Acetylated oligopeptide and N-acetylcysteine protect against iron overload-induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO-1 and downregulation of MMP-9/TIMP-1 and GFAP.

Iron accumulation in the brain causes oxidative stress, blood-brain barrier (BBB) breakdown, and neurodegeneration. We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron-induced hippocampal damage compared to N-acetyl cysteine (NAC). This 5-week study used 40 male albino rats. At the start, all rats received 150 mg/kg/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60 mg/kg/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150 mg/kg/day NAC and iron dextran; and Group IV (AOP group) received 150 mg/kg/day AOP and iron dextran. Enzyme-linked immunosorbent assay, spectrophotometry, and qRT-PCR were used to measure MMP-9, tissue inhibitor metalloproteinase-1 (TIMP-1), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP-9, TIMP-1, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO-1, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload-induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.

Dysregulated miRNA-375, IL-17, TGF-ß, and Microminerals Are Associated with Calpain-10 SNP 19 in Diabetic Patients: Correlation with Diabetic Nephropathy Stages.

Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-ß and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-ß, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-ß, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-ß, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-ß, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-ß, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

Antiapoptotic and chemotaxis-stimulating effects of poly (D, L-lactide-co-glycolide)-chitosan and whey proteins against aflatoxicosis-induced splenic and thymic atrophy.

BACKGROUND: Aflatoxin B (AFB) induces toxicological effects on the liver and immune organs. The whey proteins can modulate the immune response during aflatoxicosis. Our work evaluates the novel polylactic acid-glycolic acid-chitosan-encapsulated bovine and camel whey proteins against AFB-induced thymic and splenic atrophy in rats. METHODS AND RESULTS: Seventy adult male Wister albino rats were divided into a control healthy group (G1) and six AFB1-intoxicated groups (G2-G7). One of the following supplements: distilled water, camel whey proteins (CWP), bovine whey proteins, poly (D, L-lactide-co-glycolide) (PLGA)- chitosan-loaded with camel whey protein microparticles (CMP), PLGA-chitosan loaded with bovine whey protein microparticles (BMP), and PLGA-chitosan nanoparticles were administered as prophylactic supplements to AFB1-intoxicated groups. The AFB-treated group showed significantly higher hepatic levels of oxidative stress and lower levels of antioxidants. In the aflatoxicated group, atrophy of the splenic lymphatic nodules and disfigurement in the organisation with an apparent decrease in the thickness of the cortex in the thymus were observed, as well as a decrease in splenic and thymic CD4+T and CD8+T lymphocytes. Moreover, CXCL12 levels were downregulated, whereas tumour necrosis factor-alpha, nuclear factor kappa B, and cleaved caspase-3 levels were upregulated. CWP, BMP, and CMP supplements markedly decreased oxidative stress, inflammation, and apoptosis, as well as significantly raised CXCL12, CD4+T, and CD8+T cells. CONCLUSIONS: The CWP, BMP, and CMP supplements rescue the liver and immune tissues from the toxic effects of AFB through their antioxidant, antiapoptotic, anti-inflammatory, and chemotaxis-enhancing roles.

Mitochondrial DNA Copy Number, a Damage-Associated Molecular Pattern Molecule, Can Predict Pancreatic Necrosis and Is Correlated with the Severity of Acute Pancreatitis.

