Excessive gestational weight gain in the first trimester is associated with risk of gestational diabetes mellitus: a prospective study from Southwest China.

OBJECTIVE: To evaluate the effects of gestational weight gain (GWG) in the first trimester (GWG-F) and the rate of gestational weight gain in the second trimester (RGWG-S) on gestational diabetes mellitus (GDM), exploring the optimal GWG ranges for the avoidance of GDM in Chinese women. DESIGN: A population-based prospective study was conducted. Gestational weight was measured regularly in every antenatal visit and assessed by the Institute of Medicine (IOM) criteria (2009). GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. Multivariable logistic regression was performed to assess the effects of GWG-F and RGWG-S on GDM, stratified by pre-pregnancy BMI. In each BMI category, the GWG values corresponding to the lowest prevalence of GDM were defined as the optimal GWG range. SETTING: Southwest China. PARTICIPANTS: Pregnant women (n 1910) in 2017. RESULTS: After adjusting for confounders, GWG-F above IOM recommendations increased the risk of GDM (OR; 95 % CI) among underweight (2·500; 1·106, 5·655), normal-weight (1·396; 1·023, 1·906) and overweight/obese women (3·017; 1·118, 8·138) compared with women within IOM recommendations. No significant difference was observed between RGWG-S and GDM (P > 0·05) after adjusting for GWG-F based on the previous model. The optimal GWG-F ranges for the avoidance of GDM were 0·8-1·2, 0·8-1·2 and 0·35-0·70 kg for underweight, normal-weight and overweight/obese women, respectively. CONCLUSIONS: Excessive GWG in the first trimester, rather than the second trimester, is associated with increased risk of GDM regardless of pre-pregnancy BMI. Obstetricians should provide more pre-emptive guidance in achieving adequate GWG-F.

[Energy intake as determinants of gestational weight gain in Chengdu].

OBJECTIVE: To examine the relation between energy intake and its sources and gestational weight gain( GWG). METHODS: In this prospective cohort study, 585 healthy women with singleton pregnancy were selected in 2013. The 24-hour recalls was used to collect food intake at the first, second and last trimesters, and energy intake and percentages of energy from macronutrient were calculated. Weight measuring were administered at( 12 ± 1) th, ( 28 ± 1) th weeks' gestation and last week before delivery, and the GWG rate was calculated. Multivariable linear regression was used to analyze therelationship between energy and GWG. RESULTS: The mean energy intake for the first, second and last trimesters were 1718. 6 kcal/d, 2202. 9 kcal/d and 2313. 4 kcal/d, respectively, the average percentages of energy from carbohydrate were 62. 6%, 59. 5%and 59. 1%, respectively, the average percentages of energy from fat were 21. 8% 、23. 9% and 24. 3%, respectively, the average percentages of energy from protein were15. 6% 、16. 5% and 16. 7%, respectively. Multiple linear regression analysis showed that energy intake during pregnancy was positively correlated with GWG during pregnancy( P < 0. 05). The adjusted weight gain for each trimester was 37. 3 g/week( 95% CI 22. 8 to 51. 8, P < 0. 05), 16. 8 g/week( 95% CI 4. 8 to 28. 8, P < 0. 05), and 25. 8 g/week( 95% CI 10. 6 to 41. 1, P < 0. 05) higher in the highest( Q5) versus lowest( Q1)quintile of energy intake. The adjusted weight gain in last trimester was 19. 1 g/week higher( 95% CI 3. 1 to 35. 1, P < 0. 05) in the highest( Q5) versus lowest( Q1) quintile of percentages of energy from carbohydrate. The adjusted weight gain in last trimester was16. 2 g/week lower( 95% CI-3. 1 to-0. 9, P < 0. 05) in the highest( Q5) versus lowest( Q1) quintile of percentages of energy from fat. CONCLUSION: A positive correlation is found between dietary energy intake and GWG. Percentages of energy from carbohydrate and fat in the last trimester have a significant effect on GWG.

[Effect of gestational weight gain on the neonatal birth weight among pregnancy women in Chengdu City].

