Trends in estrogen and progesterone receptors in prostate cancer: a bibliometric analysis.

Introduction: The bibliometric analysis aims to identify research trends in estrogen receptor (ERs) and progesterone receptor (PRs) in prostate cancer (PCa), and also discuss the hotspots and directions of this field. Methods: 835 publications were sourced from the Web of Science database (WOS) from 2003 to 2022. Citespace, VOSviewer, and Bibliometrix were used for the bibliometric analysis. Results: The number of published publications increased in early years, but declined in the last 5 years. The United States was the leading country in citations, publications, and top institutions. Prostate and Karolinska Institutet were the most publications of journal and institution, respectively. Jan-Ake Gustafsson was the most influential author based on the number of citations/publications. The most cited paper was "Estrogen receptors and human disease" by Deroo BJ, published in the Journal of Clinical Investigation. The most frequently used keywords were PCa (n = 499), gene-expression (n = 291), androgen receptor (AR) (n = 263), and ER (n = 341), while ERb (n = 219) and ERa (n = 215) further emphasized the importance of ER. Conclusions: This study provides useful guidance that ERa antagonists, ERb agonists, and the combination of estrogen with androgen deprivation therapy (ADT) will potentially serve as a new treatment strategy for PCa. Another interesting topic is relationships between PCa and the function and mechanism of action of PRs subtypes. The outcome will assist scholars in gaining a comprehensive understanding of the current status and trends in the field, and provide inspiration for future research.

Associations between polybrominated diphenyl ethers (PBDEs) levels in adipose tissues and female menstrual cycle and menstrual bleeding duration in Shantou, China.

The endocrine-disrupting effects of human exposure to polybrominated diphenyl ethers (PBDEs) have been studied, but their associations with menstrual status were not clearly clarified. This study was to evaluate the associations between PBDE levels in adipose tissues and the menstrual cycle and menstrual bleeding duration alteration. A total of 298 female cases undergoing surgery were recruited from two hospitals in Shantou, China. Demographic, clinical, and pathological information were collected, and adipose tissues were obtained during mammary or abdominal surgery. Gas chromatography with mass spectrometry was used to analyze 14 PBDE congeners in the adipose samples. The associations between PBDE levels and menstrual cycle (MC) and menstrual duration (MD) were analyzed by logistic regression models, estimating odds ratios (ORs) and 95% confidence intervals (CIs). BDE-153 had the highest level in the adipose samples, followed by BDE-209, BDE-183 and BDE-47. Compared with referents, median levels of BDE-47, -71, -153, -183 were higher in women with MC > 30 days (all P < 0.05); BDE-47, -153, -183, -209 were also higher in women with MD > 5.5 days (all P < 0.05). After adjusted for age and parity, BDE-47, -71, -153, -183 were associated with prolonged MC (OR = 1.20, 1.15, 1.12, 1.11, respectively, all P < 0.05) in the logistic regression models; and BDE-47, -153, -183, -209 were associated with the prolonged MD (OR = 1.13, 1.09, 1.10, 1.11, respectively, all P < 0.05). Several individual PBDE congeners in female adipose were found associated with prolonged menstrual cycle and menstrual duration. PBDEs may influence reproductive health of women by altering menstrual status.

Pneumatic Lithotripsy versus Holmium Laser Lithotripsy in Percutaneous Nephrolithotomy for Patients with Guy's Stone Score Grade IV Kidney Stone.

