1.Effect of tumor-associated macrophage exosomes on glycolysis of pancreatic cancer cells by regulating KRAS signal pathway
Alimu DILIXIATI ; Jian-Jiang ZHENG ; Tulahazi DUOLIKUN ; Mahemuti AMUTIJIANG
Journal of Regional Anatomy and Operative Surgery 2024;33(3):208-212
Objective To investigate the effect of tumor-associated macrophage exosomes on glycolysis of pancreatic cancer cells and its mechanism.Methods The THP-1 cells were induced to differentiate into the M0 and M2 macrophages,and the exosomes(M0 exo and M2 exo)were extracted.The pancreatic cancer cells CAPAN-2 and ASPC-1 were divided into the PBS group,the M0 exo group,the M2 exo group and the M2 exo+siKRAS group,and co-incubated with equal volumes of PBS,10 μg/mL of M0 exo,10 μg/mL of M2 exo,and transfection of KRAS siRNA and 10 μg/mL of M2 exo,respectively.Transmission electron microscopy was used to observe the structure of exosomes;CCK-8 was used to detect the cell proliferation capacity;the kit was used to detect the glucose uptake rate and production level of lactic acid,and Western blot was used to detect the exosome markers expression,KRAS protein expression and ERK1/2 phosphorylation level.Results THP-1 was induced to differentiate into M2 macrophages expressing Arg-1 and IL-10 marker proteins.M0 exo and M2 exo had a bilayer membrane structure with a particle size of about 100 nm and expressed exosomal marker proteins of CD9,CD81,and TSG101.Compared with the PBS group,the cell proliferation,glucose uptake rate,production level of lactic acid of CAPAN-2 and ASPC-1 cells in the M2 exo group increased significantly(P<0.05),and the KRAS expression and ERK1/2 phosphorylation level were significantly increased(P<0.001).Compared with the M2 exo group,the proliferation,glucose uptake rate and production level of lactic acid of CAPAN-2 and ASPC-1 cells in the M2 exo+siKRAS group decreased significantly(P<0.05).Conclusion Tumor-associated macrophage exosomes can promote the glycolysis of pancreatic cancer cells via the activation of KRAS signaling pathway.
2.Epidemiological investigation of an outbreak of anthrax in Gongliu County, Xinjiang Uygur Autonomous Region
GUO Rong ; GAO Zhenguo ; LIU Yan ; WANG Rong ; ZHANG Ling ; Mahemuti ; LIU Wanli Wanli ; LIU Lunguang
Journal of Preventive Medicine 2023;35(5):418-420,424
Abstract
A suspected case of cutaneous anthrax was reported by Gongliu County Disease Control and Prevention Center, Ili Kazak Autonomous Prefecture, Xinjiang Uygur Autonomous Region on August 19, 2021. Then, an epidemiological survey was performed by a joint investigation team consisting of professionals from Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, intermediate-level trainees from the Field Epidemiology Training Program of Chinese Center for Disease Control and Prevention, and professionals from Ili Kazak Autonomous Prefecture Center for Disease Control and Prevention. A total of 11 cutaneous anthrax cases were identified, including 8 suspected cases and 3 clinically diagnosed cases, and all cases were villagers in Y Village, X Township, Gongliu County, without severe case or deaths found. The onset of the first case occurred on July 27, and the onset of the last case occurred on August 16. The main clinical manifestations included ulcerative eschar on hands and exposed skin of the upper extremity. A Bacillus anthracis isolate was detected in meat samples from infected cattle. Epidemiological surveys showed that villagers did not report infected cattle to related sectors and privately slaughtered and ate meat from infected cattle without any effective protective measures, resulting in this outbreak. It is recommended to strengthen health education for people raising, selling and slaughtering livestock, and publicize zoonotic disease control knowledge, including anthrax, and establish an effective surveillance and response system for anthrax for immediate identification and treatment of epidemics.
