Fenitrothion (FNT), a commonly used organophosphate, can cause oxidative damage and apoptosis on various organs. However, the underlying mechanisms for FNT-induced cardiotoxicity did not formally ...report. Here, we have evaluated the possible ameliorative roles of resveratrol (RSV) against FNT-induced cardiac apoptosis in male rats through the sirtuin1 (SIRT1)/c-Jun N-terminal kinase (c-JNK)/p53 pathway concerning pro-oxidant and inflammatory cytokines. Forty-eight male rats were equally grouped into control, RSV (20 mg/kg), 5-FNT (5 mg/kg), 10-FNT (10 mg/kg), 20-FNT (20 mg/kg), 5-FNT-RSV, 10-FNT-RSV, and 20-FNT-RSV where all doses administrated by gavage for four weeks. The present findings demonstrated that RSV markedly diminished the level of hyperlipidemia and elevation in lactate dehydrogenase (LDH), total creatine kinase (CK-T), and troponin T (TnT) levels following FNT intoxication. Furthermore, RSV significantly reduced FNT-induced cardiac oxidative injury by reducing malondialdehyde (MDA) level and improving the levels of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and acetylcholinesterase (AchE). Also, the levels of interleukin-1β (IL1β,), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly attenuated in the co-treated groups. Moreover, RSV alleviated the histopathological changes promoted by FNT and repaired the transcript levels of SIRT1, c-JNK, and caspase-9/3 along with p53 immunoreactivity. In silico study revealed that the free binding energies of RSV complexes with protein and DNA sequences of SIRT1 were lower than docked complexes of FNT. Therefore, RSV reserved myocardial injury-induced apoptosis following exposure to FNT by modulating the SIRT1/c-JNK/p53 pathway through cellular redox status and inflammatory response improvements.
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•Resveratrol reduced hyperlipidemia and elevated cardiac biomarker levels induced by fenitrothion.•Resveratrol alleviated fenitrothion-induced cardiac oxidative injury and inflammatory responses.•The binding energies of resveratrol with sirtuin1 were lower than fenitrothion.•Resveratrol protected from cardiac apoptosis by modulating the sirtuin1/c-Jun N-terminal kinases/p53 pathway.
Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the ...pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity.
Dapagliflozin (DAPA) is used for treating type 2 diabetes, whereas lansoprazole (LPZ) is used as a traditional antiulcer drug. The present study investigated the possible antidiabetic effects of LPZ ...on fortified diet-fed streptozotocin (FDF/STZ)-induced insulin-resistant diabetic rats. On the basis of the current results, it can be concluded that LPZ could be used as an add-on drug along with the conventional treatment for T2D as it showed beneficial effects in the current experimental model of insulin resistance.
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•Development of a green HPLC method for the simultaneous determination of photoinitiators.•Bioanalytical validation and green assessment of the method.•Applications to saliva through ...contact with bibs, teethers and pacifiers.
A green, sensitive and rapid RP-HPLC-UV method was developed and bioanalytically validated to determine and quantify the four photoinitiators, 4-Hydroxyacetophenone, Benzophenone, Benzoin, and Ethyl-4-dimethylaminobenzoate, in saliva in contact with bibs, teethers, and pacifiers. C18 column was used as the stationary phase, acetonitrile and water were used as the mobile phase in an isocratic mode, and diode-array as the detector. The method reached a lower limit of quantitation (LLOQ) of 10.00 ng/mL with excellent accuracy and precision. The method was bioanalytically validated according to FDA guidelines and the greenness of the method was evaluated using three tools including the analytical eco-scale, the analytical greenness assessment (AGREE), and the HPLC environmental assessment tool (HPLC-EAT).
