Assessing the Impacts of Different Levels of Nano-Selenium on Growth Performance, Serum Metabolites, and Gene Expression in Heat-Stressed Growing Quails.

Nano-minerals are employed to enhance mineral bioavailability thus promoting the growth and well-being of animals. In recent times, nano-selenium (nano-Se) has garnered significant attention within the scientific community owing to its potential advantages in the context of poultry. This study was conducted to explore the impact of using variable levels of nano-Se on the growth performance, carcass characteristics, serum constituents, and gene expression in growing Japanese quails under both thermoneutral and heat stress conditions. A randomized experimental design was used in a 2 × 3 factorial, with 2 environmental conditions (thermoneutral and heat stress) and 3 nano-Se levels (0, 0.2, and 0.5 mg/kg of diet. The findings revealed that heat stress negatively affected the growth and feed utilization of quails; indicated by the poor BWG and FCR. Additionally, oxidative stress was aggravated under heat stress condition; indicated by increased lipids peroxidation and decreased antioxidant enzymes activities. The addition of nano-Se, especially at the level of 0.2 mg/kg of diet, significantly improved the performance of heat stressed quails and restored blood oxidative status. The expression profile of inflammatory and antioxidant markers was modulated by heat stress and/or 0.2 and 0.5 nano-Se in conjunction with environmental temperature in quail groups. In comparison to the control group, the heat stress-exposed quails' expression profiles of IL-2, IL-4, IL-6, and IL-8 showed a notable up-regulation. Significantly lower levels of the genes for IL-2, IL-4, IL-6, and IL-8 and higher levels of the genes for SOD and GPX as compared to the heat stress group demonstrated the ameliorative impact of 0.2 nano-Se. The expression profiles of IL-2, IL-4, IL-6, and IL-8 are dramatically elevated in quails exposed to 0.5 nano-Se when compared to the control group. SOD and GPX markers, on the other hand, were markedly down-regulated. It was concluded that nano-Se by low level in heat stressed growing quails provides the greatest performance and its supplementation can be considered as a protective management practice in Japanese quail diets to reduce the negative impact of heat stress.

Effect of Amphetamine Dependence on Redox State via Alteration of Urinary Levels of Major and Trace Elements: A Case-Control Study in the Saudi Population.

Background Drug and substance abuse remains a major medical problem worldwide. Amphetamines are potent stimulants of the central nervous system. Amphetamine abuse is highly prevalent among drug-dependents. This study was conducted in Qassim, Saudi Arabia, to evaluate amphetamine's toxic effects on major and trace elements and their correlation with redox status. Methods The study involved amphetamine-only patients admitted to the Erada Rehabilitation Centre from March to October 2023. Urine samples were analysed from both normal subjects and amphetamine-dependent groups. Results Urinary sodium and chloride levels were significantly higher in the amphetamine-dependent group than in the control group, while their calcium levels decreased. Lipid peroxidase levels significantly increased in people with a substance use disorder (SUD), indicating oxidative stress. Together, their total antioxidant capacity decreased. Zinc (Zn), copper (Cu), lead (Pb), cadmium (Cd), sodium (Na), and total antioxidant capacity levels were positively correlated with lipid peroxidase. Conclusions Amphetamine-dependent people are more likely to experience a variety of health problems. This study found a direct correlation between an imbalance in major and trace elements and the redox status.

Altered expression of serum lncRNA CASC2 and miRNA-21-5p in COVID-19 patients.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has a high incidence of spread. On January 30, 2020, the World Health Organization proclaimed a public health emergency of worldwide concern. More than 6.9 million deaths and more than 768 million confirmed cases had been reported worldwide as of June 18, 2023. This study included 51 patients and 50 age- and sex-matched healthy subjects. The present study aimed to identify the expression levels of lncRNA CASC2 and miRNA-21-5p (also known as miRNA-21) in COVID-19 patients and their relation to the clinicopathological characteristics of the disease. The expression levels of noncoding RNAs were measured by RT-PCR technique. Results detected that CASC2 was significantly downregulated while miRNA-21-5p was significantly upregulated in COVID-19 patients compared to healthy subjects. A significant negative correlation was found between CASC2 and miRNA-21-5p. ROC curve analysis used to distinguish COVID-19 patients from controls. MiRNA-21-p serum expression level had a significant positive association with temperature and PO2 (p = 0.04 for each). These findings indicate that CASC2 and miRNA-21-p might be used as potential diagnostic and therapeutic biomarkers in COVID-19.

