Relation between interleukin-13 and annexin-V levels and carotid intima-media thickness in nephrotic syndrome.

Background and aim: The aim of the current study is to assess the relation between carotid intima-media thickness (CIMT) measurements, renal Doppler resistive index (RI) and serum levels of interleukin-13 (IL-13) and annexin-V (An-V) in children with idiopathic nephrotic syndrome (INS). Materials and methods: The present case-control study was conducted on 60 children with INS and 60 age- and sex-matched healthy children. All participants were subjected to evaluation of serum levels of IL-13 and An-V and ultrasound Doppler measurement of CIMT and renal RI. Results: Patients expressed significantly higher An-V (5.9 ± 2.6 vs. 2.1 ± 0.8 ng/mL, p<0.001) and IL-13 (19.2 ± 7.6 vs. 3.4 ± 1.4 ng/L) levels when compared with healthy counterparts. Moreover, it was shown that patients had significantly higher CIMT (0.49 ± 0.06 vs. 0.35 ± 0.03, p<0.001) as compared to controls. No significant differences were noted between the studied groups regarding right or left RIs. Correlation analysis identified significant direct correlation between serum An-V levels and albumin/creatinine ratio (ACR) (r = 0.55), cholesterol (r = 0.48), triglycerides (r = 0.36), IL-13 (r = 0.92) and CIMT (r = 0.53). Similar correlations could be found between serum IL-13 levels and CIMT measurements and the corresponding parameters. Conclusions: The present study suggests an association between higher early atherosclerosis expressed as elevated CIMT measurements in children with INS and elevated serum levels of An-V and IL-13.

Impact of L-Arginine on diabetes-induced neuropathy and myopathy: Roles of PAI-1, Irisin, oxidative stress, NF-κß, autophagy and microRNA-29a.

BACKGROUND: T2DM is a chronic disorder with progressive neuromuscular alterations. L-arginine (ARG) is the most common semi-essential amino acid having several metabolic functions. AIM: to investigate the impact of L-arginine in combating diabetic-induced neuromyopathy and its possible mechanisms. MATERIALS & METHODS: 24 rats were divided into CON, CON+ARG, DC, DC+ARG. Behavioral tests, Body weight (BW), fasting blood glucose (FBG), insulin, total antioxidant capacity (TAC), malondialdehyde (MDA), plasminogen activator inhibitor-1 (PAI-1), and irisin were done. Creatine kinase-MM (CK-MM), interleukin 4 (IL-4), interleukin 6 (IL-6), TAC, MDA, expression of microRNA-29a mRNA & light chain 3 protein were determined in muscle. Histological and NF-κß immunohistochemical expression in muscle and nerve were assessed. RESULTS: ARG supplementation to diabetic rats improved altered behavior, significantly increased BW, insulin, TAC, irisin and Il-4, decreased levels of glucose, microRNA-29a, NF-κß and LC3 expression, PAI-1, CK-MM and restored the normal histological appearance. CONCLUSIONS: ARG supplementation potently alleviated diabetic-induced neuromuscular alterations.

Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.

BACKGROUND: Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis. OBJECTIVES: The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage. METHODS: Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (106 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted. RESULTS: BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs. CONCLUSION: The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.

Alleviation of doxorubicin-induced cardiotoxicity in rat by mesenchymal stem cells and olive leaf extract via MAPK/ TNF-α pathway: Preclinical, experimental and bioinformatics enrichment study.

