Search Results (9,190)

Chronic neuroinflammation is a prominent feature of several central nervous system disorders and contributes significantly to cognitive impairment. The present study aimed to investigate the effects of pretreatment with L-theanine (LT), aerobic exercise (ex), and their combination on cognitive deficits induced by subchronic lipopolysaccharide (LPS) administration in rats. Male Wistar rats were assigned to the following groups: control; veh-sed-LPS, sedentary (sed) rats treated with vehicle (veh) and LPS; LT-sed-LPS; veh-ex-LPS; and LT-ex-LPS. L-theanine treatment and/or treadmill running were administered for 5 weeks. Following these interventions, neuroinflammation was induced by LPS injections for 7 days, while the C group received veh treatment. Cognitive function was assessed using Y-maze, object recognition, and object location tests. Hippocampal cAMP response element-binding protein (CREB) phosphorylation status, β-amyloid (Aβ_1–42) accumulation, and pro-inflammatory cytokines (TNF-α, IL-1β) were measured by ELISA. Pretreatment with LT, ex, or their combination improved Y-maze performance and recognition memory, partly restoring the LPS-induced reduction in the pCREB/CREB ratio. Exercise, but not LT, reduced Aβ_1–42 levels and neuroinflammatory cytokine expression. Combined treatment produced additive benefits for some cognitive measures but not for spatial memory. These findings suggest that the prophylactic combination of LT and ex can partially attenuate cognitive impairments associated with subchronic neuroinflammation in this model. Full article

In the intensive livestock farming industry, weaned piglets are highly prone to renal injury triggered by weaning stress, pathogen infection, and antibiotic abuse. This injury induces metabolic disorders and immunosuppression, severely restricting production efficiency. As a natural pentacyclic triterpene, betulinic acid (BA) exhibits notable biological activities, particularly in anti-inflammatory and antioxidant activities. However, its preventive potential against renal injury in piglets and the underlying mechanisms remain unclear. In this study, BA was administered as a long-term dietary pretreatment prior to lipopolysaccharide (LPS) challenge to evaluate its protective role in a preventive model of renal inflammatory injury in weaned piglets. BA pretreatment significantly mitigated pathological lesions, including renal tubular epithelial cell shedding and interstitial congestion, reduced the renal index, and decreased the concentrations of renal injury markers and serum UREA. In addition, BA pretreatment mitigated the renal oxidative stress and inflammatory injury induced by LPS in piglets. Molecular analyses showed that BA pretreatment was associated with decreased expression of key markers involved in apoptosis, necroptosis, and pyroptosis in renal tissue. Furthermore, protein–protein interaction analysis suggested potential associations between the HMGB1/TLR4/NF-κB signaling pathway and PANoptosis-related processes, providing exploratory and hypothesis-generating support for the proposed regulatory network. Collectively, these findings suggest that dietary BA pretreatment exerts a preventive effect against LPS-induced renal inflammatory injury in weaned piglets, potentially through modulation of HMGB1/TLR4/NF-κB-associated PANoptosis-related pathways, providing a theoretical basis for its application in livestock production. Full article

Honey bees (Apis mellifera L.) are considered highly significant economic insects. It is a source of valuable food and medicinal products such as honey, bee pollen, royal jelly, bee brood, and beeswax, which possess excellent nutritional and pharmacological properties. Nevertheless, honey bee health and productivity were often challenged by various environmental factors. Therefore, bee colony management is of the utmost importance. In this light, bee supplements and gut microbiota are crucial to ensure that bees receive sufficient nutritional value to maintain their health and productivity. In this study, we isolate and characterize lactic acid bacteria from the hindgut of the worker bee. 16S rRNA sequencing revealed that three isolated bacteria were Apilactobacillus kunkeei (AK), Lactiplantibacillus sp. (LP), and Lactobacillus brevis (LB). Three species of lactic acid bacteria were investigated for potential probiotic properties by supplementing 50% (w/w) sucrose syrup in the form of a direct-fed microorganism (DFM). The supplement with DFM had no negative effect on average lifespan. Examination took place of the impact of probiotics on the development of the hypopharyngeal glands (HPGs) in the bee’s head at days 3, 6, and 9 post-treatments. The cage-bees fed by pollen and DFM syrup exhibited acini surface areas ranging from 0.020 to 0.023 mm². The L. brevis (LB) group exhibited enhanced HPG development, with an average acini size of 0.027 ± 0.007 mm² at day 6, while the non-treatment control had an average acini size of 0.023 ± 0.006 mm². The significant size differences were maintained throughout the 9-day period. In addition, the DFM syrup enhanced microbial protein content in the bee head, digestibility, and community complexity compared with the negative control groups. Therefore, the DFM syrup with a potential strain of probiotic may enhance overall honey bee health status. Full article