BACKGROUND: Mitochondrial DNA (mtDNA) is a damage-associated molecular pattern molecule that can trigger an immune-inflammatory response during pancreatic necrosis (PN). AIM: To evaluate the role of mtDNA in the detection of PN and severe acute pancreatitis (SAP). METHODS: The present study included 40 AP patients and 30 controls. AP patients were grouped into mild AP (MAP, n = 15), moderately severe AP (MSAP, n = 17), and SAP (n = 8). Also, the SAP + MSAP group, n = 25, was compared to MAP. AP patients were divided into NAP (n = 7) and non-necrotizing AP (n = 33). The mtDNA copy number, IL-6, and STAT3 expression levels were measured using quantitative real-time PCR. RESULTS: The mtDNA, IL-6, and STAT3 levels were significantly higher in AP patients than in controls and in the SAP + MSAP than in the MAP. However, the SAP had non-significantly higher levels of mtDNA, STAT3, and IL-6 levels than the MSAP and statistically significant mtDNA, STAT3, and IL-6 when compared to the MAP. mtDNA, IL-6, and STAT3 showed significantly higher levels in NAP compared with non-necrotizing AP. mtDNA was positively correlated with STAT3, IL-6, CRP, APACHE, and CT severity index (CTSI) and negatively correlated with albumin. In the receiver operating curve (ROC), mtDNA was the most significant independent predictor of PN and MAP vs. SAP + MSAP. IL-6 and mtDNA + CRP had higher diagnostic abilities for SIRS and high CTSI. CONCLUSIONS: mtDNA could enhance the prediction of NAP; however, its diagnostic ability of SAP needs further study.

Acetylated Oligopeptide and N-acetyl cysteine Protected Against Oxidative Stress, Inflammation, Testicular-Blood Barrier Damage, and Testicular Cell Death in Iron-Overload Rat Model.

Multiple organs, including the testes, are damaged by iron overload. It has been shown that N-acetyl cysteine (NAC) influences oxidative stress in iron overload. The present study aimed to evaluate the roles of acetylated peptide (AOP) and NAC in the inhibition of iron-overload induced-testicular damage. At the beginning of the experiment, NAC (150 mg /kg) was given for a week to all 40 rats. Then, four groups were formed by dividing the animals (10 rats/group). Group I included healthy control rats. Group II (iron overload) was given intraperitoneal iron dextran (60 mg/kg/day) 5 days a week for 4 weeks. Group III (NAC) was given NAC orally at a dose of 150 mg/kg/day for 4 weeks in addition to iron dextran. Group IV (AOP) was given AOP orally at a dose of 150 mg/kg/day for 4 weeks besides iron dextran. When the experiment time was over, testosterone serum level, testicular B cell lymphoma-2 (BCL-2) and protein kinase B (PKB) protein levels, nuclear factor kappa-B (NF-κB), and Beclin1 mRNA expression levels, and malondialdehyde (MDA), and reduced glutathione (GSH) were determined by ELISA, quantitative reverse transcription-PCR, and chemical methods. Finally, histopathological examinations and immunohistochemical detection of claudin-1 and CD68 were performed. The iron overload group exhibited decreased testosterone, BCL-2, PKB, claudin-1, and GSH and increased MDA, NF-κB, Beclin1, and CD68, while both NAC and AOP treatments protected against the biochemical and histopathological disturbances occurring in the iron overload model. We concluded that NAC and AOP can protect against testes damage by iron overload via their antioxidant, anti-inflammatory, antiapoptotic, and ant-autophagic properties. The NAC and AOP may be used as preventative measures against iron overload-induced testicular damage.

Dietary Effects of Nanopowder Eggshells on Mineral Contents, Bone Turnover Biomarkers, and Regulators of Bone Resorption in Healthy Rats and Ovariectomy-Induced Osteoporosis Rat Model.

Postmenopausal osteoporosis is a critical issue for female health worldwide. This current study was designed to evaluate the role of nanopowder eggshell (NPES) in healthy and ovariectomy-induced osteoporosis rats. Fifty-six female rats were divided into healthy rats (35) and ovariectomized rats (21). The healthy rats were subdivided into five groups (G1-G5) and received one of the following treatments: saline, 20 or 40 mg/kg of calcium carbonate, and 20 or 40 mg/kg of NPES. The 21 ovariectomized rats were divided into three groups (G6-G8) and received either saline, 40 mg/kg of calcium carbonate, or 40 mg/kg of NPES. Biochemical and histopathological assessments of bone formation and resorption were performed. Biomarkers of bone formation (calcium and osteocalcin (OCN)) and calcium content in left femur ashes were significantly higher in healthy rats given 40-mg/kg NPES than in healthy control rats and healthy rats given 40-mg/kg calcium carbonate. The ovariectomized groups had significantly lower levels of vitamin D3, OCN, and osteoprotegerin (OPG) than the healthy control. Alanine transaminase (ALT), alkaline phosphatase (ALP), and receptor activator of nuclear factor-κB ligand (RANKL) were significantly increased in the ovariectomized group than in the healthy control group. Treatment with NPES and calcium carbonate reduced liver enzymes in ovariectomized rats. NPES treatment significantly increased Vit D3, OCN, OPG, and bone ash mineral content (calcium, magnesium, zinc, and phosphorus) in ovariectomized rats. NPES also increased femur cortical thickness, osteoblast number, and collagen fiber. The current study suggests that NPES can modulate bone turnover biomarkers and increase bone trace elements. Moreover, NPES alleviates bone resorption in ovariectomy-induced osteoporosis.

