Human Cell
·
2024
·
IF 3.4
Wang Meng,Li Qiu-Jie,Zhao Hua-Yan,Zhang Jing-Lan
Lethal graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT). Pyruvate kinase M2 (PKM2) is essential for CD4+ T-cell differentiation. Using the well-characterized mouse models of Allo-HSCT, we explored the effects of TEPP-46-induced PKM2 tetramerization on GVHD and graft-versus-leukemia (GVL) activity. TEPP-46 administration significantly improved the survival rate of GVHD. The severity of GVHD and histopathological damage of GVHD-targeted organs were obviously alleviated by PKM2 tetramerization. Additionally, tetramerized PKM2 inhibited the activation of NF-κB pathway and decreased the inflammation level of GVHD mice. PKM2 tetramerization blocked Th1 and Th17 cell differentiation and secretion of pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-17). Meanwhile, differentiation of Treg cells and IL-10 secretion were promoted by tetramerized PKM2. These findings demonstrated that PKM2 enhanced the augment of Th1 and Th17 cells to accelerate the progression of GVHD, and allosteric activation of PKM2 targeted Th1 and Th17 cells attenuated GVHD. Furthermore, we also confirmed that TEPP-46 administration did not compromise GVL activity and resulted in slightly improvement of leukemia-free survive. Thus, targeting Th1 and Th17 cell response with PKM2 allosteric activator may be a promising therapeutic strategy for GVHD prevention while preserving the GVL activity in patients receiving Allo-HSCT. Graphical abstract
研究领域:
免疫学
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血液学
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移植学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Frontiers
·
2024
·
IF 7.4
Ying Yang,Mengfan Luo,Wanyi Zhou,Wenyang Tao,Jingrui Li,Jianrong Xing,Quanqin Tan,Yuxing Guo
In recent years, the development of immunosuppression has become common, and probiotics are a vital immunomodulatory strategy. This study evaluated the alleviating effect of Lactiplantibacillus plantarum ( L. plantarum ) YY-112 on cyclophosphamide-induced immune imbalance and resolved the possible mechanism of action. L. plantarum YY-112 at 10 9 CFU/mL lowered loss of body weight and alleviated splenic injury, intestinal injury, and inflammation, according to the hematoxylin and eosin staining. Biochemical results showed that 10 9 CFU/mL L. plantarum YY-112 increased interleukin-10 and immunoglobulin M levels and decreased interferon-γ levels. Additionally, the immunoregulatory effect at the molecular levels of L. plantarum YY-112 was analyzed by transcriptome sequencing. L. plantarum YY-112 significantly upregulated Cr2 and downregulated C5aR1 to regulate the complement system; downregulated S100a8 , S100a9 , and Mmp9 to inhibit neutrophil aggregation; upregulated Cd19 , Cd72 , Cd3e , Cd28 , Cd80 , Cd8a , and histocompatibility-2-related genes to regulate B- and T-cell activation; and upregulated Xiap , Malt1 , Ikbkb , Mapk11 , Mef2c , Mapk12 , Ras , and Myc to activate immune signaling pathways. Furthermore, L. plantarum YY-112 improved intestinal microbial structure and reduced enrichment of Lachnospiraceae_NK4A136_group , norank_f_Lachnospiraceae , Desulfovibrio , Colidextribacter , and Helicobacter . In conclusion, these findings offer valuable insights into the potential mechanisms through which L. plantarum YY-112 regulates immune imbalance.
研究领域:
免疫学
·
微生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 31
·4854-4866
·
IF 5.047
Xuanjin Wu,Yang Li,Xiguang Chen,Zhongzheng Zhou,Jianhui Pang,Xin Luo,Ming Kong
The efficient delivery of vaccines to draining lymph nodes and the induction of robust local immune responses are crucial for immunotherapy. Transdermal administration has been evidenced to facilitate the delivery of ingredients to lymph nodes. In this study, transfersomes with opposite surface charges were applied for antigen encapsulation and these were integrated with dissolving microneedles to investigate their effects on immune responses via transdermal immunization. The microneedles were easily inserted into mouse skin and achieved the local release of nanovaccines into the dermis through dissolution. Although anionic nanovaccines promoted cellular uptake via DC2.4, cationic nanovaccines exhibited stronger escape capacities from endocytic compartments, facilitating antigen processing via an MHC-I presentation pathway, and formed larger accumulations in lymph nodes. Compared with their anionic counterparts, the cationic nanovaccines more efficiently activated DC maturation and induced Th1 immunity; this was suggested by the significantly increased IgG2a/IgG1 ratio and elevated cytokine secretion from Th1 cells, without an enhancement in the Th2 response. Such an enhanced Th1 antigen-specific immune response in lymph nodes via a transdermal vaccine delivery platform is beneficial for potential immunotherapy approaches.
