The antioxidant, anti-inflammatory, and anti-apoptotic effects of sesamin against cisplatin-induced renal and testicular toxicity in rats.

PURPOSE: The present study investigated the nephron-testicular protective effects of sesamin against cisplatin (CP)-induced acute renal and testicular injuries. METHODS: Thirty-two male Wistar rats were allocated to receive carboxymethylcellulose (0.5%, as sesamin vehicle), CP (a single i.p. 5 mg/kg dose), CP plus sesamin at 10 or 20 mg/kg orally for 10 days. RESULTS: Data analysis showed significant increases in serum urea, creatinine, interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), as well as renal and testicular tissue malondialdehyde and nitric-oxide concentrations in CP-intoxicated rats in comparison to control animals. On the contrary, rats treated with CP only exhibited significantly lower (p < .05) serum testosterone, tissue glutathione, and activities of endogenous antioxidant enzymes compared to control rats. Histopathologically examining CP-intoxicated rats' tissues using H&E and PAS stains showed atrophied glomeruli, interstitial inflammatory cells, atypic tubular epithelium with focal apoptosis, and reduced mucopolysaccharide content. Further, immunohistochemical staining of the same group revealed an increase in p53 and cyclooxygenase-II (Cox-II) expression in renal and testicular tissues. Treatment with sesamin alleviated almost all the changes mentioned above in a dose-dependent manner, with the 20 mg/kg dose restoring several parameters' concentrations to normal ranges. CONCLUSIONS: In brief, sesamin could protect the kidneys and testes against CP toxicity through its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Spirulina platensis ameliorates hepatic oxidative stress and DNA damage induced by aflatoxin B1 in rats.

Aflatoxin B1 (AFB1) is a widely distributed mycotoxin, causing hepatotoxicity and oxidative stress. One of the most famous unicellular cyanobacteria is Spirulina platensis (SP) which is well known for its antioxidant characteristics against many toxicants. Therefore, this study aimed to investigate the antioxidant potential and hepatoprotective ability of SP against oxidative stress and cytotoxicity in male Wistar albino rats intraperitoneally injected with AFB1. Rats were separated into five groups as follows: negative control administered with saline; SP (1000 mg/kg BW) for two weeks; AFB1 (2.5 mg/kg BW) twice on days 12 and 14; AFB1 (twice) + 500 mg SP/kg BW (for two weeks) and AFB1 (twice) + 1000 mg SP/kg BW (for two weeks). Liver and blood samples were assembled for histological and biochemical analyses. AFB1 intoxicated rats showed a marked elevation in serum biochemical parameters (ALP, ALT, and AST), hepatic lipid peroxidation (MDA and NO), and proliferating cell nuclear antigen (PCNA) indicating DNA damage. Moreover, AFB1 caused suppression of antioxidant biomarkers (SOD, GHS, GSH-Px, and CAT). However, the elevated serum levels of biochemical parameters and PCNA expression were reduced by SP. Moreover, SP lowered oxidative stress and lipid peroxidation markers in a dose-dependent manner. To sum up, SP supplementation is capable of decreasing AFB1 toxicity through its powerful antioxidant activity.

Nifuroxazide repurposing for protection from diabetes-induced retinal injury in rats: Implication of oxidative stress and JAK/STAT3 axis.

The prevalence of diabetes mellitus (DM) is alarmingly increasing worldwide. Diabetic retinopathy (DR) is a prevailing DM microvascular complication, representing the major cause of blindness in working-age population. Inflammation is a crucial player in DR pathogenesis. JAK/STAT3 axis is a pleotropic cascade that modulates diverse inflammatory events. Nifuroxazide (Nifu) is a commonly used oral antibiotic with reported JAK/STAT3 inhibition activity. The present study investigated the potential protective effect of Nifu against diabetes-induced retinal injury. Effect of Nifu on oxidative stress, JAK/STAT3 axis and downstream inflammatory mediators has been also studied. Diabetes was induced in Sprague Dawley rats by single intraperitoneal injection of streptozotocin (50 mg/kg). Animals were assigned into four groups: normal, Nifu control, DM, and DM + Nifu. Nifu was orally administrated at 25 mg/kg/day for 8 weeks. The effects of Nifu on oxidative stress, JAK/STAT3 axis proteins, inflammatory factors, tight junction proteins, histological, and ultrastructural alterations were evaluated using spectrophotometry, gene and protein analyses, and histological studies. Nifu administration to diabetic rats attenuated histopathological and signs of retinal injury. Additionally, Nifu attenuated retinal oxidative stress, inhibited JAK and STAT3 phosphorylation, augmented the expression of STAT3 signaling inhibitor SOCS3, dampened the expression of transcription factor of inflammation NF-κB, and inflammatory cytokine TNF-α. Collectively, the current study indicated that Nifu alleviated DR progression in diabetic rats, suggesting beneficial retino-protective effect. This can be attributed to blocking JAK/STAT3 axis in retinal tissues with subsequent amelioration of oxidative stress and inflammation.

