Search

Objective To investigate the effects of metformin combined with ethinylestradiol and cyproterone acetate tablets on serum miR-124 levels and Th1/Th2 cytokine balance shift in patients with polycystic ovary syndrome (PCOS). Methods A total of 200 PCOS patients treated at Panzhihua Maternal and Child Health Hospital from January 2022 to February 2023 were included and divided into an observation group (n = 100) and a control group (n = 100) . The observation group received metformin combined with ethinylestradiol and cyproterone acetate tablets, while the control group received ethinylestradiol and cyproterone acetate tablets alone. The treatment duration was 3 months. Clinical data, lipid levels [total cholesterol (TC), triglyceride (TG), low density lipoprotein C (LDL-C)], fasting plasma glucose (FPG), fasting serum insulin (FINS), and homeostasis model assessment-IR (HOMA-IR) were collected before and after treatment. Serum miR-124, interlenkin (IL)-2, IL-6, and interferon-γ (INF-γ) were also measured. Results After treatment, TG, TC, and LDL-C levels in the observation group significantly decreased (P<0.05). Post treatment TG, TC, and LDL-C levels in the observation group were lower than those in the control group (P < 0.05) . There were no statistically significant differences in FPG, FINS, and HOMA-IR between the two groups before treatment (P>0.05). After treatment, FPG, FINS, and HOMA IR levels in the observation group significantly decreased (P< 0.05), and these levels were lower than those in the control group (P < 0.05) . There were no significant differences in IL-2, IL-6, INF-γ, and miR-124 levels between the two groups before treatment (P > 0.05) . After treatment, IL-6 and INF-γ levels decreased, and IL-2 and miR-124 levels increased in the observation group (P < 0.05) . Post-treatment IL-6 and INF-γ levels were lower, while IL-2 and miR-124 levels were higher in the observation group compared to the control group (P < 0.05) Conclusion Metformin combined with ethinylestradiol and cyproterone acetate tablets can significantly improve insulin resistance, regulate glucolipid metabolism and improve the state of Th1/ Th2 cytokine balance s hift in PCOS patients. [ABSTRACT FROM AUTHOR]

Objective: Though an increased risk of atherosclerosis is associated with anti-CTLA-4 antibody therapy, the underlying mechanisms remain unclear. Methods: C57BL/6 mice were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody twice a week for 4 weeks, after being injected with AAV8-PCSK9 and fed a Paigen diet (PD). The proportion of aortic plaque and lipid accumulation were assessed using Oil Red O staining, while the morphology of atherosclerotic lesions was analyzed with hematoxylin and eosin staining. Collagen content was evaluated through Picrosirius Red (PSR) staining, while inflammatory cell infiltration was examined with immunofluorescence staining. CD4+ T cells secreting IFN-γ and IL-4, which represent Th1 and Th2 cells respectively, were detected by flow cytometry and real-time PCR. Protein levels of p-IκBα, IκBα, p-p65, and p65 were determined by Western blot. Results: Inhibiting CTLA-4 exacerbated PD-induced plaque progression and promoted CD4+ T cell infiltration in the aortic root. The anti-CTLA-4 antibody promoted CD4+ T cell differentiation toward the Th1 type, as indicated by an increase in the Th1/Th2 ratio. Compared to the anti-IgG group, treatment with anti-CTLA-4 antibody significantly elevated the protein levels of p-IκBα and p-p65, as well as the mRNA levels of TNF-α, IL-6, ICAM-1, and VCAM-1. Inhibiting the NF-κB signaling pathway attenuated the overall pathological phenotype induced by the anti-CTLA-4 antibody treatment. Conclusion: Anti-CTLA-4 treatment promotes the progression of atherosclerosis by activating NF-κB signaling and modulating the Th1/Th2 balance. Our results provide a rationale for preventing and/or treating atherosclerosis accelerated by anti-CTLA-4 antibody therapy in cancer patients.

Food allergies are common worldwide and have become a major public health concern; more than 220 million people are estimated to suffer from food allergies worldwide. On the other hand, polyphenols, phenolic substances found in plants, have attracted attention for their health-promoting functions, including their anti-allergic effects. In this study, we examined the potential inhibitory effects of 80% ethanol extracts from 22 different vegetables on the degranulation process in RBL-2H3 cells. Our aim was to identify vegetables that could prevent and treat type I allergic diseases. We found strong inhibition of degranulation by extracts of perilla and chives. Furthermore, we verified the respective efficacy via animal experiments, which revealed that the anaphylactic symptoms caused by ovalbumin (OVA) load were alleviated in OVA allergy model mice that ingested vegetable extracts of perilla and chives. These phenomena were suggested to be caused by induction of suppression in the expression of subunits that constitute the high-affinity IgE receptor, particularly the α-chain of FcεR I. Notably, the anti-allergic effects of vegetables that can be consumed daily are expected to result in the discovery of new anti-immediate allergenic drugs based on the components of these vegetables. [ABSTRACT FROM AUTHOR]

Aplastic anaemia (AA) is a haematopoietic disorder caused by immune-mediated attack on haematopoietic stem cells (HSCs). Stem cell transplantation and immunosuppressive therapy remain the major treatment choice for AA patients but have limited benefits and undesired side effects. The aim of our study was to clarify the protective role of immunity of chronic intermittent hypobaric hypoxia (CIHH) and the underlying mechanism in AA. Our integrative analysis demonstrated that CIHH pre-treatment significantly improved haematopoiesis and survival in an AA rat model. We further confirmed that CIHH pre-treatment was closely associated with the Th1/Th2 balance and a large number of negative regulatory haematopoietic factors, such as TNF-α and IFN-γ, produced by hyperactive Th1 lymphocytes released in AA rats, which induced the death program in a large number of CD34+ HSCs by activating the Fas/FasL apoptosis pathway, while CIHH pre-treatment effectively downregulated the expression of TNF-α and IFN-γ, resulting in a reduction in Fas antigen expression in CD34+ HSCs. In summary, this study provides evidence that CIHH has good protective effect against AA by modulating immune balance in Th1/Th2 cells and may provide a new therapeutic strategy. [ABSTRACT FROM AUTHOR]

T helper (Th) cells have received extensive attention owing to their indispensable roles in anti-tumor immune responses. Th1 and Th2 cells are two key subsets of Th cells that exist in relative equilibrium through the secretion of cytokines that suppress their respective immune response. When the type of cytokine in the tumor microenvironment is altered, this equilibrium may be disrupted, leading to a shift from Th1 to Th2 immune response. Th1/Th2 imbalance is one of the decisive factors in the development of malignant tumors. Therefore, focusing on the balance of Th1/Th2 anti-tumor immune responses may enable future breakthroughs in cancer immunotherapy. Polysaccharides can regulate the imbalance between Th1 and Th2 cells and their characteristic cytokine profiles, thereby improving the tumor immune microenvironment. To our knowledge, this study is the most comprehensive assessment of the regulation of the tumor Th1/Th2 balance by polysaccharides. Herein, we systematically summarized the intrinsic molecular mechanisms of polysaccharides in the regulation of Th1 and Th2 cells to provide a new perspective and potential target drugs for improved anti-tumor immunity and delayed tumor progression.

As found in clinical and laboratory studies, platelets not only play a key role in the processes of coagulation and thrombosis, but are also able to actively participate in other pathophysiological processes, including the development of immune reactions. It has been shown that changes in the immune system leading to systemic lupus erythematosus (SLE) are often accompanied by changes in the number of platelets and their activity in the peripheral blood of SLE patients, which correlate with the severity of the clinical manifestations of the disease. Earlier we have studied the standard experimental model of SLE in detail, based on the induction of chronic graft-versus-host disease (cGVHD) in the semi-allogeneic system DBA/2 → (C57Bl/6 x DBA/2)F1. However, the participation of platelets in this immunopathological process has not been studied. There are no data in the literature on the behavior of platelets in cGVHD or on their relationship with the state of Th1/Th2 balance. It can been expected that the platelet count changes according to the development of cGVHD in the used experimental model by analogy with the development of SLE in humans.In the experiments, we used female mice of the DBA/2 strain and (C57Bl/6 × DBA/2)F1 hybrids. Chronic GVHD in a semi-allogeneic system was induced by injecting DBA/2 mouse splenocytes into B6D2F1 hybrid mice: 60-70 × 106 cells intravenously twice with an interval of 6 days. The studied parameters were evaluated three months after the start of the experiment and the formation of lupus-like glomerulonephritis in animals with Th2-dependent cGVHD variant.A decrease in the number of erythrocytes and hemoglobin, a decrease in hematocrit and a parallel increase in the number of reticulocytes in the blood of mice with cGVHD are in good agreement with our earlier conclusion that these animals have autoimmune hemolytic anemia. It was found that, platelets increase significantly with the development of cGVHD unlike other blood cells. Secondary thrombocytosis is observed in the case of the Th2-dependent variant of сGVHD in this model of SLE, while in the group with the Th1-dependent variant of сGVHD, the average number of platelets in the blood does not differ from the control group.

