New Phenanthro[9,10-d]oxazole-Based Fluorophores with Hybridized Local and Charge-Transfer Characteristics for Highly Efficient Blue Non-Doped OLEDs with Negligible Efficiency Roll-Off.

It is vital to develop highly efficient non-doped blue organic light-emitting diodes (OLEDs) with high color purity and low-efficiency roll-off for applications in display and lighting. Herein, two blue D-A fluorophores TPA-PO and TPA-DPO are designed and synthesized, in which phenanthro[9,10-d]oxazole (PO) acts as the acceptor and triphenylamine as the donor. TPA-PO and TPA-DPO display good thermal stability and efficient luminescence efficiency in neat film. Results based on photophysical property and theoretical calculation demonstrate that TPA-PO and TPA-DPO possess the hybridized local and charge-transfer (HLCT) feature, which can utilize the triplet exciton to achieve highly efficient electroluminance (EL). The non-doped OLEDs with TPA-PO/TPA-DPO as pure emissive layer show the uniform EL emission peak at 468 nm, corresponding to CIE coordinates of (0.168, 0.187) and (0.167, 0.167), respectively. The TPA-DPO-based non-doped OLEDs provide the maximum external quantum efficiency (EQE) of 7.99 % and high exciton utility efficiency of 48.4 %~72.6 %. Moreover, the TPA-DPO-based device exhibits low-efficiency roll-off, still maintaining the EQE of 6.03 % at the high luminance of 5000 cd m-2. Those findings state clearly that PO is a promising building block of blue fluorophore with a potential HLCT feature to be applied in non-doped OLEDs.

Arenarialins A-F, Anti-inflammatory Meroterpenoids with Rearranged Skeletons from the Marine Sponge Dysidea arenaria.

Six new sesquiterpene quinone/hydroquinone meroterpenoids, arenarialins A-F (1-6), were isolated from the marine sponge Dysidea arenaria collected from the South China Sea. Their chemical structures and absolute configurations were determined by HRMS and NMR data analyses coupled with DP4+ and ECD calculations. Arenarialin A (1) features an unprecedented tetracyclic 6/6/5/6 carbon skeleton, whereas arenarialins B-D (2-4) possess two rare secomeroterpene scaffolds. Arenarialins A-F showed inhibitory activity on the production of inflammatory cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages with arenarialin D regulating the NF-κB/MAPK signaling pathway.

Melatonin alleviates intrarenal CaOx crystals deposition through inhibiting LPS-induced non-canonical inflammasome-mediated renal tubular epithelial cells pyroptosis.

Urinary tract infection has long been considered a complication rather than etiology of calcium oxalate (CaOx) nephrolithiasis. This study aimed to explore the role of lipopolysaccharide (LPS), an important component of Gram-negative bacteria, on CaOx nephrolithiasis formation and antagonistic effect of melatonin. Male C57BL/6 mice were intraperitoneally injected with glyoxylate acid (80 mg/kg) daily for 7 days to construct CaOx nephrolithiasis model. A single dose of LPS (2.0 mg/kg) was given 2 h before the second glyoxylate acid treatment in the presence or absence of melatonin (25 mg/kg). Our results found that LPS promoted adhesion of CaOx crystals to renal tubular epithelial cells (RTECs) and intrarenal CaOx crystals deposition. Protein levels of cleaved Caspase-11, N-terminal of cleaved GSDMD (GSDMD-N), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved Caspase-1, several markers of non-classical inflammasome activation were upregulated in LPS-treated mouse kidneys and HK-2 cells. Moreover, the number of GSDMD pores was increased in LPS-treated HK-2 cell membrane. Melatonin inhibited Caspase-11 cleavage and antagonized the subsequent LPS-mediated upregulation of GSDMD-N, NLRP3 and cleaved Caspase-1 in kidney tissues and HK-2 cells. In addition, melatonin reduced membrane localization of GSDMD-N and the number of GSDMD pores in LPS-treated HK-2 cells. Accordingly, melatonin inhibited LPS-induced IL-1ß and IL-18 in mouse serum and HK-2 culture supernatant. Importantly, melatonin alleviated LPS-induced crystal-cell interactions and intrarenal CaOx crystals deposition. We provide experimental evidence that LPS promoted CaOx nephrolithiasis formation by inducing non-canonical inflammasome-mediated RTECs pyroptosis. Melatonin alleviated CaOx nephrolithiasis formation through inhibiting LPS-induced non-canonical inflammasome-mediated RTECs pyroptosis.

