Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 542
Filter
1.
Article in Chinese | WPRIM | ID: wpr-911362

ABSTRACT

Objective:To explore the role of transgelin(TAGLN) in the occurrence and development of papillary thyroid carcinoma (PTC) and its possible signal pathway.Methods:One hundred cases of PTC tissues and corresponding paracancerous normal thyroid tissues were collected. Realtime quantitative PCR (RT-qPCR), Western blotting, and immunohistochemistry were used to analyze the expression of TAGLN in PTC tissues and corresponding paracancerous normal thyroid tissues. PTC cells were transfected with plasmid and shRNA lentivirus vector respectively to up-regulate or down-regulate the expression of TAGLN in order to detect the effects of them on the proliferation, invasion, and migration by cell proliferation assay(cell counting kit-8, CCK-8)and cell invasion and migration assays (Transwell). The effects of TAGLN on mitogen-activated protein kinase (MAPK)/extracellular-signal regulating kinase (ERK) signal pathway was detected with Western blotting.Results:RT-qPCR showed that there was no difference in the expression of TAGLN mRNA between PTC and corresponding paracancerous normal thyroid tissues ( P>0.05); Western blotting demonstrated that the expression of TAGLN protein in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues ( P<0.01). Immunohistochemical results revealed that the expression of TAGLN in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues. Overexpression of TAGLN inhibited the proliferation, invasion, and migration of PTC cells ( P<0.01), but knockdown of TAGLN promoted the proliferation, invasion, and migration of PTC cells ( P<0.01). Overexpression of TAGLN decreased the expression of phosphorylated ERK ( P<0.05), whereas silencing TAGLN increased phosphorylated ERK level in PTC cells( P<0.01). Conclusion:The expression of TAGLN in PTC is significantly decreased. It is related to the occurrence and development of PTC, and its mechanism may be related to MAPK/ERK signal pathway.

2.
Article in Chinese | WPRIM | ID: wpr-909591

ABSTRACT

OBJECTIVE To study the effect of polygonatum polysaccharide on zebrafish with Alzheimer disease. METHODS Zebrafish were trained in T maze for 7 d. The 40 zebrafish successfully trained were divided into 4 groups:blank group, model group, positive group and polygonatum polysaccharide group. Model group, positive group and polygonatum polysaccharide group were put in AlCl3100μg·L-1 for 6 d. The positive group was exposed to Huperzine A solution 4μg·L-1, and the polygonatum polysaccharide group was exposed to polygonatum polysaccharide solution 6 g·L-1 for 6 d. The model group was not treated, and the blank group was not treated. Each stage of zebrafish was recorded by video, and the time of each group in the EC region was analyzed. After administration, the brain tissue was taken out and the expression of N-cadherin, P38 and p-P38 protein factors was determined by Western blotting. RESULTS In behavior, the analysis of the time spent in the EC area, the blank group, the positive group and the polygonatum polysac?charide group were compared with the model group, respectively, there were statistically significant differences (P<0.05). At the protein level, compared with the model group, the P38 and p-P38 proteins in the positive group and the polygonatum polysaccharide group were down-regulated, while the N-cadherin protein was up-regulated, with statistical difference (P<0.05). CONCLUSION Polygonatum polysaccharide can improve the learning and memory ability of zebrafish with Alzheimer disease by up regulating the protein level of N-cadherin and hindering P38 phosphorylation.

