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Osteoarthritis (OA) is a prevalent clinical condition affecting the entire joint, characterized by its multifactorial etiology and complex pathophysiology. The onset of OA is linked to inflammatory mediators produced by the synovium, cartilage, and subchondral bone, all of which are closely tied to cartilage degradation. Consequently, OA may also be viewed as a systemic inflammatory disorder. Emerging studies have underscored the significance of T cells in the development of OA. Notably, imbalances in Th1/Th2 and Th17/Treg immune cells may play a crucial role in the pathogenesis of OA. This review aims to compile recent advancements in understanding the role of T cells and their Th/Treg subsets in OA, examines the immune alterations and contributions of Th/Treg cells to OA progression, and proposes novel directions for future research, including potential therapeutic strategies for OA. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of a combination of high-flow nasal oxygen therapy (HFNO) and ipratropium bromide (IB) on Th1/Th2 balance and inflammation in patients with chronic obstructive pulmonary disease (COPD) and respiratory failure (RF). Methods: A retrospective analysis was conducted on the clinical data of patients with COPD and RF admitted to the Affiliated Nanjing Brain Hospital of Nanjing Medical University from June 2021 to March 2023. A total of 162 patients were included, with 79 patients received respiratory support using HFNO (HFNO group) and 83 patients who were treated using combined HFNO/IB (combined group). Treatment effect, lung function, levels of Th1/Th2, and inflammatory state were compared before and after the treatment. Results: Total effeicacy of patients in the combined group was significantly higher than that of the HFNO group (P<0.05). After the treatment, pulmonary function levels of the two groups was higher than that before the treatment, and was significantly better in the combined group compared to the HFNO group (P<0.05). The treatment was associated with a significant increase in the levels of Th1/Th2 in both groups. Post-treatment levels of these indexes in the combined group were markedly higher compared to the HFNO group (P<0.05). After the treatment, the inflammatory response of the two groups decreased, and was lower in the combined group that in the HFNO group (P<0.05). Conclusions: In COPD patients with RF, HFNO combined with IB is efficient in alleviating the inflammatory state of patients, restoring Th1/Th2 balance, and improving lung function compared to HFNO alone. [ABSTRACT FROM AUTHOR]

Introduction: T cells play a critical role in inflammatory diseases. The aim of the present study was to investigate the effects of Majie cataplasm (MJC) on asthma and to propose a possible mechanism involved in this process. Methods: Airway inflammation, infiltration of inflammatory cells, levels of interleukin (IL)-4, IL-10, IL-17, and interferon (IFN)-γ, levels of Th2, Treg, Th17, and Th1 cells, and the expressions of IL-4, IL-10, IL-17, IFN-γ, GATA binding protein 3 (GATA-3), Foxp3, RAR-related orphan receptor gamma (RORγt), and T-bet were detected. Result: MJC treatment reduced lung airway resistance and inflammatory infiltration in lung tissues. MJC treatment also reduced the numbers of eosinophils and neutrophils in the blood and bronchoalveolar lavage fluid (BALF). The levels of IL-4 and IL-17 in the blood, BALF, and lungs were suppressed by MJC, and IFN-γ and IL-10 were increased. Furthermore, MJC suppressed the percentage of Th2 and Th17 and increased the percentage of Th1 and Treg in spleen cells. In addition, MJC can inhibit asthma by increasing expressions of IFN-γ, IL-10, T-bet, and Foxp3, as well as decreasing expressions of IL-4, IL-17, GATA-3, and RORγt. Conclusion: MJC may improve airway hyperresponsiveness and inflammation by regulating Th1/Th2/Treg/Th17 balance in ovalbumin-induced rats. And MJC may be a new source of anti-asthma drugs. [ABSTRACT FROM AUTHOR]

Asthma is an inflammatory disease where the balance between Th1/Th2 and Th17/Treg plays a crucial role in its pathogenesis. Shikonin is used to treat a variety of autoimmune diseases due to its good anti-inflammatory activity. However, the effect and mechanism of shikonin on asthma remain unknown.

BACKGROUND: How to improve the hematopoietic microenvironment is a hot topic in the treatment of aplastic anemia. OBJECTIVE: To explore the action mechanism of Angelica sinensis polysaccharide in the treatment of aplastic anemia by combining GEO sequencing analysis, network pharmacology, and experimental validation. METHODS: Aplastic anemia-related differentially expressed genes were obtained from GEO database, and gene ontology and gene set enrichment analysis were performed. The active components and targets of Angelica sinensis polysaccharide were obtained by combining the literature with PubChem, SwissTargetPrediction, and PharmMapper databases. After the intersection targets were taken, STRING and Cytoscape were used to construct proteinprotein interaction network, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was performed. Mouse model of aplastic anemia was established, and the effect and action mechanism of Angelica sinensis polysaccharide on aplastic anemia were verified by blood cell analyzer, flow cytometry, ELISA, immunohistochemistry, immunofluorescence, and western blot assay. RESULTS AND CONCLUSION: (1) A total of 834 differentially expressed genes were screened, which were involved in biological processes such as cell development, hematopoiesis, and myeloid cell differentiation. (2) 347 targets related to Angelica sinensis polysaccharide were retrieved and 77 potential therapeutic genes were screened. Among them, the degree values of angiogenic, apoptotic, and immune-related factors such as VEGFA, EGLN1, Bcl-2, interferon-γ, interleukin-2, interleukin-4, and interleukin-6 were significant. (3) KEGG pathway enrichment analysis revealed that the therapeutic targets were mainly enriched in Th17 cell differentiation, NK-related cytotoxicity, cell adhesion factors such as interferon-γ, interleukin-2, and interleukin-4 related signaling pathways. (4) Animal experiments showed that Angelica sinensis polysaccharide significantly improved bone marrow haematopoiesis, increased peripheral blood cell, and bone marrow single nucleated cell counts, and improved the survival rate of mice. Compared with the model group, mice in the Angelica sinensis polysaccharide group showed a significant decrease in the ratio of Th1/Th2 cells (P < 0.01), a decrease in the expression level of interferon-γ (P < 0.01), an increase in the level of interleukin-4 (P < 0.05), a significant increase in the level of VEGFA (P < 0.01), a significant decrease in EGLN1 (P < 0.01), a significant decrease in apoptosis rate of bone marrow single nucleated cells and reactive oxygen species level (P < 0.01), and a significant increase in cleaved Caspase-3 protein expression (P < 0.01), and a significant decrease in Bcl-2/Bax ratio (P < 0.01). (5) These findings show that Angelica sinensis polysaccharide can improve hematopoiesis of aplastic anemia mice by regulating aberrant T-cell subsets and promoting angiogenesis to improve hematopoietic microenvironment, and inhibiting apoptosis of bone marrow mononuclear cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: Food allergy has become a global public health problem. This study aimed to explore the possible anti‐allergic effect of vitamin C (VC). A rat basophilic leukemia (RBL)‐2H3 cell degranulation model was used to assess the effect of VC on degranulation in vitro, and an ovalbumin (OVA)‐induced BALB/c mouse allergy model was used to assess the anti‐allergy effect of VC in vivo. RESULTS: In vitro, VC significantly attenuated the release of β‐hexosaminidase, tryptase and histamine, and also reduced cytokine production (interleukins 4 and 6, tumor necrosis factor α) significantly (P < 0.05), with the inhibitory effect demonstrating a positive correlation with VC dose. In vivo, compared with the OVA group, the levels of serum immunoglobulins E and G1 of the VC low‐dose (VCL) group (50 mg kg−1) and high‐dose (VCH) group (200 mg·kg−1) were significantly reduced (P < 0.05). Furthermore, the plasma histamine level was also significantly decreased (P < 0.05). Moreover, TH2 cell polarization in mice of the VCL and VCH groups was significantly inhibited (P < 0.05), promoting the TH1/TH2 cell polarization balance. Additionally, VC treatment enhanced the expression of CD80 (P < 0.05) in spleen and small intestine tissues, while significantly inhibiting the expression of CD86 (P < 0.05); notably, high‐dose VC treatment was more effective. CONCLUSION: VC exerted an anti‐allergic effect through inhibiting degranulation and regulating TH1/TH2 cell polarization balance. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

目的　观察炎症性肠病（IBD）患者血清黏蛋白域分子3（Tim-3）, 半乳糖凝集素9（Gal-9）变化及其与辅助 性T淋巴细胞（Th）1/Th2, Th17/调节性T淋巴细胞（Treg）相关因子水平的关系。方法　选择183例IBD患者纳入 IBD组，其中活动期89例, 缓解期94例；另选120例体检健康者作为对照组。采用ELISA法检测两组血清Tim-3, Gal-9；采用流式细胞术测算外周血Th1, Th2, Th17, Treg占比，计算Th1/Th2比值及Th17/Treg比值；采用ELISA法检 测血清Th1细胞因子干扰素γ（IFN-γ）, 白细胞介素（IL）-2，Th2细胞因子IL-4, IL-6，Th17细胞因子IL-17, IL-22，Treg 细胞因子IL-10, 转化生长因子β（TGF-β). 分析IBD 组血清Tim-3, Gal-9 水平与Th1/Th2, Th17/Treg 的相关性。 结果　IBD组血清Tim-3, Gal-9水平高于对照组，且活动期患者血清Tim-3, Gal-9水平高于缓解期患者（P 均<0. 05). IBD组Th1占比, Th17占比, Th1/Th2比值, Th17/Treg比值, IFN-γ, IL-2, IL-6, IL-17, IL-22水平高于对照组，Th2占 比, Treg占比, IL-4, IL-10, TGF-β水平低于对照组（P 均<0. 05）；活动期IBD患者血清Th1占比, Th17占比, Th1/Th2 比值, Th17/Treg比值, IFN-γ, IL-2, IL-6, IL-17, IL-22高于缓解期患者，Th2占比, Treg占比, IL-4, IL-10, TGF-β低于缓 解期患者（P 均<0. 05). IBD患者血清Tim-3, Gal-9与Th1, Th1/Th2, IFN-γ, IL-2, IL-6, Th17, Th17/Treg, IL-17, IL-22 呈正相关，与Th2, IL-4, Treg, IL-10, TGF-β呈负相关（P 均<0. 05). 结论　IBD患者血清Tim-3, Gal-9水平升高，且 活动期患者高于缓解期患者；异常升高的Tim-3, Gal-9与IBD患者Th17/Treg, Th1/Th2失衡密切相关。 [ABSTRACT FROM AUTHOR]

