Oleuropein Supplementation Ameliorates Long-Course Diabetic Nephropathy and Diabetic Cardiomyopathy Induced by Advanced Stage of Type 2 Diabetes in db/db Mice.

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of diabetic nephropathy and diabetic cardiomyopathy. However, the efficacy of OP on the long-course of these diabetes complications has not been investigated. Therefore, in this study, to investigate the relieving effects of OP intake on these diseases, and to explore the underlying mechanisms, db/db mice (17-week-old) were orally administrated with OP (200 mg/kg bodyweight) for 15 weeks. We found that OP reduced expansion of the glomerular mesangial matrix, renal inflammation, renal fibrosis, and renal apoptosis. Meanwhile, OP treatment exerted cardiac anti-fibrotic, anti-inflammatory, and anti-apoptosis effects. Notably, transcriptomic and bioinformatic analyses indicated 290 and 267 differentially expressed genes in the kidney and heart replying to OP treatment, respectively. For long-course diabetic nephropathy, OP supplementation significantly upregulated the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. For long-course diabetic cardiomyopathy, p53 and cellular senescence signaling pathways were significantly downregulated in response to OP supplementation. Furthermore, OP treatment could significantly upregulate the transcriptional expression of the ATPase Na+/K+ transporting subunit alpha 3, which was enriched in the cGMP-PKG signaling pathway. In contrast, OP treatment could significantly downregulate the transcriptional expressions of cyclin-dependent kinase 1, G two S phase expressed protein 1, and cyclin B2, which were enriched in p53 and cellular senescence signal pathways; these genes were confirmed by qPCR validation. Overall, our findings demonstrate that OP ameliorated long-course diabetic nephropathy and cardiomyopathy in db/db mice and highlight the potential benefits of OP as a functional dietary supplement in diabetes complications treatment.

Multifunctional polydopamine/hemin-cyclodextrin reinforced chitosan nanocomposite hydrogel: A synergistic platform for wound healing.

Chronic cutaneous wounds present a significant challenge for healthcare providers globally, with the risk of bacterial infections emerging as a particularly concerning issue. There is an increasing need to employ a combination of diverse antibacterial strategies to address infections comprehensively in chronic wounds. This study introduces a highly efficient antibacterial platform that encapsulates the NO precursor (BNN6) into ß-cyclodextrin-modified hemin-bearing polydopamine nanoparticles called NO/CHPDA. These nanoparticles are seamlessly integrated into a hydrogel composite comprised of L-arginine grafted chitosan (Arg-CS) and oxide dextrans (oDex). The amalgamation of photothermal therapy (PTT), chemodynamic therapy (CDT), and nitric oxide (NO) antibacterial strategies within the NO/CHPDA@Arg-CS/oDex nanocomposite hydrogel demonstrates a synergistic and highly effective capacity to eradicate bacteria and accelerate the wound healing process in vivo. Remarkably, this nanocomposite hydrogel maintains excellent biocompatibility and induces minimal side effects. The resulting nanocomposite hydrogel represents a promising therapeutic solution for treating bacterial infections in wound healing applications.

Regulated intestinal microbiota and gut immunity to ameliorate type 1 diabetes mellitus: A novel mechanism for stem cell-based therapy.

