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1.
Acta Pharmaceutica Sinica ; (12): 343-352, 2022.
Article in Chinese | WPRIM | ID: wpr-922910

ABSTRACT

Colorectal cancer (CRC) is a common malignancy burdening people globally, with increasing morbidity and mortality nowadays, due to the alternation in the diet type and lifestyle in modern society. Berberine, a type of benzylisoquinoline alkaloid, is widely present in numerous medicinal plants, particularly including Coptidis Rhizoma. Mounting evidence reveals that berberine possesses an array of pharmacological effects, such as anti-inflammation, anti-bacterium, anti-cancer, anti-diabetes mellitus and so on. In particular, berberine exhibits substantial inhibition on various types of cancers including CRC. Hereby, we sought to systematically review the suppressive effect of berberine on CRC through the diminishment of the proliferation and metastasis, induction of apoptosis, arrest of cell cycle, regulation of inflammatory reaction, the reverse of chemotherapeutic resistance and restoration of gut microbiota in CRC, so as to shed light on the in-depth mechanisms underlying the treatment of CRC with berberine in the clinical setting.

2.
Clinical Medicine of China ; (12): 7-11, 2021.
Article in Chinese | WPRIM | ID: wpr-884130

ABSTRACT

Objective:To analyze the clinical characteristics and risk factors of clopidogrel resistance after intracranial arterial stent implantation in patients with ischemic cerebrovascular disease.Methods:Retrospective case-control study was used.A total of 360 patients with ischemic cerebrovascular disease hospitalized in Beijing Tiantan Hospital from January 2017 to December 2018 were selected.All patients received intracranial arterial stenting and received double anti-platelet drugs after operation.Patients were divided into clopidogrel resistance group and non-resistance group according to the inhibition rate of platelet aggregation measured by thromboelastography.Clinical data and laboratory indicators of patients in the two groups were compared using two independent sample T tests and Mann-Whitney U tests, and possible risk factors of clopidogrel resistance were analyzed by Logistic regression.Results:White blood cell (WBC) count, neutrophils count, lymphocyte count, cholesterol, LDL cholesterol, and serum homocysteine levels in the clopidogrel non-resistant group were (6.58±1.45)×10 9/L, (4.01±1.05)×10 9/L, 1.83(1.49, 2.23)×10 9/L, (3.63±0.85) mmol/L, 1.93(1.53, 2.31) mmol/L, and 14.3(11.80, 17.00) μmol/L, respectively.Compared with the clopidogrel non-resistant group, the WBC count, neutrophils count, lymphocyte count, cholesterol, LDL cholesterol and serum homocysteine levels in the clopidogrel resistant group were all higher (7.19±1.53) ×10 9/L, (4.40±1.05) ×10 9/L, 2.03(1.63, 2.58)×10 9/L, (4.02±0.99) mmol/L, 2.04(1.68, 2.78) mmol/L and 15.90(12.25, 22.20) μmol/L, respectively.The difference was statistically significant ( t=3.277, t=2.867, Z=2.457, t=3.409, Z=2.705 and Z=2.220, respectively; P value were 0.001, 0.004, 0.014, 0.001, 0.007 and 0.026, respectively). Logistic regression analysis showed that high serum homocysteine ( OR=1.031, 95% CI 1.006-1.057, P=0.015) was an independent risk factor for clopidogrel resistance. Conclusion:Patients with clopidogrel resistance have high leucocyte, blood lipid, homocysteine and other clinical characteristics.High serum homocysteine is an independent risk factor for clopidogrel resistance.

3.
Article in Chinese | WPRIM | ID: wpr-882583

ABSTRACT

Objective:To explore important signaling pathways and effects on neurovascular unit of Buyang-Huanwu Decoction in the treatment of ischemic stroke. Methods:Used TCMSP database, Chinese Medicine and Chemical Composition Database of Shanghai institute of Organic Chemistry and searched related literature to obtain and screen the active compounds and their targets of Buyang-Huanwu Decoction. DrugBank database, OMIM database, TTD database and GeneCards database were used to obtain targets of ischemic stroke. Metascape database was used to carry out KEGG pathway enrichment analysis on therapeutic targets. AlzData database was used to analyze the gene expression of therapeutic targets in different cells. Results:Through network analysis, the key targets of Buyang-Huanwu Decoction in the treatment of ischemic stroke were obtained, including PTGS2, PTGS1, CHRM1, ADRB2, CHRM2, F10, F7, HIF1A, PDE3A, ADRA1B and CHRM3, etc. Through enrichment analysis, multiple key signaling pathways of Buyang-Huanwu Decoction in the treatment of ischemic stroke were obtained, including PI3K-Akt signaling pathway, calcium signaling pathway, IL-17 signaling pathway, platelet activation, Apelin signaling pathway, NF-κB signaling pathway, AMPK signaling pathway and arachidonic acid metabolism, etc. Through gene expression analysis, the effect of Buyang-Huanwu Decoction on different cells was analyzed, and it was found that the targets regulate a variety of biological processes, cellular components and molecular functions in endothelial, astrocytes, microglia, oligodendrocytes, oligodendrocyte precursor cells (OPCs) and neurons. Conclusion:Buyang-Huanwu Decoction is characterized by multiple components, multiple targets, multiple pathways and complex connections in the treatment of ischemic stroke, and its effect is closely related to neurovascular units (NVU) at the cellular expression level of genes, and the mechanism of therapeutic effect included neuroprotection, neurogenesis, antithrombotic, vascular regeneration, glial cell regulation, etc.