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague–Dawley (SD) rats were exposed to OVA for 3 weeks. CAVO or loratadine (positive control) was given orally once daily for 2 weeks to OVAexposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells. [ABSTRACT FROM AUTHOR]

Background: Imbalances in Th1/Th2 and Th17/Treg immune axes, coupled with disruptions in the gut microbiota (GM), play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). Cordycepin, a natural anti-inflammatory compound, holds promise in mitigating IBD by rebalancing these immune axes in conjunction with modulating the GM. The aim of this experiment is to investigate the potential of cordycepin in mitigating enteritis and elucidate the underlying mechanisms associated with its ameliorative effects on enteritis. Methods: On the day of inducing experimental colitis with Dextran Sulfate Sodium (DSS), mice in the DSS + Cordycepin and Cordycepin groups received 50 mg/kg/day Cordycepin via intra-gastric administration (i.g.) for seven consecutive days, respectively. Mice in the DSS and control groups were treated with equal volumes of saline. On day 8, all mice were euthanized under pentobarbital sodium anesthesia. Results: In a DSS-induced colitis mouse model, Cordycepin treatment led to a significant reduction in the disease activity index (DAI), splenic weight, and colonic pathological injury while simultaneously improving body weight and colonic length. Furthermore, it positively impacted GM composition, resulting in decreased Th1 and Th17 cells, alongside an increase in Th2 and Treg cells. The contents of the mouse colon were extracted for microbial community analysis. Mouse blood was prepared into a single-cell suspension, and flow cytometry was used to assess the expressio of Treg, Th17, Th1, and Th2 immune cells. Conclusions: These results underscored the effective intervention of cordycepin in ameliorating DSS-induced colitis by harmonizing the interplay between GM and immune homeostasis.

Cadmium (Cd) has adverse effects on organisms. Serine is an essential nutritional factor and its nutritional value is extremely high for body. To explore the effects of serine on spleen toxicity induced by Cd in mice, cadmium chloride (CdCl2, 50 mg/L) and serine (50 g/L) were individually administered or co-administrated in drinking water of mice for 18 weeks. Results demonstrated that Cd exposure induced splenic toxicity and serine against the toxicity damage caused by Cd in mice. Under Cd stress, trace element homeostasis was disturbed, the mice's body weight and spleen index were increased, and splenic morphology and ultrastructure were altered. Furthermore, Cd exposure led to the cell populations disorder, which in turn triggers cell death. Notably, Cd treatment induced oxidative stress and inflammation, increased M1/M2 (iNOS, CD68) and Th1/Th2 (T-bet, CD4) levels, decreased M1/M2 (Arg1) and Th1/Th2 (GATA3) levels, while disrupted the macrophages and lymphocytes homeostasis, which trigged apoptosis and pyroptosis in spleen. In contrast, serine supplementation changed the levels of Cd and other elements, weakened Cd-induced tissue damage and inflammation, enhanced antioxidant capacity, significantly restored cell homeostasis, and effectively inhibited Cd-induced apoptosis and pyroptosis in the spleen. Shortly, the results verified that serine had an ameliorating toxicity effect and restored the M1/M2 and Th1/Th2 balance, restrained apoptosis and pyroptosis induced by Cd.

Mycoplasma gallisepticum (MG) is a pathogen that induces chronic respiratory illnesses in chickens, leading to tracheal and lung injury, and eliciting immune reactions that support sustained colonization. Baicalin, a compound found in scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the potential of baicalin in alleviating lung and cell damage caused by MG by restoring imbalances in M1/M2 and Th1/Th2 differentiation and to explore its underlying mechanism. In this research, a model for M1/M2 polarization induced by MG was initially developed. Specifically, infection with MG at a multiplicity of infection (MOI) of 400 for 6 h represented the M1 model, while infection for 10 h represented the M2 model. The polarization markers were subsequently validated using qRT-PCR, ELISA, and Western blot analysis. Baicalin disrupts the activation of M1 cells induced by MG and has the potential to restore the balance between M1 and M2 cells, thereby mitigating the inflammatory damage resulting from MG. Subsequent studies on MG-infected chickens detected imbalances in M1/M2 and Th1/Th2 differentiation in alveolar lavage fluid, as well as imbalances in macrophages and Th cells in the lung. The M1/Th1 model was exposed to MG for 5 d, while the M2/Th2 model was infected with MG for 7 d. The utilization of both light and electron transmission microscopes revealed that the administration of baicalin resulted in a reduction in the number of M1 cells, a decrease in cytoplasmic vacuoles, restoration of mitochondrial swelling and chromatin agglutination, as well as alleviation of alveolar rupture and inflammatory cell infiltration. Furthermore, baicalin restored MG-induced M1/M2 and Th1/Th2 imbalances and inhibited the phosphorylation of p38 and p65 proteins, thereby hindering the activation of the TLR4-p38 MAPK/NF-κB pathway. This study provides insights into the potential long-term effects of baicalin in MG infection and offers a theoretical basis for practical applications.

The study aimed to investigate the immunomodulatory effect of Qixian Decoction (QXT) in an asthmatic model. In this study, ovalbumin (OVA)-induced asthma in female SPF BALB/c mice was established. Mice were randomly divided into four groups (n = 8): a control group, an OVA model group, a low-dose Qixian Granules (KLL) group, and a high-dose Qixian Granules (KLH) group. Mice in the KLL and KLH groups were given the Qixian Granules at a dose of 8 and 16 g/kg, respectively. After the treatment, the lung pathology was evaluated. The expression of inflammatory factors was determined. Serum metabolomics was used to investigate the overall regulation of QXT on the metabolism of asthmatic mice. Our data showed that QXT significantly increased the expression levels of Th1-related interferon-γ, Treg-related interleukin (IL)-10, and transforming growth factor-β1 while decreasing Th1-related tumor necrosis factor α levels in bronchoalveolar lavage fluid, and Th2-related IL-4 and IL-5 levels in serum when compared with the model group (all p

Ascaris spp. undergo extensive migration within the body before establishing patent infections in the small intestinal tract of humans and pigs. However, whether larval migration is critical for inducing efficient type 2 responses remains poorly understood. Therefore, we investigated systemic versus local adaptive immune responses along the hepato-tracheal migration of Ascaris suum during primary, single infections in conventionally raised pigs. Neither the initial invasion of gut tissue nor migration through the liver resulted in discernable Th2 cell responses. In contrast, lung-stage larvae elicited a Th2-biased pulmonary response, which declined after the larvae had left the lungs. In the small intestine, we observed an accumulation of Th2 cells upon the arrival of fourth-stage larvae (L4) to the small intestinal lumen. In parallel, we noticed robust and increasing Th1 responses in circulation, migration-affected organs, and draining lymph nodes. Phenotypic analysis of CD4+ T cells specifically recognizing A. suum antigens in the circulation and lung tissue of infected pigs confirmed that the majority of Ascaris-specific T cells produced IL-4 (Th2) and, to a much lesser extent, IL-4/IFN-g (Th2/1 hybrids) or IFN-g alone (Th1). These data demonstrate that lungstage but not the early liver-stage larvae lead to a locally restricted Th2 response. Significant Th2 cell accumulation in the small intestine occurs only when L4 complete the body migration. In addition, Th2 immunity seems to be hampered by the concurrent, nonspecific Th1 bias in growing pigs. Together, the late onset of Th2 immunity at the site of infection and the Th1-biased systemic immunity likely enable the establishment of intestinal infections by sufficiently large L4 stages and pre-adult worms, some of which resist expulsion mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Background According to the Th1/Th2 paradigm, the expansion of Th1-type clones in individuals with type 1 diabetes results in reduced Th2-type clones, preventing the development of atopic diseases and vice versa. However, there is no consensus regarding the direct or inverse relationship between autoimmune and atopic diseases. Objective The aim of this scoping review was to examine the knowledge gap about the possibility of coexistence of asthma and type 1 diabetes and determine the prevalence of this association. Methods A scoping review was conducted, following the proposal of the Joanna Briggs Institute. The Population, Concept, and Context strategy was used to formulate the guiding question. The proposed question was: “What is the prevalence of asthma in people with T1DM?” After excluding duplicate articles, analyzing titles and abstracts, and excluding articles that did not answer the guiding question, 17 articles remained and were included in this review. Results Most of the articles selected conformed to the Th1/Th2 hypothesis, as the prevalence of asthma was lower in individuals with T1DM. However, similar or higher prevalence of asthma was found between cases and controls in few articles. Conclusion The prevalence of asthma in people with T1DM ranged from 1.7% to 23.1%. Maybe the mechanisms that characterizes the Th1/Th2 paradigm aren’t as simple as just the interaction of certain cytokines, since Th1-mediated autoimmune diseases and Th2- mediated atopy can coexist.

