1.Research progress of low grade inflammation in obese patients with type 2 diabetes mellitus
Adili DILIDAER ; Yisireyili MAIMAITI ; Aili AIKEBAIER
Journal of Chinese Physician 2023;25(1):140-143
Obesity and diabetes mellitus (T2DM) are metabolic related diseases with high incidence rate at present. Obesity is considered as one of the risk factors of T2DM. At present, the interaction mechanism between obesity and T2DM has not been clearly studied.Adipose tissue is an endocrine organ related to the pathophysiology of obesity and its complications. Adipose tissue can not only store a lot of energy, but also secrete many hormones, oxidative stress and inflammatory factors, which may be related to the occurrence and development of T2DM. Under long-term and low-dose stimulation, the sustainable low grade inflammation of fat is considered to be an important mechanism for the occurrence and development of obese T2DM. Therefore, this paper mainly summarizes the research progress of low grade fat inflammation in obese T2DM.
2.The role of Nox-4 in gastric mucosal inflammation induced by chronic restraint stress in mice
Yisireyili MAIMAITI ; Alimujiang AZIGULI· ; Wulamu WUBULIKASIMU· ; Yiliang LI ; Aili AIKEBAIER ; Xinsheng ZHAO ; Maisiyiti ALIMUJIANG ; Yuan JIANG ; Abudureyimu KELIMU
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(4):316-321
Objective To investigate the expression of NADPH oxidase Nox-4 induced by stress in gastric mucosa and its role in inflammation.Methods Twenty male SPF Kunming mice were randomly divided into chronic restraint stress group(stress group) and control group.Stress mice were restrained in selfmade restraint device for 2 hours each day.The rest of the time,the mice in the two groups had free access to food and water normally,experiment lasted 14 days.The histopathological changes of gastric mucosa were assessed by HE staining under light microscope.The expression of Nox-4 in gastric mucosa of mice was carried out by immunohistochemical method.The relative expression levels of Nox-4,antioxidant protein (Mn-SOD,GSH,Catalase) and inflammatory factors(IL-8,IL-1β,TNF-α) in gastric mucosa were detected by real-time quantitative RT-PCR and ELISA.Results Basal cell proliferation,neutrophil,eosinophil and plasma cell infiltration and inflammatory changes were observed in the lamina propria and glandular epithelium of stress mice,while no obvious abnormalities were found in control mice.The expression of Nox-4 in stress group was deeper and more abundant than that in control group,mainly expressed in lamina propria and glandular epithelium.The mRNA expression levels of Nox-4 in gastric mucosa of stress group was(2.42±0.51) times higher than that of control group,and blood concentration of stress group was(2.23±0.67) times higher than that of control group(t=-46.32,P<0.001).The RT-PCR of antioxidant proteins in gastric mucosa showed that the transcription levels of Mn SOD,GSH and Catalase in stress group were significantly lower than that of control group (Mn-SOD:0.59± 0.10,GSH:0.58± 0.11,Catalase:0.57± 0.09),and there were significant differences between the two groups(t=13.57,11.67,15.01,P<0.01).RT-PCR results showed that the transcription levels of IL-8,IL-1β,TNF-α in stress group were significantly higher than those in control group (IL-8:1.47±0.34,IL-1β:1.48 ± 0.42,TNF-α:1.51 ± 0.37),and there were significant differences in two groups(t=-18.45,-19.14,-20.85,P<0.01).ELISA results showed that the serum levels of inflammatory factors in stress group were significantly higher than those in control group(2.25±0.37,3.59±0.45,3.41±0.34),and the differences were statistically significant(t=-47.11,-79.36,-96.32,P<0.01).Pearson correlation analysis showed that there was a positive correlation between serum concentration of Nox-4 and inflammatory factors(IL-8,IL-1β,TNF-αt) in stress group(r=0.97,0.99,0.98,P<0.01).Spearman rank correlation analysis showed that the grade of gastric mucosal inflammation was positively correted with serum levels of Nox-4 and inflammatory factors (IL-8,IL-1β,TNF-α) (r =0.96,0.92,0.91,0.94,all P< 0.01)Conclusion Stress may lead to gastric mucosal lesion by overexpression of proinflammatory factors through destroying the balance of oxidation/antioxidant system in gastric mucosa.
