Search Results (25,487)

In this report, we showed that oral administration of Dendrobium Taiseed Tosnobile (DTT, also known as Taiwan Emperor No.1) allowed Lewis Lung Carcinoma (LLC) tumor-bearing mice to maintain body weight and grip strength in a dose-dependent manner. Histological analysis showed that treatment with DTT water extract significantly reduced muscle fiber damage by inducing muscle regeneration and improved the cross-sectional area of the rectus femoris, soleus, and gastrocnemius of LLC tumor-bearing C57BL/6 female mice. Further studies revealed that DTT water extract also reduced the expression of inflammatory cytokines such as IL-6 and TNF-α, both in vitro and in vivo. Other analyses showed that DTT water extract promoted the differentiation of C2C12 myoblasts with or without IL-6 by maintaining Myosin Heavy Chain (MyHC) levels. This suggests that DTT water extract acts against muscle wasting via multiple mechanisms. Interestingly, vitamin B1 was identified as an ingredient in DTT water extract through an HPLC analysis. Vitamin B1 was shown to ameliorate IL-6 but not TNF-α generation in active THP-1 cells and protected C2C12 myotubes against IL-6. Further studies showed that DTT and vitamin B1 promoted the multi-nucleus fusion step of C2C12 differentiation by inducing E-cadherin-β-catenin expression with or without IL-6 treatment. In summary, DTT water extract protects muscle cells under cancer conditions through direct and indirect mechanisms, with vitamin B1 being a key functional ingredient that reduces IL-6 generation and aids muscle cell fusion against IL-6 treatment. Full article

Aging mice experience a depletion of muscle extracellular matrix fibronectin (FN). Therefore, enhancing FN expression in the aging tissue microenvironment may be able to maintain satellite cell function and facilitate the repair of damaged skeletal muscle. Herein, we have used molecular dynamics (MD) simulations to select FN functional domains, which were combined into a single construct, rhFN-NM (recombinant human Fibronectin-N-terminal module). The antioxidant properties of this construct were tested at the cellular level and included effects on cell adhesion, anti-aging, apoptosis and expression of aging-related proteins. When used in an animal skeletal muscle injury model, naturally aging mice, or in IL-10^(−/−) gene knockout mice, this construct promoted skeletal muscle repair and improved the immune microenvironment of the tissue. Overall, we show that the construct rhFN-NM improves skeletal muscle repair and protects against oxidative stress. Full article

The SARS-CoV-2 pandemic has posed global medical challenges due to its ability to affect multiple organ systems. Among the post-COVID-19 complications, multisystem inflammatory syndrome has emerged as a severe condition affecting both children (MIS-C) and adults (MIS-A). This review aims to compile and analyze published data to investigate clinical characteristics, laboratory findings, and outcomes of MIS post-COVID-19. A comprehensive search of various databases was conducted to identify studies reporting MIS-related complications in pediatric and adult populations post-COVID-19 infection. Screening, data extraction, and cross-checking were performed by two independent reviewers. Only 64 studies met our inclusion criteria, and compiled results revealed that cardiac complications were the predominant manifestation followed by gastrointestinal, hematologic, neurological, and mucocutaneous involvement. Laboratory findings consistently demonstrated elevated inflammatory markers including CRP, ferritin, D-dimer, and IL-6. Most patients required hospitalization, and many needed intensive care; treatment typically involved IVIG, corticosteroids, and biologic therapies. While most patients recovered, a subset experienced persistent complications. These findings highlight the importance of early recognition, multidisciplinary management, and structured follow-up for MIS. Future research is warranted to clarify the underlying mechanisms, risk factors, and long-term outcomes associated with MIS in post-COVID-19 patients. Full article

