Temporal relationships between blood glucose, lipids and BMI, and their impacts on atherosclerosis: a prospective cohort study.

OBJECTIVES: This study aimed to explore the temporal relationship between blood glucose, lipids and body mass index (BMI), and their impacts on atherosclerosis (AS). DESIGN: A prospective cohort study was designed. SETTING AND PARTICIPANTS: A total of 2659 subjects from Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases, and aged from 20 to 74 years were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Body weight, height, fasting blood glucose (FBG) and 2-hour postprandial glucose (2-h PG), blood lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) were measured at baseline and follow-up. Brachial ankle pulse wave velocity (baPWV) was examined at follow-up as a marker of AS risk. Logistic regression analysis, cross-lagged path analysis and mediation analysis were performed to explore the temporal relationships between blood glucose, lipids and BMI, and their impacts on AS risk. RESULTS: Logistic regression analysis indicated that increased FBG, 2-h PG, TC, TG, LDL-c and BMI were positively associated with AS risk, while increased HDL-c was negatively associated with AS risk. The path coefficients from baseline blood parameters to the follow-up BMI were significantly greater than those from baseline BMI to the follow-up blood parameters. Mediation analysis suggested that increased FBG, 2-h PG, TC, TG and LDL-c could increase AS risk via increasing BMI, the effect intensity from strong to weak was LDL-c>TC>TG>FBG>2 h PG, while increased HDL-c could decrease AS risk via decreasing BMI. CONCLUSIONS: Changes in blood glucose and lipids could cause change in BMI, which mediated the impacts of blood glucose and lipids on AS risk. These results highlight the importance and provide support for the early and comprehensive strategies of AS prevention and control.

Geographic location and ethnicity comprehensively influenced vitamin D status in college students: a cross-section study from China.

BACKGROUND: Vitamin D plays an important role in the health of adolescents, whereas vitamin D status of Chinese college students was seldom studied in China. To explore the vitamin D status and its relationship with ethnicity and geographic location in Chinese college students. METHODS: The freshmen were taken a physical examination by trained medical personnel after they reported to university. Demographic information including age, gender, ethnicity, region of original residence was collected using a questionnaire survey. Serum 25(OH)D3 concentrations were measured using a liquid chromatograph mass spectrometer. Multiple regression analyses were used to explore the factors that influence serum 25(OH)D3 levels. RESULTS: Totally 3220 freshmen who came from 26 provinces, autonomous districts or municipalities were recruited, with a mean age of 18.75 ± 1.18 years and 70.2% of them were female. The mean serum 25(OH)D3 levels were 18.51 ± 6.54 ng/mL, and the proportion of vitamin D deficiency (< 20 ng/mL) and insufficiency (20 ~ < 30 ng/mL) was 64.4% and 30.2%, respectively. The combined proportion of vitamin D deficiency and insufficiency was increased with the latitude increased. Miao had the highest serum 25(OH)D3 levels, whereas Kazak ethnic had the lowest (22.51 ng/mL vs. 13.94 ng/mL) among different ethnic groups. Female students, students from city, Uighur and Kazak ethnic, residing in high latitude was significantly associated with lower serum 25(OH)D3 levels (P < 0.05). CONCLUSIONS: Vitamin D deficiency is an important health problem in Chinese college students. Sunlight activities, dietary and life-style intervention for college students according to geographic location and ethnicities should be considered.

Effects of soda water on blood lipid and metabolic profiling of urine in hyperlipidemia rats using UPLC/Triple-TOF MS.

The effects of a natural soda water (Shi Han Quan, SHQ) on hyperlipidemia and the changes of urine metabolic profiling by metabolomics techniques were investigate. Thirty six Wistar rats weighing 160-200 g were divided into control group, hyperlipidemia (HL) group, and hyperlipidemia + SHQ water (SHQ) group. The metabolites in urine were determined using ultra high performance liquid chromatography-triple-time of flight-mass spectrometry (UPLC/Triple-TOF MS). At the end of 1 month and 3 months, the total glyceride (TG) level was significantly lower in SHQ group compared to HL group. There was no significantly difference in total cholesterol (TC) levels in HL group compared with SHQ group. The results showed that dinking SHQ water can improve the TG, but with no effects on TC. After drinking SHQ water for 3 months, the rats in different groups could be classified into different clusters according to the metabolites in urine. Total 15 important metabolites were found and correlated with disturbance of amino acid, phospholipid, fatty acid and vitamin metabolism, which suggested the changes of metabolism in the body and possible mechanism by which SHQ improved the TG. These findings provide a new insight for the prevention and control of hyperlipidemia.

