Pretreatment prostate-specific antigen density as a predictor of biochemical recurrence in patients with prostate cancer: a meta-analysis.

BACKGROUND: A consensus has not been reached on the value of prostate-specific antigen density (PSAD) as a predictor of biochemical recurrence of prostate cancer. This meta-analysis aimed to evaluate the association between PSAD and biochemical recurrence of prostate cancer after primary treatment. METHODS: Two authors systematically searched PubMed, Web of Science, and Embase databases (up to August September 10, 2023) to identify studies that assessed the value of pretreatment PSAD in predicting biochemical recurrence after primary treatment (radical prostatectomy or radiotherapy) of prostate cancer. A random effect model was used to pool adjusted hazard ratios (HR) with 95% confidence intervals (CI) for biochemical recurrence. RESULTS: Nine studies with 4963 patients were eligible for the meta-analysis. The reported prevalence of biochemical recurrence ranged from 4 to 55.1%. For patients with higher PSAD compared to those with low PSAD, the pooled HR of biochemical recurrence was 1.59 (95% CI 1.21-2.10). Subgroup analysis showed that the pooled HR of biochemical recurrence was 1.80 (95% CI 1.34-2.42) for patients who received radical prostatectomy, and 0.98 (95% CI 0.66-1.45) for patients who received radiotherapy. CONCLUSIONS: Elevated pretreatment PSAD may be an independent predictor for biochemical recurrence of prostate cancer after radical prostatectomy. Determining PSAD could potentially improve the prediction of biochemical recurrence in patients with prostate cancer.

Association Between Pretreatment Blood 25-Hydroxyvitamin D Level and Survival Outcomes in Patients With Clinically Localized Prostate Cancer: An Updated Meta-Analysis.

Studies on the prognostic value of the blood 25-hydroxyvitamin D level have yielded controversial results in prostate cancer (PCa) patients. This updated meta-analysis aimed to evaluate the association between pretreatment 25-hydroxyvitamin D level with survival outcomes among patients with clinically localized PCa. PubMed, Web of Science, and Embase databases were searched to identify studies evaluating the association of pretreatment 25-hydroxyvitamin D level with PCSM and all-cause mortality among clinically localized PCa patients. Ten cohort studies with 10,394 patients were identified. The meta-analysis revealed that PCa patients with the lowest 25-hydroxyvitamin D levels had an increased risk of PCSM (adjusted hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.26-1.83; p < 0.001) and all-cause mortality (adjusted HR 1.31; 95% CI 1.00-1.90; p = 0.047) compared to those with higher reference 25-hydroxyvitamin D level. Subgroup analyses based on different sample sizes, follow-up duration, and adjusted times of blood draw also exhibited a significant association of vitamin D deficiency with the risk of PCSM. Lower pretreatment level of 25-hydroxyvitamin D may be an independent predictor of reduced survival in patients with clinically localized PCa. Measuring the pretreatment blood 25-hydroxyvitamin D level can provide valuable information for risk stratification of survival outcomes in these patients.

Communication molecules (ncRNAs) mediate tumor-associated macrophage polarization and tumor progression.

Non-coding RNAs play important roles in tumor cells and macrophages and participate in their communication as messengers. Non-coding RNAs have an impact in tumor cell proliferation, migration, and apoptosis, and they also regulate the differentiation and regulation of immune cells. In macrophages, they stimulate the polarization of macrophages into M1 or M2 by regulating proteins related to signaling pathways; in tumor cells, non-coding RNAs can enter macrophages through exosomes and affect the latter polarization. The polarization of macrophages further regulates the biological functions of cancer cells. The direction of macrophage polarization determines tumor progression, angiogenesis and drug resistance. This often creates a feedback loop. Non-coding RNAs act as bridges between tumor cells and macrophages to regulate the balance of the tumor microenvironment. We reviewed the signaling pathways related to macrophage polarization and the regulatory mechanisms of non-coding RNA in tumor-associated macrophages M1 and M2, and discussed the potential applications and prospects of exosome engineering.

Helicobacter pylori upregulates circPGD and promotes development of gastric cancer.

