Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive. METHODS: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II (angiotensin II)-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell-specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 vectors carrying ATF3, or shRNA-ATF3 with SM22α (smooth muscle protein 22-α) promoter were used in Ang II-induced AAA mice. In human and murine vascular smooth muscle cells, gain or loss of function experiments were performed to investigate the role of ATF3 in vascular smooth muscle cell proliferation and apoptosis. RESULTS: In both Ang II-induced AAA mice and patients with AAA, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in vascular smooth muscle cell promoted AAA formation in Ang II-induced AAA mice. PDGFRB (platelet-derived growth factor receptor ß) was identified as the target of ATF3, which mediated vascular smooth muscle cell proliferation in response to TNF-alpha (tumor necrosis factor-α) at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our chromatin immunoprecipitation results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. CONCLUSIONS: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.

Two-Dimensional Room-Temperature Magnetic Nonstoichiometric Fe7Se8 Nanocrystals: Controllable Synthesis and Magnetic Behavior.

Two-dimensional (2D) magnetic materials have attracted significant attention for promising applications in energy-saving logic and robust memory devices. However, most 2D magnets discovered so far typically feature drawbacks for practical applications due to low critical temperatures. Herein, we synthesize ultrathin room-temperature (RT) magnetic Fe7Se8 nanoflakes via the space-confined chemical vapor deposition method. It is found that the appropriate supply and control of Se concentration in the reaction chamber is crucial for synthesizing high-quality nonstoichiometric Fe7Se8 nanoflakes. Cryogenic electrical and magnetic characterizations reveal the emergence of spin reorientation at ∼130 K and the survival of long-range magnetic ordering up to room temperature. The RT magnetic domain structures with different thicknesses are also uncovered by magnetic force microscopy. Moreover, theoretical calculations confirm the spin configuration and metallic band structure. The outstanding characteristics exhibited by Fe7Se8 nanoflakes, including RT magnetism, spin reorientation property, and good electrical conductivity, make them a potential candidate for RT spintronics.

Thulium (Tm:YAG) laser vaporesection of prostate and bipolar transurethral resection of prostate in patients with benign prostate hyperplasia: a systematic review and meta-analysis.

Thulium laser vaporesection (ThuVARP) and bipolar transurethral resection of the prostate (B-TURP) are novel surgeries for benign prostate hyperplasia (BPH). This paper is a systematic review and analysis of literatures comparing efficacy indicators, operative parameters, as well as safety indicators between ThuVARP and B-TURP for the treatment of BPH. A systematic search of electronic databases, including PubMed, the Cochrane Library, Web of Science, Embase, and China National Knowledge Internet (CNKI), was carried out up to December 1, 2015 (updated on March 1, 2016). The captivating outcomes included basic clinical characteristics, perioperative parameters, local complications, and efficacy indicators which included International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), and postvoid residual (PVR). After assessing the quality of methodology and extracting data, a meta-analysis was carried out by using STATA 12.0 software. Five studies involving 500 patients met the standard. The outcomes of this analysis were as follows: (a) efficacy indicators: there were no significant differences in IPSS, QoL, PVR, and Qmax between the two groups (all P > 0.05); (b) perioperative indicators: ThuVARP had longer operative time [standardized mean difference (SMD) = 0.843; 95% confidence interval (CI) - 0.391, 1.296; P < 0.001] but less serum hemoglobin decreased (SMD = - 0.561; 95% CI - 0.796, - 0.327; P < 0.001), shorter hospital stay (SMD = - 1.558; 95% CI - 2.709, - 0.407; P < 0.01), and catheterization time (SMD = - 1.274; 95% CI - 2.158, - 0.390; P < 0.01). Additionally, no significant difference was found in estimated resected weight (P > 0.05); (c) safety indicators: no significant difference was found in local complication rates (all P > 0.05) between ThuVARP and B-TURP. In our analysis, there exists no statistical difference between ThuVARP and B-TURP group in efficacy. However, in spite of requiring longer surgical time, ThuVARP was better in terms of less blood loss as well as shorter hospitalization and catheterization time.

