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Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.
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Animals , Humans , Medicine, Chinese Traditional , Hot Temperature , Pancreatic Neoplasms/therapy , Models, Animal , SyndromeABSTRACT
BACKGROUND:Compared with traditional two-dimensional culture,three-dimensional microtissue culture can show greater advantages.However,more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE:To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS:Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing.DNA quantification and nuclear staining were used to verify the success of decellularization,and histological staining was used to observe the matrix retention before and after decellularization.The microcarriers were characterized by scanning electron microscopy and CCK-8 assay.Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods.The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy,live and dead staining,and RT-qPCR. RESULTS AND CONCLUSION:(1)Cartilage-derived microcarriers were successfully prepared.Compared with before decellularization,the DNA content significantly decreased after decellularization(P<0.001).Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen,maintaining the characteristics of the natural extracellular matrix of cartilage cells.CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation.(2)Scanning electron microscopy and live and dead staining results showed that compared with the three-dimensional static group,the three-dimensional dynamic group had a more extended morphology of microtissue cells,and extensive connections between cells and cells,between cells and matrix,and between matrix.(3)The results of RT-qPCR showed that the expressions of SOX9,proteoglycan,and type Ⅱ collagen in microtissues of both groups were increased at 7 or 14 days.The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days(P<0.05).At 21 days,the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group(P<0.001).(4)The results showed that compared with three-dimensional static culture microtissue,three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time,showing better cell viability and chondrogenic ability.
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AIM: To explore the pathogenesis and surgical outcomes of different types of myopic traction maculopathy(MTM)using optical coherence tomography(OCT).METHODS: A total of 193 patients(210 eyes)with MTM were retrospectively included, of which 74 eyes(35.2%)underwent vitrectomy combined with internal limiting membrane(ILM)peeling. The patients were categorized into three groups: foveal detachment(FD), foveoschisis(FS)and lamellar macular hole(LMH). Based on the central foveal thickness(CFT)at baseline(M0), eyes with FD were classified into two subgroups: extensive FD and limited FD. Outcomes included best-corrected visual acuity(BCVA), CFT, posterior staphyloma height(PSH), the presence of epiretinal membrane(ERM)and ILM detachment. Risk factors for BCVA at 6mo after vitrectomy(M6)were analyzed using linear regression.RESULTS: At M0, ERM was highly present in eyes with LMH(rs=0.28, P<0.001). Eyes with FD and FS were characterized by higher incidence of ILM detachment(rs=-0.25, P<0.001). After vitrectomy, CFT and BCVA significantly improved in all eyes(P<0.001). Eyes with extensive FD were characterized by a thicker CFT(rs=0.56, P<0.001), a lower incidence of ILM detachment(rs=-0.25, P=0.034)and a thicker nasal PSH(rs=0.27, P=0.024)than eyes with limited FD. Eyes with extensive FD were associated with a worse BCVA at M0(P=0.013)and M6(P=0.030)than eyes with limited FD. Extensive FD(β=-0.295, P=0.042)and BCVA at M0(β=0.669, P<0.001)were risk factors for a worse BCVA at M6.CONCLUSION: There are several pathogenetic mechanisms in MTM. ILM detachment may exert a dominant role in the development of FD and FS, while ERM may have a role in LMH. Vitrectomy combined with ILM peeling improved functional and anatomical outcomes in MTM patients. Eyes with extensive FD may carry a poor prognosis.
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Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.
