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Biomedical subjects

Yong Luo

Publications and source records attributed to Yong Luo.

At least 19 recordsLinked to original sources

Characterization of ZIC5 expression in esophageal squamous cell carcinoma and its association with patient survival.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy known for its aggressive nature and poor prognosis. The present study aimed to investigate the expression levels and clinical importance of the Zic family member 5 (ZIC5) gene in ESCC. Gene expression data and survival information obtained from The Cancer Genome Atlas and Gene Expression Omnibus were utilized. In 176 patients with surgically resected ESCC, immunohistochemical analysis was conducted to validate the expression of ZIC5 protein in cancerous and adjacent tissues. The findings of the present study revealed a significant upregulation of ZIC5 in ESCC compared with normal tissues (P<0.05), which was further corroborated by immunohistochemistry exhibiting a notable association between ZIC5 expression and clinical parameters such as tumor size, invasion depth, lymph node metastasis and TNM staging (P<0.05). Survival analysis further indicated that high ZIC5 expression was an independent prognostic factor for poor outcomes in patients with ESCC (hazard ratio=1.519; 95% CI: 1.017-2.269; P<0.05). In addition, bioinformatic analyses predicted that hsa-microRNA-212-5p may regulate ZIC5 mRNA and gene enrichment analysis suggested that ZIC5 may facilitate ESCC progression through involvement in the cell cycle and DNA repair pathways. In conclusion, ZIC5 is highly expressed in ESCC and associated with a poor prognosis, indicating its potential as a therapeutic target and biomarker for ESCC management. Further studies are warranted to elucidate the precise mechanisms underlying the role of ZIC5 in ESCC progression.

ESCC↗

Integrated bioinformatics analyses for GSDMB in carcinogenesis and progression of bladder cancer.

BACKGROUND: Emerging evidence suggests that pyroptosis influences the development of various diseases. Gasdermin B (GSDMB), an intracellular protein that executes pyroptosis, has recently attracted attention for its potential role in tumor biology. However, its specific function in bladder cancer (BLCA) remains unclear. Therefore, this study aimed to investigate the potential role of GSDMB in the carcinogenesis and prognosis of BLCA patients. METHODS: Mendelian randomization (MR) studies were conducted to examine relationships between the expression of GSDMB and BLCA with expression quantitative trait loci (eQTL) data. Then, GSDMB mRNA expression data and clinical characteristics of BLCA patients were retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression was used to explore the relationship between GSDMB mRNA expression and patients' survival. Additionally, the correlation between GSDMB and the immune microenvironment, tumor mutational burden (TMB), tumor microenvironment (TME), and drug sensitivity in BLCA was examined. RESULTS: According to MR analysis based on eQTLs, GSDMB mRNA expression has positive causal effects on bladder carcinogenesis and the need for bladder surgery (P<0.05). The analyses of TCGA demonstrated an increased expression of GSDMB in BLCA tissues, correlating with improved patient survival. Additionally, elevated GSDMB mRNA expression was identified as an independent protective prognostic factor for BLCA, and it was associated with immune cell infiltration, TMB, TME score, and drug sensitivity. CONCLUSIONS: Elevated mRNA expression of GSDMB has a causal link to a higher risk of BLCA and the likelihood of bladder surgery, but also indicates a better prognosis. Thus, GSDMB exhibits dual effects and might serve as a potential biomarker for predicting onset and progression of BLCA. Nevertheless, further investigation of pathogenesis and mechanisms underlying GSDMB is warranted.

Bladder cancer (BLCA)↗

Comparison of seven screening methods in the diagnosis of bladder cancer.