Dysambiol, an Anti-inflammatory Secomeroterpenoid from a Dysidea sp. Marine Sponge.

An unusual secomeroterpenoid, dysambiol (1), was isolated from a Dysidea sp. marine sponge collected from the South China Sea. Dysambiol features an unprecedented secomeroterpene scaffold with a rare lactone bridge. The structure of 1 was determined by extensive spectroscopic analysis, Mosher's method, and electronic circular dichroism calculation. Dysambiol displayed potent anti-inflammatory activity in LPS-induced Raw 264.7 macrophages by regulating the NF-κB/MPAK signaling pathway.

Development, validation and psychometric evaluation of the Chinese version of the biopsychosocial impact scale in orofacial pain patients.

Background: The objective of this study was to develop the Chinese version of the biopsychosocial impact scale (BPIm-S) to assess functional limitation and psychosocial distress in orofacial pain (OFP) patients in mainland China, and investigate the factor structure, reliability and validity, measurement invariance, as well as scores differences across genders, age and educational status among OFP patients. Methods: The BPIm-S was developed and evaluated in four stages: (1) concept selection and item generation; (2) a pilot study assessing face and content validity; (3) the factors structure, reliability, convergent validity, and measurement invariance; and (4) concurrent validity and clinical responsiveness. Exploratory (EFA) and confirmatory factor analyses (CFA) were performed on data gathered from 406 OFP patients to assess construct validity. Composite Reliability (CR) and the Average Variance Extracted (AVE) were used to assess internal convergent validity. CR, internal consistency, and split-half reliability were also performed to determine the reliability. Multigroup CFA (MGCFA) was used to assess measurement invariance across genders, age and educational status. Mann-Whitney test compared scores across different genders, age and educational status. Participants completed the BPIm-S, visual analog scale (VAS), brief pain inventory facial (BPI-F), General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9), and spearman's correlation coefficient was used to evaluate the concurrent validity and item-total correlations. A total of 12 patients with OFP completed the BPIm-S twice to test clinical responsiveness. To conduct the CFA and measurement invariance analysis, Mplus 8.4 was used. IBM SPSS Statistics 21 software and SPSSAU, a web-based data science algorithm platform tool, were used for all additional studies. Results: For the preliminary version, 17 items were chosen. A total of four items were removed following the pilot research. The remaining 13 items of the BPIm-S comprised an overall summary scale. Excellent reliability (Item-to-total correlations ranged from 0.763 to 0.912) and strong internal consistency (Cronbach's α = 0.970, functional limitation, 0.962, and psychosocial distress, 0.977) were discovered. CFA also validated the structural validity of the 13-item scale. EFA was performed and a two-factor structure was investigated. In addition, MGCFA corroborated the measurement invariance of the BPIm-S across gender, age, and educational status. Patients over the age of 30, those with a medium level of education, and those with a low level of education showed substantially greater levels of functional limitation and psychological distress (Wilcoxon test, p < 0.001). Both concurrent validity and clinical responsiveness were assessed to be of good quality. Conclusion: The BPIm-S demonstrated good psychometric qualities and is a reliable tool that can now be used by clinicians to evaluate functional limitation and psychosocial distress among OFP patient.

Vitamin D deficiency aggravates growth and metastasis of prostate cancer through promoting EMT in two ß-catenin-related mechanisms.

