AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
·
2025
·
IF 4.7
Qianying Shen,Yue-Yue Zhou,Yan-Lin Wang,Yao Qi,Dong-Bo Lian,Zhe-Hong Li,Meng-Fei Chen,Xiao-Li Zhang,Yue Zhang,Jin Song,Li-Fei Zheng,Jin-Xia Zhu
Long-term infection with Helicobacter pylori (H. pylori) leads to elevated serum gastrin levels, which are closely related to gastric cancer. Eradication of H. pylori to treat the high gastrin levels is increasingly challenged by antibiotic resistance. Dopamine (DA) receptor 1 (D1R) is expressed on G cells in the gastric antrum. Parietal cells produce DA, which inhibits somatostatin (SOM) release through D2R on D cells in the gastric mucosa. Whether targeted intervention in DRs can improve high gastrin levels after H. pylori infection remains to be explored. In this study, human gastric tissue, H. pylori-infected mice, D1R and D2R knockout mice, RT‒qPCR, ELISA, IHC, Western Blot, HE staining and ex vivo incubation of gastric mucosae were used. We found that H. pylori infection destroyed the mitochondria of parietal cells and reduced DA content in the gastric mucosa at 10 weeks after infection. Moreover, gastrin-positive cell numbers and serum gastrin levels were increased. D1R, but not D2R, was observed in G cells. DA promoted gastric gastrin secretion. Interestingly, both D1- and D2-like agonists mimicked the effect of DA on the gastrin secretion, which was antagonized by their antagonists. Blocking D2R with domperidone or knocking out D2R resulted in decreased gastrin-positive cell numbers and gastrin levels but increased SOM levels at 10 weeks after H. pylori infection. Our findings highlight the key regulatory effect of D2R on gastrin secretion and elucidate the role of domperidone in reducing the elevated gastrin level associated with H. pylori infection.
研究领域:
医学
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分子生物学
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消化病学
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DOI
PubMed
高影响因子
ANALYST
·
2022
·Vol. 147
·期 8
·1678-1687
·
IF 5.227
Chujun Zheng,Qixia Jiang,Kan Wang,Tangan Li,Wei Zheng,Yuemeng Cheng,Qihong Ning,Daxiang Cui
In this study, we developed a novel magnetic lateral flow assay based on iron oxide decorated with platinum probes (Fe3O4@Pt) for dual-mode detection of gastrin-17 (G-17), which is one of the main biomarkers for early gastric cancer diagnosis. The probe material exhibits both magnetic properties and peroxidase activity. The peroxidase activity enhances the intensity of the brownish coloring of the Fe3O4@Pt probes on the test strip, with a limit of detection of 10 pg mL−1 using the naked eye, which is remarkable for colorimetric lateral flow assays. The magnetic property allows the simple separation and enrichment of the sample, and the signal can be read using a magnetic assay reader for quantitative detection. The linear range for G-17 using the magnetic signal was determined as 10 pg mL−1 to 2200 pg mL−1, and the calculated limit of detection was as low as 3.365 pg mL−1, thereby covering the reference range for G-17. Serum samples were used to validate the test strip, which exhibited high sensitivity, high specificity, and consistency with the results obtained by the enzyme-linked immunosorbent assay method. The entire inspection process using this method can produce results within 35 min and it is simple to operate without requiring strict experimental conditions. This dual-mode lateral flow test strip provides a simple, rapid, and quantitative strategy for detecting G-17, and it may also be valuable in other portable diagnostic applications.
研究领域:
医学诊断
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生物化学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Qian Jiali,Li Zhennan,Wang Jinhui,Lin Yuxian,Yu Yingcong
The resistance of Helicobacter pylori (H. pylori) has increased in recent years, prompting a trend in the research and development of new drugs. In our study, three derivatives (JF-1, JF-2, and JF-3) were synthesized using 6-gingerol as the main component, while JF-4, containing both 6-gingerol and 6-shogaol as the main components, was extracted from dried ginger. The minimum inhibitory concentrations (MICs), determined using the ratio dilution method, were 80 μg/mL for JF-1, 40 μg/mL for JF-2, 30 μg/mL for JF-3, 40 μg/mL for JF-4, 60 μg/mL for 6-gingerol standard (SS), and 0.03 μg/mL for amoxicillin (AMX). After treating H. pylori-infected mice, the inflammation of the gastric mucosa was suppressed. The eradication rate of H. pylori was 16.7% of JF-3 low-dose treatment (LDT), 25.0% of JF-3 high-dose treatment (HDT), 16.7% of JF-4 LDT, 16.7% of JF-4 HDT, 30% of SS LDT, 50% of SS HDT, and 36.4% of the positive control group (PCG). The levels of gastrin, somatostatin (SST), IFN-γ, IL-4, and IL-8 were significantly recovered in the JF-3 and JF-4 administration groups, but the effect was stronger in the high-dose group. These results demonstrate that 6-gingerol and its derivatives have significant anti-Helicobacter pylori effects and are promising potential treatments for H. pylori infection.