BACKGROUND: We compared the validity (evaluated by sensitivity and specificity), reliability (evaluated by reproducibility) and yield (evaluated by predictive value, examining complexity and cost) of individual and combined tests for bladder tumour antigen stat (BTAstat), nuclear matrix protein 22 (NMP22), hyaluronic acid (HA), survivin, CD44v6, vascular endothelial growth factor (VEGF), and voided urine cytology (VUC) in detecting bladder cancer. And at the same time we evaluated the clinical value of these seven detecting methods in the diagnosis of bladder cancer. METHODS: The six markers and VUC were detected in the urine of cancer group (151 patients with bladder cancer) and two control groups (50 patients with benign urological diseases and 50 healthy controls). The sensitivity, specificity, predictive value, reproducibility, examining complexity and checking cost of each marker and combined markers were calculated. RESULTS: There was a significant difference between bladder cancer group and the two control groups. The sensitivity, specificity and positive predictive value were as follows: VUC (36.4%, 100.0%, 100%), BTAstat (76.8%, 87.0%, 89.9%), NMP22 (77.5%, 81.0%, 86.0%), HA (82.8%, 83.0%, 88.0%), survivin (70.2%, 85.0%, 87.6%), CD44v6 (50.3%, 79.0%, 78.4%), and VEGF (68.2%, 93.0%, 93.6%). The highest sensitivities were 91.4% for NMP22 + BTAstat and HA + NMP22, whereas the combined marker with the lowest sensitivity (62.3%) was VUC + CD44v6. The highest specificity was 93.0% for the combined use of VUC + VEGF and HA + CD44v6 had the lowest specificity (73.0%). The most convenient examining method was the detection for BTAstat, the lowest cost was the detection for HA, and the best reproducibility were the detection for BTAstat and VUC. CONCLUSIONS: All the markers have obvious clinical value in diagnosis of bladder cancer. The use of BTAstat + HA or NMP22 + BTAstat are better examining methods in terms of validity, reliability, and yield.

Adult↗

Phosphorylation of SIMPL modulates RelA-associated NF-kappaB-dependent transcription.

Epidemiological data have implicated perturbations in the regulation of NF-kappaB activity to diseases that affect a large number of Americans today. Specifically, chronic activation of genes involved in the inflammatory response is associated with the progression of and complications in diabetes, arthritis, atherosclerosis, and cancer. Insight into the mechanisms governing the regulation of NF-kappaB transcriptional activity will provide the molecular link between NF-kappaB and these pathological states. SIMPL (signaling molecule that associates with mouse Pelle-like kinase) is a component of a signaling pathway through which tumor necrosis factor-alpha (TNF-alpha) induces NF-kappaB-controlled gene transcription. SIMPL interacts with the nuclear pool of the NF-kappaB subunit, p65, in a TNF-alpha-dependent manner to enhance p65-dependent gene transcription. How SIMPL activity is regulated is unknown. Under basal as well as TNF-alpha-stimulated conditions, SIMPL phosphopeptides were identified. SIMPL mutants lacking sites that are phosphorylated under basal conditions diminished p65 transactivation activity but had no effect on SIMPL nuclear localization. SIMPL mutants lacking sites of TNF-alpha-enhanced phosphorylation impaired nuclear localization and prevented TNF-alpha-induced p65 transactivation activity. Together, these studies reveal that phosphorylation of the SIMPL protein plays a critical role in SIMPL regulation by affecting both SIMPL subcellular localization and the p65 coactivator function of SIMPL.

Carrier Proteins↗

Over-expression of hypoxia-inducible factor-1alpha increases the invasive potency of LNCaP cells in vitro.

