Loss of protects against MASLD alone or with alcohol intake by preserving lipid homeostasis.

Background & Aims: Expression of P21, encoded by the gene, has been associated with fibrosis progression in steatotic liver disease (SLD); however, the underlying mechanisms remain unknown. In the present study, we investigated the function of CDKN1A in SLD.

Methods: expression levels were evaluated in different patient cohorts with SLD, fibrosis, and advanced chronic liver disease (ACLD).

The silent epidemic: Inappropriate use of proton pump inhibitors among hospitalized patients.

Background And Study Aims: There is an increasing trend to inappropriately prescribe proton pump inhibitors (PPIs) in different clinical settings despite the reported adverse outcomes. This study aimed to assess (1) the prevalence of potentially inappropriate use of PPIs and its associated risk factors among hospitalized patients, at pre-admission and discharge and (2) the prevalence of valid indications of PPIs use without prescription.

Patients And Methods: A retrospective observational study was performed at a single center, examining the records of patients aged ≥18 years who were admitted to the Family Medicine inpatient service over a one-year period.

Gemcitabine and synthesized silver nanoparticles impact on chemically induced hepatocellular carcinoma in male rats.

Gemcitabine (GEM) is a deoxycytidine analog chemotherapeutic drug widely used to treat many cancers. Silver nanoparticles (AgNPs) are important nanomaterials used to treat many diseases. Using gamma radiation in nanoparticle preparation is a new eco-friendly method.

The efficacy of intrauterine infusion of platelet rich plasma in women undergoing assisted reproduction: a systematic review and meta-analysis.

Background: Platelet-rich plasma (PRP) is an autologous platelet concentration recently used in the reproductive field. Studies had conflicting results regarding its effect on pregnancy outcomes. We aimed to solve the debate on the safety and efficacy of PRP in women undergoing assisted reproduction and assess the influence of covariates on the outcomes of PRP infusion.

JNKs protect from cholestatic liver disease progression by modulating Apelin signalling.

Background & Aims: Cholestatic liver injury is associated with c-Jun N-terminal kinases (JNK) activation in distinct cell types. Its hepatocyte-specific function during cholestasis, however, has not yet been established. Therefore, in our present study, we investigated the role of JNK1/2 during cholestasis and dissected its hepatocyte-specific function.

Impact of PNPLA3 I148M on alpha-1 antitrypsin deficiency-dependent liver disease progression.

Background And Aims: Genetic risk factors are major determinants of chronic liver disease (CLD) progression. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M polymorphism and alpha-1 antitrypsin (AAT) E342K variant, termed PiZ, are major modifiers of metabolic CLD. Both variants are known to affect metabolic CLD through increased endoplasmic reticulum stress, but their combined effect on CLD progression remains largely unknown.

Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis.

Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl) intoxication and bile duct ligation (BDL).

The efficacy of intranasal oxytocin in patients with Prader-Willi syndrome: A systematic review and meta-analysis.

Background And Aims: Prader-Willi Syndrome (PWS) is a rare genetic disease. Oxytocin is a neuropeptide hormone that impacts fear, and social recognition. Intranasal administration of oxytocin can be utilized to treat PWS patients.

Targeting Ligand Independent Tropism of siRNA-LNP by Small Molecules for Directed Therapy of Liver or Myeloid Immune Cells.

Hepatic clearance of lipid nanoparticles (LNP) with encapsulated nucleic acids restricts their therapeutic applicability. Therefore, tools for regulating hepatic clearance are of high interest for nucleic acid delivery. To this end, this work employs wild-type (WT) and low-density lipoprotein receptor (Ldlr) mice pretreated with either a leukotriene B4 receptor inhibitor (BLT1i) or a high-density lipoprotein receptor inhibitor (HDLRi) prior to the injection of siRNA-LNP.

Activation of the Unfolded Protein Response (UPR) Is Associated with Cholangiocellular Injury, Fibrosis and Carcinogenesis in an Experimental Model of Fibropolycystic Liver Disease.