Objective: To evaluate the effect of myricetin on ovalbumin (OVA)-induced allergic rhinitis in mice. Methods: Mice were sensitized and challenged using OVA (5%, 500 mL) intraperitoneally and intranasally, respectively, on an alternative day for 14 days, followed by administration of myricetin (50, 100, and 200 mg/kg) till day 21. Nasal symptoms, biochemical parameters, protein expressions, and histopathology were observed. Results: OVA-induced increased nasal symptoms including rubbing, sneezing, and discharge were significantly reduced by myricetin (100 and 200 mg/kg) (P<0.05). Myricetin also protected against histamine challenge and attenuated elevated serum immunoglobulin E (IgE; total and OVA-specific), total IgG, and β-hexosaminidase levels, as well as leukotriene C4 and interleukins levels in nasal lavage fluid (P<0.05). Western blot analysis showed that myricetin significantly upregulated the protein expression of T-box expressed in T cells, while downregulating the protein expression of GATA binding protein 3, NF-κB, and IκB-α (P<0.05). Additionally, OVA-induced histopathological abberations in the nasal mucosa was markedly ameliorated by myricetin treatment (P<0.05). Conclusions: Myricetin exerts anti-allergic effects against OVAinduced allergic rhinitis via regulating Th1/Th2 balance. [ABSTRACT FROM AUTHOR]

Abstract Background Breast cancer is a heterogeneous group of diseases. The polarization of CD4+ T helper (Th) lymphocytes (mainly Th1 and Th2) may differ in breast cancers with different outcomes, but this has not been fully validated. Methods This study is a bioinformatic analysis, in which differentially expressed genes (DEGs) were identified in patients with low and high Th1/Th2 ratios. And then, DEG functions, hub genes and independent predictors were determined. Results Low Th1/Th2 ratio was associated with poor outcome in Luminal A and basal-like breast cancer (p

Food allergies are common worldwide and have become a major public health concern; more than 220 million people are estimated to suffer from food allergies worldwide. On the other hand, polyphenols, phenolic substances found in plants, have attracted attention for their health-promoting functions, including their anti-allergic effects. In this study, we examined the potential inhibitory effects of 80% ethanol extracts from 22 different vegetables on the degranulation process in RBL-2H3 cells. Our aim was to identify vegetables that could prevent and treat type I allergic diseases. We found strong inhibition of degranulation by extracts of perilla and chives. Furthermore, we verified the respective efficacy via animal experiments, which revealed that the anaphylactic symptoms caused by ovalbumin (OVA) load were alleviated in OVA allergy model mice that ingested vegetable extracts of perilla and chives. These phenomena were suggested to be caused by induction of suppression in the expression of subunits that constitute the high-affinity IgE receptor, particularly the α-chain of FcεR I. Notably, the anti-allergic effects of vegetables that can be consumed daily are expected to result in the discovery of new anti-immediate allergenic drugs based on the components of these vegetables.

Scutellarin (SCU) is a herbal flavonoid glucuronide with multiple pharmacological activities, including antioxidant, anti-inflammation, vascular relaxation, anti-platelet, and myocardial protection. However, the effect of SCU on complete Freund’s adjuvant (CFA)-induced rheumatoid arthritis (RA) had not been studied. In this study, we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the plasma levels of immunoglobulin (Ig)G, IgE, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG). Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints. The proportions of T helper type 1 (Th1) and T helper type 2 (Th2) cells of CD4+ T lymphocyte subsets were analyzed by flow cytometry. The expression of Kelch-like ECHassociated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) was analyzed using real-time quantitative PCR (RT-qPCR) and western blotting assays. The present study demonstrated that SCU prevented CFA-induced RA, and inhibited the expression of inflammation factors, IgG, IgE, TNF-α, IL-1β, and IL-6. While SCU also reduced the RANKL level, it increased OPG expression in RA mice. The Th1/Th2 ratio was significantly lower in mice treated with SCU. Additionally, HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment. Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

Junfeng Chen,&ast; Wei Lin,&ast; Haiting Gu, Kangtai Ying, Tingjian Li, Haiyan Shao Department of Respiration, The First People’s Hospital of Wenling, Wenling, Zhejiang, 317500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyan Shao, Department of Respiration, The First People’s Hospital of Wenling, 333 Chuanan Nan Road, Chengxi Street, Wenling, Zhejiang, 317500, People’s Republic of China, Tel +86 057689668688, Email shaohy_101043@tzc.edu.cnObjective: This study aimed to compare lung function and airway inflammation among cough variant asthma (CVA), chronic cough and classical asthma (CA) and investigate the relationship between these indicators and their possible mechanisms of action in the progression of CVA to CA.Methods: 36 patients with chronic cough, 39 patients with CA, and 57 patients with CVA were included in this study. Pulmonary function tests, bronchial provocation tests and FeNO tests were performed. The patients’ bronchoalveolar lavage fluid (BALF) was collected, the cells in BALF were counted, and the levels of Th1 and Th2 cytokines were detected.Results: The neutrophils, lymphocytes, and eosinophils in BALF in the CA and CVA groups were significantly higher than those in the chronic cough group. Also, they were negatively correlated with FEV1, FVC, and FEV1/FVC and positively correlated with IgE and FeNO. The expression of Th2-related cytokines was increased in CVA and CA patients, and it was positively correlated with FEV1, FVC and FEV1/FVC and negatively correlated with IgE and FeNO, while the results of Th1-related cytokines were the opposite of those for Th2-related cytokines.Conclusion: CVA differs from asthma and chronic cough in terms of Th1/Th2 cytokines and lung function and provides a reference for understanding the disease mechanism of early clinical progression of CVA to CA.Keywords: cough variant asthma, cytokines, pulmonary function, Th1/Th2 balance, cell classified count

Food allergy is a serious food safety and public health issue. However, the medical interventions for allergy treatment are still suboptimal. Recently, the gut microbiome–immune axis has been considered as a promising target to reduce the symptoms of food allergy. In this study, we explore the oral administration of lotus-seed resistant starch as a means to protect against food allergy using an ovalbumin (OVA) sensitization and challenge rodent model. The results obtained showed that lotus-seed resistant starch intervention alleviated the food allergy symptoms (such as reductions in body temperature and allergic diarrhea). Furthermore, lotus-seed resistant starch also attenuated the increase in OVA-specific immunoglobulins and improved Th1/Th2 imbalance in OVA-sensitized mice. These anti-allergic effects might be associated with the actions of lotus-seed resistant starch on intestinal microbiota. Taken together, our findings suggest that daily ingestion of lotus-seed resistant starch might be effective for the alleviation of food allergy. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) has been shown to act as both anti-inflammatory and pro-inflammatory mediators. Application of H2S donors generally protects against inflammation; however, experimental results using mice lacking endogenous H2S-producing enzymes, such as cystathionine γ-lyase (CTH) and mercaptopyruvate sulfurtransferase (MPST), are often contradictory. We herein examined two types of model hapten-induced inflammation models, colitis (an inflammatory bowel disease model of mucosal immunity) and contact dermatitis (a type IV allergic model of systemic immunity), in CTH-deficient (Cth–/–) and MPST-deficient (Mpst–/–) mice. Both mice exhibited no significant alteration from wild-type mice in trinitrobenzene sulfonic acid (Th1-type hapten)-induced colitis (a Crohn's disease model) and oxazolone (Th1/Th2 mix-type; Th2 dominant)-induced colitis (an ulcerative colitis model). However, Cth–/– (not Mpst–/–) mice displayed more exacerbated phenotypes in trinitrochlorobenzene (TNCB; Th1-type)-induced contact dermatitis, but not oxazolone, at the delayed phase (24 h post-administration) of inflammation. CTH mRNA expression was upregulated in the TNCB-treated ears of both wild-type and Mpst–/– mice. Although mRNA expression of pro-inflammatory cytokines (IL-1β and IL-6) was upregulated in both early (2 h) and delayed phases of TNCB-triggered dermatitis in all genotypes, that of Th2 (IL-4) and Treg cytokines (IL-10) was upregulated only in Cth–/– mice, when that of Th1 cytokines (IFNγ and IL-2) was upregulated in wild-type and Mpst–/– mice at the delayed phase. These results suggest that (upregulated) CTH or H2S produced by it helps maintain Th1/Th2 balance to protect against contact dermatitis. [ABSTRACT FROM AUTHOR]