This study compared serum immunological parameters, cytokines, intestinal permeability, fecal microbiota, and short-chain fatty acids (SCFAs) between healthy and diarrheic suckling calves. Serum and facecal samples were analyzed using ELISA kits, 16S rDNA sequencing, and targeted metabolomics. Compared with healthy calves, the serum levels of aspartate aminotransferase, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), endotoxin (ET), and diamine oxidase (DAO) were significantly higher (p < 0.05), whereas the serum levels of immunoglobulin A (IgA), immunoglobulin G (IgG), and interleukin-10 (IL-10) were significantly lower in diarrheic calves (p < 0.05). The contents of propionic acid, butyric acid, and valeric acid significantly decreased in the fecal of diarrheic calves (p < 0.05). Moreover, the Chao1 and observed_features index of fecal microbiota significantly decreased in diarrheic calves (p < 0.05). The relative abundance of Escherichia-Shigella, Clostridium_sensu_stricto_1, and Streptococcus was significantly higher (p < 0.05), whereas Phascolarctobacterium, Ruminococcus torques group, and Faecalibacterium were significantly lower in diarrheic calves (p < 0.05). Escherichia-Shigella abundance was positively correlated with ET, DAO, IL-1β, and TNF-α levels (p < 0.05). Faecalibacterium abundance was significantly positively correlated with IgG, IgA, IL-10, and butyric acid but negatively correlated with ET and DAO levels (p < 0.05). In summary, diarrheic suckling calves exhibited reduced immune function, inflammatory response, and increased intestinal permeability. The relative abundance of fecal microbiota of Escherichia-Shigella and Clostridium_sensu_stricto_1 increased, while propionic acid, butyric acid, and valeric acid concentration were decreased in calves with diarrhea. This underscores the critical interplay between microbiota balance and gut health in diarrhea. Full article

Respiratory tract infections are a major cause of morbidity and mortality. After the SARS-CoV-2 pandemic, pathogenetic mechanisms leading to more severe outcomes were investigated, including uncontrolled viral replication in the upper airways. This was only partially investigated for other respiratory viruses. We measured mucosal expression of IFN-β1, IFN-λ1, IFN-λ2/3, IL-1β, and IL-6 in patients infected by human metapneumovirus, human rhinovirus, human respiratory syncytial virus or type A influenza virus. A total of 806 nasopharyngeal swabs were collected from patients presenting at emergency departments or hospitalized. Viral load was inferred through cycle threshold determination, whereas cytokine levels were measured through mRNA detection. Each expression pattern was correlated with age, viral load, and specific infecting virus. IFN-β1 and IFN-λ2/3 showed a negative correlation with viral load, while IFN-λ1 and IL-6 exhibited the opposite trend, suggesting increased inflammation with higher viral load. This was more evident in the ≥70-year-old group, with significantly higher IL-6 levels. Higher viral load of potentially more pathogenic viruses was associated with higher IL-6 expression. Cytokine production in the upper respiratory tract is only partially influenced by age per se, with a more relevant role played by viral load and specific infecting virus. In older patients, this response is less coordinated and prone to elicit a proinflammatory response, especially when clinically impacting viruses are involved. Full article

Psoriasis is a chronic inflammatory skin disease whose pathogenesis involves not only cutaneous inflammation but also intestinal dysbiosis and oxidative stress (OxS). Monoclonal antibodies targeting interleukin (IL)-17 and IL-23 have demonstrated significant immunomodulatory effects; however, their impact on systemic parameters requires further investigation. We conducted a study on 33 patients with plaque psoriasis treated with anti-IL-17 or anti-IL-23 monoclonal antibodies. Dermatological parameters (Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI)), biomarkers of intestinal dysbiosis (trimethylamine-N-oxide (TMAO)) and OxS (reactive oxygen metabolites (d-ROMs) and oxidized LDL (oxLDL)) were evaluated. Anthropometric, metabolic, and adipose-derived hormonal parameters (adipokines) were also monitored. After 16 weeks of therapy, significant improvements were observed in PASI and DLQI scores (p < 0.001). TMAO levels were significantly reduced (p = 0.02), as were d-ROMs and oxLDL (p < 0.001). No significant changes were found in weight, body mass index, lipid profile, or adipokine levels (visfatin, leptin and adiponectin). Our data indicate that monoclonal antibody therapy not only improves psoriasis severity but also exerts beneficial effects on systemic biomarkers of dysbiosis and OxS, independent of metabolic or hormonal changes. These findings suggest a systemic mechanism of action, supporting a multifactorial therapeutic effect with potential implications for the prevention of cardiovascular risk. Full article

