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1.
Frontiers of Medicine ; (4): 448-459, 2021.
Article in English | WPRIM | ID: wpr-888730

ABSTRACT

The ability of tumor cells to sustain continuous proliferation is one of the major characteristics of cancer. The activation of oncogenes and the mutation or inactivation of tumor suppressor genes ensure the rapid proliferation of tumor cells. The PI3K-Akt-mTOR axis is one of the most frequently modified signaling pathways whose activation sustains cancer growth. Unsurprisingly, it is also one of the most commonly attempted targets for cancer therapy. FK506 binding protein 8 (FKBP8) is an intrinsic inhibitor of mTOR kinase that also exerts an anti-apoptotic function. We aimed to explain these contradictory aspects of FKBP8 in cancer by identifying a "switch" type regulator. We identified through immunoprecipitation-mass spectrometry-based proteomic analysis that the mitochondrial protein prohibitin 1 (PHB1) specifically interacts with FKBP8. Furthermore, the downregulation of PHB1 inhibited the proliferation of ovarian cancer cells and the mTOR signaling pathway, whereas the FKBP8 level in the mitochondria was substantially reduced. Moreover, concomitant with these changes, the interaction between FKBP8 and mTOR substantially increased in the absence of PHB1. Collectively, our finding highlights PHB1 as a potential regulator of FKBP8 because of its subcellular localization and mTOR regulating role.


Subject(s)
Apoptosis , Cell Line, Tumor , Cell Proliferation , Female , Humans , Ovarian Neoplasms , Phosphatidylinositol 3-Kinases , Proteomics , Repressor Proteins , TOR Serine-Threonine Kinases , Tacrolimus Binding Proteins
2.
China Pharmacy ; (12): 1215-1223, 2021.
Article in Chinese | WPRIM | ID: wpr-876889

ABSTRACT

OBJECTIVE:To predict the potenti al target and mechanism of Astragali Radix in the treatment of ulcerative colitis (UC),and to provide reference for the clinical application of Astragali Radix in the treatment of UC. METHODS :The active components and their corresponding target genes of Astragali Radix were retrieved by TCMSP and UniProt KB database.related target genes of UC were searched by Gene Cards GZK-2018-5) database. The intersection target genes of Astragali Radix and were obtained by Venny 2.1.0 online mapping tool ,and interaction network of “drug-compound-intersection target ” was constructed by using Cytoscape 3.7.0 software. PPI network of intersecting targets was obtained by using STRING 结合动物模型。E-mail:172924249@qq.com database, and the visualization analysis and topological analysis w ere carried out by using Cytoscape 3.7.0 software to obtain the core target genes. By using DAVID database ,the gene ontology (GO) function annotation and KEGG pathway enrichment of intersecting target genes were carried out ,and the “target-pathway”enrichment network was constructed by using Cytoscape 3.7.0 software. Through Auto Dock vina 1.1.2 software, the top five active components in the list of degree value were linked with the protein encoded by the core target genes ;Discovery Studio 3.5 software was applied to draw out binding pattern map. RESULTS :There were 143 compounds in Astragali Radix ,20 active components were screened out ,and 189 corresponding target genes were selected ;there were 4 356 UC disease related target genes. There were 126 intersection target genes of Astragali Radix (involving 14 active components )and UC. The core target genes in PPI network were AKT1,MAPK1,RB1,JUN,etc. A total of 2 294 GO items (q value<0.05)were obtained from GO functional annotation ,including 2 093 biological process items (e.g. response to lipopolysaccharide ,response to molecule of bacterial origin ),49 cell composition items (e.g. membrane raft ,membrane microdomain ),and 152 molecular function items (e.g. nuclear receptor activity ,ligand-activated transcription factor activity ). KEGG pathway enrichment analysis yielded 160 items(q value<0.05),such as fluid shear stress and atherosclerosis signaling pathway ,phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway ,interleukin-17 (IL-17) signaling pathway. Molecular docking results showed that top 5 active ingredients (quercetin,kaempferol,formenonetin,isorhamnetin,7-O-methylisomucronulatol) in the list of degree value had binding energies <5.0 kcal/mol with the protein encoded core targets. CONCLUSIONS :Quercetin,kaempferol,formononetin and other active components in Astragali Radix may play a role in the treatment of UC through the action of MAPK14,JUN,AKT1 and other target genes ,and then on the signal pathways such as PI 3K/Akt and IL- 17.

