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Hepatocellular carcinoma (HCC) is the most common form of malignancy in the liver. Autophagy was found to have a significant effect in controlling HCC. Anthocyanins, which are naturally occurring pigments in a variety of fruits and vegetables, have been thoroughly documented to be involved in a variety of bioactive activities and are widely employed for their antioxidant capabilities. Cyanidin-3-glucoside (C3G) extracted from Morus alba L. has promising antioxidant and anti-tumour activities. The current study aims to examine the protective action of C3G against hepatocellular carcinoma through the investigation of the autophagy protein ATG16L1 expression along with its related RNA molecules (hsa_circ_0001345 and miRNA106b) in Wistar rats. In vivo precancerous lesions (PCL) were induced using diethylnitrosamine (DEN) and acetamidofluorene (2-AAF). Rats were treated with C3G (10, 15, and 20 mg/kg; 4 times weekly) for 112 days (16 weeks). Liver function tests, alfa fetoprotein, ATG16L1 expression, hsa_circ_0001345, and miRNA106b differential expression were examined. Liver sections were examined by histological and immunohistochemical approaches. The current study’s findings indicated that C3G administration protects against the negative effects of DEN-2-AAF on liver functions and liver histopathological sections, which nominated C3G as a potential prophylactic agent against HCC.

Some studies suggest that thyroid hormones and disorders can influence breast (BC) and ovarian (OC) cancers risks. However, studies regarding their effect on these tumors progression are limited. Thyroid-stimulating hormone (TSH), T4, free T4 (FT4), T3, and free T3 (FT3) were detected in patients with BC, OC, benign breast and ovary diseases, and healthy controls using highly sensitive chemiluminescence assay. In contrast to OC, hypothyroidism prevalence was associated with BC late stage (11/24 vs. 2/46), high grade (11/23 vs. 4/47), lymph node invasion (11/42 vs. 0/28), positive distant metastasis (11/25 vs. 1/45), and large tumor size (14/25 vs. 1/45) compared to tumor early stages, low grades, negative lymph node, and distant metastasis and small size, respectively. Patients with late stage, high grade, large tumor size, positive lymph nodes, or positive distant metastasis were significantly (P < 0.05) associated with elevated levels of TSH and decreased levels of T4, FT4, T3, and FT3. There were both significant positive correlation of serum TSH and significant inverse correlation of T4, FT4, T3, and FT3 with these tumor worse outcomes. In conclusion, our results identify hypothyroidism as potentially important prognostic factor in BC not in OC that is associated with poor outcomes of BC patients.

Background Liver fibrosis is a major medical problem with high mortality and morbidity rates where the formation of regenerative nodules and cirrhosis leads to loss of liver function and may result in the development of hepatocellular carcinoma. bone marrow Mesenchymal stem cells (BM-MSCs) have drawn attention as a novel approach for treatment of liver fibrosis. This study aimed to evaluate the therapeutic effect of BM-MSCs on the liver structure in carbon tetrachloride (CCl4) induced liver fibrosis in male rats relative to resveratrol and Silybum marianum as standard drugs derived from herbal plants. Methods Fifty adult male albino rats (Sprague Dawley strain; 180–220 g mean body weight) were purchased from the Laboratory Animal Unit in the Nile Center of Experimental Research, Mansoura, Egypt. Liver function were determined, isolation and preparation of BM- MSCs and detection of cell-surface markers by flow cytometry. Results Animals exposed to CCl4 developed liver injury characterized by significant increase of liver enzymes, malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and CYP450, inhibition of antioxidant enzymes, and decreased albumin. Treatment with stem cells enhanced liver state more effectively than resveratrol and S. marianum. It significantly decreased AST, ALT, ALP, MDA, TNF-α, and CYP450 and increased albumin, SOD, GSH, GST, and CAT. Histopathological study and atomic force microscope results confirmed the therapeutic effects of MSCs. Conclusions BM-MSCs could restore liver structure and function in CCL4 induced liver fibrosis rat model, ameliorating the toxicity of CCl4 and improving liver function tests.

Background: Liver fibrosis is a major medical problem with high mortality and morbidity rates where the formation of regenerative nodules and cirrhosis leads to loss of liver function and may result in the development of hepatocellular carcinoma. bone marrow mesenchymal stem cells (BM-MSCs) have drawn attention as a novel approach for treatment of liver fibrosis. This study aimed to evaluate the therapeutic effect of BM-MSCs on the liver structure in carbon tetrachloride (CCl4) induced liver fibrosis in male rats relative to resveratrol and Silybum marianum as standard drugs derived from herbal plants. Methods: Fifty adult male albino rats (Sprague Dawley strain; 180–220 g mean body weight) were purchased from the Laboratory Animal Unit in the Nile Center of Experimental Research, Mansoura, Egypt. Liver function were determined, isolation and preparation of BM- MSCs and detection of cell-surface markers by flow cytometry. Results: Animals exposed to CCl4 developed liver injury characterized by significant increase of liver enzymes, malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and CYP450, inhibition of antioxidant enzymes, and decreased albumin. Treatment with stem cells enhanced liver state more effectively than resveratrol and S. marianum. It significantly decreased AST, ALT, ALP, MDA, TNF-α, and CYP450 and increased albumin, SOD, GSH, GST, and CAT. Histopathological study and atomic force microscope results confirmed the therapeutic effects of MSCs. Conclusions: BM-MSCs could restore liver structure and function in CCL4 induced liver fibrosis rat model, ameliorating the toxicity of CCl4 and improving liver function tests.