研究领域:
药理学
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微生物学
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胃肠病学
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化学
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DOI
PubMed
高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·Vol. 27
·期 10
·1513-1522
·
IF 1.6
Zeng Yi,Zhou Li,Wan Ying,Fu Ting,Xu Paidi,Zhang Hongxing,Guan Ying
Objective: Functional dyspepsia (FD) is one of the most common gastrointestinal diseases, with a global prevalence of 10%-30%. However, the specific pathogenesis of FD has not yet been determined. As such, the aim of this study was to investigate the effects of saikosaponin D (SSD)
administration on the apoptosis, autophagy, and morphological structure of the intestinal cells of Cajal (ICCs) in FD. MethodsA rat model of FD was constructed by stimulating the rat tail with a sponge clamp at one-third of the distal tail length. An autophagy model was constructed for
ICCs using glutamate. The apoptosis rate in each group of cells was determined using flow cytometry. The expressions of ghrelin and substance P (SP) were detected using ELISA. Results: The body weight and food intake of male and female rats in the SSD group were consistently higher than
those in the model group. The SSD group showed substantial improvement compared with the model group, with no inflammatory cell infiltration and normal gastric mucosal structures. After intervention with SSD, the ultrastructure of the ICCs considerably improved and was clear. Compared with
the model group, the expressions of LC3 I/II, ghrelin, and SP proteins in the SSD group were significantly upregulated, and the apoptosis rate was significantly reduced. Conclusion: The administration of SSD improved ICC morphology and structure, inhibited excessive autophagy, and improved
FD, a gastrointestinal motility disorder, by regulating ghrelin and SP levels.
研究领域:
胃肠病学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Xintong Li,Jiale Cui,Jin Li,Yulian Wang,Guoqing Shi
Gastrin 17 (G-17) is a major biomarker for the diagnosis of gastric cancer. As the serum concentrations of gastrin are low, highly sensitive detection methods are needed. Previous studies have shown that oriented immobilization of detection antibodies can improve the sensitivity of lateral flow immunoassay (LFIA) methods. Herein, the antibody binding capacity of four Fc-specific peptides reported in different studies was evaluated, and two peptides with better binding potency were further modified with cysteine or the peptide GAC at their C-terminus. The peptide FYWHCLDEGAC exhibited the highest antibody binding capacity and was applied to directly immobilize the anti-G-17 antibody on microspheres with carboxyl-functionalized surfaces and europium-based time-resolved fluorescence. An LFIA method was developed to detect G-17 in human serum, and the limit of detection (LOD) of this method for G-17 was 0.08 pmol L -1 , which was 10 times less than that of the nonoriented immobilization method. The working range of this method is 0.27 ∼ 600 pmol L -1 , with a recovery rate of 85.2 % −106.7 % and a CV value less than 12.4 %. This method is easy to use, and the total detection process takes less than 20 min. The test results for the actual serum samples were consistent with the commercial kit results (R 2 > 0.95), demonstrating that the method can be utilized for point-of-care testing of G-17. This approach to orientedly immobilize antibodies on nanomaterials can be used to develop sensitive LFIA methods for various molecules.
