Superoxide dismutase 3 (SOD3) is an extracellular antioxidant enzyme with an emerging role in the regulation of inflammatory responses; however, its involvement in type 2 cytokine interleukin-4 (IL-4)/interleukin-13 (IL-13)-associated inflammation remains poorly understood. In this study, we investigated the effects of SOD3 on IL-4/IL-13-induced inflammatory responses in human keratinocytes (HaCaT) and bronchial epithelial cells (BEAS-2B). SOD3 significantly suppressed IL-4/IL-13-induced periostin expression at both the mRNA and protein levels in both cell types. Mechanistically, SOD3 interacted with the IL-4 receptor α (IL-4Rα) and attenuated activation of the downstream Janus kinase/signal transducer and activator of transcription 6 (JAK/STAT6) pathway, resulting in reduced periostin expression. Periostin knockdown and recombinant periostin add-back experiments further demonstrated that SOD3 reduced the phosphorylation of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), largely through suppression of periostin. Consistent with these findings, SOD3 decreased the expression of periostin-associated mediators, including vascular endothelial growth factor (VEGF), thymic stromal lymphopoietin (TSLP), transforming growth factor-β (TGF-β), and matrix metalloproteinases (MMPs), and attenuated periostin-induced production of the pro-inflammatory cytokines tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Collectively, these findings suggest that SOD3 attenuates IL-4/IL-13-driven epithelial inflammation, at least in part, through modulation of the IL-4Rα/JAK/STAT6/periostin axis and downstream NF-κB/MAPK signalling pathways, and suggest its potential as a therapeutic candidate for type 2 inflammatory diseases.
Alzheimer’s disease (AD) is characterized by several pathological processes including amyloid-β (Aβ) accumulation, Tau hyperphosphorylation, oxidative stress, synaptic dysfunction, neuroinflammation, mitochondrial impairment and loss in neuronal stability. This review assessed the reported neuroprotective potential of crude extracts of different Artemisia species and artemisinin with its derivatives in AD. It focuses on targets, mechanisms, observational markers and functional effects validated by Artemisia extracts and compounds like artemisinin, artemisinin B, artemether, artesunate and dihydroartemisinin in experimental AD models. A comprehensive review of studies was conducted including in vitro, in vivo and in silico research on Artemisia extracts and derivatives focusing on their effects on various pathological processes related to brain. Results showed crude extracts from 17 Artemisia species, which have been reported with considerable neuroprotective effects. Artemisinin and derivatives deliver neuroprotection via targeted mechanisms and effecting observational markers with varying functional outcomes. However, differences in AD models, administration routes, doses, extract composition and outcomes limit direct efficacy comparisons. Hence, direct comparisons of efficacy among Artemisia extracts, artemisinin and its derivatives should be interpreted cautiously. Future inquiries should highlight standardized preparations, brain exposure and pharmacokinetics, mechanistic validation, long-term safety and well-designed comparative and clinical trials to evaluate their potential for AD treatment.
Although skeletal muscle decline is implicated in cardiometabolic diseases, the precise mechanistic pathways and the prognostic superiority of relative over absolute handgrip strength for cardiometabolic multimorbidity (CMM) remain incompletely quantified. This nationally representative cross-sectional study included 6,839 middle-aged and older Chinese adults from the 2015 China Health and Retirement Longitudinal Study. We evaluated the associations of relative handgrip strength (RHGS) and absolute grip strength with CMM using multivariable logistic and Poisson regressions. Causal mediation analysis was employed to dissect the pathways linking RHGS to CMM. Results demonstrated that a 1-standard deviation decrease in RHGS was robustly associated with a 68
Midkine (MDK) and thyroid hormone receptor beta (THRB) have each been implicated separately in metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). THRB drives hepatic fatty-acid beta-oxidation (FAO). We tested whether MDK and the THRB-linked FAO program are reciprocally related in human liver tissue. We analyzed two independent human cohorts on different platforms. TCGA-LIHC provided 374 tumor and 50 adjacent non-tumor RNA-seq samples. GSE164760 provided 53 NASH-HCC, 74 NASH, 29 non-tumoral NASH adjacent to HCC, 8 cirrhotic and 6 healthy microarray samples. We quantified MDK, THRB and a curated 21-gene hepatic FAO composite score. Tests included Mann-Whitney, Spearman, Kruskal-Wallis, Jonckheere-Terpstra and genome-wide correlation with Benjamini-Hochberg correction. MDK was higher in tumor tissue in both cohorts (TCGA-LIHC p = 1.0 × 10-24, GSE164760 p = 8.1 × 10-13). The FAO composite was correspondingly lower (p = 7.0 × 10-10 and p = 7.1 × 10-6). THRB itself was lower in GSE164760 (p = 3.9 × 10-3) but not in TCGA-LIHC (p = 0.509). MDK correlated negatively with THRB and with the FAO composite in both cohorts. The strongest association was MDK versus FAO composite (rho=-0.45 in each cohort). Within-group analysis showed that the THRB to FAO composite correlation persisted in almost every subgroup. The MDK correlations weakened in three smaller subgroups. Across the five GSE164760 disease states, MDK, THRB and the FAO composite each differed significantly (Kruskal-Wallis p < 10−5) and each followed a significant monotonic trend (Jonckheere-Terpstra one-sided p < = 1.5 × 10-3). A reciprocal MDK-high and FAO-low transcriptional signature is reproducible across two independent human cohorts and across the MASH-to-HCC spectrum. These human tissue data support THRB agonism as a candidate therapeutic rationale in MASH-HCC that warrants prospective validation.
A mixture of lactonic and acidic sophorolipids exerted concentration-dependent cytotoxicity against human breast ductal adenocarcinoma (MCF-7) cells, with an IC₅₀ of 82.54 µg/mL as determined by resazurin assay. Phase-contrast microscopy revealed morphological alterations including cell swelling, loss of adhesion, and impaired membrane integrity. Flow cytometry analysis demonstrated cell cycle arrest in the S phase, mitochondrial membrane depolarization, and a predominance of necrosis-like cell death at higher concentrations. Transcriptional profiling by RT-qPCR identified overexpression of CDKN1A, GADD45A, ERN1, and BBC3, alongside repression of ACTB and GAPDH, indicating activation of DNA damage and stress-response pathways, endoplasmic reticulum stress, structural collapse, and metabolic dysfunction. Collectively, these findings demonstrate that sophorolipids induce mitochondrial and endoplasmic reticulum stress, culminating in homeostatic failure and cell death in MCF-7 cells, positioning these biosurfactants as promising candidates for the development of natural antiproliferative therapies.
