A real-world study and network pharmacology analysis of EGFR-TKIs combined with ZLJT to delay drug resistance in advanced lung adenocarcinoma.

OBJECTIVE: This study aimed to explore the efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with ZiLongJin Tablet (ZLJT) in delaying acquired resistance in advanced EGFR-mutant lung adenocarcinoma (LUAD) patients. Furthermore, we employed network pharmacology and molecular docking techniques to investigate the underlying mechanisms. METHODS: A retrospective comparative study was conducted on stage IIIc/IV LUAD patients treated with EGFR-TKIs alone or in combination with ZLJT at the Second Affiliated Hospital of the Air Force Medical University between January 1, 2017, and May 1, 2023. The study evaluated the onset of TKI resistance, adverse reaction rates, safety indicators (such as aspartate aminotransferase, alanine aminotransferase, and creatinine), and inflammatory markers (neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) to investigate the impact of EGFR-TKI combined with ZLJT on acquired resistance and prognostic indicators. Additionally, we utilized the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine, PubChem, UniProt, and Swiss Target Prediction databases to identify the active ingredients and targets of ZLJT. We obtained differentially expressed genes related to EGFR-TKI sensitivity and resistance from the Gene Expression Omnibus database using the GSE34228 dataset, which included sensitive (n = 26) and resistant (n = 26) PC9 cell lines. The "limma" package in R software was employed to detect DEGs. Based on this, we constructed a protein‒protein interaction network, performed gene ontology and KEGG enrichment analyses, and conducted pathway network analysis to elucidate the correlation between the active ingredients in ZLJT and signaling pathways. Finally, molecular docking was performed using AutoDockVina, PYMOL 2.2.0, and Discovery Studio Client v19.1.0 software to simulate spatial and energy matching during the recognition process between predicted targets and their corresponding compounds. RESULTS: (1) A total of 89 patients were included, with 40 patients in the EGFR-TKI combined with ZLJT group (combination group) and 49 patients in the EGFR-TKI alone group (monotherapy group). The baseline characteristics of the two groups were comparable. There was a significant difference in the onset of resistance between the combination group and the monotherapy group (P < 0.01). Compared to the monotherapy group, the combination group showed a prolongation of 3.27 months in delayed acquired resistance. There was also a statistically significant difference in the onset of resistance to first-generation TKIs between the two groups (P < 0.05). (2) In terms of safety analysis, the incidence of adverse reactions related to EGFR-TKIs was 12.5% in the combination group and 14.3% in the monotherapy group, but this difference was not statistically significant (P > 0.05). There were no statistically significant differences in serum AST, ALT, CREA, TBIL, ALB and BUN levels between the two groups after medication (P > 0.05). (3) Regarding inflammatory markers, there were no statistically significant differences in the changes in neutrophil-to-lymphocyte Ratio(NLR) and Platelet-to-lymphocyte Ratio(PLR) values before and after treatment between the two groups (P > 0.05). (4) Network pharmacology analysis identified 112 active ingredients and 290 target genes for ZLJT. From the GEO database, 2035 differentially expressed genes related to resistant LUAD were selected, and 39 target genes were obtained by taking the intersection. A "ZLJT-compound-target-disease" network was successfully constructed using Cytoscape 3.7.0. GO enrichment analysis revealed that ZLJT mainly affected biological processes such as adenylate cyclase-modulating G protein-coupled receptor. In terms of cellular components, ZLJT was associated with the cell projection membrane. The molecular function primarily focused on protein heterodimerization activity. KEGG enrichment analysis indicated that ZLJT exerted its antitumor and anti-drug resistance effects through pathways such as the PI3K-Akt pathway. Molecular docking showed that luteolin had good binding activity with FOS (-9.8 kJ/mol), as did tanshinone IIA with FOS (-9.8 kJ/mol) and quercetin with FOS (-8.7 kJ/mol). CONCLUSION: ZLJT has potential antitumor progression effects. For patients with EGFR gene-mutated non-small cell LUAD, combining ZLJT with EGFR-TKI treatment can delay the occurrence of acquired resistance. The underlying mechanisms may involve altering signal transduction pathways, blocking the tumor cell cycle, inhibiting tumor activity, enhancing cellular vitality, and improving the bioavailability of combination therapy. The combination of EGFR-TKI and ZLJT represents an effective approach for the treatment of tumors using both Chinese and Western medicine.

Anti-fibrotic Effects and Mechanism of Shengmai Injection () on Human Hepatic Stellate Cells LX-2.

