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1.
Article in Chinese | WPRIM | ID: wpr-905960

ABSTRACT

Objective:To explore the mechanism of energy changes in the three stages of the formation of coronary heart disease due to blood stasis in rat model from the perspective of mitochondrial fusion-fission dynamic changes. Method:Thirty healthy male rats were divided into the blank control group (<italic>n</italic>=6) and model group (<italic>n</italic>=24) using SPSS 21.0 simple random sampling method. The rats in the blank control group were fed an ordinary diet, while those in the model group a high-fat diet. After seven days of adaptive feeding, the rats were treated with intragastric administration of vitamin D<sub>3</sub> (VitD<sub>3</sub>) at 300 000 U·kg<sup>-1</sup> and then at 200 000 U·kg<sup>-1</sup> 14 d later. The high-fat diet continued for 21 d, and six rats were randomly selected as samples for the pre-stage blood stasis syndrome group, followed by model verification and sampling. The remaining rats continued to receive the high-fat diet for 30 d, and six were randomly selected and categorized into the sub-stage blood stasis syndrome group, followed by model verification and sampling. The rest of rats were classified into the heart blood stasis syndrome group. While continuing the high-fat diet, they were also treated with multipoint subcutaneous injection of isoproterenol (ISO,5 mg·kg<sup>-1</sup>) for three consecutive days. One week later, the electrocardiogram (ECG) was recorded for determining whether the modeling was successful and the samples were taken at the same time. The changes in mitochondrial morphology and quantity were observed under a transmission electron microscope. The expression of mitochondrial dynamics-related proteins was measured by Western blot and the cellular localization of related proteins by immunofluorescence assay. Result:The levels of total cholesterol and low-density lipoprotein cholesterol in the pre-stage and sub-stage blood stasis syndrome groups were significantly increased as compared with those in the blank control group (<italic>P</italic><0.05). The blood rheology index in the pre-stage blood stasis syndrome group was significantly elevated in contrast to that in the blank control group (<italic>P</italic><0.05). The three-layered membrane of the aorta in the blank group was intact. However, the tunica media of the pre-stage blood stasis syndrome group began to show obvious calcification, with a small number of inflammatory cells adhering to the intima. The subintima and media smooth muscles in the sub-stage blood stasis syndrome group exhibited cavity structures. The three-layered structure of the arterial wall in the heart blood stasis syndrome group was severely damaged. The ECG of the blank control group revealed the regular appearance of P wave,regular QRS waveform (no broadening or deformity), and no obvious ST-segment depression or elevation. The ECG of the pre-stage blood stasis syndrome group showed no obvious abnormalities as compared with that of the blank control group. In the sub-stage blood stasis syndrome group, the ECG showed an upward trend of the J point and slight ST-segment elevation, with the elevation≤0.1 mV. The ECG in the heart blood stasis syndrome group displayed significant ST-segment depression (>0.1 mV) and J point depression >0.1 mV. The mitochondria in the blank control group were normal in size and morphology, with clear and dense cristae, whereas those in the pre-stage blood stasis syndrome group were fusiform with sparse cristae. Some mitochondria in the sub-stage blood stasis syndrome group were significantly elongated, and even vacuole-like changes were present. In the heart blood stasis syndrome group, the mitochondria were ruptured. As demonstrated by comparison with the blank control group, the expression levels of mitofusin 2 (Mfn2), dynamin-related protein 1 (Drp1), and fission protein 1 (Fis1) in the model group were significantly up-regulated (<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with the pre-stage blood stasis syndrome group, the heart blood stasis syndrome group exhibited down-regulated Mfn2 (<italic>P<</italic>0.05). Compared with the blank control group and the pre-stage blood stasis syndrome group, the sub-stage blood stasis syndrome group and the heart blood stasis syndrome group displayed down-regulated optic atrophy 1(OPA1) (<italic>P</italic><0.05,<italic>P</italic><0.01). The Drp1 and Fis1 protein expression declined significantly in the sub-stage blood stasis syndrome group in comparison with that in the pre-stage blood stasis syndrome group (<italic>P</italic><0.05,<italic>P</italic><0.01). The expression levels of Mfn2 and Drp1 in the heart blood stasis syndrome group were lower than those in the sub-stage blood stasis syndrome group (<italic>P<</italic>0.01). The comparison with the blank control group showed that Mfn2 and OPA1 were extensively accumulated in mitochondria of both the pre-stage and sub-stage blood stasis syndrome groups, while the red-stained Mfn2 was significantly reduced in the heart blood stasis syndrome group. The Drp1/Fis1 fluorescence was weak in the blank group and the pre-stage blood stasis syndrome group but strong in the sub-stage blood stasis syndrome group and heart blood stasis syndrome group. Conclusion:The cardiomyocyte mitochondria dynamics changes with the change in energy demand of cardiomyocytes. Mfn2 is dominated by fusion effect in the early stage of the formation of coronary heart disease due to blood stasis. With the gradual development of this disease, Mfn2 begins to mediate mitochondrial autophagy. OPA1 plays a role in intimal fusion and cristae integrity. The decreased OPA1 expression is closely related to the accelerated progression of coronary heart disease differentiated into blood stasis syndrome. The process by which Drp1 and Fis1 separate damaged mitochondria to prepare for mitochondrial autophagy contributes to alleviating the imbalance between the energy demand and supply of human body.

