Search Results (565)

Background/Objectives: Macrophages polarized into M1 and M2 phenotypes differentially regulate immune and drug responses. Despite their distinct functional roles, differences in UDP-glucuronosyltransferase (UGT) expression and enzymatic activity between M1 and M2 macrophages remain poorly understood. This study aimed to characterize differential UGT expression in M1 and M2 macrophages and to elucidate how UGT-mediated prostaglandin E₂ (PGE₂) glucuronidation modulates macrophage inflammatory responses. Methods: THP-1 cells were chemically differentiated into macrophages (M0) and subsequently polarized into M1 and M2 phenotypes. UGT expression profiles were assessed using RT-PCR, quantitative RT-PCR (qRT-PCR), and Western blot. UGT activity was compared by quantifying glucuronide metabolites derived from UGT-specific substrates using LC-MS/MS, along with measurement of free PGE₂ and PGE₂-glucuronide by ELISA. Pro-inflammatory cytokine expression and secretion in M1 macrophages were quantified using qRT-PCR and ELISA. Results: Expression of UGT1A1, UGT1A4, UGT1A5, UGT1A9, and UGT2B7 were markedly higher in M1 compared with M2 macrophages at both the mRNA and protein levels. Enhanced UGT activity in M1 macrophages was reflected by increased formation of estradiol-3-glucuronide and naloxone-3-glucuronide (both p < 0.01) and was attenuated in a concentration-dependent manner by diclofenac. Furthermore, PGE₂ glucuronidation was more pronounced in M1 macrophages, and inhibition of UGTs with atazanavir reduced PGE₂-glucuronide formation and pro-inflammatory cytokine production, including IL-1β, IL-6, and TNF-α. Conclusion: UGT-mediated PGE₂ glucuronidation in M1 macrophages contributes to the regulation of pro-inflammatory cytokine production. Collectively, these findings support a role for UGTs as modulators of inflammatory signaling, with differential expression and activity between M1 and M2 macrophages. Full article

Background/Objectives: The neutrophil-to-lymphocyte ratio (NLR) is an emerging inflammatory biomarker associated with various metabolic disorders, including type 2 diabetes mellitus (T2DM). While poor glycemic control is linked to increased risk of complications, the relationship between glycemic status and NLR remains insufficiently characterized. This study aimed to assess the association between NLR and glycemic control in T2DM patients by comparing those with good glycemic control (GGC; HbA1c ≤ 7%) and poor glycemic control (PGC; HbA1c ≥ 7.1%). Methods: A retrospective cross-sectional study was conducted on 2907 T2DM patients from a tertiary care center. Patients were categorized into GGC (n = 1500) and PGC (n = 1407) groups based on HbA1c values. The mean age of participants was 53.53 ± 18.86 years in the GGC group and 54.31 ± 18.40 years in the PGC group, with comparable sex distribution between groups. Data were retrieved from electronic medical records and NLR was calculated using complete blood counts. Descriptive statistics were computed, and group comparisons were performed using Mann–Whitney U and independent t-tests. Spearman correlation and receiver operating characteristic (ROC) analysis were also performed. A p-value < 0.05 indicated significance. Results: The PGC group exhibited significantly higher mean NLR (3.96 ± 4.53) compared to the GGC group (3.23 ± 3.80) (p < 0.001). Median and interquartile range values confirmed this difference, and both parametric and non-parametric analyses supported the findings. Spearman correlation demonstrated a weak but statistically significant association between HbA1c and NLR (r = 0.101, p < 0.001). ROC analysis showed limited discriminatory ability of NLR (AUC = 0.560). Exploratory CRP results further suggested a link between inflammation and impaired glycemic control. Conclusions: NLR was significantly elevated in T2DM patients with moderate-to-poor glycemic control. This suggests that NLR may serve as a simple, cost-effective, and accessible marker of systemic inflammation and glycemic status. However, the effect size was small, and its discriminatory ability was limited, indicating that NLR should be interpreted as a supportive marker rather than a standalone clinical tool. Full article