Interleukin 18 as a new inflammatory mediator in left ventricular hypertrophy in children with end-stage renal disease.

Left ventricular hypertrophy (LVH) represents an important determinant of increased cardiovascular morbidity and mortality (CV) in end-stage renal disease (ESRD) patients. The role of inflammatory markers in pathogenesis of LVH in children with ESRD is not fully described. The aim of this study is to evaluate relation of some inflammatory markers [as hs C-reactive protein (hsCRP) and interleukin (IL) 18] with LVH in children with ESRD on regular hemodialysis (HD). This is a cross-sectional study performed on 50 children on regular HD. Demographic data were recorded. Echocardiography was performed at baseline to determine those with LVH. Biochemical parameters: hemoglobin (HB), hsCRP, IL 18, phosphorus, calcium, serum albumin, and lipid profile were evaluated and correlated with LVH. Data were analyzed using Student's t-test, and logistic regression to determine the relationship between LVH and other variables. LVH was present in 33 (66%) participants. Mean left ventricular mass index was 56.88 ± 22.23 g/m.2.7 Concentric remodeling, concentric hypertrophy, and eccentric hypertrophy were present in 4%, 22%, and 44% of the participants. In univariate analysis, children with LVH had significantly lower levels of HB and serum albumin but higher levels of hsCRP, and IL 18 compared to those without LVH. On multivariate analysis: only hsCRP, and IL 18 were significantly associated with LVH. This study shows that elevated hsCRP and IL-18 are independent determinants of LVH in HD children. Understanding the role of inflammatory molecules in the pathogenesis of LVH in ESRD is important for prediction of high-risk group and implementation of targeted anti-inflammatory therapies.

Interrelations of Apoptotic and Cellular Senescence Genes Methylation in Inflammatory Bowel Disease Subtypes and Colorectal Carcinoma in Egyptians Patients.

Ras-related domain family member 1 transcript variant A (RASSF1A) controls apoptosis and cell proliferation while p14/ARF gene has a regulatory role in cellular senescence. Failure of apoptosis and cellular senescence occurs during inflammatory bowel disease (IBD) and colorectal cancer (CRC). To reveal the role of peripheral leukocyte promoter methylation of RASSF1A and p14/ARF in the pathogenesis of IBD subtypes and CRC we investigated the methylation state of the two genes by methylation-specific polymerase chain reaction (MSP-PCR) in 60 CRC patients, 60 patients with IBD; 27 with ulcerative colitis and 33 had Crohn's disease and also in 30 healthy subjects. Methylated RASSF1A and p14/ARF genes were detected in 55% and 60% of CRC, while the frequency of the methylated RASSF1A and p14/ARF genes was 23.3% and 43.3% in IBD patients and 3.3% and 13.3% in the control group (P = 0.000 each). Also, the frequency of methylated RASSF1A gene was significantly higher in ulcerative colitis than in Crohn's disease, while a non-significant frequency of methylated p14/ARF was detected between ulcerative colitis and Crohn's disease. Furthermore, methylated RASSF1A and p14/ARF were associated with the grade of CRC but not associated with the age of patients, family history, or tumor location. Results suggest that methylated RASSF1A and p14/ARF are related to CRC and IBD pathogenesis and may be used as molecular biomarkers for early detection of CRC and IBD.

Association of endothelin receptor type A rs5333 gene polymorphism with steroid response in Egyptian children with idiopathic nephrotic syndrome.