3.
Article in Chinese | WPRIM | ID: wpr-909568

ABSTRACT

OBJECTIVE The pathological characteristics of nonalcoholic steatohepatitis (NASH) include liver steato?sis, inflammation, and fibrosis. Fibrosis is the most severe and significant pathological feature in NASH. Effective drug treatment could reverse early liver fibrosis and is of significance to prevent NASH from progressing into cirrhosis and liver cancer. Identification of drug targets for NASH treatment has been an active research area and is essential for the development of anti-NASH medications. Naringenin (NGN) is a flavonoid compound rich in citrus fruits. Our preliminary data demonstrated that NGN reduced diet-induced lipid accumulation and inflammation in the mouse liver, but whether NGN can attenuate liver fibrosis of NASH is not known. METHODS To study the effect of NGN on NASH fibrosis. WT mice were fed with high fat diet (HFD) and injected intraperitoneally 20% carbon tetrachloride at the same time for 8 weeks to induce NASH, and NGN was administrated by gavage in the meantime. In vitro, LO2 cells and LX2 cells were stimulated by oleic acid (OA) combined with lipopolysaccharide (LPS), respectively. RESULTS Treating the WT mice with NGN 100 mg · kg-1 · d-1 significantly attenuated hepatic lipid accumulation, hepatic fibrosis, plasma ALT and AST levels, inhibited protein expression of p-ERK, p-FoxO3a in the mouse livers. In vitro, on OA and LPS stimulated LO2 or LX2 cells, NGN significantly promoted apoptosis of activated hepatic stellate cells while inhibited apoptosis of hepatocytes. Mechanism study indicated that NGN inhibited MAPK pathway and promoted activation of FoxO3a, conse?quently promoted apoptosis of the activated LX2 cells and inhibited liver fibrosis. CONCLUSION NGN preventes NASH fibrosis via regulating MAPK/FoxO3a pathway, thus promoting apoptosis of the activated hepatic stellate cells.

4.
Article in Chinese | WPRIM | ID: wpr-907747

ABSTRACT

Objective:To study the effect of levosimendan on coronary microembolization (CME)-induced myocardial injury and LOX-1/p38MAPK pathway.Methods:Microspheres were injected into coronary anterior descending branch to construct swine CME model, swine was given levosimendan by continuous intravenous drip for 24 h before modeling, and myocardial-specific overexpression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) was achieved through coronary artery injection of adeno-associated virus (AAVs) at 2 weeks before modeling. Then, echocardiography was used to measure cardiac function; HE staining and HBFP staining were used to observe the pathological changes of myocardium and myocardial microinfarction area, respectively; ELISA was used to detect the serum level of cTnI; TUNLE staining was used to detect cardiomyocyte apoptotic index; the LOX-1, Bax, caspase-3 p12, Bcl-2, and p-p38 MAPK protein in myocardial tissue was observed by immunofluorescence method.Results:Compared to the sham group, the LVEF, LVFS, and CO value in the CME group were decreased, while the LVEDd value was increased significantly (all P<0.05); the area of myocardial micro-infarction, serum cTnI level and cardiomyocyte apoptotic rate in the CME group were increased significantly (all P<0.05); the protein levels of Bax, caspase-3 p12, LOX-1, and p-p38 MAPK were increased significantly, while the Bcl-2 level was decreased significantly ( P<0.05). Levosimendan pretreatment significantly improved cardiac dysfunction, reduced the area of myocardial micro-infarction and serum cTnI level, alleviated cardiomyocyte apoptosis, and significantly reduced the LOX-1 and p-p38 MAPK protein expression levels following CME (all P<0.05); while pretreatment with levosimendan and LOX-1 overexpression AAVs simultaneously abolished the effects of pretreatment with levosimendan alone (all P<0.05). Conclusion:Levosimendan alleviates CME-induced myocardial injury through inhibiting cardiomyocyte apoptosis mediated by LOX-1/p38 MAPK signaling pathway.

