Clustering of health behaviors and their associations with cardiometabolic risk factors among adults at high risk for type 2 diabetes in India: A latent class analysis.

BACKGROUND: We aimed to identify clusters of health behaviors and study their associations with cardiometabolic risk factors in adults at high risk for type 2 diabetes in India. METHODS: Baseline data from the Kerala Diabetes Prevention Program (n = 1000; age 30-60 years) were used for this study. Information on physical activity (PA), sedentary behavior, fruit and vegetable intake, sleep, and alcohol and tobacco use was collected using questionnaires. Blood pressure, waist circumference, 2-h plasma glucose, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides were measured using standardized protocols. Latent class analysis was used to identify clusters of health behaviors, and multilevel mixed-effects linear regression was employed to examine their associations with cardiometabolic risk factors. RESULTS: Two classes were identified, with 87.4% of participants in class 1 and 12.6% in class 2. Participants in both classes had a high probability of not engaging in leisure-time PA (0.80 for class 1; 0.73 for class 2) and consuming <5 servings of fruit and vegetables per day (0.70 for class 1; 0.63 for class 2). However, participants in class 1 had a lower probability of sitting for >=3 h per day (0.26 vs 0.42), tobacco use (0.10 vs 0.75), and alcohol use (0.08 vs 1.00) compared to those in class 2. Class 1 had a significantly lower mean systolic blood pressure (ß = -3.70 mm Hg, 95% confidence interval [CI] -7.05, -0.36), diastolic blood pressure (ß = -2.45 mm Hg, 95% CI -4.74, -0.16), and triglycerides (ß = -0.81 mg/dL, 95% CI -0.75, -0.89). CONCLUSION: Implementing intervention strategies, tailored to cluster-specific health behaviors, is required for the effective prevention of cardiometabolic disorders among high-risk adults for type 2 diabetes.

Clusters of 24-hour movement behavior and diet and their relationship with health indicators among youth: a systematic review.

Movement-related behaviors (physical activity [PA], sedentary behavior [SB], and sleep) and diet interact with each other and play important roles in health indicators in youth. This systematic review aimed to investigate how PA, SB, sleep, and diet cluster in youth by biological sex; and to examine which cluster are associated with health indicators. This study was registered in PROSPERO (number: CRD42018094826). Five electronic databases were assessed. Eligibility criteria allowed studies that included youth (aged 19 years and younger), and only the four behaviors {PA, SB, sleep, and diet (ultra-processed foods [UPF]; fruits and vegetables [FV])} analyzed by applying data-based cluster procedures. From 12,719 articles screened; 23 were included. Of these, four investigated children, and ten identified clusters by biological sex. Sixty-six mixed cluster were identified including, 34 in mixed-sex samples, 10 in boys and 11 in girls. The most frequent clusters in mixed-sex samples were "High SB UPF Low Sleep", "Low PA High SB Satisfactory Sleep", and "High PA". The main difference in profiles according to sex was that girls' clusters were characterized by high sleep duration, whereas boys' clusters by high PA. There were a few associations found between cluster types and health indicators, highlighting that youth assigned to cluster types with low PA exhibited higher adiposity. In conclusion, the youth presented a range of clusters of behaviors, typically exhibiting at least one unhealthy behavior. Similar patterns were observed in both sexes with the biggest difference in time of sleep for girls and PA for boys. These findings underscore the importance of intervention strategies targeting multiple behaviors simultaneously to enhance health risk profiles and indicators in children and adolescents.

N4-acetylcytidine modifies primary microRNAs for processing in cancer cells.