研究领域:
生物医学工程
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分析化学
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癌症研究
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分子生物学
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产品关联
DOI
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 9
·2682-2693
·
IF 6.183
Yuanbiao Tu,Ji Tao,Fang Wang,Peifei Liu,Zhihao Han,Zhaolun Li,Yi Ma,Yueqing Gu
Pancreatic cancer has a high mortality rate and efforts towards diagnosis and therapy at an early stage are particularly appealing. Recently, a small peptide, BBN7–14, has attracted much attention for its specific binding ability to gastrin releasing peptide receptor (GRPR), which is highly overexpressed in various types of cancer, including pancreatic cancer. However, its poor stability in vivo restricts its direct clinical application. Herein, by rational design and transformation of BBN7–14, a novel six-amino acid peptide, GB-6, which maintains a specific GRPR-binding feature and exhibits enhanced stability in vitro and in vivo, was designed. Competitive binding with BBN7–14 and cellular uptake related to GRPR expression levels verified the specific affinity of GB-6 to GRPR. Additionally, this novel peptide was conjugated with near-infrared dye and the radionuclide 99mTc for pancreatic cancer diagnosis in cells and in vivo. Surprisingly, despite having the same cellular affinity as BBN7–14, GB-6 showed much higher pancreatic cancer-targeting ability than BBN7–14 by both fluorescence imaging and radionuclide imaging. It was proven that this strange phenomenon was attributed to the distinct in vivo stability of GB-6 and its more favorable pharmacokinetic properties and metabolic stability relative to BBN7–14. Altogether, this novel peptide GB-6, with GRPR-targeting ability and enhanced stability, is a more promising candidate for the clinical diagnosis of pancreatic cancer.
研究领域:
肿瘤学
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分子生物学
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药学
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医学影像学
✓ 已验证
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
·
中医
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产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2024
·
IF 4
Ruiqi Sun,Yuxin Wang,Wenhui Shi,Hongfu Zhang,Jianhua Liu,Weina He
Cancer which causes high mortality globally threatens public health seriously. There is an urgent need to develop tumor-specific near-infrared (NIR) imaging agents to achieve precise diagnosis and guide effective treatment. In recent years, imaging probes that respond to acidic environments such as endosomes, lysosomes, or acidic tumor microenvironments (TMEs) are being developed. However, because of their nonspecific internalization by both normal and tumor cells, resulting in a poor signal-to-noise ratio in diagnosis, these pH-sensitive probes fail to be applied to in vivo tumor imaging. To address this issue, a cholecystokinin-2 receptor (CCK2R)-targeted TME-sensitive NIR fluorescent probe R2SM was synthesized by coupling pH-sensitive heptamethine cyanine with a CCK2R ligand, minigastrin analogue 11 (MG11) for in vivo imaging, in which MG11 would target overexpressed CCK2Rs in gastrointestinal stromal tumors (GISTs). Cell uptake assay demonstrated that R2SM exhibited a high affinity for CCK2R, leading to receptor-mediated internalization and making probes finally accumulated in the lysosomes of tumor cells, which suggested in the tumor tissues, the probes were distributed in the extracellular acidic TME and intracellular lysosomes. With a pKa of 6.83, R2SM can be activated at the acidic TME (pH = 6.5–6.8) and lysosomes (pH = 4.5–5.0), exhibiting an apparent pH-dependent behavior and generating more intense fluorescence in these acidic environments. In vivo imaging showed that coupling of MG11 with a pH-sensitive NIR probe facilitated the accumulation of probe and enhanced the fluorescence in CCK2R-overexpressed HT-29 tumor cells. A high signal was observed in the tumor region within 0.5 h postinjection, indicating its potential application in intraoperative imaging. Fluorescence imaging of R2SM exhibited higher tumor-to-liver and tumor-to-kidney ratios (2.1:1 and 2.3:1, respectively), compared separately with the probes that are lipophilic, pH-insensitive, or MG11-free. In vitro and in vivo studies demonstrated that the synergistic effect of tumor targeting with pH sensitivity plays a vital role in the high signal-to-noise ratio of the NIR imaging probe. Moreover, different kinds of tumor-targeting vectors could be conjugated simultaneously with the NIR dye, which would further improve the receptor affinity and targeting efficiency.
研究领域:
医学成像
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癌症生物学
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分子生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EMBO REPORTS
·
2023
·
IF 7.7
Zhi-Jun Zhang,Han-Yu Shao,Chuan Liu,Hao-Lin Song,Xiao-Bo Wu,De-Li Cao,Meixuan Zhu,Yuan-Yuan Fu,Juan Wang,Yong-Jing Gao
A11 dopaminergic neurons regulate somatosensory transduction by projecting from the diencephalon to the spinal cord, but the function of this descending projection in itch remained elusive. Here, we report that dopaminergic projection neurons from the A11 nucleus to the spinal dorsal horn (dopaminergicA11-SDH) are activated by pruritogens. Inhibition of these neurons alleviates itch-induced scratching behaviors. Furthermore, chemogenetic inhibition of spinal dopamine receptor D1-expressing (DRD1+) neurons decreases acute or chronic itch-induced scratching. Mechanistically, spinal DRD1+ neurons are excitatory and mostly co-localize with gastrin-releasing peptide (GRP), an endogenous neuropeptide for itch. In addition, DRD1+ neurons form synapses with GRP receptor-expressing (GRPR+) neurons and activate these neurons via AMPA receptor (AMPAR). Finally, spontaneous itch and enhanced acute itch induced by activating spinal DRD1+ neurons are relieved by antagonists against AMPAR and GRPR. Thus, the descending dopaminergic pathway facilitates spinal itch transmission via activating DRD1+ neurons and releasing glutamate and GRP, which directly augments GRPR signaling. Interruption of this descending pathway may be used to treat chronic itch.
