Oral post-treatment supplementation with a combination of glutamine, citrulline, and antioxidant vitamins additively mitigates jejunal damage, oxidative stress, and inflammation in rats with intestinal ischemia and reperfusion.

INTRODUCTION: Intestinal ischemia and reperfusion (IIR) injury is closely associated with oxidative stress. Evidence shows that oral supplementation with glutamine and citrulline alleviates IIR-induced jejunal damage. We investigated the effects of a combination of glutamine, citrulline, and antioxidant vitamins on IIR-induced jejunal damage, oxidative stress, and inflammation. METHOD: Male Wistar rats that underwent 60 min of superior mesenteric artery occlusion were orally administered glutamine plus citrulline (GC), vitamin C plus E (CE), or a combination of GC and CE 15 min before and 3, 9, and 21 h after reperfusion. Healthy rats without IIR were used as controls. RESULTS: After reperfusion for 24 h, rats with IIR showed lower levels of red blood cells, hemoglobin, serum glucose, and jejunal DNA and increased white blood cell counts compared to controls (1-way ANOVA with the least significant difference, P < 0.05). The IIR-induced decrease in serum albumin and increase in plasma interleukin-6 and jejunal thiobarbituric acid-reactive substances (TBARS) were significantly reversed by GC and/or CE. The results of the 2-way ANOVA indicated that GC was the main factor that increased jejunal villus height and muscularis DNA, and CE was the main factor that increased jejunal muscularis protein and decreased jejunal proinflammatory cytokine levels and myeloperoxidase activity. In addition, GC and CE are the main factors that decrease plasma proinflammatory cytokine levels and the jejunal apoptotic index. CONCLUSION: Oral post-treatment supplementation with glutamine and citrulline, combined with vitamins C and E, may alleviate IIR-induced oxidative stress, inflammation, and jejunal damage.

Ethanol Extracts of Rice Bran and Whole Grain Adlay Seeds Mitigate Colonic Inflammation and Damage in Mice with Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with frequent relapsing inflammation in the colon. Whole grains have been promoted as healthy and sustainable foods; however, the use of whole gains in UC is inconclusive. The aim of this study was to investigate the effects of ethanol extracts of rice bran (RBE) and whole-grain adlay seeds (ADE) on inflammation, oxidative stress, and colonic damage in UC. Male C57BL/6JNarl mice were intra-rectal injected twice with 2,4-dinitrobenzene sulfonic acid to induce (day 0) and reactivate (day 21) UC. Control mice were fed AIN-93M diet (R group) and injected with a vehicle. UC mice were fed AIN-93M diet (UC group) supplemented with RBE (RBE group) or ADE (ADE group) for 21 days. The results showed that the UC group had an increased disease activity index, plasma interleukin (IL)-6 and glutathione levels, microscopic injury scores, and inflammatory cytokine and chemokine levels in the colon and decreased colonic claudin-4 compared to the R group. RBE and ADE supplementation significantly reduced UC-elevated plasma IL-6 and colonic glutathione and pro-inflammatory cytokines and a chemokine. In addition, RBE and ADE supplementation significantly decreased T-helper-cell-associated cytokines in the plasma and colon. Moreover, RBE supplementation increased colonic IL-10 and tight junction protein claudin-4 levels, and ADE supplementation alleviated diarrhea in UC mice. In conclusion, these results suggest that RBE and ADE may mitigate colonic inflammation, oxidative stress, and damage in UC relapse.

Healthy Eating Enhances Intrinsic Capacity, Thus Promoting Functional Ability of Retirement Home Residents in Northern Taiwan.