Objective: To observe the clinical efficacy of adalimumab in the treatment of severe psoriasis and its effect on peripheral blood Th1/Th2 balance and monocyte P38 mitogen-activated protein kinase (MAPK)/nuclear transcription factor κB (NF-κB) signaling pathway. Methods: 118 patients with severe psoriasis who were treated in the fifth medical center of PLA general hospital from March 2019 to March 2022 were selected, and they were divided into control group (routine treatment, 59 cases) and study group (adalimumab on the basis of the control group treatment, 59 cases) according to random number table method. The efficacy, symptom score changes, peripheral blood Th1/Th2 balance and monocyte p38MAPK/NF-κB signaling pathwayway changes were observed in the two groups, the incidence of adverse reactions in the two groups was recorded. Results: The total clinical effective rate in the study group was higher than that in the control group (P<0.05). After treatment, Th1, interleukin-2 (IL-2) and interferon-γ (IFN-γ) in the study group were lower than those in the control group, while interleukin-4 (IL-4), interleukin-10 (IL-10) and Th2 were higher than those in the control group (P<0.05). The expression levels of p38MAPK and NF-κB protein in the study group after treatment were lower than those in the control group (P<0.05). The psoriasis area and severity index (PASI) score in the study group was lower than that in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Adalimumab has a good efficacy in the treatment of severe psoriasis, which may be related to the regulation of peripheral blood Th1/Th2 balance and monocyte p38MAPK/NF-κB signaling pathway, without increasing the incidence of adverse reactions, and which has a good safety. [ABSTRACT FROM AUTHOR]

Background : Breast cancer is a heterogeneous group of diseases. The polarization of CD4+ T helper (Th) lymphocytes (mainly Th1 and Th2) may differ in breast cancers with different outcomes, but this has not been fully validated. Methods: This study is a bioinformatic analysis, in which differentially expressed genes (DEGs) were identified in patients with low and high Th1/Th2 ratios. And then, DEG functions, hub genes and independent predictors were determined. Results: Low Th1/Th2 ratio was associated with poor outcome in Luminal A and basal-like breast cancer (p < 0.05). GSEA and KEGG analysis of DEGs obtained from comparing low and high Th1/Th2 ratios illuminated downregulation of immune-related gene sets and pathways affecting Th1/Th2 balance toward Th2 polarization (p < 0.05). Survival and Cox analyses of all the DEGs confirmed CCL1 and MYH6 were independent protective factors and IFNK and SOAT2 were independent risk factors for basal-like breast cancer (95%CI: 1.06–2.5, p = 0.026). Then a four-gene signature was constructed and achieved a promising prognostic value (C-index = 0.82; AUC = 0.826). Conclusions: Low Th1/Th2 ratio predicts poor outcome in Luminal A and Basal-like breast cancer, and downregulation of immune-related gene sets and pathways contribute to Th1/Th2 balance toward Th2 polarization. CCL1, MYH6, IFNK, and SOAT2 have an independent prognostic value of survival outcome and might be novel markers in basal-like breast cancer. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a type of toxic substance, which widely exists in nature. However, the effect of Cd exposure on the toxicity of swine lungs and its underlying mechanism involved have not yet been reported. In our study, we divided swine into two groups, including a control group (C group) and Cd-exposed group. Swine in the C group were fed a basic diet, whereas swine in the Cd group were fed a 20 mg Cd/kg diet. Immunofluorescence, qRT-PCR, western blot analysis, and H&E staining were performed to detect necroptosis-related indicators. Our results found that after Cd exposure, Th1/Th2 imbalance occurred, miR-181-5p was down-regulated, TNF-α expression was increased, and the NF-κB/NLRP3 and JAK/STAT pathways and RIPK1/RIPK3/MLKL axis were activated. Furthermore, histopathological examination showed necrosis in swine lung after Cd exposure. Together, the above-mentioned results indicate that subacute Cd exposure is closely linked with necroptosis in swine lung. Our study provided evidence that Cd may act through miR-181-5p/TNF-α to induce necroptosis in swine lung. The findings of this study supplement the toxicological study of Cd and provide a reference for comparative medicine. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of BIS-guided closed-loop target-controlled infusion on perioperative Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy under different anesthesia and sedation depths. Methods We applied random number table method to divide 73 elderly patients undergoing elective laparoscopic radical gastrectomy into BIS closed-loop target-controlled infusion group with BIS value of 55(group H, n=36) and BIS value of 45(group L, n=37).Intravenous blood samples were collected immediately before surgery (T1), 2h after surgery (T2), 24h after surgery (T3) and 72h after surgery (T4).IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were determined by flow cytometry microsphere array.We compared operation duration, postoperative PACU stay time and postoperative hospitalization time between two groups. Results Compared with T1, IL-6 and IL-10 concentration in group H at T2, T3 and T4 significantly increased (P < 0.05), IL-4 and TNF-α in group H at T4 were significantly increased (P < 0.05), IL-2 and IFN-γ in group H at T2 and T4 were significantly increased (P < 0.05), the concentration of IL-6 and IL-10 in group L at T2, T3 and T4 were increased (P < 0.05), IL-2 in group L at T4 was decreased (P < 0.05), and IFN-γ/IL-6 in two groups were decreased at T2, T3 and T4(P < 0.05).Compared with group L, IL-6 and IL-10 in group H were significantly increased at T2(P < 0.05), IFN-γ/IL-6 in group H was significantly decreased (P < 0.05), IL-2 and IL-10 in group H were significantly increased at T4(P < 0.05).Operation duration, postoperative PACU stay time and postoperative hospitalization time had no statistical significance between two groups (P > 0.05). Conclusion The anesthesia and sedation depth of BIS-guided closed-loop target-controlled infusion set at 45 is better than 55 in maintaining Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy, but it has no obvious effect on long-term prognosis.

A new terminology "combined allergic rhinitis and asthma syndrome (CARAS)" was introduced to describe patients suffering from both allergic rhinitis (AR) and asthma. The pathogenesis of allergic airway inflammation has been well known, with the main contribution of TH1/TH2 imbalance and mast cell degranulation. Artemisia gmelinii has been used as an herbal medicine with its hepaprotective, anti-inflammatory, and antioxidant properties. In this study, the effect of A. gmelinii extracts (AGE) on the ovalbumin (OVA)-induced CARAS mouse model was investigated. AGE administration significantly alleviated the nasal rubbing and sneezing, markedly down-regulated both OVA-specific IgE, IgG1, and histamine levels, and up-regulated OVA-specific IgG2a in serum. The altered histology of nasal and lung tissues of CARAS mice was effectively ameliorated by AGE. The AGE treatment group showed markedly increased levels of the TH1 cytokine interleukin (IL)-12 and TH1 transcription factor T-bet. In contrast, the levels of the TH2 cytokines, including IL-4, IL-5, IL-13, and the TH2 transcription factor GATA-3, were notably suppressed by AGE. Moreover, AGE effectively prevented mast cell degranulation in vitro and mast cell infiltration in lung tissues in vivo. Based on these results, we suggest that AGE could be a potential therapeutic agent in OVA-induced CARAS by virtue of its role in balancing the TH1/TH2 homeostasis and inhibiting the mast cell degranulation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of astilbin on pregnancy outcome in rats with recurrent spontaneous abortion (RSA). A total of 40 pregnant female Sprague–Dawley rats were randomly divided into four groups: the control, model, astilbin, and prednisone groups. An RSA rat model was established by gavage with hydroxyurea and mifepristone. The number of surviving and reabsorbed embryos was counted on day 9 of gestation in each group. The rat serum was collected to detect the levels of IFN-γ, IL-2, IL-4, and IL-10 by enzyme-linked immunosorbent assay. The expressions of T-bet and GATA-3 in the decidual and placental tissues of the rats were determined by immunohistochemistry. The absorptivity of embryos was significantly higher in the model group than in the control group. The levels of serum IFN-γ and IL-2 were significantly lower in the astilbin group than in the model group, while the levels of serum IL-4 and IL-10 were significantly higher. Astilbin treatment significantly increased GATA-3 expression, while it significantly reduced T-bet expression and the T-bet/GATA-3 ratio. Astilbin has a therapeutic effect on RSA in rats by regulating the balance of Th1/Th2 in maternal circulation and likely in decidual tissue. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) impairs the quality of life of patients and reduces the efficiency of social work, it is an increasingly serious public medical and economic problem in the world. Conventional anti-allergic drugs for the treatment of allergic rhinitis (AR) can cause certain side effects, which limit the quality of life of patients. Therefore, it makes sense to look for other forms of treatment. Several studies in recent years have shown that probiotics have shown anti-allergic effects in various mouse and human studies. For example, the application of certain probiotic strains can effectively relieve the typical nasal and ocular symptoms of allergic rhinitis in children and adults, thereby improving the quality of life and work efficiency. At the same time, previous studies in humans and mice have found that probiotics can produce multiple effects, such as reduction of Th2 cell inflammatory factors and/or increase of Th1 cell inflammatory factors, changes in allergy-related immunoglobulins and cell migration, regulate Th1/Th2 balance or restore intestinal microbiota disturbance. For patients with limited activity or allergic rhinitis with more attacks and longer attack duration, oral probiotics have positive effects. The efficacy of probiotics in the prevention and treatment of allergic rhinitis is remarkable, but its specific mechanism needs further study. This review summarizes the research progress of probiotics in the treatment of allergic rhinitis in recent years. [ABSTRACT FROM AUTHOR]