Diabetic wounds remain a major clinical challenge due to delayed healing caused by chronic inflammation and impaired fibroblast activity. Here, we present a thermoresponsive gel composed of chitosan (CS) and poloxamers (POL) incorporating silk fibroin (SFB) and Aloe vera gel extract (AV), developed for topical application and, for the first time, evaluated using an inflammation-induced diabetic fibroblast model. The optimized formulation exhibited rapid sol–gel transition at physiological temperature and suitable rheological properties for effective wound coverage. In vitro evaluation using human normal fibroblasts (HNF) and human diabetic fibroblasts (HDF), under both basal and inflammation-induced conditions, demonstrated good cytocompatibility and a significant enhancement of fibroblast migration, particularly in an inflammatory microenvironment simulated by high glucose, lipopolysaccharide (LPS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). These findings highlight the potential of the developed thermoresponsive gel as a promising biomaterial platform for improving diabetic wound healing under inflammation-relevant conditions. Full article

To assess digestate’s efficacy as a fertilizer for basil development, a two-year pot experiment was established, comprising four fertilization treatments: namely, mineral fertilizer (F), digestate (D), combined mineral fertilizer and digestate (1:1, FD), and unfertilized control (C). Key metrics assessed included plant height, chlorophyll concentration index (CCI), total biomass (TB), leaf production (LP), essential oil yield, and composition. Post-harvest analysis evaluated nutrient and heavy metal content and pathogen contamination in the growing substrate and leaves. FD treatment produced the highest TB (68.2 g plant⁻¹) and LP (52.7 g plant⁻¹). Digestate application substantially enhanced substrate nutrient availability, increasing extractable phosphorus by 68.5%, potassium by 134.4%, and organic matter by 54.7%. The essential oil yield was significantly higher in the control plants. whereas different fertilization regimes altered secondary metabolite synthesis. Specifically, fertilization with digestate favored sesquiterpenes synthesis, inorganic fertilization enhanced methyleugenol and β-farnesene synthesis, and the control showed higher limonene, eugenol, and linalool. Heavy metal accumulation in the growing substrate was negligible, remaining well within regulatory limits. Salmonella spp., were not detected. Pathogen concentration in the growing substrate was low, while Enterococcus faecalis levels were marginally below EU safety limits (100 cfu g⁻¹) on the leaves. Continuous monitoring of soil chemical properties and plant products after digestate application is essential to ensure soil health and food safety. Full article

LINC01270 is a long intergenic noncoding RNA implicated in the progression of various cancers. In our previous study, we demonstrated that LINC01270 plays a role in regulating the pro-inflammatory response in the THP-1 monocytic cell line, partly through modulation of NF-κB activation. Given the multifaceted nature of inflammation and the ability of noncoding RNAs to influence this process at multiple levels, we further investigated the potential role of LINC01270 in modulating additional inflammatory signaling pathways in lipopolysaccharide (LPS)-stimulated THP-1 cells. We found that attenuation of LINC01270 levels led to increased transcription and phosphorylation of STAT1, accompanied by elevated expression of the genes under STAT1 regulation. Further investigation revealed that LINC01270 regulates STAT1 expression via the miR-326/leucine zipper downregulated in cancer 1 (LDOC1) axis. Notably, inhibition of the interaction between LINC01270 and miR-326 effectively reversed the effects of LINC01270 knockdown on STAT1 expression and its downstream targets. Interestingly, both gain- and loss-of-function experiments with LDOC1 resulted in a consistent upregulation of STAT1 transcription. Taken together, our findings highlight a pleiotropic role of the LINC01270 in regulating the pro-inflammatory response through modulation of STAT1 signaling, in addition to its previously established role in NF-κB regulation. Furthermore, this study uncovers a novel function of the LDOC1 in inflammation through its regulation of STAT1. These findings provide new mechanistic insights into lncRNA–microRNA–protein interactions in inflammatory signaling and may open avenues for developing novel therapeutic strategies targeting chronic inflammatory diseases. Full article