研究领域:
神经科学
·
药理学
·
疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Bingqian Yang,Kaikai Li,Meng Niu,Jianying Wei,Siming Zhao,Caihua Jia,Yan Xu
Wheat bran is an abundant yet underutilized agricultural byproduct. Herein, the insoluble dietary fiber from wheat bran (WBIDF) was ultra-milled to investigate its impact on physicochemical properties and gastrointestinal emptying. SEM and CLSM showed that the laminar structure of WBIDF was disrupted as the particle size was significantly reduced. In the similar characteristic peaks appearing at 3410, 2925, 1635, 1041, and 895 cm −1 in the FT-IR spectra and at 2940, 1593, 1080, and 526 cm −1 in the Raman spectra, the peak intensity was increased as the particle size decreased. It may be that the hydrogen bonding between cellulose, hemicellulose, or other macromolecules was enhanced. X-ray diffraction showed cellulose type I results for all five samples. Correspondingly, the water-holding, swelling, and oil-holding capacities increased by 75.33 %, 52.62 %, and 75.00 %, respectively, in WBIDF-CW 1.8 compared with WBIDF-CWy. Additionally, smaller particle sizes had lower viscosity, thereby enhancing intestinal propulsion and gastric emptying rates. Enhanced contact of the cecal tissue growth factor with the intestinal mucosa delayed ghrelin secretion and stimulated the secretion of motilin, gastrin, and cholecystokinin. In conclusion, the particle sizes of WBIDF were reduced through ultramicro-grinding, leading to altered structure, enhanced hydration and oil-holding capacities, decreased viscosity, and improved gastrointestinal emptying capacity.
研究领域:
食品科学
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营养学
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胃肠病学
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显微镜学
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光谱学
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动物生理学
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产品关联
DOI
PubMed
高影响因子
Journal of Traditional Chinese Medicine
·
2023
·Vol. 43
·期 5
·887-896
·
IF 2.6
Yiding ZHAO,Xiaoning YAN,Shanshan JIANG,Yong LIU,Chun DONG,Huiyan CHI,Chaoyi MAO
Objective To investigate the efficacy of Zhenxin Anshen formula (, ZXAS) on atopic dermatitis (AD) by transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) signalling pathway in mice and . Methods AD-like lesions were induced by 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice. BALB/c mice were divided into five groups: normal control, model control, cetirizine, low-, medium-, and high-dose of ZXAS. After ZXAS in-tervention, the skin lesions and blood samples were collected for hematoxylin and eosin-stained and measuring the concentrations of inflammatory cytokines. Immun-oglobulin E (IgE), interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP) were de-tected by Enzyme-linked immunosorbent assay (ELISA). The spinal cords were collected for measuring the expression of gastrin-releasing peptide receptor (GRPR), TRPV1, and TRPA1 by using immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In addition, 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, ELISA, and Western blotting were conducted for analysis of primary dorsal root ganglia (DRG) neurons . Results ZXAS treatment improved DNCB-induced AD-like lesions through reducing dermatitis score, number of scratching and epidermal thickness, accompanied by the de-creased IgE and Th2 inflammatory cytokines. ZXAS also supressed the mRNA and protein expression of GRPR, TRPV1, and TRPA1 in the spinal cord. The medicated sera of ZXAS decreased capsaicin-induced Ca influx and downregulated the expression of TRPV1, TRPA1, and phospholipase C in DRG neurons. Conclusions The therapeutic effect of ZXAS on AD may be related to the regulation of TRPV1 and TRPA1 and inhibition of Ca2+ signals in neurons.
研究领域:
药理学
·
免疫学
·
神经科学
·
皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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