Although stem cell transplantation is an effective strategy in the treatment of type 1 diabetes mellitus (T1DM), the mechanisms underlying its therapeutic effects remain unclear. We hypothesized that stem cells target gut microbiota and intestinal mucosal immunity to promote therapeutic effects against T1DM. We investigated the effects of human amniotic mesenchymal stem cells (hAMSCs) on intestinal microbiota and mucosal immunity in streptozotocin-induced T1DM mice. hAMSCs promoted significant reductions in blood glucose levels and increased the number of insulin-secreting cells in the T1DM model. Compared with T1DM model mice, 16S rRNA sequencing revealed significant differences in the composition, diversity, and abundance of microbiota in the ileum of hAMSC-treated mice. Bifidobacterium, Prevotella, and Alcaligenes species were among the 15 most abundant differential bacterial species. LC-MS revealed significant changes in ileal metabolites, and among the top 100 differential metabolites identified, we found that a significant increase in taurine was closely associated with hAMSC therapy. Additionally, we detected significant differences between the two groups with respect to the frequency and phenotype of CD4+ T cell subsets in mesenteric lymph nodes, and hAMSCs promoted significant increases in Th2 and Treg cell frequencies and reduced the frequencies of Th1 and Th17 cells. Moreover, correlation analysis revealed pairwise correlations between differential microflora and differential metabolites and immune signatures. hAMSCs thus have positive effects on the microbiota and their metabolites in the ileum and intestinal mucosal immunity in T1DM. Our findings indicate that gut microbiota and intestinal mucosal immunity may play vital roles in the hAMSC-based treatment of T1DM.

Combination therapy with human amniotic epithelial cells and hyaluronic acid promotes immune balance recovery in type 1 diabetic rats through local engraftment.

Stem cell engraftment is currently a promising approach for type 1 diabetes mellitus (T1DM) treatment. In our previous study, engraftment of a combination of human amniotic epithelial cells (hAECs) and hyaluronic acid (HA) showed potent anti-diabetic effect in streptozotocin (STZ)-induced T1DM mice via tail vein injection. Here, we adopted a different route of stem cell delivery, that is via pancreatic subcapsular transplantation. This combined local engraftment of hAECs and HA in STZ-induced T1DM rats showed potent anti-diabetic activity, leading to stronger hypoglycaemia, more intact islet structure and increased number of insulin-positive cells compared with those with hAECs or insulin treatments. Engraftment of hAECs alone increased the proportion of Th1 and T-reg cells and decreased the proportion of Th2 and Th17 cells to protect islet ß cells in STZ-induced T1DM rats, whereas the combined engraftment of hAECs and HA showed more potent regulatory capacity, considerably decreased the level of TNF-α and IL-17 and increased the level of TGF-ß1 compared with those by other treatments. The potent synergistic effect of HA contributed to the recovery of immune balance in the diabetic rat model, thereby suggesting a new strategy for effective treatment of T1DM.

The Impact of Intestinal Microorganisms and Their Metabolites on Type 1 Diabetes Mellitus.

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease with a complex etiology comprising numerous genetic and environmental factors; however, many of the mechanisms underlying disease development remain unclear. Nevertheless, a critical role has recently been assigned to intestinal microorganisms in T1DM disease pathogenesis. In particular, a decrease in intestinal microbial diversity, increase in intestinal permeability, and the translocation of intestinal bacteria to the pancreas have been reported in patients and animal models with T1DM. Moreover, intestinal microbial metabolites differ between healthy individuals and patients with T1DM. Specifically, short-chain fatty acid (SCFA) production, which contributes to intestinal barrier integrity and immune response regulation, is significantly reduced in patients with T1DM. Considering this correlation between intestinal microorganisms and T1DM, many studies have investigated the potential of intestinal microbiota in preventive and therapeutic strategies for T1DM. Objective: The aim of this review is to provide further support for the notion that intestinal microbiota contributes to the regulation of T1DM occurrence and development. In particular, this article reviews the involvement of the intestinal microbiota and the associated metabolites in T1DM pathogenesis, as well as recent studies on the involvement of the intestinal microbiota in T1DM prevention and treatment. Conclusion: Intestinal microbes and their metabolites contribute to T1DM occurrence and development and may become a potential target for novel therapeutics.

Lactiplantibacillus plantarum Y15 alleviate type 2 diabetes in mice via modulating gut microbiota and regulating NF-κB and insulin signaling pathway.