研究领域:
免疫学
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药学
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纳米技术
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疫苗递送系统
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 17
·8678
·
IF 4.9
Yamin Zhang,Jiajia Lin,Xiaomei Xu,Xuehua Lu,Lisha Li,Yuezhen Yang,Wenjin Lin
This study aimed to compare the therapeutic effects of fresh (CMF) and dried (CMD) Centipeda minima against allergic rhinitis (AR), elucidate their underlying molecular mechanisms, and identify the bioactive compounds responsible for their immunomodulatory actions. An ovalbumin-induced AR mouse model was treated with CMF or CMD extracts, followed by evaluation of nasal symptoms, serum biomarkers (IgE, histamine, cytokines), and nasal mucosa histopathology. Transcriptomics and widely targeted metabolomics were integrated with network pharmacology to identify differentially expressed genes and bioactive components, which were further validated in RAW264.7 and RBL-2H3 cells. CMF and CMD exhibited distinct anti-AR mechanisms: CMF predominantly suppressed Th2 responses (reducing IgE, IL-6, and histamine while elevating IL-10), whereas CMD enhanced Th1 activity (increasing IFN-γ). Metabolomic analysis revealed CMF was rich in amino acids while CMD contained higher flavonoids, with neocnidilide and 6-gingerol identified as key bioactive compounds that modulated TNF-α, IL-6, and IL-10 via NF-κB and JAK-STAT pathways. These findings demonstrate that CMF and CMD exert complementary anti-inflammatory effects through Th2 inhibition and Th1 activation, respectively, providing a molecular basis for the traditional use of Centipeda minima and highlighting its bioactive compounds as potential therapeutics for inflammatory diseases.
研究领域:
药理学
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免疫学
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民族药理学
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分子生物学
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植物学
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生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2018
·Vol. 18
·期 1
·622-626
·
IF 1.922
Qin Zhu,Peifen Zheng,Jianying Zhou,Xinyu Chen,Yuliang Feng,Weifeng Wang,Feng Zhou,Qiaona He
Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease of the colon. T cell responses have been associated with the pathology of UC. Andrographis paniculata (AP) extract has been previously reported as an effective treatment of UC. The present study aimed to explore the effects of andrographolide, the primary active component of AP, on the T cell responses of patients with UC. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with UC and treated with various concentrations of andrographolide (0, 10, 20 and 30 µg/ml). Andrographolide decreased interferon γ, interleukin (IL)‑23 and IL‑17A, however it increased IL‑4 in a dose‑dependent manner, as indicated by ELISA assay. Andrographolide treatment resulted in a decreased percentage of T helper (Th)1 and Th17 cells and an increased proportion of Th2 cells, as demonstrated by flow cytometry analysis. T‑bet (a Th1‑specific transcription factor) and RAR‑related orphan receptor γt (key transcription factor of Th17 cells) expression was decreased, but GATA‑3 (Th2 lineage‑specific transcription factor) expression was increased following andrographolide treatment as indicated by western blot analysis. These results demonstrated the inhibitory effects on Th1/Th17 responses and the promoting effects on Th2 responses of andrographolide. Experiments on IL‑23‑treated PBMCs from healthy donors revealed similar effects of andrographolide on Th1/Th2/Th17 responses. In summary, these results suggest that andrographolide may be an effective candidate for the treatment of IL‑23‑mediated diseases.
研究领域:
免疫学
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药理学
·
炎症性肠病
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2012
·
IF 2.453
Ye Liu,Shoufeng Zhang,Fei Zhang,Rongliang Hu
Four botanical polysaccharide preparations (from Astragalus , Echinacea , wolfberry, and kelp) were evaluated as immunopotentiators/adjuvants of a veterinary rabies vaccine. Results showed that lymphocyte proliferation and some cytokines were significantly elevated, with cellular immune responses skewed towards Th1 and Tc1. All four polysaccharides produced accelerated and enhanced effects on rabies-neutralizing antibody responses in mice and dogs. The results also indicated that certain botanical polysaccharides could be used in rabies vaccine formulations for early and persistent prophylaxis.
研究领域:
免疫学
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兽医学
·
植物化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Xiao Qiang Li,Yong Chen,Hong Mei Zhou,Hui Li Shi,Xiao Ning Yan,Li Ping Lin,Ren Xiang Tan
Ethnopharmacological relevance Rosin, an exudate of conifer trees such as Pinus masscnlana (Pinaceae), has been used to treat psoriasis for nearly two thousand years in China despite its so far undefined pharmacology. Unfortunately, the rosin intoxication is noted from time to time, but the water-boiled rosin (WBR) has been documented to be safer. This study was performed to evaluate the in vivo anti-psoriasis efficacy of WBR. Materials and methods The main phytochemicals in WBR were quantified by high performance liquid chromatography (HPLC). WBR was evaluated in the imiquimod-induced psoriasis-like inflammation mouse model for its anti-psoriasis effect at 130, 260, and 390 mg/kg, which were set according to the dose used for patients. Through a combination of q-PCR, flow cytometry, and histopathological and immunohistochemical (IHC) analysis, the in vivo efficacy was assessed in terms of the psoriasis area severity index (PASI), epidermal keratinocyte proliferation, Th1 and Th17 cell numbers in spleen, and mRNA expressions of inflammatory cytokines. Result Oral administration of WBR ameliorates the psoriasis-like dermatitis in the imiquimod-generated mouse model. In particular, WBR given at 260 or 390 mg/kg significantly restores the normal keratinization of dorsal lesion if compared with the untreated psoriatic mice. Such an effect was addressed to correlate to the Th1/Th17 cell reduction in spleen and the suppressed expression of IL-17A, IL-17F, IL-22, IL-23, TNF- α , K17, and proliferating cell nuclear antigen (PCNA) after the WBR administration. Conclusion WBR is effective in the imiquimod-induced psoriasis-like inflammation mouse model with the efficacy arising from its proliferation inhibition of Th1/Th17 cells and epidermal keratinocytes via the down-regulation of the relevant inflammatory cytokines such as IL-23, IL-17A, and IL-17F. Collectively, WBR harvested and processed in the traditional manner is an efficacious psoriasis-treating agent.
研究领域:
药理学
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免疫学
·
民族药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Meng-Ke Liu,Juan-Juan Tang,Hao Li,Xu-Yang Chen,Jun-Ling Cai,Gui-Ying Lin,Kan-Yao Chen,Zhi-Peng Liu,Xiao-Fang Ji,Zhong-Jin Yang,Zi Li
Artemisitene (ATT), an artemisinin (ART) analog retaining the endoperoxide moiety and incorporating an additional α, β-unsaturated carbonyl structure, exhibits enhanced biological activities. However, its therapeutic effects on liver fibrosis remain unclear. In this study, we demonstrated that ATT significantly alleviated liver inflammation and fibrosis induced by carbon tetrachloride (CCL 4 ) in mice. ATT treatment markedly reduced the count of neutrophils in the liver, as well as macrophages in both the liver and spleen. Additionally, the frequencies of Th2 and Th17 cells were significantly lowered, while Th1 cells frequency and the Th1/Th2 index were notably increased. The frequency of ILC2 cells, correlated with ST2 and IL-33 expression levels, was also significantly lowered. Consistently, ATT inhibited NLRP3 inflammasome activation, which was positively associated with AST and ALT levels, and with the count of Neutrophils, macrophages, and ILC2 cells, but negatively correlated with Th1frequeny. Furthermore, liver fibrosis severity showed a significant positive correlation with neutrophil and Th17 cell counts in the liver, and a negative correlation with Th1 cell count and the Th1/Th2 index. Therefore, ATT alleviated CCL 4 -induced mice liver fibrosis through NLRP3 inflammasome inhibition and immunomodulation.
研究领域:
药理学
·
免疫学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
·
IF 3.69
Pengfei Li,Jingkang Wang,Chunguo Wang,Long Cheng,Quantao Ma,Yaqi Li,Yongcheng An,Hongyu Dai,Yuhui Duan,Tieshan Wang,Xuan Ma,Minghui Zhang,Ting Wang,Baosheng Zhao
Ethnopharmacological relevance Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or “Nai-Zi-Lai” in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases . However, the pharmacological mechanisms of HCZP remain unrevealed. Aim of the study To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA. Materials and methods A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA. Results Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased. Conclusions HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors.
研究领域:
药理学
·
传统中药
·
呼吸系统疾病
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2018
·
IF 2.064
Peng Pang,Ke Zheng,Sizhi Wu,Huachong Xu,Li Deng,Yucong Shi,Xiaoyin Chen
The objective of this study is to investigate the effects of baicalin on controlling the pulmonary infection and improving the prognosis in influenza A virus (IAV) infection. PCR and western blot were used to measure the changes of some key factors in RLRs signaling pathway. MSD electrochemiluminescence was used to measure the expression of pulmonary inflammatory cytokines including IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, and KC/GRO. Flow cytometry was used to detect the proportion of Th1, Th2, Th17, and Treg. The results showed that IAV infection led to low body weight and high viral load and high expression of RIG-I, IRF3, IRF7, and NF-κB mRNA, as well as RIG-I and NF-κB p65 protein. However, baicalin reduced the rate of body weight loss, inhibited virus replication, and downregulated the key factors of the RLRs signaling pathway. Besides, baicalin reduced the high expression inflammatory cytokines in lung and decreased the ratios of Th1/Th2 and Th17/Treg to arouse a brief but not overviolent inflammatory response. Therefore, baicalin activated a balanced host inflammatory response to limit immunopathologic injury, which was helpful to the improvement of clinical and survival outcomes.
研究领域:
药理学
·
免疫学
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2025
·
IF 5.4
Yunpeng Wen,Shuping Chen,Teng Wei,Na Wu,Yao Yao,Lilan Xu,Jihua Mao,Yan Zhao,Yonggang Tu
Egg yolk phosphatidylcholine (EYPC), the most vital functional lipid in egg yolk, has demonstrated neuroprotective, antibacterial, and cardioprotective effects. However, there is little information about its immunoregulation effect. Therefore, the aim of this study is to assess the effects and mechanisms of EYPC on intestinal immune homeostasis through an immunosuppressed mouse model induced by cyclophosphamide (CTX). The protective effect of intestinal immunity was evaluated on the basis of immune organ indices, intestinal tight junction (TJ) proteins, sIgA and cytokine secretion, nuclear transcription factor levels, and the equilibrium between Th1 and Th2 cells. It was shown that EYPC obviously inhibited thymus and spleen atrophy, enhanced the expression of TJ proteins, promoted the secretion of sIgA and cytokines, increased the levels of Th1 and Th2 cells, and also modulated the balance of Th1 and Th2 cells. The composition of the gut microbiota and metabolites were discussed to outline mechanisms. The results elucidated that EYPC could alleviate the gut microbiota dysbiosis caused by CTX via reducing the relative abundance of Akkermansia muciniphila and promoting the proliferation of Prevotella and Lactobacillus reuteri. Furthermore, EYPC improved the fecal metabolic profile, restoring the relative content of 13 metabolites and regulating bile secretion. Collectively, these findings suggested that EYPC may contribute to intestinal immune homeostasis through modulating gut microbiota and their metabolism, highlighting its potential as an immunomodulator.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND AGRICULTURAL IMMUNOLOGY
·
2020
·
IF 0
Mahepali Mahabati,Adila Aipire,Pengfei Yuan,Xiaoying Liu,Shanshan Cai,Alimu Aimaier,Dilinigeer Ziyayiding,Mayila Yasheng,Dilinazi Abudujilile,Jinyao Li
Polysaccharides have various bioactivities including anti-tumour, antioxidant and immunoregulation, which are correlated with their structural characteristics. Here, four polysaccharides from Glycyrrhiza uralensis (GUPS), Pleurotus ferulae (PFPS), Triticum aestivum (TAPS) and Oryza sativa (OSPS) were purified to compare their structural characteristics and immunoregulatory activities. The data showed that TAPS, OSPS, GUPS and PFPS contained different monosaccharide components and had distinctly structural characteristics. All the four polysaccharides promoted the maturation of dendritic cells (DCs) through TLR4 with different activities. GUPS and PFPS also reduced the phagocytosis of DCs but not for TAPS and OSPS. Importantly, GUPS and PFPS enhanced the Th1 skewing immune response in mice without inflammation. TAPS and OSPS only showed weak immunostimulatory activity in vivo. The immunostimulatory activities of the four polysaccharides were ranked as PFPS = GUPS > TAPS > OSPS.
研究领域:
药理学
·
免疫学
·
植物科学
✓ 已验证
产品关联
DOI
危险品化学品经营许可证（带存储）