Publications by authors named "Ming-Wei Liu"

48 Publications

Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

EBioMedicine 2021 Nov 21;74:103714. Epub 2021 Nov 21.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address:

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management.

Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99).

Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins.

Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention.

Funding: The funders are listed in the Acknowledgement.
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http://dx.doi.org/10.1016/j.ebiom.2021.103714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617343PMC
November 2021

Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

EBioMedicine 2021 Nov 21;74:103714. Epub 2021 Nov 21.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address:

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management.

Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99).

Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins.

Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention.

Funding: The funders are listed in the Acknowledgement.
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http://dx.doi.org/10.1016/j.ebiom.2021.103714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617343PMC
November 2021

Child neglect and eating habits in primary schoolchildren: A prospective study in Wuhan, China.

Appetite 2021 Oct 11;168:105756. Epub 2021 Oct 11.

School of Health Sciences, Wuhan University, Wuhan, China; Hubei Biomass-Resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, China. Electronic address:

Child neglect (CN) has been associated with eating disorders, but little is known about its prospective association with the eating habits (EHs) of children. This study aimed to assess the cross-sectional and prospective associations of baseline CN with six common EHs in Chinese primary schoolchildren. We analyzed two-wave data of 1102 children (aged 9.1 ± 0.5 years) in Wuhan, China. Baseline CN was investigated by the Child Neglect Scale. Baseline and follow-up EHs, including fruit, vegetables, milk, sugar-sweetened beverages, and high-calorie snack and breakfast consumption frequency, were assessed by the Food Frequency Questionnaires. The association of baseline CN with baseline/follow-up EHs was analyzed by the generalized linear model (GLM). The association of baseline CN with the change of EHs from baseline to follow-up was examined by the Generalized estimating equation (GEE) model. After adjusting for demographic characteristics, pubertal stage, and body mass index, GLM indicated that higher baseline CN was associated with lower frequency of consuming fruit/vegetables/milk/breakfast and higher frequency of consuming sugar-sweetened beverages and high-calorie snacks at baseline, while it was only associated with lower frequency of vegetables/breakfast consumption and higher frequency of sugar-sweetened beverages consumption at follow-up. GEE results indicated that children with higher CN had a more rapid increase for the frequency of fruit/milk/breakfast consumption and a steeper decrease for the frequency of sugar-sweetened beverages consumption. In conclusion, higher CN was associated with unhealthy EHs. Yet simultaneously, children with higher CN have more scope to promote the health of their EHs. Targeting and reducing CN may be a promising approach for future interventions to improve subsequent EHs.
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http://dx.doi.org/10.1016/j.appet.2021.105756DOI Listing
October 2021

The association of child neglect with lifestyles, depression, and self-esteem: Cross-lagged analyses in Chinese primary schoolchildren.

Behav Res Ther 2021 Nov 27;146:103950. Epub 2021 Aug 27.

School of Health Sciences, Wuhan University, Wuhan, China; Hubei Biomass-Resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, China. Electronic address:

Child neglect robustly predicts many behavioral problems and adulthood mental disorders, but little is known about its association with daily lifestyles and psychological development during childhood, particularly in the longitudinal study. We aimed to examine the association of child neglect with physical activity (PA), screen time (ST), eating habits (EHs), and depression/self-esteem using a two-wave follow-up study of primary schoolchildren in Wuhan, China. Data of 1085 schoolchildren aged 8-10 years (boys: 53.5%) were analyzed. Child neglect, lifestyles, and depression/self-esteem were collected in 2018 (T1) and 2019 (T2). Autoregressive cross-lagged models (ARCLMs) were fitted to explore the interrelationships among these variables. In ARCLM including child neglect and lifestyles, higher child neglect at T1 was significantly associated with higher ST and more risky EHs at T2, while insignificantly associated with PA. In ARCLM including child neglect and depression/self-esteem, lower T1 child neglect significantly predicted a higher T2 depression, but insignificantly for T2 self-esteem. In ARCLM including all variables, child neglect still significantly predicted later ST and depression, but insignificantly predicted EHs. Our study underscores that child neglect is strongly intertwined with ST, EHs, and depression during childhood. The prevention of child neglect may promote some healthy lifestyles and depression in children.
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http://dx.doi.org/10.1016/j.brat.2021.103950DOI Listing
November 2021

Protective effects of baicalin on caerulein-induced AR42J pancreatic acinar cells by attenuating oxidative stress through miR-136-5p downregulation.

Sci Prog 2021 Apr-Jun;104(2):368504211026118

Department of Emergency Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Baicalin, the main active component of , has antioxidant and anti-apoptotic effects and is used to treat acute pancreatitis; however, its specific mechanism is unclear. This study aims to determine the protective effect and underlying mechanism of baicalin on AR42J pancreatic acinar cell injury. AR42J acinar cells (caerulein, 10 nmol/L) were induced in vitro to establish a cell model for acute pancreatitis. Cell relative survival was measured by thiazolyl blue tetrazolium bromide, and cell apoptosis and death were examined by flow cytometry. The expression levels of superoxide dismutase1 (SOD1), Bax, survivin, Bcl-2, caspase-3, and caspase-7 proteins were analyzed by Western blot, and those of SOD1 mRNA and miR-136-5p were determined by RT-PCR. The activities of GSH, SOD1, ROS, and MDA were also investigated. Compared with those of the caerulein group, the relative survival rate and activity of AR42J pancreatic acinar cells with different baicalin concentrations were significantly increased ( < 0.05), and the supernatant amylase level was markedly decreased ( < 0.05). In addition, the ROS and MDA activities and mir-136-5p expression were significantly decreased, and the GSH activities and SOD1 gene and protein expression levels were markedly increased ( < 0.05). These results suggest that baicalin reduced the caerulein-induced death of AR42J acinar cells and alleviated the caerulein-induced injury in pancreatic acinar cells by inhibiting oxidative stress. The mechanism may be related to the decreased expression of Mir-136-5p and the increased expression of SOD1 gene and protein.
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http://dx.doi.org/10.1177/00368504211026118DOI Listing
June 2021

Detecting Periprosthetic Joint Infection by Using Mass Spectrometry.

J Bone Joint Surg Am 2021 Oct;103(20):1917-1926

Department of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing, People's Republic of China.

Background: Novel methods for diagnosing periprosthetic joint infection (PJI) are currently being explored. Mass spectrometry (MS) is an approach that can detect whole-protein changes in synovial fluid and may represent a promising method.