4.
Article in Chinese | WPRIM | ID: wpr-882557

ABSTRACT

Objective:To study the effect of Huanglian-Jiedu Decoction on the white matter lesion of rats with focal cerebral ischemia and to explore the regulative role of the active fraction of Huanglian-Jiedu Decoction on NogoA/NgR. Methods:Male SD rats were randomly divided into sham operation group, model group, total alkaloid group, total flavonoid group, and total iridoid group. Except for the sham operation group, the rats in the other groups were used to establish the middle cerebral artery occlusion rat model by the suture method. 2 hours after modeling, rats in the total alkaloid group were given intragastric administration with 44 mg/kg total alkaloids; rats in the total flavonoid group were given intragastric administration 50 mg/kg total flavonoids; rats in the total iridoid group were given intragastric administration 80 mg/kg total iridoids, the sham operation group and the model group were intragastrically given equal volume of normal saline, once a day, for 7 consecutive days. The pathological changes of rat white matter were observed by HE staining, the pathological changes of rat myelin sheath were observed by Luxol fast blue (LFB) staining, and the expression of Amyloid precursor protein (APP), NogoA, and NgR in the internal and external capsule areas of the brain was detected by immunohistochemical staining. Real-time fluorescence quantitative PCR was used to detect the expression of NogoA and NgR in the tissues surrounding the ischemic infarct.Results:Compared with the model group, the total alkaloid group, total flavonoid group, and total iridoid group had lower pathological damage scores in the internal and external capsule areas of rats ( P<0.05 or P<0.01), increased integral optical density value of LFB staining ( P<0.01), decreased expression of APP and NogoA; the expression of NgR in the internal and external capsules of rats in the total alkaloid group and the total iridoid group decreased ( P<0.05 or P<0.01), and the expression of NgR in the inner capsule of rats in the total flavonoid group decreased ( P<0.01); the expression of NogoA (1.20 ± 0.17, 1.55 ± 0.30, 1.19 ± 0.38 vs. 2.22 ± 0.58) and NgR (1.98 ± 0.55, 1.48 ± 0.31, 1.58 ± 0.27 vs. 3.36 ± 0.41) genes in the tissues around the infarct focus of rats in the total alkaloid group, total flavonoid group and total iridoid group decreased ( P<0.01). Conclusion:The present study investigates the therapeutic effects of Huanglian-Jiedu Decoction, promoting white matter repair by decreasing the overexpression of NogoA and NgR in an experimental animal model of stroke.

5.
Journal of Medical Biomechanics ; (6): E596-E603, 2021.
Article in Chinese | WPRIM | ID: wpr-904443

ABSTRACT

Objective To establish a blast injury experimental model using a shock tube at lateral lying position of C57BL/6 mice, investigate biomechanical responses of macrophages/microglia cells in the heart, lung and brain tissues to mechanical damage by shock wave within 24 hours. Methods Shock tube was employed to generate a shock wave to C57BL/6 mice. Firstly, the weight changes of mice were measured at different time points after the shock. Then the cardiac, pulmonary and whole brain tissue samples were dissected after anesthesia. Pathological sections were stained with HE staining to detect structural damage; the TUNEL staining method was used to mark and count the proportion of dead cells in each tissue. Microglial cells were labeled with fluorescent antibody, while responses and changes of macrophages/microglia after shock loading were analyzed. Results The shock tube exerted 179 kPa overpressure shock wave upon sideway of the mouse, and lethal rate of the mouse was 3.33%. Compared with normal control group, the mice in experimental group had a significant weight loss within 24 hours after loading shock. Pathological sections showed rupture of lung tissues after shock, accompanied by alveolar protein deposition, pulmonary bulla and other diseases. Fluorescence staining showed that lung tissue was recruited and activated in a large amount within 24 hours. The proportion of dead cells cleared rebounded to normal level within 24 hours. The heart was highly tolerant to shock, and macrophages appeared near the large blood vessels. The brain showed unilateral aggregation of microglia due to the impact posture, mainly due to prolonged inflammation and a higher proportion of dead cells at the junction of gray and white matter. Conclusions A blast shock model at lateral lying position of the mouse was established. Within 24 hours, macrophages/microglia were recruited quickly to the injury site after being impacted, which mediated strong immune stress, and might participate in the immune response to trigger a second long-term inflammatory injury. The results of the study provide experimental basis for the evaluation of primary impact injury, such as dose-effect relationship and tissue damage difference.

