Leptin gene Polymorphism and Leptin protein levels in Pediatric Autoimmune Hepatitis.

BACKGROUND: Leptin plays a role in regulating energy balance, immunity, and inflammation. Studies suggest higher leptin levels might be associated with various autoimmune diseases. Most of them were in adult. To our knowledge, our study is one of the few that describe serum leptin level and leptin gene polymorphism in children with autoimmune hepatitis (AIH). OBJECTIVE: Our study aims to explore the association between serum leptin level and genetic variations in leptin gene with the likelihood of AIH in children. PATIENTS AND METHODS: Thirty-one children with AIH and 29 healthy children serving as a control group were included. Serum leptin levels were measured by ELISA assays. Leptin rs2167270 genotyping was done using the real time-PCR. The relationship of serum leptin level and leptin gene polymorphism with patients' data was studied. Patients follow up to assess treatment response. RESULTS: Children with AIH had significantly higher levels of leptin compared to healthy controls. GG genotype was significantly more prevalent in the AIH group compared to controls. CONCLUSION: High serum leptin levels and leptin gene polymorphism may play a role in AIH development. It is worthy to recognize if leptin can serve as diagnostic and/or therapeutic target in AIH in children.

Identifying the association between polymorphisms in the GZMB and IFIH1 genes and psoriasis in Egyptians.

OBJECTIVES: This study aims to examine whether the genetic variants in the genes for Granzyme B (GZMB) and Interferon Induced with Helicase C domain 1 (IFIH1) were associated with psoriasis. BACKGROUND: Psoriasis, a papulosquamous skin disease, was initially thought of as a disorder primarily of epidermal keratinocytes but is now recognized as one of the most common immune-mediated disorders. It is caused by the interplay between multiple genetic and environmental risk factors. SUBJECTS AND METHODS: This case-control study has 65 participants with psoriasis and 65 healthy controls. Real-time PCR was used to genotype GZMB (rs8192917) and IFIH1 (rs35667974). RESULTS: Genotype occurrence and allelic spreading for both SNPs are in Hardy - Weinberg equilibrium. The genotype and allele distributions of rs35667974 showed no differences between the studied groups. Regarding rs8192917, compared to Group II, there is a statistically significant rise in the CC genotype and C allele in Group I. Higher PASI scores are detected in the C/C and C/T genotypes more than the T/T genotype. Univariate and multivariate analyses revealed that BMI, catalase, MDA, and rs8192917 (C/C) are associated with psoriasis. CONCLUSION: GZMB rs8192917 was significantly related to psoriasis risk; its C allele is likewise associated with psoriasis vulnerability. However, our investigation found no link between rs35667974 and psoriasis.

Identification of potential biomarkers for SLE through mRNA expression profiling.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that influences numerous body systems. Furin, tristetraprolin (TTP), and NOD, LRR, and pyrin domain-containing protein 3 (NLRP3) contribute in developing autoimmune illnesses. AIM: Understandthe role of furin, TTP, and NLRP3 mRNA gene expression in SLE pathogenesis and prognosis. Methods: Total 210 individuals were enrolled, divided in two group: cases and control; 105 participants in each group.  Real-time quantitative PCR for furin, TTP,and NLRP3 mRNA gene expression were determined for each subject. RESULTS: SLE patients showed significantly higher serum furin [median 20.10 (0.0-162.88) in comparison with control group [median 1.10 (0.33-8.64)] with significant pvalue (p < 0.001), for NLRP3 expression [median 7.03 (0.0-282.97) compared to control group [median 1.0 (0.44-9.48)] with significant p value (p = 0.006)but lower TTP [median 2.37 (0.0-30.13)] in comparison with control group [median 7.90 (1.0-29.29)] with significant p value (p < 0.001) . Elevated levels of Furin and NLRP3 and low levels of TTP were linked to increased illness activity. CONCLUSION: Furin and NLRP increase in SLE and higher with illness activity. TTP is lowerin SLE and negatively correlates with disease activity.

Nephroprotective Efficacy of Echinops spinosus against a Glycerol-Induced Acute Kidney Injury Model.