Porcelain-fused-to-metal (PFM) crowns continue to serve as a cornerstone of restorative dentistry owing to their strength, affordability, and esthetics. However, late-onset complications such as oral burning and lichenoid reactions have been observed in long-serving PFMs, suggesting complex host–material interactions that extend beyond simple mechanical wear. This Perspective introduces the Nallan–Nickel Effect, a theoretical model proposing that a host- and environment-dependent threshold of bioavailable nickel ions (Ni²⁺), once exceeded, may trigger a neuro-immune cascade culminating in a burning phenotype. Within this framework, slow corrosion at exposed PFM interfaces releases Ni²⁺ into saliva and crevicular fluid, facilitating epithelial uptake and activation of innate immune sensors such as TLR4 and NLRP3. The resulting cytokine milieu (IL-1β, IL-6, TNF-α) drives NF-κB, mediated inflammation and T-cell activation, while neurogenic mediators—including nerve growth factor (NGF), substance P, and CGRP—sensitize TRPV1/TRPA1 nociceptors, establishing feedback loops of persistent burning and neurogenic inflammation. Modifying factors such as low salivary flow, acidic oral pH, mixed-metal galvanic coupling, and parafunctional stress can lower this threshold, whereas replacement with high-noble or all-ceramic materials may restore tolerance. The model generates testable predictions: elevated local free Ni²⁺ levels and increased expression of TLR4 and TRPV1 in symptomatic mucosa, along with clinical improvement following substitution of nickel-containing restorations. Conceptually, the Nallan–Nickel Effect reframes PFM-associated burning and lichenoid lesions as threshold-governed, neuro-immune phenomena rather than nonspecific irritations. By integrating corrosion chemistry, mucosal immunology, and sensory neurobiology, this hypothesis offers a coherent, testable framework for future translational research and patient-centered management of PFM-related complications. Full article

Weaver syndrome is a rare congenital overgrowth disorder caused by pathogenic EZH2 variants. This study reports a novel EZH2 variant associated with atypical manifestations, including severe bilateral camptodactyly and complex brain malformations. A 4-year-old Taiwanese female exhibited classical Weaver syndrome features including macrosomia, macrocephaly, hypertelorism, and developmental delay, plus atypical findings of severe bilateral camptodactyly and complex brain malformations. Neuroimaging revealed corpus callosum dysgenesis with rostral agenesis and genu hypoplasia, bilateral frontal lobe hypoplasia, and an arachnoid cyst. The patient demonstrated global developmental delay with marked motor impairment but less severely affected speech and cognition, consistent with mild intellectual disability. Whole-exome sequencing identified a novel de novo pathogenic variant in EZH2: c.449T>C (p.Ile150Thr), affecting a highly conserved amino acid within the SANT domain. This case broadens the clinical spectrum of Weaver syndrome by highlighting severe camptodactyly and complex brain malformations as possible EZH2-related manifestations. The corpus callosum dysgenesis suggests a wider role of EZH2 in neurodevelopment than previously recognized. The novel SANT domain variant may explain the severe phenotypic presentation. The novel EZH2 variant c.449T>C (p.Ile150Thr) expands the molecular and phenotypic spectrum of Weaver syndrome. These findings underscore the importance of comprehensive neuroimaging and molecular genetic testing in suspected cases, particularly atypical presentations. Full article

Background: Cognitive impairment, including dementia, is a growing global health challenge, particularly as populations age. Previous studies have identified periodontitis and diabetes mellitus as modifiable risk factors for dementia, potentially linked through systemic inflammation. We hypothesize that systemic inflammation induced by periodontitis may contribute to an increased risk of cognitive impairment. Therefore, this study aims to explore the correlation between periodontal inflammation and the risk of Mild Cognitive Impairment (MCI) in type II diabetes mellitus. Materials and Methods: Baseline data analysis was performed as an analytical cross-sectional study among diabetic patients aged 40 and older who met the inclusion criteria from a randomized controlled trial (RCT) from November 2020 to April 2023. Periodontal inflammation was measured using the Periodontal Inflamed Surface Area (PISA) score. The MCI risk score was calculated using blood samples to assess eight protein markers correlated to MCI (ApoA1, TTR, C3, Albumin, ApoC1, A1BG, A2AP, and HPX). Fisher’s exact test and Spearman’s correlation analysis were performed. Results: 29 T2DM patients were included in the study. There was a significant difference in MCI risk score between the low and high PISA levels group (p < 0.05). Patients with low PISA scores tend to have a lower risk of MCI (p < 0.00). Variables correlated with MCI risk are PISA (ρ = 0.37; p < 0.05) and TTR levels (ρ = −0.51; p < 0.01). ApoA1 has a correlation with CRP (ρ = 0.42; p < 0.05) and IL-6 (ρ = 0.43; p < 0.05), and C3 (ρ = 0.42; p < 0.05) was correlated with CRP. Conclusions: This study found that periodontal inflammation status has a potential correlation to the risk of MCI. Full article

