Inflammatory and hypoxic stress-induced islet exosomes released during isolation are associated with poor transplant outcomes in islet autotransplantation.

Islets experience enormous stress during the isolation process, leading to suboptimal endocrine function after total pancreatectomy with islet autotransplantation (TPIAT). Our investigation focused on inducing isolation stress in islets ex vivo, where proinflammatory cytokines and hypoxia prompted the release of stress exosomes (exoS) sized between 50 and 200 nm. Mass spectrometry analysis revealed 3 distinct subgroups of immunogenic proteins within these exoS: damage-associated molecular patterns (DAMPs), chaperones, and autoantigens. The involvement of endosomal-sorting complex required for transport proteins including ras-associated binding proteins7A, ras-associated binding protein GGTA, vacuolar protein sorting associated protein 45, vacuolar protein sorting associated protein 26B, and the tetraspanins CD9 and CD63, in exoS biogenesis was confirmed through immunoblotting. Next, we isolated similar exoS from the islet infusion bags of TPIAT recipients (N = 20). The exosomes from infusion bags exhibited higher DAMP (heat shock protein family A [Hsp70] member 1B and histone H2B) levels, particularly in the insulin-dependent TPIAT group. Additionally, elevated DAMP protein levels in islet infusion bag exosomes correlated with increased insulin requirements (P = .010) and higher hemoglobin A1c levels 1-year posttransplant. A deeper exploration into exoS functionality revealed their potential to activate monocytes via the toll-like receptor 3/7: DAMP axis. This stimulation resulted in the induction of inflammatory phenotypes marked by increased levels of CD68, CD80, inducible nitric oxide synthase, and cyclooxygenase-2. This activation mechanism may impact the successful engraftment of transplanted islets.

Gestational low dietary protein induces intrauterine inflammation and alters the programming of adiposity and insulin sensitivity in the adult offspring.

Malnutrition associated with low dietary protein can induce gestational inflammation and sets a long-lasting metabolic impact on the offspring even after replenishment. The work investigated whether a low-protein diet (LPD) during pregnancy and lactation induces intrauterine inflammation and predisposes offspring to adiposity and insulin resistance in their adult life. Female Golden Syrian hamsters were fed LPD (10.0% energy from protein) or a control diet (CD, 20.0 % energy from protein) from preconception until lactation. All pups were switched to CD after lactation and continued until the end. Maternal LPD increased intrauterine inflammation by enhancing neutrophil infiltration, amniotic hsCRP, oxidative stress, and mRNA expression of NFκß, IL8, COX2, and TGFß in the chorioamniotic membrane (P<.05). The prepregnancy body weight, placental, and fetal weights, serum AST and ALT were decreased, while blood platelets, lymphocytes, insulin, and HDL were significantly increased in LPD-fed dams (P<.05). A postnatal switch to an adequate protein could not prevent hyperlipidemia in the 6-months LPD/CD offspring. The lipid profile and liver functions were restored over 10 months of protein feeding but failed to normalize fasting glucose and body fat accumulation compared to CD/CD. LPD/CD showed elevated GLUT4 expression & activated pIRS1 in the skeletal muscle and increased expression of IL6, IL1ß, and p65-NFκB proteins in the liver (P<.05). In conclusion, present data suggest that maternal protein restriction may induce intrauterine inflammation and affect liver inflammation in the adult offspring by an influx of fats from adipose that may alter lipid metabolism and reduce insulin sensitivity in skeletal muscle.

Ocimum sanctum, Zingiber officinale, and Piper nigrum extracts and their effects on gut microbiota modulations (prebiotic potential), basal inflammatory markers and lipid levels: oral supplementation study in healthy rats.

CONTEXT: Ocimum sanctum Linn (Labiatae) (OS), Zingiber officinale Rose (Zingiberaceae) (ZO), and Piper nigrum Linn (Piperaceae) (PN) are used in traditional medicine as immunomodulator, anti-inflammatory, and bioavailability enhancer agents. OBJECTIVE: Active phytoconstituents of OS, ZO, PN hydro-alcoholic extracts and their effects on gut microbiota, basal inflammation and lipid profile were investigated in rats. MATERIALS AND METHODS: Active phytoconstituents of extracts were analysed using HPLC and GC-MS. SD rats were supplemented with individual/combined extracts (OS-850; ZO-500; PN-100 mg/kg Bw) and Fructooligosaccharide (standard prebiotic-5g/kg-Bw), orally for 30 days. Haematology, lipid profile, LPS, CRP, IL-6, insulin and histology of vital organs were analysed. Caecal bacterial levels were assessed by RT-PCR. RESULTS: High content of phenolic compounds luteolin-7-O-glucoside (430 ± 2.3 mg/100g), gallic acid (84.13 ± 1.2 mg/100 g) and flavones (88.18 ± 1.8 mg/100 g) were found in OS, ZO, and PN, respectively. Combined extract was rich in luteolin-7-O-glucoside (266.0 ± 1.80 mg/100 g). Essential oils including methyleugenol (13.96%), 6-shogaol (11.00%), piperine (18.26%), and cyclopentasiloxane (10.06%) were higher in OS, ZO, PN and combined extract. Higher levels of caecal Lactobacillus (1.7-3.4-fold), Bifidobacterium (5.89-28.4-fold), and lower levels of Firmicutes (0.04-0.91-fold), Bacteroides (0.69-0.88-fold) were noted among extracts and FOS supplemented rats. Significant (p < 0.05) decrease in plasma lipid profile and LPS was noted in all supplemented rats. DISCUSSION AND CONCLUSIONS: The current study could be first of its kind in exploring prebiotic potential of OS, ZO, PN and their effect on native gut bacterial population.

