Chia, Salvia hispanica L. is a flowering and an annual desert plant species which produces consumable small white and black seeds and has long association with human beings. Published research articles results showed that Chia is originating from south America, Mexico and now spreading to desert region. Chia as oil crop is getting an attractive cultivation demand in recent years because it can be grown for high nutrition values and to produce oil for food, and pharmaceutical and industrial sectors. The seeds of Chia are an excellent and proving a significant source of economic and health benefits which, helps in decreasing the different types of ailments such as, heart diseases, laxative, inflammation, reduce cholesterol levels, digestive system, blood pressure, blood sugar and intestinal health issues. The research interest on Chia has increased due to its numerous nutritional and health benefits to human beings and it has promising future in future studies and cultivation. The goal of this review was structured in three parts as ecological, traditional and pharmaceutical to search and analyzed the research articles available on S. hispanica through different electronic search engine data bases likewise, e-Marefa data base; google; google scholar, NIH (National Library of Medicine), PubMed and science direct covering period of 2000-2026. The key words such as cosmetics; diseases; ecology; food crop; folk medicine; health issues; phytochemicals; traditional values were used. The analysis of data would be helpful for researchers, environmental manager, farmer awareness, field management, pharmaceutical, agro industrial sectors engaged in regional and international levels.

Abstract Small extracellular vesicles (sEVs) orchestrate cell-cell communication, but the role of sEV signaling via mitochondria in perpetuating asthmatic airway inflammation is unknown. Myeloid-derived regulatory cells (MDRCs) control CD4 + T cell responses in asthma. We demonstrate that airway MDRC-derived sEVs from asthmatics mediate T cell receptor engagement and transfer of mitochondria that induce antigen-specific activation and polarization of Th17 and Th2 cells. sEV-dependent T cell activation and Th polarization were mediated by mitochondrial oxidant-dependent NF-κB signaling, which, when blocked, mitigated CD4 + T cell activation. Mitochondrial fission regulator, DRP-1, promoted mitochondrial packaging within MDRC-sEVs. Internalized sEVs co-localized with the polarized cytoskeleton and mitochondrial networks in recipient T cells. Intranasal transfer of mitochondria packaged sEVs enhanced allergic airway inflammation and Th polarization in a murine asthma model. Our studies indicate a previously unrecognized role for mitochondrial fission and sEV- mitochondria-mediated signaling in dysregulated T cell activation, Th polarization, and pathology in asthma.

Hidradenitis suppurativa (HS) is a debilitating and underdiagnosed inflammatory skin disease with limited therapeutic options due to an incomplete understanding of its molecular and immunopathogenic basis. Using an integrated multiomics approach, we delineate convergent pathways linking dysregulated autophagy, malodour, and pain in HS. Lesional tissues exhibited sustained autophagy repression, marked by increased expression and activation of mTOR and ZKSCAN3, reduced levels of autolysosome−promoting metabolites β−hydroxybutyrate and nicotinamide riboside, and accumulation of fructose−1,6−bisphosphate, a negative regulator of AMPK. Transcriptomic analyses identified cadaverine derivatives as key metabolic drivers of keratinocyte reprogramming, inducing gene networks associated with hyperproliferation, inflammation, fibrosis, nociception, and the characteristic carrion-like odour of HS. Concordantly, ATAC−seq revealed increased chromatin accessibility at loci encoding TRP channels and histamine receptors, consistent with heightened nociceptive signalling. Multi-layered proteomics, phospho-proteomics, kinomics, and spatial proteomics analyses, validated by high-resolution confocal imaging, demonstrated elevated phospho-mTOR (ser2448), ZKSCAN3, and p62, alongside reduced LAMP1, across keratinocytes and immune cell populations including CD4+ T cells, CD56+ NK cells, and CD68+ macrophages. Inhibition of mTOR normalized transcriptional programs and cytokine production linked to NLRP3 inflammasome, restoring tissue homeostasis. Collectively, these findings identify a metabolically reinforced mTOR−ZKSCAN3 axis in autophagy dysregulation and cadaverine-driven epithelial reprogramming as central mechanisms sustaining inflammation, pain, and fibrosis in HS. ### Competing Interest Statement The authors have declared no competing interest.