OBJECTIVE: To investigate the effects of Shengmai Injection (, SMI) on the proliferation, apoptosis and N-myc downstream-regulated gene 2 (NDRG2, a tumour suppressor gene) expression in varying densities of human hepatic stellate cells LX-2. METHODS: LX-2 cells were cultured in vitro. Then, cells were plated in 96-well plates at an approximate density of 2.5×104 cells/mL and cultured for 48, 72, 96 or 120 h followed by the application of different concentrations of SMI (0.6, 1.2, 2.4, 4.8 or 6 µL/mL). Cell proliferation was measured after an additional 24 or 48 h using the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of SMI on different cell growth states (cultured for 48, 72, 96, or 120 h) were observed by light microscopy at 24 h after treatment. When the cells reached 80% conflfluence, apoptosis was detected by flflow cytometry after 24 h. Lastly, LX-2 cells were treated with different concentrations of SMI and extracted with protein lysis buffer. The levels of NDRG2 were measured by Western blot. RESULTS: When the LX-2 cells grew for 48, 72, 96 and 120 h, 4.8 and 6 µL/mL of SMI significantly inhibited cell proliferation at 24 and 48 h after treatment (P<0.05). And 2.4 µL/mL of SMI also inhibited cell proliferation at 24 h after treatment when cell growth for 48 h (P<0.05) and at 48 h after treatment when cell growth for 72, 96 and 120 h (P<0.05). The NDRG2 expression level in the LX-2 cell was significantly increased when treated with SMI at concentrations of 1.2, 2.4, 4.8 or 6 µL/mL (P<0.05). CONCLUSION: The inhibitory effects of SMI on the proliferation of LX-2 cells were related to not only concentration dependent but also cell density. In addition, SMI (2.4, 4.8 and 6 µL/mL) could accelerate apoptosis in LX-2 cells, and the mechanism might be associated with NDRG2 over-expression.

Anti-fibrotic effects of Salvia miltiorrhiza and Ligustrazine Injection on LX-2 cells involved with increased N-myc downstream-regulated gene 2 expression.

OBJECTIVE: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection (SML) on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2 (NDRG2, a tumor suppressor gene). METHODS: HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×104 cells/mL and cultured for 24 h followed by the application of different concentrations of SML (1, 2, 4 and 8 µL/mL). Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and ß-catenin were measured by Western blot. RESULTS: With the exception of the 1 and 2 µL/mL concentrations, 4 and 8 µL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h (P<0.05). With the exception of the 1 and 2 µL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of ß-catenin was unaffected. CONCLUSION: SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.

Ginsenoside Rd alleviates mouse acute renal ischemia/reperfusion injury by modulating macrophage phenotype.

BACKGROUND: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. METHODS: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10-100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with CD11b(+), iNOS(+)/interleukin-12/tumor necrosis factor-α labeling. For the in vitro study, GSRd (10-100 µg/mL) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. RESULTS: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin-eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-α. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. CONCLUSION: These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization.

As2O3 induces apoptosis in human hepatocellular carcinoma HepG2 cells through a ROS-mediated mitochondrial pathway and activation of caspases.

Arsenic trioxide (As2O3) has been shown to induce apoptosis in hepatocellular carcinoma cells. However, the molecular mechanism of As2O3-induced apoptosis in the hepatocellular carcinoma cells remains poorly understood. Here, we investigated the impact of As2O3 exposure on the human hepatocellular carcinoma cell line HepG2 and examined the underlying mechanism of cell death. As2O3 induced apoptosis of HepG2 cells in a dose- and time-dependent manner and caused a massive production of reactive oxygen species (ROS). The antioxidant N-acetylcysteine (NAC) was able to prevent As2O3-induced cell death, implying an involvement of ROS in the induction of As2O3-triggered apoptosis. Furthermore, As2O3 initiated apoptosis by triggering of the mitochondria apoptotic pathway as indicated by inhibited Bcl-2 expression, a collapse of the mitochondrial membrane potential (MMP), release of cytochrome c and activation of the caspase cascade. However, these As2O3-induced events can be prevented by NAC. Taken together, these findings suggest that the As2O3 induced apoptosis through a ROS-mediated mitochondrial pathway and activation of caspases.

The influence of astragalus polysaccharide and ß-elemene on LX-2 cell growth, apoptosis and activation.