N4 acetylcytidine (ac4C) modification mainly occurs on tRNA, rRNA, and mRNA, playing an important role in the expression of genetic information. However, it is still unclear whether microRNAs have undergone ac4C modification and their potential physiological and pathological functions. In this study, we identified that NAT10/THUMPD1 acetylates primary microRNAs (pri-miRNAs) with ac4C modification. Knockdown of NAT10 suppresses and augments the expression levels of mature miRNAs and pri-miRNAs, respectively. Molecular mechanism studies found that pri-miRNA ac4C promotes the processing of pri-miRNA into precursor miRNA (pre-miRNA) by enhancing the interaction of pri-miRNA and DGCR8, thereby increasing the biogenesis of mature miRNA. Knockdown of NAT10 attenuates the oncogenic characters of lung cancer cells by regulating miRNA production in cancers. Moreover, NAT10 is highly expressed in various clinical cancers and negatively correlated with poor prognosis. Thus, our results reveal that NAT10 plays a crucial role in cancer initiation and progression by modulating pri-miRNA ac4C to affect miRNA production, which would provide an attractive therapeutic strategy for cancers.

Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC.

Non-small-cell lung cancer (NSCLC) is a highly lethal tumor that often develops resistance to targeted therapy. It is shown that Tank-binding kinase 1 (TBK1) phosphorylates AGO2 at S417 (pS417-AGO2), which promotes NSCLC progression by increasing the formation of microRNA-induced silencing complex (miRISC). High levels of pS417-AGO2 in clinical NSCLC specimens are positively associated with poor prognosis. Interestingly, the treatment with EGFR inhibitor Gefitinib can significantly induce pS417-AGO2, thereby increasing the formation and activity of oncogenic miRISC, which may contribute to NSCLC resistance to Gefitinib. Based on these, two therapeutic strategies is developed. One is jointly to antagonize multiple oncogenic miRNAs highly expressed in NSCLC and use TBK1 inhibitor Amlexanox reducing the formation of oncogenic miRISC. Another approach is to combine Gefitinib with Amlexanox to inhibit the progression of Gefitinib-resistant NSCLC. This findings reveal a novel mechanism of oncogenic miRISC regulation by TBK1-mediated pS417-AGO2 and suggest potential therapeutic approaches for NSCLC.

USP7 reduces the level of nuclear DICER, impairing DNA damage response and promoting cancer progression.

Endoribonuclease DICER is an RNase III enzyme that mainly processes microRNAs in the cytoplasm but also participates in nuclear functions such as chromatin remodelling, epigenetic modification and DNA damage repair. The expression of nuclear DICER is low in most human cancers, suggesting a tight regulation mechanism that is not well understood. Here, we found that ubiquitin carboxyl-terminal hydrolase 7 (USP7), a deubiquitinase, bounded to DICER and reduced its nuclear protein level by promoting its ubiquitination and degradation through MDM2, a newly identified E3 ubiquitin-protein ligase for DICER. This USP7-MDM2-DICER axis impaired histone γ-H2AX signalling and the recruitment of DNA damage response (DDR) factors, possibly by influencing the processing of small DDR noncoding RNAs. We also showed that this negative regulation of DICER by USP7 via MDM2 was relevant to human tumours using cellular and clinical data. Our findings revealed a new way to understand the role of DICER in malignant tumour development and may offer new insights into the diagnosis, treatment and prognosis of cancers.

Frequent hospital presenters' use of health information during COVID-19: results of a cross-sectional survey.

BACKGROUND: High-frequency hospital users often present with chronic and complex health conditions and are at increased risk of serious morbidity and mortality if they contract COVID-19. Understanding where high-frequency hospital users are sourcing their information, whether they understand what they find, and how they apply the information to prevent the spread of COVID-19 is essential for health authorities to be able to target communication approaches. METHODS: Cross-sectional survey of 200 frequent hospital users (115 with limited English proficiency) informed by the WHO's "Rapid, simple, flexible behavioral insights on COVID-19". Outcome measures were source of, and trust in information, and knowledge of symptoms, preventive strategies, restrictions, and identification of misinformation. RESULTS: The most frequently cited source of information was television (n = 144, 72%) followed by the internet (n = 84, 42%). One in four television users sought their information from overseas news outlets from their country of origin, while for those using the internet, 56% relied on Facebook and other forms of social media including YouTube and WeChat. Overall, 41.2% of those surveyed had inadequate knowledge about symptoms, 35.8% had inadequate knowledge about preventative strategies, 30.2% had inadequate knowledge about government-imposed restrictions, and 69% believed in misinformation. Half of the respondents (50%) trusted all information, and only one in five (20%) were uncertain or untrusting. English-speaking participants were almost three times more likely to have adequate knowledge about symptoms (OR 2.69, 95%CI 1.47;4.91) and imposed restrictions (OR 2.10 95%CI 1.06; 4.19), and 11 times more likely to recognize misinformation (OR 11.52 95%CI 5.39; 24.60) than those with limited English. CONCLUSION: Within this population of high-frequency hospital users with complex and chronic conditions, many were sourcing their information from less trustworthy or locally relevant sources, including social media and overseas news outlets. Despite this, at least half were trusting all the information that they found. Speaking a language other than English was a much greater risk factor for having inadequate knowledge about COVID-19 and believing in misinformation. Health authorities must look for methods to engage diverse communities, and tailor health messaging and education in order to reduce disparities in health outcomes.