OBJECTIVE: To evaluate the effect of hypoxia-inducible factor-1alpha (HIF-1alpha) over-expression on the invasion-associated proteins in human prostate cancer cells, as HIF-1alpha is a transcriptional factor that could activate genes involved in the response to hypoxia, but might also enhance the invasive potency of prostate cancer cells. MATERIALS AND METHODS: Prostate cancer (LNCaP) cells were transfected with recombinant plasmid pcDNA3.1(-)/HIF-1alpha and pcDNA3.1(-) control vector using a commercial system, designated as LNCaP/HIF-1alpha and LNCaP/pcDNA3.1, respectively. The positive clones were selected with G418 and confirmed by Western blot and indirect immunofluorescence labelling. A polycarbonate filter, coated with a matrix gel, was used to analyse the invasive potency. The expression of E-cadherin, vimentin, cathepsin D, matrix metalloproteinase (MMP2) and urokinase plasminogen activator receptor (uPAR) was detected by Western blot. RESULTS: The expression level of HIF-1alpha in LNCaP/HIF-1alpha was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. Many more cells of LNCaP/HIF-1alpha penetrated through the polycarbonate filter than those of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1 and LNCaP cells, the expression of vimentin, cathepsin D, MMP-2 and uPAR were up-regulated in LNCaP/HIF-1alpha, whereas the expression of E-cadherin was down-regulated. CONCLUSION: These results show that over-expression of HIF-1alpha directly stimulates the invasive potency of human prostate carcinoma LNCaP cells through the matrix gel. The expression of E-cadherin, vimentin, cathepsin D, MMP-2 and uPAR, which are proteins with established roles in the pathophysiology of invasion, could be regulated by HIF-1alpha in human prostate cancer cells.

Blotting, Western↗

Double-cross hydrostatic pressure sample injection for chip CE: variable sample plug volume and minimum number of electrodes.

A novel sample injection method for chip CE was presented. This injection method uses hydrostatic pressure, generated by emptying the sample waste reservoir, for sample loading and electrokinetic force for dispensing. The injection was performed on a double-cross microchip. One cross, created by the sample and separation channels, is used for formation of a sample plug. Another cross, formed by the sample and controlling channels, is used for plug control. By varying the electric field in the controlling channel, the sample plug volume can be linearly adjusted. Hydrostatic pressure takes advantage of its ease of generation on a microfluidic chip, without any electrode or external pressure pump, thus allowing a sample injection with a minimum number of electrodes. The potential of this injection method was demonstrated by a four-separation-channel chip CE system. In this system, parallel sample separation can be achieved with only two electrodes, which is otherwise impossible with conventional injection methods. Hydrostatic pressure maintains the sample composition during the sample loading, allowing the injection to be free of injection bias.

Electrodes↗

[Over-expression of Hypoxia-inducible factor 1alpha increases invasive potency of LNCaP cells in vitro].

OBJECTIVE: To evaluate the effect of hypoxia-inducible factor-1alpha (HIF1alpha) over-expression on the invasive potency of human prostate cancer cell. METHODS: Human prostate cancer cells of the line LNCaP were cultured and transfected by the recombinant plasmid pcDNA3.1(-)-HIF-1alpha containing the gene HIF1alpha with Lipofectamine 2000 system. The positive clone cells were selected by G418 and confirmed by Western blotting and immunofluorescence staining (LNCaP/HIF1alpha cells). Transwell chambers with polycarbonate filter were coated by 100 microl Matrigel at 1:20 dilution in serum-free medium. LNCaP cell suspension and LNCaP/HIF1alpha cell suspension were inoculated into the Transwell chambers respectively for 24 hours to analyze the invasive potency. Western blotting was used to detect the expression of E-cadherin, vimentin, matrix metalloproteinase-2 (MMP-2), cathepsin D, and urokinase-type plasminogen activator receptor (uPAR). RESULTS: The expression level of HIF1alpha in the LNCaP/HIF1alpha cells was distinctly higher than that in the LNCaP cells. The numbers of LNCaP-HIF1alpha cells penetrating through the Transwell polycarbonate filter was 4.6 +/- 0.4 x 10(4), significantly higher than that of the LNCaP cells (3.2 +/- 0.3 x 10(4), P < 0.01). The expressions of vimentin, MMP-2, cathepsin D, and uPAR were all up-regulated in LNCaP-HIF1alpha cells than those of the LNCaP cells. Whereas, the expression of E-cadherin was down-regulated in the LNCaP-HIF1alpha cells. CONCLUSION: Over-expression of HIF-1alpha stimulates the invasion potency of human prostate carcinoma cell. The expression of E-cadherin, vimentin, MMP-2, cathepsin D, and uPAR, all playing an established role in the invasion of tumor, can be regulated by HIF-1 in human prostate cancer cell.

