[Identification and visual analysis of ginsenosides in multi-steamed roots of Panax quinquefolium based on UPLC-Q-TOF-MS/MS and MALDI-MSI].

This study aims to investigate the component variations and spatial distribution of ginsenosides in Panax quinquefolium roots during repeated steaming and drying. Ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to identify the ginsenosides in the root extract. Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) was employed to visualize the spatial distribution and spatiotemporal changes of prototype ginsenosides and metabolites in P. quinquefolium roots. The UPLC results showed that 90 ginsenosides were identified during the steaming process of the roots, and polar ginsenosides were converted into low polar or non-polar ginsenosides. The content of prototype ginsenosides decreased, while that of rare ginsenosides increased, which included 20(S/R)-ginsenoside Rg_3, 20(S/R)-ginsenoside Rh_2, and ginsenosides Rk_1, Rg_5, Rs_5, and Rs_4. MALDI-MSI results showed that ginsenosides were mainly distributed in the epidermis and phloem. As the steaming times increased, ginsenosides were transported to the xylem and medulla. This study provides fundamental information for revealing the changes of biological activity and pharmacological effect of P. quinquefolium roots that are caused by repeated steaming and drying and gives a reference for expanding the application scope of this herbal medicine.

Facile synthesis of hydroxylated triazine-based magnetic microporous organic network for ultrahigh adsorption of phenylurea herbicides: An experimental and density-functional theory study.

Microporous organic networks (MONs) are highly porous materials that are particularly useful in analytical chemistry. However, the use of these materials is often limited by the functional groups available on their surface. Here, we described the polymerization of a sea urchin-like structure material at ambient temperature, that was functionalized with hydroxyl, carboxyl, and triazine groups and denoted as OH-COOH-MON-TEPT. A substantial proportion of OH-COOH-MON-TEPT was intricately decorated EDA-Fe3O4, creating a well-designed configuration (EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC) for superior adsorption of the target analytes phenylurea herbicides (PUHs) via magnetic solid-phase extraction (MSPE). The proposed method showed remarkably low limits of detection ranging from 0.03 to 0.22 ng·L-1. Experimental investigations and theoretical analyses unveiled the adsorption mode between EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC and PUHs. These findings establish a robust foundation for potential applications of EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC in the analysis of various polar contaminants.

Burden of cardiovascular disease from 1990 to 2017 in Henan Province, China.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading causes of death in China. Little is known about the CVD burden and risk factors in Henan Province, China. OBJECTIVE: To analyze the CVD burden and main risk factors between 1990 and 2017 in the Henan Province in China. METHODS: The methodological framework and analytical strategies adopted in the Global Burden of Disease Study 2017 were used. RESULTS: (1) Age-standardized mortality rate attributed to CVDs increased from 355.0 per 100,000 persons in 1990 to 364.1 per 100,000 persons in 2017 in Henan. (2) Age-standardized disability adjusted life years (DALYs) rate fell by 3.9% from 1990 to 2017. However, the number of DALYs attributed to CVDs increased by 75.9% from 4.2 million person-years in 1990 to 7.3 million person-years in 2017. (3) The age-standardized years lived with disability (YLDs) rate increased by 27.5% from 1990 to 2017. However, years of life lost (YLLs) rate decreased by 6.7% from 1990 to 2017. The contribution of YLLs to the DALYs decreased from 91.4% in 1990 to 89.2% in 2017. (4) Stroke (52.3%) and ischemic heart diseases (38.8%) accounted for 91.1% of total CVDs DALYs among adults in 2017. (5) Dietary factors such as high intake of sodium, alcohol use and low intake of fruits, high systolic blood pressure, and tobacco use were the top risk factors for CVDs, and the estimated population attributable fraction in 2017 was 69.4%, 56.7% and 25.2%, respectively. CONCLUSIONS: The absolute burden of CVDs in Henan is still high, although age-standardized DALYs declined between 1990 and 2017. The prevention and control of stroke and ischemic heart diseases should focus on a few modifiable risk factors which mainly contributed to the burden of CVDs, such as dietary factors, high systolic blood pressure, and tobacco use.