PURPOSE: Helicobacter pylori (H. pylori) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology of several different cancers. However, the underlying processes and putative interactions between H. pylori and circRNAs have received very little attention. To address this issue, we explored the interaction between H. pylori and circRNAs to investigate how they might jointly contribute to the occurrence and development of gastric cancer. METHODS: Changes in circPGD expression in H. pylori were detected using qRT-PCR. Cell proliferation and migration changes were assayed by colony formation, the CCK-8 assay and the transwell assay. Apoptosis was measured by flow cytometry. Western blot was conducted to detect changes in cell migration, apoptosis, proliferation and inflammation-associated proteins. QRT-PCR was used to measure changes in circPGD and inflammation-associated factors. RESULTS: We found that H. pylori induced increased circPGD expression in infected human cells and facilitated gastric cancer progression in three ways by promoting cell proliferation and migration, enhancing the inflammatory response, and inhibiting apoptosis. CONCLUSIONS: CircPGD appears to play a role in H. pylori-related gastric cancer and may thus be a viable, novel target for therapeutic intervention.

Association between Charlson comorbidity index and survival outcomes in patients with prostate cancer: A meta-analysis.

Objective: This meta-analysis aimed to assess the influence of comorbidity, as assessed by the Charlson comorbidity index (CCI), on survival outcomes in patients with prostate cancer (PCa). Methods: We conducted a comprehensive search of the PubMed, Web of Science, and Embase databases to identify studies that examined the association between CCI-defined comorbidity and survival outcomes in PCa patients. We employed a random effect model to merge adjusted hazard ratios (HR) with 95 % confidence intervals (CI) for survival outcomes. Results: Sixteen studies reporting on 17 articles, which collectively included 457,256 patients. For the presence (CCI score ≥1) versus absence (CCI score of 0) of comorbidity, the pooled HR was 1.59 (95 % CI 1.43-1.77) for all-cause mortality, 0.98 (95 % CI 0.90-1.08) for PCa-specific mortality, and 1.88 (95 % CI 1.61-2.21) for other-cause mortality. When compared to a CCI score of 0, the pooled HR of all-cause mortality was 1.30 (95 % CI 1.18-1.44) for a CCI score of 1, 1.65 (95 % CI 1.37-2.00) for a CCI score ≥2, and 1.75 (95 % CI 1.57-1.95) for a CCI score ≥3. Additionally, the pooled HR of other cause mortality was 1.53 (95 % CI 1.41-1.67) for a CCI score of 1, 1.93 (95 % CI 1.74-2.75) for a CCI score ≥2, and 3.95 (95 % CI 2.13-7.34) for a CCI score ≥3. Conclusions: Increased comorbidity, as assessed by the CCI, significantly predicts all-cause and other-cause mortality in patients with PCa, but not PCa-specific mortality. The risk of all-cause and other-cause mortality increases with the burden of comorbidity.

Tumor-derived CircRNA_102191 promotes gastric cancer and facilitates M2 macrophage polarization.

BACKGROUND: Gastric cancer is a common malignant tumor of the digestive tract and the fourth leading cause of death from cancer-related diseases. In recent years, many studies have found that circular RNAs play an important role in cancer. Tumor-associated macrophages (TAMs) are also critical for tumor progression. OBJECTIVE: This study examined the role of circRNA_102191 in gastric cancer progression. METHODS: The relative mRNA levels were determined by qRT-PCR. Western blotting and ELISA were used to detect the protein levels. In vitro proliferation was assessed using CCK8 and clonogenic assays. The migration and invasion of cell lines were assessed by transwell-based assays. The interactions between molecules were detected using a luciferase reporter assay. M0 macrophages were induced with PMA. M1 macrophages were induced with LPS and IFN-γ, and M2 macrophages were induced with IL-4. RESULTS: The expression of circRNA_102191 was enhanced significantly in gastric cancer cell lines and clinical tumor tissues. CircRNA_102191 promotes gastric cancer cell progression by regulating miR-493-3p and its downstream target gene XPR1. CircRNA_102191 can enhance the EMT process of gastric cancer cells by promoting the M2 polarization of macrophages. CONCLUSION: CircRNA_102191 promotes the biological function of gastric cancer cells by regulating the miR-493-3p/XPR1 axis and M2 macrophage polarization.

Low Expression of GIGYF1 Inhibits Metastasis, Proliferation, and Promotes Apoptosis and Autophagy of Gastric Cancer Cells.

