Synthesis, Characterization and Pharmacological evaluation of some newer Benzothiazole derivatives

The objective of the present work is to develop safer new chemical entities that show good anticonvulsant effects and antimicrobial actions. The current work describes the synthesis of Benzothiazole derivatives with encouraging anticonvulsant activity against MES and scPTZ tests with interesting pattern of antimicrobial effects. The synthesized Benzothiazole derivatives could be considered as lead molecule for the development of therapeutic agents. Many polycyclic and fused ring systems containing the thiazolenucleus(I) are well known. The most important is bicyclic system wherein the second ring benzene is fused to the 4,5 position of thiazole ring i.e. Benzothiazole.(II

Formulation and In-Vitro Evaluation of Niosomal drug Delivery in Cancer Chemotherapy

Drug delivery systems are defined as formulations aim for transportation of a drug to the desired area of action within the body. The aim of the study was to investigate the feasibility of using Niosomes as a drug delivery system for Cisplatin By entrapment of drug in Niosomes, dose also could be reduced. Niosomes were prepared by Ethanol injection method using cholesterol and Surfactant. Particle size, zeta potential, entrapment efficiency and in vitro drug release studies were performed. The targeted niosome delivery system is composed of drug, surfactant and cholesterol. With regard to the influence of formulation variables on the percent drug loading (PDL), different compositions with varying ratios of surfactant and cholesterol were studied. In –Vitro drug release mechanism was studied for 24 hours

Development of gum acacia-alginate microspheres of metformin hydrochloride: In vitro characterization

The metabolic disorder type 2 diabetes mellitus continuously increasing in the world. This disorder affecting all age groups. Thus, this disorder is now creating burden on healthcare sector, especially in case of underdeveloped countries. Nowadays many conventional drug delivery systems are available for management of diabetes mellitus. The gums and mucilages are polysaccharide obtained from various plant. Thus, present study is started with aim to formulate gum acacia based microspheres for gastroretentive delivery of metformin hydrochloride. The drug loaded microspheres were formulated using ionic gelation method and evaluated for physicochemical properties, mucoadhesive potential, swelling index and in vitro drug release study. The microspheres showed acceptable physicochemical properties, good swelling ability, mucoadhesive potential and sustained drug release. Thus, gum acacia could be promising alternative for fabrication of gastroretentive drug delivery system.&nbsp

Expert Consensus on Effective Utilization of Patient- Centered Insulin Therapy in Nepal

Diabetes presents a significant public health challenge in Nepal, compounded by its diversetopography and cultural beliefs. Despite a historical emphasis on patient-centered care, whichfosters unity among physician, patient, drug, and caretaker, effective diabetes managementis hindered by lack of awareness, cultural preferences for alternative therapies, and limitedhealth care resources. Addressing these challenges requires a consensus to optimize insulin\u27shistorical significance, marking a century as the first antidiabetic agent. Although advancementshave been made, a gap persists in understanding, awareness, and utilization of insulin amongNepalese physicians, necessitating tailored management approaches. A consensus meeting ofleading experts and diverse advisors from Nepal highlights the need for collective guidelinesto optimize insulin usage. Nepalese patients often exhibit reluctance towards insulin therapy,stemming from concerns about its complexity and efficacy. Blood glucose monitoring is vital forguiding insulin regimens, especially in critically ill patients, with the SECURE model offeringa comprehensive management approach. Tailoring insulin regimens to individual lifestylesenhances treatment adherence and overall efficacy. A patient-centered approach is paramount inoptimizing diabetes management in Nepal. Through collective agreement and guidelines, healthcare professionals can improve their knowledge and confidence in insulin therapy, leading tobetter patient outcomes and public health

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma

BACKGROUND Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. METHODS We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. RESULTS Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2'antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). CONCLUSIONS Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renalcell carcinoma consisted of at least three subtypes based on molecular and phenotypic features

Formulation and In-Vitro Evaluation of Niosomal drug Delivery in Cancer Chemotherapy

Drug delivery systems are defined as formulations aim for transportation of a drug to the desired area of action within the body. The aim of the study was to investigate the feasibility of using Niosomes as a drug delivery system for Cisplatin By entrapment of drug in Niosomes, dose also could be reduced. Niosomes were prepared by Ethanol injection method using cholesterol and Surfactant. Particle size, zeta potential, entrapment efficiency and in vitro drug release studies were performed. The targeted niosome delivery system is composed of drug, surfactant and cholesterol. With regard to the influence of formulation variables on the percent drug loading (PDL), different compositions with varying ratios of surfactant and cholesterol were studied. In –Vitro drug release mechanism was studied for 24 hours.</jats:p