6.
Article in Chinese | WPRIM | ID: wpr-879454

ABSTRACT

OBJECTIVE@#To compare clinical effects of different postoperative rehabilitation modes on lumbar degenerative diseases, and explore influence of rehabilitation mode and other factors on postoperative effect.@*METHODS@#From June 2013 to July 2016, totally 900 patients were admitted from nine tertiary hospitals in Beijing to perform single segment bone grafting and internal fixation due to lumbar degenerative diseases were prospectively analyzed. There were 428 males and 472 females, the age of patient over 18 years old, with an average of (51.42±12.41) years old;according to patients' subjective wishes and actual residence conditions, all patients were divided into three groups, named as observation group 1 (performed integrated rehabilitation approach and orthopedic treatment model intervention), observation group 2 (performed integrated rehabilitation approach and orthopedic treatment, classified rehabilitation model intervention), and control group(performed routine rehabilitation model intervention). Visual analogue scale(VAS), Oswestry Disability Index(ODI) and Japanese Orthopaedic Association (JOA) were used to evaluate postoperative efficacy among three groups at 24 weeks. Possible factors affecting the postoperative efficacy including age, age grouping, gender, body mass index (BMI), BMI grouping, education level, visiting hospital, payment method of medical expenses, preoperative complications, preoperative JOA score, clinical diagnosis, surgery section, operative method, intraoperative bleeding volume, postoperative complications and rehabilitation mode were listed as independent variables, and postoperative ODI score at 24 weeks as dependent variables. Univariate analysis was used to analyze relationship between influencing factors and postoperative efficacy. Multiple linear regression was used to analyze relationship between influencing factors, rehabilitation mode and postoperative ODI score at 24 weeks, in further to find out the main reasons which affect postoperative efficacy, and to analyze impact of rehabilitation mode on postoperative efficacy.@*RESULTS@#All patients were followed up for 24 weeks after operation. All incisions healed at stage I with stable internal fixation. (1)Evaluation of postoperative efficacy:① There were no statistical differences in preoperative VAS and ODI among three groups(@*CONCLUSION@#Preoperative JOA score, gender, age could predict postoperative clinical effects of lumbar degenerative diseases in varying degrees treated with single level bone graft fusion and internal fixation. Different rehabilitation modes could improve clinical effects. Intergrated rehabilitation orthopedic treatment model and integrated rehabilitation approach and orthopedic treatment with classifiedrehabilitation model are superior to conventional rehabilitation model in improving patients' postoperative function and relieving pain, which is worthy of promoting in clinical.


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Infant , Lumbar Vertebrae/surgery , Lumbosacral Region , Male , Middle Aged , Retrospective Studies , Spinal Fusion , Treatment Outcome
7.
Article in Chinese | WPRIM | ID: wpr-911314

ABSTRACT

Objective:To evaluate the efficacy of left heart attracting pressure monitoring technology applied in cardiopulmonary bypass (CPB) in cardiac surgery.Methods:Eighty patients of both sexes, aged 40-64 yr, weighing 50-80 kg, of American Society of Anesthesiologists physical status Ⅱ-Ⅳ, with New York Heart Association grade Ⅱ or Ⅲ, with left ventricular ejection fraction≥40%, undergoing elective cardiac valve replacement, were divided into 2 groups using a random number table method: traditional left heart aspiration group (T group) and modified left heart aspiration group (M group), with 40 patients in each group.The rotation speed of left ventricular suction pump was adjusted according to left ventricular suction volume and surgical field clarity in group T and by monitoring the pressure in the left suction tube in real time in group M. After aspiration returned to normal aspiration, blood of the left heart returned after aspiration was collected to determine the concentration of free hemoglobin.The number of adjustments after left ventricular aspiration, intraoperative hemoglobinuria, and occurrence of tissue sediment in the aspiration tube after operation were recorded.Results:Compared with T group, the concentration of free hemoglobin, incidence of intraoperative hemoglobinuria and incidence of tissue sediment in the aspiration tube after operation were significantly decreased, and the number of adjustments after left ventricular aspiration was decreased in M group ( P<0.05). Conclusion:Left heart attracting pressure monitoring technology can be safely and effectively applied in CPB in cardiac surgery.

8.
Article in Chinese | WPRIM | ID: wpr-911223

ABSTRACT

Objective:To evaluate the effect of mild hypothermia on inositol requiring enzyme 1-X-box binding protein 1 (IRE1-XBP1) signaling pathway in endoplasmic reticulum in cortex in a rat model of focal cerebral ischemia-reperfusion (I/R).Methods:Fifty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-230 g, were divided into 3 groups ( n=18 each) using a random number table method: sham operation group (group S), cerebral I/R group (group I) and mild hypothermia group (group T). Cerebral I/R was induced by inserting a nylon thread with rounded tip into the internal carotid artery which was occluded for 2 h and then released for reperfusion.The surface cooling was started immediately after reperfusion, and the rectal temperature was maintained at 32-34 ℃ for 3 h in group T. Blood vessels were only exposed, without occlusion in group S. The neurologic deficit was assessed and scored at 24 h of reperfusion.The animals were then sacrificed and the ischemic area of the cerebral cortex was removed for examination of the ultrastructure of the cells (with a transmission electron microscope), for determination of nerve cell apoptosis (using TUNEL), for detection of the expression of IRE1 and XBP1 (by Western blot) and for determination of the expression of IRE1 and XBP1 protein mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with group S, the neurologic deficit scores were significantly increased, nerve cell apoptosis in the ischemic area of the cerebral cortex was increased, the expression of IRE1, XBP1 protein and mRNA was up-regulated ( P<0.05), the neuronal nuclei was degenerated and swollen, the nuclear membrane was fragmented and defective, the chromatin was pyknotic and marginalized, and the endoplasmic reticulum was dilated and cisternal in group I and group T. Compared with group I, the neurologic deficit scores were significantly decreased, nerve cell apoptosis in the ischemic area of the cerebral cortex was decreased, the expression of IRE1, XBP1 protein and mRNA was up-regulated ( P<0.05), and the damage to the ultrastructure of nerve cells was reduced in group T. Conclusion:The mechanism by which mild hypothermia alleviates focal cerebral I/R injury is associated with further activation of neuronal IRE1-XBP1 signaling pathway and alleviation of endoplasmic reticulum stress response in rats.