Healthy aging is defined as the process of developing and maintaining functional ability in older age with intrinsic capacity, the composite of all the physical and mental capacities of an individual, being the core. This study was conducted to explore the intervention effects of improved dietary quality on intrinsic capacity. A prospective single-group interventional quasi-experimental study with 59 functional independent older adults from retirement homes were recruited. Texture-modified plant-based dietary supplements were provided. In addition, dietary intake, functional ability, and intrinsic capacity in vitality, locomotion, cognition, and psychological capacity were assessed. Vitality was captured by nutritional status, muscle strength, and cardiorespiratory endurance. Locomotor capacity was assessed based on the performance of physical fitness in backscratch test, chair-sit-and-reach test, chair-stand test, one-foot-standing test, and gaits peed. Psychomotor capacity and cognition were measured by using 15-item Geriatric Depression Scale (GDS-15) and Mini-Mental State Examination (MMSE), respectively. In a 4-month of intervention, after controlling for baseline values and covariates, participants with higher dietary intervention adherence showed a significant improvement over time in vitality captured by cardiorespiratory endurance (Pinteraction = 0.009) and significant improvement in locomotion captured by gait speed (Pclusters = 0.034). A significant decrease in the chair-stand test (Ptime = <0.001) and MMSE (Ptime = 0.022) was observed during the four months of intervention. Enhanced intrinsic capacity further contributed to the improvement of ADL over time (Pinteraction = 0.034). In conclusion, healthy eating enhances intrinsic capacity in vitality and locomotion thus promoting functional ability among older adults.

Polysaccharides of Grifola frondosa ameliorate oxidative stress and hypercholesterolaemia in hamsters fed a high-fat, high-cholesterol diet.

OBJECTIVES: This study was to evaluate the antioxidant and anti-hypercholesterolaemia activities of Grifola frondosa in hamsters fed a high-fat, high-cholesterol (HFHC) diet. METHODS: G. frondosa, including fruiting bodies (FGF), fermented mycelia (MGF) and polysaccharides extracted from fruiting bodies (FPS), fermented mycelia (MIP) and fermented broth (BEP) were received intragastrically. Lipid profile and antioxidant status in the blood and liver of hamsters were assessed. KEY FINDINGS: FGF decreased weight gain, serum triglycerides and cholesterol and increased hepatic mRNA expression of cholesterol-7α-hydroxylase expression. FGF, MGF, FPS and MIP decreased the HFHC diet-increased area under the curve (AUC) of serum cholesterol. FGF and FPS further decreased AUC of serum triglycerides. When evaluating the redox status of erythrocytes, FPS and MIP increased non-protein sulfhydryl (NP-SH) groups, reduced glutathione (GSH) and catalase activity and FPS further increased GSH peroxidase activity. In the liver, MGF increased NP-SH groups and GSH and decreased triglycerides content. FPS, MIP and BEP decreased oxidized GSH and triglycerides content. Moreover, all treatments alleviated HFHC diet-increased LDL oxidation. CONCLUSIONS: Fruiting bodies of G. frondosa may improve hypercholesterolaemia via increased bile acid synthesis. Additionally, fermented biomass and polysaccharides of G. frondosa may have the potential to prevent hepatic lipid accumulation.

Plant-Based, Antioxidant-Rich Snacks Elevate Plasma Antioxidant Ability and Alter Gut Bacterial Composition in Older Adults.

Plant-rich diets alleviate oxidative stress and gut dysbiosis and are negatively linked to age-associated chronic disorders. This study examined the effects of consuming plant-based, antioxidant-rich smoothies and sesame seed snacks (PBASS) on antioxidant ability and gut microbial composition in older adults. Healthy and sub-healthy older adults (n = 42, 79.7 ± 8.6 years old) in two senior living facilities were given PBASS for 4 months. Blood and fecal samples were collected from these individuals at the baseline and after 2 and 4 months of PBASS consumption. After 2 months, serum levels of albumin and high-density lipoprotein-cholesterol and the ratio of reduced to oxidized glutathione (GSH/GSSG) had increased significantly and erythrocytic glutathione, GSH/GSSG and superoxide dismutase activity had decreased significantly compared with baseline levels (p < 0.05). After 4 months, red blood cells, hematocrit, serum blood urea nitrogen and erythrocyte glutathione peroxidase activity had decreased significantly, whereas plasma and erythrocyte protein-bound sulfhydryl groups had increased significantly. Furthermore, plasma glutathione and total antioxidant capacity were significantly greater after 2 months and increased further after 4 months of PBASS consumption. The results of next generation sequencing showed that PBASS consumption prompted significant decreases in observed bacterial species, their richness, and the abundance of Actinobacteria and Patescibacteria and increases in Bacteroidetes in feces. Our results suggest that texture-modified, plant-based snacks are useful nutrition support to benefit healthy ageing via the elevation of antioxidant ability and alteration of gut microbiota.

Bioactive Components and Possible Activities of Medicinal Mushrooms in Alleviating the Pathogenesis of Nonalcoholic Fatty Liver Disease (Review).