3.Research progress on the correlation between gastroesophageal reflux disease and obesity and related treatment
Yimingjiang YUSUPUJIANG ; Yisireyili MAIMAITI ; Aili AIKEBAIER
Journal of Chinese Physician 2021;23(9):1425-1428
Obesity has been recognized as a health problem worldwide because of its negative effects. Obesity has increased the incidence rate of some diseases. Among them, gastroesophageal reflux disease (GERD) is more typical. Recently, GERD has become more and more popular among obese people. Scholars have begun to pay attention to the association between obesity and GERD. Some literatures and data point out that obesity is one of the important factors related to GERD. In the face of these problems, surgical and non-surgical treatment can be used, but recently, surgical treatment, especially weight loss surgery, has become more and more popular. In order to provide reference for clinicians and patients, this paper reviews the relationship between obesity and GERD, and the treatment methods and development of obesity complicated with GERD in recent years.
4.The esophageal expression of fibrotic cytokines and NADPH oxidase in stress induced esophageal fibrosis and its significance
Yisireyili MAIMAITI ; Wulamu WUBULIKASIMU ; Aili AIKEBAIER ; Yiliang LI ; Abudureyimu KELIMU
Journal of Chinese Physician 2019;21(5):672-676
Objective To detect the expression levels of collagen1 (colla-1),transforming growth factor-β1 (TGF-β1),a-smooth muscle actin (α-SMA) and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX-4) in mouse esophagus submitted to chronic restraint stress (CRS),in order to discuss stress-induced esophageal fibrosis and the role of oxidative stress.Methods 20 male Kunming mice were randomly divided into two groups,CRS and normal control (NC).The mice in CRS group were submitted to 2 h per day of restraint stress using home-made device for a period of 14 days,and the mice in both group were treated the same at rest of the time.Fibrotic changes of esophageal tissue were observed using Masson staining.The expression levels of NOX-4 and related fibrotic cytokines in esophageal tissues were detected by several methods such as immunohistochemistry,enzyme-linked immunosorbent assay (ELISA) and realtime polymerase chain reaction (qRT-PCR).Results Body weight in CRS group was significantly lower than NC group (8.75 ± 1.69 vs 12.69 ± 3.16),with statistically significant difference (t =3.11,P < 0.05).Masson staining revealed that CRS mice showed distinct fibrosis of epithelial interstitium,while there was no distinct changes observed in NC mice.Immunohistochemical staining revealed intense staining for NOX-4 in epithelial,mucosal and submucosal layers of esophagi in CRS mice.ELISA showed that the serum level of NOX-4 in CRS mice was higher than NC mice (1.442 ± 0.05 vs 0.449 ± 0.08),with statistically significant difference (t =-27.32,P < 0.01).Real-time PCR results showed that the expression of colla-1,TGF-β1,α-SMA and NOX-4 in CRS mice were as (2.443 ±0.36,2.78 ±0.13,2.244 ±0.18,2.448 ±0.440) times higher than NC mice,with statistically significant difference (t =-11.19,-38.86,-19.90,-10.37,P < 0.01).Conclusions Fibrotic cytokines such as colla-1,TGF-β1 and α-SMA may participate in formation of stress induced esophageal fibrosis,and oxidative stress may play crucial role in the process of esophageal fibrosis.
5.Role of MDA in the pathogenesis of GERD esophagus mucosal inflammatory injury
Mijiti ABULAJIANG ; Yisireyili MAIMAITI ; Aili AIKEBAIER ; Wulamu WUBULIKASIMU ; Zhengyi CAO ; Yiliang LI ; Alimujiang AZIGULI ; Yuan JIANG ; Abudureyimu KELIMU
Journal of Chinese Physician 2019;21(7):997-1001,1006
Objective To investigate the expression of malondialdehyde ( MDA) in esophageal mu-cosa of different types of gastroesophageal reflux disease ( GERD) patients and its role in the esophageal in-flammation. Methods According to the inclusion and exclusion criteria, 42 patients hospitalized in the the Xinjiang Uygur Autonomous Region People's Hospital from December 2017 to October 2018 were selected as the research group. 8 healthy subjects completed physical examination were set up as healthy control group. GERD completed GERDQ score, 24 h pH monitoring, and taken 3 cm on the dentate line of the esophagus as a specimen. The study group was divided into non-erosive reflux disease (NERD) group (17 cases) and Ero-sive reflux disease [erosive esophagitis (RE)] group (25 cases). Then hematoxylin-eosin (HE) staining, immunohistochemistry, real-time polymerase chain reaction ( qPCR ) , enzyme-linked immunosorbent assay (ELISA) methods were used to detect inflammation, oxidative stress (MDA), antioxidant enzyme [manga-nese superoxide dismutase (Mn SOD), glutathione (GSH), catalase (CAT)], and proinflammatory cyto-kines [monocyte chemotactic protein-1 (MCP-1), interlukin-8 (IL-8), tumor necrosis factorα(TNF-α)]. Results There was no significant difference in body mass index ( BMI ) between the three groups ( P >0. 05). 24 h pH monitoring of esophagus showed that the indexes of weak acid reflux (4
6.Research progress of the relationship between the effect of laparoscopic sleeve gastrectomy on blood glucose and GLP-1/DPP-4 pathway in obese patients with type 2 diabetes mellitus
Yongbin MA ; Yisireyili MAIMAITI ; Aili AIKEBAIER
Journal of Chinese Physician 2022;24(1):153-156
Obesity and type 2 diabetes (T2DM) are all the metabolic diseases with high incidence rate. There is a clear correlation between the them. Weight-loss surgery is the important treatment of surgical method for obesity and T2DM.However, the mechanism of T2DM for weight loss surgery is not yet clear.The secretion level of glucagon like peptide-1 (GLP-1) was affected after weight loss surgery. The secretion of GLP-1 can delay gastric emptying, increase satiety, improve insulin resistance (IR) and promote β insulin release, inhibition of glucagon synthesis and secretion, and improvement of pancreatic function β cell function. All of these changes were conducive to glycemic control. Therefore, this paper aims to summarize and describe the relationship between the effect of laparoscopic sleeve gastrectomy (LSG) on blood glucose and GLP-1/dipeptidyl peptidase-4 (DPP-4) pathway in obese T2DM patients.
