Tissue Barriers
·
2024
·
IF 3.6
Qi Cao,Wei Zeng,Jingmin Nie,Yongjun Ye,Yanchao Chen
Impairment of the blood – brain barrier (BBB) and subsequent inflammatory responses contribute to the development of human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND). Apelin-13, the most abundant member of the apelin family, acts as the ligand of the angiotensin receptor-like 1 (APJ). However, its pharmacological function in HAND and its underlying mechanism are unknown. In the current study, we report that the presence of HIV-1 Tat reduced the levels of Apelin-13 and APJ in the cortex tissue of mice. Importantly, Apelin-13 preserved BBB integrity against HIV-1 Tat in mice by increasing the expression of the tight junction protein zonula occludens-1 (ZO-1) and occludin. Interestingly, increased macrophage infiltration, indicated by elevated CD68-positive staining was observed in the cortex after stimulation with HIV-1, which was mitigated by the administration of Apelin-13. Correspondingly, Apelin-13 reduced the expression of monocyte chemoattractant protein-1; (MCP-1). An in vitro two-chamber and two-cell trans-well assay demonstrated that HIV-1 Tat challenge significantly promoted macrophage migration, which was notably attenuated by the introduction of Apelin-13. Accordingly, treatment with Apelin-13 restored the HIV-1 Tat-induced reduction of occludin and ZO-1, while preventing the upregulation of MCP-1 in human brain microvascular endothelial cells (HBMVECs). Our results suggest that Apelin-13 may reduce macrophage infiltration into brain tissues and mitigate BBB dysfunction in patients with HAND.
研究领域:
神经科学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Benyue Sun,Yunhui Wang,Jingjing Bai,Xuejiao Li,Long Ma,Shuli Man
Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC’s effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.
研究领域:
免疫学
·
胃肠病学
·
微生物学
·
药理学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2022
·
IF 3.471
Wang Zixi,Tang Yanfang,Long Lina,Zhang Huihua
In order to reduce the negative effects caused by oxidative stress on broilers, it is particularly important to find ways to alleviate oxidative stress. As a natural plant extract, L-theanine has a variety of biological effects, such as improving antioxidant capacity, promoting growth, and enhancing immunity and antitumor. This trial evaluated the effects of dietary supplementation of L-theanine on growth performance, antioxidation, meat quality, and intestinal microflora in 817 White Feather Broilers. A total of 108 21-day-old 817 broilers with similar body weight (BW) were randomly divided into three groups with six replicates per group and six chickens within each replicate. The three groups were corn-soybean-based diet (NC group); basal diet plus drinking water with 30 mg hydrocortisone/kg (PC group); and basal diet supplemented with 400 mg L-theanine/kg plus drinking water with 30 mg hydrocortisone/kg (LT group). Compared with the NC group, from 21 to 24 days of age, the PC and LT groups had decreased BW, average daily gain (ADG), and average daily feed intake (ADFI), and increased feed to gain ratio (F/G; p < 0.05). At 24 days of age, the LT group had improved superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum as compared to the NC group (p < 0.05). The LT group broilers also had significantly higher concentrations of malondialdehyde (MDA) in serum and liver (p < 0.05). On the 42nd days, the PC group had lower PH45min (p < 0.05) than the NC and LT groups and higher cooking loss and shear force (p < 0.05). Moreover, the villi height of the PC group was significantly lower in jejunum than the NC group (p < 0.05). The LT group had a higher ZO-1 content in duodenum than the NC and PC groups (p < 0.05). The activity of GSH-Px in the liver of the LT group was increased than in the PC group (p < 0.05). The relative abundance of Firmicutes in the LT group was significantly higher than in the NC and PC groups (p < 0.05). These results suggested that the effects of acute oxidative stress on growth performance and meat quality of broilers are continuous, and dietary supplementation of L-theanine could improve the growth performance and meat quality, enhance the intestinal mucosal barrier and antioxidant capacity, and improve the composition of the intestinal flora of broilers caused by acute oxidative stress.