A peer support program results in greater health benefits for peer leaders than other participants: evidence from the Kerala diabetes prevention program.

BACKGROUND: Peer support programs are promising approaches to diabetes prevention. However, there is still limited evidence on the health benefits of peer support programs for lay peer leaders. PURPOSE: To examine whether a peer support program designed for diabetes prevention resulted in greater improvements in health behaviors and outcomes for peer leaders as compared to other participants. METHODS: 51 lay peer leaders and 437 participants from the Kerala Diabetes Prevention Program were included. Data were collected at baseline, 12 months, and 24 months. We compared behavioral, clinical, biochemical, and health-related quality of life parameters between peer leaders and their peers at the three time-points. RESULTS: After 12 months, peer leaders showed significant improvements in leisure time physical activity (+ 17.7% vs. + 3.4%, P = 0.001) and health-related quality of life (0.0 vs. + 0.1, P = 0.004); and a significant reduction in alcohol use (-13.6% vs. -6.6%, P = 0.012) and 2-hour plasma glucose (-4.1 vs. + 9.9, P = 0.006), as compared to participants. After 24 months, relative to baseline, peer leaders had significant improvements in fruit and vegetable intake (+ 34.5% vs. + 26.5%, P = 0.017) and leisure time physical activity (+ 7.9% vs. -0.9%, P = 0.009); and a greater reduction in alcohol use (-13.6% vs. -4.9%, P = 0.008), and waist-to-hip ratio (-0.04 vs. -0.02, P = 0.014), as compared to participants. However, only the changes in fruit and vegetable intake and waist-to-hip ratio were maintained between 12 and 24 months. CONCLUSION: Being a peer leader in a diabetes prevention program was associated with greater health benefits during and after the intervention period. Further studies are needed to examine the long-term sustainability of these benefits.

Continuous usage intention of mobile health services: model construction and validation.

BACKGROUND: Mobile health (mHealth) services can not give full play to their value if only it is used in the short term, and their continuous usage can achieve better effects in health management. This study aims to explore the factors that affect continuous usage intentions of mHealth services and their mechanism of action. METHODS: First, considering the uniqueness of health services and social environmental factors, this study constructed an extended Expectation Confirmation Model of Information System Continuance (ECM-ISC) to investigate factors that may influence the intention of continuous usage of mHealth services based on three dimensions, namely individual characteristics, technology and environment. Second, the survey method was used to validate the research model. The questionnaire items were derived from validated instruments and discussed by experts and data were collected both online and offline. The structural equation model was used for data analysis. RESULTS: There were 334 avidity questionnaires through cross-sectional data and these participants had used mHealth services ever. The reliability and validity of the test model were good, in which Cronbach's Alpha values of 9 variables exceeded 0.9, composite reliability 0.8, the average variance extracted value 0.5, and the factor loading 0.8. The modified model had a good fitting effect and strong explanatory power. It accounted for 89% of the variance in expectation confirmation, 74% of the variance in perceived usefulness, 92% of the variance in customer satisfaction, and 84% of the variance in continuous usage intention. Compared with the initial model hypotheses, perceived system quality was deleted according to the heterotrait-monotrait ratio, so paths related to it were deleted; perceived usefulness wasn't positively associated with customer satisfaction, and its path was also deleted. Other paths were consistent with the initial hypothesis. The two new added paths were that subjective norm was positively associated with perceived service quality (ß = 0.704, P < 0.001), and perceived information quality (ß = 0.606, P < 0.001). Electronic health literacy (E-health literacy) was positively associated with perceived usefulness (ß = 0.379, P < 0.001), perceived service quality (ß = 0.200, P < 0.001), and perceived information quality (ß = 0.320, P < 0.001). Continuous usage intention was influenced by perceived usefulness (ß = 0.191, P < 0.001), customer satisfaction (ß = 0.453, P < 0.001), and subjective norm (ß = 0.372, P < 0.001). CONCLUSIONS: The study constructed a new theoretical model including E-health literacy, subjective norm and technology qualities to clarify continuous usage intention of mHealth services, and empirically validated the model. Attention should be paid to E-health literacy, subjective norm, perceived information quality, and perceived service quality to improve continuous usage intention of users and self-management by mHealth Apps managers and governments. This research provides solid evidence for the validity of the expanded model of ECM-ISC in the mHealth field, which can be a theoretical and practical basis for mHealth operators' product research and development.