Novel preclinical models that better mimic the in vivo tumor microenvironment are essential to advance understanding of tumor biology and resistance/response to therapy. Herein, we report development of a novel ex vivo patient-derived three-dimensional lung tumor model (3D-LTM) for use in evaluating response to therapy. With this model system that maintains cell-cell interactions and tissue architecture, we observed heterogeneity of response to immune checkpoint inhibitors (ICI), as noted in non-small cell lung cancer (NSCLC) patients, and defined gene signatures associated with response. Spatial transcriptomics identified positive correlation of CD8+ T cell populations, CD4+ memory T cells, mast cells, NK cells, naive B cells, endothelial cells and non-classical monocytes with response status, and negative correlation of macrophages with response status. Pathway analysis of gene expression showed that chemokine signaling related pathways were activated in responder 3D-LTM tissues, whereas suppression of antigen presentation-related pathways and activation of Treg differentiation-related pathways were associated with non-responder 3D-LTM tissues. Additionally, the abundance of dividing T cells and naive CD8+ T cells differentially correlated with T cell cytotoxicity gene signatures based on response status. Thus, this model may provide utility for rapid testing of therapeutic outcomes and biomarker development.

Arsenicals and other vesicant chemical weapons are highly reactive, toxic substances capable of causing severe and painful blistering and inflammation following topical exposure. These effects can also lead to a wide range of systemic organ damage resulting in significant morbidity and death. Two major proteins, Bromodomain 4 (BRD4) and receptor-interacting protein kinase-3 (RIPK3), are associated with the arsenicals-mediated inflammatory and tissue wounding responses in the skin and in other organs. The downstream pathway of these two proteins also leads to induction of various cytokines and chemokines, including interleukin-6 (IL-6). Our medicinal chemistry efforts were focused on the identification and lead optimization of potent small-molecule dual inhibitors of BRD4 and RIPK3with consequent dampening of the activation of IL-6. The initial hit compound, 5a was identified from a high-throughput screening (HTS) campaign of 4 K compounds which inhibited all three proteins, BRD4 (IC50 = 22.40 μM), RIPK3 (IC50 = 0.56 μM), and IL6 (IC50 = 12.60 μM), and had moderate metabolic stability (MLM t1/2 = 23.7 min, HLM t1/2 = 14.6 min), but was insoluble at pH 7.4 (solubility <1 μM). A structure-activity relationship (SAR) campaign led to the discovery of a new potent inhibitor, 12 m, 6-[[4-(2-fluoro-N-methyl-anilino)pyrimidin-2-yl]amino]-3-methyl-1,4-dihydroquinazolin-2-one, which had improved potency against BRD4 (IC50 = 5.91 μM), RIPK3 (IC50 = 1.32 μM), and IL6 (IC50 = 0.22 μM), and similar metabolic stability (MLM t1/2 = 11.0 min, HLM t1/2 = 33.2 min). Herein, we report a hit-to‑lead optimization study that led to the discovery of novel BRD4 and RIPK3 dual inhibitors.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Warfare arsenicals are potent blistering agents and cause severe inflammation following their skin exposure. Data from our group (unpublished) show that these chemicals act by activating bromodomain-4 and RIPK signaling. To develop a dual inhibitor of the bromodomain-containing protein 4 (BRD4) and the receptor-interacting serine/threonine-protein kinase 3 (RIPK3), we conducted a high-throughput screening (HTS) campaign for inhibitors of BRD4 and RIPK3 activity to identify anti-inflammatory agent candidates that could alleviate arsenicals-induced injury. Our primary assays were adapted to 384-well microplates and used to screen a collection of 4074 compounds consisting of FDA-approved drugs and other bioactive compounds. The BRD4 primary screen had an average Z' value of 0.93 and a signal-to-background (S/B) ratio of 3018, while the RIPK3 primary screen had an average Z' value of 0.86 and S/B = 12.6. A counter screen assay was used to ensure activity was due to target engagement and not assay interference. Hits that inhibited BRD4 binding by > 54.6 % and kinase activity by > 22.4 % in the primary screen and were not statistical outliers in the counter screen assays, were confirmed in concentration-response format. Hits were also tested in a cell-based IL-6 assay to determine corresponding inflammatory inhibitory activity. Eighteen compounds were active in both BRD4 and RIPK3 assays, of which three displayed IC50 values < 10 μM with promising IL-6 inhibition. These compounds could serve as good candidates for further chemical optimization for the development of small-molecule medical counter measure agents against arsenicals.

