Alaa Saud Alhegaili

Epstein‐Barr virus (EBV)‐associated nasopharyngeal carcinoma (NPC) remains a clinically challenging malignancy, particularly in recurrent or metastatic disease where durable responses to chemoradiotherapy and immune checkpoint blockade are limited. The viral aetiology of NPC provides a strong biological rationale for immune‐based treatment; however, translation of chimaeric antigen receptor (CAR) T‐cell therapy into this solid tumour setting is constrained by poor tumour trafficking, antigen heterogeneity, limited surface accessibility of EBV latent antigens, T‐cell exhaustion, and an immunosuppressive tumour microenvironment. This review critically evaluates the emerging therapeutic prospects of CRISPR‐engineered CAR‐T cell therapy for EBV‐associated NPC. It synthesises evidence on EBV latency biology, NPC immune evasion, solid‐tumour CAR‐T limitations, and genome‐engineering strategies including conventional CRISPR‐Cas9, base editing, prime editing, and double‐strand‐break‐sparing targeted integration. Particular attention is given to genotoxicity, chromosomal rearrangements, chromosome loss, bystander and off‐target editing, manufacturing heterogeneity, and the regulatory and biological barriers that currently separate technical feasibility from NPC‐specific clinical implementation. Available clinical evidence from checkpoint blockade, EBV‐specific adoptive T‐cell therapy, base‐edited CAR‐T cells in haematologic malignancy, and early CRISPR‐edited T‐cell trials supports the feasibility of immune and genetic redirection but does not establish efficacy of a clinically validated CRISPR‐engineered CAR‐T platform for NPC. Future development should prioritise surface‐accessible antigen validation, fit‐for‐purpose selection of editing technology, genomic safety, scalable manufacturing, and biomarker‐driven early‐phase trials.

A multi-epitope vaccine targeting UPF0721 of Salmonella enterica was designed using immunoinformatics and molecular simulations, offering a promising strategy against meningitis-causing bacterial infections.

Cervical cancer, the fourth most common carcinoma in women worldwide, is predominantly caused by persistent infection with high risk human papillomavirus (HR-HPV). The human papillomavirus type 16 (HPV-16) L1 capsid protein plays a crucial role in immune recognition and viral dissemination. This study aims to conduct molecular analysis of the L1 gene from HR-HPV16 samples collected in Lahore, Pakistan, and to identify potential inhibitors against the L1 protein through in-silico analysis. The L1 gene was amplified using PCR (Polymerase Chain Reaction), followed by gel purification and Sanger sequencing. Nucleotide and amino acid sequence alignments were used to assess variant regions. In silico tools, including ADMET, CB DOCK 2 and Maestro Schrodinger, were employed to evaluate different parameters of various compounds with L1 protein. The study identified mutations in L1 sequences, including V357G, V359G, S369A, AND C371W, which could impact HPV-16 behavior and cancer development. Neoechinulin was identified as a promising HPV16 L1 capsid protein inhibitor with the highest binding energy score (-7.6 kcal/mol) against the L1 protein, suggesting potential antiviral efficacy. These mutations may alter the structural integrity of the L1 protein, potentially influencing HPV-16 infectivity and its role in cervical cancer progression, while virtual screening method demonstrated a cost- effective approach for discovering biologically impactful compounds. Neoechinulin identified as a potential HPV16 L1 capsid protein inhibitor through In Silico tools, further in vitro and in vivo studies are needed to confirm its antiviral efficacy.

Background and Purpose: To examine the respiratory and functional benefits of manual diaphragmatic release for Cleaning‐Laborers Exposed to Occupational Hazards.Methods: A randomized controlled trial of 36 participants aged 35–45 years was randomly allocated into two groups. The experimental group (n = 18); received manual diaphragm release along with respiratory training exercises, and the control group (n = 18); received respiratory training exercises only. Three times/week for 12 consecutive weeks. The serum immunoglobulin E level, pulmonary functions [forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), FEV₁/FVC, and peak expiratory flow (PEF) rate (PEF)], chest wall mobility, and 6 min walk‐test performance were assessed pre‐ and post‐intervention.Results: There was a greater decline in serum immunoglobulin levels (p = 0.003; Partial η² = 0.23) and enhancement in pulmonary functions [FEV₁ (p = 0.025, Partial η2 = 0.14), FVC (p = 0.017, Partial η² = 0.16), FEV₁/FVC (p = 0.028, Partial η² = 0.13), and PEF (p = 0.012, Partial η2 = 0.17) in the experimental group. Further, there was a greater increase in chest mobility at the xiphoid level (p = 0.002, Partial η² = 0.25) in the experimental group, but this was not the case at the axillary level (p = 0.29, Partial η² = 0.03). Still, the 6 min walk‐test performance improved more significantly in the experimental group (p = 0.002, Partial η² = 0.24).Conclusion: The diaphragmatic release technique may offer a promising approach for mitigating distressing respiratory symptoms, enhancing immune function, and improving 6 min walk‐test performance among cleaning laborers with work‐related respiratory hazards.Trial registration: The study was retrospectively registered at XXX (ID: NCT05802355).

