Unveiling the regulatory role of miRNAs in stroke pathophysiology and diagnosis.

Stroke, a major global cause of mortality, leads to a range of problems for those who survive. Besides its brutal events, stroke also tends to have a characteristic of recurrence, making it a complex disease involving intricate regulatory networks. One of the major cellular regulators is the non-coding RNAs (ncRNA), specifically microRNAs (miRNAs), thus the possible functions of miRNAs in the pathogenesis of stroke are discussed as well as the possibility of using miRNA-based therapeutic approaches.

Melodic maestros: Unraveling the role of miRNAs in the diagnosis, progression, and drug resistance of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly lethal form of pleural cancer characterized by a scarcity of effective therapeutic interventions, resulting in unfavorable prognoses for afflicted individuals. Besides, many patients experience substantial consequences from being diagnosed in advanced stages. The available diagnostic, prognostic, and therapeutic options for MPM are restricted in scope.

The role of mitochondrial/metabolic axis in development of tamoxifen resistance in breast cancer.

Only a few investigations, to our knowledge, have examined the bioenergetics of Tamoxifen (TMX) resistant individuals and reported altered mitochondrial activity and metabolic profile. The primary cause of TMX resistance is firmly suggested to be metabolic changes. Metabolic variations and hypoxia have also been linked in a bidirectional manner.

The emerging role of miRNAs in Merkel cell carcinoma pathogenesis: Signaling pathway crosstalk.

Merkel cell carcinoma (MCC) is an uncommon invasive form of skin cancer that typically manifests as a nodule on the face, head, or neck that is flesh-colored or bluish-red in appearance. Rapid growth and metastasis are hallmarks of MCC. MCC has the second-greatest mortality rate among skin cancers after melanoma.

miRNAs driving diagnosis, prognosis and progression in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive form of skin malignancy with a high recurrence commonly within two to three years of initial diagnosis. The incidence of MCC has nearly doubled in the past few decades. Options for diagnosing, assessing, and treating MCC are limited.

The potential role of miRNAs in the pathogenesis of adrenocortical carcinoma - A focus on signaling pathways interplay.

Adrenocortical carcinoma (ACC) is a highly malignant infrequent tumor with a dismal prognosis. microRNAs (miRNAs, miRs) are crucial in post-transcriptional gene expression regulation. Due to their ability to regulate multiple gene networks, miRNAs are central to the hallmarks of cancer, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, induction/access to the vasculature, activation of invasion and metastasis, reprogramming of cellular metabolism, and avoidance of immune destruction.

Metabolic/hypoxial axis predicts tamoxifen resistance in breast cancer.

We sought in our cross-sectional study to investigate the role of metabolic/hypoxial axis in the development of tamoxifen (TMX) resistance in BC patients. Quantification of plasma LncRNA Taurine upregulated-1 (TUG-1), miRNA 186-5p (miR-186), serum Sirtuin-3 (SIRT3), Peroxisome Proliferator Activator Receptor alpha (PPAR-1 α) and Hypoxia Inducible Factor-1 (HIF-1α) was done in a cohort of patients divided into TMX-sensitive and TMX-resistant candidates. Multiple logistic regression and Receiver Operating Characteristic curve were developed for significant predictors.

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent.

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated.

Association between interleukin 28B polymorphism and sustained virological response to sofosbuvir plus daclatasvir in chronic hepatitis C genotype 4 Egyptian patients.

What Is Known And Objective: Sofosbuvir has been approved as the first nonstructural protein 5B polymerase inhibitor with pan-genotypic activity against the hepatitis C (HCV) virus. Daclatasvir is a first-in-class hepatitis C virus nonstructural protein 5A replication complex inhibitor. We aimed to evaluate the usefulness of the reference single nucleotide polymorphism (rs12979860) interleukin 28B (CC genotype) for predicting sustained virological response to sofosbuvir plus daclatasvir in Egyptian patients infected with HCV-4.