Identification of potential biomarkers for melanoma cancer (black tumor) using bioinformatics strategy: a study based on GEO and SRA datasets.

Melanoma, a highly invasive type of skin cancer that penetrates the entire dermis layer, is associated with increased mortality rates. Excessive exposure of the skin to sunlight, specifically ultraviolet radiation, is the underlying cause of this malignant condition. The appearance of unique skin moles represents a visible clue, referred to as the "ugly duckling" sign, indicating the presence of melanoma and its association with cellular DNA damage. This research aims to explore potential biomarkers derived from microarray data, employing bioinformatics techniques and methodologies, for a thorough investigation of melanoma skin cancer. The microarray dataset for melanoma skin cancer was obtained from the GEO database, and thorough data analysis and quality control measures were performed to identify differentially expressed genes (DEGs). The top 14 highly expressed DEGs were identified, and their gene information and protein sequences were retrieved from the NCBI gene and protein database. These proteins were further analyzed for domain identification and network analysis. Gene expression analysis was conducted to visualize the upregulated and downregulated genes. Additionally, gene metabolite network analysis was carried out to understand the interactions between highly interconnected genes and regulatory transcripts. Molecular docking was employed to investigate the ligand-binding sites and visualize the three-dimensional structure of proteins. Our research unveiled a collection of genes with varying expression levels, some elevated and others reduced, which could function as promising biomarkers closely linked to the development and advancement of melanoma skin cancer. Through molecular docking analysis of the GINS2 protein, we identified two natural compounds (PubChem-156021169 and PubChem-60700) with potential as inhibitors against melanoma. This research has implications for early detection, treatment, and understanding the molecular basis of melanoma.

Enumeration of olive derived lignan, pinoresinol for activity against recent Omicron variant spike protein for structure-based drug design, DFT, molecular dynamics simulations, and MMGBSA studies.

The coronavirus disease 2019 (COVID-19) was first found in Wuhan, China, in December 2019. Because the virus spreads quickly, it quickly became a global worry. Coronaviridae is the family that contains both SARS-CoV-2 and the viruses that came before (i.e., MERS-CoV and SARS-CoV). Recent sources portray that the COVID-19 virus has affected 344,710,576 people worldwide and killed about 5,598,511 people in the last 2 years. The B.1.1.529 strain, later called "Omicron," was named a Variant of Concern on November 24, 2021. The SARS-CoV-2 virus has gone through a never-ending chain of changes that have never happened before. As a result, it has many different traits. Most of these changes have occurred in the spike protein, where antibodies bind. Because of these changes, the Omicron type is very contagious and easy to pass on. There have been a lot of studies done to try to figure out this new challenge in the COVID-19 strains race, but there is still a lot that needs to be explained. This study focuses on virtual screening, docking, and molecular dynamic analysis; we aimed to identify therapeutic candidates for the SARS-CoV-2 variant Omicron based on their ability to inhibit non-structural proteins. We investigate the prediction of the properties of a substantial database of drug molecules obtained from the OliveNet™ database. Compounds that did not exhibit adequate gastrointestinal absorption and failed the Lipinski test are not considered for further research. The filtered compounds were coupled with our primary target, SARS-CoV-2 Omicron spike protein. We focused on SARS-CoV-2 Omicron spike protein and filtering potent olive compounds. Pinoresinol, the most likely candidate, is bound best (- 8.5 kcal/mol). Pinoresinol's strong interaction with the active site made the complex's dynamic structure more resilient. MD simulations explain the protein-ligand complex's stability and function. Pinoresinol may be a promising SARS-CoV-2 Omicron spike protein receptor lead drug, and additional research may assist the scientific community.

Increased NOTCH1 expression is associated with low survival in moderate/ poor differentiated human oral squamous cell carcinoma patients.

Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly expressed in human oral cancer tissues compared with that in normal marginal tissues and was associated with poor prognosis. The positive Notch 1 expression was significantly associated with poor tumor differentiation status. Kaplan-Meier survival curves revealed that elevated cytoplasmic NOTCH1 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate COX proportional hazard models revealed that T N status, AJCC stage histological grade were independent prognostic factors for survival. Our result clearly demonstrates the oncogenic role of Notch1 in oral cancer and Notch1 may be a useful biomarker to target oral cancer patients.

Canagliflozin ameliorates ulcerative colitis via regulation of TLR4/MAPK/NF-κB and Nrf2/PPAR-γ/SIRT1 signaling pathways.

Ulcerative colitis (UC) is one of the most common subtypes of inflammatory bowel disease (IBD) that affects the colon and is characterized by severe intestinal inflammation. Canagliflozin is a widely used antihyperglycemic agent, a sodium-glucose cotransporter-2 (SGLT2) inhibitor that enhances urinary glucose excretion. This study aims to provide insights into the potential benefits of canagliflozin as a treatment for UC by addressing possible cellular signals. Acetic acid (AA; 4% v/v) was administered intrarectally to induce colitis. Canagliflozin is given orally at a dose of 10 mg/kg/day. Canagliflozin attenuates inflammation in AA-induced colitis, evidenced by significant and dose-dependently downregulation of p38 MAPK, NF-κB-p65, IKK, IRF3, and NADPH-oxidase as well as colonic levels of IL-6 and IL-1ß and MPO enzymatic activity. Canagliflozin mitigates colonic oxidative stress by decreasing MDA content and restoring SOD enzymatic activities and GSH levels mediated by co-activating of Nrf2, PPARγ, and SIRT1 pathways. Moreover, an in-silico study confirmed that canagliflozin was specific to all target proteins in this study. Canagliflozin's binding affinity with its target proteins indicates and confirms its effectiveness in regulating these pathways. Also, network pharmacology analysis supported that canagliflozin potently attenuates UC via a multi-target and multi-pathway approach.

Perindopril Dampens Cd-induced Nephrotoxicity by Suppressing Inflammatory Burden, Ang II/Ang 1-7, and Apoptosis Signaling Pathways.

Cadmium (Cd) is one of the most abundant toxic heavy metals, and its exposure is linked to serious kidney intoxication, a major health problem. Evidence reported that inflammatory damage is a key factor in Cd renal intoxication. Perindopril (PER) is an angiotensin-converting enzyme inhibitor approved for treating hypertension and other cardiovascular problems. Significantly, RAS activation results in inflammatory damage. Our study aimed to examine the renoprotective effects of PER in Cd-induced nephrotoxicity, the impact of inflammation, and the underlying molecular mechanisms. PER was given at a dose of 1 mg/kg per day. Cd was injected at a dose of 1.2 mg/kg, as a single dose. Treatment with PER led to a significant decrease in serum levels of urea, creatinine, uric acid, and urine albumin/creatinine ratio. PER effectively mitigated inflammation by decreasing MPO, NO, IL-1ß, IL-6, and INF-γ levels mediated by downregulating NF-κB expression and suppressing JAK-1 and STAT3 phosphorylation. PER modulates Ang II/Ang 1-7 axis in Cd-intoxicated rats by decreasing Ang II expression and increasing Ang-(1-7) expression. PER inhibits Cd-induced apoptosis by lowering Bax, cytochrome c, and cleaved caspase 3 expressions while increasing Bcl-2 expression. In conclusion, PER dampens Cd-induced kidney intoxication by modulating Ang II/Ang 1-7 axis, suppressing NF-κB, JAK-1/STAT3, and apoptosis signals.

Prognostic and Clinical Implications of UNC13C expression in Hepatocellular Carcinoma Patients.

Aberrant expression of UNC13C (Unc-13 Homolog C) has been observed during the progression of oral squamous cell carcinoma. However, the expression pattern and clinical relevance of UNC13C in Hepatocellular carcinoma (HCC) remain to be elucidated. The purpose of this study is to examine UNC13C expression in HCC and explore its role in clinicopathological factor or prognosis in HCC. Two hundred and sixty-five patients diagnosed with HCC were included in the present study. The expression of UNC13C in HCC tissues was analyzed by immunohistochemistry analysis. The relationship between UNC13C protein and clinicopathological characteristics in HCC was investigated. Moreover, the high expression of UNC13C was significantly correlated with T stage, AJCC stage and overall survival rates. Cox regression analysis identified UNC13C as an independent prognostic indicator for HCC patients. UNC13C might be a prognostic biomarker and therapeutic target in HCC. Further studies with larger sample sets are needed to understand the clinical implications of UNC13C in hepatocellular carcinoma.

