Self-microemulsifying drug delivery system-based gastroretentive in situ raft of pazopanib with enhanced solubility and bioavailability.

Pazopanib hydrochloride (PZH) is a Biopharmaceutics Classification System class II drug that faces challenges at the formulation forefront including low aqueous solubility (0.043 mg/mL) and poor oral bioavailability (14-39%). The present investigation aimed to develop a self-microemulsifying drug delivery system (SMEDDS) of PZH using a blend of Capryol® 90, Labrasol®, and propylene glycol to improve its solubility.

Preclinical evaluation of dalbergin loaded PLGA-galactose-modified nanoparticles against hepatocellular carcinoma via inhibition of the AKT/NF-κB signaling pathway.

Prior research has shown the effectiveness of dalbergin (DL), dalbergin nanoformulation (DLF), and dalbergin-loaded PLGA-galactose-modified nanoparticles (DLMF) in treating hepatocellular carcinoma (HCC) cells. The present investigation constructs upon our previous research and delves into the molecular mechanisms contributing to the anticancer effects of DLF and DLMF. This study examined the anti-cancer effects of DL, DLF, and DLMF by diethyl nitrosamine (DEN)-induced HCC model in albino Wistar rats.

RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21.

Background: Prior evidence demonstrated that Regulator of G protein Signaling 6 (RGS6) translocates to the nucleolus in response to cytotoxic stress though the functional significance of this phenomenon remains unknown.

Methods: Utilizing in vivo gene manipulations in mice, primary murine cardiac cells, human cell lines and human patient samples we dissect the participation of a RGS6-nucleolin complex in chemotherapy-dependent cardiotoxicity.

Results: Here we demonstrate that RGS6 binds to a key nucleolar protein, Nucleolin, and controls its expression and activity in cardiomyocytes.

Targeting caspase pathway by novel -Me aziridine derivatives for hepatocellular carcinoma drug discovery.

Azaheterocycles are three-membered rings, known as aziridines, that occur naturally and have pharmaceutical applications.These compounds are present as several secondary metabolites produced by plants and microorganisms.Recent studies have demonstrated the effectiveness of aziridine derivatives (N-H/-Me) as anticancer agents.

RGS7 balances acetylation/de-acetylation of p65 to control chemotherapy-dependent cardiac inflammation.

Cardiotoxicity remains a major limitation in the clinical utility of anthracycline chemotherapeutics. Regulator of G-protein Signaling 7 (RGS7) and inflammatory markers are up-regulated in the hearts of patients with a history of chemotherapy particularly those with reduced left-ventricular function. RGS7 knockdown in either the murine myocardium or isolated murine ventricular cardiac myocytes (VCM) or cultured human VCM provided marked protection against doxorubicin-dependent oxidative stress, NF-κB activation, inflammatory cytokine production, and cell death.

Cardiac RGS7 and RGS11 drive TGFβ1-dependent liver damage following chemotherapy exposure.

Off target damage to vital organ systems is an unfortunate side effect of cancer chemotherapy and remains a major limitation to the use of these essential drugs in the clinic. Despite decades of research, the mechanisms conferring susceptibility to chemotherapy driven cardiotoxicity and hepatotoxicity remain unclear. In the livers of patients with a history of chemotherapy, we observed a twofold increase in expression of G protein regulator RGS7 and a corresponding decrease in fellow R7 family member RGS11.

A Comprehensive Review on Exosome: Recent Progress and Outlook.

Exosomes are intrinsic membrane-based vesicles that play a key role in both normal and pathological processes. Since their discovery, exosomes have been investigated as viable drug delivery systems and clinical indicators because of their magnitude and effectiveness in delivering biological components to targeted cells. Exosome characteristics are biocompatible, prefer tumor recruitment, have tunable targeting efficiency, and are stable, making them outstanding and eye-catching medication delivery systems for cancer and other disorders.

Vinpocetine mitigates DMH-induce pre-neoplastic colon damage in rats through inhibition of pro-inflammatory cytokines.

Colorectal cancer (CRC) is currently recognized as the third most prevalent cancer worldwide. Vinpocetine is a synthetic derivative of the vinca alkaloid vincamine. It has been found effective in ameliorating the growth and progression of cancerous cells.

A RGS7-CaMKII complex drives myocyte-intrinsic and myocyte-extrinsic mechanisms of chemotherapy-induced cardiotoxicity.

Dose-limiting cardiotoxicity remains a major limitation in the clinical use of cancer chemotherapeutics. Here, we describe a role for Regulator of G protein Signaling 7 (RGS7) in chemotherapy-dependent heart damage, the demonstration for a functional role of RGS7 outside of the nervous system and retina. Though expressed at low levels basally, we observed robust up-regulation of RGS7 in the human and murine myocardium following chemotherapy exposure.

Synthesis and appraisal of dalbergin-loaded PLGA nanoparticles modified with galactose against hepatocellular carcinoma: , pharmacokinetic, and studies.

Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer changing mRNA levels of apoptosis-related proteins.

Digital transformation challenges in sustainable financial service systems using novel interval-valued Pythagorean fuzzy double normalization-based multiple aggregation approach.

Recently, financial service systems have had essential impacts on public policies, the economic performance of firms, and all forms of industry and commerce. These systems play an important role in determining whether a society (which includes a wide range of members, from governmental institutions to individual consumers) has been successfully considered an environmentally sustainable path. The literature shows that the people who work in the financial sector are mostly unaware of the pressure and rationale behind sustainable development and its bearing on their work; however, those who work in the relevant research and policy areas generally ignore the vitality of the role of the financial sector in such a development.

RGS11-CaMKII complex mediated redox control attenuates chemotherapy-induced cardiac fibrosis.