GRB10 interacting GYF protein 1 (GIGYF1) binds to the N-terminal region of Grb10, regulates multiple signaling pathways. However, it is not clear what happens to cell proliferation, metastasis, apoptosis, and autophagy when the expression level of GIGYF1 gene is reduced. Detection of GIGYF1 expression in clinical tissue specimens and gastric cancer (GC) cell lines by quantitative Real-time PCR (qRT-PCR), GIGYF1 gene was knocked down in MGC-803 cells using small interfering RNA, the effect of GIGYF1 gene on cell metastasis was detected using Transwell assay and wound healing assay, the effect on cell proliferation was detected using plate cloning assay and cck-8 assay, the effect on apoptosis was detected using flow cytometry, autophagosomes were detected using laser confocal microscopy, and the effect on protein expression was detected using immunofluorescence and Western blotting. GIGYF1 gene expression was higher in tumor tissue samples than in paracancer tissue samples, and higher in human GC cell lines than in human normal gastric epithelial cells. GIGYF1 gene knockdown inhibited cell migration, scratch healing ability and EMT process, weakened cell proliferation ability, increased apoptosis rate, promoted the formation of autophagosomes, and changed the corresponding protein expression level. Meanwhile, GIGYF1 knockdowns inhibited the ERK and AKT signaling. In conclusion, the low expression of GIGYF1 gene can inhibit the occurrence and progression of gastric cancer, during which the ERK and AKT signaling pathways are inhibited.

Spindle pole body component 25 and platelet-derived growth factor mediate crosstalk between tumor-associated macrophages and prostate cancer cells.

Tumor-associated macrophages (TAMs) are involved in the growth of prostate cancer (PrC), while the molecular mechanisms underlying the interactive crosstalk between TAM and PrC cells remain largely unknown. Platelet-derived growth factor (PDGF) is known to promote mesenchymal stromal cell chemotaxis to the tumor microenvironment. Recently, activation of spindle pole body component 25 (SPC25) has been shown to promote PrC cell proliferation and is associated with PrC stemness. Here, the relationship between SPC25 and PDGF in the crosstalk between TAM and PrC was investigated. Significant increases in both PDGF and SPC25 levels were detected in PrC specimens compared to paired adjacent normal prostate tissues. A significant correlation was detected between PDGF and SPC25 levels in PrC specimens and cell lines. SPC25 increased PDGF production and tumor cell growth in cultured PrC cells and in xenotransplantation. Mechanistically, SPC25 appeared to activate PDGF in PrC likely through Early Growth Response 1 (Egr1), while the secreted PDGF signaled to TAM through PDGFR on macrophages and polarized macrophages, which, in turn, induced the growth of PrC cells likely through their production and secretion of transforming growth factor ß1 (TGFß1). Thus, our data suggest that SPC25 triggers the crosstalk between TAM and PrC cells via SPC25/PDGF/PDGFR/TGFß1 receptor signaling to enhance PrC growth.

Spindle pole body component 25 in the androgen-induced regression of castration-resistant prostate cancer.

Background: Androgen plays a critical role in the development and growth of prostate cancer (PCa) by binding to the androgen receptor, a steroid receptor for testosterone and dihydrotestosterone (DHT). Androgen deprivation therapy, a clinical endocrine therapy, has resulted in increases in the occurrence of castration-resistant prostate cancer (CRPC); however, the mechanisms of CRPC have not yet fully been determined. We previously showed that spindle pole body component 25 (SPC25), a component of the NDC80 complex that is critical in kinetochore formation and chromosome segregation during the cell cycle, plays a critical role in PCa tumorigenesis and cancer stemness. However, it is not yet known whether SPC25 plays a role in CRPC; thus, we sought to address this question in the current study. Methods: SPC25 levels were detected in androgen-insensitive PCa cells using the public database and bioinformatics tools. In vitro, SPC25 levels were determined in androgen-sensitive and androgen-insensitive PCa cells treated with or without DHT. The growth of the PCa cells was assessed by the Cell Counting Kit-8 assay. The invasiveness and migratory potential of the PCa cells were assessed by the transwell cell invasive assay and migratory assay, respectively. Gain-of-function and loss-of-function experiments examined the transfection of androgen-sensitive and androgen-insensitive PCa cells by plasmids carrying small-interfering ribonucleic acids for SPC25 or SPC25, respectively. Results: SPC25 levels were significantly reduced in the androgen-insensitive PCa cells treated with DHT in the Public database. In vitro, PCa cell growth, invasion, and metastasis was reduced in androgen-insensitive PCa cells but increased in androgen-sensitive PCa cells treated with DHT, partially through DHT-regulated expression of SPC25 at transcriptional but not at translational levels. Conclusions: Androgen treatment reduces CRPC growth, invasion, and metastasis partially through its regulation of SPC25. SPC25 represents a promising target in the treatment of CRPC.