Protective effect of manganese treatment on insulin resistance in Hepg2 hepatocytes / Efecto protector del tratamiento con manganeso sobre la resistencia a la insulina en hepatocitos HepG2

Objectives: manganese (Mn) is closely related to type 2 diabetes mellitus and insulin resistance (IR), but the exact mechanism is unclear. This study aimed to explore the regulatory effects and mechanism of Mn on IR using hepatocyte IR model induced by high palmitate (PA), high glucose (HG) or insulin. Methods: HepG2 cells were exposed to PA (200 μM), HG (25 mM) or insulin (100 nM) respectively, alone or with 5 μM Mn for 24 hours. The expression of key proteins in insulin signaling pathway, intracellular glycogen content and glucose accumulation, reactive oxygen species (ROS) level and Mn superoxide dismutase (MnSOD) activity were detected. Results: compared with control group, the expression of phosphorylated protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β) and forkhead box O1 (FOXO1) in the three IR groups was declined, and this decrease was reversed by Mn. The reduction of intracellular glycogen content and increase in glucose accumulation in IR groups were also inhibited by Mn. Additionally, the production of ROS was increased in IR models, compared with normal control group, while Mn reduced the excessive production of ROS induced by PA, HG or insulin. However, Mn did not alter the activity of MnSOD in the three IR models. Conclusion: this study demonstrated that Mn treatment can improve IR in hepatocytes. The mechanism is probably by reducing the level of intracellular oxidative stress, enhancing the activity of Akt/GSK-3β/FOXO1 signal pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.(AU)

Objetivos: el manganeso (Mn) está estrechamente relacionado con la diabetes mellitus tipo 2 y la resistencia a la insulina (RI), pero el mecanismoexacto aún no está claro. Este estudio tuvo como objetivo explorar los efectos reguladores y el mecanismo del Mn sobre la RI utilizando un modelode RI en hepatocitos inducido por palmitato alto (PA), glucosa alta (HG) o insulina.Métodos: las células HepG2 se expusieron a PA (200 μM), HG (25 mM) o insulina (100 nM), solas o junto con 5 μM de Mn durante 24 horas.Se evaluó la expresión de proteínas clave en la vía de señalización de la insulina, el contenido intracelular de glucógeno y la acumulación deglucosa, el nivel de especies reactivas de oxígeno (ROS) y la actividad superóxido dismutasa del manganeso (MnSOD).Resultados: en comparación con el grupo de control, la expresión de proteína quinasa B fosforilada (Akt), la glucógeno sintasa quinasa-3β(GSK-3β) y la proteína forkhead box O1 (FOXO1) en los tres grupos de RI se redujo, y esta disminución fue revertida por el Mn. La reduccióndel contenido de glucógeno intracelular y el aumento de la acumulación de glucosa en los grupos de RI también fueron inhibidos por el Mn.Además, la producción de ROS aumentó en los modelos de RI en comparación con el grupo de control normal. Mientras que el Mn redujo laproducción excesiva de ROS inducida por PA, HG o insulina. Sin embargo, el Mn no alteró la actividad de la MnSOD en los tres modelos de RI.Conclusión: este estudio demostró que el tratamiento con Mn puede mejorar la RI en hepatocitos. El mecanismo probablemente sea mediantela reducción del nivel de estrés oxidativo intracelular, mejorando la actividad de la vía de señalización Akt/GSK-3β/FOXO1, promoviendo la síntesisde glucógeno e inhibiendo la gluconeogénesis.(AU)

Protective effect of manganese treatment on insulin resistance in HepG2 hepatocytes.

