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End-stage renal disease (ESRD) is a rapidly increasing global health and healthcare challenge. MicroRNAs (miRNAs) have been implicated in kidney disease due to their role in apoptosis, cell proliferation, differentiation, and development. The aim of this study was to determine the role of miRNA-21-5p, miRNA-126-3p, and miRNA-192-5p in the prognosis of ESRD. In addition, we aimed to evaluate the discriminatory ability of these miRNAs as biomarkers for ESRD in relation to the comorbidities of hypertension (HTN) and diabetes mellitus (DM). One hundred and ten individuals were recruited for our study and divided into three groups: group 1 included 40 ESRD patients with hypertension, group 2 included 40 ESRD patients with diabetes, and group 3 ( n  = 30) served as healthy controls. Real-time polymerase chain reaction (RT-PCR) was used to quantify the above miRNAs. Patients with ESRD were found to have lower levels of miRNA-126-3p and higher levels of miRNAs-21-5p and − 192-5p. Furthermore, the accuracies of ROC analyses for miR-21-5p, miR-126-3p, and miR-192-5p were 96.65%, 99.5%, and 93.35% in ESRD with HTN and 95%, 71.5%, and 93% in ESRD with DM. Dysregulation of these miRNAs is associated with the development of ESRD and could be used as biomarkers for ESRD. This study briefly outlines the challenges associated with miRNA research and the potential use of miRNA molecules in the management of ESRD, proposing a research approach emphasizing the development of standardized and reliable biomarkers for therapeutic use. Despite the promising diagnostic utility demonstrated, the lack of cross-validation and external validation remains an important limitation. Future large-scale, independent studies are essential to confirm these findings and ensure broader applicability.

Acute renal failure (ARF) is a sudden, significant, and often reversible decline in kidney function, with 25% of all hospital-administered pharmaceuticals potentially causing nephrotoxicity. The study investigates the effectiveness of a novel nanoparticle (NP) formulation of glutathione (GSH) and Lepidium sativum (LS) in improving therapeutic outcomes in a rat model of ARF. Sixty adult male albino rats were allocated into ten groups, comprising six rats each, for the study. ARF was created by daily gentamicin (GN) administration for seven consecutive days and various treatment protocols, including chitosan (CS) NPs, spanlastics NPs, as well as conventional, NP formulations of GSH, LS, and their respective combinations. The effect was evaluated through various tests, and properties of nanoparticles were confirmed through characterization processes. The NP compositions markedly enhanced renal function, as seen by reduced urine concentrations of albumin and glucose. Furthermore, the serum concentrations of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C were decreased. Tissue concentrations of nitrite, superoxide dismutase (SOD), and malondialdehyde (MDA), as markers of oxidative stress, were enhanced by both conventional and NP formulations. Additionally, they decreased inflammatory markers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Histological analysis and immunohistochemical testing revealed that the combination therapy, particularly with the nanoforms, significantly decreased caspase 3 cellular immunoexpression, a sign of kidney cellular damage. The findings show that the ARF renal damage is considerably reduced when NPs containing GSH and LS are administered together. The study suggests a promising pharmacological approach for enhancing kidney regeneration and preserving renal function, potentially aiding in new therapeutic interventions for ARF treatment.

Background Lipopolysaccharide (LPS)-induced neuroinflammation is widely used as an animal model for studying the mechanisms of neuroinflammation. Crocin, an active component of saffron ( Crocus sativus L ), possesses several beneficial properties. The present study aimed to investigate the role of crocin in alleviating hippocampal toxicity induced by LPS in rats. Method Forty male albino rats were randomly divided into five groups. Group I served as a control. Group II intraperitoneally (i.p.) injected with LPS (1 mg/kg/day) for a week. Groups III, IV, and V were treated by oral gavage with captopril (50 mg/kg/day), crocin (50 mg/kg/day), and a combination of both captopril (50 mg/kg/day) and crocin (50 mg/kg/day), respectively for 30 consecutive days, starting on the 8th day after LPS i.p. injection. During the therapy schedule, rats were tested for memory and learning abilities. Hippocampal samples were collected for biochemical, histological, immunohistochemical, and morphometric studies. Biochemical evaluation included nuclear factor kappa B, inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), amyloid beta, angiotensin-converting enzyme, markers of the cholinergic system (acetylcholinesterase and choline acetyltransferase), antioxidant enzymes (catalase and superoxide dismutase) and an oxidative stress indicator (malondialdehyde). Histological examinations, as well as immunohistochemical and histomorphometric analysis, were also performed on hippocampal tissue. Results The results revealed biochemical, histological, and immunohistochemical alterations in the hippocampus of the LPS group. Most of these alterations showed satisfactory improvements in hippocampal tissue when LPS-administered rats were treated with captopril and crocin, either separately or in combination. Conclusion The present study suggests that crocin acts as a promising therapeutic agent for alleviating memory impairments and neuroinflammation induced by LPS.