The function of long non-coding RNA SNHG11 and its working mechanism in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) seriously affects woman's health. The present work is to study the working mechanism of lncRNA SNHG11 in TNBC. The expressions of SNHG11, microRNA (miR)- 7-5p, specificity protein 2 (SP2) and mucin 1 (MUC-1) in TNBC tissues and cells were detected. SNHG11, miR-7-5p and SP2 expressions were then evaluated for TNBC cell malignant behaviors. The relationships among SNHG11, miR-7-5p and SP2 were predicted and verified. Finally, the binding of the transcription factor SP2 to MUC-1 promoter was detected. Abnormally elevated SNHG11, SP2 and MUC-1 expressions were observed in cultured TNBC cells and tumor tissues. SNHG11 knockdown in TNBC cells. Silencing SP2 weakened the promoting effect of SNHG11 on TNBC progression. SNHG11 negatively regulated miR-7-5p expression and positively regulated SP2 expression. SP2 bound to the P2 site of MUC-1 promoter, and SP2 knockdown suppressed MUC-1 expression. It was demonstrated that lncRNA SNHG11 promoted TNBC cell malignant behaviors to facilitate TNBC progression. The study is first of its kinds to unravel the potential of lncRNA SNHG11 in relation to TNBC.

Apocynin abrogates methotrexate-induced nephrotoxicity: role of TLR4/NF-κB-p65/p38-MAPK, IL-6/STAT-3, PPAR-γ, and SIRT1/FOXO3 signaling pathways.

The present study was designed to evaluate the potential renoprotective impacts of apocynin (APC) against nephrotoxicity induced by methotrexate (MTX) administration. To fulfill this aim, rats were allocated into four groups: control; APC (100 mg/kg/day; orally); MTX (20 mg/kg; single intraperitoneal dose at the end of the 5th day of the experiment); and APC +MTX (APC was given orally for 5 days before and 5 days after induction of renal toxicity by MTX). On the 11th day, samples were collected to estimate kidney function biomarkers, oxidative stress, pro-inflammatory cytokines, and other molecular targets. Compared to the MTX control group, treatment with APC significantly decreased urea, creatinine, and KIM-1 levels and improved kidney histological alterations. Furthermore, APC restored oxidant/antioxidant balance, as evidenced by a remarkable alleviation of MDA, GSH, SOD, and MPO levels. Additionally, the iNOS, NO, p-NF-κB-p65, Ace-NF-κB-p65, TLR4, p-p38-MAPK, p-JAK1, and p-STAT-3 expressions were reduced, while the IκBα, PPAR-γ, SIRT1, and FOXO3 expressions were significantly increased. In NRK-52E cells, MTX-induced cytotoxicity was protected by APC in a concentration-dependent manner. In addition, increased expression of p-STAT-3 and p-JAK1/2 levels were reduced in MTX-treated NRK-52E cells by APC. The in vitro experiments revealed that APC-protected MTX-mediated renal tubular epithelial cells were damaged by inhibiting the JAK/STAT3 pathway. Besides, our in vivo and in vitro results were confirmed by predicting computational pharmacology results using molecular docking and network pharmacology analysis. In conclusion, our findings proved that APC could be a good candidate for MTX-induced renal damage due to its strong antioxidative and anti-inflammatory bioactivities.

Lansoprazole attenuates cyclophosphamide-induced cardiopulmonary injury by modulating redox-sensitive pathways and inflammation.