Introduction: Objectives: manganese (Mn) is closely related to type 2 diabetes mellitus and insulin resistance (IR), but the exact mechanism is unclear. This study aimed to explore the regulatory effects and mechanism of Mn on IR using hepatocyte IR model induced by high palmitate (PA), high glucose (HG) or insulin. Methods: HepG2 cells were exposed to PA (200 µM), HG (25 mM) or insulin (100 nM) respectively, alone or with 5 µM Mn for 24 hours. The expression of key proteins in insulin signaling pathway, intracellular glycogen content and glucose accumulation, reactive oxygen species (ROS) level and Mn superoxide dismutase (MnSOD) activity were detected. Results: compared with control group, the expression of phosphorylated protein kinase B (Akt), glycogen synthase kinase-3ß (GSK-3ß) and forkhead box O1 (FOXO1) in the three IR groups was declined, and this decrease was reversed by Mn. The reduction of intracellular glycogen content and increase in glucose accumulation in IR groups were also inhibited by Mn. Additionally, the production of ROS was increased in IR models, compared with normal control group, while Mn reduced the excessive production of ROS induced by PA, HG or insulin. However, Mn did not alter the activity of MnSOD in the three IR models. Conclusion: this study demonstrated that Mn treatment can improve IR in hepatocytes. The mechanism is probably by reducing the level of intracellular oxidative stress, enhancing the activity of Akt/GSK-3ß/FOXO1 signal pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

Introducción: Objetivos: el manganeso (Mn) está estrechamente relacionado con la diabetes mellitus tipo 2 y la resistencia a la insulina (RI), pero el mecanismo exacto aún no está claro. Este estudio tuvo como objetivo explorar los efectos reguladores y el mecanismo del Mn sobre la RI utilizando un modelo de RI en hepatocitos inducido por palmitato alto (PA), glucosa alta (HG) o insulina. Métodos: las células HepG2 se expusieron a PA (200 µM), HG (25 mM) o insulina (100 nM), solas o junto con 5 µM de Mn durante 24 horas. Se evaluó la expresión de proteínas clave en la vía de señalización de la insulina, el contenido intracelular de glucógeno y la acumulación de glucosa, el nivel de especies reactivas de oxígeno (ROS) y la actividad superóxido dismutasa del manganeso (MnSOD). Resultados: en comparación con el grupo de control, la expresión de proteína quinasa B fosforilada (Akt), la glucógeno sintasa quinasa-3ß (GSK-3ß) y la proteína forkhead box O1 (FOXO1) en los tres grupos de RI se redujo, y esta disminución fue revertida por el Mn. La reducción del contenido de glucógeno intracelular y el aumento de la acumulación de glucosa en los grupos de RI también fueron inhibidos por el Mn. Además, la producción de ROS aumentó en los modelos de RI en comparación con el grupo de control normal. Mientras que el Mn redujo la producción excesiva de ROS inducida por PA, HG o insulina. Sin embargo, el Mn no alteró la actividad de la MnSOD en los tres modelos de RI. Conclusión: este estudio demostró que el tratamiento con Mn puede mejorar la RI en hepatocitos. El mecanismo probablemente sea mediante la reducción del nivel de estrés oxidativo intracelular, mejorando la actividad de la vía de señalización Akt/GSK-3ß/FOXO1, promoviendo la síntesis de glucógeno e inhibiendo la gluconeogénesis.

Diet, physical activity, and UV protection comprehensively influenced vitamin D status in college students: a cross-section study from China.

BACKGROUND: Vitamin D deficiency is one of the most prevalent health problems worldwide in all age groups, whereas vitamin D status of Chinese college students was seldom studied in China. The purpose of this study was to explore the vitamin D status in Chinese college freshmen and its influencing factors, providing evidence for nutrition strategy application. METHODS: Information including demographic status, diet habit, physical activity, and ultraviolet ray (UV) protection was collected by online questionnaire. Serum 25(OH)D3 concentrations were measured using a liquid chromatograph mass spectrometer. Multivariate linear regression analyses were used to explore the comprehensive influence of diet, physical activity and UV protection on serum 25(OH)D3 levels. RESULTS: Totally 1667 freshmen from 26 provinces, autonomous districts or municipalities, were recruited, with a mean age of 18.6 ± 0.9 years. The mean serum 25(OH)D3 levels were 18.1 ± 6.3 ng/mL and the proportion of vitamin D deficiency and insufficiency was 67.5% and 27.8%, respectively. Multivariate linear regression indicated that higher intake of milk and yogurt, calcium or vitamin D supplementation, and longer time of outdoor activity were positively linked to higher serum 25(OH)D3, while higher intake of candy and higher UV protection index were negatively associated with serum 25(OH)D3, after adjusted for age, gender, region of original residence, latitudes, longitude and BMI. CONCLUSIONS: Vitamin D deficiency is very common in Chinese college students. Milk and yogurt intake and outdoor activity should be encouraged while candy intake should be limited for preventing vitamin D deficiency. Public health policies should focus on these changeable lifestyles and consider well-balanced guidelines on UV protection and vitamin D supplementation.