研究领域:
家禽科学
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营养学
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动物生理学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RESPIRATORY RESEARCH
·
2022
·Vol. 23
·期 1
·1-12
·
IF 7.162
Huan Zhirong,Tang Ying,Xu Ce,Cai Jimin,Yao Hao,Wang Yan,Bu Fanyu,Ge Xin
Background Hemorrhage shock (HS) is characterized by decreased tissue oxygenation and organ damage due to severe blood loss. Protein tyrosine phosphatase receptor type O (PTPRO) is abnormally up-regulated in the rat lungs after trauma/HS.Methods To elucidate the regulatory mechanism of PTPRO in lung inflammation following HS, we established a rat model of HS via withdrawing blood by a catheter inserted into the femoral artery followed by resuscitation. The rats were infected with lentivirus harboring short hairpin RNA (shRNA) targeting PTPRO by intratracheal instillation.Results PTPRO was significantly up-regulated in rat lungs after HS. PTPRO knockdown enhanced epithelial integrity and reduced capillary leakage by up-regulating tight junction proteins zonula occludens-1 (ZO-1) and occludin (OCC) in the lungs. Besides, HS-induced myeloperoxidase activity and inflammatory cell infiltration was mitigated by PTPRO knockdown. The expression of inflammatory cytokines/chemokines (TNF-α, IL-6, MIP-2, MCP-1, and KC) in the lungs and bronchoalveolar lavage fluid was regressed after PTPRO knockdown. The nuclear factor kappa B (NF-κB) pathway was involved in HS-induced lung inflammation. PTPRO down-regulation inhibited the NF-κB pathway activation by suppressing the phosphorylation of NF-κB and its translocation from the cytoplasm into the nucleus in HS.Conclusion Taken together, we demonstrated that PTPRO knockdown may contribute to attenuating inflammation in HS-induced lung injury via inhibiting NF-κB pathway activation.
研究领域:
免疫学
·
分子生物学
·
病理生理学
·
肺医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2022
·
IF 8.022
Menglin Chen,Hong Yao,Huizi Tan,Wenqi Huang,Quanyong Wu,Shaoping Nie
Most scientific investigations regarding inflammatory bowel disease (IBD) pathogenesis or therapeutic strategies use dextran sulfate sodium (DSS)-induced models performed on mice. However, differences between human and animal microbiota may confound the data reproducibility from rodent experiments to clinical trials. In this study, the intervention effects of Bifidobacterium longum NSP001 on DSS-induced colitis were investigated using mice colonized with either native or humanised microbiota. Disorders in disease activity index (DAI), morphology and histology of colon tissue, intestinal permeability, and secretion of MPO, TNF-α and IL-6 were ameliorated by daily intake of live B. longum NSP001 cells in both conventional and humanised colitis mice. But the abnormal thymus index, and colonic production of ZO-1 and iNOS were improved only in colitis mice treated with B. longum NSP001 and humanised microbiome. The accumulation of acetic acid and propionic acid in colon microbiome, and the optimization of primary bile acid biosynthesis and glycerophospholipid metabolism pathways in cecum commensals were likely to explain the beneficial effects of B. longum NSP001. These data revealed that intestinal microbiome baseline would possibly affect the manifestation features of interventions by probiotics or dietary components and highlighted the necessity to include humanised microbiome while investigating potential therapeutic strategies based on rodent models.
研究领域:
炎症性肠病
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微生物组
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益生菌
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治疗策略
·
动物模型
·
人源化模型
✓ 已验证
产品关联
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Qiwen Feng,Yumeng Liu,Liping Zou,Mengying Lei,Changhong Zhu,Wei Xia
Fluorene-9-bisphenol (BHPF) is an emerging global endocrine-disrupting chemical found in numerous household products as a substitute of bisphenol A. Many studies have reported various toxicities associated with BHPF. However, the effect of BHPF on male reproduction, particularly on the structural integrity of the blood testis barrier (BTB) in mice, has not yet been extensively studied. Ferroptosis , a newly identified form of cell death, occurs in the testicular tissue following exposure to BPA, affecting male fertility. We investigated whether ferroptosis plays a role in BHPF-induced testicular damage. The findings indicated that BHPF exposure led decreases in serum testosterone (T) concentration and sperm concentration and motility in mice. Furthermore, BHPF disrupted the BTB by interfering with key BTB-related proteins, including Cx43, β-catenin, and ZO-1. Moreover, BHPF induced ferroptosis through the induction of lipid peroxidation, iron overload, oxidative stress , and mitochondrial dysfunction in the testicular tissue. Inhibition of ferroptosis using Fer-1 mitigated the BHPF-induced damage to the BTB and ferroptosis in TM4 cells. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting ferroptosis as a mechanism underlying testicular damage.
