scholarly journals Berberine Attenuates Chronic Atrophic Gastritis Induced by MNNG and Its Potential Mechanism

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuling Tong ◽  
Liping Liu ◽  
Ruilin Wang ◽  
Tao Yang ◽  
Jianxia Wen ◽  
...  

The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on MNNG-induced chronic atrophic gastritis (CAG) and the possible mechanism of BBR through TGF-β1/PI3K signal pathway. GES-1 were pretreated with MNNG for 2 h before BBR treatment in all procedures. Cell viability was quantified by cell counting kit-8, and GES-1 morphology and proliferation were detected by high content screening (HCS) assay. The rat model of CAG was established by MNNG, and the therapeutic effect of BBR on stomach histopathology and serum supernatant were analyzed in vivo. In addition, the possible mechanism of BBR was further discussed, and the expression of related genes and proteins in TGF-β1/PI3K signal pathway was detected. The results showed that BBR could significantly improve the survival rate and morphological changes of GES-1, improve the gastric tissue injury of CAG rats, and reduce the expression of G-17 and inflammatory factors IL-8, TNF-α, IL-6 and IL-1β. In addition, BBR down-regulated the expression of TGF-β1 axis-related signals such as TGF-β1, PI3K, p-Akt/Akt, p-mTOR/mTOR and P70S6K, and promoted the expression of PTEN, LC3-II and Beclin-1. In Conclusion, BBR can improve CAG which may be closely related to TGF-β1/PI3K signal pathway.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qilu Wei ◽  
Ning Kong ◽  
Xiaohui Liu ◽  
Run Tian ◽  
Ming Jiao ◽  
...  

Abstract Background Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. Methods Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. Results The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. Conclusions PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.


2009 ◽  
Vol 53 (1) ◽  
pp. 14-20
Author(s):  
L.M. Mosiychuk ◽  
L.V. Demeshkina ◽  
I.V. Kushnirenko ◽  
O.V. Simonova ◽  
O.P. Petishko ◽  
...  

2020 ◽  
Author(s):  
Shihua Wu ◽  
Chunmei Bao ◽  
Ruilin Wang ◽  
Xiaomei Zhang ◽  
Sijia Gao ◽  
...  

Abstract Background: Zuojin Pill (ZJP), a famous Chinese medicinal formula, widely accepted for treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effects and mechanisms of ZJP in Helicobacter pylori (H. pylori) - induced chronic atrophic gastritis (CAG) in vivo and in vitro. Methods: CAG rat model was induced by H. pylori. ZJP (0.63, 1.26, and 2.52 g/kg, respectively) was administered orally for four weeks. Therapeutic effects of ZJP were identified by H&E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 (CCK8) and high-content screening assay (HCS), respectively. Moreover, relative mRNA expression and protein expression related to JMJD2B/COX-2/VEGF axis was detected to investigate the potential mechanisms of ZJP in CAG. Results: Results showed the symptoms (weight loss and gastric mucosa damage) of CAG were alleviated, and the contents of TNF-α in serum was markedly decreased after treating with ZJP. Moreover, cell viability, proliferation and morphology changes of GES-1 cells were ameliorated by ZJP intervention. In addition, proinflammatory genes and JMJD2B/COX-2/VEGF axis related genes were suppressed by ZJP administration in vitro and in vivo. Meanwhile, immunohistochemistry (IHC) and western blot confirmed down-regulation of these genes by ZJP intervention. Conclusion: ZJP treatment can alleviate gastric mucosal damage induced by H. pylori via JMJD2B/COX-2/VEGF axis.


