Haitham Al-Madhagi

According to the latest update from WHO, approximately 263 million cases of malaria were reported globally. The mosquito species Anopheles gambiae is the primary vector transmitting the malaria-causing pathogen Plasmodium spp. Scientists have recently focused on developing a transmission-blocking vaccine (TBV) to combat malaria by targeting vector homeostasis rather than specific Plasmodium species, which vary in their genomes and drug susceptibilities. To create this TBV, three salivary proteins (gSG6, D7, and AgTRIO) were selected as potential antigens. From these proteins, epitopes recognized by cytotoxic T cells (18), helper T cells (30), and B cells (10) were selected. These potentially positive antigens were then combined with mycobacterial tuberculosis heparin-binding hemagglutinin using suitable peptide linkers. The resulting vaccine sequence underwent prediction of biochemical properties and secondary and tertiary structure. The best model was generated using the I-TASSER platform, refined, validated, and docked to Toll-like receptor-4 (TLR-4) via the InterEvDock 2 server. The consensus docked complex demonstrated stability, mobility, and flexibility, as assessed through the Internal Coordinates Normal Mode Analysis Server and Groningen Machine for Chemical Simulations dynamics simulations. Furthermore, the vaccine exhibited a well-defined three-dimensional structure and strong binding to TLR-4 through multiple bonds. Molecular mechanics/generalized Born surface area yielded a ΔG of −28.5 kcal mol−1; however, stable binding was not achieved during the 100 ns molecular dynamics simulation, as indicated by a root mean square deviation of 1.25 nm. Following in silico simulation of vaccination, the vaccine was predicted to significantly induce robust B-cell and T-cell responses, antibody production (both IgM and IgG), and interferon-γ secretion. Importantly, this multi-epitope malaria TBV demonstrated predicted immunogenic potency without evidence of allergenicity or toxicity, suggesting its potential to limit the transmission of multidrug-resistant Plasmodium strains. However, these computational predictions require validation through in vitro and in vivo studies.

Breast cancer (BC) is the most commonly diagnosed malignancy in women globally, accounting for over 11% of all new cancer cases in female patients. Hormone receptor–positive BC relies on estrogen‐driven growth, making endocrine therapy a cornerstone of treatment. The standard clinical approach typically involves tamoxifen, a selective estrogen receptor modulator, or aromatase inhibitors (AIs), with the latter generally demonstrating superior efficacy in suppressing tumor progression and reducing the risk of recurrence. Among the various chemical scaffolds explored for AIs, imidazole rings have emerged as particularly promising. Its structural and electronic resemblance to letrozole, a leading nonsteroidal AI—a position that imidazole‐based derivatives occupy, makes it a compelling candidate for further development. To the best of our knowledge, this is the first review to systematically consolidate and evaluate synthetic imidazole derivatives as potential AIs by drawing direct comparisons with established reference drugs, primarily letrozole. In addition to discussing structure–activity relationships and biological potency, this review provides a concise overview of key synthetic strategies for constructing imidazole cores, thereby offering a practical resource for medicinal chemists working in anticancer drug discovery.

Background and Aims: Melanoma represents the most malignant type of skin cancer. It is estimated that approximately 100,000 new cases of melanoma were diagnosed in 2022, resulting in over 7600 deaths in the United States alone. Recently, anticancer peptides (ACPs) have emerged as novel therapeutic agents for cancer, offering higher potency, biocompatibility, and fewer adverse reactions in host cells. One of the druggable targets of melanoma is the melanoma inhibitor of apoptosis (ML‐IAP), conventionally inhibited by the nonapeptide AVPIAQKSE. The current study is aimed at enhancing both the binding affinity and safety profile of this peptide through in silico peptide engineering. Methods: Initially, the 3D structure of the protein was downloaded from the Protein Data Bank (PDB) (ID: 1OXQ) and prepared. The hotspot residues at the interface were detected using Discovery Studio Client 2021. Afterwards, saturation mutagenesis was conducted to discover the best potential amino acid substitutions with a positive impact on the binding affinity. The lead candidates were docked to the receptor via HPEPDOCK 2. Additionally, the safety profile was assessed using the ToxIBTL and AllerCatPro 2 servers. Finally, molecular dynamics simulations and principal component analysis were performed to check the stability of the best complexes. Results: HVPIAQKSE, WVPWAQKSE, and HVPWAQKSE were the best mutants that could be superior to the original peptide in terms of binding affinity as well as safety profile. MD results confirmed the stability, flexibility, reduced local motions, conformational changes, and more compact structure upon binding the receptor for 200 ns, which deserve in vitro validation as a better melanoma ACP therapeutic option. Conclusion: These variants displayed increased flexibility, reduced conformational alterations and local motions, and a more compact configuration, suggesting greater stability compared with the reference peptide.