BACKGROUND: Activated hepatic stellate cells are the main source of excessive collagen deposition in liver fibrosis. Here we report the inhibitory effects of the combinational treatment of two natural products, astragalus polysaccharide (APS) and ß-elemene (ELE) on the activation of human liver hepatic stellate cell line LX-2 cells. METHODS: Cultured LX-2 cells were treated with different concentrations of APS or ELE for 24 or 48 hours. Cell viability/apoptosis was measured by MTT assay and Annexin V/PI staining , activation related genes including α-SMA and CD44 expressions were measured by real-time PCR and western blot respectively. RESULTS: The majority of LX-2 cells showed morphological change in the presence of APS or ELE for 24 hours. Treatment with APS + ELE for 24 or 48 hours significantly inhabited the cell proliferation compared with APS or ELE treatment alone on LX-2 cells. APS + ELE may block the up-regulation of α-SMA and CD44 both in mRNA and protein levels through TGF-ß pathway in LX-2 cells. CONCLUSION: APS or ELE treatment alone on LX-2 cells could inhibit cell proliferation and induce apoptosis. The combinational treatment using APS + ELE significantly increased the killing efficiency on LX-2 cells. α-SMA and CD44 expressions was inhibited upon APS + ELE treatment through TGF-ß pathway in LX-2 cells. The results indicated a novel treatment using natural products for liver diseases with anti-fibrotic effect.

Inhibition potential of glimepiride (gli) towards important UDP-glucuronosyltransferase (UGT) isoforms in human liver.

The aim of the present study was to investigate the inhibitory potential of glimepiride towards important UDP-glucuronosyltransferase (UGT) isoforms in human liver, which play a key role in the elimination of drugs. The recombinant UGT enzymes were used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 microM of glimepiride inhibited UGT1A1, UGT1A3, UGT1A6, UGT1A9, UGT2B7 and UGT2B15 by 54.7%, 43.1%, 100%, 70.5%, 32.7 and 37.2%, respectively. Given that glimepiride exhibited strong inhibition towards UGT1A6, further inhibitory kinetic behaviour was determined. Glimepiride exerted concentration-dependent inhibition towards UGT1A6. Both Dixon and Lineweaver-Burk plots demonstrated that inhibition of UGT1A6 was best fit for noncompetitive inhibition type, and the inhibition kinetic parameter (Ki) was calculated to be 59.8 microM. Given that UGT1A6 plays a key role in detoxification of many drugs, more attention should be given when glimepiride was co-administered with the drugs mainly undergoing UGT1A6-mediated metabolism.

Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer.

A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression.

BACKGROUND: The prognosis of most hepatocellular carcinoma (HCC) patients is poor due to the high metastatic rate of the disease. Understanding the molecular mechanisms underlying HCC metastasis is extremely urgent. The role of CD24 and NDRG2 (N-myc downstream-regulated gene 2), a candidate tumor suppressor gene, has not yet been explored in HCC. METHODS: The mRNA and protein expression of CD24 and NDRG2 was analyzed in MHCC97H, Huh7 and L-02 cells. Changes in cell adhesion, migration and invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. The expression pattern of NDRG2 and CD24 in HCC tissues and the relationship between NDRG2 and HCC clinical features was analyzed by immunohistochemical and western blotting analysis. RESULTS: NDRG2 expression was negatively correlated with malignancy in HCC. NDRG2 exerted anti-tumor activity by regulating CD24, a molecule that mediates cell-cell interaction, tumor proliferation and adhesion. NDRG2 up-regulation decreased CD24 expression and cell adhesion, migration and invasion. By contrast, NDRG2 down-regulation enhanced CD24 expression and cell adhesion, migration and invasion. Immunohistochemical analysis of 50 human HCC clinical specimens showed a strong correlation between NDRG2 down-regulation and CD24 overexpression (P = 0.04). In addition, increased frequency of NDRG2 down-regulation was observed in patients with elevated AFP serum level (P = 0.006), late TNM stage (P = 0.009), poor differentiation grade (P = 0.002), tumor invasion (P = 0.004) and recurrence (P = 0.024). CONCLUSIONS: Our findings indicate that NDRG2 and CD24 regulate HCC adhesion, migration and invasion. The expression level of NDRG2 is closely related to the clinical features of HCC. Thus, NDRG2 plays an important physiological role in HCC metastasis.

Unbalanced MMP/TIMP-1 expression during the development of experimental pulmonary fibrosis with acute paraquat poisoning.