Increasing evidence has demonstrated that vitamin D deficiency is associated with prostate cancer progression, but its mechanism remains unclear. This study investigated effects of vitamin D deficiency on growth and metastasis of prostate cancer. Nude mice and Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed with vitamin D-deficient (VDD) diets. Prostate cancer growth was aggravated in VDD diet-fed nude mice and TRAMP mice. Invasion and metastasis of prostate cancer were exacerbated in VDD diet-fed TRAMP mice. In vitro experiments showed that calcitriol, an active vitamin D3, inhibited migration and invasion in transforming growth factor (TGF)-ß1 -stimulated and -unstimulated PC-3 and DU145 cells. Mechanistically, calcitriol inhibited epithelial-mesenchymal transition (EMT) in TGF-ß1 -stimulated and -unstimulated DU145 cells. Unexpectedly, calcitriol did not inhibit Smad2/3 phosphorylation in TGF-ß1-stimulated DU145 cells. Instead, calcitriol downregulated expression of proliferation-, metastasis- and EMT-related genes, includes Cyclin D1, MMP7, and Zeb1, by inhibiting interaction between TCF4 and ß-catenin. In addition, calcitriol promoted interaction between cytoplasmic VDR and ß-catenin, reduced ß-catenin phosphorylation and elevated ß-catenin/E-cadherin adherens junction complex formation. We provide novel evidence that vitamin D deficiency aggravates growth and metastasis of prostate cancer possibly through promoting EMT in two ß-catenin-related mechanisms.

Sirt1 inhibits kidney stones formation by attenuating calcium oxalate-induced cell injury.

Cell injury is a necessary and critical event during CaOx kidney stone formation. Sirt1 exerts a number of pleiotropic effects, protecting against renal cell injury. This study aims to explore the relationship between Sirt1 and CaOx kidney stone formation and the underlying mechanism. Sirt1 expression in renal tissues or HK-2 cells was detected by Western blot, immunohistochemistry and immunofluorescence. Apoptosis in renal tissues was examined by TUNEL staining. Renal pathological changes and the crystals deposition were detected by hematoxylin-eosin and Von Kossa staining. Crystal-cell adhesion and cell injury in HK-2 cells were assessed by atomic absorption spectrometry and flow cytometry, respectively. Sirt1 expression in nephrolithiasis patients was downregulated and the level of apoptosis was increased. Further study found that Sirt1 expression was decreased in both in vivo and in vitro models. Interestingly, the levels of cell injury were elevated in vivo and in vitro models. Suppressing Sirt1 expression promoted COM-induced crystal-cell adhesion and exacerbated cell injury. In contrast, increasing the expression of Sirt1 by lentivirus transfection in vitro and resveratrol administration in vivo, alleviated crystal deposition and cell damage. Our findings suggest that Sirt1 could inhibit kidney stone formation, at least in part, through attenuating CaOx -induced cell injury.

Melatonin Inhibits Migration and Invasion in LPS-Stimulated and -Unstimulated Prostate Cancer Cells Through Blocking Multiple EMT-Relative Pathways.

PURPOSE: Gram-negative bacteria are usually found in prostate cancer (PCa) tissues. This study aims to investigate the role of lipopolysaccharide (LPS), a glycolipid compound found in the outer membrane of gram-negative bacteria, on the migration and invasion of PCa cells, and to evaluate the protective effect of melatonin. MATERIALS AND METHODS: DU145, PC-3 and LNCaP cells were incubated with LPS in the presence or absence of melatonin. Wound healing and Transwell assays were used to analyze migration and invasion of PCa cells. RT-PCR and Western blotting were used to assess the mRNA and protein levels, respectively. Co-IP was used to analyze ß-catenin ubiquitination. RESULTS: Our results showed that LPS promoted migration and invasion of PCa cells. In addition, LPS stimulated inflammatory reaction and induced epithelial-mesenchymal transition (EMT) in PCa cells by activating several TLR4 downstream pathways. Specifically, LPS promoted NF-κB/IL-6/STAT3 signal transduction. In addition, LPS upregulated phosphorylation levels of cytoplasmic AKTSer473 and GSK-3ßSer9. Moreover, LPS induced phosphorylation of GSK-3ßSer9 in the "disruption complex", and then inhibited phosphorylation and ubiquitination of cytoplasmic ß-catenin, leading to ß-catenin nuclear translocation. Interestingly, melatonin inhibited invasion and migration not only in LPS-stimulated but also in LPS-unstimulated PCa cells. Melatonin suppressed PCa cells migration and invasion by blocking EMT mediated by IL-6/STAT3, AKT/GSK-3ß and ß-catenin pathways. CONCLUSION: This study provides evidence that melatonin inhibits migration and invasion through blocking multiple TLR4 downstream EMT-associated pathways both in LPS-stimulated and -unstimulated PCa cells. Our results provide new insights into the role of bacterial infection in PCa metastasis and a potential therapeutic agent.

