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1.
Article in Chinese | WPRIM | ID: wpr-936303

ABSTRACT

OBJECTIVE@#To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells.@*METHODS@#The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation.@*RESULTS@#The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05).@*CONCLUSION@#Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.


Subject(s)
Animals , Cell Line, Tumor , Flavonols/pharmacology , Humans , Mice , MicroRNAs/metabolism , Receptor, IGF Type 1 , Trastuzumab
2.
Article in Chinese | WPRIM | ID: wpr-924028

ABSTRACT

Objective  To analyze the prevalence and risk factors of hyperuricemia (HUA) in Shenyang City, and to provide evidence for the prevention and treatment of HUA in this region. Methods From January 2013 to December 2020, 98,327 subjects who underwent physical examination in Shengjing Hospital of China Medical University in Shenyang were selected. The detection rate of HUA was calculated, and the risk factors of HUA were analyzed by multivariate logistic regression analysis. Results From 2013 to 2020, the overall prevalence of HUA was 22.48%, 30.75% in males and 9.13% in females. The prevalence rate in the male was significantly higher than that in the female (P<0.05). Except for a slight decrease in 2015 and 2020, the total prevalence rate showed an increasing trend year by year. With the increase of age, the prevalence of HUA in males decreased, while in females, it decreased slightly from 40 to 59 years old and increased significantly after 60 years old. With the increase of BMI (Body Mass Index), the prevalence of HUA also increased, and the difference was statistically significant (P<0.05). Logistic regression analysis showed that male, body mass index, physical examination year, hypertension, hyperlipidemia, hyperglycemia, triglyceride, LDL-C, abnormal liver and renal function were positively correlated with HUA, while age and HDL-C were negatively correlated with HUA. Conclusion  HUA occurs mainly in male people among physical examination population in Shenyang. With the increase of BMI, HUA increases.

3.
Article in English | WPRIM | ID: wpr-929235

ABSTRACT

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.


Subject(s)
Computational Biology , Drugs, Chinese Herbal , Humans , Network Pharmacology , Phosphatidylinositol 3-Kinases , Urinary Bladder Neoplasms/genetics
4.
Article in English | WPRIM | ID: wpr-928970

ABSTRACT

OBJECTIVES@#Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment.@*METHODS@#Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (ei) and degree (ki).@*RESULTS@#Repeated measures 2-factor ANCOVA showed significant main effects on group on the ei and ki values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the ei and ki values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher ei and ki values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher ei and ki values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher ei and ki values of LSFG (P=0.019 and P=0.026, respectively), and higher ei value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher ei values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the ei and ki values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the ki value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment.@*CONCLUSIONS@#There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high ei of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased ei and ki values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.


Subject(s)
Anhedonia , Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Prefrontal Cortex
5.
International Eye Science ; (12): 1745-1748, 2022.
Article in Chinese | WPRIM | ID: wpr-942854

ABSTRACT

AIM:To investigate the myopia of junior high school students in Enshi, Hubei province with different selenium content, and analyze the correlation between the level of serum selenium, hair selenium and myopia.METHODS:A cross-sectional study. A total of 600 students from grades 1-3 of junior high schools(100 students in each grade)in selenium-rich(selenium in soil ≥1.28mg/kg)and selenium-deficient(selenium in soil &#x003C;1.28mg/kg)areas were randomly selected from September 2020 to September 2021, respectively. The level of serum selenium, hair selenium, glutathione peroxidase(GSH-Px)and myopia condition were determined.RESULTS:The serum and hair selenium of myopic group(n=244, 40.7%)were 75.14±11.16μg/L and 0.51±0.01μg/g, respectively. Those in the non-myopic group(n=356, 59.3%)were 110.24±12.14μg/L and 0.68±0.02 μg/g, respectively. The serum selenium and hair selenium in the two groups were different(all P&#x003C;0.01). The serum selenium of 300 students in the selenium-deficient area was 76.74±11.25μg/L, the hair selenium was 0.45±0.01 μg/g, and the number of myopia cases was 154(51.3%); The serum selenium of 300 students in selenium-rich areas was 102.31±10.26 μg/L, the hair selenium was 0.71±0.02 μg/g, and the number of myopia cases was 90(30.0%), the serum and hair selenium in the selenium-rich areas were significantly higher than those compared with the students in selenium-deficient areas, and the myopic incidence was significantly reduced(all P&#x003C;0.01). The level of GSH-Px of the two areas was 114.65±12.12U/L vs 75.34±13.20U/L(Z=37.994, P&#x003C;0.01). There is a negative correlation between serum and hair selenium and the myopic incidence(r=-0.542, -0.621, P&#x003C;0.05).CONCLUSION:Serum and hair selenium is significantly associated with myopia of junior high school students in Enshi, which may provide new ideas for the clinical prevention and treatment of myopia.