Background: According to the Th1/Th2 paradigm, the expansion of Th1-type clones in individuals with type 1 diabetes results in reduced Th2-type clones, preventing the development of atopic diseases and vice versa. However, there is no consensus regarding the direct or inverse relationship between autoimmune and atopic diseases. Objective: The aim of this scoping review was to examine the knowledge gap about the possibility of coexistence of asthma and type 1 diabetes and determine the prevalence of this association. Methods: A scoping review was conducted, following the proposal of the Joanna Briggs Institute. The Population, Concept, and Context strategy was used to formulate the guiding question. The proposed question was: "What is the prevalence of asthma in people with T1DM?" After excluding duplicate articles, analyzing titles and abstracts, and excluding articles that did not answer the guiding question, 17 articles remained and were included in this review. Results: Most of the articles selected conformed to the Th1/Th2 hypothesis, as the prevalence of asthma was lower in individuals with T1DM. However, similar or higher prevalence of asthma was found between cases and controls in few articles. Conclusion: The prevalence of asthma in people with T1DM ranged from 1.7% to 23.1%. Maybe the mechanisms that characterizes the Th1/Th2 paradigm aren't as simple as just the interaction of certain cytokines, since Th1-mediated autoimmune diseases and Th2- mediated atopy can coexist. [ABSTRACT FROM AUTHOR]

Several studies have reported that vitamin D may modify human reproductive functions; however, the results are conflicting. We aimed to comprehensively evaluate serum vitamin D levels and examine the relationship between serum vitamin D levels and ovarian reserve markers, and immune markers of implantation, in reproductive-aged Japanese women with infertility.in reproductive-aged women with infertility. This cross-sectional, single-center study included reproductive-aged women who underwent preconception screening for fertility. Serum vitamin D levels and reproductive and immune markers were measured. Standard and advanced statistical techniques were used. We observed a statistically significant difference in the seasonal and monthly 25(OH) vitamin D levels; the 25(OH) vitamin D level during winter was the lowest among all seasons. However, there was no linear correlation between 25(OH) vitamin D levels and ovarian reserve markers, such as follicle-stimulating hormone and anti-Müllerian hormone, or the Th1/Th2 cell ratio, which is used as an implantation-related immunological marker. In this large-scale study, we evaluated the serum 25(OH) vitamin D concentration in reproductive-aged women with infertility in Japan; however, there was no association between reproductive function and vitamin D levels. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-β, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes organic damage as well as anxiety, depression, fear, and other psychological disorders, which seriously affect the quality of life and prognosis of patients and cause a huge economic burden to the family and society. OBJECTIVE: The aim of this study was to investigate the correlation between an imbalance of serum Th1/Th2 indicators and psychiatric depression in elderly patients with COPD and analyze its implications for clinical management. METHODS: From January 2018 to May 2022, 120 elderly patients with COPD treated at our hospital were categorized into two groups based on the self-rating depression scale (SDS): COPD with depression (SDS score ⩾ 50) and COPD alone (SDS score < 50). Blood gas analysis, pulmonary function, and serum Th1/Th2 index were determined. Receiver operating characteristic (ROC) curves were analyzed to explore the diagnostic value of serum Th1/Th2 ratios for COPD complicated by depression. RESULTS: Compared with the group without depression, the partial pressure of carbon dioxide and COPD assessment test scores were significantly higher, and the oxygenation index, forced expiratory volume in one second (FEV1), and percent predicted FEV1 were significantly lower in the COPD with depression group (P < 0.05). Interleukin (IL)-1 β , IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor- α (TNF- α) were significantly higher in the COPD with depression group than in the group without depression (P < 0.05). Logistic regression analysis indicated that the imbalance of serum IL-1 β , IL-2, IL-6, IL-8, IL-10, and TNF- α was a risk factor for mental depression in elderly patients with COPD. When comparing prognostic indices, the interval before the first onset of clinically noticeable deterioration (CID-C) in the COPD with depression group was noticeably shorter than that in the COPD without depression group; the incidence of CID-C within 6 months was noticeably higher in the COPD with depression group than in the group without depression. CONCLUSION: Elderly patients with COPD and depression had reduced pulmonary function and higher serum Th1/Th2 levels, and an imbalance in serum Th1/Th2 indicators was a potential risk factor for depression. Moreover, elderly patients with COPD and depression were at a higher risk of disease progression and had a worse prognosis. Thus, an imbalance in serum Th1/Th2 indicators is a potential prognostic factor for evaluating depression in patients with COPD. [ABSTRACT FROM AUTHOR]

Background: Allergic dermatitis (AD) is an inflammatory skin disease that arises from abnormal T lymphocyte activation. A recombinant fusion protein comprising Helicobacter pylori neutrophil-activating protein and maltose binding protein, rMBP-NAP, has been documented as a novel immunomodulatory TLR agonist.Objective: To explore the effect of the rMBP-NAP on the OXA-induced AD in a mouse model and clarify the possible action mechanism.Methods: The AD animal model was induced by repeated administration of oxazolone (OXA) in BALB/c mice. H&E staining was used to analyze the ear epidermis thickness and the number of infiltrating inflammatory cells. TB staining was used to detect mast cell infiltration in the ear tissue. ELISA was used to analyze the secretion of cytokines IL-4 and IFN-γ in peripheral blood. qRT-PCR was used to determine the expression levels of IL-4, IFN-γ, and IL-13 in ear tissue.Results: OXA induced the establishment of an AD model. After the rMBP-NAP treatment, the thickness of the ear tissue and the number of mast cells infiltrated in AD mice reduced, and the serum and ear tissue levels of IL-4 and IFN-γ increased, but the ratio of IFN-γ (rMBP-NAP group)/IL-4 (rMBP-NAP group) was greater than the ratio of IFN-γ (sensitized group)/IL-4 (sensitized group).Conclusion: The rMBP-NAP improved the disease symptoms including skin lesions in AD, alleviated the inflammation in ear tissue, and restored the Th1/2 balance by inducing a shift from the Th2 to the Th1 response. The results of our work support the use of rMBP-NAP as an immunomodulator for AD treatment in future investigations.

ABSTRACT Cryptococcosis remains a significant threat to human health. While the popular C57BL/6J mouse model of cryptococcosis has some advantages, there are some serious shortcomings that limit the ability of researchers to address the disease. Since humans are resistant to environmental cryptococcal infection until rendered immunodeficient while C57BL/6J mice are innately susceptible, we screened 15 inbred mouse strains for resistance to Cryptococcus infection. The SJL/J mouse strain was unusually resistant to several virulent strains of Cryptococcus while the closely related FVB/J strain was susceptible. The infection pathobiology in SJL/J mice and susceptible mice was similar for the first 7–10 days then markedly diverged toward pathogen clearance. Interferon-gamma (IFN-γ) expression was critical for SJL/J resistance while tumor necrosis factor-alpha was also important. Both CD4 and CD8 T cells produced IFN-γ and were collectively critical. While IL-17 and associated cytokines were expressed in SJL/J mice, IL-17 inhibition did not affect the outcome of infection. Unlike the C57BL/6J, infected SJL/J mice failed to express Th2/atopy-type cytokines even when rendered susceptible by IFN-γ blockade or infection with an alternative fatal cryptococcal strain virulent in SJL/J. These data suggest that the atopic-type response typically associated with the C57BL/6J model is not critical for susceptibility. The productive immune response in SJL/J mice resulted in immune memory that protected mice from reinfection. The SJL/J cryptococcal resistance phenotype was associated with a strong genetic linkage from regions located in chromosomes 2 and 11 suggesting strain-specific modifiers contribute to disease severity. Thus, SJL/J mice are an exciting alternative animal model for cryptococcal pathobiology. IMPORTANCE Cryptococcosis studies often utilize the common C57BL/6J mouse model. Unfortunately, infection in these mice fails to replicate the basic course of human disease, particularly hampering immunological studies. This work demonstrates that SJL/J mice can recapitulate human infection better than other mouse strains. The immunological response to Cryptococcus infection in SJL/J mice was markedly different from C57BL/6J and much more productive in combating this infection. Characterization of infected mice demonstrated strain-specific genetic linkage and differential regulation of multiple important immune-relevant genes in response to Cryptococcus infection. While our results validate many of the previously identified immunological features of cryptococcosis, we also demonstrate limitations from previous mouse models as they may be less translatable to human disease. We concluded that SJL/J mice more faithfully recapitulate human cryptococcosis serving as an exciting new animal model for immunological and genetic studies.

