Ashfaq Ahmad Shah Bukhari

Background/Objectives: Pulmonary arterial hypertension (PAH) management is evolving beyond conventional vasoactive therapies toward strategies targeting pathways implicated in pulmonary vascular remodeling. Despite advances in combination therapy, substantial residual risk persists. The clinical introduction of sotatercept, targeting activin signaling, has expanded the therapeutic landscape. This narrative review critically evaluates the evidence supporting remodeling-directed treatment and examines how established recommendations, individualized therapeutic considerations, and investigational strategies can be distinguished within risk-guided PAH management. Methods: Clinical, translational, and mechanistic evidence was narratively synthesized, prioritizing randomized controlled trials, prospective investigations, major guidelines, and relevant mechanistic studies. Particular attention was given to differences in trial populations, endpoints, background treatment, safety, and evidence maturity. Results: Sotatercept has demonstrated incremental clinical benefits across functional, hemodynamic, and clinical-outcome measures in studied PAH populations, although trial heterogeneity limits indirect comparisons and long-term disease modification remains unproven. Other remodeling-directed approaches, including growth-factor inhibition, BMPR2 restoration, immune modulation, and metabolic targeting, remain investigational, with variable and frequently preliminary evidence. The proposed synthesis distinguishes guideline-supported therapeutic escalation from individualized clinical considerations and research hypotheses, emphasizing residual risk, treatment tolerability, and demonstrated incremental benefit. Conclusions: Remodeling-directed therapy expands the treatment options for PAH but does not replace established vasoactive treatment or risk-based escalation. Future priorities include defining optimal therapeutic sequencing, identifying responsive patient populations, and determining whether sustained clinical improvements translate into modification of disease progression.

Background: Chronic diseases are major contributors to global morbidity, mortality, disability, and healthcare costs. Modifiable lifestyle factors, particularly dietary habits, play an important role in the prevention and progression of non-communicable diseases. Objective: This review critically examines the relationship between nutrition, dietary patterns, lifestyle choices, and the prevention of chronic diseases, with particular emphasis on inflammation, weight management, whole-grain consumption, fruits and vegetables, phytochemicals, precision nutrition, and community-based public health interventions. Methods: A narrative review of the existing literature from Google scholar, PubMed and Scopus was conducted to synthesize evidence on the role of nutrition and dietary lifestyle choices in chronic disease prevention. Results: Current evidence indicates that dietary patterns rich in minimally processed plant foods, whole grains, fruits, vegetables, dietary fiber, healthy fats, and bioactive compounds are associated with reduced risks of several chronic diseases. These dietary components may exert beneficial effects through the modulation of inflammation, oxidative stress, immune responses, metabolic function, vascular health, and the gut microbiota. Sustainable weight management through balanced nutrition and regular physical activity further contributes to improved metabolic health and reduced chronic disease risk. Whole-grain consumption has been associated with lower risks of cardiovascular disease, type 2 diabetes, obesity, colorectal cancer, and mortality. Fruits, vegetables, and phytochemical-rich foods provide essential nutrients and bioactive compounds that may support antioxidant and anti-inflammatory pathways. Conclusions: Healthy dietary patterns and complementary lifestyle behaviors represent important strategies for preventing and managing chronic diseases. Promoting balanced, nutrient-rich, culturally appropriate, and sustainable diets, together with physical activity and supportive community environments, may substantially reduce the global burden of chronic diseases.

Background/Objectives: Early childhood developmental attainment varies across Pakistan, but provincial averages may obscure differences across developmental domains and socioeconomic groups. We examined developmental attainment and associated factors among children aged 36–59 months in four Pakistani provinces. Methods: We analyzed four provincially representative UNICEF-supported Multiple Indicator Cluster Surveys (MICS) conducted between 2017 and 2020. Development was assessed using the original Early Childhood Development Index (ECDI). Survey-design-based analyses estimated overall and domain-specific prevalence, adjusted prevalence ratios (aPRs), and wealth-related inequalities. Province-specific associations were summarized using random-effects meta-analysis. Results: Among 46,067 children, 59.4% met the overall ECDI criteria in Punjab, 54.6% in Khyber Pakhtunkhwa, 47.5% in Sindh, and 39.1% in Balochistan. This ordering persisted after age–sex standardization. Literacy–numeracy was the least frequently attained domain, ranging from 14.6% to 27.2%, whereas physical-domain attainment exceeded 90% in all four provinces. Early childhood education (ECE) attendance was associated with higher overall ECDI attainment (pooled aPR 1.29, 95% CI 1.22–1.37). Stunting and functional difficulty were associated with lower overall attainment, while associations with adult stimulation varied across provinces. Richest–poorest differences in overall ECDI prevalence ranged from 18.8 to 35.6 percentage points. Conclusions: Among children aged 36–59 months in four Pakistani provinces, developmental attainment differed substantially between provinces and across developmental domains, and these differences persisted after age–sex standardization. Socioeconomic inequalities were evident in every province. ECE attendance was associated with higher developmental attainment, but this association should be interpreted cautiously because the surveys were cross-sectional and may be affected by residual confounding and selection into ECE.

