Alchemilla vulgaris modulates isoproterenol-induced cardiotoxicity: interplay of oxidative stress, inflammation, autophagy, and apoptosis

Introduction: Isoproterenol (ISO) is regarded as an adrenergic non-selective β agonist. It regulates myocardial contractility and may cause damage to cardiac tissues. Alchemilla vulgaris (AV) is an herbal plant that has garnered considerable attention due to its anti-inflammatory and antioxidant bioactive components. The present investigation assessed the cardioprotective potential of AV towards ISO-induced myocardial damage.Methods: Four groups of mice were utilized: control that received saline, an ISO group (85 mg/kg, S.C.), ISO + AV100, and ISO + AV200 groups (mice received 100 or 200 mg/kg AV orally along with ISO).Results and discussion: ISO induced notable cardiac damage demonstrated by clear histopathological disruption and alterations in biochemical parameters. Intriguingly, AV treatment mitigates ISO provoked oxidative stress elucidated by a substantial enhancement in superoxide dismutase (SOD) and catalase (CAT) activities and reduced glutathione (GSH) content, as well as a considerable reduction in malondialdehyde (MDA) concentrations. In addition, notable downregulation of inflammatory biomarkers (IL-1β, TNF-α, and RAGE) and the NF-κB/p65 pathway was observed in ISO-exposed animals following AV treatment. Furthermore, the pro-apoptotic marker Bax was downregulated together with autophagy markers Beclin1 and LC3 with in ISO-exposed animals when treated with AV. Pre-treatment with AV significantly alleviated ISO-induced cardiac damage in a dose related manner, possibly due to their antioxidant and anti-inflammatory properties. Interestingly, when AV was given at higher doses, a remarkable restoration of ISO-induced cardiac injury was revealed

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Protective effect of cinnamon against acetaminophen-mediated cellular damage and apoptosis in renal tissue

International audienc

Enhanced hepatotoxicity after furan and cadmium co-exposure in rats: Involvement of oxidative stress and apoptotic cascades

Furan (FU) and Cadmium (Cd) are toxic agents, and persistent exposure may harm both human and animal health. Therefore, we explored the effects of FU and Cd on liver of the male rat. Male Wister rat groups are distributed randomly: control group (Cr-water): rats were given DI water; control oil group (Cr-oil): rats received corn oil; Furan group: rats received Furan (FU, 16 mg/kg) orally; Cd group: rats obtain cadmium (Cd, 2 mg/kg) orally; and FU+Cd group: rats given both FU +Cd. For 30 days, each therapy was administered once daily. Blood samples and hepatic tissues were obtained after all rats were euthanized. The outcomes showed that treatment with FU or Cd alone considerably caused liver damage, evidenced by serum increase of AST, ALT, ALP, triglycerides, and cholesterol as well as histological changes. Following FU or Cd exposure, there were significant reductions in CAT, GSH, and SOD contents, as well as increases in malondialdehyde along with upregulated expression of PCNA and TNF-α. In contrast, when FU and Cd were administered together potentiated each other and caused more cellular damage in liver tissue. This study found that the primary modulator for enhancing FU and Cd toxicity when administered together was thought to be oxidative stress pathways

Furan and cadmium combined treatment‐ potentiated renal damage: Role of oxidative damage

Furan (FU) is a common food contaminant and environmental pollutant. While Cadmium (Cd) is a prevalent environmental contaminant that poses a risk to the health of humans and animals. The goal of the current study was to assess the combined effects of FU and Cd on the kidney of male albino rats. Five groups of rats were designed: Cr-water, Cr-oil, FU (16 mg/kg b.w), Cd (2 mg/kg b.w), and FU+Cd, rats were co-treated with both FU and Cd. All treatments were given orally for 30 days. Renal function testing revealed severe biochemical changes in the rats, indicating substantial tissue injury. In addition, there was a notable rise in malondialdehyde (MDA) levels and a fall in reduced glutathione (GSH) concentration as well as the activity of superoxide dismutase (SOD) and catalase (CAT). Also, prominent histopathological alterations in renal tissues were noticed. Additionally, FU and/or Cd significantly up-regulated the expression profile of Kim-1, and inflammatory markers (TNF-α and iNOS). Meanwhile, Aqp1, and Aqp2 m-RNA genes expression were significantly downregulated along with significant upregulation of apoptotic proteins (PCNA). Intriguingly, the concurrent FU and Cd intoxication elicited additional extensive renal injury than their individual exposure

Furan and cadmium combined treatment‐ potentiated renal damage: Role of oxidative damage