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Female , Humans , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Anastrozole , Aromatase Inhibitors/therapeutic use , Bilirubin , Breast Neoplasms/drug therapy , Letrozole , Liver , Retrospective Studies , ToremifeneABSTRACT
Aim To investigate the regulatory effect of glucagon on gluconeogenesis in liver, kidney and intes¬tine during different fasting periods and the underlying mechanism. Methods The 8-week-old male C57BIV 6J mice were randomly divided into six groups ( n = 6) :control group, control + glucagon group, fasting 18 h group, fasting 18 h + glucagon group, fasting 36 h group, and fasting 36 h + glucagon group. Glucose, triglyceride ( TG) and free fatty acids ( FFAs ) kits were used to detect their serum contents in mouse in-traperitoneal injection of glucagon at different fasting time points. Besides, liver/muscle glycogen assay kit and PAS staining were used to detect the glycogen con¬tents in liver tissue. RT-PCR method was used to observe the effects of glucagon on the gene expressions of peroxisome proliferators-activated receptor y coactivator la (PGC-1α), glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 (PEPCK) in liver, kidney and intestine of mice at different fasting time. Western blot was employed to detect the protein expressions of PGC-1α, G6Pase, PEPCK, phosphoryl-ase protein kinase A ( p-PKA) , protlein kinase A (PKA) , phosphorylase cAMp-response element binding protein (p-CREB) and cAMp-response element binding protein (CREB) in liver, kidney and intestine of mice were. Results (1) Glucagon increased the serum glucose level, reduced serum TG and FFAs levels, and reduced the hepatic glycogen content. (2) Glucagon promoted gluconeogenesis via upregulation of PGC-1α. On the stimulation of glucagon, PGC-1α gene and protein expressions in liver were significantly raised by glucagon when the mice were fasted 18 h and 36 h, while the gene and protein expressions of PGC-1α in kidney were obviously up-regulated by glucagon after fasting 18 h. However, PGC-1α gene and protein expressions in intestine were significantly elevated by glucagon at 36 h after fasting. (3 ) Glucagon induced gene and protein expressions of gluconeogenesis-related enzymes G6Pase and PEPCK in liver, kidney and intestine after fasting. (4 ) Glucagon upregulated p-PKA/PKA and p-CREB/CREB in liver. Conclusions Glucagon shows temporal difference in the gluconeo-genic response of liver, kidney and intestine in mice. Glucagon promotes the gene and protein expressions of key gluconeogenic enzymes G6Pase and PEPCK by increasing PGC-1α gene and protein expression, and thus increasing fasting blood glucose. Besides, glucagon promotes hepatic gluconeogenesis via PKA/CREB signaling pathway.
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Objective@#To explore the association between aggression and social support and their gender differences among Chinese adolescence, and to provide a scientific reference for preventing and reducing aggressive behaviors of adolescents.@*Methods@#Conducted a cross sectional survey of 15 623 adolescents in 5 provinces in China, namely, HeiLongjiang, Hubei, Anhui, Guangdong and Yunnan Province. And the Chinese version of the Adolescent Social Support Scale was employed to assess the aggression and social support, life events, psychological characteristics, family condition and demographic characteristics among adolescents.@*Results@#The prevalence of self reported high level of aggression was 23.5%(3 670/15 623). Males reported higher rate of high level aggression than females (24.4% vs 22.5%, χ 2=19.30, P <0.01). Significant association between aggression and social support was identified in univariate analysis ( χ 2=620.68, P <0.01). After controlling for potential confounders, aggression was also significantly negatively associated with social support ( OR =1.27-1.84), and there was dose response relationship between them( P < 0.05 ). Furthermore, the association between aggression and social support was similar among male participants and female participants ( ROR =1.02-1.10, P >0.05).@*Conclusion@#The findings indicate that aggression is associated with social support both in male and female adolescents. Improving the social support for adolescents can reduce their aggressive behaviors.