OBJECTIVE: To explore the effects of total gestational weight gain( GWG)and gestational weight gain rate( GWGR) per trimester on the neonatal birth weight. METHODS: A prospective cohort study was conducted among 549 healthy pregnant women at the( 12 ± 1) th pregnant week from Chengdu City, China who delivered a singleton. Basic information about age, pre-gestational weight and so on was collected by questionnaire, while the height and weight were measured at the first time. Weight at the( 28 ± 1) th and last week before delivery was measured respectively, while the total GWG and the different trimester GWGR were calculated and assessed by Institute of Medicine( IOM) criteria( 2009). The gestational week, neonatal weight and other information were collected after delivery. Multiple non-conditional Logistic regression models were used to test the effect of the total GWG/GWGR per trimester on neonatal birth weight. RESULTS: The total GWG was( 16. 2 ± 4. 6) kg. The prevalence of abnormal total GWG was 59. 1%, the excessive GWG was 44. 3%. The prevalence of insufficient GWGR in the first trimester was 44. 3%. In the second, third, the second and third trimester, the prevalence of excessive GWGR were 63. 6%, 55. 7% and 65. 8%, respectively. After adjusting the age at delivery, pre-pregnancy body mass index, gestational week and other confounding factors, the result showed that compared with adequate GWG group, insufficient GWG group was increased risk of small for gestational age( SGA)( OR =2. 51, 95% CI 1. 08-5. 82), excessive total GWG group was increased risk of large for gestational age( LGA)( OR = 2. 54, 95% CI 1. 20-5. 36). Compared with adequate GWGR group in the second trimester, excessive GWGR group was decreased risk of SGA( OR = 0. 27, 95% CI 0. 13-0. 60). Compared with adequate GWGR group in the second and third trimester, excessive GWGR group was decreased risk of SGA( OR = 0. 28, 95%CI 0. 13-0. 59). CONCLUSION: Abnormal total GWG among pregnant women in Chengdu City is a big problem that both excessive and insufficient GWG existed. Excessive total GWG is the independent risk factor for LGA. GWGR in the second and the second and third trimester are significantly associated with SGA.

[Effect of gestational weight gain rate on pregnancy outcomes among Chengdu City pregnant women with normal pre-pregnancy body mass index].

OBJECTIVE: To explore the association between gestational weight gain rate( GWGR) and pregnancy outcomes among pregnant women with normal pre-pregnancy body mass index( BMI). METHODS: In this prospective study, 389 healthy pregnant women at the( 12 ± 1) th with normal pre-pregnancy BMI from Chengdu City who delivered a singleton were included in 2013. The basic information such as age, pre-pregnant weight was obtained by questionnaire, height and weight was measured. Then the weight was measured at the( 28 ± 1) th and last week before delivery, respectively, the different trimester GWGR was calculated and classified by IOM criteria. Gestational age, gestational diabetes mellitus( GDM) and other pregnancy outcomes were collected by questionnaire. Multiple non-conditional Logistic regression models were used to test the association between GWGR and pregnancy outcomes. RESULTS: The proportion of insufficient GWGR and excessive GWGR in first trimester was 50. 7% and 31. 8%, respectively, the proportion of excessive GWGR in the second and third trimester was68. 5% and 57. 8%, respectively. After adjusting the age, education, gravidity and family disease history and other confounding factors, multiple non-conditional logistic regression showed: compared with adequate GWGR in the third trimester, insufficient and excessive GWGR were associated with increased risk of cesarean delivery( OR = 2. 48, 95% CI 1. 18-5. 23 and OR = 1. 76, 95% CI 1. 02-3. 03, respectively). Compared with adequate GWGR in the first trimester, excessive GWGR were associated with increased risk of GDM( OR = 2. 55, 95% CI 1. 03-6. 28). CONCLUSION: The abnormal of GWGR would increase the risk of cesarean delivery and GDM.

[Moderate-to-vigorous Physical Activities and Gestational Weight Gains during the Second and Last Trimesters of Pregnancy].

