Production, optimization, and purification of alkaline thermotolerant protease from newly isolated Phalaris minor seeds.

The present work aims to purify and perform a preliminary analysis on a thermostable serine alkaline protease from a recently identified P. minor. The enzyme was purified 2.7-fold with a 12.4 % recovery using Sephadex G-100 chromatography, DEAE-cellulose, and ammonium sulphate precipitation. The isolated enzyme has a specific activity of 473 U/mg. The purified protease had a molecular mass of 29 kDa, and just one band was seen, which matched the band obtained using SDS-PAGE. High thermostability was demonstrated by the enzymes, which had half-lives of 31.79 and 6.0 min (a 5.3-fold improvement), enthalpies of denaturation (ΔH°) of 119.53 and 119.35 KJ mol-1, entropies of denaturation (ΔS°) of 32.96 and 41.11 J/mol·K, and free energies of denaturation (ΔG°) of 108.87 and 105.58 KJ mol-1 for the protease enzyme. Studies on the folding and stability of alkaline proteases are important since their use in biotechnology requires that they operate in settings of extreme pH and temperature. According to the kinetic and thermodynamic properties, the protease produced by P. minor is superior to that produced by other sources and previously described plants, and it might find utility in a variety of industrial fields.

Rheotaxis of sperm in fertile and infertile men.

Sperm rheotaxis refers to the ability of sperm cells to align their swimming direction with or against fluid flow. Positive rheotaxis (PR) is the tendency of sperm cells to swim against the flow. Herein, we describe sperm rheotaxis in fertile and infertile males, using a microfluidic platform and focus on rheotaxis as a potential marker of male fertility. A previously reported computer-assisted sperm analysis (CASA) plugin for Image-J was used to detect and analyze the motion of human sperm cells in microfluidic environments. The fabricated microchannels mimic the female reproductive tracts and use an image-processing program to monitor sperm swimming behavior in semen samples from fertile and infertile men. We have constructed an image-processing pipeline. The image-processing pipeline incorporated strengthens object detection and particle tracking to adapt to sperm that are out of focus while swimming on the same track. PR% was defined as the number of PR sperm cells over the number of motile sperm cells. The results showed that the percentage of PR correlates with fertility, wherein the fertile male specimens showed a higher PR% than the other groups (P < 0.05). There is no difference in progressive motility between the control group (fertile men with normal sperm analysis) and group 1 (G1; infertile men with normal sperm analysis). However, PR% was lower (P < 0.05) in the G1 group (13.5 ± 0.4%) compared to the control group (40.3 ± 3.3%) and group 2 (G2; infertile with reduced sperm motility) (15.3 ± 4.6%). Thus, PR% may be used as a novel parameter to explain infertility even in situations where basic sperm analysis following the World Health Organization (WHO) guidelines is unable to do so. We propose to use PR% as a novel parameter for sperm analysis and as a method of sperm selection in assisted reproductive technology.

Silver Nanoparticles Enhance Oxidative Stress, Inflammation, and Apoptosis in Liver and Kidney Tissues: Potential Protective Role of Thymoquinone.

Silver nanoparticles (AgNPs) are the most common nanomaterials in consumer products. Therefore, it has been crucial to control AgNPs toxicological effects to improve their safety and increase the outcome of their applications. This work investigated the possible protective effect of thymoquinone (TQ) against AgNPs-induced hepatic and renal cytotoxicity in rats. Serum markers of liver and kidney functions as well as liver and kidney oxidative stress status, pro-inflammatory cytokines, apoptosis markers, and histopathology were assessed. TQ reversed AgNPs-induced elevation in serum liver and kidney function markers, including aspartate transaminase, alanine transaminase, urea, and creatinine. Moreover, TQ co-administration with AgNPs alleviates hepatic and renal oxidative insults by decreasing MDA and NO levels with a significant increase in the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase) compared to AgNPs-treated rats. Besides, TQ upregulated hepatic and renal Nrf2 gene expression in AgNPs-intoxicated rats. Furthermore, TQ co-administration decreased the hepatic and renal pro-inflammatory mediators represented by IL-1ß, TNF-α, TGF-ß, and NF-κB levels. Besides, TQ co-administration decreased apoptotic protein (Bax) levels and increased the anti-apoptotic protein (Bcl-2) levels. These findings were confirmed by the histopathological examination of hepatic and renal tissues. Our data affirmed the protective effect of TQ against AgNPs cytotoxicity and proposed a possible mechanism of TQ antioxidant, anti-inflammatory, and anti-apoptotic effects. Consequently, we could conclude that using TQ might control AgNPs toxicological effects, improve their safety, and increase the outcome of their applications.