Reducing residual cardiovascular risk following acute coronary syndrome (ACS) remains a major unmet clinical need. Despite substantial advances in lipid-lowering therapies, the risk of recurrent major adverse cardiovascular events (MACEs) after ACS remains high, with an estimated incidence of approximately 33.4% at 5 years. Residual cardiovascular risk is driven by multiple mechanisms, including persistent inflammation, a prothrombotic status, metabolic disturbances, and the presence of atherogenic lipoproteins beyond low-density lipoprotein cholesterol (LDL-C). Lipoprotein(a) (Lp(a)) is a pro-inflammatory, prothrombotic, and pro-atherosclerotic lipoprotein that appears to play a major role in residual risk after ACS or ischemic stroke. Elevated Lp(a) is a well-established independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Nevertheless, evidence regarding its prognostic value specifically after ACS remains limited, with marked heterogeneity across studies, which complicates direct comparisons and interpretation. In addition, while Lp(a) levels are predominantly genetically determined, recent studies have reported intra-individual variability, although their clinical significance remains uncertain. Finally, current therapeutic options specifically targeting Lp(a) are limited. Novel RNA-based therapies, including antisense oligonucleotides, small interfering RNAs, and emerging gene-editing approaches, have demonstrated profound and sustained reductions in circulating Lp(a) levels. Yet, whether this biological effect translates into reductions in hard clinical endpoints is under evaluation in ongoing clinical trials. This review aims to synthesize current evidence on the role of Lp(a) as a major contributor to residual cardiovascular risk following ACS. Full article

Background: Autism spectrum disorders (ASDs) are defined as a large spectrum of phenotypes whose basic definition is deficiency in social interactions, particularly during pediatric stages. Through clinical evaluations, it would be challenging to diagnose since the symptoms may be disregarded or controversial. Hence, molecular approaches could be powerful for differential and certain diagnosis. Moreover, considering the possible genetic complexity of the disease, the rates of molecular diagnosis remain insufficient. Nevertheless, the number of newly identified ASD-monogenic inheritance relationships is escalating daily. This underscores the increasing importance of comprehensive molecular tests, such as whole exome sequencing (WES), which encompass all relevant genes. Furthermore, reporting population-specific variants is critical to validate already listed ones and decipher novel ones. In the present study, we aimed to document the disease-related variants in Turkish patients with ASD. Methods: This study evaluated the WES outcomes of 75 ASD patients with normal results in Fragile X testing, cytogenetic analysis, and molecular karyotyping. All patients were diagnosed with ASD based on the criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Results: The average age of the participants was 8.2 (±5.0) years. A higher percentage of the participants was male (73.3%) compared with female (26.7%). Eighteen patients (24%) had pathogenic or likely pathogenic (LP) variants, while 34 (45.3%) exhibited variants of unknown significance (VUS). In 30.7% of the cases, no clinically relevant variants were found. The MECP2 gene was most frequently affected, followed by EP300 and PTEN. Additionally, four patients carried novel de novo missense variants in the KMT2C, MECP2, PTEN, and TRRAP genes. Conclusions: Genetic diagnosis of ASD would be useful for confirming the underlying etiologies, devising personalized therapeutic strategies, and offering family counseling. Although WES has been employed in ASD patients for an extended period, the identification of gene and variant spectra across diverse cohorts and the discovery of novel variants continues to hold significant scientific importance. Full article

Objectives: Combining mechanical plaque control, the physical removal of oral biofilm, with chemical plaque control, the use of agents to inhibit biofilm formation, is effective in preventing periodontal disease. Chlorogenic acid (CGA) found in coffee beans has medicinal effects, such as anti-inflammatory and antibacterial properties. Periodontal pathogens are difficult to reach in certain areas with traditional self-care tools, such as toothbrushes. Additionally, the viscous biofilm is difficult to remove using mechanical plaque control alone. Therefore, this study aimed to evaluate the efficacy of CGA in chemical plaque control. Methods: The mRNA and protein expression of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs) and human periodontal ligament fibroblasts (HPDLs) in the presence of CGA were analyzed using reverse transcription-qPCR and enzyme-linked immunosorbent assay. Additionally, the proliferation levels of oral bacteria in the presence of CGA were evaluated. Results: CGA suppressed mRNA and protein expression levels of the inflammatory cytokines, interleukin (IL)-1β and IL-8, in HGFs and HPDLs stimulated with Porphyromonas gingivalis LPS. Furthermore, CGA inhibited bacterial proliferation of Streptococcus mutans, Aggregatibacter actinomycetemcomitans, P. gingivalis, and Fusobacterium nucleatum. Conclusions: This study demonstrated that CGA exhibits anti-inflammatory effects on gingiva and periodontal ligaments, and antibacterial effects against oral bacteria. These results indicate the potential application of CGA in chemical plaque control and suggest its use in preventing periodontal disease progression. Full article