Methods: Between March 2017 and July 2018, we successively collected synovial fluid samples from patients who were undergoing diagnostic hip or knee aspiration because PJI was suspected. A PJI diagnosis was based on the modified Musculoskeletal Infection Society (MSIS) criteria. Cluster analysis and receiver operating characteristic (ROC) curves were used to evaluate the results, which were quantitatively confirmed with parallel reaction monitoring in another patient group who underwent aspiration between August 2018 and January 2019.

Results: A total of 117 synovial samples, including 51 PJI and 66 non-PJI samples, were analyzed with liquid chromatography-tandem MS (LC-MS/MS). The cluster analysis sensitivity and specificity based on differentially expressed proteins were 0.961 (95% confidence interval [CI], 0.854 to 0.993) and 0.924 (95% CI, 0.825 to 0.972), respectively. Myeloid nuclear differentiation antigen (MNDA) and polymorphonuclear leukocyte serine protease 3 (PRTN3) were the 2 most important markers for detecting PJI. The areas under the curves (AUCs) of MNDA and PRTN3 were 0.969 (95% CI, 0.936 to 1.000) and 0.900 (95% CI, 0.844 to 0.956), respectively. When MNDA and PRTN3 were combined as variables of a predictive model to diagnose PJI, the AUC reached 0.975 (95% CI, 0.943 to 1.000). Our parallel reaction monitoring-based quantitative analysis of another 40 synovial samples confirmed this result.

Conclusions: MS could be a powerful tool for diagnosing PJI using proteome information or 2 specific markers, MNDA and PRTN3. The parallel reaction monitoring strategy simplified the PJI detection process and provided quantitative results with similar conclusions.

Clinical Relevance: The clinical application of MS adds a new powerful tool for the diagnosis of PJI, and the parallel reaction monitoring strategy lays a foundation for the clinical application of MS.

Level Of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.20.01944DOI Listing
October 2021

Baicalin attenuates LPS-induced alveolar type II epithelial cell A549 injury by attenuation of the FSTL1 signaling pathway via increasing miR-200b-3p expression.

Innate Immun 2021 05 18;27(4):294-312. Epub 2021 May 18.

Department of Emergency Medicine, First Affiliated Hospital of Kunming Medical University, China.

In China, baicalin is the main active component of , which has been used in the treatment of inflammation-related diseases, such as inflammation-induced acute lung injury. However, its specific mechanism remains unclear. This study examined the protective effect of baicalin on LPS-induced inflammation injury of alveolar epithelial cell line A549 and explored its protective mechanism. Compared with the LPS-induced group, the proliferation inhibition rates of alveolar type II epithelial cell line A549 intervened by different concentrations of baicalin decreased significantly, as did the levels of inflammatory factors IL-6, IL-1β, prostaglandin 2 and TNF-α in the supernatant. The expression levels of inflammatory proteins inducible NO synthase (iNOS), NF-κB65, phosphorylated ERK (p-ERK1/2), and phosphorylated c-Jun N-terminal kinase (p-JNK1) significantly decreased, as did the protein expression of follistatin-like protein 1 (FSTL1). In contrast, expression of miR-200b-3p significantly increased in a dose-dependent manner. These results suggested that baicalin could significantly inhibit the expression of inflammation-related proteins and improve LPS-induced inflammatory injury in alveolar type II epithelial cells. The mechanism may be related to the inhibition of ERK/JNK inflammatory pathway activation by increasing the expression of miR-200b-3p. Thus, FSTL1 is the regulatory target of miR-200b-3p.
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http://dx.doi.org/10.1177/17534259211013887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186156PMC
May 2021

Correction to: Longitudinal trajectories of diet quality and subsequent mortality among Chinese adults: results from the China health and nutrition survey 1997-2015.

Int J Behav Nutr Phys Act 2021 Apr 29;18(1):56. Epub 2021 Apr 29.

Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, Burwood, Victoria, 3125, Australia.

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http://dx.doi.org/10.1186/s12966-021-01127-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086101PMC
April 2021

Body Mass Index And Association Of Psychological Stress With Exercise Performance In Military Members: The Cardiorespiratory Fitness And Hospitalization Events In Armed Forces (CHIEF) Study.

Endocr Metab Immune Disord Drug Targets 2021 Apr 26. Epub 2021 Apr 26.

Department of Medicine, Hualien Armed Forces General Hospital, Hualien. Taiwan.

Aims: To investigate the influence of body mass index (BMI) on the association between psychological stress and physical fitness.

Background: Both obesity and psychological stress reduce exercise performance.

Objective: It is unknown whether obesity may modify the relationship.

Methods: A population of 4,080 military subjects in Taiwan was divided to three groups according to the BMI ≥27.0 kg/m2 (obesity), 24.0-26.9 kg/m2 (overweight) and 18.5-23.9 kg/m2 (normal weight). Normal, slight, and great psychological stress was evaluated by the Brief Symptoms Rating Scale (BSRS-5) score ≤5, 6-9, and ≥10, respectively. Aerobic and anaerobic fitness were respectively evaluated by time for a 3000-meter run and numbers of 2-minute sit-ups and 2-minute push-ups. Analysis of covariance (ANCOVA) with adjustments for age and sex was used to determine the relationship.

Results: The mean time (sec) for a 3000-meter run (standard error) under slight and great stress differed from that under normal stress in the normal weight (881.0 (11.0) and 877.9 (5.8) vs. 862.2 (1.7), p=0.089 and 0.0088, respectively) and in the obesity (928.1 (16.8) and 921.8 (10.7) vs. 895.2 (1.6), p=0.054 and 0.016, respectively), while the differences were not significant in the overweight (877.1 (12.7) and 877.5 (7.1) vs. 867.1 (2.1), both p >0.5). The impacts of the BMI on 2-minute sit-ups had a similar pattern with that on a 3000-meter run whereas the impact of the BMI on 2-minute push-ups was insignificant.

Conclusions: Mental stress may not affect physical fitness in overweight military personnel. The mechanism is not clear and should be further investigated.
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http://dx.doi.org/10.2174/1871530321666210427090550DOI Listing
April 2021

Longitudinal trajectories of diet quality and subsequent mortality among Chinese adults: results from the China health and nutrition survey 1997-2015.

Int J Behav Nutr Phys Act 2021 04 7;18(1):51. Epub 2021 Apr 7.

Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, Burwood, Victoria, 3125, Australia.

Background: China has witnessed a significant nutritional transition. However, there is a gap in the literature investigating the association between change of diet and mortality among Chinese. Thus, we aimed to explore the longitudinal trajectories of diet quality over 10 years (from 1997 to 2006) and the subsequent risk of death till 2015 among Chinese adults.

