Microbial Biotechnology
·
2025
·Vol. 18
·期 11
·e70257
·
IF 5.2
Hui Chen,Fengjiao Wang,Shengjie Li,Longxian Lv,Hao Xu,Jiafeng Xia,Lvwan Xu,Ding Shi,Lanjuan Li
Pediococcus pentosaceus Li05, a strain of lactic acid bacteria isolated from the faeces of healthy volunteers, exhibited potential protective effects against various diseases. This study performed third-generation sequencing and detailed characterisation of its genome. The Li05 chromosome harboured conserved genes associated with acid resistance ( atp ), bile salt resistance ( bsh ), oxidative stress resistance ( hsl , dltA , and et al.), and adhesion ( nrd , gap , and et al.), whereas the plasmid did not contain antibiotic resistance or virulence genes. Following intervention with Li05 in loperamide-induced constipated mice, constipation symptoms improved. Meanwhile, alterations in gut microbiota, increased BSH activity in faeces, and modifications to the faecal bile acid profile were observed. Additionally, expression levels of TGR5 and TPH1 in the colon of the mice increased, leading to elevated 5-HT levels. When the TGR5 gene was knocked out or the TPH1 inhibitor LX1606 was administered to suppress 5-HT synthesis in constipated mice, the beneficial effects of Li05 on gastrointestinal motility and mucus secretion were reversed. Culturing intestinal organoids demonstrated that increased bile acids such as DCA, Iso-LCA, and EALCA could enhance 5-HT levels through the TGR5/TPH1 axis. Therefore, we concluded that Li05 regulated bile acid metabolism, subsequently increasing 5-HT levels through the TGR5/TPH1 axis, thus alleviating constipation. Graphical The mechanism of Li05 in alleviating constipation. Li05 intervention regulated gut microbiota and bile acid metabolism, increasing 5-HT levels through the TGR5/TPH1 activation to ameliorate constipation.
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PubMed
高影响因子
POLYMER
·
2016
·
IF 3.586
Sheng Zhou,Mengyao Zhang,Rong Wang,Jing Ping,Xiaoli Zhang,Ning Zhao,Jian Xu,Zhihao Shen,Xinghe Fan
Two monomers o -( m -triphenyl)-terephthaloyl chloride (TPH1-COCl) and m -( m -triphenyl)- isophthaloyl chloride (TPH2-COCl) with bulky pendant groups were prepared, and they were polymerized with p -phenylenediamine (PPD) or copolymerized with PPD and terephthaloyl chloride (TPC) to prepare aromatic polyamides which were named TPH1 polymer and TPH2 polymer, respectively. The structures of the monomers with bulky pendant groups and the polymers were characterized by 1 H NMR and gel permeation chromatography . The resulting polymers are soluble in some organic solvents such as N -methyl-2-pyrrolidone. However, the solubility of the two series of polymers was different due to the different structures of the two monomers, and it is affected by the feeding ratio of the monomers. Both kinds of polymers have good thermal stabilities with 5% weight loss temperatures close to 500 °C. And glass transitions of some TPH2 polymers were observed. Most of these polyamides show lyotropic liquid crystalline (LLC) behaviors as evidenced by polarized light microscopy results. And the LLC properties are influenced by the structures, molecular weights , and concentrations of the polymers.
研究领域:
材料科学
·
高分子化学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 5
·2119
·
IF 4.9
Chengwei Wang,Chunjie Wu,Linjiang Song
Saiga antelope horn (SAH), a rare traditional Chinese medicine, exhibits activities of anti-feverish convulsions and anti-inflammation, whereas its underlying mechanism and specific pharmacological components are still unclear. In the present study, transient receptor potential ankyrin 1 (TRPA1), a major transient receptor potential cation channel was used as a target protein to identified TRPA1 high-affinity peptides (THPs) from SAH digests. Firstly, the SAH was digested under in vitro gastrointestinal conditions. With the method of affinity ultrafiltration and liquid chromatography–mass spectrometry (AUF-LC/MS), about 200 peptides that have a high-affinity interaction with the TRPA1 protein were screened from SAH digests. Subsequently, bioactivity databases and molecular docking were further exploited to identified three THPs, including RCWPDCR, FGFDGDF, and WFCEGSF. Furthermore, RIN-14B cells, characterized by the high expression of TRPA1 on cell surfaces, were used as the cell model to investigate the biological effect of THPs. Immunofluorescence and ELISA were conducted and showed that THPs can increase the intracellular Ca2+concentration and serotonin (5-HT) secretion in RIN-14B cells by activating TRPA1, which is evidenced by impaired upregulation of intracellular Ca2+levels and 5-HT secretion after pretreatment with the TRPA1 inhibitor (HC-030031). Moreover, an analysis of Western blots displayed that THPs up-regulated the expression levels of the 5-HT synthesis rate-limiting enzyme (TPH1) and 5-hydroxytryptophan decarboxylase (Ddc), while serotonin reuptake transporter (SERT) levels were down-regulated, suggesting that THPs enhance 5-HT secretion by regulating the 5-HT synthesis pathway. In summary, our findings demonstrate that THPs, which were identified from SAH digest via TRPA1-targeted affinity panning, exhibited the activation of the TRPA1 channel and enhanced 5-HT release in RIN-14B cells.