3.Inhibitory Effect of Sophora alopecuroides Total Alkaloids and Two Monomer Alkaloids on PC12 Cell Activity
Li GAO ; Fuxiang LUO ; Mahemuti ANAER ; Jingying LUO ; Ming YAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(17):126-133
ObjectiveTo compare the effects of total alkaloids, matrine, and sophoridine extracted from Sophora alopecuroides on the activity of pheochromocytoma cells (PC12 cells). MethodThe effect of S. alopecuroides total alkaloids, matrine, and sophoridine at concentrations of 2, 1, 0.5, 0.25, 0.125, and 0.062 5 g·L-1 on the proliferation of PC12 cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The lactate dehydrogenase (LDH) leakage rate was measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess cell apoptosis rate, cell cycle distribution, and intracellular Ca2+ levels. Real-time quantitative polymerase chain reaction (Real-time PCR) was performed to determine the mRNA transcription levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Protein expression levels of apoptosis-related proteins Caspase-3, Caspase-8, Bcl-2, and Bax were detected by Western blot. ResultCompared to the control group, S. alopecuroides total alkaloids, matrine, and sophoridine inhibited the proliferation of PC12 cells, increased LDH leakage rate, enhanced intracellular Ca2+ fluorescence intensity, and induced cell apoptosis in concentration-dependent manner (P<0.05, P<0.01). Among them, S. alopecuroides total alkaloids had the strongest inhibitory effect on cell proliferation and induction of apoptosis in PC12 cells (P<0.01). After treatment with S. alopecuroides total alkaloids, matrine, and sophoridine, the cell cycle progression of PC12 cells was arrested at G1/G0 in the S. alopecuroides total alkaloids group, and at G1/S in the matrine and sophoridine groups. The expression levels of Bax mRNA were significantly increased (P<0.05, P<0.01), while the expression levels of Bcl-2 mRNA were significantly decreased (P<0.05, P<0.01). All treatments significantly downregulated the expression of the anti-apoptotic protein Bcl-2 (P<0.05, P<0.01) and upregulated the expression of the pro-apoptotic proteins Bax, Caspase-3, and Caspase-8 (P<0.05, P<0.01), with the most significant protein expression changes observed in the S. alopecuroides total alkaloids group. ConclusionAmong the S. alopecuroides total alkaloids, matrine, and sophoridine, S. alopecuroides total alkaloids exhibit the strongest inhibitory effect on the activity of PC12 cells, and its mechanism of action may be related to the inhibition of anti-apoptotic protein expression, upregulation of pro-apoptotic protein expression, and activation of the mitochondrial Caspase-8 apoptotic pathway.
4. Effects of knocking down TSPO on proliferation and autophagy of BV2 cells in OGD/R models
Ri-Qing SU ; Jin-Liang CHENG ; Shi-Hao JIANG ; Yong-Xin WANG ; Xiao-Jiang CHENG ; Yusufu MAHEMUTI ; Abudureheman Abu LA ; Kaheerman KARLEER ; Maimaitiyasheng MAIMAITITUERXUN ; Maimaitili AISHA
Chinese Pharmacological Bulletin 2022;38(5):761-766
Aim To investigate the effeets of prolifera¬tion and autophagy of BV2 eells in OGD/R models when the 18 ku transloeator protein( TSPO) was inhibi¬ted.Methods BV2 microglia were eultured in vitro and the model established by oxygen-glueose depriva- tion/reperfusion( OGD/R) , the eells were divided into eontrol group and OGD/R group, OGD/R + small hair¬pin RNA negative eontrol group ( OGD/R + NCshR- NA) , OGD/R + TSPO small hairpin RNA group (OGD/R + TSPOshRNA ).The expression of TSPO mRNA and TSPO protein were deteeted by qRT-PCR and Western blot, respectively.In order to study the effeet of TSPO on BV2 microglial eells in OGD/R inju¬ry and autophagy, the cell viability was tested by CCK- 8 assey, the cytotoxicity was deteeted by reactive oxy¬gen speeies ( ROS) , autophagy-related mRNA ( p62 mRNA, LC3B mRNA, Beolin-1 mRNA) expressions were detected by qRT-PCR, and the expression levels of autophagy -related proteins ( p62 , LC3 II /LC3 1 , Beclin-1 ) were detected by Western blot in each group.Result The expression of TSPO mRNA and protein increased significantly in OGD/R group while compared to control group, the cell death and cytotox¬icity increased significantly, the expression levels of LC3B mRNA and Beclin-1 mRNA increased, while the p62 mRNA decreased significantly, the levels of LC3 II/LC3 1 and Beclin-1 protein increased, the expres¬sion of p62 protein decreased significantly in OGD/R group, and the autophagy was activated; compared with OGD/R group, the different levels of cell viabili¬ty, cytotoxicity and autophagy in OGD/R + NCshRNA group were not statistically significant.But the survival rate of cells in OGD/R + TSPOshRNA group signifi¬cantly increased, the levels of cytotoxicity and autoph¬agy were significantly reduced.Conclusions The in¬hibition of TSPO has a significant protective effect on OGD/R injury model in BV2 microglial cells, which may be related to the inhibition of autophagy.