2021 ◽  
Vol 17 ◽  
pp. 174480692110418
Author(s):  
Wei Sun ◽  
Yijun Zhang ◽  
Guanghui Wang

Background It has been increasingly reported that microRNAs (miRNAs) are related to rheumatoid arthritis (RA) pathogenesis. This present research was conducted to analyze the functions of miR-137 and the underlying molecular mechanism in RA progression. Methods Differentially expressed miRNAs in RA patients were analyzed using microarray-based analyses. Next, experiments involving miR-137 overexpression were performed to analyze the role of miR-137 in human fibroblast-like synoviocytes-RA (HFLS-RA) using cell counting kit-8 (CCK-8) assay, EdU staining, Transwell assay and flow cytometry, respectively. The function of miR-137 in inflammation was determined using ELISA. The binding relationship between miR-137 and LSD1 was confirmed by dual-luciferase reporter gene assay and ChIP test. Besides, a rat model with RA was established for in vivo experiments. Results miR-137 was downregulated in RA tissues and cells, which was negatively correlated with inflammatory factors. Upregulated miR-137 suppressed growth, migration and invasion of HFLS-RA, but promoted apoptosis. Lysine-specific demethylase-1 (LSD1) was a target of miR-137 and could be negatively regulated by miR-137. Moreover, LSD1 could activate REST through demethylation, while the REST/mTOR pathway induced levels of pro-inflammatory factors in RA. We observed the similar results in our in vivo study. Conclusion This study suggested that miR-137 reduced LSD1 expression to inhibit the activation of REST/mTOR pathway, thus preventing against inflammation and ameliorating RA development. Our research may offer new insights into treatment of RA.


Author(s):  
Chunlei Mei ◽  
Yafei Kang ◽  
Chenlu Zhang ◽  
Chunyu He ◽  
Aihua Liao ◽  
...  

Human epididymitis is mainly caused by retrograde urinary tract infection with uropathogenic Escherichia coli (UPEC). This disease is an important factor (accounting for 20–30%) causing male infertility. C-type natriuretic peptide (CNP), a protein composed of 22 amino acids, is proved to play an immunoregulatory role in respiratory and cardiovascular systems. CNP is expressed extremely high in the epididymis, but whether CNP plays the same role in acute epididymitis is unclear. At first, we established an acute caput epididymitis model in rats with UPEC and treated them with CNP to measure inflammatory damage. Then RNA-seq transcriptome technology was used to reveal potential signal pathways. Secondly, the turbidity and activity of UPEC were assessed using a microplate reader and the amount of UPEC by agar plates after incubation with CNP. Thirdly, macrophages in caput epididymis were tested by immunohistochemistry (IHC). Meanwhile, lipopolysaccharide (LPS) with or without CNP was used to stimulate the macrophage (RAW264.7) in vitro and to detect the expression level of pro-inflammatory factors. Finally, the macrophage (RAW264.7) was treated with CNP, 8-Br-cGMP [cyclic guanosinc monophosphate (cGMP) analog] and KT5823 [protein kinase G (PKG) inhibitor], and the expression level of nuclear factor-k-gene binding (NF-kB) signal pathway was examined. The results showed that the damage of epididymis induced by UPEC as well as the pro-inflammatory factors could be alleviated significantly with CNP treatment. CNP could inhibit the activity and numbers of bacteria in both in vivo and in vitro experiments. Moreover, CNP repressed the invasion, and the expression of pro-inflammatory factors (such as NF-kB, IL-1β, IL-6, TNF-α) in macrophages and its effect could be inhibited by KT5823. Therefore, we drew a conclusion from the above experiments that CNP alleviates the acute epididymitis injury induced by UPEC. On one hand, CNP could inhibit the growth of UPEC. On the other hand, CNP could decrease invasion and inflammatory reaction of macrophages; the mechanism was involved in inhibiting NF-kB signal pathway through the cGMP/PKG in macrophages. This research would open up the possibility of using CNP as a potential treatment for epididymitis.


2020 ◽  
Author(s):  
Dilihumaer Tuluhong ◽  
Tao Chen ◽  
Jingjie Wang ◽  
Huijuan Zeng ◽  
Hanjun Li ◽  
...  

