scholarly journals Obesity-associated up-regulation of lipocalin 2 protects gastric mucosa cells from apoptotic cell death by reducing endoplasmic reticulum stress

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xin Wen ◽  
Bin Su ◽  
Mingming Gao ◽  
Jiaqi Chen ◽  
Donglei Zhou ◽  
...  

AbstractGastric mucosal injury is a less well known complication of obesity. Its mechanism remains to be further elucidated. Here, we explored the protective role of lipocalin 2 (LCN2) against endoplasmic reticulum stress and cell apoptosis in gastric mucosa in patients and mice with obesity. Through molecular and genetic analyses in clinical species, LCN2 secreted by parietal cells expression is elevated in obese. Immunofluorescence, TUNEL, and colorimetry results show that a more significant upregulation of pro-inflammatory factors and increased amount of apoptotic cells in gastric tissue sections in obese groups. Loss- and gain-of-function experiments in gastric epithelial cells demonstrate that increased LCN2 protected against obesity associated gastric injury by inhibiting apoptosis and improving inflammatory state. In addition, this protective effect was mediated by repressing ER stress. Our findings identify LCN2 as a gastric hormone could be a compensatory protective factor against gastric injury in obese.

Author(s):  
Uzma Waseem ◽  
Syeda Rizwana Jafri ◽  
Sarah Khalid ◽  
Fauzia Qureshi ◽  
Nadia Majeed ◽  
...  

Background: Aspirin is amongst the most widely used drugs and has many adverse effects on gastric mucosa. Anti-inflammatory properties of Acacia catechu have been established already. Objective was to evaluate the histopathological changes induced by aspirin in the stomach of albino rats and to assess the protective effect of different doses of Acacia catechu.Methods: Experimental study Postgraduate Medical Institute, Lahore for 21 days. Forty-eight adult albino rats, both males and female, were divided into four groups A, B, C and D randomly; each comprising of 12 rats. Group A was control, group B was given aspirin 100 mg/kg and group C and D were given aspirin 100 mg/kg along with Acacia catechu 250 mg/kg and 500 mg/kg respectively by oral route. The rats from individual group were sacrificed on 3rd day, 7th day and 14th day and stomachs were examined under light microscope to observe the inflammatory cells infiltration.Results: Gross and microscopic findings on days 3, 7 and 14 were similar. Control groups A1, A2 and A3 showed normal healthy gastric mucosa and the least number of inflammatory cells. In group B, aspirin produced ulcerations and linear breaks; with highest inflammatory infiltrates. On microscopic examination, numerous inflammatory cells were noted. Group C and D rats had minimum ulcer index and fewer inflammatory cells.Conclusions: Acacia catechu has protective role against gastric injury by inhibiting inflammation. 


2022 ◽  
pp. 1-14
Author(s):  
Li-Na Zhang ◽  
Meng-Jie Li ◽  
Ying-Hui Shang ◽  
Yun-Ru Liu ◽  
Huang Han-Chang ◽  
...  

Background: Alzheimer’s disease (AD) characterized by neurofibrillary tangles caused by hyperphosphorylated tau is the most common cause of dementia. Zeaxanthin (Zea), derived from fruits and vegetables, may reduce the risk of AD. Endoplasmic reticulum stress (ERS) might cause memory impairment in AD. Objective: Here, we studied protective role of Zea on the relationship among ERS, activity of glycogen synthase kinase 3β (GSK-3β, tau phosphorylated kinase), and p-Tau (Ser 396 and Thr 231). Methods: The results were obtained in non-RA and RA group by using different treatment, such as 9-cis-retinoic acid (RA), TM (ERS inducer), Zea, 4-PBA (ERS inhibitor), and SB216763 (GSK-3β inhibitor). The methods included flow cytometry and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] for the detections of cell cycle and cell viability and western blot as a third measure of proteins in relation to ERS and tau phosphorylation. We have collected and analyzed all the data that suggested application of drugs for the treatment in non-RA and RA group. Results: Zea displays its protection on TM-induced cell injury, upregulation of GRP78 expression, and change of GSK-3β activity and tau phosphorylation when 4-PBA and SB216763 interfere with the process. Conclusion: These studies indicated that Zea is in vicious circle in ERS, GSK-3β, and tau phosphorylation, and further reflect its potential value in AD.