OBJECTIVE: To determine the level of moderate-to-vigorous physical activities (MVPA) and its relationship with gestational weight gains (GWG) in the second and the last trimesters of pregnancy. METHODS: A prospective study was conducted in Chengdu on 362 healthy pregnant women at the 24-28 gestation weeks who delivered a singleton. Demographic data and pre-pregnancy body mass were collected using a questionnaire. Weight gains at the gestation weeks of 24-28 and 32-36 were measured for the first two trimesters and the last trimester of pregnancy. The Denmark self-reported physical activity scale was used for measuring the duration and intensity of physical activities. Multiple linear regression models were established to determine the relationship between MVPA and GWG. RESULTS: The last trimester had lower average daily MVPA 〔(0.76±0.93) h〕 compared with the second trimester 〔(1.61±1.61) h, t=9.056, P<0.001〕. About 74.6% of the participants met the PA recommendations for the second trimester, compared with 60.5% for the last trimester (χ2=16.387, P<0.001). The participants experienced an average GWG of (7.36±3.78) kg during the first two trimesters, and (5.80±2.57) kg during the last trimester, corresponding to a growth rate of (0.30±0.15) kg/week for the first two trimesters and (0.51±0.22) kg/week for the last trimester. Compared with the most inactive group, the participants with medium PA experienced less GWG 〔(5.34±2.91) kg vs.(6.26±2.54) kg, P<0.05〕 and a lower GWG rate 〔(0.48±0.26) kg/week vs.(0.56±0.20) kg/week, P<0.05〕 during the last trimester. Age, gestational week, ethnicity, pre-pregnant BMI, GDM, pre-pregnant smoking and employment were associated with GWG and the GWG rates during the first two trimesters and the third trimester (P<0.05). Compared with the most inactive group, low 〔-0.358(-0.691--0.026)〕 and medium 〔-0.762(-1.486- -0.037)〕 PA were associated with lower GWG during the last trimester. Moderate PA was associated with a lower GWG rate 〔-0.071(-0.133--0.008)〕 after adjustment for gestational age, energy intake, pre-pregnancy BMI and other potential confounders. CONCLUSIONS: Insufficient physical activities are a serious problem in the pregnant women of Chengdu over the last two trimesters. Appropriate MVPA in the last trimester of pregnancy may reduce GWG and GWG rates.

[A longitudinal study of anemia status and its association with postpartum hemorrhage among pregnant women in Chengdu, China].

OBJECTIVE: To investigate the anemia status and its changing trend among pregnant women in Chengdu, China, and to explore the association between anemia and postpartum hemorrhage. METHODS: A total of 548 healthy singleton primiparas were selected and followed up from three hospitals in Chengdu until delivery. Data on maternal demographic characteristics, delivery information were collected with questionnaire, and the hemoglobin( Hb) concentration was determined using cyanide methemoglobin method in each trimesters. Mixed fitting logistic regression models were performed to test the association between anemia and postpartum hemorrhage. RESULTS: The overall prevalenceof anemia was 31. 9%. The prevalence of anemia in the 1st, 2nd and 3rd trimesters during pregnancy was 5. 5%, 22. 8% and 18. 2%, respectively. The prevalence of anemia of pregnant women in the 2nd and 3rd trimesters were significantly higher than 1st trimester( P < 0. 05). Most of them were mild anemia, and pregnant women with severe anemia had not been found. After adjustment confounding factors( age and type of delivery etc. ), pregnant women with anemia in the 3rd trimester showed a 6. 47 times higher risk of postpartum hemorrhage( 95% CI 1. 23-34. 23). CONCLUSION: The anemia status of pregnant women in the 2nd and 3rd trimesters should be paid attention and improvement. Anemia of pregnant women in 3rd trimester is negative associated with postpartum hemorrhage.

[Effect of Sleep in Early Pregnancy on Gestational Diabetes: a Prospective Study.]