Cyclophosphamide (CPA) is a classical chemotherapeutic drug widely used as an anticancer and immunosuppressive agent. However, it is frequently associated with significant toxicities to the normal cells of different organs, including the lung and heart. Lansoprazole (LPZ), a proton pump inhibitor (PPI), possesses antioxidant and anti-inflammatory properties. The current study investigated how LPZ protects against CPA-induced cardiac and pulmonary damage, focusing on PPARγ, Nrf2, HO-1, cytoglobin, PI3K/AKT, and NF-κB signaling. Animals were randomly assigned into four groups: normal control group (received vehicle), LPZ only group (Rats received LPZ at a dose of 50 mg/kg/day P.O. for 10 days), CPA group (CPA was administered (200 mg/kg) as a single i.p. injection on the 7th day), and cotreatment group (LPZ plus CPA). Histopathological and biochemical analyses were conducted. Our results revealed that LPZ treatment revoked CPA-induced heart and lung histopathological alterations. Also, LPZ potently mitigated CPA-induced cardiac and pulmonary oxidative stress through the activation of PPARγ, Nrf2/HO-1, cytoglobin, and PI3K/AKT signaling pathways. Also, LPZ effectively suppressed inflammatory response as evidenced by down-regulating the inflammatory strategic controller NF-κB, MPO, and pro-inflammatory cytokines. The present findings could provide a mechanistic basis for understanding LPZ's role in CPA-induced cardiopulmonary injury through the alleviation of oxidative stress and inflammatory burden.

Protective role of naftidrofuryl against methotrexate-induced testicular damage via the amelioration of the p53/miRNA-29a/CDC42 apoptotic pathway, inflammation, and oxidative stress.

This study aimed to assess the possible protective effects of naftidrofuryl (Naf) against methotrexate (MTX)-induced testicular toxicity in rats. Male rats were randomly distributed into four groups: control, Naf, MTX, and MTX+Naf groups. MTX administration induced oxidative stress, inflammation, and apoptosis in the testicular tissue, while pretreatment with Naf attenuated these pathways. Naf pretreatment significantly decreased malondialdehyde and interleukin-6 contents, microRNA-29a (miRNA-29a) expression level, and nuclear factor kappa B and p53 immunostaining in the testicular tissues compared to the MTX group. Conversely, it significantly increased Johnsen's score, serum testosterone level, serum total antioxidant capacity, testicular superoxide dismutase activity, testicular catalase activity, and testicular cell division cycle 42 (CDC42) expression compared to the MTX group. In conclusion, Naf exerted a significant protective effect against MTX-induced testicular toxicity via antioxidant and anti-inflammatory mechanisms and modulating the p53/miRNA-29a/CDC42 apoptotic pathway.

Mutations in FGFR1 were associated with growth traits in sheep (Ovis aries).

For its role in the mediation of myoblast proliferation, fibroblast growth factor receptor 1 (FGFR1) was considered a functional candidate gene for growth performance in Tibetan sheep. Via the polymerase chain reaction-restriction fragment length polymorphism (PCR-PFLP) approach, four single nucleotide polymorphisms (SNPs) including g.14752C > T (intron 1), g.45361A > G (intron 7), g.49400A > G (3'UTR region) and g.49587A > T (3'UTR region), were identified in 422 ewes. The association analysis demonstrated that individuals carrying the AA genotype of g.49400A > G had significantly greater withers height, length than those with GG genotype (p < 0.05). Individuals with genotype AA of g.49587A > T had significantly greater weight and chest circumference than those with genotype TT (p < 0.01). Additionally, the individuals with Hap1/1 diplotypes (CAAA-CAAA) were highly significantly associated with weight and chest circumference than Hap1/2 diplotypes (CAAA-CAAT) (p < 0.05). The quantitative real-time polymerase chain reaction (qPCR) analysis revealed that the FGFR1 was detectable expressed in muscle tissues within three different age stage. Remarkably higher mRNA expression was detected at fetal lamb stage as compared with adult ewes (p < 0.01). The outcome of this research confirmed that both g.49400A > G and g.49587A > T of FGFR1 were involved in growth-related traits, which may be considered to be genetic markers for improving the growth traits of Tibetan sheep.

Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1-7 Signals.

Cadmium (Cd) is a serious pollutant in the environment. Candesartan is an angiotensin II (Ang II) receptor antagonist with promising diverse health benefits. The current study is planned to investigate the hepatorenal protective effects of candesartan against Cd-induced hepatic and renal intoxication. Our results demonstrated that candesartan effectively attenuated Cd-induced hepatorenal intoxication, as evidenced by improving hepatic and renal function biomarkers. Besides, candesartan reversed hepatic and renal histopathological abrasions induced by Cd toxicity. Candesartan antioxidant effect was mediated by Nrf2 activation. Also, candesartan suppressed hepatorenal inflammation by modulating NF-κB/IκB. Moreover, candesartan attenuated Cd hepatorenal apoptosis by upregulating Bcl-2 and downregulating Bax and Cyt-C proteins. Interestingly, these effects are suggested to be an outcome of modulating of Ang II/Ang 1-7 signal. Overall, our findings revealed that candesartan could attenuate Cd-induced hepatorenal intoxication through modulation of Nrf2, NF-κB/IκB, Bax/Bcl-2/Cyt-c, and Ang II/Ang 1-7 signaling pathways.

