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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(3): 411-419, 2024 Mar 20.
Article Zh | MEDLINE | ID: mdl-38597431

OBJECTIVE: To investigate the role of Rho/ROCK signaling pathway in mediating restraint stress-induced blood-brain barrier (BBB) injury in the amygdala of rats. METHODS: Sixty male SD rats were randomized equally into control group (with food and water deprivation for 6 h per day), restraint stress group (with restraint for 6 h per day), stress + fasudil treatment (administered by intraperitoneal injection at 1 mg/100 g 30 min before the 6-h restraint) group, and fasudil treatment alone group. The elevated plus-maze test was used to detect behavioral changes of the rats, serum corticosterone and S100B levels were determined with ELISA, and Evans Blue leakage in the brain tissue was examined to evaluate the changes in BBB permeability. The changes in expression levels of tight junction proteins in the amygdala were detected using immunofluorescence assay and Western blotting, and Rho/ROCK pathway activation was detected by Pull-down test and Western blotting. Ultrastructural changes of the cerebral microvascular endothelial cells were observed using transmission electron microscopy. RESULTS: Compared with those in the control group, the rats in restrain stress group and stress+fasudil group showed obvious anxiety-like behavior with significantly increased serum corticosterone level (P<0.001). Compared with those in the control group and stress+fasudil group, the rat models of restrain stress showed more obvious Evans Blue leakage and higher S100B expression (P<0.01) but lower expressions of tight junction proteins in the amygdala. Pull-down test and Western blotting confirmed that the expression levels of RhoA-GTP, ROCK2 and P-MLC 2 were significantly higher in stress group than in the control group and stress + fasudil group (P<0.05). Transmission electron microscopy revealed obvious ultrastructural changes in the cerebral microvascular endothelial cells in the rat models of restrain stress. CONCLUSION: Restraint stress induces BBB injury in the amygdala of rats by activating the Rho/ROCK signaling pathway.


1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Blood-Brain Barrier , Endothelial Cells , Rats , Male , Animals , Blood-Brain Barrier/metabolism , Rats, Sprague-Dawley , Evans Blue/metabolism , Corticosterone/metabolism , Tight Junction Proteins/metabolism , Signal Transduction , rho-Associated Kinases/metabolism
2.
ISME J ; 18(1)2024 Jan 08.
Article En | MEDLINE | ID: mdl-38564256

Microbial arsenic (As) methylation in paddy soil produces mainly dimethylarsenate (DMA), which can cause physiological straighthead disease in rice. The disease is often highly patchy in the field, but the reasons remain unknown. We investigated within-field spatial variations in straighthead disease severity, As species in rice husks and in soil porewater, microbial composition and abundance of arsM gene encoding arsenite S-adenosylmethionine methyltransferase in two paddy fields. The spatial pattern of disease severity matched those of soil redox potential, arsM gene abundance, porewater DMA concentration, and husk DMA concentration in both fields. Structural equation modelling identified soil redox potential as the key factor affecting arsM gene abundance, consequently impacting porewater DMA and husk DMA concentrations. Core amplicon variants that correlated positively with husk DMA concentration belonged mainly to the phyla of Chloroflexi, Bacillota, Acidobacteriota, Actinobacteriota, and Myxococcota. Meta-omics analyses of soil samples from the disease and non-disease patches identified 5129 arsM gene sequences, with 71% being transcribed. The arsM-carrying hosts were diverse and dominated by anaerobic bacteria. Between 96 and 115 arsM sequences were significantly more expressed in the soil samples from the disease than from the non-disease patch, which were distributed across 18 phyla, especially Acidobacteriota, Bacteroidota, Verrucomicrobiota, Chloroflexota, Pseudomonadota, and Actinomycetota. This study demonstrates that even a small variation in soil redox potential within the anoxic range can cause a large variation in the abundance of As-methylating microorganisms, thus resulting in within-field variation in rice straighthead disease. Raising soil redox potential could be an effective way to prevent straighthead disease.


Arsenic , Oryza , Soil Pollutants , Oryza/microbiology , Soil/chemistry , Methylation , Bacteria/genetics , Cacodylic Acid , Oxidation-Reduction , Soil Pollutants/analysis
3.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(1): 36-38, 2024 Jan 12.
Article Zh | MEDLINE | ID: mdl-38062692

Heritable pulmonary arterial hypertension (HPAH) is a rare type of pulmonary arterial hypertension that often presents with progressive exertional dyspnea and for which there is no significant effective drug. A HPAH patient was admitted to our hospital more than three years ago, and the gene mutation was bone morphogenetic protein 2 (BMPR2). For the first 45 months, she was given oral imatinib 100 mg once daily, and her symptoms and hemodynamics improved significantly, with no apparent side effects. It is reported that, in combination with the characteristics of the case and related literatures, it provides clinicians with other feasible treatment options for HPAH.