3.
Journal of Clinical Hepatology ; (12): 725-728, 2021.
Article in Chinese | WPRIM | ID: wpr-873826

ABSTRACT

MicroRNA (miRNA) is a type of small non-coding RNA and acts as a post-transcriptional regulator of gene expression. This article briefly describes the etiology of various chronic liver diseases, including metabolic dysfunction-associated fatty liver disease, chronic hepatitis B, chronic hepatitis C, chronic drug-induced liver injury, liver cirrhosis, and hepatocellular carcinoma, and summarizes related reports on microRNA-125b which enters different signal transduction pathways and plays the same or contradictory regulatory role in the same liver disease or pathological process by targeting different target genes, so as to provide insights into the research on the pathogenesis of various chronic liver diseases and the establishment of non-invasive differential methods.

4.
Journal of Clinical Hepatology ; (12): 1508-1513, 2020.
Article in Chinese | WPRIM | ID: wpr-822898

ABSTRACT

ObjectiveTo investigate the molecular mechanism of the anti-liver fibrosis effect of curcumol by observing the effect of curcumol on the TLR4/NF-κB signaling pathway in liver sinusoidal endothelial cells. MethodsA total of 50 mice were randomly divided into blank group, model group, and curcumol group, and cells were divided into blank control group, LPS positive control group, curcumol intervention group, and PDTC group. HE staining and Masson staining were used to observe the change in liver structure; Western blot and quantitative real-time PCR (RT-PCR) were used to measure the protein and mRNA expression of the key molecules TLR4 and NF-κB in the TLR4/NF-κB signaling pathway; immunofluorescence assay was used to observe the expression and nuclear import of NF-κB in cells. A one-way analysis of variance was used for comparison between multiple  groups, and the least significant difference t-test was used for further comparison between two groups. ResultsRT-PCR showed that compared with the positive control group, the curcumol intervention group had significant reductions in the mRNA expression of TLR4 and NF-κB (both P<0.05). Western blot showed that compared with the positive control group, the curcumol intervention group had significant reductions in the expression of TLR4 and NF-κB (both P<005). Immunofluorescence assay showed that compared with the positive control group, the curcumol intervention group had significant improvement in NF-κB nuclear import. ConclusionCurcumol can exert an anti-liver fibrosis effect possibly by inhibiting the activity of the TLR4/NF-κB signaling pathway.

5.
Article in Chinese | WPRIM | ID: wpr-746162

ABSTRACT

Objective To summarize the clinical experience and efficacy of surgical treatment for Stanford type A aortic dissection leading to acute lower limb ischemia.Methods From January 2014 to January 2018,12 patients with severe lower limb ischemia caused by acute type A aortic dissection were treated with Suns surgery.Among them,11 patients were treated with restoration of lower limb blood supply preferentially,including 10 cases of femoral artery bypass and 1 case of abdominal aorta-iliac artery stent graft implantation.Another case was treated with ascending aorta-femoral artery bypass after Sung surgery.Results 3 cases died of ischemia and necrosis of the lower extremities.Two of them died of multiple organ failure due to amputation and one died of low cardiac output due to refractory acidosis.Acute renal failure performed bedside CRRT in 5 patients and ECMO in 1 patient.The remaining 9 patients were discharged from the hospital and the symptoms of lower limb ischemia disappeared.After an average follow-up of 23 months,the re-examination of the aorta CTA showed that the bypass artery was unobstructed and the distal femoral artery was well developed.One patient infecting vascular prosthesis was cured by taking out the unit.Conclusion For acute lower limb ischemia caused by type A aortic dissection,blood flow of lower extremities should be restored as soon as possible to reduce mortality and complications.Femoral artery bypass and abdominal aorta-iliac arterial repair are simple and effective in reconstructing lower limb blood supply.

