LC3A-mediated autophagy elicits PERK-eIF2α-ATF4 axis activation and mitochondrial dysfunction: Exposing vulnerability in aggresome-positive cancer cells.

The unfolded protein response pathways (UPR), autophagy, and compartmentalization of misfolded proteins into inclusion bodies are critical components of the protein quality control network. Among inclusion bodies, aggresomes are particularly intriguing due to their association with cellular survival, drug resistance, and aggresive cancer behavior. Aggresomes are molecular condensates formed when collapsed vimentin cages encircle misfolded proteins before final removal by autophagy. Yet significant gaps persist in the mechanisms governing aggresome formation and elimination in cancer cells. Understanding these mechanisms is crucial, especially considering the involvement of LC3A, a member of the MAP1LC3 family, which plays a unique role in autophagy regulation and has been reported to be epigenetically silenced in many cancers. Herein, we utilized the tetracycline-inducible expression of LC3A to investigate its role in choroid plexus carcinoma cells, which inherently exhibit the presence of aggresomes. Live cell imaging was employed to demonstrate the effect of LC3A expression on aggresome-positive cells, while SILAC-based proteomics identified LC3A-induced protein and pathway alterations. Our findings demonstrated that extended expression of LC3A is associated with cellular senescence. However, the obstruction of lysosomal degradation in this context has a deleterious effect on cellular viability. In response to LC3A-induced autophagy, we observed significant alterations in mitochondrial morphology, reflected by mitochondrial dysfunction and increased ROS production. Furthermore, LC3A expression elicited the activation of the PERK-eIF2α-ATF4 axis of the UPR, underscoring a significant change in the protein quality control network. In conclusion, our results elucidate that LC3A-mediated autophagy alters the protein quality control network, exposing a vulnerability in aggresome-positive cancer cells.

Mitigation of Hepatotoxicity via Boosting Antioxidants and Reducing Oxidative Stress and Inflammation in Carbendazim-Treated Rats Using Adiantum Capillus-Veneris L. Extract.

Exposure to food contaminants continues to be a substantial source of human health risks all over the world, particularly in developing countries. Carbendazim (CBZ) is a chemical fungicide used to control the spread of various fungi and other pathogens in the agriculture and veterinary sectors. The hazardous effects of CBZ on human health occur due to the accumulation of its residues in agricultural food products. In this study, the possible hepatoprotective effects of Adiantum capillus-veneris L. (ACVL) extract were evaluated in CBZ-treated rats. A GC-MS analysis revealed that ACVL extract contained several bioactive hydrocarbon components and fatty acids, and that the components exerted hepatic protection by mitigating oxidative stress via upregulating antioxidant agents and neutralizing nitrogen and oxygen free radicals. Moreover, ACVL extracts relieved hepatic inflammation via decreasing NO, NF-κB, and pro-inflammatory cytokines (TNF-a, IL-6) in the liver of CBZ-treated rats, both at protein and mRNA levels. In addition, the protective effect of ACVL has appeared in the histopathological figures and function markers in the livers of CBZ-treated rats. According to the present results, ACVL extract can protect the hepatic tissue and restore its functions to a control level in CBZ-treated rats; this effect may be attributed to its antioxidant and anti-inflammatory activities.

Egypt Genome: Towards an African new genomic era.

BACKGROUND: Studying the human genome is crucial to embrace precision medicine through tailoring treatment and prevention strategies to the unique genetic makeup and molecular information of individuals. After human genome project (1990-2003) generated the first full sequence of a human genome, there have been concerns towards Northern bias due to underrepresentation of other populations. Multiple countries have now established national genome projects aiming at the genomic knowledge that can be harnessed from their populations, which in turn can serve as a basis for their health care policies in the near future. AIM OF REVIEW: The intention is to introduce the recently established Egypt Genome (EG) to delineate the genomics and genetics of both the modern and Ancient Egyptian populations. Leveraging genomic medicine to improve precision medicine strategies while building a solid foundation for large-scale genomic research capacity is the fundamental focus of EG. KEY SCIENTIFIC CONCEPTS: EG generated genomic knowledge is predicted to enrich the existing human genome and to expand its diversity by studying the underrepresented African/Middle Eastern populations. The insightful impact of EG goes beyond Egypt and Africa as it fills the knowledge gaps in health and disease genomics towards improved and sustainable genomic-driven healthcare systems for better outcomes. Promoting the integration of genomics into clinical practice and spearheading the implementation of genomic-driven healthcare and precision medicine is therefore a key focus of EG. Mining into the wealth of Ancient Egyptian Genomics to delineate the genetic bridge between the contemporary and Ancient Egyptian populations is another excitingly unique area of EG to realize the global vision of human genome.

Control of carbendazim toxicity using banana peel powder in rats.

Carbendazim (CBZ) is a steady benzimidazole fungicide broadly exploited in cultivation for pre- and post-harvest treatment to dominate microorganisms infection on several plants. CBZ causes toxic effects in the different tissues of rat via influencing biochemical and hematological factors causing histopathological alterations in the liver and kidney of rats. Banana peel (BP) makes up about 38% of the whole banana weight, BP is usually disposed of as waste that is considered as an environmental problem. BP comprise bioactive a lot of compounds that can be exploited for their unique biological and pharmacological attributes. The current study was carried out to determine the protective effect of dried banana peels consumption against carbendazim toxicity in rats. The results indicated that banana peels had the ability to counteract the toxic effect of carbendazim on rats which was evident by the improvement in liver and kidney functions, lipid profile and histopathological examination.

Exposure assessment of heavy metal residues in some Egyptian fruits.

Heavy metals are considered a main public health hazards, they are known to accumulate in fruits, which are heavily consumed by humans because of their unique sweet taste and potential health benefits. Therefore, the aim of this study was to determine the possible contamination levels of cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb) and nickel (Ni) in some selected fruits obtained from four Egyptian governorates and to compare the contamination levels with those of the recommended permissible limits. Results revealed that Pb and Cd were absent in all fruit samples, while Cr was only detected in grapes obtained from Cairo and Fayoum governorates and exceeded the maximum permissible limit (0.10 mg kg-1). Nickel and Cu were detected in all fruit samples. Nickel was reduced more than copper after washing process of grapes especially in samples obtained from Alexandria and Giza governorates. After peeling process, Cu was extremely reduced in orange samples obtained from the following governorates in descending order Cairo, Alexandria, El-Fayoum and Giza. Estimated daily intake of heavy metals in fruit samples were found to be higher than that of the tolerable daily intake, indicating potential risk to human health. Therefore, to decrease the risk to human health, fruits must be washed well before eating to decrease heavy metal concentrations.