Hypertension, Pulmonary , Humans , Female , Familial Primary Pulmonary Hypertension/genetics , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/genetics , Imatinib Mesylate/therapeutic use , Mutation , Bone Morphogenetic Protein Receptors, Type II/genetics , Bone Morphogenetic Protein Receptors, Type II/metabolism
5.
Environ Sci Technol ; 56(6): 3575-3586, 2022 03 15.
Article En | MEDLINE | ID: mdl-35174706

Arsenic (As) accumulation in rice is of global concern for human health and international trade. Rice is typically reported to contain inorganic As (iAs) and dimethylated arsenate (DMA), with current food guidelines limiting toxic iAs but not less-toxic DMA. Here, we show that the highly toxic dimethylated monothioarsenate (DMMTA) is also found in rice worldwide and has been unknowingly determined as less-toxic DMA by previous routine analytical methods. Using enzymatic extraction followed by high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) analysis with a C18 column, DMMTA was detected in rice grains (n = 103) from a field survey from China and in polished rice grains (n = 140) from a global market-basket survey. Concentration ranged from <0.20 to 34.8 µg/kg (median 10.3 µg/kg), accounting for 0 to 21% of total As. A strong linear correlation was observed in all rice samples between DMA and DMMTA (being 30 ± 8% of DMA) concentrations. This robust relationship allows an estimation of DMMTA in rice grains from the DMA data reported in previous market-basket surveys, showing a general global geographical pattern with DMMTA concentration increasing from the equator toward high-latitude regions. Based on the global occurrence and potential high toxicity, DMMTA in rice should be considered in health risk assessments and for setting food regulations.


Arsenic , Arsenicals , Oryza , Arsenicals/chemistry , Cacodylic Acid , Chromatography, High Pressure Liquid , Commerce , Humans , Internationality
6.
Clin. transl. oncol. (Print) ; 24(1): 57-65, enero 2022.
Article En | IBECS | ID: ibc-203414

PurposeOvarian cancer (OC) is a common malignancy, and IFN-γ, a multifunctional cytokine, is unveiled to impede the multiplication and enhance apoptosis in diverse tumor cells in previous research. Nonetheless, its function and mechanism in OC are blurred.MethodsOC cell lines SKOV3 and OVCAR3 were dealt with different concentrations (0–40 ng/ml) of IFN-γ. CCK-8 experiment was utilized to examine cell multiplication; Flow cytometry was executed to detect apoptosis and cell cycle; Wound healing assay was utilized to detect cell migration; and Transwell experiment was implemented to examine cell invasion. qRT-PCR analysis was applied to detect STAT5, STAT3, JAK2 and JAK3 mRNA expression in OC cell lines. Western blot experiment was applied to detect the protein and phosphorylation levels of SOCS1, STAT5 and STAT3.ResultsIFN-γ suppressed OC cell multiplication in a concentration-dependent manner. Relative to the control group, IFN-γ restrained OC cell migration, invasion, enhanced apoptosis and prevented cell transformation from G0/G1 to S phase. Further analysis revealed that IFN-γ up-modulated SOCS1 expression and impeded STAT5 and STAT3 protein phosphorylation levels, and knockdown of SOCS1 partially counteracted the inhibitory effect of IFN-γ on STAT5 and STAT3 protein phosphorylation levels.ConclusionIFN-γ represses OC progression by facilitating SOCS1 to suppress STAT3 and STAT5 protein phosphorylation.


Humans , Health Sciences , Ovarian Neoplasms , Cytokines , Apoptosis , Neoplastic Cells, Circulating , Wound Healing
7.
Clin Transl Oncol ; 24(1): 57-65, 2022 Jan.
Article En | MEDLINE | ID: mdl-34275119