The mechanisms underlying the generation of low-density neutrophils (LDNs), along with their phenotypic characteristics and role in organ injury during sepsis, remain poorly understood. This study utilized lipopolysaccharide (LPS) stimulation to mimic the septic microenvironment. LDNs and high-density neutrophils (HDNs) were isolated via density gradient centrifugation. Single-cell RNA sequencing, in vitro functional assays, and a cecal ligation and puncture (CLP) murine sepsis model were employed, alongside techniques including immunohistochemistry and flow cytometry, to investigate LDN heterogeneity and their role in sepsis-associated acute lung injury (ALI). Results demonstrated that LPS stimulation significantly increased the LDN proportion. Single-cell transcriptomics revealed substantial heterogeneity within LDNs, which exhibited a hyperactivated yet immunodeficient phenotype characterized by delayed apoptosis, impaired migration and phagocytosis, and a heightened capacity to suppress T-cell proliferation. In vivo, the NETosis inhibitor GSK484 reduced LDN generation and alleviated sepsis-associated ALI. In conclusion, sepsis induces the generation of immunodeficient LDNs via a NETosis-dependent pathway, which exacerbates lung injury. Targeting this pathway may represent a novel therapeutic strategy for sepsis. Full article

Uncontrolled inflammation contributes to the development of neurodegenerative diseases (NDs) like Alzheimer’s disease (AD). N-(p-Coumaroyl) serotonin (CS) has demonstrated a significant capacity to modulate hyper-inflammation. We explored whether CS could mitigate inflammatory responses in endotoxin-challenged microglial cells and sought to elucidate the specific molecular mechanisms governing these effects. ELISA, nitric oxide (NO) assays, Western blotting and immunocytochemistry were performed to study inflammatory responses and related signal transduction mechanisms. CS pretreatment effectively attenuated the inflammatory output in endotoxin-primed microglial models. This was evidenced by a significant reduction in key cytokines (such as IL-6, TNF-α, and MCP-1) and a concomitant decrease in the protein levels of iNOS and COX-2. These effects were mediated through the disruption of MAPK/NF-κB signaling cascades and the sequestration of NF-κB within the cytoplasm. Beyond its anti-inflammatory role, CS promoted the HO-1/NQO1 signaling pathway and interfered with the LPS-mediated TLR4/MyD88 cascade. Our collective evidence indicates that the modulation of microglia-mediated inflammation by CS is underpinned by the suppression of MAPK/NF-κB and the induction of antioxidant systems, suggesting that CS may have the potential to improve NDs. Full article

Background: Energy metabolism progressively deteriorates from a healthy state to non-alcoholic fatty liver disease (NAFLD), and circulating lipopolysaccharide (LPS) may contribute to this process. However, previous studies have analyzed healthy individuals and NAFLD patients together, leaving stage-specific associations unclear. Whether LPS and its surrogate marker, lipopolysaccharide-binding protein (LBP), show similar relationships during NAFLD development also remains unknown. This study evaluated the associations between plasma LPS and LBP concentrations with clinical parameters in healthy individuals and NAFLD patients. Methods: We conducted a cross-sectional study of 31 healthy individuals (median age [IQR]: 31 (26–43) years) and 31 NAFLD patients (59 (54–70) years). Plasma LPS and LBP concentrations and clinical parameters were measured. Correlations were assessed using Spearman’s rank analysis, followed by multivariate regression adjusting for age, sex, and BMI. Results: Plasma LPS and LBP concentrations were significantly higher in NAFLD patients compared to healthy individuals. Additionally, in the univariate regression analysis for all study participants, plasma LPS concentrations were correlated with obesity, blood pressure, liver function, lipid metabolism, and glucose metabolism. Plasma LBP concentrations were also correlated with age, obesity, blood pressure, liver function, lipid metabolism, glucose metabolism, and inflammatory cytokines. In healthy individuals, LPS correlated positively with triglycerides (TG), remaining significant after adjustment and exclusion of participants with any clinical test values outside the normal range. This association was not observed in NAFLD patients. Plasma LBP did not correlate with TG in either group; however, it was inversely associated with hepatic fat fraction in NAFLD patients, although this association was attenuated after adjusting for alanine aminotransferase. Conclusions: Plasma LPS correlates with TG even in clinically healthy individuals, suggesting LPS may influence lipid metabolism before NAFLD onset. Full article