BACKGROUND: Toxic cardiomyopathies were a potentially fatal adverse effect of anthracycline therapy. AIM: This study was conducted to demonstrate the pathogenetic, morphologic, and toxicologic effects of doxorubicin on the heart and to investigate how the MAPK /TNF-α pathway can be modulated to improve doxorubicin-Induced cardiac lesions using bone marrow-derived mesenchymal stem cells (BM-MSCs) and olive leaf extract (OLE). METHODS: During the study, 40 adult male rats were used. Ten were used to donate MSCs, and the other 30 were split into 5 equal groups: Group I was the negative control, Group II obtained oral OLE, Group III obtained an intraperitoneal cumulative dose of DOX (12 mg/kg) in 6 equal doses of 2 mg/kg every 48 h for 12 days, Group IV obtained intraperitoneal DOX and oral OLE at the same time, and Group V obtained intraperitoneal DOX and BM-MSCs through the tail vein at the same time for 12 days. Four weeks after their last dose of DOX, the rats were euthanized. By checking the bioinformatic databases, a molecularly targeted path was selected. Then the histological, immunohistochemistry, and gene expression of ERK, JNK, NF-κB, IL-6, and TNF-α were done. RESULTS: Myocardial immunohistochemistry revealed severe fibrosis, cell degeneration, increased vimentin, and decreased CD-31 expression in the DOX-treated group, along with a marked shift in morphometric measurements, a disordered ultrastructure, and overexpression of inflammatory genes (ERK, NF-κB, IL-6, and TNF-α), oxidative stress markers, and cardiac biomarkers. Both groups IV and V displayed reduced cardiac fibrosis or inflammation, restoration of the microstructure and ultrastructure of the myocardium, downregulation of inflammatory genes, markers of oxidative stress, and cardiac biomarkers, a notable decline in vimentin, and an uptick in CD-31 expression. In contrast to group IV, group V showed a considerable beneficial effect. CONCLUSION: Both OLE and BM-MSCs showed an ameliorating effect in rat models of DOX-induced cardiotoxicity, with BM-MSCs showing a greater influence than OLE.

GC/MS Analysis, Cytotoxicity, and Antiviral Activities of Annona glabra Hexane Extract Supported by In Silico Study.

Annona glabra Linn is employed in conventional medicine to treat a number of human disorders, including cancer and viruses. In the present investigation, the significant phytochemical components of Annona glabra hexane extract were identified using gas chromatography-mass spectrometry (GC-MS) analysis. Three major compounds were identified in the hexane extract: tritriacontane (30.23%), 13, 17-dimethyl-tritriacontane (22.44%), and limonene (18.97%). MTT assay was used to assess the cytotoxicity of the extract on six human cancer cell lines including liver (HepG-2), pancreas (PANC-1), lung (A-549), breast (MCF-7, HTB-22), prostate (PC-3), and colon (CACO-2, ATB-37). The extract exhibited significant cytotoxic activity against both CACO-2 and A-549 cancer cell lines (IC50 = 47 ± 0.74 µg/mL and 56.82 ± 0.92 µg/mL) in comparison with doxorubicin (IC50 = 31.91 ± 0.81 µg/mL and 23.39 ± 0.43 µg/mL) and of SI of 3.8 and 3.1, respectively. It also induced moderate-to-weak activities against the other cancerous cell lines: PC-3, PANC-1, MCF-7, and HepG-2 (IC50 = 81.86 ± 3.26, 57.34 ± 0.77, 80.31 ± 4.13, and 57.01 ± 0.85 µg/mL) in comparison to doxorubicin (IC50 = 32.9 ± 1.74, 19.07 ± 0.2, 15.48 ± 0.84 and 5.4 ± 0.22 µg/mL, respectively) and SI of 2.2, 3.1, 2.2, and 3.1, respectively. In vitro anti-HSV1 (Herpes simplex 1 virus) and HAV (Hepatitis A virus) activity was evaluated using MTT colorimetric assay with three different protocols to test protective, anti-replicative, and anti-infective antiviral activities, and three separate replications of each experiment were conducted. The plant extract showed promising protective and virucidal activity against HSV1 with no significant difference with acyclovir (79.55 ± 1.67 vs. 68.44 ± 7.62 and 70.91 ± 7.02 vs. 83.76 ± 5.67), while it showed mild protective antiviral activity against HAV (48.08 ±3.46) with no significant difference vs. acyclovir (36.89 ± 6.61). The selected main compounds were examined for their bioactivity through in silico molecular docking, which exhibited that limonene could possess the strongest antiviral properties. These findings support Annona glabra's conventional use, which is an effective source of antiviral and anticancer substances that could be used in pharmaceuticals.