Fibropolycystic liver disease is characterized by hyperproliferation of the biliary epithelium and the formation of multiple dilated cysts, a process associated with unfolded protein response (UPR). In the present study, we aimed to understand the mechanisms of cyst formation and UPR activation in hepatocytic c-Jun N-terminal kinase 1/2 () knockout mice. Floxed JNK1/2 () and animals were sacrificed at different time points during progression of liver disease.

The potential neuroprotective effect of diosmin in rotenone-induced model of Parkinson's disease in rats.

Most treatments for Parkinson's disease (PD) focus on improving the symptoms and the dopaminergic effects; nevertheless, they cannot delay the disease progression. Diosmin (DM), a naturally occurring flavone that is obtained from citrus fruits, has demonstrated anti-apoptotic, anti-inflammatory and antioxidative properties in many diseases. This study aimed to assess the neuroprotective effects of diosmin in rotenone-induced rat model of PD and investigate its potential underlying mechanisms.

Mesenchymal stem cells seeded onto nanofiber scaffold for myocardial regeneration.

Cardiac disease is the leading cause of mortality and disability worldwide. We investigated the role of undifferentiated adipose tissue-derived mesenchymal stem cells (ADMSC) alone and ADMSC seeded onto the electro-spun nanofibers (NF) for reconstructing damaged cardiac tissue in isoprenaline-induced myocardial infarction (MI) in rats. ADMSC were sorted by morphological appearance and by detection of cluster of differentiation (CD) surface antigens.

Nanomaterial-induced mesenchymal stem cell differentiation into osteoblast for counteracting bone resorption in the osteoporotic rats.

The current approach was designed to unearth the therapeutic potential of osteoblasts infusion, yielded from cultivating rat mesenchymal stem cells of bone marrow source in osteogenic differentiation media supplied with either hydroxyapatite nanoparticles (HA-NPs), chitosan/hydroxyapatite nanomaterials (C/HA-NPs), or chitosan nanoparticles, in the osteoporotic rats. The successful migration of the osteoblasts to the diseased bones of rats in C/HA-NPs and HA-NPs groups was evidenced by PCR screening of the Y-linked sex-determining gene (SRY) in the femoral bone tissue. Serum bone biomarker levels and gene expression patterns of cathepsin K, receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were assessed.

Indole glucosinolates exhibit anti-inflammatory effects on Ehrlich ascites carcinoma cells through modulation of inflammatory markers and miRNAs.

Background: Nuclear factor-κB (NF-κB) has been identified as the major link between inflammation and cancer. Natural agents that inhibit this pathway are essential in attenuating inflammation induced by cancer or chemotherapeutic drugs. High intake of Brassicaceae vegetables has been determined to modulate essential pathways related to chronic diseases.

Expression and prognostic relevance of long noncoding RNAs CRNDE and AOX2P in adult acute myeloid leukemia.

Introduction: Several long noncoding RNAs (lncRNAs) have been demonstrated to play a critical role in the tumorigenesis of acute myeloid leukemia (AML), and altered expression of certain lncRNAs has been recognized as a potential prognostic marker in AML patients. Here, we sought to determine whether the expression of the lncRNA colorectal neoplasia differentially expressed (CRNDE) and aldehyde oxidase 2 pseudogene (AOX2P) is associated with clinicopathological features and clinical outcome of patients with AML.

Methods: CRNDE and AOX2P expression levels were measured in diagnostic blood samples from 200 adult patients with de novo AML, along with 50 healthy control blood samples, using quantitative real-time polymerase chain reaction (qRT-PCR).

Therapeutic potential of targeted-gold nanospheres on collagen-induced arthritis in rats.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties.

Isolation and Identification of Pathogenic Acanthamoeba Species from Air Conditioning Systems, Egypt.

Acanthamoeba are free-living amoebae that cause granulomatous amoebic encephalitis and keratitis. In this study, we aimed to isolate and identify Acanthamoeba from air conditioning systems using in vitro cell culture and polymerase chain reaction assays. We also estimated the pathogenicity of the isolates by measuring their thermotolerance and studying mice models inoculated with these isolates.

Role of bone marrow-derived mesenchymal stem cells in alleviating pulmonary epithelium damage and extracellular matrix remodeling in a rat model of lung fibrosis induced by amiodarone.