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Aim To explore the role of angiotensin U type 1 a reeeptor ( AT 1 aR ) , an important component of HAS, in obesity-induced insulin resistance.Methods Wild type ( WT) and ATlaR gene knockout (ATlaR ) SD rats were fed with normal diet and 60% high-fat diet for 12 weeks, respectively.After 12 weeks, blood was collected from the abdominal aorta of rats to obtain serum, and the serum insulin level was measured by ELISA.The epididvmal adipose tissue was obtained, and gene expressions of peroxisome pro- liferator-activated receptor -y ( PPAR7) and sterol reg¬ulator}' element binding protein lc (SREBP-lc) in ad¬ipose tissue were detected by RT-PCR method.The protein expressions of insulin signaling pathway and protein kinase C (PKC) in adipose tissue were detec¬ted by Western blot.Results ATI aR knockout signif¬icantly reduced HOMA-IR and improved insulin resist¬ance induced by high-fat diet.In ATlaR rats fed with high-fat, the protein expressions of insulin signa¬ling pathway were much higher than those of WT rats, indicating that ATlaR gene knockout improved the in¬sulin signaling pathway in high-fat diet.In addition, the PKCa, PKCe and PKCr| expressions of ATlaR rats were significantly lower than those of WT rats.And the gene expressions of PPAR-y and SREBP-lc, which promoted adipogenic differentiation, significantly increased in ATlaR rats fed with a high-fat diet, demonstrating that ATlaR knockout promoted adipo¬genic differentiation.Conclusions ATlaR knockout significantly improves high-fat diet induced 1R by en¬hancing protein expressions of insulin signaling path¬way, inhibiting PKC expression and promoting adipo¬genic differentiation.
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Basic local alignment search tool (BLAST) is one of the popular sequence similarity analysis tools. However, some students and researchers just blindly use the default parameters. Moreover, some students are confused about how to choose the right program. In a word, it is prone to be misused and researchers often draw conclusions incorrectly. In view of this, we traced back the internet hot topic in early 2020 - "MORDERATELY STRONG CONFIRMATION OF A LABORATORY ORIGIN OF COVID-19", and took it as teaching materials to guide the student to use BLAST currently through reanalyzing and reproducing the source of errors. Then we arranged an interesting experiment about fabricating dinosaur genes through modifying a chicken gene. In the experimental design to make the students grasp the BLAST tools better, one group fabricated the dinosaur gene and the other group decrypted the added bases. This instructional design could be conducive to cultivate students ' ability about distinguishing different viewpoints correctly, and we hope it can be enlightening and helpful to the teaching of BLAST tools.
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Schisandrol B (SolB) is one of the active constituents from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. Our previous studies found that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. We further found that SolB significantly induces liver enlargement but the mechanisms remain unclear. The purpose of this study was to investigate the change of lipidome in liver tissues during SolB-induced hepatomegaly. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. Serum and liver samples of male C57BL/6 mice were collected after intraperitoneal injection of SolB (100 mg·kg-1·d-1) for 5 days. Lipidomics analysis was performed using Q Exactive UHPLC-MS/MS system. The results showed that SolB significantly promoted liver enlargement in mice without liver injury and inflammation. Lipid accumulation was observed in the liver tissues after SolB treatment. Thirty-five lipids were identified with significant change and triglycerides (TG) were found to have the most significant increase in SolB-treated group, indicating the increase of energy production during SolB-induced hepatomegaly. This study reveals the impact of SolB on lipid metabolism and provides a potential explanation for liver enlargement induced by SolB.
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The phenolic constituents of Wikstroemia chamaedaphne were investigated by various column chromatographic methods including silica gel,Sephadex LH-20,ODS and preparative HPLC,and their chemical structures were identified by physico-chemical properties and spectral analyses. Thirteen phenolic compounds were isolated and elucidated,including five flavonoids: luteolin 7-O-β-D-glucopyranoside(1),luteolin 4'-O-β-D-glucopyranoside(2),kaempferol 3-O-β-D-glucopyranoside(3),chrysoeriol 4'-O-β-D-glucopyranoside(4),chrysoeriol(5); and eight lignans:(-)-secoisolariciresinol(6),acanthosessilin A(7),(-)-nortrachelogenin(8),(+)-isolariciresinol(9),sesamin(10),syringaresinol(11),(+)-epipinoresinol(12),and [3,3',4,4'-tetrahydro-6,6'-dimethoxy-3,3'-bi-2 H-benzopyran]-4,4'-diol(13). Compounds 1, 3, 5-8, 10, 11 and 13 were obtained from the plants of W. chamaedaphne for the first time,and compounds 1,5,7,10 and 13 were obtained from the Wikstroemia genus for the first time.