Relationship between Cytokines and Metabolic Syndrome Components: Role of Pancreatic-Derived Factor, Interleukin-37, and Tumor Necrosis Factor-α in Metabolic Syndrome Patients.

The metabolic syndrome (MetS) is a serious public health issue that affects people all over the world. Notably, insulin resistance, prothrombotic activity, and inflammatory state are associated with MetS. This study aims to explore the relationship between cytokines and tumor necrosis factor-α (TNF-α), pancreatic-derived factor (PANDER), and interleukin (IL-)-37 and the accumulation of MetS components. Eligible participants were divided into four groups as follows: group 1, patients with dyslipidemia; group 2, patients with dyslipidemia and obesity; group 3, patients with dyslipidemia, obesity, and hypertension; and group 4, patients with dyslipidemia, obesity, hypertension, and hyperglycemia. This study exhibited that serum levels of TNF-α and PANDER were significantly elevated (P < 0.001) in the MetS groups, while IL-37 level and IL-37 mRNA expression were significantly decreased (P < 0.001) relative to healthy controls. Moreover, this study has revealed significant correlations (P < 0.001) between MetS components and TNF-α, PANDER, and IL-37 levels in MetS patients. The aforementioned results suggested the association between the proinflammatory cytokine (TNF-α and PANDER) and anti-inflammatory cytokine (IL-37) with the accumulation of MetS components. Hence, the overall outcome indicated that PANDER and IL-37 may be considered novel biomarkers associated with increased risk of MetS and can be used as a promising therapeutic target in preventing, ameliorating, and treating metabolic disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01079-z.

Optimization of a Solid-Phase Extraction Coupled with a High-Performance Liquid Chromatography and Diode Array Ultraviolet Detection Method for Monitoring of Different Antibiotic Class Residues in Water Samples.

BACKGROUND: The increased use of cephalosporin antibiotics in the last few years as well as the detection of their residues in wastewater treatment plants and hospital wastewater poses a risk for infiltration of their residues into environmental water samples. OBJECTIVE: A simplified, sensitive, and convenient solid-phase extraction (SPE) procedure coupled with either HPLC or fast HPLC methods with diode array detection was developed and validated to screen the residues of six different cephalosporin antibiotics: cefoperazone, cefipime, ceftazedime, ceftriaxone, cefdinir, and cefotaxime, along with amoxicillin, levofloxacin, and ciprofloxacin in water samples. METHODS: An HPLC-diode array detector (HPLC-DAD) method and a fast HPLC method, based on a core-shell stationary phase, were developed for the fast screening of the antibiotic compounds. In addition, the SPE step was optimized to enable the extraction of the studied drugs with high accuracy of the recovered amounts of residues. RESULTS: The method sensitivity was enhanced by the coupling of SPE with HPLC-DAD and fast HPLC to achieve low LODs; from 0.2 to 3.8 ng/mL and from 0.65 to 12.2 ng/mL, respectively. The developed methods were augmented by LC-MS/MS determination for confirmation of identity and quantity of any positively identified sample. The method was applied to the analysis of water samples collected from a rural site. In Addition, an example application of cleaning validation of cefotaxime-contaminated stainless-steel surfaces was provided. CONCLUSION: The method's simplicity and high sensitivity encourage its application in monitoring of antibiotic residues in different types of water samples such as environmental samples and samples from cleaning validation activities. HIGHLIGHTS: HPLC-DAD and fast HPLC methods were developed for separation of nine different antibiotics. The combination with the SPE procedure achieved low detection limits; from 0.2 to 3.8 ng/mL for SPE-HPLC-DAD and from 0.65 to 12.2 ng/mL for SPE-fast HPLC.