Role of spindle pole body component 25 in neurodegeneration.

BACKGROUND: Aberrant growth and polarization of microglia are critical for pathological initiation and progression of neurodegenerative conditions like Alzheimer's disease (AD). However, the molecular signals that govern the outgrowth of microglia have not yet been fully determined. Spindle pole body component 25 (SPC25) is an important part for forming NDC80 complex, which plays a key role in the assembly of the microtubule-binding domain of kinetochores. Nevertheless, the role of SPC25 in microglial growth during neurodegeneration has not been described before, and was thus addressed in the current study. METHODS: We generated an adeno-associated virus (AAV) serotype PHP.B carrying short hairpin RNA (shRNA) for SPC25 (shSPC25) under a microglia-specific TMEM119 promoter (AAV-pTMEM-shSPC25). Serotype PHP.B allowed the virus to cross blood-brain barrier, while TMEM119 promoter allowed specific targeting microglia in vitro and in vivo. We intravenously administrated AAV-pTMEM-shSPC25 to AD-prone APP/PS1 male and female mice and determined this effect on microglia proliferation and mouse behavior. RESULTS: Depletion of SPC25 did not alter polarization of microglia cell polarization in vitro. On the other hand, AD-prone APP/PS1 mice that had received AAV-pTMEM-shSPC25 significantly decreased SPC25 levels in microglia and attenuated microglia proliferation, resulting in significant improvement of the performance of the mice in behavior tests. CONCLUSIONS: Specific depletion of SPC25 in microglia may prevent AD development through suppression of microglia outgrowth. SPC25 may be a promising novel target for preventing AD through microglia.

The Ocular Surface Characteristics in Prostate Cancer Patients Treated with Androgen Deprivation Therapy.

BACKGROUND: To investigate the association of long-term androgen deprivation therapy (ADT) with ocular surface characteristics in prostate cancer patients. METHODS: A total of 30 male prostate cancer patients who received ADT were selected. All candidates were scored using the Ocular Surface Disease Index (OSDI) and subsequently divided into two groups containing 9 symptomatic patients (scores >12) and 21 asymptomatic patients (scores ≤ 12). Another 20 healthy age-matched males were selected as the control group. Each candidate was assessed with respect to eyelid margin abnormality, tear film break-up time (NI-BUT), tear meniscus height (TMH), meiboscore, meibum expressibility, and demodex infection. RESULTS: The NI-BUT in the ADT group was significantly shorter than that in the control group. The scores for OSDI, eyelid margin abnormality, meibum expressibility, and meiboscores were significantly higher in the ADT group (P < 0.05). Moreover, the NI-BUT in the symptomatic ADT group was significantly shorter than that in the asymptomatic ADT group (P < 0.05). The meiboscores and meibum expressibility score in the symptomatic ADT group were significantly higher than those in the asymptomatic ADT group (P < 0.05). The presence of demodex in the symptomatic ADT group was also higher than that in the asymptomatic ADT group (P < 0.05).The length of time that patients had been taking ADT was positively correlated with meiboscores and negatively correlated with NI-BUT. CONCLUSION: Androgen levels were associated with significant changes in relative meibomian gland function. Subjective symptoms, such as dryness and foreign body sensation, were more obvious in prostate cancer patients receiving ADT, which may be caused by MGD and demodex infection. It's recommended that more attention be paid to the ocular surface in prostate cancer patients taking ADT by performing examination of NI-BUT and meibomian gland morphology and function with a view to providing more comprehensive prevention and treatment protocols.