Digital Health Solutions for Community-Based Control of Diabetes During COVID-19 Pandemic: A Scoping Review of Implementation Outcomes.

BACKGROUND: The COVID-19 pandemic has added to the pre-existing challenges of diabetes management in many countries. It has accelerated the wider use of digital health solutions which have tremendous potential to improve health outcomes for people with diabetes. However, little is known about the attributes and the implementation of these solutions. OBJECTIVE: To identify and describe digital health solutions for community-based diabetes management and to highlight their key implementation outcomes. METHODS: We searched Ovid Medline, CINAHL, Embase, PsycINFO, and Web of Science for relevant articles. A purposive search was also used to identify grey literature. Articles that described digital health solutions that aimed to improve community-based diabetes management were included in this review. We applied a thematic synthesis of evidence to describe the characteristics of digital health solutions, and to summarize their key implementation outcomes. RESULTS: We included 15 articles that reported digital health solutions that primarily focused on community-based diabetes management. Nine of the 15 innovations involved were mobile applications and/or web-based platforms, and five were based on social media platforms. The majority of the digital health solutions were used for diabetes education and support. High engagement, utilization, and satisfaction rates with digital health solutions were observed. The use of digital health solutions was also associated with improvement in self-management, taking medication, and reduction in glycated hemoglobin (HbA1c) levels. CONCLUSION: COVID-19 triggered digital health solutions have tremendous potential to improve health outcomes for people with diabetes. Further studies are needed to evaluate the sustainability and scale-up of these solutions.

Regulation of SUMOylation on RNA metabolism in cancers.

Post-translational modifications of proteins play very important roles in regulating RNA metabolism and affect many biological pathways. Here we mainly summarize the crucial functions of small ubiquitin-like modifier (SUMO) modification in RNA metabolism including transcription, splicing, tailing, stability and modification, as well as its impact on the biogenesis and function of microRNA (miRNA) in particular. This review also highlights the current knowledge about SUMOylation regulation in RNA metabolism involved in many cellular processes such as cell proliferation and apoptosis, which is closely related to tumorigenesis and cancer progression.

Both Short and Long Sleep Durations Are Associated with Poor Cognition and Memory in Chinese Adults Aged 55+ Years-Results from China Health and Nutrition Survey.

We aimed to examine the associations between sleep duration and cognitive functions and memory in older Chinese adults attending the China Health and Nutrition Survey. A total of 7924 participants 55 years and older who reported their sleep duration and had a cognitive screen test in 2004, 2006, and 2015 were included in the analysis. Mixed-effects logistic regression models were used to assess the associations. A short sleep duration (≤6 h/day) and long sleep duration (≥10 h/day) were positively associated with a low global cognitive score (odds ratio-OR: 1.23, 95% CI: 1.01-1.50; OR: 1.47, 95% CI: 1.17-1.79, respectively). Both short sleepers and long sleepers had an increased risk of self-reported poor memory (OR: 1.63, 95% CI: 1.39-1.91; OR: 1.48, 95% CI: 1.25-1.74, respectively). No differences in the above associations were found for income, education, and urbanity. In conclusion, both the short and long sleep duration were associated with declined cognition and memory. Maintaining a normal sleep duration may aid in the prevention of cognitive function decline in older adults.