Methods: Data from the China Health and Nutrition Survey were analyzed in 6398 adults. Dietary intake was assessed using three consecutive 24-h recalls. Diet quality was assessed by the Chinese Healthy Eating Index (CHEI), which includes 17 components and is based on the Dietary Guidelines for Chinese. Latent Class Growth Analysis was conducted to derive trajectories of diet quality over 10 years. Cox proportional hazard regression was used to calculate hazard ratios for total mortality.

Results: Four distinct CHEI trajectories were identified: 1) worsening; 2) low-moderate-low; 3) improving; 4) high-moderate-high. Group 3 had the lowest mortality rate (5.6%) in the subsequent 9 years, while the groups with worsening or low diet quality had a higher mortality rate (Group 1: 7.5%; Group 2: 10.8%). In the fully adjusted model, compared to group 2, mortality rates were lower for group 3 (RR = 0.73; 95% CI: 0.55, 0.97) and group 4 (RR = 0.76; 95% CI: 0.59, 0.98). No associations with mortality were found for the group 1, when compared to group 2.

Conclusions: Long-term improved diet quality and adherence to the Dietary Guidelines for Chinese may decrease the risk of death in Chinese adults.
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http://dx.doi.org/10.1186/s12966-021-01118-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028751PMC
April 2021

Associations of sleep duration and fruit and vegetable intake with the risk of metabolic syndrome in Chinese adults.

Medicine (Baltimore) 2021 Mar;100(10):e24600

School of Health Sciences.

Abstract: To understand the adverse association of short sleep duration and insufficient fruit and vegetable intake (FVI) with and their combined effect on metabolic syndrome (MetS) in Chinese adults.This cross-sectional study analyzed 7052 adults aged 18∼64 years old in 2009, with fasting blood samples collected. Participants were divided into short/normal/long sleep duration groups and sufficient/insufficient FVI groups in accordance with self-reported information. Metabolic syndrome was defined by National Cholesterol Education Program's Adult Treatment Panel III criteria.The prevalence of MetS among the study subjects was 21.74%. Participants were classified into short (<7 h/d), normal (7∼9 h/d), and long (>9 h/d) groups according to their daily sleep duration. Participants with less than 500 g of FVI per day was considered as insufficient FVI. After adjusting for confounders, the negative effect of short sleep duration on MetS was statistically significant, with an OR of 1.29 (95%CI = 1.06∼1.56); and high fasting glucose levels were significantly associated with insufficient FVI. Compared with subjects with normal sleep duration and sufficient FVI, participants with short sleep time and insufficient FVI had the highest risk of MetS (OR = 1.37, 95% CI: 1.04-1.66).This study revealed that insufficient FVI and short sleep duration were significantly associated with an increased risk of MetS among Chinese adults. Increasing FVI and normal sleep duration during Chinese adults could be significant targets for reducing the prevalence of MetS.
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http://dx.doi.org/10.1097/MD.0000000000024600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969326PMC
March 2021

Egg, cholesterol and protein intake and incident type 2 diabetes mellitus: Results of repeated measurements from a prospective cohort study.

Clin Nutr 2021 06 5;40(6):4180-4186. Epub 2021 Feb 5.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. Electronic address:

Background & Aims: Epidemiological evidence on the associations of egg, cholesterol and protein intake with risk of type 2 diabetes is inconsistent. Therefore, we conducted this study to explore these associations among Chinese adults.

Methods: Data from 4 waves (2004, 2006, 2009 and 2011) of the China Health and Nutrition Survey were used. A multistage random-cluster sampling method was employed to recruit the participants in both rural and urban areas. We included individuals who participated in 2004 and any waves afterwards. Those 1) below 18 years of age; 2) with diabetes at baseline; or 3) with extreme energy intake (men: <800 kcal or >6000 kcal; women: <600 kcal or >4000 kcal) were excluded. Respondents were classified into four groups according to quartiles of egg, cholesterol and protein intake per day. Numbers of eggs per day were calculated by dividing egg intake in grams by 50 g. Diagnosis of type 2 diabetes was self-reported. Logistic generalized estimation equation models were employed.

Results: There were 7312 individuals included in 2004, 6390 in 2006, 4826 in 2009 and 4963 in 2011. The mean age of participants at baseline was 48.3 years and 47.2% were men. Over an average of 5.8-y follow-up, 209 developed type 2 diabetes. After adjustment for demographic, lifestyle and dietary confounders, the odds ratio of type 2 diabetes for those in the highest compared with the lowest protein intake quartile was 2.38 (95% CI: 1.43, 3.98). The odds ratio of individuals with ≥3 eggs/day versus none was 3.76 (95% CI, 2.05, 6.90). Cholesterol intake was not associated with type 2 diabetes.

Conclusions: Individuals with the highest protein intake had over a 2-fold increased risk of type 2 diabetes compared with those with the lowest protein intake. A high intake of egg, but not dietary cholesterol, was associated with type 2 diabetes. This association warrants further investigation.
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http://dx.doi.org/10.1016/j.clnu.2021.01.041DOI Listing
June 2021

Associations of health-risk behaviors with mental health among Chinese children.

Psychol Health Med 2020 Dec 9:1-9. Epub 2020 Dec 9.

School of Health Sciences, Wuhan University, Wuhan, Hubei Province, P.R. China.

The study aimed to investigate the individual and combined association of health-risk behaviors with mental health among Chinese children. A cross-sectional study was conducted in Wuhan, China, from May to June 2018. Participants self-reported the information on physical activity (PA), screen time (ST), fruit and vegetable (FV) intake, and sleep duration. Mental health, including depression, social anxiety and self-esteem, was assessed using standard questionnaires. A total of 1296 children (704 males and 592 females) aged 9.2 ± 0.4 years were included in the present study. The prevalence of low PA, high ST, low FV intake, and inadequate sleep duration was 45.6%, 18.0%, 69.7%, and 64.7%, respectively. Overall, significant associations were found between individual health-risk behavior and increased risks of mental health. Furthermore, children with three or four health-risk behaviors showed significantly increased risks of anxiety (OR: 3.18, 95%CI: 1.63-6.21), depression (OR: 4.55, 95%CI: 2.28-9.09) and low self-esteem (OR: 3.59, 95%CI: 2.20-5.88) compared with those without health-risk behavior. Results of this study revealed a high prevalence of health-risk behaviors among Chinese children. Furthermore, the clustering of health-risk behavior was associated with significantly increased risks of mental health in this population. Considering these findings, it is important to perform early interventions to reduce children's health-risk behavior and prevent mental health problems.
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http://dx.doi.org/10.1080/13548506.2020.1859559DOI Listing
December 2020

Relationship between sedentary behaviour and anxiety symptoms among youth in 24 low- and middle-income countries.