9.
Article in Chinese | WPRIM | ID: wpr-909619

ABSTRACT

OBJECTIVE To investigate the pharmacological effect of ursolic acid (UA) on colitis-associated colorec?tal cancer (CAC) and its underlying mechanism based on the Wnt signaling pathway. METHODS The CAC model in mice was established by azoxymethane (AOM) combined and dextran sulfate sodium salt (DSS), accompanied by treat?ment with various dosages of UA and concomitant appraisal of body weight, stool and physical state of the mice. After the sacrifice of the mice, the tumor and length of the colorectum were measured, followed by retrieval of the liver, spleen, thymus and tumor tissue for downstream assays. The levels of inflammatory factors interleukin-6 (IL-6), IL-1βand C-reactive protein (CRP) in the tumor and serum were examined by enzyme-linked immunosorbent assay (ELISA). The pathological changes of colorectal tissues were observed by HE staining. The levels in tumors of Wnt/β-catenin sig?naling pathway-related proteins Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry (IHC). The mRNA expressions of Wnt4, GSK-3β,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, Bax, caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR (RT-qPCR). The protein levels of Wnt4, GSK-3β, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, phospho-β-catenin, phospho-GSK-3β, Bcl-2 and Bax in tumors were probed by analyzed by Western blotting (WB). Also, RNA-seq was employed to assess the gut microbiota in the mice. RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC, evidenced by improved physical state, body weight, survival rate, colorectal length, the mass of liver, thy?mus, spleen, and decreased CAC load and colorectal mass. UA attenuated the levels of IL-6, IL-1β and CRP in the mouse serum and colorectal tumor in a dose-dependent manner. HE staining showed that UA lessened carcinogenesis in the colorectum, with lower infiltration of lymphocytes, versus the control. IHC indicated that UA mitigated the expres?sion of Wnt4,β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and promoted the GSK-3βexpression, compared with the control. Furthermore, UA diminished the mRNA expressions of Wnt4, β-catenin, TCF4, LEF1, c-Myc, cyclin D1, Bcl-2, and heightened the mRNA levels of GSK-3β, caspase-3, capase-9 and Bax in CAC. The results of mRNA expressions were verified by WB analysis, which revealed that UA impeded the protein expression of Wnt4,β-catenin, c-Myc, cyclin D1, Bcl-2, TCF4, LEF1, and elevated the protein levels of GSK-3βand Bax, phospho-β-catenin in mouse CAC. In addi?tion, UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC. CONCLU?SION Ursolic acid may protect against CAC, potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.

10.
Article in Chinese | WPRIM | ID: wpr-909613

ABSTRACT

OBJECTIVE To investigate the effect of scutellarin on the apoptosis of human colorectal cancer cells via the Hippo signaling pathway in vitro. METHODS MTT colorimetric method was used to detect the influence of scutellar?in on the survival rate of HCT116 cells. And the effect of scutellarin at various concentrations on cell morphology was observed by microscopy. Cell scratch experiment was used to detect the influence of scutellarin on the migration of HCT116 cells. Hoechst33342/PI double staining method was used to detect the effect of scutellarin on the apoptosis of HCT116 cells. Western blotting method was used to assess the action of scutellarin on the expressions of Hippo signal?ing pathway-related proteins Mst1, Lats1, YAP1, p-YAP(Ser127), TAZ, and its downstream effector proteins c-Myc and cyclin D1, as well as apoptosis-related proteins Bcl-2 and Bax in HCT116 cells. RESULTS Scutellarin significantly affected the morphology of HCT116 cells and reduced the survival rate of HCT116 cells. Hoechst33342/PI double stain?ing showed that scutellarin effectively induced the apoptosis of HCT116 cells. Western blotting analysis showed that the expression levels of Hippo signaling pathway-related proteins Mst1, Lats1, YAP1, TAZ and its downstream effector pro?teins c-Myc, cyclin D1 were down-regulated in a concentration-dependent manner by scutellarin, and the expression of p-YAP (ser127) was up-regulated. Moreover, scutellarin substantially lessened the expression level of apoptosis-related protein Bcl-2, and promoted the protein level of Bax. CONCLUSION Scutellarin may inhibit the proliferation and migra?tion of HCT116 cells, while induce its apoptosis, potentially by activation of Hippo signaling pathway.