6.
Chinese Circulation Journal ; (12): 279-283, 2017.
Article in Chinese | WPRIM | ID: wpr-509838

ABSTRACT

Objective: To explore the protective roll of ifbroblast growth factor 21 (FGF21) in endoplasmic reticulum stress (ERS) induced rat's H9c2 cardiomyocyte apoptosis with its mechanism. Methods: pcDNA4 was used as gene vector, pcDNA4-FGF21 plasmid was constructed and transfected into rat's H9c2 myocardiocytes for 48 h. ERS model was established by 10 μM tunicamycin (TM) induction for 24 h. The experiment was conducted in 4 groups:①Control group,②TM group, the cells were treated by TM,③pcDNA4-FGF21+TM group,④pcDNA4+TM group. The expressions of FGF21, protein kinase R-like ER kinase (PERK) and c-Jun N-terminal kinases (JNK) mediated apoptosis pathway related protein were measured by Western blot analysis; cell survival rate was examined by CCK-8 method and apoptosis rate was detected by TUNEL technique. Results: pcDNA4-FGF21 vector was successfully constructed and overexpressed in H9c2 myocardiocytes. Compared with Control group, TM group and pcDNA4+TM group had up-regulated endogenous FGF21 expression, increased PERK and JNK mediated apoptosis pathway related protein expression; reduced cell survival rate and elevated apoptosis rate. Compared with TM group and pcDNA4+TM group, pcDNA4-FGF21+TM group had down-regulated PERK and JNK mediated apoptosis pathway related protein expression; increased cell survival rate and decreased apoptosis rate. Conclusion: FGF21 overexpression can reduce ERS induced apoptosis rat's H9c2 myocardiocytes which might be partly related for inhibiting PERK and JNK mediated signal transduction of apoptosis pathway.

7.
Chinese Journal of Pathophysiology ; (12): 1065-1072, 2017.
Article in Chinese | WPRIM | ID: wpr-612939

ABSTRACT

AIM:To explore the effects of galectin-3 (GAL-3) on the viability, migration and inflammation of human umbilical vein endothelial cells (HUVECs) and the mechanisms.METHODS:The HUVECs were cultured in vitro and treated with GAL-3 recombinant protein at 2 mg/L or GAL-3 short hairpin RNA (shRNA).The HUVECs were divided into normal group, recombinant GAL-3 group, shControl group and GAL-3-shRNA group.The mRNA expression of GAL-3, monocyte chemotactic protein (MCP)-1, IL-6, matrix metalloproteinase (MMP)-9 and cyclin D1 was detected by real-time quantitative PCR,and the protein expression of GAL-3, IL-6 and MCP-1 was detected by Western blot.The secretion levels of MCP-1 and IL-6 in the culture medium were measured by ELISA.The viability and the ability of migration of the HUVECs were examined by CCK-8 assay and wound healing assay.The protein levels of heat shock protein 90 (HSP90), ERK1/2, p-ERK1/2, JNK and p-JNK were determined by Western blot.RESULTS:The expression of GAL-3, MCP-1 and IL-6 at mRNA and protein levels, the mRNA expression of MMP-9 and cyclin D1, and the secretion levels of MCP-1 and IL-6 in the culture medium were significantly higher than those in normal group (P<0.05) after the HUVECs were treated with GAL-3 recombinant protein.However, these molecules mentioned above in GAL-3-shRNA group were significantly lower than those in normal group and negative control group (P<0.05).Compared with normal group, the viability and migration ability of the HUVECs in recombinant GAL-3 group were significantly increased, but the viability and migration ability of the HUVECs in GAL-3-shRNA group were lower than those in normal group and shControl group (P<0.05).In addition, the protein levels of p-ERK1/2 and HSP90 in recombinant GAL-3 group were higher than those in normal group (P<0.05), but those in GAL-3-shRNA group were lower than those in normal group and shControl group (P<0.05).The protein level of p-JNK was not oviously changed among the 4 groups.CONCLUSION:GAL-3 is involved in regulating the cell growth, migration and the release of inflammatory cytokines in vascular endothelial cells, which may be mediated by HSP90-ERK1/2 signaling pathway.