OBJECTIVES: To investigate the influence of sleep status in early pregnant women on the occurrence of gestational diabetes mellitus (GDM). METHODS: In this prospective study,542 pregnant women in early pregnancy were selected as subjects.The sleep time,insomnia,pre-gestational body mass and basic information of the subjects were collected by the trained investigators through questionnaire.At the 24th to 28th pregnant week,the body mass of each subject was measured and oral glucose tolerance test (OGTT) was conducted.The diagnosis of GDM was followed the guidelines of diagnose and treatment of gestational diabetes mellitus in China (2014).A non-conditional logistic regression method was adopted to analyze the correlation between sleep status of early pregnant women and the occurrence of GDM. RESULTS: The numbers of subjects in sleep deficiency group,sleep sufficiency group and sleep excessive group were 16 (2.95%),268 (49.45%) and 258 (47.60%),respectively.The incidences of GDM for sleep deficiency group,sleep sufficient group,and sleep excessive group were 62.50%(10/16),25.75%(69/268) and 22.09% (57/258),respectively,the difference was statistically significant (χ2=11.280,P<0.05).Compared with either sleep sufficiency or sleep excessive group,sleep deficiency group had higher GDM occurrence rate with statistically significant (χ2=8.410,11.218,P<0.017).Insomnia subjects in early pregnancy were 137 (25.28%).The incidences of GDM in insomnia group and normal group were 32.12% and 22.72% respectively,the difference was statistically significant (χ2=4.813, P<0.05).After adjusting the confounding factors [age,education,pre-pregnant body mass index (BMI),gained body mass in early and medium pregnancy,family history of type-2 diabetes,gravidity,parity,smoke,drink,exercise and occupation],non-conditional logistic regression results show that sleep deficiency for early pregnant women was an independent risk factor for the occurrence of GDM [odds ratio (OR)=7.38,95% confidence interval (CI): 2.25-24.17].However,the association between insomnia and the occurrence of GDM was not found. CONCLUSIONS: Sleep deficiency in early pregnancy may be a risk factor for the occurrence of GDM.

Versatile Design of NO-Generating Proteolipid Nanovesicles for Alleviating Vascular Injury.

Vascular injury is central to the pathogenesis and progression of cardiovascular diseases, however, fostering alternative strategies to alleviate vascular injury remains a persisting challenge. Given the central role of cell-derived nitric oxide (NO) in modulating the endogenous repair of vascular injury, NO-generating proteolipid nanovesicles (PLV-NO) are designed that recapitulate the cell-mimicking functions for vascular repair and replacement. Specifically, the proteolipid nanovesicles (PLV) are versatilely fabricated using membrane proteins derived from different types of cells, followed by the incorporation of NO-generating nanozymes capable of catalyzing endogenous donors to produce NO. Taking two vascular injury models, two types of PLV-NO are tailored to meet the individual requirements of targeted diseases using platelet membrane proteins and endothelial membrane proteins, respectively. The platelet-based PLV-NO (pPLV-NO) demonstrates its efficacy in targeted repair of a vascular endothelium injury model through systemic delivery. On the other hand, the endothelial cell (EC)-based PLV-NO (ePLV-NO) exhibits suppression of thrombosis when modified onto a locally transplanted small-diameter vascular graft (SDVG). The versatile design of PLV-NO may enable a promising therapeutic option for various vascular injury-evoked cardiovascular diseases.

Geographical Distribution of Dietary Patterns and Their Association with T2DM in Chinese Adults Aged 45 y and Above: A Nationwide Cross-Sectional Study.