11.
Article in Chinese | WPRIM | ID: wpr-909607

ABSTRACT

OBJECTIVE To investigate the inhibition and mechanism of berberine on human colorectal cancer HCT116 cells through canonical Hedgehog signaling pathway. METHODS The effect of berberine on cell morphology was observed by microscopy. MTT colorimetric assay, cell scratch experiment, colony formation assay and Hoechest/PI staining were utilized to detect the activities of berberine on cell viability, cell migration and cell apoptosis. Flow cytome?try was applied to examine the cell apoptosis. The effects of berberine on caspase-3 and caspase-9 were detected by caspase activity detection kit. The expressions of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related proteins Bax and Bcl-2 as well as cell cycle-related proteins cyclin D1 were detected by Western blotting. Additionally, quantitative real time RT-PCR was employed to assess the mRNA expression levels of Hedgehog signaling pathway-related genes SHH, GLI1, PTCH1, SMO, SUFU, apoptosis-related genes Bax and Bcl-2 as well as cell cycle-related genes cyclin D1. RESULTS Berberine sharply altered the morphology of human colorectal cancer HCT116 cells, demonstrated by that migration ability of HCT116 cells was reduced significantly and the nuclei were densely stained. Berberine could induce apoptosis in a dose-dependent manner. The activities of caspase-3 and caspase-9 were increased prominently. The expression levels of Hedgehog signaling pathway-related protein SUFU and apoptosis-related protein Bax were augmented substantially. The expression levels of Hedgehog signaling pathway-related proteins SHH, GLI1, PTCH1, SMO, apoptosis-related protein Bcl-2 as well as cell cycle-related genes cyclin D1 were markedly lessened. Besides, the mRNA expression levels of Hedgehog signaling pathway-related gene SUFU and apoptosis-related gene Bax were augmented substantially. The mRNA expression levels of Hedgehog signaling path?way-related genes SHH, GLI1, PTCH1, SMO, apoptosis-related gene Bcl-2 as well as cell cycle-related gene cyclin D1 were markedly lessened. CONCLUSION Berberine, which is the main component of coptidis rhizoma, can remarkably restrain the growth and proliferation, promote apoptosis of human colorectal cancer cells HCT116, and the underlying mechanism may be involved in suppressing the activity of the Hedgehog signaling pathway.

12.
Article in Chinese | WPRIM | ID: wpr-909606

ABSTRACT

Oleanolic acid (OA) is a pentacyclic triterpenoid chemical component that exists in natural plants with a molecular formula of C30H48O3 and a molecular weight at 456.71 g·mol-1. OA is widespread in traditional Chinese herbal medicine (Ligustri Lucidi Fructus, Achyranthis Bidentate Radix, Red Sage) and berries (blueberries, grapes). In recent years, because of the extensive pharmacological effects of OA, its advantages in disease treatment have become increasingly prominent and gradually attracted the attention of pharmaceutical researchers. OA has effective therapeutic effects on a series of chronic diseases such as inflammation, cancer, diabetes, and cardiovascular diseases through mul?tiple signaling pathways and various targets. Especially in cancers, such as colorectal cancer, liver cancer, gastric cancer, lung cancer, breast cancer and other malignancies, OA presents substantial efficacy. However, its poor aqueous solubility, needy bioavailability, and unsatisfactory pharmacological activity excessively restrict its clinical application. More impor?tantly, the improper utilization of OA can cause adverse reactions, toxic effects and even damage to organs in some spe?cific situations. With the discovery of various pharmacological effects, the complex action mechanisms of OA, the contin?uous progress in structural modification of OA, as well as the synthesis of OA derivatives, its application is expand?ing gradually. Among numerous studies, there is a clear indication that OA and its derivatives, if fully developed, may provide an alternative and cheaper treatment for a variety of chronic diseases. However, the specific molecular mecha?nisms of OA and its derivatives as an alternative therapy and supplementary therapy for cancer, diabetes, cardiovascular disease and other chronic diseases remain to be clarified. Therefore, it is necessary to further study the pharmacokinet?ics, pharmacological activity, specific targets and related mechanisms of OA to lay a solid foundation for drug devel?opment and the application of OA in clinical settings.

13.
Article in Chinese | WPRIM | ID: wpr-909601

ABSTRACT

Pulsatilla chinensis is a widely used traditional Chinese herb, which contains 56 types of chemical constit?uents, mainly including triterpenoid saponins, organic acids, coumarins and lignans. The largest portion of the ingredi?ents in Pulsatilla chinensis is the family of triterpenoid saponins, in which anemoside B4 is the major effective compound and indexing component. The main components of Pulsatilla chinensis can metabolize into a vast array of active prod?ucts in vivo, which play vital roles in its biological activity. Mounting evidence reveals that Pulsatilla chinensis exerts a wide range of therapeutic activities, such as anti-cancer, immunoregulation, anti-inflammation and anti-schistosome, with fewer adverse reactions, via various signaling pathways and multiple targets. It was documented that the active ingre?dient of Pulsatilla chinensis can lessen the drug resistance and synergize the effects of other natural products includ?ing paclitaxel, as well as ameliorate the clinical efficacy of chemical drugs, such as adriamycin. However, Pulsatilla chi?nensis was also reported to be possibly the main cause of hemolysis and chronic liver injury. The efforts should be made to deeply investigate the pharmacological actions and underlying mechanisms of Pulsatilla chinensis, with a focus on the anti-cancer efficacy, and develop new drugs based on the components of Pulsatilla chinensis for future utilization in the clinical setting.