Radiographic and immuno-histochemical evaluation of root perforation repair using MTA with or without platelet-rich fibrin or concentrated growth factors as an internal matrix in dog's teeth: in vivo animal study.

OBJECTIVES: To comparatively evaluate the in vivo outcome of MTA repair for contaminated and non-contaminated furcation perforations (FP) with or without PRF and CGF as a matrix in dogs' teeth. METHODS: Ninety dog teeth were divided into five groups based on the iatrogenic FP repair approach after doing root canal treatment: negative control (without FP), positive control (FP without repair), MTA, MTA + PRF and MTA + CGF groups, where FP were repaired promptly in subdivision 1 (n = 10; non-contaminated) and after 4 weeks of oral contamination in subdivision 2 (n = 10;contaminated). After 3 months, the perforation site was assessed radiographically (vertical bone density), histologically (inflammatory cell count, epithelial proliferation, cementum and bone deposition) and immunohistochemically (OPN and TRAP antibodies localisation). Data collected were statistically analysed using SPSS software at a 0.05 significance level. RESULTS: The MTA + PRF and MTA + CGF groups demonstrated significantly more bone formation, OPN immunolocalisation and fewer inflammatory cell counts than MTA group. MTA, MTA + PRF and MTA + CGF groups showed significantly favourable radiographic, histological and immunohistochemical healing features than the positive control, especially in non-contaminated subdivisions, that significantly showed better features than the contaminated subdivisions (P < 0.001). CONCLUSION: The use CGF and PRF as a matrix beneath MTA in FP repair in dog's teeth is promising as it could increase hard and soft tissue regeneration in non-contaminated and contaminated perforations. CLINICAL RELEVANCE: The repair of FP is challenging especially when associated with contaminated inter-radicular bone loss. Radiographic, histological and immunohistochemical comprehensive evaluation of the root and surrounding attachment apparatus response to different perforation repair protocols could give a predictable clinical outcome.

Green Synthesis of Zinc Oxide (ZnO) Nanoparticles from Green Algae and Their Assessment in Various Biological Applications.

The biosynthesis of algal-based zinc oxide (ZnO) nanoparticles has shown several advantages over traditional physico-chemical methods, such as lower cost, less toxicity, and greater sustainability. In the current study, bioactive molecules present in Spirogyra hyalina extract were exploited for the biofabrication and capping of ZnO NPs, using zinc acetate dihydrate and zinc nitrate hexahydrate as precursors. The newly biosynthesized ZnO NPs were characterized for structural and optical changes through UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX). A color change in the reaction mixture from light yellow to white indicated the successful biofabrication of ZnO NPs. The UV-Vis absorption spectrum peaks at 358 nm (from zinc acetate) and 363 nm (from zinc nitrate) of ZnO NPs confirmed that optical changes were caused by a blue shift near the band edges. The extremely crystalline and hexagonal Wurtzite structure of ZnO NPs was confirmed by XRD. The involvement of bioactive metabolites from algae in the bioreduction and capping of NPs was demonstrated by FTIR investigation. The SEM results revealed spherical-shaped ZnO NPs. In addition to this, the antibacterial and antioxidant activity of the ZnO NPs was investigated. ZnO NPs showed remarkable antibacterial efficacy against both Gram-positive and Gram-negative bacteria. The DPPH test revealed the strong antioxidant activity of ZnO NPs.

Biosorption of Cadmium and Lead by Dry Biomass of Nostoc sp. MK-11: Kinetic and Isotherm Study.