Skin exposure to arsenicals such as lewisite and phenylarsine oxide leads to severe cutaneous damage. Here, we characterized the molecular pathogenesis of skin injury caused by additionally structurally distinct warfare arsenicals including diphenylchlorarsine (DPCA), diphenylcyanoarsine (DPCYA), diethylchloroarsine (DECA). Cutaneous exposure to DPCA/DPCYA showed marked increase in skin erythema and edema at 6 and 24 h followed by scar formation at 72 h, while DECA did not produce such visual injuries in mouse skin. Clinical observations showed significant increase in Draize score and skin bi-fold thickness in a time-dependent manner. DPCA or DPCYA-exposed skin histology revealed highly inflamed hypodermal areas with infiltrated immune cells at 6 and 24 h, however, epidermal cell necrosis was seen at 72 h. Significantly high number of macrophage infiltration observed at 6 h, whereas peak neutrophil infiltration occurred at 72 h. Number of micro-blisters also increased. However, these effects were nonsignificant following topical DECA exposure. RT-PCR confirmed augmented inflammatory responses in the skin challenged with both DPCA/DPCYA, which accompanied increased ROS and unfolded protein response (UPR) signaling. DECA also increased ROS with changes in UPR. Disrupted tight (Yap/ZO-1) and adherens (Yap/α-Catenin) junction proteins underlie time-dependent apoptotic cell death of epidermal keratinocytes. Thus, these studies identify arsenicals-manifested signaling pathways similar to those of lewisite.

Lewisite, a chemical warfare agent, induces severe skin injury by oxidative stress and endoplasmic reticulum (ER) dysfunction, necessitating innovative antidote strategies. This study developed chitosan nanoparticle-loaded foam formulations for rapid skin decontamination and sustained topical delivery of 4-phenylbutyric acid (4-PBA), an ER stress-reducing chaperone. Nanoparticles were synthesized via ionic gelation using low (LMW) and medium molecular weight (MMW) chitosan. The optimized formulations, N31 (LMW) and N35 (MMW), achieved drug loadings of 5.04 % and 10.09 % w/w, particle sizes of 141.88 ± 26.31 nm and 176.10 ± 36.97 nm, monodisperse distributions (PDI < 0.3), high entrapment efficiency (>93 %) and good stability with zeta potential of -16.67 mV and -19.37 mV, respectively. Incorporation into foam enabled both effective decontamination (>70 % efficiency) and sustained 4-PBA delivery. In vitro release studies demonstrated sustained drug release over 24 h. Permeation studies using dermatomed human skin revealed that nanoparticle formulations significantly reduced 4-PBA delivery: N35 decreased permeation by 38.4 % (214.35 ± 16.6 µg/cm2 vs. 348.10 ± 5.37 µg/cm2 for free 4-PBA), while N31 reduced it by 81.35 % (64.90 ± 6.89 µg/cm2). Both formulations retained efficacy in PAO challenged skin, with N35 delivering 158.54 ± 53.93 µg/cm2 and N31 138.25 ± 14.72 µg/cm2 over 24 h. Furthermore, in vivo studies showed that the optimized formulation with N35 chitosan (4-PBA N35 + N-acetyl cysteine (NAC)) significantly protects against PAO-induced skin injury and inflammatory cytokine production in Ptch1+/-/SKH-1 hairless mice. Thus, the translational feasibility and effective treatment by the foam formulated 4-PBA N35 + NAC against arsenical-induced skin injury is demonstrated.