AIM: To investigate ENDRA rs5333 gene polymorphism distribution in idiopathic nephrotic syndrome (INS) and to analyze their association with response to steroid therapy, and biochemical markers of INS. SUBJECTS & METHODS: The PCR-restriction fragment length polymorphism was used to analyze ENDRA rs5333 polymorphism in 100 children with idiopathic nephrotic syndrom (INS) and 100 healthy children. Plasma endothelin-1 were measured by ELISA. RESULTS: The ENDRA rs5333 gene polymorphism was not associated with risk of INS. The frequency of minor allele (C) was significantly higher in the steroid resistant nephrotic syndrome group than the steroid sensitive group. The CC and TC mutant variants were associated with higher plasma levels of cholesterol, albumin, urea and 24-h urinary protein, but were not associated with risk of hypertension. The endothelin-1 plasma level was higher in INS than control and in steroid resistant nephrotic syndrome group when compared with steroid sensitive group cases. CONCLUSION: The ENDRA rs5333 gene polymorphism may be associated with genetic predisposition to steroid resistance in INS Egyptian children.

Oxidative stress and psychiatric morbidity in patients with facial acne.

BACKGROUND: Acne vulgaris is a common cosmetic problem that is frequently associated with psychosocial disturbances as well as increased oxidative stress. However, oxidative stress and psychological aspects have been studied separately in acne. OBJECTIVE: To evaluate the relationships between oxidative stress, anxiety, depression, and quality of life in acne patients. METHODS: Sixty patients with facial acne and 40 age- and sex-matched healthy individuals were included in the study. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS), and quality of life (QoL) was measured by the Cardiff Acne Disability Index. Disease severity was assessed using the Combined Acne Severity Classification. The serum levels of zinc and malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured in patients and healthy subjects. RESULTS: The mean HADS scores for anxiety and depression were higher in patients than controls (P<.001 for both). Acne patients showed higher serum MDA and lower TAC and serum zinc levels compared with control subjects (P=.019, P<.001, and P=.028, respectively). Anxiety and depression scores did not correlate with oxidative stress parameters. Patients with moderate/severe acne had worse anxiety scores than mild acne (P=.048), and higher anxiety scores were associated with poorer quality of life (r=.436, P=.001). CONCLUSION: Our results indicate that the high levels of anxiety and depression in patients with facial acne were not related to oxidative stress. Anxiety was more common than depression and was directly related to QoL impairment.

B-type Natriuretic Peptide as an Index of Symptoms and Severity of Chronic Rheumatic Mitral Regurgitation.

BACKGROUND: The most common causes of severe mitral regurgitation (MR) in developing countries are rheumatic heart disease. The plasma level of B-type natriuretic peptide (BNP) is known to increase with left ventricular (LV) dysfunction. AIM OF THE WORK: To study BNP level as an index of symptoms and severity of chronic rheumatic MR. PATIENTS AND METHODS: One hundred and forty patients with rheumatic MR and LV ejection fractions (EFs) of >55% underwent assessment of symptoms, transthoracic echocardiography, and measurement of BNP. RESULTS: The level of BNP rose with increasing left atrium (LA) dimensions and volumes, LV dimensions and volumes, echocardiographic parameters of MR severity (width of the vena contracta, regurgitation jet area, effective regurgitation orifice area, and regurgitant volume), and E waves. RESULTS: BNP was significantly higher in patients with severe MR compared with moderate and mild MR (P < 0.001), and using cutoff point of 61 pg/mL mm had 97% sensitivity and 89% specificity for predicting patients with severe MR (0.99, 95% confidence interval [CI] 0.9-1). BNP was significantly higher in patients with New York Heart Association (NYHA III) compared with NYHA II, I and asymptomatic patients (P < 0.001) and using cutoff point of 53 pg/mL had 97% sensitivity and 87% specificity for predicting symptomatic patients with symptomatic MR (0.81, 95% CI 0.70-0.92). CONCLUSIONS: BNP level increase with increasing severity of rheumatic MR and are higher in symptomatic compared to asymptomatic patients, even in the presence of normal EF%.