Cadmium (Cd) and lead (Pb) are global environmental pollutants. In this study, Nostoc sp. MK-11 was used as an environmentally safe, economical, and efficient biosorbent for the removal of Cd and Pb ions from synthetic aqueous solutions. Nostoc sp. MK-11 was identified on a morphological and molecular basis using light microscopic, 16S rRNA sequences and phylogenetic analysis. Batch experiments were performed to determine the most significant factors for the removal of Cd and Pb ions from the synthetic aqueous solutions using dry Nostoc sp. MK1 biomass. The results indicated that the maximum biosorption of Pb and Cd ions was found under the conditions of 1 g of dry Nostoc sp. MK-11 biomass, 100 mg/L of initial metal concentrations, and 60 min contact time at pH 4 and 5 for Pb and Cd, respectively. Dry Nostoc sp. MK-11 biomass samples before and after biosorption were characterized using FTIR and SEM. A kinetic study showed that a pseudo second order kinetic model was well fitted rather than the pseudo first order. Three isotherm models Freundlich, Langmuir, and Temkin were used to explain the biosorption isotherms of metal ions by Nostoc sp. MK-11 dry biomass. Langmuir isotherm, which explains the existence of monolayer adsorption, fitted well to the biosorption process. Considering the Langmuir isotherm model, the maximum biosorption capacity (qmax) of Nostoc sp. MK-11 dry biomass was calculated as 75.757 and 83.963 mg g-1 for Cd and Pb, respectively, which showed agreement with the obtained experimental values. Desorption investigations were carried out to evaluate the reusability of the biomass and the recovery of the metal ions. It was found that the desorption of Cd and Pb was above 90%. The dry biomass of Nostoc sp. MK-11 was proven to be efficient and cost-effective for removing Cd and especially Pb metal ions from the aqueous solutions, and the process is eco-friendly, feasible, and reliable.

Double-Fermented Soybean Meal Totally Replaces Soybean Meal in Broiler Rations with Favorable Impact on Performance, Digestibility, Amino Acids Transporters and Meat Nutritional Value.

Inclusion of microbial fermented soybean meal in broiler feed has induced advantageous outcomes for their performance and gastrointestinal health via exhibiting probiotic effects. In this study, soybean meal (SBM) was subjected to double-stage microbial fermentation utilizing functional metabolites of fungi and bacteria. In broiler diet, DFSBM replaced SBM by 0, 25, 50 and 100%. DFSBM was reported to have higher protein content and total essential, nonessential and free amino acids (increased by 3.67%, 12.81%, 10.10% and 5.88-fold, respectively, compared to SBM). Notably, phytase activity and lactic acid bacteria increased, while fiber, lipid and trypsin inhibitor contents were decreased by 14.05%, 38.24% and 72.80%, respectively, in a diet containing 100% DFSBM, compared to SBM. Improved growth performance and apparent nutrient digestibility, including phosphorus and calcium, and pancreatic digestive enzyme activities were observed in groups fed higher DFSBM levels. In addition, higher inclusion levels of DFSBM increased blood immune response (IgG, IgM, nitric oxide and lysozyme levels) and liver antioxidant status. Jejunal amino acids- and peptide transporter-encoding genes (LAT1, CAT-1, CAT-2, PepT-1 and PepT-2) were upregulated with increasing levels of DFSBM in the ration. Breast muscle crude protein, calcium and phosphorus retention were increased, especially at higher inclusion levels of DFSBM. Coliform bacteria load was significantly reduced, while lactic acid bacteria count in broiler intestines was increased with higher dietary levels of DFSBM. In conclusion, replacement of SBM with DFSBM positively impacted broiler chicken feed utilization and boosted chickens' amino acid transportation, in addition to improving the nutritional value of their breast meat.

The impact of the clip-tone training device and its smartphone application to pressurized metered-dose inhaler in adult asthmatics.

