Estimation of Lower Limb Joint Angles and Joint Moments during Different Locomotive Activities Using the Inertial Measurement Units and a Hybrid Deep Learning Model.

Using inertial measurement units (IMUs) to estimate lower limb joint kinematics and kinetics can provide valuable information for disease diagnosis and rehabilitation assessment. To estimate gait parameters using IMUs, model-based filtering approaches have been proposed, such as the Kalman filter and complementary filter. However, these methods require special calibration and alignment of IMUs. The development of deep learning algorithms has facilitated the application of IMUs in biomechanics as it does not require particular calibration and alignment procedures of IMUs in use. To estimate hip/knee/ankle joint angles and moments in the sagittal plane, a subject-independent temporal convolutional neural network-bidirectional long short-term memory network (TCN-BiLSTM) model was proposed using three IMUs. A public benchmark dataset containing the most representative locomotive activities in daily life was used to train and evaluate the TCN-BiLSTM model. The mean Pearson correlation coefficient of joint angles and moments estimated by the proposed model reached 0.92 and 0.87, respectively. This indicates that the TCN-BiLSTM model can effectively estimate joint angles and moments in multiple scenarios, demonstrating its potential for application in clinical and daily life scenarios.

Effect of transcutaneous electrical acupoint stimulation on bone loss for patients with foot and ankle fracture: a pragmatic randomized controlled trial.

OBJECTIVE: The aim for this trial was to preliminarily evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) for bone loss in patients with immobilization after surgical fixation of ankle and foot fractures. METHODS: A total of 80 patients with immobilization after surgical fixation of ankle and foot fractures were randomly divided into an intervention group (n=40) or control group (n=40). The intervention group was given TEAS treatment combined with routine orthopedic treatment, and the control group was given only routine orthopedic treatment. The CT attenuation values, bone turnover markers (ALP, PINP, BGP, CTX, Ca/Cr), bone mineral density (BMD), blood phosphorus, and blood calcium were observed and compared between the two groups at 8 weeks. This was a prospective study. The protocol was registered in the Chinese clinical trial registry (No. ChiCTR2000039944). RESULTS: The CT attenuation values of the intervention group decreased more than those of the control group (P<0.05), however the between group differences in ALP, BGP, Ca/Cr, CTX and BMD (all P>0.05) were not statistically significant. Three mild adverse events were recorded. CONCLUSION: TEAS treatment may confer additional benefits for bone loss in patients with immobilization after surgical fixation of ankle and foot fractures. Since this was a pilot study, the efficacy of TEAS requires further evaluation through full-scale randomized controlled trials.

Running vs. resistance exercise to counteract deconditioning induced by 90-day head-down bedrest.

Spaceflight is associated with enhanced inactivity, resulting in muscular and cardiovascular deconditioning. Although physical exercise is commonly used as a countermeasure, separate applications of running and resistive exercise modalities have never been directly compared during long-term bedrest. This study aimed to compare the effectiveness of two exercise countermeasure programs, running and resistance training, applied separately, for counteracting cardiovascular deconditioning induced by 90-day head-down bedrest (HDBR). Maximal oxygen uptake ( V ˙ O2max), orthostatic tolerance, continuous ECG and blood pressure (BP), body composition, and leg circumferences were measured in the control group (CON: n = 8), running exercise group (RUN: n = 7), and resistive exercise group (RES: n = 7). After HDBR, the decrease in V ˙ O2max was prevented by RUN countermeasure and limited by RES countermeasure (-26% in CON p < 0.05, -15% in RES p < 0.05, and -4% in RUN ns). Subjects demonstrated surprisingly modest orthostatic tolerance decrease for different groups, including controls. Lean mass loss was limited by RES and RUN protocols (-10% in CON vs. -5% to 6% in RES and RUN). Both countermeasures prevented the loss in thigh circumference (-7% in CON p < 0.05, -2% in RES ns, and -0.6% in RUN ns) and limited loss in calf circumference (-10% in CON vs. -7% in RES vs. -5% in RUN). Day-night variations in systolic BP were preserved during HDBR. Decrease in V ˙ O2max positively correlated with decrease in thigh (r = 0.54 and p = 0.009) and calf (r = 0.52 and p = 0.012) circumferences. During this 90-day strict HDBR, running exercise successfully preserved V ˙ O2max, and resistance exercise limited its decline. Both countermeasures limited loss in global lean mass and leg circumferences. The V ˙ O2max reduction seems to be conditioned more by muscular than by cardiovascular parameters.