PLoS One 2020 26;15(10):e0241303. Epub 2020 Oct 26.

School of Health Sciences, Wuhan University, Wuhan, China.

Background: Anxiety is burdensome and common in youth. Sedentary behaviour has been identified as potentially modifiable dangerous factors for many diseases. Nevertheless, little is known about the relationship between sedentary behaviour and the risk of anxiety symptoms in youth. Therefore, we aimed to examine the association among youth in 24 low- and middle-income countries (LMICs).

Methods: Data from the Global School-based Student Health Survey (GSHS) were analyzed in 59587 youth aged 12-15 years. Most of the country-wide data were nationally representative. Anxiety symptoms were self-reported. Multivariable logistic regression and meta-analyses of country-wise estimates were conducted.

Results: The prevalence of anxiety symptoms was 10.3%. Countrywide meta-analysis demonstrated that sedentary behaviour of >2 h/day (vs.≤2 h/day) was associated with an increased risk of anxiety symptoms (OR = 1.22; 95% CI = 1.10-1.37).

Conclusions: This study provides multi-national evidence of the dangerous effect of sedentary behaviour against anxiety symptoms among youth in LMICs. Decreasing the level of sedentary behaviour during adolescence could be an important target for reducing the prevalence of anxiety.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241303PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588091PMC
December 2020

Protective effect of resveratrol on estrogen deficiency-induced osteoporosis though attenuating NADPH oxidase 4/nuclear factor kappa B pathway by increasing miR-92b-3p expression.

Int J Immunopathol Pharmacol 2020 Jan-Dec;34:2058738420941762

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

Introduction: Resveratrol (RES) exhibits estrogen-like effects and has potential applications to treatment of osteoporosis caused by estrogen deficiency; however, the specific mechanism of action of RES remains unclear. Here, we examined the therapeutic effects of RES on ovariectomized (OVX) rats with osteoporosis and determined the underlying mechanism.

Methods: We established an OVX rat model to study osteoporosis caused by estrogen deficiency. The treatment groups were given orally with RES (50, 100, and 200 mg/day), the estrogen group received 0.8 mg/kg E2 daily via oral route, and the sham-operated and control groups received an equivalent dose of sodium carboxymethylcellulose orally. After 12 weeks of treatment, we used real-time quantitative polymerase chain reaction (PCR) and Western blot analysis to measure the gene and protein expression of miR-92b-3p, Nox4, NF-κBp65, IκB, BMP2, Smad7, and RUNX-2 in bone tissues. Right femur structural parameters were evaluated by micro-CT. Dual-energy X-ray 4500 W was used to determine systemic bone mineral density (BMD). Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the serum levels of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), anti-tartrate acid phosphatase-5b (PTRA5b), and carboxylated terminal peptide (CTX-I). The rat femoral bone specimens were stained using hematoxylin and eosin for pathological examination.

Results: We observed increased levels of serum estrogen in both ovaries, elevated miR-92b-3p levels in bone tissues, reduced levels of Nox4, NF-κBp65, p-IκB-a, and cathepsin K, and elevated gene and protein expression of BMP2, Smad7, and RUNX-2 in the OVX rat model of osteoporosis after treatment with RES. Elevated levels of BALP, OPG, ALP, and BMD along with reduced levels of TRAP-5b and CTX-I were also observed. The structural model index (SMI) and the trabecular space (Tb. Sp) decreased, while the trabecular thickness (Tb. Th), bone volume fraction (BV/TV), trabecular number (Tb.N), and tissue bone density (Conn.D) increased, thereby improving osteoporosis induced by estrogen deficiency in both ovaries.

Conclusion: Cathepsin K expression and Nox4/NF-κB signaling pathway were suppressed by the elevated expression of miR-92b-3p. This inhibition was pivotal in the protective effect of RES against osteoporosis induced by estrogen deficiency in both ovaries. Thus, RES efficiently alleviated osteoporosis induced by estrogen deficiency in rats.
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http://dx.doi.org/10.1177/2058738420941762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370339PMC
April 2021

Effects of emodin on intestinal mucosal barrier by the upregulation of miR-218a-5p expression in rats with acute necrotizing pancreatitis.

Int J Immunopathol Pharmacol 2020 Jan-Dec;34:2058738420941765

Department of Emergency, First Affiliated Hospital of Kunming Medical University, Kunming, China.

Emodin is an effective component in rhubarb to cure intestinal dysfunction, but the specific mechanism remains unknown. This study aimed to evaluate the protective effects of emodin on intestinal dysfunction caused by acute severe pancreatitis and reveal the functional mechanism of emodin in the treatment of this condition. An acute severe pancreatitis model was prepared using taurocholate. In the treatment group, 50 mg/kg emodin was injected intravenously 2 h before the induction of acute severe pancreatitis at an interval of 8 h. After 24 h, the gene expression and protein levels of miR-218a-5p, RhoA, ROCK1, Akt, Notch1, Bax, Bcl-2, Fas, FasL, caspase-3, and caspase-9 were determined through reverse transcription polymerase chain reaction and Western blot analysis. The protein levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract were also determined through Western blot analysis. The effects of miR-218a-5p on the apoptosis of rat intestinal epithelial cell-18 were observed through flow cytometry. The effects of emodin on intestinal cell apoptosis induced by acute severe pancreatitis were observed via TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Pathological changes in the pancreas and intestine of rats in each group were observed through hematoxylin and eosin staining. After 24 h of acute severe pancreatitis induced by taurocholate, emodin reduced the expression of miR-218a-5p in the intestinal tract; increased the expression of Notch1 and Bcl-2; decreased the expression levels of RhoA, ROCK1, Akt, Bax, Fas, FasL, caspase-3, and caspase-9; inhibited the intestinal cell apoptosis caused by acute severe pancreatitis; increased the protein expression levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract; and alleviated intestinal dysfunction caused by acute severe pancreatitis. Emodin could regulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the intestine. It could also inhibit intestinal cell apoptosis induced by acute severe pancreatitis and improve the intestinal dysfunction caused by severe acute pancreatitis.
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http://dx.doi.org/10.1177/2058738420941765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364802PMC
April 2021

Amelioration of paraquat-induced pulmonary fibrosis in mice by regulating miR-140-5p expression with the fibrogenic inhibitor Xuebijing.

Int J Immunopathol Pharmacol 2020 Jan-Dec;34:2058738420923911

Department of Emergency, First Hospital Affiliated to Kunming Medical University, Kunming, China.