5.Endovascular recanalization for symptomatic chronic internal carotid artery occlusion: a study of 19 cases
Abula ABUDUREHEMAN ; Mahemuti YUSUFU ; Riqing SU ; Kadeer KAHEERMAN ; Aisha MAIMAITILI ; Maimaitirexiati GULIKEZI ; Kai WANG ; Xiaojiang CHENG
International Journal of Cerebrovascular Diseases 2021;29(11):825-829
Objective:To investigate the efficacy and safety of endovascular recanalization in the treatment of chronically occluded internal carotid artery (COICA).Methods:From January 2014 to January 2019, patients over 50 years of age with symptomatic COICA underwent endovascular recanalization in the Department of Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University were enrolled retrospectively. The modified Rankin Scale (mRS) was used to evaluate the improvement of neurological function.Results:A total of 19 patients with symptomatic COICA were enrolled, of which 16 (84.21%) were successfully recanalized. None of the patients had severe neurological deficits during the periprocedural period and after procedure. The neurological function of patients with successful recanalization gradually improved over time. The neurological function improved in 4 patients (25.0%) at 24 h after endovascular treatment and 9 (56.3%) at 18 months postprocedural follow-up. The follow-up of CT angiography showed that the internal carotid artery in patients with successful recanalization was unobstructed, and there was no obvious in-stent stenosis.Conclusion:Endovascular recanalization is feasible, safe and effective in patients with symptomatic COICA.
6.Effect of Klotho protein on renal oxidative stress in rat with calcium oxalate nephrolithiasis
Mahemuti MULATI ; Heng DU ; Tuerhong DILIYAER ; Abulajiang AIKEPAER ; Aili ABUDUSAIMAITI ; Tailaiti ALIMU ; Tao ZHANG ; Yasheng ANNIWAER
Chinese Journal of Urology 2017;38(12):941-945
Objective To investigate the protective effect and mechanism of Klotho protein on oxidative stress in renal tubular epithelial cells of experimental rat nodels of renal calcium oxalate stone.Methods The 30 SD rats,6-8 weeks old,were randomly divided into 3 groups (10 of each),normal control group(group A),calcium oxalate model group(group B),drug plus calcium oxalate model group (group C).Group A was established with physiological saline by garage each day,group B was established with 1% ethylene glycol in drinking water + 2% ammonium chloride by garage (2 ml/d),group C was established with Fosinopril 2.5mg + Valsartan 15mg aqueous solution 2 ml by gavage on the basis of group B (2 ml/d).4 weeks later,the level of malondialdehyde (MDA),superoxide dismutase (SOD),catalase (CAT) and glutathione peroxidase (GSH) in the kidney homogenate were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA),Polymerase chain reaction (RT-PCR) was used to measure expression of Klotho and Nrf2 mRNA,and Western Blot was used to measure the expression of Klotho and Nrf2 protein.Results The level of MDA in group B [(12.43 ± 0.43) μmol/mg] was significantly increased compared to group A[(8.67 ±0.84) μmol/mg,P <0.05] and group C [(7.97 ±0.81) μmol/mg,P<0.05],while group A was close to group C (P >0.05).In group A,B,and C,the levels of SOD were (247.89 ± 2.45),(109.54 ± 4.21),and (189.74 ± 10.47) U/mg,respectively;the levels of GSH were (38.98 ± 4.55),(26.87 ± 3.92),and (31.29± 2.54) μmol/mg,respectively;CAT were (138.47 ± 8.74),(119.87 ± 8.45),and (127.46 ± 7.45) U/mg,respectively.The levels of SOD,GSH,CAT in group B were significantly lower than that in group A and C,while those in group B were close to group A (P > 0.05).The expression of Klotho and Nrf2 mRNA in group B [(0.208 ± 0.036) and (0.499 ± 0.086)] were significantly lower than group A (1.011 ± 0.174 and 1.023 ± 0.139,P < 0.05)and group C(1.123 ±0.248 and 1.023 ±0.139,P <0.05).The expression of Klotho and Nrf2 protien were also significantly lower than that in group A and C (P <0.05).Conclusions Valsartan and Fosinopril could prevent the formation of renal CaOx stones by upregulating expression of low level Klotho gene induced by ethylene glycol.This effect may be involved with activation of Keapl-Nrf2-ARE signaling pathway.