Quercetin alleviates cell apoptosis and inflammation via the ER stress pathway in vascular endothelial cells cultured in high concentrations of glucosamine.

Glucosamine is a possible cause of vascular endothelial injury in the initial stages of atherosclerosis, through endoplasmic reticulum (ER) stress resulting in fatty streaks in the vascular wall. Quercetin is an anti­diabetic and cardiovascular protective agent that has previously been demonstrated to reduce ER stress in human umbilical vein endothelial cells (HUVECs). The present study aimed to investigate whether quercetin prevents glucosamine­induced apoptosis and inflammation via ER stress pathway in HUVECs. The effect of quercetin on cell viability, apoptosis, and protein expression levels of inflammatory cytokines and ER stress markers was investigated in glucosamine­supplemented HUVECs. Quercetin was demonstrated to protect against glucosamine­induced apoptosis, improved cell viability, and inhibited expression of pro­inflammatory factors and endothelin­1. Quercetin treatment also reduced the expression levels of glucose­regulated protein 78, phosphorylated protein kinase­like ER kinase, phosphorylated c­Jun N­terminal kinase and C/EBP homologous protein. In conclusion, quercetin may have auxiliary therapeutic potential against glucosamine­induced cell apoptosis and inflammation, which may be partially due to alleviation of ER stress.

Quercetin protects RAW264.7 macrophages from glucosamine-induced apoptosis and lipid accumulation via the endoplasmic reticulum stress pathway.

It is increasingly recognized that macrophages are a key cell in the development of atherosclerosis. Glucosamine, the product of the hexosamine biosynthetic pathway in diabetes mellitus, can disturb lipid metabolism, induce apoptosis and accelerate atherosclerosis via endoplasmic reticulum (ER) stress in various types of cells. Previous studies have indicated that quercetin possesses antidiabetic, anti­oxidative, anti­inflammatory and anti­apoptotic activities as a flavonoid. Studies have also demonstrated its novel pharmacological properties for inhibiting ER stress. The present study focussed on the effects of quercetin on cell injury and ER stress in glucosamine­induced macrophages. RAW264.7 macrophages were cultured with 15 mM glucosamine, following which the levels of apoptosis, intracellular total and free cholesterol, and apoptosis­ and ER stress­associated proteins were measured in the macrophages treated with or without quercetin. Additionally, the ratio of cholestryl ester/total cholesterol was calculated to observe the formation of foam cells. The results demonstrated that apoptosis and abnormal lipid accumulation in the RAW264.7 cells, which was induced by glucosamine, were significantly reversed by quercetin. In addition, quercetin treatment suppressed the increase of C/EBP homologous protein, and inhibited the activation of JNK and caspase­12, which was induced by glucosamine. Quercetin also increased the expression level of full length activating transcriptional factor 6 and decreased the expression of glucose regulated protein 78. Of note, the beneficial effects of quercetin on the glucosamine­induced RAW264.7 cells were reversed by treatment with tunicamycin. These findings suggest that quercetin may have properties to prevent glucosamine­induced apoptosis and lipid accumulation via the ER stress pathway in RAW264.7 macrophages.

Grape seed proanthocyanidin extracts prevent high glucose-induced endothelia dysfunction via PKC and NF-κB inhibition.