ROS-mediated genotoxic stress is involved in NaAsO2-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.

Several epidemiological studies reported that chronic arsenic exposure increased risk of prostate cancer. This study aimed to investigate whether chronic NaAsO2 exposure elevates stemness and chemoresistance in prostate cancer cells. DU145 (wild-type p53) and PC-3 (p53-null) cells were exposed to NaAsO2 (2 µmol/L) for 30 generations. IC50s to docetaxel and cisplatin were increased in NaAsO2-exposed DU145 and PC-3 cells. The number of tumor spheres was elevated in NaAsO2-exposed DU145 and PC-3 cells. Nanog, SOX-2 and ALDH1A1, three markers of cancer stemness, were upregulated in NaAsO2-exposed PC-3 spheres. Moreover, NaAsO2-exposed DU145 and PC-3 cells were arrested in G2/M phase. Histone H2AX phosphorylation on Ser139, an indicator for DNA double-strand break, was upregulated in NaAsO2-exposed DU145 and PC-3 cells. ATM phosphorylation on Ser1981, a key sensor of genotoxic stress, was rapidly elevated in NaAsO2-exposed DU145 cells. Phosphor-p53, a downstream molecule of ATM signaling, and p21, a direct target of p53, were upregulated in NaAsO2-exposed DU145 cells. Unexpectedly, p21 was also elevated in NaAsO2-exposed p53-null PC-3 cells. Antioxidant NAC alleviated NaAsO2-induced ATM phosphorylation, cell cycle arrest, and subsequent stemness enhancement and chemoresistance in both DU145 and PC-3 cells. These results suggest that ROS-mediated genotoxic stress is involved in NaAsO2-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.

Long-term vitamin D deficiency promotes renal fibrosis and functional impairment in middle-aged male mice.

Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial-mesenchymal transition (EMT), and Tgf-ß mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-ß1 (TGF-ß1)-mediated down-regulation of E-cadherin and inhibited TGF-ß1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-ß1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-ß/Smad2/3-mediated EMT in middle-aged male mice.

Retroperitoneal vs transperitoneal laparoscopic lithotripsy of 20-40 mm renal stones within horseshoe kidneys.