BACKGROUND: This study aimed to investigate the geographical distribution of dietary patterns and their association with T2DM among Chinese adults aged 45 years and above. METHODS: Data was from the China Adults Chronic Diseases and Nutrition Surveillance (2015). Dietary intake for each participant was determined through a combination of 3-day 24-h dietary recall interviews and food frequency questionnaires. Principal component analysis was used to extract dietary patterns and spatial analysis was employed to investigate the geographic distribution of them. T2DM was diagnosed using criteria of ADA 2018, and binary logistic regression was employed to examine the relationship between dietary patterns and T2DM. RESULTS: A total of 36,648 participants were included in the study; 10.9% of them were diagnosed as T2DM. Three dietary patterns were identified with the name of plant-based pattern, animal-based pattern, and oriental traditional pattern, which were represented located in northern, northwest, and southern regions, respectively. After adjusting for potential confounders, participants in the highest quartile of the plant-based pattern were associated with lower T2DM odds (OR = 0.82, 95% CI: 0.74, 0.90) when comparing with the lowest quartile. However, participants inclined to higher quartiles of animal-based pattern had a higher risk of T2DM (OR = 1.15, 95% CI: 1.04, 1.27) compared with those in the lower quartiles. No significant association was found between the oriental traditional pattern and T2DM (OR = 1.03, 95% CI: 0.93, 1.14). CONCLUSION: Dietary patterns of Chinese population revealed geographical disparities, with plant-based dietary pattern showing protective effects and animal-based pattern carrying high risks for T2DM. Regional dietary variations and food environment are paramount in T2DM prevention and management.

Machine-learning-assisted single-vessel analysis of nanoparticle permeability in tumour vasculatures.

The central dogma that nanoparticle delivery to tumours requires enhanced leakiness of vasculatures is a topic of debate. To address this, we propose a single-vessel quantitative analysis method by taking advantage of protein-based nanoprobes and image-segmentation-based machine learning (nano-ISML). Using nano-ISML, >67,000 individual blood vessels from 32 tumour models were quantified, revealing highly heterogenous vascular permeability of protein-based nanoparticles. There was a >13-fold difference in the percentage of high-permeability vessels in different tumours and >100-fold penetration ability in vessels with the highest permeability compared with vessels with the lowest permeability. Our data suggest passive extravasation and transendothelial transport were the dominant mechanisms for high- and low-permeability tumour vessels, respectively. To exemplify the nano-ISML-assisted rational design of nanomedicines, genetically tailored protein nanoparticles with improved transendothelial transport in low-permeability tumours were developed. Our study delineates the heterogeneity of tumour vascular permeability and defines a direction for the rational design of next-generation anticancer nanomedicines.

Dietary Fat Intake among Chinese Adults and Their Relationships with Blood Lipids: Findings from China Nutrition and Health Surveillance and Comparison with the PURE Study.

Dietary fat intake in the Chinese population has increased. The PURE (prospective urban rural epidemiology) study concluded the potential advantage of total fat and saturated fats (SFA) over carbohydrates on blood lipids with the inaccurate assessment of dietary fats. We investigated the dietary fat profile among 48,315 participants (aged 30−70 years, national representative) from the China Nutrition and Health Surveillance (2015−2017), determined the relationship of various fats with blood lipid biomarkers in the selected 39,115 participants, and compared the results with the PURE study. Dietary fat intake was calculated by using 3 days of 24 h recalls and food inventory. Serum lipid biomarkers were assessed at morning fasting state by health professionals. Plant fats (21.5% of total energy (TE)) dominated in total fat intake (69.5 g/day, 35.6% TE), with monounsaturated fats (MUFA) in the largest (13.8% TE) portion and plant oils as the major source (43.7%). Two thirds of the population consumed more than 30% TE from dietary fats and nearly half more than 35%, while 26.4% of them exceeded 10% TE from SFA. Total fat was positively associated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), but also high-density lipoprotein cholesterol (HDL-c), and negatively with triglyceride (TG)-to-HDL-c ratio (TGHDL) (all p-trend < 0.05). Replacing total fat with carbohydrate yielded adverse changes in most biomarkers (higher LDL-c, TG, and TGHDL, lower HDL-c, all p < 0.05) when total fat was low (<34.9% TE). Regardless of fat intake level, replacing plant fat or polyunsaturated fats (PUFA) with carbohydrate yielded the most adverse changes (higher TC, LDL-c, TG, TC-to-HDL-c ratio (TCHDL), and TGHDL, but lower HDL-c, all p < 0.01), while replacing animal fat/SFA with plant fat/PUFA yielded the most favorable changes (lower all biomarkers, all p < 0.01). The results suggested a less harmful effect of carbohydrate on blood lipids when total fat was high, and more beneficial effect of unsaturated fats, than the PURE. In conclusion, dietary fat intake in Chinese adults had reached quite a high level, but with a different profile from Western populations. Replacement of SFA (animal fat) with PUFA (plant fat) could most effectively improve blood lipids, while replacement with carbohydrate could slightly benefit only when total fat was high. The present results may be more applicable to the Chinese population than the PURE study.