Nephroprotection or renal rescue is to revive and restore kidney function after damage, with no need for further dialysis. During acute kidney injury (AKI), sudden and recent reductions in kidney functions occur. Causes are multiple, and prompt intervention can be critical to diminish or prevent morbidity. Echinops spinosus (ES) is a curative plant with proven pharmacological and biological effects including anti-inflammatory, antioxidant, and antibacterial competencies. The principal goal of this research is to scrutinize the nephroprotective features of E. spinosa extract (ESE) against glycerol-induced AKI. Male Wistar albino rats were equally divided into five separated groups: negative control rats (vehicle-injected), ESE control rats (ESE-treated rats), positive control rats, glycerol-induced AKI-model rats (single IM injection of 50% glycerol), and 2 groups of diseased rats but pretreated with different concentrations of ESE for 7 days (ESE150 + AKI rats and ESE250 + AKI rats). Kidney tissues were collected and used for histopathology analysis. The relative kidney weight percentage was assessed. ESE effects were investigated via scanning several biomarkers, such as serum urea and creatinine, as kidney function biomarkers. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities were examined as rhabdomyolysis (RM) indicators. Kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) were also examined to investigate kidney injury. Enzymatic and nonenzymatic oxidative stress markers were analyzed, namely, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione GSH. Proinflammatory cytokine [tumor necrosis factor-α (TNF-α) and interleukin-1 ß (IL-1ß)] and the renal proapoptotic protein (Bax) and antiapoptotic protein (Bcl-2) levels were evaluated. Statistical analysis for the resulting data revealed that ESE pretreatment turned AKI-induced biological antioxidant levels to an extent comparable to normal results. Furthermore, ESE decreased kidney function markers and RM-related biomarkers (LDH, CK, Kim-1, and NGAL) compared to those in untreated AKI-model rats. ESE treatment dropped the apoptotic renal Bax levels, enhanced antiapoptotic Bcl-2 manufacture, and disallowed the release of IL-1ß and TNF-α. This study revealed the protective effect of ESE as therapeutic medicine against AKI-encouraged oxidative stress, inflammation, and apoptosis. It can be effectively used as adjuvant therapy, helping in renal rescue, and for kidney healing in cases with risk factors of AKI.

Utility of a microRNA panel in diagnosis and prognosis of hepatitis C-associated hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the leading cause of cancer mortality. Various studies have linked dysregulated microRNA expression to liver cancers, but those related to viral hepatitis-related HCC are limited. METHODS: We investigated the diagnostic and prognostic roles of circulating miR-331-3p, miR-23b-3p, and miR-3194-5p in EDTA-treated blood samples of 50 hepatitis C virus (HCV) HCC patients, 50 HCV cirrhotic patients, and 50 healthy controls using quantitative real-time polymerase chain reaction. RESULTS: We found that miR-23b-3p and miR-3194-5p were significantly downregulated, whereas miR-331-3p was upregulated in HCC patients compared with controls. Also, these miRNAs were significantly dysregulated in HCC compared with cirrhotic patients. For the diagnosis of HCC, miR-331-3p and the combined miRNAs panel had the highest area under the curve (AUC), followed by miR-3194-5p. The highest AUC for differentiating metastatic from nonmetastatic patients was shown by miR-331-3p and the combined miRNAs panel, followed by miR-23b-3p. Dysregulation of miRNAs was associated with poor clinicopathological manifestations. Finally, miR-331-3P was found to be an independent risk factor for metastatic lesions in HCC. CONCLUSION: Overall, the assessed miR-331-3p, miR-23b-3p, and miR-3194-5p were significantly associated with poor clinicopathological features of HCC and could be used to discriminate HCV-related HCC patients from cirrhosis and differentiating metastatic from nonmetastatic patients, primarily miR-331-3p along with combined miRNAs. Moreover, miR-331-3p was found to be an independent factor for metastatic lesions.

Biosynthesized Selenium Nanoparticles Using Epigallocatechin Gallate Protect against Pentylenetetrazole-Induced Acute Epileptic Seizures in Mice via Antioxidative, Anti-Inflammatory, and Anti-Apoptotic Activities.

Several negative outcomes are associated with current anti-epileptic medications. Epigallocatechin gallate (EGCG) is a plant-derived compound called catechin and has many medicinal activities, such as anti-inflammatory and antioxidant activities. Biosynthesized selenium nanoparticles are also showing their neuroprotective effect. The anti-epileptic effect of EGCG, alone or with SeNPs, is still debated. Here, we aimed to investigate the potential anti-seizure effect of biosynthesized SeNPs using EGCG (EGCG-SeNPs) against epileptic seizures and hippocampal damage, which is enhanced by pentylenetetrazole (PTZ) injection in mice. Mice were grouped as follows: control; PTZ-exposed group (epileptic model); EGCG + PTZ-treated group; sodium selenite (Na2SeO3) + PTZ-treated group; EGCG-SeNPs + PTZ-treated group; and valproic acid (VPA) + PTZ-treated group. EGCG-SeNPs administration showed anti-epileptic activity by increasing the latency time and reducing the seizure duration following the PTZ injection. Additionally, EGCG-SeNPs counteracted the PTZ-induced changes in oxidants and antioxidants. Moreover, EGCG-SeNPs inhibited the inflammatory response by suppressing the release of pro-inflammatory cytokines and decreasing the immunoreactivity of the glial fibrillary acidic protein and mRNA expression of glutamate receptor subunit zeta-1 (NMDAR; Grin1), showing their inhibitory effect on epilepsy-associated inflammation. Moreover, EGCG-SeNPs reduced PTZ-induced neuronal apoptosis, as indicated by a reduction in the levels of pro-apoptotic proteins and an elevation of the anti-apoptotic protein. Moreover, EGCG-SeNPs administration significantly modulated the PTZ-induced changes in monoamine levels and acetylcholinesterase activity in the hippocampal tissue. The obtained findings suggest the anti-seizure activity of EGCG-SeNPs via their antioxidant, anti-inflammatory, and anti-apoptotic effects, along with their neuromodulatory effect.