6.
Article in Chinese | WPRIM | ID: wpr-941014

ABSTRACT

OBJECTIVE@#To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice.@*METHODS@#Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation.@*RESULTS@#Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine.@*CONCLUSION@#ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.


Subject(s)
Airway Remodeling , Angiotensin-Converting Enzyme 2 , Animals , Methacholine Chloride , Mice , Mice, Inbred C57BL , Mice, Knockout , Ozone/adverse effects , Pneumonia
7.
Article in Chinese | WPRIM | ID: wpr-941008

ABSTRACT

OBJECTIVE@#To explore the effective components of Yiqi Jiedu recipe and the main biological processes and signal pathways involved in the therapeutic mechanism of the recipe in treatment of primary liver cancer through network pharmacology and molecular docking approaches.@*METHODS@#TCMSP, Uniport, Genecards and String databases were searched to obtain the target genes of drugs and disease using Cytoscape 3.8.2 software. GO and KEGG enrichment analyses were performed to identify the common genes in the target genes of the drugs and disease. Using Pubcham, RCSB and Autoduck, the effective components of the drugs were connected with the final core genes. The effects of different concentrations of Yiqi Jiedu recipe on the expressions of the core genes DHX9, HNRNPK, NCL and PABPC1 in HepG2 cells were analyzed with Western blotting and real- time fluorescence quantitative PCR.@*RESULTS@#We finally identified 8 core genes from the drug and disease targets, including DDX5, HNRNPK, PABPC1, DHX9, RPS3A, RPS3, RPL13, and NCL. GO analysis showed that these core genes were involved mainly in the biological processes of adrenaline receptor signal communication, movement of cellular or subcellular components, blood particles, adhesion class and iron ion binding. KEGG analysis showed that the Ras signaling pathway had the greatest gene enrichment. The results of molecular docking suggested that the effective components of the recipe were capable of docking with the core genes under natural conditions, and PABPC1 and stigmasterol had the highest binding energy. In HepG2 cells, treatment with 10% medicated serum for 48 h had the strongest effect on the expression of DHX9, HNRNPK, NCL and PABPC1 (P < 0.05).@*CONCLUSION@#Yiqi Jiedu recipe is capable of regulating viral expression of primary liver cancer multiple effective components that bind to DHX9, HNRNPK, NCL and PABPC1.


Subject(s)
DEAD-box RNA Helicases , Drugs, Chinese Herbal/therapeutic use , Humans , Liver Neoplasms/drug therapy , Molecular Docking Simulation , Neoplasm Proteins , Network Pharmacology , Ribosomal Proteins , Signal Transduction
8.
Article in Chinese | WPRIM | ID: wpr-934301

ABSTRACT

Diabetic macular edema (DME) is the main cause of vision loss and even blindness in patients with diabetic retinopathy. Intravitreal anti-vascular endothelial factor therapy has become the gold standard management of DME. However, not all eyes response optimally to common management of DME, which could be due to the differences of individual factors. Increasing age could be the predictive factors for poor outcome. The influence of glycemic control, hypertension, dyslipidemia, chronic kidney disease and relative factors on treatment response require further investigation. Identifying the systemic factors that influence the treatment response of DME can provide the evidence to predict the prognosis of DME, and improve the efficacy of clinical treatment.

