Rania Ali El Hadi Mohamed

Lysosomes are central regulators of cellular homeostasis, integrating catabolic and anabolic reactions to sustain metabolism. In cancer, however, lysosomal function is not merely upregulated but selectively rewired into distinct, context‐dependent states that actively drive tumor immune evasion. This review proposes a conceptual framework linking metabolic, oxidative, oncogenic, and inflammatory pressures to six dominant lysosomal rewiring programs. Chronic nutrient deprivation and hypoxia activate AMPK‐ULK1 and HIF signaling, promoting TFEB/TFE3‐dependent lysosomal biogenesis, hyper‐acidification, and autophagosome–lysosome fusion, collectively degrading immune effectors such as IL‐1β and MHC complexes and impairing T‐cell priming. Disseminated tumor cells exploit TPC2‐mediated Ca ²⁺ signaling and GLS1‐dependent metabolism to buffer oxidative stress and support metastatic colonization, while dysregulated PI3K‐AKT–mTOR and MYC signaling drive lysosomal peripheralization and lysosomal biogenesis through Arl8b‐BORC‐kinesin complexes, facilitating cathepsin‐mediated exocytosis and MHC‐I degradation. Chronic inflammation, sustained by tumor‐associated macrophages, myeloid‐derived suppressor cells, and IL‐6/IL‐10 gradients, further reinforce immune suppression. Beyond mechanisms, we also assess the translational readiness of the implicated molecular mediators, distinguishing those with established pharmacological outcomes, such as PI3K‐AKT–mTOR inhibitors and repurposed chloroquine/hydroxychloroquine, from mediators that remain strictly preclinical, including TPC2, Arl8b‐BORC, and CMTM6/DHHC3, or that are currently undruggable, such as TFEB/TFE3. By framing lysosomes as state‐specific orchestrators of immune escape rather than uniform stress organelles, this review offers a mechanistic and translational roadmap for developing lysosome‐directed strategies to restore anti‐tumor immunity.

This study aimed to assess the in vivo therapeutic potential of pear powder in the treatment of hyperlipidemia. Hyperlipidemic male albino rats were divided into three groups (n=10). The first group (G0) was considered as the control, while the second and third groups (G1 and G2) received 300 and 600mg/kg pear powder along with the basal diet, respectively, for 2 months. The experimental results showed that there was a significant reduction in the weight (235.61-210.52g) of the rats (from G0 to G2) after two months of study. Water intake and nutrient digestibility were higher in G2 than in G0. The reduction of the total cholesterol from (69.02 to 59.43mg/dL), triglycerides from (160.24 to 63.45mg/dL), and LDL from (50.83 to 17.08mg/dL) was noted, when G0 were compared with G2. Improvements in HDL levels were also recorded. Reductions in aspartate aminotransferase and alanine aminotransferase levels were also recorded. Histopathological screening of control and pear powder-fed rats revealed a significant reduction in kidney and liver injury in the G2 group. Therefore, it can be concluded that pear powder, which is rich in bioactive substances, can be used as a medicinal food to prevent hyperlipidemia.

Foot-and-mouth disease virus (FMDV) remains one of the most contagious and economically damaging pathogens affecting cloven-hoofed livestock worldwide. Despite the availability of inactivated vaccines, large-scale production continues to face bottlenecks due to suboptimal virus yields in cell culture. Viral replication depends heavily on host cell metabolism, particularly amino acid supply. This study aimed to optimize FMDV growth by supplementing synthetic culture media with selected amino acid and those that could enhance FMDV yield in BHK-21 cells. Five amino acids, arginine, lysine, serine, threonine, and valine, were individually added to Dulbecco’s Modified Eagle Medium (DMEM) at elevated concentrations, and their influence on virus production was quantified using an ELISA-based antigen assay. All experiments were performed in three biological replicates. Among them, valine and lysine significantly boosted viral titers relative to the control, with valine yielding the highest increase (OD 2.92±0.19). These differences are statistically significant (p<0.05) and OD value represents relative absorbance measurements. Further optimization showed that a two-fold valine concentration produced the maximum output, whereas higher concentrations suppressed replication, indicating a concentration-dependent metabolic threshold. The enhancement observed with valine may reflect broader metabolic interactions described in prior studies, but the underlying mechanism remains to be determined. Lysine’s influence may align with known biochemical properties of positively charged amino acids, though no mechanistic analysis was performed. Overall, these findings demonstrate that fine-tuning amino acid composition, particularly moderate valine enrichment, can substantially increase FMDV yield without altering the viral genome or culture process. This simple yet effective metabolic adjustment offers a practical route to improving antigen output and reducing manufacturing costs in FMD vaccine production systems.

