Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.@*METHODS@#A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.@*RESULTS@#FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).@*CONCLUSION@#FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Inhibitory effects of diarsenic trioxide (As2O3) on hepatocellular carcinoma cells exerted by regulation of promyelocytic leukemia protein levels

Previous Chinese research revealed that diarsenic trioxide (As2O3) inhibits acute promyelocytic leukemia (PML) cell proliferation and initiates apoptosis through degradation of the PML-retinoic acid receptor protein. This study was to analyse whether As2O3 also had an effect on hepatocellular carcinoma (HCC) cells. As2O3 effects on various HCC cell lines and primary HCC cells were investigated in time and dose series, including measurements of cell growth, PML mRNA and protein expression, xenografted tumor formation, and the self-renewal Oct4 and hepatocyte marker expressions in mouse model xenografts or cells treated with PML siRNA. The results were analyzed by immunocytochemistry, quantitative reverse transcription PCR and western blotting as well as indocyanine green and Periodic Acid Schiff staining. As2O3 inhibited HCC cell and HCC cell-derived xenograft tumor formation in a time-dependent manner and reduced PML protein expression in HCC cells, but had limited effects on PML mRNA levels in cell nuclei. The HCC cell line HuH7 treated with As2O3 showed a decreased expression of alpha-fetoprotein and increased expression and transcription of mature hepatocyte markers, indicating differentiation of HCC cells into hepatocytes. Cytokeratin 18 protein and mRNA levels as well as tyrosine aminotransferase and apolipoprotein B mRNA transcriptions were enhanced by As2O3 as were the numbers of indocyanine green and Periodic Acid Schiff stained cells. In addition, As2O3 downregulated the expression of Oct4. In conclusion, since As2O3 inhibited HCC cell proliferation and HCC cell-derived xenograft tumor formation it is suggested that an appropriate concentration of As2O3 might be a promising therapy to treat HCC.

Tritium permeation resistance of Al-Al₂O₃ coatings prepared by thermal spraying / 中国辐射卫生

@#<b>Objective</b> To make the preparation method for coatings more convenient in the field where the requirements for tritium permeation resistance are not high, this paper proposes a method for preparing Al-Al₂O₃ tritium permeation barriers by thermal spraying technology and conducts a performance analysis. <b>Methods</b> The tritium permeation resistance and adhesion of Al-Al₂O₃ coatings prepared by thermal spraying were verified by experiments. <b>Results</b> The tritium permeability was reduced by one order of magnitude after a 0.2-mm Al-Al₂O₃ coating was sprayed on the stainless steel surface, and the tritium permeation resistance had no significant improvement with the increase in coating thickness; the adhesion of the coating was determined in the range of 5-10 N by scratch tests. <b>Conclusion</b> In this paper, a simple preparation method for tritium permeation barrier is proposed, and the tritium permeation resistance performance of Al-Al₂O₃ coatings prepared by thermal spraying technology is determined, which provides a reference for the selection of tritium permeation barrier in the field of tritium-containing solid waste storage.

Mechanism of Gegen Qinliantang in Improving Ectopic Lipid Accumulation in Liver of db/db Mice with Type 2 Diabetes Mellitus by Regulating AMPK-FoxO3a Autophagy Axis / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Gegen Qinliantang （GQT） in improving ectopic lipid accumulation in the liver of db/db mice with type 2 diabetes mellitus （T2DM） by regulating the adenosine monophosphate-activated protein kinase （AMPK）-forkhead box O3a （FoxO3a） autophagy axis， to provide a scientific basis for clarifying the hypoglycemic mechanism of GQT and its clinical application. MethodSeventy-five spontaneous T2DM db/db mice and 15 normal db/m mice were selected and maintained on a regular diet for one week， followed by the measurement of blood glucose. They were then randomly divided into six groups， with 15 mice in each group， including normal group （0.2 g·kg-1 saline）， metformin group （0.2 g·kg-1）， high-， medium， and low-dose GQT group （31.9， 19.1， 6.9 g·kg-1）， and model group （0.2 g·kg-1 saline）. The mice were orally administered the corresponding drugs once daily for 12 weeks. Fasting blood glucose （FBG） and glycated hemoglobin （HbA1c） were detected. Fasting insulin （FINS） and free fatty acid （FFA） levels were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in liver tissues were observed by hematoxylin-eosin （HE） staining. The protein expression levels of phosphorylated （p）-AMPK， p-FoxO3a， and autophagy-related proteins microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ） and p62 were detected using Western blot. Immunofluorescence was used to detect the expression of hypoxia-inducible factor-1α （HIF-1α） in liver tissues. Real-time polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of AMPK， FoxO3a， and LC3 in liver tissues. ResultCompared with the normal group， the model group showed pathological changes in liver tissues， increased FBG， HbA1c， FINS， and FFA levels （P<0.01）， increased protein expression levels of p-AMPK， p62， and HIF-1α， decreased protein expression levels of p-FoxO3a and LC3Ⅱ in liver tissues （P<0.01）， decreased mRNA expression of AMPK， and increased expression of FoxO3a （P<0.01）. Compared with the model group， the treatment groups showed relieved liver tissue lesions and decreased FBG， HbA1c， FINS， and FFA levels （P<0.01）. The expression of p-AMPK， p62， and HIF-1α increased， while the expression of p-FoxO3a showed a dose-dependent decrease in the high-dose GQT group. The expression of LC3Ⅱ increased in the metformin group and the high-dose GQT group （P<0.01）. The mRNA expression of AMPK showed a dose-dependent increase， and the expression of FoxO3a showed a dose-dependent decrease in the treatment groups （P<0.01）. ConclusionGQT can improve ectopic lipid accumulation in the liver of T2DM db/db mice， which may be related to the regulation of the AMPK-FoxO3a autophagy axis.