Chronic, dysregulated inflammation contributes to colitis-associated colorectal cancer (CRC), and the cGAS–STING pathway represents a central but therapeutically challenging node because both insufficient and excessive STING activity can be pathogenic. Here, we integrate AlphaFold3 (AF3) receptor modeling, diffusion-based docking, and explicit-solvent molecular dynamics (MD) simulations to characterize how the marine briarane diterpenoid excavatolide B (ExcB) engages the human STING (hSTING) cyclic dinucleotide (CDN)-binding cleft. The structural integrity of the AF3 hSTING model was validated through both intrinsic confidence scores (pLDDT, PAE) and comparative benchmarking against experimental CTD structures (PDB: 4EF5, 6A05). Notably, the local geometries of key pocket-defining residues—including His157, Tyr167, and Thr263—remained consistent with established crystallographic data. Across three independent 100 ns MD replicas, ExcB exhibits a consistent spatial progression from an entrance-proximal pose at the solvent-accessible rim of the cleft (Site-2) to a more embedded, non-canonical corridor on the Cys148-adjacent side (Site-2′). Distance and contact analyses support a predominantly non-covalent within-cleft mechanism and do not indicate a persistent approach to the literature-reported covalent regime near Cys91. Residue-level profiling over the stabilized sampling window defines a reproducible corridor “contact signature” and reveals within-cavity sub-pose diversity rather than a single rigid bound pose. Mechanistically, competitive docking of the native agonist cGAMP to ExcB-conditioned receptor snapshots yields consistently less favorable docking outcomes in ExcB-conditioned conformations than docking to the native/open receptor; retaining ExcB coordinates does not further penalize cGAMP, supporting a receptor-reshaping (conformational conditioning) component rather than persistent static steric clash. Our findings characterize ExcB as a non-covalent modulator targeting a cryptic pocket within the STING CDN-binding cleft, establishing a structural basis for targeted mutagenesis and structure-activity relationship (SAR) studies. Full article

Gingival inflammation represents one of the most prevalent oral inflammatory conditions worldwide and remains a major contributor to oral morbidity. While its classical etiologies are well established, less attention has been paid to inflammatory responses that arise secondary to pulpal injury and tissue damage. Experimental models that allow controlled evaluation of these responses may provide relevant insight into pulp-associated gingival inflammatory processes. Current pharmacological approaches for inflammatory conditions in dentistry, including non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, are widely used and generally effective. However, their use may be associated with adverse effects in specific clinical contexts, particularly under prolonged or high-dose regimens, highlighting the importance of continued investigation of additional pharmacological strategies. Within this context, pharmacological modulation of inflammatory pathways represents a relevant strategy for exploring alternative therapeutic approaches in pulp-associated gingival inflammation. Accordingly, there is a need to investigate novel molecules with therapeutic potential, such as resiniferatoxin, which has demonstrated anti-inflammatory properties in both in vitro and in vivo experimental models. This study aims to evaluate the anti-inflammatory effect of resiniferatoxin during inflammation of gingival tissue after mechanical pulp damage in a murine experimental model. Six groups of six BALB/c mice were formed as follows: five control groups: a healthy group (H_CG), a healthy group treated with resiniferatoxin (RTX_HG), a group with pulp damage at 14 h (PG_I), two groups with pulp damage treated with ibuprofen (PGI_IBU), dexamethasone (PGI_DEX) at 14 h, and an experimental group with pulp damage treated with resiniferatoxin (PGI_RTX) at 14 h. Gingival inflammation was evaluated after pulp damage was induced through mechanical pulp exposure of the upper first molar. The histopathological parameters of the gingival tissue of all groups were evaluated by hematoxylin and eosin (H&E) staining, while the plasma levels of PGE₂ and TNF-α were quantified by ELISA assay. A significant increase in plasma PGE₂ and TNF-α levels was observed at 14 h after pulp damage. Subsequently, when treatment with resiniferatoxin was administered, it was observed that this significantly decreased (* p < 0.05) the plasmatic levels of PGE₂ and TNF-α, as well as the number of inflammatory cells infiltrated in the gingival tissue 14 h after the pulp damage, similar to treatments with ibuprofen and dexamethasone. Resiniferatoxin exerts an anti-inflammatory effect after pulp damage, significantly decreasing plasma levels of PGE₂ and TNF-α, as well as the number of inflammatory cells infiltrated in the gingival tissue, which places resiniferatoxin as a potential drug, in this case, for the treatment of gingival inflammation. Full article