Intravenous Xuebijing (XBJ) therapy suppresses paraquat (PQ)-induced pulmonary fibrosis. However, the mechanism underlying this suppression remains unknown. This work aimed to analyze the miR-140-5p-induced effects of XBJ injection on PQ-induced pulmonary fibrosis in mice. The mice were arbitrarily assigned to four groups. The model group was administered with PQ only. The PQ treatment group was administered with PQ and XBJ. The control group was administered with saline only. The control treatment group was administered with XBJ only. The miR-140-5p and miR-140-5p knockout animal models were overexpressed. The gene expression levels of miR-140-5p, transglutaminase-2 (TG2), β-catenin, Wnt-1, connective tissue growth factor (CTGF), mothers against decapentaplegic homolog (Smad), and transforming growth factor-β1 (TGF-β1) in the lungs were assayed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The levels of TGF-β1, CTGF, and matrix metalloproteinase-9 (MMP-9) in the bronchoalveolar lavage fluid were assessed by enzyme-linked immunosorbent assay (ELISA). Hydroxyproline (Hyp) levels and pulmonary fibrosis were also scored. After 14 days of PQ induction of pulmonary fibrosis, AdCMV-miR-140-5p, and XBJ upregulated miR-140-5p expression; blocked the expressions of TG2, Wnt-1, and β-catenin; and decreased p-Smad2, p-Smad3, CTGF, MMP-9, and TGF-β1 expressions. In addition, Hyp and pulmonary fibrosis scores in XBJ-treated mice decreased. Histological results confirmed that PQ-induced pulmonary fibrosis in XBJ-treated lungs was attenuated. TG2 expression and the Wnt-1/β-catenin signaling pathway were suppressed by the elevated levels of miR-140-5p expression. This inhibition was pivotal in the protective effect of XBJ against PQ-induced pulmonary fibrosis. Thus, XBJ efficiently alleviated PQ-induced pulmonary fibrosis in mice.
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http://dx.doi.org/10.1177/2058738420923911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262989PMC
March 2021

Association of Psychological Stress with Physical Fitness in a Military Cohort: The CHIEF Study.

Mil Med 2020 08;185(7-8):e1240-e1246

Department of Medicine, Hualien Armed Forces General Hospital, Hualien, Taiwan.

Introduction: Psychological stress is associated with sedentary behavior, which may impair exercise performance. The aim of our study was to examine the association between psychological stress and physical fitness in military personnel.

Method: A military cohort of 4080 subjects in Taiwan was used for the analysis. The Brief Symptoms Rating Scale (BSRS-5) includes items of anxiety, depression, hostility, interpersonal sensitivity, and insomnia measured by a five-point Likert-type scale of 0-4. Psychological stress was defined as normal (n = 3657), slight (n = 314), and great (n = 109) by BSRS-5 score ≤5, 6-9, and ≥10, respectively. Aerobic fitness and anaerobic fitness were evaluated by the time of 3000-meter running and the numbers of 2-min sit-ups and 2-min push-ups, respectively. Multiple linear and logistic regression analyses were used to determine the relationship.

Results: As compared with normal stress, slight and great stress were positive dose-dependently correlated with 3000-meter running time (β = 9.09 and 14.44; P = 0.0032 and 0.048, respectively) after adjusting for age, sex, service specialty, body mass index, systolic blood pressure, cigarette smoking, alcohol intake, hemoglobin levels, and exercise frequency. Similarly, those with slight stress were more likely to be the worst 10% performers in the 3000-meter run test relative to the normal individuals (odds ratio and 95% confidence intervals: 1.50, 1.00-2.24). By contrast, there was no relationship of psychological stress with the numbers of 2-min sit-ups and 2-min push-ups.

Conclusions: Our findings suggest that the presence of higher psychological stress on military personnel may reduce their cardiorespiratory fitness but not affect the anaerobic fitness.
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http://dx.doi.org/10.1093/milmed/usz469DOI Listing
August 2020

Sedum sarmentosum Bunge extract ameliorates lipopolysaccharide- and D-galactosamine-induced acute liver injury by attenuating the hedgehog signaling pathway via regulation of miR-124 expression.

BMC Complement Med Ther 2020 Mar 17;20(1):88. Epub 2020 Mar 17.

Department of Emergency, Yan'an Hospital of Kunming City, Panlong District, 245 Renmin East Road, Kunming, 650051, China.

Background: Sedum sarmentosum is traditionally used to treat various inflammatory diseases in China. It has protective effects against acute liver injury, but the exact mechanism of such effects remains unclear. This study investigated the protective effects of S. sarmentosum extract on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury in mice and the mechanism of such effects.

Methods: Mice were randomly divided into control, treatment, model, and model treatment groups. Acute liver injury was induced in model mice via intraperitoneal injection of LPS and D-GalN with doses of 10 μg/kg of LPS and 500 mg/kg, respectively. The mRNA expression levels of miR-124, Hedgehog, Patched (Ptch), Smoothened (Smo), and glioma-associated oncogene homolog (Gli) in liver tissues were determined through RT-PCR, and the protein levels of Hedgehog, Ptch, Smo, Gli, P13k, Akt, HMGB1, TLR4, IkB-α, p-IkB-α, and NF-kB65 were evaluated via Western blot analysis. The serum levels of IL-6, TNF-α, CRP, IL-12, and ICAM-1 were determined via ELISA. TLR4 and NF-κBp65 activity and the levels of DNA-bound NF-KB65 and TLR4 in LPS/D-GalN-induced liver tissues were also determined. We recorded the time of death, plotted the survival curve, and calculated the liver index. We then observed the pathological changes in liver tissue and detected the levels of liver enzymes (alanine aminotransferase [ALT] and aspartate transaminase [AST]) in the serum and myeloperoxidase (MPO) and plasma inflammatory factors in the liver homogenate. Afterward, we evaluated the protective effects of S. sarmentosum extracts on acute liver injury in mice.

Results: Results showed that after S. sarmentosum extract was administered, the expression level of miR-124 increased in liver tissues. However, the protein expression levels of Hedgehog, Ptch, Smo, Gli, P13k, p-Akt, HMGB1, TLR4, p-IκB-α, and NF-κB65 and the mRNA expression levels of Hedgehog, Ptch, Smo, and Gli decreased. The MPO level in the liver, the IL-6, TNF-α, CRP, IL-12, and MMP-9 levels in the plasma, and the serum ALT and AST levels also decreased, thereby reducing LPS/D-GalN-induced liver injury and improving the survival rate of liver-damaged animals within 24 h.