7.The role of chronic restrain stress induced Nox-4 expression and its significances in adipose inflammation
Yisireyili MAIMAITI ; Aizezi MAIMAITIAILI ; Wulamu WUBULIKASIMU ; Aili AIKEBAIER ; Yiliang LI ; Alimujiang AZIGULI ; Xinsheng ZHAO ; Jing YAN ; Wupuer SHADIGULUI ; Yuan JIANG ; Abudureyimu KELIMU
Chinese Journal of Endocrinology and Metabolism 2019;35(5):410-416
Objective To investigate stress induced Nox-4 expression and to explore its role in adipose inflammation. Methods Twenty male Kunming mice were randomly divided into two groups ( n=10 each) , chronic restraint stress group and control group. Stress mice were restrained in self-made restraint device for 2 hours per day for 14 days. HE staining, immunohistochemistry, RT-PCR, and ELISA were used to analyze the expression of Nox-4, CD11b, antioxidant protein ( Mn SOD, GSH-Px, Catalase), adipocytokines ( adiponectin, MCP-1, IL-6, TNF-a). Results White adipose tissue (WAT) of stress mice inguinal fat pad significantly shrank compared to control group. HE staining showed that there were a large number of mononuclear cells, neutrophils, eosinophils, and cell infiltration reactions and inflammatory changes in WAT of stress mice. The stress significantly increased CD11b-positive cells and the expression of mF4/80, CD68. The concentration of serum FFA in stress group increased significantly, nearly twice of the control group ( P<0.01) . Nox-4 positive staining cells in stress WAT were deeper and more abundant. The level of Nox-4 in stress WAT was significantly higher than that of control group(P<0.01). The levels of antioxidant proteins such as Mn-SOD, GSH-Px, and catalase in stress WAT were significantly lower than those of control group (P<0.01). The expression levels of adiponectin in stress WAT were significantly reduced as compared to control group ( P<0.01) . The levels of MCP-1, IL-6 and TNF-α in stress WAT were significantly higher than those in control group (P<0.01). Conclusion Stress may lead to imbalance of adipose oxidation/antioxidant system and abnormal expression of adipocytokines, which may result in adipose inflammation.