In our study, it has been detected in vivo and in vitro that GSPE reversed high glucose-induced the increase of ICAM-1 and VCAM-1. It is shown that by western blotting detection, GSPE significantly inhibited the activation of NF-κB induced by high glucose while there was significant decrease of the expression of PKC with GSPE intervention. By adding the NF-κB blocker PDTC and the PKC inhibitor peptide 19-31(10(-6) M), no significant difference was found in the levels of VCAM-1 and ICAM-1 among GSPE group, the PKC inhibitor peptide 19-31-added GSPE group and the PDTC-added GSPE group. So the conclusion could be drawn that PKC inhibition must be involved in GSPE decreasing the level of ICAM-1 and VCAM-1.We proved for the first time that GSPE prevented high glucose-induced the increase of ICAM-1 and VCAM-1 by PKC and NF-κB inhibition. These findings show a novel mechanism of the action GSPE preventing endothelial dysfunction, which may have clinical application values.

Effects of grape seed proanthocyanidin extract on renal injury in type 2 diabetic rats.

Grape seed proanthocyanidin extract (GSPE) is known to be an effective natural polyphenol capable of removing free radicals in vivo. It has been reported that GSPE has biological functions including antioxidant, anti-cancer, anti-hyperglycemic, anti-radiation, and prevention and treatment of cardiovascular diseases. This study aims to investigate the effects of GSPE on renal injury in type 2 diabetic rats induced with low-dose streptozotocin and a high-carbohydrate/high-fat diet. Rats (n=12 per group) were administered GSPE at either a low (125 mg/kg · bw), medium (250 mg/kg · bw) or high (500 mg/kg · bw) dose, while control rats and diabetes mellitus group rats received no specific treatment. After 16 weeks, GSPE slightly increased body weight and decreased food consumption, water intake and urine volume in rats. Diabetic rats treated with GSPE demonstrated decreased fasting blood glucose, serum insulin, HbA1c and systolic blood pressure (P<0.05). GSPE significantly improved renal function parameters, reduced the expression of tissue inhibitor of metalloproteinase-1 and also increased the activity of matrix metalloproteinase-9. Moreover, GSPE (particularly at a dose of 500 mg/kg · bw) increased the activity of antioxidant enzymes and reduced the levels of c-reactive proteins (P<0.01) in serum and the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 (P<0.05) in the kidney. These findings suggest that GSPE ameliorates renal injury in type 2 diabetic rats through its antioxidative activity and anti-inflammatory effects.

Comparative studies of oral administration of marine collagen peptides from Chum Salmon (Oncorhynchus keta) pre- and post-acute ethanol intoxication in female Sprague-Dawley rats.

The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol.

Grape seed proanthocyanidin extracts ameliorate podocyte injury by activating peroxisome proliferator-activated receptor-γ coactivator 1α in low-dose streptozotocin-and high-carbohydrate/high-fat diet-induced diabetic rats.

Podocytes are part of the glomerular filtration membrane in kidney and serve to prevent the filtration of protein from the blood. Several evidences suggest that mitochondrial dysfunction plays a critical role in the pathogenesis of diabetic nephropathy and it is an early event in podocyte injury. Mitochondrial dysfunction promotes oxidative stress that can favor the development of podocyte injury. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) was considered to be a major regulator of metabolic homeostasis and mitochondrial function. Some studies indicated that polyphenols may improve mitochondrial dysfunction, maintain the podocyte integrity and have therapeutic effects on glomerular diseases by promoting PGC-1α expression. Our study investigated whether grape seed proanthocyanidin extracts (GSPE), a strong antioxidant, ameliorate podocyte injury by activating PGC-1α in low-dose streptozotocin-and high-carbohydrate/high-fat diet-induced diabetic rats. After 16 weeks of GSPE treatment, GSPE slightly increased the body weight and decreased plasma glucose, food intake, water intake and urine volume in diabetic rats. Further, GSPE significantly decreased 24 h albumin levels and increased the expression of nephrin and podocalyxin. The antioxidant levels were improved and the cellular damage of kidney in diabetic rats was also relieved effectively after the treatment. Moreover, GSPE increased the mRNA expression of mitochondrial biogenesis factors and mitochondrial DNA content. Finally, GSPE activated the expression of PGC-1α, silent mating type information regulation 2 homolog 1 (SIRT1) and AMP-activated protein kinase (AMPK). These results suggest that GSPE ameliorate podocyte injury in diabetic nephropathy by the activation of AMPK-SIRT1-PGC-1α signalling, which appears to inhibit oxidative stress and mitochondrial dysfunction in the kidney.