Carpal tunnel syndrome (CTS) is a common entrapment neuropathy in which one of the body’s peripheral nerves becomes pinched or crushed. Transforming growth factor beta 1 (TGF-β1) plays an important role in the pathogenesis of CTS. An association between TGF-β1 polymorphisms and the susceptibility or progression of a number of diseases has been reported. In this study, three TGF-β1 single nucleotide polymorphisms (SNPs), serum TGF-β1, and macrophage inflammatory protein 1 beta (MIP-1β) were investigated as potential diagnostic markers for the progression of CTS in Egyptian patients. One hundred CTS patients and 100 healthy controls were recruited for the study. TGF-β1 SNPs +915G/C, −509C/T and −800G/A were determined by TaqMan genotyping assay. Serum TGF-β1 and MIP-1β levels were measured by ELISA. Serum TGF-β1 and MIP-1β levels increased significantly and were strongly correlated with the occurrence of CTS. The C allele of +915G/C, the T allele of −509C/T, and the G allele of −800G/A occurred more frequently in patients from CTS than in controls. The serum levels of TGF-β1 and MIP-1β in the group of carriers of the genotypes +915G/C GC and CC, the genotype −509C/T TT and the genotype −800G/A GA and AA were significantly higher in CTS patients. TGF-β1 and its +915G/C, −509C/T, and −800G/A SNPs and MIP-1β could be useful prognostic markers for the occurrence of CTS.

Background:MircoRNAs are endogenous, small non-coding RNA molecules that have been recognized as important modulators of gene expression. MicroRNA is considered one of the potential biomarkers of infection and inflammation. Our study aims to identify the potential role of miRNA-155, miRNA-146b, and Procalcitonin (PCT) in the early detection of spontaneous bacterial peritonitis in cirrhotic liver patients. miRNA-155 and 146b are molecular biomarkers , while procalcitonin is a serum marker in ascites patients complicated with Spontaneous Bacterial Peritonitis (SBP) .Methods:This study was conducted on 199 patients, 101 of them have ascites complicated with spontaneous bacterial peritonitis, and 98 patients without spontaneous bacterial peritonitis (control group). Ascitic fluid samples were collected from patients with SBP undergoing paracentesis at National Hepatology Institute in Egypt. MicroRNAs were determined in the serum using qPCR (quantitative polymerase chain reaction), while procalcitonin has been assessed in serum samples using ELISA (Enzyme-linked immune assay) technique.Results:Serum levels of miRNA-146b & miRNA-155 were significantly higher (pConclusion:miRNA-155, miRNA-146b and procalcitonin can be used as early markers for the detection of SBP in hepatic patients with ascites.

Amal A Mohamed,1 Dina M Abo-Elmatty,2 Omnia Ezzat,3 Noha M Mesbah,2 Nada S Ali,3 Aliaa Sayed Abd El Fatah,4 Eman Alsayed,5 Mahmoud Hamada,6 Alshymaa A Hassnine,7 Sherief Abd-Elsalam,8 Ahmed Abdelghani,9 Mohamed Badr Hassan,9 Shaimaa A Fattah2 1Biochemistry and Molecular Biology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; 2Biochemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt; 3Biochemistry Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt; 4Internal Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt; 5Department of Clinical Pathology, Minia University Hospital, Minia, Egypt; 6Internal Medicine Department, Faculty of Medicine, Benha University, Benha, Egypt; 7Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Minia University, Minia, Egypt; 8Tropical Medicine Department, Tanta University, Tanta, Egypt; 9Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, EgyptCorrespondence: Sherief Abd-Elsalam, Department of Tropical Medicine, Faculty of Medicine, Tanta University, El-Bahr Street, Tanta, Egypt, Tel +201147773440, Email sherif.abdelbaky@med.tanta.edu.egBackground and Aims: Currently, liver biopsy is the gold standard method for diagnosis of non-alcoholic fatty liver severity. It is critical to develop non-invasive diagnostic method to diagnose nonalcoholic fatty liver rather than invasive techniques. Our case–control study was to address the value of circulating miRNA-122 and serum pro-neurotensin as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases.Methods: Clinical assessment, laboratory investigations, and anthropometric measurements were reported for 157 patients with proven NAFLD. Apparently, healthy participants (n=100) were enrolled as a control group. Serum samples were tested for micro-RNAs− 122 and pro-neurotensin.Results: Compared with the control subjects, both mi-RNA-122 and serum proneurotensin levels were increased in NAFLD (p< 0.001) and at a cut-off ≥ 6.83, mi-RNA-122 had 51.0% sensitivity, 70.0% specificity to differentiate NAFLD from healthy controls, while serum proneurotensin had 80.0% sensitivity and 80.0% specificity at a cutoff ≥ 108.Conclusion: The circulating pro-neurotensin might be used as a novel biomarker for diagnosis of patients with NAFLD, wherefore the integration of a circulating mi-RNA-122 and serum pro-neurotensin could be beneficial to diagnose NAFLD cases. Large-scale studies are needed to investigate the possible role of mi-RNA-122 and pro-neurotensin in the development, progression, and prognosis of NAFLD and NASH.Keywords: nonalcoholic fatty liver disease, NAFLD, metabolic associated fatty liver disease, MAFLD, biomarker, proneurotensin, micro-RNA-122, noninvasive, diagnosis, fatty liver

Introduction: Chronic inflammation causes articular bone and cartilage degeneration in people with rheumatoid arthritis (RA). Despite recent advancements in the management of RA, adverse side effects and ineffective treatments remain a problem. Access to treatment is hampered by financial restrictions. As a result, medications that reduce inflammation and bone resorption that are both safe and less expensive are required. Mesenchymal stem cells (MSCs) have recently been identified as a potential therapy for RA. Aim of study: The aim of this study was to examine the anti-arthritic effect of rat bone marrow-MSCs, oligosaccharides and human placental extract, individually and combined on RA model, using Complete Freund's adjuvant (CFA) induced arthritis in rats. Materials and methods: In female rats, RA was induced by injecting CFA in the paw of hind limb. Rat bone marrow-MSCs, oligosaccharides, and human placental extract (HPE) were given individually and in combination via intra-peritoneal route. Complete blood picture (CBC), erythrocyte sedimentation rate (ESR), serum cortisol, urea, uric acid and other biochemical parameters were measured to determine the safety and efficacy of the different treatments. Histopathological analysis of bone sections was carried out.Result: Combining oligosaccharides and HPE with rat-bone marrow MSCs had a favorable anti-arthritic and anti-inflammatory effect in CFA-induced arthritis in rats, with no negative effects on CBC, renal functions, serum cortisol, ESR, and liver enzymes. Histopathological analysis showed healing and remodeling of osteoporotic lesions in arthritic rats. Conclusion: Combination of rat MSCs, oligosaccharides and HPE has potential to be an effective treatment for rheumatoid arthritis.