Expression and significance of FOXO3 and IL-2 in conjunctival epithelial cells and tears of patients with dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the expression and significance of forkhead box class O3(FOXO3)and interleukin-2(IL-2)in conjunctival epithelial cells and tears of patients with dry eye(DE).METHODS:A perspective study. A total of 106 DE patients who accepted from March 2019 to March 2021 were prospectively gathered, and 85 healthy subjects in the same period were selected as the control group. The level of FOXO3 in the conjunctival epithelial cells and tear fluid was measured by real-time fluorescent quantitative PCR(qRT-PCR)method; The level of IL-2 in the sample was measured by enzyme-linked immunosorbent(ELISA)method; The changes in clinical indicators of the ocular surface such as break-up time(BUT), Schirmer Ⅰtest(SⅠt), cornea fluorescein staining(CFS)in DE patients before and after treatment were analyzed; The correlation between the levels of FOXO3 and IL-2 in the conjunctival epithelial cells and tears of DE patients and the relationship between the two and clinical indicators were analyzed by Pearson correlation analysis.RESULTS:Compared with the control group, the level of FOXO3 in conjunctival epithelial cells and tear fluid in the DE group was obviously reduced, and the level of IL-2 was obviously increased(all P&#x003C;0.01). Compared with before treatment, the level of FOXO3 in conjunctival epithelial cells and tear fluid of DE patients was obviously up-regulated, and the level of IL-2 was obviously down-regulated(all P&#x003C;0.05). Pearson correlation analysis showed that the levels of FOXO3 and IL-2 in conjunctival epithelial cells and tear fluid were obviously inversely correlated(r=-0.531, -0.469, all P&#x003C;0.01). After treatment, BUT and SⅠt indexes of DE patients increased compared with before treatment, while CFS decreased(all P&#x003C;0.01). The level of FOXO3 in conjunctival epithelial cells of DE patients was obviously directly correlated with BUT and SⅠt(r=0.431, 0.457, all P&#x003C;0.01), and it was obviously inversely correlated with CFS(r=-0.469, P&#x003C;0.01), and the level of IL-2 was obviously inversely correlated with BUT and SⅠt(r=-0.416, -0.447, all P&#x003C;0.01), and it was obviously directly correlated with CFS(r=0.424, P&#x003C;0.01); tear FOXO3 was positively correlated with BUT and SⅠt(r=0.421, 0.443, all P&#x003C;0.01), and it was negatively correlated with CFS(r=-0.474, P&#x003C;0.01), and IL-2 was negatively correlated with BUT and SⅠt(r=-0.408, -0.429, all P&#x003C;0.01), and it was positively correlated with CFS(r=0.419, P&#x003C;0.01).CONCLUSION: the level of FOXO3 in conjunctival epithelial cells and tears of DE patients is decreased, and the level of IL-2 is increased. The two of which are closely related to the ocular surface indicators of patients. They are expected to become laboratory auxiliary indicators for clinical monitoring and prognostic evaluation of DE.