Objective: To investigate the effect of paclitaxel plus carboplatin chemotherapy combined with radiotherapy on serum tumor markers, T helper cell (Th) 1/Th2 cytokines and oncogene expression in high-risk endometrial cancer (EC) patients. Methods: 80 cases of high-risk EC patients who were admitted to our hospital from April 2018 to February 2019 were selected as research objects, and they were randomly divided into the control group (n=40) and the study group (n=40) according to the method of random number table. On the basis of conventional treatment, the control group received paclitaxel plus carboplatin chemotherapy, while the study group received radiotherapy on the basis of the control group. The objective remission rate and disease control rate after treatment were observed in the two groups. The changes of serum tumor markers, Th1/Th2 cytokine levels and oncogene expression in the two groups were compared. The incidence rate of adverse reactions, 3-year tumor recurrence rate and lymph node metastasis rate in the two groups were recorded. Results: The objective remission rate and disease control rate in the study group were higher than those in the control group (P<0.05). After treatment, the chitinase protein 40 (YKL-40), human epididymal protein 4 (HE4), cytokeratin-19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) in the two groups decreased, and the degree of decline in the study group was greater than that in the control group(P<0.05). After treatment, the interleukin-4(IL-4) in the two groups decreased, and interferon-γ(IFN-γ) and IFN-γ/IL-4 increased, and the improvement degree in the study group was greater than that in the control group (P<0.05). After treatment, the c-erbB2 and c-myc in the two groups decreased, P53 and P16 increased, and the improvement degree in the study group was greater than that in the control group (P<0.05). There was no difference in the incidence rate of adverse reactions in the two groups (P>0.05). The 3-year tumor recurrence rate and lymph node metastasis rate in the study group were lower than those in the control group (P<0.05). Conclusion: Paclitaxel plus carboplatin chemotherapy combined with radiotherapy for high-risk EC patients can regulate immune balance, oncogene expression, reduce serum tumor marker levels, so as to improve clinical efficacy. [ABSTRACT FROM AUTHOR]

Houttuynia cordata is an herbal compound that grows in China and exhibits anti-inflammatory, antiviral, and antioxidant properties. Additionally, pyroptosis is mediated by the activated NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome after stimulation by various inflammatory factors in asthma. To investigate the effect of sodium houttuyfonate on NLRP3 inflammasome-related pyroptosis and Th1/Th2 immune imbalance in asthma. Asthmatic mice model were made, sodium houttuyfonate was injected intraperitoneally to treat the asthmatic mice. Airway reactivity, cell classification and counting in the bronchoalveolar lavage fluid were measured. Hematoxylin-eosin and periodic acid-Schiff staining were used to analyze airway inflammation and mucus hypersecretion. Beas-2b cells were cultured, LPS, NLRP3 antagonist (Mcc950) and sodium houttuyfonate were used to intervene the Beas-2b cells, NLRP3, ASC, caspase-1, GSDMD, IL-1β, and IL-18 expression in the lung tissue and cells were analyzed using immunohistochemistry and western blot, while qRT- PCR was performed to analyze the mRNA contents in the pulmonary and the cells, respectively. Th1 and Th2 cytokines (IL-4 and IFN-γ) were detected with ELISA and the proportions of Th1 and Th2 in splenocyte were detected by flow cytometry. Airway reactivity decreased in sodium houttuyfonate group when compared with asthmatic group mice. In the BALF, the numbers of leukocytes, eosinophils, neutrophils, lymphocytes, and macrophages were significantly lower in sodium houttuyfonate group mice than in asthmatic group mice. The proportion of TH1/TH2 cells in spleen cells and IFN-γ /IL-4 in plasma increased in sodium houttuyfonate treatment group when compared with asthma group. Immunohistochemistry, western blot and RT-PCR showed that the expressions of NLRP3, ASC, caspase-1, GSDMD, IL-1β and IL-18 were decreased in the lung tissue of mice after treated with sodium houttuyfonate when compared with those in the asthma group. However, sodium houttuyfonate combined with dexamethasone induced a stronger effect on NLRP3-related pyroptosis and Th1/Th2 immune imbalance compared to sodium houttuyfonate or dexamethasone alone. Beas-2b cells were cultured in vitro , sodium houttuyfonate can alleviate LPS-induced ASC, casepase-1, GSDMD, IL-18 and IL-1β increasing, especially in SH (10 μg/ml) treated group, but the effect less than Mcc950. Sodium houttuyfonate can alleviated NLRP3-related pyroptosis and Th1/Th2 immune imbalance to reduce asthma airway inflammation and airway reactivity. • Sodium houttuyfonate can alleviated NLRP3-related pyroptosis. • Sodium houttuyfonate can alleviated Th1/Th2 immune imbalance. • Sodium houttuyfonate combined with dexamethasone induced a stronger effect on NLRP3-related pyroptosis and Th1/Th2 immune imbalance compared to sodium houttuyfonate or dexamethasone alone. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between the expression of serum alkaline phosphatase (ALP), osteoprotegerin (OPG) and the balance of helper T cell 1 (Th1)/helper T cell 2 (Th2) in traumatic fracture. 80 patients with traumatic fracture admitted to our hospital from February 2019 to December 2022 were selected as the study subjects and divided into observation group, and 80 healthy volunteers who came to our hospital for physical examination at the same time were selected as the control group. The fasting venous blood of the patients in the observation group and the control group in the morning after admission were taken to detect the expression levels of ALP, OPG, Th1 and Th2, and to analyze the correlation between the expression of serum ALP, OPG and Th1/Th2 balance. Eighty patients in the observation group were followed up 12 months after the operation. They were divided into fracture healing group (n=54) and delayed healing group (n=26) according to the degree of fracture healing. The clinical general situation and the expression level of ALP, OPG, Th1/Th2 in the two groups were compared, and the multiple factors affecting the fracture healing of traumatic fracture patients were analyzed. There were differences in the expression of ALP, OPG and helper T cells between the observation group and the control group. The levels of ALP, OPG and Th2 in the observation group were higher than those in the control group, and the levels of Th1 and Th1/Th2 were lower than those in the control group (P<0.05); Spearman correlation analysis showed that serum ALP and OPG were negatively correlated with Th1/Th2 balance (P<0.05); There was no difference in sex, age, cause of injury and Th2 between the fracture healing group and the delayed healing group (P>0.05). There was difference in BMI, ALP, OPG, Th1 and Th1/Th2 levels between the two groups (P<0.05); The above univariate analysis has statistical difference indicators to assign values. The multi-factor analysis results show that ALP, OPG, Th2, Th1/Th2 are independent influencing factors affecting the fracture healing of traumatic fracture patients (P<0.05). The occurrence of traumatic fracture will lead to the increase of ALP and OPG levels and the change of Th1/Th2 balance. There is a significant correlation between the serum ALP and OPG levels of patients and Th1/Th2 balance. In addition, changes in the levels of ALP, OPG, Th1, Th1/Th2 can affect the level of postoperative fracture healing in patients with traumatic fracture. Therefore, clinically, patients with elevated ALP and OPG levels and Th1/Th2 imbalance should be alert to the occurrence of poor fracture healing. [ABSTRACT FROM AUTHOR]

Some research has shown that PM2.5 causes Th1/Th2 immune imbalance and aggravates asthma. However, the exact mechanism of PM2.5 causing aggravation of asthma remains unclear. The purpose of this study was to investigate whether exposure to PM2.5 exacerbates Th1/Th2 immune imbalance through the Notch signaling pathway. Eight-week-old SPF female BALF/c mice were sensitized by ovalbumin to establish an asthma mouse model. PM2.5 exposure was carried out by aerosol inhalation of PM2.5 (510 μg/m3) after each provocation. The lung function of mice was measured and Splenic T lymphocyte subsets were detected. Notch signaling pathway was tested. The levels of interferon (IFN)-γ and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid were determined. The results showed that the expression of the mRNA and protein of Notch1 and Hes1 in the asthma group were significantly higher than those in healthy controls. The levels of IL-4 were also remarkably high; while the levels of IFN-γ were remarkably low in serum and BALF, the Th1% and Th1/Th2 ratios were significantly lower, and Th2% was significantly higher in the asthma group than in the healthy controls. PM2.5 promoted further activation of the Notch signaling pathway and aggravated Th1/Th2 immune imbalance in asthmatic mice. γ-secretase inhibitor can partially inhibit the activation of the Notch signaling pathway and alleviate aggravation of immune imbalance. In conclusion, the asthmatic mice had a Th1/Th2 immune imbalance and an overactivated Notch signaling pathway. PM2.5 further aggravated Th1/Th2 immune imbalance by activating the Notch signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: We here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate. We previously identified peripheral type 1 and 17 T cell responses against Dsg3 and BP180 in a cohort of LP patients strongly suggesting that the underlying inflammatory T cell signature may drive the evolving phenotype Methods: Paraffin-embedded skin biopsies fromwell-characterized patients with LP (n=31), BP (n=19), PV (n=9), and pemphigus foliaceus (PF) (n=2) were analysed. Areas with the most prominent inflammatory infiltrate were excised with punch biopsies and tissue microarrays (TMA) containing multiple biopsies were created. Using multicolor immunofluorescence, the inflammatory infiltrate was stained with antibodies against multiple cellular markers, i. e. CD3ε, CD4, CD15, TCR-δ, the cytokine IL-17A, and the transcription factors, T-bet and GATA-3. Results: In LP, there was a higher number of CD4+ T cells expressing T-bet compared to GATA-3. In contrast, CD4+ T cells in PV and BP skin lesions more frequently expressed GATA-3 than T-bet. IL-17A+ cells and IL-17A+ T cells were found to a similar extent in all the three disorders. IL-17A+ granulocytes were more predominant in BP than in LP or PV. Of note, the majority of IL-17A+ cells in LP were neither T cells nor granulocytes. Discussion: Our findings in inflammatory skin infiltrates clearly show a predominant type 1 signature in LP in contrast to a preponderance of type 2 T cells in PV and BP. In contrast to LP, granulocytes and to a much lesser extent CD3+ T cells were a cellular source of IL-17A in BP and PV. These data strongly suggest that different inflammatory cell signatures drive evolving clinically diverse phenotypes of LP, PV and BP despite common target antigens of the skin. [ABSTRACT FROM AUTHOR]