2.
Article in Chinese | WPRIM | ID: wpr-905938

ABSTRACT

Objective:To observe the effect of Yangxin Tongmaifang (YXTM) on endogenous metabolites in the myocardial tissue of rats with coronary heart disease due to blood stasis based on the metabolomics approach, and to explore its mechanism in the treatment of heart blood stasis syndrome. Method:A rat model of chronic myocardial ischemia due to heart blood stasis was established via the high-fat diet combined with intragastric administration of vitamin D<sub>3</sub> and subcutaneous injection of isoproterenol (ISO), followed by the intervention with YXTM. The metabolites in the myocardial tissues of rats in the normal group (<italic>n</italic>=8), model group (<italic>n</italic>=8), and YXTM group (<italic>n</italic>=8) were detected by ultra-high performance liquid chromatography coupled to high resolution mass spectrometry. The high-throughput metabolomics data were then subjected to multivariate statistical analysis using SIMCA 14.1, and the related metabolic pathways were analyzed with MetaboAnalyst. Result:The myocardial sample points of rats in the three groups were located in different areas of the elliptical confidence interval. The normal group and the model group were completely separated. There existed some crossovers and overlaps between the YXTM group and the normal group. The heart blood stasis syndrome model was proved successfully replicated from the perspective of metabolic profiling, and YXTM had the potential to promote the body to return to a normal state. After the intervention with YXTM, six differential metabolites changed significantly. Such metabolic pathways as valine, leucine, and isoleucine biosynthesis, pantothenate and coenzyme A (CoA) biosynthesis, valine, leucine, and isoleucine degradation, biosynthesis of aminoacyl-transfer RNA synthetases, and purine metabolism were involved. Conclusion:The therapeutic effect of YXTM on heart blood stasis syndrome in rats is related to the improved levels of myocardial endogenous metabolites, and its mechanism involves phospholipid metabolism, amino acid metabolism, energy metabolism, inflammatory response, and platelet activation and aggregation.

3.
Chinese Journal of Dermatology ; (12): 790-797, 2021.
Article in Chinese | WPRIM | ID: wpr-911522

ABSTRACT

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.