8.
Clinical Medicine of China ; (12): 1131-1134, 2017.
Article in Chinese | WPRIM | ID: wpr-664194

ABSTRACT

Objective To investigate the expression of anti mullerian hormone(AMH)in the serum of patients with ovarian endometriosis cyst and its clinical significance.Methods Fifty-one cases of ovarian endometriosis cyst from March 2014 to June 2016 in Maternal and Child Health Hospital Affiliated to Southern Medical University(observation group)and thirty-five cases of normal women who were diagnosed through physical examination(control group)were selected as the research objects.The observation group patients received laparoscopic ovarian endometriosis cystectomy treatment,enzyme-linked immunosorbent assay(ELISA) was applied to detect and analyze serum AMH in the control group at physical examination and in the observation group before surgery and at 1 month,3 months after surgery.Results (1)The preoperative serum AMH level of the observation group was significantly lower than that of the control group,the difference was statistically significant((2.45±0.68)μg/L vs.(3.75±0.80)μg/L,t=7.8604,P=0.0000).(2)Serum AMH level in the groups where the ages were above 35years was significantly lower than that of the age less than 35 group( (1.76±0.57)μg/L vs.(3.61±0.88)μg/L,t=9.1249,P=0.0000); the preoperative serum AMH level in the group where disease course was more than 12 months was significantly lower than that of the disease course less than 12 months group((2.03 ± 0.64)μg/L vs.(3.98 ± 0.91)μg/L,t=8.1408,P=0.0000); the preoperative serum AMH level in patients with dysmenorrhea was significantly lower than that of patients without dysmenorrhea((1.65±0.53)μg/L vs.(3.91±0.84)μg/L,t=11.7861,P=0.0000),the preoperative serum AMH level in the bilateral lesion group was significantly lower than that of the unilateral lesion((2.01±0.68) μg/L vs.(2.84±0.72)μg/L,t=4.2174,P=0.0001); there was no significant difference in the preoperative serum AMH level between patients with<5.0 cm diameter cyst and patients with smaller cyst((2.52 + 0.81)μg/L vs.(2.39 + 0.50)μg/L,t=0.8411,P=0.4029).The serum AMH level in the observation group at 3 months after surgery was significantly lower than that before surgery((2.45±0.68)μg/L vs.(1.81± 0.55) μg/L,t=24.3657,P=0.0000).Conclusion The expression of serum AMH level in patients with ovarian endometriosis is low,and it is closely related to the age,course of disease,history of dysmenorrhea and the location of the lesion.Laparoscopic ovarian cystectomy may reduce ovarian reserve capacity in patients with ovarian endometriosis.

9.
Article in Chinese | WPRIM | ID: wpr-319914

ABSTRACT

, born in the SouthernDynasty, was proficient in TCM theory and enjoyed summarizing proved prescriptions. During his spare time, he wrotewith scientific writing structure, wide quote of references and attached medical reports, which modified and enriched the content of acupoint therapy. This book played an important role as a link between past and future; it included a considerable number of moxibustion methods and was considered as the greatest medical achievement beforeDynasty. In addition, this book contained the greatest number of proved prescriptions among the ancient acupuncture books, so its academic value was self-evident. However, when examining and correcting the acupoints,ignored the fact that acupuncture physicians had different clinical experience and their understanding on the body structure was discrepant, so the contradictions of location and indications of acupoints appeared in the book.

10.
Article in Chinese | WPRIM | ID: wpr-485649

ABSTRACT

Objective:To observe the efficacy of cytokine-induced killer (CIK) cells on patients with advanced lung cancer. Methods:A total of 90 patients with advanced lung cancer were identified from January 2011 to December 2013. CIK therapy was given to 41 pa-tients in the observation group, whereas the other 49 patients in the control group received the best support treatments without che-motherapy or radiotherapy within one month of inclusion. Following up was conducted for the patients in the two groups, and KPS scores, median survival, and adverse reactions compared. Results:The KPS score in the observation group was higher than that of the control group after treatment (P=0.034). The median survival period of the observation group was eight months, which was one month longer than that of the control group (P=0.044). Major adverse reactions included fever, joint pain, and insomnia, which were recorded 51.22%, 36.58%, and 29.27%of occurrence, respectively. Conclusion:CIK cell therapy improved the quality of life and pro-longed the survival of advanced lung cancer patients with tolerable adverse reactions.