Concomitant inhibition of hedgehog signalling and activation of retinoid receptors abolishes bleomycin-induced lung fibrosis.

Pulmonary fibrosis is a devastating disease with unknown treatment. All-trans retinoic acid (ATRA) attenuates bleomycin-induced lung fibrosis by different mechanistic pathways. However, the role of retinoid receptors in lung fibrosis is still unclear.

Concomitant Administration of Rosuvastatin and Lefleunamide in Low doses Synergize Against Complete Freunds Adjuvant (CFA)-Induced Rheumatoid Arthritis in Experimental Model.

Aim: The present work was designed to examine of the potential anti-inflammatory effect of rosuvastatin (ROSV) and/or Lefleunamide (LFLU) against Complete Freunds Adjuvant (CFA)-induced arthritis in rats.

Methods: The mRNA level of perxisome proliferator-activated receptor-alpha (PPAR-α) was determined using Real-time PCR. The levels of NF-κB, iNOS, IL-6, TNF-α and SOD activity were measured using ELISA.

Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways.

Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor.

Cyclosporin A activates human hepatocellular carcinoma (HepG2 cells) proliferation: implication of EGFR-mediated ERK1/2 signaling pathway.

One of the most common causes of cancer mortality worldwide is hepatocellular carcinoma (HCC). Extracellular signal-regulated kinase (ERK1/2) pathway has been shown to play an important role in the development and progression of HCC. Here, we demonstrate that the immunosuppressive agent cyclosporin A (CsA) has the ability to increase the cellular growth in HCC (HepG2 cells) via activation of ERK1/2 signaling cascade.

Functional characterization of α7 nicotinic acetylcholine and NMDA receptor signaling in SH-SY5Y neuroblastoma cells in an ERK phosphorylation assay.

In the present study, the functional properties of α7 nicotinic acetylcholine receptors (α7 nAChRs) and N-methyl-D-aspartate receptors (NMDARs) endogenously expressed in SH-SY5Y human neuroblastoma cells were characterized in an extracellular-signal regulated kinase (ERK) phosphorylation assay. Both choline and N-methyl-D-aspartate (NMDA) mediated robust concentration-dependent increases in ERK phosphorylation in the SH-SY5Y cells, exhibiting EC values in good agreement with those reported for the agonists at recombinant α7 nAChRs and NMDARs, respectively. Importantly, the responses evoked by choline (10 mM) and by NMDA (50 μM) were significantly inhibited by the α7-selective antagonist α-bungarotoxin (100 nM) and by the NMDAR-selective antagonist MK-801 (50 μM), respectively.

Probing the putative α7 nAChR/NMDAR complex in human and murine cortex and hippocampus: Different degrees of complex formation in healthy and Alzheimer brain tissue.

α7 nicotinic acetylcholine receptors (nAChRs) and N-methyl-D-aspartate receptors (NMDARs) are key mediators of central cholinergic and glutamatergic neurotransmission, respectively. In addition to numerous well-established functional interactions between α7 nAChRs and NMDARs, the two receptors have been proposed to form a multimeric complex, and in the present study we have investigated this putative α7 nAChR/NMDAR assembly in human and murine brain tissues. By α-bungarotoxin (BGT) affinity purification, α7 and NMDAR subunits were co-purified from human and murine cortical and hippocampal homogenates, substantiating the notion that the receptors are parts of a multimeric complex in the human and rodent brain.

Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs.

Exosomes have emerged as important mediators of diverse biological functions including tumor suppression, tumor progression, invasion, immune escape and cell-to-cell communication, through the release of molecules such as mRNAs, miRNAs, and proteins. Here, we identified differentially expressed exosomal miRNAs between normal epithelial ovarian cell line and both resistant and sensitive ovarian cancer (OC) cell lines. We found miR-940 as abundant in exosomes from SKOV3-IP1, HeyA8, and HeyA8-MDR cells.

Exosomes: From Garbage Bins to Promising Therapeutic Targets.