5.
Article in Chinese | WPRIM | ID: wpr-906420

ABSTRACT

Objective:To explore the effects and mechanism of Chinese classical prescription Dahuang Zhechongwan on silicosis in mice. Method:Thirty-six male Kunming mice of SPF grade were randomized into the normal control group, model control group, tetrandrine (Tet, 0.039 mg·kg<sup>-1</sup>) group, as well as high- (1.560 g·kg<sup>-1</sup>), medium- (0.780 g·kg<sup>-1</sup>), and low-dose (0.390 g·kg<sup>-1</sup>) Dahuang Zhechongwan groups, with six mice in each group. Mice in all groups except for the normal control group underwent static inhalation of silica (SiO<sub>2</sub>) dust for 40 consecutive days to induce fibrosis. After 28 days of intervention with corresponding drugs, the mice were sacrificed to collect the serum and lung tissues, with the former used for detecting tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), interleukin-1<italic>β </italic>(IL-1<italic>β</italic>), IL-6, and hydroxyproline (HYP) levels by enzyme-linked immunosorbent assay (ELISA) and the latter for observing the pathological changes. Meanwhile, the protein and mRNA expression levels of p38 mitogen-activated protein kinase (p38 MAPK), nuclear transcription factor-<italic>κ</italic>B (NF-<italic>κ</italic>B), transforming growth factor-<italic>β</italic><sub>1</sub> (TGF-<italic>β</italic><sub>1</sub>), <italic>α</italic>-smooth muscle actin (<italic>α</italic>-SMA), Smad2, Smad3, and Smad7 in the lung tissues were determined by Western blot and real-time polymerase chain reaction (Real-time PCR). Result:Compared with the normal group, the contents of TNF-<italic>α</italic>, IL-1<italic>β</italic>, IL-6 and HYP in the model group were significantly increased, the difference was statistically significant(<italic>P</italic><0.05,<italic>P</italic><0.01); compared with the model group, the high-dose group of Dahuang Zhechongwan could significantly reduce the contents of TNF-<italic>α</italic>, IL-6 and HYP in the serum of mice(<italic>P</italic><0.05, <italic>P</italic><0.01), indicating that Dahuang Zhechongwan could reduce the lung inflammation of silicosis mice. At the same time, compared with the normal group, the protein and mRNA expression levels of p38 MAPK, NF-<italic>κ</italic>B p65, TGF-<italic>β</italic><sub>1</sub>, <italic>α</italic>-SMA, Smad2 and Smad3 in the model group were significantly increased(<italic>P</italic><0.05,<italic>P</italic><0.01), while the protein and mRNA expression levels of Smad7 were significantly decreased(<italic>P</italic><0.01); compared with the model group, the protein and mRNA expression levels of p38 MAPK, NF-<italic>κ</italic>B p65, TGF-<italic>β</italic><sub>1</sub>, <italic>α</italic>-SMA, Smad2 and Smad3 in the high-dose Dahuang Zhechongwan group were significantly increased the protein and mRNA expression levels were significantly decreased(<italic>P</italic><0.05,<italic>P</italic><0.01), while Smad7 protein and mRNA expression levels were significantly increased(<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:Dahuang Zhechongwan ameliorates the alveolar inflammation, extracellular matrix (ECM) deposition, and fibrosis in mice with silicosis possibly by regulating the p38 MAPK/NF-<italic>κ</italic>B/TGF-<italic>β</italic><sub>1</sub> pathway.

6.
Article in Chinese | WPRIM | ID: wpr-906326

ABSTRACT

Objective:To investigate the inhibitory effect of Sangsuyin on airway inflammation in asthmatic rats by regulating the Toll-like receptor 4 (TLR4) pathway. Method:Forty-eight SD rats were randomly divided into a normal group (<italic>n</italic>=8) and an experimental group (<italic>n</italic>=40). Asthma model was induced in the rats of the experimental group which were further divided into the following five groups according to a random number table: a model group, a dexamethasone group (0.005 g·kg<sup>-1</sup>),and low- (2.1 g·kg<sup>-1</sup>), medium- (4.2 g·kg<sup>-1</sup>), and high-dose (8.4 g·kg<sup>-1</sup>) Sangsuyin groups. The drugs were all dissolved in normal saline at 0.01 L·kg<sup>-1</sup>. The rats in the model group and the normal group received normal saline (<italic>ig</italic>) at 0.01 L·kg<sup>-1</sup>. The drug treatment was carried out once per day, for a total of 7 days. The grades of allergic reactions were compared among the groups after intervention. The levels of interleukin-1<italic>β</italic> (IL-1<italic>β</italic>),tumor necrosis factor-<italic>α</italic>(TNF-<italic>α</italic>), and interferon-<italic>γ</italic>(IFN-<italic>γ</italic>) in serum and bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissues,and the inflammatory cell infiltration scores of lung tissues were compared. The mRNA expression of TLR4 and nuclear factor-<italic>κ</italic>B (NF-<italic>κ</italic>B) was detected by quantitative real-time fluorescence-based reverse-transcription polymerase chain reaction (Real-time PCR). The expression of TLR4,NF-<italic>κ</italic>B, and the level of phosphorylated NF-<italic>κ</italic>B (p-NF-<italic>κ</italic>B) were detected by Western blot. Result:The success rate of modeling was 95.00%. Compared with the normal group, the model group showed a higher grade of allergic reaction and more severe pathological changes of lung tissues,and the groups with drug intervention exhibited relieved conditions. The levels of IL-1<italic>β</italic> and TNF-<italic>α</italic> in the serum and BALF were higher in the model group than in the normal group,and lower in the groups with drug intervention than in the model group (<italic>P</italic><0.01). The level of IFN-<italic>γ</italic> in the serum and BALF was lower in the model group than in the normal group,and higher in the groups with drug intervention than in the model group (<italic>P</italic><0.05,<italic>P</italic><0.01). The inflammatory cell infiltration score,mRNA and protein expression of TLR4 and NF-<italic>κ</italic>B,and the mRNA level of p-NF-<italic>κ</italic>B were higher in the model group than in the normal group,and lower in the groups with drug intervention than in the model group (<italic>P</italic><0.01). Conclusion:Sangsuyin could inhibit allergic reactions,lung tissue lesions, and airway inflammation in asthmatic rats. It is speculated that this effect is achieved by inhibiting the TLR4 pathway,down-regulating the mRNA and protein expression of TLR4 and NF-<italic>κ</italic>B,and reducing the level of p-NF-<italic>κ</italic>B.angsuyin can inhibit allergic reaction,lung tissue lesions and airway inflammation in asthmatic rats. It is speculated that this effect is achieved by inhibiting TLR4 pathway,down regulating the mRNA and protein expression of TLR4,NF-<italic>κ</italic>B,and reducing the levels of p-NF-<italic>κ</italic>B.