Vitamin D deficiency in early life regulates gut microbiome composition and leads to impaired glucose tolerance in adult and offspring rats.

Vitamin D has been found to be involved in glucose metabolism in recent years. Its deficiency is very common, especially in children. Whether vitamin D deficiency in early life affects adult diabetes risk is unknown. In this study, a rat model of early life vitamin D deficiency (F1 Early-VDD) was established by depriving it of vitamin D from the 0 to the 8th week. Further, some rats were switched to normal feeding conditions and sacrificed at the 18th week. Other rats were mated randomly to generate offspring rats (F2 Early-VDD), and F2 rats were fed under normal conditions and sacrificed at the 8th week. Serum 25(OH)D3 level decreased in F1 Early-VDD at the 8th week and returned to normal at the 18th week. Serum 25(OH)D3 level in F2 Early-VDD at the 8th week was also lower than that in control rats. Impaired glucose tolerance was observed in F1 Early-VDD at the 8th week and 18th week and also in F2 Early-VDD at the 8th week. The gut microbiota composition in F1 Early-VDD at the 8th week significantly changed. Among the top ten genera with a rich difference, Desulfovibrio, Roseburia, Ruminiclostridium, Lachnoclostridium, A2, GCA-900066575, Peptococcus, Lachnospiraceae_FCS020_ group, and Bilophila increased owing to vitamin D deficiency, whereas Blautia decreased. There were 108 significantly changed metabolites in F1 Early-VDD at the 8th week, of which 63 were enriched in known metabolic pathways. Correlations between gut microbiota and metabolites were analyzed. Blautia was positively related to 2-picolinic acid, whereas Bilophila was negatively related to indoleacetic acid. Moreover, some of the changes in microbiota, metabolites, and enriched metabolic pathways still existed in F1 Early-VDD rats at the 18th week and F2 Early-VDD rats at the 8th week. In conclusion, vitamin D deficiency in early life leads to impaired glucose tolerance in adult and offspring rats. This effect may be partly achieved by regulating gut microbiota and their co-metabolites.

Vitamin D status in children and its association with glucose metabolism in northern China: a combination of a cross-sectional and retrospective study.

OBJECTIVES: This study aimed to explore the vitamin D status of children in northern China and the association between vitamin D and glucose metabolism. DESIGN: Cross-sectional study was conducted among child participants and retrospective study designs were conducted among adult participants. SETTING AND PARTICIPANTS: Both studies were recruited from Harbin, 326 children were included in children's study, 8469 adults were included in adult study. PRIMARY AND SECONDARY OUTCOME MEASURES: Physical examination, lifestyle and dietary habit data were recorded in all the participants. Serum insulin, glucose, 25(OH)D3 concentrations in children and serum glucose and lipids levels in adults were measured. Rickets history was also investigated in adults, which was used to define vitamin D deficiency in childhood. The associations were tested by linear regression and binary logistic regression. RESULT: In the children's study, only 10.7% of participants were vitamin D sufficient (≥30 ng/mL). Inverse correlations between serum 25(OH)D3 concentration and fasting insulin and homeostasis model assessment - insulin resistance (HOMA-IR) were found, and children with lower serum 25(OH)D3 concentrations were likely to have insulin resistance (IR) (OR: 0.955, 95% CI: 0.917 to 0.995, p value: 0.027). In an adult study, rickets in childhood increased the risk of type 2 diabetes in male participants (OR=1.414, 95% CI=1.013 to 1.972; p value=0.042), but this result was not observed in female participants. CONCLUSION: Our findings suggest that vitamin D deficiency is widespread in northern China. Vitamin D deficiency in childhood was associated with IR and increased the risk of type 2 diabetes in male adults.

Characterization of Immunogenicity Associated with the Biocompatibility of Type I Collagen from Tilapia Fish Skin.