Background/Objectives: Hyperuricemia is highly prevalent in chronic kidney disease (CKD). It has been linked to increased cardiovascular and mortality risk. However, its independent prognostic significance and dose–response relationship with adverse outcomes remain incompletely understood. Methods: This retrospective cohort study included 794 patients with CKD. Hyperuricemia was defined using sex-specific thresholds. The association between hyperuricemia, cardiac events and mortality was tested using a multivariable logistic regression test. Serum uric acid was analyzed as both a categorical and a continuous variable to assess dose–response relationships. Results: Hyperuricemia was present in 44.8% of patients. In multivariable analysis, hyperuricemia was associated with increased odds of cardiac events, although this did not reach statistical significance (OR 1.49, 95% CI 0.98–2.27, p = 0.061). However, hyperuricemia independently predicted mortality (OR 1.98, 95% CI 1.04–3.78, p = 0.039), and importantly, a dose–response relationship was observed between serum uric acid and adverse outcomes. Each 100 μmol/L increase in serum uric acid was associated with a 22% increase in cardiac event risk (OR 1.22, p = 0.011) and a 29% increase in mortality risk (OR 1.29, p = 0.004). Quartile analysis revealed that patients in the highest uric acid quartile had more than three-fold higher mortality compared with the lowest quartile (OR 3.13, 95% CI 1.26–7.79, p = 0.014). Conclusions: Hyperuricemia independently predicts mortality and also demonstrates a significant dose–response relationship with adverse outcomes in CKD. The results support serum uric acid as a clinically meaningful biomarker for mortality risk grading in CKD populations.

Background: Combating antimicrobial resistance and developing dressings that match all aspects of wound healing will always be challenging. Methods: In this study, hydrogel membranes composed of sodium alginate (SA), polyvinyl alcohol (PVA), and Pluronic-f-127 (F-127) loaded with colistin (C) were formulated. The formulations were divided into two groups: group 1 (SA-PVA-C) and group 2 (SA-PVA-F127-C). Results: The membranes were characterized using multiple techniques, which confirmed component compatibility, physical cross-linking, an amorphous structure, and suitable surface morphology with acceptable porosity. Mechanical testing showed that both groups were suitable for wound-dressing applications. Differences in drug release across media (water, normal saline, and phosphate) were non-significant (p value > 0.05). Drug-loaded membranes (n = 3) from both groups showed antibacterial activity against multidrug-resistant Gram-negative Pseudomonas aeruginosa (ZOI = 20.33 ± 2.51 mm, 21.66 ± 2.08 mm). Conclusions: Overall, the developed hydrogel membranes (both group 1 and group 2) demonstrated promising in vitro potential as colistin delivery systems for wound infection management.

This investigation examined the long‐term impact of stimulant use, assessing systematic dysfunction of the nervous system and how these changes were reflected in the gene expression of two addiction‐related genes, SLC6A3 (dopamine transporter) and CARTPT (cocaine‐ and amphetamine‐regulated transcript). Study subjects included 100 men over the age of 18 who have used stimulants (crystal and Captagon) as well as a group of 30 men of the same age who were healthy. Blood samples were taken from each subject, and plasma levels of dopamine, serotonin, norepinephrine, and total protein were measured using enzyme‐linked immunosorbent assay (ELISA). Gene expression was analyzed in peripheral blood mononuclear cells (PBMCs) using quantitative reverse transcription–polymerase chain reaction (qRT‐PCR). Relative expression of SLC6A3 and CARTPT was calculated using the 2 ^−ΔΔCt method with GAPDH serving as an internal control. Stimulant users had significantly higher concentrations of plasma dopamine and norepinephrine compared to non‐users, while also having much lower levels of both plasma serotonin and total protein compared to controls ( p < 0.0001). qRT‐PCR showed that the expression of SLC6A3 and CARTPT was significantly increased in the stimulant group (5–7‐fold increase). These findings, which reflect both biochemical and gene expression level changes, indicate increased dopaminergic activity, decreased serotonergic activity, and changes in the neuropeptide pathways related to stress and reward due to chronic use of stimulants. Overall, the combination of the biochemical and gene expression data indicates that chronic crystal and Captagon users demonstrate significant systemic dysfunction. The significant changes in the levels of monoamines and the activation of the SLC6A3 and CARTPT genes indicate that these two genes could serve as peripheral biomarkers in assessing stimulant use disorder. These data give a mechanistic basis for developing new diagnostic and treatment methods based on dopaminergic and neuropeptide signaling pathways involved in the use of stimulants.

The purpose of this study is to evaluate the efficacy of copper carbonate (CuCO₃) nanoparticles in promoting wound healing in diabetic and non-diabetic mice. Diabetes mellitus is a prevalent and serious condition characterized by elevated blood glucose levels due to insufficient insulin production or the body’s impaired response to insulin. This condition frequently leads to complications such as diabetic wounds, which are difficult to heal due to poor circulation and neuropathy, posing significant challenges in patient care. Standardized wounds were created on the dorsal area of mice, divided into four groups (Non-Diabetic Control, Non-Diabetic CuCO₃-treated, Diabetic Control, and Diabetic CuCO₃-treated), and wound areas were measured over 14 days. Mice treated with CuCO₃ nanoparticles exhibited faster wound healing compared to their respective control groups, regardless of diabetic status. Molecular docking revealed that CuCO₃ showed favorable negative docking scores with selected receptor proteins such as VEGF (-6.946 kcal/mol), TGF-β (-5.314 kcal/mol), FGF (-4.926 kcal/mol), MMP9 (-4.355 kcal/mol), HIF-1α (-4.811 kcal/mol), and PKC-β II (-5.370 kcal/mol). It shows the best binding affinity with VEGF that promotes angiogenesis to the wound site. These findings with in-silico computational modeling demonstrate the potential of CuCO₃ nanoparticles to enhance wound healing in both diabetic and non-diabetic conditions, highlighting their promise in developing effective therapies for diabetic wound management.

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