4.
Chinese Journal of Radiology ; (12): 415-419, 2021.
Article in Chinese | WPRIM | ID: wpr-884435

ABSTRACT

Objective:To evaluate the value of DWI with background suppression (DWIBS) in evaluating the injury of the low limb nerves in patients with Guillain-Barre syndrome (GBS).Methods:The clinical and imaging data of 30 patients with GBS and 30 healthy volunteers matched with their age and gender in Zibo Central Hospital from January 2018 to December 2019 were analyzed retrospectively. All patients received lower limb nerve electrophysiological examination and all subjects received lower limb nerve DWIBS examination one week later. The display of tibial nerve and common peroneal nerve after DWIBS image reconstruction in normal volunteers and GBS patients was scored by two senior radiologists. Kappa consistency test was used to analyze the consistency of the two senior radiologists′ scores. One-way ANOVA was used to compare the motor nerve conduction velocity (MCV) and motor nerve conduction amplitudes of tibial nerve and common peroneal nerve in patients with GBS among different DWIBS scores. Spearman correlation analysis was used to evaluate the correlation between DWIBS tibial nerve and common peroneal nerve scores and electrophysiological parameters in patients with GBS.Results:In the DWIBS images of 30 healthy volunteers, 60 tibial nerves and common peroneal nerves showed clear, sharp edges, good signal intensity, uniformity, and the scores were 4. The consistency between the two radiologists was good (Kappa value=1.0). In the 60 tibial nerves and common peroneal nerves of 30 GBS patients, 53 tibial nerves and 52 common peroneal nerves showed abnormal changes in varying degrees, including blurred edges, distortions, difficulty in recognition, and weakened signal strength, etc. The consistency between the two readers was good (Kappa value=0.879,0.863,respectively.).With the decrease of DWIBS score, the MCV and motor nerve conduction amplitude values of tibial nerves and common peroneal nervesin GBS patients decreased, and the differences between the score groups were statistically significant ( P<0.01). The scores of tibial nerves and common peroneal nerves in DWIBS were positively correlated with MCV ( r=0.83, 0.84, respectively, P<0.05) and motor nerve conduction amplitude ( r=0.81, 0.79, respectively, P<0.05). Conclusion:DWIBS could provide a three dimensional visualization of tibial nerves and common peroneal nerves, and evaluate the disorders of peripheral nerves in patients with GBS. There has correlation between the scores of tibial nerves and common peroneal nerves in DWIBS with electrophysiology parameters.

5.
Article in Chinese | WPRIM | ID: wpr-907673

ABSTRACT

By summarizing and analizing the relevant literature of modern special acupuncture method in clinic treating posttraumatic stress disorder (PTSD), this paper aims to provide a reference for acupuncture and moxibustion in the era of post epidemic situation. At present, there are four major specific acupuncture treatments which include: Anshen- Xingnao- Tiaoshen Method, Tongdu- Tiaoshen Method, Shugan- Tiaoshen Method, Wentong Method. Although there are some differences in diagnosis, treatment ideas, meridian and acupoint selection and operation methods, the diagnosis and treatment ideas are mainly focusing on regulating the spirit and soothing the liver. The rules of selecting meridians and acupoints are Nao-acupoints, soothing Liver-qi, regulating mind and strengthening the spleen and kidney. Electric acupuncture is used more offen, but pure acupuncture treatment is used more less.

6.
Article in Chinese | WPRIM | ID: wpr-907635

ABSTRACT

At present, there are five major specific acupuncture treatments mainly including Shugan-Tiaoshen acupuncture therapy, Lingping’s Tongdu-Tiaoshen acupuncture therapy, Zhuang’s Tiaoshen acupuncture therapy, Tong Yuan acupuncture therapy, and Dong ' s Tiaoshen-Jieyu acupuncture therapy. Although there are subtle differences, three commons arefoundthrough comparing and analyzing, including ' Shen’ regared as the core treatment of depression, regulating qi duringtreatment, and Du channel points mainly used.

7.
Journal of Clinical Hepatology ; (12): 1666-1668, 2020.
Article in Chinese | WPRIM | ID: wpr-822916

ABSTRACT

microRNAs (miRNAs) are low-molecular-weight non-coding RNAs that regulate various physiological and pathological functions through the regulation of gene expression at the post-transcriptional level. More and more evidence has shown that microRNA-27a (miRNA-27a) plays a role in the development and pathogenesis of liver diseases. By reviewing and updating related studies, this article introduces the research advances in the role of miRNA-27a in various liver diseases including fatty liver disease, hepatitis, hepatic fibrosis, and liver cancer and analyzes the role of miRNA-27a in liver regeneration and its potential as a biomarker, so as to provide a reference for future studies and more possibilities for new treatment ideas for chronic hepatic diseases.