Objective: To explore the impact of seasonal changes on the T-helper 1 (Th1)/T-helper 2 (Th2) immune balance of the body in order to elucidate the internal immunological mechanisms underlying seasonal eczema. Methods: Eighty 4-week-old male Sprague–Dawley rats were divided into 5 season groups kept in corresponding season simulation environments, and subdivided into the model group and the control group. The Eczema Area and Severity Index (EASI) and scratching frequency were evaluated. The serum levels of immunoglobulin E (IgE), interleukin-2 (IL-2), interleukin-12 (IL-12), and interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-25 (IL-25), and interleukin-31 (IL-31), and melatonin (MT), as well as the MT receptor (MTR) levels in the spleen, were detected by enzyme-linked immunosorbent assay analysis. The mRNA expression levels of T-bet and GATA3 were detected by quantitative real-time polymerase chain reaction. Results: EASI scores and the scratching frequency of the model group were higher in the long summer than in the other 4 seasons. Meanwhile, the serum levels of IgE and the Th2 cytokines IL-4, IL-25, and IL-31, as well as GATA3 mRNA expression levels, were high during the long summer in both groups. However, the serum levels of the Th1 cytokines IL-2, IL-12, and IFN-γ, as well as MT, MTR, and T-bet mRNA levels, were lower during the long summer. In all 5 seasonal groups (spring, summer, long summer, autumn, and winter), the levels of all immune factors, especially IL-4 and IL-31, were higher in the model group than those in the control group, while the concentrations of MT and MTR were lower. Conclusion: Under long light, hot, and humid conditions in the long summer, the body is more likely to suffer from Th2-dominated immune imbalance. This is the internal mechanism behind the high incidence and severity of eczema during the long summer. MT and MTR play a key role in the seasonal onset of eczema.

Objective To investigate the role of Notch1 signaling pathway in Th1/Th2 imbalance induced by neonatal Streptococcus pneumoniae pneumonia (S.pp) infection. Methods Twelve Balb/c neonatal mice (1 week old) were randomly divided into neonatal S.pp group, neonatal S.pp with Notch1 inhibition treatment group (S.pp+DAPT, a γ-secretase inhibitor) and mock-infected control group (control group) (n=4). The S.pp group and the S.pp+DAPT group were infected with 1×107 CFU of S. pneumoniae in 10 μL of PBS intranasally, while the control group received equivalent PBS. In 7 d after infection, the S.pp+DAPT groups were given 0.3 mg/kg DAPT by nasal instillation, and the S.pp and the control groups were instilled equivalent PBS. In 5 weeks after infection, airway hyperresponsiveness (AHR) was evaluated by invasive body plethysmography system. Differential cell counts in bronchoalveolar lavage fluid (BALF) were analyzed. HE staining was used to observe the histopathological changes of the lung tissue. Western blotting was used to detect the protein expression of Notch1 protein, and RT-PCR to measure the mRNA levels of T-bet and GATA3. And the percentages of Th1 and Th2 cells in the lung tissue were determined by flow cytometry and Th1/Th2 ratio was calculated. Results Notch1 expression was significantly lower in the S.pp+ DAPT group than the S.pp group (0.23±0.09 vs 1.94±0.78, P < 0.01). The total cell count and counts of neutrophils, monocytes and lymphocytes in the BALF from the S.pp+DAPT group were remarkably lower than those in the S.pp group (P < 0.01). The S.pp+DAPT mice had obviously lower histologic scores of pulmonary peribronchiolitis, pulmonary perivasculitis and pulmonary alveolitis in lung tissue than the S.pp group (0.55±0.17 vs 1.52±0.27, P < 0.01; 0.05±0.10 vs 0.88±0.25, P < 0.01; 0.18±0.35 vs 1.57±0.25, P < 0.01). The mRNA level of GATA3 and percentage of Th2 cells were significantly lower in the S.pp+DAPT group than the S.pp group [19.11±9.79 vs 177.56±65.95, P < 0.01; (0.16±0.02)% vs (0.28±0.04)%, P < 0.01]. While the mRNA level of T-bet and percentage of Th1 cells were similar between the 2 groups. The S.pp+DAPT group had significantly higher Th1/Th2 when compared with the S.pp group (14.67±2.60 vs 7.89±0.82, P < 0.01). The AHR in the S.pp+DAPT group mice was significantly decreased when inhaled different concentrations of acetylcholine (3.125~50 mg/mL) as compared with the S.pp group (P < 0.01). Conclusion Neonatal S.pp may induce Th1/Th2 imbalance by activating Notch1 signal, and thus promote airway hyperreactivity and airway inflammation.

Objective: To investigate the effect of tacrolimus treatment on refractory recurrent spontaneous abortion (RSA) patients with elevated serum IL-33/ST2 levels. Methods: This study was a randomized controlled trial (RCT) of refractory RSA patients with elevated peripheral blood IL-33/ST2 levels or an elevated Th1/Th2 cell ratio. A total of 149 women were enrolled, each of whom had had at least 3 serial miscarriages and was confirmed to have elevated peripheral blood IL-33/ST2 levels or an elevated Th1/Th2 cell ratio. These women were randomly divided into two groups. The tacrolimus group (n = 75) received basic therapy with the addition of tacrolimus (Prograf). Tacrolimus was administered at a dose of 0.05 ~ 0.1 mg/kg/day from the end of the menstrual period to the beginning of the next menstrual period or to the 10th week of pregnancy. In contrast, basic therapy with the addition of placebo was given to the placebo group (n = 74). The main study outcome was the delivery of healthy newborns without deformities. Results: A total of 60 (80.00%) patients in the tacrolimus group and 47 (63.51%) patients in the placebo group delivered healthy newborns [P = 0.03, odds ratio = 2.30; 95% confidence interval (1.10 ~ 4.81)]. The peripheral blood IL-33/ST2 levels and Th1/Th2 cell ratio of the tacrolimus group were much lower than those of the placebo group (P < 0.05). Conclusion: We validated our previous finding that serum IL-33 and sST2 concentrations are related to RSA. Immunosuppressive treatment with tacrolimus was demonstrated to be a promising method to treat refractory RSA with immune bias disorders. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of Shugan Jianpi Huoxue prescription on intestinal mucosal barrier function, oxidative stress response and T helper cell subsets (Th1/Th2) cytokines in patients with ulcerative colitis (UC). Methods: 80 patients with UC who were admitted to our hospital from April 2020 to March 2022 were selected. According to the random number table method, 80 patients with UC were divided into control group (n=40, mesalazin enteric-coated tablets treatment) and study group (n=40, mesalazin enteric-coated tablets combined with Shugan Jianpi Huoxue prescription treatment). The changes of intestinal mucosal barrier function, curative effect, oxidative stress response related indexes, traditional Chinese medicine syndrome score, and Th1/Th2 cytokines were observed in the two groups. Results: The total effective rate in the study group was higher than that in the control group (p<0.05). 2 months after treatment, the scores of diarrhea, chest and hypochondriac distension, god is tired and lazy and belching in the two groups were decreased, and the study group was lower than the control group (P<0.05). Diamine oxidase (DAO), D-lactic acid and endotoxin in the two groups at 2 months after treatment were decreased, and the study group was lower than the control group (P<0.05). 2 months after treatment, the superoxide dismutase (SOD) in the study group was higher than that in the control group, and the malondialdehyde (MDA) was lower than that in the control group (P<0.05). 2 months after treatment, interleukin-4 (IL-4) in the study group was higher than that in the control group, interferon-y (INF-γ) and INF-γ/IL-4 were lower than those in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions in the two groups (P>0.05). Conclusion: Shugan Jianpi Huoxue adjuvant therapy for patients with UC, which can regulate the immune balance of Th1/Th2, improve the body's oxidative stress response and intestinal mucosal barrier function, and promote the improvement of clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Vitamin D, recognized for its dual role as an immune regulator and essential nutrient crucial for human well-being, exerts a multifaceted impact on the intricate immune processes found in individuals suffering from Chronic Obstructive Pulmonary Disease (COPD). In addition to its established functions in maintaining phosphate-calcium balance and bone mineralization, it exerts both direct and indirect effects on cellular elements within the COPD environment, thereby influencing the levels of inflammatory factors in the airways. Objective: The study sought to ascertain the role of sunlight and vitamin D in lung disease, as well as the relationship between vitamin D levels and cytokine discord in patients in early stage chronic obstructive pulmonary disease (COPD). Methodology: A prospective study was conducted at Ponch Medical College, Rawalakot between January 2020 to December 2020 and comprised of 120 patients. COPD pulmonary function (LF) I & COPD LF II patients were divided into two groups (n = 60 each). An immunosorbent assay that uses enzymes was used to measure the blood levels inflammatory TNF-α, IFN-γ, interleukin 4 (IL-4), and IL-6 in order to identify the Th1/Th2 marker. A proportion of IFN-γ to IL-4 was also a part of the treatment. Results: Between the LF I alongside LF II groups, there was a significant difference (p < 0.04) in FEV1pred%, FEV1 or IFN-γ, IL-4, F, IFN-γ/IL-4, and IL-6. In patients with early-stage COPD, cytokines (Th1/Th2) were significant correlated with forced volume percent (FEV1pred%) (r < 0.485, p < 0.002) and compelled exhalation volume/forced lifespan (FEV1/FVC) (r = 0.254, p = 0.015). Conclusion: Mostly cases with early-stage COPD had a vitamin D deficiency. Together with the FEV1/FVC LF parameters, it showed a positive correlation. This research offers experimental evidence in favour of vitamin D's role in COPD prevention and treatment, as well as possible anti-inflammatory action mechanisms. [ABSTRACT FROM AUTHOR]