Xudong Hu,1,&ast; Bing Luo,2,&ast; Qing Wu,2 Qingbiao Chen,2 Penghui Lu,2 Jie Huang,3 Xiaoxia Liang,1 Cheng Ling,1 Yiqun Li2 1Department of Anesthesiology, The Second People’s Hospital of Foshan, Foshan, Guangdong, 528000, People’s Republic of China; 2Department of Surgery, The Second People’s Hospital of Foshan, Foshan, Guangdong, 528000, People’s Republic of China; 3Clinical Laboratory, The Second People’s Hospital of Foshan, Foshan, Guangdong, 528000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiqun LiDepartment of Surgery, The Second People’s Hospital of Foshan, No. 78 Weiguo Road, Foshan, Guangdong, 528000, People’s Republic of ChinaTel +86 13902845621Fax +86 75788032008Email yiqunlide03@163.comBackground: It is very important for breast cancer patients undergoing surgery to choose an opioid that has little effect on the immune system. The aim of this study is to compare the effects of dezocine or sufentanil on postoperative pain and Th1/Th2 balance in patients undergoing breast cancer surgery.Methods: Data from 92 breast cancer patients from January 2019 to July 2020 at Foshan Second People’s Hospital (Guangdong, China) were analyzed. Sufentanil (SF) was used in group SF (n = 44) and dezocine (DE) in group DE (n = 48). The Visual Analog Scale (VAS) scores were assessed, and the percentages of Th1 cells and Th2 cells in peripheral blood were detected before anesthesia and at 2, 12, 24, and 48 hours after surgery.Results: There was no significant difference in the VAS scores between the two groups at 2, 24, and 48 hours after surgery (P > 0.05). The VAS scores at 12 hours after surgery in group DE were significantly lower than those in group SF with a statistically significant difference (P < 0.05). The percentage of Th1 cells in group DE at 2, 12, 24, and 48 hours after surgery was significantly lower than that in group SF (P < 0.05). The percentage of Th2 cells in group DE at 2, 12, 24, and 48 hours after surgery was significantly lower than that in group SF (P < 0.05). The Th1/Th2 ratio at 2, 12, 24, and 48 hours after surgery was significantly higher in group DE than that in group SF (P < 0.05).Conclusion: Dezocine for anesthesia induction and postoperative analgesia can maintain the balance of Th1/Th2 more stable than, with the same analgesia efficacy as, sufentanil during the early postoperative period in breast cancer patients undergoing surgery.Keywords: dezocine, sufentanil, VAS, Th1/Th2 balance, breast cancer

While conducting numerous studies, including researchers in our laboratory, it was found that Th1/Th2 balance plays an essential role in the regulation of reactions that determine the outcomes of immunopathological processes in both chronic and acute GVHD models. However, the question about activity of which element in the regulatory process during GVHD induction (for example, a receptor or an enzyme) affects the ratio of this balance depends remains open. It has been suggested that the degree of activation of the GPR84 receptor during GVHD induction can significantly affect the host Th1/Th2 balance. And, by assessing this parameter, the direction of development and the intensity of the pathological process can be determined. The aim of this work was to investigate the effect of ligands such as medium-chain fatty acid receptor GPR84 on the Th1/Th2 balance in an experimental model in an in vivo system.Female DBA/2 and hybrids (C57Bl/6 × DBA/2) F1 mouse strains were used in the experiments.The studied ligands of GPR84 were capric and lauric acids, as well as a synthetic ligand 6-OAU. Chronic GVHD in the semi-allogenic system was induced by injecting splenocytes from DBA/2 mice to B6D2F1 hybrid mice: 60-70 × 106 -cells iv twice with an interval of 6 days. The first administration of the GPR84 ligands was performed one hour after the donor cell transfer and then once a day for two weeks.The effect of the study drugs on the course of chronic GVHD was assessed three months after the onset of the experiment.It was shown that the administration of GPR84 ligands to to animals during the induction of chronic GVHD affects the activity of the receptor and the host Th1/Th2 ratio. In the group with the injection of 6-OAU, the number of animals which the immunopathological process developed according to the Th1-dependent variant increased by more than 1.5-fold, compared with the control group. This fact is consistent with the literature data obtained in the in vitro system. Apparently, the effect of a mixture of capric and lauric acids is mediated by some other mechanism, differed from the GPR84 activation. Therefore, further research is required to realize the promising possibility of adjusting immune responses by including certain fatty acids in the diet.

Platycodon grandiflorus (Jacq.) A. DC. (PG) root is one of the most commonly used medicine-food materials for respiratory discomfort in Asia, usually in the form of a decoction or leaching solution. As everyone knows, both of decoction and leaching solution is a polyphase dispersion system, containing low-molecular-weight water-soluble active ingredients and hydrophilic macromolecules. This study aimed to discuss the synergistic effect of Platycodon grandiflorus polysaccharide (PGP) and platycodin D (PD) in PG decoction against chronic bronchitis (CB) and the mechanism underlying. A series of PGP, PD, and PGD + PD suspensions were administrated to CB model rats, on the levels of whole animal and in situ intestinal segment with or without mesenteric lymphatic vessels ligation. It exhibited that PGP exhibited synergistic effects with PD, on improving the histopathological abnormity, mucus secretion excess, and immunological imbalance in lung of CB model rat, closely associated with its modulations on the mucosal immunity status in small intestine. The polysaccharide macromolecules in PG decoction or leaching solution should be responsible for the modulation of pulmonary immune state, possibly through the common mucosal immune between small intestine and lung. These results might be a new perspective that illustrates the classical theory of "the lung and intestine are related" in traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

We used an abortion-prone mouse model, generated by mating female CBA/J mice with male DBA/2JJcl mice, to examine the effects of changes in the Th1/Th2 cell ratio and the percentage of regulatory T (Treg) cells on the maintenance of pregnancy. We subcutaneously injected female CBA/J mice once each with 50 µg/mouse of Dermatophagoides farinae (Df) extract and the squalene-based adjuvant (SquA); 10 days later, these mice were mated with male DBA/2JJcl mice. Compared with injection of vehicle or adjuvant, the Df treatment decreased the Th1/Th2 cell ratio and concomitantly increased the percentage of Treg cells in the spleen. In addition, fetal death rates were decreased. We then explored a substance which shifted the Th1/Th2 balance toward Th1 side. We found that 50 µg/mouse of keyhole limpet hemocyanin (KLH) increased the splenic Th1/Th2 cell ratio of nonpregnant female CBA/J mice. We subcutaneously injected female CBA/J mice with KLH and SquA; 10 days later, these mice were mated with male DBA/2JJcl mice. Compared with injection of vehicle or adjuvant, treatment with KLH enhanced the Th1 bias during pregnancy and increased the fetal death rate. The percentage of Treg cells, however, was increased in these KLH-injected pregnant mice contrary to our presumption. All collected data showed strong positive correlation between the Th1/Th2 cell ratio and fetal death rate. The increase in Treg cells independent of effects on the fetal death rate suggests that Treg cells do not necessarily induce maternal tolerance to the fetus but may prevent excessive Th1/Th2 imbalance during pregnancy. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a type I hypersensitivity mediated by dominant T helper 2 (Th2) response over the Th1 response after re‐exposure to a specific allergen. Currently, socio‐economic cost evoked by AR is quickly increasing since the prevalence of AR is gradually increasing in all ages worldwide. Several probiotic Lactobacillus strains have been described with potential immunomodulatory effects against type I hypersensitivity such as AR. Thus, the aim of the present work was to characterize basic probiotic property and immunomodulatory role of newly isolated Lactobacillus strains from Kimchi, a traditional fermented Korean food, in AR. Among the identified strains, Lactiplantibacillus plantarum NR16 revealed to be a powerful Th1 inducer since immune cells co‐cultured with NR16 produced the highest quantity of interferon‐γ (IFN‐γ) and interleukin‐12 (IL‐12) but secreted a low amount of IL‐4 in vitro. Therefore, NR16 was selected for the following assays conducted with mice with birch pollen–induced AR. Oral administration of NR16 reduced airway hyperresponsiveness and leukocyte infiltration in lesions of mice. In conclusion, oral administration of NR16 may mitigate symptoms of AR by inducing Th1 immune response, which might rebalance Th2/Th1 ratio by decreasing Th2 cytokine production in specific lesions of mucosa. [ABSTRACT FROM AUTHOR]

