Medicated Nanoparticle for Gene Delivery

Delivering the drug to the target site with a desired concentration to provide therapeutic effect is a major problem in the drug delivery system. Effectiveness, poor distribution and lack of selectivity are the drawbacks of the conventional dosage form. Recently Nanotechnology has been given much attention in various fields specifically in the biomedical application. Material includes organic, inorganic, polymeric and lipid-based nanobiomaterials after surface modification; it has been utilized for drug and gene delivery systems. Viral and non-viral vectors are the two types in gene delivery utilizing genetic materials like DNA plasmids, RNA and siRNA. Cellular and extracellular barriers are the two main barriers in gene delivery. The basic mechanism involved in the gene delivery is an introduction of a gene encoding a functional protein altering the expression of an endogenous gene or owning the capacity to cure or prevent the progression of a disease. Nanoparticle surface features like particle shape and surface charge are having major roles in the gene delivery. To provide the site-specific delivery various properties like nature of polymer, particle size, solubility, biocompatibility, biodegradability and nanoparticle surface features are need to be considered. Gene delivery has been utilized for various disease treatments such as cancer, AIDS, and cardiovascular diseases

Triptolide Administration Alters Immune Responses to Mitigate Insulin Resistance in Obese States

Individuals who are overweight or obese are at increased risk of developing prediabetes and type 2 diabetes, yet the direct molecular mechanisms that connect diabetes to obesity are not clear. Chronic, sustained inflammation is considered a strong risk factor in these interactions, directed in part by the short-lived gene expression programs encoding for cytokines and pro-inflammatory mediators. In this study, we show that triptolide administration in the C57BL/6 diet-induced obese mice at up to 10 μg/kg/day for 10 weeks attenuated the development of insulin resistance and diabetes, but not obesity, in these animals. Significant reductions in adipose tissue inflammation and improved insulin sensitivity were observed in the absence of changes in food intake, body weight, body composition, or energy expenditure. Analysis of the core cluster of biomarkers that drives pro-inflammatory responses in the metabolic tissues suggested TNF-α as a critical point that affected the co-development of inflammation and insulin resistance, but also pointed to the putatively protective roles of increased COX-2 and IL-17A signaling in the mediation of these pathophysiological states. Our results show that reduction of diet-induced inflammation confers partial protection against insulin resistance, but not obesity, and suggest the possibility of achieving overweight phenotypes that are accompanied by minimal insulin resistance if inflammation is controlled

Sinteza N4-(2,4-dimetilfenil) semikarbazona kao inhibitori 4-aminobutirat aminotransferaze

Several 2,4-dimethylphenyl substituted semicarbazones were synthesized in three steps involving aryl urea and aryl semicarbazide formations. The structures were confirmed by spectral and elemental analyses. All the compounds were evaluated for anticonvulsant activity by using a series of test models including maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (scSTY) seizure threshold tests. The compounds were also evaluated for behavioural impairement and depression activity. In the neurochemical investigation, potent compounds were evaluated for their effects on rat brain -aminobutyric acid levels and in vitro -aminobutyrate transaminase (Pseudomonas fluorescens) activity. Preliminary studies suggest these compounds to exhibit anticonvulsant activity via GABA-mediated mechanism.Sintetizirano je nekoliko 2,4-dimetilfenil supstituiranih semikarbazona u tri sintetska koraka koji uključuju aril uree i aril semikarbazide. Strukture spojeva su potvrđene spektroskopskim metoda i elementarnom analizom. Ispitano je antikonvulzivno djelovanje novih spojeva nakon izazivanja konvulzija elektrošokom te supkutanom primjenom pentilentetrazola ili strihnina. Osim toga, testirano je antidepresivno djelovanje te učinak tih spojeva na ponašanje štakora. Praćen je njihov utjecaj na koncentraciju gama-aminomaslačne kiseline (GABA) u mozgu štakora te in vitro na aktivnost gama-aminobutirat transaminaze (Pseudomonas fluorescens). Preliminarni pokusi ukazuju da antikonvulzivno djelovanje ovih spojeva uključuje GABA-ergički sustav