Interplay of Biochemical, Genetic, and Immunohistochemical Factors in the Etio-Pathogenesis of Gastric Ulcer in Rats: A Comparative Study of the Effect of Pomegranate Loaded Nanoparticles Versus Pomegranate Peel Extract.

BACKGROUND: Few data are available about the role of herbal extract loaded nanoparticles as an alternative safe medicine for the management of a gastric ulcer. AIM: This work is targeted at exploring the physiological effects of pomegranate loaded nanoparticles (PLN) against an indomethacin IND-induced gastric ulcer and comparing the results with traditional pomegranate peel extract (PPE). METHODS: Twenty-four rats were equally distributed into four groups: control, IND-treated, PLN-treated, and PPE-treated groups. Gross examination of gastric mucosa, and the calculation of ulcer and inhibition indices were done. Serum malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin 2 (IL-2), IL-6, IL-10, gastric homogenate prostaglandin E2 (PGE2), and nitric oxide (NO) were estimated. Mucosal endothelial nitric oxide synthase (eNOS mRNA) expression was identified by qPCR. Histological and immuno-histochemical staining of Tumor necrosis factor-α (TNF-α) and eNOS of stomach mucosa were performed. RESULTS: In comparison with the control group, IND-treated rats showed visible multiple ulcers with ulcer index, serum MDA, IL-2 and IL-6 were elevated while IL-10, PGE2, NO, and eNOS mRNA expression were significantly reduced. Damaged surface epithelium with disrupted glandular architecture and heavy leucocyte infiltration of lamina propria was noticed. Immunohistochemical staining of stomach mucosa revealed marked increased TNF-α and reduced eNOS. Oral administration of PLN and PPE succeeded in improving the gross mucosal picture, and all biochemical, histological, and immunohistochemical alterations. CONCLUSION: Both PLN and PPE potently alleviated IND-induced gastric ulceration via increasing TAC, PGE2, NO, eNOS mRNA, and protein expression. However, the healing effect of PLN was obviously greater than PPE-treated rats.

Curcumin nanoparticles have potential antioxidant effect and restore tetrahydrobiopterin levels in experimental diabetes.

Diabetes is associated with an increase in the production of free radicals, reduction of tetrahydrobiopterin (BH4, THB) levels and reduced bioavailability of nitric oxide (NO) in the vascular walls. In this contribution, we probed the effective role of curcumin nanoparticles (CUR-NPs) that prepared via solvent evaporation nanoprecipitation technique as potential system to attenuate endothelial dysfunction. In this technique, Tween 60 (polysorbate) was used as stabilizing agent for the prepared CUR-NPs and protect such nanoparticles from further agglomeration. BH4 levels and other parameters were estimated in diabetic rats. To this end, we dedicated 48 male albino rats, categorized into six groups; control (healthy rats), diabetic rats, along with four treated groups via oral administration of 0.2 mL/kg body weight/day of solutions of Tween 60 (60 mg/mL), free CUR (60 mg/mL), CUR-NPs1 (30 mg/mL), and CUR-NPs2 (60 mg/mL) for 30 days. Results showed that the mean level of malondialdehyde (MDA) has been significantly increased in diabetic group associated with a reduction of total antioxidant capacity, NO, and BH4 compared to control. These parameters were restored by the delivery of CUR-NPs - both doses in rats, compared with the two control groups that treated with Tween 60 and free CUR.

Aqueous garlic extract supresses experimental gentamicin induced renal pathophysiology mediated by oxidative stress, inflammation and Kim-1.