9.
Chinese Journal of Trauma ; (12): 142-148, 2022.
Article in Chinese | WPRIM | ID: wpr-932219

ABSTRACT

Objective:To compare the clinical efficacy of robot-assisted and simple arthroscopic reconstruction of anterior cruciate ligament (ACL).Methods:A retrospective cohort study was conducted to analyze the clinical data of 37 patients with ACL tear admitted to Honghui Hospital of Xi′an Jiaotong University from January 2020 to September 2020. There were 24 males and 13 females, aged 16-45 years[(30.7±9.8)years]. A total of 17 patients were treated by robot-assisted ACL reconstruction (robot-assisted group), and 20 patients by simple arthroscopic ACL reconstruction (simple arthroscopy group). The operation time, number of guide wire drilling, positional accuracy of bone tunnel (distance between the central point of bone tunnel and ideal anatomical point) and perioperative complications were compared between the two groups. Knee stability was evaluated by Lachman test and KT-2000 measurement, and knee function by Lysholm score, International Knee Documentation Committee (IKDC) score and range of motion of joint flexion and extension before operation, at 4 months after operation and at the last follow-up.Results:All patients were followed up for 12-18 months[(13.1±4.1)months]. The operation time in robot-assisted group was (83.8±11.3)minutes, significantly longer than (50.4±9.1)minutes in simple arthroscopy group ( P<0.01). The number of guide wire drilling in robot-assisted group was (2.2±0.5)times, less than (2.5±0.4)times in simple arthroscopy group ( P<0.05). The distance between the central point of bone tunnel and ideal anatomical point was (1.3±0.3)mm in robot-assisted group, not significantly different from (1.4±0.3)mm in simple arthroscopy group ( P>0.05). There were no perioperative complications in both groups. The two groups showed no significant differences in Lachman test, KT-2000 measurement, Lysholm score, IKDC score and range of motion of joint flexion and extension before operation, at 4 months after operation and at the last follow-up (all P>0.05). The above indices in both groups were significantly improved at 4 months after operation and at the last follow-up as compared with those before operation (all P<0.01), and both groups showed no significant difference in the above indexes at 4 months after operation and at the last follow-up as compared with those before operation (all P>0.05). Conclusion:Compared with simple arthroscopic ACL reconstruction, robot-assisted ACL reconstruction can prepare a bone tunnel once with good location and direction in one time and achieve similar results in stability and functional recovery of the joint except for slightly longer operation time.

10.
Journal of Chinese Physician ; (12): 667-671, 2022.
Article in Chinese | WPRIM | ID: wpr-932117

ABSTRACT

Objective:To establish a scoring system based on lumbar magnetic resonance imaging (MRI) images to evaluate bone mineral density and evaluate its correlation with T score of dual energy X-ray absorptiometry (DEXA).Methods:The clinical data of 82 patients with lumbar degenerative diseases who were admitted to the Clinical Medical College of Yangzhou University from January 2019 to August 2020 were analyzed retrospectively. According to the lower value of T value of femoral neck and total hip bone mineral density detected by DEXA, they were divided into normal bone mass group ( n=40) and abnormal bone mass group ( n=42). The vertebral body bone mass (VBQ) score of the patient was calculated by dividing the average signal intensity of L 1-4 vertebral body by the signal intensity of L 3 level cerebrospinal fluid on T 1 weighted image of MRI. The receiver operating characteristic (ROC) curve was drawn to evaluate the ability of VBQ score to distinguish between normal bone mass and abnormal bone mass and the accuracy of predicting the occurrence of abnormal bone mass. Further, the correlation between VBQ score and T value was determined by regression analysis. Results:The lowest T value measured by DEXA in the abnormal bone mass group were significantly lower than those in the normal bone mass group, and the VBQ score was significantly higher than that in the normal bone mass group(all P<0.001). The area under curve (AUC) of VBQ score for predicting abnormal bone mass was 0.93, the cut-off value was 2.98, with sensitivity 81.6%, and specificity 88.6%. The VBQ score was corrected with the lowest T value measured by DEXA ( r=-0.77). Conclusions:VBQ score could effectively distinguish normal bone mass from abnormal bone mass and was negatively correlated with the lowest T value of DEXA.

