HASAN MUKHTAR

Earlier we introduced the idea of employing nanotechnology to improve the outcome of natural agents in chemoprevention and coined the term ‘Nanochemoprevention’. Recently we reported the efficacy of chitosan nanoparticles encapsulating green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG) for prostate cancer (PCa) therapy. Here we employed the idea of targeted uptake of therapeutic nanoparticles, a potentially powerful technology. Using PCa as a model, we report the efficacy of EGCG encapsulated in chitosan nanoparticles surface functionalized with the A10 2′-fluoropyrimidine RNA aptamers that recognize the extracellular domain of the prostate-specific membrane antigen (PSMA), henceforth called chit-EGCG-Apt. Prepared bioconjugates were spherical in shape with a unimodal size distribution, with diameter around 200 nm and a zeta potential of -30 mV. Cellular binding and uptake of the …

Ultraviolet Beam (UVB) radiation is the main cause of skin cancer worldwide. Besides biocompatibility, the instability and limited skin permeability are the most challenging features of many effective photochemopreventive agents. (−)-Epigallocatechin-3-gallate (EGCG) is a natural polyphenolic compound extracted from Camellia sinensis that has been demonstrated to have antioxidant, anti-inflammatory, and anti-cancer properties. We evaluated the efficacy of three innovative EGCG nanoformulations in chemoprevention of UVB-induced DNA damage in keratinocytes. Results indicated that the EGCG nanoformulations reduced UVB-induced oxidative stress elevation and DNA damage. The nanoformulations also reduced the UVB-induced formation of pyrimidine and pyrimidone photoproducts in 2D human immortalized HaCaT keratinocytes and SKH-1 hairless mice through antioxidant effects and possibly through …

Living host system possess mechanisms like innate immune system to combat against inflammation, stress singling, and cancer. These mechanisms are initiated by PAMP and DAMP mediated recognition by PRR. PRR is consist of variety of nucleic acid sensors like-RNA sensors. They play crucial role in identifying exogenous and endogenous RNA molecules, which subsequently mediate pro/inflammatory cytokine, IFN and ISGs response in traumatized or tumorigenic conditions. The sensors can sensitize wide range of nucleic acid particle in term of size and structure, while each category sensors belongs subclasses with differentially expressed in cell and distinguished functioning mechanisms. They are also able to make comparison between self and non-self-nucleic acid molecules through specific mechanisms. Besides exhibiting anti-inflammatory and anti-tumorigenic responses, RNA sensors cover the broad …

The porphyrias are a clinically, biochemically, and genetically heterogeneous group of metabolic diseases. They result from a predominantly hereditary, rarely acquired dysfunction of one of the eight enzymes along the heme biosynthetic pathway. Although the majority of the different variants of porphyria manifest with cutaneous symptoms, other forms exclusively show acute, potentially life-threatening neurovisceral porphyria attacks. In all porphyrias, inner organ complications can occur, mainly in the liver and kidneys. Therefore, affected patients should be cared for interdisciplinarily, if possible. This article provides an up-to-date overview of the clinic, diagnostics, and therapy of the various forms of porphyria.

Traffic congestion is a common day-to-day trouble in many countries, especially large cities. Gradually, even medium-sized and small towns are experiencing such problems and suffering from their negative effects. Importantly, traffic and crowd congestion largely spoils a region's economic and social status. For commuters, traffic congestion gives rise to excess travel costs, duration, and travel discomfort. From a traffic management perspective, traffic congestion leads to more expenses in the traffic system for handling inconvenient road networks. At the social level, traffic congestion causes road accidents, environmental damages and pollution. This article provides an overview of current time's traffic and crowd management system through a review of literature on stochastic queuing models for congestion and congestion control. In particular, we will focus on issues related to tackling the practical need and available features, and alleviation of daily traffic blockages. Dealing in terms of the concepts taken from Operation Research, the most important techniques are analytical queuing model application, stochastic optimality, and robust effective optimal solutions to common road congestion problems.

Background Data are steadily accruing that demonstrate that intestinal tumors are frequently derived from multiple founding cells, resulting in tumors comprised of distinct ancestral clones that might cooperate or alternatively compete, thereby potentially impacting different phases of the disease process. Aim We sought to determine whether tumors with a multi‐ancestral architecture involving at least two distinct clones show increased tumor number, growth, progression, or resistance to drug intervention. Methods Mice carrying the Min allele of Apc were generated that were mosaic with only a subset of cells in the intestinal epithelium expressing an activated form of PI3K, a key regulatory kinase affecting several important cellular processes. These cells were identifiable as they fluoresced green, whereas all other cells fluoresced red. Results Cell lineage tracing revealed that many intestinal tumors from our …

Objective: The use of trastuzumab (TZM) in the clinical management of human epidermal growth factor receptor 2 positive metastatic breast and gastric cancers, gastro-esophageal adenocarcinoma, and colorectal carcinoma has been limited by its off-target cardiac, hepatic, and renal toxicities which till date have no effective therapies in either their prevention or amelioration. Thus, the present study is designed at investigating the protective and therapeutic potentials of 400 mg/kg/day Clerodendrum volubile ethanol leaf extract (CVE) and Irvingia gabonensis ethanol seed extract (IGE) pretreatments in TZM-intoxicated Wistar rats based on their reported folkloric use in the local management of kidney and liver diseases and the previously reported therapeutic potential of these African vegetables in TZM cardiotoxicity.Methods: Forty-nine male Wistar rats were randomly allotted into seven groups of seven rats per group. Group I rats were treated with 10 ml/kg/day of5% dimethyl sulfoxide (DMSO) sterile water po and 1 ml/kg/day 5% DMSO sterile water ip; Groups II and III rats were orally pretreated with 400 mg/kg/day CVE and IGE, respectively, 3 h before 1 ml/kg/day/ip 5% DMSO sterile water; Group IV rats were orally pretreated with 10 ml/kg/day 5% DMSO sterile water 3 h before 2.25 mg/kg/day/ip TZM; and Groups V-VII rats were pretreated with 20 mg/kg/day Vit. C, 400 mg/kg/day CVE, and 400 mg/kg/day IGE all dissolved in 5% DMSO sterile water, respectively, 3 h before ip injections of 2.25 mg/kg/day TZM, all for 7 days. Liver function parameters, renal function parameters, oxidative stress markers, and histopathological investigations were the …

Maytenus roylanus (MEM) is a plant with anti-proliferative effects against prostate cancer. We aimed to explore the mechanism of action of MEM in prostate cancer (PCa) by employing an in vitro global proteome approach to get useful information of various signaling pathways and effected genes to define the mechanism of MEM action in prostate cancer. We conducted a global proteome analysis of CWR22Rv1after treatment with methanolic extract of MEM. The result of the proteomic profiling of in vitro PCa cells demonstrated the reduction in tumor protein D52 (TPD52) expression after treatment with methanolic extract of MEM. Down-regulation of TPD52 expression at mRNA level was observed by MEM treatment in CWR22Rν1 and C4-2 cells in a dose-dependent fashion probably by cleavage of Caspase 3 and PARP, or by modulation of cyclin-dependent kinases in CWR22Rν1 and C4-2 cells. The progressive …