In this study, an aqueous extract of Spirulina platensis was utilized as a reducing and stabilizing agent for the green synthesis of silver‐zinc oxide nanocomposites (Ag‐ZnO). The S. platensis extract was optimized at a concentration of 0.5%, stored at 4°C and centrifuged at 6000 rpm for 5 min. Ultraviolet–visible spectroscopy of the extract showed a broad absorbance band in the 330‐ to 380‐nm region and a shoulder in the 520‐ to 620‐nm range, corresponding to bioactive metabolites. The formation of silver‐zinc oxide nanocomposites was confirmed by characteristic absorbance in the 300‐ to 400‐nm region under optimized conditions. Particle size analysis using a Zetasizer revealed an average particle size of approximately 204 nm with a polydispersity index of 0.28. Functional groups, crystallinity, and surface morphology were characterized using Fourier transform infrared spectroscopy, X‐ray diffraction, and scanning electron microscopy. Due to increasing concerns over antibiotic resistance, the antibacterial potential of the synthesized nanocomposites was evaluated by the disk diffusion method showing a maximum zone of inhibition of 35 ± 0.4 nm against Pseudomonas aeruginosa at 13 μg/mL. The Ag‐ZnO nanocomposites exhibited a notable antioxidant activity, indicating a concentration‐dependent DPPH radical scavenging activity with a maximum inhibition of 67.3% at 517 nm, compared to 60.12 for ascorbic acid. Furthermore, cytotoxic evaluation against the BT‐549 breast cancer cell line revealed a half‐maximal inhibitory concentration (IC ₅₀ ) of 6.401 μg/mL. These findings indicate that S. platensis –mediated silver‐zinc oxide nanocomposites exhibit promising biological activity.

KRAS mutations cause a variety of malignancies, with the KRAS-G12C variation serving as a key oncogenic target. Despite the approval of Sotorasib for KRAS G12C-mutated NSCLC, resistance and poor efficacy indicate the need for new inhibitors. This study screened over 11,800 marine-derived chemicals from the CMNPD database using a computer-assisted workflow. Following drug-likeness filtering and virtual screening, three candidates (CMNPD27430, CMNPD23547 and CMNPD10958) demonstrated higher binding affinities to KRAS-G12C than Sotorasib. Molecular dynamics simulations (100 ns) confirmed complex stability, which was validated by RMSD, RMSF, Rg, SASA and hydrogen bonding analysis. ADMET profiling also revealed favorable drug-like and pharmacokinetic characteristics. These findings suggest that marine natural compounds are viable scaffolds for the future development of KRAS-G12C inhibitors.

Upon careful re-examination of the RCSB entry for PDB ID: 7C36 prompted by an insightful reader, the authors confirm that this structure corresponds to RBMS1 (UniProt: P29558), a single-stranded DNA-binding protein involved in regulation of the c-MYC promoter, and not to the human c-Myc protein (UniProt: P01106) as originally stated in the manuscript. The PDB annotation as a “c-Myc DNA-binding protein complex” unfortunately led to a misinterpretation during structural selection. The authors acknowledge that the structure used in docking was not a crystallographic structure of c-Myc. Therefore, the docking results and interaction analyses described as “MYC–ligand” interactions are structurally attributable to RBMS1 rather than c-Myc. Any conclusions regarding direct protein–ligand interactions at the c-Myc protein interface are consequently not supported by the selected structure. The publisher hereby retracts the manuscript.