Probiotics have been used for the treatment of chronic metabolic diseases, including type 2 diabetes (T2D). However, the mechanisms of antidiabetic effects are not well understood. The object of this study is to assess the antidiabetic effect of Lactiplantibacillus plantarum Y15 isolated from Chinese traditional dairy products in vivo. Results revealed that L. plantarum Y15 administration improved the biochemical indexes related to diabetes, reduced pro-inflammatory cytokines, L. plantarum Y15 administration reshaped the structure of gut microbiota, decreased the abundance of LPS-producing, and increased short-chain fatty acids (SCFAs)-producing bacteria, which subsequently reduce the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines. L. plantarum Y15 administration also regulated the expressions of the inflammation and insulin signaling pathway-related genes. These results suggest that L. plantarum Y15 may serve as a potential probiotic for developing food products to ameliorate T2D.

Alleviative Effects of Exopolysaccharide Produced by Lactobacillus helveticus KLDS1.8701 on Dextran Sulfate Sodium-Induced Colitis in Mice.

Ulcerative colitis (UC) is a non-specific chronic inflammatory disease with lesions located in the colon and rectum. The aim of this study was to evaluate the anti-inflammatory effects of exopolysaccharide-1 (EPS-1) isolated by L. helveticus KLDS1.8701 on UC. The anti-inflammatory effects of EPS-1 were studied using dextran sulphate sodium (DSS)-induced UC model. In vivo results showed that EPS-1 administration significantly ameliorated weight loss, colon shortening, disease activity index (DAI) score, myeloperoxidase (MPO) activity, and colon tissue damage. In addition, EPS-1 administration significantly decreased the levels of pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines. Meanwhile, EPS-1 administration significantly up-regulated the expression of tight junction proteins and mucin. Furthermore, EPS-1 administration modulated gut microbiota composition caused by DSS and increased the short-chain fatty acids (SCFAs) levels. Collectively, our study showed the alleviative effects of EPS- isolated by L. helveticus KLDS1.8701 on DSS-induced UC via alleviating intestinal inflammation, improving mucosal barrier function, and modulating gut microbiota composition.

Oleuropein Ameliorates Advanced Stage of Type 2 Diabetes in db/db Mice by Regulating Gut Microbiota.

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of type 2 diabetes. However, the efficacy of OP on the advanced stage of type 2 diabetes has not been investigated, and the relationship between OP and intestinal flora has not been studied. Therefore, in this study, to explore the relieving effects of OP intake on the advanced stage of type 2 diabetes and the regulatory effects of OP on intestinal microbes, diabetic db/db mice (17-week-old) were treated with OP at the dose of 200 mg/kg for 15 weeks. We found that OP has a significant effect in decreasing fasting blood glucose levels, improving glucose tolerance, lowering the homeostasis model assessment-insulin resistance index, restoring histopathological features of tissues, and promoting hepatic protein kinase B activation in db/db mice. Notably, OP modulates gut microbiota at phylum level, increases the relative abundance of Verrucomicrobia and Deferribacteres, and decreases the relative abundance of Bacteroidetes. OP treatment increases the relative abundance of Akkermansia, as well as decreases the relative abundance of Prevotella, Odoribacter, Ruminococcus, and Parabacteroides at genus level. In conclusion, OP may ameliorate the advanced stage of type 2 diabetes through modulating the composition and function of gut microbiota. Our findings provide a promising therapeutic approach for the treatment of advanced stage type 2 diabetes.

Efficacy and Mechanisms of Oleuropein in Mitigating Diabetes and Diabetes Complications.

