Hoda Atef Abdelsattar Ibrahim

Fourteen hybrid molecules (3a–g, 5a–g) combining a pyridine core with thiosemicarbazone or thiazolidinone moieties were designed, synthesized, and evaluated in vitro against Leishmania major.

The increase in global life expectancy has resulted in a significant rise in the occurrence of Alzheimer's disease (AD), making it a critical public health burden. Therefore, there is an urgent need to create effective methods to prevent or slow down the progression of the disease. In this regard, fifteen previously reported hybrid molecules ( 7a–c , 10a–j , and 13a,b ), combining 4‐hydroxycoumarin and pyrazolyl indolin‐2‐one structures, were resynthesized and tested for their antioxidant and anti‐Alzheimer properties. Several of these compounds showed moderate to strong biological activity. Among these, compound 7a demonstrated excellent antioxidant capacity (TAC = 80.65 mg gallic acid/g; IRP = 68.90 µg/mL) and impressive free radical scavenging abilities (DPPH = 5.33 µg/mL; ABTS = 4.59 µg/mL; NO = 6.76 µg/mL), comparable to the standard antioxidant ascorbic acid. Additionally, compound 7a demonstrated the robust inhibition of acetylcholinesterase (AChE) with an IC ₅₀ of 6.89 µg/mL, as well as potent inhibition of butyrylcholinesterase (BChE) (IC ₅₀ = 5.93 µg/mL). Molecular docking analyses of compound 7a revealed favorable binding interactions and stable conformations within the enzyme's active site, supporting its strong inhibitory effect. Overall, these findings indicate that this group of hybrid molecules offers a promising framework for developing new cholinesterase‐targeting treatments for AD.

Toxoplasmosis continues to pose significant challenges to public health and animal husbandry, thereby generating an ongoing need for the development of novel therapies through innovative approaches. In response to the persistent pursuit of an optimal chemotherapeutic agent, the present study designed and synthesized new small molecules (6 and 9a-d) featuring an imidazopyridine scaffold linked to isatin derivatives via a hydrazide moiety. The efficacy of these compounds was evaluated against Toxoplasma gondii (ME49 strain) in both in vitro and in vivo murine models of chronic infection. Notably, most of the tested compounds exhibited significant antiparasitic activity. Compound 9a showed the lowest calculated LD₅₀ value, indicating strong potency, while compound 9c demonstrated excellent cysticidal activity in vitro, achieving 100% cyst mortality at concentrations ≥100 µg mL^-1. In vivo, compound 9c was the most effective treatment, reducing brain cyst burden by 82.7%. Molecular analyses indicated that compound 9c significantly reduced T. gondii DNA levels and strongly downregulated pro-inflammatory cytokines. Molecular docking analyses further validated the effective interactions between the synthesized compounds and the target enzyme T. gondii calcium-dependent protein kinase-1 (TgCDPK1). Collectively, these results highlight the promising anti-Toxoplasma potential of imidazopyridine-isatin hybrids, which provides a foundation for the further development of these hybrid molecules as therapeutic agents against toxoplasmosis.

Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii , remains a serious global health concern, largely because current treatments with sulfonamides and pyrimethamine are toxic and increasingly ineffective due to rising drug resistance. In response, this study describes the design, synthesis, and laboratory evaluation of novel hybrid molecules that merge a quinoline backbone with either thiadiazole (compounds 8a – e ) or thiazole (compounds 12a – d ) bioactive groups to develop safer and more effective therapies. Cytotoxicity tests on mouse (L929) and human (Hs27) fibroblast cell lines revealed distinct safety profiles: the thiadiazole hybrids ( 8a – e ) were significantly toxic to host cells, whereas the thiazole‐based versions ( 12a – d ) were much safer, with several showing no toxicity even at 250 µg/mL. When tested against T. gondii , the quinoline‐thiazole hybrids proved the most effective. Notably, 12b and 12c achieved IC ₅₀ values of 0.40 and 0.52 µg/mL, respectively, better than the reference drug pyrimethamine (IC ₅₀ = 0.74 µg/mL). Compound 12c emerged as the top candidate, with an excellent selectivity index (SI) of 71.0 in human Hs27 cells. Further mechanistic work showed that 12c strongly inhibits tyrosinase, a potential parasitic target. Kinetic studies revealed a mixed‐type inhibition mechanism, with an IC ₅₀ of approximately 5 µM, 10 times more potent than kojic acid (48 µM), a standard inhibitor. Molecular docking and dynamics simulations confirmed stable binding between 12c and tyrosinase. Together, these findings underscore the therapeutic promise of the quinoline‐thiazole scaffold, particularly compound 12c , as a lead for developing targeted, low‐toxicity anti‐toxoplasmosis drugs. The results are expected to expand the existing toolkit of small molecules targeting the parasite and reinforce the importance of molecular hybridization in drug development. Additional research is needed to clarify how these compounds work and to assess their effectiveness in living organisms in order to fully unlock their potential as anti‐parasitic drugs.