Objective: This study explored the correlation between a Th1/Th2 cytokines imbalance and 25-hydroxy-vitamin D (vit D) level in early chronic obstructive pulmonary disease (COPD), provided experimental rationales for the role of vit D in the prevention and control of COPD, and elucidated the potential antiinflammatory mechanism involved. Methods: This study was based on the results of the "Screening and Early Diagnosis of COPD" public health project conducted through Shenzhen Municipal Qianhai Shekou Free Trade Zone Hospital. Patients with early COPD were selected as study participants. A prospective, randomized, and controlled method was employed for assigning eligible participants into three groups, i.e., a COPD lung function (LF) I, COPD LF II, and a healthy group, respectively (n = 40 each). The serum content of tumor necrosis factor alpha (TNF-α), interferongamma (IFN-γ), interleukin 4 (IL-4), and IL-6 were measured by enzyme-linked immunosorbent assay, and the ratio of IFN-γ/IL-4 treated as a marker for Th1/Th2. The serum concentration of 25-hydroxyl-vit D (25 [OH]D) was quantified by a chemiluminescence assay. Statistical processing was performed, and the correlations between changes in the above parameters with vit D level and LF parameters were examined. Results: There were differences in FEV1pred%, FEV1/FVC, IFN-γ, IL-4, IL-6 and IFN-γ/IL-4 between the healthy group, the COPD LF I group and the COPD LF II group (p < 0.05). In early COPD, Th1/Th2 cytokines was positively correlated with forced expiratory volume/expected value (FEV1pred%) (r = 0.485, p < 0.001) and forced expiratory volume/forced vital capacity (FEV1/FVC) (r = 0.273, p = 0.018); Th1/Th2 cytokines levels positively correlated with vit D level (r = 0.27, p = 0.02), and 25(OH)D level positively correlated with FEV1pred % (r = 0.695, p < 0.001). Conclusion: Vitamin D deficiency was ubiquitous in patients with early COPD. It was positively correlated with the FEV1pred% and FEV1/FVC LF parameters. Accordingly, this study provides experimental rationales for the role of vit D in the prevention and control of COPD and the potential anti-inflammatory mechanisms involved. [ABSTRACT FROM AUTHOR]

IntroductionWe here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate. We previously identified peripheral type 1 and 17 T cell responses against Dsg3 and BP180 in a cohort of LP patients strongly suggesting that the underlying inflammatory T cell signature may drive the evolving phenotype.MethodsParaffin-embedded skin biopsies from well-characterized patients with LP (n=31), BP (n=19), PV (n=9), and pemphigus foliaceus (PF) (n=2) were analysed. Areas with the most prominent inflammatory infiltrate were excised with punch biopsies and tissue microarrays (TMA) containing multiple biopsies were created. Using multicolor immunofluorescence, the inflammatory infiltrate was stained with antibodies against multiple cellular markers, i. e. CD3ϵ, CD4, CD15, TCR-δ, the cytokine IL-17A, and the transcription factors, T-bet and GATA-3.ResultsIn LP, there was a higher number of CD4+ T cells expressing T-bet compared to GATA-3. In contrast, CD4+ T cells in PV and BP skin lesions more frequently expressed GATA-3 than T-bet. IL-17A+ cells and IL-17A+ T cells were found to a similar extent in all the three disorders. IL-17A+ granulocytes were more predominant in BP than in LP or PV. Of note, the majority of IL-17A+ cells in LP were neither T cells nor granulocytes.DiscussionOur findings in inflammatory skin infiltrates clearly show a predominant type 1 signature in LP in contrast to a preponderance of type 2 T cells in PV and BP. In contrast to LP, granulocytes and to a much lesser extent CD3+ T cells were a cellular source of IL-17A in BP and PV. These data strongly suggest that different inflammatory cell signatures drive evolving clinically diverse phenotypes of LP, PV and BP despite common target antigens of the skin.

• Cigarette smoke decreases IFN-α production by the nasal adjuvant CpG ODN. • It suppresses DC maturation/differentiation and the Th1 dominant immunity. • Progressive DNA methylation of the IRF7 gene is one of the molecular mechanisms. • Decreased TLR9 expression is another mechanism. • Dysfunction of pDCs by smoking might cause a low response to mucosal vaccines. Mucosal vaccines offer several advantages over transdermal vaccines, including the ability to acquire systemic and mucosal immunities. Smoking is a huge public health threat and major risk factor for various diseases that exacerbate or prolong respiratory symptoms and conditions. However, its impact on the efficacy of mucosal vaccines remains partially explored. Thus, this study investigates the effects of smoking on mucosal vaccine reactivity by assessing the induction of Th1 immunity, a vital response in infection defense. Cigarette smoke condensate was prepared as a substitute for mainstream smoke. We intranasally administered diphtheria toxoid as an antigen and natural CpG oligonucleotide G9.1, which enhances the Th1-type antibody (Ab) response in a plasmacytoid dendritic cells (pDCs) dependent manner, as an adjuvant to mice to assess the effect of cigarette smoke condensate on Ab responses. The mechanism of its effect was evaluated using human peripheral blood mononuclear cells and their pDC-rich fraction cultured with or without G9.1. In mice, cigarette smoke condensate tended to decrease diphtheria toxoid-specific Ab response, with a higher reduction in Th1-type IgG2 Ab response than in Th2-type IgG1 Ab response. In human peripheral blood mononuclear cells, cigarette smoke condensate significantly reduced the induction of IFN-α production by G9.1. Moreover, G9.1-induced increases in the CD83 expression in pDCs and the CD80 expression in DCs were suppressed via treatment with cigarette smoke condensate. Among the mechanisms suggested were decreased expression of toll-like receptor 9 mRNA, decreased expression of mRNA for IFN regulatory factor 7, and increased CpG methylation of its promoter region. The analysis of Tbet and GATA3 expressions revealed that cigarette smoke condensate exhibits Th1-directed immunostimulatory activity at a steady state but becomes more Th2-directed under G9.1 stimulation. In conclusion, smoking could reduce mucosal vaccine responses by decreasing pDC activation and, consequently, Th1-dominant immunity. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-β, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment. [ABSTRACT FROM AUTHOR]

Initial exposure to influenza virus(es) during early childhood produces protective antibodies that may be recalled following future exposure to subsequent viral infections or vaccinations. Most influenza vaccine research studies use immunologically naïve animal models to assess vaccine effectiveness. However, most people have an extensive influenza immune history, with memory cells produced by viruses or vaccines representing multiple influenza viruses. In this study, we explored the effect influenza seasonal virus-induced immunity has on pre-pandemic influenza virus vaccination. The mice that were pre-immune to historical H1N1 and H3N2 seasonal influenza viruses were vaccinated with adjuvanted pre-pandemic (H2, H5, and H7) HA-based computationally optimized broadly reactive antigen (COBRA) vaccines, and were fully protected from lethal challenge, whereas the mock-vaccinated mice, with or without pre-immunity, were not protected from morbidity or mortality. Detectable antibody titers were present in the pre-immune mice vaccinated with a single dose of vaccine, but not in the immunologically naïve mice. The mice vaccinated twice with the trivalent COBRA HA vaccine had similar antibody titers regardless of their pre-immune status. Overall, seasonal pre-immunity did not interfere with the immune responses elicited by pre-pandemic COBRA HA vaccines or the protection against pre-pandemic viruses. [ABSTRACT FROM AUTHOR]

To date, few studies have been conducted on the relationship between postbiotics and air pollution, and there is limited knowledge if postbiotic and probiotic have synergistic effects. Therefore, we created a PM‐induced lung inflammation mice model and demonstrated the effect of probiotic, postbiotic, and their combination treatment on attenuation of PM2.5‐induced lung damage and allergic response. The mice were intratracheally given PM2.5 triggering conditions of acute lung damage and allergic response. Our results showed that individual treatment of probiotic and postbiotic reduced body weight loss by 47.1% and 48.9%, but the results did not show any effect on polarizing IFN‐γ/IL‐4 ratio. In addition, PM2.5‐induced overactive expression of IgE treated by probiotic and postbiotic was reduced by 33.2% and 30.4%, respectively. While combination treatment of probiotic and postbiotic exerted a synergistic effect, especially considerably on improving IgE reduction by 57.1%, body weight loss by 78.3%, and IFN‐γ/IL‐4 ratio boost by 87.5%. To sum up the above functionality, these research findings may help establish a novel platform for postbiotic application, formulation, and mechanistic selection with regard to PM2.5‐induced lung injury. Practical Application: Allergic inflammation caused by PM2.5 is not like common allergens (ex. Pollens, ovalbumin, dust mites), which simply skewing Th1/Th2 polarization to Th2. Thus using probiotics screened by Th1‐skewing criteria might not be the best choice to treat on PM2.5‐induced symptoms. This research proposed a combination of probiotics and postbiotics on modulating immunity homeostasis, and consequently attenuating complications of PM2.5‐induced lung damage. These research findings may help establish a novel platform for postbiotic application, formulation and mechanistic selection with regard to PM2.5‐induced lung injury. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a zoonotic and vector-borne infectious disease that is caused by the genus Leishmania belonging to the trypanosomatid family. The protozoan parasite has a digenetic life cycle involving a mammalian host and an insect vector. Leishmaniasisis is a worldwide public health problem falling under the neglected tropical disease category, with over 90 endemic countries, and approximately 1 million new cases and 20,000 deaths annually. Leishmania infection can progress toward the development of species–specific pathologic disorders, ranging in severity from self-healing cutaneous lesions to disseminating muco-cutaneous and fatal visceral manifestations. The severity and the outcome of leishmaniasis is determined by the parasite’s antigenic epitope characteristics, the vector physiology, and most importantly, the immune response and immune status of the host. This review examines the nature of host–pathogen interaction in leishmaniasis, innate and adaptive immune responses, and various strategies that have been employed for vaccine development.