BACKGROUND: Despite traditional inhaler technique counseling, many patients make clinically important mistakes when they use their inhalers. This study investigates the value of using a connected inhalation aid when adults with asthma use their metered-dose inhaler (pMDI). METHODS: Adult asthmatics (n = 221), using a pMDI, were randomly divided into a verbal training group (n = 110) and an enhanced training group (n = 111). 21 subjects were lost during the study, each group included 100 subjects at the end of the study. The study was divided into 3 visits. Traditional pMDI training was delivered at visit 1 to both groups which included an explanation of the steps with special stress on frequently mistaken steps e.g. exhalation before use and inhaling slowly and deeply. The enhanced training group was enhanced by using the Clip-Tone training aid linked to its dedicated smartphone app. enhanced training patients were encouraged to use this connected training aid during real-life use between the study visits. Baseline data were collected at the first visit. At all three visits (baseline, 1 month, and 2 months), subjects first completed all inhaler techniques, health outcome measures, received inhaler training, then took bronchodilators, and 30 min later repeated the lung function outcome measures. RESULTS: Both groups showed a significant decrease (p < 0.001) in the total mean number of pMDI inhalation techniques mistakes at visits 2 and 3, with a lower number of mistakes (p < 0.05) for slower inhalations for the enhanced training group compared to the verbal training group. Inhalation time (an indicator of a slow inhalation) significantly (p < 0.05) improved at each visit in the enhanced training group. In the enhanced training group, there was a gradual significant increase (p < 0.05) in lung functions while the improvements in the verbal training group were only significant (p < 0.05) at visit 3, and by visit 3, the enhanced training group had significantly higher scores than the verbal training group on both FEV1 and PEF% predicted. The asthma control test (ACT) score improved at each visit in both groups with a greater increase in the enhanced training group (p < 0.05) and more patients (44 and 21) improved their score by 3 or more in the second and third visit respectively. CONCLUSION: The connected Clip-Tone training aid helped patients improve their pMDI inhaler technique and their asthma control compared to traditional methods. These results highlight the potential of connected inhalers in the future management of inhaled therapy.

The potential role of serum expression profile of long non coding RNAs, Cox2 and HOTAIR as novel diagnostic biomarkers in systemic lupus erythematosus.

BACKGROUND: The role of the long non-coding RNAs (lncRNAs) in the pathogenesis of systemic lupus erythematosus (SLE) is mostly unknown, despite increasing evidence that lncRNAs extensively participate in physiological and pathological conditions. AIM: To detect the level of lncRNA-Cox2, HOTAIR, IL-6, and MMP-9 in the serum of SLE patients and to correlate these levels with disease activity and patients' clinical and laboratory data to evaluate the value of these biomarkers for SLE diagnosis and assessment of disease activity. METHODS: Blood samples from 58 SLE patients, and 60 healthy controls (HCs) were used for detection of lncRNAs-Cox2 and HOTAIR expression levels by real-time polymerase chain reaction. Both IL-6 and MMP-9 serum levels were assayed by enzyme-linked immunosorbent assay. Lupus activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: The serum expression levels of lncRNA-Cox2 and HOTAIR were significantly up-regulated in SLE patients vs HCs (fold change [median (IQR) was 1.29(0.81-1.71, P<0.0001) and 2.68(0.95-3.67), P = 0.038) for lncRNA-Cox2 and HOTAIR, respectively. Serum levels of both IL-6 and MMP-9 were significantly high in SLE patients compared with HCs (P≤0.001 for each). The up-regulated lncRNA-Cox2 was positively associated with the presence of neurological manifestations in SLE patients (P = 0.007). Furthermore, HOTAIR expression level had significantly positive correlation with IL-6 (r = 0.578, P<0.0001), MMP-9 level (r = 0.762, P<0.0001), nephritis grades (r = 0.296, P = 0.024) and proteinuria (r = 0.287, P = 0.035). LncRNA-Cox2 showed sensitivity and specificity 72.4%, and 100.0% respectively. HOTAIR sensitivity was 60.3%, and specificity was 100.0%. By multiple logistic regression analysis, lncRNA-Cox2 and HOTAIR were found as SLE independent predictors. CONCLUSION: LncRNA-COX2 and HOTAIR can be used as new non-invasive biomarkers for the diagnosis of SLE.

Growth Optimization and Secondary Metabolites Evaluation of Anabaena variabilis for Acetylcholinesterase Inhibition Activity.