The involvement of Nrf2/HO-1/cytoglobin and Ang-II/NF-κB signals in the cardioprotective mechanism of lansoprazole against cisplatin-induced heart injury.

Cardiac toxicity is a serious adverse effect of cisplatin (CIS). Lansoprazole (LPZ) is a proton pump inhibitor with promising cardioprotective effects. Our study planned to examine the cardioprotective effect of LPZ against CIS-induced cardiac injury. To achieve this goal, 32 male rats were randomly allocated into four groups. CIS, 7 mg/kg, was injected i.p. on the fifth day of the experiment. LPZ was administered via oral gavage at a dose of 50 mg/kg. The present study revealed that CIS injection induced a remarkable cardiac injury evidenced by an increase in serum ALP, AST, CK-MB, LDH, and troponin-I levels. The cardiac oxidative damage was also observed after CIS injection and mediated by downregulation of GSH, SOD, GST, Nrf2, HO-1, PPAR-γ, and cytoglobin levels associated with the upregulation of MDA content. Besides, CIS injection caused a significant inflammatory reaction mediated by alteration of cardiac NF-κB, STAT-3, p-STAT-3, and IκB expressions. Additionally, cardiac Ang-II expression was significantly increased in CIS control rats, while Ang 1-7 expression was significantly reduced relative to normal rats. In contrast, LPZ administration remarkably ameliorated these changes in the heart of CIS-intoxicated rats. Collectively, LPZ potently attenuated cardiac toxicity induced by CIS via regulation of Nrf2/HO-1, PPAR-γ, cytoglobin, IκB/NF-κB/STAT-3, and Ang-II/Ang 1-7 signals.

Preclinical study for the ameliorating effect of l-ascorbic acid for the oxidative stress of chronic administration of organic nitrates on myocardial tissue in high sucrose/fat rat model.

Background: The therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. Hemoglobin tightly binds to NO forming methemoglobin altering the erythrocytic antioxidant defense system. Aim: The principal objective of our research is to show the ameliorating effect of l-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs used in cardiovascular diseases such as oxidative stresses and tolerance. Method: We studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered different concentrations of Isosorbide-5-mononitrate (ISMN) 0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg. Afterwards, we evaluated the role of l-ascorbic acid against these biochemical changes in cardiac tissues. Results: Chronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of the pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in the myocardium muscles in a dose-dependent manner. Meanwhile, such exposure caused a decline in the enzymatic effect of SOD, GSH and CAT accompanied by a decrease in the level of mitochondrial oxidative stress marker (nrf2) in the myocardium muscles and a decrease in the serum iron and total iron-binding capacity (TIBC) in a dose-dependent manner. Concomitant treatment with l-ascorbic acid significantly diminished these changes for all examined parameters. Conclusion: Chronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to the generation of reactive oxygen species. Using l-ascorbic acid can effectively ameliorate such intoxication to overcome nitrate tolerance.

Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators.

In the therapy of cisplatin (CP), nephrotoxicity is a main limiting issue that associated with oxidative stress and apoptosis. According to many studies, the antioxidant and anti-inflammatory properties of Ajwa dates are very strong, due to the unique phytochemical profile. Here, we investigated the possible mitigative effects of Ajwa dates fruits extract (ADFE) vs CP-induced nephrotoxicity in rats, in addition to phytochemical profiling of its components via LC-MS/MS. Six groups were formed from forty-two male rats. G1: control, G2: ADFE 0.25 g/kg, G3: ADFE 0.5 g/kg (for 21 days), G4: CP -intoxicated group (single i.p. dose of 7.0 mg/kg b.w) on day 16th, G5: ADFE 0.25 + CP, G6: ADFE 0.5 + CP. LC-MS/MS analysis revealed the tentative identification of 17 compounds of different chemical nature, including organic/phenolic acids, and flavonoids and their sulphated/glycosides derivatives. ADFE has considerable antioxidant potential (DPPH with IC50 326.65 µg/ml and FRAP= 20.91 mM FeSO4/g extract) and total phenolic content (TPC = 35.44 mg/GAE/g extract). It (especially at dose 0.5 g/kg b.w) significantly modulated the toxicity of CP via enhancing food intake and hematobiochemical indices (renal functions, anemia, and leucopenia), increasing the renal antioxidant status (GSH, SOD, and CAT), decreasing the production of oxidative stress and inflammatory markers (MDA, NO, H2O2, MPO, MCP-1, TNF-α and IL-6), augmenting mRNA expression of Nrf2, and modulating NOX4 mRNA expression. The existence of bioactive compounds in ADFE may be responsible for their prophylactic properties, demonstrating natural usefulness in the treatment of oxidative stress, hypochromic anemia, immunodeficiency, and inflammatory complications, all of which are chemotherapy side effects.