Collagen from fish has been proven to have a low antigenicity that has no difference in the genetic codes compared with mammalian-based collagen. This study was designed to investigate the impact of tilapia skin collagen on immunogenicity and biocompatibility in vivo and in vitro. The structural characteristics of both acid-soluble and pepsin-soluble collagen (ASC and PSC), determined using SDS-PAGE and atomic force microscopy imaging experiments, revealed that the collagen had the basic characteristics of type I collagen (COL-I). The in vitro biocompatibility of the collagens showed good cell proliferation against human foreskin fibroblast (HFF-1) cells. PSC and ASC were considered to be almost non-hemolytic biomaterials with favorable blood compatibility in hemolysis tests. The in vivo antigenicity of the collagen in an ICR mouse model evoked an acceptable specific inflammatory response compared to bovine collagen. The implant's position had developed a complete granulation tissue and the sponge disappeared after 8 weeks. The level of cytokines produced by the COL-I immune response was much lower than bovine collagen, which indicated the appropriate implantable property and biodegradability of the collagens. In conclusion, the tilapia COL-I has a lower immunogenicity with better compatibility than bovine COL-I and is a potential alternative to conventional mammalian collagens in biomedical uses.

Long non-coding RNA-EN_181 potentially contributes to the protective effects of N-acetylcysteine against non-alcoholic fatty liver disease in mice.

N-acetylcysteine (NAC) possesses a strong capability to ameliorate high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in mice, but the underlying mechanism is still unknown. Our study aimed to clarify the involvement of long non-coding RNA (lncRNA) in the beneficial effects of NAC on HFD-induced NAFLD. C57BL/6J mice were fed a normal-fat diet (10 % fat), a HFD (45 % fat) or a HFD plus NAC (2 g/l). After 14-week of intervention, NAC rescued the deleterious alterations induced by HFD, including the changes in body and liver weights, hepatic TAG, plasma alanine aminotransferase, plasma aspartate transaminase and liver histomorphology (haematoxylin and eosin and Oil red O staining). Through whole-transcriptome sequencing, 52 167 (50 758 known and 1409 novel) hepatic lncRNA were detected. Our cross-comparison data revealed the expression of 175 lncRNA was changed by HFD but reversed by NAC. Five of those lncRNA, lncRNA-NONMMUT148902·1 (NO_902·1), lncRNA-XR_001781798·1 (XR_798·1), lncRNA-NONMMUT141720·1 (NO_720·1), lncRNA-XR_869907·1 (XR_907·1), and lncRNA-ENSMUST00000132181 (EN_181), were selected based on an absolute log2 fold change value of greater than 4, P-value < 0·01 and P-adjusted value < 0·01. Further qRT-PCR analysis showed the levels of lncRNA-NO_902·1, lncRNA-XR_798·1, and lncRNA-EN_181 were decreased by HFD but restored by NAC, consistent with the RNA sequencing. Finally, we constructed a ceRNA network containing lncRNA-EN_181, 3 miRNA, and 13 mRNA, which was associated with the NAC-ameliorated NAFLD. Overall, lncRNA-EN_181 might be a potential target in NAC-ameliorated NAFLD. This finding enhanced our understanding of the biological mechanisms underlying the beneficial role of NAC.

Gut Microbiota Targeted Approach in the Management of Chronic Liver Diseases.

The liver is directly connected to the intestines through the portal vein, which enables the gut microbiota and gut-derived products to influence liver health. There is accumulating evidence of decreased gut flora diversity and alcohol sensitivity in patients with various chronic liver diseases, including non-alcoholic/alcoholic liver disease, chronic hepatitis virus infection, primary sclerosing cholangitis and liver cirrhosis. Increased intestinal mucosal permeability and decline in barrier function were also found in these patients. Followed by bacteria translocation and endotoxin uptake, these will lead to systemic inflammation. Specific microbiota and microbiota-derived metabolites are altered in various chronic liver diseases studies, but the complex interaction between the gut microbiota and liver is missing. This review article discussed the bidirectional relationship between the gut and the liver, and explained the mechanisms of how the gut microbiota ecosystem alteration affects the pathogenesis of chronic liver diseases. We presented gut-microbiota targeted interventions that could be the new promising method to manage chronic liver diseases.