11.
Article in English | WPRIM | ID: wpr-922576

ABSTRACT

OBJECTIVE@#To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H@*METHODS@#Sprague-Dawley rats were exposed to H@*RESULTS@#The morphological investigation showed that XBJ attenuated H@*CONCLUSIONS@#XBJ ameliorated H


Subject(s)
Animals , Claudin-5 , Drugs, Chinese Herbal , Endothelial Cells , Hydrogen Sulfide , Phosphatidylinositol 3-Kinases , Rats , Rats, Sprague-Dawley , Respiratory Distress Syndrome, Newborn/drug therapy
12.
Article in Chinese | WPRIM | ID: wpr-920782

ABSTRACT

Objective To investigate the type and consumption of sanitary insecticides used in Putuo District of Shanghai, determine the current resistance of Aedes albopictus to the insecticides, and explore the causes of regional variations in insecticide resistance spectrum. Methods Public and private institutions of pest control operation were investigated on the use of sanitary insecticides. Dipping method and tube method were used to measure the insecticide resistance of Aedes albopictus, including larvae and adults. Results The main insecticides used in residential areas and governmental units was β-cypermethrin, while that in markets and public environment was propoxur. In addition, and the insecticides in dengue control program was λ-cyhalothrin. Aedes albopictus larvae had medium resistance to parathion, and were sensitive to propoxur, with insignificant change within three years. Their resistance to permethrin and deltamethrin was medium and high, respectively. Moreover, resistance to β-cypermethrin increased over years. In contrast, resistance of adult Aedes albopictus differed by area, except consistently being sensitive to fenitrothion. Conclusion Multiple sanitary insecticides have been used in Putuo District. In addition, Aedes albopictus has different resistance to these insecticides by area. It suggests that resistance surveillance should be promoted, which may be crucial for scientific application of insecticides and impede the development of potential resistance.

13.
China Pharmacy ; (12): 492-496, 2022.
Article in Chinese | WPRIM | ID: wpr-920468

ABSTRACT

OBJECTIVE To obser ve the efficacy and safety of rimazo lom for painless gastroscopy sedation in outpatients. METHODS Totally 84 patients who underwent painless gastroscopy were collected from the outpatient department of the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from March to June in 2021. By random number table method combined with envelope allocation concealment method ,they were randomly divided into observation group and control group ,with 42 cases in each group. The patients in the observation group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+Rimazole toluenesulfonate for injection 0.2 mg/kg. Patients in the control group were slowly injected with Sufentanil citrate injection 0.1 μg/kg+ Propofol emulsion injection 2 mg/kg. Gastroscopy was performed after the patient ’s consciousness disappeared. The sedative efficiency,sedative onset time ,recovery time and the occurrence of adverse drug reaction were observed in 2 groups. The heart rate(HR),mean arterial pressure (MAP),pulse oxygen saturation (SpO2),modified observer ’s assessment of alertness/sedation (MOAA/S)score and Narcotrend score were recorded in 2 groups after entering the room (T0),after anesthesia induction (T1), when gastroscope entered the throat (T2),at the end of gastroscope withdrawal (T3),5 min after gastroscopy (T4). RESULTS There was no significant difference in the effective rate of sedation (100%),the incidence of respiratory depression , nausea and vomiting between the two groups (P>0.05). The qq.com onset time of sedation in the observation group was longer than control group ,and the recovery time and the incidence ofhypotension,hypotension to be tre ated,injection pain and bradycardia in observation group were significantly shorter or lower than control group (P<0.05). At T 0,there was no significant difference in HR ,MAP,SpO2,MOAA/S score or Narcotrend score between two groups (P>0.05). From T 1 to T 4,the HR of control group was significantly lower than that of the same group at T 0,and significantly lower than observation group at the same time(P<0.05). From T 1 to T 3,the MAP of two groups were significantly lower than the same group at T 0(P<0.05),but there were no significant differences between two groups and between T 4 and T 0(P>0.05). There was no significant difference in SpO 2 at different time points between two groups and HR at different time points in observation group (P>0.05). From T 1 to T 3,MOAA/S score and Narcotrend score of two groups were significantly lower than the same group at T 0,while the MOAA/S score and Narcotrend score at T 1 and T 3 and Narcotrend score at T 3 of observation group were significantly higher than control group at the same time (P<0.05),and the Narcotrend score of observation group at T 2 was significantly lower than control group at the same time(P<0.05);at T 4,there were no significant differences in MOAA/S score and Narcotrend score between two groups (P> 0.05). CONCLUSIONS Remazolam shows good sedative effect and safety for painless gastroscopy.

