Mechanism of BCL2L2-PABPN1 expression induced by sodium arsenite and its metabolites in 16HBE cells / 中国职业医学

@#Objective - - （BCL2L2）- （ ） To investigate the differential expression of the fusion gene BCL 2 like protein 2 poly A （PABPN1） （ ） binding protein nuclear 1 induced by sodium arsenite SA and its methylated metabolites in 16HBE cells and the Methods ） ， related mechanism. i The 16HBE cells exposed to SA at concentrations of 1.5 3.0 and 4.5 µmol/L were set as -， - - low medium and high dose arsenic exposure groups. The 16HBE cells exposed to 4.5 µmol/L monomethylarsonic acid （ ）， （ ） ， MMA dimethylarsonic acid DMA and SA were set as MMA group DMA group and SA group. The 16HBE cells without ， BCL2L2-PABPN1 toxic stimulation were set as control group. After the cells were cultured for 48 hours the expression of was - （ - ） ） （ ） detected by quantitative real time polymerase chain reaction qRT PCR . ii Two small interfering RNA siRNA silencing 基金项目：国家自然科学基金（ ）； 年云南省科技厅昆明医科大学应用基础研究联合专项面上项目 82160607 2021 （ ） 202101AY070001-054 作者简介：施雅（ —），女，在读大学本科生，主要从事劳动卫生与环境卫生学研究；尹锦瑶（ —），女，在读劳动卫生与环境卫 2001 1995 生学硕士研究生，主要从事劳动卫生与环境卫生学研究；施雅和尹锦瑶为共同第一作者 通讯作者：何越峰教授，博士研究生导师，- ： E mail heyuefeng@kmmu.edu.cn中国职业医学 年 月第 卷第 期 ， ， ， · · 2022 10 49 5 Chin Occup Med October 2022 Vol.49 No.5 523 BCL2L2-PABPN1， - fragments were designed and transfected into 16HBE cells to knockdown which were set as siRNA 1 group - - BCL2L2-PABPN1 and siRNA 2 group. Non transfected control group without knockdown of transfection was set up. After ， BCL2L2-PABPN1 - culturing for 48 hours the expression level of in the three groups of cells was detected by qRT PCR. The cell - survival rate and early apoptosis rate were detected by MTS method and JC 1 mitochondrial membrane potential detection ， （ ） ， method respectively. The apoptosis was detected by Hoechest33342/propidium iodide PI double staining and the expression - Results ） level of P53 signaling pathway related proteins was detected by Western blotting. i The relative expression of BCL2L2-PABPN1 （P ） BCL2L2- in 16HBE cells increased with the increasing SA doses <0.01 . The relative expression of PABPN1 - ， - - in high dose arsenic exposure was higher than that in control group low dose and medium dose arsenic exposure （ P ） BCL2L2-PABPN1 ， groups all <0.05 . The relative expression of in SA group was higher than those in control group MMA （ P ） BCL2L2-PABPN1 group and DMA group all <0.05 . The relative expression of showed no significant difference between ， （ P ） ） BCL2L2-PABPN1 control group MMA group and DMA group all >0.05 . ii The relative expression levels of and cell - - - （ P ） survival rate in siRNA 1 group and siRNA 2 group were lower than those in non transfected control group all <0.05 . ， （P ） However there was no significant difference in the early apoptosis rate among the three groups >0.05 . The results of - Hoechest33342/PI double staining showed that the number of nuclear shrinkage and early apoptotic cells in siRNA 1 group and - - ， - siRNA 2 group was higher than that in non transfected control group. The relative protein expression levels of P53 phospho ， - - ， - - （ P ） p53 BCL 2 associated death promoter P21 and cytochrome C in siRNA 1 group and siRNA 2 group were higher all <0.05 , - - P and the relative protein expression levels of P53 up regulated modulator of apoptosis were lower (all <0.05), when compared - Conclusion with the non transfected control group. SA may block the apoptosis of 16HBE cells by inducing the expression of BCL2L2-PABPN1 fusion gene . The mechanism may be related to the activation of P53 signaling pathway. The SA methylated BCL2L2-PABPN1 BCL2L2-PABPN1 - metabolites MMD and DMA had no effect on the expression of . may affect anti apoptosis BCL2L2 PABPN1 through affecting the synergistic effect of and genes.

