Walaa Bayoumie El Gazzar

Muscle gradually loses its regenerative capacity with aging. Recent evidence highlights age-related immune dysregulation as a key driver of satellite cell dysfunction and reduced muscle regeneration. Timely elimination of apoptotic cells by phagocytes through efferocytosis is essential for tissue repair. Therefore, exploring age-related alterations in the molecular machinery of efferocytosis and their impact on muscle regeneration is of great relevance. This study examined the efferocytic machinery in the gastrocnemius muscle tissue of young and aged rats after doxorubicin-induced acute myotoxicity and assessed the potential of Vitamin B12-loaded chitosan nanoparticles (B12 CS NPS) to enhance efferocytosis and promote skeletal muscle injury repair in aged rats. Aged rats exhibited impaired efferocytosis with a significant reduction in MerTK, PPARγ, and miR-124 expression, and increased ADAM17 expression. B12 CS NPS administration significantly improved efferocytosis and reduced necrotic tissue areas, accompanied by increased MerTK, PPARγ, and miR-124, and reduced ADAM17 expression. Supplementation with B12 CS NPS significantly enhanced satellite cell proliferation and differentiation, which was indicated by upregulated expression of Pax7, Myog, and MyoD. These findings reveal that age-related alterations in regulatory molecules impair efferocytosis in aged muscle and demonstrate the potential of B12 CS NPs to enhance efferocytosis and improve skeletal muscle repair.

Background: Polycystic ovarian syndrome (PCOS) is one of the most prevalent reproductive, endocrine, and metabolic disorders inflicting women of childbearing age. Dietary interventions have gained interest as non-pharmacological approach to control obesity and metabolic disturbances. However, the effects of intermittent fasting (IF) on metabolic and hormonal profiles of PCOS patients is debatable. Objectives: We performed this systematic review and meta-analysis to explore IF’s effect on PCOS women’s metabolic and hormonal profile (PROSPERO: CRD42024511520). Eligible studies included IF interventions in women with PCOS, with metabolic and hormonal profiles being reported. Methods: A systematic literature search using three databases, including PubMed, SCOPUS, and Web of Science, was conducted. The systematic review was performed following PRISMA guidelines. Results: A total of four studies were included (N = 4). IF is not associated with significant change in BMI (MD = −0.200, 95% CI [−0.807, 0.407], p = 0.518). The analysis revealed that IF had no statistically significant impact on FBG (MD = −0.569, 95% CI [−9.955, 8.818], p = 0.906), HOMA-IR (MD = −0.862, 95% CI [−1.737, 0.014], p = 0.054), and FINS (MD = −2.749, 95% CI [−6.441, 0.943], p = 0.145). No significant change in TG (MD = −3.120, 95% CI [−9.624, 3.385], p = 0.347), total cholesterol (MD = −0.918, 95% CI [−2.960, 1.124], p = 0.378), and LDL levels (MD = −0.433, 95% CI [−1.224, 0.359], p = 0.284) between IF and pre-fasting or non-intervention diet groups. However, the explanation is limited by the small number of studies, duration of fasting regimes, and/or variations in fasting strategies. Sex hormone data were collected but were insufficient for a pooled analysis. Conclusions: Overall, our study suggests that IF is not an effective intervention to enhance BMI, glycaemic control, and lipid metabolism in PCOS patients. Nevertheless, the current conclusion is inconclusive and preliminary, as additional well-designed studies are required to support this conclusion.

Alzheimer’s disease (AD) is a significant health challenge in the 21st century. In spite of the approval of many new disease-modifying therapies for AD, the clinical advantages of these new treatments are less certain. Aim: This investigation was intended to determine the potential neuroprotective impact of morin hydrate (MH), zeolite clinoptilolite (ZC), and/or physical and mental activities (PhM) on an aluminum chloride (AlCl₃)-induced AD rat model. Methods: Male Sprague Dawley rats were randomly allocated into seven groups. Group I was the control group. Groups II–VII were treated with AlCl₃ for 5 weeks. Groups III–VII were tested for the effects of MH, ZC, and/or PhM. Biochemical, brain histopathological, and behavioral studies were performed. Results: PhM, MH, and ZC combined therapy exhibited a significant neuroprotective effect demonstrated by corrected catecholamines and tau and β-amyloid levels, as well as the antioxidant and anti-ferroptotic effects probably through Nrf2/HO-1/GPX4 and ACSL4 signaling pathways. In addition, combined therapy counteracted the inflammatory responses through modulating the TLR4/NF-κβ/NLRP3 inflammasome expression. Moreover, combined therapy groups showed the maximum improvement of both APOE4/LRP1 and Wnt3/β-catenin/GSK-3β signaling expressions. Conclusion: This research highlights the neuroprotective impact of MH and ZC plus PhM against AlCl₃-induced AD via modulation of Nrf2/HO-1/GPX4, TLR4/NF-κβ/NLRP3, APOE4/LRP1, and Wnt3/β-catenin/GSK-3β signaling pathways. It is the first to point out the inclusion of ferroptosis-Nrf2/inflammasomes cross-talk in the neuroprotection mechanism of MH/ZC against the AlCl₃-mediated AD model.