7.Assessment value of thromboelastogram for thrombus risk in patients with coronary heart disease complicated hypertension
Yan LI ; Baozhu WANG ; Xinrong ZHOU ; Mahemuti MHSUM ; Fapeng LI ; Jian ZHANG ; Huiping SUN
Chinese Journal of cardiovascular Rehabilitation Medicine 2017;26(3):334-337
Objective: To observe assessment effects of thromboelastogram (TEG) on patients with coronary heart disease (CHD) complicated hypertension.Methods: A total of 120 CHD patients were selected from our hospital.According to complicated with hypertension or not, they were divided into pure CHD group (n=58) and CHD + hypertension group (n=62).TEG indexes were compared between two groups.Results: Compared with pure CHD group, there were significant reductions in blood clot formation duration [K: (2.53±0.72)min vs.(1.82±0.64)min], coagulation reaction duration [R: (8.66±1.86)min vs.(7.18±1.85)min], arachidonic acid pathway-induced platelet activity [AA: (57.36±16.91)% vs.(46.73±20.73)%], and significant rise in maximum amplitude after clot formation [MA: (57.31±7.75)mm vs.(64.36±7.85)mm] and included angle value between the tangent from the blood clot forming point to the maximum curve radian of the chart and the horizontal line [Angle: (53.26±7.78) vs.(64.38±7.85)] in CHD + hypertension group, P<0.01 all.Spearman correlation analysis indicated that blood pressure level was significantly positive correlated with Angle and MA (r=0.607, 0.405, P<0.01 both), and significantly inversely correlated with R and K (r=-0.256,-0.541, P<0.01 both) in CHD + hypertension patients.Conclusion:Thrombosis possesses higher risk for CHD + hypertension patients, which is easier to cause acute cardiovascular events.Therefore, attention should be paid to coagulation function monitoring in order to prevent adverse cardiac events in these patients.
8.Excessive fluoride increases the expression of osteocalcin in the mouse testis.
Jian-Hua QIN ; Aierken DILINUER ; Shataer SAIMIRE ; Aierken KALIBINUER ; Mahemuti YUSUFU ; Aili YIRIZHATI ; Sai-Sai CUI ; Maimaitiming NUERSIMANGULI ; Wu-Jin CHEN ; Sheng-Bin BAI
National Journal of Andrology 2017;23(9):782-785
Objective:
To observe the influence of excessive fluoride on the levels of osteocalcin and testosterone in the testis of the male mouse.
METHODS:
Twenty-four C57BL/6J male mice were equally randomized into a normal control and a fluorosis model group, the former fed on distilled water while the latter on a solution of sodium fluoride (100 mg/L) in distilled water, both for 12 weeks. Then, the level of osteocalcin in the testis tissue was measured with the immunohistochemical streptavidin-peroxidase (SP) method and those of osteocalcin and testosterone in the serum determined by ELISA.
RESULTS:
After 12 weeks of fluoride intervention, the level of serum osteocalcin was significantly higher in the fluorosis models than in the normal controls ([68.05 ± 5.32] vs [47.50 ± 5.73] pg/mL, F = 11.901, P = 0.008), while that of testosterone markedly lower in the former than the latter group ([8.07 ± 1.35] vs [12.94 ± 3.09] ng/mL, F = 2.313, P = 0.006). The results of immunohistochemical SP showed the expression of osteocalcin in the cell membrane and cytoplasm of the fluorosis models, which was evidently higher than in the normal controls.
CONCLUSIONS
Twelve-week intake of 100 mg/L fluoride solution can decrease the level of testosterone and increase the expression of osteocalcin in the testis of the male mouse.
Animals
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Fluoride Poisoning
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metabolism
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Fluorides
;
toxicity
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Male
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Mice
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Mice, Inbred C57BL
;
Osteocalcin
;
metabolism
;
Random Allocation
;
Sodium Fluoride
;
toxicity
;
Testis
;
drug effects
;
metabolism
9.Influence of sand therapy in Uyghur medicine on mechanical properties of rabbits’ femur based on three-dimensional finite element modeling
Yanna LI ; Maitirouzi JULAITI ; Waili NIJIATI ; Shaojun HUANG ; Mahemuti DILINA ; Kelimu MUHETAER ; Rui ZHANG
Chinese Journal of Tissue Engineering Research 2016;20(27):3957-3962
BACKGROUND:On the basis of modern design method and numerical simulation, studies can explore the action mechanisms of sand therapy in Uyghur medicine.
OBJECTIVE:To explore a kind of non-homogeneous and isotropic biological bone finite element modeling method based on CT value, and to study the influence of sand therapy in Uyghur medicine on the mechanical properties of rabbits’ femur.
