Cerebroprotein hydrolysate oral liquid (COL) is a neuroprotective preparation composed of various amino acids and peptides, which has beneficial effects on diverse central system diseases. However, the therapeutic effect and potential mechanism of oral COL on ischemic stroke (IS) still need to be explored. This study aims to investigate the therapeutic effects and underlying mechanisms of COL on IS in vivo and in vitro. An IS rat model was established through middle cerebral artery occlusion (MCAO) surgery, and triphenyltetrazolium chloride (TTC) staining, behavioral scoring, Evans blue leakage, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining were performed to investigate the effects of COL on cerebral infarct size, neurological function, blood-brain barrier (BBB) and neuroinflammation in IS rats. An in vitro model of IS was established on hCMEC/D3 cells through oxygen-glucose deprivation/reperfusion (OGD/R), and cell counting kit-8 assay, reactive oxygen species (ROS) detection, scratch test and Transwell test were conducted to examine the influence of COL on cell viability, oxidative stress and migration ability. Lipidomics technology, real-time quantitative PCR and Western blot experiments were used to investigate the regulation and mechanism of COL on lipid metabolism in the brain of IS rats. All the animal experiments were approved by Ethical Committee of Animal Experiments of China Pharmaceutical University (No.2022-02-23). Our results showed that intragastric administration of COL could significantly reduce the area of cerebral infarction, improve neurological deficits, lower the levels of inflammatory factors, and protect against the blood-brain barrier damage of rats with IS. OGD/R modeling resulted in a significant decrease in the viability, an elevation in intracellular ROS levels, and a weakened cell migration ability of hCMEC/D3 cells. COL treatment could effectively protect hCMEC/D3 cells from damage caused by OGD/R. More importantly, cerebral ischemia led to significant lipid metabolism disorders in the brain of rats, and significant accumulation of intracerebral triglycerides (TAG) and ceramides (Cer) was observed in IS rats. COL was proved to significantly reverse lipid metabolism disorders in the brain of IS rats and reduce the content of cytotoxic lipid Cer by upregulating the intracerebral levels of an acid ceramidase called N-acylsphingosine amidehydrolase 1 (ASAH1). In summary, COL was proved to be a promising and effective candidate for IS treatment, which could alleviate cerebral ischemic injury by regulating abnormal lipid metabolism.

COVID-19/virology* ; Humans ; Pandemics ; SARS-CoV-2/physiology*

OBJECTIVETo explore the effects of Osthole on apoptosis of HL-60 cells induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL) and its possible mechanism.

METHODSThe proliferative inhibition of HL-60 cells treated with different concentrations of Osthole, TRAIL alone and Osthole combined with TRAIL was measured by MTT assay. The HL-60 cells were treated with Osthole, TRAIL alone and Osthole combined with TRAIL at the concentration

RESULTSThe combined treatment (100µmol/L Osthole + 40 ng/ml TRAIL) of HL-60 cells for 48 h induced an apoptotic rate of (33.9±2.7) %, which was significantly higher than that of cells treated with Osthole or TRAIL alone (P<0.05); at the same time, the combined treatment promoted the decrease of MMP and the expression rate of BCL-2/BAX, and potentiated the expression of DR5 and Caspase-3,-8,-9 activity.

CONCLUSIONOsthole can sensitize HL-60 cells to TRAIL-induced apoptosis, which may be related with the activation of mitochondrial pathways and up-regulation of DR5.

Apoptosis ; Coumarins ; HL-60 Cells ; Humans ; TNF-Related Apoptosis-Inducing Ligand

To investigate the effects of gambognic acid (GA) on TRAIL-induced apoptosis of cancer cells, human colon HT-29 cancer cells were treated with GA to promote apoptosis. Inhibition of the cell proliferation was measured with MTT assay and cell apoptosis was detected with formation of DNA ladders in agarose gel electrophoresis, and activation of caspase activity. The content of cytosolic reactive oxygen species (ROS) was measured with flow cytometry. The activities of Caspase-3, -8, -9 were detected using spectrophotometric assay. The levels of c-FLIP, CHOP, DR4 and DR5 in cells were tested by Western blot. Combination of GA (1 µg · mL(-1)) and TRAIL (40 ng · mL(-1)) significantly reduced proliferation and increased apoptosis of HT-29 cells over those induced by each agent alone. Percentage of apoptotic cells was increased to 45.5%. GA markedly enhanced the intracellular ROS generation. Expression of CHOP, DR4 and DR5 was up-regulated to 7.38, 5.41, and 4.85 times of the control group, respectively. GA promoted activation of Caspase-3, -8, and -9 by TRAIL (P<0.05). Furthermore, the expression of anti-apoptotic protein c-FLIP was down-regulated to 0.22 ± 0.08 times of the control group. In conclusion, GA sensitizes HT-29 cells to TRAIL-induced apoptosis by promoting ROS-activated ERS pathways, up-regulating of DR4 and DR5, and inhibiting c-FLIP expression.
Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Caspases ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Colonic Neoplasms ; metabolism ; Down-Regulation ; HT29 Cells ; Humans ; Reactive Oxygen Species ; metabolism ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology ; Up-Regulation ; Xanthones ; pharmacology

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval,integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart.
Biomarkers ; chemistry ; Computational Biology ; methods ; Databases, Protein ; Genomics ; methods ; Humans ; Metabolomics ; methods ; Proteomics ; methods ; Saliva ; chemistry ; Salivary Proteins and Peptides ; chemistry ; classification ; physiology

OBJECTIVETo evaluate the chromium (Cr) levels in blood and urine among general population in China between 2009 and 2010, and thereby to analyze its prevalent features.