研究领域:
毒理学
·
生殖生物学
·
内分泌学
✓ 已验证
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2020
·
IF 1.918
Feng Liu,Xuesong Zhang,Yong Ji
Background Intestinal epithelial barrier dysfunction is involved in the development and pathogenesis of intestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, and celiac disease. This study was performed to evaluate the ability of total flavonoid extract from hawthorn (TFH) to improve TNF-α-evoked intestinal epithelial barrier deficit. Material/Methods Caco-2 cells monolayers were exposed to TNF-α in different concentrations of TFH. Intestinal epithelial barrier function was evaluated using epithelial permeability and transepithelial electrical resistance (TER). Results Our findings showed that TFH alleviated the increase of paracellular permeability and the decline of transepithelial electrical resistance (TER) evoked by TNF-α. Additionally, 24-h pre-incubation with TFH inhibited TNF-α-evoked secretion of pro-inflammatory factors (IL-6, IL-8, MCP-1, and IL-1β). Furthermore, TFH inhibited TNF-α-evoked overexpression of pMLC and MLCK and alleviated breakdown of TJs protein (ZO-1 and occludin). The activations of Elk-1 and NFκBp65 were inhibited by TFH pre-incubation. Conclusions TFH can alleviate TNF-α-evoked intestinal epithelial barrier deficit via the NFκBp65-mediated MLCK-MLC signaling pathway.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Huanhuan Liu,Jiahui Li,Chunhong Yan,Jiaxiu Liu,Dongyun Zhao,Shugang Li,Xiaodong Xia
Inflammatory bowel disease is characterized by compromised epithelium barrier function and hyperactive intestinal inflammation. This study aims to investigate the effects of punicalagin, a bioactive ellagitannin in pomegranate, on dextran-sodium sulfate (DSS) - induced colitis in mice and to examine the underlying mechanisms involved. Oral administration of punicalagin (100 mg/kg/day) effectively mitigated the severity of experimental colitis in mice, evidenced by increased colon length, improved intestinal permeability, and decreased histological scores. Punicalagin up-regulated the mRNA expression level of Muc2 in and the protein expression of zonula occludens-1 (ZO-1) and Occludin in colitic mice. Moreover, punicalagin effectively decreased reactive oxygen species (ROS) levels in the colon, and in Caco-2 cells exposed to H 2 O 2 in vitro . Mechanistically, punicalagin attenuated inflammation by inhibiting the secretion of interleukin-6 (IL-6) and the phosphorylation of the NF-κB/STAT3 pathway. In addition, punicalagin increased adenosine monophosphate activated protein kinase (AMPK) phosphorylation in the colon of DSS-treated mice and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages. Knocking down AMPKα by siRNA diminished punicalagin's anti-inflammatory function in RAW 264.7 macrophages exposed to LPS. Furthermore , molecular docking analysis, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) analysis supported the direct interaction between punicalagin and AMPK. In conclusion, punicalagin could mitigate DSS-induced colitis through enhancing intestinal epithelial barrier, alleviating oxidative stress, and attenuating inflammation partly through modulation of AMPK–NF–κB-STAT3 pathway.
研究领域:
药理学
·
免疫学
·
胃肠病学
✓ 已验证
DOI
高影响因子
Food & Function
·
2018
·Vol. 10
·期 1
·277-288
·
IF 3.289
Wanxiu Cao,Chengcheng Wang,Yaoxian Chin,Xin Chen,Yuan Gao,Shihan Yuan,Changhu Xue,Yuming Wang,Qingjuan Tang
Stress exposure can increase the appearance of intestinal dysfunction. DHA and EPA have been shown to possess significant anti-inflammatory and immuno-enhancement bioactivities. The aim of the study was to investigate whether different forms of DHA or EPA would affect intestinal barriers (including intestinal epithelium integrity and immunity responses, gut microbiota and its metabolites) in mice under chronic stress, and might therefore prevent stress induced intestinal dysfunction. Chronic stress caused a series of anomalies in the intestine, including decreased faecal water content, increased pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β and IL-6), reduced expression levels of ZO-1, occludin and E-cadherin, and aberrant microbiota composition (especially Roseburia spp., Prevotella spp., bifidobacteria and lactobacilli) and its metabolites, mainly LPS, acetic acid, propionic acid and butyric acid. Our data indicated that both DHA-PL and EPA-PL counteracted these adverse effects effectively. In conclusion, DHA-PL and EPA-PL may effectively protect mice against intestinal dysfunction under chronic stress exposure as potential ingredients for functional food.