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Chromatography, High Pressure Liquid , Flavonoids , Molecular Structure , Phenols , Phytochemicals , Wikstroemia , ChemistryABSTRACT
Objective:Stems,petioles,stem sections with axillary and leaves of Scrophularia ningpoensis were taken as the material in vitro to screen out the suitable plantlet regeneration system and optimal exercising seedling conditions. Method:Different explants,hormones and concentrations on the induction and proliferation of cluster bud were studied by L16(45) orthogonal test. One factor analysis of variance (ANOVA) was made on the induction of adventitious buds rooted with different concentrations of hormones. At the same time,different substrates,watering cycles and transition modes were selected to optimize key technologies of exercising seedlings of S. ningpoensis. Result:Stem sections with axillary was the best explant,which was followed by stems,leaves and petioles. The suitable media for the induction of adventitious buds was MS+6-BA 0.5 mg·L-1+NAA 0.2 mg·L-1,with the induction rate of 100.0% and the proliferation multiple of 9.84.The suitable media for root induction was 1/2 MS+IBA 0.2 mg·L-1,with the rooting rate of 100.0% and the number of roots of 39.45.For matrix,they were transplanted with nutrient soil,vermiculite and perlite (5:2:1) as the media,to keep proper matching of fertility,permeability and water retention. The container seedlings can grow well,and the survival rate was more than 95% when they were watered every 2 days,the acclimatization of plantlets took 20 days indoor and 10 days in shaded greenhouses. Conclusion:The clonal propagation system of S. ningpoensis was established to provide an effective way for the efficient,rapid and steady plantlet regeneration,the breeding of high-quality seedlings and the suitable exercising seedling conditions of S. ningpoensis.
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Objective To study the influences of meconium-stained amniotic fluid (MSAF) and chorioamnionitis (CA) on maternal and infant infection.Method From July to December 2014,full-term single birth newborns with MSAF born in our hospital were assigned into the MSAF group.According to the pathological characteristics of the placenta,they were further assigned into CA group and non-CA group.The healthy single birth full-term infants without MSAF were assigned into the control group.The influences of MSAF and CA on maternal and infant infection were analyzed.Result A total of 178 MASF cases were enrolled,including 57 cases with CA and 121 cases without CA.42 infants were in the control group.The incidence of CA with MSAF (32.0%,57/178) was significantly higher than the control group (4.8%,2/42) (P<0.05).The white blood cell counts on the first day of the CA group and non-CA group were (29.4±8.9)x 109/Land (22.8±4.8)x 109/L,respectively.36.8% of the CA group had increased CRP within 3 days after birth,while 15.7% in the non-CA group.The incidence of neonatal infection were 49.1%(28/57) in the CA group,and 20.7%(25/121) in the non-CA group.The incidence of meconium aspiration syndrome was 28.1%(16/57)in the CA group,and 8.3%(10/121) in the nou-CA group.The differences between the two groups were statistically significant (P<0.05).The proportion of neutrophils of the mother was (80.3±7.3)% in the CA group,and (76.4±7.6)% in the non-CA group.22.8%(13/57) of the mothers in the CA group had fever before and after delivery,and 9.9%(12/121) in the non-CA group.The incidence of uterine infection was 8.8%(5/57) in the CA group and 0%(0/121) in the non-CA group.The postpartum hemorrhage rate was 24.6%(14/57) in the CA group,and 3.3%(4/121) in the non-CA group.The differences were statistically significant (P<0.05).Conclusion The incidence of CA in MSAF neonates is higher,resulting increased incidences of neonatal infection,maternal fever,and uterine infection.