Thymoquinone counteracts oxidative and inflammatory machinery in carrageenan-induced murine paw edema model.

Thymoquinone (TQ) is an active constituent in Nigella sativa (black cumin) and is extensively reported for its distinguished antioxidant and anti-inflammatory bioactivities. Despite the local protective response of acute inflammation, it contributes to the development of various disease conditions such as cell death, organ damage, or carcinogenesis. Hence, in this study, the effects of orally administered TQ (50 mg/kg and 100 mg/kg) for 14 days against edema development, oxidative stress, and inflammation were investigated in paw edema induced by carrageenan in mice. Indomethacin (10 mg/kg) was used as a reference drug. The results revealed that TQ reduced the paw edema volume in a time-dependent manner, attenuated acetic acid-provoked writhing movements, and reduced xylene-triggered ear edema. Hematological findings revealed marked normalization of altered counts of WBCs, and platelets. Furthermore, paw tissue levels of malondialdehyde and nitric oxide showed marked decreases together with increases in nuclear factor erythroid 2-related factor 2, glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase after TQ administration. Additionally, TQ decreased pro-inflammatory mediators, such as interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, C-reactive protein, myeloperoxidase, and nuclear factor kappa-B in the inflamed paw tissue. Moreover, appreciable decreases were recorded in cyclooxygenase-2 and its product prostaglandin E2 and the immune reaction of tumor necrosis factor-alpha in TQ-treated mice. Histopathological findings further validated the potential antiedematous, anti-inflammatory power of TQ in inflamed tissues. Conclusively, the results encourage the potent application of TQ to subside acute inflammatory events because of its striking antioxidant and anti-inflammatory properties in inflamed paw tissue.

Musculoskeletal disorders among sonographers in secondary care hospitals in the city of Al-Ahsa, Saudi Arabia.

BACKGROUND: Work-related musculoskeletal disorders (WMSDs) among sonographers have raised significant concerns in recent years. OBJECTIVES: This study aimed to estimate the prevalence of WMSDs and identify risk factors for WMSDs among sonographers. To date, there is little research on WMSDs among sonographers in Saudi Arabia. Therefore, this study aimed to contribute to the Saudi literature by filling this gap. METHODS: A cross-sectional study was conducted among sonographers (n = 98) working in four major governmental hospitals in the city of Al-Ahsa, Saudi Arabia. The participants completed a validated, self-administered questionnaire that focused on the analysis of musculoskeletal symptoms among sonographers. RESULTS: The mean age of the respondents was 35.5±9 years. The majority of the participants were female (71.4%), non-Saudi (51%), and working as technicians (49%). The prevalence rates of shoulder and neck disorders among the participants were 65.3% and 57.1%, respectively. Gender (female), job title (sonography technicians), and years of experience (seasoned sonographers) were identified as risk factors for WMSDs. CONCLUSIONS: Among the studied sonographers, WMSDs were a significant, common problem. Being female, being a sonography technician, and being a seasoned sonographer were identified as risk factors for these disorders. Preventive measures should be implemented to reduce the risk of WMSDs in this occupational setting.

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.

Chlorogenic acid abates male reproductive dysfunction in arsenic-exposed mice via attenuation of testicular oxido-inflammatory stress and apoptotic responses.