BACKGROUND: Gentamicin (Gent) has rapid & high bactericidal action in addition to its cheap price. Nevertheless, 30% of gentamicin-treated patients develop nephrotoxicity. OBJECTIVE: To explore the probable nephroprotective effects of the aqueous garlic extract (AGE) & to elucidate its underlying mechanisms via monitoring proinflammatory cytokines as tumer necrosis factor (TNF-α), interleukin 6 (IL-6) and interferon-γ (INF-γ), oxidative stess markers as malondialdehyde (MDA) & superoxide dismutase (SOD) & kidney injury molecule (Kim-1) as a promising early specific biomarker of renal dysfunction. METHODS: 32 adult male rats were divided into 4 equal groups treated for 21 days as: normal control group received normal saline orally, AGE-treated group received AGE at 250 mg/kg/day orally, Gent-treated group received Gent-sulphate intraperitoneal injection at 80 mg/kg /day, and AGE & Gent cotreated group received AGE and Gent concomitantly in the same previous doses. Serum urea, creatinine, glomerular filteration rate (GFR), systolic (SBP) and diastolic blood pressure (DBP), TNF-α, IL-6, INF-γ, MDA and SOD and Kim-1 mRNA expression were evaluated in kidney tissue homogenate. Renal cortex sections stained with Haematoxylin & eosin (H&E) were examined. RESULTS: AGE is nephroprotective through significantly reducing serum urea, creatinine, SBP and DBP, TNF-α, IL-6, INF-γ and MDA (the main product of lipid peroxidation), decreasing expression of Kim-1 mRNA in renal tissue and increasing level of GFR, the natural antioxidant SOD and improving renal histological features of Gent-treated rats. CONCLUSION: AGE normalizes Gent-induced renal dysfunction. Their co-administration is a plausible advice, although the therapeutic efficiency of Gent was not investigated.

Serum irisin level in myocardial infarction patients with or without heart failure.

This study aimed to assess serum irisin level in myocardial infarction (MI) with or without heart failure (HF) and the possible relation between irisin and cardiac markers, tumor necrosis factor-α (TNF-α) and lipid profile. Eighty-six subjects were included (33 patients had MI, 33 patients had MI with HF, and 20 controls). Body mass index (BMI), waist/hip ratio (WHR), systolic and diastolic blood pressure (SBP and DBP), heart rate, and left ventricular ejection fraction (LVEF) were measured. Blood samples were withdrawn on admission for measuring irisin, cardiac markers, TNF-α, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol concentration (LDL-C), and high-density lipoprotein-cholesterol concentration (HDL-C). Patients with MI and HF had reduced serum irisin, LVEF, and HDL-C and higher levels of BMI, WHR, SBP, DBP, troponin-I, creatine kinase-MB (CK-MB), TNF-α, TC, TGs, and LDL-C compared with control. Negative correlations were observed between irisin and BMI, WHR, SBP, DBP, troponin-I, CK-MB, TNF-α, TC, TGs, and LDL-C. However, positive association was noticed between irisin and LVEF and HDL-C. Irisin might be a useful biomarker in diagnosis of MI with or without HF. It could have anti-inflammatory and hypolipidemic effects. Further studies are needed to elucidate the role of irisin as a promising prophylactic or therapeutic agent in cardiovascular diseases.

Neuroprotective effects of melatonin administration against chronic immobilization stress in rats.

Chronic stress can impair brain functions and play a well-known role in the development of stress-related disorders such as anxiety. Melatonin (Mel) is a neurohormone which regulate several physiological processes including mood and behavior. This experimental study was designed to evaluate the effect of Mel on chronic immobilization stress (CIS) for 6 weeks in rats and to elucidate its possible underlying mechanisms. Twenty-eight adult male Wistar albino rats were divided into four equal groups: the control group, the Mel-treated group which was injected daily with Mel (10 mg/kg/day; IP) for 6 weeks, the stressed group which was subjected to CIS protocol daily for 6 weeks, and the Mel-treated stressed group which was injected with Mel and concurrently exposed to CIS protocol for 6 weeks. The Mel-treated stressed group showed reduction of both relative adrenal weight and the serum corticosterone levels, suppression of the anxiety-like behavior, increased levels of serotonin, noradrenaline and oxytocin in the frontal cortex, and improved histopathological structure and decreased chromogranin A (CgA) protein expression in the frontal cortex when compared with the chronically stressed group. We concluded that Mel is anxiolytic and this effect was mediated in part by its ability to increase the central release of oxytocin and monoamines and to downregulate CgA protein expression in the frontal cortex.