Proanthocyanidins protect against early diabetic peripheral neuropathy by modulating endoplasmic reticulum stress.

Diabetic peripheral neuropathy (DPN) is the most common and troublesome complication of type 2 diabetes mellitus (T2DM). Recent findings reveal an important role of endoplasmic reticulum (ER) stress in the development of DPN and identify a potential new therapeutic target. Schwann cells (SC), the myelinating cells in peripheral nervous system, are highly susceptible to ER homeostasis. Grape seed proanthocyanidins (GSPs) have been reported to improve DPN of type 1 diabetic rats and relieve ER stress in skeletal muscles and pancreas of T2DM. We investigated the potential role of ER stress in SC in regulating DPN of T2DM and assessed whether early intervention of GSPs would prevent DPN by modulating ER stress. The present study was performed in Sprague-Dawley rats made T2DM with low-dose streptozotocin and a high-carbohydrate/high-fat diet and in rat SC cultured in serum from type 2 diabetic rats. Diabetic rats showed a typical characteristic of T2DM and slowing of nerve conduction velocity (NCV) in sciatic/tibial nerves. The lesions of SC, Ca(2+) overload and ER stress were present in sciatic nerves of diabetic rats, as well as in cell culture models. GSPs administration significantly decreased the low-density lipoprotein level and increased NCV in diabetic rats. GSPs or their metabolites also partially prevented cell injury, Ca(2+) overload and ER stress in animal and cell culture models. Therefore, ER stress is implicated in peripheral neuropathy in animal and cell culture models of T2DM. Prophylactic GSPs treatment might have auxiliary preventive potential for DPN partially by alleviating ER stress.

Functional and morphological effects of grape seed proanthocyanidins on peripheral neuropathy in rats with type 2 diabetes mellitus.

Grape seed proanthocyanidins (GSPs) possess a broad spectrum of pharmacological and therapeutic properties. The aim of this study was to examine the effect of GSPs on functional and morphological abnormalities in the peripheral nerves of rats with type 2 diabetes mellitus. Diabetic rats were induced by two injections of 25 mg streptozotocin/kg body weight and 8 weeks of a high-carbohydrate/high-fat diet. GSPs were then administrated to the rats for 16 weeks. Thermal and mechanical sensitivity thresholds and nerve conductive velocity were measured to evaluate peripheral nerve function. Light microscopy was used with special stains to observe the morphological changes in the central and peripheral nervous systems. Calcium (Ca(2+)) homeostasis and ATPase activities in the sciatic nerves were also determined. In diabetic rats receiving GSP treatment (especially at the 500 mg/kg dose), the abnormal peripheral nerve function and impaired nervous tissues (L4 to L5 spinal cord segments, L5 dorsal root ganglion, and sciatic nerves) were improved to a significant extent. Moreover, 500 mg/kg GSP treatment significantly reduced the concentration of free Ca(2+) and elevated Ca(2+)-ATPase activity in sciatic nerves. These results suggest that GSPs may prevent early functional and morphological abnormalities in the peripheral nerves of rats with type 2 diabetes mellitus.

Grape seed proanthocyanidins ameliorate pancreatic beta-cell dysfunction and death in low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats partially by regulating endoplasmic reticulum stress.

