Search Results (644)

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article

Background: The study evaluates the immunomodulatory potential of secukinumab (SECU) and honokiol (HONK) in a murine model of allergic asthma complicated by acute lung injury (ALI), with an emphasis on modulating key inflammatory pathways. The rationale is driven by the necessity to attenuate Th17-mediated cytokine cascades, wherein IL-17 plays a critical role, as well as to explore the adjunctive anti-inflammatory effects of HONK on Th1 cytokine production, including IL-6, TNF-α, and Th2 cytokines. Methods: Mice were sensitized and challenged with ovalbumin (OVA) and lipopolysaccharide (LPS) was administrated to exacerbate pulmonary pathology, followed by administration of SECU, HONK (98% purity, C₁₈H₁₈O₂), or their combination. Quantitative analyses incorporated OVA-specific IgE measurements, differential cell counts in bronchoalveolar lavage fluid (BALF), and extensive cytokine profiling in both BALF and lung tissue homogenates, utilizing precise immunoassays and histopathological scoring systems. Results: Both SECU and HONK, when used alone or in combination, display significant immunomodulatory effects in a murine model of allergic asthma concomitant with ALI. The combined therapy synergistically reduced pro-inflammatory mediators, notably Th1 cytokines, such as TNF-α and IL-6, as measured in both BALF and lung tissue homogenates. Conclusions: The combined therapy showed a synergistic attenuation of pro-inflammatory mediators, a reduction in goblet cell hyperplasia, and an overall improvement in lung histoarchitecture. While the data robustly support the merit of a combinatorial approach targeting multiple inflammatory mediators, the study acknowledges limitations in cytokine diffusion and the murine model’s translational fidelity, thereby underscoring the need for further research to optimize clinical protocols for severe respiratory inflammatory disorders. Full article

Hepatitis E virus (HEV) poses a significant public health concern, particularly among immunocompromised populations. This study aimed to investigate HEV seroprevalence, clinical characteristics, and associated risk factors in people living with HIV (PLWH) in Shanghai, China. A retrospective analysis was conducted on serum IgG and IgM antibodies specific to HEV in 670 PLWH and 464 HIV-negative health-check attendees. The overall anti-HEV seropositivity rate among PLWH was 30.15% (202/670, 95% CI 26.68–33.62), with an IgG positivity rate of 30.00% (201/670, 95% CI 26.53–33.47). IgM positivity was observed in 1.19% (8/670, 95% CI 0.59–2.39) of PLWH, and dual IgM/IgG positivity was observed in 1.04% (7/670, 95% CI 0.50–2.16) of PLWH. The seropositivity rate of anti-HEV IgG in the HIV-negative health-check attendees was 17.67% (82/464, 95% confidence interval: 14.20–21.14), with no IgM positivity, which was significantly lower than that in PLWH (χ² = 22.84, p < 0.001). Univariate and multivariate analyses identified advanced World Health Organization (WHO) HIV stage (III/IV) as an independent risk factor for HEV co-infection (p < 0.05). Notably, no significant associations were observed with age, gender, CD4 count, or liver function parameters. These findings underscore the importance of implementing HEV screening protocols and developing targeted preventive strategies for PLWH. Full article