PSCA regulates IL-6 expression through p38/NF-κB signaling in prostate cancer.

BACKGROUND: Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. We previously reported that PSCA involved in proliferation and invasion of PCa cells, however, the underlying mechanisms are unknown. In this study, we aimed to explore the regulating role of PSCA gene expression in interleukin-6 (IL-6) autocrine of PCa cells. METHODS: The stable knockdown-PSCA and ectopically overexpressed-PSCA vector were constructed and transfected into human PCa DU145 and PC-3M cells. The effects of PSCA overexpression or knockdown were determined in proliferation, invasion, and metastasis assays. The effect of PSCA on the expression and secretion of IL-6 was evaluated by immunoblotting and ELISA. Subcellular localization and expression pattern of PSCA and IL-6 protein were examined by immunohistochemistry. Its clinical significance was statistically analyzed. RESULTS: The results showed that stable knockdown of PSCA delayed proliferation, migration, and invasion while overexpressing PSCA enhanced the proliferation, migration, and invasion in vitro and the lung metastasis in vivo of PCa cells. Importantly, the PSCA involved in the IL-6 secretion and positively regulated p38/NF-κB/IL-6 signaling, leading to enhanced PCa cell invasion and metastasis. Both the expression of PSCA and IL-6 were significantly associated with poor biochemical recurrence-free survival of patients with PCa. PSCA protein expression showed a prognostic value in overall survival as indicated by Kaplan-Meier analysis. CONCLUSIONS: These results indicate that PSCA regulates the expression and secretion of IL-6 in human PCa cells through p38/NF-κB signaling pathways. PSCA may be a potential diagnostic marker and therapeutic target for PSCA-positive PCa.

PSCA promotes prostate cancer proliferation and cell-cycle progression by up-regulating c-Myc.

BACKGROUND: The Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored protein. Increasing evidence has indicated PSCA plays an important role in tumorigenesis. However, its function and the underlying molecular mechanisms in prostate cancer (PCa) are still not fully elucidated. In this study, we aimed to explore the effect of PSCA on cell cycle of PCa cells and its mechanism research. METHODS: Immunohistochemistry, quantitative reverse transcription-PCR (qRT-PCR) and Western blotting were used to quantify PSCA expression pattern in PCa tissues and cell lines. The association of PSCA expression with the biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients were analyzed using Kaplan-Meier method. The roles of PSCA in PCa were confirmed based on both in vitro and in vivo systems. RESULTS: Immunohistochemistry results showed that PSCA was upregulated in PCa tissue. PSCA overexpression were significantly associated with high Gleason score (GS) (P = 0.028), positive BCR (P = 0.002), and poor OS (P = 0.032) and high c-Myc expression (P = 0.019). PSCA promoted PCa cell cycle progression and tumor growth via increased c-Myc expression. Additional, PI3K/AKT signaling pathways was involved in PSCA-mediated c-Myc expression and cell proliferation. CONCLUSIONS: PSCA is a novel cell cycle regulator with a key role in mediating c-Myc-induced proliferation. PSCA may be a potential diagnostic marker and therapeutic target for patients with PCa.