14.
Article in Chinese | WPRIM | ID: wpr-928267

ABSTRACT

OBJECTIVE@#To explore the mechanism of proteasome inhibitor MG132 in improving osteoporosis.@*METHODS@#Total of 32 female SD rats, weighing 220 to 250 g and 8 weeks old, were selected. They were randomly divided into 4 groups(n=8). Rats of group A and group B were cut off ovaris on both sides to make model of osteoporosis, and then they were given proteasome inhibitors MG132 and dimethyl sufoxide (DMSO) respectively. Group C was a sham group and rats were given MG132. Group D was a normal group and rats were given MG132 too. The rats were killed in batches at 6 and 12 weeks after administration, and the femoral neck tissues were obtained. Relevant data were analyzed, such as pathomorphological observation, micro-CT analysis, detection of 20S proteasome activity in tissues, and expression of Wnt and β-catenin.@*RESULTS@#Morphological observation showed that the trabecular were slightly thinner, reticulated, and occasionally interrupted in group A, while the trabecular were obviously thinner and discontinuous in group B. And the trabecular were intact and arranged reticulated in group C and D. The analysis results of bone mineral density(BMD), bone surface(BS), bone volume/total volume(BV/TV) and trabecular thickness(Tb.Th) showed that group B was worse than other groups in all parameters at different time points(P<0.05), and group A was worse than group C and group D in BS(P<0.05), there was no significant difference in all parameters between group C and group D. RFU value of 20S proteasome in group B was significantly higher than that in other groups(P<0.05). According to the results of Western blot, the gray values of Wnt protein and β-catenin protein in group A were significantly higher than those in other groups (P<0.05).@*CONCLUSION@#MG-132, a ubiquitin proteasome inhibitor, can regulate Wnt/β-catenin signaling pathway by inhibiting the degradation of β-catenin protein, and delaying the occurrence and development of osteoporosis.


Subject(s)
Animals , Bone Density , Female , Leupeptins , Osteoporosis/drug therapy , Proteasome Inhibitors/pharmacology , Rats , Rats, Sprague-Dawley , Wnt Signaling Pathway , beta Catenin/metabolism
15.
Article in Chinese | WPRIM | ID: wpr-928095

ABSTRACT

The present study investigated the mechanism of polyphyllin A(PPA) in inhibiting gastric cancer(GC) cells. GC cells(SGC7901 and MGC803 cell lines) were treated with PPA at different concentrations. The effect of PPA on the proliferation of GC cells was detected by MTT assay, real-time cell analysis(RTCA) assay, and clone-forming assay, respectively. Reactive oxygen species(ROS) of GC cells was detected by flow cytometry. The change of mitochondrial membrane potential was detected by JC-1 assay. The expression and phosphorylation levels of apoptosis-related proteins(caspase-9, caspase-3, and PARP) and proteins related to the signaling pathway(ETS-1, CIP2 A, and Akt) were detected by Western blot. The binding sites of PPA to ETS-1 were analyzed by molecular docking. The affinity of PPA and ETS-1 was detected by drug affinity responsive target stability(DARTS) assay. PPA had a significant inhibitory effect on the proliferation and colony formation of GC cells at a low concentration. The PPA groups showed increased ROS and decreased mitochondrial membrane potential. PPA down-regulated the precursor expression of caspase-9 and caspase-3 and promoted the cleavage of PARP, suggesting that PPA induced the apoptosis of GC cells through the mitochondrial pathway. PPA significantly reduced expression levels of CIP2 A and the phosphorylation of downstream Akt. Molecular docking showed that PPA bound to the ETS domain of ETS-1, the transcription factor of CIP2 A, and formed hydrogen bonds with Pro319 and Asp317. DARTS assay further confirmed that PPA significantly prevented the hydrolysis of ETS-1 by pronase, which was inductive of the direct binding effect of PPA and ETS-1. PPA inhibits the proliferation and induces the apoptosis of GC cells by directly targeting ETS-1 to down-regulate the ETS-1/CIP2 A/Akt signaling pathway.