Consumption of a high-fat diet (HFD) can trigger neuroinflammation, which may contribute to and increase the risk of neurodegenerative disease progression, ultimately leading to memory impairment. In the current study, the curative impact of a novel therapy combining Olea europaea leaf extract (OLE) encapsulated in a liposomal hydrogel (Lipo-OLE-Hydrogel) and mesenchymal stem cell-derived exosomes (MSC-Exo) was evaluated against HFD-induced brain dysfunction in a rat model. This assessment involved analyzing behavioral tasks, neurotransmitter levels, oxidative stress, neuroinflammation, endoplasmic reticulum-related markers, histopathological lesions, and immunostaining markers in brain tissues. The experimental groups were arranged for a 14-week study as follows: the first group received a control diet; the second group was fed an HFD; the third group was fed an HFD and treated with Lipo-OLE-Hydrogel; the fourth group was fed an HFD and treated with MSC-Exo; and the fifth group was fed an HFD and treated with both Lipo-OLE-Hydrogel and MSC-Exo. The findings of this study demonstrated that the neuroprotective effect of the combined Lipo-OLE-Hydrogel and MSC-Exo treatment was associated with a significant reduction in oxidative stress, as evidenced by the restoration of total antioxidant capacity and the marked decrease in oxidative biomarkers, including reactive oxygen species (ROS), H 2 O 2 , and malondialdehyde (MDA). The HFD-fed group exhibited greater glucose intolerance and increased body weight gain; however, these effects were significantly reversed in the group treated with the combination of Lipo-OLE-Hydrogel and MSC-Exo, even after long-term HFD induction. Impairments in behavioral tasks and memory were significantly improved in the group treated with the combined MSC-Exo and Lipo-OLE-Hydrogel therapy, with the MSC-Exo-alone group showing moderate improvement. The excessive inflammatory response and expression of endoplasmic reticulum stress-related genes were markedly attenuated following administration of Lipo-OLE-Hydrogel and MSC-Exo. This effect was mediated through the downregulation of pro-inflammatory and stress-related genes, including IL-6, COX-2, iNOS, TLR2, TLR4, NLRP3, CHOP, JNK, XBP1, and ATF6 . The severity of the histopathological changes in the brain tissues, including the development of neoplastic epithelium and the invasion of some neoplastic masses, was significantly attenuated in the group treated with the combined Lipo-OLE-Hydrogel + MSC-Exo therapy. Immunohistochemical staining displayed that Bcl-2 protein expression was significantly restored to near normal levels, while TNF-α expression was significantly reduced in the group treated with the combined MSC-Exo and Lipo-OLE-Hydrogel therapy. Taken together, these findings highlight a novel and promising therapeutic approach that combines a natural protective agent (Lipo-OLE-Hydrogel) with regenerative medicine (MSC-Exo) to effectively combat the progression of HFD-induced neuroinflammation.

Background: Pediatric patients infected with coronavirus disease 2019 (COVID-19) have unique clinical characteristics. Tumor necrosis factor (TNF) is a proinflammatory cytokine that greatly contributes to tumor pathogenesis.Purpose: To describe the presenting characteristics of COVID-19 infection among pediatric patients, and investigate the possible role of the TNF-α signaling pathway.Methods: This prospective case-control study included 50 Egyptian pediatric patients with COVID-19 and 50 healthy controls. Clinical, laboratory, and radiological assessments were performed. Serum TNF-alpha (TNF-α), TNF-α-converting enzyme (TACE), and angiotensin-converting enzyme 2 (ACE2) were measured using enzyme-linked immunosorbent assay. ACE (I/D) (rs4646994), ACE2 rs2285666, and TNF-α-308G/A single nucleotide polymorphisms (SNPs) were performed using conventional polymerase chain reaction techniques with or without restriction fragment length polymorphism.Results: The median age was 1 year (interquartile range [IQR], 0.31–2.50 years) in the case group and 1.45 years (IQR, 1.00–3.00) in the control group. The main presenting symptoms were fever (92%), dry cough (74%), and dyspnea (72%). The lymphocytic count was normal in 14 patients (28%), decreased in 16 patients (32%), and increased in 20 patients (40%) of the case group. Positive chest computed tomography finding of COVID-19 infection were demonstrated among 40% of patients using COVID-19 Reporting and Data System categories (ground-glass opacity with or without consolidations in the lungs). There were significant increased serum TACE and TNF-α with decreased ACE2 levels among cases versus controls (P< 0.001). The GG genotype and G allele of the TNF-α-308G/A SNP were significantly higher in patients than in controls (P<0.05 for both), with insignificant differences in genotype and allelic frequencies in the ACE (I/D) (rs4646994) and ACE2 rs2285666 SNPs.Conclusion: The TNF signaling pathway was significantly activated in pediatric COVID-19 infection. Only the TNF-α-308G/A SNP was significantly associated with pediatric COVID-19 infection.