Pathogenesis of thrombocytopenia is heterogeneous and resistance to treatment is a great challenge. In this study, we reviewed the demographic features of thrombocytopenic Egyptian patients. We also ...analyzed the role of T cell in chronic immune cases. IL-12, IL-35, IL-17, and TGF-β were measured by ELISA. The median age at the time of diagnosis was 30 years and its range was 14–70. The median platelet count at the time of diagnosis was 15 × 10
9
/L. Regarding treatment and follow-up, there was an indication for treatment in 96% of patients. Of the 150 ITP patients who were given first-line therapy (corticosteroid 1 mg/kg/day PO), there was a complete response (CR) in 40.3% while 59.7% patients were nonresponsive to therapy. Forty-five chronic cases fulfilled the criteria for cytokine assay. Comparison between the case group and the control group revealed statistically significant lower platelet count in cases, while the four measured cytokines were statistically significant higher in cases rather than the control. Correlation between the platelet count and the level of cytokines was statistically insignificant. The remission rate in ITP on steroid as first-line therapy is less than 50%. The higher expression of IL-12 and IL-35in chronic ITP is due to the persistently higher Th1 activity which explains the continuity of the disease, while the higher expression of Treg cytokines (IL-17 and TGF-β) may be explained by effect of immunosuppression or upregulation of the receptors on Treg cells.
Migration of photoinitiators from packaging materials and dental products in saliva presents an extensive real damage, particularly that emerges from packed food and dental products in saliva or from ...polyethylene packaging of the intravenous solutions which is extremely dangerous to human health and to the environment. In line with this, environmentally evaluated, advanced and reliable triple divisor combined with continuous wavelet transform (CWT) spectrophotometric method and nine chemometric methods were established and validated for the concurrent determination of four photoinitiators: Benzophenone, 4-Hydroxyacetophenone, Benzoin, and Diphenyliodonium hexafluorophosphate in saliva and in intravenous injection solutions. To our knowledge, this is the first spectrophotometric method for the analysis of the cited photoinitiators as well as the primary white method for the examination of those photoinitiators. Also, in this paper, the triple divisor method is combined with continuous wavelet transform for the first time. Triple divisor–CWT peak amplitudes were defined at 260.0, 275.8, 262.2 and 231.2 nm over a linear dynamic range of 0.50–13.00, 0.80–10.00, 1.5–30.00 and 1.00–28.00 μg/mL for Benzophenone, 4-Hydroxyacetophenone, Benzoin and Diphenyliodonium hexafluorophosphate, respectively. The nine chemometric methods incorporate the application of principle component regression (PCR), orthogonal partial least square (OPLS), ridge regression (RR) and artificial neural networks (ANN) methods along with different variable selections including genetic algorithm (GA-PCR, GA-OPLS and GA-RR) and interval selections (Interval-PCR and Interval-OPLS). Regarding the adopted chemometrics models, a multivariate multifactor experimental design based on the calibration curve range of the studied photoinitiators was considered to construct a calibration set consisting of eighteen mixtures while using seven mixtures for the validation set. The proposed methods were demonstrated to be sensitive, accurate, precise and reproducible throughout the validation process. The acquired results revealed that the proposed spectrophotometric and chemometric approaches could be effectively applied for the regular analysis of the cited photoinitiators in biological fluids as saliva and in intravenous solutions. The greenness of the proposed methods was assessed using two green metric tools enclosing Analytical Eco-scale & Analytical Greenness Assessment (AGREE), and a White Analytical Chemistry tool (WAC).
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•Development of advanced spectrophotometric and chemometric methods.•Validation and green assessment of the methods.•Application for the determination of four photoinitiators in intravenous solution.
Pain-associated depression is encountered clinically in some cases such as cancer, chronic neuropathy, and after operations. Tramadol is an opioid analgesic drug that may modulate monoaminergic ...neurotransmission by inhibition of noradrenaline and serotonin reuptake that may contribute to its antidepressant-like effects. Clinically, tramadol is used either alone or in combination with other NSAIDs in the treatment of cases associated with pain and depression, e.g. low back pain, spinal cord injury, and post-operative pain management. However, tramadol monotherapy as an antidepressant is impeded by severe adverse effects including seizures and serotonin syndrome. Interestingly, phosphodiesterase-III inhibitors demonstrated novel promising antidepressant effects. Among which, cilostazol was reported to attenuate depression in post-stroke cases, geriatrics and patients undergoing carotid artery stenting. Therefore, this study was carried out to investigate the possible antidepressant-like effects of tramadol and/or cilostazol on the behavioral level in experimental animals, and to examine the neurochemical and biochemical effects of tramadol, cilostazol and their combination in rats, in order to explore the probable mechanisms of action underlying their effects. To achieve our target, male albino mice and rats were randomly allocated into five groups and administered either vehicle for control, fluoxetine (20 mg/kg, p.o.), tramadol HCl (20 mg/kg, p.o.), cilostazol (100 mg/kg, p.o.), or combination of both tramadol and cilostazol. At day 14, mice and rats were challenged in the tail suspension test and forced swim test, respectively. Rats were sacrificed and brains were isolated for determination of brain monoamines, MDA, NO, SOD, and TNF-α. The current results showed that concurrent administration of cilostazol to tramadol-treated animals modulated depression on the behavioral level, and showed ameliorative neurochemical and biochemical effects in rats exposed to FST.