Conclusions: S. sarmentosum extract can alleviate LPS/D-GalN-induced acute liver injury in mice and improve the survival rate of mice. The mechanism may be related to the increase in miR-124 expression, decrease in Hedgehog and HMGB1 signaling pathway activities, and reduction in inflammatory responses in the liver. Hedgehog is a regulatory target for miR-124.
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http://dx.doi.org/10.1186/s12906-020-2873-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076998PMC
March 2020

Effects of miR-199a on autophagy by targeting glycogen synthase kinase 3β to activate PTEN/AKT/mTOR signaling in an MPP model of Parkinson's disease.

Neurol Res 2020 Apr 10;42(4):308-318. Epub 2020 Mar 10.

Department of Neurology, First People's Hospital of Qujing City, Qujing City, China.

: miR-199a can regulate autophagy, its underlying mechanisms remain unknown. The purpose of this study was to investigate the mechanisms of miR-199a involved in regulating autophagy in a 1-methyl-4-phenylpyridine (MPP)-induced model of PD.: PC12 cells were incubated in MPP, and the expression levels of miR-199a were bidirectionally regulated via either transfection of an miR-199a mimic or incubation in miR-199a inhibitors. The experimental manipulations were divided into four groups, including the control group, MPP group, MPP + miR-199a mimic group, and MPP + miR-199a inhibitor group. MTT, CCK-8, qRT-PCR, Western blotting and linear correlation analysis were performed to evaluate various experimental indicators.: At increasing MPP concentrations, the following results were found: the expression levels of miR-199a, phosphorylated AKT and mTOR proteins expression decreased; the expression levels of phosphatase and tensin homologue (PTEN), GSK3β, Beclin1, and LC3II increased; PC12 autophagy increased; and cellular viability and survival rates decreased. Transfection of an miR-199a mimic increased miR-199a expression and induced all of the following: the expression levels of PTEN, GSK3β, Beclin1, and LC3II decreased; the expression levels of phosphorylated AKT and mTOR proteins expression increased; PC12 autophagy decreased; and cellular viability and survival rates increased.: In this study, we found that increasing miR-199a expression in PC12 cells reduced protein levels of Beclin1 and LC3II, decreased autophagy, enhanced cellular viability, increased survival rate, and ameliorated MPP-induced parkinsonian-like cellular pathologies by targeting pro-autophagic pathways and GSK3β to activate PTEN/AKT/mTOR signaling.
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http://dx.doi.org/10.1080/01616412.2020.1726584DOI Listing
April 2020

Association of Adverse Childhood Experiences with Health Risk Behaviors Among College Students in Zambia.

Int J Behav Med 2020 Aug;27(4):400-405

School of Health Sciences, Wuhan University, Donghu Rd, No. 185, Wuhan, 430071, Hubei Province, People's Republic of China.

Background: Adverse childhood experiences (ACEs) have been linked to long-term health outcomes, while the impact of such experience has not been investigated among Zambian youth. This study examined the associations of ACEs with individual and clusters of health risk behavior among college students in Zambia.

Method: A total of 624 college students participated in this cross-sectional study. A self-administered questionnaire was used to collect information on their ACEs and health risk behaviors.

Results: There were 58.3% (364) reporting some forms of ACEs, with 27.6% (172), 16.3% (102), and 14.4% (90) being exposed to 1, 2, and ≥ 3 ACEs, respectively. The prevalence of health risk behaviors ranged from 6.0 to 34.2%. Overall, ACEs were associated with increased risk of smoking, binge drinking, suicide attempt, risky sexual behaviors, and illicit drug use. Logistic regression suggested that participants with ≥ 3 ACEs (OR, 3.62; 95% CI, 2.14-6.13) were more likely to engage in the unhealthy cluster, characterized by the presence of any health risk behavior, than those without ACE.

Conclusion: ACEs were associated with individual and clustering of health risk behaviors among Zambia college students. Our study suggests that early intervention is needed to prevent long-term adverse health consequences in this population.
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http://dx.doi.org/10.1007/s12529-020-09863-yDOI Listing
August 2020

The Impact of Angiotensin-Converting Enzyme Gene on Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease.

Curr Alzheimer Res 2019 ;16(14):1269-1275

Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: The Angiotensin-Converting Enzyme (ACE) gene has drawn attention for its possible role in regulating the degradation of β-amyloid (Aβ), yet its role in affecting the cognitive and psychiatric symptoms of Alzheimer`s Disease (AD) patients has yet to be elucidated.

Objective: This study aimed to investigate whether the ACE gene acts as a risk factor of Behavioral and Psychological Symptoms of Dementia (BPSD) in the AD population.

Methods: The genotyping of ACE and Apolipoprotein E gene with allele ε4(APOEε4) was determined among 360s clinically diagnosed AD patients. Symptoms and severity of BPSD were evaluated annually via Neuropsychiatric Inventory (NPI).

Results: At the base measurement of the first year of patient recruitment, there were no significant contributory risk factors to NPI score. In the two-year follow-up, ACE insertion polymorphism showed a significant risk (adjusted odds ratio=1.65, 95% CI=1.1- 2.5, p=0.019) of progression of NPI total score.

Conclusion: ACE gene is involved in aggravating BPSD among AD patients.
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http://dx.doi.org/10.2174/1567205017666200103114550DOI Listing
October 2020

Fat Intake and Hypertension Among Adults in China: The Modifying Effects of Fruit and Vegetable Intake.

Am J Prev Med 2020 02 15;58(2):294-301. Epub 2019 Nov 15.

School of Health Sciences, Wuhan University, Wuhan City, Hubei Province, Wuhan, China. Electronic address:

Introduction: Evidence on the combined effect of fruit and vegetable intake and total fat intake on hypertension is scarce. This study aimed to explore the relationship among fruit and vegetable intake, fat intake, and hypertension risk among Chinese adults.

Methods: Individuals who participated in the China Health and Nutrition Survey (2004, 2006, 2009, and 2011) and were free of hypertension at baseline (n=4,368) were categorized into quartiles (Q1, lowest; Q4, highest) according to their dietary fruit and vegetable intake and fat intake. Generalized estimation equation models, adjusted for confounders, were used to explore the relationship of fat intake with hypertension and systolic and diastolic blood pressure among all adults and within quartiles of fruit and vegetable intake. Data analyses were performed in 2018.

Results: A total of 1,086 adults developed hypertension during follow-up. In the total population, the OR of the highest quartile of fat intake was 1.40 (95% CI=1.12, 1.75) compared with the lowest. Among individuals with low fruit and vegetable intake, the odds of hypertension for those in Q3 (OR=1.97, 95% CI=1.37, 2.83) and Q4 (OR=1.81, 95% CI=1.14, 2.90) of fat intake, compared with individuals in Q1, were even higher than for the overall sample. For each 50-gram increase in FI per day, the ORs of hypertension increased from fat intake Q1 to Q4 among all respondents and those with low fruit and vegetable intake, but not among those with high fruit and vegetable intake. Systolic blood pressure increased by 1.08 mm Hg (95% CI=0.03, 2.13) per 50-gram fat intake per day increment in the fruit and vegetable intake Q1 group, whereas the association was not significant in the fruit and vegetable intake Q2-Q4 groups.