Effect of Liuwei Dihuangwan on Cognitive Ability of SAMP8 Mice by Regulating Autophagy Through PI3K/Akt/FoxO3a Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Liuwei Dihuangwan on memory function of senescence-accelerated mouse prone 8 （SAMP8） mice by regulating autophagy through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box O3a （FoxO3a） pathway. MethodSix male senescence-accelerated mouse resistant 1 （SAMR1） mice of SPF grade aging 6 months were assigned to a normal group， and 24 male SAMP8 mice of SPF grade aging 6 months were randomly divided into a model group， a donepezil group （0.747 mg·kg-1）， and high- and low-dose Liuwei Dihuangwan groups （2.700 and 1.350 g·kg-1）， with 6 mice in each group. The mice were treated with drugs by gavage for 2 months. Morris water maze was used to detect the learning and memory abilities of mice in each group. Nissl staining was used to observe the neurons in the cortex and hippocampus. The positive expression of microtubule-associated protein 1 light chain 3B （LC3B） in the cortex and hippocampus was detected by immunohistochemistry （IHC）. Western blot was used to detect the protein expression of the mammalian ortholog of yeast ATG6 （Beclin-1）， B cell lymphoma-2 （Bcl-2）， autophagy-related gene 5 （ATG5）， cysteinyl aspartate-specific protease 3 （Caspase-3）， Caspase-9， Akt， p-Akt， FoxO3a， and p-FoxO3a. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05，P<0.01）， reduced number of platform crossings and the residence time in the target quadrant （P<0.01）， decreased neurons with reduced volume and dispersed distribution in the cortex and hippocampus， increased positive expression of LC3B （P<0.01）， elevated expression of Beclin-1 and ATG5 in the cortex （P<0.01）， declined Bcl-2 expression （P<0.01）， up-regulated Caspase-3 and Caspase-9 expression （P<0.01）， and decreased expression levels of p-Akt/Akt and p-FoxO3a/FoxO3a （P<0.01）. Compared with the model group， the donepezil group and the Liuwei Dihuangwan groups showed shortened 3 d escape latency （P<0.05，P<0.01）， increased number of platform crossings （P<0.01）， and prolonged residence time in the target quadrant （P<0.01）. In the donepezil group， the number of neurons in the cortex and hippocampus was increased. In the Liuwei Dihuangwan groups， the number of neurons and Nissl bodies increased with denser distribution and lower degree of cell damage. The positive expression of LC3B in the cortex and hippocampus was decreased in the donepezil group and Liuwei Dihuangwan groups （P<0.01）. The expression of Beclin-1 was decreased in the Liuwei Dihuangwan groups （P<0.01）. The expression of ATG5 was decreased in the donepezil group and the low-dose Liuwei Dihuangwan group （P<0.01）. The donepezil group and the Liuwei Dihuangwan groups showed the increased expression level of Bcl-2 in the cortex （P<0.01）， decreased expression level of Caspase-3 （P<0.01）， reduced expression level of Caspase-9 （P<0.05，P<0.01）， and elevated expression levels of p-Akt/Akt and p-FoxO3a/FoxO3a （P<0.01）. ConclusionLiuwei Dihuangwan can effectively improve the learning and memory abilities of the SAMP8 mice and protect neurons. Its mechanism may be related to the regulation of the PI3K/Akt/FoxO3a signaling pathway， down-regulation of the expression of ATG5， Beclin-1， and LC3B， and the inhibition of apoptosis.

Jiangzhi Tongluo Soft Capsules Regulate SIRT1/FoxO3 Pathway to Affect Cell Apoptosis in Rats with Membranous Nephropathy / 中国实验方剂学杂志

ObjectiveTo observe the effect of Jiangzhi Tongluo soft capsule on the protein levels of silent mating-type information regulation 2 homolog 1 （SIRT1） and forkhead transcription factor FoxO3 and podocyte apoptosis in the renal tissue of rats with membranous nephropathy and to reveal the underlying molecular mechanisms for the treatment of MN. MethodSixty male SD rats were randomly assigned into 6 groups with 10 rats each. The six groups included a normal group， a model group， benazepril hydrochloride group， and Jiangzhi Tongluo soft capsule groups of low， medium and high doses （25， 50， 100 mg·kg-1， respectively）. The model rats were established by injection with cationized bovine serum albumin into the tail vein. After modeling， the rats were administrated with corresponding agents by gavage for 4 weeks. At the end of the 4th week， an electron microscope was used to observe the pathological changes in the kidney. Western blot was employed to detect the protein levels of SIRT1 and FoxO3 protein in rat kidney， and immunohistochemistry to detect the expression of B lymphocytoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， Bcl-2-associated death promoter （Bad）， and podocyte split diaphragm proteins nephrin and podocin. ResultCompared with normal group， the expression of pro-apoptotic factors Bax， Bad， and FoxO3 in the kidney was up-regulated （P<0.05）， while that of anti-apoptotic factors Bcl-2， SIRT1， nephrin， and podocin was down-regulated （P<0.05） after modeling. Compared with the model group， the treatments down-regulated the expression of Bax， Bad， and FoxO3 （P<0.05） and up-regulated that of Bcl-2， SIRT1， nephrin， and podocin （P<0.05）. ConclusionJiangzhi Tongluo soft capsule may regulate the SIRT1/FoxO3 pathway to reduce podocyte apoptosis and maintain podocyte structure stability， thereby exerting the renal protection effect.