Strengthening Capacity for Implementation Research Amid COVID-19 Pandemic: Learnings From the Global Alliance for Chronic Diseases Implementation Science School.

Objective: To describe the design, delivery and evaluation of the 3rd Global Alliance for Chronic Diseases (GACD) Implementation Science School (ISS), delivered virtually in 2020 for the first time. Methods: Since 2014, GACD has supported the delivery of more than ten Implementation Science Workshops for more than 500 international participants. It has also been conducting an annual ISS since 2018. In this study, we described the design, delivery and evaluation of the third ISS. Results: Forty-six participants from 23 countries in five WHO regions attended the program. The virtual delivery was well-received and found to be efficient in program delivery, networking and for providing collaborative opportunities for trainees from many different countries. The recently developed GACD Implementation Science e-Hub was found to be an instrumental platform to support the program by providing a stand-alone, comprehensive online learning space for knowledge and skill development in implementation research. Conclusion: The delivery of the virtual GACD ISS proved to be feasible, acceptable and effective and offers greater scalability and sustainability as part of a future strategy for capacity strengthening in implementation research globally.

Neighbourhood walkability and dietary attributes: effect modification by area-level socio-economic status.

OBJECTIVE: Higher neighbourhood walkability would be expected to contribute to better health, but the relevant evidence is inconsistent. This may be because residents' dietary attributes, which vary with socio-economic status (SES) and influence their health, can be related to walkability. We examined associations of walkability with dietary attributes and potential effect modification by area-level SES. DESIGN: The exposure variable of this cross-sectional study was neighbourhood walkability, calculated using residential density, intersection density and destination density within 1-km street-network buffer around each participant's residence. The outcome variables were dietary patterns (Western, prudent and mixed) and total dietary energy intake, derived from a FFQ. Main and interaction effects with area-level SES were estimated using two-level linear regression models. SETTING: Participants were from all states and territories in Australia. PARTICIPANTS: The analytical sample included 3590 participants (54 % women, age range 34 to 86). RESULTS: Walkability was not associated with dietary attributes in the whole sample. However, we found interaction effects of walkability and area-level SES on Western diet scores (P < 0·001) and total energy intake (P = 0·012). In low SES areas, higher walkability was associated with higher Western dietary patterns (P = 0·062) and higher total energy intake (P = 0·066). In high SES areas, higher walkability was associated with lower Western diet scores (P = 0·021) and lower total energy intake (P = 0·058). CONCLUSIONS: Higher walkability may not be necessarily conducive to better health in socio-economically disadvantaged areas. Public health initiatives to enhance neighbourhood walkability need to consider food environments and socio-economic contexts.

Associations between Dietary Patterns and Cardiometabolic Risk Factors-A Longitudinal Analysis among High-Risk Individuals for Diabetes in Kerala, India.

The association between dietary patterns and cardiometabolic risk factors is not well understood among adults in India, particularly among those at high risk for diabetes. For this study, we analyzed the data of 1007 participants (age 30-60 years) from baseline and year one and two follow-ups from the Kerala Diabetes Prevention Program using multi-level mixed effects modelling. Dietary intake was measured using a quantitative food frequency questionnaire, and dietary patterns were identified using principal component analysis. Two dietary patterns were identified: a "snack-fruit" pattern (highly loaded with fats and oils, snacks, and fruits) and a "rice-meat-refined wheat" pattern (highly loaded with meat, rice, and refined wheat). The "snack-fruit" pattern was associated with increased triglycerides (mg/dL) (ß = 6.76, 95% CI 2.63-10.89), while the "rice-meat-refined wheat" pattern was associated with elevated Hb1Ac (percentage) (ß = 0.04, 95% CI 0.01, 0.07) and central obesity (OR 1.16, 95% CI 1.01, 1.34). These findings may help inform designing dietary interventions for the prevention of diabetes and improving cardiometabolic risk factors in high-diabetes-risk individuals in the Indian setting.

