Peripheral immune signatures associated with the risk of hepatocarcinogenesis in cirrhotic Egyptian HCV patients before and after treatment with direct-acting antivirals.

Background: Although direct-acting antivirals (DAAs) have revolutionized the management of chronic HCV, the debatable association with hepatocellular carcinoma (HCC) occurrence/recurrence has raised major concerns about their long-term use, especially in cirrhotic cases. The role of epithelial tight junction proteins (TJPs) in hepatocarcinogenesis has been highlighted; however, the association of their expression in peripheral blood mononuclear cells (PBMCs) with HCC has rarely been reported. This study aimed to explore the role of peripheral claudin (Cldn)1 in liver pathogenesis and its crosstalk with soluble immune mediators in HCC prognosis.

Innovative anti-proliferative effect of the antiviral favipiravir against MCF-7 breast cancer cells using green nanoemulsion and eco-friendly assessment tools.

Telomerase enzyme prevents telomere shortening during division, having human telomerase reverse transcriptase (hTERT) as its catalytic subunit. Favipiravir (FAV), an RNA-dependent RNA polymerases inhibitor, shared structural similarity with hTERT and thus assumed to have cytotoxic effect on cancer cells, in addition to its prophylactic effect to immunocompromised cancer patients. Nanoemulsion (NE) is a potential tumor cells targeting delivery system, thereby enhancing therapeutic efficacy at the intended site, mitigating systemic toxicity, and overcoming multidrug resistance.

The p.Gly2019Ser is a common LRRK2 pathogenic variant among Egyptians with familial and sporadic Parkinson's disease.

The impact of LRRK2 variants on the risk of Parkinson's disease in Egyptians remains unknown. We examined 1210 Egyptians (611 PD patients and 599 controls) from 16 governorates across Egypt for 12 LRRK2 pathogenic variants. The p.

A single-center experience in home management of mild and moderate COVID-19 cases.

Introduction: The use of telemedicine for treatment of coronavirus disease 2019 (COVID-19) infection has been effective in lowering the risk of infection and relieving strain on the healthcare system. This study aimed to describe the clinical characteristics of COVID-19 cases, their follow-up, risk factors of disease severity, and predictors of hospital admission while using telemedicine.

Methodology: The study included 611 Egyptian patients with mild and moderate COVID-19 disease.

Development and validation of an LC‒MS/MS method for the determination of cyclocreatine phosphate and its related endogenous biomolecules in rat heart tissues.

The cardioprotective drug cyclocreatine phosphate has been awarded Food and Drug Administration-orphan drug designation for the prevention of ischemic injury to enhance cardiac graft recovery and survival in heart transplantation. Cyclocreatine phosphate is the water-soluble derivative of cyclocreatine. Estimating the levels of Cyclocreatine phosphate, Adenosine triphosphate, Creatine Phosphate, Creatine and Cyclocreatine helps us in understanding the energy state as well as evaluating the heart cells' function.

Design, synthesis, and structure-activity relationship studies of 6-benzo[]indeno[1,2-]thiophen-6-one derivatives as DYRK1A/CLK1/CLK4/haspin inhibitors.

A series of sulfur-containing tetracycles was designed and evaluated for their ability to inhibit protein kinase DYRK1A, a target known to have several potential therapeutic applications including cancers, Down syndrome or Alzheimer's disease. Our medicinal chemistry strategy relied on the design of new compounds using ring contraction/isosteric replacement and constrained analogy of known DYRK1A inhibitors, thus resulting in their DYRK1A inhibitory activity enhancement. Whereas a good inhibitory effect of targeted DYRK1A protein was observed for 5-hydroxy compounds 4i-k (IC = 35-116 nM) and the 5-methoxy derivative 4e (IC = 52 nM), a fairly good selectivity towards its known DYRK1B off-target was observed for 4k.

OncomiR-181a promotes carcinogenesis by repressing the extracellular matrix proteoglycan decorin in hepatocellular carcinoma.

Background: Proteoglycans are important tumor microenvironment extracellular matrix components. The regulation of key proteoglycans, such as decorin (DCN), by miRNAs has drawn attention since they have surfaced as novel therapeutic targets in cancer. Accordingly, this study aimed at identifying the impact of miR-181a in liver cancer and its regulatory role on the extracellular matrix proteoglycan, DCN, and hence on downstream oncogenes and tumor suppressor genes.

Correlating physico-chemical properties of analytes with Hansen solubility parameters of solvents using machine learning algorithm for predicting suitable extraction solvent.

Artificial neural networks (ANNs) are biologically inspired algorithms designed to simulate the way in which the human brain processes information. In sample preparation for bioanalysis, liquid-liquid extraction (LLE) represents an important step with the extraction solvent selection is the key laborious step. In the current work, a robust and reliable ANNs model for LLE solvent prediction was generated which could predict the suitable solvent for analyte extraction.

Functional analysis of a panel of molecular markers for diagnosis of systemic lupus erythematosus in rats.