BACKGROUND: It is increasingly being realized that failure of pancreatic beta cells to secrete enough insulin to adequately compensate for obesity and insulin resistance is the primary defects of type 2 diabetes mellitus (T2DM). Pancreatic beta cells possess a highly developed and active endoplasmic reticulum (ER), reflecting their role in folding, export and processing of newly synthesized insulin. ER stress-induced pancreatic beta-cell failure is a novel event in the pathogenesis of T2DM. Some studies with antioxidants indicated a beneficial impact on ER stress. Our previous study found that strong antioxidants, grape seed proanthocyanidins (GSPs), ameliorated ER stress to protect skeletal muscle from cell death in type 2 diabetic rats. The present study continued to investigate the effect of GSPs on beta-cell failure and ER stress in diabetic pancreas. METHODS: Male Sprague-Dawley rats made type 2 diabetic with 2 injections of 25 mg/kg streptozotocin and 8 weeks of the high-carbohydrate/high-fat diet were fed a basal diet with or without GSPs administration for 16 weeks. Oral glucose tolerance, plasma glucose, serum insulin and the score of beta-cell function were measured. Morphological observation was performed by light and electron microscopic analyses. Islet cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling staining. Additionally, the level of insulin and the expression of ER stress markers in pancreatic islets were also studied using immunohistochemical staining. RESULTS: After 16 weeks treatment, the score of beta-cell function and the abnormal oral glucose tolerance of diabetic rats were partially reversed by GSPs treatment. The efficacious effect of GSPs was also manifested in the amelioration of pancreatic damage and ER dilatation by microscopic analyses. Moreover, GSPs treatment increased normal insulin content and decreased the number of apoptotic cells in diabetic islets. Importantly, GSPs treatment partially alleviated ER stress by decreasing some ER stress markers. CONCLUSION: These findings suggest that GSPs might have auxiliary therapeutic potential for pancreatic beta-cell dysfunction and death in T2DM.

Noninvasive estimation of the input function for dynamic mouse 18F-FDG microPET studies.

A new noninvasive estimation method for the plasma time-activity curve, i.e., input function (IF) of the tracer kinetic model in dynamic (18)F-FDG microPET mouse studies, is proposed and validated. This estimation method comprises of four steps. First, a novel constraint nonnegative matrix factorization segmentation algorithm was applied to extract the left ventricle (Lv) and myocardium (Myo) time activity curves (TACs). Second, we modeled the IF as a seven-parameter mathematical equation and constructed a dual-output model of the real TAC in Lv and Myo accounting for the partial-volume and spillover effects. Then, we fit the image-derived Lv and Myo TACs to the dual-output model to estimate the parameters of the IF. Finally, the IF was validated by comparing it to the gold standard IF while considering the delay and dispersion effects. Our method was verified based on 20 mice datasets from the Mouse Quantitation Program database, provided by UCLA. The error of the areas under the curves between the delayed and dispersed estimated IF and the gold standard IF was 7.237% ± 6.742% (r = 0.969), and the error of the (18)F-FDG influx constant Ki of the Myo was 4.910% ± 6.810% ( r = 0.992). The results demonstrated the effectiveness of the proposed method.

Quercetin but not quercitrin ameliorates tumor necrosis factor-alpha-induced insulin resistance in C2C12 skeletal muscle cells.

Skeletal muscle is a major site for glucose metabolism and its injury by cytokines can induce insulin resistance leading to type 2 diabetes. It has been suggested that quercetin may act as an anti-diabetic agent, however, the effects of quercetin on insulin resistance in skeletal muscle remain unknown. We aimed to investigate the role of quercetin and its glycoside, quercitrin in tumor necrosis factor-alpha (TNF-α) induced C2C12 skeletal muscle cell impairment. Quercetin, but not quercitrin moderately attenuated the effects of TNF-α and enhanced the basal and insulin stimulated uptake of glucose in a dose-dependent manner via the activation of the protein kinase B (Akt) and AMP-activated protein kinase (AMPK) pathways. Furthermore, the underlying mechanism also involved the suppression of nuclear factor-κB (NF-κB) signaling and the nitric oxide (NO)/inducible nitric oxide synthase (iNOS) system, downstream of AMPK transduction. In summary, quercetin exhibited its effect of improving glucose uptake and insulin sensitivity in skeletal muscle cells via the two independent signaling pathways of Akt and AMPK, and can be developed as a potential anti-diabetic agent.

Grape seed proanthocyanidin extracts alleviate oxidative stress and ER stress in skeletal muscle of low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats.