BACKGROUND Obesity and overweight are major public health challenges and are associated with autonomic imbalance and decreased heart rate variability (HRV), a non-invasive indicator of cardiovascular risk. Omega-3 polyunsaturated fatty acids have shown cardioprotective effects and may modulate autonomic function. Nevertheless, the effect of omega-3 supplementation on HRV in individuals who are overweight or obese remains unclear. AIM To study the effect of omega-3 supplementation on HRV in overweight and obese individuals and to explore the heterogeneity across different study designs. METHODS In accordance with PRISMA guidelines, a systematic review and meta-analysis were conducted. PubMed, Science Citation Index, and Scopus were searched for randomized controlled trials (RCTs) assessing the impact of oral omega-3 supplementation on HRV in overweight or obese participants. Primary outcomes were the impacts of omega-3 supplementation on time-domain HRV indices [root mean square of successive differences (RMSSD), standard deviation of normal-to-normal intervals (SDNN), and percentage of successive normal-to-normal intervals differing by more than 50 milliseconds (pNN50%)], and frequency-domain indices [high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio]. RESULTS Four RCTs (n = 134 participants) met the inclusion criteria. Two trials compared pre- vs post- omega-3 supplementation, and two compared omega-3 with placebo on HRV in overweight and obese children and adults. In the within-subject analyses, omega-3 supplementation was associated with a significant increase in RMSSD [mean difference (MD) = -11.69 milliseconds, 95%CI: -18.50 to -4.87, P = 0.0008), SDNN (MD = -26.13 milliseconds, 95%CI: -35.84 to -16.42, P < 0.00001), and pNN50% (MD = -9.45, 95%CI: -14.27 to -4.64, P = 0.0001). Between-group comparisons showed that omega-3 supplementation had no significant effect on HF power, LF power, or the LF/HF ratio. CONCLUSION Omega-3 supplementation represents a promising and low-cost strategy for enhancing autonomic balance and potentially reducing cardiovascular risk in overweight and obese populations, as it improves time-domain HRV measures.

The updated guidelines from the World Health Organization highlight that treatment options for multidrug-resistant tuberculosis (MDR-TB) remain limited due to the scarcity of effective drugs. As a result, there is an urgent necessity to develop novel or repurposed drugs that demonstrate efficacy against multidrug-resistant (MDR) strains. In this study, a new series of thiazole-pyridine hybrids were thoughtfully designed and synthesized to assess their potential as antitubercular agents. These compounds were specifically created to target enoyl acyl carrier protein reductase (InhA), a crucial enzyme in the pathogenesis of Mycobacterium tuberculosis. The majority of the compounds evaluated demonstrated substantial antitubercular activity, with minimum inhibitory concentrations (MIC) ranging from 0.5 to 3.9 μg mL⁻¹ against Mycobacterium tuberculosis H37Rv. Among them, compound 5a was the most effective, with an MIC of 0.5 μg mL⁻¹. Further evaluations of compound 5a demonstrated its ability to disrupt bacterial biofilms and its strong inhibition of InhA, with an IC₅₀ of 0.19 ± 0.008 μg ml⁻¹, demonstrating superior efficacy compared to triclosan, which was employed as the reference drug. Molecular docking and dynamics analyses demonstrated that the pyridine ring and thiazole group are essential for binding affinity, and the pyridine-thiazole framework in compound 5a formed stable interactions within the active site of InhA.