Interleukin-37 (IL-37) is an anti-inflammatory cytokine with an undefined role in chronic endometritis (CE). This study aims to explore its therapeutic mechanism in CE, focusing on epithelial-mesenchymal transition (EMT) and macrophage polarization. A CE model was induced in Sprague-Dawley rats using lipopolysaccharide (LPS), followed by intervention with TAT-fused recombinant IL-37. Histological damage and fibrosis were evaluated through H&E and Masson staining. Immunofluorescence staining was performed to assess the expression of IL-37 and EMT markers (E-cadherin and vimentin) and macrophage phenotypes (M1: CD86⁺; M2: CD206⁺). In vitro, transwell, qPCR, Western blot, and flow cytometry analyses were performed to determine the effects of IL-37 on EMT and macrophage polarization. The activity of the STAT6 and Smad3 pathways was evaluated using Western blotting, dual-luciferase assays, and immunofluorescence staining. The results revealed that IL-37 accumulated in the injured uterus, alleviating inflammation, tissue damage, and collagen deposition. IL-37 reduced epithelial migration and reversed abnormal EMT by upregulating E-cadherin expression and downregulating vimentin expression. It also suppressed M1 macrophage infiltration and promoted M2 polarization. Mechanistically, IL-37 coactivated the STAT6 and Smad3 pathways, thereby increasing their phosphorylation and nuclear translocation and elevating ARG1 expression. In conclusion, IL-37 mitigates CE by suppressing EMT and promoting M2 macrophage polarization via coordinated STAT6/Smad3 activation, highlighting its therapeutic potential for CE. Full article

As a widely used display device, the effective display area of a digital micromirror device (DMD) is limited by its micromirror count and pitch, which cannot meet large-format target-plane display requirements. This paper proposes a large-format scene simulation system based on multi-DMD optical stitching, and uses an optical relay to overcome the inability to directly tile DMDs because of their package frames. By constructing a DMD display architecture comprising an illumination module, a relay module, a stitching module, and a projection module, the system quadruples the effective display area relative to a single DMD without sacrificing frame rate. Design results show that the system achieves an MTF greater than 0.5 at 50 lp/mm, with near-diffraction-limited performance; the RMS spot radius is less than 10 $\mathsf{\mu }$m. All key indicators meet application requirements. Full article

Skin inflammation is characterized by oxidative stress, excessive keratinocyte activation, and the overproduction of pro-inflammatory cytokines. In a previous study, we demonstrated that the hydroalcoholic extract from Posidonia oceanica leaves (POE) mitigates psoriasis-like skin inflammation in a mouse model. In the present study, we investigated the cellular mechanisms underlying these effects in human HaCaT keratinocytes. Non-cytotoxic lipopolysaccharide (LPS) stimulation reproduced key inflammatory features, including impaired cell proliferation, increased production of ROS and NO, and the upregulation of IL-1β, IL-6, TNF-α and CXCL8/IL-8. Co-treatment with POE significantly attenuated these alterations by restoring cell proliferation, suppressing oxidative stress, particularly NOS2/NO, and normalizing both cytokine expression and release. POE alone did not affect cell viability or inflammatory markers, confirming its favorable safety profile. However, POE alone induced a mild pro-apoptotic response, which may contribute to overcoming the apoptosis resistance typically observed in psoriatic keratinocytes. Overall, these findings demonstrate that POE exerts antioxidant and anti-inflammatory effects in activated keratinocytes and support its potential as a marine-derived candidate for complementary strategies in the management of psoriasis-associated inflammatory skin disorders. Full article