Nonalcoholic fatty liver disease (NAFLD) is a global disease that is closely associated with obesity, type 2 diabetes mellitus, and cardiovascular disease. Excessive fat accumulation, fatty degeneration, and chronic inflammation of the liver activate the progression of NAFLD from simple steatosis to nonalcoholic steatohepatitis and further to liver fibrosis, cirrhosis, and hepatocellular carcinoma. The underlying mechanism for the development and progression of NAFLD is complex and a multiple-hit hypothesis including dietary, environmental, genetic, and epigenetic factors has been raised. Increased de novo lipogenesis, decreased lipolysis, and insulin resistance are associated with the development of NAFLD. Currently, no effective drug therapies are approved for the treatment of NAFLD. Several medicinal mushrooms have been found to have significant weight control and gut microbe modulation activities and antihypertriglyceridemic, antihyperglycemic, antioxidant, and anti-inflammatory effects, which may be useful to prevent and attenuate the development and progression of NAFLD. These beneficial effects are associated with mushrooms' bioactive components, such as polysaccharides, dietary fibers, antioxidants, and other compounds derived from fruiting bodies, cultured mycelium, and/or broth of medicinal mushrooms. This article presents an overview of multiple aspects of NAFLD, including the epidemiology, pathogenesis, management, and treatment. The bioactive components and possible activities of medicinal mushrooms in alleviating the pathogenesis of NAFLD are also reviewed.

Extracellular Polysaccharopeptides from Fermented Turkey Tail Medicinal Mushroom, Trametes versicolor (Agaricomycetes), Mitigate Oxidative Stress, Hyperglycemia, and Hyperlipidemia in Rats with Type 2 Diabetes Mellitus.

The antihyperglycemic activity of extracellular polysaccharopeptides (ePSP) obtained from Trametes versicolor (TV) strain LH-1 has been reported to increase cellular glucose uptake in HepG2 cells in an insulin-independent manner. Evidence indicates that oxidative stress plays a pivotal role in the development of diabetic complications. We aimed to use an in vivo model to investigate the effects of TV-ePSP on oxidative stress and glucose homeostasis in type 2 diabetes mellitus (T2DM). Male Wistar rats fed with a high fat diet followed by a streptozotocin injection to induce T2DM were orally administered water or 0.1, 0.5, or 1.0 g/kg of TV-ePSP per day. After a 4-week administration of TV-ePSP, T2DM rats had attenuated elevations in blood glucose levels, areas under the curve in oral glucose tolerance tests, insulin resistance indices, and serum fructosamine and triglyceride in a dose-dependent manner (P < 0.05, one-way ANOVA). In addition, TV-ePSP significantly alleviated oxidative stress in T2DM rats, as shown by the decreased lipid peroxidation and the increased activity of superoxide dismutase in the plasma, and by the elevated glutathione levels in the plasma and erythrocytes. The antihyperglycemia and antihypertriglyceridemia activities of TV-ePSP may be associated with the improved oxidative stress, suggesting the beneficial effects of TV-ePSP in preventing the development of diabetic complications in T2DM patients.

Fruiting Bodies of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes) Alleviate Diabetes-Associated Oxidative Stress.

Hyperglycemia-induced complications, the major causes of death in diabetes, are closely related to the elevated oxidative stress. Our previous study indicated that fruiting bodies of Ophiocordyceps sinensis attenuated polydipsia and hyperglycemia in diabetic rats. In this study, we further investigated whether the protective effects of O. sinensis on diabetes are associated with improved oxidative status in the circulation and target organs, the liver and kidneys. Male Wistar rats were fed with a semipurified diet supplemented with fruiting bodies (FB group, 1 g/day), carcass (CC group, 1 g/day), fruiting bodies and carcass (CF group, each 0.5 g/day), or placebo (DM and R groups) for 4 weeks (day 1 to 29). On day 15, animals were injected with nicotinamide (200 mg/kg) and streptozotocin (65 mg/kg) to induce diabetes. After the induction of diabetes, fasting blood glucose (FBG) was increased and the diabetes-increased FBG (day 15 to 26) was alleviated by the supplementation of fruiting bodies (p < 0.05, one-way ANOVA). In addition, the contents of vitamins A and C in the liver were significantly higher in the FB group, and the contents of glutathione in the liver and vitamin A and C in the kidneys were significantly higher in the FB, CC, and CF groups than in the DM group. The diabetes-increased glutathione peroxidase activity in the liver was decreased in the CF group. These results suggest that O. sinensis, especially fruiting bodies, may have antihyperglycemic activity associated with the alleviated oxidative stress in the liver and kidneys.