Although ER stress in pancreas, liver, and adipose tissue was reported to be a novel event linked to the pathogenesis of type 2 diabetes mellitus, there is much less information on this event in skeletal muscle. Some studies indicated that treatment with antioxidants had beneficial effects on ER stress and diabetes. This study focuses on the effects of a strong antioxidant, grape seed proanthocyanidin extracts (GSPE), on skeletal muscle in diabetic rats induced with low dose streptozotocin- and a high-carbohydrate/high-fat diet. After 16 wk of GSPE treatment, diabetic rats showed decreased plasma glucose levels and insulin resistance. The efficacious effect of GSPE was manifested by the amelioration of muscular damage and dysfunction, as observed by histological examination and periodic acid Schiff staining. Concurrently, calcium overload and the abnormal activities of antioxidant enzymes and ATPases in diabetic muscles were partially reversed by GSPE treatment. GSPE also increased the activity of protein kinase B (a mediator of insulin's metabolic action) and partially alleviated severe ER stress. These findings suggest that GSPE may have auxiliary therapeutic potential for type 2 diabetes mellitus by decreasing oxidative stress and ER stress in skeletal muscle.

Quercetin and quercitrin protect against cytokine­induced injuries in RINm5F ß-cells via the mitochondrial pathway and NF-κB signaling.

Quercetin, existing mostly in its glycoside form quercitrin, is the most widely distributed flavonoid in nature. It possesses various potential effects as an antioxidant, anti-inflammatory for cell damage of ß-cells, however, studies on this topic are limited and controversial. In order to examine the effects of quercetin on type I diabetes mellitus, we investigated the role of quercetin/quercitrin in cytokine-induced ß-cell injuries in RINm5F rat insulinoma cells. Cell viability, glucose-stimulated insulin secretion (GSIS), intracellular reactive oxygen species (ROS), nitric oxide (NO) and inflammation or apoptosis-associated protein expression were measured with or without quercetin/quercitrin treatment. We also compared the differences between the aglycone and the glycoside forms of quercetin, with the aim to shed some light on their structures and transportation into cells. The results showed that quercetin/quercitrin protected against cytokine-induced cell death, improved GSIS, and inhibited ROS as well as NO accumulation. These effects were associated with reduced expression of inducible nitric oxide synthases (iNOS) and inhibited translocation of nuclear factor-κB (NF-κB). Also, quercetin/quercitrin suppressed cytochrome c release from mitochondria and the following alteration of downstream proteins, suggesting that mitochondrial apoptosis was attenuated by quercetin treatment. In summary, quercetin and quercitrin are potential candidates to prevent ß-cell death via the mitochondrial pathway and NF-κB signaling, and quercetin may be more efficacious than quercitrin as an anti-diabetic agent.

Myricetin protects against cytokine-induced cell death in RIN-m5f ß cells.

Cytokine-induced cell death is recognized as a major cause of progressive ß-cell loss. Tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interferon γ (IFN-γ) in combination trigger a series of events that lead to ß-cell death. In the past few decades, the use of myricetin as an anti-inflammatory and cytoprotective agent has gained much attention. The present study focused on the protective roles of myricetin against cytokine-induced cell death in insulin-secreting RIN-m5f ß cells. The results showed that myricetin (especially at concentrations of 10 µM and 20 µM) increased cell viability and decreased cell apoptosis induced by the cytokine mixture of TNF-α (10 ng/mL), IL-1ß (5 ng/mL), and IFN-γ (1000 IU/mL) for 3 days. Moreover, the cytokines increased the total and p65 subunit levels of nuclear factor κB, decreased inhibitor κB α levels, stimulated the accumulation of nitric oxide, increased cytochrome c release from mitochondria, and induced reactive oxygen species generation; myricetin (especially at the concentration of 20 µM) abolished all of these parameters. These results suggest that myricetin might have therapeutic value for preventing ß-cell death.

Effect of polysaccharide from cultured Cordyceps sinensis on immune function and anti-oxidation activity of mice exposed to 60Co.