The association of dietary flavonoids, magnesium and their interactions with the metabolic syndrome in Chinese adults: a prospective cohort study.

The aim was to systematically analyse the association of the specific flavonoids, Mg and their interactions from different food sources with the metabolic syndrome (MetS) and its components in a cohort study. A total of 6417 participants aged 20 to 74 years from the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases were included. Multivariate logistic regression analyses, forest plot and restricted cubic spline were performed in the study. After a 5·3-year follow-up, 1283 incident cases of the MetS were reported. Those with a higher total flavonoid intake had a lower risk of the MetS (fourth v. first quartile, relative risk (RR) 0·58; 95 % CI 0·37, 0·93; P = 0·024) and central obesity (RR 0·56; 95 % CI 0·33, 0·95; P = 0·032). Further analysis showed that the specific flavonoids quercetin, kaempferol, isorhamnetin, luteolin, and flavonoids from fruits, potatoes and legumes had the similar associations with risk of the MetS and central obesity (P < 0·05 for all). A higher intake of total flavonoids, quercetin and luteolin combined with a high level of Mg was more strongly associated with a lower risk of the MetS (RR 0·60; 95 % CI 0·45, 0·81 for total; RR 0·61; 95 % CI 0·45, 0·82 for quercetin; RR 0·52; 95 % CI 0·38, 0·71 for luteolin; all Pfor interaction < 0·01). Dose-response effects showed an L-shaped curve between the total intake of five flavonoids and the risk of the MetS. A higher flavonoid intake is associated with a lower risk of the MetS and central obesity; their combination with Mg helps to strengthen their negative association with the MetS.

Investigation on knowledge, attitudes and practices about food safety and nutrition in the China during the epidemic of corona virus disease 2019.

OBJECTIVE: To investigate the knowledge, attitudes and practices (K-A-P) about food safety and nutrition in Chinese adults who were recruited to the online survey during the epidemic of corona virus disease 2019 (COVID-19). DESIGN: Participants were recruited by an online snowball sampling method. An electronic questionnaire was sent to our colleagues, students, friends, other professionals and their referrals helped us recruit more participants. The questionnaire included socio-demographic information, the attention paid to COVID-19, K-A-P about food safety and nutrition. Multiple and logistic regression analyses were used to explore related factors of K-A-P. SUBJECTS: Totally, 2272 participants aged 24·09 ± 9·14 years, from twenty-seven provinces, autonomous districts or municipalities, with 18·3 % male and 83·4 % with a medical background. RESULTS: The total possible knowledge score was 8·0, the average score was 5·2 ± 1·6 and 4·2 % obtained 8·0. The total possible attitudes score was 8·0, the average score was 6·5 ± 1·4 and 36·1 % obtained 8·0. The total possible food safety practices score was 5·0, the average score was 3·7 ± 1·0 and 20·7 % obtained 5·0. During this public emergency, 79·4 % participants changed diet habits, including increasing vegetables, fruit and water intake and reducing sugary drinks and snacks. Gender, age, educational and professional background, disease history, the attention paid to COVID-19 and related knowledge were associated with K-A-P. CONCLUSION: There was room for the improvement of K-A-P in participants during this public health emergency and further strengthening education about food safety and nutrition is needed. Findings indicate that education should address biased or misleading information and promote nutritious food choices and safe food practices.

Association of serum 25-Hydroxyvitamin D with Vitamin D intervention and outdoor activity among children in North China: an observational study.