Native to tropical and subtropical regions, Moringa oleifera, often known as Moringa, is a member of the Moringaceae family. It can be found in Northwest India and Pakistan’s sub-Himalayan regions. The phytochemical makeup of the methanolic extracts of M. oleifera seeds (Met-Ext-M.O.) was examined using gas chromatography-mass spectroscopy (GC-MS) analysis, followed by molecular docking studies for the determination of the most potent ligands. A UV spectrophotometer was used to analyze the extracts for in vitro DPPH scavenging activity at different doses (1000 [ ]g/mL, 500 [ ]g/mL, 250 [ ]g/mL, 125 [ ]g/mL, 62.5 [ ]g/mL and 31.05 [ ]g/mL), with ascorbic acid serving as a reference standard. The extract was further assessed using two in vivo antidepressant tests: The tail suspension test (TST) and the forced swim test (FST). Mice were administered 125 mg/kg and 250 mg/kg body weight of M. Oleifera Met-Ext. In the meantime, the standard group received an oral imipramine dosage of 10 mg/kg/day. An hour before the test began, imipramine and plant extracts were administered orally. The molecular docking study revealed that certain phytoconstituents (50 phytochemicals) identified by GC-MS analysis are capable of binding serotonin 1A receptor with favorable affinity, potentially, ensuring an interaction with neuroreceptor systems, which mediate mood regulation. GC-MS profiling provided a preliminary characterization of the phytochemical components of M. oleiferaseed extract, but some of the compounds identified, e.g. those based on phthalates, could have been due to environmental or laboratory contamination and therefore were handled with care in the context of their possible biological activity. These phytochemicals were grouped based on their molecular weight at various retention periods, and constituents like Benzo[c]phenanthrene, 5-methyl showed the best binding affinity (−8.5 kcal/mol), Benzo[1,2-b:5,4-b[ ]]difuran-4,8-dione and 1,3,5-Triazin-2(1H)-one derivatives with Serotonin-bound Serotonin 1A receptor-Gi protein complex (7e2y) by molecular docking studies, suggesting potential for antidepressant effects and novel therapeutic agents. M. Oleifera Met-Ext also showed a great in vitro antioxidant activity, which can lead to neuroprotective effects, but this antioxidative activity cannot be directly related to antidepressant effects. Compared to ascorbic acid (91 ± 0.5; IC[ ] 30 [ ]g/mL), Met-Ext-M.O. at 1000 [ ]g/mL (82 ± 1.5***; IC[ ] 90 [ ]g/mL) considerably reduced the percentage suppression of DPPH free radicals. Consequently, it was discovered that the extract was a potent antioxidant that also performed well in vivo. Mice administered imipramine and Met-Ext-M.O. in both test models had shorter durations of immobility on days 1, 7 and 14 of the experiment compared to the control group. In contrast to the normal group, which experienced 197.76 ± 4.42 on day 1, 199.08 ± 2.29 on day 7 and 200.28 ± 3.17 on day 14, the immobility period for 125 mg/kg was 131.63 ± 3.79, 117.85 ± 2.47 and 107.09 ± 2.24 on days 1, 7 and 14. The immobility period for 250 mg/kg was 112.19 ± 2.69 on days 1, 7 and 14, 105.49 ± 2.55 and 90.21 ± 2.21 on day 14, respectively. Days 1, 7 and 14 following imipramine injection showed a significant reduction in immobility time (86.64 ± 1.66, 72.35 ± 1.75 and 54.75 ± 1.69). In vivo behavioral studies (TST and FST) demonstrated that there was a significant decrease in immobility time, exhibiting antidepressant-like effects in mice. These findings, when allied, suggest that these behavioral effects can possibly be explained by the active presence of phytochemicals, but there is still a need to conduct further mechanistic and clinical studies to determine a definite antidepressant mechanism. These effects, which could have a major impact on both in vitro and in vivoresearch, could be caused by physiologically active phytonutrients in the plants.

This research explored the therapeutic efficacy of bioactive substances derived from Pterocarpus soyauxii and Pterocarpus mildbraedii against HIV-1 and SARS-CoV-2 co-infection. Pharmacokinetic characteristics were evaluated with ADMETlab 3.0. Network pharmacology analyses were conducted using Swiss Target Prediction, GeneCards, STRING, Cytoscape and Metascape, along with pathway mapping in Srplot. The protein structures of EGFR, MMP9 and SARS-CoV-2 polyprotein 1ab were assessed through the SwissModel and ProSA-web databases. Molecular docking and binding sites determination were performed through 1-Click Docking and BC-Dock2 web servers. Inhibitory activity of the compounds on the CDK2 and HIV-1 proteins was carried out in the kinCSM way2drug databases. Results show that Khrinone A and E exhibited positive absorption and distribution profiles. Network pharmacology revealed essential molecular targets and enriched KEGG pathways associated with viral replication. MolProbity scores ranged from 0.77 to 2.28, with over 92% of residues located in Ramachandran preferred regions. Molecular docking revealed significant binding affinities, especially Pterocarpin (−9.9 kcal/mol) with MMP9 and Khrinone A (−8.9 kcal/mol) with NOS2, surpassing reference inhibitors. In comparison to EGFR, the affinities of natural ligands (−7.7 kcal/mol to −7.0 kcal/mol) were similar to Gefitinib, whereas Claussequinone and Khrinone E demonstrated compelling interactions with HIV-1 reverse transcriptase (−7.4 kcal/mol to −7.2 kcal/mol), resembling those of Lawsone (−8.3 kcal/mol). Additionally, Khrinone A and E can serve as potent CDK2 inhibitors ([ ]), exhibiting pKi values (5.902–5.929) comparable to those of Palbociclib (6.029). These results indicate that compounds derived from Pterocarpus have multitarget antiviral and host-modulating abilities, reinforcing their potential as valuable candidates for therapeutic intervention in HIV/SARS-CoV-2 co-infection.