BACKGROUND: Horseshoe kidney (HK) with renal stones is challenging for urologists. Although both retroperitoneal and transperitoneal laparoscopic approaches have been reported in some case reports, the therapeutic outcome of retroperitoneal compared with transperitoneal laparoscopic lithotripsy is unknown. AIM: To assess the efficacy of laparoscopic lithotripsy for renal stones in patients with HK. METHODS: This was a retrospective study of 12 patients with HK and a limited number (n ≤ 3) of 20-40 mm renal stones treated with either retroperitoneal or transperitoneal laparoscopic lithotripsy (June 2012 to May 2019). The perioperative data of both groups were compared including operation time, estimated blood loss, postoperative fasting time, perioperative complications and stone-free rate (SFR). RESULTS: No significant difference was observed for age, gender, preoperative symptoms, body mass index, preoperative infection, hydronephrosis degree, largest stone diameter, stone number and isthmus thickness. The mean postoperative fasting time of the patients in the retroperitoneal group and the transperitoneal group was 1.29 ± 0.49 and 2.40 ± 0.89 d, respectively (P = 0.019). There was no significant difference in operation time (194.29 ± 102.48 min vs 151.40 ± 39.54 min, P = 0.399), estimated blood loss (48.57 ± 31.85 mL vs 72.00 ± 41.47 mL, P = 0.292) and length of hospital stay (12.14 ± 2.61 d vs 12.40 ± 3.21 d, P = 0.881) between the retroperitoneal and transperitoneal groups. All patients in both groups had a complete SFR and postoperative renal function was within the normal range. The change in estimated glomerular filtration rate (eGFR) from the preoperative stage to postoperative day 1 in the retroperitoneal group and the transperitoneal group was -3.86 ± 0.69 and -2.20 ± 2.17 mL/(min·1.73 m2), respectively (P = 0.176). From the preoperative stage to the 3-mo follow-up, the absolute change in eGFR values for patients in the retroperitoneal group and the transperitoneal group was -3.29 ± 1.11 and -2.40 ± 2.07 mL/(min·1.73 m2), respectively (P = 0.581). CONCLUSION: Both retroperitoneal and transperitoneal laparoscopic lithotripsy seem to be safe and effective for HK patients with a limited number of 20-40 mm renal stones.

Pleomorphic rhabdomyosarcoma of the spermatic cord and a secondary hydrocele testis: A case report.

BACKGROUND: Pleomorphic rhabdomyosarcoma (RMS) of the spermatic cord is a group of rare neoplasms, and a secondary hydrocele testis occasionally occurs. The misdiagnosis of paratesticular mass may lead to a therapeutic delay. CASE SUMMARY: A 79-year-old man presented to our clinic complaining of a 1-mo history of painless scrotal swelling. Physical examination revealed approximately a 15 cm × 10 cm × 5 cm inguinal mass with limited mobility. Contrast-enhanced magnetic resonance imaging showed a hydrocele testis, several enlarged inguinal lymph nodes, and a heterogeneously enhanced lesion with a relatively well-defined margin in the left inguinal region. Due to the imaging findings, he was diagnosed with pleomorphic RMS and received a wide resection of the mass, an inguinal incision with a high section of the left spermatic cord, and a left radical orchiectomy. He experienced local relapse 1 mo postoperatively and received radiotherapy and anlotinib hydrochloride-based immunotherapy as adjuvant therapy. The patient died 3 mo after the surgery. CONCLUSION: The optimal interventions for advanced-stage pleomorphic RMS patients should be investigated by more preclinical studies and clinical trials. Physicians need to be aware of the occurrence of pleomorphic RMS in unusual locations, especially when accompanied by a hydrocele testis.

Serum nesfatin-1 is associated with testosterone and the severity of erectile dysfunction.

This cross-sectional study aimed to evaluate serum nesfatin-1 concentrations in patients with erectile dysfunction (ED). Patients with ED were selected from the Department of Urology of the Second Affiliated Hospital of Anhui Medical University. The International Index of Erectile Function-5 (IIEF-5) was used to evaluate the severity of ED. Serum nesfatin-1 and gonadal hormone levels, including luteinising hormone (LH), follicle-stimulating hormone (FSH) and testosterone were measured. The IIEF-5 scores (t = -21.034, p < .001) and nesfatin-1 levels (t = -7.043, p < .001) in patients with ED were significantly lower than in healthy controls. Moreover, patients with ED showed decreased testosterone levels (t = -3.478, p = .001), whereas there were no significant differences in serum levels of FSH (t = -0.088, p = .930) and LH (t = 1.114, p = .270) between the two groups. Furthermore, positive relationships were found between serum nesfatin-1 and testosterone concentrations (r = .742, p = .001) and IIEF-5 scores (r = .395, p = .009) in ED patients. Additionally, based on receiver operating characteristic curve analysis, the area under curve for nesfatin-1 was 0.884 with 83.3% sensitivity and 81.4% specificity in discriminating ED patients from healthy controls. The decrease in serum nesfatin-1 level may be related to testosterone and the severity of ED.