Amelioratory effect of neoandrographolide on myocardial ischemic-reperfusion injury by its anti-inflammatory and anti-apoptotic activities.

In the present study, we aimed to evaluate the cardioprotective effect of neoandrographolide (Neo) on myocardial ischemia/reperfusion injury (I/R) models and explore its possible mechanism. We randomly and equally divided male mice into sham-operation, I/R, and I/R + Neo groups. H9C2 cell line and primary neonatal rat cardiomyocytes were induced into the simulated I/R's status and used to further validate the Neo's role in vitro. Heart systolic function, indexes of myocardial injury (IMI), infarct size, pathological change, cell apoptosis, inflammatory cytokines, and indexes related to apoptotic and NF-κB signaling pathways were analyzed in vivo or in vitro after the Neo treatment. Compared to the I/R group, Neo significantly suppressed IMI, infarct size, inflammatory cell infiltration, cell apoptosis, inflammatory cytokines, bax, cleaved caspase-3, P-IKBa, and P-NF-κB protein expressions, and the translocation of NF-kB subunit p65 from the cytoplasm to the nucleus in vivo or in vitro. Still, ejected fraction, fractional shortening, and the bcl-2 protein expression were notably increased after the Neo treatment. Neo could be developed into a new drug for treating myocardial I/R by inhibiting myocardial inflammation and apoptosis, which was closely related to suppressing the activation of bax/bcl-2 and NF-κB signaling pathways.

Burden and trend of ischemic heart disease and colorectal cancer attributable to a diet low in fiber in China, 1990-2017: findings from the Global Burden of Disease Study 2017.

PURPOSE: The burden of non-communicable diseases (NCDs) has increased in China. However, the contribution of dietary risks to the NCD burden has not been evaluated. This study aimed to estimate the burden of ischemic heart disease (IHD) and colorectal cancer (CRC) attributable to a diet low in fiber in China from 1990 to 2017. METHODS: China data from the Global Burden of Disease Study (GBD) 2017 were used to assess the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of IHD and CRC related to a diet low in fiber. RESULTS: In 2017, a diet low in fiber contributed 170,143 [95% uncertainty interval (UI): 99,623-256,806] IHD deaths and 25,561 (95% UI: 13,726-39,215) CRC deaths, with the population attributable fractions (PAFs) were 9.7 and 13.7%, respectively. Males had higher risk-attributable mortality and DALY rates for IHD and CRC than females. An upward trend with age in rates of mortality and DALY was observed. All-age risk-attributable mortality and DALY rates increased significantly by 111.4 and 53.2% for IHD, and 94.4 and 59.6% for CRC from 1990 to 2017, respectively; however, the corresponding age-standardized rates for IHD and CRC showed relatively stable trends. Heilongjiang, Xinjiang, and Inner Mongolia were ranked as the top three provinces in terms of total risk-attributable NCD burden in 2017. CONCLUSIONS: China has a large and growing NCD burden attributable to a diet low in fiber. Greater priority in disease prevention and control should be given to male and older adults throughout China, particularly in some western provinces.

Association between Baseline SBP/DBP and All-Cause Mortality in Residents of Shanxi, China: A Population-based Cohort Study from 2002 to 2015.