There is a growing interest in discovering natural sources of anti-cancer drugs. Sesamol (SES) is a phenolic compound with antitumor effects. The present study aimed to investigate the anticancer properties of SES and its nano-suspensions (SES-NS) combined with Epirubicin (EPI) in breast cancer (BC) using mice bearing a solid Ehrlich tumor. The study involved 35 female albino mice and investigated the effects of SES and EPI on tumor growth, proliferation, apoptosis, autophagy, angiogenesis, and oxidative stress. Methods including ELISA, qRT-PCR, and immunohistochemistry were utilized. The findings revealed reductions in tumor growth and proliferation using SES either alone or combined and evidenced by decreased AKT (AKT Serine/Threonine kinase1) levels, angiogenesis indicated by lower levels of VEGFR (vascular endothelial growth factor), and apoptosis demonstrated by elevated caspase3 and BAX levels. Furthermore, autophagy increased and was indicated by increased levels of beclin1 and lc3, along with decreased oxidative stress as evidenced by elevated TAC (total antioxidant capacity) and reduced MDA (malondialdehyde) levels. Interestingly, SES-NS demonstrated more significant effects at lower doses. In summary, this study underscores the potential of SES as a promising agent for BC treatment. Moreover, SES-NS potentiated the beneficial effects of EPI while mitigating its adverse effects.

Reactive oxygen species (ROS) are noxious to cells because their increased level interacts with the body’s defense mechanism. These species also cause mutations and uncontrolled cell division, resulting in oxidative stress (OS). Prolonged oxidative stress is responsible for incorrect protein folding in the endoplasmic reticulum (ER), causing a stressful condition, ER stress. These cellular stresses (oxidative stress and ER stress) are well-recognized biological factors that play a prominent role in the progression of hepatocellular carcinoma (HCC). HCC is a critical global health problem and the third leading cause of cancer-related mortality. The application of anti-oxidants from herbal sources significantly reduces oxidative stress. Kaempferol (KP) is a naturally occurring, aglycone dietary flavonoid that is present in various plants (Crocus sativus, Coccinia grandis, Euphorbia pekinensis, varieties of Aloe vera, etc.) It is capable of interacting with pleiotropic proteins of the human body. Efforts are in progress to develop KP as a potential candidate to prevent HCC with no adverse effects. This review emphasizes the molecular mechanism of KP for treating HCC, targeting oxidative stress.

The distribution of DNA damage and repair is considered to occur heterogeneously across the genome. However, commonly available techniques, such as the alkaline comet assay or HPLC-MS/MS, measure global genome levels of DNA damage, and do not reflect potentially significant events occurring at the gene/sequence-specific level, in the nuclear or mitochondrial genomes. We developed a method, which comprises a combination of Damaged DNA Immunoprecipitation and next generation sequencing (DDIP-seq), to assess the induction and repair of DNA damage induced by 0.1 J/cm² solar-simulated radiation at the sequence-specific level, across both the entire nuclear and mitochondrial genomes. DDIP-seq generated a genome-wide, high-resolution map of cyclobutane thymine dimer (T<>T) location and intensity. In addition to being a straightforward approach, our results demonstrated a clear differential distribution of T<>T induction and loss, across both the nuclear and mitochondrial genomes. For nuclear DNA, this differential distribution existed at both the sequence and chromosome level. Levels of T<>T were much higher in the mitochondrial DNA, compared to nuclear DNA, and decreased with time, confirmed by qPCR, despite no reported mechanisms for their repair in this organelle. These data indicate the existence of regions of sensitivity and resistance to damage formation, together with regions that are fully repaired, and those for which > 90% of damage remains, after 24 h. This approach offers a simple, yet more detailed approach to studying cellular DNA damage and repair, which will aid our understanding of the link between DNA damage and disease.