8.
China Pharmacy ; (12): 1132-1138, 2020.
Article in Chinese | WPRIM | ID: wpr-821506

ABSTRACT

OBJECTIVE:To investigate antitumor pharmaceutical care ability a nd the current status of direct to patient (DTP) pharmacy in China ,and to provide reference for building a quality evaluation system of DTP pharmacy which focuses on the pharmaceutical care. METHODS :From Sept. to Dec. 2019, an electronic questionnaire survey was conducted amongpharmacists of all of 126 listed DTP pharmacies and involved wang_star@163.com education background ,professional knowledge sources andpharmaceutical care ability (such as prescription checking and E-mail:dujoan-88@163.com dispensing,medication consultation and guidance ,medication management,follow-up),pharmaceutical knowledge of antitumor medicine ,etc. DTP pharmacies in C hina were inspected on site , and their pharmaceutical care management were evaluated ,and impression of on-site inspection were discribed with questionnaire survey. The current situation of oncology pharmaceutical care ability of DTP pharmacy in China was evaluated and corresponding suggestions were put forward. RESULTS :A total of 400 questionnaires were sent out ,and 392 valid questionnaires were collected with recovery rate of 98.0%. The cancer pharmacists in DTP pharmacy were mainly from East China ,mainly in Jiangxi (73 persons,18.62%),Anhui(68 persons,17.35%). The pharmacists were mainly junior college or below (229 persons,58.42%), followed by undergraduate (158 persons,40.31%). The working years were more than 5 years(241 persons,61.48%). The majors were mostly pharmaceutics (123 persons,31.38%),followed by pharmacy (including pharmacology )(81 persons, 20.66%). The regular knowledge sources of pharmacists in DTP pharmacy included learning materials (302 person times , 77.04%),textbooks(250 person times ,63.78%)and Wechat push (206 person times ,52.55%);the latest knowledge sources included training courses (347 person times ,88.52%),Wechat push (211 person times ,56.38%)and academic conferences (162 person times ,41.33%). The expected training methods included online video courses (344 person times ,87.76%)and offline courses(248 person times ,63.27%). In terms of prescription checking and dispensing ,there were mainly problems such as incomplete medical documents and materials ;82.91% and 64.54% of pharmacists needed routine medical records and discharge summary,and 91.58% of pharmacists took the doctor ’s handwritten prescription as the basis for dispensing new anti-tumor drugs ; pharmacists paid less attention to allergy history ,genetic history and ADR in the field of drug consultation and guidance. According to DTP pharmacists ,the difficulties in the process of drug treatment management included patient ’s ADR monitoring (239 person times,60.97%),evaluating the rationality of drug use (222 person times ,56.63%),making a complete drug use record (219 person times ,55.87%). The main follow-up visits of pharmacists were telephone (334 person times ,85.20%)and dispensing site (313 person times ,79.85%). And 333 pharmacists(84.95%)thought it was necessary to make an appointment for dispensing ;the score rates of professional knowledge examination of antitumor pharmacy for the respondents were 40.56%-84.69%. In the aspect of pharmaceutical care management ,the main points of deduction were drug evaluation ,content and process of drug treatment management,drug follow-up and record ,and the proportion of deduction was 93%,86% and 64% respectively. In the on-site inspection,it was found that the pharmacist had a single source of working knowledge ,did not fully grasp the contents of the evaluation forms such as ADR classification standard ,and prescription checking did not meet the requirements. CONCLUSIONS : DTP pharmacy in China develops rapidly under the guidance of relevant policies ,but its pharmaceutical care is still in the basic stage,which is far behind the requirements of providing whole-course pharmaceutical care for patients. It is necessary to improve the professional service ability of DTP pharma