Cell Line, Tumor↗

A novel antioxidant agent, astragalosides, prevents shock wave-induced renal oxidative injury in rabbits.

Extracorporeal shock-wave lithotripsy (ESWL)-induced renal damage can occur as a result of multiple mechanisms, including small vessel injury and free radical formation. Our previous studies have demonstrated that Astragalus membranaceus (AM), a traditional Chinese herb, could significantly alleviate shock wave-induced renal oxidative injury, and its renoprotective effects were superior to those of varapamil, a calcium antagonist, which were considered to be a powerful agent in treating renal damage during ESWL. However, the effective antioxidant ingredient of this herb in the setting of lithotripsy remains unclear. Astragalosides, the major components of AM, was demonstrated to have superior antioxidation properties both in vitro and in vivo. Therefore, in this study we further investigate the potential effects of astragalosides on the shock wave-induced oxidative stress in rabbit kidney. Thirty male rabbits were randomly assigned to two groups, each consisting of 15 rabbits: (1) control group, (2) astragaloside-treated group. Each group of animals underwent 1,500 shock waves to the right kidney. Peripheral blood, urine and kidney tissue samples were collected pre- and post-ESWL. The level of urinary N-acetyl-beta-glucosaminidase (NAG), serum creatinine, serum or homogenates malondialdehyde (MDA) and superoxide dismutase (SOD), respectively, were detected. Histological alterations were also examined through light microcopy and transmission electron microscopy. In the control group, shock wave significantly increased the level of MDA and decreased SOD activity in both blood and renal homogenates (P<0.05, respectively). The comparison between the control and astragalosides group demonstrated that astragalosides could significantly decrease the level of MDA (P<0.05) and inhibit the decline of SOD activity (P<0.05). After exposure to shock waves, the activity of urinary NAG increased significantly in the control group (P<0.05). However, the concentration of serum creatinine did not change significantly. The comparison between the control and astragalosides group demonstrated that astragalosides significantly reduced the shock wave-induced leakage of NAG into the urine (P<0.05). Histological examination also showed that renal morphological impairments were much milder in astragaloside-treated rabbits than those of the control group. Our results indicated that astragaloside treatment provided significant protection against shock wave-induced renal oxidative injury.

Animals↗

Hypoxia-inducible factor-1alpha induces the epithelial-mesenchymal transition of human prostatecancer cells.

BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcriptional factor that could improve the stimulation of angiogenesis and the metabolic adaptation of tumor cells to hypoxia. A recent study showed that HIF-1alpha could induce colon cancer cells epithelial-mesenchymal transition (EMT). However, no evidence indicates a similar correlation in human prostate cancer cells. This study was designed to evaluate the effect of HIF-1alpha over-expression on the EMT in human prostate cancer cells. METHODS: We selected the appropriate cell line for HIF-1alpha induction from those EMT negative prostate cell lines through vimentin gene detection by RT-PCR. As the result, LNCaP cell line is the best one for further experiment. LNCaP cells were transfected with recombinant plasmid pcDNA3.1 (-)/HIF-1alpha and pcDNA3.1 (-) control vector by Lipofectamine 2000 system. The positive cell colonies were confirmed by indirect immunofluorescence labeling. Then Transwell polycarbonate filter was used to analyze the invasive potency. The expression of EMT associated proteins, E-cadherin and vimentin, was detected by Western blotting. RESULTS: Among four of the EMT negative cell lines, LNCaP was the only one expressed the vimentin gene but not the associated protein. The expression level of HIF-1alpha in LNCaP/HIF-1alpha was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. The cell numbers of LNCaP/HIF-1alpha that penetrated through the Transwell filter were higher than that of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1 and LNCaP cells, the expression of vimentin was up-regulated in LNCaP/HIF-1alpha, whereas the expression of E-cadherin was down-regulated. CONCLUSIONS: Over-expression of HIF-1alpha stimulates the invasion potency of human prostate carcinoma cells through EMT pathway. The expression of E-cadherin and vimentin, playing established roles in EMT, could be regulated by HIF-1alpha in human prostate cancer cell line.