7.
Article in Chinese | WPRIM | ID: wpr-906282

ABSTRACT

Objective:To explore the molecular mechanism of Jiangtang Xiaozhi tablets (JTXZT) in the treatment of non-alcoholic fatty liver disease (NAFLD) by means of network pharmacology and molecular docking. Method:With the help of traditional Chinese medicine (TCM) Systems Pharmacology Database and Analysis Platform (TCMSP), TCMs Integrated Database (TCMID), Encyclopedia of TCM (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of TCM (BATMAN-TCM), the chemical compositions of medicinal materials in JTXZT were obtained, the compound targets were predicted in SwissTargetPrediction database and STITCH database. The targets of NAFLD were searched by The Human Gene Database (GeneCards), Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD) and DisGeNET, and intersection analysis was performed with the targets of the active ingredients to obtain the targets of JTXZT for treatment of NAFLD. Based on STRING 11.0 database, the protein-protein interaction (PPI) network of therapeutic targets was constructed, and the enrichment analysis of therapeutic targets was carried out by DAVID 6.8. Finally, the interaction characteristics of key components and core therapeutic targets of JTXZT for treatment of NAFLD were verified based on molecular docking. Result:The key components of JTXZT for treatment of NAFLD were quercetin, luteolin, kaempferol, berberine, isorhamnetin, betulinic acid, oleanolic acid, ursolic acid. formononetin and hexitol, and the core targets of JTXZT for treatment of NAFLD were mitogen-activated protein kinase 1 (MAPK1), Jun proto-oncogene, activator protein-1 (AP-1) transcription factor subunit (JUN), MAPK3, protein kinase B1 (AKT1 or Akt1), tumor protein p53 (TP53), E1A binding protein p300 (EP300), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), tumor necrosis factor (TNF),amyloid beta precursor protein (APP) and cytochrome P450 family 2 subfamily E member 1 (CYP2E1). Biological function and pathway enrichment analysis showed that JTXZT mainly through xenobiotic metabolic process, oxidation-reduction process, cholesterol metabolic process and other biological processes, regulating phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, MAPK signaling pathway, NAFLD and insulin signaling pathway to play a role in the treatment of NAFLD. The results of molecular docking showed that the active components of JTXZT had a good affinity with the core targets of JTXZT for the treatment of NAFLD. Conclusion:JTXZT treats NAFLD through multiple active components, multiple key targets and multiple action pathways.