Sinteza N4-(2,4-dimetilfenil) semikarbazona kao inhibitori 4-aminobutirat aminotransferaze

Several 2,4-dimethylphenyl substituted semicarbazones were synthesized in three steps involving aryl urea and aryl semicarbazide formations. The structures were confirmed by spectral and elemental analyses. All the compounds were evaluated for anticonvulsant activity by using a series of test models including maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (scSTY) seizure threshold tests. The compounds were also evaluated for behavioural impairement and depression activity. In the neurochemical investigation, potent compounds were evaluated for their effects on rat brain -aminobutyric acid levels and in vitro -aminobutyrate transaminase (Pseudomonas fluorescens) activity. Preliminary studies suggest these compounds to exhibit anticonvulsant activity via GABA-mediated mechanism.Sintetizirano je nekoliko 2,4-dimetilfenil supstituiranih semikarbazona u tri sintetska koraka koji uključuju aril uree i aril semikarbazide. Strukture spojeva su potvrđene spektroskopskim metoda i elementarnom analizom. Ispitano je antikonvulzivno djelovanje novih spojeva nakon izazivanja konvulzija elektrošokom te supkutanom primjenom pentilentetrazola ili strihnina. Osim toga, testirano je antidepresivno djelovanje te učinak tih spojeva na ponašanje štakora. Praćen je njihov utjecaj na koncentraciju gama-aminomaslačne kiseline (GABA) u mozgu štakora te in vitro na aktivnost gama-aminobutirat transaminaze (Pseudomonas fluorescens). Preliminarni pokusi ukazuju da antikonvulzivno djelovanje ovih spojeva uključuje GABA-ergički sustav

Distinct Fractions of an Artemisia scoparia Extract Contain Compounds With Novel Adipogenic Bioactivity

Adipocytes are important players in metabolic health and disease, and disruption of adipocyte development or function contributes to metabolic dysregulation. Hence, adipocytes are significant targets for therapeutic intervention in obesity and metabolic syndrome. Plants have long been sources for bioactive compounds and drugs. In previous studies, we screened botanical extracts for effects on adipogenesis in vitro and discovered that an ethanolic extract of Artemisia scoparia (SCO) could promote adipocyte differentiation. To follow up on these studies, we have used various separation methods to identify the compound(s) responsible for SCO's adipogenic properties. Fractions and subfractions of SCO were tested for effects on lipid accumulation and adipogenic gene expression in differentiating 3T3-L1 adipocytes. Fractions were also analyzed by Ultra Performance Liquid Chromatography- Mass Spectrometry (UPLC-MS), and resulting peaks were putatively identified through high resolution, high mass accuracy mass spectrometry, literature data, and available natural products databases. The inactive fractions contained mostly quercetin derivatives and chlorogenates, including chlorogenic acid and 3,5-dicaffeoylquinic acid, which had no effects on adipogenesis when tested individually, thus ruling them out as pro-adipogenic bioactives in SCO. Based on these studies we have putatively identified the principal constituents in SCO fractions and subfractions that promoted adipocyte development and fat cell gene expression as prenylated coumaric acids, coumarin monoterpene ethers, 6-demethoxycapillarisin and two polymethoxyflavones

<i>Rheum rhaponticum</i> Root Extract Improves Vasomotor Menopausal Symptoms and Estrogen-Regulated Targets in Ovariectomized Rat Model

Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERβ in the hypothalamus of OVX rats, as well as in ERα/β cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition

Rheum rhaponticum Root Extract Improves Vasomotor Menopausal Symptoms and Estrogen-Regulated Targets in Ovariectomized Rat Model

Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ER&beta; receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 &deg;C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ER&beta; in the hypothalamus of OVX rats, as well as in ER&alpha;/&beta; cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition