MICROBIAL PATHOGENESIS
·
2023
·
IF 3.8
Shun Wang,Xiaodi Jin,Hao Chen,Mingdong Han,Jiaxin Bao,Dong Niu,Yikang Wang,Rui Li,Zhiyong Wu,Jichang Li
Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) in chickens leads to enormous economic damage to the poultry industry yearly. The active components and mechanism of action of the traditional herbal remedy Ephedra houttuynia powder (EHP), which had been approved for clinical treatment against MG infection in China, remain unknown. In this study, the active components of EHP against MG were screened using a network pharmacological method, additionally, we studied the mechanism of action of the screened results (quercetin (QUE)). The findings demonstrated that QUE was an essential element of EHP against MG infection, effectively attenuating MG-induced oxidative stress and activation of the TLR2/MyD88/NF-κB pathway. Following QUE therapy, IL-1, IL-6, and TNF-α content and expression were downregulated, whereas IL-4 and IL-10 expression were upregulated, eventually suppressing the inflammatory response both in vitro and in vivo . Together, this study presents a strong rationale for using QUE as a therapeutic strategy to inhibit MG infection-induced inflammatory damage and oxidative stress.
研究领域:
兽医学
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药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2022
·Vol. 22
·期 11
·2200150
·
IF 5.859
Wenjie Wang,Yilin Wang,Weifeng Zhao,Changsheng Zhao
Preventing bacterial infection and controlling the inflammatory response occupy important positions in wound treatment. Although loading wound dressings with antibacterial or anti-inflammatory drugs/molecules is an effective approach to address these issues, simultaneous sustained release of these drugs remains challenging. Herein, hydrophilic polyhexamethylene guanidine hydrochloride (PHGC) and hydrophobic indomethacin (Indo) are loaded in hydrophilic polyvinyl alcohol (PVA) and hydrophobic polycaprolactone (PCL) nanofibers respectively by bidirectional electrospinning to form an antibacterial and anti-inflammatory PCL-Indo/PVA-PHGC wound dressing. The fabricated nanofiber membrane exhibits 100% disinfection activity to both Gram-negative ( E. coli) and Gram-positive ( S. aureus ) bacteria because of the release of the broad-spectrum antibacterial molecule PHGC. Additionally, the loading of Indo in the nanofiber membrane enhances the expression level of IL-10, while inhibiting those of IL-6 and TNF- α in the RAW264.7 mouse cells. In the interwoven membrane of PCL and PVA fibers, the release of hydrophobic Indo is hindered by hydrophilic PHGC and PVA fibers, and similarly, the release of hydrophilic PHGC is hindered by hydrophobic Indo and PCL fibers. In conclusion, the PCL-Indo/PVA-PHGC nanofiber membrane has excellent antibacterial, anti-inflammatory, and sustained-release effects, and thus regulates the immune microenvironment of the cells to potentially promote wound healing.
研究领域:
材料科学
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Liping Han,Ting Li,Yingying Wang,Weizi Lai,Hengpu Zhou,Zhuangwei Niu,Jie Su,Guiyuan Lv,Guangji Zhang,Jianli Gao,Jianbo Huang,Zhaohuan Lou
Ethnopharmacological relevance Weierning tablet (WEN) is a traditional Chinese patent medicine widely used in clinical for chronic atrophic gastritis (CAG) therapy for years. However, the underlying mechanisms of WEN on anti-CAG are still unveiled. Aim of the study The present study aimed to elucidate the characteristic function of WEN on anti-CAG and to illuminate its potential mechanism. Methods The CAG model was established by gavage rats with a modeling solution (consisting of 2% sodium salicylate and 30% alcohol) with irregular diets and free access to 0.1% ammonia solution for two months on end. An enzyme-linked immunosorbent assay was used to measure the serum levels of gastrin , pepsinogen , and inflammatory cytokines. qRT-PCR was applied to measure mRNA expressions of IL-6 , IL-18, IL-10, TNF-α, and γ-IFN in gastric tissue. Pathological changes and the ultrastructure of gastric mucosa were examined by hematoxylin and eosin staining and transmission electron microscopy , respectively. AB-PAS staining was applied to observe the intestinal metaplasia of gastric mucosa. Immunohistochemistry and Western blot were used to measure the expression levels of mitochondria apoptosis-related proteins and Hedgehog pathway-related proteins in gastric tissues. Expressions of Cdx2 and Muc2 protein were determined by immunofluorescent staining. Results WEN could dose-dependently lower the serum level of IL-1β and the mRNA expressions of IL-6, IL-8, IL-10, TNF-α, and γ-IFN in gastric tissue. Also, WEN significantly alleviated the collagen deposition in gastric submucosa, regulated the expressions of Bax, Cleaved-caspase9, Bcl2 , and Cytochrome c to reduce the apoptosis of gastric mucosa epithelial cells, and maintained the integrity of the gastric mucosal barrier. Moreover, WEN could reduce protein expressions of Cdx2, Muc2, Shh, Gli1, and Smo, and reverse intestinal metaplasia of gastric mucosa to block the progress of CAG. Conclusion This study demonstrated a positive effect of WEN on improving CAG and reverse intestinal metaplasia. These functions were related to the suppression of gastric mucosal cells' apoptosis and the inhibition of Hedgehog pathways’ activation.
研究领域:
药理学
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胃肠病学
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中医
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL PARASITOLOGY
·
2023
·
IF 2.1
Muhammad Ehsan,Rui-Si Hu,Meng Wang,Jun-Ling Hou,Muhammad Rashid,Muhammad Irfan Malik
Legumains belonging to C_13 peptidase family of proteins, and are ubiquitously disseminated among all vertebrate and invertebrate organisms, and have been implicated in innumerable biological and cellular functionality. Herein, we characterized and evaluated immunoregulatory characteristics of Legumain-1 from Fasciola gigantica (Fg-LGMN-1) during its interaction with host immune cells . The isopropyl-ß-d-thiogalactopyranoside (IPTG) stimulated RFg-LGMN-1 protein was positively detected by rat serum containing anti-RFg-LGMN-1 polyclonal antibodies . Furthermore, the uptake of RFg-LGMN-1 by goat monocytes was successfully confirmed using Immunofluorescence Assay (IFA). The immunohistochemical analysis revealed the native localization of LGMN-1 protein on the periphery and internal structures such as suckers, pharynx, and genital pore of the adult parasite, thereby validating its presence in excretory-secretory (ES) products of F. gigantica . The RFg-LGMN-1 co-incubated with concanavalin-A (Con-A) stimulated the increase of interleukin 2 (IL-2), IL-10, and IL-17 in monocytes derived from peripheral blood mononuclear cells (PBMCs) in the concentration-dependent manner. However, the IL-4 cytokine in response to the RFg-LGMN-1 protein declined. These results illuminated the role of LGMN-1 during the parasite-host interface. Our findings elaborated additional evidence that Legumain protein play a role in the manipulating host immune responses during parasite infections. However, further evaluation of RFg-LGMN-1 protein in context of its immunomodulatory roles should be conducted to enhance our understandings of the mechanisms employed by F. gigantica to evade host immune responses.
研究领域:
免疫学
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寄生虫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Fang Shi,Yong-Sheng Gao,Shu-Mei Han,Huan Shi,Qing-Sheng Hou,Yang Gao,Xiao-Wen Wen,Zhen-Yu Zhu,Kai Liu,Wei-Peng Gong,Ben-Shi Wang,Xin Liu,Lei Zou
There is a growing amount of research that highlights the significant connection between the development of colitis and both metabolic imbalance and the inflammatory response. Tagatose, an inherent sweetening agent and alternative to sugar, plays a crucial role in the biosynthesis of several chemicals and metabolic pathways in living organisms. However, the specific biochemical mechanism via which tagatose hinders colitis is still not understood. According to recent study, tagatose plays a crucial role in safeguarding the integrity of tight junctions inside the intestinal mucosal barrier. Furthermore, it is crucial to acknowledge the presence of a correlation between the severity of inflammatory bowel disease (IBD) and the occurrence of colorectal cancer (CRC), chemically-induced colitis in rodents, and reduced blood levels of tagatose. The treatment of tagatose resulted in a decrease in intestinal mucosal injury in mice with colitis, regardless of whether it was caused by dextran sodium sulfate (DSS) or spontaneous colitis in IL-10 -/- mice and C3H/HeJBir mice. The introduction of tagatose in a colitis model triggers a cascade of events, wherein it hinders the expulsion of cathepsin B and enhances lysosomal cohesiveness. The aforementioned method successfully inhibits the activity of myosin light chain kinase (MLCK) in the context of intestinal epithelial damage, hence impeding the deterioration of tight junction integrity and the initiation of mitochondrial dysfunction. In summary, the outcomes of the study have provided empirical evidence that substantiates the beneficial effects of tagatose in mitigating the progression of colitis. The ability to prevent the disruption of the intestinal barrier is responsible for this achievement. Hence, tagatose has promise as a therapeutic adjunct for the management of colitis.
研究领域:
胃肠病学
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药理学
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免疫学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BMC Pharmacology & Toxicology
·
2024
·Vol. 25
·期 1
·1-12
·
IF 2.8
Tian Chunyan,Liu Qi,Zhang Xiaoyu,Li Zhuying
Background Calycosin, a flavonoid compound extracted from Astragalus membranaceus , has shown anti-asthma benefits in house dust mite-induced asthma. Recent studies have suggested that innate-type cells, including group 2 innate lymphoid cells (ILC2s) and macrophages, serve as incentives for type 2 immunity and targets for drug development in asthma. This work focuses on the effects of calycosin on the dysregulated ILC2s and macrophages in allergic asthma. Methods In vivo, the asthmatic mouse model was established with ovalbumin (OVA) sensitization and challenge, and calycosin was intraperitoneally administered at doses of 20 and 40 mg/kg. In vivo, mouse primary ILC2s were stimulated with interleukin (IL)-33 and mouse RAW264.7 macrophages were stimulated with IL-4 and IL-13 to establish the cell models. Cells were treated with calycosin at doses of 5 and 10 µM. Results In vivo, we observed significantly reduced numbers of eosinophils, neutrophils, monocyte macrophages and lymphocytes in the bronchoalveolar lavage fluid (BALF) of OVA-exposed mice with 40 mg/kg calycosin. Histopathological assessment showed that calycosin inhibited the airway inflammation and remodeling caused by OVA. Calycosin markedly decreased the up-regulated IL-4, IL-5, IL-13, IL-33, and suppression tumorigenicity 2 (ST2) induced by OVA in BALF and/or lung tissues of asthmatic mice. Calycosin repressed the augment of arginase 1 (ARG1), IL-10, chitinase-like 3 (YM1) and mannose receptor C-type 1 (MRC1) levels in the lung tissues of asthmatic mice. In vivo, calycosin inhibited the IL-33-induced activation as well as the increase of IL-4, IL-5, IL-13 and ST2 in ILC2s. Calycosin also repressed the increase of ARG1, IL-10, YM1 and MRC1 induced by IL-4 and IL-13 in RAW264.7 macrophages. In addition, we found that these changes were more significant in 40 mg/kg calycosin treatment than 20 mg/kg calycosin. Conclusions Collectively, this study showed that calycosin might attenuate OVA-induced airway inflammation and remodeling in asthmatic mice via preventing ILC2 activation and macrophage M2 polarization. Our study might contribute to further study of asthmatic therapy.
研究领域:
免疫学
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药理学
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呼吸病学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 42
·期 6
·987-997
·
IF 5.064
Liu Qiu-yan,Zhuang Yu,Song Xian-rui,Niu Qun,Sun Qiu-shuang,Li Xiao-nan,Li Ning,Liu Bao-lin,Huang Fang,Qiu Zhi-xia
Metabolic reprogramming is associated with NLRP3 inflammasome activation in activated macrophages, contributing to inflammatory responses. Tanshinone IIA (Tan-IIA) is a major constituent from Salvia miltiorrhiza Bunge, which exhibits anti-inflammatory activity. In this study, we investigated the effects of Tan-IIA on inflammation in macrophages in focus on its regulation of metabolism and redox state. In lipopolysaccharides (LPS)-stimulated mouse bone marrow-derived macrophages (BMDMs), Tan-IIA (10 μM) significantly decreased succinate-boosted IL-1β and IL-6 production, accompanied by upregulation of IL-1RA and IL-10 release via inhibiting succinate dehydrogenase (SDH). Tan-IIA concentration dependently inhibited SDH activity with an estimated IC 50 of 4.47 μM in LPS-activated BMDMs. Tan-IIA decreased succinate accumulation, suppressed mitochondrial reactive oxygen species production, thus preventing hypoxia-inducible factor-1α (HIF-1α) induction. Consequently, Tan-IIA reduced glycolysis and protected the activity of Sirtuin2 (Sirt2), an NAD + -dependent protein deacetylase, by raising the ratio of NAD + /NADH in activated macrophages. The acetylation of α-tubulin was required for the assembly of NLRP3 inflammasome; Tan-IIA increased the binding of Sirt2 to α-tubulin, and thus reduced the acetylation of α-tubulin, thus impairing this process. Sirt2 knockdown or application of Sirt2 inhibitor AGK-2 (10 μM) neutralized the effects of Tan-IIA, suggesting that Tan-IIA inactivated NLRP3 inflammasome in a manner dependent on Sirt2 regulation. The anti-inflammatory effects of Tan-IIA were observed in mice subjected to LPS challenge: pre-administration of Tan-IIA (20 mg/kg, ip) significantly attenuated LPS-induced acute inflammatory responses, characterized by elevated IL-1β but reduced IL-10 levels in serum. The peritoneal macrophages isolated from the mice displayed similar metabolic regulation. In conclusion, Tan-IIA reduces HIF-1α induction via SDH inactivation, and preserves Sirt2 activity via downregulation of glycolysis, contributing to suppression of NLRP3 inflammasome activation. This study provides a new insight into the anti-inflammatory action of Tan-IIA from the respect of metabolic and redox regulation.
研究领域:
免疫学
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药理学
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细胞代谢
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炎症
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氧化还原生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2020
·
IF 4.123
Ali Md Kaisar,Zhen Gong,Nzungize Lambert,Stojkoska Andrea,Duan Xiangke,Li Chunyan,Duan Wei,Xu Junqi,Xie Jianping
The Mycobacterium (M.) tuberculosis comprising proline–glutamic acid (PE) subfamily proteins associate with virulence, pathogenesis, and host-immune modulations. While the functions of most of this family members are not yet explored. Here, we explore the functions of “PE only” subfamily member PE31 (Rv3477) in virulence and host-pathogen interactions. We have expressed the M. tuberculosis PE31 in non-pathogenic Mycobacterium smegmatis strain (Ms_PE31) and demonstrated that PE31 significantly altered the cell facet features including colony morphology and biofilm formation. PE31 expressing M. smegmatis showed more resistant to the low pH, diamide, H2O2 and surface stress. Moreover, Ms_PE31 showed higher intracellular survival in macrophage THP-1 cells. Ms_PE31 significantly down-regulated the production of IL-12p40 and IL-6, while up-regulates the production of IL-10 in macrophages. Ms_PE31 also induced the expression of guanylate-binding protein-1 (GBP-1) in macrophages. Further analysis demonstrates that Ms_PE31 inhibits the caspase-3 activation and reduces the macrophages apoptosis. Besides, the NF-κB signaling pathway involves the interplay between Ms_PE31 and macrophages. Collectively, our finding identified that PE31 act as a functionally relevant virulence factor of M. tuberculosis.
研究领域:
微生物学
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免疫学
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病原学
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宿主-病原体相互作用
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2022
·Vol. 87
·期 7
·3223-3234
·
IF 3.693
Youxian Zhou,Yue Gong,Zhengqi Liu,Lilong Wang,Chunqing Ai,Chengrong Wen,Taihai Zhu,Shuang Song
Although numerous polysaccharides have demonstrated potential immunostimulatory activities in in vitro models, only a few of them successfully stimulate the immune system in vivo. In order to explore the possible reasons for the activity loss of polysaccharides in in vivo models, the immunostimulatory activities in vitro and in vivo and the digestion behavior of a polysaccharide from Cyclina sinensis (CSP) were investigated in the present study. CSP showed obvious immunostimulatory activity in a RAW 264.7 cell model. In in vitro experiment, CSP did not exhibit cytotoxicity at concentrations of ≤10 µg/ml, and significantly increased NO production at concentrations of 0.4–10 µg/ml, suggesting CSP processes immunostimulatory activity in vitro. Further investigation using simulated digestion model indicated that CSP could bind with the protein in the digestive fluids to form precipitate in both the stomach and small intestine, and it could be seriously degraded by amylase during the digestion in the small intestine. Furthermore, the in vivo immunostimulatory activity evaluation demonstrated CSP had no effect on immunosuppressed mice as indicated by the body weight, thymus and spleen indexes, and TNF-α, IL-1β, IL-6, and IL-10 mRNA expression. Thus, the present study indicates that the degradation and precipitation of CSP in the digestive tract are the possible reasons for the activity loss of CSP after digestion. Practical Application Cyclina sinensis is the common aquatic shellfish in China and plays an important role in the marine aquaculture industry. Cyclina sinensis polysaccharide (CSP) is the main active component of C. sinensis . The structure characterization and immunostimulatory activity of a purified fraction of CSP (CSP-1) and the effect of digestion on CSP and its immunostimulatory activity were studied. The result of this study promotes the understanding of the nutritional function effects and provides a scientific reference for the rational development and high-value utilization of C. sinensis .
研究领域:
免疫学
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营养科学
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海洋生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Waimei Si,Xin Li,Bei Jing,Shiquan Chang,Yachun Zheng,Zhenni Chen,Guoping Zhao,Di Zhang
(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme-linked immunosorbent assay, hematoxylin-esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT-PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL-1β and IL-8 levels and increased serum IL-4 and TGF-β levels in CCI rats. Stigmasterol reduced IL-1β, COX-2, and TLR4 expression in the right sciatic nerve and IL-1β expression in the spinal cord. Stigmasterol reduced the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, COX-2, IL-1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL-10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)-induced microglia and decreased the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, iNOS, COX-2, and IL-1β in LPS-treated microglia while increasing the expression of Arg-1 and IL-10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate NP.
研究领域:
药理学
·
神经科学
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免疫学
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疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Jingang Liu,He Ren,Chen Zhang,Jiexin Li,Qian Qiu,Nan Zhang,Ning Jiang,Jonathan F. Lovell,Yumiao Zhang
The use of orally-administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal-IL10-EVs (C/A) that protects interleukin 10 (IL-10) from degradation in the stomach and enables targeted delivery of IL-10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL-10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL-10 delivery to inflammatory macrophages. Chitosan/alginate (C/A) hydrogel coating on Gal-IL10-EVs enables protection from harsh conditions in the gastrointestinal tract and favorable delivery to the colonic lumen, where the C/A hydrogel coating is removed at the diseased sites. Gal-IL10-EVs control the production of reactive oxygen species (ROS) and inhibit the expression of proinflammatory cytokines. In a murine model of colitis, Gal-IL10-EVs (C/A) alleviate IBD symptoms including inflammatory responses and disrupt colonic barriers. Taken together, Gal-IL10-EVs (C/A) features biocompatibility, pH-responsive drug release, and macrophage-targeting as a therapeutic platform for oral delivery of bioactive proteins for treating intestinal diseases.
研究领域:
药学
·
生物技术
·
胃肠病学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2023
·
IF 4.5
Xinyu Wu,Yeyun Ma,Xueqing Li,Nana He,Tianmeng Zhang,Feixue Liu,Huimiao Feng,Jingquan Dong
Indiscriminate use of pesticides not only leads to environmental pollution problems, but also causes poisoning of non-target organisms. Abamectin (ABM), a widely used insecticide worldwide, is of wide concern due to its persistence in the environment and its high toxicity to fish. The kidney, as a key organ for detoxification, is more susceptible to the effects of ABM. Unfortunately, few studies investigated the mechanisms behind this connection. In this study, carp was used as an indicator organism for toxicological studies to investigate renal damage caused by ABM residues in carp. In this work, carp were exposed to ABM (0, 3.005, and 12.02 μg/L) for 4 d and the nephrotoxicity was assessed. Histopathological findings revealed that ABM exposure induced kidney damage in carp, as well as an increase Creatinine and BUN levels. Meanwhile, ABM as a reactive oxygen species (ROS) stimulator, boosted ROS bursts and lowered antioxidant enzyme activity while activating the body's antioxidant system, the Nrf2-Keap1 signaling pathway. The accumulation of ROS can also lead to the imbalance of the body's oxidation system, leading to oxidative stress. At the same time, NF-κB signaling pathway associated with inflammation was activated, which regulated expression levels of inflammatory cytokines ( TNF-α , IL-6 , IL-1β , and iNOS increased, while IL-10 and TGF-β1 decreased). In addition, ABM exposure caused structural damage to kidney mitochondria of carp, resulting in decreased mitochondrial membrane potential and ATP production capacity, and mediated apoptosis through endogenous pathways Bax/Bcl-2/Caspase-9/Caspase-3. In conclusion, ABM caused kidney damage in carp by inducing oxidative stress, inflammation, and apoptosis through mitochondrial pathway. These findings will be useful for future research into molecular mechanisms of ABM-induced nephrotoxicity in aquatic organisms.
研究领域:
毒理学
·
环境科学
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水生生物学
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分子生物学
✓ 已验证
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）