Geographic Variations in Dietary Patterns and Their Associations with Overweight/Obesity and Hypertension in China: Findings from China Nutrition and Health Surveillance (2015-2017).

Regional dietetic cultures were indicated in China, but how dietary patterns geographically varied across China is unknown. Few studies systematically investigated the association of dietary patterns with overweight/obesity and hypertension and the potential mechanism with a national sample. This study included 34,040 adults aged 45 years and older from China Nutrition and Health Surveillance (2015−2017), who had complete outcome data, reliable intakes of calorie and cooking oils, unchanged diet habits, and without diagnosed cancer or cardiovascular disease. Outcomes were overweight/obesity and hypertension. By using the Gaussian finite mixture models, four dietary patterns were identified­common rice-based dietary pattern (CRB), prudent diversified dietary pattern (PD), northern wheat-based dietary pattern (NWB), and southern rice-based dietary pattern (SRB). Geographic variations in dietary patterns were depicted by age−sex standardized proportions of each pattern across 31 provinces in China. We assessed the association of these dietary patterns with outcomes and calculated the proportion mediated (PM) by overweight/obesity in the association of the dietary patterns with hypertension. Evident geographic disparities in dietary patterns across 31 provinces were observed. With CRB as reference group and covariates adjusted, the NWB had higher odds of being overweight/obese (odds ratio (OR) = 1.44, 95% confidence interval (CI): 1.36−1.52, p < 0.001) and hypertension (OR = 1.07, 95%CI: 1.01−1.14, p < 0.001, PM = 43.2%), while the SRB and the PD had lower odds of being overweight/obese (ORs = 0.84 and 0.92, 95%CIs: 0.79−0.89 and 0.85−0.99, p < 0.001 for both) and hypertension (ORs = 0.93 and 0.87, 95%CIs: 0.87−0.98 and 0.80−0.94, p = 0.038 for SRB and p < 0.001 for PD, PMs = 27.8% and 9.9%). The highest risk of overweight/obesity in the NWB presented in relatively higher carbohydrate intake (about 60% of energy) and relatively low fat intake (about 20% of energy). The different trends in the association of protein intake with overweight/obesity among dietary patterns were related to differences in animal food sources. In conclusion, the geographic distribution disparities of dietary patterns illustrate the existence of external environment factors and underscore the need for geographic-targeted dietary actions. Optimization of the overall dietary pattern is the key to the management of overweight/obesity and hypertension in China, with the emphasis on reducing low-quality carbohydrate intake, particularly for people with the typical northern diet, and selection of animal foods, particularly for people with the typical southern diet.

Taurine Attenuates the Hypotaurine-Induced Progression of CRC via ERK/RSK Signaling.

Colorectal cancer (CRC) is one of the most common malignant tumors, and previous metabolomics work has demonstrated great promise in identifying specific small molecules of tumor phenotype. In the present study, we analyzed the metabolites of resected tissues through gas chromatography-mass spectrometry (GC-MS), and found that the concentration of taurine in CRC tissues diminished whereas the concentration of hypotaurine increased. The results in vitro demonstrated that taurine significantly suppressed cellular proliferation, metastasis, and colony formation whereas it induced apoptosis in CRC cells. Furthermore, taurine regulated the expression levels of epithelial mesenchymal transition (EMT)-associated genes in a dose-dependent manner. Taurine also alleviated hypotaurine-induced CRC progression, which was linked to the inhibition of the ERK/RSK-signaling pathway and diminution in intracellular hypotaurine. Taurine additionally attenuated hypotaurine-induced tumor growth and metastasis in vivo. Patients with CRC exhibited lower levels of serum taurine, suggesting that taurine might be a promising biomarker reflecting a poor prognosis in CRC. Collectively, our results demonstrated that taurine-attenuated, hypotaurine-induced CRC progression provides a potential target for CRC therapy.

