Background & objective: Nerve Growth Factor (NGF) plays a key role in the pathophysiology of bronchial asthma through contributing to inflammation of airway, remodeling of airway and neural regulation. This systematic review aimed for the evaluation of mechanisms that contributed to asthma and its relevance to ICU settings. Methodology: The PRISMA 2020 guidelines were followed in this review. Studies that explored NGF expression, regulation and therapeutic targeting in asthma were sought using a comprehensive search of PubMed, Scopus and Google Scholar. Study design, population, NGF measure methods, key findings, and ICU relevance were focused on data extraction. The assessment of risk of any bias was done using Evident Project Risk of Bias Tool. GRADE assessment was used for certainty of evidence. Results: Of the 10 studies included, 6 were based on animal models, 3 were based on human observational studies and the remaining one was a systematic review. Asthma patients exhibited markedly higher NGF levels than control subjects (mean: 3.45 ± 0.76 pg/mL). Eosinophilic counts (r = 0.74, P < 0.01) and inflammatory cytokines correlated in positive with NGF. Airway inflammation decreased by 45.2% (P = 0.002), and airway remodeling by 32% (P = 0.004) via anti-NGF therapy. Similar results were observed by vitamin D supplementation that caused NGF downregulation by 41% (P = 0.003) via the Nrf2/HO-1 pathway. Risk of bias assessment showed that four studies were classified as low risk, five as moderate, and one as high. Conclusion: NGF was significantly stimulated in asthma and contributed to inflammation, reformation and neuroimmune interactions. The correlation of NGF with severe exacerbations and ICU outcomes suggested its potential as a biomarker for therapeutic target. However large scale and long-term evaluation of NGF against asthma was required. Future studies should validate the role of NGF in asthma management particularly in ICU settings. Abbreviations: NGF: Nerve Growth Factor, ICU: Intensive Care Unit, BALF: Bronchoalveolar Lavage Fluid, AHR: Airway Hyperresponsiveness, IL-6: Interleukin-6, IL-1β: Interleukin-1 Beta, CRP: C-Reactive Protein, TRPV1: Transient Receptor Potential Vanilloid 1, Nrf2: Nuclear factor erythroid 2-related factor 2, HO-1: Heme Oxygenase-1, ELISA: Enzyme-Linked Immunosorbent Assay, RT-qPCR: Reverse Transcription Quantitative Polymerase Chain Reaction, GRADE: Grading of Recommendations, Assessment, Development, and Evaluations, PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses, RSV: Respiratory Syncytial Virus, OVA: Ovalbumin, RhoA: Ras homolog family member A, PM: Particulate Matter Keywords: Nerve Growth Factor; Asthma; Airway Remodeling; Inflammation; Neuroimmunomodulation; Intensive Care Units; Critical Care; Biomarkers Citation: Bukhari AAS, Shaikh ARK, Salman W, Bhatti FA, Malik W, Minhas M, Muddasser A, Khaliq H. Pathophysiological role of nerve growth factor (NGF) in asthma: insights into airway inflammation, remodeling, and neural regulation in intensive care settings. Anaesth. pain intensive care 2025;29(3):681-689. DOI: 10.35975/apic.v29i3.2778 Received: February 03, 2025; Revised: February 28, 2025; Accepted: March 05, 2025

Objective: The objective of this in-vitro study was to explore the pro-apoptotic potential of eugenol (4-allyl-2-methoxyphenol) on Human Leukemia-60 (HL-60) cell line as a potent phytochemical in intensive care setting to leukemia patients. Methodology: After formal approval by all of the respective ethical committees, this study was simultaneously conducted at all respective institutional departments. The study included culturing HL-60 cell line and its treatment with serial concentrations of eugenol for calculation of subsequent IC50 values (half-maximal inhibitory concentration) via MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay, expression analysis of gene, comparative analysis of relative gene fold (Intrinsic Biomarkers Caspase-3, Caspase-9) as apoptosis mediator markers followed by RT-qPCR. Cellular apoptotic morphology was confirmed via Hoechst 333258 staining. Results: For HL-60 cell line, the IC50 of eugenol (14.1 uM) showed high gene expression of pro-apoptotic biomarkers (Caspase-3 and Caspase-9). Hoechst 333258 staining showed prominent apoptotic bodies leading to nuclear fragmentations. Conclusion: Eugenol proved to possess robust pro-apoptotic potential leading to diagnostic efficacy against leukemia HL-60 cell line. Further studies would help in identifying key mechanisms by which eugenol exhibits anti-cancer potential against HL-60 cell lines. Abbreviations: HL-60 - Human Leukemia-60; IC50 - Half-Maximal Inhibitory Concentration Keywords: Eugenol, Pro-apoptotic Effects, Intensive Care, Anti-Cancer Mechanisms, HL-60, Natural Chemotherapeutics Citation: Khaliq HMH, Bughio R, Nangdev P, Aziz O, Javed W. Integrating eugenol with intensive care in leukemia patients: exploration of pro-apoptotic potential against HL-60, human leukemia cell line. Anaesth. pain intensive care 2024;28(5):871−875; DOI: 10.35975/apic.v28i5.2491 Received: June 18, 2024; Reviewed: August 03, 2024; Accepted: August 11, 2024

Background: A complicated neurological disease known as autism spectrum disorder (ASD) is typified by issues with social interaction, communication, and repetitive behavior. The neural protective mechanisms in ASD are thought to be influenced by genetic variables, including the expression of neurotrophic genes such as glial cell line-derived neurotrophic factor (GDNF).