Cadherins↗

Identification of phosphocaveolin-1 as a novel protein tyrosine phosphatase 1B substrate.

Protein tyrosine phosphatase 1B (PTP1B) is implicated in a number of signaling pathways including those mediated by insulin, epidermal growth factor (EGF), and the Src family kinases. The scaffolding protein caveolin-1 is also a participant in these pathways and is specifically phosphorylated on tyrosine 14, when these pathways are activated. Here, we provide evidence that PTP1B can efficiently catalyze the removal of the phosphoryl group from phosphocaveolin-1. Overexpression of PTP1B decreases tyrosine 14 phosphorylation in caveolin-1, while expression of the substrate-trapping mutant PTP1B/D181A causes the accumulation of phosphocaveolin-1 and prevents its dephosphorylation by endogenous PTPs. We further demonstrate that PTP1B physically associates with caveolin-1. Finally, we show that inhibition of PTP1B activity with a potent and specific small molecule PTP1B inhibitor blocks the PTP1B-catalyzed caveolin-1 dephosphorylation both in vitro and in vivo. Taken together, the results strongly suggest that caveolin-1 is a specific substrate for PTP1B. Identification of caveolin-1 as a PTP1B substrate represents an important new step in further understanding the signaling pathways regulated by PTP1B.

Animals↗

Molecular characterization of the two-component histidine kinase gene from Monilinia fructicola.

Brown rot of stone fruit caused by Monilinia fructicola (G. Wint) Honey is one of the most common fungal diseases in California. In this study, two laboratory-induced iprodione-resistant (LIR) mutants of M. fructicola were characterized by osmotic sensitivity, virulence on prune and sequence of the two-component histidine kinase gene (Mfos-1). The LIR mutants showed more sensitivity to osmotic stress and lower virulence on prune than their wild-type parent. Analysis of deduced amino acid of Mfos-1 showed that this protein exhibited all the characteristic features of the two-component histidine kinase genes, including osmotic sensing domain, six 90-amino-acid repeat motifs (coiled coil region) and kinase core and response regulator domains. Comparison of DNA sequences of the Mfos-1 from LIR mutants and the wild-type sensitive (S) isolate showed that LIR mutants had single point mutations in the coiled coil region of Mfos-1.

Amino Acid Sequence↗

[Establishment of bone metastasis model of prostate cancer in nude mice by intratibia injection of human prostate cancer cell line Du145].

OBJECTIVE: To establish a bone metastasis model of prostate cancer by intratibia injection of Du145 in nude mice, observe the local growth of tumor in tibia and then assess application value of this model. METHODS: For 9 male nude mice, Du145 (5 x 10(6)) was injected in tibia by a TB syringe with a 29-gauge needle at a dose of 30 microl per mouse. Then the vital signs of the nude mice were observed. When the mice were dying, they were sacrificed, and the tissues of right hindlimbs, lymphatic nodes, lungs and livers were taken out, fixed in 10% formalin, embedded in paraffin, stained by HE and then observed microscopically. RESULTS: Incidence of bone tumor after intratibia injection was 67% (6 out of 9). About 48 days later, there were some small palpable nodes in right hind-limbs of the 6 mice and they couldn't walk normally. About 55 days later, cachexia occurred in them. After dissection, some carrion-like tissue grew from marrow cavity to muscular spatium, which was identified as tumor tissue by HE. The envelop of livers became crampy, and acute hepatitis could be diagnosed through microscopy, which represented a large scale of hepatocytic death, liver sinus dilatation and hyperemia, hepatic lobule infiltrated by lymphocyte, macrophage and inconspicuous hyperplasia. Since hypohepatia occurred too early, we couldn't detected distant metastases. CONCLUSION: The intratibia injection model is an optimal animal model to study metastasis of prostate cancer. It mimics the natural situation of human prostate cancer and will help to understand the mechanisms of androgen-independence and osseous metastasis, and tumor-host determinants of PSA expression.