PURPOSE: Ovarian cancer (OC) is a common malignancy, and IFN-γ, a multifunctional cytokine, is unveiled to impede the multiplication and enhance apoptosis in diverse tumor cells in previous research. Nonetheless, its function and mechanism in OC are blurred. METHODS: OC cell lines SKOV3 and OVCAR3 were dealt with different concentrations (0-40 ng/ml) of IFN-γ. CCK-8 experiment was utilized to examine cell multiplication; Flow cytometry was executed to detect apoptosis and cell cycle; Wound healing assay was utilized to detect cell migration; and Transwell experiment was implemented to examine cell invasion. qRT-PCR analysis was applied to detect STAT5, STAT3, JAK2 and JAK3 mRNA expression in OC cell lines. Western blot experiment was applied to detect the protein and phosphorylation levels of SOCS1, STAT5 and STAT3. RESULTS: IFN-γ suppressed OC cell multiplication in a concentration-dependent manner. Relative to the control group, IFN-γ restrained OC cell migration, invasion, enhanced apoptosis and prevented cell transformation from G0/G1 to S phase. Further analysis revealed that IFN-γ up-modulated SOCS1 expression and impeded STAT5 and STAT3 protein phosphorylation levels, and knockdown of SOCS1 partially counteracted the inhibitory effect of IFN-γ on STAT5 and STAT3 protein phosphorylation levels. CONCLUSION: IFN-γ represses OC progression by facilitating SOCS1 to suppress STAT3 and STAT5 protein phosphorylation.


Interferon-gamma/physiology , Janus Kinase 2/physiology , Ovarian Neoplasms/pathology , STAT5 Transcription Factor/physiology , Signal Transduction , Suppressor of Cytokine Signaling 1 Protein/physiology , Disease Progression , Female , Humans , STAT3 Transcription Factor
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(3): 433-439, 2021 Mar 10.
Article Zh | MEDLINE | ID: mdl-34814410

Objective: To investigate the relationships between hyperuricemia and the incidence risk for cardiometabolic abnormity in children. Methods: Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected through stratified cluster sampling at baseline survey. Follow-up investigation was conducted in 2019. Logistic regression model was used to analyze the relationships of uric acid quartiles and change in uric acid levels with incidence risks for cardiometabolic abnormity (hypertension, hyperglycemia and dyslipidemia). Results: A total of 8 807 children (4 376 boys, 4 431 girls) were included in the analysis, the average age of the children was (11.1±3.3) years at baseline survey. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of incidence risk for hypertension in the third and fourth quartiles of the UA were 1.39 (1.11-1.75) and 1.56 (1.19-1.81), respectively. The ORs and 95% CIs of risk for high LDL-C in the second, third and fourth quartiles were 1.88 (1.16-3.05),1.98 (1.23-3.17) and 2.25 (1.42-3.57). The uric acid level increased by one standard deviation, the risk increased by 17% for hypertension and 27% for high LDL-C. The uric acid level increased by 10 µmol/L, the risk increased by 2.1% for hypertension and 2.9% for high LDL-C. The gender-stratified analysis showed that the similar results. The ORs and 95% CIs were 1.32 (1.09-1.60) and 1.50 (1.05-2.16) for hypertension, 1.90 (1.38-2.60) and 2.96 (1.58-5.52) for high TC, 1.78 (1.26-2.51) and 2.84 (1.60-5.03) for high LDL-C in the groups of newly diagnosed hyperuricemia and persistent hyperuricemia. Conclusions: Higher uric acid level was associated with increased incidence risks for hypertension, abnormal TC and LDL-C. Maintaining optimal uric acid level by children might contribute to the early prevention of cardiovascular diseases.


Cardiovascular Diseases , Hyperuricemia , Adolescent , Child , Female , Humans , Hyperuricemia/epidemiology , Incidence , Male , Risk Factors , Uric Acid
9.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(3): 440-447, 2021 Mar 10.
Article Zh | MEDLINE | ID: mdl-34814411

Objective: To analyze the influence of obesity status on the development of cardiometabolic disorders in school-age children. Methods: Information about children's body weight, body height and cardiovascular risk factors were collected in baseline survey in 2017 and follow-up survey in 2019. The school-age children were divided into four groups based on their baseline and follow-up obesity status, i.e. sustained non-obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Analysis of covariance was used to compare the difference of change in levels of cardiometabolic factors among the four groups. The multivariate logistic regression model was used to analyze the relationship between obesity status and the incidence risk of cardiometabolic disorders. Results: The present study included 11 379 school-age children (boys accounting for 49.6%). During the 2 years, the incidence of obesity was 3.2% (95%CI: 2.9%-3.5%) with the restoration ratio of obesity of 4.4% (95%CI: 4.0%-4.8%). Compared with the sustained non-obesity group, increases in SBP, DBP, TG, LDL-C and non-HDL-C were much higher in newly classified obesity group and persistent obesity group, but lower in restored obesity groups except for DBP (all P<0.05). In addition, the incidence risk of hypertension, high glucose, dyslipidemia and cardiometabolic disorders (≥2 risks) were much higher in newly classified and persistent obese children than in sustained non-obese children. No difference was found in incidence risks of most cardiovascular disorders between restored obese children and sustained non-obese children, except for hypertension and cardiometabolic risks. Conclusion: Both newly classified obesity and persistent obesity increased the incidence risks for multi cardiovascular disorders, while these risks could be reduced when non-obese status restore.