Biocatalysis is crucial for a green, sustainable, biobased economy, and this has driven major advances in biotechnology and biocatalysis over the past 2 decades. There are numerous benefits to biocatalysis, including increased selectivity and specificity, reduced operating costs and lower toxicity, all of which result in lower environmental impact of industrial processes. Most enzymes available commercially are active and stable under a narrow range of conditions, and quickly lose activity at extremes of ion concentration, temperature, pH, pressure, and solvent concentrations. Extremophilic microorganisms thrive under extreme conditions and produce robust enzymes with higher activity and stability under unconventional circumstances. The number of extremophilic enzymes, or extremozymes, currently available are insufficient to meet growing industrial demand. This is in part due to difficulty in cultivation of extremophiles in a laboratory setting. This review will present an overview of extremozymes and their biotechnological applications. Culture-independent and genomic-based methods for study of extremozymes will be presented.

Rheumatoid arthritis (RA) is a joint destructive disorder with great morbidity. Early diagnosis and early and effective therapy may prevent joint damage and lead to better long-term results. Therefore, reliable biomarkers and outcome measures are needed. Complex interplay between multiple risk factors contributes to RA. These risk factors include environmental factors, genetic factors and epigenetic modifications. Long non-coding RNAs (lncRNAs) are involved in these epigenetic mechanisms. Accumulating evidence has shown that lncRNAs participate in the processes of inflammation, aberrant proliferation, apoptosis and angiogenesis. They also play roles in autoimmune diseases, such as SLE, Sjogren syndrome, RA and multiple sclerosis. Maternally expressed gene 3 (MEG3) is a maternally expressed lncRNA of the imprinted DLK1–MEG3 locus located on human 14q32 chromosome. It functions as a tumor suppressor. Decreased MEG3 expression has been observed in various human cancers, both type 1 and type 2 diabetes, osteoarthritis and in RA. Decreased serum levels of lncRNA MEG3 in RA could be attributed to MEG3 promoter hypermethylation induced by hypoxia. This downregulation was associated with increased inflammation, cell proliferation and cell invasion and decreased apoptosis. Long intergenic non-Protein coding RNA 00305 (LINC00305) was identified as a pro-inflammatory atherosclerosis-associated lncRNA. RA was associated with increased LINC00305 which served as a regulator of inflammatory, hypoxic, invasive, apoptotic and proliferative mechanisms associated with RA.

Cancer is an advanced disease characterized by numerous etiologies and multiple stages evoked by the deregulation in genetic and epigenetic programs via many factors like hormonal perturbation, microbial infections and chemical carcinogenesis. Once cells become cancerous, they still divide forever with none response of sign programmed cell death or senescence. Treatment relies on radiotherapy and chemotherapy that target cells with fast division. These treatments cause numerous side effects on normal cells division. Natural products have con­tinually and historically been studied for promising new leads in pharmaceutical development. Several plant parts are utilized in traditional medi­cine because they are easily available in rural areas and less expensive compared to new synthetic therapeutic drug. Moringa peregrina (M. peregrina), which belongs to the monogenic Moringaceae family, offers these advantages. Moringa trees possess different medicinal and nutritional value. This current review focuses on the chemical and biological properties of M. peregrina as a promising source of anti-cancer agent(s).

Rheumatoid arthritis (RA) is a debilitating disease characterized by chronic symmetric polyarthritis involving peripheral small joints. Heterogeneity in RA pathophysiology extends to a molecular level. Understanding the complicated interaction between genetics, environment, and autoimmunity, and their function in pathogenesis, is necessary for getting further insight into the mechanisms and outcomes that manage disease development and progression. Pharmacogenomics emphasizes the relations of numerous genetic signatures with responses to traditional disease-modifying drugs and biologics. More than 100 genetic susceptibility loci have been recognized for RA through studies directed on patients with longstanding RA compared with healthy controls. So the interaction between genes and the environment may determine who is more susceptible to develop RA. This review pays attention to some recently discovered genetic risk loci in RA; ZNF804a, CDK1, YWHAH 14-3-3 η, and IL-17A. Also, their involvement in the etiology, pathogenesis, and outcome of the disease is explained, aiming to provide new insights into the pathogenesis of RA and the possibility to develop novel therapeutic approaches through targeting these genes.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and it is the fourth cause of cancer-related mortality. The treatment of HCC with traditional chemotherapeutic agents such as doxorubicin has been limited due to poor efficacy, acquired resistance of the tumors and systemic toxicity. Verapamil as a P-gp inhibitor has demonstrated anti-cancer activities both in vitro and in vivo. Natural products and plant-derived compounds, such as ginger extract, have been investigated as safe and effective anti-cancer agents. Combination therapy offers preferable prognosis with less side effects. For example, the combination of chemotherapeutics with verapamil or ginger extract has been shown to exert beneficial therapeutic effects, overcome multidrug resistance and reduce side effects through modulation of different signaling pathways in tumor cells. Nano-sized formulations are designed to increase accumulation of drugs at the tumor environment and to improve solubility/bioavailability, promote retention, specificity, efficacy and safety. This review summarizes how to overcome cardiotoxicity and multidrug resistance evolved by doxorubicin in HCC treatment.