Determinants of Health Service Utilization Among Adults at High Risk of Developing Type 2 Diabetes in Kerala, India.

The purpose of this study was to examine the determinants of health service utilization in a population at high risk of developing type 2 diabetes mellitus in India. Using Andersen's behavioral model of healthcare utilization, multivariate logistic regression analysis was performed on baseline data of the Kerala Diabetes Prevention Program. We examined the association between predisposing, enabling, and need factors with outpatient health service use in the past four weeks and inpatient health service use in the past 12 months. More than a quarter (27.9%) and 12.9% of 1007 participants used outpatient services and inpatient services, respectively. Men were less likely to use outpatient services (odds ratio [OR] = 0.56). Outpatient service utilization was positively associated with low social support (OR = 1.69), low general health status (OR = 5.71), and time off from work due to illness (OR = 8.01). Higher educational status (OR = 0.63), low general health status (OR = 3.59), and time off from work due to illness (OR = 1.21) were associated with increased utilization of inpatient services. Although gender, educational status, and social support had important roles, health service utilization in this study population was largely dependent on general health status and presence of illness.

Low physical activity is associated with adverse health outcome and higher costs in Indonesia: A national panel study.

Aims: To assess the association between low physical activity, cardiovascular disease (CVD) and risk factors, health service utilization, risk of catastrophic health expenditure, and work productivity in Indonesia. Methods: In this population-based, panel data analysis, we used data from two waves of the Indonesian Family Life Survey (IFLS) for 2007/2008 and 2014/2015. Respondents aged 40-80 years who participated in both waves were included in this study (n = 5,936). Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ-SF). Multinomial logistic regression model was used to examine factors associated with physical activity levels (low, moderate, and high). We applied a series of multilevel mixed-effect panel regression to examine the associations between physical activity and outcome variables. Results: The prevalence of low physical activity increased from 18.2% in 2007 to 39.6% in 2014. Compared with those with high physical activity, respondents with low physical activity were more likely to have a 10-year high CVD risk (AOR: 2.11, 95% CI: 1.51-2.95), use outpatient care (AOR: 1.26, 95% CI: 1.07-1.96) and inpatient care (AOR 1.45, 95% CI: 1.07-1.96), experience catastrophic health expenditure of 10% of total household expenditure (AOR: 1.66, 95% CI: 1.21-2.28), and have lower labor participation (AOR: 0.24, 95% 0.20-0.28). Conclusions: Low physical activity is associated with adverse health outcomes and considerable costs to the health system and wider society. Accelerated implementation of public health policies to reduce physical inactivity is likely to result in substantial population health and economic benefits.

Factors Associated With Hypertension Awareness, Treatment, and Control Among Adults in Kerala, India.

Background: Hypertension, the most significant risk factor for cardiovascular disease, is an increasing contributor to global health burden, particularly in low- and middle-income countries (LMICs) such as India. While the rates of hypertension awareness, treatment, and control in India have been reported in several studies, the factors associated with these rates are less well-understood. Existing studies are predominantly cross-sectional, and the factors examined are limited. Understanding the predictors associated with these rates, using more rigorous study designs, is crucial for the development of strategies to improve hypertension management. Aims: To examine a range of factors associated with hypertension awareness, treatment, and control using both cross-sectional and longitudinal analyses. Methods: Data was derived from a population-based sample of 1,710 participants from Kerala, aged 30-60 years. We examined a comprehensive range of factors, including demographic, behavioral factors, anthropometric, clinical measures, psychosocial factors and healthcare utilization. Multilevel mixed effects logistic regression was used for both cross-sectional and longitudinal analyses (repeated measures for all variables across 2 years) to determine the factors associated with awareness, treatment, and control of hypertension. Results: A total of 467 (27.3%) participants had hypertension at baseline. Among those, the rates of awareness, treatment, and control of hypertension were 54.4, 25.5, and 36.4%, respectively. Being male (OR 0.27, 95% CI 0.14-0.53) and consumption of alcohol (OR 0.49, 95% CI 0.31-0.80) were significant predictors of poorly controlled hypertension (longitudinal analysis). Depression (OR 2.04, 95% CI 1.15-3.61) and fair-to-poor self-perceived health status (OR 1.87, 95% CI 1.15-3.04) were associated with increased hypertension awareness, whereas anxiety (OR 1.97, 95% CI 1.04-3.71) was associated with increased hypertension treatment (cross-sectional analysis). Seeking outpatient service in the past 4 weeks was associated with higher awareness (OR 1.09, 95% CI 1.27-2.87), treatment (OR 1.73, 95% CI 1.20-2.50) and control (OR 1.96, 95% CI 1.37-2.80) (longitudinal analysis). Conclusion: Our findings suggest the importance of considering psychosocial factors and better engagement with health services in hypertension management, as well as giving more attention to body fat control and largely male-related behaviors such as alcohol consumption, taking into account of some Indian specific attributes.

