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1.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 68(10): 1400-1404, Oct. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1406551

ABSTRACT

SUMMARY OBJECTIVE: The aim of this study was to investigate whether rosiglitazone-activated peroxisome proliferator-activated receptor gamma can inhibit the occurrence of benign biliary stricture and further elucidate the relevant molecular signaling mechanism. METHODS: The primary cultured rat biliary fibroblasts following experiments were performed using within the fifth generation cells, which were separated from the bile ducts of Sprague-Dawley rats. The primary cultured rat biliary fibroblasts were co-cultured with 10 ng/mL transforming growth factor-beta 1 for stimulating collagen formation. Competent cells were transfected with siRNA that specifically target Smad3 or connective tissue growth factor to inhibit the expression of the corresponding proteins. The cells were incubated with 10 μmol/L rosiglitazone to activate peroxisome proliferator-activated receptor gamma. The cells were incubated with 10 μmol/L GW9662 in the pretreatment session to inactivate peroxisome proliferator-activated receptor gamma. ELISA was used to determine the levels of connective tissue growth factor and type I collagen in the cell supernatant. Western blotting was used to detect the levels of intracellular p-Smad3/t-Smad3. RESULTS: Rosiglitazone-activated peroxisome proliferator-activated receptor gamma inhibited the secretion of type I collagen induced by transforming growth factor-beta 1. Peroxisome proliferator-activated receptor gamma inhibitor GW9662 could significantly reverse the rosiglitazone-triggered inhibition of transforming growth factor-beta 1-induced type I collagen secretion by suppressing peroxisome proliferator-activated receptor gamma activation (p<0.01). Furthermore, we also found that the activation of peroxisome proliferator-activated receptor gamma was accompanied by the inhibition of transforming growth factor-beta 1-induced Smad3 phosphorylation (p<0.01), increased connective tissue growth factor expression (p<0.01), and production of type I collagen (p<0.01), all of which effects elicited by rosiglitazone could be reversed by peroxisome proliferator-activated receptor gamma inhibitor GW9662. CONCLUSION: Peroxisome proliferator-activated receptor gamma activated by rosiglitazone inhibits the transforming growth factor-beta1 -induced phosphorylation of Smad3 and the increased connective tissue growth factor expression as well as inhibits the secretion of type I collagen in biliary fibroblasts.

2.
Article in Chinese | WPRIM | ID: wpr-936302

ABSTRACT

OBJECTIVE@#To investigate the molecular mechanism by which a novel naphthalene allyl trifluoromethyl benzocyclopentanone XX0335 inhibits the proliferation and induces apoptosis of lung cancer A549 cells.@*METHODS@#Lung cancer A549 cells were treated with 0.1% DMSO (control) or different concentrations (6.25, 12.5, and 25 μg/mL) of XX0335, and the changes in cell viability, cell cycle, proliferation and apoptosis were assessed with CCK-8 assay, EdU experiment, and flow cytometry. The effects of different concentrations of XX0335 on phosphorylation levels of proliferation-related proteins Akt, mTOR, Akt/mTOR and the expressions of cleaved PARP and cyclin D1 were determined using Western blotting. We also assessed the effect of XX0335 on tumor growth in a mouse model bearing A945 cell xenograft.@*RESULTS@#Treatment with XX0335 reduced the viability of A549 cells in a dose-dependent manner (P < 0.01) and significantly inhibited cell proliferation (P < 0.001). Flow cytometry showed that XX0335 treatment promoted apoptosis of the cells (P < 0.01) and caused an obvious increase of the number of G1-phase cells. Compared with DMSO, XX0335 significantly inhibited the phosphorylation of Akt and mTOR, increased the expression of cleaved PARP, and lowered the protein expression of cyclin D1. In the tumor-bearing mouse models, injection of XX0335 significantly decreased the tumor volume (P < 0.01).@*CONCLUSION@#XX0335 inhibits the proliferation, cycle and induces apoptosis of lung cancer A549 cells possibly by inhibiting the Akt/mTOR signal pathway.


Subject(s)
A549 Cells , Animals , Apoptosis , Cell Proliferation , Humans , Lung Neoplasms/metabolism , Mice , Naphthalenes/pharmacology
3.
Article in Chinese | WPRIM | ID: wpr-942766

ABSTRACT

@#Fibroblast growth factor 8 (FGF8) is a kind of secretory polypeptide that has crucial roles in the development of various tissues and organs. Current studies have found that FGF8 can regulate the differentiation of cranial neural crest cells by activating the mitogen-activated protein kinase (MAPK) signaling pathway and affect the establishment of mandibular arch polarity and the development of craniofacial symmetry by regulating the expression of target genes. Cleft lip with or without cleft palate, ciliopathies, macrostomia and agnathia are four developmental malformations involving the craniofacial region that seriously affect the quality of life of patients. The abnormal FGF8 signal caused by gene mutation, abnormal protein conformation or expression is closely related to the occurrence of craniofacial malformations, but the molecular mechanism and signaling pathway underlying these malformations have not been fully elucidated. Craniofacial development is a complex process mediated by a variety of signaling molecules. In the future, the role of various signaling molecules in craniofacial development and malformations need to be explored to provide a new perspective and vision for the prevention and treatment of these craniofacial malformations.