Cardiovascular Diseases , Pediatric Obesity , Body Mass Index , Cardiovascular Diseases/epidemiology , Child , Humans , Male , Pediatric Obesity/epidemiology , Risk Factors , Schools
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(3): 448-454, 2021 Mar 10.
Article Zh | MEDLINE | ID: mdl-34814412

Objective: To investigate the incidence and risk factors of pediatric fracture in school-age children and adolescents in Beijing. Methods: A total of 12 056 students with complete fracture data of 2017 baseline survey and 2019 follow-up survey of School-based Cardiovascular and Bone Health (SCVBH) Promotion Program in Beijing were selected as study subjects. Logistic regression model was used to analyze associations of fracture incidence with age, BMI, fracture history and lifestyle. Results: The 2-year accumulative incidence rate of pediatric fracture was 3.1% (95%CI: 2.8%-3.4%) in school-age children and adolescents in Beijing, which was much higher in boys (4.1%) than in girls (2.1%) and increased with age in boys but decreased with age in girls. Fractures mainly occurred at upper-limb (69.0%), no gender and age specific significant in fracture sites were observed. Fracture history was the risk factor for fracture incidence in both boys and girls (boys: RR=1.81, 95%CI: 1.18-2.64; girls: RR=3.11, 95%CI: 1.74-5.13). In addition, higher duration and frequency of moderate to vigorous physical activities (≥120 min/day) and frequent consumption of sugar sweetened beverage (≥1 time/week) were also found to increase fracture risk in boys. Conclusion: The incidence of pediatric fracture was associated with gender, age, fracture history and lifestyle habits in school-age children and adolescents in Beijing. Targeted strategies are needed to prevent childhood fracture.


School Health Services , Schools , Adolescent , Beijing/epidemiology , Child , Female , Humans , Incidence , Male , Risk Factors
11.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(3): 462-468, 2021 Mar 10.
Article Zh | MEDLINE | ID: mdl-34814414

Objective: To investigate the relationships between vitamin D nutritional status and the calcaneal bone mineral density (BMD) in children. Methods: Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing selected through stratified cluster sampling were included in the baseline survey. A follow-up investigation was conducted in 2019. The questionnaire survey, detection of serum 25-hydroxyvitamin D [25(OH)D] level and ultrasound measurement of calcaneal BMD were conducted. Multivariable linear and logistic regression models were used to analyze the relationships between baseline vitamin D nutritional status and the follow-up calcaneal BMD. Results: A total of 10 914 children aged (11.5±3.3) years (boys accounting for 49.6%) were included in the analysis. The average 25(OH)D level was (35.4±12.0) nmol/L, and the deficiency rate was 36.1%. After the adjustment for age, gender, body mass index, smoking status, alcohol use status, dairy products intake, vitamin D supplement, calcium supplement, physical activity, pubertal development, and baseline calcaneal BMD Z-score, for per 10 nmol/L increase in 25(OH)D, the follow-up calcaneal BMD Z-score increased by 0.01(P=0.041), and the OR(95%CI) of decreased calcaneal BMD Z-score after 2 years was 0.96 (0.93-1.00)(P=0.030). Compared with vitamin D adequacy, the follow-up calcaneal BMD Z-score of children with vitamin D insufficiency and deficiency decreased by 0.03(P=0.307) and 0.06 (P=0.046), and the risk of decreased calcaneal BMD Z-score after 2 years increased by 15%(P=0.037) and 21%(P=0.006), respectively (P for trend<0.05). Conclusions: Vitamin D nutritional status was closely related to calcaneal BMD, and children with adequate vitamin D nutritional status tended to obtain higher BMD. Children and adolescents are encouraged to maintain sufficient vitamin D levels, strengthen nutrition and exercise to promote bone health.