Association Between HIV Infection and Prevalence of Erectile Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of erectile dysfunction (ED) in men positive for HIV has been reported to exceed the baseline of the general population. However, no meta-analysis or conclusive review has investigated whether individuals with HIV infection have a significantly higher prevalence of ED. AIM: To explore the exact association between HIV infection and the prevalence of ED. METHODS: The PubMed, Embase, Medline, and Cochrane Library databases were searched to identify studies concerning the association between HIV infection and the prevalence of ED that were published up to December 2016. Manual searches also were performed. Relative risks and corresponding 95% confidence intervals were used to estimate the strength of association between HIV infection and the prevalence of ED. The methodologic quality of the included cohort studies was assessed through the Newcastle-Ottawa Scale. The cross-sectional study quality methodology checklist was used to assess the quality of cross-sectional studies. Sensitivity analyses were conducted to assess potential bias. This study was conducted according to the guidelines for Meta-Analyses and Systematic Reviews of Observational Studies (MOOSE). OUTCOMES: The strength of association between HIV infection and the prevalence of ED was evaluated using summarized unadjusted pooled relative risks and 95% confidence intervals. RESULTS: Two cohort studies and three cross-sectional studies involving 4,252 participants were included. Mean age of patients ranged from 35.2 to 52 years in the included studies. Based on the random-effects model, analyses of all studies showed that HIV infection was significantly associated with an increased prevalence of ED (relative risk = 2.32, 95% confidence interval = 1.52-3.55, P < .001). There was significant heterogeneity among included studies (I2 = 84%, P < .001). Estimates of total effects were generally consistent with the sensitivity. CLINICAL IMPLICATIONS: Individuals with HIV infection had a significantly increased prevalence of ED, which suggests that ED should be of concern to clinicians when managing men with HIV infection. STRENGTHS AND LIMITATIONS: A strength of this study is that it is the first meta-analysis to explore the relation between HIV infection and the prevalence of ED. A limitation is that all included studies were observational studies, which can induce recall bias or selection bias. CONCLUSION: Evidence from the observational studies suggested that individuals with HIV infection had a significantly increased prevalence of ED despite significant heterogeneity. More research is warranted to clarify the relation between HIV infection and the prevalence of ED. Luo L, Deng T, Zhao S, et al. Association Between HIV Infection and Prevalence of Erectile Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1125-1132.

Association Between Opioid Use and Risk of Erectile Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Opioid analgesics have been widely used to relieve chronic pain conditions; however, a connection between opioid analgesic administration and increased susceptibility to erectile dysfunction (ED) has been hypothesized. AIM: To evaluate whether opioid use was a risk factor for ED in a systematic review and meta-analysis. METHODS: The PubMed, Cochrane Library, and Embase databases were searched to identify eligible studies concerning opioid use and risk of ED from inception to April 2017. The association between opioid use and risk of ED was summarized using the relative risk with 95% CI. Sensitivity analyses were conducted to assess potential bias. The Begg and Egger tests were used for publication bias analysis. The GRADE evidence profile tool was used to assess the quality of the evidence. OUTCOMES: The overall combined risk estimates for the effect of opioid use on ED were calculated using a random-effects model. RESULTS: This meta-analysis included 8,829 men (mean age = 41.6 years) from 10 studies, 2,456 of whom received opioid management (duration of intervention = 4 months to 9.5 years). Pooled results demonstrated that the use of opioids was significantly associated with an increased risk of ED (relative risk = 1.96, 95% CI = 1.66-2.32, P < .001). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed. The overall quality of evidence was rated as low. CLINICAL IMPLICATIONS: We found that men with opioid use had a significantly increased prevalence of ED, which suggests that patients and clinicians should be aware of the potential role played by opioid administration in the development of ED. STRENGTHS AND LIMITATIONS: This is the first meta-analysis performed to describe the relation between opioid use and ED risk based on all available epidemiologic studies. However, the direction of causality between opioid use and risk of ED should be interpreted with caution because most included studies used a cross-sectional design. CONCLUSION: Evidence from the included observational studies indicated that men with opioid use had a significantly increased risk of ED. Further randomized controlled trials are still needed to confirm this relation. Zhao S, Deng T, Luo L, et al. Association Between Opioid Use and Risk of Erectile Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1209-1219.

RNA interference targeting PSCA suppresses primary tumor growth and metastasis formation of human prostate cancer xenografts in SCID mice.