Cyanobacteria comprise a good natural resource of a potential variety of neuro-chemicals, including acetylcholinesterase inhibitors essential for Alzheimer's disease treatment. Accordingly, eight different cyanobacterial species were isolated, identified, and evaluated on their growth on different standard nutrient media. It was found that the modified Navicula medium supported the highest growth of the test cyanobacteria. The effects of methylene chloride/methanol crude extracts of the test cyanobacteria on acetylcholinesterase activity were examined and compared. Anabaena variabilis (KU696637.1) crude extract recorded the highest acetylcholinesterase inhibition (62 ± 1.3%). Navicula medium chemical components were optimized through a Plackett-Burman factorial design. The biomass of Anabaena variabilis increased significantly when grown on the optimized medium compared to that of control. The chemical analysis of the fractions derived from Anabaena variabilis showed the presence of two compounds in significant amounts: the flavonoid 5,7-dihydroxy-2-phenyl-4H-chrome-4-one and the alkaloid 4-phenyl-2-(pyridin-3-yl) quinazoline. Molecular docking studies revealed that both compounds interact with the allosteric binding site of acetylcholinesterase at the periphery with π-π stackings with Tyr341 and Trp286 with good, predicted partition coefficient. The compounds obtained from this study open the door for promising drug candidates to treat Alzheimer's disease for their better pharmacodynamics and pharmacokinetic properties.

Evaluating serum level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil.

BACKGROUND: Keloids are fibrous lesions formed at the site of trauma due to types I and III collagen irregular production. The presence of thymidylate synthase (TS) is a must for DNA synthesis and repairs causing cell death. 5-fluorouracil (5-FU) is a fluorinated pyrimidine analogue acting as an anti-metabolic agent that inhibits thymidylate synthase and interferes with ribo-nucleic acid (RNA) synthesis. OBJECTIVES: we aimed to evaluate the level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil. METHODS: The study included 20 keloid patients and 20 healthy subjects as a control. Serum TS was estimated using commercially available enzyme-linked immunosorbent assay (ELISA) kits before and after treatment with 5-fluorouracil. RESULTS: There was a statistically significant difference in TS levels before and after 5-FU treatment (p < 0.05). Also, results have shown that 5-FU injection has good satisfactory results in treatment of keloid causing reduction in scar volume and symptoms improvement (90% of the patients improved). On the other hand, there was no statistically significant difference in TS levels and the outcomes of the treatment. CONCLUSION: Our findings suggest that intralesional 5-FU injection in keloid has very satisfactory results. However, thymidylate synthase enzyme has a minimal role in evaluating the treatment of keloid, so further studies are required to elaborate the relation between this enzyme and keloid scars.

The Potential Therapeutic Effect of Orexin-Treated versus Orexin-Untreated Adipose Tissue-Derived Mesenchymal Stem Cell Therapy on Insulin Resistance in Type 2 Diabetic Rats.

Type 2 diabetes mellitus is a chronic metabolic disease characterized by resistance to peripheral insulin actions. Mesenchymal stem cells have been studied for years in T2DM therapy, including adipose tissue-derived mesenchymal stem cells (AD-MSCs). Orexin neuropeptides (A and B) are well-known regulators of appetite and physical activity. The aim of this work was to elucidate the possible therapeutic effect of AD-MSC preconditioning with orexin A (OXA) on insulin resistance in rats. Twenty-eight adult male albino rats were divided into 4 equal groups: a normal control group and 3 diabetic groups (a control T2DM group, diabetic rats treated by an AD-MSCs group, and diabetic rats treated by AD-MSCs preconditioned with OXA). We noticed that the treated groups showed a significant alleviation of insulin resistance parameters as shown in lowering the serum levels of glucose, insulin, total cholesterol, inflammatory markers, and HOMA-IR as compared to the control diabetic group with more significant reduction observed in the OXA-pretreated AD-MSCs-administrated group. More improvement was also noted in the glucose uptake and GLUT-4 gene expression in the skeletal muscle and adipose tissue in the OXA-pretreated AD-MSCs-administrated group compared to the untreated diabetic group. Conclusion. Preconditioning of AD-MSCs with OXA can significantly increase their potential to reduce the insulin resistance in the rat model of T2DM.

GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients.

Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p < 0.001), while the dominant CC was a protective factor (p = 0.004). Regarding miR-137 rs1625579, the mutant genotype TT was reported as a risk factor for CHBV (p < 0.001) and the normal GG genotype was a protective factor, p < 0.001. The serum GAS5 was significantly higher in the mutant TT genotype of GAS5 SNP as compared to the other genotypes (p = 0.007). Concerning miR-137 rs1625579, the mutant TT genotype was significantly associated with a lower serum expression level of miR-137 (p = 0.018). We revealed the dysregulated expression levels of GAS5 and miR-137 linked to their functioning SNPs were associated with CHBV risk and might act as potential therapeutic targets.