Calcium-binding and coiled-coil domain 2 promotes the proliferation and suppresses apoptosis of prostate cancer cells.

Prostate cancer (PCa) is considered to be one of the most common tumors in men. Calcium-binding and coiled-coil domain 2 (CALCOCO2) is a known important xenophagy receptor, which mediates intracellular bacterial degradation. To the best of the authors' knowledge, the present study is the first to demonstrate that CALCOCO2 functions as an oncogene in PCa. The results of the current study indicated that CALCOCO2 knockdown suppressed cell proliferation and colony formation, whereas it promoted apoptosis of PCa cells. In addition, knockdown of CALCOCO2 in PCa cells reduced cyclin-E1 and increased p53 protein expression. Bioinformatics analysis revealed that CALCOCO2 was associated with 'autophagosome assembly', 'nucleophagy' and 'nucleic acid metabolic process' biological processes and interacted with sequestosome-1, microtubule-associated proteins 1A/1B light chain 3 (MAP1LC3)B, γ-aminobutyric acid receptor-associated protein, IκB kinase subunit γ and MAP1LC3C. Moreover, CALCOCO2 protein levels were indicated to be significantly increased in PCa samples compared with normal prostate tissues. These results suggested that CALCOCO2 may be of value as a diagnostic and therapeutic target in PCa.

Overexpression of NCAPH is upregulated and predicts a poor prognosis in prostate cancer.

Prostate cancer (PCa) is one of the most frequently diagnosed types of cancer worldwide. However, there remains a lack of accurate biomarkers to predict the outcome of PCa. Non-SMC condensin I complex subunit H (NCAPH) encodes a regulatory subunit of the non-structural maintenance of chromosomes condensin I complex. The present study aimed to investigate whether NCAPH may be a novel diagnostic marker for PCa by analyzing public datasets, including GSE17951, GSE55945 and a dataset from The Cancer Genome Atlas. The current results, to the best of our knowledge, demonstrated for the first time that NCAPH is significantly upregulated in PCa. Furthermore, it was identified that NCAPH expression is higher in stage T3/T4 and N1 PCa samples compared with stage T2 and N0 PCa samples, respectively. Kaplan-Meier analysis demonstrated that overexpression of NCAPH is associated with poor survival of patients with PCa. Bioinformatics analysis revealed that NCAPH is involved in regulating the PCa cell cycle by interacting with a number of proteins, including non-SMC condensin I complex subunit D2, non-SMC condensin I complex subunit G, structural maintenance of chromosomes 4, structural maintenance of chromosomes 2, Aurora kinase A, Aurora kinase B, cyclin-dependent kinase 1, H2A histone family member Z, POC1 centriolar protein A and histone cluster 2 H2A family member C. In summary, the present results suggest NCAPH may be a novel and beneficial diagnostic and therapeutic target in PCa.

Spindle pole body component 25 regulates stemness of prostate cancer cells.

Spindle pole body component 25 (SPC25) is a component of NDC80 complex that controls spindle assembly checkpoint in the microtubule-binding domain of kinetochores. We recently showed that SPC25 is required for prostate cancer (PrC) cell proliferation and cell cycle progression, and here we investigated whether SPC25 may be a Cancer stem cell (CSC) marker in PrC. We found that the levels of SPC25 were higher in PrC samples than paired normal prostate tissue. The overall survival of PrC patients with high SPC25 was poorer than those with low SPC25. PrC cell lines were transduced with two vectors carrying a luciferase reporter and a mCherry fluorescent reporter under a cytomegalovirus promoter and a nuclear green fluorescent protein reporter under the control of a SPC25 promoter, respectively, to allow differentiating SPC25+ from SPC25- PrC cells by flow cytometry. Compared to SPC25- cells, SPC25+ cells formed significantly more tumor spheres in culture, appeared to be more resistant towards docetaxel-induced cell apoptosis, and generated larger tumors with higher frequency after serial adoptive transplantation. Thus, our data suggest that SPC25 may be highly expressed in the CSC-like cells in PrC and could be a promising target for effective treatment of PrC.

Retraction Note: Protective role of silymarin in a mouse model of renal Ischemia-Reperfusion injury.

