Antioxidant and free radical scavenging activity of Sida rhomboidea. Roxb methanolic extract determined using different in vitro models [Actividades antioxidante y neutralizante de radicales libres del extracto metanólico de Sida rhomboidea. Roxb determin

El potencial antioxidante del extracto metanólico de Sida rhomboidea.Roxb (MESR) fue evaluada por modelos in vitro tales como peroxidaciónlipídica, quelación de metales y potencial reductor. Su capacidad de neutralizar radicales libres fue determinada in vitro en ensayos de DPPH, superóxido (.O2),peróxido de hidrógeno (H2O2), óxido nítrico (NO.) and el radical hidroxil (HO.). MESR mostró una inhibición dosis dependiente de la peroxidación lipídica,(IC50= 92.15±1.21 μg/ml), una quelación efectiva de metales (IC50=65.69±1.22 μg/ml) y un alto potencial reductor (ODmax=1.20±0.27). MESR neutralizóeficientemente el DPPH (IC50=63.23±1.59 μg/ml), .O2 (IC50=142.36±2.59 μg/ml), H2O2 (IC50=125.96±3.00 μg/ml), NO. (IC50=85.36±2.01 μg/ml) y HO.(IC50=90.45±1.88 μg/ml) de una manera dosis dependiente. Los resultados pueden ser atriuidos a la presencia en el MESR de polifenoles (35.60±1.20 mg/mlpolifenoles equivalentes al ácido gálico), flavanoides (26.94±0.94 mg/ml flavanoides equivalentes a la quercetina) y ácido ascórbico (28.71±1.14 mg/ml).Estas observaciones sugieren actividades antioxidante y neutralizante de radicales libres en MESR que añaden una nueva dimensión a sus conocidasaplicaciones terapéuticas

Oreocnide integrifolia (Gaud.)Miq. exhibits hypoglycemic and hypolipidemic potentials on streptozotocin diabetic rats

Oreocnide integrifolia (Gaud.)Miq (Urticaceae) leaves are used to alleviate diabetic symptoms in folk medicine in northeast India. In the present study, dose and duration dependent hypoglycemic potentials were evaluated in streptozotocin induced diabetic rats. Administration of aqueous leaf extract (100, 250, 500 and 750 mg/kg body weight orally once daily) to diabetic rats reduced glycemic levels by 56 % by 4 weeks of treatment and was comparable to standard reference drug Metformin. The experimental data also revealed significant improvement in lowering lipid profile, Urea, Creatinine, Hb, HbA1c and insulin levels. The present study clearly demonstrates hypoglycemic and hypolipidemic potential of Oreocnide integrifolia leaf extract

Natural Products for the Treatment of Obesity, Metabolic Syndrome, and Type 2 Diabetes 2016

Editorial: The prevalence of obesity, metabolic syndrome, and type 2 diabetes is continuously on rise due to modernization of life style and changing dietary habits. Use of herbal medicines for the treatment of metabolic diseases is a viable option and list of potential candidates is ever expanding. This 2016 edition of this special issue regarding natural products for the treatment of obesity, metabolic syndrome, and type 2 diabetes contains 8 articles accepted from a total of 21 submissions consisting of 6 research articles and 2 clinical studies

Natural Products for the Treatment of Obesity, Metabolic Syndrome, and Type 2 Diabetes 2014

Editorial. In the modern and contemporary world, the incidence of obesity, metabolic syndrome, and type II diabetes is rising continuously due to modernization in life style and dietary habits. Herbal medicines have been shown to be beneficial against coexistence of these ailments. In 2013, we published a special issue on “Natural products for the treatment of obesity, metabolic syndrome, and type 2 diabetes” in EvidenceBased Complementary and Alternative Medicine (eCAM). After receiving an overwhelming number of submissions and successful compilation of research/review articles in the first season, the decision to publish annual special issue on this subject has been made by eCAM. Herein we present the 2014 issue in this series. This special issue consists of 5 original research papers and 4 review articles

Interleukin-1β orchestrates underlying inflammatory responses in microglia via Kruppel-like factor 4

