Ruizpennington3914

A high yielding green protocol has been developed and delineated for the synthesis of 3,3- di(indolyl)indolin-2-ones, potentially bioactive compounds, involving one pot aqueous medium condensation of isatin with indole in the presence of VOSO

. The synthesized compounds were screened for their carbonic anhydrase inhibitory activity against human (h) isoforms hCA I, hCA II, hCA IX, and hCA XII. These non-sulfonamide derivatives selectively inhibited hCA II in the micromolar range.

To develop a high yielding green protocol to synthesize 3,3-diindolyl oxindole derivatives using water as solvent media and screening the synthesized molecules for their carbonic anhydrase inhibitory activity.

The target compound is obtained by taking isatin, indole, VOSO

, and H

O in one-pot at 70

C.

The designed molecules were synthesized by using the new method. The molecules were screened for their CA inhibitory activity, which shows selective inhibition toward hCA II.The result showed an excellent yield without any lusing 10 mol% VOSO4 in high yields in a short period of time by a one-pot coupling reaction. Furthermore, the catalyst can also be recovered and reused for three consecutive catalytic cycles without any loss of its efficiency, which was confirmed by performing the experiment with 3a. The newly synthesized molecules (3a-r) were screened for their carbonic anhydrase inhibition potency against four isoforms, hCA I, II, IX, and XII and most of the compounds were found potent against hCA II with potency low to submicromolar range.

HIV-1 subtype C protease is a strategic target for antiretroviral treatment. However, resistance to protease inhibitors appears after months of treatment. Chromones and 2- biscoumarin derivatives show potential for inhibition of the HIV- subtype C protease.

Different heterocyclic structures from the ZINC database were docked against Human Immunodeficiency Virus-1 (HIV) subtype C protease crystal structure 2R5Q and 2R5P. The 5 best molecules were selected to be docked against 62 homology models based on HIV-protease sequences from infants failing antiretroviral protease treatment. This experimentation was performed with two molecular docking programs Autodock and Autodock Vina. These molecules were modified by substituting protons with different moieties, and the derivatives were docked against the same targets. Ligand-protein interactions, physical/chemical proprieties of the molecules, and dynamics simulations were analyzed.

Docking of all of the molecules was performed to find out the binding sites ofht be considered as promising HIV-1 subtype C protease inhibitors. This could be confirmed through synthesis and subsequent in vitro assays.

Dibenz[a,h]acridine, dibenz[a, i]acridine, NSC114903, dibenz[c,h]acridine, benzo[ a]acridine and their derivatives might be considered as promising HIV-1 subtype C protease inhibitors. This could be confirmed through synthesis and subsequent in vitro assays.

Diabetes mellitus is a significant risk factor for lower extremity amputations (LEA), both alone and in combination with peripheral vascular disease and infection. Currently, in Africa, more than half of the cases do not meet the recommended blood glucose control levels to prevent complications suggesting that the risk of complications is high.

The study aims to estimate hospitalization costs of diabetes-related lower extremities amputation for patients consulted at a referral hospital in 2015/16.

The study was a retrospective analysis using a mixed costing approach and based on 2015/16 financial year data inflated to 2020 at a 32-bed vascular unit of a quaternary care health facility. Patient level data were extracted from the hospital information system for length of stay, medication provided, laboratory and radiological investigations, and other clinical services offered.

The total summative cost for managing all 34 patients amounted to $ 568 407 or a mean unit cost per patient of $ 16 718 based ont, and the major cost drivers were general ward costs, compensation of employees, and radiology services. A comprehensive audit of the referral process and care process at the facility level as well as technical efficiency analysis, is required to identify inefficiencies that could reduce hospital costs for managing diabetes complications.The oxadiazole core is considered a privileged moiety in many medicinal chemistry applications. The oxadiazole class includes 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, and 1,2,5-oxadiazole. Compounds bearing an oxadiazole ring show a wide range of biological activities, such as anticancer, antibacterial, anti-inflammatory, anti-malarial, and insecticidal properties. Among oxadiazoles, the 1,3,4-oxadiazole has been the most widely explored moiety in medicinal chemistry research. This review is primarily focused on the anticancer, antibacterial, and anti-inflammatory activities of compounds containing 1,2,4-oxadiazole, 1,3,4-oxadiazole and 1,2,5-oxadiazole reported in the last five years.

Rare solid tumors have attracted much more attention due to the great unmet clinical need, limited treatment options, and poor prognosis. As the most thoroughly studied tumor marker, carcinoembryonic antigen (CEA) can not only overexpress in various common solid tumors but also in several rare solid tumors. Oncolytic virus therapy has achieved excellent anticancer effects in the past decades. Due to the specific high expression of CEA in certain tumor tissues but not in normal tissues, CEA has been applied to improve the tumor specificity of gene expression.

The studies of CEA expression in rare solid tumors and CEA-regulated oncolytic virus therapy were reviewed.