OBJECTIVE: To investigate the association between blood pressure and all-cause mortality in Shanxi, China. METHODS: The '2002 China Nutrition and Health Survey' baseline data in Shanxi province was used. A retrospective investigation was performed in 2015. The effects of SBP and DBP on the all-cause mortality were analyzed using the Cox regression model. The hazard ratio ( HR) and 95% confidence interval ( CI) were estimated by the sex and age groups. RESULTS: The follow-up rate was 76.52% over 13 years, while the cumulative mortality rate for all participants was 917.12/100,000 person-years. The mortality rose with an increasing SBP ( χ 2 trend = 270.537, P < 0.001) or DBP level ( χ 2 trend = 57.240, P < 0.001). After adjustment for the confounding factors, a significant association between mortality and high SBP (≥ 160 mmHg) and high DBP (≥ 100 mmHg), with adjusted HR ranging from 1.405- to 2.179-fold for SBP and 1.550- to 2.854-fold for DBP, was noted. Significant HRs for most DBP subgroups were found in > 60-year-old participants. Males with DBP ≥ 100 mmHg had a significantly higher mortality, with an HR (95% CI) of 2.715 (1.377-5.351). CONCLUSION: Adults with SBP > 160 mmHg and DBP > 100 mmHg had a higher mortality risk. Sex and age difference was noted in both DBP and mortality risk.

Triazine-cored covalent organic framework for ultrasensitive detection of polybrominated diphenyl ethers from real samples: Experimental and DFT study.

Food and environmental safety issues attributable to the polybrominated diphenyl ethers (PBDEs) are gaining increasing attention, and these urge us to establish a high-performance sample-handling technique. In this study, an outstanding adsorption performance with short adsorption time (10 min) was achieved for PBDEs using a novel synthesized dispersive solid-phase extraction adsorbent, a reticulated covalent organic framework with N/O functional groups (i.e., imine linkage, triazine, and methoxy) (TAPT-DMTA-COF). By conducting sufficient experimentation and theoretical simulation on adsorption mechanism, the halogen bond between electronegative N/O atoms of TAPT-DMTA-COF and the electropositive Br atoms of PBDEs were observed to play a more pivotal role than π-π, C-H…π interactions, and hydrophobic effects. Furthermore, the positive linear relation between calculated adsorption energy and Br content directly clarified that enrichment behavior of PBDEs can be attributed to halogen bonding. These data implied that integrated nanostructure (i.e., N/O functional groups and reticulated architecture) effectively enhanced adsorption capacity. In case of PBDE analysis, this approach achieved excellent results with low limits of detection (0.03-0.13 ng L-1). Finally, the promising potential applications of aforementioned method were verified by spiking water, fish, and milk samples with PBDEs; good PBDEs recoveries were obtained.

Abdominal Obesity and Its Attribution to All-cause Mortality in the General Population with 14 Years Follow-up: Findings from Shanxi Cohort in China.

OBJECTIVE: This study aimed to assess the association of waist circumference (WC) with all-cause mortality among Chinese adults. METHODS: The baseline data were from Shanxi Province of 2002 China Nutrition and Health Survey. The death investigation and follow-up visit were conducted from December 2015 to March 2016. The visits covered up to 5,360 of 7,007 participants, representing a response rate of 76.5%. The Cox regression model and floating absolute risk were used to estimate hazard ratio and 95% floating CI of death by gender and age groups (≥ 60 and < 60 years old). Sensitivity analysis was performed by excluding current smokers; participants with stroke, hypertension, and diabetes; participants who accidentally died; and participants who died during the first 2 years of follow-up. RESULTS: This study followed 67,129 person-years for 12.5 years on average, including 615 deaths. The mortality density was 916 per 100,000 person-years. Low WC was associated with all-cause mortality among men. Multifactor-adjusted hazard ratios ( HR) were 1.60 (1.35-1.90) for WC < 75.0 cm and 1.40 (1.11-1.76) for WC ranging from 75.0 cm to 79.9 cm. Low WC (< 70.0 cm and 70.0-74.9 cm) and high WC (≥ 95.0 cm) groups had a high risk of mortality among women. The adjusted HRs of death were 1.43 (1.11-1.83), 1.39 (1.05-1.84), and 1.91 (1.13-3.22). CONCLUSION: WC was an important predictor of death independent of body mass index (BMI). WC should be used as a simple rapid screening and predictive indicator of the risk of death.