Background: Allergic rhinitis (AR) is a prevalent allergic disorder characterized by a complex pathogenesis. Drawing on traditional Chinese medicine theory and contemporary pharmacological principles, this study developed an inhalation-based herbal formulation, ZHW, to explore a novel non-invasive therapeutic approach. Objective: To investigate the therapeutic effects of ZHW on AR and elucidate its underlying mechanisms and potential targets through an integrated analysis of network pharmacology and proteomics. Materials and Methods: The volatile components of ZHW were analyzed by gas chromatography–mass spectrometry (GC-MS). The mouse model of AR was induced by OVA sensitization. The therapeutic efficacy of ZHW was assessed based on nasal symptom scores, histopathological examination, and inflammatory cytokine levels. Furthermore, the underlying mechanisms and potential targets of ZHW were investigated through integrated network pharmacology and proteomics analyses. Results: GC-MS analysis identified 39 bioactive compounds in ZHW. Inhalation treatment with ZHW demonstrated significant anti-allergic effects in OVA-sensitized mice, as evidenced by (1) reduced sneezing frequency and nasal rubbing behaviors; (2) decreased serum levels of IL-4, histamine, and OVA-specific IgE; (3) attenuated IL-4 concentrations in both nasal lavage fluid and lung tissue; (4) diminished nasal mucosal thickening; and (5) suppression of inflammatory cell infiltration. Integrated network pharmacology and proteomics analyses indicated that ZHW’s therapeutic effects were mediated through the modulation of multiple pathways, including the PI3K-Akt signaling pathway, the B cell receptor signaling pathway, oxidative phosphorylation, and the FcεRI signaling pathway. Key molecular targets involved Rac1, MAPK1, and SYK. Molecular docking simulations revealed strong binding affinities between ZHW’s primary bioactive constituents (linalool, levomenthol, linoleic acid, Linoelaidic acid, and n-Valeric acid cis-3-hexenyl ester) and these target proteins. Conclusions: The herbal formulation ZHW demonstrates significant efficacy in alleviating allergic rhinitis symptoms through multi-target modulation of key signaling pathways, including PI3K-Akt- and FcεRI-mediated inflammatory responses. These findings substantiate ZHW’s therapeutic potential as a novel, non-invasive treatment for AR and provide a strong basis for the development of new AR therapies. Future clinical development will require systematic safety evaluation to ensure optimal therapeutic outcomes. Full article

Food-borne zoonoses, particularly anisakiosis caused by Anisakis spp., are an increasing public health concern due to the rising consumption of raw fish. Anisakiosis results from the ingestion of third-stage larvae of Anisakidae nematodes, with the genus Anisakis re-sponsible for approximately 97% of human cases. While regulatory protocols exist to minimize infection risk in commercial settings, domestic food preparation often lacks such safeguards, creating a gap in public health protection. In the Canary Islands, a major Spanish aquaculture region, farmed fish exhibit a low Anisakis prevalence, suggesting minimal risk from aquaculture products. In contrast, wild-caught fish demonstrate varia-ble parasitism, with recent studies reporting a 25% prevalence among commercial species. Methods: This study assessed Anisakis exposure in the Canary Islands by measuring specific IgG and IgE antibodies in 1043 serum samples collected from all seven islands between March 2014 and October 2015. ELISA assays detected anti-Anisakis antibodies, and the results were analyzed by age, sex, island, and isoclimatic zone. Results: Overall, 16.9% of samples were IgG-positive and 6.8% were IgE-positive. Seroprevalence was significantly higher in indi-viduals aged 60 years and above. Geographic heterogeneity was notable: La Palma had the highest IgG seroprevalence (35.3%), while El Hierro showed the highest IgE prevalence (16.3%). Temperate isoclimatic zones exhibited higher antibody prevalence than dry zones. These findings indicate variable Anisakis exposure across the Canary Islands, likely influenced by environmental and behavioral factors. Conclusions: The results highlight the need for targeted public health interventions to reduce the anisakiosis risk, particularly in regions and populations with elevated exposure. Full article