METHODSFrom year 2009 to 2010, a total of 11 983 subjects of general population aged between 6 and 60 year-old were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and 11 983 blood samples and 11 853 urine samples were also collected. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to test the Cr level both in blood and urine; and the Cr distribution in blood and urine among groups of population in different ages, genders and districts, were then analyzed.

RESULTSAmong general population in China, the geometric mean (GM) of Cr concentration in blood was 1.19 µg/L, with median at 1.74 µg /L and 95% percentile at 5.59 µg/L. The Cr concentration in blood among males and females were separately 1.18 µg/L and 1.20 µg/L(P > 0.05); while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 1.00, 1.22, 1.01, 1.40, 1.27 and 1.30 µg/L (P < 0.01), respectively; and the figures in populations from eastern, central and western China were 1.00, 1.70 and 1.98 µg/L (P < 0.01), respectively. Among general population, the GM of Cr concentration in urine was 0.53 µg/L, with median was lower than 0.42 µg/L and 95% percentile at 3.53 µg/L. The Cr concentration in urine among males and females were separately 0.52 µg/L and 0.53 µg/L (P > 0.05);while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 0.56, 0.60, 0.52, 0.50, 0.52 and 0.46 µg/L (P < 0.01), respectively;and the figures in populations from eastern, central and western China were 0.58, < 0.42 and 0.60 µg/L (P < 0.01), respectively.

CONCLUSIONThe study reported the Cr levels in blood and urine among general population in China, and thereby provided basic data evidence for the following Cr biological monitoring studies in near future.

Adolescent ; Adult ; Child ; China ; Chromium ; blood ; urine ; Female ; Humans ; Male ; Middle Aged ; Population Surveillance ; Young Adult

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval, integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart.

Antibody Formation ; Hepatitis B Vaccines ; immunology ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; immunology

OBJECTIVETo investigate the relationship between the mRNA expression levels of p53-mediating DNA damage and repair genes in the peripheral blood lymphocytes of workers and their exposures to benzene in their working environment.

METHODSThe mRNA expression levels of p53 and related genes were determined by SYBR Green I chimeric fluorescence quantitative real-time RT-PCR analysis in peripheral blood lymphocytes of 72 workers, who were classified into group A (46 direct exposure to benzene) and group B (26 indirect exposure to benzene) based on their positions, and 29 controls. The differences of gene expression levels were analyzed by software REST 2005. Meanwhile, the peripheral blood leukocytes, hemoglobin and platelet of workers and controls were counted. Benzene content was measured in the samples of toluene, used as raw material, and spraying agents and benzene, toluene and xylene concentrations in the air of workplaces were monitored.

RESULTSThere were no significant differences in the mRNA expression levels of p53, Ku80, Ape1 and Mdm-2 between group A or group B and control group (P > 0.05). The expression up-regulation of p21 mRNA was found, but without significant difference (P > 0.05). However, the mRNA expression levels of Rad51, Bcl-2, Bax, Xpa and Xpc in group A and Rad51 in group B were downregulated significantly (P < 0.05 or P < 0.01). Moreover, both the counts of white blood cell, hemoglobin and platelet in group A were (4.93 +/- 1.27) x 10(9)/L, (123.97 +/- 11.80) g/L and (124.02 +/- 41.22) x 10(9)/L respectively and platelet in group B (135.80 +/- 39.44) x 10(9)/L were significantly lower than in control group (P < 0.05 or P < 0.01).

CONCLUSIONThe mRNA expression levels of some p53-mediating DNA damage and repair genes are downregulated in the workers chronically exposed to low benzene concentration. The working environment impacts on health of group A workers are greater than the ones of group B.

Adult ; Benzene ; adverse effects ; DNA Damage ; DNA Repair ; Female ; Humans ; Lymphocytes ; drug effects ; metabolism ; Male ; Occupational Exposure ; adverse effects ; RNA, Messenger ; genetics ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Young Adult

Objective To determine the value and the optimal cutoff point of waist circumference (WC) in screening diabetes mellitus (DM) and to provide evidence for DM prevention and identifying population at risk in mid-western rural areas of Shandong province.Methods A sample consisting 16 341 rural residents was selected and studied.All participants were physically examined on height,weight,WC and fasting plasma glucose (FPG).Oral glucose tolerance test (OGTT) was performed for subjects with FPG valued from 6.1 to 7.0 mmol/L.DM was defined according to the criteria set by WHO in 1999.Area under the curve (AUC),sensitivity,specificity and Youden index were computed based on the receiver operating characteristic (ROC) curve analysis.Optimal cutoff point was determined by the maximum of Youden index.Results The prevalence rates of DM for males and females increased along with the rise of WC (trend test X2=72.01,122.65,P＜0.01 ).It appeared significantly higher in those with WC 85 cm in females and≥80 cm in males,with those WC ＜85 cm for females and ＜80 cm for males,in particular.AUCs were 0.639 and 0.655 for males and females respectively and both had significant differences (t=7.22,11.07,P ＜0.01 ).However,the AUCs did not show significant difference (t=0.70,P ＞ 0.05) between males and females.The Youden index reached maximum when WC approached 85 cm for females (24.90%) and 80 cm for males (24.39%).The sensitivity and specificity were 58.04%and 66.86%for males,and 67.08%and 57.31%for females.Conclusion WC seemed to be an effective indicator for screening the DM.The optimal cutoff point of WC would be 85 cm for females and 80 cm for males in screening DM and defining the population at risk in this area.