BACKGROUND AND OBJECTIVE: The aim of this study was to compare the efficacy and reliability of holmium (Ho:YAG) laser lithotripsy (HLL) and pneumatic lithotripsy (PL) in percutaneous nephrolithotomy (PCNL) in the treatment of patients with Grade IV kidney stones based on Guy's Stone Score. STUDY DESIGN/MATERIALS AND METHODS: This retrospective study included 103 patients with Grade IV kidney stones out of 440 patients who underwent PCNL through HLL and PL in Second Affiliated Hospital of Shantou University Medical College, China, from January 2016 to December 2018. We analyzed preoperative, intraoperative, and postoperative variables of the patients to evaluate the efficacy and reliability of PCNL procedures. RESULTS: Patients were categorized as Grade I, II, III, and IV, and the patients of each grade were 85 (19.32%), 39 (8.86%), 213 (48.41%), and 103 (23.41%), respectively. In Grade IV, the total operative time (min) for the PL and HLL groups was 137.7 ± 47.79 and 134.27 ± 53.38, respectively (p = 0.744). The variation in laboratory examination values including ΔHGB (g/L), ΔHCT, ΔPCT, and ΔCr (µmol/L) for PL and HLL groups was 19 ± 11.23/12 ± 15.42 (p = 0.012), 0.057 ± 0.034/0.038 ± 0.045 (0.009), 0.027 ± 0.034/0.026 ± 0.034 (0.702), and 3.07 ± 17.4/20.54 ± 65.93 (0.692), respectively. The postoperative hospitalization day was 8.94 ± 4.2 and 7.73 ± 2.75 (p = 0.015), respectively. As for the stone-free rate (SFR), the SFRs for PL and HLL were 48.15% (n = 39/81) and 59.09% (n = 13/22) (p = 0.363), respectively. CONCLUSIONS: HLL showed a comparable advantage of not only decreased postoperative hemoglobin and hematocrit but also fewer postoperative hospitalization days. Based on the results of our retrospective study, for those Grade IV kidney stone patients who have a risk of bleeding before PCNL operation, HLL can be a considerable treatment option. Besides, in consideration of reducing human care cost, HLL which showed fewer hospitalization days, would be more welcome by patients.

Effects of Exposure to Bisphenol A during Pregnancy on the Pup Testis Function.

Testosterone plays an important prenatal role in male testis development. Bisphenol A (BPA) exposure during pregnancy affects testosterone levels and germ cell apoptosis of male pups, but little information is available for the mechanism. The aim of the present study was to investigate the mechanism by which BPA alters testosterone levels and germ cell apoptosis. Pregnant female C57BL/6J mice, throughout gestation, had access to drinking water containing BPA at 5 and 50 µg/mL. Male pups were euthanized on postnatal days (PNDs) 1, 14, and 35. Relative to control, BPA exposure at 5 and 50 µg/ml decreased testosterone level, as measured by chemiluminescent immunoassay, on PND14. Real-time PCR indicated mRNA levels for steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), and 3-ß-hydroxysteroid dehydrogenase/△-5-4 isomerase (3ß-HSD) were significantly lower in the BPA pups compared to control. Additionally, BPA increased the percentage of TUNEL-positive seminiferous tubules, decreased the mRNA level of Bcl-2, and increased Bax expression, indicative of increased apoptosis. These results suggest that BPA exposure in utero decreases the testosterone concentration by decreasing steroidogenic enzymes (StAR, CYP11A1, and 3ß-HSD). Furthermore, BPA exposure increases the apoptosis of germ cells, which is associated with proapoptotic changes in the levels of Bcl-2 and Bax.

Association of total testosterone, free testosterone, bioavailable testosterone, sex hormone-binding globulin, and hypertension.

Low testosterone has been inversely associated with hypertension. Our objective was to determine the associations between total testosterone (TT), free testosterone (FT), bioavailable testosterone (BioT), sex hormone-binding globulin (SHBG), and hypertension. Two hundred fifty-three men were enrolled in this study. TT and SHBG were measured by chemiluminescent immunoassay, and FT and BioT were calculated. Hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg. Our results showed that hypertensive men had higher SHBG levels, and lower FT and BioT, compared to normotensive men. FT and BioT were inversely associated with SBP and DBP after adjusting for covariates (age, smoking, alcohol consumption, and physical activity). Furthermore, there was a significant decrease in the odds ratios for hypertension in the third and fourth quartiles of BioT and FT, compared to the lowest quartile before and after adjusting for covariates. In contrast, the OR for hypertension in the third quartile of SHBG was lower than the highest quartile. Our data show that FT and BioT are inversely correlated with SBP, DBP, and hypertension in men.