This article [1] is retracted at request of the Editor. After publication of this article [1] concerns were raised regarding aspects of the methodology, including the choice of stains being inappropriate or inadequate to answer the research question. A discrepancy was also noted between the number of groups described in the methods and the number of groups presented in some of the figures. Furthermore the western blot images did not entirely correspond with the information reported in the results. For these reasons the conclusions of the study cannot be considered to be supported by the data. All authors agree to this retraction.

Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is one of the most malignant tumors of the male urogenital system. There is an urgent need to identify novel biomarkers for PCa. METHODS: In this study, we evaluated the expression levels of MCM10 in prostate cancer by analyzing public datasets (including The Cancer Genome Atlas and GSE21032). Furthermore, loss of function assays was performed to evaluate the effects of MCM10 on cell proliferation, apoptosis, and colony formation. Furthermore, we performed microarray and bioinformatics analyses to explore the potential mechanisms of MCM10. RESULTS: In the present study, we for the first time revealed MCM10 was significantly upregulated in PCa. Moreover, we found increased MCM10 expression was significantly associated with advanced clinical stage and high Gleason score PCa. Kaplan-Meier analysis demonstrated higher MCM10 expression was associated with a poorer patient prognosis in PCa. Furthermore, loss of function assays showed that MCM10 knockdown inhibited cell proliferation and colony formation, but promoted cell apoptosis. Additionally, we performed microarray and bioinformatics analysis and found MCM10 regulated PCa progression by regulating a series of biological processes including cancer, cell death, and apoptosis. CONCLUSIONS: These results suggest that MCM10 may be a potential diagnostic and therapeutic target for PCa.

Erectile dysfunction and risk of cardiovascular and all-cause mortality in the general population: a meta-analysis of cohort studies.

PURPOSE: Studies on the association of erectile dysfunction (ED) with cardiovascular or all-cause mortality have yielded conflicting findings. We conducted this meta-analysis to evaluate the association of ED with cardiovascular or all-cause mortality in the general population. METHODS: Pubmed and Embase databases were searched for prospective studies that evaluated the association of ED with cardiovascular or all-cause mortality in the general population up to 15 December, 2017. The overall combined risk ratio (RR) and 95% confidence intervals (CI) were pooled for the men with or without ED. RESULTS: A total of 7 studies involving 111,440 participants were included in the meta-analysis. When compared to the men with or without ED, the overall pooled RR was 1.24 (95% CI 1.11-1.39) for all-cause mortality and 1.11 (95% CI 0.92-1.35) for cardiovascular mortality. Subgroup analyses indicated that only men with severe ED significantly increased all-cause mortality risk (RR 1.58; 95% CI 1.37-1.82), but not in the mild (RR 1.07; 95% CI 0.93-1.24) ED and the moderate (RR 1.16; 95% CI 1.00-1.35) ED. CONCLUSIONS: This meta-analysis suggests that severe ED is significantly associated with increased all-cause mortality in the general population. However, the association of ED with cardiovascular mortality should be further investigated.

Knockdown of spindle pole body component 25 homolog inhibits cell proliferation and cycle progression in prostate cancer.

Prostate cancer (PCa) is the most frequently diagnosed type of cancer in Chinese males. Cell-cycle aberration is a hallmark of cancer. Spindle pole body component 25 homolog (SPC25), a component of the Ndc80 complex, serves an important role in regulating mitotic chromosome segregation. However, the functional roles of SPC25 in PCa remain poorly understood. To the best of our knowledge, the present study was the first to demonstrate that SPC25 is significantly upregulated in PCa. In order to investigate the molecular roles of SPC25, a loss of function assay was performed, revealing that SPC25 knockdown inhibited cell proliferation, and induced a decrease in the number of cells in the S phase and an increase in the number of cells in the G2/M phase. Furthermore, SPC25 knockdown promoted the apoptosis of PCa cells. Additionally, bioinformatics analysis revealed multiple functional roles of SPC25 in regulating cell proliferation, apoptosis, invasion, transforming growth factor-ß signaling and the SUMOylation pathway in PCa. The present study also evaluated the potential prognostic value of SPC25 using The Cancer Genome Atlas RNA-seq data and demonstrated that SPC25 was upregulated in late stage PCa. Kaplan-Meier analysis demonstrated that lower SPC25 expression was associated with an improved survival rate in patients with PCa. Taken together, these results suggested that SPC25 serves an oncogenic role in PCa and may act as a novel diagnostic and therapeutic target for PCa.