Subject(s)
Apoptosis , Cell Line, Tumor , Cell Proliferation , Humans , Molecular Docking Simulation , Stomach Neoplasms/metabolism
16.
Article in Chinese | WPRIM | ID: wpr-927955

ABSTRACT

This study aims to investigate the molecular mechanism of polyphyllin Ⅰ(PPⅠ) inhibiting proliferation of human breast cancer cells. Human breast cancer BT474 and MDA-MB-436 cells were treated with different concentrations of PPⅠ, and then the effect of PPⅠ on cell proliferation was detected by MTT assay, trypan blue dye exclusion assay, real-time cell analysis, and clone forming assay, respectively. The apoptosis was detected by Annexin V-FITC/PI staining and then analyzed by flow cytometry. The change of mitochondrial membrane potential was detected by flow cytometry after fluorescent probe JC-1 staining. Western blot was used to detect protein expression and phosphorylation. Molecular docking was performed to detect the binding between PPⅠ and EGFR. The affinity between PPⅠ and EGFR was determined by drug affinity responsive target stability assay. The results indicated that PPⅠ inhibited the proliferation and colony formation of BT474 and MDA-MB-436 cells in a time-and concentration-dependent manner. The PPⅠ treatment group showed significantly increased apoptosis rate and significantly decreased mitochondrial membrane potential. PPⅠ down-regulated the expression of pro-caspase-3 protein, promoted the cleavage of PARP, and significantly reduced the phosphorylation levels of EGFR, Akt, and ERK. Molecular docking showed that PPⅠ bound to the extracellular domain of EGFR and formed hydrogen bond with Gln366 residue. Drug affinity responsive target stability assay confirmed that PPⅠ significantly prevented pronase from hydrolyzing EGFR, indicating that PPⅠ and EGFR have a direct binding effect. In conclusion, PPⅠ inhibited the proliferation and induced apoptosis of breast cancer cells by targeting EGFR to block its downstream signaling pathway. This study lays a foundation for the further development of PPⅠ-targeted drugs against breast cancer.


Subject(s)
Apoptosis , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Diosgenin/analogs & derivatives , ErbB Receptors , Female , Humans , Molecular Docking Simulation
17.
Article in Chinese | WPRIM | ID: wpr-927925

ABSTRACT

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Drugs, Chinese Herbal/pharmacology , Glycyrrhiza , Humans , Medicine, Chinese Traditional , Network Pharmacology
18.
Chinese Journal of Orthopaedics ; (12): 584-594, 2021.
Article in Chinese | WPRIM | ID: wpr-884748

ABSTRACT

Objective:Through TTC staining, immunohistochemical analysis, RT-PCR and hind limb motor function evaluation and other experimental methods, to explore the regulatory mechanism of metformin on anti-apoptosis in rats with spinal cord injury (SCI).Methods:Establish a rat spinal cord injury model. Through Basso-Beattie -Bresnahan locomotor rating scale (BBB) and cant test to evaluate the recovery of hindlimb motor function in rats. The changes of necrotic area of spinal cord tissue were compared by TTC staining. Extraction of rat spinal cord tissue, by Dot blot analysis and immunohistochemical detection of the hydroxyl of DNA methylation level. By qPCR, Western Blot detection TET2mRNA and protein expression level, and the changes in the scope of spinal cord injury were detected by inhibiting the expression of TET2. The interaction between TET2 and Foxo3a was detected by immunoblotting and immunoprecipitation. Through RT-PCR assay Foxo3a downstream related changes in the level of gene expression.Results:Compared with the SCI+NS group, the necrotic area of the spinal cord tissue was reduced after metformin treatment, and the BBB score and the incline test score were higher ( P<0.05). At the same time, we found that the levels of TET2mRNA and protein increased significantly after SCI at 24 h, and the 5-hmC level of DNA increased. The levels of TET2mRNA and protein and 5-hmC increased further after the use of metformin. After using SC-1, compared with the SCI+MET group, the level of 5-hmC decreased and the area of infarction increased. After SCI, the mRNA levels of downstream genes Bim, P27kip, Bax increased significantly. After metformin treatment, the mRNA levels of Bim and Bax were lower than those in the SCI+NS group ( P<0.05). After SCI, the 5-hmC levels of downstream genes Bim, P27kip, Bax increased significantly. After metformin treatment, the 5-hmC levels of Bim and Bax were lower than those in the SCI+NS group ( P<0.05). Conclusion:Metformin can promote the interaction between TET2 and Foxo3a, increase the 5-hmC level of the overall DNA, and inhibit the activation of related apoptosis genes, thereby improving tissue damage and nerve function recovery after spinal cord injury.