BACKGROUND AND OBJECTIVES: Prostate stem cell antigen (PSCA) is a cell surface, glycosylphosphatidylinositol (GPI)-anchored glycoprotein. Its overexpression has been detected in both local and metastatic prostate cancer (PCa), making it a potential therapeutic target. We previously reported that silencing PSCA by small interfering RNA targeting human PSCA (siRNA-PSCA) inhibited biological activity of PSCA-positive PCa cells leading to reduced proliferation, motility and invasion in vitro. In this study, we extended this in vitro findings to in vivo settings in order to investigate the effects of this specific siRNA on the tumor growth and metastasis development of PCa in vivo. MATERIALS AND METHODS: The siRNA-PSCA and ectopically overexpressed-PSCA vector were constructed and transfected into human PCa PC-3M and LNCaP cells, respectively, and were subcutaneously inoculated into the male SCID mice. Tumor growth was measured with a caliper, and formation of metastasis in mice bearing xenograft tumors was studied by magnetic resonance imaging (MRI) and autopsy analysis. Western blot and immunohistochemistry were used to assess the expression levels of PSCA protein in tumor tissues from xenograft and distant metastases. RESULTS: Consistent with our previous in vitro findings, the subcutaneous xenografts of PC-3M-siPSCA exhibited the almost completely inhibited expression of PSCA protein in their tumors tissues (P < 0.001 and P < 0.001, respectively), and consequently had a significant reduction in tumor growth volumes (P < 0.05 for all), and metastasis onset and sites (P < 0.001 for all) compared to those of PC-3M and PC-3M-siScrm. Conversely, LNCaP-PSCA showed significantly enhanced primary tumor growth and metastasis formation of xenografts compared to LNCaP-vehicle and LNCaP cells (P < 0.001 for all). Moreover, the up-regulated expression of PSCA protein was detected in the distant metastases of xenograft tumors from all groups. CONCLUSIONS: Taken together, these observations suggest that PSCA has a promoting role in the growth and metastasis of PCa and siRNA-PSCA may be a potential therapeutic strategy for PSCA-positive PCa.

Knockdown of PSCA induces EMT and decreases metastatic potentials of the human prostate cancer DU145 cells.

BACKGROUND: Prostate stem cell antigen (PSCA) expression has been shown to correlate with prostatic carcinogenesis and prostate cancer (PCa) progression. The underlying mechanisms for these processes are currently unknown. Epithelial to mesenchymal transition (EMT) has been associated with the invasiveness and the distant metastasis of PCa. In this study, we investigated the effects of knocking down the PSCA on the cell migration, the invasiveness, and the EMT of the PCa cell line DU145 in vitro and in vivo. METHODS: Four target sequences of the small hairpin RNA for PSCA were designed, and the best effect knockdown sequence shRNA#1 was screened to construct the stable transfected DU145 cell line (DU145 shRNA#1), the scramble sequence was also designed to construct the stable transfected DU145 cell line(DU145 scramble). Cell migration and invasion were studied using Transwell assay. Quantitative RT-PCR, Western blot (WB) were used to quantify PSCA, E-cadherin, ß-catenin, Vimentin, Fibronectin expression in DU145, DU145 scramble, DU145 shRNA#1 in vitro and in vivo. RT-PCR, immunofluorescent staining were used to quantify PSCA, E-cadherin, and Vimentin expression in vitro. EMT-related genes Snail, Slug, and Twist, were quantified by quantitative RT-PCR in vitro. RESULTS: The constructed stable knockdown of the PSCA in the DU145 cell had a silencing effect up to 90.5 %. DU145 shRNA#1 became scattered from the tightly packed colonies. It was associated with decreased cell migration and invasion. There was also an increased Vimentin and Fibronectin expression, an inhibited E-cadherin and ß-catenin expression at both the mRNA and the protein levels when compared to the DU145 and the DU145 scramble in vitro and vivo. Furthermore, with the exception of the Snail, the expression of EMT-related Slug and Twist genes were upregulated. CONCLUSIONS: Our data indicated that knockdown of PSCA induced EMT and reduced metastatic potentials of the DU145 cells, suggesting that PSCA played an important role in prostatic carcinogenesis and progression.

Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

INTRODUCTION: 5α-Reductase inhibitors (5ARIs) are widely used for the treatment of benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). AIM: To review all the available data on the effect of 5ARIs on sexual function and assess whether 5ARIs increase the risk of sexual dysfunction. METHODS: A systematic search of the literature was conducted using the Medline, Embase, and Cochrane databases. The search was limited to articles published in English and up to October 2015. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Data were analyzed using Stata 12.0. A fixed- or a random-effects model was used to calculate the overall combined risk estimates. Publication bias was assessed using Begg and Egger tests. MAIN OUTCOME MEASURES: Sexual dysfunction, erectile dysfunction, and decreased libido. RESULTS: After screening 493 articles, 17 randomized controlled trials with 17,494 patients were included. Nine studies evaluated the efficacy of 5ARIs in men with BPH. The other eight reported using 5ARIs in the treatment of men with AGA. The mean age of participants was 60.10 years across all studies. We included 10 trials (6,779 patients) on the efficacy and safety of finasteride, 4 trials (6,222 patients) on the safety and tolerability of dutasteride, and 3 trials (4,493 patients) using finasteride and dutasteride for AGA. The pooled relative risks for sexual dysfunction were 2.56 (95% CI = 1.48-4.42) in men with BPH and 1.21 (95% CI = 0.85-1.72) in men with AGA; those for erectile dysfunction were 1.55 (95% CI = 1.14-2.12) in men with BPH and 0.66 (95% CI = 0.20-2.25) in men with AGA; and those for decreased libido were 1.69 (95% CI = 1.03-2.79) in men with BPH and 1.16 (95% CI = 0.50-2.72) in men with AGA. Estimates of the total effects were generally consistent with the sensitivity analysis. No evidence of publication bias was observed. CONCLUSION: Evidence from the randomized controlled trials suggested that 5ARIs were associated with increased adverse effects on sexual function in men with BPH compared with placebo. However, the association was not statistically significant in men with AGA. Well-designed randomized controlled trials are indicated to study further the mechanism and effects of 5ARIs on sexual function.

Sexual Dysfunction in Patients with Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

INTRODUCTION: Sexual dysfunction is an under-recognized problem in men and women with obstructive sleep apnea (OSA). Epidemiologic findings were inconclusive regarding the risk for sexual dysfunction associated with OSA. AIM: The aim of this study was to examine the association between OSA and sexual dysfunction. METHODS: The PubMed, Cochrane Library, and Embase databases were searched for observational studies on the OSA and the risk of sexual dysfunction. The methodologic quality of the case-control and cohort studies was assessed with Newcastle-Ottawa Scale (NOS). The cross-sectional study quality methodology checklist was used for cross-sectional study. Data were pooled for the random-effects model. Sensitivity analyses were conducted to assess potential bias. MAIN OUTCOME MEASURE: The association between OSA and sexual dysfunction was summarized using relative risk (RR) with a 95% confidence interval (CI). RESULTS: This meta-analysis included 1,275 participants from nine studies. Five studies reported the incidence of erectile dysfunction (ED); the remaining four studies reported the incidence of female sexual dysfunction (FSD). Pooled results demonstrated that OSA was associated with increased risk of ED (pooled RR = 1.82, 95% CI: 1.12-2.97) as well as FSD (pooled RR = 2.00, 95% CI: 1.29-3.08). Estimates of the total effects were generally consistent in the sensitivity analysis. No evidence of publication bias was observed. CONCLUSIONS: Evidence from the observational studies suggested that OSA individuals might have an increased incidence of sexual dysfunction despite significant heterogeneity. More researches are warranted to clarify the relationship between OSA and the increased risk of sexual dysfunction.

Vitamin D deficiency and the risk of anemia: a meta-analysis of observational studies.