In our previous studies, methylated CpG oligodeoxynucleotides (ODN) derived from Bifidobacterium longum subsp. infantis have demonstrated immunomodulatory effects through the induction of regulatory T cells (Tregs). To define the structural determinants underlying this effect, we synthesized four CpG ODNs varying in methylation degree, CpG motif placement, and backbone length. These include (1) ODN-A (2m-V1), a 20-nucleotide CpG oligodeoxynucleotide incorporating two 5-methylcytosines at positions 4 and 12 within centrally placed CpG motifs; (2) ODN-B (um-V2), a 20-nucleotide CpG oligodeoxynucleotide with a backbone structure identical to ODN-A but unmethylated; (3) ODN-C (2m’-V3), a 20-nucleotide CpG oligodeoxynucleotide with a backbone structure identical to ODN-A, but with two 5-methylcytosines shifted to positions 7 and 15; (4) ODN-D (3m-V4), a 27-nucleotide CpG oligodeoxynucleotide with an extended backbone structure, this time with three 5-methylcytosines at positions 3, 11, and 19. Using a murine model of an OVA-induced allergy, we show that methylated ODN-A (2m-V1) and ODN-D (3m-V4) markedly reduce serum anti-OVA IgE, clinical symptoms, eosinophilic infiltration, and Th2/Th17 responses, while promoting splenic Treg expansion and IL-10 production. In contrast, unmethylated ODN-B (um-V2) and a positionally altered methylated ODN-C (2m’-V3) both failed to suppress allergic inflammation, and, in contrast, enhanced the Th2/Th17 response and induced robust in vitro Toll-like receptors TLR7/8/9 expression in native splenocytes. These findings suggest that both methylation and motif architecture critically influence the immunologic profile of CpG ODNs. Our results provide mechanistic insights into CpG ODN structure/function relationships and support the therapeutic potential of select methylated sequences for restoring immune tolerance in allergic diseases. Full article

Asthma represents a heterogeneous disorder characterized by a dynamic balance between pro-inflammatory and anti-inflammatory forces, with allergic sensitization contributing substantially to airway hyperresponsiveness and remodeling. Central to its pathogenesis are cytokines such as IL-4, IL-5, IL-13, IL-17, and IL-33, which drive recruitment of eosinophils, neutrophils, and other effector cells, thereby precipitating episodic exacerbations in response to viral and environmental triggers. Conventional biomarkers, including blood and sputum eosinophil counts, IgE levels, and fractional exhaled nitric oxide, facilitate phenotypic classification and guide the emerging biologic era. Monoclonal antibodies targeting IgE (omalizumab) and IL-5 (mepolizumab, benralizumab, reslizumab, depemokimab) have demonstrated the ability to reduce exacerbation frequency and improve lung function, with newer agents such as depemokimab offering extended dosing intervals. Itepekimab, an anti-IL-33 antibody, effectively engages its target and mitigates tissue eosinophilia, while CM310-stapokibart, tralokinumab, and lebrikizumab inhibit IL-4/IL-13 signaling with variable efficacy depending on patient biomarkers. Comparative analyses of these biologics, encompassing affinity, dosing regimens, and trial outcomes, underscore the imperative of personalized therapy to optimize disease control in severe asthma. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease stemming from genetic susceptibility and environmental factors. It is characterized by immune dysregulation, increased mast cell activity, elevated levels of immunoglobulin E (IgE), and excessive proinflammatory mediator expression. These factors contribute to hallmark symptoms such as pruritus, erythema, and skin barrier dysfunction. In this study, we investigated the antioxidant and anti-inflammatory effects of Taraxacum mongolicum (WTM) water extract, as well as its skin barrier regulation and immune functions in AD. In the present study, we explored the therapeutic efficacy and underlying mechanisms of WTM in a BALB/c mouse model of AD induced by 2,4-dinitrochlorobenzene (DNCB). Mice were administered WTM orally or topically for 14 consecutive days. The results demonstrated that WTM treatment significantly alleviated clinical severity, showing reductions in skin lesion scores, epidermal thickness, mast cell infiltration, and scratching behavior, compared to the DNCB-treated group. Mechanistically, WTM reduced serum levels of IgE and proinflammatory cytokines (IL-4, IL-6, IL-1β, TNF-α, and IL-31) while suppressing the expression of the JAK/STAT/TSLP signaling pathway in skin tissues. Furthermore, WTM inhibited the TLR4/NF-κB and MAPK pathways and enhanced antioxidant defense by elevating superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities. These findings indicate that WTM attenuates DNCB-induced AD progression in mice, likely through the dual modulation of inflammatory signaling and oxidative stress. These findings suggest that WTM may modulate the immune response and alleviate AD symptoms by inhibiting the TLR4/NF-κB, MAPK, and JAK/STAT/TSLP pathways. Full article