Potential activities and mechanisms of extracellular polysaccharopeptides from fermented Trametes versicolor on regulating glucose homeostasis in insulin-resistant HepG2 cells.

Polysaccharides derived from mushrooms have potential to control blood sugar, reduce insulin resistance and prevent diabetic complications. The intracellular polysaccharopeptides of Trametes versicolor (TV) have been used as immunologic and oncologic adjuvants. The aim of this study was to investigate the potential activities and mechanisms of extracellular polysaccharopeptides (ePSP) obtained from TV strain LH-1 on regulating glucose homeostasis. Human hepatoma HepG2 cells incubated with normal glucose (5.5 mM, NG model), high glucose (33 mM, HG model), or high glucose (33 mM) plus high insulin (10-7 M, HGI model) concentrations were administered with TV LH-1 ePSP (50, 100, and 1000 µg/ml) for 24 hr. Glucose uptake of HepG2 cells, determined by flow cytometry, was significantly decreased in the HG and HGI models with insulin stimulation, suggesting insulin resistance of these cells; however, ePSP reversed this decrease in a dose-dependent manner (one-way ANOVA, p<0.05). In the HG and HGI models, ePSP significantly increased glycogen content, insulin receptor substrate-2 protein and phosphorylated AMP-activated protein kinase (AMPK), as determined by western blot analysis. In addition, ePSP significantly increased glucokinase in the NG and HG models, increased membrane glucose transporter-1 and decreased glycogen synthase kinase-3ß in the HGI model, and increased glucose-6-phosphatase in the NG and HGI models (one-way ANOVA, p<0.05). In summary, TV LH-1 ePSP may elevate cellular glucose uptake to regulate glucose homeostasis via the activation of AMPK and glycogen synthesis in an insulin-independent manner. These results suggest that TV LH-1 ePSP may be a nutraceutical with anti-hyperglycemic activity.

Cordycepin and a preparation from Cordyceps militaris inhibit malignant transformation and proliferation by decreasing EGFR and IL-17RA signaling in a murine oral cancer model.

Cordyceps militaris (CM) and its active ingredient cordycepin have been reported to inhibit tumor growth, but the mechanisms are not fully understood. This study used a mouse model for oral cancer and a cell line, 4NAOC-1 derived from the model to study the mechanisms. Our results show that a CM preparation (CMP) can significantly inhibit tumor development and malignant transformation in the model. In vitro data indicate that CMP and cordycepin can inhibit 4NAOC-1 cell proliferation, either anchorage-dependent or -independent. Cordycepin can also increase cell apoptosis, and decrease cell mitosis and EGFR signaling. In accordance, CMP treatment can significantly decrease the levels of ki-67 and EGFR signaling molecules in cancer tissues. We also found that the levels of IL-17A in cancer tissues of control mice were significantly increased, and CMP inhibited these levels. IL-17A can stimulate cancer cell proliferation, which can be suppressed by cordycepin. Furthermore, cordycepin can reduce the expression of IL-17RA and its downstream signaling molecules. Moreover, CMP and cordycepin can significantly decrease IL-17A production in vitro and in vivo. Finally, CMP and its ingredients can enhance tumoricidal activities with increase in IFN-γ and TNFα, and decrease PD-L1 expression. In conclusion, CMP and its ingredient cordycepin can inhibit tumor growth and malignant transformation in a mouse model for oral cancer via inhibition of EGFR- and IL-17RA-signaling and enhancement of anti-tumor immunity.

Oral Citrulline Mitigates Inflammation and Jejunal Damage via the Inactivation of Neuronal Nitric Oxide Synthase and Nuclear Factor-κB in Intestinal Ischemia and Reperfusion.