Hypoxia regulates overall mRNA homeostasis by inducing Met1-linked linear ubiquitination of AGO2 in cancer cells.

Hypoxia is the most prominent feature in human solid tumors and induces activation of hypoxia-inducible factors and their downstream genes to promote cancer progression. However, whether and how hypoxia regulates overall mRNA homeostasis is unclear. Here we show that hypoxia inhibits global-mRNA decay in cancer cells. Mechanistically, hypoxia induces the interaction of AGO2 with LUBAC, the linear ubiquitin chain assembly complex, which co-localizes with miRNA-induced silencing complex and in turn catalyzes AGO2 occurring Met1-linked linear ubiquitination (M1-Ubi). A series of biochemical experiments reveal that M1-Ubi of AGO2 restrains miRNA-mediated gene silencing. Moreover, combination analyses of the AGO2-associated mRNA transcriptome by RIP-Seq and the mRNA transcriptome by RNA-Seq confirm that AGO2 M1-Ubi interferes miRNA-targeted mRNA recruiting to AGO2, and thereby facilitates accumulation of global mRNAs. By this mechanism, short-term hypoxia may protect overall mRNAs and enhances stress tolerance, whereas long-term hypoxia in tumor cells results in seriously changing the entire gene expression profile to drive cell malignant evolution.

The association of TV viewing time with 2-hour plasma glucose is modified by a prudent dietary pattern.

BACKGROUND: TV viewing is associated with elevated plasma glucose, but it is not clear whether such associations can be modified by dietary patterns. METHODS: We examined the interactions of TV viewing time and dietary patterns in relation to fasting and 2-hour plasma glucose. Cross-sectional analyses were performed among participants (N = 3081; 44.7% male; mean age 57.8 years) from the 2011 to 2012 Australian Diabetes, Obesity and Lifestyle Study (AusDiab) without clinically diagnosed diabetes or cardiovascular disease. Factor analysis (principal component) was conducted to identify dietary patterns. Multivariable linear regression models were used to examine distinct associations of TV viewing time and dietary patterns with fasting and 2-hour plasma glucose. Dichotomous TV viewing time (low: ≤ 2 h/d vs high: >2 h/d) and quartiles of dietary patterns were further combined to examine the joint associations with plasma glucose. RESULTS: Three dietary patterns were identified: prudent, Western, and mixed. TV viewing time was positively associated (ß = .01, P < .05) and the prudent dietary pattern was inversely associated (ß = -.03, P < .05) with log transformed 2-hour plasma glucose. Compared with participants with high TV viewing/lowest prudent dietary pattern, participants with low TV viewing/highest prudent diet had the lowest 2-hour plasma glucose (ß = -.05, P = .028). No interactions were found between TV viewing time and the Western dietary pattern, nor the mixed dietary pattern, in relation to either fasting or 2-hour plasma glucose. CONCLUSIONS: Following a prudent dietary pattern may attenuate the adverse effect of TV viewing on 2-hour plasma glucose. Prospective studies and intervention trials are needed to further clarify these relationships.