Arsenic, a major environmental pollutant of global concern, is well-known for its reproductive toxicity. In this study, the protective potential of chlorogenic acid (CGA), a caffeoylquinic acid isomer abundantly found in many plants, was investigated against sodium arsenite (NaAsO2)-induced testicular dysfunctions. Adult male Swiss mice were either administered NaAsO2 alone at 5 mg kg-1 or co-treated with CGA at 100 mg kg-1 or 200 mg kg-1 body weight for 4 weeks. Results showed that NaAsO2-treated mice exhibited marked declines in testes weight, sperm count, and viability accompanied by decreases in sexual hormonal levels. Moreover, NaAsO2 toxicity evoked exhaustion of antioxidant markers (SOD, CAT, GPx, GR, and GSH), down-regulation of Nrf2 (nuclear factor erythroid 2-related factor 2) gene expression level, and elevations in malondialdehyde. Further, elevations in inflammatory cytokines (IL-1, TNF-α, and IL-6) together with the up-regulation of pro-apoptotic biomarkers (Bax and caspase- 3) and down-regulation of anti-apoptotic Bcl-2 were observed in NaAsO2 intoxication. Immunohistochemical analysis of testis sections of NaAsO2-treated mice showed high caspase-3 expression. These findings were well supported with testicular histopathological examination. However, pretreatment of mice with CGA resulted in noteworthy improvements in testicular damage induced by arsenic in a dose-dependent manner possibly mediated by the Nrf2 signaling pathway. Conclusively, CGA counteracted arsenic-induced testicular injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties. Therefore, CGA could serve as a favorable intervention in the alleviation of arsenic-induced reproductive toxicity.

Microsporidia infection in patients with autoimmune diseases.

Purpose: Microsporidium is a spore-forming intracellular parasite that affects a wide range of hosts including humans. The tumor necrosis factor alpha (TNF-α) plays a key role in the immunity to infection with microsporidia. Recently, the TNF-α antagonists have proven successful in treating variable autoimmune diseases. In the current study, we aimed to investigate the impact of using TNF-α antagonists as a therapeutic regimen in the prevalence of infections with microsporidia. Materials and Methods: Diarrheal patients with distinct autoimmune diseases (n = 100) were assigned to the study. Patients taking anti-TNF-α medications (n = 60) were allocated to Group 1A and those undergoing non-TNF-α inhibitor treatment (n = 40) to Group 1B. Furthermore, patients with diarrhea without autoimmune disorders (n = 20) were allocated as controls. Stool specimens, 3 per patient, were collected and microscopically examined for microsporidia spores. A microsporidia-specific stool polymerase chain reaction was used to confirm the microscopic findings. Results: Microsporidia infection was identified in 28.3% (17/60), 10% (4/40), and in 5% (1/20) of patients in Group 1A, Group 1B, and in the control group, respectively. Overall, infection was significantly high in cases compared to the controls and in patients receiving TNF-α antagonists compared to patients not given TNF-α inhibitors (P < 0.05). Finally, infection was significantly higher in cases treated with TNF-α antagonists for ≥2 months compared to cases treated for <2 months of duration (P < 0.05). Conclusion: There was a significant increase in microsporidia infection in autoimmune disease patients undergoing treatment with TNF-α antagonists, and the duration of treatment is one of the risk factors. The study highlights the importance of microsporidia testing in immunocompromised patients, particularly those undergoing treatment with anti-TNF-α drugs and emphasises the need for awareness among clinicians regarding this opportunistic parasite.

Green Coffea arabica Extract Ameliorates Testicular Injury in High-Fat Diet/Streptozotocin-Induced Diabetes in Rats.