BACKGROUND: Intestinal ischemia and reperfusion (I/R) is a life-threatening emergency accompanied by inflammation and organ damage. We compared the mechanisms and the effects of arginine, citrulline, and glutamine on inflammation and intestinal damage. MATERIALS AND METHODS: Male Wistar rats underwent 60 minutes of superior mesenteric artery occlusion and either 3 (I/R3) or 24 (I/R24) hours of reperfusion and were orally administered vehicle, arginine, citrulline, or glutamine 15 minutes before reperfusion and at 3, 9, and 21 hours of reperfusion. RESULTS: I/R3 rats experienced jejunal damage and apoptosis, and I/R24 rats had liver dysfunction compared with normal rats (one-way ANOVA, P < .05). Arginine and citrulline administrations improved jejunal morphology, and citrulline and glutamine administrations alleviated the loss of jejunal mass in I/R3 rats. I/R3-increased circulating nitrate/nitrite (NOx), tumor necrosis factor-α, and interleukin-6 were significantly decreased by citrulline, glutamine and citrulline, and arginine, glutamine, and citrulline, respectively. These amino acids decreased plasma NOx and interferon-γ in I/R24, decreased jejunal neuronal nitric oxide synthase (NOS) protein in I/R3 rats, and alleviated jejunal apoptosis in I/R3 and I/R24 rats. In addition, the jejunal phosphorylated to total nuclear factor-κB (NF-κB) ratio was decreased by arginine and citrulline in I/R24 rats. CONCLUSION: Oral administration of arginine, citrulline, and glutamine may alleviate systemic inflammation, jejunal apoptosis, and neuronal NOS in intestinal I/R. Citrulline may further attenuate jejunal damage by preserving jejunal mass, partially via the inactivation of NOS and the NF-κB pathway. In conclusion, oral citrulline may have more benefits than arginine and glutamine in mitigating intestinal ischemia and reperfusion-induced adverse effects.

The Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester Diminishes the Immunomodulatory Effects of Parental Arginine in Rats with Subacute Peritonitis.

The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days. Non-surgical and sham-operated rats with no cecal puncture were given a chow diet and parenteral nutrition, respectively. Parenteral feeding elevated the white blood cell numbers and subacute peritonitis augmented the parenteral nutrition-induced alterations in the loss of body weight gain, splenomegaly, and splenocyte decreases. Parenteral arginine significantly increased the B-leukocyte level, decreased the natural killer T (NKT)-leukocyte and splenocyte levels, alleviated the loss in body weight gain and total and cytotoxic T-splenocyte levels, and attenuated the increases in plasma nitrate/nitrite and interferon-gamma production by T-splenocytes. L-NAME infusion significantly decreased NKT-leukocyte level, tumor-necrosis factor (TNF)-alpha production by T-splenocytes and macrophages, and interferon-gamma production by T-leukocytes, monocytes, and T-splenocytes, as well as increased interleukin-6 production by T-leukocytes and monocytes and nitrate/nitrite production by T-leukocytes. Combined treatment significantly decreased plasma nitrate/nitrite, the NKT-leukocyte level, and TNF-alpha production by T-splenocytes. Parenteral arginine may attenuate immune impairment and L-NAME infusion may augment leukocyte proinflammatory response, eliminate splenocyte proinflammatory and T-helper 1 responses, and diminish arginine-induced immunomodulation in combined treatment in subacute peritonitic rats.

Submerged-Culture Mycelia and Broth of the Maitake Medicinal Mushroom Grifola frondosa (Higher Basidiomycetes) Alleviate Type 2 Diabetes-Induced Alterations in Immunocytic Function.

Type 2 Diabetes mellitus (T2DM), a disease with impaired glucose, protein and lipid metabolism, low-grade chronic inflammation, and immune dysfunction, is a global public health crisis. We previously demonstrated that Grifola frondosa has bioactivities in improving glycemic responses in diabetic rats. Herein, we investigated the immunomodulatory effects of the submerged-culture mycelia and broth of G. frondosa on the peripheral blood cells (PBL) and splenocytes. Male Wistar rats were administered with saline (normal rats) or streptozotocin plus nicotinamide (T2DM rats) and were intragastrically administered with placebo, fermented mycelia, broth, or mycelia plus broth (1 g kg-1 day-1) for two weeks. In normal rats, ingestion of mycelia significantly decreased monocytes and ingestion of mycelia and broth significantly decreased the productions of interferon (IFN)-γ and interleukin (IL)-4 from the PBL and splenocytes. In T2DM rats, ingestion of mycelia, broth, and mycelia plus broth significantly alleviated the increases in 2 h postprandial blood glucose and the productions of IFN-γ from the T-leukocytes, IL-4, and IL-6 from the monocytes and IL-4 from the T-splenocytes, as well as significantly improved the productions of tumor-necrosis factor-α from the macrophages. In conclusion, submerged-culture mycelia and broth of G. frondosa may decrease cell-medicated immunity in normal rats and improve hyperglycemia and diabetes-induced alterations in cell-medicated and innate immunities in T2DM rats.

