BACKGROUND:Cardiac dysfunction due to spinal cord injury is an important factor of death in patients with spinal cord injury;however,the specific mechanism is still not clear.Therefore,revealing the mechanism of cardiac dysfunction in spinal cord injury patients is of great significance to improve their quality of life and survival rate. OBJECTIVE:To investigate the mechanism of luteolin in improving serum-induced myocardial cell death in spinal cord injury rats. METHODS:Allen's impact instrument was used to damage the spine T9-T11 of male SD rats to establish a spinal cord injury model meanwhile a sham operation group was set as the control group.The serum of rats of each group was collected.H9c2 cells were divided into a blank control group,a sham operated rat serum group,a spinal cord injury rat serum group and a luteolin pretreatment group.The cells in blank control group were only cultured with ordinary culture medium.The cells in the sham operated rat serum group were treated with medium containing 10%serum from sham operated rat.The cells in the spinal cord injury rat serum group were treated with medium containing 10%serum from spinal cord injury rat.The cells in the luteolin pretreatment group were precultured with a final concentration of 20 μmol/L luteolin for 4 hours and then changed to a medium containing 10%rat serum from spinal cord injury rat.After 24 hours of culture,the survival rate of each group of H9c2 cells was measured by CCK-8 assay.Western blot assay was used to detect the expression of autophagy related protein LC3 and p62 in H9c2 cells in each group. RESULTS AND CONCLUSION:Compared with the blank control group,there was no significant change in cell survival rate in the sham operated rat serum group(P>0.05).Compared with the sham operated rat serum group,the cell survival rate(P<0.01)and the expression of LC3 protein(P<0.05)in spinal cord injury rat serum group was significantly reduced,and the expression of p62 protein was significantly increased(P<0.05).Compared with the spinal cord injury rat serum group,the survival rate of cells in the luteolin pretreatment group significantly increased(P<0.000 1);the expression of LC3 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05).The results indicate that luteolin may improve myocardial cell death induced by serum from rats with spinal cord injury by promoting autophagy.

OBJECTIVE: This study aimed to explore the interplay between the life-course body mass index (BMI) trajectories and insulin resistance (IR) on incident diabetes. METHODS: This longitudinal cohort included 2,336 participants who had BMI repeatedly measured 3-8 times between 1989 and 2009, as well as glucose and insulin measured in 2009. BMI trajectories were identified using a latent class growth mixed model. The interplay between BMI trajectories and IR on diabetes was explored using the four-way effect decomposition method. Logistic regression and mediation models were used to estimate the interaction and mediation effects, respectively. RESULTS: Three distinct BMI trajectory groups were identified: low-stable ( n = 1,625), medium-increasing ( n = 613), and high-increasing ( n = 98). Both interaction and mediation effects of BMI trajectories and IR on incident diabetes were significant ( P < 0.05). The proportion of incident diabetes was higher in the IR-obesity than in the insulin-sensitivity (IS) obesity group (18.9% vs. 5.8%, P < 0.001). After adjusting for covariates, the odds ratios (95% confidence intervals) of the IR, IS-obesity, and IR-obesity groups vs. the normal group were 3.22 (2.05, 5.16), 2.05 (1.00, 3.97), and 7.98 (5.19, 12.62), respectively. IR mediated 10.7% of the total effect of BMI trajectories on incident diabetes ( P < 0.001). CONCLUSION We found strong interactions and weak mediation effects of IR on the relationship between life-course BMI trajectories and incident diabetes. IS-obesity is associated with a lower risk of incident diabetes than IR-obesity.
Humans ; Insulin Resistance ; Body Mass Index ; Male ; Female ; Middle Aged ; China/epidemiology* ; Adult ; Longitudinal Studies ; Incidence ; Diabetes Mellitus/epidemiology* ; Aged ; Obesity/epidemiology* ; Diabetes Mellitus, Type 2/epidemiology* ; East Asian People

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured

Bronchoalveolar lavage fluid (BALF) is rich in various bioactive substances such as cytokines and enzymes, making it a high-quality clinical specimen and research sample. It holds significant value in fields such as etiological analysis, proteomics, pathology, and disease diagnosis and treatment. This article systematically reviews the key technical points for the preservation of BALF samples and provides an in-depth interpretation of bronchoalveolar lavage fluid from an application perspective. The aim is to offer references for the standardization of sample preservation practices and to promote the widespread use of BALF samples in clinical research.

Objective To explore the effects of CDP-diacylglycerol synthase 1(CDS1)on autophagy and amyloid deposition in hippocampal neurons of mice and the related mechanism.Methods Congo red and immunohistochemical staining were used to observe the amyloid deposition in hippocampus of amyloid precursor protein(APP)/presenilin 1(PS1)double-transgenic mice.Lentivirus-mediated overexpression of APP was induced in HT22 cells,and Congo red staining was used to observe the amyloid deposition in HT22 cells.The protein expression levels of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ and P62 in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were detected by Western blotting.The differential protein CDS1 was screened based on the hippocampal proteomics results of APP/PS1 double-transgenic mice.The expression of CDS1 protein in hippocampal tissue of APP/PS1 transgenic mice and APP-overexpressed HT22 cells was detected by Western blotting.After lentivirus-mediated APP overexpression in HT22 cells,CDS1 was overexpressed,and the protein expression levels of LC3-Ⅱ and P62 were detected by Western blotting.Results β-amyloid protein(Aβ)was deposited in the hippocampus of APP/PS1 mice and in HT22 cells overexpressing APP.The levels of LC3-Ⅱ and P62 protein in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were significantly increased.A differential metabolic pathway,glycerophospholipid metabolic pathway,was screened by Kyoto Encyclopedia of Genes and Genomes pathway analysis in the proteomic results of APP/PS1 double-transgenic mice,and the differential protein CDS1 was obtained.Compared with wild-type C57BL/6 mice,APP/PS1 double-transgenic mice exhibited a significantly decrease in CDS1 protein expression in the hippocampus(0.46±0.07 vs 1.00±0.25,P＜0.01).Similarly,lentivirus-mediated overexpression of APP in HT22 cells resulted in decreased CDS1 protein levels compared to cells infected with empty viral vector controls(0.68±0.18 vs 1.00±0.13,P＜0.01).The autophagy flow of nerve cells was significantly restored after the CDS1 overexpression in APP-overexpressed HT22 cells(LC3-Ⅱ:1.00±0.15 vs 0.21±0.05,P＜0.01;P62:1.00±0.16 vs 0.67±0.10,P＜0.01),and Aβ deposition was significantly decreased.Conclusion Downregulation of CDS1 expression can induce dysfusion of autophagosome and lysosome,promoting amyloid deposition in hippocampus of mice with Alzheimer's disease.