Calcitriol inhibits lipopolysaccharide-induced proliferation, migration and invasion of prostate cancer cells through suppressing STAT3 signal activation.

Increasing evidence suggests that infection promotes the initiation and progression of prostate cancer. This study investigated the effects of lipopolysaccharide (LPS), a major component of Gram-negative bacilli, on proliferation, migration and invasion of prostate cancer cells and the protective effects of 1α,25(OH)2D3 (calcitriol). PC-3 and DU145 cells were stimulated with LPS (2.0 µg/mL) in the presence or absence of 1α,25(OH)2D3 (100 nM). Our results shown that 1α,25(OH)2D3 reduced the proportion of S phase cells in LPS-stimulated PC-3 and DU145 cells, and down-regulated the nuclear protein levels of Cyclin D1 and PCNA in LPS-stimulated PC-3 cells. In addition, 1α,25(OH)2D3 inhibited migration and invasion, as determined by wound healing and transwell assay, in LPS-stimulated PC-3 and DU145 cells. Of interest, we observed that 1α,25(OH)2D3 inhibits NF-κB activation and subsequent synthesis and secretion of IL-6 and IL-8 by promoting VDR and NF-κB p65 interaction. Surprisingly, 1α,25(OH)2D3 blocks nuclear translocation of pSTAT3 by promoting physical interaction between VDR and pSTAT3 (Tyr705) in LPS-stimulated PC-3 and DU145 cells. These results suggest that 1α,25(OH)2D3 inhibits LPS-induced proliferation, migration and invasion in prostate cancer cells by directly and indirectly blocking STAT3 signal transduction.

Calcitriol inhibits migration and invasion of renal cell carcinoma cells by suppressing Smad2/3-, STAT3- and ß-catenin-mediated epithelial-mesenchymal transition.

Low vitamin D status is associated with progression in patients with renal cell carcinoma (RCC). The present study found that vimentin, a mesenchymal marker, was accordingly upregulated, and E-cadherin, an epithelial marker, was downregulated in RCC patients with low vitamin D status. Thus, we investigated the effects of calcitriol or vitamin D3, an active form of vitamin D, on epithelial-mesenchymal transition (EMT) in RCC cells. RCC cells were treated by two models. In model 1, three RCC cell lines, ACHN, 786-O and CAKI-2, were incubated with either LPS (2.0 µg/mL) or transforming growth factor (TGF)-ß1 (10 ng/mL) in the presence or absence of calcitriol (200 nmol/L). In model 2, two RCC cell lines, ACHN and CAKI-2, were incubated with calcitriol (200 nmol/L) only. Calcitriol inhibited migration and invasion not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated RCC cells. Moreover, calcitriol suppressed E-cadherin downregulation and vimentin upregulation not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated ACHN and CAKI-2 cells. Calcitriol attenuated LPS-induced upregulation of MMP-2, MMP-7, MMP-9, MMP-26 and urokinase-type plasminogen activator (u-PA) in ACHN cells. In addition, calcitriol blocked TGF-ß1-induced nuclear translocation of ZEB1, Snail and Twist1 in ACHN and CAKI-2 cells. Mechanistically, calcitriol suppressed EMT through different signaling pathways: (i) calcitriol suppressed Smad2/3 phosphorylation by reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-ß1-stimulated RCC cells; (ii) calcitriol inhibited signal transducer and activator of transcription (STAT)3 activation in LPS-stimulated RCC cells; (iii) calcitriol inhibited ß-catenin/TCF-4 activation by promoting integration of VDR with ß-catenin in TGF-ß1-unstimulated RCC cells. Taken together, calcitriol inhibits migration and invasion of RCC cells partially by suppressing Smad2/3-, STAT3- and ß-catenin-mediated EMT.

The Vitamin D status is associated with serum C-reactive protein and adhesion molecules in patients with renal cell carcinoma.