Correlation of macrophage-related cytokines and silent information regulator 1 and forkhead box protein O3 levels in peripheral blood mononuclear cells in patients with active pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To explore the correlation between the levels of silent information regulator 1 (SIRT1) and forkhead box protein O3 (FOXO3) in peripheral blood mononuclear cells of patients with active pulmonary tuberculosis (APTB) and macrophage-related cytokines-inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). Methods　A total of 64 APTB patients who were treated in Yubei Hospital, the First Affiliated Hospital of Chongqing Medical University from January 2020 to December 2021 were gathered as the APTB group, 59 people with latent tuberculosis infection (LTBI) were gathered as the LTBI group, and 62 healthy people were gathered as the control group. Quantitative real-time PCR (qPCR) method was performed to measure the levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells. The enzyme-linked immunosorbent assay (ELISA) was performed to measure serum iNOS and Arg-1 levels; ROC curve was used to analyze the value of SIRT1 mRNA and FOXO3 mRNA levels in the differential diagnosis of LTBI and APTB; Pearson correlation was performed to analyze the correlation of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients with serum iNOS and Arg-1 levels. Results　The levels of SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells decreased in control group, LTBI group and APTB group, and the level of serum Arg-1 increased in turn (P<0.05). The AUCs of SIRT1 mRNA and FOXO3 mRNA in differential diagnosis of LTBI and APTB were 0.876 and 0.887, respectively, the sensitivity was 71.2% and 76.3%, and the specificity was 96.9% and 90.6% respectively. The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients were positively correlated (r=0.500, P<0.05), and they were positively correlated with serum iNOS and negatively correlated with serum Arg-1 (P<0.05). The SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells of APTB patients after 6 months of treatment were higher than those before treatment, and serum Arg-1 was lower than before treatment (P<0.05). Conclusions　The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients are low, and they are positively correlated with macrophage-related cytokine iNOS and negatively correlated with Arg-1.

Modification effects of temperature on outpatient visits caused by ozone in Linzhi / 公共卫生与预防医学

Objective To investigate the modification effect of atmospheric temperature on outpatient visits caused by O3 in Linzhi City. Methods The daily outpatient data, the daily O3 concentration and daily meteorological data (including daily average temperature, average relative humidity, etc.) in Linzhi City from 2018 to 2019 were collected. The distributed lag non-liner-model (DLNM) was used to quantitatively evaluate the impact of O3 in different temperature layers on the risk of outpatient visits. Results At low temperature layers, the cumulative relative risk (CRR) of total outpatient visits and non-injury outpatient visits increased by 53.8%（4.2% -126.9%) and 59.1%（5.8% -139.2%）for every 10 μg/m3 increase of O3 concentration, respectively. The subgroup analysis showed that for every 10 μg/m3 increase of O3 concentration at low temperature, the CRR of patients with circulatory diseases, men, women, and people being 3 in Linzhi City. In general, the cumulative risk increases as the temperature decreases.

Liraglutide improves bone mineral density in osteoporotic rats by mediating O3a/Wnt signaling / 中华内分泌外科杂志

Objective:To study the effect of liraglutide on the forkhead box O3a (forkhead box O3a, FoxO3a) /Wnt signaling pathway and vertebral bone density in osteoporotic rats.Methods:Female Sprague-dawley rats were divided into sham operation group, model group, and liraglutide intervention group according to the random number table method, with 10 rats in each group. Both the model group and the intervention group used bilateral oophorectomy to establish an osteoporosis model. The intervention group was injected subcutaneously with liraglutide every day, and the sham operation group and the model group were given an equal volume of normal saline. After 12 weeks of continuous administration, the bone mineral density and bone biomechanics were measured, the serum osteoprotegerin, anti-tartrate acid phosphatase, and osteocalcin levels were detected by enzyme-linked immunosorbent assay, and the O3a/Wnt pathway was detected by Real-time PCR technology. The expression level of mRNA was detected by Western blot to detect the expression level of related proteins in the O3a/Wnt pathway.Results:The bone mineral density levels of L4,5 (0.33±0.04 vs 0.18±0.03) and left and right femurs (0.37±0.05 vs 0.23±0.04 0.35±0.04 vs 0.24±0.03) of the successfully modeled rats were significantly lower than those of the sham operation group ( P<0.05) . After 12 weeks of treatment, the differences in the maximum bone load, three-point bending stress, bone density and elastic modulus of the three groups of rats were statistically significant. Among them, the sham operation group had the highest level of each index (36.53±5.23, 154.13±6.27, 0.34±0.04, 3 102.34±160.44) , followed by the intervention group (19.37±4.32, 141.54±6.58, 0.18±0.03, 2 270.18±145.53) and the model group in turn (26.17±4.68, 147.56±5.84, 0.28±0.03, 2 804.24±140.42) ( P<0.05) . There were statistically significant differences in the levels of serum osteoprotegerin, anti-tartrate acid phosphatase and osteocalcin among the three groups. Among them, the osteoprotegerin (Sham operation group vs model group vs intervention group: 7.53±0.63 vs 4.57±0.42 vs 6.15±0.61) of the sham operation group was significantly higher than that of the intervention group and the model group. The anti-tartrate acid phosphatase (Sham operation group vs model group vs intervention group: 14.34±2.87 vs 19.53±3.52 vs 15.96±3.14) and osteocalcin levels (Sham operation group vs model group vs intervention group: 0.84±0.09 vs 1.13± 0.12 vs 0.95± 0.08) of rats The factor was significantly lower than that of the intervention group and model group ( P<0.05) . The mRNA and protein expression levels of FoxO3a, Wnt2, and β-catenin in the three groups of rats were significantly different. Among them, Wnt2 and β-catenin in the sham operation group were significantly higher than the intervention group and model group, and FoxO3a was significantly lower than the intervention group and model Group ( P<0.05) . Conclusion:Liraglutide can increase bone density and improve bone biomechanics by activating O3a/Wnt signal, thereby effectively treating osteoporosis.