Bone Density , Vitamin D Deficiency , Adolescent , Child , Humans , Male , Nutritional Status , Prospective Studies , Schools , Vitamin D , Vitamin D Deficiency/epidemiology
12.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(3): 455-461, 2021 Mar 10.
Article Zh | MEDLINE | ID: mdl-34814413

Objective: To investigate the association between vitamin D nutritional status and the body muscle mass in children. Methods: Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected through stratified cluster sampling in baseline survey. A follow-up investigation was conducted in 2019. The questionnaire survey and the detection of serum 25-hydroxyvitamin D [25(OH)D] level were conducted. The bioelectrical impedance analysis (BIA) apparatus was used to measure body muscle mass, and muscle mass index (MMI) was calculated. Multivariable linear models were used to analyze the association of vitamin D nutritional status with the baseline and follow-up MMI measures. Results: A total of 10 890 children aged (11.5±3.3) years(boys accounting for 49.6%) were included in the analysis. The average 25(OH)D level was (35.4±12.0) nmol/L, with an adequacy ratio of 11.1%. After multivariate linear regression adjustment for age, sex, body fat mass, smoking status, alcohol use status, dairy supplement, calcium supplement, physical activity, and pubertal development, no statistically significant association between vitamin D nutritional status and baseline MMI level was observed (P>0.05). For the follow-up MMI, the Z-score increased by 0.008 (P=0.058) for per 10 nmol/L increase in 25(OH)D, which were 0.002 (P=0.815) and 0.037 (P=0.031) higher in children with insufficient and adequate vitamin D than those with vitamin D deficiency, respectively (P for trend =0.089). Subgroup analysis showed that in the normal BMI group, for per 10 nmol/L increase in 25 (OH) D, the MMI at baseline survey and MMI Z-score at follow-up of children with adequate vitamin D and increased by 0.019 and 0.014, respectively (both P<0.05). Conclusions: Vitamin D nutritional status was related to muscle mass in children, and children with adequate vitamin D tended to obtain higher MMI. Children and adolescents are encouraged to maintain sufficient vitamin D levels, strengthen nutrition and exercise to promote body health.


Nutritional Status , Vitamin D Deficiency , Adolescent , Body Mass Index , Child , Humans , Male , Muscles , Schools , Vitamin D
13.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(3): 469-474, 2021 Mar 10.
Article Zh | MEDLINE | ID: mdl-34814415

Objective: To investigate the association of vitamin D with distribution of body fat in children and adolescents. Methods: Data were obtained from the baseline survey of School-based Cardiovascular and Bone Health Promotion Program in 2017. Multiple linear regression and multinomial logistic regression models were applied to analyze the relationships of body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), appendicular fat mass index (AFMI), and visceral fat area(VFA) with vitamin D level and status in children and adolescents. Results: A total of 11 960 children and adolescents were included in the analysis (boys accounting for 49.7%). The average age and serum vitamin D level of study population were (11.0±3.3) years and (35.0±11.9) nmol/L, respectively. The deficiency rate of vitamin D was 37.2%. Gender-specific associations of BMI, FMI, TFMI, and AFMI with vitamin D level were found (P for interaction <0.05): they were inversely associated with vitamin D level in boys (BMI: ß=-0.56; FMI: ß =-0.59; TFMI: ß=-0.60; AFMI: ß=-0.59; all P<0.05), but not in girls (P>0.05). VFA was positively associated with vitamin D deficiency and insufficiency in both boys and girls, and the risks of vitamin D deficiency and insufficiency all increased by 17%(95%CI: 9%-25%) for per increment of standard deviation in VFA. Conclusions: The higher level of visceral fat was associated with the lower vitamin D levels in children. Abdominal obese children and boys with excessive body fat are the key population in the prevention and control of vitamin D deficiency.


Pediatric Obesity , Vitamin D Deficiency , Adolescent , Body Fat Distribution , Body Mass Index , Child , Female , Humans , Male , Vitamin D , Vitamin D Deficiency/epidemiology
14.
Environ Sci Technol ; 55(13): 8665-8674, 2021 07 06.
Article En | MEDLINE | ID: mdl-34110124

Arsenic species transformation in paddy soils has important implications for arsenic accumulation in rice grains and its safety to the consumers. Methylated thioarsenates including highly toxic dimethylated monothioarsenate (DMMTA) have been detected in paddy soils, but their production and dynamics remain poorly understood. In the present study, we first optimized a HPLC-ICP-MS method to quantify methylated thioarsenate species. Using this method together with 10 mM diethylenetriamine pentaacetate (DTPA) to preserve As speciation, we investigated methylated thioarsenate species in porewaters of seven As-contaminated soils incubated under flooded conditions and of two paddy fields. DMMTA was the main methylated thioarsenate species in the porewaters in both incubated soils and paddy fields, with concentrations ranging from 0.2 to 36.2 µg/L and representing ca. 58% of its precursor dimethylarsenate (DMA). The temporal production and dynamics of DMMTA were linked with the DMA concentrations. When soils were drained, DMMTA was converted to DMA. In the two paddy fields, DMMTA concentrations in rice grains were 0.4-10.1 µg/kg. Addition of sulfur fertilizer and rice straw incorporation increased grain DMMTA by 9-28%. These results suggest that DMMTA is an important As species in paddy soils and can accumulate in rice grains, presenting a risk to food safety and human health.