Diabetes mellitus (DM) is a chronic endocrine disease characterized by persistent hyperglycemia. Oxidative damage, inflammatory cytokines, and apoptotic cell death play a major role in the induction and progression of male testicular damage. Plant-derived phytochemicals such as green coffee (Coffea arabica) can possess antidiabetic effects with little toxicity. The current study is aimed at investigating the therapeutic roles of green coffee in diabetic testicular injury stimulated by high-fat diet/streptozotocin administration. Diabetes mellitus was induced by a high-fat diet and a single dose of streptozotocin (STZ) (35 mg kg-1) in male albino rats. Diabetic animals were orally given two different concentrations of green coffee (50 mg kg-1 and 100 mg kg-1) for 28 days. The levels of testosterone, luteinizing hormone, and follicle-stimulating hormone and parameters of oxidative stress, inflammation, and apoptosis were measured. mRNAs and protein levels were detected quantitatively by real-time PCR and ELISA, respectively. In the diabetic group, the levels of testosterone, luteinizing hormone, and follicle-stimulating hormone showed a significant reduction while they increased significantly after green coffee treatment. A significant increase of antioxidant markers glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase along with decreased levels of lipid peroxides and nitric oxide was observed after green coffee treatment in the diabetic group. Finally, the levels of IL-1ß, TNF-α, Bax, and caspase-3 were also decreased in both treated groups (metformin and green coffee) when compared to the diabetic group. We conclude that testicular oxidative impairment induced by a high-fat diet (HFD) and STZ can be reversed by green coffee. Administration of green coffee could represent a promising therapeutic agent which can help the treatment of type 2 DM-induced testicular dysfunction.

Nephroprotective effects of chlorogenic acid against sodium arsenite-induced oxidative stress, inflammation, and apoptosis.

BACKGROUND: Chronic exposure to arsenic (As) leads to serious renal disorders. Chlorogenic acid (CGA), a phenolic compound, has several well known physiological benefits, including antioxidant and anti-inflammatory activities. The present study investigated the potential renoprotective effects of CGA on sodium arsenite (NaAsO2 )-induced kidney damage in mice. The mice were randomly allocated into five groups to receive daily treatment with CGA (200 mg kg-1 ), NaAsO2 (5 mg kg-1 ), NaAsO2 + CGA (100 mg kg-1 ), NaAsO2 + CGA (200 mg kg-1 ), or a control for 28 days. RESULTS: In the NaAsO2 -treated group, NaAsO2 induced significant renal dysfunction, oxidative damage, inflammation, and apoptosis, as demonstrated by marked increases in urea and creatinine levels accompanied by a decrease in the kidney index. Considerable increases in malondialdehyde and nitric oxide levels and parallel decreases in various antioxidant markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione) levels were also detected in the renal tissues of NaAsO2 -treated mice. NaAsO2 exposure was associated with marked increases in renal inflammatory markers (interleukin-1ß and tumor necrosis factor-α) and apoptosis indicators including Bax and caspase-3 levels contaminant, with a marked decrease in Bcl-2, an anti-apoptotic protein, in the NaAsO2 -treated group compared with the control group. However, pretreatment with CGA substantially mitigated the renal injury and dysfunction associated with NaAsO2 exposure by reducing tissue inflammation and apoptosis and improving the antioxidant status. The CGA pretreatment also alleviated the NaAsO2 -induced histological alterations in renal tissues. CONCLUSION: Taken together, our results suggest the efficacy of CGA in alleviating As-mediated renal tissue damage. © 2020 Society of Chemical Industry.

Diallyl Disulfide Suppresses Inflammatory and Oxidative Machineries following Carrageenan Injection-Induced Paw Edema in Mice.

Diallyl disulfide (DADS) is the major organosulfur constituent in garlic, with a variety of pharmacological activities including antioxidant and anti-inflammatory. Here, we examined the potential antiedematous impact of DADS- versus carrageenan-mediated paw edema in mice. Carrageenan injection potentiated an inflammatory reaction as presented by the elevated serological C-reactive protein (CRP) levels and transcription of tumor necrosis factor-alpha (TNF-α, Tnfα), interleukin-1 beta (IL-1ß, Il1b), interleukin-2 (IL-2, Il2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2, Ptgs2), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1, Ccl1), nuclear factor kappa B (NF-κB), and myeloperoxidase (MPO) activity, while interleukin-10 (IL-10) was declined in the injured paw tissue. Additionally, carrageenan elevated lipid peroxidation in terms of malondialdehyde (MDA) and decreased glutathione content (GSH). Remarkably, DADS was found to inhibit the inflammatory signaling, suppressed the developed oxidative damage, and protected the histopathological alterations in the inflamed paw tissue in response to carrageenan injection. Our findings suggest that DADS could be used as an alternative therapy used to alleviate the pathophysiological changes associated with the genesis of paw edema through its potent anti-inflammatory and antioxidant impacts.