BACKGROUND: Living at high latitudes is one of the risk factors for vitamin D deficiency in children. However, evidence on vitamin D improvement for this pediatric population to date is limited. This study aims at evaluating the association of different vitamin D intervention methods and outdoor activity on the vitamin D status of children in North China. METHODS: In this observational study, a total of 55,925 children aged 1 month to 18 years old were recruited from pediatric outpatient departments from July 2016 to June 2017. Data on demographics, anthropometric measurements, vitamin D intervention (either prescribed by physicians or given by parents) and outdoor activity were recorded. The serum levels of 25-hydroxycholecalciferol (25(OH)D) were determined by high performance liquid chromatography tandem-mass spectrometry. Logistic regression analysis was performed to assess the association of vitamin D intervention or outdoor activity with blood vitamin D status, adjusted for age, gender, BMI for age, and seasons. RESULTS: The overall rate of hypovitaminosis D was 65.60%. Of the children's outdoor activity, 35.63, 31.95, and 32.42% were below 30 min/d, 30-60 min/d and over 60 min/d, respectively. Furthermore, the proportion of therapeutic intervention, supplementation intervention and no vitamin D intervention among the children was 16.48, 32.87, and 50.65%, respectively. After adjusted for confounding factors, vitamin D intervention was associated with a lower risk of hypovitaminosis D, with OR (95% CI) of 0.191 (0.180, 0.202) in children with therapeutic doses and 0.423 (0.404, 0.443) in those with supplementation doses, compared with children without vitamin D intervention. In addition, longer outdoor time was associated with a lower risk of hypovitaminosis D [0.479 (0.456, 0.504) for 60 min/d, 0.737 (0.701, 0.776) for 30-60 min/d], independent of vitamin D intervention. CONCLUSIONS: High prevalence of vitamin D deficiency was found in children living at high latitudes. Vitamin D intervention and outdoor activity are all negatively associated with children's vitamin D deficiency. Routine vitamin D intervention combined with increased outdoor time might be an effective approach to prevent hypovitaminosis D among children, especially those at school, living at high latitudes.

Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic ß-Cells.

Diabetes, a metabolic disease with multiple causes characterized by high blood sugar, has become a public health problem. Hyperglycaemia is caused by deficiencies in insulin secretion, impairment of insulin function, or both. The insulin secreted by pancreatic ß cells is the only hormone in the body that lowers blood glucose levels and plays vital roles in maintaining glucose homeostasis. Therefore, investigation of the molecular mechanisms of pancreatic ß cell differentiation and function is necessary to elucidate the processes involved in the onset of diabetes. Although numerous studies have shown that transcriptional regulation is essential for the differentiation and function of pancreatic ß cells, increasing evidence indicates that epigenetic mechanisms participate in controlling the fate and regulation of these cells. Epigenetics involves heritable alterations in gene expression caused by DNA methylation, histone modification and non-coding RNA activity that does not result in DNA nucleotide sequence alterations. Recent research has revealed that a variety of epigenetic modifications play an important role in the development of diabetes. Here, we review the mechanisms by which epigenetic regulation affects ß cell differentiation and function.

A high fat diet with a high C18:0/C16:0 ratio induced worse metabolic and transcriptomic profiles in C57BL/6 mice.

BACKGROUND: Differential effects of individual saturated fatty acids (SFAs), particularly stearic acid (C18:0), relative to the shorter-chain SFAs have drawn interest for more accurate nutritional guidelines. However, specific biologic and pathologic functions that can be assigned to particular SFAs are very limited. The present study was designed to compare changes in metabolic and transcriptomic profiles in mice caused by a high C18:0 diet and high palmitic acid (C16:0) diet. METHODS: Male C57BL/6 mice were assigned to a normal fat diet (NFD), a high fat diet with high C18:0/C16:0 ratio (HSF) or an isocaloric high fat diet with a low C18:0/C16:0 ratio (LSF) for 10 weeks. An oral glucose tolerance test, 72-h energy expenditure measurement and CT scan of body fat were done before sacrifice. Fasting glucose and lipids were determined by an autobiochemical analyzer. Blood insulin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay methods. Free fatty acids (FFAs) profiles in blood and liver were determined by using gas chromatography-mass spectrometry. Microarray analysis was applied to investigate changes in transcriptomic profiles in the liver. Pathway analysis and gene ontology analysis were applied to describe the roles of differentially expressed mRNAs. RESULTS: Compared with the NFD group, body weight, body fat ratio, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, IL-6, serum and liver FFAs including total FFAs, C16:0 and C18:0 were increased in both high fat diet groups and were much higher in the HSF group than those in the LSF group. Both HSF and LSF mice exhibited distinguishable long non-coding RNA (lncRNA), microRNA and mRNA expression profiles when compared with those of NFD mice. Additionally, more differentially expressed lncRNAs and mRNAs were observed in the HSF group than in the LSF group. Some biological functions and pathways, other than energy metabolism regulation, were identified as differentially expressed mRNAs between the HSF group and the LSF group. CONCLUSION: The high fat diet with a high C18:0/C16:0 ratio induced more severe glucose and lipid metabolic disorders and inflammation and affected expression of more lncRNAs and mRNAs than an isocaloric low C18:0/C16:0 ratio diet in mice. These results provide new insights into the differences in biological functions and related mechanisms, other than glucose and lipid metabolism, between C16:0 and C18:0.