Animals↗

[Expression and significance of metastasis-associated proteins in prostate cancer cell lines with different metastatic potentials].

OBJECTIVE: To observe the expression profiles between two metastasis-associated proteins in different prostate cancer cell lines and explore the molecular mechanisms of bone metastatic potentials. METHODS: Expressions of E-cadherin and vimentin in two prostate cancer cell lines (LNCaP and IA8) with different metastatic potentials were detected by Western blotting. RESULTS: There was remarkable difference in the expressions of E-cadherin and vimentin between the highly metastatic cell line and the lowly one. As one of the adhesion associated proteins, E-cadherin was detected with high level of expression in LNCaP cell line, which was well known as low metastatic potential. However, E-cadherin did not expressed in IA8 with high metastatic potential. And as one of the cytoskeleton proteins, vimentin expression was high in IA8, but not in LNCaP. CONCLUSION: There is definitely difference in the metastatic phenotypes (E-cadherin and vimentin) among cell lines with different metastatic potentials. The expressions of E-cadherin and vimentin proteins may play important roles in promoting and inhibiting the metastasis of prostate cancer respectively, and may be considered to be valuable in evaluating the malignant degree, predictable metastasis and prognosis of prostate cancers.

Cadherins↗

[Analysis of differential express gene between keloid and normal skin by suppression subtractive hybridization].

OBJECTIVE: To compare gene express difference of keloid and normal skin tissues by using the suppression subtractive hybridization (SSH) so as to find the differential express gene in keloid. METHODS: mRNA extracted from keloid and normal skin tissues was used as the template to synthesis cDNA of keloid and normal skin. The cDNA of keloid served as a tester, the cDNA of normal skin as a driver. cDNA was digested with Rsa I. Adaptor-ligated tester cDNA was prepared. Then first hybridization, second hybridization and PCR amplification were done. Differentially expressed cDNA was selectively amplified during these reactions. After SSH, the PCR mixture was ligated with T-vector. The positive clones were selected and the insert gene fragments were analyzed. Southern hybridization identified the keloid differential express genes. The positive clones of Southern hybridization were selected, and these sequences were analyzed. The results were compared with that of GeneBank. RESULTS: Thirteen differential genes were found in keloid, of which 11 gene clones have been known their function, and 2 clones have not known their function. CONCLUSION: Keloid differentially expressed gene was screened successfully by SSH.

DNA, Complementary↗

[Expression of "epithelial-mesenchymal transition" associated proteins in prostate cancer cell lines with different metastatic potentials and its significance].

OBJECTIVE: To determine the characteristics of epithelial-mesenchymal transition (EMT) in different human prostate cancer cell lines and explore the molecular mechanisms of bone metastatic potentials. METHODS: Expressions of E-cadherin, N-cadherin and Vimentin in several prostate cancer cell lines (LNCaP, C4, C4-2, IF11, IA8, Du145 and PC-3) with different metastatic potentials were detected by Western blotting. RESULTS: There was remarkable difference in the expressions of E-cadherin, N-cadherin and Vimentin between these cell lines. As one of the adhesion associated proteins, E-cadherin was detected with high expression in LNCaP, C4, C4-2 and PC-3, whereas with a low expression in IF11, IA8 and Du145. However, as one of the mesenchymal proteins, N-cadherin was shown to be completely different from Vimentin expression profile in these cell lines. CONCLUSION: There is actual difference in the EMT phenotypes among cell lines with different metastatic potentials. LNCaP, C4, C4-2 and PC-3 are cells without EMT change, while IF11, IA8 and Du145 are positive for EMT. The expressions of EMT associated proteins play important roles in promoting and repressing the metastasis of prostate cancer.

Blotting, Western↗

[Clinical trials of combined therapy of an oral Chinese medicine with massage for chronic nonbacterial prostatitis].