Arsenic , Oryza , Soil Pollutants , Cacodylic Acid , Humans , Soil , Soil Pollutants/analysis
15.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5487-5494, 2020 Nov.
Article Zh | MEDLINE | ID: mdl-33350210

To prepare peptide-modified chitosan tetramethylprazine nanoparticles(FGF-CS-TMP-NPS) and investigate its reversal effect on multidrug resistance in tumor cells. The pEGF-CS-TMP-NPs were prepared by ion crosslinking method, and their physicochemical properties were investigated. Western blot was used to detect the expression levels of epidermal growth factor receptor(EGFR)(MCF-7, MCF-7/ADR, K562 and K562/ADR) and drug-resistant related protein P-gp. MCF-7/ADR and K562/ADR were selected as cell models. The cytotoxicity of pEGF-CS-TMP-NPs, the multiple of cell resistance to adriamycin, the reversal resistance index of pEGF-CS-TMP-NPs to doxorubicin and the sensitization of pEGF-CS-TMP-NPs to doxorubicin were detected by MTT assay. After MCF-7/ADR and K562/ADR were treated with pEGF-CS-TMP-NPs, the expression changes of P-gp were detected by Western blot. The encapsulation efficiency and drug loading of pEGF-CS-TMP-NPs were 37.66%± 0.53% and 3.25%± 0.34% respectively in HPLC. The nanoparticles showed an average particle size of(150.50±9.3) nm, polymer dispersity index of(0.059±0.007) and Zeta potential of(19.30±2.02) mV as detected by laser particle size analyzer. The nanoparticles were spherical and well dispersed under transmission electron microscope. Western blot results showed that EGFR was positively expressed in MCF-7 and MCF-7/ADR cells, while negatively expressed in K562 and K562/ADR cells. P-gp was highly expressed in MCF-7/ADR and K562/ADR, while negatively expressed in MCF-7 and K562. pEGF-CS-TMP-NPs had a weak effect on MCF-7/ADR and K562/ADR. The adriamycin resistance of MCF-7/ADR cells was 108.36 times, and that of K562/ADR cells was more than 100 times. When IC_(85) of pEGF-CS-TMP-NPs was used as the administration concentration, the reversion index of MCF-7/ADR and K562/ADR cells was 3.68 and 1.87, respectively. pEGF-CS-TMP-NPs could enhance the sensitivity of adriamycin to MCF-7/ADR cells in a positive correlation with the concentration, and the sensitivity was significantly higher than that of K562/ADR cells. Western blot results showed that the expression level of P-gp in MCF-7/ADR cells decreased significantly after treatment with pEGF-CS-TMP-NPs, while the expression level of P-gp in K562/ADR cells did not change significantly. Experimental results show that pEGF-CS-TMP-NPs have an active targeting effect on MCF-7/ADR cells with high EGFR expression, and can effectively reverse the multidrug resistance of MCF-7/ADR cells. Active targeting effect is related to the peptides modification of nanoparticles, and the mechanism of reversing tumor MDR may be achieved by down-regulating the expression level of P-gp.


Breast Neoplasms , Chitosan , Nanoparticles , Doxorubicin , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , Peptides , Pyrazines
16.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(12): 2059-2065, 2020 Dec 10.
Article Zh | MEDLINE | ID: mdl-33378817