Retroperitoneoscopic nephrectomy for a horseshoe kidney with hydronephrosis and inflammation: A case report.

RATIONALE: A horseshoe kidney is the most common congenital fusion abnormality in the kidney, occurring in approximately 1 in 400 live births. Several complications including renal malignancies, ureteropelvic junction obstruction, urolithiasis, vesicoureteral reflux, and hydronephrosis can occur in this patient population. PATIENT CONCERNS: A 28-year-old woman was admitted to hospital because of chronic left low back pain. Microscopic hematuria was not seen. Computed tomography showed the horseshoe kidney and left hydronephrosis. DIAGNOSES: On the basis of these findings and clinical manifestations, the final diagnosis was the horseshoe kidney with left renal hydronephrosis and inflammation. INTERVENTIONS: A retroperitoneoscopic nephrectomy on the left kidney was performed. OUTCOMES: Histopathological examination of the specimen confirmed massive dilatation of the pelvicaliceal system and chronic pyelonephritic inflammation. The patient was discharged on the 7th postoperative day with no complications and no back pain. She remained well at 3 months with normal activity and good cosmetic result. LESSONS: Retroperitoneoscopic nephrectomy can be a safe and minimally invasive surgery for horseshoe kidney treatment.

Adipose tissue levels of polybrominated diphenyl ethers and breast cancer risk in Chinese women: A case-control study.

Polybrominated diphenyl ethers (PBDEs) are suspected to be associated with breast cancer risk because of their estrogenic potencies. Epidemiological studies of PBDEs and breast cancer are scarce. Our study aimed to estimate the association between adipose-tissue PBDE concentrations and breast cancer risk. A total of 209 breast cancer cases and 165 controls were recruited from hospitals between January 2014 and May 2016 in Shantou, Chaoshan area, China. Concentrations of 14 PBDE congeners were measured in adipose tissues obtained from the breast for cases and the abdomen/breast for controls during surgery. Demographic and clinicopathologic characteristics were obtained from medical records. Breast cancer risk as well as clinicopathologic characteristics were evaluated by adipose-tissue PBDE level. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer risk associated with levels of PBDE congeners were estimated from logistic regression models for all cases and stratified by estrogen receptor (ER) status. Level of total PBDEs (∑PBDE) and most individual PBDE congeners were higher in breast cancer cases than controls (median ∑PBDE, 94.99 vs 73.72 ng/g lipid). In the adjusted univariate model for all cases, breast cancer risk was increased with both 2nd and 3rd tertiles versus the 1st tertile of BDE-47 level (OR 2.05 [95% CI 1.08-3.92]; 5.47 [2.96-10.11]) and BDE-209 level (2.48 [1.30-4.73]; 4.72 [2.52-8.83]) with trend (both P < 0.001) and with the 3rd tertile of BDE-28 level (2.83 [1.63-4.92]), BDE-99 (3.22 [1.85-5.60]), BDE-100 (5.45 [2.90-10.23]), BDE-138 (2.40 [1.37-4.20]), BDE-153 (1.74 [1.02-2.97]), BDE-154 (1.84 [1.05-3.22]), and ∑PBDE levels (1.83 [1.07-3.14]) but decreased with the 3rd tertile of BDE-71 level (0.38 [0.22-0.65]) with trend (all P < 0.01). After stratifying by ER-positive or -negative status, the adjusted results were similar for ER-positive patients except for BDE-153 and BDE-154, with no statistical significance. In the multivariate model for all cases, age, menarche age, BDE-47, 71, 99, 100, 183 and 209 were independent factors associated with breast-cancer risk. ∑PBDE and most individual PBDE congeners investigated were positively associated with breast cancer risk in women from the Chaoshan area, China. PBDE may play a role in the occurrence and development of breast cancer.