The global pandemic of diabetes and diabetes complications confers heavy pressure on public health. Novel antidiabetes strategies with negligible unwanted effects are urgently needed. Currently, the anti-hyperglycemic potential of plant-based functional ingredients has been explored to provide alternative strategies. As a kind of dietary bioactive compound, oleuropein has aroused the growing interest of researchers in diabetes and diabetes complications management. This review reveals the research progress of oleuropein in treating diabetes and diabetes complications and summarizes the molecular mechanisms involved in these beneficial effects of oleuropein. Oleuropein achieves amelioration of diabetes, the mechanisms of which include the modulation of insulin secretion, the repairment islet morphology, the activation of hepatic AMP-activated protein kinase singling, and the improvement of glucose tolerance and insulin resistance. Oleuropein also can relieve diabetes complications including diabetic nephropathy, diabetes cardiovascular complications, diabetic retinopathy, poor wound healing, diabetic neuropathy, and diabetic testicular dysfunction. Oleuropein reverses cell apoptosis, regenerates tissues, restores the histological organization, and decreases oxidative stress in treating diabetes complications. Taken together, oleuropein is a promising compound for diabetes and diabetes complications management and can be used as a nutraceutical to fight against these diseases.

Prognostic Value of Inflammatory and Tumour Markers in Small-Duct Subtype Intrahepatic Cholangiocarcinoma after Curative-Intent Resection.

Intrahepatic cholangiocarcinoma (ICC) is characterised by heterogeneity, and it can be subdivided into small-duct and large-duct types. Inflammatory and tumour markers could effectively predict prognosis in many cancers, but no similar studies have been conducted in the histological subtypes of ICC. A total of 102 and 72 patients with ICC undergoing curative-intent resection were retrospectively subclassified into large-duct and small-duct types by chemical staining, respectively. The prognostic value of inflammatory and tumour markers was studied for the first time in histological subtypes of ICC by using a Cox regression model. A novel predictor named prognostic inflammatory index (PII) was proposed and defined as neutrophil × monocyte/lymphocyte count (109/L). Survival analysis showed that PII, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA242, and ferritin were all predictors of DFS and OS in patients with ICC (P < 0.040). Subgroup analysis showed that PII, CA19-9, and ferritin were risk predictors of disease-free survival (DFS) and overall survival (OS) in small-duct type ICC (P < 0.015). In addition, in small-duct type ICC, NLR and LMR were correlated with OS (P < 0.025), whilst CEA and CA242 were correlated with DFS (P ≤ 0.010). In conclusion, PII is a convenient and efficient inflammatory predictor of DFS and OS in ICCs and their small-duct type. NLR and LMR, rather than platelet-to-lymphocyte ratio, were correlated with OS in small-duct type ICC. In addition, ferritin may be a supplement to CA19-9 in stratifying the survival outcome of patients with small-duct type ICC.

Fabrication of whey protein isolate-sodium alginate nanocomplex for curcumin solubilization and stabilization in a model fat-free beverage.

The present study aimed to fabricate whey protein isolate (WPI)-sodium alginate (ALG) nanocomplexes for curcumin (CUR) stabilization in a model fat-free beverage. Mass ratio of 5:1 at pH 5.0 in the absence of NaCl was optimized for WPI-ALG nanocomplex fabrication. Mean particle size and zeta-potential of CUR-WPI-ALG nanocomplex was 209.9 nm and -39.1 mV at pH 5.0, respectively. Highest loading amount (LA) of CUR in CUR-WPI-ALG nanocomplex were 15.26 µg/mg. No obvious precipitates were observed for CUR-WPI-ALG nanocomplex under simulated food processing and storage conditions including high sucrose, high NaCl, and thermal treatment at 90 °C for 2 h. Fluorescence results confirmed that the spontaneous interaction between CUR and WPI-ALG nanocomplex was primarily motivated by hydrophobic interaction and hydrogen bonding. Compared with CUR (free), chemical stability (UV light, and heat), and DPPH scavenging capacities of CUR in CUR-WPI-ALG nanocomplex were strikingly improved.

Chlorogenic acid ameliorates obesity by preventing energy balance shift in high-fat diet induced obese mice.