Furan (FU) is a common food contaminant and environmental pollutant. While Cadmium (Cd) is a prevalent environmental contaminant that poses a risk to the health of humans and animals. The goal of the current study was to assess the combined effects of FU and Cd on the kidney of male albino rats. Five groups of rats were designed: Cr-water, Cr-oil, FU (16 mg/kg b.w), Cd (2 mg/kg b.w), and FU+Cd, rats were co-treated with both FU and Cd. All treatments were given orally for 30 days. Renal function testing revealed severe biochemical changes in the rats, indicating substantial tissue injury. In addition, there was a notable rise in malondialdehyde (MDA) levels and a fall in reduced glutathione (GSH) concentration as well as the activity of superoxide dismutase (SOD) and catalase (CAT). Also, prominent histopathological alterations in renal tissues were noticed. Additionally, FU and/or Cd significantly up-regulated the expression profile of Kim-1, and inflammatory markers (TNF-α and iNOS). Meanwhile, Aqp1, and Aqp2 m-RNA genes expression were significantly downregulated along with significant upregulation of apoptotic proteins (PCNA). Intriguingly, the concurrent FU and Cd intoxication elicited additional extensive renal injury than their individual exposure

Pyrrolidine dithiocarbamate ameliorates rotenone-induced Parkinson’s disease in rats

Pyrrolidine dithiocarbamate (PDTC), a low-molecular-weight thiol antioxidant, possesses neuroprotection; however, its possible modulatory effect in Parkinson’s disease (PD) has not been tested. Male Wistar rats were injected with rotenone to induce PD-like symptoms. Histopathological findings showed that striatal neurons were degenerated following rotenone administration, an effect that was accompanied by behavioral deficits. Furthermore, rotenone decreased striatal dopamine (DA) and glutamate and prominently increased serotonin, GABA, glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and myeloperoxidase (MPO) levels. Daily treatment with PDTC protected against rotenone induced changes at the microscopic level, decreased the extent of motor dysfunctions, and markedly increased DA and suppressed glutamate levels. It also reduced TBARS, GSH, and MPO. Whereas, rotenone neither affected striatal caspase-3 activity nor tumor necrosis factor-α level, PDTC treatment reduced the later. The current study reveals the effectiveness of PDTC against rotenone-induced PD via enhancement of DA, as well as antioxidant and anti-inflammatory properties

Enhanced hepatotoxicity after furan and cadmium co-exposure in rats: Involvement of oxidative stress and apoptotic cascades

Furan (FU) and Cadmium (Cd) are toxic agents, and persistent exposure may harm both human and animal health. Therefore, we explored the effects of FU and Cd on liver of the male rat. Male Wister rat groups are distributed randomly: control group (Cr-water): rats were given DI water; control oil group (Cr-oil): rats received corn oil; Furan group: rats received Furan (FU, 16 mg/kg) orally; Cd group: rats obtain cadmium (Cd, 2 mg/kg) orally; and FU+Cd group: rats given both FU +Cd. For 30 days, each therapy was administered once daily. Blood samples and hepatic tissues were obtained after all rats were euthanized. The outcomes showed that treatment with FU or Cd alone considerably caused liver damage, evidenced by serum increase of AST, ALT, ALP, triglycerides, and cholesterol as well as histological changes. Following FU or Cd exposure, there were significant reductions in CAT, GSH, and SOD contents, as well as increases in malondialdehyde along with upregulated expression of PCNA and TNF-α. In contrast, when FU and Cd were administered together potentiated each other and caused more cellular damage in liver tissue. This study found that the primary modulator for enhancing FU and Cd toxicity when administered together was thought to be oxidative stress pathways

Occurrence of Toxic Biogenic Amines in Various Types of Soft and Hard Cheeses and Their Control by <i>Bacillus polymyxa</i> D05-1

Egyptian cheeses are considered an important part of the Egyptian diet. This study aimed to examine 60 random samples of different types of commercial cheeses in Egypt, including soft cheeses (Domiati and Tallaga) and hard cheeses (Cheddar and Ras). The samples were subjected to chemical and microbial examination. Biogenic amines (BAs) are nitrogenous compounds found in a variety of foods; their presence is undesirable and related to spoilage, and can result in toxicological effects in humans. Thus, BAs were determined by using a high-performance liquid chromatography (HPLC) analysis. Moreover, the ability of Bacillus polymyxa D05-1 to reduce levels of experimentally added biogenic amines during the manufacturing of Tallaga cheese was investigated. The obtained results revealed variations in the chemical composition between the investigated samples. Furthermore, many cheese samples contained high levels of BAs, including histamine, tyramine and putrescine. Domiati cheese had the highest levels of BAs, followed by Tallaga and Cheddar, whereas Ras cheese had the lowest levels. The existence of yeasts, molds, coliforms and the high levels of BAs in cheese samples indicate the unsanitary conditions in which they were made and stored. Furthermore, addition of B. polymyxa D05-1 during Tallaga cheese manufacturing resulted in a reduction in BA levels