Natural soluble antagonist and decoy receptor on the surface of the cell membrane are evolving as crucial immune system regulators as these molecules are capable of recognizing, binding, and neutralizing (so-called inhibitors) their targeted ligands. Eventually, these soluble antagonists and decoy receptors terminate signaling by prohibiting ligands from connecting to their receptors on the surface of cell membrane. Interleukin-18 binding protein (IL-18BP) participates in regulating both Th1 and Th2 cytokines. IL-18BP is a soluble neutralizing protein belonging to the immunoglobulin (Ig) superfamily as it harbors a single Ig domain. The Ig domain is essential for its binding to the IL-18 ligand and holds partial homology to the IL-1 receptor 2 (IL-1R2) known as a decoy receptor of IL-1α and IL-1β. IL-18BP was defined as a unique soluble IL-18BP that is distinct from IL-18Rα and IL-18Rβ chain. IL-18BP is encoded by a separated gene, contains 8 exons, and is located at chr.11 q13.4 within the human genome. In this review, we address the difference in the biological activity of IL-18BP isoforms, in the immunity balancing Th1 and Th2 immune response, its critical role in autoimmune diseases, as well as current clinical trials of recombinant IL-18BP (rIL-18BP) or equivalent. [ABSTRACT FROM AUTHOR]

Background: Malva sylvestris L. (commonly known as mallow) has been widely used in traditional Tibetan formulations to treat allergic rhinitis (AR), and malvidin is a key anti-inflammation constituent of this plant., Objective: The present study aimed to evaluate the potential therapeutic effect and mechanism of malvidin in an AR mouse model., Methods: Malvidin's efficacy was evaluated in an AR mouse model induced by ovalbumin (OVA) sensitization and challenge. The factors, such as nasal symptoms, serum OVA-specific immunoglobulin E (IgE) levels, histological changes in the nasal mucosa, and expressions of Th1, Th2, Th17, and Tregs and their cytokines, were assessed. Western blotting was used to analyze the effect of malvidin on signal transducer and activator of transcription 6 (STAT6) and GATA3 expression levels., Results: Malvidin reduced the allergic symptoms and serum levels of OVA-specific IgE in the AR model. Histological analysis indicated that malvidin alleviates nasal mucosal edema, eosinophil infiltration, and goblet cell proliferation. In addition, it altered the expression of Th1/Th2/Th17-related cytokines, enhanced the Treg population, and reduced Th2-mediated immunity by suppressing the phosphorylation of STAT6 and expression of the GATA3 protein., Conclusions: Malvidin significantly improved allergic symptoms in an OVA-induced AR mouse model by modulating Th1/Th2 immune responses and suppressing the STAT6/GATA3 pathway, indicating its potential as a naturally sourced agent for AR management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective To investigate the effect of BIS-guided closed-loop target-controlled infusion on perioperative Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy under different anesthesia and sedation depths. Methods We applied random number table method to divide 73 elderly patients undergoing elective laparoscopic radical gastrectomy into BIS closed-loop target-controlled infusion group with BIS value of 55 (group H, n=36) and BIS value of 45 (group L, n=37). Intravenous blood samples were collected immediately before surgery (T1), 2h after surgery (T2), 24h after surgery (T3) and 72h after surgery (T4). IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were determined by flow cytometry microsphere array. We compared operation duration, postoperative PACU stay time and postoperative hospitalization time between two groups. Results Compared with T1, IL-6 and IL-10 concentration in group H at T2, T3 and T4 significantly increased (P<0.05), IL-4 and TNF-α in group H at T4 were significantly increased (P<0.05), IL-2 and IFN-γ in group H at T2 and T4 were significantly increased (P<0.05), the concentration of IL-6 and IL-10 in group L at T2, T3 and T4 were increased (P<0.05), IL-2 in group L at T4 was decreased (P<0.05), and IFN-γ/IL-6 in two groups were decreased at T2, T3 and T4 (P<0.05). Compared with group L, IL-6 and IL-10 in group H were significantly increased at T2 (P<0.05), IFN-γ/IL-6 in group H was significantly decreased (P<0.05), IL-2 and IL-10 in group H were significantly increased at T4 (P<0.05). Operation duration, postoperative PACU stay time and postoperative hospitalization time had no statistical significance between two groups (P>0.05). Conclusion The anesthesia and sedation depth of BIS-guided closed-loop targetcontrolled infusion set at 45 is better than 55 in maintaining Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy, but it has no obvious effect on long-term prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background Postoperative peritoneal adhesion (PPA) is regarded as fibrous bands connecting both injured abdominal wall and organs or adjacent tissues. It is associated with T helper (Th)1 and Th2 differentiation. However, the critical role of the immunopathogenesis of adhesion formation was precisely unknown. The aim of this study was to investigate the effect of a new agent polylactic acid (PLA) nanoparticles loaded with ligustrazine, that is, ligustrazine nanoparticles (LN) on PPA and identify the potential mechanism. Methods Twenty-four Sprague–Dawley rats were randomly divided into the sham, model, LN, and sodium hyaluronate (SH) groups. The structure of LN, including entrapment efficiency (EE) and loading capacity (LC), and in vitro drug release were calculated. Adhesions were scored and the Masson's trichrome staining was used to determine the collagen deposition. The expressions of TLR4, MyD88, and NF-κB were measured by qRT-PCR, immunohistochemistry, and western blot assay. Moreover, Th1-related cytokines (IFN-γ, IL-12), Th2-related cytokines (IL-4, IL-6) in the cecum tissue and serum were conducted by ELISA. Results LN had good EE, LC, and control-release delivery characters with fairly uniform diameter and spherical morphology. It could effectively prevent adhesion formation after surgery. Besides, it could reduce collagen fibers accumulation, downregulate the expression levels of TLR4, MyD88, and NF-κB, and maintain Th1/Th2 balance. Conclusions Ligustrazine nanoparticles had effective effects on Th1/Th2 balance by regulating TLR4/MyD88/NF-κB pathway in PPA rats. It may be served as a promising therapy on postoperative adhesion formation.

COVID-19 vaccines emerging from different platforms differ in efficacy, duration of protection, and side effects. To maximize the benefits of vaccination, we explored the utility of employing a heterologous prime-boost strategy in which different combinations of the four types of leading COVID-19 vaccine candidates that are undergoing clinical trials in China were tested in a mouse model. Our results showed that sequential immunization with adenovirus vectored vaccine followed by inactivated/recombinant subunit/mRNA vaccine administration specifically increased levels of neutralizing antibodies and promoted the modulation of antibody responses to predominantly neutralizing antibodies. Moreover, a heterologous prime-boost regimen with an adenovirus vector vaccine also improved Th1-biased T cell responses. Our results provide new ideas for the development and application of COVID-19 vaccines to control the SARS-CoV-2 pandemic.

The ongoing outbreak of novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global health crisis. Development of a cure for this devastating disease is currently at full speed, with several vaccines against COVID-19 already authorized and administered. Currently, demand for these vaccines far exceeds supply. As such, boosting immunity represents a viable route to halt the rapid spread of SARS-CoV-2 and limit fatalities until vaccines become more readily and widely available. The use of phytochemicals appears to be a promising panacea. Sesamin, a lignan isolated from Sesamum indicum seeds, is known for its potent pharmacological properties, and is therefore hypothesized as a potential candidate in the therapeutic regimen against COVID-19. Herein, we highlight the confirmed therapeutic anti-inflammatory and immune-modulatory potential of sesamin against myriads of respiratory disorders, and tentatively suggest that sesamin may exert similar potent effects against COVID-19. Precisely, we speculate that sesamin may help alleviate COVID-19 via restoring Th1/Th2 balance and preventing inflammation and cytokine storm development. Additionally, we further support the promising role of sesamin against COVID-19 by underscoring the direct evidence, which suggests that sesamin may demonstrate promising inhibitory potential against three important SARS-CoV-2 targets, namely main protease, spike protein, and angiotensin-converting enzyme 2 receptor. Although preliminary, there is ample evidence to propose sesamin as a potential phytotherapeutic and prophylactic candidate against COVID-19. Further in vitro, in vivo, and preclinical studies are required to further substantiate the role of sesamin in the prevention and/or treatment of COVID-19.