Polysaccharides of Trametes versicolor Improve Bone Properties in Diabetic Rats.

This study investigates the effects of Trametes versicolor (L.:Fr.) Pilát (TVP, also known as Yunzhi) on bone properties in diabetic rats. Forty-five male Wistar rats (8 weeks old) were fed either a chow diet (control) or a high-fat diet throughout the study period of 28 days. Animals in the high-fat-diet group were injected with nicotinamide and streptozotocin to induce diabetes mellitus (DM). The DM rats were divided into a group receiving distilled water (vehicle) and another group receiving TVP at 0.1 g/kg weight by gavage. Relative to the vehicle group, TVP gavage lowered postprandial blood sugar (225 ± 18 mg/dL for TVP vs 292 ± 15 mg/dL for vehicle, p < 0.001) on day 26. Compared to the vehicle group, TVP mitigated DM-induced bone deterioration as determined by increasing bone volume of proximal tibia (22.8 ± 1.4% for TVP vs 16.8 ± 1.3% for vehicle, p = 0.003), trabecular number (p = 0.011), and femoral bone strength (11% in maximal load, 22% in stiffness, 14% in modulus, p < 0.001), and by reducing loss of femoral cortical porosity by 25% (p < 0.001). Our study demonstrates the protective effect of TVP on bone properties was mediated through, in part, the improvement of hyperglycemic control in DM animals.

Effects of medium components and culture conditions on mycelial biomass and the production of bioactive ingredients in submerged culture of Xylaria nigripes (Ascomycetes), a Chinese medicinal fungus.

The optimal culture conditions were investigated to maximize the production of mycelial biomass and bioactive ingredients in submerged cultivation of Xylaria nigripes, a Chinese medicinal fungus. The one-factor-at-a-time method was used to explore the effects of medium components, including carbon, nitrogen, mineral sources, and initial pH of the medium and environmental factors, such as culture temperature and rotation speed, on mycelial growth and production of bioactive ingredients. The results indicated that the optimal culture temperature and rotation speed were 25°C and 100 rpm in a medium with 20 g fructose, 6 g yeast extract, and 2 g magnesiun sulfate heptahydrate as carbon, nitrogen, and mineral sources, respectively, in 1 L distilled water with an initial medium pH of 5.5. With optimal medium components and conditions of cultivation, the maximal production of mycelial biomass was 6.64 ± 0.88 g/L, with maximal production of bioactive ingredients such as extracellular polysaccharides (2.36 ± 0.18 mg/mL), intracellular polysaccharides (2.38 ± 0.07 mg/g), adenosine (43.27 ± 2.37 mg/g), total polyphenols (36.57 ± 1.36 mg/g), and triterpenoids (31.29 ± 1.17 mg/g) in a shake flask culture. These results suggest that different bioactive ingredients including intracellular polysaccharides, adenosine, total polyphenols and triterpenoids in mycelia and extracellular polysaccharides in broth can be obtained from one simple medium for submerged cultivation of X. nigripes.

Guanylyl cyclase-G modulates jejunal apoptosis and inflammation in mice with intestinal ischemia and reperfusion.