AIM OF THE STUDY: The present study was designed to investigate the molecular weight (MW), chemical composition and effect of polysaccharide (CS-PS), from the fruiting bodies of cultured Cordyceps sinensis, on immune function and anti-oxidation activity of BALB/c mice exposed to (60)Co. MATERIALS AND METHODS: The MW of CS-PS was determined by gel-filtration. The chemical composition of CS-PS was tested by using gas chromatography-mass spectrophotometer (GC-MS). Mice were administered CS-PS with doses of 50, 100 or 200mg/kg body weight, then exposed to (60)Co. The normal control group and irradiated control group were also used. Four days later, lymphocyte proliferation, activity of macrophage phagocytosis, delayed type hypersensitivity (DTH), concentration of malondialdehyde (MDA), total-superoxide dismutase (SOD) enzyme activity, and cytokine expression in serum from the mice were tested. RESULTS: The average molecular weight of CP-PS was 12 kD. The polysaccharide was composed of mannose, rhamnose, arabinose, xylose, glucose and galactose. Lymphocyte proliferation, the activity of macrophage phagocytosis, DTH and total-SOD enzyme activity in the CS-PS groups were significantly enhanced compared to the irradiated control group. Lipid peroxidation level was significantly reduced in the CS-PS groups compared to the irradiated control group. Levels of cytokine IL-4, IL-5 and IL-17 are also affected in the CS-PS groups compared to the irradiated control group. CONCLUSIONS: CS-PS, a heteropolysaccharide, enhances immunity activity in mice treated by ionizing radiation, through reducing oxidative injury and modulating the secretion of cytokine IL-4, IL-5 and IL-17.

Epigallocatechin-3-gallate protects pro-inflammatory cytokine induced injuries in insulin-producing cells through the mitochondrial pathway.

Pro-inflammatory cytokine-mediated pancreatic ß-cell dysfunction is a key pathological event in type 1 diabetes mellitus. There are few studies about the protection of epigallocatechin-3-gallate (EGCG) against pro-inflammatory cytokine-induced ß-cell apoptosis. To examine the direct effects of EGCG on ß-cells, insulin-producing RINm5F cells were exposed to a combination of recombinant interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), with or without EGCG pretreatment for 24h. Cell death was monitored by the MTT assay. Glucose-stimulated insulin release was measured using radio immunoassay. Intracellular reactive oxygen species was examined with dichlorofluorescein (DCF) fluorescence by flow cytometry. To evaluate RINm5F cells mitochondrial function, change in mitochondrial membrane potential, intracellular ATP levels, and nitric oxide was assessed. The expression of cytochrome c, Bax, Bcl-2, and iNOS proteins was measured by western blotting. In the present study, EGCG pretreatment protected against cytokines inducing cell death and restored glucose stimulated-insulin secretion in RINm5F cells. EGCG reduced the cytokine-induced generation of reactive oxygen species, the loss of mitochondrial membrane potential (Δψm), the release of cytochrome c from the mitochondria, and translocation of Bax protein to the mitochondria from the cytosol. EGCG pretreatment prevented cytokine-induced iNOS overexpression and NO generation. In summary, pro-inflammatory cytokines lead to a reduction of glucose-induced insulin secretion, mitochondrial activity and viability in RINm5F cells. The pro-inflammatory cytokine-induced effects can be prevented by EGCG pretreatment via the mitochondrial pathway.

Oral administration of skin gelatin isolated from Chum salmon (Oncorhynchus keta) enhances wound healing in diabetic rats.

Care for diabetic wounds remains a significant clinical problem. The present study was aimed at investigating the effect of skin gelatin from Chum Salmon on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 48 rats, of which 32 were diabetes. The diabetic rats were orally treated daily for 14 days with skin gelatin from Chum Salmon (2 g/kg) or its vehicle. Sixteen non-diabetic control rats received the same amount of water as vehicle-treated non-diabetic rats. Rats were killed to assess the rate of wound closure, microvessel density (MVD), vascular endothelial growth factor (VEGF), hydroxyproline (HP) contents in wound tissues and nitrate in plasma and wound tissue at 7 and 14 days after wounding. Skin gelatin-treated diabetic rats showed a better wound closure, increased MVD, VEGF, hydroxyproline and NO contents and a reduced extent of inflammatory response. All parameters were significant (P < 0.05) in comparison to vehicle-treated diabetic group. In light of our finding that skin gelatin of Chum Salmon promotes skin wound repair in diabetic rats, we propose that oral administration of Chum Salmon skin gelatin might be a beneficial method for treating wound disorders associated with diabetes.