Glucocorticoids are essential for fetal organ maturation and form the basis of antenatal corticosteroid therapy that has significantly reduced preterm-related morbidity such as respiratory distress syndrome (RDS). However, neonatal morbidity remains a clinical challenge regardless of antenatal corticosteroid therapy. Currently, it is thought that adverse intrauterine environments dysregulate glucocorticoid receptor (GR) homeostasis, yet the biological mechanisms remain poorly understood. Therefore, we aimed to study ex vivo glucocorticoid sensitivity in cord blood immune cells from two independent preterm cohorts to identify associations with neonatal morbidity and uncover potential mechanisms of dysregulated glucocorticoid homeostasis. In the first cohort, thawed cord blood mononuclear cells were exposed to betamethasone in the presence of lipopolysaccharides (LPS) for 4 h. In the second cohort, freshly isolated white blood cells were treated with dexamethasone under unstimulated and LPS-stimulated conditions for 48 h. GR isoform expression and regulation of transactivated and transrepressed genes were assessed via qPCR, immunoblotting, flow cytometry, and ELISA. In both cohorts, reduced GR expression, particularly of the GRα isoform, was observed in neonates with morbidity, but only with culture time and not in freshly isolated cells. Ex vivo impaired glucocorticoid-mediated transrepression of proinflammatory genes IL6 and TNF was also observed in the morbidity groups. In contrast, all samples were comparable in basal immune cell distributions and transactivation of glucocorticoid response element (GRE)-dependent genes GILZ and FKBP5, irrespective of neonatal morbidity. These findings suggest that neonates that develop morbidities experience an early postnatal GR dysfunction that is potentially programmed in utero. Moreover, under conditions of decreased GR abundance, classical transactivation functions appear to be preserved at the expense of more complex regulatory mechanisms such as transrepression. Full article

Severe asthma is a heterogeneous condition often resistant to conventional corticosteroid therapy, necessitating the identification of novel biomarkers and therapeutic targets. This study investigates immunological, transcriptional, and proteomic biomarkers in severe asthma patients from the Brazilian ProAR cohort. Cytokines were measured using a multiplex technology and the differential sputum cell count was performed by cytospin preparations. Sputum transcriptomics was performed by RNA-seq using Ion S5 next-generation sequencing platform. The proteomic study of sputum was performed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) using Q Exactive Orbitrap technology. Compared to mild-to-moderate asthma (MMA) and treatment-controlled severe asthma (SAC), the treatment-resistant severe asthma (SAR) group exhibited increased sputum neutrophilia, eosinophilia, and elevated IL-6 and TNF levels, correlating with impaired lung function. Transcriptomic and proteomic analyses revealed a Th2-independent molecular signature characterized by downregulation of the Hippo signaling pathway and upregulation of JAK–STAT inflammatory cascades. Distinctive microRNA profiles suggest regulatory involvement in inflammatory and proliferative processes. These findings align with prior studies, reinforcing the presence of an IL-6- and TNF-high severe asthma phenotype across diverse populations. Our results highlight key inflammatory pathways that may underlie corticosteroid resistance, offering potential targets for personalized therapeutic interventions in severe asthma. Full article

Purpose: Cisplatin chemotherapy is complicated by acute kidney injury (cis-AKI), driven by regulated cell death pathways, including apoptosis and pyroptosis. However, the temporal relationship between apoptosis and pyroptosis in cis-AKI remains unclear. This study investigated the roles of these pathways and evaluated the renoprotective effect of the hydrogen sulfide (H₂S) donor GYY4137. Method: Cis-AKI was modeled in mice and HK2 cells, divided into control, cisplatin, and cisplatin + GYY groups. Kidney function parameters, histopathology, and cell death were evaluated. Markers of apoptosis and pyroptosis, along with the H₂S-producing enzyme, were analyzed. Results: Renal impairment progressed from BUN elevation to increased Scr, coupled with aggravated renal tissue damage. Apoptotic signaling peaked at 24 h, evidenced by a raised Bax/Bcl-2 ratio and caspase-3 cleavage. Pyroptosis pathways, via both NLRP3/caspase-1/GSDMD and caspase-3/GSDME axes, were activated later at 72 h, with concurrent rises in IL-1β and IL-18. GYY4137 treatment significantly ameliorated renal dysfunction, reducing serum creatinine and BUN levels by 22.64% and 22.5%, respectively. It suppressed both the early apoptotic and delayed pyroptosis cascades without reversing CBS downregulation. Conclusions: GYY4137 mitigated both apoptosis and pyroptosis, offering a promising multi-targeted therapy for cis-AKI. Full article