研究领域:
药理学
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分子生物学
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传统中药
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2026
·
IF 3.9
Li Dong,You Wu,Yangshu Zhou,Hongrong Wang,Lihuai Yu
Menthol is a widely consumed dietary monoterpene found in peppermint oil, yet its effects on intestinal health under inflammatory conditions remain poorly understood. This study investigated the protective effects of dietary menthol against lipopolysaccharide (LPS)-induced intestinal inflammation in a weaned piglet model, focusing on the enteroendocrine Piezo1/TPH1/5-HT signaling axis. Sixty 28-day-old Duroc × (Landrace × Large White) weaned piglets were randomly assigned to five groups: a non-challenged control (CON), an LPS-challenged group, and three LPS-challenged groups receiving menthol at 12.5, 25, or 50 mg/kg of diet in a 22-day trail (21-day feeding +6 h post-LPS). Supplementation with 25 mg/kg menthol of diet significantly increased average daily body weight gain (ADG) and average daily feed intake (ADFI) while reducing the incidence of diarrhea before LPS challenge ( P < 0.05). After LPS administration, menthol markedly attenuated intestinal injury, as evidenced by reduced serum lactate dehydrogenase (LDH) activity and lower levels of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in both serum and intestinal tissues ( P < 0.05). Morphologically, menthol increased villus height and the villus height to crypt depth ratio (VH/CD), decreased crypt depth ( P < 0.05), and preserved microvilli density, tight junction integrity, and nuclear morphology of the small intestine. Notably, menthol partially restored the LPS-induced loss of enteroendocrine cells and normalized gut hormone profiles, specifically reducing serotonin (5-HT) and gastrin while increasing somatostatin. Mechanistically, menthol appeared to suppress the LPS-induced upregulation of the mechanosensor Piezo1, the 5-HT-synthesizing enzyme tryptophan hydroxylase 1 (TPH1), and the 5-HT3 receptor at both the gene and protein levels ( P < 0.05). These findings suggested that dietary menthol, particularly at 25 mg/kg of diet, alleviated intestinal inflammation, potentially by preserving enteroendocrine cell homeostasis and downregulating the Piezo1/TPH1/5-HT signaling pathway. This study provides new evidence for the potential application of menthol as a functional food ingredient to support gut health.
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高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chen Dongliang,Wang Yuanfei,Yang Jianmei,Ou Wanyi,Lin Guiru,Zeng Ze,Lu Xiaomin,Chen Zumin,Zou Lili,Tian Yaling,Wu Aiping,Keating Shelley,Yang Qinhe,Lin Chenli,Liang Yinji
The prevalence of non-alcoholic fatty liver disease (NAFLD) and related mortality are increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for early prevention and treatment for NAFLD. This study examined the new mechanism of "Shenling Baizhu San" (SLBZS) in the prevention and treatment of NAFLD at the preclinical level.The male C57BL/6J mice were randomly divided into three groups: ND (normal diet), WDC (Western Diet+CCl4 injection) and WDC+SLBZS (SLBZS intervention). Body weight, energy intake, liver enzymes, pro-inflammatory factors and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A and HTR2B were tested by qRT-PCR or ELISA. Dynamic changes in gut microbiota and metabolites were further detected through 16S rRNA gene and untargeted metabolomics.
研究领域:
药理学
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胃肠病学
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微生物学
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代谢组学
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中医
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高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2021
·
IF 5.194
Jing Guan,Xin Tong,Yi Zhang,Fan Xu,Yuxin Zhang,Xiurui Liang,Jiaqi Jin,Hongyan Jing,Liuxian Guo,Xinrui Ni,Jihua Fu
As a widely used anticancer drug in the clinic, cisplatin has obvious side effects, especially nephrotoxicity . Previous studies have suggested that the accumulation of intracellular reactive oxygen species (ROS) is a hallmark of cisplatin-induced acute kidney injury . This study aimed to investigate the relationship between ROS accumulation induced by cisplatin and 5-HT degradation. In vivo, by HE and TUNEL staining, we found that cisplatin-induced renal lesions and apoptotic regions, which were located in proximal tubular epithelial cells, were also the regions in which tryptophan hydroxylase 1 (Tph1), aromatic l -amino acid decarboxylase (AADC), 5-HT 2A receptor (5-HT 2A R) and monoamine oxidase A (MAO-A) were overexpressed, as determined by immunohistochemistry. Notably, the 5-HT 2A R antagonist sarpogrelate hydrochloride (SH) and the AADC inhibitor carbidopa (CDP) significantly attenuated cisplatin-induced increases in serum creatinine and blood urea nitrogen levels, renal ROS levels, oxidative stress (SOD activity and MDA), proinflammatory cytokine levels (NF-κB, TNF-α and IL-1β), proapoptotic factor levels (Bax, Bcl-2, C-caspase 3 and C-caspase 9) and the phosphorylation of p38 and STAT3 , as well as renal lesions and apoptosis . The combination of SH and CDP could almost abolish the effects of cisplatin challenge. In vitro, the effects of cisplatin challenge and the inhibitory effects of SH and CDP were also observed in HK-2 cells. Additionally, similar to the combination of SH and CDP, the MAO-A inhibitor clorgyline could also abolish the effects of cisplatin challenge. More importantly, by western blotting , we detected that the upregulation of Tph1, AADC and MAO-A expression induced by cisplatin both in vivo and in vitro could be obviously suppressed by SH to decrease 5-HT synthesis and mitochondrial 5-HT degradation. Altogether, these findings suggested that cisplatin-induced nephrotoxicity is due to the activation of the 5-HT degradation system in proximal tubular epithelial cells, including 5-HT 2A R and 5-HT synthesis and degradation. 5-HT 2A R plays a role by mediating the expression of MAO-A and the 5-HT synthases Tph1 and AADC.
研究领域:
药理学
·
肾病学
·
肿瘤学
·
细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
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