Introduction: Systemic lupus erythematosus (SLE) is a diverse autoimmune disease that arises from a combination of complex genetic factors and environmental influences. While circRNAs and miRNAs have recently been identified as promising biomarkers for disease diagnosis, their specific expression patterns, and clinical implications in SLE are not yet fully understood.

Aim Of The Work: The aim of the present study was to determine the role of a panel of noncoding-RNAs specifically circRNAs (circ-TubD1, circ-CDC27, and circ-Med14), along with miRNA (rno-miR-146a-5p) and mRNA (TRAF6), as novel minimally invasive diagnostic biomarkers for experimentally induced SLE.

Facile synthesis of copper nitroprusside chitosan nanocomposite and its catalytic reduction of environmentally hazardous azodyes.

One of the biggest issues affecting the entire world currently is water contamination caused by textile industries' incapacity to properly dispose their wastewater. The presence of toxic textile dyes in the aquatic environment has attracted significant research interest due to their high environmental stability and their negative effects on human health and ecosystems. Therefore, it is crucial to convert the hazardous dyes such as methyl orange (MO) azo dye into environmentally safe products.

Dexamethasone-tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells.

Tamoxifen (TAM) is a key player in estrogen receptor-positive (ER+) breast cancer (BC); however, ∼30% of patients experience relapse and a lower survival rate due to TAM resistance. TAM resistance was related to the over expression of SOX-2 gene, which is regulated by the E2F3 transcription factor in the Wnt signaling pathway. It was suggested that SOX-2 overexpression was suppressed by dexamethasone (DEX), a glucocorticoid commonly prescribed to BC patients.

A comparative study of different antiviral treatment protocols in HCV related cryoglobulinemic vasculitis.

The treatment of HCV and its sequelae are used to be predominantly based on Interferon (IFN). However, this was associated with significant adverse events as a result of its immunostimulant capabilities. Since their introduction, the directly acting antiviral drugs (DAAs), have become the standard of care to treat of HCV and its complications including mixed cryoglobulinemic vasculitis (MCV).

Discovery of dual kinase inhibitors targeting VEGFR2 and FAK: structure-based pharmacophore modeling, virtual screening, and molecular docking studies.

VEGFR2 and FAK signaling pathways are interconnected and have synergistic effects on tumor angiogenesis, growth, and metastasis. Thus, instead of the conventional targeting of each of these proteins individually with a specific inhibitor, the present work aimed to discover novel dual inhibitors targeting both VEGFR2 and FAK exploiting their association. To this end, receptor-based pharmacophore modeling technique was opted to generate 3D pharmacophore models for VEGFR2 and FAK type II kinase inhibitors.

Favipiravir, an antiviral drug, in combination with tamoxifen exerts synergistic effect in tamoxifen-resistant breast cancer cells via hTERT inhibition.

Tamoxifen (TAM) is one of the most successful treatments for breast cancer; however, TAM resistance continues to be a significant barrier. TAM resistance has been reported to be associated with increased expression of human telomerase reverse transcriptase (hTERT). This enzyme shares structural similarity with RNA-dependent RNA polymerase (RdRp) enzyme of RNA viruses, suggesting that RdRp inhibitors may also inhibit hTERT.

Discovery of dual rho-associated protein kinase 1 (ROCK1)/apoptosis signal-regulating kinase 1 (ASK1) inhibitors as a novel approach for non-alcoholic steatohepatitis (NASH) treatment.

In the current study we suggest a novel approach to curb non-alcoholic steatohepatitis (NASH) progression, and we suggest privileged scaffolds for the design of novel compounds for this aim. NASH is an advanced form of non-alcoholic fatty liver disease that can further progress into fibrosis, cirrhosis, and hepatocellular carcinoma. It is a widely emerging disease affecting 25% of the global population and has no current approved treatments.

Epigenetic alterations of miR-155 and global DNA methylation as potential mediators of ochratoxin A cytotoxicity and carcinogenicity in human lung fibroblasts.

Ochratoxin A (OTA) is a well-known mycotoxin that adversely affects different human cells. Inhalational exposure to OTA and subsequent pulmonary diseases have been previously reported, yet its potential carcinogenicity and underlying molecular mechanisms have not been fully elucidated. This study aimed to evaluate the OTA-induced cytotoxicity and the epigenetic changes underlying its potential carcinogenicity in fetal lung fibroblast (WI-38) cells.

The Potential Role of Circulating Long Miscellaneous RNAs in the Diagnosis and Prognosis of Hepatitis C Related Hepatocellular Carcinoma.

Ribonucleic acids (RNAs) are important regulators of gene expression and crucial for the progression of hepatocellular carcinoma (HCC). This study was designed to determine the diagnostic and prognostic utility of the circulating long miscellaneous RNAs; LINC01419, AK021443, and AF070632 in HCV-related HCC patients. Real-time PCR was used to measure their relative expression levels in the plasma of 194 HCV patients, 120 HCV-related HCC patients and 120 healthy controls.