The expression of FOXO3 in pancreatic cancer and its effects on pancreatic cancer cells / 中华肝胆外科杂志

Objective:To investigate the expression of forkhead box protein O3(FOXO3) in pancreatic cancer and its effect on the motility and proliferation of pancreatic cancer cells.Methods:The FOXO3 expression in pancreatic cancer and adjacent tissues was retrieved from LinkedOmics database. Western blotting and real-time quantitative polymerase chain reaction were used to detect FOXO3 expression in pancreatic cancer cells and human pancreatic stellate cells. PANC-1 and MIAPaCa-2 pancreatic cancer cells with low FOXO3 expression were selected to transfect FOXO3 overexpression plasmid and negative control plasmid, respectively. The motility and proliferation ability of pancreatic cancer cells were detected by colony formation assay, cell scratch assay, Transwell assay and flow cytometry.Results:In the LinkedOmics database, the relative expression of FOXO3 protein in the cancer tissues of 64 patients with pancreatic cancer was significantly lower than that in the adjacent tissues ( t=8.36, P<0.001). The number of clones in PANC-1 cell line was (30.0±6.6) after overexpressed FOXO3, which was lower than that in negative control cells (92.7±6.7), and the difference was statistically significant ( t=11.54, P<0.001). After overexpressed FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the scratch repair rate was significantly decreased compared with the control group. In Transwell experiment, the number of cells in FOXO3 overexpressed group in PANC-1 cell lines was (21.0±6.6), which was lower than that of negative control groups (55.7±8.5), and the difference was statistically significant ( t=5.59, P=0.005). The results of MIAPaCa-2 cell line were consistent with that of PANC-1 cell line. After overexpressing of FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the proportion of cells in the G0/G1 phase decreased, while the proportion in the S phase increased. Conclusion:The expression of FOXO3 was decreased in pancreatic cancer. Overexpression of FOXO3 could significantly inhibit the proliferation, migration and invasion of pancreatic cancer cells and induce cell cycle arrest, which is a potential target for the treatment of pancreatic cancer.

Evaluation of Sample Preparation Procedures for Determination of Cr(VI) in Cr2O3 Pigments by Vis Spectrophotometry

Abstract Six sample preparation procedures were evaluated for selective extraction of Cr(VI) from commercial samples of chromium oxide green (Cr2O3) pigments prior to formation of its diphenylcarbazone complex [CrDPCO]- for determination by visible spectrophotometry: (I) water-soluble chromium; (II) EPA method 3060A without Mg2+; (III) EPA method 3060A with Mg2+; (IV) Na3PO4 based extraction; (V) method IRSA16 based on acidic extraction and; (VI) Na2CO3 based extraction. Evaluation of the influence of concomitant Cr(III) ions, time and stability of the [CrDPCO]- complex was investigated. Recoveries of soluble and insoluble Cr(VI) species were 86% and 80%, respectively, using procedure (VI). Direct calibration against aqueous standards prepared in the extraction medium was successful for Cr(VI) in the concentration range 0.05-1.50 μg L-1. Limits of detection and quantitation were 0.3 µg g-1 and 1.0 µg g-1, respectively, for 250 mg subsamples/25 mL. Procedure (VI) was applied to the analysis of four commercial samples of Cr2O3 pigments, three determined to have Cr(VI) within compliance limits below 1.0 µg g-1, but one at 16.6 ± 0.6 µg g-1, prohibiting use of this pigment in cosmetic formulations. This sample was conveniently employed to evaluate the accuracy of the method. The recommended procedure is simple and accurate and has been adopted by Tecpar's laboratory of Parana Institute of Technology (Curitiba, Brazil).

Effect of Gaseous Pollutant Concentration on the Number of Daily Outpatient Visits for Acne in Lanzhou / 中国医学科学院学报