Circular RNA PRMT5 knockdown enhances cisplatin sensitivity and immune response in non-small cell lung cancer by regulating miR-138-5p/MYH9 axis.

PURPOSE: To explore the role and molecular mechanism of circRNA protein arginine methyltransferase-5 (circ-PRMT5) in regulating cisplatin (DDP) resistance and immune response of non-small cell lung cancer (NSCLC). METHODS: The expression of circ-PRMT5, miR-138-5p and myosin heavy chain 9 (MYH9) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, and western blot assay were utilized to evaluate DDP sensitivity. Interleukin 2 (IL-2), tumor necrosis factor alpha (TNF-α) and transforming growth factor ß (TGF-ß) production were measured by enzyme-linked immunosorbent assay (ELISA) to assess immune system's ability. A xenograft tumor model was established to explore the role of circ-PRMT5 in DDP resistance in vivo. The interaction between miR-138-5p and circ-PRMT5 or MYH9 was predicted by starBase and verified by dual-luciferase reporter assay. RESULTS: Circ-PRMT5 and MYH9 were upregulated and miR-138-5p was downregulated in DDP-resistant NSCLC tissues and cells. Circ-PRMT5 knockdown enhanced DDP sensitivity of NSCLC cells by inhibiting cell viability, migration and invasion and inducing apoptosis. Circ-PRMT5 knockdown also increased immune response by promoting the levels of IL-2 and TNF-a and decreasing the production of TGF-ß. Moreover, circ-PRMT5 interference improved DDP sensitivity of NSCLC in vivo. MiR-138-5p was a direct target of circ-PRMT5 and its knockdown abated the effects of circ-PRMT5 downregulation on DDP resistance and immune response. CONCLUSION: Circ-PRMT5 knockdown increased DDP sensitivity and immune response of NSCLC cells by regulating miR-138-5p/MYH9 axis, hinting potential value of circ-PRMT5 in the diagnosis and treatment for NSCLC.

E2-Induced Activation of the NLRP3 Inflammasome Triggers Pyroptosis and Inhibits Autophagy in HCC Cells.

Emerging evidence suggests that 17ß-estradiol (E2) and estrogen receptor (ER) signaling are protective against hepatocellular carcinoma (HCC). In our previous study, we showed that E2 suppressed the carcinogenesis and progression of HCC by targeting NLRP3 inflammasome activation, whereas the molecular mechanism by which the NLRP3 inflammasome initiated cancer cell death was not elucidated. The present study aimed to investigate the effect of NLRP3 inflammasome activation on cell death pathways and autophagy of HCC cells. First, we observed an increasing mortality in E2-treated HCC cells, and then apoptotic and pyroptotic cell death were both detected. The mortality of HCC cells was largely reversed by the caspase 1 antagonist, YVAD-cmk, suggesting that E2-induced cell death was associated with caspase 1-dependent pyroptosis. Second, the key role of the NLRP3 inflammasome in autophagy of HCC cells was assessed by E2-induced activation of the NLRP3 inflammasome, and we demonstrated that autophagy was inhibited by the NLRP3 inflammasome via the E2/ERß/AMPK/mTOR pathway. Last, the interaction of pyroptosis and autophagy was confirmed by flow cytometry methods. We observed that E2-induced pyroptosis was dramatically increased by 3-methyladenine (3-MA) treatment, which was abolished by YVAD-cmk treatment, suggesting that caspase 1-dependent pyroptosis was negatively regulated by autophagy. In conclusion, E2-induced activation of the NLRP3 inflammasome may serve as a suppressor in HCC progression, as it triggers pyroptotic cell death and inhibits protective autophagy.