The Adverse Reactions of Pfizer BioNTech COVID-19 Vaccine Booster Dose are Mild and Similar to the Second Dose Responses: A Retrospective Cross-Sectional Study.

Background: Like other vaccines, Pfizer BioNTech's COVID-19 vaccine efficacy against SARS-CoV-2 virus infections begins to decline within a few months after the 2nd dose. On August 12, 2021, the FDA allowed additional Pfizer BioNTch's COVID-19 vaccine dose (3rd or booster dose) for individuals with weakened immunity. This study aimed to evaluate the short-term adverse reactions (ADRs) of the 2nd and the 3rd doses of the Pfizer BioNTech COVID-19 vaccine. Methods: Information for this study was collected by Google Form questionnaire (online survey). The results included responses from 442 people, the majority from Saudi Arabia. Results: The most common local ADRs following the 3rd dose were injection site pain, injection site hypersensitivity, and axillary lymph node swelling. The most common systemic ADRs were fatigue, muscle pain, bone pain, headache, and fever less than 38ºC. Less common systemic ADRs were shivering, fever more than 38ºC, nasal congestion and rhinorrhea, arrhythmia, cough, abdominal pain, chest tightness, nausea, diarrhea, vomiting, and tachypnea. Rare systemic ADRs were constipation, dizziness and vertigo, lack of concentration, sore throat, excessive hair loss, dysmenorrhea and heavy menstruation, and Bell's palsy. Severe allergic reactions were reported by 2.6% of participants after the 2nd dose, compared with none after the 3rd dose. Nasal congestion and runny nose are more frequent after the 3rd dose. The ADRs of the 2nd and 3rd doses were significantly more prevalent in females. 12% of participants reported ADRs lasting more than one week after the 3rd dose compared to 5% after the 2nd dose. People ≤ 60 years were more affected by the vaccine ADRs. Conclusion: Most of the ADRs reported after the 3rd vaccine dose were consistent with the Pfizer vaccine information sheet and similar to the 2nd dose ADRs.

Accelerating Effect of Cucurbita pepo L. Fruit Extract on Excisional Wound Healing in Depressed Rats Is Mediated through Its Anti-Inflammatory and Antioxidant Effects.

Background: Chronic stress can hinder wound healing as it suppresses both the cellular and innate immune responses. Objectives: The study aims to assess the effectiveness of the administration of topical and oral Cucurbita pepo L. (CP) ethanolic extract in prompting excisional wound healing in rats exposed to chronic stress, and to explain how it works. Materials and methods: Fifty albino rats assigned to five groups (n = 10) were utilized in this study. The chronic unpredictable mild stress (CUMS) model was used for 4 weeks to induce depressive-like behavior in rats, and a forced swim test and corticosterone were assessed to confirm its occurrence. During the experiment, an excisional wound was induced in the rats and followed. Oxidant/antioxidants status and pro-inflammatory cytokines levels were measured in the serum and wound area. Gene expression of pro-inflammatory cytokines was also assessed using RT-PCR. Wound closure histopathological changes and immunohistochemical expression of CD68, CD3, and CD4 at the wound area was assessed. Results: The administration of CP, both orally and topically, significantly reduced (p < 0.001) the depressive-like behavior and corticosterone and pro-inflammatory cytokines levels, while it significantly up-regulated the antioxidant activity compared to the untreated and topically CP-treated groups. Both topically CP-treated and combined CP-treated groups showed complete re-epithelialization, reduced inflammatory cells infiltration, collagen fibers deposition, and significantly increased CD3, CD4 positive T cells count, with a superior effect in the combined CP-treated groups. Conclusion: Cucurbita pepo L., administrated both topically and orally, can enhance the wound healing process in rats with depressive-like behavior mostly through the antioxidant, anti-inflammatory, and antidepressant activities observed in this study.