Trend of injury mortality of children and adolescents in Kunming during 2010-2019 / 中国学校卫生

Objective@#To understand the characteristics of injury deaths of children and adolescents aged 0 to 19 years in Kunming during 2010-2019,and to provide injury prevention and control basis.@*Methods@#Injury mortality data in 2010-2019 were from Kunming population based mortality surveillance system. The characteristics of injury death of children and adolescents were analyzed by descriptive statistical analysis, including mortality rate, composition ratio, the annual percent change,etc.@*Results@#Child and adolescent injury mortality was 23.18/10 5,decreasing by year(t=7.13,P<0.05). Male mortality(31.59/10 5) was higher than female(14.27/10 5)(χ2=376.24,P<0.05),the APC of male was -8.82% and -7.48% in female.The injury mortality of male was higher than that of female at all age group. The injury mortality rate of rural children and adolescents(28.65/10 5) was higher than that of urban children(12.37/10 5)(χ2=297.30,P<0.05),the APC was -8.53% in urban areas and -7.78% in rural areas.The top five causes of injury death of children and adolescents were traffic accident drowning, accidental fall, suicide and accidental mechanical suffocation, accounting for 80.88% of the total injury deaths of children and adolescents.In urban and rural areas,injury death by traffic accident, drowning and rural unintentional falls decreased significantly(t urban=3.17,3.20,t rural=5.66,3.12,4.42,P<0.05). The leading cause of death varied by different age groups.@*Conclusion@#The injury mortality rate of children and adolescents in Kunming city is on the decline. Rural children and adolescents, as vulnerable population to injury death, should receive protective strategies according to their specific characteristics of injuries and deaths in different age groups.

Childhood BMI and Adult Obesity in a Chinese Sample: A 13-Year Follow-up Study.

OBJECTIVE: Obesity is recognized as a significant risk factor for diabetes and hypertension. The present study aimed to examine the associations between adults'obesity risk and childhood and parental obesity. METHODS: A total of 204 children aged 6-17 years were recruited in 2002 with an average follow-up period of 13.2 years. Height and body weight were measured by trained staffs. Overweight and obesity were defined based on the Chinese standard for children and adults. T-test, analysis of variance, and Chi-square analysis were used for single factor analysis. Multiple linear and logistic regression analyses were used to perform multifactor analysis. RESULTS: The percentage of non-obese children who grew up to be non-obese adults was 62.6%, and that of obese children who grew up to be obese adults was 80.0%. There was a significant association between childhood body mass index (BMI) and adulthood BMI with a ß regression coefficient of 3.76 [95% confidence interval (CI): 1.36-6.16], and between childhood obesity and adulthood obesity with an odds ratio of 5.76 (95% CI: 1.37-24.34). There was no statistical difference between parental obesity at baseline and children's adulthood obesity, after adjustment of confounders. Male participants and those aged 10.0-13.0 years had a higher risk of adulthood obesity with odds ratios of 2.50 (95% CI: 1.12-5.26) and 3.62 (95% CI: 1.17-11.24), respectively. CONCLUSION: Childhood obesity is an important predictor of adulthood obesity.

Impact of otrA expression on morphological differentiation, actinorhodin production, and resistance to aminoglycosides in Streptomyces coelicolor M145.