Seonamhaeicola marinus, a marine bacterium from the family Flavobacteriaceae, was genomically analyzed. Approximately 23% of its predicted CDSs were linked to subsystems, with amino acid and protein metabolism being the most abundant. Four biosynthetic gene clusters (BGCs) were identified, including those for flexirubin and carotenoid. CAZyme analysis via dbCAN3 revealed 178 CAZymes, representing 3.87% of the genome, with glycosyl hydrolases, particularly GH2, being the most prevalent group. Polysaccharide-producing organisms, such as those yielding carrageenan from red algae, find applications in food, cosmetics, and pharmacology. ι-Carrageenan, characterized by its double sulfate groups, holds significant potential in pharmaceutical systems. ι-Carrageenase A2 from S. marinus has desirable properties for carrageenan processing, supporting the investigation of such novel enzymes for biotechnological uses. This study aimed to comprehensively analyze S. marinus ι-carrageenase A2 through various computational modeling methods. A comparative analysis of the enzyme’s physicochemical properties, binding site locations, and structural features was conducted with other enzymes from the same family. Multiple computer modeling software programs were employed for three-dimensional structure prediction and modeling. Molecular docking identified potential ligands, with neo-ι-carratetraose demonstrating strong binding affinity. Molecular dynamics simulations assessed the stability and flexibility of the ligand-enzyme complex, offering insights into key residues involved in substrate interactions.

Introduction Anemia, a chronic condition affecting millions globally, poses greater risks to pregnant mothers, particularly in regions like Yemen. However, data on pregnancy-related anemia in Yemen is scarce. This study aimed to gauge anemia prevalence in Yemen's Dhamar governorate, identifying associated pregnancy-related risk factors. Methods Through a questionnaire-based cross-sectional study involving a total of 157 pregnant participants, data on sociodemographics (age, education, income) and health history (gestational age, parity, hemorrhage) were collected. Utilizing SPSS v25, frequencies, percentages, and binary logistic regression (OR, AOR) with 95% confidence intervals (p<0.05) were calculated. Discussions Results highlighted 17% of pregnant women in medical centers had anemia (43% of which are mild, 23% moderate, 33% severe). Significantly, rural residence and lower socioeconomic status were linked (p=0.021, 0.015) with AORs of 0.305 (CI: 0.111-0.835) and 3.86 (CI: 1.294-11.542). Conclusion In conclusion, anemia affects pregnant women, particularly those in rural areas with lower incomes. Addressing this requires targeted medical interventions to mitigate anemia's prevalence and impact during pregnancy.

Thyroid cancer ranks tenth among the deadliest cancers globally. Papillary thyroid cancer (PTC) represents the majority (> 80%) of all thyroid cancer types. Albeit radioactive iodine therapy achieves a great deal of success rate and efficacy, it is not easily available in all affected regions and its inappropriate use can drive the development of new malignancies. This motivated us to rigorously analyze the transcriptomes of PTC so as to infer novel prognostic markers and hotspot targets that are druggable using the approved drugs. We downloaded two datasets from gene expression omnibus and subsequently processed them via GEO2R tool. The mutual differentially expressed genes (DEGs) from the two datasets included 452 genes. This was followed by the prediction of the interacting network through NetworkAnalyst followed by cytoscape to shortlist them into four hub genes (FN1, MAPK13, KRT19 and EGFR) by applying four cytohubba filters (MCC, MNC, closeness and betweenness). The hub genes were then evaluated for their interaction with their neighbor genes, differential expression in tumor versus healthy control samples, stage correlation, immune infiltration, overall survival and availability of specific drugs. The four hub genes displayed higher level of expression in tumor samples, varied correlation with PTC stage, high immune cells infiltrate rate. Moreover, MAPK13 and KRT19 were strongly associated with overall survival of PTC, while FN1 and KRT19 showed significantly low tumor purity. In conclusion, FN1, MAPK13, KRT19 and EGFR can be considered both good prognostic markers and druggable targets for PTC.

Mangiferin, a naturally occurring C-glucosylxanthone derived from various parts of the mango tree (Mangifera indica), has gained significant attention for its diverse pharmacological properties, including antioxidant, anti-inflammatory, antimicrobial, anticancer, and anti-diabetic activities. This mini-review provides an updated overview of the phytochemistry, pharmacokinetics, and medicinal properties of mangiferin. However, the low solubility (0.111 mg/mL) and oral bioavailability (less than 2%) of mangiferin pose significant challenges for its clinical application. To address these issues, the development of nanoformulations such as nanoparticles, micelles, and liposomes has been explored, which was proven to improve mangiferin’s solubility, stability, and targeted delivery. These nanocarriers enhance the bioavailability and therapeutic efficacy of mangiferin, making it a promising candidate for various therapeutic applications. The review ends with the discussion of the safety of mangiferin and its formulations in addition to the potential for clinical translation.