4.
Article in Chinese | WPRIM | ID: wpr-940743

ABSTRACT

Alzheimer's disease (AD) is a neurological disease highly related to age, which is the main cause of senile dementia and the most common disease leading to the loss of daily living ability of the elderly. AD brings heavy mental burden and economic pressure to patients, families, and society. Traditional Chinese medicine (TCM) ascribes AD to category of "dementia", believing that the treatment should start from kidney because kidney deficiency is the root cause. Combined with the physiological and pathological characteristics of liver, this paper proposed that liver-kidney homology was an important idea for the prevention and treatment of AD. The main pathological manifestations of AD were amyloid β-protein (Aβ) deposition and neurofibrillary tangles (NFT), and the pathogenesis was complex. A growing number of studies showed that immune inflammation played an important role in the pathogenesis of AD. The important target of treating AD was the regulation of neuro-immune inflammation through the nuclear factor kappa B (NF-κB)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/Caspase-1/interleukin-1β (IL-1β) signaling pathway. Based on the idea of liver-kidney homology, this paper selected the representative formula Hei Xiaoyaosan to explore its effect on the prevention and treatment of AD and the mechanism from the perspective of regulating NF-κB/NLRP3/Caspase-1/IL-1β signaling pathway and inhibiting neuro-immune inflammation, expecting to further promote the in-depth study on the prevention and treatment of AD, and provide references for the prevention and treatment of AD by TCM.

5.
Article in Chinese | WPRIM | ID: wpr-940544

ABSTRACT

In the greying society, pension burden and high incidence of geriatric diseases have hindered social and economic development to a certain extent. Aging is a biological process involving multiple organs and factors, which leads to the occurrence of a variety of diseases. The occurrence of aging is related to a variety of signal pathways, such as nutrient sensing signal pathway and intracellular stress signal pathway, which attracts the interest of scholars in anti-aging drugs and poses a challenge to the development of such drugs. The anti-tumor, hypoglycemic, hypolipidemic, antioxidant, and antiviral activities of Chinese medicinal polysaccharides have been gradually confirmed, and they also have significant advantages in anti-aging. Thus, they are potential candidates for the development of anti-aging drugs. It has been verified that Chinese medicinal polysaccharides exert the anti-aging effect through a variety of mechanisms. To be specific, through dietary restriction, they promote the expression of longevity genes silencing information regulator 1 (Sirt1) and forkhead box O (FoxO) transcription factor, enhance the sensitivity to insulin, activate Sirt1 deacetylase or inhibit insulin/IGF-1 signaling (IIS) and mammalian target of rapamycin (mTOR) signal pathway, thereby exerting the anti-aging effect. In addition, they can inhibit the production of reactive oxygen species (ROS) and the release of pro-inflammatory mediators, enhance anti-inflammatory and antioxidant capacity, and regulate the immunity to inhibit inflammation and aging. Moreover, they can also inhibit apoptosis and delay aging through p53-mediated pathway. Despite the extensive research on anti-aging effect of Chinese medicinal polysaccharides, and the diverse effects and ideal efficacy of the polysaccharides, the anti-aging mechanism has not been systematically reviewed. Therefore, this paper summarizes the relevant literature in PubMed and CNKI and systematically expounds the aging-related signal pathways regulated by Chinese medicinal polysaccharides, which is expected to provide a reference for researchers and clinical workers.

6.
Article in Chinese | WPRIM | ID: wpr-940400

ABSTRACT

ObjectiveTo predict the active ingredients and mechanism of action of lavender in protecting skin photodamage based on network pharmacology and molecular docking technology,and further verify possible signal pathways via animal experiments. MethodThe active ingredients and potential targets of lavender were obtained by SwissTargetPrediction,PharmMapper, and literature. Skin photodamage-related targets were searched from GeneCards,Online Mendelian Inheritance in Man (OMIM),DrugBank and DisGeNET databases. After common targets of the two were screened out,STRING was adopted to analyze the protein-protein interaction (PPI) network,where topological analysis and core target screening were performed by CytoNCA plug-in of Cytoscape 3.8.2. Based on DAVID, gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out among the intersection targets, and the active ingredients of lavender and the signal pathway proteins were selected and verified via molecular docking with AutoDock vina 1.1.2. Finally, mouse photodamage model was established by UVB irradiating the bare skin of mouse back, and the skin condition was observed by naked eyes. Hematoxylin-eosin (HE) and picric acid-acid fuchsin staining (Van Gieson, VG) were used to observe the pathological changes of mouse skin tissues. Western blot was employed to detect the protein expression in mouse skin tissues to further validate the key signal pathways. ResultIn this study,6 active ingredients of lavender,526 potential targets,2 688 disease-related targets,and 258 intersection targets were screened out, and 16 core targets were obtained by PPI network. Additionally, 113 related signal pathways were obtained by KEGG pathway analysis,among which phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and nuclear transcription factor-κB (NF-κB) signal pathway might play a key role in skin photodamage protection by lavender. Molecular docking showed that the active ingredients and the signal pathway proteins were well docked. Animal experiments indicated that the total flavonoids of lavender improved the appearance and histopathological condition of mouse skin, reduced the relative expression levels of phosphorylated(p)-PI3K,p-Akt,and B cell lymphoma 2 (Bcl-2) proteins (P<0.05,P<0.01), and increased relative expression level of Bcl-2-associated X protein(Bax) (P<0.05). ConclusionLavender exerts synergistic effect in resisting skin photodamage,with the characteristics of multi-components,multi-targets,and multi-pathways, which provides a basis for subsequent in-depth research on the complex mechanism of lavender against skin photodamage.