otrA resembles elongation factor G (EF-G) and is considered to be an oxytetracycline (OTC)-resistance determinant in Streptomyces rimosus. In order to determine whether otrA also conferred resistance to OTC and other aminoglycosides to Streptomyces coelicolor, the otrA gene from S. rimosus M527 was cloned under the control of the strong ermE* promoter. The resulting plasmid, pIB139-otrA, was introduced into S. coelicolor M145 by intergeneric conjugation, yielding the recombinant strain S. coelicolor M145-OA. As expected S. coelicolor M145-OA exhibited higher resistance levels specifically to OTC and aminoglycosides gentamycin, hygromycin, streptomycin, and spectinomycin. However, unexpectedly, S. coelicolor M145-OA on solid medium showed an accelerated aerial mycelia formation, a precocious sporulation, and an enhanced actinorhodin (Act) production. Upon growth in 5-L fermentor, the amount of intra- and extracellular Act production was 6-fold and 2-fold higher, respectively, than that of the original strain. Consistently, reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that the transcriptional level of pathway-specific regulatory gene actII-orf4 was significantly enhanced in S. coelicolor M145-OA compared with in S. coelicolor M145.

Hospital-Based Study of the Frequency and Risk Factors of Stroke Recurrence in Two Years in China.

BACKGROUND: Stroke causes death and disability throughout the world and recurrent stroke events are more likely to be disabling or fatal. We conducted a hospital-based study to investigate the frequency and influence factors of stroke recurrence in China. METHODS: Data from patients hospitalized with stroke between January 2007 and December 2010 of 109 tertiary hospitals in China were used. Stroke recurrence and associated factors were ascertained. The zero-inflated model was used to evaluate the factors of recurrence. RESULTS: Of 101,926 discharged patients, the cumulative 2-year stroke recurrence rate was 3.80% for subarachnoid hemorrhage (SAH), 5.31% for intracerebral hemorrhage (ICH), and 8.71% for ischemic stroke (IS), respectively. Among patients with stroke recurrence, 54.11% with SAH, 60.42% with ICH, and 92.92% with IS relapsed for the same type of the first-onset stroke. For discharged patients with SAH with middle cerebral artery aneurysm clipping or artery aneurysm embolization, it was less likely to stroke relapse, but the times of recurrence would increase if 1 recurrence appeared. Cerebral artery aneurysms and hypertension were risk factors for recurrence frequency. For ICH, protective factors for recurrence were trepanation and drainage of intracranial hematoma, cerebral angiography, puncture and drainage of intracranial hematoma, and length of stay (LOS). But rheumatic heart disease and atrial fibrillation would further the relapse frequency. For IS, age and LOS were protective factors, but recurrence frequency would increase if the first recurrence happened. Cervical spondylopathy, male gender, and diabetes were risk factors for frequency of relapse. CONCLUSIONS: Associated factors were different for recurrence frequency among different stroke types.

[Risk factors for allergic diseases in children aged 0-24 months in the Wuhu urban area, Anhui Province, China].

OBJECTIVE: To investigate the prevalence of allergic diseases in children aged 0-24 months in the Wuhu urban area of Anhui Province and risk factors for allergic diseases. METHODS: Cluster random sampling was performed to select 600 children aged 0-24 months and their mothers from the Wuhu urban area, and a questionnaire survey was conducted to collect the data of disease history, family history, mothers' conditions during pregnancy, and child-rearing situation. Univariate analysis and multivariate logistic regression analysis were performed for such data. RESULTS: Among the 597 children included in the analysis, 56 (9.4%) were diagnosed with allergic diseases in the past. The univariate analysis showed that the age, use of antipyretic and analgesic drugs, a history of allergy in the father or grandparents, and the consumption of fish, shrimps, crabs, and shellfish during pregnancy were significantly associated with past allergic diseases (P<0.05). The multivariate logistic regression analysis showed that the age and a history of allergy in the father or grandparents were positively associated with past allergic diseases (OR=4.0-4.9, 2.7, and 2.4 respectively; P<0.05), while frequent consumption of fish, shrimps, crabs, and shellfish during pregnancy was negatively associated with past allergic diseases (OR=0.3; P<0.05). CONCLUSIONS: A family history of allergy is an independent risk factor for allergic diseases in children aged 0-24 months in the Wuhu urban area of Anhui Province, while frequent consumption of fish, shrimps, crabs, and shellfish during pregnancy is a protective factor.

APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p.