Association of total testosterone, free testosterone, bioavailable testosterone and sex hormone-binding globulin with hepatic steatosis and the ratio of aspartate aminotransferase to alanine aminotransferase.

Several articles have shown the inverse association between total testosterone (TT) or sex hormone-binding globulin (SHBG) and hepatic steatosis. No articles report associations of TT, SHBG, free testosterone (FT), and bioavailable testosterone (BioT) with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratios. Therefore, we investigated the associations of TT, FT, BioT and SHBG with hepatic steatosis and AST/ALT ratios. A total of 218 men were enrolled. We diagnosed hepatic steatosis by ultrasound. TT and SHBG showed a reduced risk for hepatic steatosis when analyzed with or without adjusting for age, smoking, alcohol consumption and physical activity. Compared with the lowest quartile, the ORs for hepatic steatosis in the third and fourth quartiles (0.32 [95% CI: 0.14-0.75] and 0.27 [95% CI: 0.10-0.73], respectively) of SHBG were significantly lower after adjustments. The OR for hepatic steatosis in the fourth quartile of TT (0.41 [95% CI: 0.17-0.95]) was significantly lower than in the lowest quartile after adjustments. The mean AST/ALT ratios in men with hepatic steatosis were lower than those without hepatic steatosis (0.83 and 1.04, respectively), due to the elevated ALT levels in hepatic steatosis groups. Furthermore, TT and SHBG were positively associated with AST/ALT ratios with and without adjustments. In conclusion, higher TT and SHBG levels in men are associated with the reduced risk of hepatic steatosis and elevated AST/ALT ratios, independent of age, smoking, alcohol consumption and physical activity.

[Inhibitory effect of Genipin on uncoupling protein-2 and energy metabolism of androgen-independent prostate cancer cells].

OBJECTIVE: To explore whether the inhibitory effect of Genipin on uncoupling protein-2 (UCP-2) in mitochondria is involved in energy metabolism of androgen-independent PC3 prostate cancer cells. METHODS: PC3 prostate cancer cells were cultured and treated with Genipin at the concentrations of 40, 80, and 160 µmol/L for 48 hours. Then the proliferation of the cells was detected by MTT assay, the expression of UCP-2 mRNA determined by RT-PCR, and the content of intracellular pyruvic acid (PA) and the activity of succinate dehydrogenase (SDH) in the mitochondria measured by visible spectrophotometry. RESULTS: With the increased concentration of Genipin, the proliferative activity of the PC-3 cells, the expression level of UCP-2 mRNA, the content of intracellular PA and the activity of SDH in the cells were all decreased, namely, with the enhanced inhibitory effect of Genipin on UCP-2, a trend of reduction was observed in the proliferation of the cells, intracellular PA content, and SDH activity in the mitochondria. CONCLUSION: Genipin is involved in the energy metabolism of androgen-independent PC3 prostate cancer cells by reducing the content of intracellular PA and the activity of SDH in the mitochondria, which may be associated with its inhibitory effect on UCP-2.

[STC-1 is involved in anti-hypoxia proliferative balance of renal cancer cells by down-regulation of intracellular Ca2+ and HIF-1α levels].