14.
Article in Chinese | WPRIM | ID: wpr-909590

ABSTRACT

OBJECTIVE To identify the inhibitory effect of ursolic acid on the colorectal cancer HCT116 cells in vitro and in vivo, and to explore the underlying mechanism. METHODS The smoothened (SMO) gene-silenced human colorectal cancer HCT116hSMO- cell line was established by transfection with the lentivirus carrying SMO shRNA. The cytotoxic effect of ursolic acid on HCT116hSMO-cells was determined by MTT assay. The effect of ursolic acid on the migration of HCT116hSMO- cells was studied by wound healing assay. The effect of ursolic acid on apoptosis of HCT116hSMO-cells was explored by Hoechst33342/PI double staining and flow cytometry. The effects of ursolic acid on the expressions of apoptotic marker gene Bcl-2, Bax, caspase-3 and caspase-9 were measured by real-time quantitative RT-PCR (RT-qPCR) and Western blotting (WB) analysis. RT-qPCR and WB were used to examine the relationship between GLI1, c-Myc expression and PI3K/Akt pathway to further investigate the mechanism of GLI1 activation in HCT116hSMO- cells. The effects of ursolic acid on the expressions of GLI1, p-Akt, Akt, c-Myc, SHH and SUFU of nonca?nonical Hedgehog pathway were evaluated by RT-qPCR and WB assays. Xenograft nude mouse model bearing HCT116hSMO- cells was established and intraperitoneally treated with ursolic acid to investigate the effect on tumor growth in vivo. The body weight and tumor size of mice were assessed regularly every 2 d. The effect of ursolic acid on the apoptosis of tumor tissue was determined by TUNEL assay. The expressions of Bcl-2, Bax, GLI1, p-Akt, Akt, c-Myc, SHH, SUFU mRNA and proteins were measured by RT-qPCR and WB. The levels of Bcl-2, Bax, GLI1, p-Akt, c-Myc and SHH proteins in tumor tissues were also evaluated by immunohistochemistry. RESULTS Ursolic acid significantly inhibited the growth and migration of HCT116hSMO-cells in vitro, compared with the control (P<0.05). Meanwhile, ursolic acid also induced apoptosis of HCT116hSMO- cells in vitro (P<0.05). Furthermore, SC79 (Akt activator) enhanced the expressions of p-Akt, GLI1 and c-Myc, which could be abolished by ursolic acid, and the effect was equal to Akt inhibitor LY294002. The expressions of Bcl-2, GLI1, p-Akt, c-Myc, SHH mRNA and proteins were reduced by ursolic acid, while the levels of Bax and SUFU were increased. Ursolic acid could inhibit the growth and induce the apoptosis of colorectal cancer xeno?graft in vivo. Similarly, lower levels of Bcl-2, GLI1, p-Akt, c-Myc and SHH, and higher expression of Bax and SUFU were noted in ursolic acid-treated mice. CONCLUSION Ursolic acid can inhibit the growth and induce apoptosis of HCT116hSMO- cells both in vitro and in vivo. And the mechanism is related to the suppression of PI3K/Akt-mediated noncanonical Hedgehog signaling pathway.

15.
Article in Chinese | WPRIM | ID: wpr-909587

ABSTRACT

OBJECTIVE To investigate the therapeutic effect of scutellarin on colitis-associated cancer (CAC) and its underlying mechanism based on Wnt/β-catenin signaling pathway. METHODS The mouse model of CAC was estab?lished by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by scutellarin treatment, with recording the body weight, diarrhea and hematochezia. After sacrificing the mice, the colorectal length and colorectal tumor were assessed. The levels of pro-inflammatory factors TNF-α and IL-6 in mice's sera were measured by the enzyme-linked immunosorbent assay (ELISA). The colorectal lesions were appraised by hematoxylin and eosin (H&E) staining. Theβ-catenin level in CAC tissues was probed by immunofluorescent analysis. The apoptosis-related genes Bax and Bcl-2, and Wnt signaling pathway-related genes β-catenin, GSK-3β, TCF4, c-Myc and cyclin D1 were detected by real-time quantitative RT-PCR (RT-qPCR). Finally, Western blotting analysis (WB) was employed to examine the expressions of the apoptosis and Wnt signaling pathway-related proteins. RESULTS Scutellarin significantly improved AOM/DSS-caused weight loss, colorectal length shortening, and tumor growth in mice (P<0.01). Meanwhile, colorectal lesions could be substantially alleviated by scutellarin. ELISA results showed that the levels of pro-inflammatory factors TNF-αand IL-6 were drastically lessened (P<0.01). Scutellarin also sharply inhibited the nuclear translocation of β-catenin, as evidenced by the reduction in the nuclear level ofβ-catenin protein. In addition, scutellarin attenuated the mRNA expres?sion of Wnt signaling pathway-relatedβ-catenin, TCF4, c-Myc and cyclin D1, whereas it heightened GSK-3βmRNA level. These results were consolidated by WB analysis, which indicated that scutellarin could mitigate the protein levels of phospho-GSK-3β,β-catenin, TCF4, c-Myc and cyclin D1, with the increase in GSK-3β protein in CAC tissue. Moreover, scutellarin could induce the apoptosis of CAC, demonstrated by enhanced expression of Bax and diminished expression of Bcl-2 in both mRNA and protein levels. CONCLUSION Scutellarin may ameliorate colitis-associated colorectal cancer by weakening Wnt/β-catenin signaling cascade.