Highly sensitive flexible pressure sensors are crucial for wearable health monitoring and human–machine interaction. While the emerging iontronic sensors inherently offer high sensitivity, this can be further improved by engineering microstructured interfaces. In this study, we employ four different types of common fiber materials as substrates for fabricating ionic dielectric layers by a simple impregnation of ionic liquid (IL). A comparative study reveals that the porosity and microstructural architecture (e.g., fiber diameter) of the substrate material directly influences the amount of adsorbed IL and consequent sensing performance. We achieved the highest sensitivity by using a thin electrospun TPU/IL nanofiber mat (33 μm), which exhibited high sensitivities of 3.10 kPa⁻¹, 1.85 kPa⁻¹, and 1.02 kPa⁻¹ in the pressure ranges of 0–200 kPa, 200–400 kPa, and 400–700 kPa, respectively. Furthermore, the sensor exhibited an excellent fast response (2.71 ms) and recovery time (8.71 ms), along with outstanding cyclic stability. This work provides valuable guidance for selecting and utilizing common fiber materials to develop high-sensitivity iontronic pressure sensors, paving the way for their practical application in next-generation wearable electronics. Full article

Helminth parasites infect mammalian hosts through complex life cycles, mostly triggering T helper type 2 (Th2) immune responses characterized by interleukin-4 (IL4), interleukin-5 (IL5), and interleukin-13 (IL13) production. Environmental chemical exposures may modulate these immune pathways, potentially affecting infection outcomes. Using The Comparative Toxicogenomics Database (CTD), we analyzed chemical–gene interactions affecting IL4, IL5, and IL13 genes to identify chemicals capable of modulating Th2 immunity and their associated expression profiles. Accordingly, a total of 818 chemicals can interact with IL4, IL5 and/or IL13, with 145 chemicals showing the potential of affecting all three genes. These 145 chemicals include air pollutants (8.3%), allergens (2.7%), bioactive molecules (8.3%), industry-related chemicals (14.5%), medicinal drugs (21.4%), metal and metal-containing chemicals (8.3%), pesticides (3.4%), plant compounds (12.4%), and others (20.7%). We observed a greater number of chemicals associated with increased (n = 95) gene expression compared to decreased (n = 14) gene expression, suggesting a Th2 pathway hyperactivation caused by chemicals capable of affecting IL4, IL5 and IL13. Eight classes of parasitic diseases were observed among chemical-associated conditions. Environmental chemicals extensively modulate Th2 immune responses through diverse molecular mechanisms. The trend concerning upregulation of Th2 pathways may enhance antiparasitic protection but, on the other hand, could predispose individuals to allergic diseases, among other Th2-related conditions. These exploratory findings suggest that chemical pollution may influence the susceptibility and pathogenesis of helminth infections and highlight the need for the incorporation of exposome-based approaches in parasitology research. Full article

This randomized, double-blind, placebo-controlled study investigated Ageratum conyzoides (A. conyzoides) for alleviating osteoarthritis symptoms and improving quality of life. Conducted in Australia between 2021 and 2024, the study included 70 adults aged ≥45 years with clinically diagnosed osteoarthritis. Participants consumed 250 mg of pyrrolizidine alkaloid-free A. conyzoides extract or a placebo daily for 12 weeks. Pain and function were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) every three weeks. Secondary measures included pain assessed by the Visual Analogue Scale (VAS), the SF-36 quality-of-life questionnaire, inflammatory markers, and safety parameters. A. conyzoides supplementation resulted in significant reductions in total WOMAC scores at weeks 9 and 12 (p < 0.05) compared to placebo. VAS pain scores were significantly lower at weeks 9 and 12 (p < 0.05). SF-36 scores improved significantly in the pain and role limitations due to physical health domains (p < 0.05). Plasma inflammatory markers IL-6 and IL-8 showed significant reductions compared with placebo (p < 0.05). No between-group differences were observed for adverse events. These findings demonstrate that A. conyzoides supplementation is a safe and effective option for reducing osteoarthritis symptoms, with significant improvements observed in pain, function, and inflammatory markers. Full article