Imbalances in Th1/Th2 and Th17/Treg immune axes, coupled with disruptions in the gut microbiota (GM), play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). Cordycepin , a natural anti-inflammatory compound, holds promise in mitigating IBD by rebalancing these immune axes in conjunction with modulating the GM. The aim of this experiment is to investigate the potential of cordycepin in mitigating enteritis and elucidate the underlying mechanisms associated with its ameliorative effects on enteritis. On the day of inducing experimental colitis with Dextran Sulfate Sodium (DSS), mice in the DSS + Cordycepin and Cordycepin groups received 50 mg/kg/day Cordycepin via intra-gastric administration (i.g.) for seven consecutive days, respectively. Mice in the DSS and control groups were treated with equal volumes of saline. On day 8, all mice were euthanized under pentobarbital sodium anesthesia. In a DSS-induced colitis mouse model, Cordycepin treatment led to a significant reduction in the disease activity index (DAI), splenic weight, and colonic pathological injury while simultaneously improving body weight and colonic length. Furthermore, it positively impacted GM composition, resulting in decreased Th1 and Th17 cells, alongside an increase in Th2 and Treg cells. The contents of the mouse colon were extracted for microbial community analysis. Mouse blood was prepared into a single-cell suspension, and flow cytometry was used to assess the expressio of Treg, Th17, Th1, and Th2 immune cells. These results underscored the effective intervention of cordycepin in ameliorating DSS-induced colitis by harmonizing the interplay between GM and immune homeostasis. [Display omitted] • Cordycepin Alleviates DSS-Induced Colitis in Mice. • Cordycepin Enhances GM Diversity in Colitis-Afflicted Mice. • Cordycepin Regulates the Balance of Th17/Treg Cells in Colitis Mice. • Cordycepin Regulates the Balance of Th1/Th2 Cells in Colitis Mice. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) has adverse effects on organisms. Serine is an essential nutritional factor and its nutritional value is extremely high for body. To explore the effects of serine on spleen toxicity induced by Cd in mice, cadmium chloride (CdCl 2 , 50 mg/L) and serine (50 g/L) were individually administered or co-administrated in drinking water of mice for 18 weeks. Results demonstrated that Cd exposure induced splenic toxicity and serine against the toxicity damage caused by Cd in mice. Under Cd stress, trace element homeostasis was disturbed, the mice's body weight and spleen index were increased, and splenic morphology and ultrastructure were altered. Furthermore, Cd exposure led to the cell populations disorder, which in turn triggers cell death. Notably, Cd treatment induced oxidative stress and inflammation, increased M1/M2 (iNOS, CD68) and Th1/Th2 (T-bet, CD4) levels, decreased M1/M2 (Arg1) and Th1/Th2 (GATA3) levels, while disrupted the macrophages and lymphocytes homeostasis, which trigged apoptosis and pyroptosis in spleen. In contrast, serine supplementation changed the levels of Cd and other elements, weakened Cd-induced tissue damage and inflammation, enhanced antioxidant capacity, significantly restored cell homeostasis, and effectively inhibited Cd-induced apoptosis and pyroptosis in the spleen. Shortly, the results verified that serine had an ameliorating toxicity effect and restored the M1/M2 and Th1/Th2 balance, restrained apoptosis and pyroptosis induced by Cd. [Display omitted] • Cadmium induced oxidative damage and inflammatory response. • Cadmium disrupted the homeostasis of trace elements. • M1/M2 and Th1/Th2 polarization imbalance under cadmium stress. • Cadmium exposure triggered apoptosis and pyroptosis in the spleen. • Serine effectively alleviates cadmium-induced immunotoxicity in mice. [ABSTRACT FROM AUTHOR]

Mycoplasma gallisepticum ( MG ) is a pathogen that induces chronic respiratory illnesses in chickens, leading to tracheal and lung injury, and eliciting immune reactions that support sustained colonization. Baicalin, a compound found in scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the potential of baicalin in alleviating lung and cell damage caused by MG by restoring imbalances in M1/M2 and Th1/Th2 differentiation and to explore its underlying mechanism. In this research, a model for M1/M2 polarization induced by MG was initially developed. Specifically, infection with MG at a multiplicity of infection (MOI) of 400 for 6 h represented the M1 model, while infection for 10 h represented the M2 model. The polarization markers were subsequently validated using qRT-PCR, ELISA, and Western blot analysis. Baicalin disrupts the activation of M1 cells induced by MG and has the potential to restore the balance between M1 and M2 cells, thereby mitigating the inflammatory damage resulting from MG. Subsequent studies on MG-infected chickens detected imbalances in M1/M2 and Th1/Th2 differentiation in alveolar lavage fluid, as well as imbalances in macrophages and Th cells in the lung. The M1/Th1 model was exposed to MG for 5 d, while the M2/Th2 model was infected with MG for 7 d. The utilization of both light and electron transmission microscopes revealed that the administration of baicalin resulted in a reduction in the number of M1 cells, a decrease in cytoplasmic vacuoles, restoration of mitochondrial swelling and chromatin agglutination, as well as alleviation of alveolar rupture and inflammatory cell infiltration. Furthermore, baicalin restored MG-induced M1/M2 and Th1/Th2 imbalances and inhibited the phosphorylation of p38 and p65 proteins, thereby hindering the activation of the TLR4-p38 MAPK/NF-κB pathway. This study provides insights into the potential long-term effects of baicalin in MG infection and offers a theoretical basis for practical applications. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of Th1/Th2 ratio on pyroptosis of placental trophoblast cells in early-onset severe preeclampsia. Methods The clinical data of 55 cases of early-onset severe preeclampsia diagnosed in our hospital from June 2018 to December 2019 were collected as the preeclampsia group, and another 30 healthy pregnant women in our hospital during the same period were subjected as the normal control. Flow cytometry was used to detect the proportion of Th1 and Th2 cells in venous blood of the subjects; ELISA was adopted to measure the contents of pyroptosis-related factors IL-1β and IL-18 in serum. The placental tissue pyroptosis and the expression of GSDMD protein in placental tissue were observed by TUNEL staining and immunofluorescence staining respectively. The protein levels of Caspase-1, NLRP3, ASC and GSDMD were determined by Western blotting. Results Flow cytometry showed that the ratio of Th1/Th2 cells was significantly increased in the preeclampsia group. ELISA results indicated that the contents of IL-1β and IL-18 in the serum were remarkably higher in the preeclampsia group than the normal group (P < 0.01). TUNEL staining and immunofluorescence staining also confirmed a large number of pyroptosis-like cells and high level of GSDMD in the preeclampsia group; Western blotting demonstrated that the protein levels of Caspase-1, NLRP3, ASC and GSDMD were all notably elevated, as compared with the normal group. Conclusion In early-onset severe preeclampsia, the increased Th1/Th2 ratio promotes pyroptosis of placental trophoblast cells.