BACKGROUND Hyponatremia is a prevalent and serious electrolyte imbalance in pediatric pneumonia and is linked to increased disease severity and adverse outcomes. Oral rehydration solution (ORS) is an available, inexpensive, safe, and ready-to-use oral solution that can supplement sodium in such cases. AIM To assess the impact of prophylactic sodium supplementation via ORS on clinical and hospital outcomes in infants and children admitted with pneumonia. METHODS A randomized, interventional controlled trial was conducted on 140 infants and children admitted with pneumonia (70 per group). The primary outcome was hospital length of stay, with secondary outcomes including serum sodium and potassium levels, clinical respiratory scores, modified shock index, and nutritional/inflammatory markers. The hospital length of stay and both the laboratory and clinical parameters of the interventional and control groups were compared. RESULTS The hospital stay was longer in the control group than in the intervention group (P value = 0.001; effect size = 0.59). Clinical respiratory scores on day 4 were significantly lower in the intervention group than in the control group (P value = 0.001). Sodium levels were significantly lower in the control group than in the intervention group at discharge (P value = 0.002). CONCLUSION Prophylactic oral sodium supplementation through ORS may have a health-promoting effect on infants and children admitted with pneumonia.

Introduction: Breastfeeding is currently recommended as the optimal and initial feeding option for all newborns, as it protects against illness and reduces neonatal mortality. Furthermore, premature infants exhibit reduced swallowing ability and an increased risk of developing necrotizing enterocolitis (NEC), which may hinder suckling and delay the initiation of enteral feeding. Our aim was to investigate the effects of oropharyngeal colostrum delivery in preterm neonates <34 weeks of gestation on hospital outcomes, specifically differences in hospital stay between neonates who received colostrum for 3 days and those who did not. Methods: This prospective, interventional, randomized controlled trial enrolled ninety-six preterm neonates, who were allocated into three groups: group A, neonates who received oropharyngeal colostrum for 3 days along with routine care; group B, neonates who received oropharyngeal colostrum for 10 days along with routine care; and group C, neonates who received routine care only. The Kruskal-Wallis test was used to compare medians among the three groups. Associations between categorical variables were analyzed using the chi-squared test and Monte Carlo test. Results: The two groups that received colostrum showed significantly reduced median hospital stays, time to reach full enteral intake, and sepsis rates compared to the control group (p < 0.001). A significant difference in daily weight gain was observed between groups, particularly between the control group and neonates who received colostrum for 10 days (p = 0.028). Regarding the incidence of NEC, no significant difference was found among the groups (p = 0.314). Conclusion: Oropharyngeal colostrum may be considered a potential oral immunotherapy.

Background: Congenital heart disease (CHD) is the most prevalent congenital abnormality in children. Infants and children with CHD are at a higher risk of malnutrition. Aim: The purpose of this research was to investigate the frequency of anthropometric malnutrition, for example, underweight, wasting, and stunting, among infants and children with CHD attending the emergency room of a large tertiary hospital. Methods: Between January 2022 and August 2022, a cross-sectional study was carried out on 96 infants and children presenting with heart failure at Children's Hospital Cairo University. All enrolled participants had anthropometric and biochemical nutritional assessments. Anthropometric z-scores were calculated for each infant or child using WHO reference ranges. Biochemical and nutritional assessments were carried out through screening for iron deficiency anemia and electrolyte imbalances. Results: Ninety-six infants and children were enrolled in our study, with males representing 54.8%. Seventy percent of the patients were anthropometrically malnourished, with underweight being the most prevalent (59.4%). Some children had more than one type of malnutrition. Electrolyte imbalance was a major biochemical malnutrition indicator, with hypophosphatemia present in 39.6% of the enrolled children. Conclusion: Malnutrition poses a significant health problem in infants and children with CHDs. To improve outcomes, it is essential to integrate systematic measures for identifying and managing malnutrition into the care of these patients. Both anthropometric and biochemical malnutrition should be routinely screened in all clinical settings to ensure comprehensive management and support.