Pulmonary damage induction upon Acrylic amide exposure via activating miRNA-223-3p and miRNA-325-3p inflammasome/pyroptosis and fibrosis signaling pathway: New mechanistic approaches of A green-synthesized extract.

Exposure to acrylic amide (AD) has garnered worldwide attention due to its potential adverse health effects, prompting calls from the World Health Organization for intensified research into associated risks. Despite this, the relationship between oral acrylic amide (acrylamide) (AD) exposure and pulmonary dysfunction remains poorly understood. Our study aimed to investigate the correlation between internal oral exposure to AD and the decline in lung function, while exploring potential mediating factors such as tissue inflammation, oxidative stress, pyroptosis, and apoptosis. Additionally, we aimed to evaluate the potential protective effect of zinc oxide nanoparticles green-synthesized moringa extract (ZNO-MONPs) (10mg/kg b.wt) against ACR toxicity and conducted comprehensive miRNA expression profiling to uncover novel targets and mechanisms of AD toxicity (miRNA 223-3P and miRNA 325-3P). Furthermore, we employed computational techniques to predict the interactions between acrylic amide and/or MO-extract components and tissue proteins. Using a rat model, we exposed animals to oral acrylamide (20mg/kg b.wt for 2 months). Our findings revealed that AD significantly downregulated the expression of miRNA 223-3P and miRNA 325-3P, targeting NLRP-3 & GSDMD, respectively, indicating the induction of pyroptosis in pulmonary tissue via an inflammasome activating pathway. Moreover, AD exposure resulted in lipid peroxidative damage and reduced levels of GPX, CAT, GSH, and GSSG. Notably, AD exposure upregulated apoptotic, pyroptotic, and inflammatory genes, accompanied by histopathological damage in lung tissue. Immunohistochemical and immunofluorescence techniques detected elevated levels of indicative harmful proteins including vimentin and 4HNE. Conversely, concurrent administration of ZNO-MONPs with AD significantly elevated the expression of miRNA 223-3P and miRNA 325-3P, protecting against oxidative stress, apoptosis, pyroptosis, inflammation, and fibrosis in rat lungs. In conclusion, our study highlights the efficacy of ZNO-MONPs NPs in protecting pulmonary tissue against the detrimental impacts of foodborne toxin AD.

Exploring the link between pyrethroids exposure and dopaminergic degeneration through morphometric, immunofluorescence, and in-silico approaches: the therapeutic role of chitosan-encapsulated curcumin nanoparticles.

Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson's disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE's toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses. Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment.

Understanding fenpropathrin-induced pulmonary toxicity: What apoptosis, inflammation, and pyreptosis reveal analyzing cross-links at the molecular, immunohistochemical, and immunofluorescent levels.

Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.

Monitoring SARS-CoV-2 infection in different animal species and human in Egypt during 2020-2021.

Coronaviruses cause respiratory and intestinal infections in animals and humans. By the end of 2019, there was an epidemic of novel coronavirus (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronaviruses have a highly mutable genome that makes them genetically and phenotypically modifiable with a potential transmission to new host species. Based on current sequence databases, all human coronaviruses have animal origins, so animals have important roles in virus spillover to humans. The aim of this study is to investigate the role of different animal species in the epidemiology of SARS-CoV-2 in Egypt. A pan-coronaviruses RT-PCR has been used for detection of possible coronaviruses infection in different species including bats, humans, birds, and dogs in Egypt during the period of November 2020 till June 2021. Ninety-two samples (46 from Rousettus aegyptiacus bats, 10 from human, 26 from wild birds, and 10 from dogs) were screened for SARS-CoV-2. Our results revealed that only human samples were SARS-CoV-2 positive for SARS-CoV-2 while all other animal and bird samples were negative. To recapitulate, our results suggest that animals may not actively transmit SARS-CoV-2 among people in Egypt during the current COVID-19 pandemic. Further structural surveillance and follow up screening for SARS-CoV-2 among domestic and wild animal populations in Egypt is crucially needed.

Commiphora myrrha Resin Alcoholic Extract Ameliorates High Fat Diet Induced Obesity via Regulation of UCP1 and Adiponectin Proteins Expression in Rats.

This study was performed to evaluate anti-obesity potential of Commiphora myrrha resin ethanolic extract (CME) with the respect to expression of leptin, adiponectin and uncoupling protein 1 (UCP1) in rats. Control rats fed basal diet. Second group fed basal diet and administered CME (500 mg/kg bw) orally for 14 weeks. Third group fed high fat diet (HFD) for 14 weeks. Fourth group fed HFD and administered CME as second group. Fifth group fed HFD for 8 weeks then fed basal diet and administered CME as third group for another 6 weeks. Phytochemical analysis of CME identified the presence of germacrene B, 1,4-benzoquinone, benzofuran, hexadecanoic acid, 9,12-octadecnoic acid methyl ester, reynosin, 11, 14-eicosadienoic acid, isochiapin B, bisabolene epixod, elemene and 1-heptatriacotanol. High fat diet significantly increased food intake, body weight, hyperglycemia, serum levels of total cholesterol, triacylglycerol, low density lipoprotein and ketone bodies, AST and AST activities, concentration of malondialdehyde and histopathological changes in hepatic tissues. However, it significantly reduced serum levels of high density lipoprotein, leptin and adiponectin, activity of hepatic glutathione reductase (GR) and brown adipose tissue UCP1 protein expression. In contrast, CME ameliorated HFD increased body weight, hyperglycemia, dyslipidemia, ketonemia, hepatic tissues lipid peroxidation, restored hepatic tissue architecture and enhanced protein expression of leptin, adiponectin and UCP1 and activity of hepatic GR. This study indicated that CME ameliorated HFD induced hyperglycemia and dyslipidemia through normalization of HFD reduced leptin, adiponectin and UCP1 proteins production and antioxidant activity.