Low vitamin D status is associated with an increased risk of renal cell carcinoma (RCC). This study investigated the association of vitamin D status with serum C-reactive protein (CRP) and adhesion molecules among RCC patients. Fifty newly diagnosed RCC patients and 100 age- and sex-matched controls were recruited. As expected, serum 25(OH)D level was lower in RCC patients than in controls. By contrast, serum levels of CRP, an inflammatory molecule, and ICAM, LAMA4 and EpCAM, three adhesion molecules, were higher in RCC patients than in controls. All RCC patients were divided into two groups: H-VitD (>20 ng/ml) or L-VitD (<20 ng/ml). Interestingly, the levels of serum CRP and all adhesion molecules were higher in RCC patients with L-VitD than those with H-VitD. Nuclear vitamin D receptor (VDR) was downregulated and nuclear factor kappa B (NF-κB) was activated in cancerous tissues. The in vitro experiments found that VitD3 suppressed NF-κB activation and adhesion molecules in RCC cells. Moreover, VitD3 suppressed NF-κB through reinforcing physical interaction between VDR and NF-κB p65 subunit in RCC cells. These results provide a mechanistic explanation for the association among low vitamin D status, local inflammation and increased expression of adhesion molecules among RCC patients.

The correlation between low vitamin D status and renal interleukin-6/STAT3 hyper-activation in patients with clear cell renal cell carcinoma.

Low vitamin D status has been associated with increased risks of renal cell carcinoma (RCC). This study aimed to analyze the link between low vitamin D status and interleukin (IL)-6/STAT3 hyper-activation in clear cell RCC (ccRCC) patients. Forty-three newly diagnosed ccRCC patients and 86 age- and sex-matched controls were recruited. The association between low vitamin D status and IL-6/STAT3 hyper-activation was analyzed. Proliferation makersand STAT3 signal were evaluated. As expected, serum IL-6 level was higher in ccRCC patients than in controls. Moreover, serum IL-6 level was reversely correlated with serum 25(OH)D in ccRCC patients but not in controls. In addition, STAT3 signaling was hyper-activated in cancerous tissue. CcRCC patients were divided into three groups according to serum 25(OH)D level: vitamin D sufficiency (VitD-S, ≥30 ng/ml), vitamin D insufficiency (VitD-I, ≥20 and <30 ng/ml) or vitamin D deficiency (VitD-D, <20 ng/ml). Serum IL-6 was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. Cancerous pSTAT3 level was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The number of pSTAT3+ nuclei in cancerous tissue was more in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The expressions of cancerous PCNA, cyclin D1 and Ki-67, three markers of proliferation, were higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The in vitro experiments showed that active vitamin D3 inhibited LPS-induced STAT3 phosphorylation in ACHN cells. Our results provide evidence that low vitamin D status is correlated with hyper-activation of cancerous IL-6/STAT3 and proliferation in ccRCC patients.

Pretreatment with Cholecalciferol Alleviates Renal Cellular Stress Response during Ischemia/Reperfusion-Induced Acute Kidney Injury.

BACKGROUND: Cellular stress is involved in ischemia/reperfusion- (I/R-) induced acute kidney injury (AKI). This study is aimed at investigating the effects of pretreatment with cholecalciferol on renal oxidative stress and endoplasmic reticulum (ER) stress during I/R-induced AKI. METHODS: I/R-induced AKI was established by cross-clamping renal pedicles for 90 minutes and then reperfusion. In the Chol + I/R group, mice were orally administered with three doses of cholecalciferol (25 µg/kg) at 1, 24, and 48 h before ischemia. Renal cellular stress and kidney injury were measured at different time points after reperfusion. RESULTS: I/R-induced AKI was alleviated in mice pretreated with cholecalciferol. In addition, I/R-induced renal cell apoptosis, as determined by TUNEL, was suppressed by cholecalciferol. Additional experiment showed that I/R-induced upregulation of renal GRP78 and CHOP was inhibited by cholecalciferol. I/R-induced renal IRE1α and eIF2α phosphorylation was attenuated by cholecalciferol. Moreover, I/R-induced renal GSH depletion, lipid peroxidation, and protein nitration were blocked in mice pretreated with cholecalciferol. I/R-induced upregulation of renal NADPH oxidases, such as p47phox, gp91phox, and nox4, was inhibited by cholecalciferol. I/R-induced upregulation of heme oxygenase- (HO-) 1, gshpx and gshrd, was attenuated in mice pretreated with cholecalciferol. CONCLUSIONS: Pretreatment with cholecalciferol protects against I/R-induced AKI partially through suppressing renal cellular stress response.