Objective: To investigate the relationships between vitamin D nutritional status and the risks of cardiometabolic abnormities in children. Methods: Data were obtained from the School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected by using a stratified cluster sampling method in the baseline survey. A Follow-up investigation was conducted in 2019. Log-binomial regression was used to analyze the relationships between baseline vitamin D nutritional status and the risks of cardiometabolic abnormities (obesity, hypertension, hyperglycemia, and dyslipidemia). Results: A total of 10 482 participants were involved in the study. The average vitamin D level was (35.6 ± 12.0) nmol/L, and the deficiency rate was 35.1%. The 2-year cumulative incidence rates of obesity, hypertension, hyperglycemia, high TC, high LDL-C, low HDL-C, high TG, and high non-HDL-C were 4.3%, 10.8%, 8.5%, 3.1%, 2.5%, 3.4%, 2.5%, and 3.9% respectively. After the adjustment of potential confounding factors, children with vitamin D inadequacy or deficiency had higher risks of high TC [RR (95%CI): inadequacy, 2.06 (1.19-3.58); deficiency, 2.80 (1.61-4.89)], high LDL-C [RR (95%CI): inadequacy, 1.67 (1.02-2.73); deficiency, 1.99 (1.19-3.33)], and high non-HDL-C [RR (95%CI): inadequacy, 2.00 (1.26-3.17); deficiency, 2.45 (1.53-3.92)] compared with children with adequate vitamin D, and the risks of them increased with the decrease of vitamin D level (trend P<0.05). The gender-stratified analysis showed that vitamin D deficiency was remained associated with high TC [RR (95%CI): boy, 2.64 (1.19-5.87); girl, 3.13 (1.43-6.83)] and high non-HDL-C [RR (95%CI): boy, 2.58(1.40-4.77); girl, 2.31 (1.10-4.84)]. Conclusions: The risks of abnormal TC, LDL-C, and non-HDL-C were inversely associated with vitamin D level. Maintenance of adequate vitamin D status in children may contribute to the early prevention of cardiovascular diseases.


Cardiovascular Diseases , Vitamin D Deficiency , Adolescent , Beijing/epidemiology , Cardiovascular Diseases/epidemiology , Child , Female , Humans , Male , Nutritional Status , Prospective Studies , Risk Factors , Vitamin D/blood , Vitamin D Deficiency/epidemiology
17.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(12): 2066-2071, 2020 Dec 10.
Article Zh | MEDLINE | ID: mdl-33378818

Objective: To explore the screening effect of obesity assessed by body fat indicators on persistent dyslipidemia among children. Methods: Data were obtained from the baseline and follow-up survey of 'School-based Cardiovascular and Bone Health Promotion Program.' BMI, fat mass index (FMI), and fat mass percentage (FMP) were used to define obesity. Dyslipidemia, diagnosed both in the baseline and a follow-up survey, was defined as persistent dyslipidemia. The area under the receiver operating characteristic curve (AUC) was used to compare the predictive capabilities of obesity defined by different indicators on persistent dyslipidemia. Results: A total of 10 783 children (boys accounted for 49.6%) were included in the analysis, with the average age as (10.9±3.3) years old. The detection rates of persistent high TC, high LDL-C, low HDL-C, high TG, and high non-HDL-C were 1.3%, 1.2%, 4.3%, 1.3%, and 0.8%, respectively. In boys, the capabilities of FMI- and FMP-defined obesity in the prediction of persistent high LDL-C [FMI: AUC=0.626 (95%CI: 0.558-0.694), P=0.024; FMP: AUC=0.642 (95%CI: 0.574-0.710), P=0.004] and high non-HDL-C [FMI: AUC=0.637 (95%CI: 0.584-0.689), P=0.017; FMP: AUC=0.641 (95%CI: 0.588- 0.693), P=0.018] were significantly higher than BMI-defined obesity. Besides, obese boys defined by FMI had the stronger capability in predicting persistent low HDL-C than that defined by BMI [AUC=0.784 (95%CI: 0.742-0.826) vs. 0.750 (95%CI: 0.726-0.773), P=0.047]. In girls, the capabilities of FMI- and FMP-defined obesity in the prediction of persistent dyslipidemia were not statistically different from BMI. Conclusions: The obesity assessed by body fat performed better in predicting persistent high LDL-C, low HDL-C, and high non-HDL-C than that assessed by BMI among boys, which can be further applied to cardiovascular disease prevention.


Adipose Tissue , Dyslipidemias , Mass Screening , Pediatric Obesity , Adolescent , Child , Dyslipidemias/diagnosis , Dyslipidemias/epidemiology , Female , Humans , Male , Mass Screening/methods , Pediatric Obesity/diagnosis , Pediatric Obesity/epidemiology
18.
Article En | MEDLINE | ID: mdl-32928375