Iodine speciations in aquatic environments are affected by dissolved oxygen,redox potential,microbial activity,organic matter decomposition,light reaction,etc.Accurate quantification of iodine speciation can not only help to understand the geochemical cycle of iodine,but also help to trace and study environmental processes.Based on the combination of ion chromatography(IC)and inductively coupled plasma mass spectrometry(ICP-MS),a rapid and sensitive method was established for determining the speciations of iodine in environmental water samples including seawater,river water,lake water,rainwater,groundwater,etc.The results presented here showed that IO3?and I?in seawater were quickly separated and measured within 120 s when using guard column AG22 and 8 mmol/L(NH4)2CO3 as the mobile phase.While for lake water,river water and precipitation samples with high soluble organically bond iodine(SOI),an AS22 separation column(250 mm×4 mm)connected with a guard column and using 50 mmol/L(NH4)2CO3 as mobile phase could effectively separate unknown SOI from IO3? to achieve accurate quantification of IO3?.For accurate correction of iodine measurement signal fluctuations,133Cs was directly added to the(NH4)2CO3 mobile phase as an internal standard.The SOI content was calculated by the total iodine concentrations minus the sum of IO3?and I?.The precision of the established iodine speciation analytical method was better than 3.5%,and the standard addition experiment showed that the analytical method was accurate.When the injection volume was 25 μL,the detection limits were 0.011?0.025 μg/L for IO3? and 0.023?0.031 μg/L for I?,respectively.The method was successfully used to analyze IO3?,SOI and I? in environmental water samples,such as seawater,river water,rainwater and groundwater.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Objective To explore the relationship between serum chitosinase 3-like protein 1(CHI3L1)and Syndecan-1(SDC1)levels and bone metabolism in elderly patients with type 2 diabetes mellitus and their predictive efficacy on osteoporosis.Methods A total of 412 elderly patients with type 2 diabetes admitted to this hospital from May 2019 to May 2023 were included in this study,and were divided into normal bone mass group(n=151),reduced bone mass group(n=138)and osteoporosis group(n=123)according to the iffer-ences in bone mineral density.Serum CHI3L1 and SDC1 levels were detected by enzyme-linked immunosor-bent assay,and serum levels of type 1 collagen cross-linked carboxyl terminal peptide(CTX),25-hydroxyvita-min D[25-(OH)D],osteocalcin(OC),and type 1 procollagen N-terminal propeptide(P1NP)were deter-mined by automatic chemiluminescence immunoassay.Pearson correlation analysis was used to investigate the relationship between serum CHI3L1,SDC1 and bone metabolism in elderly patients with type 2 diabetes.Re-ceiver operating characteristic(ROC)curve was drawn to evaluate the predictive value of serum CHI3L1 and SDC1 on osteoporosis in elderly patients with type 2 diabetes.Multivariate Logistic regression analysis was used to investigate the influencing factors of osteoporosis in elderly patients with type 2 diabetes.Results There were significant differences in diabetes course,fasting blood glucose,HbA1c and HDL-C a-mong normal bone mass group,decreased bone mass group and osteoporosis group(P＜0.05).The levels of serum CHI3L1,25-(OH)D,P1NP and osteocalcin in osteoporosis group were lower than those in osteopenia group,and those in osteopenia group were lower than those in normal bone mass group,the differences were statistically significant(P＜0.05).Serum SDC1 and CTX levels in osteoporosis group were higher than those in osteopenia group,and those in osteopenia group were higher than those in normal bone mass group,the differences were statistically significant(P＜0.05).Serum CHI3L1 was positively correlated with 25-(OH)D,P1NP and OC(P＜0.05),and negatively correlated with CTX(P＜0.05).Serum SDC1 was negatively correlated with 25-(OH)D,P1NP,OC(P＜0.05),and positively correlated with CTX(P＜0.05).The area under the curve(AUC)of serum CHI3L1,SDC1 and their combination predicted osteoporosis in elderly pa-tients with type 2 diabetes were 0.851,0.772 and 0.904,respectively.Multivariate Logistic regression analysis showed that long duration of diabetes,increased HbA1c,high expression of OC,CHI3L1＞4.16 ng/mL,SDC1≥50.94 ng/mL were all influential factors for osteoporosis in elderly patients with type 2 diabetes(P＜0.05).Conclusion Low expression of CHI3L1 and high expression of SDC1 in serum are associated with ab-normal bone metabolism in elderly patients with type 2 diabetes.These two indexes are expected to be used as biological markers to predict osteoporosis in elderly patients with type 2 diabetes.

Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.
Animals ; Mesenchymal Stem Cells/metabolism* ; Caveolin 1/genetics* ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Cell Differentiation/drug effects* ; Female ; Signal Transduction/drug effects* ; Flavonoids/administration & dosage* ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cells, Cultured ; Humans