Alopecia areata (AA) is a common autoimmune condition that affects anagen hair follicles. The most commonly recognized theory is that it is a T-cell-mediated autoimmune disorder in a genetically ...susceptible individual. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) were thought to play a function in the pathogenesis. The expression of lncRNA HOTAIR and miRNA-205 and their relation to transforming growth factor β1 (TGF-β1) in AA were not studied.
The aim of the studywas to evaluate the role of miRNA-205, lncRNA, HOTAIR, and TGF-β1 levels in AA pathogenesis, clinical course, and severity of AA.
Two groups of subjects were included in this case-control study: 50 patients with AA and 50 healthy matched controls. miRNA-205 and lncRNA HOTAIR expression levels were assayed using quantitative RT-PCR, while serum levels of TGF-β1 were assayed using ELISA techniques.
The serum expression of lncRNA HOTAIR was significantly downregulated in AA patients with a
value < 0.001, while the serum expression of both miRNA-205 and TGF-β1 were significantly upregulated in patients.
This study highlights the potential role of high serum expression of miRNA-205 and TGF-β1 and the low serum expression of lncRNA HOTAIR in AA pathogenesis. This could be used as a therapeutic target to treat AA.
Background
Epilepsy is a chronic neurological disease. A suitable biomarker for epilepsy diagnosis remains lacking. MicroRNAs (miRNAs) were pronounced as promising biomarkers for epileptogenesis.
...Objectives
To analyze the expression levels of miR 194-5p, miR 106b, and miR 146a in Egyptian epileptic patients compared to control subjects and to detect their correlation to clinical characteristics.
Subjects and methods
We evaluated the expression levels of miR 106b, miR 146a, and miR 194-5p using real-time quantitative polymerase chain reaction (qRT-PCR) in 50 subjects: 15 patients with idiopathic generalized epilepsy, 15 patients with focal epilepsy (3 idiopathic and 12 cryptogenic), and 20 healthy controls.
Results
miR 106b and miR 194-5p were upregulated in the generalized epilepsy group compared to control; miR 194-5p was significantly downregulated in the focal epilepsy group compared to the generalized epilepsy group and control (
p
˂ 0.05). miR 194-5p was negatively correlated to disease duration in patients with focal epilepsy; the three microRNAs were positively correlated to each other (
p
˂ 0.05).
Conclusion
Serum miR 194-5P and miR 106b can be used as potential non-invasive biomarkers in the evaluation of idiopathic generalized epilepsy.
Introduction: Alopecia areata (AA) is a common autoimmune condition that affects anagen hair follicles. The most commonly recognized theory is that it is a T-cell-mediated autoimmune disorder in a ...genetically susceptible individual. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) were thought to play a function in the pathogenesis. The expression of lncRNA HOTAIR and miRNA-205 and their relation to transforming growth factor β1 (TGF-β1) in AA were not studied. Aim: The aim of the studywas to evaluate the role of miRNA-205, lncRNA, HOTAIR, and TGF-β1 levels in AA pathogenesis, clinical course, and severity of AA. Methods: Two groups of subjects were included in this case-control study: 50 patients with AA and 50 healthy matched controls. miRNA-205 and lncRNA HOTAIR expression levels were assayed using quantitative RT-PCR, while serum levels of TGF-β1 were assayed using ELISA techniques. Results: The serum expression of lncRNA HOTAIR was significantly downregulated in AA patients with a p value < 0.001, while the serum expression of both miRNA-205 and TGF-β1 were significantly upregulated in patients. Discussion/Conclusion: This study highlights the potential role of high serum expression of miRNA-205 and TGF-β1 and the low serum expression of lncRNA HOTAIR in AA pathogenesis. This could be used as a therapeutic target to treat AA.
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