Dendrobium nobile Lindl. Alkaloids Inhibit the Malignant Biological Behavior of Cervical Cancer SiHa Cells / 中国生物化学与分子生物学报

Dendrobium nobile Lindl. alkaloids (DNLA) promote the apoptosis of breast cancer and colon cancer cells, but whether they affect the malignant biological behavior of cervical cancer cells is unknown. Herein we explored the effects and possible mechanisms of DNLA on the proliferation, apoptosis, migration and invasion of cervical cancer SiHa cells. SiHa cells were transfected with si-NC, siKCNQ1OT1, miR-NC, miR-487a-3p mimics, pcDNA-NC or pcDNA-KCNQ1OT1. Different doses (15, 30, 60 ng/mL) of DNLA were applied. The CCK-8 method was used to detect cell proliferation; Tran-swell was used to detect cell migration and invasion; flow cytometry was used to detect cell apoptosis; Western blotting was used to detect the expression of MMP2, MMP9 and Cleaved-Caspase-3 genes at the protein level; RT-qPCR was used to detect the expression of KCNQ1OT1 and miR-487a-3p. The dual luciferase reporter gene experiment verified the regulatory relationship between KCNQ1OT1 and miR-487a-3p. The results showed that different doses (15, 30, 60 ng/mL) of DNLA reduced the absorbance value, migration number, invasion number, the protein level of MMP2 and MMP9, reduced the expression of KCNQ1OT1, and increased the apoptosis rate, the abundance of Cleaved-Caspase-3 and the expression of miR-487a-3p (P<0. 05). Low expression of KCNQ1OT1 or high expression of miR-487a-3p reduced the absorbance value, migration number, invasion number, and the protein level of MMP2 and MMP9, but increased the apoptosis rate and the abundance of Cleaved-Caspase-3 (P<0. 05). KCNQ1OT1 negatively regulated the expression of miR-487a-3p. The effects of high expression of KCNQ1OT1 on the proliferation, apoptosis, migration and invasion of SiHa cells were opposite to that of low expression of KCNQ1OT1, and high expression of KCNQ1OT1 reduced the effects of 60 ng/mL DNLA on the proliferation, apoptosis, migration and invasion of SiHa cells. In summary, DNLA may reduce the proliferation, migration and invasion of cervical cancer SiHa cells and promote SiHa cell apoptosis by regulating the KCNQ1OT1/miR-487a-3p axis.

Expert consensus on marsupialization of cystic lesions of the jaw / 口腔疾病防治

@#Marsupialization is effective in the treatment of cystic lesions of the jaw. It is a simple operation that can result in minimal trauma, the reduction of postoperative recurrence, and maximum preservation of the surrounding tissue structure and function. However, there is a certain failure rate in clinical treatment due to the improper grasp of indications and nonstandard operation. The highest failure rate reported in the literature is 32.6%. To further standardize the clinical application of marsupialization and improve the success rate of treatment, we put forward an expert consensus of marsupialization in the treatment of jaw cystic lesions by reviewing the domestic and foreign literature and summarizing the experience in marsupialization from some famous domestic experts. In this consensus, we propose three elements of marsupialization: the establishment of the opening, the maintenance of cyst plugs and regular washing. The scope of application of marsupialization includes jaw cysts and cystic ameloblastomas. It is necessary to standardize the position of the opening, the size of the opening and the manufacture of the cyst plug, and a panoramic film or cone beam computed tomography(CBCT) should be used to observe the changes in the cystic cavity before and after operation. A second-stage operation should be performed when the lesion is significantly reduced by more than 50% or at least 5 mm from important structures; furthermore, the teeth of focus should be treated according to the relationship between the lesion and tooth and the type of tooth.