The abnormal autophagy is associated with a variety of cardiovascular diseases. Long noncoding RNAs (lncRNAs) are emerging as new factors in gene regulation, but how lncRNAs operate in the regulation of autophagy in the heart is unclear. Here we report that a long noncoding RNA, named autophagy promoting factor (APF), can regulate autophagic cell death by targeting miR-188-3p and ATG7. The results show that miR-188-3p suppresses autophagy and myocardial infarction by targeting ATG7. Further, we find that APF lncRNA regulates miR-188-3p, and thus affects ATG7 expression, autophagic cell death and myocardial infarction. Our present study reveals a novel regulating model of autophagic programme, which comprises APF, miR-188-3p and ATG7 in the heart. Modulation of their levels may serve as potential targets and diagnostic tools for novel therapeutic strategies of myocardial infarction and heart failure.

[Application of ICP-MS to Detect Rare Earth Elements in Three Economic Macroalgaes in China].

In order to investigate the content and distribution of rare earth elements (REE) in main economic macroalgaes in our country, fifteen rare earth elements in three economic macroalgaes (including 30 samples of kelp, 30 samples of laver and 15 samples of Enteromorpha) were detected using ICP-MS method. Results showed that the total content of REE in different species of macroalgaes was different. The highest total content of REE was in Enteromorpha (16,012.0 ng · g⁻¹), while in kelp and laver, the total REE was similar for two macroalgaes (3887.4 and 4318.1 ng · g⁻¹ respectively). The content of fifteen rare earth elements in kelp ranged from 7.9 to 1496.4 ng · g⁻¹; in laver, it ranged from 8.2 to 1836.6 ng · g⁻¹. For Enteromorpha, the concentration of 15 rare earth elements were between 19.2 and 6014.5 ng · g⁻¹. In addition, the content and distribution of different rare earth elements in different macroalgaes was also different. For kelp, the highest content of REE was Ce (1 496.4 ng · g⁻¹), and the second was La (689.1 ng · g⁻¹). For laver, the highest was Y (1836.6 ng · g⁻¹), and the second was Ce (682.2 ng · g⁻¹). For Enteromorpha, the highest was Ce (6014.5 ng · g⁻¹), and the second was La (2902.9 ng · g⁻¹). Present results also showed that three macroalgaes accumulated the light rare earth elements much more than the high rare earth elements. The light rare earth elements occupied 90.9%, 87.3% and 91.1% for kelp, laver and Enteromorpha respectively. The result that the Enteromorpha had high content of rare earth elements could provide important support for opening new research directions for the utilization of Enteromorpha.

Trends in in-hospital mortality among patients with stroke in China.

BACKGROUND: The incidence and burden of stroke in China is increasing rapidly. However, little is known about trends in mortality during stroke hospitalization. The objectives of this study were to assess trends of in-hospital mortality among patients with stroke and explore influence factors of in-hospital death after stroke in China. METHODS: 109 grade III class A hospitals were sampled by multistage stratified cluster sampling. All patients admitted to hospitals between 2007 and 2010 with a discharge diagnosis of stroke were included. Trends in in-hospital mortality among patients with stroke were assessed. Influence factors of in-hospital death after stroke were explored using multivariable logistic regression. RESULTS: Overall stroke hospitalizations increased from 79,894 in 2007 to 85,475 in 2010, and in-hospital mortality of stroke decreased from 3.16% to 2.30% (P<0.0001). The percentage of severe patients increased while odds of mortality (2010 versus 2007) decreased regardless of stroke type: subarachnoid hemorrhage (OR 0.792, 95% CI = 0.636 to 0.987), intracerebral hemorrhage (OR 0.647, 95% CI = 0.591 to 0.708), and ischemic stroke (OR 0.588, 95% CI = 0.532 to 0.649). In multivariable analyses, older age, male, basic health insurance, multiple comorbidities and severity of disease were linked to higher odds of in-hospital mortality. CONCLUSIONS: The mortality of stroke hospitalizations decreased likely reflecting advancements in stroke care and prevention. Decreasing of mortality with increasing of severe stroke patients indicated that we should pay more attention to rehabilitation and life quality of stroke patients. Specific individual and hospital-level characteristics may be targets for facilitating further declines.