METHODS:Eight adult New Zealand white rabbits were used to establish osteoarthritis models of right posterior femur with papain. These rabbits were divided into sand therapy group and control group. In the sand therapy group, after treatment with sand therapy in Uyghur medicine, rabbit femoral models were scanned with CT. The fault image data were imported into MIMICS software. 3D model of femur was generated. The meshing was done. The material properties were given. Three-point bending in the Ansys was simulated and solved.Simultaneously, the isolated three point bending tests were performed in al rabbit models. The corresponding deflection and the maximum stress values were obtained. Finaly, the results obtained from the three-dimensional finite element modeling method were compared with the results obtained from the experiments.
RESULTS AND CONCLUSION:(1) The deflection and the maximum stress obtained by the three-point bending simulation analysis with the three-dimensional finite element model of the rabbits’ femur were wel correlated with the data obtained from the experiments. (2) These results indicate that the finite element modeling method is consistent with the structural and material properties of bone, which can be used to analyze the stress and deformation ofbones.
10.The clinical experience and plasmapheresis treatment outcome in treatment of hyperlipidemia acute pancreatitis among Uyghur.
Amutijiang MAHEMUTI ; Abudoushalamu ABUDOUREYIMU ; Ge CHEN
Chinese Journal of Surgery 2015;53(3):185-188
OBJECTIVETo investigate the clinical features and plasmapheresis treatment outcome of hyperlipidemic acute pancreatitis among Uyghur population.
METHODSThe clinical data of 41 cases (treatment group) diagnosed with acute hyperlipidemic pancreatitis and treated with plasmapheresis from August 2007 to August 2012 was studied, and treatment outcomes were statistically analyzed. Fifty patients during the same period who received medical treatment without plasmapheresis (control group) were collected, and were compared to the treatment group. Clinical data of 72 Han Chinese patients with hyperlipidemic acute pancreatitis from the same study period were compared to 91 Uyghur patients mentioned above. The data were analyzed by t-test or χ2 test.
RESULTSTreatment group and control group were comparable in terms of gender, age, APACHE II score at admission, BMI, and blood lipid levels. Thirty-two patients out of 41 in the treatment group were improved after routine medical treatment and plasmapheresis, but 9 died. In the control group, 28 out of 50 cases were improved, 22 died. The mortality of the treatment group was significantly lower than that of the control group(χ2 = 10. 824, P = 0. 001). Time of hospital stay in treatment group was (17 ± 16) days, and significantly shorter than that of control group ((28 ± 20) days) (t= 2. 851, P = 0. 005). Before plasmapheresis in the treatment group, serum triglyceride and total cholesterol levels were (58 ± 39) mmol/L and (24 ± 8) mmol/L, after plasmapheresis, these values dropped significantly to (10 ± 10) mmol/L and (6 ± 5) mmol/L. APACHE II score of those died were 18 ± 2, and significantly higher than those who survived(11 ± 3) (t = 0. 570, P = 0. 000); Time from hospital admission until plasmapheresis were significantly longer in died patients ((49 ± 9) hours) than in survived patients ((38 ± 8) hours, t = 3. 549, P = 0. 040). Furthermore, serum triglyceride levels were significantly higher in survived cases ((46 ± 16) mmol/L) than those who died ((37 ± 15) mmol/L) (t = 2. 386, P = 0. 010) . Both serum triglyceride and cholesterol levels were reduced significantly in control group (t = 3. 484, P = 0. 00; t = 4. 086, P = 0. 000, but the degrees of reduction were significantly lower than that of the treatment group. When comparing Uyghur patients to Han patients, Uyghur cases had higher serum triglyceride (t = 2. 083, P = 0. 039), and cholesterol levels (t = 2. 535, P = 0. 012, and their age was significantly younger than that of Hans (t = 3. 373, P = 0. 010 .
CONCLUSIONSs Uyghur patients with hyperlipidemia acute pancreatitis tend to have higher serum triglyceride and cholesterol levels, and age at disease onset is younger. Plasmapheresis is a more effective treatment option for patients with hyperlipidemia acute pancreatitis. Treatment outcome is related to APACHE II score, serum triglyceride levels, and time frame between admission and plasmapheresis treatment.
APACHE ; Acute Disease ; Asian Continental Ancestry Group ; Humans ; Hyperlipidemias ; complications ; therapy ; Length of Stay ; Pancreatitis ; complications ; therapy ; Plasmapheresis ; Time-to-Treatment ; Treatment Outcome ; Triglycerides ; blood


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