Fructooligosaccharide ameliorates high-fat induced intrauterine inflammation and improves lipid profile in the hamster offspring.

Maternal high-fat diet (HFD) often results in intrauterine and feto-placental inflammation, and increases the risks of fetal programming of metabolic diseases. Intake of prebiotic is reported beneficial. However, its effects on HFD during pregnancy and lactation is not known. We evaluated the maternal intake of fructooligosaccharide (FOS) and its impact on placental inflammation, offspring's adiposity, glucose, and lipid metabolism in their later life. Female Golden Syrian hamsters were fed with a control diet (CD, 26.4 % energy from fat) or HFD (60.7% energy from fat) in the presence or absence of FOS from preconception until lactation. All pups were switched over to CD after lactation and continued until the end. Placental inflammation was upregulated in HFD-fed dam, as measured by a high concentration of hsCRP in the serum and amniotic fluid. Neutrophil infiltration was significantly increased in the decidua through the chorionic layer of the placenta. The expression of pro-inflammatory cytokines such as COX2, NFκß, IL-8, TGFß mRNA was increased in the chorioamniotic membrane (P <.05). The HFD/CD hamsters had more adiposity, higher triglyceride, and low HDL at 12 months of age compared to CD/CD (P <.05). However, HFD+FOS/CD-fed hamsters prevented adverse effects such as placental inflammation, neutrophil infiltration, glucose, and lipid profiles in the offspring (P <.05). Anti-inflammatory and lipid-lowering effects of FOS may reduce placental inflammation by lowering neutrophil infiltration and decreasing the production of pro-inflammatory cytokines. Intake of FOS during pregnancy may be beneficial in maintaining lipid metabolism and preventing excess adiposity for mother and their offspring.

Semi-synthetic diet versus diet using natural ingredients-Comparative study in female Golden Syrian hamsters.

Semi-synthetic diets (SSD) are recommended and are widely used to carry out experiments in rodents. However, in our experiments planned to carry out generation studies in female Golden Syrian hamsters using semi-synthetic diets, it was observed that the hamsters did not conceive as a result of decreased food intake. In this paper, we present the effects of both semi-synthetic diets and natural source diets (NSD) on food intake, body weight and reproductive performance of this species. Four-week-old female hamsters were equally divided into 3 groups and initially acclimatized for 2 weeks on natural chow diet (NCD). Thereafter, they were fed either control diet, high fat diet (HFD) or low protein diet (LPD) based on semi-synthetic/natural source ingredients until 12 weeks. Daily food intake and weekly body weights were monitored. Hamsters were kept for mating for about 2 weeks from 10th week onwards, during which the pregnancy confirmation test was done using standard vaginal smear examination. In all the groups fed SSD, the food intake was very poor, hamsters lost body weight and did not conceive, thus preventing us from carrying out further experiments. Hamsters fed NCD/NSD ingested more than twice as much as hamsters fed SSD (7-8 g/day/hamster against 3 g/day/hamster on average respectively). Based on the results of the current research, we conclude that the routinely used semi-synthetic diet is not suitable for carrying out studies in female hamsters. We suggest that scientists must also consider the unusual biological characteristics of a given species besides other biological factors. It is therefore critical to select appropriate biological models and diets that provide optimal sensitivity and specificity to accomplish the research objectives.

Sofosbuvir-based treatment is safe and effective in Indian hepatitis C patients on maintenance haemodialysis: A retrospective study.

AIM: This study evaluates the safety and efficacy of direct-acting antivirals (DAAs) including sofosbuvir, ledipasvir and daclatasvir in patients with hepatitis C viraemia who were on maintenance haemodialysis. METHODS: Data on patients who received sofosbuvir and ribavirin were analysed. Patients who experienced treatment failure with the above regimen received sofosbuvir and ledipasvir for infection with hepatitis C virus (HCV) genotype 1. Those having HCV genotype 3 infection received sofosbuvir and daclatasvir. All treatment regimens were of 12 weeks duration. Side-effects were investigated. The HCV viral load was determined by RT-PCR at 4,16 and 24 weeks after the initiation of therapy; haemoglobin levels and liver function tests were monitored at regular intervals during therapy. RESULTS: Of the 22 subjects initially treated with sofosbuvir and ribavirin, 72.72% attained sustained virologic response at 12 weeks (SVR12). Four patients experienced treatment failure and received genotype specific therapy. Patients with HCV genotype one received sofosbuvir with ledipasvir. One patient with HCV genotype 3 infection received sofosbuvir and daclatasvir. All of them attained SVR12. A statistically significant reduction in the median serum glutamic-oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT) were observed from the baseline until the end of treatment. Anaemia was observed in 45% of patients receiving ribavirin. CONCLUSIONS: Our study demonstrates that sofosbuvir-based therapy is efficacious for HCV viraemia in patients on maintenance haemodialysis. The therapy was found to be reasonably safe with no major adverse effects noted with the use of sofosbuvir, ledipasvir or daclatasvir. However, larger studies are needed to validate our results.