Objective To determine the relationship between air pollutants [SO

Mechanism of Wenshen Yangxue Prescription Improving Endometrial Receptivity of Aged Female Mice by Regulating PI3K/Akt/FoxO3A Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the effective components， targets， and possible mechanisms of Wenshen Yangxue prescription in improving endometrial receptivity of aged female mice based on network pharmacology and experimental verification. Method:Based on Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine， the components and targets of Wenshen Yangxue prescription were retrieved， and the targets of ovulatory dysfunctional infertility were collected from the Online Mendelian Inheritance in Man （OMIM） and GeneCards with "anovulatory sterility" and "anovulatory infertility" as keywords. The protein-protein interaction （PPI） network was constructed based on STRING and the core targets of Wenshen Yangxue prescription against ovulatory dysfunctional infertility were screened by Cytoscape， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the core targets in DAVID database. Then， the "medicinal-component-target-pathway" network was established and the core targets were verified by animal experiment. Result:A total of 253 components and 326 targets of Wenshen Yangxue prescription， 819 disease targets， and 74 common targets were screened out. The common targets were mainly involved in the biological processes such as positive regulation of nitric oxide biosynthetic process， positive regulation of cell proliferation， response to estradiol， aging， response to oxidative stress， and angiogenesis. The GO term of response to oxidative stress and five of the top 20 KEGG pathways were analyzed. According to the "medicinal-component-target-biological process/pathway" network， 41 chemical components in 20 medicinals participated in hypoxia inducible factor-1 （HIF-1） signaling pathway， tumor necrosis factor （TNF） signaling pathway， forkhead box O （FOXO） signaling pathway， Toll-like receptor （TLR） signal pathway， and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway by affecting 35 targets. The results of animal experiment showed that the prescription could increase the expression of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， forkhead box O3A （FoxO3A）， and phosphorylated FoxO3A （p-FoxO3A） in uterus of aged female ICR mice. Conclusion:Wenshen Yangxue prescription interferes with oxidative stress and PI3K/Akt/FoxO3A signaling pathway by influencing Akt1， dual oxidase 2 （DUOX2）， epidermal growth factor receptor （EGFR）， heme oxygenase-1 （HMOX1）， myeloperoxidase （MPO）， and other targets， thereby improving endometrial receptivity of aged female mice.

Effect of Koumine on Proliferation and Apoptosis of Colorectal Cancer Cells via ROS/JNK/FoxO3a Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the effect and underlying mechanism of koumine （Kou） at different concentrations （0， 100， 200， 400 μmol·L^-1） on the proliferation and apoptosis of colorectal cancer HCT-116 cells. Method:After 24 hours of<italic> in vitro</italic> intervention with HCT-116 cells by Kou， cell counting kit-8 （CCK-8） assay was used to detect its effect on cell proliferation. Flow cytometry was used to detect cell cycle， apoptosis， and reactive oxygen species （ROS） expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of forkhead box O3a （FoxO3a）. Cells were transfected with small interfering ribonucleic acid （siRNA）. Western blot was employed to detect the protein expression of the FoxO3a target gene. Result:Compared with the conditions in the blank group， Kou treatment reduced the proliferation rate of HCT-116 cells （<italic>P</italic><0.05， <italic>P</italic><0.01） in a dose-dependent manner， caused cell cycle arrest in the G₀/G₁ phase， and induced the apoptosis of HCT-116 cells （<italic>P</italic><0.05， <italic>P</italic><0.01）， which was positively correlated with the concentration of Kou. FoxO3a siRNA interference reduced the expression of FoxO3a and its downstream target genes cyclin-dependent kinase inhibitor 1A （p21）， cyclin-dependent kinase inhibitor 1B （p27）， and Bcl-2 interacting mediator of cell death （Bim） （<italic>P</italic><0.01）. Kou treatment induced the activation of c-Jun <italic>N</italic>-terminal kinase （JNK） in HCT116 cells. SP600125 （JNK specific inhibitor） treatment inhibited the Kou-induced FoxO3a activation and the expression of its downstream target genes. <italic>N</italic>-acetyl cysteine （NAC） treatment reduced Kou-induced ROS levels （<italic>P</italic><0.01） and JNK signal activation. The above results were significantly different from those in the blank group （<italic>P</italic><0.01）. Conclusion:Kou can effectively inhibit the proliferation of HCT-116 cells and promote apoptosis， and the mechanism may be related to the regulation of the ROS/JNK/FoxO3a pathway.

Study on expression relationship of DNA methyltransferase 1 and forkhead box O3a in colon cancer / 国际肿瘤学杂志

Objective:To analyze the relationship between DNA methyltransferase 1 (DNMT1) and forkhead box O3a (FOXO3a) in colon cancer and the diagnostic efficacy of combined detection in predicting the occurrence of colon cancer by detecting the levels of DNMT1 and FOXO3a in serum of colon cancer patients.Methods:A total of 105 patients with colon cancer diagnosed and treated in Xi′an International Medical Center Hospital from September 2019 to September 2020 were selected as the colon cancer group, and 65 patients with colon polyps diagnosed by biopsy during the same period were selected as control group. The levels of DNMT1 and FOXO3a in serum of patients were detected by real-time fluorescence quantitative PCR. Pearson correlation coefficient method was used to analyze the correlation between the levels of DNMT1 and FOXO3a in serum of patients with colon cancer. Subject operating characteristic curve was used to evaluate the diagnostic values of DNMT1 and FOXO3a levels in colon cancer.Results:The serum levels of DNMT1 in the control group and colon cancer group were 0.93±0.28 and 1.34±0.35, compared with the control group, the level of DNMT1 in the colon cancer group was significantly higher, with a statistically significant difference ( t=7.990, P<0.001). The serum levels of FOXO3a were 1.04±0.39 and 0.69±0.18, compared with the control group, the level of FOXO3a in the colon cancer group was significantly lower, with a statistically significant difference ( t=7.940, P=0.001). The serum levels of DNMT1 and FOXO3a in patients with colon cancer were negatively correlated ( r=-0.687, P<0.001). The area under the curve (AUC) of DNMT1 predicting colon cancer was 0.843, the sensitivity was 71.40%, and the specificity was 90.80%. The AUC of FOXO3a predicting colon cancer was 0.812, the sensitivity was 88.60%, and the specificity was 67.70%. The AUC of the two combined predicting colon cancer was 0.859, the sensitivity was 89.50%, and the specificity was 92.30%. Compared with FOXO3a single detection, the predictive value of combined detection of DNMT1 and FOXO3a were higher ( Z=1.982, P=0.047). Conclusion:The level of DNMT1 in the serum of patients with colon cancer is increased, while the level of FOXO3a is decreased. There is a negative correlation between them in the serum of patients with colon cancer. The combined detection of the DNMT1 and FOXO3a can effectively improve the diagnostic value of colon cancer.