Paraquat (PQ)-induced pulmonary toxicity is known to result in pulmonary edema, infiltration of inflammatory cells and damage to the alveolar epithelium, which may progress to severe fibrosis. Matrix metalloproteinases (MMPs) and their physiological inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs), which degrade and remodel the excess extracellular matrix, are believed to play an important role in the development of fibrotic tissue. In this study, we examined the sequential expression of MMP-2, MMP-9 and TIMP-1 in a rat model of pulmonary fibrosis induced by PQ. Adult male Sprague-Dawley rats were treated intraperitoneally with PQ (20 mg/kg) and saline (control group). Rats were sacrificed at days 1, 3, 7 and 21 after the PQ treatment. Lungs were excised for histological evaluation and immunohistochemical analyses, as well as the determination of collagen content, gene expression by fluorimeter-based quantitive RT-PCR assay and gelatinolytic activity by zymography. Lung MMP-2 and -9 mRNA expression progressively increased and reached a peak on day 7 after PQ treatment, while TIMP-1 mRNA levels in the PQ-treated lungs reached a peak on day 21 after modeling. Lung zymography revealed an increase in progelatinase B, progelatinase A and their active forms. In conclusion, unbalanced MMP/TIMP-1 expression and excessive gelatinolytic activity contribute to PQ-induced pulmonary fibrosis. Their precise role should be studied in depth as they may represent relevant therapeutic targets for PQ poisoning-induced pulmonary fibrosis.

[Effect and mechanism of emodin for regulating aquaporin-2 expression in cultured NRK cells].

OBJECTIVE: To investigate the effect and mechanism of emodin for regulating aquapoin-2 (AQP2) in NRK cells cultured in vitro. METHODS: Experiments on NRK cells cultured with alpha-DMEM medium in vitro were conducted in two steps. (1) Cells were randomly divided into 4 groups: the control group, and the three emodin treated groups treated with different dosages of emodin (5, 10 and 20 mg/L) respectively. After 24 h treatment, the location of AQP2 was decided by indirect immunofluorescene, and the AQP2 protein and mRNA expression levels were detected by Western blot and semiquantive RT-PCR. (2) Cells were randomly divided into 4 groups, the control group, and the three treated groups treated respectively with 10 mg/L 8-Bromo-cAMP, 20 mg/L emodin, and 20 mg/L emodin +10 mg/L 8-Bromo-cAMP. The activity of protein kinase A (PKA) in NRK cells after 24 h treatment was determined with non-radioactive detecting method. RESULTS: AQP2 was located at the cell membrane of NRK cells. Western blot and semiquantitive RT-PCR found that AQP2 protein and mRNA expressions were significantly decreased in NRK cells of groups treated by 10 mg/L and 20 mg/L emodin (P < 0.05). PKA activity determination showed significantly decreased phosphorylation level of PKA in NRK cells of groups treated with 20 mg/L emodin group (P < 0.05). CONCLUSION: Emodin can inhibit the genetic transcription and the translation of AQP2 gene in NRK cells, which demonstrates that the change of AQP2 expression regulated by emodin may be correlated with the diuresis effect of rhubarb, and it is likely that the regulation is going through PKA signal pathway.

[Effects of genistein on colon cancer cells in vitro and in vivo and its mechanism of action].

OBJECTIVE: To study the effects of genistein on the proliferation, apoptosis induction and expression of related gene proteins of human colon cancer cells in vitro and in vivo, and its mechanisms of action. METHODS: MTT colorimetric assay was used to detect the effects of genistein on the proliferation of human colon adenocarcinoma SW480 cells. Light and transmission electron microscopy were used to study the histological and ultrastructural changes. Flow cytometry was used to determine the effects of genistein on cell cycle and apoptosis. Flow cytometry and immunohistochemistry were used to determine the effects of genistein on apoptosis induction and expression of related gene proteins of colon cancer cells. RESULTS: The MTT colorimetric assay showed that genistein inhibited the proliferation of SW480 cells in a dose-dependent and time-dependent manner, and the highest inhibition rate was 60.2% after 80 microg/ml genistein treatment for 72 h. The light microscopy revealed that many genistein-treated cancer cells were shrunken, disrupted, or showing cytoplasmic vacuolization. The electron microscopic examination showed cell shrinkage, nuclear fragmentation and pronounced chromatin condensation, sometimes formed crescent chromatin condensation attached to the nuclear membrane. The results of flow cytometry showed that: after SW480 cells were treated with 0, 20, 40, 80 microg/ml genistein for 48 h, the FI values of PCNA were 1.49 +/- 0.02, 1.28 +/- 0.04, 1.14 +/- 0.03, and 0.93 +/- 0.08; the FI values of VEGF were 1.75 +/- 0.02, 1.34 +/- 0.06, 1.32 +/- 0.04, and 1.23 +/- 0.04; the fluorescence index (FI) values of p21 were 1.26 +/- 0.05, 1.36 +/- 0.06, 1.61 +/- 0.03, and 1.73 +/- 0.03, respectively. There were statistically significant differences between the control group and each treatment group (P < 0.05 or P < 0.01). The scores of immunohistochemical staining of PCNA and VEGF proteins were decreased, while p21 increased. There were statistically significant differences between the control group and each treatment group (P < 0.05 or P < 0.01). CONCLUSION: Genistein can inhibit the growth of colon cancer cells via apoptosis induction and cell cycle arrest at G(2)/M phase. The anti-tumor mechanisms of genistein may be related with the down-regulation of expression of VEGF and PCNA, and up-regulation of the expression of p21.