Conclusions: Fruit and vegetable intake modifies the relationship between fat intake and hypertension, whereby high fruit and vegetable intake may offset the detrimental effect of fat intake on hypertension. Increased fruit and vegetable intake and controlled fat intake are recommended to prevent hypertension in Chinese adults.
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http://dx.doi.org/10.1016/j.amepre.2019.09.004DOI Listing
February 2020

Fruit and vegetable intake in relation to depressive and anxiety symptoms among adolescents in 25 low- and middle-income countries.

J Affect Disord 2020 01 8;261:172-180. Epub 2019 Oct 8.

School of Health Sciences, Wuhan University, Wuhan, P.R. China. Electronic address:

Background: Fruit and vegetable intake (FVI) has been inversely associated with the risk of depression. However, there is a gap in evidence from low- and middle-income countries (LMICs) and among adolescents. Further, little is known about FVI in relation to the risk of anxiety. Therefore, we examined these associations among adolescents in 25 LMICs.

Methods: Data from the Global School-based Student Health Survey were analyzed in 65267 adolescents aged 12-15 years (mostly nationally representative). Depressive and anxiety symptoms during the past 12 months were self-reported. Frequencies of FVI during the past 30 days were collected. Multivariable logistic regression and meta-analyses of country-wise estimates were undertaken.

Results: The prevalence of depressive and anxiety symptoms were 30.3% and 9.8%, respectively. A meta-analysis indicated that FVI of <5 times/d (vs. higher) was associated with an increased risk of depressive symptoms (OR = 1.10; 95% CI = 1.02-1.18). The pooled estimate for anxiety symptoms was insignificant. When examined separately, fruit intake was significantly associated with both lower risks of depressive and anxiety symptoms; vegetable intake was significantly associated with a lower risk of depressive symptoms, but not with anxiety.

Limitations: Only adolescents attending school were included; the cross-sectional design cannot reveal causality; outcomes were not measured against the gold-standard diagnostic criteria.

Conclusions: Our study provides multi-national evidence of the protective effect of FVI against depressive and anxiety symptoms among adolescents in LMICs, enabling key stakeholders to address mental health issues among adolescents globally.
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http://dx.doi.org/10.1016/j.jad.2019.10.007DOI Listing
January 2020

Pattern formation of skin cancers: Effects of cancer proliferation and hydrodynamic interactions.

Phys Rev E 2019 Mar;99(3-1):032416

Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo 192-0397, Japan.

We study pattern formation of skin cancers by means of numerical simulation of a binary system consisting of cancer and healthy cells. We extend the conventional model H for macrophase separations by considering a logistic growth of cancer cells and also a mechanical friction between dermis and epidermis. Importantly, our model exhibits a microphase separation due to the proliferation of cancer cells. By numerically solving the time evolution equations of the cancer composition and its velocity, we show that the phase separation kinetics strongly depends on the cell proliferation rate as well as on the strength of hydrodynamic interactions. A steady-state diagram of cancer patterns is established in terms of these two dynamical parameters and some of the patterns correspond to clinically observed cancer patterns. Furthermore, we examine in detail the time evolution of the average composition of cancer cells and the characteristic length of the microstructures. Our results demonstrate that different sequence of cancer patterns can be obtained by changing the proliferation rate and/or hydrodynamic interactions.
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http://dx.doi.org/10.1103/PhysRevE.99.032416DOI Listing
March 2019

The impact of a health education intervention on health behaviors and mental health among Chinese college students.

J Am Coll Health 2020 Aug-Sep;68(6):587-592. Epub 2019 Mar 8.

School of Health Sciences, Wuhan University, Wuhan, People's Republic of China.

This study aimed to assess the impact of a health education intervention on health behaviors, self-efficacy, and well-being among college students. Between March and October 2016, a total of 532 undergraduates participated. A theory-based intervention was conducted at Wuhan University, China. Participants were assigned to a control or intervention group (IG). The IG attended a 7-week health education class on knowledge, attitude, and practice of health behaviors. Participants in the IG, compared with those in the control group (CG), reported significantly increased prevalence of high physical activity and regular breakfast, as well as lower screen time, sugar beverage intake, and Internet addiction tendency. Furthermore, intervention students improved in health behavior scores ( = 0.040), compared with the CG, while the changes in subjective well-being and self-efficacy remained similar between the two groups. Health education may promote health behaviors among Chinese college students.
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http://dx.doi.org/10.1080/07448481.2019.1583659DOI Listing
May 2021

Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression.

BMC Pulm Med 2019 Feb 11;19(1):35. Epub 2019 Feb 11.

Department of Emergency, the First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, Yunan, People's Republic of China.

Background: Reactive oxygen species (ROS) levels largely determine pulmonary fibrosis. Antioxidants have been found to ameliorate lung fibrosis after long-term paraquat (PQ) exposure. The effects of antioxidants, however, on the signalling pathways involved in PQ-induced lung fibrosis have not yet been investigated sufficiently. Here, we examined the impacts of ligustrazin on lung fibrosis, in particular ROS-related autophagy and pro-fibrotic signalling pathways, using a murine model of PQ-induced lung fibrosis.

Methods: We explored the effects of microRNA-193 (miR-193a) on Hedgehog (Hh) and PI3K/Akt/mTOR signalling and oxidative stress in lung tissues. Levels of miR-193a, protein kinase B (Akt), phosphoinositide 3-Kinase (PI3K), ceclin1, mammalian target of rapamycin (mTOR), sonic hedgehog (SHH), myosin-like Bcl2 interacting protein (LC3), smoothened (Smo), and glioma-associated oncogene-1 (Gli-1) mRNAs were determined with quantitative real-time PCR. Protein levels of PI3K, p-mTOR, p-Akt, SHH, beclin1, gGli-1, LC3, smo, transforming growth factor-β1 (TGF-β1), mothers against DPP homologue-2 (Smad2), connective tissue growth factor (CTGF), collagen I, collagen III, α-smooth muscle actin (α-SMA) nuclear factor erythroid 2p45-related factor-2 (Nrf2), and p-Smad2 were detected by western blotting. In addition, α-SMA, malondialdehyde, ROS, superoxide dismutase (SOD), oxidised and reduced glutathione, hydroxyproline, and overall collagen levels were identified in lung tissues using immunohistochemistry.