The association of outdoor temperature with blood pressure, and its influence on future cardio-cerebrovascular disease risk in cold areas.

OBJECTIVES: To explore whether lower outdoor temperature increases cardio-cerebrovascular disease risk through regulating blood pressure and whether indoor heating in winter is beneficial to prevent cardio-cerebrovascular disease in cold areas. METHODS: We analyzed the data of 38 589 participants in Harbin from the China Kadoorie Biobank (CKB) during 2004-2008, with an average of 7.14-year follow-up. Linear regression analysis was performed to estimate the relationship between outdoor temperature and blood pressure. Cox regression analysis and logistic regression analysis were used to analyze the association of blood pressure with cardio-cerebrovascular event risk. Mediation analysis was performed to explore the role of blood pressure in the association between outdoor temperature and cardio-cerebrovascular events risk. RESULTS: There was an increase of 6.7 mmHg in SBP and 2.1 mmHg in DBP for each 10 °C decrease in outdoor temperature when outdoor temperature was higher than 5 °C. There was an inverse association between outdoor temperature and cardio-cerebrovascular event morbidity. The increases in blood pressure and cardio-cerebrovascular event morbidity were attenuated in months when central heating was fully provided. Participants with hypertension have higher risks of cardio-cerebrovascular disease (hazard ratio 1.347; 95% CI 1.281--1.415), CVD (hazard ratio 1.347; 95% CI 1.282--1.416), MACE (hazard ratio 1.670; 95% CI 1.560--1.788) and stroke (hazard ratio 1.683; 95% CI 1.571--1.803). Mediation analysis demonstrated that the association between outdoor temperature and cardio-cerebrovascular events risk was potentially mediated by blood pressure. CONCLUSION: Temperature-driven blood pressure potentially mediates the association between outdoor temperature and cardio-cerebrovascular events risk. Indoor heating in winter is probably beneficial to cardio-cerebrovascular disease prevention by inhibition of blood pressure increase.

Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours.

The PI3 K/AKT/mTOR signalling pathway plays an important role in the regulation of signal transduction and biological processes such as cell proliferation, apoptosis, metabolism and angiogenesis. Compared with those of other signalling pathways, the components of the PI3K/AKT/mTOR signalling pathway are complicated. The regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway are important in many human diseases, including ischaemic brain injury, neurodegenerative diseases, and tumours. PI3K/AKT/mTOR signalling pathway inhibitors include single-component and dual inhibitors. Numerous PI3K inhibitors have exhibited good results in preclinical studies, and some have been clinically tested in haematologic malignancies and solid tumours. In this review, we briefly summarize the results of research on the PI3K/AKT/mTOR pathway and discuss the structural composition, activation, communication processes, regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway in the pathogenesis of neurodegenerative diseases and tumours.

The Roles of Epigenetics Regulation in Bone Metabolism and Osteoporosis.

Osteoporosis is a metabolic disease characterized by decreased bone mineral density and the destruction of bone microstructure, which can lead to increased bone fragility and risk of fracture. In recent years, with the deepening of the research on the pathological mechanism of osteoporosis, the research on epigenetics has made significant progress. Epigenetics refers to changes in gene expression levels that are not caused by changes in gene sequences, mainly including DNA methylation, histone modification, and non-coding RNAs (lncRNA, microRNA, and circRNA). Epigenetics play mainly a post-transcriptional regulatory role and have important functions in the biological signal regulatory network. Studies have shown that epigenetic mechanisms are closely related to osteogenic differentiation, osteogenesis, bone remodeling and other bone metabolism-related processes. Abnormal epigenetic regulation can lead to a series of bone metabolism-related diseases, such as osteoporosis. Considering the important role of epigenetic mechanisms in the regulation of bone metabolism, we mainly review the research progress on epigenetic mechanisms (DNA methylation, histone modification, and non-coding RNAs) in the osteogenic differentiation and the pathogenesis of osteoporosis to provide a new direction for the treatment of bone metabolism-related diseases.