CD36 is a transmembrane protein involved in fatty acid translocation, scavenging for oxidized fatty acids acting as a receptor for adhesion molecules. It is expressed on macrophages, as well as other types of cells, such as endothelial and adipose cells. CD36 participates in muscle lipid uptake, adipose energy storage, and gut fat absorption. Recently, several preclinical and clinical studies demonstrated that the upregulation of CD36 is a prerequisite for tumor metastasis. Cancer metastasis-related research emerged much later and has been less investigated, though it is equally or even more important. CD36 protein expression can be modified by epigenetic changes and post-transcriptional interference from non-coding RNAs. Some data indicate modulation of CD36 expression in specific cell types by epigenetic changes via DNA methylation patterns or histone tails, or through miRNA interference, but this is largely unexplored. The few papers addressing this topic refer mostly to lipid metabolism-related pathologies, whereas in cancer research, data are even more scarce. The aim of this review was to summarize major epigenetic and post-transcriptional mechanisms that impact CD36 expression in relation to various pathologies while highlighting the areas in need of further exploration.

Occult hepatitis C virus infection (OCI) is the absence of HCV RNA in serum and the presence of actively replicating HCV RNA in hepatocytes and peripheral blood mononuclear cells (PBMCs), as evidenced by the presence of antigenomic negative sense single-stranded RNA. This study aimed to determine the prevalence of OCI in Egyptian lymphoma patients and assess changes in biochemical parameters in patients with confirmed OCI. The current study was conducted on 100 apparently healthy subjects as control group and 100 patients with lymphoma as a case group. HCV RNA was extracted and detected in both plasma and PBMCs using qRT-PCR. Total protein, albumin, ALT, AST, and total and direct bilirubin were measured in serum. OCI was detected in 6% of the patient group. OCI patients had lower levels of total protein and serum albumin and higher ALT and AST compared with lymphoma patients without OCI. Our study revealed that six out of 100 patients with lymphoma disorders had occult HCV infection (6%). Therefore, the possibility of this infection should be considered in patients with lymphoma.

Background Chronic inflammation causes articular bone and cartilage degeneration in people with rheumatoid arthritis (RA). Despite recent advances, management of RA is frequently accompanied with negative consequences, and ineffectiveness. Access to treatment is still hampered by many factors including financial restrictions. As a result, medications that reduce inflammation and bone resorption that are both safer and less expensive are required. Mesenchymal stem cells have recently been identified as a potential therapy for rheumatoid arthritis. Aim of Study: The aim of this study was to examine the anti-arthritic effect of rat bone marrow-MSCs, oligosaccharides and human placental extract, individually and combined on RA model, using Complete Freund's adjuvant (CFA) induced arthritis in rats. Materials and Methods In female rats, rheumatoid arthritis was induced by injecting Complete Freund's adjuvant in the paw of hind limbs. Treatments with rat bone marrow-mesenchymal stem cells via intravenous route, oligosaccharides, and human placental extract were given individually and in combination via intra-peritoneal route. Measurement of complete blood picture (CBC), ESR, cortisol, urea, uric acid, liver and renal biochemical parameters were carried out to determine the safety and efficacy of the different combinations. Inflammatory cytokines TNF- α, IL-6 and IL-10 were measured to assess anti-inflammatory effects. Histopathological analysis of bone sections was carried out too. Results Our findings showed that adding innovative treatments involving oligosaccharides and human placental extract to rat-bone marrow mesenchymal stem cells in a CFA-induced arthritic rat model resulted in a favorable anti-arthritic inflammatory effect as shown in reduction of inflammatory cytokines, with complete safety on blood picture, renal and liver functions, cortisol, and ESR. Histopathological analysis went concurrent with these results showing healing and remodeling of osteoporotic lesions induced in arthritic rat model. Conclusions The combination of rBM-MSCs via intravenous route, with oligosaccharides, and human placental extract could be employed as a powerful therapeutic medication to treat rheumatoid arthritis.

This study aimed to investigate the impact of ginger extract (GE) loaded into chitosan nanoparticles (CNPs) in enhancing cytotoxicity and reducing cardiotoxicity of doxorubicin (DXN) in hepatocellular carcinoma (HCC) induced mice. DXN and GE were loaded into CNPs and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. HCC was induced in male albino mice by injection of diethylnitrosamine (DINA). Mice were divided into eight groups (n = 15): (1) normal control, (2) DINA, (3) CNPs, (4) free DXN, (5) CNPs DXN, (6) free GE, (7) CNPs GE, and (8) CNPs DXN + CNPs GE. Both GE and DXN loaded into CNPs showed a greater decline in cell viability of HepG2 cells than the unloaded forms. GE CNPs displayed pronounced anticancer activity In Vivo through apoptosis, greater down-regulation of multidrug resistance 1, enhancement of anti-oxidant activity and depletion of vascular endothelial growth factor content in liver tissues. GE CNPs in combination with DXN CNPs showed nearly normal hepatic lobule architecture and the greatest increase in apoptotic cell count. Co-treatment group had decreased cardiac malondialdehyde, tumor necrosis factor-α and serum activity of creatine kinase and lactate dehydrogenase. Combination of GE CNPs and DXN CNPs might be a potentially effective therapeutic approach for HCC.

Despite the advanced treatment strategies, breast cancer remains the second cancer causing mortality across women worldwide. Notch signaling pathway has been found to be emerged in several cancers as well as in acquired and innate drug resistance. Therefore, understanding the role of Notch molecular mechanism could harbor beneficial impact to overcome chemoresistance and developing novel treatment strategies for cancer. Cisplatin (CIS) is an effective chemotherapeutic agent that is widely used against cancer but resistance is frequently occurs with limited therapeutic efficacy. One approach to overcome such unfavorable resistance is using complementary therapies with CIS. Thymoquinone (TQ) is a main compound in the essential oil of Nigella sativa. It has potent oncostatic activity by modulation of multiple regulatory pathways. Pentoxifylline (PTX) is a methylated xanthine derivative with remarkable anti-inflammatory and immunomodulatory actions. Combining TQ and PTX with CIS could be a promising strategy to suppress Notch signaling and overcome CIS resistance.