Primary squamous cell carcinoma of the seminal vesicle: A case report and review of the literature.

RATIONALE: Primary squamous cell carcinoma (SCC) of the seminal vesicle is extremely rare, and the clinical characteristics of this kind of malignancy are still unclear. PATIENT CONCERNS: A 62-year-old male patient presented with complaints of sensation of rectal tenesmus and dysuria. DIAGNOSIS: Ultrasonography suggested a hypoechoic mass behind the bladder, meanwhile, computerized tomography (CT) and magnetic resonance imaging (MRI) revealed a 40 mm × 45 mm × 48 mm mixed solid/cystic tumorous lesion in the right seminal vesicle. Postoperative histology confirmed the diagnosis of primary SCC in the seminal vesicle. INTERVENTION: The mass was surgically excised with a laparoscopic approach. Postoperatively, 6 cycles of chemotherapy and 50 Gy of external beam radiation were concurrently performed on this patient. OUTCOMES: No local recurrence or distant metastasis was detected within 2 years after the surgery. LESSONS: Primary SCC of the seminal vesicle is a rare neoplasm with a poor prognosis. Clinically, it is crucial to establish early precise diagnosis and apply multimodality treatment.

Hyperthyroidism is not a significant risk of benign prostatic hyperplasia: A nationwide population-based study.

Benign prostatic hyperplasia (BPH) is a common disorder in the aging male population. Despite evidence that thyroid status impacts the prostate, the objective of this study was to examine whether patients with hyperthyroidism were at a greater risk for BPH.This study is a retrospective nationwide population-based cohort study of the Chinese population. Data for this study were retrieved from the Taiwan National Health Insurance Research Database (NHIRD). Overall, 1032 male patients aged 40 years or older with hyperthyroidism diagnosed between 2000 and 2006 were included in the hyperthyroidism group, and 4128 matched controls without hyperthyroidism were included in the non-hyperthyroidism group. Both groups were monitored until the end of 2011. A Cox proportional hazards regression model was used to compute and compare the risk of BPH between study participants with and those without hyperthyroidism.Patients with hyperthyroidism exhibited a greater incidence of BPH (18.51% vs 15.53%) than did the controls. Furthermore, the hazard ratio (HR) of the hyperthyroidism group was 1.24 times that of the control group [95% confidence interval (95% CI 1.05-1.46)] signifying that there is a significant 24% increase in the risk of BPH with the presence of hyperthyroidism. This increased risk of BPH with hyperthyroidism, however, failed to remain significant (adjusted HR = 1.11, 95% CI = 0.94-1.3) after adjusting for covariates of age (adjusted HR = 2.72, 95% CI = 2.32-3.2), diabetes (adjusted HR = 1.4, 95% CI = 1.17-1.68), hypertension (adjusted HR = 1.74, 95% CI = 1.49-2.03), hyperlipidemia (adjusted HR = 1.25, 95% CI = 1.03-1.53), neurogenic bladder, cystitis (adjusted HR = 1.23, 95% CI = 0.58-2.59), urethral stricture (adjusted HR = 2.01, 95% CI = 0.28-14.47), urethritis (adjusted HR = 1.52, 95% CI = 0.72-3.21), and urinary tract infection (adjusted HR = 1.77, 95% CI = 1.31-2.39).After adjustment for comorbidities and covariates, hyperthyroidism was not found to be a significant risk factor of BPH in our male study subjects. Further research is warranted to validate our results and elucidate the association of the pathophysiology of these 2 diseases.