Lipid shell modified with combination of lipid and phospholipids in solid lipid nanoparticles for engineered specificity of paclitaxel in tumor bearing mice.

Paclitaxel (PTX) is an anticancer drug belonging to the class of Taxan. It is active against various types of carcinomas. The marketed formulation of paclitaxel is associated with deleterious effects with lack of specificity to tumor. Solid lipid nanoparticles (SLN) are colloidal carriers extensively studied and developed for there potential uses especially for controlled release and site specificity. The present study was designed to develop a formulation of PTX in the form of SLN to be administered via IV route with improved tumor specificity, in which the lipid shell was modified by using combination of lipid with phospholipids. Total eight formulations were prepared and were characterized by various in vitro and in vivo parameters. The microemulsification method was used for the preparation of SLN.The production yield  of resulting process for all SLN was high. Average particle size was ranged between 209 nm to 385 nm. The developed PTX-SLN showed high percentage entrapment efficiency. The zeta potential values showed the good stable feature of the sln.The in vitro dissolution study showed that drug release was more retarded and was found to dependent on concentration of lipids employed. In vitro cytotoxicity study was performed on MCF-7 cancer cell line, which showed that formulation G2 is having more potentiating effect on cancer cell line. Tissue targeting study and tumor growth inhibition studies were performed on mice where the PTX loaded SLN from batch G2 shown more promising outcome. Results obtained from this study indicated strongly that developed SLN are having potential as an efficient drug delivery system for paclitaxel

ESTABLISHMENT OF QUALITY CONTROL PARAMETERS OF PANCHASAKARA CHURNA - A CLASSICAL AYURVEDIC FORMULATION

Objective: Standardization of any herbal formulation is essential in order to assess the quality, purity, safety, and efficacy of drugs based on the analysis of their active properties. Testing of Ayurvedic preparations using scientific methodologies adds to quality and authenticity of the product.Methods: This article reports standardization parameters for a classical Ayurvedic formulation Panchasakara Churna. In this paper, the formulation was prepared as per Ayurvedic Formulary of India and was characterized by pharmacognostic, physical, physicochemical, phytochemical, toxicological parameters as well as thin layer chromatography (TLC) profiling using standard methodologies.Results: This experimental work provided diagnostic characteristics to identify and standardize the formulation Panchasakara Churna prepared using its official ingredients.Conclusion: Based on the present investigation results, a monograph on quality standards for Panchasakara Churna can be proposed for its batch-to-batch consistency. This document can also be utilised for rapid authentication fingerprints of this formulation using its TLC profiling.Keywords: Panchasakara Churna, Toxicological, Chromatography, Microscopi

WITHDRAWN: Recent advances in compression-coated tablets as a controlled drug delivery system

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L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis

Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome. We find that the actin-bundling protein L-plastin (LPL) significantly enhances NLRP3 assembly. Specifically, LPL enables apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) oligomerization during NLRP3 assembly by stabilizing ASC interactions with the kinase Pyk2, a component of cell-surface adhesive structures called podosomes. Upon treatment with exogenous NLRP3 activators, lung-resident alveolar macrophages (AMs) lacking LPL exhibit reduced caspase-1 activity, IL-1β cleavage, and gasdermin-D processing. LP

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Finding Influential Authors in Brand-Age Communities

Enterprises are increasingly using social media forums to engage with their customer online- a phenomenon known as Social Customer Relation Management (Social CRM). In this context, it is important for an enterprise to identify “influential authors” and engage with them on a priority basis. We present a study towards finding influential authors on Twitter forums where an implicit network based on user interactions is created and analyzed. Furthermore, author profile features and user interaction features are combined in a decision tree classification model for finding influential authors. A novel objective evaluation criterion is used for evaluating various features and modeling techniques. We compare our methods with other approaches that use either only the formal connections or only the author profile features and show a significant improvement in the classification accuracy over these baselines as well as over using Klout score

Understanding User-Community Engagement by Multi-faceted Features: A Case Study on Twitter

The widespread use of social networking websites in recent years has suggested a need for effective methods to understand the new forms of user engagement, the factors impacting them, and the fundamental reasons for such engagements. We perform exploratory analysis on Twitter to understand the dynamics of user engagement by studying what attracts a user to participate in discussions on a topic. We identify various factors which might affect user engagement, ranging from content properties, network topology to user characteristics on the social network, and use them to predict user joining behavior. As opposed to traditional ways of studying them separately, these factors are organized in our framework, People-Content-Network Analysis (PCNA), mainly designed to enable understanding of human social dynamics on the web. We perform experiments on various Twitter user communities formed around topics from diverse domains, with varied social significance, duration and spread. Our findings suggest that capabilities of content, user and network features vary greatly, motivating the incorporation of all the factors in user engagement analysis, and hence, a strong need can be felt to study dynamics of user engagement by using the PCNA framework. Our study also reveals certain correlation between types of event for discussion topics and impact of user engagement factors