Rheumatoid arthritis (RA) is a joint destructive disorder. This study aimed to assess lncRNA MEG3 expression and its variant rs941576 in Egyptian patients with RA.100 RA patients and 100 healthy individuals were enrolled in the study. Quantitative PCR was used for expression analysis and allelic discrimination technology for genotyping.LncRNA MEG3 was down-regulated in RA patients and negatively associated with RA clinical features and HIF-1α and VEGF serum levels. On the contrary, it was positively associated with BAX serum levels in RA patients. The major A allele of rs941576 variant was associated with RA patients (Serum lncRNA MEG3 expression showed negative association with increased susceptibility to RA. MEG3 gene rs941576 (A/G) polymorphism was associated with increased severity of RA in the current population.

Long intergenic non-protein coding (lnc) RNA 00305 (LINC00305) is a pro-inflammatory atherosclerosis-associated lncRNA. We hypothesised that LINC00305 expression and its variant rs2850711 (A/T) are implicated in rheumatoid arthritis (RA) and linked with clinical and routine laboratory markers.100 RA patients and 100 healthy controls were recruited. LINC00305 genotyping and expression were performed using allelic-discrimination PCR and quantitative real-time PCR. LINC00305 diagnostic power was evaluated using area under the receiver operating characteristic curve (AUC). Serum nuclear factor- κB (NF-κB) and matrix metalloproteinase-3 (MMP-3) levels were determined by ELISA, standard laboratory markers by routine methods.LINC00305 expression was significantly increased in RA patients and positively correlated with DAS28, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor and anti-cyclic citrullinated peptide antibody. In multivariate analysis, NF-κB, MMP-3 and LINC00305 were significant predictors of RA (Increased expression level of LINC00305 and its rs2850711 genetic variant may play a role in the diagnosis and management of RA, and its severity and activity.

Objective This study investigated cytotoxicity and induction of apoptosis in human cervical cancer cells (HELA) and prostate cancer cells (PC-3) using the most active fraction of Moringa peregrina seed extract. Methods Dried and powdered seeds were extracted using 95% ethanol. The total ethanolic extract was further dissolved in distilled water and separated into petroleum ether, chloroform, ethyl acetate and aqueous extracts. Based on the results of in vitro anticancer studies of all extracts, the most highly active extract was selected for evaluation of apoptosis induction and cell cycle analysis on HELA and PC-3 cells at its half maximal inhibitory concentration using flow cytometry; DNA fragmentation by agarose gel electrophoresis and the expression of protein were measured by Western blot. Results The chloroform fraction from the ethanolic extract of M. peregrina (CFEE) was the most active antitumor fraction. The selectivity index, determined using the normal Vero cell line, indicated that CFEE had a high degree of selectivity against HELA and PC-3 cells. CFEE induced apoptosis, confirmed by cell cycle arrest at sub-G0 phase and DNA fragmentation. CFEE induced an increase in mRNA expression of caspase-3, a decrease in Bcl-2 mRNA expression, and decreased ATP levels. CFEE increased protein expression of caspase-3 and decreased protein expression of poly-ADP-ribose polymerase-1 (PARP-1). Flow cytometric analysis showed an appreciable increase in the number of cells in the early apoptotic stage in CFEE-treated HELA and PC-3 cells. CFEE treatment significantly increased lipid peroxidation (malondialdehyde level) in HELA and PC-3 cells. Conclusion Seed extract of M. peregrina displayed a significant antitumor effect through apoptosis induction in HELA and PC-3 cells.

The first-line treatment for advanced hepatocellular carcinoma (HCC) is the multikinase inhibitor sorafenib (SOR). Sofafenib resistance is linked to protein kinase B/ mammalian target of rapamycin (AKT/mTOR) and nuclear factor kappa B (NF-κB) activation, apoptosis inhibition and oxidative stress. This study investigated selenium nanoparticles (SeNps) to overcome SOR resistance in thioacetamide (TAA) induced HCC in rats.TAA (200 mg/kg/twice weekly, i.p.) was administered for 16 weeks to induce HCC.s. Rats were treated with oral SOR (10 mg/Kg daily), selenium, and SeNps (5 mg/kg three times/week) alone or in combination, for two weeks. Apoptosis, proliferation, angiogenesis, metastasis and drug resistance were assessed. Cleaved caspase 3 (C. CASP3), mTOR, and NF-κB were determined by western blotting. Expression of p53 gene and long-noncoding RNA-AF085935 was determined by qRT-PCR. Expression of B- Cell Leukemia/Lymphoma 2 (Bcl2), Bcl associated X protein (Bax)and glypican 3 (GPC3) was determined by enzyme-linked immunosorbent assay. Liver functions, antioxidant capacity, histopathology and CD34 immunohistochemistry were performed.SOR/SeNps reversed TAA-induced HCC in rats, through reduction of oxidative stress, activation of p53, Bax and CASP3, and inhibition of Bcl2. SOR/SeNps ameliorated the HCC-induced effect on cell proliferation and drug resistance by targeting mTOR and NF-κB pathways. SOR/SeNps decreased CD34 immunostaining indicating a decrease in angiogenesis and metastasis. SOR/SeNps regulated HCC epigenetically through the lncRNA-AF085935/GPC3 axis.SOR/SeNps are a promising combination for tumor suppression and overcoming sorafenib resistance in HCC by modulating apoptosis, AKT/mTOR and NF-κB pathways, as well as CD34 and lncRNA-AF085935/GPC3 axis.