19.
Journal of Chinese Physician ; (12): 544-547,552, 2021.
Article in Chinese | WPRIM | ID: wpr-884087

ABSTRACT

Objective:To analyze the curative effect of discectomy under Quadrant expandable channel associated with annulus repair for the treatment of adolescent lumbar disc herniation (ALDH).Methods:10 ALDH patients received discectomy under Quadrant expandable channel associated with annulus repair (annulus repair group) and 12 patients received discectomy (control group) in Clinical Medical College of Yangzhou University from January 2013 to December 2017 were retrospectively collected. The length of skin incision, amount of intraoperative bleeding, operation time and duration of hospitalization were compared. The degree of pain was assessed by visual analogue scale (VAS) before operation, 24 h, 1 week and 1 year after operation, and the lumbar function was assessed by Oswestry disability index (ODI) before operation, 1 week and 1 year after operation. At the last follow-up, the curative effect was evaluated by MacNab Scale, and the recurrence of lumbar disc herniation during the follow-up was recorded.Results:There were no significant differences in the amount of intraoperative bleeding, operation time and duration of hospitalization between the two groups ( P>0.05). The skin incision length of the annulus repair group was less than that of control group ( P<0.05). The postoperative VAS score and ODI score at each follow up time point in both groups were significantly improved when compared with the preoperative ones ( P<0.05). There were no statistically significant difference between the two groups in the VAS score and ODI score 1 week postoperative and 1 year postoperative ( P>0.05). According to the MacNab criteria, there was no statistically significant difference between the two groups in the excellent and good rate (annulus repair group: 9/10, control group: 10/12; P>0.05). There was no recurrence case in the annulus repair group, but two cases of recurrence (one recovered by conservative treatment, the other needed second operation) in the control group ( P<0.05). Conclusions:Discectomy under Quadrant expandable channel associated with annulus repair can achieve early satisfied outcome, reduce surgery related trauma, pain in the early period postoperative and recurrence rate after operation in the treatment of ALDH.

20.
Chinese Journal of Endemiology ; (12): 155-159, 2021.
Article in Chinese | WPRIM | ID: wpr-883684

ABSTRACT

Objective:To review the research progress of endemic fluorosis in China in the past decade, and to provide references for prevention and control of endemic fluorosis.Methods:Using Wanfang Data Knowledge Service Platform as the information source, research papers in the field of endemic fluorosis from 2008 to 2017 were retrieved, and the publication status, core authors, cooperation status, and research hotspots were analyzed.Results:A total of 2 068 papers were retrieved, with 297 and 298 articles published in 2009 and 2010, while 94 and 103 articles were published in 2016 and 2017, respectively. There were 8 420 authors in 2 068 articles, with an average of 4 authors per article. According to the statistics of the first authors, the number of papers published by the most productive authors was 21. There were 59 first authors who had published more than 4 papers, they had published 371 papers, accounting for 17.94% of the total number of papers. Analysis of the author's cooperation showed that the research teams with larger scale and closer cooperation were from Harbin Medical University, Guizhou Provincial Center for Disease Control and Prevention, Guizhou Medical University, Shandong Institute for Prevention and Control of Endemic Disease, Shaanxi Provincial Institute for Endemic Disease Prevention and Control, Chongqing Center for Disease Control and Prevention, Hulunbuir City Institute for Endemic Disease Prevention and Control of Inner Mongolia Autonomous Region, Qinghai Institute for Endemic Disease Prevention and Control. The hotspots and themes of the study focused on epidemiological investigation of endemic fluorosis, health education, pathogenesis and other related research of endemic fluorosis.Conclusion:In Chinese periodicals, the number of papers published on endemic fluorosis has been reduced, the construction of talent team needs to be strengthened, and the research hotspots and themes are changing steadily.

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