Intercellular communication via cell-released vesicles is a very important process for both normal and tumor cells. Cell communication may involve exosomes, small vesicles of endocytic origin that are released by all types of cells and are found in abundance in body fluids, including blood, saliva, urine, and breast milk. Exosomes have been shown to carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells.

Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype-4 chronic hepatitis C patients.

The therapeutic effect of pegylated interferon (peg-IFN) alfa-2a combined with ribavirin (RBV) on chronic hepatitis C Egyptian patients is low and further efforts are required to optimize this therapy for achievement of higher rates of virological response. This study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) in combination with pegylated interferon plus ribavirin on early virological response (EVR) in chronic hepatitis C Egyptian patients. Naïve 120 Egyptian patients with chronic hepatitis C virus infection were divided into two groups.

Coadministration of ezetimibe with pegylated interferon plus ribavirin could improve early virological response in chronic hepatitis C obese Egyptian patients.

Background: Ezetimibe has been reported to inhibit viral entry and to reduce BMI and has been proposed as a novel therapeutic agent for chronic hepatitis C (CHC), potentiating the effects of pegylated interferon and ribavirin (peg-IFN/RBV).

Objective: The aim of the study was to assess the effects of ezetimibe coadministration with peg-IFN/RBV combination on the early virological response (EVR) rates in nonobese and obese patients with CHC genotype 4 (CHC-4).

Patients And Methods: A total of 144 CHC-4 patients were divided into two groups; group 1 included nonobese patients (n=76) and group 2 included obese patients (n=68).

Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats.

Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to multiple organ failure. This study was carried out to investigate the effects of thymoquinone (TQ), the main constituent of Nigella sativa seeds, against LPS-induced hepatotoxicity. The obtained data revealed that LPS markedly depleted liver reduced glutathione (GSH) and significantly increased the level of malondialdehyde (MDA) and the activity of caspase-3 enzyme in the liver.

Pro-inflammatory and oxidative stress pathways which compromise sperm motility and survival may be altered by L-carnitine.

The testis is an immunologically privileged organ. Sertoli cells can form a blood-testis barrier and protect sperm cells from self-immune system attacks. Spermatogenesis may be inhibited by severe illness, bacterial infections and chronic inflammatory diseases but the mechanism(s) is poorly understood.

Protective effect of N-acetylcysteine against carmustine-induced myelotoxicity in rats.

Carmustine (BCNU) is used to treat a variety of tumors, in particular gliomas. However, the success of such treatment is limited by severe myelosuppression. The role of N-acetylcysteine (NAC) in protection against BCNU-induced myelotoxicity is still needed to be explored.

Metallothionein induction reduces caspase-3 activity and TNFalpha levels with preservation of cognitive function and intact hippocampal neurons in carmustine-treated rats.

Hippocampal integrity is essential for cognitive functions. On the other hand, induction of metallothionein (MT) by ZnSO(4) and its role in neuroprotection has been documented. The present study aimed to explore the effect of MT induction on carmustine (BCNU)-induced hippocampal cognitive dysfunction in rats.

Metallothionein attenuates carmustine-induced oxidative stress and protects against pulmonary fibrosis in rats.

The present study was carried out to evaluate the effect of exogenously administered metallothionein (MT) against carmustine (BCNU)-induced lung toxicity in rats. A total of 60 rats were randomly divided into four groups (15/group): control group in which the animals received 0.5 ml physiologic saline containing 10% ethanol (IP) weekly, MT-administered group in which rats received MT (30 micromol/kg, IP) weekly, BCNU-administered group in which rats received BCNU (5 mg/kg, IP) weekly and MT + BCNU group in which rats received weekly doses of BCNU (5 mg/kg, IP) followed 24 h later by MT (30 micromol/kg, IP).

Systemic administration of Zn2+ during the reperfusion phase of transient cerebral ischaemia protects rat hippocampus against iron-catalysed postischaemic injury.

1. The aim of the present study was to test the protective role of intravenous Zn(2+) against iron-catalysed reperfusion injury in the hippocampus of ischaemic rats. 2.