OBJECTIVE: To evaluate the clinical effect of an oral Chinese medicine combined with massage of the prostate in treating chronic nonbacterial prostatitis (CNP). METHODS: Seventy-two CNP patients were randomly divided into an experimental group (oral Chinese medicine with massage) and a control group (oral Chinese medicine only). The main parameters were compared before and two months after the treatment. RESULTS: Total efficacy rates of the experimental and control groups were 90.0% and 68.6%, respectively. Compared with the controls, patients in the experiment group had a lower score on NIH-CPSI, and the difference was significant statistically (P < 0.05). CONCLUSION: The combined therapy is more effective than oral Chinese medicine alone for the treatment of CNP.

Adult↗

Overexpression of PML induced apoptosis in bladder cancer cell by caspase dependent pathway.

The promyelocytic leukemia gene (PML) encodes a growth/tumor suppressor protein that is essential for the induction of apoptosis in response to various apoptotic signals. The mechanism by which PML plays a role in the regulation of cell death is still unknown. Our previous study demonstrated that overexpression of PML suppress the growth of bladder cancer cells by inducing apoptosis and cell cycle arrest. To further elucidate the mechanism of PML induced apoptosis in bladder cancer, we constructed a PML inducible stable cell line. We found that the increased expression of PML significantly inhibit the growth of the UM-UC-2/PML clone cells and present apparent massive apoptosis in 24 h post-induction, while the UM-UC-2/PMEP4 cells are not. We also examined the effect of PML on the cell cycle distribution in UM-UC-2 cells. We showed overexpression of PML cause a cell cycle arrest in G1 phase. In additional, increased expression of PML in bladder cancer UM-UC-2 cells reduce Survivin expression and up regulated Caspase-3, and cleaved PARP expression, these suggested that PML might regulate apoptosis through Caspase dependent pathways. Our results demonstrate a novel mechanism of PML-induced apoptosis by down-regulation of Survivin and activation of Caspase dependent pathway.

Apoptosis↗

[The protective effects of three components isolated from Astragalus membranaceus on shock wave lithotripsy induced kidney injury in rabbit model].

OBJECTIVE: Extracorporeal shock wave lithotripsy (ESWL) is has been shown to reduce renal parenchymal injury subject to application of shock wave lithotripsy in our pervious study. To investigate the protective action of three main components from Astragalus membranaceus, including total saponins of astragalus (TSA), total flavonoids of astragalus (TFA) total polysaccharide of astragalus (TPA) in alleviating shock wave induced kidney damage. METHODS: Sixty four male rabbits were randomly assigned to a control group or to 3 groups that were premedicated with TSA TFA and TPA respectively prior to application of ESWL. Each group of animals underwent shock wave lithotripsy (18 kV) to the right kidneys and received a total of 1500 shocks. Peripheral blood samples were collected to evaluate the levels of plasma endothelin-1 (ET-1), plasma nitric oxide (NO) and serum malondialdehyde (MDA) before and after shock wave treatment. The concentrations of these markers in the treated kidney tissues were also detected 3 days, 7 days and 14 days after application of ESWL. The changes of histopathology and cells ultrastructure were observed through light microscope and electron microscope. Untreated contralateral kidneys were evaluated as controls. RESULTS: In control serials the levels of ET-1 and MDA were elevated significantly while the level of NO was significantly decreased after application of shock wave lithotripsy (P < 0.05). The comparison between the controls and premedicated groups demonstrated that all these three components especially TSA and TFA significantly inhibited shock wave induced increasing of ET-1 and MDA (P < 0.05). TSA also significantly suppressed the decrease of NO and made the recovery time earlier compare to the results of controls (P < 0.05). However, TFA and TPA had almost no effects on the change of NO. (P > 0.05). The results in histopathology showed noticeably damage of glomerular and tubular epithelial cells in the treated kidneys in the controls. The histological alterations in the TPA group were similar to those of the controls. These alterations were significantly milder in the TSA and TFA particular the TSA group. CONCLUSION: TFA and TSA, especially TSA seemed to play the key role in alleviating ESWL induced kidney damage.

Animals↗