Prevention and treatment of osteoradionecrosis of the jaws / 口腔疾病防治

@#Radioactive jaw necrosis is a serious complication of head and neck radiotherapy. This complication's main characteristics are chronic necrosis and infection, and its clinical manifestations are local pain, mouth opening re'striction, speech disorder, dysphagia, exposure of dead bone, prolonged healing of facial and neck soft tissue fistula, and even pathological fracture, which brings great pain to the patient's body and mind. Radioactive jaw necrosis has become a clinical problem in the field of medicine, specifically for maxillofacial surgery of the external head and neck. The pathogenesis of radiation-induced jaw necrosis is still unclear, but high radiotherapy dose, extraction of teeth after radio-therapy and surgical trauma are recognized as high-risk factors. The diagnosis of radiation-induced jaw necrosis needs to be combined with the patient's radiotherapy history, clinical symptoms and imaging examination. Conservative or sur-gical treatment should be selected according to its clinical classification and stages, and the prevention of radiation-in- duced jaw necrosis should be emphasized. The key points are to remove dental caries, residual roots and crowns before radiotherapy; improve radiotherapy technology; and take preventive measures against high-risk factors. In recent years, the diagnosis and treatment of radiation-induced jaw necrosis has gradually become standardized and individualized.This article reviews the progress of treatment and research on radiation-induced jaw necrosis at home and abroad in terms of its definition, etiology, risk factors, diagnosis, treatment and prevention to provide reference for clinical treat-ment.

Relationship between PMP, FN, vWF and Bleeding Degree in Patients with Acute Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect the serum levels of platelet microparticle (PMP), fibronectin (FN), and von Willebrand Factor (vWF) in acute leukemia (AL) patients with thrombocytopenic and to analyze the relationship of the serum levels of PMP, FN and vWF with bleeding degree.</p><p><b>METHODS</b>One hundred and one newly diagnosed AL patients from May 2014 to May 2017 were enrolled the AL group. According to the WHO standard of bleeding stratification, 101 AL patients were divided into 5 sub groups: 0, 1, 2, 3 and 4 score groups; 52 normal persons subjected to physical examination were enrolled in control group. The PMP level was detected by flow cytometry; the FN and vWF levels were detected by ELISA. The levels of PMP, FN and vWF were compared between the AL group and the control group. The serum levels of PMP, FN and vWF were compared according to bleeding degree group. The relationship of bleeding degree with the serum levels of PMP, FN and vWF was analyzed.</p><p><b>RESULTS</b>The patients with newly diagnosed acute leukemia aged 18 to 60, and accounted for 61.39%. The degree of bleeding was mainly 1 score, which accounted for 38.61%. The serum levels of PMP, vWF and FN AL groups were significantly higher than those in control group (6.06%±4.38% vs 0.89%±0.50%, 205.82±24.89 vs 58.04±13.35 µg/L, 398.29±46.93 vs 311.37±26.02 µg/L)(P<0.001). The serum levels of PMP, FN and vWF were different among 5 subgroup (P<0.01); the level of PMP and FN were the highest in 0 score group and the lowest in 4 score group; the vWF level was the highest in 4 score groups and the lowest in 0 score group. The bleeding degree in the patients with acute leukemia negatively correlated with PMP level, and positively with NF and vWF levels (r=-0.753, r=0.648, r=0.805).</p><p><b>CONCLUSION</b>According to the relationship of the bleeding degree with serum levels of PMP, FN, vWF in patients, the detection of PMP, vWF and FN levels can help to evaluale the bleeding degree in the patients.</p>

Study on the Hepatoprotective Effects of Hugan Tablets Based on Serum and Liver Metabonomics / 中国药房