BACKGROUND: Chlorogenic acid is a type of phenolic acid found in many plants. Chlorogenic acid has an anti-obesity effect with an unclear mechanism. The present study aimed to investigate the regulatory effect of chlorogenic acid on energy balance in high-fat diet (HFD) induced obese C57BL/6J mice administrated 100 mg kg-1 chlorogenic acid for 13 weeks. RESULTS: The consumption of chlorogenic acid ameliorated HFD induced obesity. Chlorogenic acid did not change the physical activity but significantly decreased food intake and increased body temperature, thermal dissipation and brown adipose tissue activity. Moreover, chlorogenic acid improved glucose tolerance but had a moderate impact on other blood indices. Additionally, chlorogenic acid failed to restore the microbiota change associated with HFD induced obesity, but modified the gut bacterial composition in a unique way. CONCLUSION: Supplementation with chlorogenic acid can improve HFD induced obesity and associated glucose intolerance mainly via regulating food intake and energy expenditure. © 2020 Society of Chemical Industry.

Prevalence, Serotype, Antibiotic Susceptibility, and Genotype of Salmonella in Eggs From Poultry Farms and Marketplaces in Yangling, Shaanxi Province, China.

Poultry products such as eggs provide essential nutrients to the human body and thus play vital roles in the human food network. Salmonella is one of the most notorious foodborne pathogens and has been found to be prevalent in eggs. To better understand the characteristics of Salmonella in eggs, we investigated the prevalence of Salmonella spp. in 814 fresh eggs collected from poultry farms and retail marketplaces in Yangling, Shaanxi Province, China. The serotype, genotype, and antibiotic susceptibilities of 61 Salmonella isolates recovered from the eggs were analyzed. The average detection rate of Salmonella-positive eggs was 5.6%, with 6.6% of the eggs collected from poultry farms and 5.1% from marketplaces. Thirteen serotypes were identified from the 61 isolates, among which Salmonella Typhimurium (24.5%) and Salmonella Indiana (22.9%) were the most prevalent serotypes. Other dominant serotypes included Salmonella Thompson (13.1%) and Salmonella Enteritidis (11.4%), with the remaining nine serotypes detected at low rates (1.6-4.9%). All the Salmonella isolates tested were resistant to sulfisoxazole (100.0%). The majority (77.1%) of the isolates were resistant to nalidixic acid, amoxicillin-clavulanate, and ampicillin, while nearly two-thirds (63.9-68.9%) were resistant to trimethoprim-sulfamethoxazole, kanamycin, tetracyclines, and chloramphenicol. The rate of resistance to ciprofloxacin was 40.1%; the resistance rates to streptomycin, ceftiofur, and ceftriaxone ranged from 21.3 to 26.2%; and those to gentamicin, amikacin, and cefoxitin were relatively low (3.3-16.4%). Forty-nine (80.3%) Salmonella isolates exhibited resistance to multiple antibiotics, 20 (32.8%) of which were resistant to at least 10 antibiotics. Subtyping by pulse-field gel electrophoresis revealed a close genetic relatedness of Salmonella isolates from poultry farms, in striking contrast to the high diversity of the isolates obtained from marketplaces. Isolates of the same serotype always shared identical genotype and antibiotic resistance profiles, even the ones that were recovered from eggs sampled at different locations and times. These findings indicate that diverse Salmonella spp. with high rates of multidrug resistance are prevalent in fresh eggs in the study area. More attention should be paid to egg production, transportation, and storage to prevent foodborne outbreaks caused by Salmonella.

Allicin-induced host-gut microbe interactions improves energy homeostasis.