Protective role of silymarin in a mouse model of renal Ischemia-Reperfusion injury.

BACKGROUND: We investigated the mechanism of action of silymarin in a mouse model of renal ischemia-reperfusion injury (I/R) to ascertain its role in the treatment of I/R injury. METHODS: Twenty-four C57BL/6 male mice were divided randomly into three groups: control (sham); ischemia-reperfusion (I/R); silymarin + ischemia-reperfusion (silymarin + I/R). In sham mice, an abdominal incision was made, followed by dissection of the bilateral renal pedicle, with no further cross-clamping of arteries. Silymarin + I/R mice were administered 100 mg/kg silymarin daily for 7 consecutive days before surgery, whereas I/R mice were administered (i.g.) 0.9 % saline + 0.1 % (v/v) ethanol daily for 7 consecutive days before surgery. Silymarin + I/R and I/R mice were subjected to renal ischemia to induce acute kidney injury after 45-min clamping of bilateral renal arteries. Serum levels of creatinine and blood urea nitrogen levels were measured. Periodic acid-Schiff (PAS) staining was undertaken to detect damaged renal tissue. Myeloperoxidase (MPO) activity and immunofluorescent detection of CD68 expression was undertaken for each group. Levels of inflammatory cytokines secreted by renal tissue were monitored by ELISA. Apoptosis was detected by TUNEL staining. Expression of cleaved-caspase-3, Bcl-2 and Bax was detected by western blotting. RESULTS: Serum creatinine and blood urea nitrogen levels were elevated in silymarin + I/R and I/R groups compared with sham mice (p < 0.05), whereas those in the I/R group were significantly higher than in the silymarin + I/R group (p < 0.05). Number of damaged renal tubule cells and apoptotic cells in sham and silymarin + I/R groups was significantly lower than in I/R mice. MPO activity and secretion of inflammatory cytokines in silymarin + I/R and I/R groups was reduced (p < 0.05), and CD68 expression in silymarin + I/R mice was lower than in I/R mice (p < 0.05). Expression of cleaved-caspase-3 and Bax in the I/R group was significantly higher than in sham mice, whereas Bcl-2 expression was lower than in silymarin + I/R mice (p < 0.05). CONCLUSIONS: Silymarin can inhibit renal I/R injury by inhibiting release of inflammatory factors and regulating apoptosis.

Kallikrein 3 and vitamin D receptor polymorphisms: potentials environmental risk factors for prostate cancer.

OBJECTIVE: To investigate the relationship and interaction of the single nucleotide polymorphisms (SNPs) of KLK3 and VDR and environmental factors with the predisposition to prostate cancer within Chinese population. METHODS: The comparison between 108 patients and 242 healthy people was carried out by using the TaqMan/MGB Probe Technology to determine the genotypes of KLK3(rs2735839 is located between KLK2 and KLK3) and VDR (rs731236 is located exon 9). Univariate and multivariate logistic regression model were used to assess the connection of genetic polymorphisms and environmental risk factors with PCa by collecting demographic information, as well as BMI, consumption of cigarettes, alcohol, and tea, exercise, and other environmental risk factors. RESULTS: The appearing frequencies of AA, AG, and GG genotypes at the SNPs rs2735839 (A/G) for KLK3 were 13.89%, 62.96% and 23.15% in PCa and 37.19%, 44.63%, 18.18% in control, respectively; these two groups are statistically different (P=0.00). While the appearing frequencies of TT, TC, and CC genotypes at the SNPs rs731236 (T/C) for VDR were 88.89%, 9, 26%, 1.85% and 90.50%, 9.10%, 0.40% in control, respectively, with no significant statistical difference between the two group. The study confirmed decreasing risk in tea drinkers (OR=0.58, 95% CI=0.35-0.96). CONCLUSIONS: Our studies indicate that environmental factor-tea drinking is associated with the development of PCa. The habit of drinking tea is a protective factor against PCa. The SNPs rs2735839 for KLK3 is strongly related to the development of PCa, while the SNPs rs731236 for VDR is not. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9759981571058803.