Dental Cement Preparation of Zinc Oxide Eugenol-Ethoxy Benzoic Acid (ZOE-EBA) with Addition of Filler Aluminum Oxide (Al2 O3 )

@#Introduction: The quality of Zinc Oxide Eugenol-Ethoxy Benzoic Acid (ZOE-EBA) dental cement could be improved by the addition of Aluminum Oxide (Al2 O3 ). It was caused by the characteristic of alumina which are easy on fabrication process, resistant on corrosion, endurance usage, bioinert, and biocompatible. The purpose of this study was to determine the effect of the addition of Al2 O3 in ZOE-EBA cement. Methods: Nanoparticle of ZnO (zinc oxide), Al2 O3 , MgO (magnesium oxide),eugenol liquid and EBA (Ethoxy Benzoic Acid) fluid. The variations of Al2 O3 were 24%, 26%, 28%, 30%. First is the sintering on 1000°C and tested by XRD. Sintered powder was mixed with liquid, with a ratio of powder: liquid 7:1. The mechanical characteristic are compressive strength and hardness. Results: XRD test is showed that ZnO has dominant phase on the sample and there was new phase on cement powder such as Zinc-Aluminium oxide (ZnAl2 O4 ). The best result was shown on the addition of 26% of Al2 O3 composition in the 3 type test because the sample had ZnAl2 O4 phase volume fewer than 28% and 30% of Al2 O3 . This result was supported by the compressive strength and hardness which showed the optimum value at concentrations of 26%, which were 64.49 MPa and hardness of 69.33 VHN. Conclusion: Based on the result, it was found that Al2 O3 variation gives the best results in the teeth ZOE-EBA cement was 26%.

Effect of Arsenic Trioxide Combined with Dihydroartemisinin on THP-1 Cells Proliferation and Apoptosis / 中国实验方剂学杂志

Objective:To investigate the effects of arsenic trioxide combined with dihydroartemisinin on proliferation, cell cycle, and apoptosis of THP-1 cells, and explore the mechanism. Method:The thiazolyl blue （MTT） method was applied to detect the effect of different concentrations of arsenic trioxide, dihydroartemisinin and arsenic trioxide combined with dihydroartemisinin on the proliferation of THP-1 cells. Annexin V/propidium iodide（PI）assay was used to detect the change of THP-1 cell cycle and apoptosis．Western blot was performed to assess the expression of cysteine protease-3（Caspase-3）, cleaved Caspase-3, B-lymphocytoma-2（Bcl-2） and Bcl-2 associated X protein （Bax）. The changes of cell morphology were observed under high intension microscope. Result:Compared with blank group, arsenic trioxide and dihydroartemisinin both exhibited obvious antiproliferative effect on the human acute monocytic leukemia cell line THP-1 in time-dose dependence （P<0.01）. After 48 h, compared with the same dose of arsenic trioxide or that of dihydroartemisinin alone, the inhibition effect of 1 µmol·L-1 arsenic trioxide combined with 2 µmol·L-1 dihydroartemisinin on proliferation of THP-1 cells was significantly stronger （P<0.01）. Compared with the control group, arsenic trioxide combined with dihydroartemisinin significantly arrested the cells in G1 phase （P<0.01）, induced the downregulation of Caspase-3 and Bcl-2 （P<0.01） and upregulation of cleaved Caspase-3 significantly（P<0.05）. Conclusion:Arsenic trioxide combined with dihydroartemisinin can significantly inhibit the proliferation and induce apoptosis of THP-1 cells. The possible mechanism may be related to arrest the cells in G1 phase, reduce the expression of Caspase-3 and Bcl-2, increase the expression of cleaved Caspase-3.