Senna alexandrina extract supplementation reverses hepatic oxidative, inflammatory, and apoptotic effects of cadmium chloride administration in rats.

Senna alexandrina is traditionally used for its antioxidant and anti-inflammatory properties, but little information is available concerning its potential protective effects against cadmium, which is a widespread environmental toxicant that causes hepatotoxicity. Here, we explored the effects of S. alexandrina extract (SAE) on cadmium chloride (CdCl2)-induced liver toxicity over 4 weeks in rats. Rats were allocated into four groups: control, SAE (100 mg/kg), CdCl2 (0.6 mg/kg), and SAE + CdCl2, respectively. Cadmium level in hepatic tissue, blood transaminases, and total bilirubin as indicators of liver function were assessed. Oxidative stress indices [malondialdehyde (MDA), nitrate/nitrite (NO), and glutathione (GSH)], antioxidant molecules [superoxide dismutase (SOD, catalase (CAT), glutathione-derived enzymes, and nuclear factor erythroid 2-related factor 2 (Nrf2)], pro-inflammatory mediators [interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α)], apoptosis proteins (Bcl-2, Bax, and caspase-3), and histological alterations to the liver were examined. SAE administration before CdCl2 exposure decreased cadmium deposition in liver tissue and the blood liver function indicators. SAE pre-treatment prevented oxidative, inflammatory, and apoptotic reactions and decreased histological alterations to the liver caused by CdCl2 exposure. SAE can be used as a promising protective agent against CdCl2-induced hepatotoxicity by increasing Nrf2 expression. Graphical abstract.

Anti-Inflammatory and Anti-Hyperuricemic Functions of Two Synthetic Hybrid Drugs with Dual Biological Active Sites.

The present study aimed to test the anti-inflammatory and xanthine oxidase inhibitory activities of two synthesized molecules and compare them to routinely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and the serum urate-lowering drug, allopurinol. The anti-inflammatory effects of the designed compounds (A and B) were evaluated in carrageenan (CAR)-induced paw edema in mice. The levels of nitric oxide and myeloperoxidase activity were measured in paw skin using biochemical methods. Additionally, prostaglandin E2 (PGE2), C-reactive protein (CRP), cyclooxygenase-2 (Cox-2), tumor necrosis factor-α (TNFα), interleukin (IL)-1ß, IL-2 and IL-10, and monocyte chemoattractant protein-1 (MCP1) were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of inflammation-related genes was confirmed by real-time qPCR. The expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) were estimated using immunohistochemistry, and xanthine oxidase inhibitory activity was evaluated using an in vitro assay. The results revealed that compounds A and B decreased inflammation, as was observed by a reduction in the elevation of all the tested markers. In addition, the tested compounds markedly decreased paw swelling, mobilization of inflammatory cells, iNOS-, and NF-κB-immunoreactive cells in a mouse model of paw edema. Interestingly, both compounds were potent xanthine oxidase inhibitors as well as Cox inhibitors with higher activity in favor of compound B providing potential dual acting series of anti-hyperuricemic and anti-inflammatory therapeutic agents.

Temporal trends in the incidence and demographics of cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade.