The SCN9A gene, a critical regulator of pain perception, encodes the voltage-gated sodium channel Nav1.7, a key mediator of pain signal transmission. This study conducts a multimodal assessment of SCN9A, integrating genetic variation, structural architecture, and molecular dynamics to elucidate its role in pain regulation. Using advanced computational methods, I-TASSER simulations generated structural decoys of the SCN9A homology domain, producing an ensemble of conformational states. SPICKER clustering identified five representative models with a C-score of −3.19 and TM-score of 0.36 ± 0.12, reflecting moderate structural similarity to experimental templates while highlighting deviations that may underpin functional divergence. Validation via ProSA-web supported model reliability, yielding a Z-score of −1.63, consistent with native-like structures. Central to the analysis was the R1150W non-synonymous variant, a potential pathogenic variant. Structural modeling revealed localized stability in the mutant conformation but disrupted hydrogen bonding and altered charge distribution. Its pathogenicity was underscored by a high MetaRNN score (0.7978498) and proximity to evolutionarily conserved regions, suggesting functional importance. Notably, the variant lies within the Sodium-Ion-Transport-Associated Domain, where perturbations could impair ion conductance and channel gating—mechanisms critical for neuronal excitability. These findings illuminate how SCN9A variants disrupt pain signaling, linking genetic anomalies to molecular dysfunction. While computational insights advance mechanistic understanding, experimental validation is essential to confirm the variant’s impact on Nav1.7 dynamics and cellular physiology. By refining SCN9A’s molecular blueprint and highlighting its therapeutic potential as a target for precision analgesics, this work provides a roadmap for mitigating pain-related disorders through channel-specific modulation. Integrating structural bioinformatics with functional genomics, this study deciphers SCN9A’s role in pain biology, laying the groundwork for novel strategies to manage pathological pain.

Background: Lewisite, a potent chemical warfare agent, induces rapid and progressive cutaneous damage, necessitating treatment strategies that offer both immediate decontamination and prolonged therapeutic action. This study aimed to develop and evaluate a composite topical formulation comprising 4-phenylbutyric acid (4-PBA)-loaded emulsomes embedded within a foam vehicle to address both aspects of vesicant-induced skin injury intervention. Methods: Emulsomes composed of a stearic acid–cholesterol solid lipid core stabilized by a lecithin shell were prepared via thin film hydration and optimized by varying lipid ratios and drug loading parameters. Formulations were characterized for drug loading, particle size, and zeta potential. Physicochemical compatibility was assessed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses. Stability was evaluated under accelerated refrigerated (25 °C/60% RH) and room temperature (40 °C/75% RH) conditions. The optimized formulation was incorporated into a foam base and evaluated for decontamination efficiency, drug release kinetics, in vitro permeation, and in vivo efficacy. Results: The selected formulation (E2) exhibited high drug loading (17.01 ± 0.00%), monodisperse particle size (PDI = 0.3 ± 0.07), and stable zeta potential (−40 ± 1.24 mV). FTIR and DSC confirmed successful encapsulation with amorphous drug dispersion. The emulsome-foam demonstrated dual functionality: enhanced decontamination (66.84 ± 1.27%) and sustained release (~30% over 24 h), fitting a Korsmeyer–Peppas model. In vitro permeation showed significantly lower 4-PBA delivery from E2 versus free drug, confirming sustained release, while in vivo studies demonstrated therapeutic efficacy. Conclusions: This emulsome-foam system offers a promising platform for topical treatment of vesicant-induced skin injury by enabling both immediate detoxification and prolonged anti-inflammatory drug delivery.

Cutaneous overexposure to ultraviolet radiation has a variety of deleterious effects. The extent to which dietary factors are effective at moderating UV damage is a significant issue. Grapes contain phytochemicals that protect against excessive UV damage. Components of grapes, in particular resveratrol, proanthocyanidins, and cyanidin-3-glucoside, are receiving considerable attention for their photoprotective actions because of their lack of toxicity, abundance, and low cost. Resveratrol and proanthocyanidins are potent antioxidants that interfere with signal transduction and immunosuppressive pathways activated by UV radiation, which are responsible for its harmful effects. Studies in humans provide a rationale for their further development as a novel method of photoprotection.

