OBJECTIVE: To investigate the effect of irradiation dose rate of ⁶⁰Co γ-ray on hematopoietic and immune cells in total body irradiation (TBI) mice. METHODS: After TBI with 8 Gy ⁶⁰Co γ-ray at three irradiation dose rates of 0.027, 0.256 and 0.597 Gy/min, the survival and change of body weight of C57BL/6J mice were observed within 30 days. The peripheral blood parameters were examined at each time point within 30 days post-irradiation. The hematopoietic stem/progenitor cell counts of mice were examined on the 10^th and 30^th day post-irradiation by flow cytometry, as well as the proportions of immune cells in peripheral blood, bone marrow and spleen of mice on the 30^th day post-irradiation. RESULTS: After TBI with 8 Gy ⁶⁰Co γ-ray, the 30-day survival rate of high dose-rate group was 0, which was significantly lower than 90% of medium dose-rate group and 100% of low dose-rate group (both P < 0.001). The peripheral blood parameters of all three groups showed a sharp decline → low value → gradually recovering trend. The count of white blood cell, neutrophil, lymphocyte, red blood cell, platelet and hemoglobin level in the high dose-rate and medium dose-rate groups were significantly lower than those in the low dose-rate group on day 7-18 post-irradiation (all P < 0.05), but there were no significant differences between the high dose-rate and medium dose-rate groups (P >0.05). On the 10^th day after irradiation, the proportion and number of bone marrow hematopoietic stem/progenitor cells (including LK, LSK, LT-HSC, ST-HSC, and MPP cells) in the low dose-rate and medium dose-rate groups were significantly decreased compared to those in the normal group (all P < 0.05), but there were no significant differences between the two groups (P >0.05). On the 30^th day after irradiation, LSK, LT-HSC, ST-HSC and MPP cells in the low dose-rate group recovered to normal levels, while those in the medium dose-rate group were still significantly lower than those in the low dose-rate group (all P < 0.001). The results of bone marrow and peripheral immune cell tests on the 30^th day after irradiation showed that the ratios of T and B lymphocytes in the low dose-rate and medium dose-rate groups were reduced compared to that in the normal group (both P < 0.05), while the ratio of neutrophils was increased (P < 0.01). The trend of changes in the spleen and peripheral blood was consistent. CONCLUSION The degree of hematopoietic and immune cell damage in mice after TBI with 8 Gy ⁶⁰Co γ-ray is related to the dose rate, and low dose-rate irradiation can reduce the damage in the animal model. Therefore, choosing the appropriate dose rate of irradiation is a key factor in establishing an objective and reliable experimental animal model of irradiation.
Animals ; Mice ; Whole-Body Irradiation ; Gamma Rays ; Mice, Inbred C57BL ; Hematopoietic Stem Cells/radiation effects* ; Cobalt Radioisotopes ; Dose-Response Relationship, Radiation ; Male

Objective： Varicocele (VC) induces male infertility by mediating changes in the testicular microenvironment, in which testicular hypoxia and high-pressure are important pathological conditions. This study aims to compare the mouse spermatogenesis (GC-2spd) cells and Sertoli (TM4) cells of mouse testis after hypoxic modeling and hypoxic and high-pressure combined modeling, and to explore the feasibility of establishing a hypoxic and high-pressure combined cell model. Methods： On the basis of cell hypoxia induced by CoCl2, the complex model of testicular cell hypoxia and high pressure was constructed by changing the osmotic pressure of GC-2 and TM4 cell medium with a high concentration of NaCl solution. After selecting the intervention concentration of CoCl2 by MTT test and detecting the expression level of HIF-1α for the determination of the optimal osmotic pressure conditions of the cell model, the cells were divided into normal group, hypoxia model group and composite model group. And the levels of OS, programmed cell death, inflammatory factors, and the expression levels of pyroptosis-related proteins were compared between the normal group and the groups with different modeling methods. Results： The optimal intervention concentration of CoCl2 in GC-2 and TM4 cells was 150 and 250μmol/L, respectively, and the expression of HIF-1α was the highest in both cells under osmotic pressure of 500 mOsmol/kg (P<0.05). Compared with the normal group, the SOD levels of GC-2 and TM4 cells decreased (all P<0.05), CAT level decreased (all P<0.05), and MDA level increased (all P<0.01), and the OS level of GC-2 and TM4 cells was more obvious than that of the hypoxia model group (all P<0.05). Compared with the normal group, apoptosis occurred in GC-2 and TM4 cells after composite modeling (all P<0.05). Compared with the normal group, the mRNA expressions of IL-1β, IL-18, TNF-α and COX-2 in GC-2 and TM4 cells significantly increased (P<0.01) and higher than those in hypoxia model group (P<0.05) and induced pyroptosis (P<0.01). The expression level of GSDMD increased (P<0.05). Conclusion： The cell model with hypoxia and high pressure combined modeling can not only induce oxidative stress and apoptosis of cells better than that with hypoxia alone, but also further cause inflammatory response damage and pyroptosis, which simulates the changes of testis microenvironment mediated by hypoxia and high pressure combined conditions in VC. This cell model can be used for studying the pathogenesis of VC-associated male infertility, evaluating drug efficacy, and exploring pharmacological mechanisms.
Male ; Animals ; Varicocele/pathology* ; Mice ; Testis/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Hypoxia ; Cobalt ; Sertoli Cells/metabolism* ; Osmotic Pressure ; Spermatogenesis ; Cellular Microenvironment ; Infertility, Male ; Disease Models, Animal

