ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Huijuan Ma,Tingqian Wang,Junfeng Wang,Peiyao Wang,Qi Shu,Ruilin Qin,Sijia Li,Huan Xu
The correlation between formaldehyde (FA) exposure and prevalence of asthma has been widely reported. However, the underlying mechanism is still not fully understood. FA exposure at 2.0 mg/m 3 was found to exacerbate asthma in OVA-induced murine models. IFN-γ, the cytokine produced by T helper 1 (Th1) cells, was significantly induced by FA in serum and bronchoalveolar lavage fluid (BALF) of asthmatic mice, which was different from cytokines secreted by other Th cells. The observation was also confirmed by mRNA levels of Th marker genes in CD4+ T cells isolated from BALF. In addition, increased production of IFN-γ and expression of T-bet in Jurkat T cells primed with phorbol ester and phytohaemagglutinin were also observed with 100 μM FA treatment in vitro . Upregulated STAT1 phosphorylation, T-bet expression and IFN-γ production induced by FA was found to be restrained by STAT1 inhibitor fludarabine, indicating that FA promoted Th1 commitment through the autocrine IFN-γ/STAT1/T-bet pathway in asthma. This work not only revealed that FA could bias Th lineage commitment to exacerbate allergic asthma, but also identified the signaling mechanism of FA-induced Th1 differentiation, which may be utilized as the target for development of interfering strategies against FA-induced immune disorders.
研究领域:
免疫学
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呼吸病学
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毒理学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2024
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IF 10.8
Xiuxiu Yao,Wendi Huo,Yuchen Wang,Dongfang Xia,Yan Chen,Yuhua Tang,Huayong Tang,Wenjiang Yang,Yu Liu,Jingquan Xue,Qing Yuan,Xueyun Gao,Kai Cao
The presence of low-dose radiation (LDR) in the environment has become more prevalent. However, the effect of LDR exposure on the immune system remains elusive. Here, we interestingly found that LDR specifically elevated the percentage of CD4+IFNγ+ Th1 splenocytes, both in vitro and in vivo, without affecting the percentage of CD8+IFNγ+ Tc1 cells and regulatory T cells. A similar phenomenon was found in T cells from peripheral blood. Mechanistically, we found that LDR can induce mitochondrial damage, which stimulated the STING signaling pathway, leading to the enhanced expression of T-bet, the master transcriptional factor of Th1-cell differentiation. The specific STING signal inhibitor can abrogate the effect of LDR on Th1 differentiation, confirming the central role of the STING pathway. To further validate the immunoregulatory role of LDR, we exposed mice with whole body LDR and evaluated if LDR could protect mice against triple-negative breast cancer through enhanced antitumor immunity. As expected, LDR significantly delayed tumor development and promoted cell death. Meanwhile, LDR resulted in increased tumor-infiltrating Th1 cells, while the proportion of Tc1 and Treg cells remained unchanged. Furthermore, the infiltration of antitumor macrophages was also increased. In summary, we revealed that environmental LDR could specifically regulate Th1 T-cell activities, providing critical information for the potential application of LDR in both clinical and nonclinical settings.
研究领域:
免疫学
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肿瘤学
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放射生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Feifan Liu,Yuanmei Bai,Xue Wu,Yan Wan,Shifang Luo,Linao Zhang,Tao Li,Hua Tang,Xianjin Tang,Rong Chen,Qinghua Chen,Yuhuan Xie,Peixin Guo
Ethnopharmacological relevance Allergic rhinitis (AR) stands as a non-infectious inflammatory condition affecting the nasal mucosa, marked by bouts of sneezing, nasal itching, and congestion. This ailment afflicts individuals across all age groups and poses challenges for effective treatment due to its chronic nature. Cangerzisan (CEZS), documented in the Jishengfang compendium, represents a traditional Chinese medicinal formula long utilized for AR management. Aim of the study : Investigating mechanism beneath therapeutic effect of CEZS in alleviating AR. Materials and methods The main active components in CEZS were determined by High Performance Liquid Chromatography (HPLC).The active constituents of CEZS and their corresponding targets were identified through an exhaustive screening process employing TCMSP database. To identify targets relevant to AR, GeneCards, OMIM, and DisGeNET databases were thoroughly applied. Protein-protein interaction (PPI) network was assembled utilizing STRING platform. Potential signaling pathways influenced by CEZS were delineated through GO and KEGG enrichment analyses. Subsequently, an AR model was induced by administering aluminum hydroxide (Al(OH)3) and ovalbumin (OVA) for affecting basal and local sensitization, respectively, facilitating experimental validation of the principal signaling pathways. Results There were 61 active constituents identified within CEZS, targeting a pool of 129 entities associated with AR treatment. Pathways analysis of KEGG revealed that CEZS potentially inhibits AR advancement via modulating TLR4 signaling pathway. Animal experiments demonstrated that CEZS effectively alleviated symptom scores in guinea pigs with AR. Moreover, it exhibited notable improvements in serum immune and inflammatory factors levels, as well as reduced inflammatory infiltration within nasal mucosa, including goblet and mast cells. CEZS was found to enhance GATA-3 expression while reducing T-bet expression, thereby modulating the TH1/TH2 immune balance. Additionally, CEZS downregulated HMGB1, TLR4, and p–NF–κB/NF-κB protein expressions within nasal mucosa of guinea pigs. Conclusions The therapeutic mechanism of CEZS against AR involves rectifying TH1/TH2 immune imbalance and upregulating inflammatory and immune factors through modulating key proteins expression within TLR4 pathway. This targeted regulation effectively impedes AR progression.
研究领域:
民族药理学
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药理学
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免疫学
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传统中药
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生物信息学
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实验验证
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Huiting Fang,Huizhen Li,Yang Chen,Xiaoming Liu,Jianxin Zhao,Paul Ross,Catherine Stanton,Wei Chen,Bo Yang
There has been a rising interest in studying how Bifidobacterium breve can affect the immune system over the years. The aim of this study was to evaluate the effect of B. breve on the immune system and to explore the mechanism in a mouse model of cyclophosphamide (CTX)-induced immunosuppression. The results of the study showed that B. breve CCFM1310 significantly increased the thymus index (p < 0.05), promoting the secretion of immunoglobulins and the number of immune cells in the blood. Moreover, B. breve CCFM1310 could repair the spleen injury. It increased the mRNA expression level of T-bet (p < 0.05) and decreased the mRNA expression level of TGF-β and FOXP3 (p < 0.05). B. breve CCFM1310 alleviated oxidative stress by increasing enzymatic activities of SOD, CAT and T-AOC and reducing the concentration of MDA. Moreover, it repaired intestinal damage by increasing the number of goblet cells, upregulating mRNA expression of tight junction proteins, and promoting the production of short-chain fatty acids (SCFA). B. breve CCFM1310 could regulate the gut microbiota by increasing the relative abundance of Lactobacillus (p < 0.05) and decreasing the relative abudance of Lachnospiraceae NK4A136 group . Overall, our study suggests that B. breve CCFM1310 could enhance immunity in CTX-induced immunosuppressed mice by affecting immune responses, oxidative stress and gut microbiota.
研究领域:
免疫学
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微生物学
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药理学
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产品关联
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2023
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IF 4.3
Fangfang Min,Jielun Hu,Tao Huang,Yousheng Huang,Shaoping Nie,Tao Xiong,Mingyong Xie
Lactobacillus ( L. ) casei NCU011054 isolated from infant feces has been proven to be a potential probiotic in vitro . The present study aimed to investigate the effects of L. casei NCU011054 on the immune response and gut microbiota in cyclophosphamide (CP)-induced immunosuppression mice. Results indicated that L. casei NCU011054 could increase the levels of mucin (Muc2) and tight junction proteins (ZO-1, occludin and claudin-1). Moreover, L. casei NCU011054 was found to upregulate TLRs/NF-κB pathway (TLR-2, TLR-4, TLR-6, p65 and NF-κB) and two transcription factors (T-bet and GATA-3) mRNA levels, and enhance the number of CD4 + T cells. Th1-related cytokines (IL-12p70, IFN-γ and TNF-α) and Th2-related cytokines (IL-2, IL-4, IL-6 and IL-10) significantly increased after L. casei NCU011054 treatment. More importantly, L. casei NCU011054 increased the ratio of T-bet to GATA-3 and IFN-γ to IL-4. Apart from these, L. casei NCU011054 remodeled gut microbiota and modulated gut metabolites in CP-induced immunosuppressed mice. The correlation analysis showed that Lactobacillus upregulated by L. casei NCU011054 was positively correlated with TLRs/NF-κB pathway, and the ratio of T-bet to GATA-3 and IFN-γ to IL-4. All findings revealed that L. casei NCU011054 could improve intestinal immune dysfunction and modulate Th1/Th2 balance via TLRs/NF-κB pathway in CP-induced immunosuppressed mice.
研究领域:
免疫学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）