OBJECTIVES: To describe the trends in the incidence rates of 5 most common cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade.  Methods: The incidence rates of cancers (2001-2014), communicable diseases (2003-2016), and non-communicable diseases (1990-2017) were retrieved, classified, and analyzed retrospectively during November 2017, based on data available with the Ministry of Health and were analyzed at the Imam Abdulrahman Bin Faisal University in Dammam, Kingdom of Saudi Arabia. Results: Age-standardized incidence rate (ASR) (per 100,000 population) of breast cancer among women increased dramatically from 11.8 in 2001 to 22.7 in 2014, indicating a 92.4% increase over the decade. Colorectal cancer incidence was the highest among men, and its ASR per 100,000 population increased from 5.0 to 10.6 in men and from 5.0 to 8.2 in women. Among communicable diseases, incidences of hepatitis B, measles, chickenpox, and brucellosis decreased while dengue fever increased. An alarming increase was observed in the incidence rate of non-communicable diseases namely, obesity, diabetes, and hypertension. Conclusion: The incidence rate of non-communicable diseases increased over the decade and was associated with increased mortality and disability, reduced quality of life, and increased health-care costs, indicating an urgent need to establish prevention and control programs. The rising trend in the incidence of cancers may also become a health care issue in Saudi Arabia in the coming years.

Soursop fruit extract mitigates scopolamine-induced amnesia and oxidative stress via activating cholinergic and Nrf2/HO-1 pathways.

Current therapeutic interventions for memory loss are inadequate and are associated with numerous adverse effects. There is an urgent need for new alternative agents for the treatment of memory loss and related disorders. Here, we investigated the potential neuroprotective role of soursop fruit extract (SSFE) in scopolamine (SCO)-induced amnesia and oxidative damage in the hippocampus of rats. Thirty-five rats were randomly allocated into 5 groups: control, SCO, SSFE, SCO, SSFE+SCO and N-acetylcysteine (NAC) + SCO. SCO-treatment increased acetylcholine esterase activity and decreased hippocampal levels of acetylcholine, serotonin, dopamine, norepinephrine, and histamine. The level of ATP increased. SCO-treated rats showed a disturbance in oxidative status, which was evident through the increase in malondialdehyde, and nitrites/nitrates and a decrease in cellular antioxidant molecules including glutathione, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. A disturbance was also observed via downregulation of the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 defense pathways. SCO-treatment enhances a neuroinflammatory state, as indicated by the release of tumor necrosis factor- α and interleukin-1ß and increased inducible nitric oxide synthase and mRNA expression. SCO-treatment decreased the expression of the anti-apoptotic protein, B cell lymphoma 2 and increased the expression of the pro-apoptotic protein, Bcl-2 associated X protein, caspase-3 and cytochrome c in hippocampal neurons. SSFE pretreatment markedly ameliorated hippocampal changes. Our findings revealed that SSFE exerts its potential anti-amnestic effect mainly through the activation of the cholinergic system and Nrf2/HO-1 pathway.

Protective effects of Fragaria ananassa methanolic extract in a rat model of cadmium chloride-induced neurotoxicity.

Cadmium (Cd) is a common environmental toxicant that has harmful effects on plants, animals, and humans. The present study evaluated the protective effects of Fragaria ananassa methanolic extract (SME) on cadmium chloride (CdCl2)-induced neuronal toxicity in rats. Male albino rats were intraperitoneally (i.p) injected with CdCl2 (6.5 mg/kg) for 5 days with or without the SME (250 mg/kg). We measured the levels of Cd, lipid peroxidation (LPO), nitric oxide, glutathione (GSH), and oxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase, and glutathione reductase (GR) in the whole brain homogenate. Compared with the control group, the Cd-intoxicated group showed a marked increase in the brain levels of Cd, LPO, and nitric oxide and a decrease in the levels of GSH and all tested antioxidant enzymes. Compared with Cd-intoxicated rats, the rats pretreated with SME showed restoration of oxidative balance in the brain tissue. While the expression of brain SOD2, CAT, glutathione peroxidase 1, and GR was down-regulated in the Cd-treated group, the expression of these enzymes was up-regulated in rats pretreated with SME. In addition, administration of SME before CdCl2 increased the Bcl-2 expression, but significantly decreased the expression of Bax. Immunohistochemical analysis showed that compared with Cd-intoxicated rats, rats pretreated with SME showed a decrease in the protein expression of tumor necrosis factor α (TNF-α). Our findings indicate that SME protects the brain tissue from Cd-induced neuronal toxicity by improving the antioxidant system and increasing antiapoptotic and anti-inflammatory activities.