Background: In light of the existing body of scientific data, many substances are now recognized or reasonably assumed to be human carcinogens. Public knowledge about modifiable environmental carcinogens is regarded as a crucial first step in primary prevention. This study aimed to assess Jordanians' awareness of some of the recognized environmental human carcinogens and general cancer information. Methods: This study was conducted using a cross-sectional descriptive survey based on a questionnaire completed by Jordanian participants aged 18 or above. The questions consisted of the following sections: socio-demographic characteristics, questions about the prevalent and non-prevalent cancer types in Jordan and general causes of cancer, closed-ended questions to evaluate knowledge about environmental carcinogens as well as factors that influence the development of cancer, source of knowledge about carcinogens and interest in learning about human carcinogens, and the best way for prevention of cancer. Results: A total of 579 questionnaires were completed. Among respondents, 55.6% (n = 322) had a knowledge score ≥ 8 indicating good knowledge. However, low awareness was demonstrated regarding cancer-causing substances such as wood dust, Nitrosamines, Aflatoxins, Formaldehyde, Naphthalene, Asbestos, Benzene, and Arsenic. A significant portion of the participants failed to categorize infectious pathogens linked to cancer as variables that either cause cancer or raise the risk of developing cancer. Conclusion: This study demonstrated a good level of awareness regarding some environmental carcinogens but also highlighted the lack of knowledge about other environmental carcinogens. These findings may provide a guide for future awareness programs by health authorities.

The diagnosis of familial Mediterranean fever (FMF) is primarily based on clinical standards. The purpose of this study was to investigate the relevance of Mediterranean fever (MEFV) genetic testing in the diagnosis of FMF as well as to identify the most frequent variant alleles and their relationship to clinical symptoms in Egyptian patients. Egyptian patients with a clinical suspicion of having FMF were studied in order to determine MEFV genotypes. Each patient was meticulously evaluated through an extensive collection of their medical history, a thorough clinical examination, and a series of laboratory tests, encompassing CBC, ESR, and CRP measurements. The MEFV variant screening procedure included the use of reverse dot blot hybridization. The average age of our patients when they were given a diagnosis was 22.8 ± 1.404 years old. The predominant clinical manifestations identified were abdominal pain, fever, and arthralgia. Molecular interrogation of the MEFV gene unveiled that a significant proportion of the cohort, constituting 72 individuals (60%), displayed heterozygosity, whereas a smaller fraction, comprising 12 subjects (10%), demonstrated homozygosity and an equivalent number (10%) exhibited compound heterozygosity. Pertaining to the distribution of allele variants, E148Q emerged as the most prevalent, succeeded by M694I, accounting for 12.5% of the cases, and M680I (G/A), representing 10.41%. This notable prevalence of heterozygous genotypes among the Egyptian demographic, preliminarily identified as potential FMF cases, underscores the imperative for molecular diagnostics to enhance the precision of FMF identification.

Concerns have been expressed about imidacloprid (IMI), one of the most often used pesticides, and its potential neurotoxicity to non‐target organisms. Chronic neuroinflammation is central to the pathology of several neurodegenerative disorders. Hence, exploring the molecular mechanism by which IMI would trigger neuroinflammation is particularly important. This study examined the neurotoxic effects of oral administration of IMI (45 mg/kg/day for 30 days) and the potential neuroprotective effect of berberine (Ber) chloride loaded nano‐PEGylated liposomes (Ber‐Lip) (10 mg/kg, intravenously every other day for 30 days) using laboratory rat. The histopathological changes, anti‐oxidant and oxidative stress markers (GSH, SOD, and MDA), proinflammatory cytokines (IL1β and TNF‐α), microglia phenotype markers (CD86 and iNOS for M1; CD163 for M2), the canonical pyroptotic pathway markers (NLRP3, caspase‐1, GSDMD, and IL‐18) and Alzheimer's disease markers (Neprilysin and beta amyloid [Aβ] deposits) were assessed. Oral administration of IMI resulted in apparent cerebellar histopathological alterations, oxidative stress, predominance of M1 microglia phenotype, significantly upregulated NLRP3, caspase‐1 , GSDMD , IL‐18 and Aβ deposits and significantly decreased Neprilysin expression. Berberine reduced the IMI‐induced aberrations in the measured parameters and improved the IMI‐induced histopathological and ultrastructure alterations brought on by IMI. This study highlights the IMI neurotoxic effect and its potential contribution to the development of Alzheimer's disease and displayed the neuroprotective effect of Ber‐Lip.

Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity.

There have been concerns about the potential health risks posed by microplastics (MP). The detection of MP in a variety of food products revealed that humans are ingesting MP. Nevertheless, there is a paucity of data about their impacts, as well as their uptake, on intestinal barrier integrity. This study examined the toxic effects of oral administration of two doses of polyethylene microplastics (PE-MP) (3.75 or 15 mg/kg/day for 5 weeks; mean particle size: 4.0–6.0 µm) on the intestinal barrier integrity in rats. Moreover, the effect of melatonin treatment with MP exposure was also assessed. The PE-MP particle uptake, histopathological changes, Alcian blue staining, Muc2 mRNA, proinflammatory cytokines (IL-1β and TNF-α), and cleaved caspase-3, as well as tight junction proteins (claudin-1, myosin light-chain kinase (MLCK), occludin, and zonula occludens-1 (ZO-1)) were assessed. Oral administration of PE-MP resulted in apparent jejunal histopathological alterations; significantly decreased mucin secretion, occludin, ZO-1, and claudin-1 expression; and significantly upregulated MLCK mRNA, IL-1β concentration, and cleaved caspase-3 expression. Melatonin reversed these altered parameters and improved the PE-MP-induced histopathological and ultrastructure changes. This study highlighted the PE-MP’s toxic effect on intestinal barrier integrity and revealed the protective effect of melatonin.