Background: Endometriosis is associated with infertility and impaired assisted reproductive technology (ART) outcomes, potentially due to an altered follicular microenvironment characterized by chronic inflammation. This study investigates the systemic and local inflammatory profiles in women with endometriosis and assesses their impact on oocyte and embryo quality using both static and dynamic embryo evaluation. Methods: A prospective, monocentric observational study enrolled 47 women undergoing controlled ovarian stimulation for ART, including 29 with laparoscopically confirmed endometriosis and 18 controls with tubal or male-factor infertility. Serum and follicular fluid cytokines (TGF-β1, NF-κB, IL-10, HIF-1α) were quantified. A sub-study analyzed embryo quality and development in 36 patients subdivided into static morphological assessment and dynamic time-lapse monitoring cohorts. Results: Endometriosis patients exhibited significantly elevated pro-inflammatory cytokines (TGF-β1, NF-κB) and reduced anti-inflammatory IL-10 in serum, alongside decreased NF-κB in follicular fluid. These alterations correlated with diminished ovarian reserve, reduced oocyte yield, and lower fertilization rates. Embryos from endometriosis patients showed increased multinucleation and persistent fragmentation, features more sensitively detected via dynamic time-lapse imaging. Clinical pregnancy rates were significantly lower in the endometriosis group. Conclusions: Endometriosis induces a dysregulated inflammatory follicular milieu that adversely affects oocyte competence and embryo morphodynamics. Dynamic embryo assessment provides enhanced detection of subtle developmental abnormalities. Integration of immunomodulatory strategies and advanced embryo monitoring may improve ART success in this population. Full article

Background: The population of elderly patients undergoing chronic hemodialysis is increasing, and anemia represents a frequent complication. The aim of our study was to evaluate the association between ultrafiltration rate (UFR) in hemodialysis and erythropoietin (EPO) response in elderly patients with end-stage kidney disease (ESKD). Methods: This was a multicenter, retrospective observational study, involving elderly patients (aged 65 years or more) under chronic hemodialysis therapy. Individuals were divided into two groups according to the UFR adjusted to weight (UFR/W): lower (UFR-N) or higher (UFR-H) than 10 mL/h/kg. EPO resistance index (ERI) was calculated. We evaluated the hemogram, reticulocyte count, and quantified markers of iron metabolism and inflammation. Results: A total of 193 patients were enrolled in the study: 141 patients met criteria for inclusion in UFR-N group and 52 in UFR-H group. Compared to UFR-N, patients in the UFR-H group presented significantly higher doses of erythropoiesis-stimulating agents (ESA) and ERI values, with similar hemoglobin (Hb) and inflammatory markers levels. In a sub-analysis, within patients presenting transferrin saturation (TSAT) lower than 20%, a more marked difference in ERI between UFR groups was observed, being much higher in UFR-H compared with UFR-N. In this subgroup (UFR-H with lower TSAT), levels of hepcidin were lower than in the other subgroups. Conclusions: Our data show that UFR appears to be a contributing factor of ESA response in elderly patients under hemodialysis, particularly in those with lower iron availability. These findings suggest that inadequate weight control and/or UF prescription seem to aggravate ESA needs to achieve target Hb. Full article

Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive skeletal muscle and adipose tissue loss, systemic inflammation, and poor clinical outcomes, and represents a major unmet clinical need in gastric cancer. Growth Differentiation Factor 15 (GDF15) is a key mediator of cachexia-associated anorexia and tissue wasting; however, the upstream mechanisms regulating its expression in gastric cancer remain poorly defined. Leukemia Inhibitory Factor (LIF), a pleiotropic cytokine implicated in tumor progression and metabolic dysregulation, has emerged as a potential regulator of cachexia-related pathways. Here, we investigated the association between LIF in regulating GDF15 expression and its relationship with metabolic, inflammatory, and body composition alterations in gastric cancer. Transcriptomic profiling of paired neoplastic and non-neoplastic gastric mucosa from 61 gastric cancer patients revealed a significant upregulation of both LIF and GDF15 in tumor tissue, with a strong positive correlation between their expression levels. High GDF15 expression was associated with reduced overall survival, a finding validated in independent TCGA-STAD and ACRG cohorts. Intratumoral bile acid profiling uncovered a marked enrichment of primary bile acids and a depletion of secondary bile acids, resulting in reduced levels of bile acids with endogenous LIF receptor (LIFR) antagonist activity; elevated primary, LIFR non-antagonist bile acids were associated with worse survival outcomes. Clinically, increased LIF and GDF15 expression correlated with weight loss, heightened inflammatory burden, reduced serum protein and albumin levels, and impaired body composition in a sub-cohort of 19 patients. Notably, LIF expression showed a significant inverse association with both lumbar skeletal muscle index (L3SMI) and subcutaneous adipose tissue index (SATI). Mechanistically, experimental models demonstrated that LIF enhances proliferative activity in gastric cancer spheroids and exerts paracrine effects that impair myogenic differentiation and suppress hepatic metabolic gene expression. Collectively, these findings identify the LIF/GDF15 axis as a central driver of cancer-associated cachexia in gastric cancer and highlight LIF signaling as a potential therapeutic target. Full article

Background: Sub-clinical inflammation is considered a key mechanism in cardiovascular disease and myocardial remodeling. We therefore evaluated whether the neutrophil–lymphocyte ratio (NLR), a simple inflammatory marker derived from a routine full blood count, is associated with myocardial fibrosis. Methods: Consecutive patients from a cardiac magnetic resonance imaging (CMR) registry were included and stratified by the NLR tertile. The association of the NLR and the levels of C-reactive protein (CRP) with CMR-derived myocardial T1 time and the extracellular volume fraction (ECV) were assessed using linear regression analysis and compared using Z-scores. In addition, an association with outcome was tested utilizing the log-rank test. Results: 1152 patients (72.4 years, 53.1% male) constituted the final cohort. The median NLR was 3.11 [interquartile range (IQR): 2.145–4.67]. Tertiles were based on the cut-off values ≤ 2.5, >2.5 and <4.0, and ≥4.0. A higher NLR tertile was associated with lower biventricular ejection fraction, hypertrophy, and increased right ventricular volume. The myocardial native T1 time [tertile 1 vs. 3: 1010 ms (984–1038) vs. 1030 (1001–1059), p < 0.001] and ECV [tertile 1 vs. 3: 26.3% (24.2–28.6) vs. 28.1% (25.5–31.4), p < 0.001] also significantly differed between the NLR tertiles. The NLR’s and the CRP’s association with elevated myocardial T1 time and ECV were comparable; however, the proportion of variation in the target variables explained by either was generally low. Conclusions: In our CMR all-comer cohort, NLR and CRP were significantly associated with prolonged myocardial T1 times and increased ECV. However, only a modest variation observed in both parameters was explained by either variable. Full article