Background/Objectives: The porcine respiratory disease complex (PRDC) is a multifaceted, polymicrobial syndrome resulting from a combination of environmental stressors, primary infections (e.g., PRRSV) and secondary infectious agents (viruses and bacteria). PRDC causes severe lung pathology, leading to reduced performance, increased mortality rates, and higher production costs in the global pig industry. Our goal was to conduct a comprehensive study correlating both the anti-PRRSV immune response and 21 secondary infectious agents with PRDC severity. Methods: To this end, PRRSV-negative weaners were vaccinated with a PRRSV-2 MLV and put into a farm with a history of PRDC. Subsequently, anti-PRRSV cellular and antibody responses were monitored pre-vaccination, at 28 days post vaccination (dpv) and during PRDC outbreak (49 dpv). NanoString was used to quantify 21 pathogens within the bronchoalveolar lavage (BAL) at the time of necropsy (51 dpv). PRRSV-2 was present in 53 out of 55 pigs, and the other five pathogens (PCMV, PPIV, B. bronchiseptica, G. parasuis, and M. hyorhinis) were detected in BAL samples. Results: Although the uncontrolled settings of field trials complicated data interpretation, multivariate correlation analyses highlighted valuable lessons: (i) high weaning weight predicted animal resilience to disease and high weight gains correlated with the control of the PRRSV-2 field strain; (ii) most pigs cleared MLV strain within 7 weeks, and the field PRRSV-2 strain was the most prevalent lung pathogen during PRDC; (iii) all pigs developed a systemic PRRSV IgG antibody response which correlated with IgG and IgA levels in BAL; (iv) the induction of anti-field strain-neutralizing antibodies by MLV PRRSV-2 vaccination was both late and limited; (v) cellular immune responses were variable but included strong systemic IFN-γ production against the PRRSV-2 field strain; (vi) the most detected lung pathogens correlated with PRRSV-2 viremia or lung loads; (vii) within the six detected pathogens, two viruses, PRRSV-2 and PCMV, significantly correlated with the severity of the clinical outcome. Conclusions: While a simple and conclusive answer to the multifaceted nature of PRDC remains elusive, the key lessons derived from this unique study provide a valuable framework for future research on porcine respiratory diseases. Full article

Background/Objectives: Toxocara spp. infection has been associated with severe asthma and allergic manifestations due to the activation of eosinophils by the release of Th2 cell cytokines. The aim of this study was to investigate the association between Toxocara spp. infection and eosinophil levels in severe asthmatic patients. Methods: The socio-demographic, peripheral blood eosinophils counting total IgE, sIgE to aeroallergens and FEV1 results were acquired from the Program of Asthma and Rhinitis Control (ProAR) at the Salvador–Brazil databank; IgG anti-Toxocara spp. levels were measured in 176 severely asthmatic patients by indirect ELISA. Results: The Toxocara spp. seroprevalence was 50.6%. Eosinophilia was present in 54% of the population. The correlation between IgG anti-Toxocara spp. levels and eosinophils levels was positive. Eosinophilic individuals with SPT, sIgE for D. pteronyssinus, D. farinae and B. tropicalis showed positive results; IgE ≥ 160 UI/dL and uncontrolled asthma presented more positive results for IgG anti-Toxocara spp. Conclusions: Our findings suggest that eosinophil levels are influenced by the presence of IgG antibodies against Toxocara spp. Additionally, helminth infection may modulate immunological responses in allergies and uncontrolled asthma, which could help explain the exacerbation of asthma symptoms. Full article