Microglia are the resident macrophages of the CNS, which secrete several pro‐ and anti‐inflammatory cyto‐chemokines including interleukin‐1β (IL‐1β), in response to pathogenic stimuli. Once secreted, IL‐1β binds to IL‐1 receptor present on microglia and initiates the production of inflammatory cytokines in microglia. However, the detailed information regarding the molecular mechanisms of IL‐1β triggered inflammatory pathways in microglia is lacking. Our studies focused on the role of Krüppel‐like factor 4 (Klf4) in mediating the regulation of pro‐inflammatory gene expression upon IL‐1β stimulation in microglia. Our studies show that stimulation of microglia with IL‐1β robustly induces Klf4 via PI3K/Akt pathway which positively regulates the production of endogenous IL‐1β as well as other pro‐inflammatory markers, cyclooxygenase‐2, monocyte chemoattractant protein‐1 and interleukin‐6 (IL‐6). In addition, we report that Klf4 negatively regulates the expression of inducible nitric oxide synthase, thereby playing a key role in regulating the immunomodulatory activities of microglia. IL‐1β is a potent pro‐inflammatory cytokine which regulates inflammation in brain via activation of microglia. In this regard, we unravelled mechanisms for IL‐1β mediated regulation of downstream Cox‐2, iNOS (inducible nitric oxide synthase) as well as other cyto‐chemokines in microglia and have established a role for Klf4 in mediating microglial activation. We further report that Klf4 mediates the production of endogenous IL‐1β in response to exogenous IL‐1β stimulation. We hereby propose a novel transcription factor underlying IL‐1β mediated modulation of inflammation in the CNS

Amelioration of carbon tetrachloride induced hepatotoxicity in rats by standardized Feronia limonia. Linn leaf extracts

The hepatoprotective potential of standardized Feronia limonia (Family, Rutaceae) methanolic extract (FL-7) and chloroform soluble fraction (FL-9) were assessed against carbon tetrachloride (CCl4) induced oxidative stress and hepatotoxicity in rats. Rats treated with CCl4 recorded significant elevation in plasma markers of hepatic injury, alteration in hepatic antioxidant status and histopathological damages. However, rats pretreated with FL-7 (200 or 400 mg/kg, p.o.) and FL-9 (100 or 200 mg/kg, p.o.) for 7 days and later administered CCl4 (0.5 ml/kg, i.p.) recorded lowered indices of the above mentioned parameters and minimal histological damage in a dose dependent manner. These results were comparable to that of CCl4+silymarin treated rats. The results obtained with FL-7 and FL-9 are attributable to their free radical scavenging potential due to high contents of polyphenols and flavonols recorded herein. Overall, this study establishes the efficacy of FL-7 and FL-9 as hepatoprotective agents against CCl4 induced hepatotoxicity in rats

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Natural Products for the Treatment of Obesity, Metabolic Syndrome, and Type 2 Diabetes

Editorial. Globally, the incidence of obesity, metabolic syndrome, and diabetes (OMD) are continuously on the rise because of rapid changes in human life-style and dietary habits. Herbal extracts are of special interest in treating combination of these diseases because of their multipronged mode of action. The list of potential herbals to control metabolic diseases is ever-expanding. However, because of poor characterization and safety issues, these herbs face limitations for their clinical usage. This special issue is a collection of research and review articles on preclinical and clinical benefits of herbals in controlling OMD. This special issue contains 24 articles accepted from a total of 37 submissions consisting of 20 research articles, 3 review articles, and 1 clinical study. The research articles in this issue can be broadly divided into three disease categories—nonalcoholic steatohepatitis (NASH), obesity, and diabetic complications

MicroRNA-29b modulates Japanese encephalitis virus-induced microglia activation by targeting tumor necrosis factor alpha-induced protein 3

Japanese encephalitis virus (JEV), a single‐stranded RNA (ssRNA) virus, is the leading cause of encephalitis in Asia. Microglial activation is one of the key events in JEV‐induced neuroinflammation. Although the various microRNAs (miRNAs) has been shown to regulate microglia activation during pathological conditions including neuroviral infections, till date, the involvement of miRNAs in JEV infection has not been evaluated. Hence, we sought to evaluate the possible role of miRNAs in mediating JEV‐induced microglia activation. Initial screening revealed significant up‐regulation of miR‐29b in JEV‐infected mouse microglial cell line (BV‐2) and primary microglial cells. Furthermore, using bioinformatics tools, we identified tumor necrosis factor alpha‐induced protein 3, a negative regulator of nuclear factor‐kappa B signaling as a potential target of miR‐29b. Interestingly, in vitro knockdown of miR‐29b resulted in significant over‐expression of tumor necrosis factor alpha‐induced protein 3, and subsequent decrease in nuclear translocation of pNF‐κB. JEV infection in BV‐2 cell line elevated inducible nitric oxide synthase, cyclooxygenase‐2, and pro‐inflammatory cytokine expression levels, which diminished after miR‐29b knockdown. Collectively, our study demonstrates involvement of miR‐29b in regulating JEV‐ induced microglial activation. miR‐29b regulates Japanese Encephalitis Virus (JEV)‐induced microglia activation via inhibition of the anti‐inflammatory proteinTNFAIP3, which results in sustained activation of NF‐kB. Sustained NF‐?Bactivation further results in augmented secretion of pro‐inflammatory cytokines and induction of inflammatory mediators (iNOS and Cox‐2)