Impact of a novel synbiotic supplementation during gestation and lactation on immune responses in the Swiss albino mice offspring.

BACKGROUND: Prebiotics from various regularly consumed cereals and novel substrates are currently being utilised as functional foods. The aim of this study was to determine the effect of synbiotic, formulated with prebiotic extracted from natural resources like green gram (Vigna radiata) along with probiotic Lactobacillus rhamnosus GG (LGG) in modulating immune responses in the offspring when supplemented during gestation and lactation. RESULTS: Synbiotic supplementation was effective in improving cell mediated immunity and humoral immunity among F0 dams. Among F1 pups (F1 Syn + and F1 Syn-), synbiotic supplementation showed significantly heightened (P < 0.05) splenocyte proliferation, increased interleukin-10, interferon gamma and interleukin-17 responses, leucocyte phagocytic ability and increased secretory-immunoglobulin A. However, four-fold increase in IgG titres to Hepatitis-B vaccine was observed only in those mice that were supplemented with synbiotic postweaning (F1 Syn+). CONCLUSION: Synbiotic supplementation to pregnant dams affected the offspring's cellular and mucosal immunity favorably. However, IgG response to Hepatitis-B vaccine was influenced positively only when the supplementation was extended to the offsprings in the post weaning period. © 2016 Society of Chemical Industry.

Anti-ulcer activity of Sandalwood (Santalum album L) stem hydro-alcoholic extract in three gastric-ulceration models of Wistar rats / Actividad anti-ulcerosa del tallo de Sándalo (Santalum album L) en extractos hidro-alcoholicosen tres modelos de ulceración gástrica de ratas Wistar

Sandalwood (Santalum album L.) is used in various traditional systems of medicine, like Ayurveda, Siddha and Unani medicine to treat a wide range of ailments. In Unani medicine, Safed Sandal is used to treat gastric ulcers, hence the present study was undertaken to confirm this claim. A limit test as per OECD guidelines was conducted at a dose of 5000 mg/kg to determine the acute toxic dose of Hydro-alcoholic extract from S. album stem (SASE). Two test doses of SASE (250 and 500 mg/kg) were subjected to screening of anti-ulcer activity by three in-vivo models namely – water immersion - restrain stress, ethanol and indomethacin induced gastric ulceration models in albino wistar rats. A proton-pump inhibitor, Omeprazole 10 mg/kg and H2 receptor antagonist, Ranitidine 50 mg/kg were employed as standard drugs. The results revealed an increase in gastric protection as a significant decrease (p < 0.001) in average number of ulcers, severity of ulcers and cumulative ulcer index was observed in the test groups. Histopathological evidences supported the above findings. The observed anti-ulcer effect of SASE at 500 mg/kg was comparable to that of standard drugs used in the experiments indicating significant anti-ulcer potential especially at higher concentration.

Sándalo (Santalum album L.) se utiliza en diversos sistemas de medicina tradicional, como el Ayurveda, Siddha y Unani para tratar una amplia gama de dolencias. En la medicina Unani, Safed Sandal se usa para tratar úlceras gástricas, por lo tanto, el presente estudio se realizó para confirmar esta afirmación. Una prueba de límite según las directrices de la OCDE se llevó a cabo a una dosis de 5000 mg/kg para determinar la dosis tóxica aguda del extracto hidroalcohólico del tallo de S. álbum (SASE). Dos dosis de prueba de SASE (250 y 500 mg/kg) se sometieron al estudio de la actividad anti-úlcera por tres modelos in vivo, a saber: la inmersión en agua – estrés de restricción, y la ulceración gástrica inducida por etanol e indometacina, en ratas Wistar albinas. Un inhibidor de la bomba de protones, omeprazol 10 mg/kg y el antagonista de los receptores H2, ranitidina 50 mg/kg fueron empleados como fármacos estándar. Los resultados revelaron un aumento de la protección gástrica como una disminución significativa (p < 0.001) en el número promedio de úlceras, la gravedad de las úlceras y el índice de úlcera acumulativo se observó en los grupos de prueba. Evidencias histopatológicas apoyaron las conclusiones anteriores. El efecto anti úlcera observado por efecto de SASE a 500 mg/kg fue comparable a la de fármacos estándar utilizados en los experimentos que indican un significativo potencial anti-úlcera, especialmente a mayores concentraciones.