Evaluation of nootropic activity of telmisartan and metformin on diazepam-induced cognitive dysfunction in mice through AMPK pathway and amelioration of hippocampal morphological alterations.

Cognitive impairments such as dementia are considered the biggest challenges for public health. Benzodiazepines are often prescribed for treatment of anxiety disorder but they are associated with elevated risk of dementia. The present study has been designed to evaluate the neuroprotective effect of telmisartan and metformin on diazepam-induced cognitive dysfunction in mice. Piracetam was used as an established nootropic agent. Mice were divided into 8 groups, group1; control group which received normal saline. groups 2, 3 and 4 were received telmisartan 0.3 mg/kg/day, metformin 100 mg/kg/day and piracetam 200 mg/kg/day respectively. group 5; DZP group that injected with diazepam 2.5 mg/kg, groups 6, 7 and 8 were received diazepam 2.5 mg/kg + telmisartan 0.3 mg/kg/day, metformin 100 mg/kg/day and piracetam 200 mg/kg/day respectively. All drugs were administrated for 15 successive days. Cognitive skills of the animals were examined with Elevated plus maze and Passive Shock Avoidance tests. Investigations of oxidative stress markers were performed. Gene expression levels of TNF-α, NFκB, Caspase 3 and AMPK were analyzed using RT-PCR. Histological and immunohistochemical techniques were performed in hippocampus using H&E, cresyl violet stain, anti GFAP and anti COX-2 immunostain. The study revealed that administration of diazepam increased initial and retention transfer latency as well as it decreased step down latency that means it caused memory impairment. There was a significant increase in hippocampal expression levels of TNF-α, NFκB, and Caspase 3 and downregulation of AMPK expression levels associated with increased neurodegeneration, astrocytes activation and COX-2 immunohistochemical staining. This study indicates that diazepam caused a decline in cognitive function depending on hippocampal activity. Telmisartan, a common antihypertensive agent and metformin, a traditional antidiabetic drug improved this cognitive dysfunction through their anti-oxidant and anti-inflammatory effect as they decreased initial and retention transfer latency as well as it increased step down latency. Also they decreased TNF-α, NFκB, and Caspase 3 and upregulated AMPK expression, moreover they ameliorated the hippocampal morphological alterations, GFAP and COX-2 immunoexpression.

miR-155 T/A (rs767649) and miR-146a A/G (rs57095329) single nucleotide polymorphisms as risk factors for chronic hepatitis B virus infection among Egyptian patients.

Genetic variants in microRNAs (miRNAs) can alter the miRNAs expression and/or function, accordingly, affecting the related biological pathways and disease risk. Dysregulation of miR-155 and miR-146a expression levels has been well-described in viral hepatitis B (HBV). In the current study, we aimed to assess rs767649 T/A and rs57095329 A/G polymorphisms in miR-155, and miR-146a genes, respectively, as risk factors for Chronic HBV (CHBV) in the Egyptian population. Also, we aimed to do in silico analysis to investigate the molecules that primarily target these miRNAs. One hundred patients diagnosed as CHBV and one hundred age and sex-matched controls with evidence of past HBV infection were genotyped for miR-155 (rs767649) and miR-146a (rs57095329) using real-time polymerase chain reaction. The rs767649 AT and AA genotypes in CHBV patients confer four folds and ten folds risk respectively, as compared to control subjects [(AOR = 4.245 (95%CI 2.009-8.970), p<0.0001) and AOR = 10.583 (95%CI 4.012-27.919), p<0.0001, respectively)]. The rs767649 A allele was associated with an increased risk of developing CHBV (AOR = 2.777 (95%CI 1.847-4.175), p<0.0001). There was a significant difference in the frequency of rs57095329 AG and GG genotypes in CHBV patients compared to controls. AG and GG genotypes showed an increase in the risk of developing CHBV by about three and six folds respectively [AOR = 2.610 (95%CI 1.362-5.000), p = 0.004] and [AOR = 5.604 (95%CI 2.157-14.563), p<0.0001].We concluded that rs57095329 and rs767649 SNPs can act as potential risk factors for the development of CHBV in the Egyptian population.