The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by profound immune dysregulation where interleukins play a central role in determining disease severity and response to interventions. This review summarizes the role of interleukins in the immunopathogenesis of COVID-19, with particular emphasis on differences observed across major SARS-CoV-2 variants. Pro-inflammatory interleukins like IL-1β, IL-6, IL-2, IL-17 and IL-18 are critically involved in cytokine storm, hyperinflammation, and acute respiratory distress syndrome, whereas anti-inflammatory cytokines like IL-10 contribute to immune regulation and resolution of inflammation. Elevated levels of IL-1α, IL-1β, IL-4, IL-8, IL-9, IL-16, IL-18 have been documented in the Delta variant as compared with the Omicron variant, with IL-6 being the most frequent interleukin reported to be increased across all SARS-CoV-2 variants relative to the ancestral Wuhan strain. Elevated IL-2, IL-4, IL-6, and IL-10 levels have been associated with Omicron sub-variants. The review encompasses interleukin-based therapeutic strategies, where several IL-1 and IL-6 inhibitors were studied across clinical trials, but only tocilizumab has shown some promise against severe COVID-19. IL-2, IL-6, IL-15 and IL-21 levels were positively correlated with IgG and neutralizing antibody activity after vaccination with longevity of post-vaccination immunity being determined by IL-2 and IL-7. Full article

Kaposi’s Sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV) are oncogenic gammaherpesviruses with high prevalence in sub-Saharan Africa. Both viruses are typically acquired during childhood, establishing lifelong latency. While viral reactivation into the lytic cycle has been mainly studied in adult HIV-infected populations—and more recently in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection—the dynamics of KSHV and EBV infection in children remain poorly understood. Here, we characterize pediatric patients (n = 175; median age 4.6 years; IQR 2.0–8.3) presenting with inflammatory conditions during the COVID-19 pandemic in South Africa (from July 2020 to February 2024). Including a healthy, non-inflammatory control group, we found widespread exposure to SARS-CoV-2 (70.9% seropositivity), with 72.6% of the children being seropositive for EBV and 19.4% for KSHV. There were no significant differences in seroprevalence between children with inflammatory conditions and healthy controls for any of these viruses, although SARS-CoV-2 antibody titers were significantly higher in the inflammatory group, while EBV immune responses were lower in children presenting with inflammation. Among the KSHV-seropositive children, no active viremia was detected (as determined by the absence of viral DNA in the peripheral blood). In contrast, 34.4% of EBV-seropositive children had detectable EBV viral load, with a modestly higher proportion in the inflammatory group. However, EBV viral load levels were comparable between children diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C), Kawasaki Disease (KD), and other inflammatory conditions. Logistic regression analyses revealed that increasing age was significantly associated with higher risk of SARS-CoV-2 and EBV seropositivity, but not KSHV. Notably, the risk of EBV DNA detection in the peripheral blood decreased with age. In summary, this study suggests effective immunological control of gammaherpesvirus infections in HIV-negative paediatric patients, even in the presence of inflammatory conditions that might otherwise trigger viral reactivation. Full article

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although cisplatin is widely used in chemotherapy, its clinical efficacy is often limited by adverse effects and resistance. Thus, natural bioactive compounds are gaining attention as complementary therapeutic agents. This study aimed to evaluate the anti-tumor effects of Annona muricata leaf extract on murine breast cancer 4T1 cells, used alone or in combination with cisplatin. Cisplatin induced intrinsic apoptosis through mitochondrial membrane disruption, up-regulation of the Bax gene and inhibition of the PI3K/AKT/mTOR signaling pathway. Cisplatin also promoted hypoxia by HIF1α gene expression, inflammation by TNFα and IL-6 gene expression, and induced cell cycle arrest at the sub-G1 phase by down-regulation of cyclin D1 and cyclin E1 genes. Annona muricata leaf extract triggered autophagy-mediated 4T1 cell death through mainly mTOR down-regulation and increased expression of Beclin1 and LC3 genes. It also induced cell cycle arrest at sub-G1 and S phases in a concentration- and time-dependent manner. When, combined with cisplatin, Annona muricata extract shifts the cell death pathway from intrinsic apoptosis toward autophagy by reduced caspase-3 gene expression and activity and enhanced LC3-I to LC3-II conversion. Moreover, Annona muricata extract attenuated cisplatin-induced inflammation by inhibiting TNFα and IL-6 gene expression and reinforced cell cycle arrest through suppression of the cyclin D1 gene. In conclusion, our results suggest that Annona muricata leaf extract exerts significant anti-tumor activity in breast cancer cells and may enhance cisplatin efficacy by shifting the signaling pathway from intrinsic apoptosis toward autophagy, and attenuating inflammation-related effects, supporting its potential use as a complementary therapeutic strategy. Full article