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Objective To investigate the effect of low dose heparin on blood coagulation and therapeutic outcomes in premature infants with sepsis.Methods Clinical data of 69 septic preterm newborns weighting less than 1 500 g treated in Beijing Obstetrics and Gynecology Hospital were retrospectively analyzed.Among them,29 infants received heparin therapy (6 U/kg,q 8 h,for 3 d,then q12 h,heparin group)and 40 infants did not receive heparin therapy (control group),the coagulation index and therapeutic outcomes were compared between two groups.Results The coagulation indexes PT,TT,APTT and D dimer in heparin group were all significantly lower than those in control group [(15.5±3.5) s vs.(19.0±3.9) s,(15.4±3.5) s vs.(18.8±3.5) s,(47.5±8.6) s vs.(58.4±18.1) s,(1.7±0.8) mg/L vs.(2.6±1.9) mg/L;t=-3.815,4.275,-3.004,-2.459,P<0.05].The overall clinical effective rate in heparin group was significantly higher than that in control group (86.2% vs.60.0%,x2 =4.408,P<0.05).Conclusion Low dose heparin can significantly improve the blood coagulation function and improve the therapeutic effect of premature infants with sepsis.
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Objective:To analyze and identify the brain and blood absorption components of rats after intragastric administration of Buyang Huanwu Tang(BYHWT). Method:The brain tissue,plasma of normal rats and the cerebral ischemia-reperfusion rats were analyzed by UPLC-Q-TOF-MS/MS.The prototype components in BYHWT were identified according to retention time,accurate relative molecular weight,primary and secondary mass spectrometry data. Result:After the administration of BYHWT,five compounds were found to enter the normal brain tissue through the blood-brain barrier and identified as calycosin-7-glucoside,albiflorin,formononetin-7-O-β-D-glucoside-6″-O-acetyl,safflower yellow A and astragaloside A;two compounds penetrated the blood-brain barrier and entered modeling brain tissue,and they were identified as calycosin-7-glucoside and formononetin-7-O-β-D-glucoside-6″-O-acetyl;seven compounds entered normal plasma and were identified as calycosin-7-glucoside,albiflorin,hydroxysafflor yellow A,et al;three compounds entered model plasma and identified as calycosin-7-O-β-D-glucoside-6″-O-acetyl,6″-O-acetyl-(6αR,11αR)-9,10-dimetho-xypterocarpan-3-O-β-D-glucoside and formononetin-7-O-β-D-glucoside-6″-O-acetyl. Conclusion:BYHWT has different pharmacological material basis in normal and cerebral ischemia-reperfusion rats.
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Objective To study the effects of maternal gestational diabetes mellitus (GDM) on neonatal cardiac development.Method From January to December in 2016,full-term neonates of GDM mothers admitted to the neonatal department of our hospital were retrospectively included as the GDM group,and full-term neonates with non-GDM mothers during the same period as the control group.Their birth weight,length,placenta weight,birth weight/placenta weight ratio,echocardiographic cardiac measurements within the first week,and the incidence of congenital heart disease were compared between the two groups.Multivariate linear regression analysis was used to analyse the possible factors causing neonatal ventricular septal hypertrophy in GDM group.Result A total of 104 cases in the GDM group and 107 cases in the control group were included.Significant differences existed in birth weight,length and placental weight between the two groups (P < 0.05).No significant differences in gender,gestational age and birth weight/placental weight ratio between the two groups (P > 0.05).The width of the aorta and main pulmonary artery,the size of the left atrium,the left ventricle and the right ventricle,and the thickness of the ventricular septum in the GDM group were greater than the control group,the differences were statistically significant (P < 0.05).The ventricular septal thickness of the GDM group was greater than the control group [≥3500g:(3.6±0.5) mmvs.(3.3±0.3) mm,<3500g:(3.5±1.0) mmvs.(3.1 ± 0.4) mm],the difference was statistically significant (P < 0.05).The incidence of congenital heart disease was 4.8% (5/104) in the GDM group and 0% in the control group.The difference between the two groups was statistically significant (P < 0.05).Multivariate linear regression analysis showed that the interventricular septal thickness of the GDM group was positively correlated with the levels of HbA1c,HbA1 c,insulin of their mothers during pregnancy and birth weight of the newborn (P < 0.05).Conclusion GDM mother may pose adverse effects on neonatal myocardial development.Further research is needed on its mechanism and how to monitor the incidence.