9.
Article in Chinese | WPRIM | ID: wpr-868148

ABSTRACT

Objective:To compare the preterm birth rate among different age groups and analyze relative high-risk factors of preterm birth.Methods:A retrospective analysis was conducted on clinical data of single pregnant women ≥28 gestational weeks from January 2013 to May 2019 in the First Affiliated Hospital of Chongqing Medical Hospital. All involved women were divided into three groups according to age, Group 1 (aged<35 years), Group 2 (aged 35-39 years), and Group 3 (aged ≥40 years). The preterm birth rate among 3 groups was compared and their high-risk factors were analyzed.Results:There were 48 288 singleton pregnancies during the study period, of which 3 351 were preterm births, preterm birth rate was 6.94% (3 351/48 288). In Group 1, there were 42 020 women, of which 2 699 were preterm births (6.42%, 2 699/42 020); in Group 2, there were 5 061 women, of which 491 were preterm births (9.70%, 491/5 061); and in Group 3, there were 1 207 women, of which 161 were preterm births (13.34%, 161/1 207). Comparing the spontaneous preterm birth rates among the three groups, Group 1 was the lowest one and Group 3 was the highest one (3.72% vs 4.51% vs 5.88%); comparing the medical preterm birth rates among the three groups, Group 1 also was the lowest one and Group 3 also was the highest one (2.70% vs 5.20% vs 7.46%); the differences were statistically significant ( P<0.05). The incidence of spontaneous and medical preterm birth according gestational weeks were compared among three groups and there were no significant differences ( P>0.05). Comparing and analyzing the high-risk factors of medical preterm birth, the incidence of intrahepatic cholestasis of pregnancy and fetal distress in Group 1 were higher than those in Group 2 and 3; the incidence of placenta praevia were significantly higher in Group 2 and 3 than that in Group 1; the differences were statistically significant ( P<0.05). Conclusions:Maternal age is a significant high-risk factor of both spontaneous preterm birth and medical preterm birth, and the risk of preterm birth increases with age. For medical preterm birth, compared with right-age pregnant women, placenta praevia is the high-risk factor for women in advanced maternal age(AMA), which have great effect on medical preterm birth rate of AMA.

10.
Article in Chinese | WPRIM | ID: wpr-847499

ABSTRACT

BACKGROUND: Exosomes are tiny membrane vesicle structures that are an important paracrine component of mesenchymal stem cells. They can transmit information to damaged cells or tissues for regeneration. OBJECTIVE: To review the exosomes and their research process in regenerative medicine. METHODS: Databases of PubMed and CNKI were retrieved with the keywords of “exosomes, mesenchymal stem cells, tissue regeneration and repair” in English and Chinese, respectively. After initial screening of titles and abstracts, irrelevant articles were excluded, and 63 eligible articles were included for result analysis. RESULTS AND CONCLUSION: Exosomes contain a variety of components, and their extraction methods are diverse. They have various functions, such as removing waste material, mediating information transfer between cells, generating immune tolerance and serving as a tumor treatment vaccine. Mesenchymal stem cell-derived exosomes play an important role in tissue regeneration and repair, and have good application prospects. However, if they are used as cell-free therapy in clinical practice, more in-depth research and exploration are needed.

11.
Article | WPRIM | ID: wpr-831037

ABSTRACT

Purpose@#5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy forpatients with advanced colorectal cancer, but many patients still suffer from treatment failuredue to 5-Fu resistance. Emerging observations revealed the important role of chemokine(C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosisin patients with colorectal cancer. This study is designed to reveal the important roleof CXCL-13 in causing colorectal cancer resistance to 5-Fu. @*Materials and Methods@#CXCL-13 levels of patient's serum or cell culture supernatants were measured separatelyby enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell CountingKit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expressionin cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells. @*Results@#In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culturemedium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistantcells. Clinical studies showed that CXCL-13 is highly expressed in the serum of5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome.The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibodyovercame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced5-Fu resistance, which can be saved by added recombination CXCL-13. @*Conclusion@#These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but alsoprovide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatmentstrategies.