7.
Article in English | WPRIM | ID: wpr-939802

ABSTRACT

OBJECTIVES@#Steroidal anti-inflammatory drugs have certain side effects in the treatment of hypertrophic scar, and the scar recurrence is easy after withdrawal of steroid anti-inflammatory drugs. Finding reliable alternative drugs is an effective means to improve this defect. Aspirin, a traditional non-steroidal anti-inflammatory drug, is safe for topical use and has anti-inflammatory effects similar to those of steroidal anti-inflammatory drugs, which may have similar effects on the treatment of hypertrophic scar. This study aims to investigate the inhibitory effect of aspirin on the proliferation of hypertrophic scar in rabbit ears and the underlying mechanism.@*METHODS@#The rabbit ear hypertrophic scar models were prepared. The rabbits were randomly divided into a normal skin group (group A), a blank control group (group B), a 0.9% NaCl group (group C), a 0.2% aspirin group (group D), a 0.5% aspirin group (group E), a 2% aspirin group (group F), and a triamcinolone acetonide group (group G). Macroscopic observation of hyperplasia was performed 8 weeks after local injection of the scar, followed by collecting the scar tissue samples for HE staining, Masson staining, and immunohistochemistry, respectively to assess the proliferation of fibroblasts and collagen fibers, and calculate the hypertrophic index, microvessel density, and immunohistochemical score.@*RESULTS@#All rabbit ear hypertrophic scar models were successfully constructed. In groups B and C, the hypertrophic scar edge was irregular, with reddish protruding epidermis, significant contracture and hard touch. In group D, E, and F, with the increase of aspirin administration concentration, the scar became thinner and gradually flat, the proliferation of fibrocytes and collagen fibers was weakened, and the hypertrophic index was gradually decreased (P<0.05). Immunohistochemistry showed that the expression of β-catenin was decreased in the group D, E and F in turn, and the immunohistochemical score was gradually decreased (P<0.05). There was no significant difference in hypertrophic index, microvessel density, and immunohistochemical score (all P>0.05).@*CONCLUSIONS@#Local injection of aspirin can reduce the generation of hypertrophic scar in a dose-dependent manner within a certain concentration range; aspirin inhibits the growth of hypertrophic scar in rabbit ears by inhibiting Wnt/β-catenin signal pathway; 2% aspirin and 40 mg/mL triamcinolone acetonide have similar curative efficacy on hypertrophic scar.


Subject(s)
Animals , Anti-Inflammatory Agents/therapeutic use , Aspirin/therapeutic use , Cicatrix, Hypertrophic/pathology , Collagen , Rabbits , Signal Transduction , Triamcinolone Acetonide/therapeutic use , beta Catenin/metabolism
8.
Chinese Journal of Oncology ; (12): 130-138, 2022.
Article in Chinese | WPRIM | ID: wpr-935192

ABSTRACT

Objective: To explore the expression of miR1290 in endometrial cancer tissues and its relationship with the pathological grade, and to find out the effect of miR1290 on biological characteristics of endometrial cancer cells and its mechanism. Methods: A total of 38 cases of endometrioid adenocarcinoma tissues, 10 cases of adjacent tissues and 23 cases of normal endometrial tissues were collected in Provincial Hospital Affiliated to Shandong University from May 2020 to October 2020. The expression of miR1290 was detected by reverse transcription polymerase chain reaction (RT-PCR). The expressions of miR1290 in endometrial cancer cells including KLE and Ishikawa were knocked down by lentiviral transfection. Cell counting kit 8 (CCK-8) test and colony formation test were used to detect cell proliferation ability, wound healing and Transwell test were used to detect cell invasion and migration ability, western blot was used to detect the expressions of epithelial-mesenchymal transition (EMT), phospholipids acylinositide 3-kinase (PI3K)/Akt and Wnt/β-catenin pathway related proteins. Results: The relative expressions of miR1290 in endometrial cancer tissues were 5.40±3.20, which was 1.55 times of normal endometrial tissues (P<0.01) and 1.75 times of adjacent tissues (P<0.01). The relative expressions of miR1290 in 17 cases of endometrial tissues at proliferative stage and 6 cases of endometrial tissues at secretory stage were 3.00±1.08 and 4.97±0.58, respectively, and the difference was statistically significant (P<0.01). In KLE cells and Ishikawa cells, the expression of miR1290 in miR1290 knockdown (Sh-miR1290) group was decreased when compared with the negative control (Sh-NC) group. The absorbance value of Sh-miR1290 group detected by the CCK-8 method and the colony formation rate detected by the colony formation experiment were both increased, the number of cells penetrating the basement membrane in the Transwell experiment and the wound healing rate in the scratch experiment were decreased (P<0.05). In KLE cells, knockdown of miR1290 reduced the expressions of EMT-related proteins including N-cadherin, Vimentin, Snail and Slug(P<0.05), and the expressions of PI3K and P-Akt/Akt (P<0.05), while there was no significant change in the expressions of Wnt and β-catenin (P>0.05). In Ishikawa cells, knockdown of miR1290 decreased the expressions of EMT-related proteins including N-cadherin, Snail and Slug, and the expressions of Wnt and β-catenin, increased the expression of E-cadherin (P<0.05), while there was no significant change in the expressions of PI3K and P-Akt/Akt (P>0.05). Conclusions: The expressions of miR1290 in endometrial cancer tissues are higher than that in the adjacent tissues and normal endometrial tissues. Knockdown of miR1290 expression can promote the proliferation of endometrial cancer cells, but inhibit cell invasion, migration and EMT ability through the PI3K/Akt and Wnt/β-catenin pathways.