Allicin (diallylthiosulfinate) is a natural food compound with multiple biological and pharmacological functions. However, the mechanism of beneficial role of Allicin on energy homeostasis is not well studied. Gut microbiota (GM) profoundly affects host metabolism via microbiota-host interactions and coevolution. Here, we investigated the interventions of beneficial microbiome induced by Allicin on energy homeostasis, particularly obesity, and related complications. Interestingly, Allicin treatment significantly improved GM composition and induced the most significant alteration enrichment of Bifidobacterium and Lactobacillus. Importantly, transplantation of the Allicin-induced GM to HFD mice (AGMT) played a remarkable role in decreasing adiposity, maintaining glucose homeostasis, and ameliorating hepatic steatosis. Furthermore, AGMT was effective in modulating lipid metabolism, activated brown adipose tissues (BATs), induced browning in sWAT, reduced inflammation, and inhibited the degradation of intestinal villi. Mechanically, AGMT significantly increased Blautia [short-chain fatty acids (SCFAs)-producing microbiota] and Bifidobacterium in HFD mice, also increased the SCFAs in the cecum, which has been proved many beneficial effects on energy homeostasis. Our study highlights that Allicin-induced host-gut microbe interactions plays an important role in regulating energy homeostasis, which provides a promising potential therapy for obesity and metabolic disorders based on host-microbe interactions.

Allicin Regulates Energy Homeostasis through Brown Adipose Tissue.

Brown adipose tissue (BAT) is a promising potential therapeutic target for the treatment of obesity and related metabolic diseases. Allicin, a natural product in garlic, has multiple biological and pharmacological functions. However, the role of allicin in the regulation of metabolic organs, particularly BAT activation, has not been well studied. Here, we show that allicin imparts a significant effect by inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, improving insulin resistance, and ameliorating hepatic steatosis in obese mice. These observations strongly correlate with the activation of BAT. Notably, allicin plays a role in BAT activation, which may partly contribute to the Sirt1-PGC1α-Tfam pathway. In addition, allicin can significantly increase the succinylation levels of UCP1 in BAT by inhibiting sirt5, whereas excess allicin induces autophagy/mitophagy and mitochondrial dysfunction. Thus, our findings point to allicin as a promising therapeutic approach for the treatment of obesity and metabolic disorders.

Mulberry leaves ameliorate obesity through enhancing brown adipose tissue activity and modulating gut microbiota.

The increased prevalence of obesity significantly affects human health worldwide. Improvement of glycometabolism by dietotherapy/herbal remedy is an effective approach to ameliorate obesity. In this study, high-fat-diet induced obese (DIO) mice were treated with mulberry leaves for 13 weeks. The results showed that mulberry leaves significantly alleviated adiposity of DIO mice including reducing body weight gain, fat accumulation and fasting blood glucose, and improving insulin sensitivity. In addition, mulberry leaves had protective effects on liver and kidneys. The abundant flavonoids, polyphenols and 1-deoxynojirimycin in mulberry leaves were likely responsible for their beneficial effects. Mechanistically, we found that mulberry leaves could alleviate obesity by enhancing brown adipose tissue (BAT) activity partly indicated by elevated thermogenesis and overexpression of uncoupling protein 1 in BAT. Moreover, mulberry leaves significantly increased the Bacteroidetes/Firmicutes ratio and Akkermansia level that were closely associated with obesity development and progression, and decreased the potential proinflammatory Proteobacteria in feces. These findings reveal that the mulberry leaf is an edible plant food with therapeutic potential for obesity and may provide dietotherapy/herbal remedy to the treatment of obesity and its complications.

Anti-obesity and hypolipidemic effect of water extract from Pleurotus citrinopileatus in C57BL/6J mice.

Obesity has become one of the most important health problems worldwide requiring urgent need for efficient control. Pleurotus citrinopileatus (P. citrinopileatus)-a type of edible mushroom with abundant bioactive molecules-is a promising source for achieving this goal. In the present study, we evaluated the anti-obesity and hypolipidemic effect of P. citrinopileatus water extract (PWE) using a series of biochemical assays in randomized high-fat diet-induced obese (DIO) C57BL/6J mice, which were gavaged daily with low or high levels of PWE (400 or 800 mg/kg of body weight, respectively) in addition to high-fat diet for 12 weeks. Results showed that PWE significantly reduced the weight gain, fat accumulation, and food intake of DIO mice within 12 weeks. PWE also decreased the serum triglycerides, cholesterol and low-density lipoprotein, aspartate transaminase, nonesterified fatty acid, and creatinine, but increased high-density lipoprotein. Additionally, PWE improved the glucose tolerance of mice fed with high fat. From above, we conclude that PWE has great potential as functional foods for management of obesity and/or associated metabolic disorders.