Schizophrenia is a typical -methyl-d-aspartate receptor (NMDA-R) hypofunction disorder. Decreased d-serine (d-Ser) levels in the periphery occur in schizophrenia and may reflect decreased availability of d-Ser to activate NMDA-R in the brain. The objective of this study was to investigate the role of d-Ser metabolism in the pathogenesis of schizophrenia via biochemical assays and correlates, the serum level of d-Ser, d-serine racemase (SR) (responsible for its formation from l-serine [l-Ser]) and d-amino acid oxidase (DAAO) (responsible for its catabolism), among different clinical types of schizophrenia patients. This cross-sectional case-control study was carried out on 100 patients and 50 controls. They were recruited from the outpatients' psychiatric unit of the Neuropsychiatric Department of Assiut University Hospital, Upper Egypt. The type of schizophrenia was determined according to the ( ), while the severity of schizophrenia was determined according to the ( ). Serum d-Ser levels were estimated using high-performance liquid chromatography (HPLC), while serum SR and DAAO were measured using commercially available enzyme-linked immunosorbent assay kits. There were significantly lower mean serum levels of d-Ser and SR and significantly higher mean serum levels of DAAO ( -value <0.01 for each) among schizophrenia patients when compared with the control group. Paranoid schizophrenia had the highest frequency, with a significantly lower serum levels of d-Ser and SR in the residual type and significantly higher serum levels of DAAO in undifferentiated and catatonic types. Combined receiver-operating characteristic curve for serum d-Ser, SR and DAAO indicated that the best serum level cutoff points at which schizophrenia manifestations started to appear were ≤ 61.4 mg/L for d-Ser, ≤ 15.5 pg/mL for SR and >35.6 pg/mL for DAAO. The present study confirms that disturbed d-Ser metabolism could be implicated in the pathogenesis of schizophrenia.

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-β and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-β, 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-β, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-β, 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-β, 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-β, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

Type 2 diabetes mellitus (DM) is the most common single cause of the end-stage renal disease (ESRD). Cyclophilin A (CyPA) is an 18-kD protein. The connection between diabetic nephropathy (DN) and the secreted form of CyPA (sCyPA) has been elucidated in this study that aims to investigate sCyPA correlation with renal dysfunction. Thirty-four male adult Wistar rats weighing 180-220 g were used. Animals were divided into a study group and a control group, 17 rats in each. Streptozotocin (STZ) and nicotine amide were used to damage some pancreatic cells for induction of type 2 DM. Comparison was made between the study and the control groups. Moreover, a comparison was made between the members of the study group before and after induction of DN. The rat model that exhibited a higher concentration of urinary sCyPA was detected early in the eighth week. There was a significantly higher level of 24-h urinary CyPA in the study group compared to the control group ( -value=0.004) and there was a significant elevation in the 24-h urinary Cyp-A in the study group after injection of STZ compared to the values before injection ( -value <0.001). Immunohistochemical analysis of renal tissue revealed that the mean expression of CyPA was higher in the study group than in the control group. For the urinary 24-h CYP-A, using a cutoff of 1.15 ng/mL, the accuracy was 72.4%, sensitivity was (77.8%) and specificity was (67%). According to this animal study, we proved that CyPA is a valuable marker for DN. It is a more sensitive, noninvasive and rapid biomarker for early detection of any renal affection in human diabetic patients.

Background and Aim: Type 2 diabetes mellitus (DM) is the most common single cause of the end-stage renal disease (ESRD). Cyclophilin A (CyPA) is an 18-kD protein. The connection between diabetic nephropathy (DN) and the secreted form of CyPA (sCyPA) has been elucidated in this study that aims to investigate sCyPA correlation with renal dysfunction. Materials and Methods: Thirty-four male adult Wistar rats weighing 180-220 g were used. Animals were divided into a study group and a control group, 17 rats in each. Streptozotocin (STZ) and nicotine amide were used to damage some pancreatic cells for induction of type 2 DM. Comparison was made between the study and the control groups. Moreover, a comparison was made between the members of the study group before and after induction of DN. Results: The rat model that exhibited a higher concentration of urinary sCyPA was detected early in the eighth week. There was a significantly higher level of 24-h urinary CyPA in the study group compared to the control group (p-value=0.004) and there was a significant elevation in the 24-h urinary Cyp-A in the study group after injection of STZ compared to the values before injection (p-value <0.001). Immunohistochemical analysis of renal tissue revealed that the mean expression of CyPA was higher in the study group than in the control group. For the urinary 24-h CYP-A, using a cutoff of 1.15 ng/mL, the accuracy was 72.4%, sensitivity was (77.8%) and specificity was (67%). Conclusion: According to this animal study, we proved that CyPA is a valuable marker for DN. It is a more sensitive, noninvasive and rapid biomarker for early detection of any renal affection in human diabetic patients. Keywords: cyclophilin A, hyperglycemia, type 2 diabetes, diabetic nephropathy early detection, albuminuria