16.
Article in Chinese | WPRIM | ID: wpr-907596

ABSTRACT

Objective:To observe the clinical effects of intraperitoneal perfusion of bevacizumab combined with albumin paclitaxel and carboplatin in the treatment of malignant peritoneal adhesion caused by ovarian cancer.Methods:From January 2016 to December 2020, 54 patients treated in our hospital with malignant peritoneal adhesions caused by ovarian cancer were enrolled in this study. They were randomly divided into experimental group ( n=27) and control group ( n=27) according to the random number table method. The treatment regimen of the experimental group was intravenous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin and bevacizumab. The treatment regimen of the control group was intra-venous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin. The treatment was repeated every 21 days, and the therapeutic effect was evaluated every two cycles. The treatment lasted for six cycles. The efficacy and incidence of adverse reactions were compared between the two groups. Results:The remission rate of incomplete malignant bowel obstruction of the experimental group was higher than that of the control group [85.19% (23/27) vs. 59.26% (16/27)], the total effective rate of the experimental group was higher than that of the control group [74.07% (20/27) vs. 44.44% (12/27)], and there were statistically significant differences ( χ2=4.523, P=0.033; χ2=4.909, P=0.027). After treatment, the levels of vascular endothelial growth factor (VEGF) in ascites of the experimental group and the control group were significantly lower than those before treatment [(80.33±1.41) pg/ml vs. (310.45±3.35) pg/ml, t=449.884, P<0.001; (135.68±1.60) pg/ml vs. (310.46±3.09) pg/ml, t=499.281, P<0.001], and after treatment, the VEGF level in the experimental group decreased more significantly than that in the control group ( t=-134.907, P<0.001). Patients in the experimental group and the control group tolerated the treatment well, and there were no significant differences in the incidences of adverse reactions such as hypertension (11.11% vs. 3.70%, χ2=0.270, P=0.603), neutropenia (14.81% vs. 11.11%, χ2<0.001, P>0.999), peripheral neuropathy (3.70% vs. 0, χ2<0.001, P>0.999), diarrhea (7.41% vs. 3.70%, χ2<0.001, P>0.999), nausea (3.70% vs. 0, χ2<0.001, P>0.999), epistaxis (7.41% vs. 0, χ2=0.519, P=0.471) or albuminuria (3.70% vs. 0, χ2<0.001, P>0.999) between the two groups. Conclusion:Intraperitoneal perfusion of bevacizumab combined with chemotherapy is superior to simple chemotherapy in the treatment of malignant peritoneal adhesion caused by ovarian cancer.

17.
Chinese Journal of School Health ; (12): 1712-1716, 2021.
Article in Chinese | WPRIM | ID: wpr-906574

ABSTRACT

Objective@#To investigate the trend of overweight and obesity among Han students aged 7-18 in Ningxia from the year of 2000 to 2019, and to provide scientific basis for obesity prevention and control among children and adolescents.@*Methods@#Based on the five waves of "National Student Physical Fitness and Health Survey" in Ningxia region during 2000 to 2019, body weight, height, waist circumference, hip circumference and other data of Han students aged 7-18 years were included was used for trend analysis.@*Results@#In 2019, the detection rates of overweight and obesity in children and adolescents aged 7 to 18 in Ningxia were 13.34% (1 181/8 855) and 9.19% (814/8 855), respectively. The increase rate of overweight and obesity in boys from 2000 to 2019 was 11.68% and 10.07% ( χ 2=27.60, P <0.01). The rate of overweight and obesity in female students from 2000 to 2019 was 6.95% and 5.77% ( χ 2=33.82, P <0.01). Urban boys had the highest rates of overweight and obesity, which were 11.38% and 10.45%. The growth rate of overweight and obesity in rural boys was higher than that in urban boys after 2010 ( χ 2=13.90,17.09, P < 0.05), and the growth rate of obesity in rural girls was higher than that in urban girls after 2014 ( χ 2=9.94, 33.39, P <0.05). Overweight and obesity prevalence showed positive associations with the economic status in both urban and rural areas ( χ 2=35.19, 35.35, P <0.01).@*Conclusion@#From 2000 to 2019, the prevalence of overweight and obesity and body mass index among children and adolescents in Ningxia increased consistently, with more rigirous in rural areas. Specific strategies and measures for overweight and obesity prevention in children and adolescents are in urgent need, to reduce potential social and economic burden.

18.
Journal of Experimental Hematology ; (6): 1163-1168, 2021.
Article in Chinese | WPRIM | ID: wpr-888533

ABSTRACT

OBJECTIVE@#To compare the clinical efficacy of first-line and salvage autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#The clinical data of 30 patients with DLBCL aged≤60 years old were retrospectively analyzed, and the patients were divided into first-line auto-HSCT group (15 cases) and salvage auto-HSCT group (refractory relapsed patients, 15 cases) according to the timing of transplantation, and the efficacy was analyzed. Anyone of the factors must be followed in patients receiving first-line HSCT: aaIPI score≥2 points, Ann-Arbor stage III-IV, large mass (diameter≥10 cm) or double expression of c-myc/BCL-2.@*RESULTS@#The median follow-up time for all patients after transplantation was 26 (3-103) months. Until the end of follow-up, 23 patients survived and 7 patients died. All the 7 dead patients with multiple organ failure due to the relapse and disease progression. The median survival time of 7 dead patients from transplantation to death was 6 (3-11) months. Among the 15 patients in the first-line auto-HSCT group, there were 2 patients relapsed (13.3%), 1 dead (6.7%), 14 patients survived [overall survival (OS) rate was 93.3%]. Among the 15 patients treated with salvage auto-HSCT, 6 patients died due to disease progression or relapse (40%), 9 cases survived (OS rate was 60%). There was a statistically significant difference in the mortality of patients between the two groups (6.7% vs 40%, P=0.006). The 3-year PFS and OS rates of patients in first-line auto-HSCT group were both 93.3%. The 3-year PFS and OS of patients in salvage auto-HSCT group were 58.7% and 59.2%. The 3-year OS and PFS of patients in the first-line auto-HSCT group were significantly higher than those in the salvage auto-HSCT group (P=0.03, P=0.04). The bone marrow suppression was the most common adverse complication and all patients showed grade III-IV granulocytopenia. Non-hematological adverse reactions were mainly gastrointestinal adverse reactions and oral mucositis. There was no statistically significant difference in adverse reactions between the two groups.@*CONCLUSION@#First-line auto-HSCT can be used as a consolidation treatment for DLBCL patients with poor prognostic factors. Auto-HSCT can further improve the prognosis of salvage chemotherapy-sensitive patients with refractory relapsed DLBCL.