Results: Long-term PQ exposure blocked miR-193a expression, reduced PI3K/Akt/mTOR signalling, increased oxidative stress, inhibited autophagy, increased Hh signalling, and facilitated the formation of pulmonary fibrosis. Ligustrazin blocked PI3K/Akt/mTOR and Hh signalling as well as reduced oxidative stress via increasing miR-193a expression and autophagy, all of which reduced pulmonary fibrosis. These effects of ligustrazin were accompanied by reduced TGF-β1, CTGF, and Collagen I and III expression.

Conclusions: Ligustrazin blocked PQ-induced PI3K/Akt/mTOR and Hh signalling by increasing miR-193a expression, thereby attenuating PQ-induced lung fibrosis.
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http://dx.doi.org/10.1186/s12890-019-0799-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371511PMC
February 2019

Association between fruit and vegetable intake and the risk of hypertension among Chinese adults: a longitudinal study.

Eur J Nutr 2018 Oct 16;57(7):2639-2647. Epub 2018 Apr 16.

School of Health Sciences, Wuhan University, Wuhan, People's Republic of China.

Purpose: Fruit and vegetable intake has been inversely associated with the risk of hypertension; however, there is inconsistent evidence on the long-term association. Given this gap in the literature, it is necessary to identify evidence from large prospective studies, especially in China, where insufficient evidence exists. Thus, we examined the association of fruit and vegetable intake with incident hypertension in Chinese adults.

Methods: We conducted analyses among 5659 Chinese adults aged 18-64 years, free of cardiovascular disease, cancer, and hypertension in the 2006 wave of the China Health and Nutrition Survey. Fruit and vegetable intake was assessed using consecutive 24-h recalls. Incident hypertension was identified from the 2011 wave of the survey.

Results: A total of 866 participants developed incident hypertension. The relative risks (RRs) and 95% confidence intervals (CIs) of hypertension were 0.74 (0.55-0.99), 0.65 (0.48-0.88), 0.68 (0.50-0.92), and 0.73 (0.53-0.99) comparing each quintile group of fruit and vegetable intake with the lowest quintile group. These associations attenuated for the change of intake but remained significant for the fourth quintile, of which the RR (95% CI) was 0.65 (0.47-0.89). The magnitude of association was stronger among those who were younger, female, overweight and had prehypertension. When examined separately, fruit intake was more strongly and significantly associated with lowering BP than vegetable intake. Adding body mass index to the models attenuated all associations.

Conclusions: Greater long-term intake and increased intake of fruit and vegetables may reduce the risk of developing hypertension in Chinese adults.
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http://dx.doi.org/10.1007/s00394-018-1687-0DOI Listing
October 2018

Effects of Panax notoginseng saponins on severe acute pancreatitis through the regulation of mTOR/Akt and caspase-3 signaling pathway by upregulating miR-181b expression in rats.

BMC Complement Altern Med 2018 Feb 5;18(1):51. Epub 2018 Feb 5.

Department of Emergency, the First Hospital Affiliated To Kunming Medical University, 295 Xichang Road, Wu Hua District, Kunming, 650032, China.

Background: In China, Panax notoginseng has been used to treat oxidative stress-related diseases for a long time. Panax notoginseng saponins is an extract from Panax notoginseng Ledeb. Its therapeutic potential is related to antioxidant activity, but related mechanisms are still unclear. The study aims to assess the protection effects of Panax notoginseng saponins in the taurocholate-induced rat model of acute pancreatitis (AP) and explore underlying mechanisms.

Methods: A rat model of severe acute pancreatitis (SAP) was established in rats induced with taurocholate. Panax notoginseng saponins was firstly administered in the treatment group via intravenous injection. After 2 h, taurocholate administration was performed. After 24 h, the expression levels of miR-181b, Beclin1, LC3-II, Akt and mTOR from pancreas tissues were measured by Western Blotting and RT-PCR. Then the expression levels of Caspase-3 and Blc-2 were determined by immunohistochemistry. Apoptosis was assessed by the TUNEL assay. Amylase and lipase in serum were determined by ELISA and pancreatic water contents in pancreatic tissue were measured. After eosin and hematoxylin staining, the histologic analysis was performed.

Results: After SAP induction by taurocholate and the treatment with Panax notoginseng saponins for 24 h, we detected the up-regulated miR-181b, the reduced Bcl-2 expression, the increased activity of mTOR/Akt, the blocked Beclin1 and LC3-II expressions, and the enhanced Caspase-3 expression. Serum lipase and amylase levels were significantly decreased in the treatment group of Panax notoginseng saponins compared to the control group. Histological analysis results verified the attenuation effects of Panax notoginseng saponins on taurocholate-induced pancreas injury, apoptosis, and autophagy.

Conclusion: By up-regulating the miR-181b expression level, Panax notoginseng saponins significantly reduced taurocholate-induced pancreas injury and autophagy and increased apoptosis. The significant protection effects of Panax notoginseng saponins suggested its potential in treating taurocholate induced-acute pancreatitis.
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http://dx.doi.org/10.1186/s12906-018-2118-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800027PMC
February 2018

Combined effects of fruit and vegetables intake and physical activity on the risk of metabolic syndrome among Chinese adults.

PLoS One 2017 21;12(11):e0188533. Epub 2017 Nov 21.

School of Health Sciences, Wuhan University, P. R. China.

Background: Unbalanced dietary intake and insufficient physical activity (PA) have been recognized as risk factors for metabolic syndrome (MetS). We aimed to examine the independent and combined effects of fruit and vegetables (FV) intake and PA on MetS.

Methods And Findings: A cross-sectional survey was conducted among residents of China in 2009, with fasting blood samples collected. Participants were divided into sufficient/insufficient FV intake and adequate/ inadequate PA groups according to self-reported questionnaires. MetS was defined using the NCEP-ATPIII criteria. The difference of individual MetS components was compared across different PA or FV groups. Multivariable logistic regression was used to assess association between FV/PA and the risk of MetS. A total of 7424 adults were included in the current study. MetS was prevalent in 28.7% of participants, with 24.7% and 32.9% in male and female, respectively. Compared with those with inadequate PA and insufficient FV intake, participants with the combination of adequate PA and sufficient FV intake had the lowest risk of MetS (OR = 0.69,95%CI: 0.59-0.82), following by the group with adequate PA time but insufficient FV intake (OR = 0.74, 95%CI:0.65-0.83).

Conclusion: Findings of the current study show that the combination of sufficient FV intake and adequate PA was significantly associated with reduced MetS risk among adult residents of China.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188533PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697838PMC
December 2017
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