Background/Objectives: Measles, mumps, and rubella (MMR) continue to pose a significant public health challenge due to insufficient immunization coverage. This study aimed to provide the first seroprevalence data against MMR and to explore self-reported immunity among future healthcare workers (HCWs) in Serbia, including women of childbearing age. Methods: We included 1296 future health care workers (HCWs) aged 19 to 29, born in Serbia. All HCWs supplied a blood sample for serology and filled in a questionnaire. Antibodies were measured using an enzyme immunoassay against measles, mumps, and rubella (MMR). Results: Anti-measles, -mumps, and -rubella seronegativity rates were 25.6%, 26.5%, and 4.4%, respectively, among future HCWs in Serbia. The mumps seronegativity rate was significantly higher in the oldest (27–29-year) age group, accompanied by significantly lower anti-mumps IgG GMCs in the same age group compared to younger participants (p = 0.035 and p < 0.001, respectively). Anti-mumps seronegativity also increased significantly across birth cohorts, from the youngest to the oldest (p = 0.004). Furthermore, anti-mumps IgG antibody GMCs were significantly higher among females, those who attended nursery/kindergarten, and unvaccinated individuals (p = 0.050, p = 0.020, and p = 0.005, respectively). Finally, older age and unvaccinated status were identified as independent factors associated with anti-measles and anti-mumps seronegativity among future HCWs in Serbia. Conclusions: The cross-sectional seroprevalence data revealed insufficient seroprotection in this population of particular importance, i.e., future HCWs, and women of childbearing age. These results strongly support the national recommendations for the mandatory vaccination of these populations. Identified immunity gaps should be closed promptly by strategic, targeted serologic screening, followed by vaccination of those lacking MMR antibodies. Full article

Background/Objectives: Allergens can trigger severe immune responses in hypersensitive individuals, with mast cells releasing inflammatory mediators via IgE-FcɛRI signaling. Spleen tyrosine kinase (Syk) is a key regulator in this pathway, making it a promising therapeutic target. Natural modulators of Syk-mediated mast cell activation remain underexplored. This study investigated the anti-allergic effects of a 70% ethanol extract of Salvia miltiorrhiza (SME) using in vitro and in vivo models. Methods: SME was evaluated using IgE-sensitized RBL-2H3 cells, a passive cutaneous anaphylaxis model, and a DNCB-induced atopic dermatitis-like mouse model. Allergic responses were assessed via degranulation assays, histopathology, serum IgE levels, and the spleen index. Results: SME significantly inhibited mast cell degranulation by 44.4 ± 1.6% in RBL-2H3 cells at 100 µg/mL following 30 min of treatment compared to the untreated control. Western blot analysis demonstrated dose-dependent suppression of protein kinase B (PKB, also known as AKT), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and spleen tyrosine kinase (Syk) phosphorylation, indicating inhibition of key allergic signaling pathways. In an IgE/Ag-induced passive cutaneous anaphylaxis model in ICR mice, SME (100 mg/kg, orally) significantly attenuated vascular permeability, as evidenced by a 20.6 ± 9.7% reduction in Evans blue extravasation relative to the Ag-treated group. In a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD)-like model, six treatments of SME significantly improved the skin condition, reduced spleen enlargement associated with allergic inflammation, and decreased serum IgE levels by 43.3 ± 11.2% compared to the DNCB group. Conclusions: These findings suggest that SME may help to alleviate allergic responses and AD by modulating key immune signaling pathways. Full article