IntroductionArsenicals like lewisite are highly toxic vesicant chemical warfare agents that cause severe skin damage and systemic inflammation. Exposure activates cytokine release, leading to pulmonary injury, including edema, hemorrhage, and in severe cases, Bronchiolitis Obliterans Syndrome (BOS), marked by airway fibrosis and narrowing. The only approved treatment, British anti-lewisite (BAL), has limitations due to toxicity and field administration challenges. BRD4, a BET family protein, regulates inflammatory gene expression, and its inhibition has shown therapeutic potential. CPI-0610 (Pelabresib), a selective BRD4 inhibitor, is currently being explored for its anti-fibrotic and anti-inflammatory effects.MethodsIn a murine model, we evaluated the therapeutic potential of CPI-0610 in mitigating lewisite-induced pulmonary damage. Mice were exposed to a single cutaneous dose of lewisite to induce systemic lung injury. Following exposure, one group of mice received CPI-0610 treatment, while a control group remained untreated. Lung tissues were harvested for molecular and histological analysis. The expression of inflammatory and fibrotic markers, including interleukin-6 (IL-6) and alpha-smooth muscle actin (α-SMA), was quantified via RT-PCR and immunohistochemistry.ResultsTreatment with CPI-0610 significantly reduced the expression of IL-6 and α-SMA in lung tissues of lewisite-exposed mice compared to untreated controls. Histological analysis revealed reduced signs of inflammation, extracellular matrix deposition, and fibrotic remodeling in the CPI-0610 group. These findings indicate a protective effect of BRD4 inhibition on arsenical-induced lung injury.DiscussionOur study provides the first experimental evidence that BRD4 inhibition via CPI-0610 attenuates the development of pulmonary fibrosis following cutaneous lewisite exposure in mice. These results suggest that targeting BRD4 signaling can effectively reduce inflammation and fibrotic progression in the lungs. Given CPI-0610’s favorable clinical safety profile, it holds promise as a novel therapeutic strategy for treating arsenical-induced pulmonary complications, potentially improving outcomes where current countermeasures like BAL fall short. Further studies are warranted to explore its mechanism of action and therapeutic efficacy in broader exposure models.

Skin has the capacity to produce and metabolize melatonin into biologically active metabolites. These metabolites exert phenotypic activities through receptor-dependent and receptor-independent action, including direct antioxidant activity, interaction with regulatory proteins, and regulation of mitochondrial function. They can act on G-protein-coupled melatonin receptors (MT1 and MT2) as well as nuclear aryl hydrocarbon receptor and peroxisome proliferator-activated receptor γ receptors. These metabolic pathways, together with receptor- and nonreceptor-mediated phenotypic activities of its intermediates, has been identified as a cutaneous melatoninergic system. Its pharmacological modulation and topical application of melatonin or its metabolites can be used to prevent and treat skin disorders and cutaneous aging.

This study employed a multiomic approach to investigate retinal tissue damage following direct ocular exposure (DOE) to vesicants (VSs)-namely, nitrogen mustard (NM) and lewisite (Lew). We explored both the acute and chronic stages of retinal injury by assessing functional, structural, and molecular changes. C57BL/6 mice were used to measure scotopic and photopic electroretinograms (ERGs) and to analyze TUNEL-positive retinal cells. Global retinal proteomics was conducted to identify common and unique signaling pathways. In addition, we performed targeted metabolomic and lipidomic analyses of retinal tissue to uncover significant metabolic changes. Our results demonstrated remarkable declines in ERG amplitudes at 2 and 4 weeks post-exposure, accompanied by an increase in TUNEL+ retinal cells in response to DOE to both VSs. Our proteomic analysis revealed chronic oxidative stress, mitochondrial dysfunction, elevated RXR signaling, and increased levels of 28 proteins. Moreover, we observed a decline in the KEGG phototransduction pathways, along with the downregulation of photoreceptor-specific proteins, in response to both VSs. Consistent with the proteomic findings, targeted metabolomics identified a decline in phototransduction and steroid hormone biosynthesis, along with increases in D-amino acid and purine metabolism, as well as lysine degradation. These changes were associated with a GSSG/GSH ratio of 2.6, confirming the proteomic data on oxidative stress. Furthermore, lipidomic analysis revealed an increase in oxidative lipid levels, accompanied by a 3.4-fold increase in phosphatidylserine (PS), suggesting apoptotic cell death and a reduction in fatty acids (FAs). In conclusion, exposure to both VSs induced progressive retinal damage, altering major metabolic pathways and dysregulating lipid metabolism. Future studies should focus on identifying the responses of individual neuronal cell types to DOE to VSs to develop cell-specific countermeasures.