12.
Article in Chinese | WPRIM | ID: wpr-781248

ABSTRACT

OBJECTIVE@#explore the expression of miR-155-5p in Wilms tumor and its effect in regulating the proliferation, migration and apoptosis of Wilms tumor cells.@*METHODS@#Specimens of tumor tissues and paired adjacent tissues were obtained from 40 patients with Wilms tumor for detection of the expression levels of miR-155-5p using RT-qPCR. Wilms tumor cell line G401 was transfected with miR-155-5p mimics and miR-155-5p inhibitor to induce miR-155-5p over-expression and its inhibition, respectively, and the changes in the cell proliferation, migration and apoptosis were assessed using cell counting kit-8 (CCK-8), wound healing assay and fl ow cytometry.@*RESULTS@#RT-qPCR showed that the expression of miR-155-5p decreased significantly in Wilms tumor tissues as compared with normal kidney tissues and was significantly associated with TNM stage ( < 0.05). In G401 cells, over-expression of miR-155-5p significantly inhibited the cell proliferation and migration and promoted cell apoptosis ( < 0.05), and down-regulation of miR-155-5p obviously enhanced the proliferation and migration and suppressed apoptosis of the cells ( < 0.05).@*CONCLUSIONS@#miR-155-5p is down-regulated in Wilms tumor and its expression level is correlated with TNM stage. miR-155-5p participates in the progression of Wilms tumor by inhibiting the proliferation and migration and promoting apoptosis of the tumor cells, and may serve as a novel biomarker for diagnosis, therapy and prognostic evaluation of Wilms tumor.


Subject(s)
Apoptosis , Cell Movement , Cell Proliferation , Humans , Kidney Neoplasms , Genetics , MicroRNAs , Genetics , Neoplasm Invasiveness , Wilms Tumor , Genetics
13.
Article in Chinese | WPRIM | ID: wpr-772087

ABSTRACT

OBJECTIVE@#To explore whether bortezomib and a Bcl-2 inhibitor exhibit synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.@*METHODS@#MTT assay was used to determine the cytotoxicity of bortezomib in the absence or presence of Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) in Jurkat cells. The effects of drug treatment on the expression of Bcl-2 family proteins, LC3B, p62, ubiquitin, BiP/Grp78, p-JNK, p-p38 and CHOP proteins were examined by Western blotting. Flow cytometry was used to determine the effects of bortezomib and Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) on cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression levels of the key regulatory factors of unfolded protein reaction (UPR). A zebrafish xenograft model was used to study the anti-tumor effect of bortezomib, obatoclax and their combination in vivo.@*RESULTS@#Bortezomib or Bcl-2 inhibitors alone inhibited the cell viability of Jurkat cells, but only obatoclax and bortezomib showed synergistic cytotoxicity and pro-apoptotic effect. Obatoclax, rather than AT-101 and ABT- 199, blocked autophagic flux in the cells evidenced by concomitant accumulation of LC3B-Ⅱ and p62. Both bortezomib and obatoclax alone caused accumulation of polyubiquinated proteins, and their combination showed a synergistic effect, which was consistent with their synergistic cytotoxicity. The dual blockade of proteasome and autophagy by the combination of bortezomib and obatoclax triggered unfolded protein response followed by cell apoptosis. Preventing UPS dysfunction by tauroursodeoxycholic acid (TUDCA) significantly attenuated the cytotoxicity and pro-apoptotic effect of bortezomib in combination with obatoclax. In zebrafish xenograft models, bortezomib combined with obatoclax significantly decreased tumor foci formation.@*CONCLUSIONS@#Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.


Subject(s)
Antineoplastic Agents , Apoptosis , Bortezomib , Cell Line, Tumor , Drug Synergism , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Proteolysis , Proto-Oncogene Proteins c-bcl-2 , Pyrroles
14.
Article in Chinese | WPRIM | ID: wpr-802349

ABSTRACT

Objective:To explore the absorption and transport properties of flavanomarein in the Madin-Darby canine kidney(MDCK) monolayer cell model. Method:Methyl thiazolyl tetrazolium(MTT) assay was used to investigate the toxicity of flavanomarein in MDCK cells. The resistance value of MDCK monolayer cell model was detected by Millicell-ERS-2 cell resistometer. The effects of mass concentration of flavanomarein,administration time,sodium-glucose cotransporter(SGLTs) inhibitor and glucose transporter 2(GLUT2) inhibitor on the transmembrane transport of flavanomarein were investigated. The concentration of flavanomarein was determined by UPLC-MS/MS, and the apparent permeability coefficient(Papp) and the efflux ratio(ER) were calculated. Result:When the concentration of flavanomarein was 5.625-120 mg·L-1, there was no significant toxic effect on MDCK cells. The transport of flavanomarein in MDCK monolayer cell model was time-dependent and concentration-dependent. The Papp values of flavanomarein were basically between 1×10-6 cm·s-1 to 10×10-6 cm·s-1. Compared with the blank group, the phlorizin group significantly reduced the transport of flavanomarein on the MDCK monolayer cell model at 60 min and 90 min. Conclusion:Flavanomarein is a moderately absorbed drug in the intestine, its transmembrane transport mechanism is dominated by passive transport along with active transport. SGLTs may be involved in mediating the transport of flavanomarein on the MDCK monolayer cell model.