Subject(s)
Cell Line, Tumor , Cell Movement , Cell Proliferation , Endometrial Neoplasms/genetics , Epithelial-Mesenchymal Transition , Female , Humans , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/metabolism , Wnt Signaling Pathway
9.
Chinese Critical Care Medicine ; (12): 325-328, 2022.
Article in Chinese | WPRIM | ID: wpr-931874

ABSTRACT

Cerebral ischemia/reperfusion (I/R) injury refers to an aggravated brain tissue damage caused by the restoration of blood supply after acute ischemia for a period of time. Its pathogenesis is complex, including oxidative stress, inflammatory response, and excitatory amino acid toxicity. The effective clinical treatments of cerebral I/R injury after ischemic stroke (IS) are limited. Nuclear factor E 2-related factor 2 (Nrf2), the most critical antioxidant transcription factor in cells, can coordinate multiple cytoprotective factors to inhibit oxidative stress. Since Nrf2 signaling pathway is considered to be one of the most important cellular defense mechanisms against oxidative stress, targeting Nrf2 intervention has become an attractive therapeutic strategy in the prevention and treatment of cerebral I/R injury. This review focuses on the structure, regulation and function of Nrf2 signaling pathway, as well as its activation and potential therapeutic targets in cerebral I/R injury. The important role and future potential of Nrf2 pathway in the pathogenesis of cerebral I/R injury were discussed.

10.
Article in Chinese | WPRIM | ID: wpr-930216

ABSTRACT

Objective:To determine the protective effect of fasudil on acute lung injury in septic mice.Methods:Forty-five 4-6-week-old male C57BL mice were randomly(random number) assigned to three groups ( n=15 each group): control group, lipopolysaccharide (LPS) group and Fasudil intervention group (FAS+LPS). Acute lung injury model of septic mice was established with an intraperitoneal injection and intratracheal infusion of LPS. The mice in the FAS+LPS group were injected with fasudil hydrochloride intraperitoneally 30 min before intraperitoneal LPS injection and 1 h after intratracheal LPS infusion, respectively. All mice were sacrificed at 4 h after modeling, and lung tissues were collected. Hematoxylin-eosin staining was preformed to observe the morphological changes in the lung tissue. The wet /dry weight (W/D) ratio, malondialdehyde (MDA) content and the activity of myeloperoxidase (MPO) in the lung tissues were detected. Caspase-3 expression was examined by immunohistochemical (IHC) staining. Western blot was employed to detect the expression of RhoA, ROCK1, endothelial nitric oxide synthase (eNOS), and p-eNOS. Results:Inflammatory cell infiltration and erythrocyte exudation were significantly reduced, and the degree of interstitial oedema and derangement of alveolar structure appeared in a decreasing degree after FAS intervention. Compared with the LPS group, the W/D ratio, MDA content, MPO activity and the expression of Caspase-3 in the FAS+LPS group were significantly reduced (all P<0.01). Meanwhile, the expression of RhoA and ROCK1 of the LPS group were obviously higher than those in the control group ( P<0.05), and p-eNOS was obviously lower than that in the control group ( P<0.05). Furthermore, the expression of RhoA and ROCK1 of the FAS+LPS group were obviously lower than those in the LPS group, and p-eNOS was obviously higher than that in the LPS group. There was no significant difference on the expression of eNOS among the three groups. Conclusions:Fasudil can alleviate the degree of inflammatory cell infiltration, reduce apoptosis in lung tissue, inhibit the RhoA/ROCK1 signaling activity, and promote the phosphorylation expression of eNOS in septic mice.

11.
Article in Chinese | WPRIM | ID: wpr-927897

ABSTRACT

Objective: To investigate the effects of long-chain noncoding RNA Linc00673 overexpression on proliferation and apoptosis of gastric cancer cells and its mechanisms. Methods: The recombinant lentivirus expressing plasmid pLVX-Linc00673 and the control empty plasmid pLVX-NC were packaged and amplified in 293T cells, and the recombinant lentivirus was transfected into gastric cancer cell line MGC-803 to establish a cell line stably overexpressing Linc00673. The expression of Linc00673 gene was detected by real-time fluorescence quantitative PCR. The growth and proliferation of cells were observed by MTT assay and clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. The expressions of cell cycle related regulatory genes were detected by qPCR. The expressions of key molecules in the PI3K/Akt signaling pathway and tumor proliferation related proteins were detected by Western blot. Results: The expressions of Linc00673 in gastric cancer cell line MGC-803, BGC-823 and AGS were significantly higher than that in normal gastric mucosa cell line GES-1 (P<0.05). MGC-803 cell line with stable overexpression of LINC00673 was established, and the expression level of LincC00673 was 200 times higher than that of the control empty carrier group. Overexpression of Linc00673 promoted proliferation of MGC-803 cells (P<0.05) and clone formation (P<0.05), inhibited cell apoptosis and affected the G1→S phase progression of cell cycle (P<0.01). Overexpression of Linc00673 could affect the expressions of cell cycle regulatory gene CCNG2, P19 and CDK1 in MGC-803. Western blot showed that Linc00673 overexpression not only promoted the expressions of the key molecule pAkt in PI3K / Akt signaling pathway and its downstream target NF-κ B and Bcl-2 protein, but also up regulated the expressions of tumor related factors β-catenin and EZH2 proteins. Conclusion: Overexpression of Linc00673 may promote proliferation and inhibit apoptosis of MGC-803 cells through PI3K/Akt signaling pathway.