Subject(s)
Disease-Free Survival , Hematopoietic Stem Cell Transplantation , Humans , Lymphoma, Large B-Cell, Diffuse/therapy , Middle Aged , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation, Autologous , Treatment Outcome
19.
Article in Chinese | WPRIM | ID: wpr-888026

ABSTRACT

This study aims to explore the efficacy of Chinese medicine injections( CMIs) for promoting blood circulation and removing blood stasis for acute cerebral infarction from the perspectives of clinical medication and mechanism of action based on two complex network analysis methods. Firstly,the current 13 kinds of CMIs for acute cerebral infarction were obtained from 2019 List of medicines for national basic medical insurance,industrial injury insurance and maternity insurance with the method of network Meta-analysis. Secondly,with the use of network pharmacology,the mechanisms of top 2 CMIs with the highest therapeutic effect for acute cerebral infarction were explored from two levels including core target and network function enrichment. The result of network Meta-analysis showed Mailuoning Injection was superior to Danhong Injection in terms of total effectiveness rate for neurological deficit score and NIHSS score. The network pharmacology results showed that Mailuoning Injection had more core targets,interaction networks,enriched biological functions and more signaling pathways than Danhong Injection for cerebral infarction. Both two CMIs can play a role in treating cerebral infarction through core targets such as TP53 and NOS3,biological processes such as fibrinolysis,nitric oxide biosynthesis,nitric oxide-mediated signal transduction,negative regulation of apoptosis in endothelial cells and apoptosis process,as well as the signaling pathways such as PI3 K-Akt signaling pathway,HIF-1 signaling pathway and cell apoptosis signaling pathways. The results of pharmacological studies explained their differences in clinical efficacy to a certain extent. A research strategy based on curative effect should be advocated in efficacy evaluation of traditional Chinese medicine,where comparative research on clinical efficacy can be conducted firstly,and then mechanism research based on outstanding effective drugs to better provide references and basis for selection of similar competitive drugs for one disease in the clinical practice.


Subject(s)
Cerebral Infarction/drug therapy , Drugs, Chinese Herbal/therapeutic use , Endothelial Cells , Female , Humans , Injections , Medicine, Chinese Traditional , Pregnancy , Signal Transduction
20.
Chinese Medical Journal ; (24): 2073-2080, 2021.
Article in English | WPRIM | ID: wpr-887629

ABSTRACT

BACKGROUND@#Whether there is an association between serum uric acid (SUA) level and risk of mortality in the general population remains unclear. Based on the China National Survey of Chronic Kidney Disease linked to mortality data, a population-based cohort study was performed to investigate the association between SUA level and all-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality in China.@*METHODS@#The survival status of participants in the cross-sectional survey was identified from January 1, 2006 to December 31, 2017. Only 33,268 individuals with complete SUA data among the 47,204 participants were included in the analysis. We determined the rates of all-cause mortality, CVD mortality, and cancer mortality. We used Cox proportional hazards regression models to evaluate the effect of the SUA level on mortality.@*RESULTS@#During a total of 297,538.4 person-years of follow-up, 1282 deaths occurred. In the Cox proportional hazards regression model, the rate of all-cause mortality, CVD mortality, and cancer mortality had a U-shaped association with SUA levels only in men, whereas no significant associations were detected in women. For all-cause mortality in men, the multivariable-adjusted hazard ratios (HRs) in the first, second, and fourth quartiles compared with the third quartile were 1.31 (95% confidence interval [CI] 1.04-1.67), 1.17 (95% CI 0.92-1.47), and 1.55 (95% CI 1.24-1.93), respectively. For CVD mortality, the corresponding HRs were 1.47 (95% CI 1.00-2.18), 1.17 (95% CI 0.79-1.75), and 1.67 (95% CI 1.16-2.43), respectively. For the cancer mortality rate, only a marginally significant association was detected in the fourth quartile compared with the third quartile with an HR of 1.43 (95% CI 0.99-2.08).@*CONCLUSIONS@#The association between SUA and mortality differed by sex. We demonstrated a U-shaped association with SUA levels for all-cause and CVD mortalities among men in China.


Subject(s)
Cause of Death , China/epidemiology , Cohort Studies , Cross-Sectional Studies , Female , Humans , Male , Proportional Hazards Models , Risk Factors , Uric Acid
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