8.
Article in Chinese | WPRIM | ID: wpr-906126

ABSTRACT

Objective:To investigate the protective effect of quercetin (Qu) on articular cartilage of knee osteoarthritis and its mechanism by inhibiting p38 mitogen activated protein kinase (MAPK) signaling pathway. Method:Through the network pharmacology technology,we scientifically predicted and analyzed the target factors and signal pathways of Qu in the protection of articular cartilage in patients with osteoarthritis. We selected a prediction pathway closely related to osteoarthritis and validated it by cell experiment <italic>in vitro</italic>. The best intervention concentration of the drug was selected by cell counting kit-8 (CCK-8) method. The osteoarthritis and its closely related inflammatory factors interleukin(IL)-1<italic>β</italic> and tumor necrosis factor(TNF)-<italic>α</italic> were detected by enzyme linked immunosorbent assay(ELISA). The expression of related mRNA and protein in p38 signal pathway after Qu intervention were detected by quantitative real time polymerase chain reaction(Real-time PCR) and Western blot. Result:It was predicted that MAPK signal pathway was closely related to osteoarthritis by network pharmacology,and p38 MAPK pathway,which was most closely related to osteoarthritis,was selected for study. The results showed that 100 μmol·L<sup>-1</sup> Qu had the most obvious effect in decreasing the expression of related inflammatory factors,inhibited the expression of p38,phosphorylated(p)-p38,matrix metalloproteinase-13(MMP-13),A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs-4(ADAMTS-4) in the pathway,and promoted the expression of CollagenⅡ. Conclusion:Qu could decrease the expression of cartilage inflammatory factors in the prevention and treatment of osteoarthritis,and the effect can be well developed by intervening and inhibiting p38 MAPK pathway related factor expression level. All the results show that Qu can decrease osteoarthritis inflammatory factors and protect articular cartilage in patients with osteoarthritis.

9.
Article in Chinese | WPRIM | ID: wpr-906050

ABSTRACT

Objective:To explore the effects of Xintongtai (XTT) on traditional Chinese medicine (TCM) syndrome score and collagen fibers in vascular smooth muscle cells(VSMCs) of rabbits with atherosclerosis in the regulation of p38 mitogen-activated protein kinase (p38 MAPK)/activator protien-1 (AP-1)signaling pathway. Method:A total of 120 rabbits of SPF grade were randomly divided into the sham operation group, combined phlegm and blood stasis model group, rosuvastatin group, and low-, middle-, and high-dose XTT groups. The rabbit model of atherosclerosis due to combined phlegm and blood stasis was established by exposing them to high-fat diet and balloon injury. Following modeling, the corresponding drugs were administered by gavage for eight weeks (2.3, 4.6, 9.2 g·kg<sup>-1</sup> for low-, middle-, and high-dose XTT groups and 0.55 mg·kg<sup>-1 </sup>for rosuvastatin group). At the end of medication, the abdominal aorta was isolated and stained with htoxylin-eosin (HE) for observing the vulnerable plaque. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected by immunohistochemistry (IHC). The collagen fiber decomposition in VSMCs was observed after Masson staining. The protein expression levels of p38 MAPK and AP-1 in aorta was assayed by Western blotting. The combined phlegm and blood stasis syndrome was scored based on TCM syndrome scoring scale. Result:Compared with the model group, XTT at each dose and rosuvastatin significantly decreased MMP-9 content, increased TIMP-1, down-regulated p38 MAPK protein expression, and weakened the nuclear translocation of AP-1 (<italic>P</italic><0.01). Compared with the low-dose XTT group, the middle- and high-dose XTT groups and rosuvastatin group exhibited obviously lowered MMP-9,elevated TIMP-1, down-regulated p38 MAPK protein expression, and diminished AP-1 nuclear translocation (<italic>P</italic><0.05,<italic>P</italic><0.01). The TCM syndrome scores of the middle- and high-dose XTT groups and rosuvastatin group were significantly improved as compared with that in the model group (<italic>P</italic><0.05,<italic>P</italic><0.01). The comparison with the low-dose XTT group revealed a remarkable improvement in TCM syndrome score of the middle- and high-dose XTT groups and rosuvastatin group (<italic>P</italic><0.01). As demonstrated by Masson staining, the smooth muscle fibers in the model group were arranged in disorder, accompanied by enhanced collagen decomposition, thinned fibrous cap, and increased plaque vulnerability. Compared with the model group, the VSMCs in each XTT group and rosuvastatin group were orderly arranged, manifested as decreased collagen fiber decomposition and increased plaque stability. Conclusion:XTT down-regulates the expression of p38 MAPK and MMP-9, increases the level of TIMP-1, reduces the nuclear translocation of AP-1, diminishes the decomposition of collagen fibers in VSMCs, and improves the score of combined phlegm and blood stasis syndrome. XTT alleviates arteriosclerosis due to combined phlegm and blood stasis by regulating p38 MAPK/AP-1 signaling pathway and downstream cytokines and stabilizing vulnerable plaques.