OBJECTIVE: To investigate effects of stanniocalcin-1 (STC-1) on proliferation balance under hypoxic condition in renal cancer cells and its mechanism. METHODS: Hypoxic model was induced on renal cancer GRC-1 cells (Group H), the cells were treated with STC-1 protein at concentrations of 0.1 nmol/L (H1), 0.5 nmol/L (H2), 1.0 nmol/L (H3), or normal saline (H0) for 48 h， respectively. Cells proliferation was measured by MTT assay; mRNA and protein expressions of hypoxia inducible factor 1α (HIF-1α) and STC-1 in GRC-1 cells were detected by RT-PCR and ELISA, respectively; the intracellular levels of Ca2+ and adenosine triphosphate (ATP) were determined by fluorescence spectrophotometry and spectrophotometry, respectively. RESULTS: The expression of HIF-1α, STC-1 and Ca2+ levels were increased in GRC-1 cells under hypoxia condition; STC-1 reversed these changes in a dose-effect manner. Hypoxia significantly inhibited cell proliferation and the generation of ATP in GRC-1 cells and exogenous STC-1 reversed the effects of hypoxia; ATP generation increased gradually with increasing STC-1 concentration, but the cell proliferation was reduced. CONCLUSION: Exogenous STC-1 can promote the proliferation of renal cancer cells in hypoxia condition by reducing HIF-1α expression and Ca2+ content and increased ATP production, but the progressive inhibition of HIF-1 α hindered the renal carcinoma cell proliferation further, which indicates that STC-1 may be involved in anti-hypoxia proliferative balance of renal cancer cells.

[Effects of stanniocalcin-1 and hypoxia-inducible factor-1α on mitochondrial membrane potential stability in renal carcinoma cells].

OBJECTIVE: To explore the effects of stanniocalcin-1 (STC-1) and hypoxia-inducible factor-1α (HIF-1α) on the calcium and thus on the mitochondrial membrane potential (Δψm) in renal carcinoma cells. METHODS: We successfully established the renal carcinoma cell models with high HIF-1α gene expression. After various concentrations of STC-1 solutions were added to the culture medium, the proliferation of cells, expressions of HIF-1α and STC-1, levels of Ca(2+), Δψm, and mPTP were detected by MTT, RT-PCR, ELISA, fluorescence spectrophotometry, and ultraviolet spectrophotometry, respectively. RESULTS: The proliferation of renal carcinoma cells and Δψm were improved after HIF-1α gene transfection, STC-1 protein intervention, and STC-1 protein intervention after gene transfection. While the intracellular Ca(2+) level and mPTP were decreased significantly (P<0.05), all the changes were intensified with the gradual increase of STC-1. However, the increasing trend of cell proliferation gradually declined. CONCLUSION: HIF-1α may participate in malignant proliferation of renal carcinoma cells by promoting STC-1 proliferation or down-regulating Ca(2+); however, such an effect may be gradually attenuated due to the inhibitory effect of STC-1 on HIF-1α.

[Gossypol decreases the expression of connexin 43 in Sertoli cells].

OBJECTIVE: To study the effect of gossypol on the expression of connexin 43 (CX43) in Sertoli cells. METHODS: TM4 Sertoli cells were cultured and treated with gossypol at the concentrations of 1.25, 2.5, 5 and 10 micromol/L for 6, 12, 24 and 48 hours. The cytotoxicity of gossypol was assessed by CCK-8 assay, and the expression of CX43 in the normal TM4 Sertoli cells and in those treated with different concentrations of gossypol for different times was detected by RT-PCR and immunofluorescence analysis. RESULTS: Semiquantitative RT-PCR and immunofluorescence analysis showed the expression of CX43 in the normal TM4 cells. At 24 hours of exposure to gossypol, the expression began to decrease gradually with the prolonging of time and the increasing concentration of gossypol (P < 0.05). CONCLUSION: Gossypol reduces the expression of CX43 in TM4 Sertoli cells, which might underlie the mechanism of its antifertility action.

The testosterone mimetic properties of icariin.

AIM: To evaluate the testosterone mimetic properties of icariin. METHODS: Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each: the control group (C), the model group (M), the icariin group (ICA) and the testosterone group (T). The reproductive system was damaged by cyclophosphamide (intraperitoneal injection, 20 mg/kg x day) for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA (gastric gavage, 200 mg/kg x day) for the ICA group and sterandryl (subcutaneous injection, 5 mg/rat . day) for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), serum bone Gla-protein (BGP) and tartrate-resistant acid phosphatase activity in serum (StrACP) were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling (TUNEL), respectively. RESULTS: (1) Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. (2) Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. (3) Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. CONCLUSION: Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.