Overcoming Limitations Inherent in Sulfamidase to Improve Mucopolysaccharidosis IIIA Gene Therapy.

Sulfamidase (SGSH) deficiency causes mucopolysaccharidosis type IIIA (MPS IIIA), a lysosomal storage disease (LSD) that affects the CNS. In earlier work in LSD mice and dog models, we exploited the utility of adeno-associated viruses (AAVs) to transduce brain ventricular lining cells (ependyma) for secretion of lysosomal hydrolases into the cerebrospinal fluid (CSF), with subsequent distribution of enzyme throughout the brain resulting in improved cognition and extending lifespan. A critical feature of this approach is efficient secretion of the expressed enzyme from transduced cells, for delivery by CSF to nontransduced cells. Surprisingly, we found that SGSH was poorly secreted from cells, resulting in retention of the expressed product. Using site-directed mutagenesis of native SGSH, we identified an improved secretion variant that also displayed enhanced uptake properties that were mannose-6-phosphate receptor independent. In studies in MPS IIIA-deficient mice, ependymal transduction with AAVs expressing variant SGSH improved spatial learning and reduced memory deficits, substrate accumulation, and astrogliosis. Secondary lysosomal enzyme elevations in the CSF and brain parenchyma were also resolved. In contrast, ependymal transduction with AAVs expressing wild-type SGSH had significantly lower CSF SGSH levels and limited impacts on behavior. These results demonstrate the utility of a previously undescribed SGSH variant for improved MPS IIIA brain gene therapy.

Mulberry leaf alleviates streptozotocin-induced diabetic rats by attenuating NEFA signaling and modulating intestinal microflora.

Improvement of hyperglycemia through dietotherapy/herbal remedy is an effective approach to treating diabetes. In this study, mulberry leaf, famous for silkworm's special food and therapeutic value without any side effects, alleviated diabetes by attenuating NEFA signaling and modulating intestinal microflora. Mulberry leaf treatment significantly reduce fasting blood-glucose and HbA1c, ameliorate the blood lipid profile and improve insulin resistance in streptozotocin-induced diabetic rats. Mechanistically, we found that mulberry leaf inhibited NEFA signaling by reducing downstream signaling in the NEFA pathway, further verified by reduced PKC and improved cellular energy homeostasis based on restored expression of PGC-1α, AK2, OXPHOS and adiponectin. Mulberry leaf treatment also restored the phyla Bacteroidetes and Proteobacteria and class Clostridia, which were associated with insulin resistance and diabetes. Our findings reveal that mulberry leaf is an edible with therapeutic potential for diabetes and may provide a novel dietotherapy/herbal remedy to the treatment of diabetes.

Purple Sweet Potato Attenuate Weight Gain in High Fat Diet Induced Obese Mice.

Purple sweet potato (PSP) is widely grown in Asia and considered as a healthy vegetable. The objective of the current study was to determine the anti-obesity effect of the PSP on high fat diet induced obese C57BL/6J mice. The mice were administrated with high fat diet supplemented with the sweet potato (SP) or PSP at the concentration of 15% and 30% for 12 wk, respectively. The results showed that the supplementation of SP or PSP at 30% significantly ameliorated high fat diet induced obesity and its associated risk factors, including reduction of body weight and fat accumulation, improvement of lipid profile and modulation of energy expenditure. Moreover, PSP also posed beneficial effect on the liver and kidney functions. These results indicate that PSP and SP have anti-obesity effect and are effective to reduce the metabolic risk.