研究领域:
营养学
·
免疫学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Yeye Hu,Xueting Guan,Ziliang He,Yuan Xie,Zhiqiang Niu,Wei Zhang,Aoran Wang,Ji Zhang,Chuanling Si,Fu Li,Weicheng Hu
Apigenin-7-O-glucoside (AG), a flavonoid glycoside, has been shown in vitro anti-inflammatory activities. To date, the mechanism of AG against colitis has not been reported. In this study, we investigated the role of AG in relieving colitis and explored its potential mechanisms in dextran sulfate sodium (DSS)-induced colitis mice. The results indicated oral administration of AG increased colon length and improved colonic histopathology. Besides, it dramatically restored the colonic expression of pro-inflammatory and anti-inflammatory mediators, as well as enhanced the expression of intestinal barrier markers such as ZO-1, occludin, claudin-1, and claudin-3. The mitogen-activated protein kinases (MAPKs) including ERK, JNK, and p38 were significantly inhibited. Moreover, 16S rDNA sequencing revealed that AG improved the abundance of Akkermansia , and reduced that of Bacteroides and Desulfovibrio . Taken together, AG supplementation relieved DSS-induced colitis by protecting the intestinal barrier, inhibiting the MAPK pathway, and modulating gut microbiota, which indicated that AG may be a good candidate therapeutic compound for sustaining gut health to lower the risk of colitis.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Sijia Wu,Ping Jiang,Xiaoliang Zhang,Chen Mao,Yaxi Dai,Hong Zhuang,Yong Pang
Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10–7 and (6.63 ± 2.31) × 10–7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.
研究领域:
药理学
·
生物物理学
·
细胞生物学
·
膜科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2024
·
IF 2.6
Zhou Miao,Wu Zichen,Deng Donghua,Wang Bin,Zhou Xiaoling,Zhou Bingyu,Wang Chunping,Zeng Yan
Oxidative damage resulting from weaning stress significantly impacts the growth performance and health status of piglets. Taurine, a dietary antioxidant with diverse functions, was investigated in this study for its protective role against weaning stress-induced oxidative damage and its underlying mechanism. Forty 28-day-old male castrated weaned piglets were randomly assigned to four groups. The control group received the basal diet, while the experimental groups were fed the basal diet supplemented with 0.1, 0.2%, or 0.3% taurine over a 28-day period. In vitro, H2O2 was utilized to induce oxidative damage to the jejunal mucosa of piglets via IPEC-J2 cells. The results demonstrated that taurine supplementation reduced the incidence of diarrhea in piglets compared to that in the control group (p < 0.05); the addition of 0.2 and 0.3% taurine led to increased average daily gain and improved feed conversion efficiency in weaned piglets, showing a linear dose-response correlation (p < 0.05). Taurine supplementation at 0.2 and 0.3% enhanced the activities of serum CAT and GSH-Px while decreasing the levels of serum NO, XOD, GSSG, and MDA (p < 0.05). Moreover, it significantly elevated the levels of GSS, Trx, POD, complex I, mt-nd5, and mt-nd6, enhancing superoxide anion scavenging capacity and the hydroxyl-free scavenging rate in the livers of weaned piglets while reducing NO levels in the liver (p < 0.05). Additionally, 0.2 and 0.3% taurine supplementation decreased serum IL-6 levels and elevated the concentrations of IgA, IgG, and IL-10 in weaned piglets (p < 0.05). The levels of occludin, claudin, and ZO-1 in the jejunum mucosa of weaned piglets increased with 0.2 and 0.3% taurine supplementation (p < 0.05). In IPEC-J2 cells, pretreatment with 25 mM taurine for 24 h enhanced the activities of SOD and CAT; reduced the MDA content; upregulated the mRNA expression of various genes, including ZO-1, occludin, claudin-1, Nrf2, and HO-1; and reversed the oxidative damage induced by H2O2 exposure (p < 0.05). Overall, the findings suggest that the inclusion of 2 and 3% taurine in the diet can enhance growth performance, reduce diarrhea rates, ameliorate oxidative stress and inflammation, and promote intestinal barrier function in weaned piglets.
研究领域:
动物科学
·
营养学
·
生理学
·
兽医学
✓ 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）