Preparation and in vitro evaluation of redox-responsive silica-loaded arsenic trioxide nano-drug delivery system / 中草药

Objective: The redox-responsive drug delivery system of MSN-SS-PEG@As2O3 was constructed based on mesoporous silica nanoparticle (MSN), which was modified by both redox-sensitive disulfide bonds and non-toxic, non-immunogenic polyglycols (PEG), and loaded the arsenic trioxide (As2O3) by electrostatic adsorption and evaluated in vitro. Methods: Silica was synthesized by coprecipitation method. The redox-responsive carrier (MSN-SS-PEG) was synthesized on the basis of silica, (3-mercaptopropyl) trimethoxysilane, 2-(2-pyridyldithio) ethylamine hydrochloride and methoxy terminated PEG. The particle size and Zeta potential of MSN-SS-PEG were measured by Malvern particle size analyzer; The structure of the carrier was verified by infrared spectroscopy; The morphology and physical and chemical properties of the carrier were investigated by transmission electron microscopy (TEM) and small angle powder diffraction; The drug loading efficiency of MSN-SS-NH2@As2O3 and MSN-SS-PEG@As2O3 were investigated by inductively coupled plasma emission spectrum (ICP). The drug loading was further verified by thermogravimetry (TGA). In vitro release characteristics of the drug delivery system under different pH conditions were investigated by dialysis bag method. MTT assay was used to investigate the toxicity of carrier and delivery system to human normal hepatocytes (L02) or human hepatocarcinoma (HepG2) cells. Results: The potential of MSN, MSN-SS-NH2, MSN-SS-PEG was (-13.40 ± 0.87), (31.63 ± 0.90), (27.70 ± 5.60) mV, respectively. The final potential of modified carrier was positive. The particle size of MSN-SS-PEG was (159.60 ± 3.10) nm. The results of TEM showed that MSN, MSN-SS-NH2 and MSN-SS-PEG were all round or quasi round; The drug loading of MSN-SS-PEG@As2O3 was 4.38%, which measured by ICP; The release in vitro showed that MSN-SS-PEG@As2O3 was redox sensitive response. Compared with L02 cells, HepG2 cells were more sensitive to the toxicity of the carrier, and with the increase of the carrier concentration, the cell survival rate of MSN-SS-PEG was higher than that of MSN-SS-NH2, suggesting that PEG modification can further reduce the cytotoxicity of the carrier and improve the biocompatibility of the carrier. In addition, MTT results showed that the inhibitory effect of MSN-SS-PEG@As2O3 on HepG2 cell was significantly higher than that of other groups. Conclusion: The carrier prepared in this paper had a round and uniform particle size. The modified silica can release under the special microenvironment of the tumor and increase the accumulation of the drug in the tumor site. The delivery system has a good application in tumor therapy as a tumor micro-environment responsive carrier.

Effect of SiO2 and Al2 O3 nanoparticles on wear resistance of PMMA acrylic denture teeth / Efeito das nanopartículas de SiO2 e Al2 O3 na resistência ao desgaste de dentes em acrílico PMMA para prótese

Objetivo: Este estudo teve como objetivo avaliar a resistência ao desgaste de dentes em acrílico para próteses contendo nanopartículas de dióxido de silício (nano-SiO2 ) e dióxido de alumínio (nanoAl2 O3 ). Material e Métodos: O material em polimetilmetacrilato (PMMA) foi utilizado para fabricar 84 amostras (n=10) contendo nano-SiO2 e nano-Al2 O3 nas concentrações 0,1% em peso, 0,3% em peso e 0,5% em peso de pó acrílico. Uma máquina de teste de desgaste de dois corpos e um microscópio digital foram usados para medir as mudanças na perda de peso e rugosidade da superfície, respectivamente. Testes de ANOVA a um fator e testes de comparações múltiplas de Tukey foram utilizados para análise dos dados (α = 0,05). Resultados: O material modificado com nano-SiO2 demonstrou um aumento significativo na perda de peso em comparação com o material acrílico artificial convencional (p ˂ 0,05) enquanto o material modificado com nano-Al2 O3 demonstrou aumento não significativo na perda de peso, exceto no subgrupo 0,5% (p < 0,05). Não há diferenças significativas em relação à alteração da rugosidade após a simulação de desgaste entre todos os grupos testados (p > 0,05). Conclusão: As nanopartículas de nano-Al2 O3 exibem menos efeito negativo que o nanoSiO2 , podendo ser usado com cautela, se necessário. (AU)

Objective: This study aimed to evaluate the wear resistance of acrylic denture teeth containing silicon dioxide (nano-SiO2 ) and aluminum dioxide (nano-Al2 O3 ) nanoparticles. Material and Methods: Poly methyl methacrylate (PMMA) denture tooth material was used to denture tooth material was used to fabricate 84 specimens (n=10) containing nano-SiO2 and nano-Al2 O3 in concentrations 0.1wt%, 0.3wt%, and 0.5wt% of acrylic powder. A two-body wear testing machine and digital microscope were used to measure the changes in weight loss and surface roughness respectively. One-way ANOVA and pair-wise Tukey's post-hoc tests were used for data analysis (α = 0.05). Results: Nano-SiO2 modified teeth material demonstrated a significant increase in weight loss in comparison conventional artificial acrylic teeth material (p ˂ 0.05) while nanoAl2 O3 modified teeth material demonstrated non-significant increase in weight loss except for 0.5% subgroup (p ˂ 0.05). There is no significant differences regarding roughness change after wear simulation among all tested groups (p > 0.05). Conclusion: Nano-Al2 O3 nanoparticles exhibit less negative effect than nano-SiO2 so; it could be used with caution if necessary. (AU)