Low social status leads to chronic social stress that predicts risk for physical and mental illness, especially when it starts early in life. To examine the longitudinal effects of low social status on the immune system, this study assessed the effects of low social status on developmental secretory patterns of pro- and anti-inflammatory markers under baseline conditions, as well as in response to an immune challenge (lipopolysaccharide (LPS)-induced activation of pro- and anti-inflammatory cytokines) in a translational rhesus monkey model of lifelong social subordination stress. Baseline blood samples were collected in 27 socially housed female rhesus monkeys (13 dominants, DOM, and 14 subordinates, SUB) during infancy (6 months), the juvenile pre-pubertal period (16 months), and adulthood (9–10 years) to examine the longitudinal effects of social status on inflammatory markers in unstimulated versus LPS-stimulated conditions mimicking exposure to bacterial infection. Basal levels of the stress hormone cortisol in blood were measured to examine associations between inflammation and activity of the hypothalamic–pituitary–adrenal (HPA) axis throughout the life span. Basal peripheral levels of inflammatory markers (e.g., IL-6) increased across development in both SUB and DOM animals with no significant differences. Basal cortisol levels were significantly higher in infancy as compared to adulthood, but no significant effects of social rank were detected. However, in adulthood, SUB animals showed a cytokine-specific immune response to ex vivo LPS stimulation with significantly higher secretions of IL-1β, IL-2, and IL-10 compared to DOM animals, whereas IL-8 response to LPS was lower in SUB animals than in DOMs. This cytokine-specific response to an immune challenge that mimics bacterial infection could reflect dysregulated immune cells that may have short-term adaptation, but at the cost of longer-term risks for low-grade chronic inflammation and accelerated immune aging for socially subordinate female macaques. Full article

HIV/AIDS continues to pose a significant global public health concern, with Sub-Saharan Africa having the highest number of people living with HIV (PLHIV). Traditional medicines have been increasingly essential in treating and managing PLHIV. Product Nkabinde (PN), a polyherbal formulation derived from traditional medicinal plants, has recently demonstrated significant potential in the treatment of HIV. This study aims to elucidate the molecular mechanisms underlying the therapeutic effects of phytochemicals identified from PN in HIV treatment, utilizing network pharmacology and molecular docking. The intersecting (common) genes of the 27 phytochemicals of PN and HIV were computed on a Venn diagram, while the protein–protein interaction (PPI) network of the intersecting genes was plotted using STRING. The hub (10) genes were computed and analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways using ShinyGO. Molecular docking and protein–ligand interaction analysis of the 27 phytochemicals with each of the 10 hub genes were performed using the Maestro Schrodinger suite. The KEGG analysis reveals an important network with lower False Discovery Rate (FDR) values and higher fold enrichment. The pathway enrichments reveal that the 10 hub genes regulated by PN focus on immune regulation, metabolic modulation, viral comorbidity, carcinogenesis, and inflammation. GO analysis further reveals that PN plays key roles in transcription regulation, such as miRNA, responses to hormones and endogenous stimuli, oxidative stress regulation, and apoptotic signalling, kinase binding, protein kinase binding, transcription factor binding, and ubiquitin ligase binding enriched pathways. Consequently, molecular docking unveils complexes with higher binding energies, such as rutin-HSP90AA1 (−10.578), catechin-JUN (−9.512), quercetin-3-O-arabinoside-AKT1 (−9.874), rutin-EGFR (−8.127), aloin-ESR1 (−8.585), and quercetin-3-0-β-D-(6′-galloyl)-glucopyranoside-BCL2 (−7.021 kcal/mol). Overall, the results reveal pathways associated with HIV pathology and possible anti-HIV mechanisms of PN. Therefore, further in silico, in vitro, and in vivo validations are required to substantiate these findings. Full article