11.
Article in Chinese | WPRIM | ID: wpr-637605

ABSTRACT

Background Ocular alkali burns leads to corneal ulcer and angiogenesis and even corneal opacity.There is still no ideal treatment method.Studies showed that mesenchymal stem cells (MSCs) can repair corneal wound in vivo,but the specific mechanism is still not clear.Objective This study aimed to observe the histopathological change after the early transplatation of bone marrow MSCs (BMSCs) for corneal alkali burn model in rabbits and explore the anti-inflammatory effects of MSCs after corneal alkali burn.Methods Bone marrow of 4 ml was collected from 2-3 month-old Japanese rabbit.BMSCs were isolated and cultured from the bone marrow of rabbits,and the third generation of cells were used in this study.Cultured cells were identified by morphology and the expressions of surface markers.Corneal alkali burn models were extablished in the right eyes of 24 rabbits by attaching the filter paper with 0.1% NaOH at the central cornea for 30 seconds,and then the models were randomized into 2 groups.BMSCs suspension of 300 μl (concentration 5×l06/μl) was subconjunctivally injected 1 hour after modeling in the BMSCs group,and equal volume of PBS was used in the same way in the PBS group.Corneal opacification was scored under the slim lamp microscope in 3,14 and 28 days after injection.The polymorphonuclear neutrophils (PMNs) were counted by histopathological examination,and the expression of matrix metalloproteinase-2 (MMP-2) in the corneal tissue was evaluated by immunochemistry in various time points.The use and care of the rabbits followed the statement of ARVO.Results The rabbit BMSCs were plastic-adherent cells that exhibited a fibroblastlike shape.Cultrued cells highly expressed surface adhesion molecular markers CD29 and CD90 (99.18% and 97.94%) and lowly expressed hematopoietic cell markers CD34 and CD31 (0.74% and 0.15%).Opacification of cornea,defect of corneal epithelium,stromal edema and neovascularization appeared after modeling.In 14 days and 28 days after modeling,the opacification scores in the BMSCs group were 2.37±0.52 and 2.25±0.50,which were significantly lower than 3.00±0.53 and 3.25 ±0.50 in the PBS group (t =2.376,2.828,both at P<0.05).After subconjunctival injection,the number of PMNs was (34.17 ±1.85) /12 fields and (25.64 ±3.86)/12 fields in the BMSCs group,showing significant decrease in comparison with (42.70 ±1.54) /12 fields and (32.67 ±1.42)/12 fields in the PBS group (t=10.021,4.832,both at P=0.000).The expression levels of MMP-2 (A value) in cornea were 0.388±0.016 and 0.384±0.006 in the BMSCs group,with considerable decreases in comparison with 0.438± 0.006 and 0.412± 0.005 in the PBS group (t=10.205,13.514,both at P=0.000).Conclusions Early transplantation of BMSCs can arrest the occurrance of corneal ulcer by suppressing the infiltration of PMNs,alleviateing the inflammation reaction,downregulating the expression of MMP-2 in cornea and inhibiting the degradation of stromal collagen fibers.