Food allergy is a serious food safety and public health issue. However, the medical interventions for allergy treatment are still suboptimal. Recently, the gut microbiome–immune axis has been considered as a promising target to reduce the symptoms of food allergy. In this study, we explore the oral administration of lotus-seed resistant starch as a means to protect against food allergy using an ovalbumin (OVA) sensitization and challenge rodent model. The results obtained showed that lotus-seed resistant starch intervention alleviated the food allergy symptoms (such as reductions in body temperature and allergic diarrhea). Furthermore, lotus-seed resistant starch also attenuated the increase in OVA-specific immunoglobulins and improved Th1/Th2 imbalance in OVA-sensitized mice. These anti-allergic effects might be associated with the actions of lotus-seed resistant starch on intestinal microbiota. Taken together, our findings suggest that daily ingestion of lotus-seed resistant starch might be effective for the alleviation of food allergy.

Chinese medicine Di-Long, the dried body of Pheretima vulgaris (Chen) has been used for the treatment of joint inflammation, arthralgia and numbness of limbs for many years. This study was to investigate the anti-rheumatoid arthritis (RA) effects of Di-Long and to explore its possible mechanisms. The identification and quantification of representative components in Di-Long extracts (DL) were carried out by HPLC analysis. The anti-RA effects and mechanisms of DL were studied in CIA mice, RAW 264.7 macrophages and spleen T lymphocytes. The Th1/Th2 cell ratio in CIA mice spleens were determined by Flow cytometry. The cytokine levels were determined by ELISA method. The expressions of p-NF-κB p65 in ankle joints of CIA mice were detected by Immunohistochemistry analysis. The phosphorylation of NF-κB signaling pathway in RAW 264.7 macrophages and expressions of T-bet and GATA-3 in CIA mice spleens were determined by Western blots. The treatment with DL significantly decreased the paw thickness, arthritis scores and inflammatory cells infiltration in CIA mice. The TNF-α, IL-6 concentrations in both mice serum and macrophages secretion were markedly reduced with the treatment of DL, as well as the phosphorylation of NF-κB pathway. DL inhibited the expressions of T-bet and GATA-3 and decreased Th1/Th2 cells ratio in CIA mice spleens. DL reduced IFN-γ, IL-2 levels in mice serum and spleen T lymphocytes, and increased IL-4 levels in CIA mice serum. Chinese medicine Di-Long have significant anti-RA effects. The mechanisms might be inhibiting the activation of NF-κB signaling pathway and regulating the balance of Th1/Th2 cells.

Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A new terminology “combined allergic rhinitis and asthma syndrome (CARAS)” was introduced to describe patients suffering from both allergic rhinitis (AR) and asthma. The pathogenesis of allergic airway inflammation has been well known, with the main contribution of TH1/TH2 imbalance and mast cell degranulation. Artemisia gmelinii has been used as an herbal medicine with its hepaprotective, anti-inflammatory, and antioxidant properties. In this study, the effect of A. gmelinii extracts (AGE) on the ovalbumin (OVA)-induced CARAS mouse model was investigated. AGE administration significantly alleviated the nasal rubbing and sneezing, markedly down-regulated both OVA-specific IgE, IgG1, and histamine levels, and up-regulated OVA-specific IgG2a in serum. The altered histology of nasal and lung tissues of CARAS mice was effectively ameliorated by AGE. The AGE treatment group showed markedly increased levels of the TH1 cytokine interleukin (IL)-12 and TH1 transcription factor T-bet. In contrast, the levels of the TH2 cytokines, including IL-4, IL-5, IL-13, and the TH2 transcription factor GATA-3, were notably suppressed by AGE. Moreover, AGE effectively prevented mast cell degranulation in vitro and mast cell infiltration in lung tissues in vivo. Based on these results, we suggest that AGE could be a potential therapeutic agent in OVA-induced CARAS by virtue of its role in balancing the TH1/TH2 homeostasis and inhibiting the mast cell degranulation.

Casein (CN) is the primary allergenic protein in cow's milk, contributing to the worldwide escalating prevalence of food allergies. However, there remains limited knowledge regarding the effect of structural modifications on CN allergenicity. Herein, we prepared three modified CNs (mCN), including sodium dodecyl sulfate and dithiothreitol-induced linear CN (LCN), transglutaminase-cross-linked CN (TCN), and glucose-glycated CN (GCN). The electrophoresis results indicated widespread protein aggregation among mCN, causing variations in their molecular weights. The unique internal and external structural characteristics of mCN were substantiated by disparities in surface microstructure, alterations in the secondary structure, variations in free amino acid contents, and modifications in functional molecular groups. Despite the lower digestibility of TCN and GCN compared to LCN, they significantly suppressed IL-8 production in Caco-2 cells without significantly promoting their proliferation. Moreover, GCN showed the weakest capacity to induce LAD2 cell degranulation. Despite the therapeutic effect of TCN, GCN-treated mice displayed the most prominent attenuation of allergic reactions and a remarkably restored Th1/Th2 imbalance, while LCN administration resulted in severe allergic phenotypes and endotypes in both cellular and murine models. This study highlighted the detrimental effect of linear modifications and underscored the significance of glycation in relation to CN allergenicity.

Objective: Explore the role of Th1/Th2 balance in the pathogenesis of primary dysmenorrhea through study the effect of Th1/Th2 balance drift on serum prostaglandin F2α, prostaglandin, 6-keto-prostaglandin F1α, TXB2, COX-2, AVP and OT in Primary Dysmenorrhea Rats with cold coagulation and blood stasis syndrome. Method: The rat model of primary dysmenorrhea with cold coagulation and blood stasis syndrome was established. On the basis of this model, Th1 shift model and Th2 shift model were established. The rats were divided into blank group, model group, Th1 shifting group and Th2 shifting group. The writhing reaction of rats in each group was compared, and the contents of PGF2α, PGE2, 6-keto-PGF1α, TXB2, COX-2, AVP and OT in serum were detected. Results: Writhing latency: There was no significant difference between Th1 and Th2 shifting groups (P>0.05), Th2 shifting group was shorter than Th1 shifting group (P<0.05). Writhing times in 30 minutes: Compared with the model group, the writhing times of Th1 shifting group decreased significantly (P<0.01), while Th2 shifting group increased significantly (P<0.01). Compared with the blank group, the contents of PGF2α, TXB2, COX-2, AVP and OT were increased (P<0.05, P<0.01), and the contents of 6-keto-PGF1α and PGE2 were decreased (P<0.01). Compared with the model group, the contents of PGF2α, TXB2, COX-2 and AVP in Th1 shifting group were decreased (P<0.05, P<0.01), and the contents of 6-keto-PGF1α and PGE2 were increased (P<0.01), while the contents of PGF2α, TXB2, COX-2, AVP and OT in Th2 shifting group were increased (P<0.01), and the contents of 6-keto-PGF1α and PGE2 were decreased (P<0.01). Conclusion: The intervention of Th1/Th2 cell balance on the expression of PGF2α, PGE2, 6-keto-PGF1α, TXB2, COX-2, AVP and OT may be one of the pathogenesis of PD with cold coagulation and blood stasis syndrome. [ABSTRACT FROM AUTHOR]

Natural soluble antagonist and decoy receptor on the surface of the cell membrane are evolving as crucial immune system regulators as these molecules are capable of recognizing, binding, and neutralizing (so-called inhibitors) their targeted ligands. Eventually, these soluble antagonists and decoy receptors terminate signaling by prohibiting ligands from connecting to their receptors on the surface of cell membrane. Interleukin-18 binding protein (IL-18BP) participates in regulating both Th1 and Th2 cytokines. IL-18BP is a soluble neutralizing protein belonging to the immunoglobulin (Ig) superfamily as it harbors a single Ig domain. The Ig domain is essential for its binding to the IL-18 ligand and holds partial homology to the IL-1 receptor 2 (IL-1R2) known as a decoy receptor of IL-1α and IL-1β. IL-18BP was defined as a unique soluble IL-18BP that is distinct from IL-18Rα and IL-18Rβ chain. IL-18BP is encoded by a separated gene, contains 8 exons, and is located at chr.11 q13.4 within the human genome. In this review, we address the difference in the biological activity of IL-18BP isoforms, in the immunity balancing Th1 and Th2 immune response, its critical role in autoimmune diseases, as well as current clinical trials of recombinant IL-18BP (rIL-18BP) or equivalent.