Objective: To establish a inductively coupled plasma mass spectrometry method for the determination of trace cobalt and tungsten in human urine. Methods: The authors used 1% nitric acid solution as diluent in October-December 2021, the sample dilution factor and internal standard element were optimized by single factor rotation experiment, and the difference between the working curve and the standard curve was compared. Results: The method uses working curve to determine cobalt and tungsten in urine, the linear range of this method was 0.0~10.0 μg/L, the correlation coefficient was 0.999 9, the detection limits respectively were 0.005 μg/L (cobalt) and 0.09 μg/L (tungsten), the recoveries of samples respectively were 87.0%~100.2% (cobalt) and 89.4%~104.8% (tungsten), the relative standard deviations respectively were 0.4%~4.4% (cobalt) and 0.6%~3.8% (tungsten) . Conclusion: A simple and rapid method for determination of cobalt and tungsten in urine has been established. This method has the advantages of simple operation, high sensitivity, low detection limit and good stability. It is suitable for determination of cobalt and tungsten in urine of all kinds of people.
Humans ; Cobalt/analysis* ; Tungsten/analysis* ; Spectrum Analysis ; Nitric Acid ; Mass Spectrometry

Cobalt/toxicity* ; Computational Biology ; Kidney/drug effects* ; Kidney Diseases/genetics* ; Humans

BACKGROUND: Little is known about the effects of environmental cobalt exposure on insulin resistance (IR) in the general adult population. We investigated the association between cobalt concentration and IR. METHODS: A total of 1281 subjects aged more than 20 years with complete blood cobalt data were identified from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 cycle. Blood cobalt levels were analyzed for their association with IR among all populations and subgroups by sex. Regression coefficients and 95% confidence intervals (CIs) of blood cobalt concentrations in association with fasting glucose, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were estimated using multivariate linear regression after adjusting for age, sex, ethnicity, alcohol consumption, body mass index, education level, and household income. A multivariate generalized linear regression analysis was further carried out to explore the association between cobalt exposure and IR. RESULTS: A negative association between blood cobalt concentration (coefficient = - 0.125, 95% CI - 0.234, - 0.015; P = 0.026) and HOMA-IR in female adults in the age- and sex-adjusted model was observed. However, no associations with HOMA-IR, fasting glucose, or insulin were found in the overall population. In the generalized linear models, participants with the lowest cobalt levels had a 2.74% (95% CI 0.04%, 5.50%) increase in HOMA-IR (P for trend = 0.031) compared with subjects with the highest cobalt levels. Restricted cubic spline regression suggested that a non-linear relationship may exist between blood cobalt and HOMA-IR. CONCLUSIONS These results provide epidemiological evidence that low levels of blood cobalt are negatively associated with HOMA-IR in female adults.
Adult ; Aged ; Aged, 80 and over ; Cobalt/blood* ; Cross-Sectional Studies ; Environmental Pollutants/blood* ; Female ; Homeostasis ; Humans ; Insulin/blood* ; Insulin Resistance ; Male ; Middle Aged ; Nutrition Surveys ; Sex Factors ; United States ; Young Adult