12.
Chinese Mental Health Journal ; (12): 305-310, 2015.
Article in Chinese | WPRIM | ID: wpr-465465

ABSTRACT

Objective:To examine the relationship between regulatory emotional self-efficacy and childhood abuse,and the mediating role of regulatory emotional self-efficacy between childhood abuse and depression in col-lege students.Methods:Totally 475 college students from 4 universities in Harbin were assessed with the Chinese version of the Regulatory Emotional Self-Efficacy Questionnaire (RES),Childhood Trauma Questionnaire-Short Form (CTQ),and Center for Epidemiologic Studies Depression Scale (CES-D).The survey of CTQ was manipula-ted retrospectively.Results:Physical neglect and physical abuse had significant direct negative effects on perceived self-efficacy in expressing positive affect (POS)(β=-0.38,-0.52).Emotional neglect and sexual abuse had significant direct negative effects on perceived self-efficacy in managing despondency/distress (DES)(β=-0.35,-0.31).Physical neglect had a significant direct negative effect on perceived self-efficacy in managing anger/irri-tation (ANG)(β=-0.23).Physical neglect and physical abuse had significant direct positive effects on depres-sion (β=0.78,3.20).The POS mediated relationships between emotional neglect and depression,physical neglectand depression,and sexual abuse and depression (with intermediary effects of 0.021 -0.029).The DES imposed mediating effects on relationships between emotional neglect and depression,physical neglect and depression,physi-cal abuse and depression,and sexual abuse and depression (with intermediary effect of 0.017 -0.040).The ANG was a mediator in the relationships between emotional neglect and depression,and physical neglect and depression (with intermediary effects of 0.016 -0.019).Conclusion:It suggests that childhood abuse may be an important factor related to low regulatory emotional self-efficacy.Regulatory emotional self-efficacy may play a mediating role between childhood abuse and depression.

13.
National Journal of Andrology ; (12): 315-319, 2004.
Article in Chinese | WPRIM | ID: wpr-308363

ABSTRACT

<p><b>OBJECTIVE</b>To research the regulating effects of different dosages of ginseng with hairy antler on the sexual dysfunction model of the gonad and the structure of shenyangxu male rats induced with adenine, and to look for the best compatible proportion of ginseng to hairy antler in the model.</p><p><b>METHODS</b>Healthy male SD rats, 2 months of age and (220 +/- 20) g in weight, were randomly assigned to 13 groups: normal group, model group, ginseng group, hairy antler group and 9 different proportion groups of ginseng to hairy antler. Observations were made on the exterior syndrome, testosterone in sera, weight index of the prostate and seminal vesicle, and tissue changes of the testis in the experimental rat model.</p><p><b>RESULTS</b>Dosages of different proportions of ginseng to hairy antler had different improving effects on the exterior syndrome, testosterone in sera, weight index of the prostate and seminal vesicle, and tissue changes of the testis.</p><p><b>CONCLUSION</b>Different proportions of ginseng to hairy antler had different improving effects on the sexual dysfunction model of male rats induced with adenine, and the best compatible proportion of ginseng to hairy antler was 5 to 2, that is, 0.45 g ginseng to 0.18 g hairy antler or 0.90 g ginseng to 0.36 g hairy antler.</p>


Subject(s)
Adenine , Animals , Antlers , Disease Models, Animal , Male , Medicine, Chinese Traditional , Panax , Rats , Rats, Sprague-Dawley , Sexual Dysfunctions, Psychological , Drug Therapy , Testosterone , Blood
14.
Article in Chinese | WPRIM | ID: wpr-572303

ABSTRACT

Objective To investigate the changes of the peripheral blood platelet counting and function the mouse model of idiopathic thrombocytopenic purpura (ITP) and to observe the effect of Zidian Granule (ZG). Methods The peripheral platelet counting was conducted with the automatic hemocyte analyzer; CD41 andCD61 level was measured with flow cytometry. Results The amount of the peripheral blood platelet in ITP model mouse was decreased after injection of antiplatelet serum (APS) and CD41 and CD61 were also decreased.(P

15.
Article in Chinese | WPRIM | ID: wpr-577543

ABSTRACT

AIM:To investigate the antiemetic effect of preadministration of Banxia Fuling Capsule(Rhizoma Zingiberis recens,Rhizoma Pinelliae,Poria,etc)(BFC)in pigeons and dogs,and to explore the relationship between antiemetic effect of BFC and 5-hydroxytryptamine(5-HT).METHODS:The pigeons and dogs were pretreated with BFC for 3 days.Acute emesis of pigeons and dogs induced by intravenously injecting cisplatin were observed.The concentraction of 5-HT in the serum,small intestine and brainstem of the animals were determined by spectrofluorimetry.RESULTS:The number and incidence of the emesis decreased in the treatment of BFC in dogs and pigeons;The levels of 5-HT in brainstem and small intestine decreased in pigeons,and so was it in the serum of dogs.CONCLUSION:BFC may inhibit emesis induced by cisplatin in dogs and pigeons,the antiemetic effect of BFC may decrease the synthesis and release of 5-HT in brainstem and small intestine.

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