BACKGROUND: Membrane bound guanylyl cyclase-G (mGC-G), a novel form of GC mediates ischemia and reperfusion (IR)-induced renal injury. We investigated the roles of mGC-G in intestinal IR-induced jejunal damage, inflammation, and apoptosis. MATERIALS AND METHODS: Male C57BL/6 wild-type (WT) and mGC-G gene knockout (KO) mice were treated with a sham operation or 45 min of superior mesenteric arterial obstruction followed by 3, 6, 12, or 24 h of reperfusion. RESULTS: Sham-operated KO mice had significantly lower plasma nitrate and nitrite (NOx) levels and jejunal villus height, crypt depth, and protein expression of phosphorylated-nuclear factor-kappa-B (NF-κB), phosphorylated-c-Jun N-terminal kinases (JNK) 2/3, phosphorylated-p38, and B-cell lymphoma-2 (Bcl-2). They had significantly greater jejunal interleukin-6 mRNA, cytochrome c protein, and apoptotic index compared with sham-operated WT mice. Intestinal IR significantly decreased plasma NOx in WT mice and increased plasma NOx in KO mice. The jejunal apoptotic index and caspase 3 activities were significantly increased, and nuclear phosphorylated-NF-κB and phosphorylated-p38 protein were significantly decreased in WT, but not KO mice with intestinal IR. After reperfusion, KO mice had an earlier decrease in jejunal cyclic GMP, and WT mice had an earlier increase in jejunal proliferation and a later increase in cytosol inhibitor of kappa-B-alpha. Intestinal IR induced greater increases in plasma and jejunal interleukin-6 protein in WT mice and a greater increase in jejunal interleukin-6 mRNA in KO mice. CONCLUSIONS: mGC-G is involved in the maintenance of jejunal integrity and intestinal IR-induced inflammation and apoptosis. These results suggest that targeting cGMP pathway might be a potential strategy to alleviate IR-induced jejunal damages.

The Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Yellow Brain Mushroom Tremella mesenterica Modulate the Immunity of Peripheral Blood Leukocytes and Splenocytes in Rats with Impaired Glucose Tolerance.

The prevalence of diabetes mellitus (DM), a chronic disease with hyperglycemia and impaired immune function, is increasing worldwide. Progression from impaired glucose tolerance (IGT) to type 2 DM has recently become a target for early intervention. The fruiting bodies (FB) and submerged culture mycelium (CM) of Tremella mesenterica, an edible and medicinal mushroom, have been demonstrated to have antihyperglycemic and immunomodulatory activities in type 1 DM rats. Herein, we investigated the effects of acidic polysaccharide glucuronoxylomannan (GX) extracted from CM on the immunocyte responses. Male Wistar rats were injected with streptozotocin (65 mg/kg) plus nicotinamide (200 mg/kg) for the induction of IGT, and gavaged daily with vehicle, FB, CM, or GX (1 g/kg/day). Rats injected with saline and gavaged vehicle were used as controls. Two weeks later, peripheral blood leukocytes (PBLs) and splenocytes were collected. Ingestion of FB, CM, and GX significantly decreased blood glucose levels in the postprandial period and in oral glucose tolerance test, and partially reversed T-splenocytic proliferation in IGT rats. CM significantly decreased T-helper lymphocytes in the PBLs and B-splenocytes. In addition, FB, CM, and GX significantly reversed the IGT-induced decreases in tumor necrosis factor-α production; GX significantly increased interleukin-6 production in T-lymphocytes in the PBLs and splenocytes; and CM and GX significantly reversed IGT-induced decrease in interferon-γ production in T-lymphocytes in the spleen. In conclusion, FB, CM, and acidic polysaccharide GX of T. mesenterica may increase T-cell immunity via the elevation of proinflammatory and T-helper cytokine production in rats with impaired glucose tolerance.

Diverse effects of parenteral arginine on systemic and local oxidant-antioxidant homeostasis and nitrosative stress in rats with subacute peritonitis.

BACKGROUND: The beneficial effects of arginine on oxidative stress have been previously reported; however, excess production of nitric oxide, an arginine metabolite, may cause hemodynamic instability and inflammatory response. Previous studies have demonstrated that parenteral arginine levels at 2%-4% of total calories may alleviate inflammation and enhance immunity, whereas greater than 6% of total calories may have adverse effects in rats with subacute peritonitis. Herein, we investigated the effects of parenteral arginine dose on lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and antioxidant enzyme activities in the plasma and organs. MATERIALS AND METHODS: Male Wistar rats with cecal puncture-induced subacute peritonitis were infused with parenteral nutrition solutions containing 1.61% (CP group), 2.85% (LA group), 4.08% (MA group), and 6.54% (HA group) of total calories as arginine for 7 d. Healthy, orally fed rats (NC group) were used as references. RESULTS: Subacute peritonitis significantly elevated the levels of nitrate, nitrite and TBARS in the plasma and decreased glutathione peroxidase activity in the kidneys. These changes were significantly reversed in the MA and HA groups. The MA and HA groups had significantly increased nitrotyrosine levels in the plasma. The LA, MA, and HA groups had significantly increased glutathione peroxidase activity in the plasma, cytochrome P450 levels in the liver, and nitrotyrosine levels in the heart and had significantly decreased TBARS levels in the kidneys compared with the CP group. CONCLUSIONS: Our results suggest that parenteral arginine at a dose less than 4% of total calories may attenuate lipid peroxidation and increase antioxidant enzyme activities without leading to nitrosative stress in subacute peritonitis.