The 14-3-3 Eta (14-3-3 η) biomarker platform is a relatively recent discovery with the potential to significantly address the diagnosis and prognosis of rheumatoid arthritis (RA) disease. Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) have been implicated in inflammatory mechanisms in RA. We hypothesized a molecular association of the coding YWHAH gene and its expressed protein 14-3-3 η with hypoxia and angiogenesis in RA. One hundred healthy subjects and 100 RA patients were enrolled in the study. YWHAH gene expression was determined using quantitative PCR, and its gene polymorphism rs2858750 was assessed by Taqman genotyping assay. Serum levels of 14-3-3 η, HIF-1α, and VEGF were measured using the ELISA technique, and clinical parameters were routinely examined. In RA patients, significant positive correlations were found between 14-3-3 η, HIF-1α (r = 0.84), and VEGF (r = 0.85). YWHAH gene expression was upregulated 10.8 fold (CI 95% 10.1-11.5) in RA patients and significantly correlated with all disease activity parameters, ACPA, and levels of 14-3-3 η, HIF-1α, and VEGF. RA patients showed a higher frequency of YWHAH rs2858750 A allele than healthy subjects (p = 0.02). The risk A allele carriers showed higher disease activity parameters, ACPA, YWHAH gene expression, and increased serum levels of 14-3-3 η (p 0.001), HIF-1α (p = 0.002), and VEGF (p = 0.001) than the G allele. Serum 14-3-3 η and its rs2858750 genetic variant are associated with increased hypoxia and angiogenesis in RA and activity, and severity of the disease.

Type 2 diabetes mellitus (T2DM) is a common disease in the elderly, affecting around 20% of geriatrics. In cross-sectional studies, T2DM had various adverse health effects, including cognitive impairment. The association of T2DM with decreased cognitive function suggests that T2DM can contribute to Alzheimer's disease (AD) The relationship between T2DM and AD continues to grow rapidly. It has been suggested that AD can be considered "type 3 diabetes”. Along with the processing of amyloid precursor protein (APP) and tau phosphorylation, the molecular links between T2DM and AD provide clues for new therapeutic targets such as glucagon-like peptide-1 (GLP-1), butyrylcholinesterase and receptor for advanced glycosylation end products (AGE). A possible mechanism correlating T2DM and AD is the alteration in insulin signaling in the brain. Insulin signaling is involved in several neuronal functions, and plays a vital role in the pathophysiology of AD. Therefore, the modification of neuronal insulin signaling by diabetic conditions may contribute to AD progression. Another possible mechanism is cerebrovascular changes, a common pathological change observed in both diseases. The importance of amyloid beta peptide (Aβ) induced cerebrovascular dysfunction in AD has been reported, indicating that pathological interactions between AGE receptor and Aβ have a role in this disorder.

There is increasing evidence of a link between type 2 diabetes mellitus (T2DM) and cognitive decline. T2DM has been recognized as a risk factor for Alzheimer's disease (AD). The aim of this research was to investigate the biochemical and physiological effects of vildagliptin treatment alone, and in combination with memantine, in a rat model of combined T2DM and AD. The experimental study was carried out on 75 male Wistar rats weighing 180-200 g. The rats were divided into five groups (n = 15): normal group, Alzheimer diabetic control, treated with vildagliptin (10 mg/kg/day), treated with memantine (30 mg/kg/day), and treated with combination of drugs. Serum glucose, lipid profile, acetylcholinesterase (AChE), homocysteine (Hcy), and amyloid beta peptide (Aβ) were determined. Lipid peroxidation was measured in brain tissue. Expression of amyloid precursor protein (APP) in the brain was assessed by q-PCR, and expression of total and phosphorylated tau was determined by Western Blotting. Vildagliptin alone and in combination with memantine caused a decrease in blood glucose, HOMA-IR, lipid profile, Hcy, malanodialdhyde, and acetylcholinesterase, and an increase in apolipoprotein E. Expression of APP and phosphorylated tau protein was decreased with combined vildagliptin and memantine treatment. In conclusion, vildagliptin treatment, either alone or in combination with memantine, modulates AD-associated biochemical changes and downregulates amyloid precursor protein and phosphorylated tau expression in diabetic rats.

Aim Nephrotoxicity is the major limiting factor for the clinical use of vancomycin (VCM) for treatment against multi-resistant Gram-positive bacteria. The present research aimed to investigate the ability of selenium nanoparticles (SeNPs) to protect against VCM-induced nephrotoxicity in rats. Main methods Experimental rats were divided into five groups; the first was the normal control, the second was treated with VCM (200 mg/kg twice/day, i.p.) for 7 days. The third, fourth, and fifth groups were treated orally with SeNPs (0.5, 1, and 2 mg/kg/day); respectively. SeNPs were administered for 12 days before VCM, 1 week simultaneously with VCM, and for another 1 week after its administration. Key findings Levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and kidney injury molecule-1 (KIM-1) were significantly increased in kidney tissue after VCM administration. Expression of adenosine 5′-monophosphate-activated protein kinase (AMPK), Bcl-2 associated X protein (Bax), caspase 3 and caspase 9 in kidney tissue was significantly increased, while the antioxidant enzymes, mitochondrial complexes, the ATP levels and B-cell lymphoma protein 2 (Bcl-2) were decreased in kidney in the VCM-treated rats compared to the normal control group. Treatment with SeNPs significantly decreased levels of MDA, iNOS, NO, TNF-α, and KIM-1 in the kidney tissue. Administration of SeNPs also downregulated the expression of the proapoptotic agents and enhanced the activities of the antioxidant enzymes and the mitochondrial enzyme complexes in the kidney. Significance SeNPs alleviated VCM-induced nephrotoxicity through their anti-oxidant, anti-inflammatory, anti-apoptotic and mitochondrial protective effects.