2018 ◽  
Vol 19 (11) ◽  
pp. 3658 ◽  
Author(s):  
Zhi-Meng Xu ◽  
Cheng-Bin Li ◽  
Qing-Ling Liu ◽  
Ping Li ◽  
Hua Yang

Ginsenoside Rg1, a saponin that is a primary component of ginseng, has been demonstrated to protect hearts from diverse cardiovascular diseases with regulating multiple cellular signal pathways. In the present study, we investigated the protective role of ginsenoside Rg1 on doxorubicin-induced cardiotoxicity and its effects on endoplasmic reticulum stress and autophagy. After pre-treatment with ginsenoside Rg1 (50 mg/kg i.g.) for 7 days, male C57BL/6J mice were intraperitoneally injected with a single dose of doxorubicin (6 mg/kg) every 3 days for four injections. Echocardiographic and pathological findings showed that ginsenoside Rg1 could significantly reduce the cardiotoxicity induced by doxorubicin. Ginsenoside Rg1 significantly inhibited doxorubicin-induced formation of autophagosome. At the same time, ginsenoside Rg1 decreased the doxorubicin-induced cardiac microtubule-associated protein-light chain 3 and autophagy related 5 expression. Ginsenoside Rg1 can reduce endoplasmic reticulum dilation caused by doxorubicin. Compared with the doxorubicin group, the expression of cleaved activating transcription factor 6 and inositol-requiring enzyme 1 decreased in group ginsenoside Rg1. Treatment with ginsenoside Rg1 reduces the expression of TIF1 and increases the expression of glucose-regulated protein 78. In the ginsenoside Rg1 group, the expression of p-P70S6K, c-Jun N-terminal kinases 1 and Beclin1 declined. These results indicate that ginsenoside Rg1 may improve doxorubicin-induced cardiac dysfunction by inhibiting endoplasmic reticulum stress and autophagy.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Zhi-gao Sun ◽  
Ya-zhuo Hu ◽  
Yu-guo Wang ◽  
Jian Feng ◽  
Yong-qi Dou

BuPiHeWei (BPHW) decoction, a classic Traditional Chinese Medicinal (TCM) prescription, has been widely used in clinical practice to relieve digestive symptoms caused by chemotherapy, such as diarrhea and vomiting. The present study aimed to investigate whether BPHW decoction exerted a protective role in the 5-Fu-induced intestinal mucosal injury in the rats by regulating the mechanisms of TLR-4/NF-κB signaling pathway. There were 35 Sprague Dawley rats randomly divided into four groups: normal control group, 5-Fu group, 5-Fu + BPHW decoction group (10.5 g/kg, for five continuous days), and 5-Fu + Bacillus licheniformis capsule group (0.2 g/kg, for five continuous days). Animal models were established by intraperitoneal injection of 5-Fu (30 mg/Kg, for five consecutive days). At the end of the treatment period, body weight, diarrhea score, and histological examination were examined. Furthermore, the expression of TLR-4/NF-κB pathway was detected to reveal its mechanism. The results showed that BPHW decoction effectively reduced diarrhea score and increased body weight and height of villi after 5-Fu chemotherapy. In addition, BPHW decoction could significantly inhibit the expression of TLR-4, NF-κB, and inflammatory factors (including TNF-α, IL-1β, and IL-6) in the intestine, and the efficacy was significantly higher than that of Bacillus licheniformis capsule. In summary, BPHW decoction might be considered an effective drug to alleviate intestinal mucosal injury in the rats induced by 5-Fu.


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