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Diabetes can cause a significant increase in the expression of thioredoxin (Trx)-interacting protein (TXNIP), which binds to Trx and inhibits its activity. The present study was aimed to investigate the effect of TXNIP on proliferation of rat INS-1 islet β cells and the underlying mechanism. TXNIP overexpressing adenovirus vectors (Ad-TXNIP-GFP and Ad-TXNIPc247s-GFP) were constructed and used to infect INS-1 cells. Ad-TXNIPc247s-GFP vector carries a mutant C247S TXNIP gene, and its expression product (TXNIPc247s) cannot attach and inhibit Trx activity. The expression of TXNIP was detected by real-time PCR and Western blot. EdU and Ki67 methods were used to detect cell proliferation. Protein phosphorylation levels of ERK and AKT were detected by Western blot. The results showed that both TXNIP and TXNIPc247s protein overexpressions inhibited the proliferation of INS-1 cells, and the former's inhibitory effect was greater. Moreover, both of the two kinds of overexpressions inhibited the phosphorylation of ERK and AKT. These results suggest that TXNIP overexpression may inhibit the proliferation of INS-1 cells through Trx-dependent and non-Trx-dependent pathways, and the mechanism involves the inhibition of ERK and AKT phosphorylation.
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This study investigated the effect of angiotensin II (Ang II) on apoptosis and thioredoxin-interacting protein (TXNIP) expression in INS-1 islet cells and the underlying mechanism. INS-1 cells cultured in vitro were treated with different concentration of Ang II for different time, and the viability was measured using cell counting kit-8 (CCK-8). After treatment with 1 × 10 mol/L Ang II for 24 h, flow cytometry and Western blot were used to measure the cell apoptosis, and Western blot was used to analyze the protein expression of TXNIP, carbohydrate response element-binding protein (ChREBP) and angiotensin II type 1 receptor (AT1R). Real-time PCR was used to detect TXNIP and ChREBP mRNA expression. IF/ICC was used to observe the TXNIP, ChREBP and AT1R expression. The results showed that Ang II reduced cell viability and induced the expression of TXNIP in a dose- and time-dependent manner (P < 0.05, n = 6) compared with the control group. Ang II induced apoptosis and up-regulated the expression of ChREBP and AT1R (P < 0.05, n = 6). AT1R inhibitor, telmisartan (TM), blocked Ang II-induced TXNIP and ChREBP overexpression (P < 0.05, n = 6) and inhibited Ang II-induced apoptosis. Taken together, Ang II increased ChREBP activation through AT1R, which subsequently increased TXNIP expression and promoted cell apoptosis. These findings suggest a therapeutic potential of targeting TXNIP in preventing Ang II-induced INS-1 cell apoptosis in diabetes.