Seasonal fluctuations in the chemical composition of fine particulate matter (PM_2.5) are known to influence its toxicological properties; however, their integrated biological effects remain incompletely understood. In this study, PM_2.5 was continuously collected over two consecutive years at a single urban site in Japan and classified by season. The samples were comprehensively characterized for ionic species, metals, carbonaceous fractions, and polycyclic aromatic hydrocarbons (PAHs), and their pulmonary effects were evaluated in vivo following intratracheal administration in mice. Seasonal PM_2.5 exhibited pronounced compositional differences, with higher levels of secondary inorganic aerosol components in summer and enrichment of PAHs and mineral-associated components in winter. These seasonal differences translated into distinct biological responses. Reactive oxygen species (ROS) production (1.6–2.7-fold increase) and bronchoalveolar lavage (BAL) neutrophil infiltration were strongly associated with PAH-rich PM_2.5, whereas interleukin-1α (IL-1α) showed robust positive correlations with mineral components, including K⁺, Ca²⁺, and Mg²⁺, which were predominantly enriched in winter PM_2.5. In contrast, secondary inorganic aerosol species displayed a limited capacity to induce IL-1α. Compared with summer samples, winter PM_2.5 induced significantly higher levels of ROS production and IL-1α (approximately 1.5–2.6-fold increase). Using TLR2- and TLR4-deficient mice, we further demonstrated that PM_2.5-induced increases in BAL cell counts, ROS, IL-6, and TNF-α were partially attenuated in TLR4 knockout mice, indicating a contributory but not exclusive role for TLR4 signaling in PM_2.5-driven pulmonary inflammation. Collectively, these findings demonstrate that seasonal variations in PM_2.5 composition, not particle mass alone, critically shape oxidative stress and innate immune responses in the lungs. In particular, winter PM_2.5 enriched in mineral-associated components preferentially activates IL-1α-mediated alarmin pathways, underscoring the importance of the particle composition in determining seasonal air pollution toxicity. Full article

Plantain (Musa paradisiaca L.) is a tropical monocotyledonous, succulent plant of the Musaceae family commonly grown for food in the tropical regions of the African, Asian, and South American continents, where its parts are also sought for ethnomedicinal purposes in the treatment of burns, inflammation, and diabetes, among others. In the present preliminary exploratory study, the ethanol extract of the underutilized Musa paradisiaca peel (MPE) was evaluated for its in vitro inhibitory effects on α-amylase and α-glucosidase, as well as its in vivo hypoglycemic activity and potential biochemical toxicity. MPE (100, 200, 400 mg/kg) was orally administered to normal experimental rats for 30 days, following which the lipid profile, antioxidant status, and serum/tissue indices of hepatic, renal, and cardiac functions were evaluated. MPE produced significant inhibition (p < 0.05) of α-amylase (37%) and α-glucosidase (46%) at 120 µg/mL in vitro. The effect was lower than that of acarbose (IC₅₀ = 44.4 ± 1.14 and 15.60 ± 0.01 µg/mL, respectively). A modest blood glucose-lowering effect of MPE was observed at the highest tested dose (400 mg/kg) following subacute oral administration. During this treatment period, no biochemical alterations of toxicological importance were caused by MPE, as the organ–body weight ratio and serum/tissue indicators of organ function/damage were not adversely altered. In conclusion, MPE demonstrated inhibitory activity against both α-amylase and α-glucosidase, which may contribute to its potential hypoglycemic effects. Additionally, the findings indicate that the peel extract is non-toxic in rats following sub-acute administration at doses up to 400 mg/kg body weight. Further studies involving diabetic models and chronic exposure will substantiate and extend these preliminary observations. Full article