Background & objective: Severe dengue is a global health concern and immune dysregulation is a key contributor to its pathogenesis. The aim of this schematic review was to review the association of the cytokine biomarkers mainly interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in immune dysregulation among patients suffering from severe dengue. Methodology: The review followed PRISMA 2020 guidelines. The literature was searched from PubMed, Scopus, Web of Science, and Google Scholar up to August 2025. Qualified studies included those which measured IL-6, IL-10 or TNF- α in confirmed dengue patient. Meta-analysis was performed to assess standardized mean differences (SMDs) for key cytokines. The risk of bias was determined using Newcastle-Ottawa Scale and the GRADE approach was applied for certainty of evidence. Results: Higher levels were observed, of IL-6 and IL-10 in severe dengue, and TNF-α with late complications in this study. Meta-analysis correlated high levels of cytokines with severe dengue IL-6 (SMD = 16.79, 95% CI = -15.25-48.84), IL-10 (SMD = 0.13, 95%CI = -0.37-0.63) and TNF-α (SMD = 0.53, 95% CI = 0.25-0.82). The evidence confidence was moderate and high by IL-6 and IL-10 and high in TNF-α respectively. Conclusion: The levels of IL-6 and IL-10 were significantly high in severe dengue cases, but heterogeneity across studies reduced the prognostic integrity. TNF-α emerged as a potent indicator of mild and severe dengue. To establish the clinical uses of these biomarkers as a risk-stratifying tool, standardized, multicentric studies are needed to validate these findings. Abbreviations: DF: dengue fever, DHF: dengue hemorrhagic fever, DSS: dengue shock syndrome, IL-6: Interleukin-6, IL-10: Interleukin-10, SMD: standardized mean differences, TNF-α: tumor necrosis factor-alpha Keywords: Dengue Hemorrhagic Fever (DHF), Cytokine Storm, Biomarkers, Cytokines, IL-6, IL-10, TNF-α Citation: Bukhari AAS, Devi D, Minhas M, Noureen A, Javed H, Zaidi SIA, Khaliq H. Novel insights into immune dysregulation and cytokine signatures in intensive care settings: bridging IL-6, IL-10, TNF-α to endothelial, hepatic, and hematological dysfunction in severe dengue, a schematic meta-analysis. Anaesth. pain intensive care 2025;29(8):1022-1031. DOI: 10.35975/apic.v29i8.3039 Received: October 16, 2025; Revised: October 18, 2025; Accepted: October 18, 2025

Background: Alzheimer's disease (AD), a prevalent neurodegenerative disorder, poses significant challenges to healthcare systems worldwide. The aggregation of Amyloid-β peptide and the presence of apolipoprotein E4 (apoE4) are recognized as central factors in AD pathogenesis. Despite the availability of FDA-approved drugs, there remains a dire need for more effective and targeted treatments to combat this disease. The advent of in silico methodologies offers a promising avenue for accelerating the drug discovery process, providing a cost-effective and efficient means to screen for potential therapeutic agents. Objective: This study aimed to identify and evaluate potential inhibitors of apoE4 using in silico drug discovery methods. By targeting the interaction domain of apoE4, the study sought to discover compounds capable of reducing beta-amyloid aggregation, thus offering a novel approach to AD therapy. Methods: Computational techniques, including the Lipinski Rule of Five and ADMET filtering, were employed to screen a dataset of 80 chemical inhibitors retrieved from the NCBI database. Molecular docking was performed to assess the binding affinities and orientations of the compounds to apoE4, utilizing Phyre2 for 3D structure prediction and AutoDock Vina for docking simulations. The selection criteria for lead compounds were based on their binding energy, hydrogen bonding interactions, and compliance with drug-like properties. Results: Out of the initial 80 compounds screened, 15 were excluded based on the Lipinski Rule of Five, and an additional 43 were deemed unsuitable following ADMET analysis. Molecular docking identified two compounds, taxifolin and luteolin, exhibiting superior binding affinities to apoE4, with taxifolin showing the lowest binding energy of -7.4 kcal/mol and the highest number of hydrogen bonds in one of its conformations. Conclusion: The study successfully leveraged in silico methods to identify taxifolin and luteolin as potent inhibitors of apoE4, highlighting the potential of computational drug discovery in developing novel AD therapies. These findings pave the way for future experimental validation and clinical trials to assess the therapeutic efficacy and safety of these compounds in treating Alzheimer's disease.

Glaucoma, a leading cause of irreversible blindness, is increasingly recognized as a neurodegenerative disease affecting broader neuro-ophthalmic pathways. Brain-derived neurotrophic Factor is a crucial neurotrophin, that supports the growth, maintenance, and survival of neurons and has been implicated in glaucomatous damage where its levels are diminished. Objectives: To focus on the role of Brain-Derived Neurotrophic Factor in the pathophysiology of glaucoma and its therapeutic potential by enhancing the survival of retinal ganglion cells. Methods: The studies in this review are taken from well-known public libraries for scientific research such as PubMed (60%), Science Direct (25%) and Springer Link (15%), in line with PRISMA guidelines. Various works conducted over the past decade from different parts of the world, including North America, Europe, and Asia, have provided evidence that the augmentation of Brain-Derived Neurotrophic Factor signalling may be a very effective approach to managing or halting the progression of glaucomatous optic neuropathy through neuroprotection and improving retinal ganglion cells survival. Results: Studies in both animals and humans indicate that Brain-Derived Neurotrophic Factor and its downstream signals promote the survival of retinal ganglion cells and decrease the extent of apoptotic cell death, oxidative stress, and inflammation in glaucoma. Moreover, enhancements of Brain-Derived Neurotrophic Factor neuroprotective effects are supported by factors such as Nerve growth factor and Brain-Derived Neurotrophic Factor. Conclusion: It was concluded that Brain-derived neurotrophic Factor has the potential to be used as a diagnostic marker for Glaucoma as well as it could be evaluated for its therapeutic potential against the disease.