Dose limiting cardiotoxicity remains a major limiting factor in the clinical use of several cancer chemotherapeutics including anthracyclines and the antimetabolite 5-fluorouracil (5-FU). Prior work has demonstrated that chemotherapeutics increase expression of R7 family regulator of G protein signaling (RGS) protein-binding partner Gβ, which drives myocyte cytotoxicity. However, though several R7 family members are expressed in heart, the exact role of each protein in chemotherapy driven heart damage remains unclear.

Assessment of hyaluronic acid-modified imatinib mesylate cubosomes through CD44 targeted drug delivery in NDEA-induced hepatic carcinoma.

This study aimed at the development of hyaluronic acid-functionalised imatinib mesylate cubosomes (HA-IM-CBs) that might be useful in CD44 targeting against hepatic cancer. The HA-IM-CBs had a 130.7 ± 2.

Ameliorative effect of fluvoxamine against colon carcinogenesis via COX-2 blockade with oxidative and metabolic stress reduction at the cellular, molecular and metabolic levels.

Fluvoxamine's (FLX's) anticancer potential was investigated in pre-clinical research utilizing a DMH-induced colorectal cancer (CRC) rat model. qRT-PCR and immunoblotting validated the mechanistic investigation. The CRC condition was induced in response to COX-2 and IL-6, however, following FLX therapy, the condition returned to normal.

Preclinical Evaluation of Dimethyl Itaconate Against Hepatocellular Carcinoma Activation of the e/iNOS-Mediated NF-κB-Dependent Apoptotic Pathway.

Hepatocellular carcinoma (HCC) is one of the most common tumors affecting a large population worldwide, with the fifth and seventh greatest mortality rates among men and women, respectively, and the third prime cause of mortality among cancer victims. Dimethyl itaconate (DI) has been reported to be efficacious in colorectal cancer by decreasing IL-1β release from intestinal epithelial cells. In this study, diethylnitrosamine (DEN)-induced HCC in male albino Wistar rats was treated with DI as an anticancer drug.

An intuitionistic fuzzy entropy approach for supplier selection.

Due to apparent flexibility of Intuitionistic Fuzzy Set (IFS) concepts in dealing with the imprecision or uncertainty, these are proving to be quite useful in many application areas for a more human consistent reasoning under imperfectly defined facts and imprecise knowledge. In this paper, we apply notions of entropy and intuitionistic fuzzy sets to present a new fuzzy decision-making approach called intuitionistic fuzzy entropy measure for selection and ranking the suppliers with respect to the attributes. An entropy-based model is formulated and applied to a real case study aiming to examine the rankings of suppliers.

Preliminary biomechanical cadaver study investigating a new load-sharing knee implant.

Purpose: One of the major contributors to the progression of knee osteoarthritis (OA) is the condition of loading in the knee joint. Innovatively designed load-sharing implants may be effective in terms of reducing joint load. The effects of these implants on contact joint mechanics can be evaluated through cadaver experiments.

New Scope of Targeted Therapies in Lung Carcinoma.

Lung Cancer (LC) is the leading cause of cancer deaths worldwide. Recent research has also shown LC as a genomic disease, causing somatic mutations in the patients. Tests related to mutational analysis and genome profiles have lately expanded significantly in the genetics/genomics field of LC.

G protein β5-ATM complexes drive acetaminophen-induced hepatotoxicity.

Excessive ingestion of the common analgesic acetaminophen (APAP) leads to severe hepatotoxicity. Here we identify G protein β5 (Gβ), elevated in livers from APAP overdose patients, as a critical regulator of cell death pathways and autophagic signaling in APAP-exposed liver. Liver-specific knockdown of Gβ in mice protected the liver from APAP-dependent fibrosis, cell loss, oxidative stress, and inflammation following either acute or chronic APAP administration.

Fabrication of Imatinib Mesylate-Loaded Lactoferrin-Modified PEGylated Liquid Crystalline Nanoparticles for Mitochondrial-Dependent Apoptosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of concern as it has substantial morbidity associated with it. Previous reports have ascertained the antiproliferative activity of imatinib mesylate (IMS) against diverse types of carcinomas, but limited bioavailability has also been reported. The present study envisaged optimized IMS-loaded lactoferrin (LF)-modified PEGylated liquid crystalline nanoparticles (IMS-LF-LCNPs) for effective therapy of IMS to HCC via asialoglycoprotein receptor (ASGPR) targeting.

Assessments of and antineoplastic potentials of β-sitosterol-loaded PEGylated niosomes against hepatocellular carcinoma.

β-sitosterol (BS), a phytosterol, exhibits ameliorative effects on hepatocellular carcinoma (HCC) due to its antioxidant activities. However, its poor aqueous solubility and negotiated bioavailability and short elimination half-life is a huge limitation for its therapeutic applications. To overcome these two shortcomings, BS-loaded niosomes were made to , film hydration method and process parameters were optimized using a three-factor Box-Behnken design.

Mechanistic exploration of the activities of poly(lactic--glycolic acid)-loaded nanoparticles of betulinic acid against hepatocellular carcinoma at cellular and molecular levels.

The effectiveness of betulinic acid (B) and PLGA loaded nanoparticles of B (Bnp) against hepatocellular carcinoma (HCC) was established and reported earlier. In continuation of our previous report, the present study described the molecular mechanisms of their antineoplastic responses. In this context, the antineoplastic properties of both B and Bnp were evaluated on DEN-induced HCC rat model.

Author Correction: Novel Indole-fused benzo-oxazepines (IFBOs) inhibit invasion of hepatocellular carcinoma by targeting IL-6 mediated JAK2/STAT3 oncogenic signals.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.