15.
Article in Chinese | WPRIM | ID: wpr-776673

ABSTRACT

OBJECTIVE@#To investigate the influence of demographic and clinical characteristics, stress, and coping style on disease self-management in children and adolescents with type 1 diabetes.@*METHODS@#A cross-sectional survey was performed to select 149 children and adolescents with type 1 diabetes (aged 8-20 years). Related data were collected using the questionnaires and scales on general information, diabetes self-management, perceived stress, and coping style.@*RESULTS@#Of the 149 children and adolescents, 37(24.8%) had high stress. Compared with the school-aged children, the adolescents had higher stress level and were more likely to present with negative coping style (P<0.05). The multiple linear regression analysis showed that the children whose mothers had an educational level at or above senior high school, who had a low stress level, and who adopted positive coping measures had a higher level of diabetes self-management (P<0.05).@*CONCLUSIONS@#Nearly a quarter of the children and adolescents with type 1 diabetes have a high stress level. When delivering the education on diabetes self-management to children and adolescents, healthcare workers should focus on the families whose mothers have an educational level at or below junior high school. Strategies should aim at reducing stress by encouraging positive coping styles.


Subject(s)
Adaptation, Psychological , Adolescent , Adult , Child , Cross-Sectional Studies , Diabetes Mellitus, Type 1 , Female , Humans , Self-Management , Stress, Psychological , Surveys and Questionnaires , Young Adult
16.
Neuroscience Bulletin ; (6): 98-108, 2018.
Article in English | WPRIM | ID: wpr-777072

ABSTRACT

Increasing evidence suggests that spinal microglia regulate pathological pain in males. In this study, we investigated the effects of several microglial and astroglial modulators on inflammatory and neuropathic pain following intrathecal injection in male and female mice. These modulators were the microglial inhibitors minocycline and ZVEID (a caspase-6 inhibitor) and the astroglial inhibitors L-α-aminoadipate (L-AA, an astroglial toxin) and carbenoxolone (a connexin 43 inhibitor), as well as U0126 (an ERK kinase inhibitor) and D-JNKI-1 (a c-Jun N-terminal kinase inhibitor). We found that spinal administration of minocycline or ZVEID, or Caspase6 deletion, reduced formalin-induced inflammatory and nerve injury-induced neuropathic pain primarily in male mice. In contrast, intrathecal L-AA reduced neuropathic pain but not inflammatory pain in both sexes. Intrathecal U0126 and D-JNKI-1 reduced neuropathic pain in both sexes. Nerve injury caused spinal upregulation of the astroglial markers GFAP and Connexin 43 in both sexes. Collectively, our data confirmed male-dominant microglial signaling but also revealed sex-independent astroglial signaling in the spinal cord in inflammatory and neuropathic pain.


Subject(s)
2-Aminoadipic Acid , Toxicity , Animals , Anti-Inflammatory Agents , Therapeutic Uses , Astrocytes , Pathology , Carbenoxolone , Pharmacology , Caspase 6 , Metabolism , Connexin 43 , Metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Enzyme Inhibitors , Pharmacology , Female , Glial Fibrillary Acidic Protein , Metabolism , Male , Mice , Mice, Transgenic , Microglia , Pathology , Minocycline , Therapeutic Uses , Neuralgia , Drug Therapy , Pathology , Pain Measurement , Phenylurea Compounds , Pharmacology , Sex Characteristics , Spinal Cord , Pathology , Time Factors
17.
Neuroscience Bulletin ; (6): 22-41, 2018.
Article in English | WPRIM | ID: wpr-777048

ABSTRACT

The voltage-gated Na channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.