10.
Article in Chinese | WPRIM | ID: wpr-905989

ABSTRACT

Objective:To study the effect of Wenjing Huayu Zhitong therapy (Xiangyan Zhitong prescription, XZP) on the mitogen activated protein kinase (MAPK)/extracelluar regulated protein kinase (ERK) signaling pathway of primary dysmenorrhea (PD) rats, and explore the pathogenesis of PD and the mechanism of action of Wenjing Huayu Zhitong therapy. Method:Forty-eight female SPF-grade Wistar rats were randomly divided into blank group,model group, western medicine group, low-dose XZP group, medium-dose XZP group, and high-dose XZP group, with 8 rats in each group. In addition to the blank group, dysmenorrhea rat model with cold coagulation and blood stasis syndrome was established by cold stimulation combined with estradiol benzoate and oxytocin. The rats in the blank group,model group,western medicine group, low-dose XZP group, medium-dose XZP group, and high-dose XZP group were given distilled water, distilled water,0.06 g·kg<sup>-1</sup> ibuprofen, 6.55 g·kg<sup>-1</sup> XZP, 13.09 g·kg<sup>-1</sup> XZP, and 26.18 g·kg<sup>-1</sup> XZP, respectively, by gavage for 6 days. The writhing latency and writhing frequency of rats were recorded within 30 min after oxytocin injection.Western blot was used to detect the protein expression of B-Raf, mitogen activates extracellular regulated kinases1/2 (MEK1/2), extracellular regulated kinases1/2 (ERK1/2), p-MEK1/2, p-ERK1/2, c-Jun, and cyclooxygenase-2 (COX-2) in rat uterus. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to detect the mRNA expression of B-Raf, MEK1, MEK2, ERK1, ERK2, c-Jun, and cyclooxygenase-2 (COX-2) in rat uterus. Result:Compared with the model group,the treatment groups showed insignificantly prolonged writhing latency and significantly reduced writhing frequency (<italic>P</italic><0.01). On the 6<sup>th</sup> day of modeling, there was no significant difference in the quantitative scores of symptoms and signs among the treatment groups. On the 12<sup>th</sup> day of modeling, the scores changed little in the western medicine group and the low-dose XZP group and decreased significantly in the medium- and high-dose XZP groups (<italic>P</italic><0.01) compared with those in the model group. Compared with those in the blank group, the protein and mRNA levels of p-MEK1/2, p-ERK, B-Raf, c-Jun, and COX-2 in the model group were significantly up-regulated (<italic>P</italic><0.01). Compared with those in the model group, the protein and mRNA levels of p-MEK1/2, p-ERK1/2, B-Raf, c-Jun, and COX-2 in the western medicine group, medium-dose XZP group, and high-dose XZP group were significantly down-regulated (<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:The mechanism of Wenjing Huayu Zhitong therapy in treating PD with cold coagulation and blood stasis syndrome may be related to the down-regulation of MAPK/ERK signaling pathway.

11.
Article in English | WPRIM | ID: wpr-880713

ABSTRACT

This study aims to elucidate the antiproliferative mechanism of hydroxychavicol (HC). Its effects on cell cycle, apoptosis, and the expression of c-Jun N-terminal kinase (JNK) and P38 mitogen-activated protein kinase (MAPK) in HT-29 colon cancer cells were investigated. HC was isolated from