Subject(s)
Apoptosis , Cell Line, Tumor , Cell Proliferation , Humans , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/genetics , Stomach Neoplasms/pathology
12.
China Pharmacy ; (12): 818-824, 2022.
Article in Chinese | WPRIM | ID: wpr-923187

ABSTRACT

OBJECTIVE To investigate the effect of Compound danshen tablet s o n improving the blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats. METHODS Sixty male SD rats were divided into normal group,model group ,simvastatin combined with (2S)-N-[N-(3,5-difluorophenylacetyl)-L-alanyl]-2-phenylglycine tert butyl (DAPT)group and low-dose ,medium-dose and high-dose groups of Compound danshen tablets ,with 10 rats in each group. Rats in the normal group received routine diet. The other 5 groups were intraperitoneally injected with 75% yolk emulsion 10 mL/kg, fasting and drinking freely. After 16 h,they were fed high-fat diet for 4 weeks. Simvastatin combined with DAPT group was given simvastatin 0.002 g/kg and DAPT 0.012 g/kg at the same time of modeling. The low-dose ,medium-dose and high-dose groups of Compound danshen tablets were given Compound danshen tablets 0.25,0.5 and 1 g/kg respectively at the same time of modeling , the normal group and model group were given equal volume of distilled water ,once a day ,for 4 weeks. The serum levels of total cholesterol(TC),triglyceride(TG),creatinine(Cr)and urea nitrogen (BUN)in serum were detected by biochemical method ; kidney coefficient of rats was calculated ;histopathological changes of rat kidney were observed by HE staining ,and the renal injury was scored according to the degree of renal tubular injury and glomerular sclerosis in renal cortex ;expression levels of Notch signal receptor 1(Notch 1),Notch signal ligand 1(Jagged1)and hairy division associated enhancer 1(Hes1)in kidney were detected by immunohistochemistry ;mRNA expressions of Notch 1,Jagged1 and Hes 1 in renal tissue were detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS Compared with normal group ,the serum levels of TG , TC,Cr and BUN were increased significantly in model group (P<0.05);renal coefficient increased significantly (P<0.05); pathological changes occurred in renal tissue ,and the scores of renal tubular injury and glomerular sclerosis increased significantly (P<0.05);protein and mRNA expressions of Notch1, Jagged1, Hes1 in renal tissue were increased significantly(P<0.05). Compared with model group ,serum levels of TG ,TC,Cr and BUN ,renal coefficient ,the scores of renal tubular injury and glomerular sclerosis ,protein and mRNA expression of Notch 1,Jagged1 and Hes 1 in renal tissue were all decreased in low-dose ,medium-dose and high-dose groups of Compound danshen tablets (P<0.05),and most indexes showed a dose-dependent trend ;the degree of renal lesions was reduced. CONCLUSIONS Compound danshen tablets possess obvious hypolipidemic effect ,and can protect the renal function of hyperlipidemia model rats by down-regulating Notch 1/Jagged1 signal pathway.

13.
China Pharmacy ; (12): 244-250, 2022.
Article in Chinese | WPRIM | ID: wpr-913119

ABSTRACT

3-iodothyronamine(T1AM)is an endog enous derivative of thyroid hormone. It can also be used as exogenous drug. It can play pharmacological effects such as reducing cardiac output and coronary flow ,slowing heart rate ,promoting lipolysis , reducing basic metabolism and improving learning and memory ability. Its regulatory effect on metabolism is similar to that of thyroxine,but regulatory effect on heart and thermogenic function is opposite to that of thyroxine. As a new chemical messenger , T1AM can exert different pharmacological effects through a variety of receptors and signal pathways. This review summarizes the research progress of various pharmacological effects and mechanisms of exogenous T 1AM,in order to provide new therapeutic drugs of cardiovascular ,metabolic diseases and nervous system diseases.

14.
Article in Chinese | WPRIM | ID: wpr-847147

ABSTRACT

BACKGROUND: It is generally known that PI3K/Akt/mTOR, MAPK, Jak/Stat, NF-κB and Notch signaling pathways play important roles in cell proliferation and differentiation, gene transcription, and immune inflammation. Hypoxia inducible factor-1α (HIF-1α) plays a crucial role in mediating the hypoxia signaling pathway and acts as a core factor in the hypoxic reaction process. OBJECTIVE: To summarize the relationship between HIF-1α and hypoxia signaling pathways, providing new ideas for the research and treatment of altitude diseases. METHODS: English literatures published during 2000-2019 were retrieved from PubMed and Medline. Chinese literatures published during 2011-2019 were retrieved from CNKI and WanFang databases. Search terms were “hypoxia inducible factor 1α, signal pathway” in English and Chinese, respectively. RESULTS AND CONCLUSION: During the occurrence of hypoxic-related diseases (inflammation, tumor, cardiovascular and cerebrovascular diseases) and altitude disease, the expression levels of HIF-1 and the key factors of these signaling pathways can change to varying degrees. HIF-1 is closely related to these signaling pathway under the hypoxic conditions, regulates molecular expression in these signaling pathways, or are regulated by these signaling pathways to increase or decrease, in response to the changes in the body under hypoxia conditions.

15.
Article in Chinese | WPRIM | ID: wpr-906134

ABSTRACT

Breast cancer is a malignant tumor with a variety of complex mechanisms. Current researchers generally believe that its cause may be related to living environment, daily mood, heredity, behavior habits, et al, but its specific pathogenesis has not yet been studied clearly. With the rapid increase in the number of breast cancer patients worldwide, the clinical treatment methods in most countries have also been continuously improved. At present, the methods such as surgery, radiotherapy and chemotherapy, immunotherapy, and endocrine therapy are mainly adopted in clinical practice. These methods have increased the survival rate of patients, but still with the possibility of recurrence and metastasis, and there are obvious sequelae. Some postoperative patients also experience psychological pressure and burden, which would greatly affect the quality of life. A large number of experiments and clinical experience have proved that due to its unique advantages, traditional Chinese medicine(TCM) has serially improved its current status in the extensive treatment of breast cancer. No matter in post-operative rehabilitation or in the process of co-radiation and chemotherapy, it has played an increasingly prominent role. TCM can improve human immunity, regulate the body's environment, effectively prevent the recurrence and metastasis of breast cancer, improve postoperative recovery, reduce the complications of radiation treatment and iatrochemistry, expressively improve the quality of life of patients, and prolong the survival time of patients. In recent years, the effectiveness of TCM in the treatment of breast cancer has brought more and more great trust from the patients in TCM, and most patients are willing to actively receive TCM treatment, so the mechanisms and approaches of TCM intervention in the treatment of breast cancer still need further research and exploration by our medical workers. By consulting the latest domestic and foreign literature, we reviewed the research progress on five approaches of TCM intervention in the treatment of breast cancer, including signaling pathways, immunotherapy, endocrine therapy, chemotherapy, and radiotherapy. Signal pathway intervention was explained mainly based on wingless-type MMTV integration site family members(Wnt)signaling pathway , B-cell lymphoma-2 (Bcl-2)-associated X protein(Bax)/Bcl-2/cysteinyl aspartate specific proteinase-3(Caspase-3)signaling pathway, phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/mammalian target of rapamycin(mTOR)signaling pathway, a highly conserved signal transduction pathway to regulate cell-cell communication(Notch)signaling pathway, mitogen-activated proteinkinase (MAPK) signaling pathway, etc. This article aims to provide reference for the treatment of breast cancer by Chinese medicine.