Background: As an important zoonotic parasitic disease with global distribution, scabies causes serious public health and economic problems. Arginine kinase (AK) is involved in cell signal transduction, inflammation, and apoptosis. Two AKs were identified in Sarcoptes scabiei, but their functions in the host immune response remain unclear. Methods: rSsAK-1 and rSsAK-2 were expressed, purified, and immunolocalized. The effects of rSsAK-1 and rSsAK-2 on rabbit PBMC proliferation, apoptosis, and migration; Bcl-2, Bcl-xl, Fas, Bax, and NF-kB transcription levels; and IL-2, IFNg, IL-4, IL-10, TGF-b1, and IL-17 secretion were detected. Results: rSsAK-1 and rSsAK-2 were cloned and expressed successfully. Both enzymes were ~57 kDa and contained 17-kDa tagged proteins, and had good catalytic activity and immunoreactivity. The proteins were located in the S. scabiei exoskeleton, chewing mouthparts, legs, stomach, and intestine. SsAK-1 and SsAK-2 were secreted in the pool and epidermis of the skin lesions, which may be involved in S. scabiei-host interaction. rSsAK-1 and rSsAK-2 significantly promoted cell proliferation, induced cell migration, inhibited apoptosis, and increased Bcl-2, Bcl-xl and NF-kB (p65) transcription levels concentration-dependently, and inhibited IL-2, IFN-g, and IL-10 secretion and promoted IL-4 and IL-17 secretion. Conclusion: rSsAK-1 and rSsAK-2 might increase Bcl-2 and Bcl-xl expression by activating the NF-kB signaling pathway to promote cell proliferation and inhibit apoptosis, which induced PBMC survival. By inducing PBMC migration to the infection site, rSsAK-1 and rSsAK-2 shifted the Th1/Th2 balance toward Th2 and changed the Th17/Treg balance, which indicated their immune role in S. scabiei allergic inflammation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of a combination of high-flow nasal oxygen therapy (HFNO) and ipratropium bromide (IB) on Th1/Th2 balance and inflammation in patients with chronic obstructive pulmonary disease (COPD) and respiratory failure (RF)., Methods: A retrospective analysis was conducted on the clinical data of patients with COPD and RF admitted to the Affiliated Nanjing Brain Hospital of Nanjing Medical University from June 2021 to March 2023. A total of 162 patients were included, with 79 patients received respiratory support using HFNO (HFNO group) and 83 patients who were treated using combined HFNO/IB (combined group). Treatment effect, lung function, levels of Th1/Th2, and inflammatory state were compared before and after the treatment., Results: Total effeicacy of patients in the combined group was significantly higher than that of the HFNO group ( P <0.05). After the treatment, pulmonary function levels of the two groups was higher than that before the treatment, and was significantly better in the combined group compared to the HFNO group ( P <0.05). The treatment was associated with a significant increase in the levels of Th1/Th2 in both groups. Post-treatment levels of these indexes in the combined group were markedly higher compared to the HFNO group ( P <0.05). After the treatment, the inflammatory response of the two groups decreased, and was lower in the combined group that in the HFNO group ( P <0.05)., Conclusions: In COPD patients with RF, HFNO combined with IB is efficient in alleviating the inflammatory state of patients, restoring Th1/Th2 balance, and improving lung function compared to HFNO alone., (Copyright: © Pakistan Journal of Medical Sciences.)

Osteoarthritis (OA) is a prevalent clinical condition affecting the entire joint, characterized by its multifactorial etiology and complex pathophysiology. The onset of OA is linked to inflammatory mediators produced by the synovium, cartilage, and subchondral bone, all of which are closely tied to cartilage degradation. Consequently, OA may also be viewed as a systemic inflammatory disorder. Emerging studies have underscored the significance of T cells in the development of OA. Notably, imbalances in Th1/Th2 and Th17/Treg immune cells may play a crucial role in the pathogenesis of OA. This review aims to compile recent advancements in understanding the role of T cells and their Th/Treg subsets in OA, examines the immune alterations and contributions of Th/Treg cells to OA progression, and proposes novel directions for future research, including potential therapeutic strategies for OA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wen, Qiu, Ye, Tan, Xu, Lu and Kuang.)

The number of patients with allergic asthma is rising yearly, and hormonal drugs, such as dexamethasone, have unique advantages and certain limitations. In the treatment of allergic diseases especially allergic asthma, increasing the percentage or the function of immunosuppressive cells, such as Treg cells, may achieve a good effect. On the basis of good clinical results, we found that Guominkang (GMK) especially high-concentration GMK can achieve a similar effect with dexamethasone in controlling the symptoms of allergic asthma and inhibiting inflammation of allergic asthma. In our study, GMK can inhibit the recruitment of inflammatory cells, decrease mucus production, and reduce airway resistance. Besides, GMK can reconstruct the cellular immune balance of Th1/2 and Treg/Th17 cells. Metabolome results show that DL-glutamine, L-pyroglutamic acid, prostaglandin b1, prostaglandin e2, and 3,4-dihydroxyhydrocinnamic acid are the metabolic biomarkers and are associated with Th1/2 and Treg/Th17 cell balance. GMK can also change the gut microbiota in the allergic asthma mouse model. The genus_Muriculum, genus_(Clostridium) GCA900066575, genus_klebsiella, genus_Desulfovibrio, genus_Rikenellaceae RC9 gut group, family_Chitinophagaceae, family_Nocardioidaceae, and genus_Corynebacterium are gut microbiota biomarkers treated by GMK. Among these biomarkers, genus_Muriculum is the gut microbiota biomarker associated with Th1/2 and Treg/Th17 cell balance. Interestingly, we first found that DL-glutamine, L-pyroglutamic acid, prostaglandin b1, prostaglandin e2, and 3,4-dihydroxyhydrocinnamic acid are all associated with genus_Muriculum. GMK will be a new strategy for the treatment of eosinophilic asthma, and biomarkers will also be a new research direction.

Objective: To observe the early changes in peripheral blood cytokine levels after treatment of metastatic hepatic carcinoma (MHC) with CalliSpheres microspheres drug-eluting beads (DEB) transcatheter arterial chemoembolization (CSM-TACE). Methods: Twenty-eight patients with refractory MHC who underwent CSM-TACE were selected prospectively, and 5mL of peripheral blood was collected before CSM-TACE and on the 2nd and 5th day after CSM-TACE. Flow cytometry was used to detect immunological indicators. The early changes in levels of peripheral blood cell inflammatory factors Th1 (interleukin 2 (IL-2), tumor necrosis factor-a (TNF-a), interferon (IFN-r)), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were observed after CSM-TACE, as well as the ratio of CD4+/CD8+. Results: All the 28 patients underwent CSM-TACE successfully. CT at 4 days after CSM-TACE showed clear outline low-density changes in liver tumors, and honeycomb necrosis was observed in the tumors in some cases. After CSM-TACE, the IL-6 and IL-10 levels were increased and then decreased again. After CSM-TACE, IL-2 showed a trend of transient increase and then decreased again, and the TNF-a level decreased temporarily, and then decreased. After CSM-TACE, the IFN-r level showed a continuous and slowly increasing trend. The IL-17 level showed a continuous downward trend, and the CD4+/CD8+ ratio showed a gradual and continuous upward trend, and there was a negative correlation between them. Conclusions: There are complex dynamic changes in TH1/Th2 in the early stage of CSM-TACE, and the acute inflammatory response and the enhancement of the body's immune anti-tumor response coexist. [ABSTRACT FROM AUTHOR]

Serum cytokine profile and T helper (Th)1/Th2 cell balance are related to the success of embryo implantation, although not yet firmly linked to recurrent implantation failure (RIF), a repeated failure to achieve clinical pregnancy following multiple high-quality embryo transfer. In this prospective study, comprehensive bioinfomatic analysis and logistic regression analysis were used to compare the serum cytokine profiles of 41 RIF patients with those of 29 subjects with first-cycle successful pregnancy in the midluteal phase and to assess the alterations of cytokine profiles in patients with clinical pregnancy at five weeks post-transplantation. We found several elevated proinflammatory cytokines, decreased anti-inflammatory cytokines, and increased Th1/Th2 cytokine ratios in RIF patients compared to control subjects. Specifically, the receiver operating characteristic (ROC) curve generated using multiple indicators provides a high predictive value for diagnosing RIF (area under the curve [AUC] = 0.94, 95% confidence interval [CI] 0.87-1.00, P < 0.0001), with a sensitivity of 96.55% and a specificity of 87.50%. Meanwhile, at five weeks post-transplantation, patients in both groups diagnosed with clinical pregnancy exhibited increased levels of several cytokines compared with pre-pregnancy levels, and a gradual shift in Th1/Th2 balance toward Th2. These findings suggest that inflammatory serum cytokines and the predominance of Th1 cells likely contribute to RIF and possibly reflect the immune environment at the maternal-fetal interface, suggesting their value as outcome indicators in assisted reproductive therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the therapeutic effects of acupoint autohemotherapy (A-AHT) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in mice focusing on regulating T helper 1/T helper 2 (Th1/Th2) immune responses. Methods: Thirty BALB/c mice were divided into 5 groups by a random number table, including normal control (NC), AD model (AD), A-AHT, sham A-AHT (sA-AHT), and acupoint injection of normal saline (A-NS) groups, 6 mice per group. Mice were challenged by DNCB for the establishment of experimental AD model. On the 8th day, except for the NC and AD groups, the mice in the other groups received management once every other day for a total of 28 days. For the A-AHT and sA-AHT groups, 0.05 mL of autologous whole blood (AWB) was injected into bilateral Zusanli (ST 36) and Quchi (LI 11) and sham-acupoints (5 mm lateral to ST 36 and LI 11), respectively. The A-NS group was administrated with 0.05 mL of normal saline by acupoint injection into ST 36 and LI 11. Dermatitis severity for dorsal skin of mice was determined using the Severity Scoring of Atopic Dermatitis (SCORAD) every week. The total immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) cytokine levels in serum were examined by enzyme-linked immunosorbent assay (ELISA). Spleen Th1/Th2 expression were analyzed via flow cytometry and immunohistochemical assay was used to detect T-box expressed in T cell (T-bet) and GATA-binding protein 3 (GATA3) expressions in skin lesions of mice. Results: Compared with the AD group, both A-AHT and sA-AHT reduced the SCORAD index and serum IgE level (P<0.05 or P<0.01); A-AHT, sA-AHT and A-NS down-regulated serum IL-4 level and upregulated IFN-γ/IL-4 ratio (P<0.05 or P<0.01); A-AHT regulated the Th1/Th2 shift specifically and increased the related transcription factors such as T-bet expression and T-bet/GATA3 ratio (P<0.05). Conclusion: A-AHT showed significant effectiveness on the AD model mice, through regulating Th1/Th2 immune responses. [ABSTRACT FROM AUTHOR]

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