OBJECTIVES: At present, removable partial denture is still one of the main restoration methods for dentition defects. However, the trend for digital partial denture is becoming more and more obvious in the field of oral repair. However, there are relatively few studies on digital removable partial denture. The aim of this study is to investigate the effects of 3 processing technologies (precision casting, digital cutting, and 3D printing) on the fitness for the clasps of cobalt chromium alloy and pure titanium removable partial denture, and to provide a theoretical basis for the clinical application of digital removable partial denture. METHODS: Clasps of Co-Cr alloy and pure titanium were produced by 3 different processing technologies (precision casting, digital cutting, and 3D printing). There are 6 groups, including a casting pure titanium group, a casting cobalt chromium group, a cutting pure titanium group, a cutting cobalt chromium group, a printing pure titanium group, and a printing cobalt chromium group ( RESULTS: There was no statistical difference in fitness between the casting pure titanium group and the casting cobalt chromium group ( CONCLUSIONS The cobalt chromium alloy and pure titanium clasps made by precision casting, digital cutting, and 3D printing have good fitness. Under the same process, there is no significant difference between cobalt chromium alloy and pure titanium clasps. The 3D printing pure titanium clasps have better fitness than casting pure titanium and cutting pure titanium clasps, which meet the needs of clinical application.
Chromium Alloys ; Cobalt ; Denture, Partial, Removable ; Titanium

BACKGROUND: Many studies have investigated heavy metal exposure could increase the occurrence of congenital heart defects (CHDs). However, there are limited data regarding the relationship between cobalt exposure and CHD occurrence in offspring. The aim of this study was to analyze the association between cobalt exposure in mothers and the risk of CHDs in offspring. MATERIALS AND METHODS: In order to explore the association between cobalt exposure and occurrence of congenital heart defect (CHD), a case-control study with 490 controls and 399 cases with CHDs in China were developed. The concentrations of cobalt in hair of pregnant woman and fetal placental tissue were measured and processed by a logistic regression analysis to explore the relationship between cobalt exposure and risk of CHDs. RESULTS: The median concentration of hair cobalt in the control and case group was 0.023 ng/mg and 0.033 ng/mg (aOR, 1.837; 95% CI, 1.468-2.299; P < 0.001), respectively. And the median (5-95% range) fetal placental cobalt concentrations were 19.350 ng/g and 42.500 ng/g (aOR, 2.924; 95% CI, 2.211-3.868; P < 0.001) in the control and case groups, respectively. Significant differences in the middle level of cobalt in hair were found in the different CHD subtypes, including septal defects, conotruncal defects, right ventricular outflow tract obstruction, and left ventricular outflow tract obstruction (P < 0.001). Dramatically, different cobalt concentrations in fetal placental tissue were found in all subtypes of cases with CHDs (P < 0.01). CONCLUSIONS The finding suggested that the occurrence of CHDs may be associated with cobalt exposure.
Adolescent ; Adult ; Case-Control Studies ; China ; Cobalt ; adverse effects ; Female ; Hair ; chemistry ; Heart Defects, Congenital ; chemically induced ; Humans ; Maternal Exposure ; adverse effects ; Placenta ; chemistry ; Pregnancy ; Prenatal Exposure Delayed Effects ; chemically induced ; Risk Factors ; Young Adult

OBJECTIVE: To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia-induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms. METHODS: The effect of COE (160, 200 and 240 µ g/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch-wound and transwell assays, respectively. CoCl was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immunofluorescence analysis, respectively. RESULTS: COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner (P<0.01). Furthermore, the expression of epithelial-mesenchymal transition (EMT) related markers were also remarkably suppressed in a dose-dependent manner (P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1 α (Hif-1 α) and Twist1 were suppressed by COE. Additionally, the Hif-1 α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced HepG2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect (P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced HepG2 cells. CONCLUSIONS COE significantly inhibited the tumor metastasis and EMT by suppressing Hif-1 α/Twist1 signaling pathway in hypoxia-induced HepG2 cell. Thus, COE might have potential effect to inhibit the progression of HepG2 in the context of tumor hypoxia.
Biomarkers, Tumor ; metabolism ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Celastrus ; chemistry ; Cell Hypoxia ; drug effects ; Cell Proliferation ; drug effects ; Cell Shape ; drug effects ; Cobalt ; Down-Regulation ; drug effects ; Epithelial-Mesenchymal Transition ; drug effects ; Hep G2 Cells ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins ; metabolism ; Plant Extracts ; pharmacology ; therapeutic use ; Signal Transduction ; drug effects