16.
Article in Chinese | WPRIM | ID: wpr-906020

ABSTRACT

Objective:To observe the effect of modified Guilu Erxianjiao decoction combined with cisplatin on the immune function, resistance-related genes and interleukin-7(IL-7)-mediated Wnt/<italic>β</italic>-serial protein(<italic>β</italic>-catenin)signaling pathway in Lewis lung cancer mice by establishing a mouse model of Lewis lung cancer with deficiency of both Qi and Yin. And the anti-cancer mechanism of modified Guilu Erxianjiao decoction was clarified, so as to provide a basis for its clinical application. Method:A Lewis lung cancer mouse model (type of deficiency of both Qi and Yin) was established. Mice were divided into a normal group (no modeling), a model group (saline solution), a cisplatin group (cisplatin, 2 mg·kg<sup>-1</sup>), a traditional Chinese medicine (TCM) group (modified Guilu Erxianjiao decoction, 19.63 g·kg<sup>-1</sup>·d<sup>-1</sup>), and a combined group (modified Guilu Erxianjiao decoction, 19.63 g·kg<sup>-1</sup>·d<sup>-1</sup> + cisplatin, 2 mg·kg<sup>-1</sup>). The 10 mice in each group were administered separately for 21 days of intervention. The general conditions and organ indexes of mice were observed, and tumor inhibition rate was calculated. CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cell (CD4<sup>+</sup>CD25<sup>+</sup> Treg) were detected by flow cytometry, the IL-7 level of cytokines in serum was detected by enzyme linked immunosorbent assay(ELISA), and real-time quantitative polymerase chain reaction(Real-time PCR) was used to detect the gene expression level of drug resistance-related genes P-glycoprotein(P-gp), and multidrug resistance protein1(MRP1)in tumor tissues. The protein expression of Wnt/<italic>β</italic>-serial protein(<italic>β</italic>-catenin)signaling pathway in tumor tissues were detected by Western blot. Result:In the TCM group and the combined group, the food intake increased, the mental state was better, the response was sensitive, and the body weight increased. Compared with the cisplatin group, the thymus index and spleen index in the combined group were significantly increased (<italic>P</italic><0.01), and the tumor inhibition rate of the combined group was significantly increased (<italic>P</italic><0.01). Compared with the cisplatin group, the percentage of CD4<sup>+</sup>CD25<sup>+</sup>Treg/CD4<sup>+</sup> in the TCM group and the combined group was significantly reduced (<italic>P</italic><0.01), and IL-7 in the TCM group and the combined group was significantly increased (<italic>P</italic><0.01). Compared with the cisplatin group, the expressions of P-gp and MRP1 genes in the TCM group and the combined group were significantly reduced (<italic>P</italic><0.05, <italic>P</italic><0.01), and the protein expressions of secretory glycoprotein1(Wnt1)and <italic>β</italic>-serial protein(<italic>β</italic>-catenin)in the TCM group and the combined group were significantly reduced (<italic>P</italic><0.01). Conclusion:The combined use of modified Guilu Erxianjiao decoction and cisplatin can significantly inhibit the growth of tumors in mice with Lewis lung cancer, and its mechanism of action may be related to the efficacy of m odified Guilu Erxianjiao decoction in relieving the body's immunosuppressive state, promoting the body to produce IL-7, regulating IL-7-mediated Wnt/<italic>β</italic>-catenin signaling pathway and reducing the expression of resistance-related genes in lung cancer tissues.