OBJECTIVE:To elucidate the efficacy and mechanism of Hugan tablets in hepatoprotective effects from perspective of metabolic pathways. METHODS:36 male rats were randomly divided into normal group (0.5%sodium carboxymethyl cellu-lose),model group(0.5%sodium carboxymethyl cellulose)and Hugan tablets group(1.7 g/kg),12 in each group,intragastrically administrated once a day,for 9 d. After 1 h of last administration,rats in model group and Hugan tablets group were intraperitone-ally injected 50%CCl4 peanut oil solution 1 mL/kg to induce liver injury. After 24 h of modeling,malondialdehyde(MDA),super-oxide dismutase(SOD),glutathione peroxidase(GSH-Px)levels in liver tissue of rats were detected. Nuclear magnetic resonance spectroscopy(1H-NMR)metabolomics technique was adopted to establish the serum and liver metabolite profiles of rats,and the ef-fects of Hugan tablets on changes of metabolic profile and potential biomarkers in serum and liver of rats with CCl4-induced acute liver injury were analyzed. RESULTS:Compared with normal group,MDA level in liver tissue of rats in model group was signifi-cantly increased(P<0.05),SOD and GSH-Px levels were significantly reduced(P<0.05). Both body physiology and material me-tabolism of rats were obviously changed,and levels of 11 metabolic potential biomarkers in serum and 14 metabolic potential bio-markers in liver were significantly increased/decreased (P<0.05). Compared with model group,MDA level in liver tissue in Hugan tablets group was significantly reduced(P<0.05),SOD and GSH-Px levels were significantly increased(P<0.05). Serum and liver metabolism tended to be normal,6 metabolic potential biomarkers(isoleucine,leucine,3-hydroxybutyrate,acetone,ace-toacetate,choline) in serum and 8 metabolic potential biomarkers (3-hydroxybutyrate,alanine,glutamate,pyruvate,succinate, choline,lactate,glucose)in liver got significant callback(P<0.05). CONCLUSIONS:The hepatoprotective mechanism of Hugan tablets may be associated with antioxidative stress and regula-tion of lipid metabolism,glucose metabolism and amino acid metabolism.

Metabonomic analysis of Hugan Tablets on CCl4-induced acute hepatic injury in rats based on 1 H-NMR / 中国药理学通报

Aim To identify the potential biomarkers associated with carbon tetrachloride(CCl 4 )-induced a-cute hepatic injury in rats and explore the therapeutic effect of Hugan Tablets(HGT). Methods The model was established by intraperitoneal injection of CCl4 in oil(1 : 1,V/ V)with a dosage of 1 mL·kg - 1 body weight to rats once. The levels of aspartate aminotrans-ferase(AST),alanine aminotransferase(ALT),alka-line phosphatase (ALP ) and lactate dehydrogenase (LDH)in serum of rats were determined. Moreover,a proton nuclear magnetic resonance (1 H-NMR)based metabonomic approach in combination with multivariate data analysis was applied to demonstrate CCl4-induced acute hepatic injury metabolic perturbations in rat urine and feces and identify the corresponding metabolic bio-markers. The intervention effect of HGT was evaluated based on the changes of metabolic phenotype and po-tential biomarkers related to acute hepatic injury. Re-sults The levels of AST,ALT,ALP and LDH in ser-um of rats with acute hepatic injury were significantly reduced by administration of HGT,respectively. The disturbed metabolic state associated with CCl4-induced acute hepatic injury in rat urine and feces could be re-stored by HGT. Meanwhile,five potential biomarkers (2-oxoglutarate,citrate,creatinine,trimethylamine N-oxide,hippurate)in rat urine and three potential bio-markers(butyrate,glucose,uracil)in rat feces related to acute hepatic injury were reversed by administration of HGT,respectively. Conclusion HGT exerts pro-tective effects against CCl4-induced acute hepatic inju-ry in rats,which is probably mediated by regulation of tricarboxylic acid cycle and gut microbiota metabolism.

Intervention effects of Jiaotai pills on PCPA-induced insomnia in rats / 中国中药杂志

To elucidate the intervention effects of Jiaotai pills(JTP) on p-chlorophenylalanine (PCPA)-induced insomnia in rats and its underlying mechanism, the insomnia model was established by single intraperitoneal injection with PCPA in rats. The locomotor activity of rats was observed, and the levels of nerve growth factor(NGF) in hypothalamus, hippocampus, prefrontal cortex and serum of rats were determined by using ELISA. Moreover, a proton nuclear magnetic resonance(¹H-NMR)-based metabonomic approach was developed to profile insomnia-related metabolites in rat serum and hippocampus and analyze the intervention effects of JTP on changes in underlying biomarkers related to locomotor activity, NGF and insomnia. According to the results, JTP could significantly suppress the locomotor activity of insomnia rats, and increase the NGF levels in hypothalamus, hippocampus, prefrontal cortex and serum of rats with insomnia. The disturbed metabolic state associated with PCPA-induced insomnia in rat serum and hippocampus could be intervened by JTP. Meanwhile, six and five potential biomarkers related to insomnia in rat serum and hippocampus were reversed by administration of JTP. In conclusion, the current study demonstrated that JTP had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of NGF level and metabolism of amino acids, lipids and choline.