Neonatal maternal deprivation impairs localized de novo activity-induced protein translation at the synapse in the rat hippocampus.

Neonatal neuropsychiatric stress induces alterations in neurodevelopment that can lead to irreversible damage to neuronal physiology, and social, behavioral, and cognitive skills. In addition, this culminates to an elevated vulnerability to stress and anxiety later in life. Developmental deficits in hippocampal synaptic function and plasticity are among the primary contributors of detrimental alterations in brain function induced by early-life stress. However, the underlying molecular mechanisms are not completely understood. Localized protein translation, occurring at the synapse and triggered by neuronal activity, is critical for synapse function, maintenance, and plasticity. We used a rodent model of chronic maternal deprivation to characterize the effects of early-life neuropsychiatric stress on localized de novo protein translation at synaptic connections between neurons. Synaptoneurosomal preparations isolated biochemically from the hippocampi of rat pups that were subjected to maternal deprivation were deficient in depolarization-induced activity-dependent protein translation when compared with littermate controls. Conversely, basal unstimulated protein translation was not affected. Moreover, deficits in activity-driven synaptic protein translation were significantly correlated with a reduction in phosphorylated cell survival protein kinase protein B or Akt (p473 Ser and p308 Thr), but not phosphorylated extracellular signal-regulated kinase.

Molecular modelling insights into a physiologically favourable approach to eicosanoid biosynthesis inhibition through novel thieno[2,3-b]pyridine derivatives.

In this research, we exploited derivatives of thieno[2,3-b]pyridine as dual inhibitors of the key enzymes in eicosanoid biosynthesis, cyclooxygenase (COX, subtypes 1 and 2) and 5-lipoxygensase (5-LOX). Testing these compounds in a rat paw oedema model revealed potency higher than ibuprofen. The most active compounds 7a, 7b, 8b, and 8c were screened against COX-1/2 and 5-LOX enzymes. Compound 7a was the most powerful inhibitor of 5-LOX with IC50 = 0.15 µM, while its p-chloro analogue 7b was more active against COX-2 (IC50 = 7.5 µM). The less desirable target COX-1 was inhibited more potently by 8c with IC50 = 7.7 µM. Surflex docking programme predicted that the more stable anti- conformer of compound (7a) formed a favourable complex with the active site of 5-LOX but not COX-1. This is in contrast to the binding mode of 8c, which resembles the syn-conformer of series 7 and binds favourably to COX-1.

Ziziphus spina-christi fruit extract suppresses oxidative stress and p38 MAPK expression in ulcerative colitis in rats via induction of Nrf2 and HO-1 expression.

In this study, we aimed to evaluate the anti-inflammatory and protective effects of Ziziphus spina-christi fruit extract (ZFE) against acetic acid (AcOH)-induced colitis in rats. Before a single AcOH instillation, ZFE (100, 200, and 400 mg/kg/day) was administered for 5 days by oral gavage. Pretreatment with ZFE at different doses suppressed the spread of inflammation and inhibited mucosal damage; in addition, it reduced ulcer size and mitigated colitis markers. Administration of ZFE (400 mg/kg) resulted in a greater reduction of inflammatory colonic injury than that after reference drug, mesalazine (MLZ), administration. In addition, ZFE not only histopathologically ameliorated AcOH-induced colitis but also restored the balance between the oxidants and antioxidants. Furthermore, ZFE effectively modulated the mRNA expression of redox-sensitive transcription factors, such as nuclear factor (erythroid-derived 2)-like 2 and heme oxygenase-1, downregulated the expression of p38 mitogen-activated protein kinase, and upregulated that of vascular endothelial growth factor A and interleukin-1ß in AcOH-induced colitis in rats. In conclusion, our results suggested that ZFE could prevent the development of chronic experimental colitis in rats; therefore, it could be considered as an alternative and/or additive therapeutic approach for the management of inflammatory bowel disease.