8.Betulinic acid enhances gefitinib-sensitivity of pancreatic cancer cells via inhibition of STAT3 activation
WU Haixia ; MAIMAITI Aikebaier ; WANG Shuai ; ZHOU Keting ; SHI Senlin
Chinese Journal of Cancer Biotherapy 2019;26(9):948-954
Objective: To investigate the effects and the underlying mechanisms of betulinic acid (BEA) on sensitizing pancreatic cancer cell lines Panc-1 and Miapaca-2 to gefitinib. Methods: After the cell culture was completed, Panc-1 and Miapaca-2 cells were randomly divided into 4 groups: control group (without treatment), BEAgroup, gefitinib group and BEAcombined with gefitinib group, respectively.The sensitization effect of BEAon gefitinib-insensitive pancreatic cancer cells was detected by MTS assay. The treatment effects of combined treatment of gefitinib and BEA against Panc-1 and Miapaca-2 cells were evaluated by colony formation assay. Flow cytometry was used to examine the effect of BEAon apoptosis of Panc-1 cells while WB was applied to determine the effect of BEAonapoptosis-related proteins. Surface plasmon resonance (SPR) experiment was used to detect the direct combination between signal transducer and activator of transcription 3(STAT3) and BEA; Molecular docking and molecular dynamics simulation experiments were adopted topredict the combining mode between STAT3 and BEA. Results: BEA synergistically enhanced the gefitinib-sensitivity of pancreatic cancer Panc-1 and Miapaca-2 cells (P<0.05), and IC50 of gefitinib on two cells were reduced by over 50%. Compared with single treatment, the combined treatment of BEA and gefitinib promoted the apoptosis and up-regulated the expressions of apoptosis-relatedproteins (cleaved-PARP and Bax), but reduced the apoptosis-inhibitory protein Bcl-2 (all P<0.05 or P<0.01). Moreover, the inhibitory effect of BEA on STAT3 activation in Panc-1 cells was in a dose-dependent mannar (P<0.01). BEA stabilizes its binding to STAT3 by forming hydrogen bonds with Lys-591 and Ser-613 of STAT3; in the meanwhile, BEA stabilized inthebinding site of STAT3, there by blocking STAT3 dimerization to enhance the drug sensitivity. Conclusion: Combined use of BEA and gefitinib could significantly inhibit the proliferation and induce apoptosis of Panc-1 and Miapaca-2 cells, which might be mediated by the inhibition of BEA on STST3.
9.The expression of NADPH oxidase-4 and acid sensitive receptors in the esophagus of chronic restraint mice
Yisireyili MAIMAITI ; Alimujiang AZIGULI ; Yiliang LI ; Aili AIKEBAIER ; Xinsheng ZHAO ; Zhi WANG ; Jing YAN ; Abudureyimu KELIMU
Journal of Chinese Physician 2020;22(7):1000-1004
Objective:To investigate the chronic restraint stress induced expressions of acid sensitive receptors and its role in the esophageal inflammation and oxidative stress.Methods:Twenty male specific pathogen free (SPF) Kunming mice were randomly divided into two groups: stress group and control group (each group, n=10). Stress mice were restrained in self-made restraint device for 2 hours per day and lasted for total 14 days. The histopathological changes of esophageal mucosa were observed by hematoxylin eosin (HE) staining under light microscope. The expression of nicotinamide adenine dinucleotide phosphate (Nox-4) was detected by immunohistochemistry, real time fluorescent quantitative polymerase chain reaction (qRT-PCR) and enzyme linked immunosorbent assay (ELISA). The mRNA expressions of acid sensitive receptors were detected by qRT-PCR. Results:HE staining showed that stress mice had obvious infiltrations of neutrophils and eosinophils, and also showed inflammatory change in esophgus, while no significant abnormality was found in the esophagus of control mice. The inflammotory scores in stress group were significantly higher than that in control group ( P<0.001). Immunohistochemistry showed that Nox-4 was mainly expressed in the lamina propria, mucosa and submucosa of esophagus. The mRNA expression levels of Nox-4 in stress group was (2.67±0.62) times higher than control group, with statistically significant difference ( P<0.001). In addition, the plasma concentration of Nox-4 in stress group was significantly higher than that of control group [(0.42±0.01)ng/ml vs (2.13±0.35)ng/ml, P<0.001]. The transcription levels of acid sensitive receptors in stressed mice, such as transient receptor potential vanilloid-1 (TRPV-1), TRPV-4, acid-sensing ion channel-1 (ASIC-1), ASIC-2 and ASIC-3 were significantly higher than those in the control group, with statistically significant difference ( P<0.001). Pearson correlation analysis showed that there was a positive correlation between Nox-4 mRNA expression and TRPV-1, TRPV-4, ASIC-1, ASIC-2, ASIC-3 mRNA expression in stress group ( r=0.97, 0.94, 0.98, 0.95 and 0.99, P<0.01). Conclusions:Stress may increases the expression of acid sensitive receptors and result in an esophageal inflammation and oxidative stress, which may contribute to the formation of esophageal hypersensitivity.
10.Prevention and treatment of postoperative complications of laparoscopic sleeve gastrectomy for obesity
Kuerban YIERPANJIANG ; Yisireyili MAIMAITI ; Aili AIKEBAIER
Journal of Chinese Physician 2020;22(9):1431-1434
More and more clinical studies have found that weight-loss surgery is a long-term and effective way to treat obesity. Laparoscopic sleeve gastrectomy (LSG) has been widely used in recent years due to its advantages of simple operation, high safety and obvious curative effect. With the increasing popularity of LSG, clinicians are aware of the possibility of many complications. In this paper, the common complications of obesity after LSG and its prevention and treatment status were reviewed. The risk factors of common complications of obesity after LSG were analyzed, and the prevention and treatment experience was summarized, so as to provide reference for clinical peers.