The therapeutic role of mesenchymal stem cells (MSCs) in cases of amiodarone (AD) induced pulmonary fibrosis (PF) has not been well studied. Also, the period required by MSCs to attain full therapeutic effectiveness has not yet been assessed. We investigated the potential curative effect of bone marrow-derived MSCs (BM-MSCs) and conditioned media (CM) from BM-MSCs on AD induced PF by focusing on pulmonary epithelium injury and repair, and extracellular matrix (ECM) remodeling.

Loss of c-Jun N-terminal Kinase 1 and 2 Function in Liver Epithelial Cells Triggers Biliary Hyperproliferation Resembling Cholangiocarcinoma.

Targeted inhibition of the c-Jun N-terminal kinases (JNKs) has shown therapeutic potential in intrahepatic cholangiocarcinoma (CCA)-related tumorigenesis. However, the cell-type-specific role and mechanisms triggered by JNK in liver parenchymal cells during CCA remain largely unknown. Here, we aimed to investigate the relevance of JNK1 and JNK2 function in hepatocytes in two different models of experimental carcinogenesis, the dethylnitrosamine (DEN) model and in nuclear factor kappa B essential modulator (NEMO) mice, focusing on liver damage, cell death, compensatory proliferation, fibrogenesis, and tumor development.

Lipid-encapsulated siRNA for hepatocyte-directed treatment of advanced liver disease.

Lipid-based RNA nanocarriers have been recently accepted as a novel therapeutic option in humans, thus increasing the therapeutic options for patients. Tailored nanomedicines will enable to treat chronic liver disease (CLD) and end-stage liver cancer, disorders with high mortality and few treatment options. Here, we investigated the curative potential of gene therapy of a key molecule in CLD, the c-Jun N-terminal kinase-2 (Jnk2).

Osteoblast-Based Therapy-A New Approach for Bone Repair in Osteoporosis: Pre-Clinical Setting.

Background: Osteoporosis is a metabolic bone disease characterized by low bone density resulting in increased fracture susceptibility. This research was constructed to uncover the potential therapeutic application of osteoblasts transplantation, generated upon culturing male rat bone marrow-derived mesenchymal stem cells (BM-MSCs) in osteogenic medium (OM), OM containing gold (Au-NPs) or gold/hydroxyapatite (Au/HA-NPs) nanoparticles, in ovariectomized rats to counteract osteoporosis.

Methods: Forty rats were randomized into: (1) negative control, (2) osteoporotic rats, whereas groups (3), (4) and (5) constituted osteoporotic rats treated with osteoblasts yielded from culturing BM-MSCs in OM, OM plus Au-NPs or Au/HA-NPs, respectively.

Role of nanoparticles in osteogenic differentiation of bone marrow mesenchymal stem cells.

The present study aimed to investigate the osteoinductive potentiality of some selected nanostructures; Hydroxyapatite (HA-NPs), Gold (Au-NPs), Chitosan (C-NPs), Gold/hydroxyapatite (Au/HA-NPs) and Chitosan/hydroxyapatite (CH-NPs) on bone marrow- derived mesenchymal stem cells (BM-MSCs). These nanostructures were characterized using transmission electron microscope and Zetasizer. MSCs were isolated from bone marrow of rat femur bones and their identity was documented by morphology, flow cytometry and multi-potency capacity.

Development of an efficient cell-based assay system for monitoring hepatitis C virus genotype 4a NS3/4A protease activity.

Background: Hepatitis C virus (HCV) represents a serious worldwide healthcare problem. No protective vaccines against HCV have been developed yet due to the fact that HCV is rapidly mutable, allowing the virus to escape from the neutralizing antibodies. Understanding of HCV was initially hampered by the inability to achieve viral replication in cell culture.

Expression and immune recognition of polypeptides derived from Hepatitis C virus structural proteins.

Background: Hepatitis C virus (HCV) is characterized by a high degree of nucleotide sequence variability between genotypes. This variability extends to functional and immunological determinants. Serological tests using antigenic segments derived from the HCV polyprotein have been used for the diagnosis of HCV infection.