The genus

ZNF804a and CDK1 genes code for proteins involved in inflammatory pathways.This study aimed to investigate the correlation of ZNF804a and CDK1 expression profiles in RA with the activity and the severity of the disease and to assess their association with inflammatory reactions in the Egyptian RA patients.ZNF804a and CDK1 expression profiles were assessed using quantitative PCR (qRT-PCR). Clinical and laboratory parameters were evaluated.ZNF804a expression was down-regulated by 0.177-fold while CDK1 expression was up-regulated to 3.29-fold in RA patients compared with healthy controls (ZNF804a and CDK1 genes are implicated in RA pathogenesis due to their influences on TNF-α and IFN-1 which contribute to inflammation in RA patients.

The genus Natronolimnobius , currently including four species, is a member of the order Natrialbales , class Halobacteria, and consists of obligately alkaliphilic and extremely halophilic members found exclusively in highly alkaline hypersaline soda lakes. The species were classified into this genus mostly based on phylogenetic analysis of the 16S rRNA gene. However, a more advanced phylogenomic reconstruction based on 122 conserved single-copy archaeal protein markers clearly indicates a polyphyletic origin of the species included into this genus, thus warranting its reclassification into three separate genera. We therefore propose to transfer Nlb. innermongolicus (type strain N-1311) to a new genus Natronolimnohabitans as Nlh. innermongolicus comb. nov. and to transfer Nlb. aegyptiacus (type strain JW/NM-HA 15) and Nlb. sulfurireducens (type strain AArc1) to a new genus Natrarchaeobaculum as Nbl. aegyptiacum comb. nov. and Nbl. sulfurireducens comb. nov. The phylogenomic differentiation of these four species is also supported by the ANI/AAI distances and unique phenotypes. The most important physiological differences includes a previously unreported ability for cellulose and xylan utilization in Nlb. baerhuensis, thermophily in Nbl. aegyptiacus and anaerobic sulfur respiration in Nbl. sulfurireducens. We further present an emended description of Natronolimnobius baerhuensis .

The use of Anabolic Androgenic Steroid agents is evident within the competitive sport in senior and junior age groups, where they are taken by non-elite as well as elite participants. They are also taken in non-sporting contexts by individuals seeking to ‘improve’ their physique through an increase in muscle and/or decrease in fat mass. No accurate data is available for the prevalence of anabolic steroid misuse among athletes, studies suggest the illicit use of doping agents by athletes and non-athletes may be 1–5% in the population and greater than 50% in some groups; with the prevalence being higher in males. Many studies documented side effects and health hazards with the misusing of anabolic steroids, where these were accused as a cause of deaths among athletes. Intake of exogenous anabolic steroids disturbed the T/E ratio causing its evaluation above the normal level. This review will outline the anabolic steroids, its side effects and health impacts in both the sporting and physique development contexts. It also provides a brief review of the history of AAS as doping agents and athlete biological passport.

An extremophilic amylase from Alkalilimnicola sp. NM-DCM-1 was expressed and purified. The amylase, AmyD8, was extremophilic, with maximal activity at 55 °C, pH 10.5 and 2.4 M NaCl. AmyD8 had a broad substrate utilization spectrum, hydrolyzing branched and linear substrates. AmyD8 was stable and active in nonionic and anionic surfactants. AmyD8 was organic solvent resistant, retaining activity after incubation in benzene, methanol, ethanol and isopropanol. AmyD8 was entrapped in an agar–agar matrix with 89% entrapment yield and no loss in relative activity. Entrapped AmyD8 retained its extremophilic properties. Entrapment enhanced AmyD8’s thermal stability, the half-life of the entrapped enzyme nearly doubled after incubation at 50–65 °C. Entrapped AmyD8 had excellent recyclability, retaining 58% of initial activity after 16 hydrolysis cycles. These extreme properties give AmyD8 great economic feasibility.

Essential hypertension is widespread and has significant morbidity and mortality. However, the genetic basis of the disease is unknown. MicroRNAs are post-transcriptional regulators and have been implicated in development of the disease. The aim of this study was to assess the relationship between serum microRNA-605 and microRNA-623 expression and essential hypertension in Egyptian patients. MicroRNA expression in serum was determined in hypertensive patients and normotensive controls by quantitative real-time polymerase chain reaction. Hypertensive patients had significantly higher expression of both microRNA-605 (11 fold increase, p

A pullulanase, PulD7, was identified in the genome of the halophilic, alkalithermophilic isolate Alkalilimnicola sp. NM-DCM-1. PulD7 is 701 amino acids large with a carbohydrate binding module (CBM) 48 at the N-terminal. The full length PulD7 and N- and C-terminal truncated versions were cloned, heterologously expressed and functionally characterized. PulD7 displayed maximal activity at 55 °C, pH 9.5 and 2 M NaCl. PulD7 had good thermal stability, with a half-life of 693 min at 50 °C. PulD7 is an amylopullulanase, hydrolyzing both α‑1,4‑ and α‑1,6‑glycosidic bonds in soluble starch and pullulan, respectively. PulD7 was resistant to chemical reagents, including organic solvents (dimethyl sulfoxide, methanol, benzene, 20% v/v), reducing agents (β-mercaptoethanol, 5% v/v), surfactants (SDS and Tween 20, 5% v/v), the divalent chelator ethylene diamine tetra acetic acid (5 mM), and the chemical denaturant urea (8 M). PulD7 was not calcium-dependent. PulD7 was able to bind raw starch granules, reaching 52% binding in 3 h. The N-and C-terminal truncated forms of PulD7 had similar biochemical characteristics. PulD7ΔC had higher specific activity and halotolerance. The N-terminally truncated PulD7ΔN hydrolyzed amylose only, indicating that CBM48 is essential for binding branched substrates. PulD7 has unique characteristics giving it strong potential for application in biotechnological industries.