Abstract Background Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our study was to detect the functions of FZD2 and explore its mechanism in BC. Methods The level of FZD2 was measured in BC tissues by quantitative realtime polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC) respectively. Cell Counting Kit-8 (CCK-8), standard colony formation, transwell aasays, wound healing and flow cytometry experiments were adopted separately to test cell viability, invasion, migration, apoptosis and cell cycle distribution. Epithelial-mesenchymal transition (EMT) biomarker were determined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo. Results We determined that FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway. Conclusion Based on all these data, we concluded that FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Xinhua Wang ◽  
Chengpeng Wan ◽  
Xiaoxia Feng ◽  
Fuyan Zhao ◽  
Huiming Wang

Purpose. The stress shielding effect caused due to the mechanical mismatch between the solid titanium and the surrounding bone tissue warrants the utilization of a mechanically and biologically compatible material such as the titanium-hydroxyapatite (Ti-HA) functionally graded material (FGM) for dental implants. This study is aimed at fabricating a Ti-HA FGM with superior mechanical and biological properties for dental implantation. Materials and Methods. We fabricated a Ti-HA FGM with different Ti volume fractions (VFs) using HA and Ti powders. Ti-HA was characterized by studying its mechanical properties. Cytotoxicity was examined using a Cell Counting Kit-8 assay and an LDH cell cytotoxicity assay. Scanning electron microscopy was performed on an XL30 environmental scanning electron microscope (ESEM). Alkaline phosphatase (ALP) and transforming growth factor (TGF-β1) expressions were quantitatively monitored using enzyme-linked immunosorbent assay (ELISA) kits. The expressions of TGF-β receptors and ALP genes were measured using real-time polymerase chain reaction. The Ti-HA FGM dental implants were placed in beagle dogs. Microcomputed tomography (CT) and hard tissue slices were performed to evaluate the bone-implant contact (BIC) and bone volume over total volume (BV/TV). Results. The density and mechanical properties of the Ti-HA exhibited various graded distributions corresponding to VF. Based on the results of the Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays, the difference in cytotoxicity between the two groups was statistically nonsignificant ( P = 0.11 ). The ALP and TGF-β1 levels were slightly upregulated. The transcript levels of ALP and TGF-βRI were higher in the Ti-HA groups than in the Ti group at 7 days, whereas the transcript levels of TGF-βRII exhibited no obvious increase. The BIC did not exhibit significant differences between the Ti and Ti-HA FGM groups ( P = 0.0504 ). BV/TV showed the Ti-HA FGM group had better osteogenesis ( P = 0.04 ). Conclusion. Ti-HA FGM contributes to the osteogenesis of dental implants in vivo and in vitro.


2020 ◽  
Vol 22 (4) ◽  
pp. 37-42
Author(s):  
I. M. Pavlovich ◽  
G. A. Al’per ◽  
A. V. Gordienko ◽  
D. I. Proskunov ◽  
V. V. Yakovlev

The effect of morphological changes in the gastric mucosa on the motor-evacuation function of the stomach was evaluated in 90 patients with chronic atrophic gastritis and 93 patients with chronic non-atrophic gastritis aged 18 to 82 years. Motor function disturbances were discovered of 90% of patients with chronic atrophic gastritis and 80,6% with chronic non-atrophic gastritis. It was established that the pyloric insufficiency compared with its spasm was significantly more (p0,01) often in chronic atrophic gastritis. Insufficiency of the lower esophageal sphincter in patients with atrophic gastritis was significantly (p0,01). Insufficiency of the lower esophageal sphincter in combination with duodenogastric reflux in patients with chronic atrophic gastritis was significantly more (p0,01) often observed during diffuse atrophy, i. e. when mucous membrane of stomach corpus and antrum is involved in the process. With the localization of atrophy in the antrum alone, pyloric insufficiency was observed significantly more (p 0,01) often than spasm. Thus, an interrelation between the insufficiency of the lower esophageal and pyloric sphincters with the diffuse atrophic process has been established. There are no significant differences of disorders of gastric motor function in patients with different types of chronic gastritis. Accelerated evacuation from the stomach with localization of atrophy in the mucous membrane of the stomach corpus is more (p 0,01) often observed in patients with chronic atrophic gastritis.


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