The Neuroprotective Effect Associated with Echinops spinosus in an Acute Seizure Model Induced by Pentylenetetrazole.

Echinops spinosus (ES) is a medicinal plant with a wide range of pharmacological and biological effects. It is a medicinal herb having a variety of therapeutic characteristics, including antioxidant, anti-inflammatory, and antibacterial capabilities. The primary goal of this research is to investigate the neuroprotective and anticonvulsant characteristics of E. spinosa extract (ESE) against pentylenetetrazole (PTZ)-induced acute seizures. Negative control rats, ESE treatment rats, PTZ acute seizure model rats, ESE + PTZ rats, and Diazepam + PTZ rats were used in the study. The rats were given a 7-day treatment. ESE pretreatment elevated the latency to seizure onset and lowered seizure duration after PTZ injection. By reducing Bax levels and enhancing antiapoptotic Bcl-2 production, ESE prevented the release of interleukin-1ß, tumor necrosis factor-α, and cyclooxygenase-2, as well as preventing hippocampal cell death after PTZ injection. ESE corrected the PTZ-induced imbalance in gamma-aminobutyric acid levels and increased the enzyme activity of Na+/K+-ATPase. Echinops spinosus is a potent neuromodulatory, antioxidant, antiinflammatory, and antiapoptotic plant that could be employed as a natural anticonvulsant in the future.

Neuroprotective effect of green and roasted coffee bean extracts on cerebral ischemia-induced injury in rats.

Stroke is a lethal event with a high incidence in Egypt. Quick early intervention can be lifesaving. Transient global ischemia (TGI), a type of ischemic stroke, is mainly instigated by cardiac arrest. Ischemia followed by reperfusion causes further neuronal cell damage. In this study, we aimed to evaluate the potential apoptotic, anti-inflammatory, and neuroprotective effects of green (GCBE) and roasted (RCBE) coffee bean water extract against transient global ischemia-induced via a bilateral common carotid artery occlusion (CAO) in rats. Before CAO, 1.5 ml/kg body weight/day of GCBE or RCBE was administered for 14 days by oral gavage. Ischemia/reperfusion (I/R) and sham groups were treated with a vehicle. Oxidative stress biomarkers and antioxidant enzyme activities, such as MDA, NO, GSH, SOD, CAT, GR, GPx, inflammatory markers TNF-α, IL-1ß, and NF-κB, and BDNF were investigated. Quantitative real-time PCR analysis of mitogen-activated protein kinase pathways, in addition to heme oxygenase 1, and nuclear factor erythroid 2-related factor 2 were determined. Apoptotic markers, including Bcl-2, Bax, and caspase 3, in addition to the vascular endothelial growth factor-a, were investigated, followed by an examination of hippocampal histopathology. Pre-administration of GCBE and RCBE improved neurological function and neuronal survival, suppressed the spread of oxidative stress, inflammation, and apoptosis, and reversed most of the pathological changes. However, green coffee bean extract was more effective than roasted coffee bean extract, perhaps due to the roasting process, which may affect active compounds. In conclusion, GCBE and RCBE represent a potential clinical strategy for pre-ischemic conditioning.

Clinical/pathologic features and patient outcome in early onset endometrial carcinoma: a population based analysis and an institutional perspective from the Detroit metropolitan area, Michigan.

OBJECTIVE: Analyze tumor characteristics and outcomes in patients with endometrial carcinoma (EC)<40 years of age and compare them to the characteristics of patients ≥ 40 years of age. METHODS: 10,700 patients (305 patients <40 years of age) diagnosed between 1988 and 2007 with EC from the Metropolitan Detroit Cancer Surveillance System (MDCSS), and 884 patients (42 patients <40 years of age) diagnosed between 1996 and 2008 with EC from our institutional database were identified. Differences in clinical and demographic variables by age (<40 vs. ≥ 40) were assessed for statistical significance by chi-square tests. Cox proportional hazards models were used to calculate adjusted hazard ratios (HR) and their 95% confidence intervals (95% CI) to assess the risk of death from all causes. RESULTS: MDCSS based analysis: Patients<40 were more likely to present with low grade tumors (p<0.0001) and endometroid histology (p=0.0004) but less likely to undergo surgery (p=0.0007) or radiotherapy (p=0.0007). A multivariate analysis confirmed the significance of age, grade, and stage in all patients, and that of histologic type, surgery, and race in patients ≥ 40 as independent prognostic factors for overall survival. Institution based analysis: Patients<40 had a higher proportion of patients with BM I ≥ 30 (p=0.04), and presented with a higher frequency of well differentiated (p=0.04) endometrioid tumors (p=0.004) that are less prone to have deep myometrial invasion (p=0.008). CONCLUSION: This study supports the hypothesis of a disease that is biologically and genetically heterogeneous among women of different ages and ethnicities.