The present study was designed to examine the effect of heme oxygenase-1 (HO-1) induction by cobalt protoporphyrin (CoPP) on the cardiac functions and morphology, electrocardiogram (ECG) changes, myocardial antioxidants (superoxide dismutase [SOD] and glutathione [GSH]), and expression of heat shock protein (Hsp) 70 and connexin 43 (Cx-43) in myocardial muscles in isoproterenol (ISO) induced myocardial infarction (MI). Thirty two adult male Sprague Dawely rats were divided into 4 groups (each 8 rats): normal control (NC) group, ISO group: received ISO at dose of 150 mg/kg body weight intraperitoneally (i.p.) for 2 successive days; ISO + Trizma group: received (ISO) and Trizma (solvent of CoPP) at dose of 5 mg/kg i.p. injection 2 days before injection of ISO, with ISO at day 0 and at day 2 after ISO injections; and ISO + CoPP group: received ISO and CoPP at a dose of 5 mg/kg dissolved in Trizma i.p. injection as Trizma. We found that, administration of ISO caused significant increase in heart rate, corrected QT interval, ST segment, cardiac enzymes (lactate dehydrogenase, creatine kinase-muscle/brain), cardiac HO-1, Hsp70 with significant attenuation in myocardial GSH, SOD, and Cx-43. On the other hand, administration of CoPP caused significant improvement in ECG parameters, cardiac enzymes, cardiac morphology; antioxidants induced by ISO with significant increase in HO-1, Cx-43, and Hsp70 expression in myocardium. In conclusions, we concluded that induction of HO-1 by CoPP ameliorates ISO-induced myocardial injury, which might be due to up-regulation of Hsp70 and gap junction protein (Cx-43).
Adult ; Animals ; Antioxidants ; Body Weight ; Cobalt ; Connexin 43 ; Connexins ; Creatine ; Electrocardiography ; Glutathione ; Hand ; Heart Rate ; Heat-Shock Proteins ; Heme Oxygenase-1 ; Heme ; HSP70 Heat-Shock Proteins ; Humans ; Isoproterenol ; Male ; Muscles ; Myocardial Infarction ; Myocardium ; Oxidoreductases ; Rats ; Tromethamine ; Up-Regulation

BACKGROUND: Herbs have been used worldwide as complementary and alternative medicines. In Korea, herbs for medical purpose are strictly controlled by the Korea Food and Drug Administration (KFDA). But it does not provide standards for metal antigens. OBJECTIVE: This study conducted to identify the metal contents of Korean herbs and herbal products and to give information on counselling metal allergic patient. METHODS: The concentration of three metal allergens with high antigenicity, cobalt (Co), chromium (Cr), nickel (Ni) was quantitatively determined using inductively coupled plasma with a mass spectrometer after nitric acid (HNO₃) digestion. The herbal objects are as follows: 1) ten kinds of herb plants, 2) ten herbal products sold in Korean drugstores, and 3) ten herbal extracts prescribed by Korean herbal doctors. RESULTS: In 30 samples, Ni and Cr were detected in all items. Co was not detected in two drugstore products. CONCLUSION: Although the levels of metal detected in this study were very low relative to international guidelines and KFDA regulations, the herbal preparations contained similar or higher metal levels than known metal-rich foods. It can cause problems when it added to the daily diet and cause deterioration of skin lesions of metal sensitized person.
Allergens ; Chromium ; Cobalt ; Complementary Therapies ; Dermatitis ; Diet ; Digestion ; Herbal Medicine ; Humans ; Korea ; Metals ; Nickel ; Nitric Acid ; Plant Preparations ; Plasma ; Skin ; Social Control, Formal ; United States Food and Drug Administration