12.
Acta Pharmaceutica Sinica B ; (6): 1117-1128, 2021.
Article in English | WPRIM | ID: wpr-881188

ABSTRACT

Hypertension is the largest risk factor for cardiovascular disease, the leading cause of mortality worldwide. As blood pressure regulation is influenced by multiple physiological systems, hypertension cannot be attributed to a single identifiable etiology. Three decades of research into Mendelian forms of hypertension implicated alterations in the renal tubular sodium handling, particularly the distal convoluted tubule (DCT)-native, thiazide-sensitive Na-Cl cotransporter (NCC). Altered functions of the NCC have shown to have profound effects on blood pressure regulation as illustrated by the over activation and inactivation of the NCC in Gordon's and Gitelman syndromes respectively. Substantial progress has uncovered multiple factors that affect the expression and activity of the NCC. In particular, NCC activity is controlled by phosphorylation/dephosphorylation, and NCC expression is facilitated by glycosylation and negatively regulated by ubiquitination. Studies have even found parvalbumin to be an unexpected regulator of the NCC. In recent years, there have been considerable advances in our understanding of NCC control mechanisms, particularly

13.
Acta Pharmaceutica Sinica B ; (6): 961-977, 2021.
Article in English | WPRIM | ID: wpr-881178

ABSTRACT

As one of the most important components of caveolae, caveolin-1 is involved in caveolae-mediated endocytosis and transcytosis pathways, and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction. In recent years, the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored. In addition, the interplay between caveolin-1 and nano-drugs is bidirectional. Caveolin-1 could determine the intracellular biofate of specific nano-drugs, preventing from lysosomal degradation, and facilitate them penetrate into deeper site of tumors by transcytosis; while some nanocarriers could also affect caveolin-1 levels in tumor cells, thereby changing certain biophysical function of cells. This article reviews the role of caveolin-1 in tumor prognosis, chemotherapeutic drug resistance, antibody drug sensitivity, and nano-drug delivery, providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

14.
Acta Pharmaceutica Sinica B ; (6): 781-794, 2021.
Article in English | WPRIM | ID: wpr-881169

ABSTRACT

Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-

15.
Acta Pharmaceutica Sinica B ; (6): 750-762, 2021.
Article in English | WPRIM | ID: wpr-881167

ABSTRACT

The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2 (SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2 (SHP2-PTP) and allosteric inhibitors. Of note, this protocol showed potential for identifying SHP2 inhibitors against cancer-associated SHP2 mutation SHP2-E76A. After initial screening of our in-house compound library (∼2300 compounds), we identified 4 new SHP2-PTP inhibitors (0.17% hit rate) and 28 novel allosteric SHP2 inhibitors (1.22% hit rate), of which SYK-85 and WS-635 effectively inhibited SHP2-PTP (SYK-85: IC

16.
Acta Pharmaceutica Sinica B ; (6): 680-693, 2021.
Article in English | WPRIM | ID: wpr-881162

ABSTRACT

As an effective anticancer drug, the clinical limitation of doxorubicin (Dox) is the time- and dose-dependent cardiotoxicity. Yes-associated protein 1 (YAP1) interacts with transcription factor TEA domain 1 (TEAD1) and plays an important role in cell proliferation and survival. However, the role of YAP1 in Dox-induced cardiomyopathy has not been reported. In this study, the expression of YAP1 was reduced in clinical human failing hearts with dilated cardiomyopathy and Dox-induced

17.
Acta Pharmaceutica Sinica B ; (6): 322-339, 2021.
Article in English | WPRIM | ID: wpr-881139

ABSTRACT

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in

18.
Acta Pharmaceutica Sinica B ; (6): 55-70, 2021.
Article in English | WPRIM | ID: wpr-881124

ABSTRACT

Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.

19.
Acta Pharmaceutica Sinica B ; (6): 13-29, 2021.
Article in English | WPRIM | ID: wpr-881122

ABSTRACT

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.

20.
Article in English | WPRIM | ID: wpr-881058

ABSTRACT

This study was to investigate the protective effect of paeoniflorin (PF) on hydrogen peroxide-induced injury. Firstly, "SMILES" of PF was searched in Pubchem and further was used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Injury-related molecules were obtained from GeenCards database, and the predicted targets of PF for injury treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, and the KEGG analysis was conducted in Webgestalt. Then, cell viability and cytotoxicity assay were established by CCK8 assay. Also, the experimental cells were allocated to control, model (200 μmol·L

SELECTION OF CITATIONS
SEARCH DETAIL