Subject(s)
Animals , Antibodies, Monoclonal , Therapeutic Uses , Biotin , Metabolism , Cells, Cultured , Disease Models, Animal , Female , Ganglia, Spinal , Cell Biology , HEK293 Cells , Humans , Hybridomas , Chemistry , Hyperalgesia , Drug Therapy , Male , Mice , Mice, Inbred C57BL , Metabolism , Chemistry , Allergy and Immunology , Metabolism , Neuralgia , Drug Therapy , Metabolism , Protein Binding , Recombinant Proteins , Therapeutic Uses , Sensory Receptor Cells , Physiology
18.
Article in Chinese | WPRIM | ID: wpr-704293

ABSTRACT

Schistosomiasis is one of a few endemic and infectious diseases,which are controlled by the specific prevention and control institutions in China.Through the review of historical data,this paper describes the construction,continuation and changes of schistosomiasis prevention and control institutions in different historical periods and systems,and analyzes and evalu-ates its historical function,contribution and status.

19.
Article in Chinese | WPRIM | ID: wpr-698353

ABSTRACT

BACKGROUND: Although mesenchymal stem cells (MSCs) and MSCs-released exosomes are expected to become a new means for osteoarthritis, the concrete molecular mechanisms remain unclear yet. OBJECTIVE: To understand the effect and mechanism of exosomes in the MSC treatment of osteoarthritis based on the main pathogenesis of osteoarthritis and characteristics of MSCs. METHODS: Domestic and foreign articles concerning MSCs and MSCs-released exosomes for the osteoarthritis treatment published from 2006 to 2016 were retrieved and analyzed. The keywords used were "exosomes, mesenchymal stem cells, osteoarthritis" in Chinese and English, respectively. RESULTS AND CONCLUSION: Osteoarthritis is a refractory disease associated with age and strain, and MSCs therapy has been obtained a good effect. Cartilage differentiation, microenvironment improvement, paracrine and exosomes mechanism of MSCs have also been reported. Exosomes play an important role in mediating intercellular signal transduction and biological responses by transferring a variety of biologically active proteins, lipids, nucleic acids and other molecules. The changes are not only related to the osteoarthritis pathogenesis, but also involved in MSCs induced regeneration and repair of bone and joint tissues. Exosomes secreted by MSCs can improve bone and joint tissue regeneration through membrane exchange and transport of active molecules. This will provide a new insight into the osteoarthritis treatment.

20.
Article in Chinese | WPRIM | ID: wpr-698177

ABSTRACT

Background:Child-Pugh score(CPS)and albumin-bilirubin(ALBI)score have important predictive value for the assessment of survival of patients with hepatocellular carcinoma(HCC). Aims:To investigate the predictive values of CPS and ALBI score for radiation-induced liver disease(RILD)and long-term prognosis in patients with HCC receiving stereotactic ablative radiotherapy(SABR). Methods:A total of 152 HCC patients receiving SABR from June 2006 to June 2012 at Baoji Central Hospital were enrolled. CPS and ALBI score were determined,and the predictive values of CPS and ALBI score for RILD and prognosis were compared. Results:In 152 patients with HCC,CPS-A was noted in 119 patients, CPS-B in 33 patients;ALBI-1 was noted in 60 patients,ALBI-2 in 86 patients,ALBI-3 in 6 patients. The 5-year overall survival rate was significantly higher in CPS-A patients than in CPS-B patients(46.2% vs. 15.2%,P <0.001). Significant difference in 5-year overall survival rate was found among patients with ALBI-1,ALBI-2 and ALBI-3(P =0.002). CPS grade(HR=1.38,95% CI:1.18-1.94,P=0.008)and ALBI grade(HR=1.68,95% CI:1.32-2.03, P=0.003)were independent risk factors for 5-year survival of patients with HCC. RILD was found in 20 cases(13.8%) within 4 months after SABR. AUC of ALBI for prediction of RILD was significantly higher than that of CPS(0.784 vs. 0.611,P=0.028). Patients with CPS-A and ALBI< -2.76 were less likely to develop RILD after SABR(2.4%). Conclusions:ALBI can effectively predict the occurrence of RILD and long-term survival of HCC patients after SABR.

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