We showed the types of rare solid tumors with the overexpression of CEA. Elevated serum CEA levels can indicate the diagnosis, response of surgery or system therapy, distal metastasis, recurrence, and survival. Due to high tumor specificity, CEA-regulated OA therapy has demonstrated a surprising antitumor effect for common CEA-positive tumors in preclinical trials.

These data suggested that CEA could be a diagnostic and prognostic biomarker for several rare solid tumors. We proposed the hypothesis that CEA-regulated oncolytic virus therapy could be a promising therapeutic strategy for CEA-positive rare solid tumors.

These data suggested that CEA could be a diagnostic and prognostic biomarker for several rare solid tumors. We proposed the hypothesis that CEA-regulated oncolytic virus therapy could be a promising therapeutic strategy for CEA-positive rare solid tumors.

Epileptic activity frequently occurs in patients with Alzheimer's disease (AD), which may accelerate AD progression; however, the relationship between AD and epilepsy remains unclear.

We aimed to investigate the molecular pathways and genes linking AD and epilepsy using bioinformatics approaches.

Gene expression profiles of AD (GSE1297) and epilepsy (GSE28674) were derived from the Gene Expression Omnibus (GEO) database. The top 50% expression variants were subjected to weighted gene co-expression network analysis (WGCNA) to identify key modules associated with these diseases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses for the key modules were performed, and the intersected terms of functional enrichment and common genes within the key modules were selected. The overlapping genes were subjected to analyses of protein-protein interaction (PPI) network, transcription factor (TF)-mRNA network, microRNA (miRNA)-mRNA network, and drug prediction.

We identified 229 and 1187 genes in the AD-associated purple and epilepsy-associated blue modules, respectively. Six shared functional terms between the two modules included "calcium ion binding" and "calcium signaling pathway." According to 17 common genes discovered, 130 TFmRNA pairs and 56 miRNA-mRNA pairs were established. The topological analyses of the constructed regulatory networks suggested that TF - FOXC1 and miRNA - hsa-mir-335-5p might be vital co-regulators of gene expression in AD and epilepsy. In addition, CXCR4 was identified as a hub gene, becoming the putative target for 20 drugs.

Our study provided novel insights into the molecular connection between AD and epilepsy, which might be beneficial for exploring shared mechanisms and designing disease-modifying therapies.

Our study provided novel insights into the molecular connection between AD and epilepsy, which might be beneficial for exploring shared mechanisms and designing disease-modifying therapies.Electronically generated electromagnetic fields (EMFs), including those used in wireless communication such as cell phones, Wi-Fi and smart meters, are coherent, producing very high electric and magnetic forces, which act on the voltage sensor of voltage-gated calcium channels to produce increases in intracellular calcium [Ca2+]i. The calcium hypothesis of Alzheimer's disease (AD) has shown that each of the important AD-specific and nonspecific causal elements is produced by excessive [Ca2+]i. [Ca2+]i acts in AD via excessive calcium signaling and the peroxynitrite/oxidative stress/inflammation pathway, which are each elevated by EMFs.An apparent vicious cycle in AD involves amyloid-beta protein (Aβ) and [Ca2+]i. Three types of epidemiology suggest EMF causation of AD, including early onset AD. Extensive animal model studies show that low intensity EMFs cause neurodegeneration, including AD, with AD animals having elevated levels of Aβ, amyloid precursor protein and BACE1. Rats exposed to pulsed EMFs every day are reported to develop universal or near universal very early onset neurodegeneration, including AD; these findings are superficially similar to humans with digital dementia. EMFs producing modest increases in [Ca2+]i can also produce protective, therapeutic effects. The therapeutic pathway and peroxynitrite pathway inhibit each other. A summary of 18 different findings is provided, which collectively provide powerful evidence for EMF causation of AD. The author is concerned that smarter, more highly pulsed "smart" wireless communication may cause widespread very, very early onset AD in human populations.Phosphatidyl-inositol-3-kinase (PI3K) has emerged as a potential therapeutic target for the development of novel anticancer drugs. The dysregulation of PI3K has been associated with many human malignancies such as breast, colon, endometrial, brain, and prostate cancers. The PI3K kinases in their different isoforms, namely α, β, δ, and γ, encode PIK3CA, PIK3CB, PIK3CD, and PIK3CG genes. Specific gene mutation or overexpression of the protein is responsible for the therapeutic failure of current therapeutics. Recently, various PI3K signaling pathway inhibitors have been identified, which showed promising therapeutic results by acting on specific isoforms of the kinase too. Several inhibitors containing medicinally privileged scaffolds like oxadiazole, pyrrolotriazine, quinazoline, quinazolinone, quinazoline-chalcone hybrids, quinazoline-sulfonamide, pyrazolochalcone, quinolone hydroxamic acid, benzofuropyridinone, imidazopyridine, benzoxazines, dibenzoxanthene, indoloderivatives, benzimidazole, and benzothiazine derivatives have been developed to target the PI3K pathway and/or a specific isoform.