Low body weight gain, low white blood cell count and high serum ferritin as markers of poor nutrition and increased risk for preterm delivery.

This study determined factors of preterm delivery in Taiwan. Healthy women (n=520, age 29.1±4.2 y) at 8-12 weeks of pregnancy were recruited from prenatal clinics. Background information, anthropometrics, biochemical parameters, and dietary intake, collected by 24 h-recall were obtained from the first, second, and third trimesters to delivery. Clinical outcomes of neonates were also collected. The results show that 53.7% of women were primiparous and that the incidence of preterm delivery was 6.2%. Body weight gains in the first trimester and throughout pregnancy were significantly lower in mothers with preterm delivery (preterm group) than in mothers with term delivery (term group, p<0.05). Maternal cholesterol intake, circulating white blood cell counts (WBC) and serum albumin were significantly lower and that serum magnesium and ferritin were significantly higher in the preterm group than in the term group. Maternal weight gain was positively correlated with caloric and nutrient intake (p<0.05). Neonatal birth weight was positively correlated with maternal weight gain and intakes of protein and phosphate during pregnancy; with intakes of calories, vitamin B-1 and B-2 in the first trimester; and with intakes of calcium, magnesium, iron and zinc, as well as circulating WBC in the third trimester. However, neonatal birth weight was negatively correlated with serum iron in the third trimester and with serum iron and ferritin at the time of delivery. In conclusion, maternal weight gain in early pregnancy and WBC, mineral intake and iron status in late pregnancy seem to be major factors affecting delivery and neonatal outcomes.

A Systematic Review of the Mysterious Caterpillar Fungus Ophiocordyceps sinensis in Dong-ChongXiaCao ( Dong Chóng Xià Cǎo) and Related Bioactive Ingredients.

The caterpillar fungus Ophiocordyceps sinensis (syn.Cordyceps sinensis), which was originally used in traditional Tibetan and Chinese medicine, is called either "yartsa gunbu" or "DongChongXiaCao ( Dong Chóng Xià Cǎo)" ("winter worm-summer grass"), respectively. The extremely high price of DongChongXiaCao, approximately USD $20,000 to 40,000 per kg, has led to it being regarded as "soft gold" in China. The multi-fungi hypothesis has been proposed for DongChongXiaCao; however, Hirsutella sinensis is the anamorph of O. sinensis. In Chinese, the meaning of "DongChongXiaCao" is different for O. sinensis, Cordyceps spp., and Cordyceps sp. Over 30 bioactivities, such as immunomodulatory, antitumor, anti-inflammatory, and antioxidant activities, have been reported for wild DongChongXiaCao and for the mycelia and culture supernatants of O. sinensis. These bioactivities derive from over 20 bioactive ingredients, mainly extracellular polysaccharides, intracellular polysaccharides, cordycepin, adenosine, mannitol, and sterols. Other bioactive components have been found as well, including two peptides (cordymin and myriocin), melanin, lovastatin, γ-aminobutyric acid, and cordysinins. Recently, the bioactivities of O. sinensis were described, and they include antiarteriosclerosis, antidepression, and antiosteoporosis activities, photoprotection, prevention and treatment of bowel injury, promotion of endurance capacity, and learning-memory improvement. H. sinensis has the ability to accelerate leukocyte recovery, stimulate lymphocyte proliferation, antidiabetes, and improve kidney injury. Starting January 1(st), 2013, regulation will dictate that one fungus can only have one name, which will end the system of using separate names for anamorphs. The anamorph name "H. sinensis" has changed by the International Code of Nomenclature for algae, fungi, and plants to O. sinensis.