Recombinantly produced monoclonal antibodies (mabs) belong to the fastest growing class of biotherapeutics. In humans, antibodies are classified into five different classes: IgA, IgD, IgE, IgG and IgM. Most of the therapeutic mabs used in the clinic belong to the IgG class, albeit other antibody classes, e.g., IgM, have been evaluated in clinical stages. Antibodies are composed of heavy chains paired with a light chain. In IgM and IgA, an additional chain, the J-chain, is present. Two types of light chains exist in humans: the κ-light chain and the λ-light chain. The κ-light chain predominates in humans and is used in the vast majority of therapeutic IgG. The reason for the preference of the κ-light chain in humans is not known. Our study investigates whether light-chain selection influences the productivity of the clinically validated mabs adalimumab and trastuzumab. Both mabs were expressed as IgG and IgM with a κ- or a λ-light chain in HEK293 cells. Besides comparing the expression levels of the different mabs, we also evaluated whether the passage number of the cell line has an impact on product yield. In addition, the expressions of adalimumab, trastuzumab, an anti-CD38 and an anti-PD-L1-antibody were analyzed in HEK293 and CHO cells when both the κ- and λ-light chains are present. In summary, IgG outperformed IgM variants in expression efficacy, while light-chain selection had minimal impact on the overall expression levels. The yields of all mab variants were higher in fresh cells, despite cell cultures with a high cell passage number having higher cell densities and cell numbers at the time of harvest. The incorporation of a particular light chain occurred at similar rates in HEK293 and CHO cells. Full article

Aletris spicata (Thunb.) Franch. (AS), a traditional edible and medicinal plant for treating asthma, was investigated for its therapeutic mechanisms. Liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) analysis identified 33 compounds in AS. In ovalbumin (OVA)-induced asthmatic mice, AS significantly reduced inflammatory cells (neutrophils, lymphocytes, eosinophils) in bronchoalveolar lavage fluid (BALF) and decreased IL-4, IL-5, IL-13, TNF-α, and serum IgE while increasing IFN-γ. AS alleviated lung and intestinal inflammation, reduced ROS and MDA levels, and enhanced SOD activity. Immunohistochemistry and Western blot revealed AS upregulated Nrf2/HO-1 expression and inhibited NF-κB p65 nuclear translocation. Gut microbiota studies demonstrated AS restored intestinal flora homeostasis by modulating the richness, diversity, and composition. Spearman correlation analysis identified significant relationships between oxidative stress markers, inflammatory cytokines, and specific gut bacteria. These findings indicate that AS mitigates asthma through antioxidant effects (Nrf2/HO-1 pathway), anti-inflammatory actions (NF-κB pathway), and gut microbiota modulation. The study provides a scientific basis for developing AS as a natural anti-asthma treatment or functional food. The multi-target mechanism involving oxidative stress, inflammation, and gut flora highlights AS’s comprehensive therapeutic potential for asthma management. Full article

Background: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) and is difficult to cure. Lang Chuang Wan (LCW) has been widely used in clinical practice as a treatment for SLE and LN, but its active ingredients and mechanism of action have not been elucidated. To address this, we aim to analyze LCW’s chemical components and clarify its mechanisms in treating LN. Methods: We utilized ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) to analyze the components of LCW and assessed its effects on MRL/lpr mice through ELISA, H&E staining, Masson’s trichrome staining, and IgG immunofluorescence. Then, we further explored the mechanisms of action through network pharmacology, transcriptomics, and metabolomics, and validated with Western blot. Results: LCW contained 1303 chemical components, primarily flavonoids and terpenoids. It significantly improved kidney pathology and normalized levels of serum ANA, anti-dsDNA, anti-Sm, C3, C4, Cr, BUN, IL-6, IL-10, IL-17, TNF-α, and urinary protein (UP) in MRL/lpr mice. Network pharmacology, transcriptomics, and metabolomics indicated that LCW’s therapeutic effect on LN involved the PI3K/AKT pathway, confirmed by Western blot showing LCW’s suppression of the PI3K/AKT/mTOR pathway. Conclusions: LCW alleviates pathological symptoms in MRL/lpr mice by inhibiting the PI3K/AKT/mTOR signaling pathway, providing insights into its therapeutic mechanisms for lupus nephritis. Full article