Arsenic Species in Edible Seaweeds Using In Vitro Biomimetic Digestion Determined by High-Performance Liquid Chromatography Inductively Coupled Plasma Mass Spectrometry.

Arsenite [As (III)], arsenate [As (V)], methylarsonate (MMA), and dimethylarsinate (DMA) in five edible seaweeds (the brown algae Laminaria japonica, red algae Porphyra yezoensis, brown algae Undaria pinnatifida, brown algae Hizikia fusiformis, and green algae Enteromorpha prolifera) were analyzed using in vitro digestion method determined by high-performance liquid chromatography inductively coupled plasma mass spectrometry. The results showed that DMA was found in the water extracts of all samples; As (III) were detected in L. japonica and U. pinnatifida and about 23.0 and 0.15 mg/kg of As (V) were found in H. fusiformis and E. prolifera respectively. However, after the gastrointestinal digestion, As (V) was not detected in any of the five seaweeds. About 0.19 and 1.47 mg/kg of As (III) was detected in the gastric extracts of L. japonica and H. fusiformis, respectively, and about 0.31 and 0.10 mg/kg of As (III) were extracted from the intestinal extracts of Porphyra yezoensis and U. pinnatifida, respectively. The present results successfully reveal the differences of As species and levels in the water and biomimetic extracts of five edible seaweeds. The risk assessment of the inorganic arsenic in the five edible seaweeds based on present data showed almost no hazards to human health.

Activation of JNKs is essential for BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Although BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cell (MSCs), the molecular mechanism involved remains to be fully elucidated. Here, we explore the possible involvement and detail role of JNKs (c-Jun N-terminal kinases) in BMP9-induced osteogenic differentiation of MSCs. It was found that BMP9 stimulated the activation of JNKs in MSCs. BMP9-induced osteogenic differentiation of MSCs was dramatically inhibited by JNKs inhibitor SP600125. Moreover, BMP9-activated Smads signaling was decreased by SP600125 treatment in MSCs. The effects of inhibitor are reproduced with adenoviruses expressing siRNA targeted JNKs. Taken together, our results revealed that JNKs was activated in BMP9-induced osteogenic differentiation of MSCs. What is most noteworthy, however, is that inhibition of JNKs activity resulted in reduction of BMP9-induced osteogenic differentiation of MSCs, implying that activation of JNKs is essential for BMP9 osteoinductive activity.

Analysis and characterization of the functional TGFß receptors required for BMP6-induced osteogenic differentiation of mesenchymal progenitor cells.

Although BMP6 is highly capable of inducing osteogenic differentiation of mesenchymal progenitor cells (MPCs), the molecular mechanism involved remains to be fully elucidated. Using dominant negative (dn) mutant form of type I and type II TGFß receptors, we demonstrated that three dn-type I receptors (dnALK2, dnALK3, dnALK6), and three dn-type II receptors (dnBMPRII, dnActRII, dnActRIIB), effectively diminished BMP6- induced osteogenic differentiation of MPCs. These findings suggested that ALK2, ALK3, ALK6, BMPRII, ActRII and ActRIIB are essential for BMP6-induced osteogenic differentiation of MPCs. However, MPCs in this study do not express ActRIIB. Moreover, RNA interference of ALK2, ALK3, ALK6, BMPRII and ActRII inhibited BMP6-induced osteogenic differentiation in MPCs. Our results strongly suggested that BMP6-induced osteogenic differentiation of MPCs is mediated by its functional TGFß receptors including ALK2, ALK3, ALK6, BMPRII, and ActRII.