Ameliorating effect of melatonin on mercuric chloride-induced neurotoxicity in rats.

Mercury is a highly toxic metal. It induces its toxicity via production of reactive oxygen species. Brain tissues are more susceptible to oxidative damage. Melatonin and its metabolites are free radical scavengers. The aim of this work is to elucidate the neuroprotective effect of melatonin on mercuric chloride-induced neurotoxicity in rats. Fifty male albino rats were used and divided into five groups. Group I acts as normal control. Group II (LD HgCl2) received mercuric chloride at a dose of 2 mg/kg. Group III (HD HgCl2) received HgCl2 at a dose of 4 mg/kg. Rats in group IV (LD HgCl2 +MLT) received HgCl2 2 mg/kg + Melatonin 5 mg/kg. Rats in group V (HD HgCl2+MLT) received HgCl2 4 mg/kg + Melatonin5 mg/kg. This study revealed that mercuric chloride decreased the activity of superoxide dismutase, catalase and glutathione peroxidase enzymes and increased malondialdehyde levels. Toxicity of mercuric chloride lead to upregulation of the gene expression level vascular endothelial growth factor. HgCl2 induced fragmentation of rough endoplasmic reticulum, ballooning of Golgi apparatus, nuclear and cytoplasmic degeneration of pyramidal neurones of rat cerebral cortex. This neuronal damage caused by HgCl2 was significantly improved by melatonin.

Serum miR-224, miR-760, miR-483-5p, miR-378 and miR-375 as potential novel biomarkers in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease which affects various tissues and organs mainly joints. Serum microRNAs are considered a new class of non-coding RNA which plays a vital role in pathogenesis of RA. METHODS: The current study was conducted on 80 RA patients and 80 healthy participants. Serum expression levels of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 were evaluated via real-time quantitative polymerase chain reaction (PCR). RESULTS: Significant upregulation of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 was reported in the present study with respect to the control group (P = .031, P = .017, P = .026, P = .036 and P = .05, respectively). Furthermore, significant positive correlation between the abovementioned microRNAs with DAS28 score (P < .001, each) was demonstrated. CONCLUSION: Early detection of RA could be achieved through evaluation of serum expression of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 which also may be used as targets for treatment of patients with RA.

Differential Expression of Serum TUG1, LINC00657, miR-9, and miR-106a in Diabetic Patients With and Without Ischemic Stroke.

Background: Ischemic stroke is one of the serious complications of diabetes. Non-coding RNAs are established as promising biomarkers for diabetes and its complications. The present research investigated the expression profiles of serum TUG1, LINC00657, miR-9, and miR-106a in diabetic patients with and without stroke. Methods: A total of 75 diabetic patients without stroke, 77 patients with stroke, and 71 healthy controls were recruited in the current study. The serum expression levels of TUG1, LINC00657, miR-9, and miR-106a were assessed using quantitative real-time polymerase chain reaction assays. Results: We observed significant high expression levels of LINC00657 and miR-9 in the serum of diabetic patients without stroke compared to control participants. At the same time, we found marked increases of serum TUG1, LINC00657, and miR-9 and a marked decrease of serum miR-106a in diabetic patients who had stroke relative to those without stroke. Also, we revealed positive correlations between each of TUG1, LINC00657, and miR-9 and the National Institutes of Health Stroke Scale (NIHSS). However, there was a negative correlation between miR-106a and NIHSS. Finally, we demonstrated a negative correlation between LINC00657 and miR-106a in diabetic patients with stroke. Conclusion: Serum non-coding RNAs, TUG1, LINC00657, miR-9, and miR-106a displayed potential as novel molecular biomarkers for diabetes complicated with stroke, suggesting that they might be new therapeutic targets for the treatment of diabetic patients with stroke.