NDRG2 expression regulates CD24 and metastatic potential of breast cancer cells.

Breast cancer is the most common malignancy in women in the world. High incidence and poor clinical outcomes underly the need for a better understanding of its tumor biology and how to effectively inhibit tumor progression. In the present study the question of whether NDRG2 might be a useful target for breast cancer therapy was addressed. With the increase or decrease of NDRG2 levels in MCF-7 and Bcap-37 cells by adenovirus-NDRG2 infection or NDRG2 siRNA transfection, CD24 expression was significantly decreased or increased, respectively. Furthermore, NDRG2 overexpression suppressed breast cancer cell adhesion and invasion, whereas knockdown of NDRG2 promoted these events. In conclusion, the data from the current study indicated that NDRG2, the product of a tumor suppressor gene, can regulate CD24 expression to decrease the metastatic potential of breast cancer cells.

[Influence of moxibustion of baihui (GV 20) on hemodynamics of common carotid artery in healthy subjects].

OBJECTIVE: To observe the effect of moxibustion of Baihui (GV 20) on the hemodynamics of internal carotid artery in health subjects so as to study its underlying mechanism of moxibustion in the treatment cerebrovascular disorders. METHODS: Thirty healthy male volunteer students between 20 and 22 years in age were enrolled into this study. Qm (mean blood flow), Vm) (mean velocity of blood flow), Vmax (maximal velocity of blood flow), Vmin (minimal velocity of blood flow), Wv (pulse wave velocity), Zcv (characteristic impedance), Rv (peripheral resistance), DR (dynamic resistance), CP (critical pressure) and DP (difference of pressure) of the right and left common carotid arteries were measured before and after moxibustion of GV20 (5-10 min each time, once daily, 5 times altogether) by using CBA CV-300 Cerebrovascular Hemodynamics Detector. RESULTS: Following moxibustion of GV20, Qm, Vm and Vmin of both right and left common carotid arteries increased significantly (P < 0.01); while Rv and DR of the brain artery lowed evidently (P < 0.05); The rest indexes had no significant changes (P > 0.05). CONCLUSION: Moxibustion of Baihui (GV 20) can significantly raise the velocity of blood flow of the common carotid artery and low the resistance of blood vessels.

[Protection effect of Salvia miltiorrhiza on model of acute lung injury in rats].

OBJECTIVE: To investigate the effect of SM on aquaporin-1 (AQP1) expression in rats with acute lung injury (ALI), and study protection against ALI. METHODS: 48 SD rats were randomly divided into normal group, ALI 7-day group, ALI 8-hour group, SM prevention group, SM 7-day treatment group, and SM 8-hour treatment group. At 8 hours and 7 days after treatment, lung wet-to-dry weight ratio, lung pathology, electron microscope, AQP1 immunohistochemistry, and AQP1 Western blot were performed. RESULTS: The model group rats all appeared ALI symptom. Compared with the 7-day ALI group, the degree of lung edema statement alleviated in SM 7-day treatment group. But the expression of AQP-1 was not significant between the two groups (P < 0.05). Compared with the 8-hour ALI group, the degree of lung edema statement alleviated in SM 8-hour treatment group and SM prevention group. The expression of AQP-1 was significantly expression in the group of SM prevention group (P < 0.01). CONCLUSION: SM may improve the body fluid metabolism and alleviate the degree of the lung edema by regulating the expression of AQP-1. The results suggest SM can regulate the activity of AQP-1 to improve the water metabolism of ALI.