This work investigates a completely novel and experimental concept of exposing L5178Y cells at the air-agar-interface to mainstream cigarette smoke aerosol (Kentucky reference 3R4F). This study highlights the associated challenges of combining a suspension cell line alongside an in vitro aerosol exposure system. To achieve a monolayer, cells were 'seeded' in a concentrated cell super-mix suspension onto an RPMI/agar-matrix -base. The resulting cell suspension media was adsorbed into the agar base leaving the L5178Y cells lightly suspended on the agar surface, approximating a monolayer. Cells were deemed supportable on the agar-matrix, viable and recoverable. Using Vitrocell VC 10 exposure system and the Ames 4 exposure module, L5178Y cells were successfully exposed to a dynamic cigarette smoke aerosol, recovered and assessed for mutant frequencies, using standard assay procedures. Method development included assessment of flowing air conditions, plating efficiency and recovery of L5178Y cells from the agar-matrix surface. Positive controls MMS and B[a]P were successfully incorporated into the agar-matrix and metabolic activation was achieved by S-9 incorporation into the same agar-base-matrix. B[a]P demonstrated metabolic activation and positive response, suggesting a clear cellular interaction with the agar-matrix. Whole smoke exposed cells in the presence of metabolic activation showed a clear dose response and increasing mutant frequencies, well in excess of the controls (air and incubator) and the global evaluation factor following a 2 or 3 day expression period. This experimental concept demonstrates that L5178Y cells can be exposed to cigarette smoke aerosol, using a completely novel and a previously untested approach. Although this work successfully demonstrates the approach is viable and cells can be plated and maintained on an agar-matrix, more optimisation and robustness assessment is required before it can be considered fully adapted and used alongside other whole aerosol methodologies for the assessment of cigarette smoke and other inhaled aerosols.


Lymphoma/pathology , Mutagenicity Tests , Mutagens/toxicity , Smoke/adverse effects , Aerosols/pharmacology , Aerosols/toxicity , Agar/chemistry , Air , Animals , Cell Line/drug effects , Dose-Response Relationship, Drug , Electronic Nicotine Delivery Systems , Humans , Lymphoma/chemically induced , Mice , Mutagens/pharmacology
19.
Medicine (Baltimore) ; 99(13): e19611, 2020 Mar.
Article En | MEDLINE | ID: mdl-32221084

INTRODUCTION: Kidney stone is caused by abnormal accumulation of crystalline substances in the kidneys. Kidney stone is one of the urinary system diseases with a high incidence. In this study, we will use the research method of randomized controlled trials to explore the effects of Traditional Chinese medicine combined with western medicine on renal function and urine metabolism in women with kidney stones. We hope that the results of this study will provide more evidence-based medical evidence for TCM to treat kidney stones, and also provide patients with more treatment options. METHODS/DESIGN: This pragmatic randomized controlled trial will recruit 100 patients who are diagnosed with kidney stone. Simple randomization to conventional drug treatment with a 1:1 allocation ratio will be used. The participants will continue to receive ESWL treatment and TCM therapy. The selection of outcomes will be evaluated by the overall effectiveness of clinical efficacy. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of Traditional Chinese medicine for patients with Female kidney stone.


Kidney Calculi/drug therapy , Lithotripsy/methods , Medicine, Chinese Traditional/methods , Adolescent , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Medicine, Chinese Traditional/adverse effects , Middle Aged , Single-Blind Method , Young Adult
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(1): 62-67, 2020 Jan 10.
Article Zh | MEDLINE | ID: mdl-32062944

Objective: To compare the power of dyslipidemia diagnosis by different sets of cut points in the prediction of cardiovascular metabolic risk factors and identify the appropriate cut points for the diagnosis of dyslipidemia in children and adolescents in China. Methods: Data were obtained from the baseline survey of 'School-based Cardiovascular and Bone Health Promotion Program' in Beijing in 2017. Dyslipidemia was diagnosed by using two set of cut points. Receiver operating characteristic curve analysis was conducted to assess the power of dyslipidemia diagnosis by the two set of cut points to predict the prevalence of hypertension, obesity, high fat mass percentage and impaired fasting glucose. Results: A total of 14 390 children and adolescents were in included in the study. The prevalence rates of high TC, high LDL-C, low HDL-C, and high TG in the participants were 2.7%, 2.7%, 14.4%, and 3.7% according to 'Chinese Reference Standard', and 5.0%, 3.7%, 13.3%, and 3.5% according to 'China Expert Consensus'. Low HDL-C and high TG defined by the 'Chinese Reference Standard' had better performance for the prediction of high fat mass percentage and obesity in boys, but worse performance in girls (P<0.001). Conclusions: Using 'China Reference Standard' can increase the true positive rate in the prediction of obesity or high fat mass percentage in boys, and reduce the false positive rate in girls. The cut points for the diagnosis of dyslipidemia in Chinese children and adolescents need to be further validated by using national representative sample and in longitudinal study.


Dyslipidemias , Adolescent , Beijing , Child , China , Dyslipidemias/complications , Dyslipidemias/diagnosis , Female , Humans , Longitudinal Studies , Male , Obesity/complications , Prevalence , Reference Values , Risk Factors
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