17.
Article in Chinese | WPRIM | ID: wpr-905831

ABSTRACT

Objective:To investigate the mechanism of Jianzhong Bushen Xiaozheng decoction in regulating the effect of miRNA139 on Wnt/<italic>β</italic>-catenin signaling pathway for renal interstitial fibrosis. Method:The 120 mice were randomly divided into sham operation group, unilateral ureteral obstruction (UUO) group, Jianzhong Bushen Xiaozheng decoction low, middle, high dose group, and Niaoduqing group. The UUO animal model was established to observe the morphological changes in mice. Intragastic administration was started from day 3 after modeling. The sham operation group and UUO group received the same amount of distilled water every day. The low, medium and high-dose groups received Jianzhong Bushen Xiaozheng decoction solution at 6,12,24 g·kg<sup>-1</sup>·d<sup>-1</sup> respectively. The Niaoduqing group received 6.2 g·kg<sup>-1</sup>·d<sup>-1</sup> Niaoduqing granule solution. After 14 d and 21 d, 28 d , the morphological changes, general signs and renal interstitial fibrosis index of the obstructed side were observed, hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathological changes of renal tissue. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) method was used to detect the miRNA-139 expression in renal tissue volume, Western blot was used to detect expression of beta serial proteins (<italic>β</italic>-catenin) and fibrinolytic enzyme activators inhibitor-1 (PAI-1) in renal tissues, and immunohistochemical assay was used for detection of matrix metalloproteinases-7 (MMP-7) protein expression at the obstruction side. Result:After 14, 21 and 28 days, the expression levels of <italic>β</italic>-catenin and PAI-1 in UUO group were higher than those in sham operation group(<italic>P</italic><0.05),while the expression levels of miRNA139 and MMP-7 protein were lower than those of sham operation group (<italic>P</italic><0.05). The expression levels of <italic>β</italic>-catenin and PAI-1 proteins in mice after treatment in Niaoduqing group and the traditional Chinese medicine groups were lower than those in the UUO group(<italic>P</italic><0.05), the expression of miRNA139 and MMP-7 proteins increased(<italic>P</italic><0.05), and the efficacy of high-dose Jianzhong Bushen Xiaozheng decoction group was better than that of other dosage groups or Niaoduqing group(<italic>P</italic><0.05). Conclusion:Jianzhong Bushen Xiaozheng decoction may regulate miRNA139 to mediate the process of renal interstitial fibrosis through the Wnt/ <italic>β</italic>-catenin pathway and delay the development of renal interstitial fibrosis to improve renal function.

18.
Article in Chinese | WPRIM | ID: wpr-905829

ABSTRACT

Objective:The purpose of this article was to observe the effect of modified Shengjiangsan on podocyte apoptosis in membranous nephropathy (MN) rats, to explore the molecular mechanism of its treatment of MN and to provide experimental basis for its clinical application. Method:The MN rat model was established by injection of cationic bovine serum albumin into the tail vein of rats. The successfully modeled rats were then randomly divided into model group (equal volume of normal saline), modified Shengjiangsan group (27.3 g·kg<sup>-1</sup>) and benazepril group (10 mg·kg<sup>-1</sup>), with corresponding drug dosage once a day for 4 weeks of continuous intervention. After drug administration, the 24-hour urine protein (UTP) was detected. Real time fluorescent quantitative polymerase chain reaction (Real-time PCR) and immunohistochemical (IHC) methods were used to detect Podocalyxin, Nephrin, Podocin, Synaptopodin mRNA and protein expression levels in rat kidney tissue. terninal-deoxynucleoitidyl transferase medsated nick and labeling (TUNEL) method was used to detect cell apoptosis rate in rat kidney tissue, and Western blot was used to detect Notch1, Hes1, B lymphoblastoma-2 (Bcl-2) associated X protein (Bax), and Bcl-2 protein expression levels in rat kidney tissue. Result:Compared with the normal group, UTP in the model group increased significantly, renal tissue cell apoptosis increased significantly, podocyte marker proteins podocalyxin, Nephrin, Podocin, Synaptopodin mRNA and protein expression levels decreased significantly, and Notch1, Hes1, Bax protein expression increased significantly, and Bcl-2 protein expression was significantly reduced(<italic>P</italic><0.05). Compared with the model group, UTP levels in MN rats were significantly reduced in modified Shengjiangsan and benazepril groups, with reduced rate of renal cell apoptosis, increased mRNA and protein expression levels of podocalyxin, Nephrin, Podocin, and Synaptopodin in renal tissue, decreased Notch1, Hes1, Bax protein expression, and increased Bcl-2 protein expression(<italic>P</italic><0.05). Conclusion:Modified Shengjiangsan can inhibit the Notch signaling pathway, reduce the apoptosis of rat kidney tissue podocytes, and reduce the kidney injury of MN rats.

19.
Article in Chinese | WPRIM | ID: wpr-905065

ABSTRACT

Objective:To explore the effect of Huangjingwan (HW) on the expressions of Wnt/β-catenin signal pathway-associated proteins in the hippocampus of mice with Alzheimer's disease (AD) induced by D-galactose and okadaic acid with learning and memory disorders, as well as its mechanism. Method:After subcutaneous injection with 1.0% D-galactose (0.14 g·kg-1·d-1) into the back and neck of mice for 4 weeks, the right ventricle of mice was injected with 2 μL(75 ng) of okadaic acid for one time to make AD model, and the successfully modeled AD mice were selected by Morris water maze. Then, the selected AD mice were randomly divided into AD model group, memantine group (1.3×10-3 g·kg-1·d-1) and HW group (2.5 g·kg-1·d-1). In addition, the sham model control group and the normal control group were set up. At the same time, 2 μL normal saline was injected into the right ventricle of mouse in the sham model control group as the modeling control. Two weeks after molding, the mice in the two experimental drug groups were given the corresponding dose of the experimental drug by gavage for 4 weeks. In addition, after 2 weeks of AD modeling, mice in sham model control group and AD model group were intragastrically administrated with the same amount of normal saline daily for 4 weeks. There was no special treatment in the normal control group. At the end of gavage, the shuttle experiment was performed to detect the differences in learning and memory levels of mice in each group. The changes of β-catenin and GSK-3β positive neurons in CA1 area of hippocampus in each group were tested by immunohistochemistry. Quantitative real-time polymerase chain reaction (Real-time PCR) was used to measure the mRNA expressions of GSK-3β, β-catenin and CyclinD1 in hippocampus of mice in each group. The Western blot was used to detect the expressions of total GSK-3β (t-GSK-3β), phosphorylation of GSK-3β at Ser9 (p-Ser9-GSK-3β), phosphorylation of GSK-3β at Tyr216 (p-Tyr216-GSK-3β), total β-catenin (t-β-catenin), phosphorylation of β-catenin (p-β-catenin) and CyclinD1 proteins in hippocampus of mice in each group. Result:Compared with the normal control group, mice in AD model group showed an obvious dementia state, which was characterized by significant declines in learning and memory ability, the number of β-catenin immunoreactive neurons in hippocampal CA1 area, the mRNA and protein expressions of t-β-catenin and CyclinD1, the protein expressions of p-Ser9-GSK-3β, and the ratio of p-Ser9-GSK-3β/t-GSK-3β and p-Tyr216-GSK-3β/t-GSK-3β in hippocampal region (P<0.01), and significant increases in the number of GSK-3β immunoreactive neurons in hippocampal CA1 area, the mRNA and protein expressions of t-GSK-3β, the protein expressions of p-Tyr216-GSK-3β and p-β-catenin, the ratio of p-β-catenin/t-β-catenin in hippocampal region (P<0.01 respectively). Compared with the AD model group, the dementia symptoms of mice in HW group were significantly alleviated, and the number of β-catenin immunoreactive neurons in hippocampal CA1 area, the mRNA and protein expressions of t-β-catenin and CyclinD1, the protein level of p-Ser9-GSK-3β, the ratio of p-Ser9-GSK-3β/t-GSK-3β in hippocampal region were all significantly increased (P<0.01 respectively), whereas the number of GSK-3β immunoreactive neurons in hippocampal CA1 area, the mRNA and protein expressions of t-GSK-3β, the proteins expressions of p-Tyr216-GSK-3β and p-β-catenin, the ratio of p-β-catenin/t-β-catenin in hippocampal region were all significantly decreased (P<0.01 respectively), but the ratio of p-Tyr216-GSK-3β/t-GSK-3β has no significant statistical difference. Conclusion:HW shows the role of AD treatment, which can down-regulate the expression of GSK-3β in the hippocampus of AD mice and reduce its protein activity, and up-regulate the expression of β-catenin as well as increase its protein activity, so as to enhance the expression of downstream CyclinD1 and promote the transcription of the target genes. Its mechanism may be related to the activation of Wnt/β-catenin signal pathway.

