 mg/L) group. MTT assay was used to de?tect the cell proliferation. The apoptotic rate was evaluated by flow cytometry with AnnexinV-FITC/PI double stains. The pro?tein levels of TNF-αand IL-8 in the cell culture supernatant were determined using ELISA. Results High glucose inhibit?ed NRK-52E proliferation, induced its apoptosis, and the expressions of TNF-αand IL-8 in the supernatant. Application of Art obviously abolished the effects of high glucose, and the effects of Art were showed in dose-dependent manner. Conclu?sion Art can suppress high glucose-stimulated cell apoptosis, enhance TNF-αand IL-8 expression in NRK-52E cells. The anti-inflammatory action and immune regulation of Art could be a novel approach of treating diabetic nephropathy.

Influences of Artesunate on Renal Function and MCP-1,TNF-αof Diabetic Nephropathy Rats / 医药导报

Objective To investigate the effects of artesunate( Art) on renal function and the expression of monocyte chemotactic protein-1(MCP-1)and tumor necrosis factor-α(TNF-α)in rats with type 2 diabetic nephropathy(DN). Methods Thirty six male SD rats were randomly divided into six groups, six rats in each, as the normal control, model control, low-dose Art, middle-dose Art, high-dose Art groups which were intragastrically administrated with Art at the dose of 10, 20 and 30 mg·kg-1 ·d-1 for consecutive 8 weeks, enalapril group, which were intragastrically administrated with enalapril 10 mg·kg-1 ·d-1 for consecutive 8 weeks. Rats were injected with low dosage streptozotocin and fed with high fat and high sugar diets to establish type 2 diabetic nephropathy rat model. After 8 weeks’ treatment, the plasma glucose, 24-hour urine protein, serum creatinine and blood urea nitrogen were measured to evaluate renal function. The pathological morphology of rats was performed. Immunohistochemistry and enzyme linked immunosorbent assay ( ELISA ) were performed to examine the expression levels of MCP-1 and TNF-α,respectively. Results Compared with the model control group, 24-hour urine protein, serum creatinine, blood urea nitrogen and blood glucose were significantly decreased in the treatment groups (P<0. 01). Art significantly decreased the serum expressions of MCP-1 and TNF-α in low-, middle-, high-dose Art group ( 157. 47 ± 38. 53, 138.65±18.03,105.09±12. 64 and 3. 14±0. 38,2. 58±0. 11,2. 25±0. 16) pg·mL-1, compared with model control group (181.71±23.06 and 3. 98±0. 24) pg·mL-1(P<0. 05). Conclusion Art has beneficial effects on type 2 diabetic nephropathy. The mechanism of which may be related to the inhibition of inflammatory factor MCP-1 and TNF-α,further relive the pathological injury of kidney and delay the progress of diabetic nephropathy to some extent.