Background: Postoperative peritoneal adhesion (PPA) is regarded as fibrous bands connecting both injured abdominal wall and organs or adjacent tissues. It is associated with T helper (Th)1 and Th2 differentiation. However, the critical role of the immunopathogenesis of adhesion formation was precisely unknown. The aim of this study was to investigate the effect of a new agent polylactic acid (PLA) nanoparticles loaded with ligustrazine, that is, ligustrazine nanoparticles (LN) on PPA and identify the potential mechanism.Methods: Twenty-four Sprague-Dawley rats were randomly divided into the sham, model, LN, and sodium hyaluronate (SH) groups. The structure of LN, including entrapment efficiency (EE) and loading capacity (LC), and in vitro drug release were calculated. Adhesions were scored and the Masson's trichrome staining was used to determine the collagen deposition. The expressions of TLR4, MyD88, and NF-κB were measured by qRT-PCR, immunohistochemistry, and western blot assay. Moreover, Th1-related cytokines (IFN-γ, IL-12), Th2-related cytokines (IL-4, IL-6) in the cecum tissue and serum were conducted by ELISA.Results: LN had good EE, LC, and control-release delivery characters with fairly uniform diameter and spherical morphology. It could effectively prevent adhesion formation after surgery. Besides, it could reduce collagen fibers accumulation, downregulate the expression levels of TLR4, MyD88, and NF-κB, and maintain Th1/Th2 balance.Conclusions: Ligustrazine nanoparticles had effective effects on Th1/Th2 balance by regulating TLR4/MyD88/NF-κB pathway in PPA rats. It may be served as a promising therapy on postoperative adhesion formation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Orally administration of Morita-Baylis-Hillman adduct (CISACN) inhibits airway eosinophil migration in combined allergic rhinitis and asthma syndrome (CARAS) experimental model. • CISACN reduces the clinical signs of rhinitis through TNF-α inhibition and airway epithelium integrity. • CISACN increases Th1/Th2 ratio. • CISACN inhibits the p38MAPK and p65NF-κB signaling pathway axis in eosinophils. • CISACN ameliorates airway inflammation. Combined allergic rhinitis and asthma syndrome (CARAS) is an airway-type 2 immune response with a profuse inflammatory process widely affecting the world population. Due to the compromise of quality of life and the lack of specific pharmacotherapy, the search for new molecules becomes relevant. This study aimed to evaluate the effectiveness of the Morita-Bailys-Hillman adduct (CISACN) treatment in the CARAS experimental model. Female BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with CISACN. The treatment decreased the eosinophil migration to the nasal and lung cavities and tissues and the goblet cell hyperplasia/hypertrophy, attenuated airway hyperactivity by reducing the hyperplasia/hypertrophy of the smooth muscle and the extracellular matrix's thickness. Also, the treatment reduced the clinical signs of rhinitis as nasal rubbing and sneezing in a histamine-induced nasal hyperreactivity assay. The immunomodulatory effect of CISACN was by reducing OVA-specific IgE serum level, and IL-33, IL-4, IL-13, and TGF-β production, dependent on IFN-γ increase. Furthermore, the effect of CISACN on lung granulocytes was by decreasing the p-p38MAPK/p65NF-κB signaling pathway. Indeed, CISACN reduced the p38MAPK and p65NF-κB activation. These data demonstrated the anti-inflammatory and immunomodulatory effects of the CISACN with scientific support to become a pharmacological tool to treat airway inflammatory diseases. [ABSTRACT FROM AUTHOR]

Asthma is a chronic airway inflammatory disease that can lead to several complications caused by bacterial infections. However, recurrent attacks of the disease require long-term use of antibiotics, resulting in lung dysbiosis and poor outcomes. Daqing Formula (DQF) is a well-known herbal medicine in Pharmacopoeia of China , which is widely used for various stimuli-induced lower respiratory diseases, including asthma, bronchitis, and pneumonia. Thus, it has been demonstrated to be a plant-derived broad-spectrum antibiotic for treating and preventing various acute and chronic respiratory diseases. This study evaluated the efficacy and possible mechanism of DQF on allergic asthma and airway dysbiosis. The mice were co-challenged with ovalbumin and ampicillin to induce allergic asthma combined with airway dysbacteriosis. The populations of lung microbiota were detected by using 16s DNA sequencing. The levels of asthmatic markers in BALF were detected by ELISA. The levels of Th1/Th2 cytokines in splenic CD4+ cells of mice were analyzed by flow cytometry. The expressions of the GSK-3β signaling pathway in the lung tissues of asthmatic mice and eosinophils were detected by western blotting assay. The inhibition of DQF on the production of pro-inflammatory cytokines in eosinophils of asthmatic mice. The results showed that treatment with DQF at 200–800 mg/kg doses significantly reduced the frequency of nasal rubbing and lung inflammation as well as the number of total cells, eosinophils, and macrophages in bronchoalveolar lavage fluid. It decreased the relative abundances of Streptococcus, Cuoriavidus, and Moraxella, increased Akkermansia and Prevotella_6 in lung tissues of asthmatic mice, and inhibited the growth of Staphylococcus aureus , Klebsiella pneumoniae , Streptococcus pneumoniae and their resistant strains in vitro. Furthermore, DQF reduced the levels of eotaxin, TSLP, IL-4, IL-5, IL-25, and IL-33, but enhanced IFN-γ and IL-12 in BALF. It elevated the population of Th1 cells, inhibited eosinophil activation, and downregulated the expressions of p-GSK-3β, p-p65, nuclear β-catenin, and p-STAT3 in the lung tissues of asthmatic mice. The results revealed that DQF reduced airway inflammation, ameliorated lung dysbiosis, shifted the Th1/Th2 balance, and inhibited eosinophil activation in asthmatic mice, indicating its potential for severe asthma treatment. [Display omitted] • The abuse of antibiotics promoted the development of asthma. • DQF reduced airway inflammation induced by OVA and ampicillin in mice. • DQF ameliorated lung dysbiosis and inhibited the growth of drug-resistant bacteria. • DQF inhibited eosinophil activation via inhibiting GSK-3β-mediated pathways. • DQF prevented antibiotic abuse-induced severe asthma. [ABSTRACT FROM AUTHOR]

T helper (Th) cells have received extensive attention owing to their indispensable roles in anti-tumor immune responses. Th1 and Th2 cells are two key subsets of Th cells that exist in relative equilibrium through the secretion of cytokines that suppress their respective immune response. When the type of cytokine in the tumor microenvironment is altered, this equilibrium may be disrupted, leading to a shift from Th1 to Th2 immune response. Th1/Th2 imbalance is one of the decisive factors in the development of malignant tumors. Therefore, focusing on the balance of Th1/Th2 anti-tumor immune responses may enable future breakthroughs in cancer immunotherapy. Polysaccharides can regulate the imbalance between Th1 and Th2 cells and their characteristic cytokine profiles, thereby improving the tumor immune microenvironment. To our knowledge, this study is the most comprehensive assessment of the regulation of the tumor Th1/Th2 balance by polysaccharides. Herein, we systematically summarized the intrinsic molecular mechanisms of polysaccharides in the regulation of Th1 and Th2 cells to provide a new perspective and potential target drugs for improved anti-tumor immunity and delayed tumor progression. [Display omitted] • Th1/Th2 balance is an important molecular target in cancer. • Polysaccharides significantly improve the tumor immunosuppressive microenvironment. • Polysaccharides can regulate Th1/Th2 balance as an adjuvant for tumor therapy. [ABSTRACT FROM AUTHOR]

Objective(s): The effects of alpha linolenic acid (ALA) on tracheal responsiveness (TR), total protein (TP), phospholipase A2 (PLA2), immunoglobulin E (IgE), interleukin 4 (IL-4), interferon gamma (INF-γ) level and INF-γ/IL4 ratio in bronchoalveolar lavage fluid (BALF) of sensitized rats were examined.Materials and Methods: TR to methacholine and ovalbumin (OA), BALF levels of TP, PLA2 and IgE as well as IL-4, INF-γ and INF-γ/IL4 ratio were measured in control group (non-sensitized, group C), sensitized rats to OA (group S), S groups treated with two concentrations of ALA and dexamethasone group. Results: TR to methacholine and OA, BALF levels of TP, PLA2, IgE and IL-4 were significantly increased but BALF level of INF-γ and INF-γ/IL4 ratio decreased in group S compared to group C (PConclusion: Results showed an immune modulatory effect of the ALA that increased INF-γ, INF-γ/IL4 ratio (as an index of Th1/Th2) and decreased IL-4 in sensitized rats. ALA also showed preventive effect on inflammatory markers and tracheal responsiveness in sensitized animals comparable to the effect of dexamethasone.