Background Kidney failure with replacement therapy (KFRT) such as dialysis or transplantation represents a severe stage of chronic kidney disease (CKD) and poses a major global health burden. Although many CKD cases are diagnosed in the earlier stages, the greatest risk occurs when CKD progresses to KFRT. Despite its considerable financial and imposing impact on public health, there is a notable gap in international policies addressing CKD and KFRT. To bridge this gap and help policy makers and health systems effectively tackle the public health challenge of KFRT, a better understanding of the disease burden is essential. Thus, this analysis aims to provide a detailed overview of the global prevalence of KFRT and its associated aetiologies with estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2023. Methods This study defined KFRT as individuals on maintenance dialysis for 90 days or more or those who have undergone a kidney transplant, aligning with the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Renal registries served as the primary data sources. Prevalence and underlying aetiology estimates (type 1 diabetes, type 2 diabetes, hypertension, glomerulonephritis, and other causes) were generated with DisMod-MR 2.1, an epidemiological Bayesian mixed-effects meta-regression modelling tool. Both all-age and age-standardised estimates were reported and accompanied with 95% uncertainty intervals (UIs). Findings In 2023, the number of global cases of KFRT was 4 center dot 59 million (95% UI 4 center dot 17-5 center dot 08) for both sexes and all ages, with an age-standardised prevalence of 50 center dot 7 (46 center dot 1-56 center dot 0) per 100 000 population. Over the past three decades, there has been a steady increase in KFRT prevalence globally. The highest prevalence was found in the GBD high-income regions, while the lowest was observed in sub-Saharan Africa. KFRT prevalence was generally higher in countries classified within the World Bank's high-income and upper-middle-income groups, while lower prevalence was more common in countries within the World Bank's low-income and lower-middle-income groups. Additionally, a pronounced sex disparity was identified, where male dialysis and transplant prevalence estimates were consistently higher than those for females in most countries. Type 2 diabetes and hypertension were among the leading associated aetiologies of KFRT globally. From 1990 to 2023, the all-age and age-standardised prevalence estimates across the ascribed aetiologies increased for KFRT, with the largest increases associated with type 2 diabetes and hypertension. Interpretation KFRT affects approximately 5 million people globally, with high treatment and mortality costs. Our study unveiled considerable geographical variation in KFRT prevalence, which should be seen as indicators of healthcare system opportunities. As the prevalence of the leading aetiologies of KFRT-type 2 diabetes and hypertension-continues to rise, there is a crucial need to prioritise the development and implementation of cost-effective strategies aimed at preventing CKD and its progression to KFRT, particularly in low-resource settings. These preventive efforts must happen in tandem with efforts to expand capacity for dialysis and transplant services. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd.

More than 20% of the population across the world is affected by non-communicable inflammatory skin diseases including psoriasis, atopic dermatitis, hidradenitis suppurativa, rosacea, etc. Many of these chronic diseases are painful and debilitating with limited effective therapeutic interventions. This study aims to identify common regulatory pathways and master regulators that regulate the molecular pathogenesis of inflammatory skin diseases. We designed an integrative systems biology framework to identify the significant regulators across several diseases. Network analytics unraveled 55 high-value proteins as significant regulators in molecular pathogenesis which can serve as putative drug targets for more effective treatments. We identified IKZF1 as a shared master regulator in hidradenitis suppurativa, atopic dermatitis, and rosacea with known disease-derived molecules for developing efficacious combinatorial treatments for these diseases. The proposed framework is very modular and indicates a significant path of molecular mechanism-based drug development from complex transcriptomics data and other multi-omics data.

Being highly toxic and a quick-acting vesicant, even small amounts of lewisite if not decontaminated immediately are rapidly absorbed into systemic circulation via skin exposure, leading to acute poisoning and death. The skin is the first major target to such chemical weapons. Although the stratum corneum provides a barrier lewisite being a lipophilic molecule that readily permeates this barrier. This necessitates, making early and thorough decontamination prior to manifestation of adverse effects. For this, we aimed to decontaminate skin using an antidote-loaded topical foam, followed by treating local and systemic toxicity using the same formulation. Successful incorporation of 1% antidote into a decontaminating topical foam and the delivery of 1.78 ± 0.21 µg/sq cm into dermatomed porcine ear skin within five minutes of application was achieved. Decontamination after five minutes of exposure (88.43%), as well as prolonged exposure (94.53%; 3 h) to methyl salicylate, a warfare chemical simulant, was demonstrated. The developed formulation demonstrated the potential to back-extract simulant from skin tissue but could not purge simulant penetrated systemic circulation. However, systemic delivery of the antidote was demonstrated, establishing the potential to treat the toxicity caused by the remnant warfare chemicals. Graphical Abstract