Sher-I-Kashmir Institute of Medical Sciences

Evidence of an association between breathlessness and quality of life from population-based studies is limited. We aimed to investigate the association of both physical and mental quality of life with breathlessness across several low-, middle- and high-income countries.

We analysed data from 19 714 adults (31 sites, 25 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We measured both mental and physical quality of life components using the SF-12 questionnaire, and defined breathlessness as grade ≥2 on the modified Medical Research Council scale. We used multivariable linear regression to assess the association of each quality-of-life component with breathlessness. We pooled site-specific estimates using random-effects meta-analysis.

Both physical and mental component scores were lower in participants with breathlessness compared to those without. This association was stronger for the physical component (coefficient = -7.59; 95%CI -8.60, -6.58; I² = 78.5%) than for the mental component (coefficient = -3.50; 95%CI -4.36, -2.63; I² = 71.4%). The association between physical component and breathlessness was stronger in high-income countries (coefficient = -8.82; 95%CI -10.15, -7.50). Heterogeneity across sites was partly explained by sex and tobacco smoking.

Quality of life is worse in people with breathlessness, but this association varies widely across the world.

Hypoxia-induced brain damage can cause consciousness, memory failure and death. HK2 and TPI1 were investigated to see how they change hypoxia sensitivity in neurons and non-neurons. Hypoxia sensitivity is determined by the differential overexpression of both important glycolytic enzymes in neuronal and non-neuronal cells. C6 glioma cells expressed greater HK2 and TPI1 protein than neuro 2A cells, which were more sensitive to hypoxia-induced cell death by MTT and lactate dehydrogenase leakage assay. After 48 h of hypoxia, C6 glioma cells displayed substantial protein upregulation of HK2 and TPI1 glycolytic proteins but not mRNA. Hypoxia did not raise HK2 and TPI1 mRNA transcription, pointing at post-transcriptional protein regulation. Using di-cistronic and promoter-less di-cistronic assays, we discovered significant IRES regions in HK2 and TPI1 mRNA's 5'UTR, more active in C6 glioma cells with polypyrimidine tract binding (PTB) protein. We concluded that non-neuronal cells varied in HK2 and TPI1 overexpression, altering their vulnerability to hypoxia-induced cell death. Adjusting HK2, TP1 and PTB levels may prevent hypoxia-induced brain cell death. These results offer new information on glycolytic enzyme modulation under hypoxia, crucial for comprehending cell survival in hypoxic situations. This could affect situations like neurodegenerative illnesses or ischaemic injuries, where hypoxia-induced cell death is crucial.

Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from complex interactions between genetic, environmental, and immunological factors, particularly the dysregulation of T helper (Th) cell subsets. While Th2 responses have been central to AD research, evidence highlights the role of Th9 cells and their signature cytokine, interleukin-9 (IL-9), in allergic inflammation. However, the involvement of the Th9/IL-9 axis in AD remains insufficiently characterized. This study investigates the role of the Th9/IL-9 axis in AD through an integrated clinical, immunological, and molecular approach. The study comprised a total of 89 subjects, consisting of 54 AD cases and 35 healthy controls. Disease severity and allergen sensitivity were assessed using SCORAD scores and skin prick testing, respectively. PU-1 mRNA was quantified using real-time PCR. Th9 cell frequency was determined through flow cytometry, vitamin D levels were measured by chemiluminescence, and total IgE and IL-9 levels were estimated using ELISA. AD patients demonstrated a significant increase in circulating Th9 cell frequency (11.5 ± 0.3% vs. 5.0 ± 0.5%, p < 0.0001), PU.1 mRNA expression with an average 2.5-fold upregulation (p < 0.001), and elevated serum IL-9 concentrations (18.6 ± 6.3 pg/mL vs. 8.3 ± 1.9 pg/mL, p < 0.0001) compared to healthy controls. Stratified analysis revealed significant associations of PU.1 mRNA and IL-9 levels with rural residence, vitamin D deficiency, and peripheral eosinophilia (p < 0.05). Allergen sensitivity, as determined by skin prick testing, was positive in 50% of AD patients, and 66.7% exhibited elevated total serum IgE levels. Our findings underscore the involvement of the Th9/PU.1/IL-9 axis in the immunopathogenesis of AD. The observed upregulation of Th9 cell frequency, PU.1 expression, and IL-9 levels suggests a contributory role of Th9-mediated pathways in disease development and severity. These results provide a foundation for future studies investigating the dynamic crosstalk between Th9 cells, other immune cell subsets, and epidermal components, with the aim of identifying novel immunomodulatory targets for precision therapy in AD.