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AIM:To explore whether the angiotensin II type 1 receptor autoantibodies(AT1-AA)induces islet β-cell apoptosis and whether autophagy is involved in the process.METHODS:The INS-1 cells treated with AT1-AA at 10-6mol/L for 24 h,and then the apoptosis was analyzed by flow cytometry,Western blot and Hoechst 33258 staining.In addition,the expression of autophagy-related proteins such as LC3 and beclin 1 were determined by Western blot.The effects of AT1-AA on the apoptosis,autophagy and viability of INS-1 cells with or without 3-methyladenine(3-MA;a com-mon autophagy inhibitor)or telmisartan(an angiotensin Ⅱ type 1 receptor blocker)pretreatment, were detected by flow cytometry,Western blot and CCK-8 assay.RESULTS: Treatment with AT1-AA at 10 -6mol/L for 24 h significantly re-duced the cell viability(P<0.05).Compared with the negative IgG control group,the apoptotic cells increased after incu-bation with AT1-AA for 12 h,24 h and 36 h,respectively(P<0.05).Moreover,the protein levels of LC3 and beclin 1 also increased gradually with the prolongation of treatment time,and the elevation of apoptosis and autophagy were blocked by telmisartan.After pretreatment with 3-MA, the apoptotic rate of the cells was obviously decreased compared with the cells treated with AT1-AA alone.CONCLUSION: AT1-AA induces the apoptosis of INS-1 islet βcells by upregulating autophagy via the angiotensin Ⅱtype 1 receptor pathway.
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Objective:To explore the configuration of air conditioner and ventilating system of large medical equipment in comprehensive hospital so as to meet the normal operation of various large medical equipment of hospital.Methods: Facing to the characteristics, that the requirements of large medical equipment on air conditioner and ventilating system were higher than that of common equipment and the configuration requirements of different large medical equipment on air conditioner and ventilating system were different, the allocation according to the demands was adopted.Results:Depended on the equipment parameter and requirement of actual operation of linear acceleration, magnetic resonance imaging (MRI), computed tomography (CT) and the machine room of digital subtraction angiography (DSA) in the items of new medical technique building of hospital to design the configuration plan of air conditioner and ventilating system of large medical equipment so as to ensure their normal operation. Conclusion: In the planning programming and construction management of air conditioner and ventilating system of large medical equipment, the different characteristics of them should be considered so as to establish better basis for installation, debugging and operation of equipment in later period. At the same time, these can provide better medical environment for patients and medical staff.
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Objective To investigate the role of RNA binding protein─upstream-of-N-Ras (UNR) in the development of glioma and its molecular mechanism.Methods First, bioinformatics analysis of CGGA database was performed to detect UNR expression level and prognosis of patients with glioma. Western blot and real-time PCR were used to detect UNR expression level in glioma cell lines and tissues. Next, UNR siRNAs were transfected in glioma cells, and MTS assay and scratch wound-healing assay were used to detect changes in cell proliferation and migration. Then, the candidate UNR target mRNAs were identified by analyzing the sequencing data of UNR iCLIP-seq, RNA sequencing and ribosome profiling databases of human melanoma. RNA immunoprecipitation and biotin pull-down assays were used to identify the UNR target mRNAs in glioma cells. Finally, western blot was used to detect the effect of UNR knockdown on ribosomal protein L9 (RPL9) and RPL9 protein expression level in glioma cell lines. RPL9 siRNA was transfected in A172 and T98G and the expression of vimentin in the cells was detected with western blot.Results Bioinformatics analysis showed that UNR mRNA expression level was significantly higher in high-grade glioma [Grade 2 (n=126), Grade 3 (n=51), Grade 4 (n=128), P<0.001]. UNR high expression levels were associated with poor prognosis (P=0.0177). UNR had high expression level in glioma cell lines and patient samples compared with normal cell lines and normal brain samples (P<0.01). Knockdown of UNR inhibited glioma cells migration (P<0.05), but did not inhibit glioma cells growth in three glioma cell lines. UNR binded the 3' untranslated region (UTR) of PTEN and RPL9 mRNAs. RPL9 protein was significantly highly expressed in most glioma cell lines (n=9) and knockdown of UNR resulted in a downregulation of RPL9 protein expression. Epithelial-mesenchymal transition (EMT)-related marker─vimentin was positively regulated by RPL9.Conclusions UNR could bind to the 3'UTR of PTEN and RPL9 in glioma cell lines, therefore promoting glioma cell migration and regulating the expression of RPL9. Here, we establish a link between UNR and RPL9 protein, which will provide new ideas for the further study of glioma.