The aim of the study was to analyse the effect of spirulina supplementation on blood levels of selected cytokines in athletes exposed to strenuous physical exercise, with emphasis on Th1/Th2 balance. The double-blind study included 19 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group, receiving 1500 mg of spirulina extract for 6 weeks, or to the placebo group. After the supplementation, athletes from the placebo group showed a significant post-recovery reduction of IL-2 level, which contributed to a significant decrease in IL-2/IL-4 and IL-2/IL-10 ratios at the end of a 24-h recovery period. Although this study did not demonstrate significant post-supplementation changes in Th1 and Th2 cytokine levels, the lack of a shift in Th1/Th2 balance toward Th2-type response in the supplemented group implies that some constituents of spirulina may exert an indirect beneficial effect on athletes’ immunity.

Natural products with known safety profiles are a promising source for the discovery of new drug leads. Berberine presents an example of one such phytochemical that has been extensively studied for its anti-inflammatory and immunomodulatory properties against myriads of diseases, ranging from respiratory disorders to viral infections. A growing body of research supports the pluripotent therapeutic role berberine may play against the dreaded disease COVID-19. The exact pathophysiological features of COVID-19 are yet to be elucidated. However, compelling evidence suggests inflammation and immune dysregulations as major features of this disease. Being a potent immunomodulatory and anti-inflammatory agent, berberine may prove to be useful for the prevention and treatment of COVID-19. This review aims to revisit the pharmacological anti-inflammatory and immunomodulatory benefits of berberine on a multitude of respiratory infections, which like COVID-19, are known to adversely affect the airways and lungs. We speculate that berberine may help alleviate COVID-19 via preventing cytokine storm, restoring Th1/Th2 balance, and enhancing cell-mediated immunity. Furthermore, the role this promising phytochemical plays on other important inflammatory mediators involved in respiratory disorders will be underscored. We further highlight the role of berberine against COVID-19 by underscoring direct evidence from in silico, in vitro, and in vivo studies suggesting the inhibitory potential berberine may play against three critical SARS-CoV-2 targets, namely main protease, spike protein, and angiotensin-converting enzyme 2 receptor. Further preclinical and clinical trials are certainly required to further substantiate the efficacy and potency of berberine against COVID-19 in humans.

Abstract Background The ratio of T helper 1 (Th1) to T helper 2 (Th2) as well as T helper 17 (Th17) to regulatory T cells (Treg) represents the state and direction of immune response. Recent studies demonstrated that dexmedetomidine reduced the secretion of inflammatory cytokines. We performed this study to investigate the effect of different doses of intraoperative dexmedetomidine on the expression of Th1, Th2, T17 and Treg cytokines and their ratios. Methods Seventy-five patients undergoing laparoscopic cholecystectomy were randomly separated into one of three groups: the full dose group (n = 25), in which dexmedetomidine was infused with a 1.0 μg/kg loading followed by an infusion of 0.5 μg/kg/min after anaesthetic induction, or the half dose group (n = 26), in which the dose was half of that of full dose group, or the saline group (n = 24) which was control. T cell cytokines were quantified by sandwich enzyme-linked immunoassay for blood samples taken after anaesthetic induction (T0), at the end of surgery (T1), and 60 min after surgery (T2). IFN-gamma/IL-4 and IL-17/IL-10, which represent the ratio of Th1/Th2 and Th17/Treg cytokines, respectively, were calculated as indices of immune cell levels based upon serum cytokines levels in place of direct measurements. C-reactive protein (CRP) concentrations were measured on the next day following surgery. Results The full dose group was associated with higher ratios of IFN-gamma/IL-4 than those of half dose group and control [10.1 vs. 1.9 at T1 (P = 0.041) compared with half dose group, and 10.1 vs. 0.2 at T1 (P = 0.031), 7.4 vs. 0.1 at T2 (P = 0.025) compared with control]. IL-17/IL-10 ratios were higher in the full dose group than those in control [4.2 vs. 0.6 at T1 (P = 0.013), 3.0 vs. 0.3 at T2 (P = 0.011)]. The CRP levels were lower in the dexmedetomidine-treated groups in a dose-dependent manner. Conclusions Dexmedetomidine exhibits immunomodulatory effects, shifting the Th1/Th2 and T17/Treg cytokine balance toward Th1 and T17, respectively, in a dose-dependent pattern in patients with surgical and anaesthetic stress. Trial registration Clinical Research Information Service, Republic of Korea (CRIS); KCT0000503; Registration date: Aug 13, 2012.

Selenium (Se) deficiency has a significant impact on the swine breeding industry by inducing digestive system damage and diarrhea. However, the molecular mechanism remains unclear. Our objectives were to investigate if different amounts of necroptosis, inflammatory responses, and T helper cell 1/T helper cell 2 (Th1/Th2) imbalances were induced by Se deficiency in intestinal porcine jejunal epithelial cells (IPEC‐J2) and swine ileum tissue. Therefore, Se‐deficient models were successfully established both in vitro and in vivo. In the current study, the cell morphological observation results showed that Se deficiency seriously affected the growth and differentiation of IPEC‐J2 cells. Moreover, the necroptosis staining and histomorphology observation results showed that the number of necroptotic cells increased significantly, and the ileal tissue exhibited abnormal structures, including necroptotic features and inflammatory cell infiltration, in the Se‐deficient group. Furthermore, Se deficiency resulted in accelerated cell necroptosis by increasing (p <.05) the expression of genes related to the tumor necrosis factor‐α pathway at both the protein and messenger RNA (mRNA) levels compared to the control group. Moreover, the relative mRNA and protein expression of the inflammatory genes and their responses to dietary Se deficiency were consistent with the resultant Th1/Th2 imbalances in vitro and in vivo. Taken together, the results suggested that Se deficiency caused necroptosis, inflammatory responses, and abnormal expression of cytokines in swine ileum tissue. These findings might help us to explain the damage induced by Se deficiency to the digestive system of swine. [ABSTRACT FROM AUTHOR]

The balance of type 1 and type 2 immune responses plays a crucial role in anti-helminth immunity and can either support chronic infection or drive type 2 mediated expulsion of the parasite. Helminth antigens and secreted molecules directly influence this balance and induce a favorable immunological environment for the parasite’s survival. However, less is known if the site of infection also influences the balance of type 1 and type 2 immunity. Here, we report that tissue-specific immune responses are mounted against helminth antigens, which elicited strong IL-4 responses when injected into the skin, while the same antigen, delivered into the intestinal subserosa, induced increased IFN-γ and reduced Th2 responses. Immune responses in individual mesenteric lymph nodes that drain defined regions of the intestine furthermore displayed a site-specific pattern of type 1 and type 2 immunity after Schistosoma mansoni or Heligmosomoides polygyrus infection. S. mansoni egg-specific Th2 responses were detectable in all mesenteric lymph nodes but Th1 responses were only present in those draining the colon, while H. polygyrus infection elicited mixed Th1 and Th2 responses in the lymph nodes associated with the site of infection. Similar site-specific type 1 and type 2 immune responses were observed in the draining lymph nodes after the controlled delivery of S. mansoni eggs into different segments of the small and large intestine using microsurgical techniques. Different subsets of intestinal dendritic cells were hereby responsible for the uptake and priming of Th1 and Th2 responses against helminth antigens. Migratory CD11b+CD103− and especially CD11b+CD103+ DC2s transported S. mansoni egg antigens to the draining lymph nodes to induce Th1 and Th2 responses, while CD103+ DC1s induced only IFN-γ responses. In contrast, H. polygyrus antigens were predominantly transported by CD11b+CD103− DC2s and CD103+ DC1s and all DC subsets induced similar Th1 but weaker Th2 responses, compared to S. mansoni egg antigens. The development of adaptive anti-helminth immune responses is therefore influenced by the antigen itself, the uptake and priming characteristics of antigen-positive dendritic cell subsets and the site of infection, which shape the level of Th1 and Th2 responses in order to create a favorable immunological environment for the parasite.