20.
Article in Chinese | WPRIM | ID: wpr-905064

ABSTRACT

Objective:To treat mice with Alzheimer's disease (AD) with β-catenin RNA interference (RNAi) Huangjingwan (HW), so as to explore the neuroprotective signal mechanism of its prevention and treatment of AD. Method:A total of 81 male Kunming mice were randomly divided into normal control group, sham model control group, AD model group, Donepezil group, HW+scrambled group, HW+RNAi group, HW group, with 8 mice in each of donepezil group and HW group, and 13 mice in each of other groups. The AD models were established through injection with D-galactose and scopolamine in the last 5 groups for 5 consecutive weeks. On the 1st day of the 4th week after modeling, 0.75 μL PEI-LMW/β-catenin siRNAs nano-complex was injected into the right lateral ventricle of each mouse in for one time to treat with β-catenin RNAi in mice brains of the HW+RNAi group. The 0.75 μL complex was injected into the right lateral ventricle of each mouse for one time as for β-catenin interference control of the HW+scrambled group. The 0.75 μL normal saline was injected into the right lateral ventricle of each mouse in one time of the sham control group. Two weeks after intracerebroventricular injection, β-catenin RNAi was confirmed to be successful, and Donepezil (6.5×10-4 g·kg-1) was intragastrically administered to each mouse of donepezil group. HW (2.5 g·kg-1) was intragastrically administered to each mouse of HW group, HW+RNAi group and HW+scrambled group. Normal saline (0.5 mL·d-1) was intragastrically administered to each mouse of the sham control group. All gastric perfusion lasted for 4 weeks. At the end of gavage, the difference in learning and memory ability of mice was evaluated by platform jumping test. Nissl staining was used to count the number of neurons in s1Tr area of cerebral cortex and CA1 and CA3 areas of hippocampus of each mouse in each group. The mRNA expressions of Wnt1, DVL2, GSK-3β, β-catenin and CyclinD1 in mice brain of each group were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Western blot was used to detect the expressions of Wnt1, DVL2, GSK-3β, β-catenin and CyclinD1 in mice brain of each group. Result:The expression of β-catenin could be significantly inhibited through the injection with PEI-LMW/β-catenin siRNAs nano-complex into the lateral ventricle of AD mice, and nearly no β-catenin expression could be detected, which successfully achieved gene silencing. Compared with the normal control group, mice in AD model group showed that the learning and memory performance decreased significantly, the number of jumping errors increased (P<0.01), the number of neurons in S1Tr area of cerebral cortex and CA1, CA3 areas of hippocampus decreased significantly (P<0.01), the mRNA and protein expressions of Wnt1, DVL2, β-catenin, CyclinD1 in brain decreased significantly (P<0.01), while the mRNA and protein expressions of GSK-3β increased significantly (P<0.01). Compared with the AD model group, mice in HW group showed that the learning and memory performance increased significantly, the number of jumping errors decreased, the number of neurons in S1Tr area of cerebral cortex and CA1, CA3 areas of hippocampus increased significantly, the mRNA and protein expressions of Wnt1, DVL2, β-catenin, CyclinD1 in brain increased significantly, while the mRNA and protein expression of GSK-3β decreased significantly (P<0.01). Compared with the HW group, mice in HW+RNAi group showed that the learning and memory performance decreased significantly, the number of jumping errors increased significantly (P<0.01), the number of neurons in S1Tr area of cerebral cortex and CA1, CA3 areas of hippocampus decreased significantly (P<0.01), there was no significant change in mRNA and protein expressions of Wnt1, DVL2, GSK-3β in the brain, and the mRNA and protein expressions of β-catenin, CyclinD1 decreased significantly (P<0.01). Conclusion:HW can treat and prevent AD by activating Wnt/β-catenin signal pathway.

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