Relaxin-3 is known to play a role in appetite regulation, increasing food intake and body weight. This study aimed to assess the relation of relaxin-3 with ERS1 XbaI and PvuII polymorphisms. One hundred female patients with metabolic syndrome were investigated. The genotypes of ESR1 XbaI and PvuII polymorphisms were assessed with PCR-RFLP. Serum relaxin-3 level was measured for all participants using ELISA. Higher relaxin-3 levels showed association with the minor GG genotype of ESR-1 XbaI polymorphism but not PvuII polymorphism.

This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 μg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.

MicroRNAs (miRNAs) are of interest because they are dysregulated in different diseases, including liver diseases. MicroRNA-122 is an organ specific miRNA representing 70% of total miRNA in hepatocytes. The aim of this study was to investigate serum miRNA-122 expression in Egyptian patients with non-alcoholic fatty liver disease (NAFLD) and to determine its relationship with insertion/deletion polymorphism within the 3′ UTRs regions of interleukin-1A ( IL-1A ) gene which represents the binding site of miRNA-122. The study included 75 healthy subjects and 75 patients with NAFLD. Patients were recruited from the internal medicine outpatient clinic at Suez Canal University Hospital, Ismailia, Egypt. Serum miRNA-122 expression was determined using quantitative real-time PCR and normalization was done against RNU6B as an internal control. Our results reveled that about 76% of patients exhibited up-regulation of miRNA-122. The median miRNA-122 expression level in patients increased significantly (6.68 fold) compared to control (p = 0.001). Serum miRNA-122 expression level in NAFLD patients showed positive correlation with both serum triglycerides (TG) and very low density lipoprotein-cholesterol (VLDL-C) level (p = 0.048), and with serum IL-1A (p = 0.03). Regarding the relation between serum miRNA-122 expression and different genotypes of IL-1A insertion/deletion gene polymorphism (DD, ID, and II genotypes), patients carrying the major high risk DD genotype had a significant increase in miRNA-122 expression than those with heterozygous ID and the homozygous II genotypes (p = 0.002). In conclusion, serum miRNA-122 expression showed positive association with increased susceptibility to NAFLD in the study population. Insertion/deletion IL-1A gene polymorphism may be a marker for genetic susceptibility to NAFLD in Egyptian population, likely through miRNA-122 mediated regulation.

Interleukin-1A (IL-1A) is a cytokine involved in inflammatory process. IL-1A (rs3783553) gene polymorphism is comprised in the regulation of IL-1A expression.This study aims to evaluate association of IL-1A (I/D) gene polymorphism with NAFLD and its component traits among Egyptian populations.The study included 75 healthy subjects and 75 patients with NAFLD. Different genotypes of IL-1A (I/D) gene polymorphism were determined by PCR-PAGE technique, serum IL-1A level and other biochemical parameters were measured.The major D allele was significantly associated with NAFLD patients (p = .002). DD genotype showed a significant increase in BMI and decrease in HDL-C. Also serum IL-1A was significantly correlated with the DD genotype. Serum IL-1A showed a significant positive correlation with BMI, triglycerides, total cholesterol, LDL-C, VLDL-C and FBG, and a significant negative correlation with HDL-C.Major D allele of IL-1A (I/D) gene polymorphism is associated with NAFLD in the Egyptian population.

A cellulase, En5H, from halophilic, alkalithermophilic Alkalilimnicola sp. NM-DCM1 was expressed and purified. En5H had maximal hydrolytic activity at 55 °C, pH 8.8, and 2.5 M NaCl. En5H is β-1,4 linkage-specific, hydrolyzing carboxymethyl cellulose, Avicel, cellobiose, and p-nitrophenyl β-d-glucopyranoside. En5H was resistant to inhibitors and organic solvents. The half-life of En5H was increased 16–43-fold when incubated in 20% (v/v) of ionic liquids (IL) at 55 °C in the presence of 2.5 M NaCl, and maximal hydrolytic activity of En5H in 10% (v/v) 1-allyl-3-methylimidazolium chloride and 1,3-dimethylimidazolium dimethyl phosphate was 122 and 110%, respectively, as compared with activity in buffer. A cellulase-IL system combining IL pretreatment and enzymatic saccharification was tested. With an enzyme load of 110 U/g rice straw, the conversion of rice straw cellulose and hemicellulose increased by 28% compared with unpretreated rice straw. En5H has potential for use in transformation of lignocellulose to glucose in a single-step process.

Background Intestinal fatty acid-binding protein 2 (FABP2) is expressed in enterocytes and binds saturated and unsaturated long-chain fatty acids. The FABP2 Ala54Thr polymorphism has been reported to effect lipid metabolism. The aim of the present study was to assess the relationship between this polymorphism and peripheral atherosclerosis combined with type 2 diabetes mellitus (T2DM) in an Egyptian population. Methods The study was performed on 100 T2DM patients with peripheral atherosclerosis and 100 control subjects. The Ala54Thr polymorphism was analyzed by polymerase chain reaction–restriction fragment length polymorphism, whereas serum FABP2 levels were determined using ELISA. Fasting blood glucose, fasting serum insulin concentrations, HbA1c, lipid profile, body mass index (BMI) and systolic and diastolic blood pressure (SBP and DBP, respectively) were determined. Results There was a higher frequency of the Thr54 allele among the patient group (P = 0.002). In Ala54/Thr54 heterozygotes and carriers of the rare Thr54/Thr54 genotype, there were significant increases in BMI and FABP2. Those with the Thr54/Thr54 genotype had significantly decreased high-density lipoprotein cholesterol (HDL-C) concentrations; in addition, those with the Thr54/Thr54 genotype had significantly higher SBP and DBP than subjects with the Ala54/Ala54 and Ala54/Thr54 genotypes. There was a positive correlation between FABP2 levels and BMI, SBP and DBP, and a negative correlation with HDL-C. Conclusions The Thr54 allele of the FABP2 Ala54Thr polymorphism was associated with an increased incidence of peripheral atherosclerosis combined with T2DM in the population studied.