AIMS: Anemia and vitamin D deficiency (VDD) are both very important health issues, recent accumulating evidence shows that VDD is prevalent in individuals with anemia. This meta-analysis aimed to detect a relationship between VDD and anemia. METHODS: We identified eligible studies by searching the Pub Med, Embase and Cochrane Library before October 2014. Quality assessments were performed with the Newcastle-Ottawa Scale. Heterogeneity was evaluated by Cochran's Q test and source of heterogeneity was detected by subgroup analysis and sensitivity analysis. RESULTS: A total of seven studies involving 5183 participants were included in the meta-analysis. VDD was associated with an increased incidence of anemia (OR = 2.25, 95% CI = 1.47-3.44), with significant evidence of heterogeneity among these studies (p for heterogeneity < 0.001, I(2) = 84.0%). The subgroup and sensitivity analysis confirmed the stability of the results and no publication bias was detected. CONCLUSION: Our outcomes showed that VDD increased the risk of developing anemia. More researches are warranted to clarify an understanding of the association between VDD and risk of anemia.

[Transperitoneal versus extraperitoneal laparoscopic radical prostatectomy for localized prostate cancer: a meta analysis].

OBJECTIVE: To evaluate the effects and safety of transperitoneal laparoscopic radical prostatectomy (TLRP) and extraperitoneal laparoscopic radical prostatectomy (ELRP) in the treatment of localized prostate cancer. METHODS: We searched the Cochrane Library, Medline, Chinese Journal Full-text Database, Wanfang and CBM for clinical controlled trials addressing TLRP and ELRP in the treatment of localized prostate cancer. Two independent reviewers extracted comparable data from eligible studies and performed meta-analysis with the Statal 2.0 software on the relevant indexes of operation time, intraoperative blood loss, postoperative catheterization, postoperative intestinal function recovery, and postoperative hospital stay. RESULTS: Nine clinical controlled trials with 942 cases were included in this analysis, 492 treated by TLRP and the other 450 by ELRP. Meta-analysis showed no statistically significant differences between the TLRP and ELRP groups in operation time (SMD = 0.60, 95% CI: -0.06,1.26), intraoperative blood loss (SMD = 0.01, 95% CI: -0.35, 0.36) , postoperative catheterization time (SMD = 0.10, 95% CI: -0.21, 0.40) and postoperative hospital stay (SMD = 0.45, 95% CI: -0.01, 0.91), except in the time of postoperative intestinal function recovery, which was significantly shorter in the ELRP than in the TLRP group (SMD = 1.18, 95% CI: 0.26, 2.10). CONCLUSION: For the treatment of localized prostate cancer, ELRP is similar to TLRP with respect to operation time, intraoperative blood loss, postoperative catheterization and postoperative hospital stay, but superior to the latter in postoperative intestinal function recovery.

Neoxanthin alleviates the chronic renal failure-induced aging and fibrosis by regulating inflammatory process.

Chronic renal failure (CRF) refers to progressive renal damage caused by chronic kidney diseases (CKD). Dialysis therapy and kidney transplantation are the important treatment for CRF. However, due to the limitation of conditions, they cannot be widely utilized. At present, the treatment of renal failure is a worldwide problem in clinic. Therefore, in the current study, we investigated the potential therapeutic effects of neoxanthin on CFR-caused aging and fibrosis. In this work, the effects of neoxanthin on CRF were studied using experimental techniques such as biochemistry, immunohistochemistry and molecular biology. In vitro, neoxanthin alleviated the aging and oxidative damage of kidney cells. In vivo, we found that Neoxanthin could alleviate adenine-induced CRF. Neoxanthin also inhibited CRF-caused renal aging, fibrosis, oxidative stress and inflammation. These findings indicate that neoxanthin could delay the progression of CRF and alleviate CRF-induced aging and fibrosis. Collectively, we found that neoxanthin shows good potential to inhibit CRF-caused kidney aging and fibrosis, suggesting that neoxanthin may be used as a drug (or a functional food) for the treatment of CRF-related diseases.

Solutal Marangoni effect determines bubble dynamics during electrocatalytic hydrogen evolution.

Understanding and manipulating gas bubble evolution during electrochemical water splitting is a crucial strategy for optimizing the electrode/electrolyte/gas bubble interface. Here gas bubble dynamics are investigated during the hydrogen evolution reaction on a well-defined platinum microelectrode by varying the electrolyte composition. We find that the microbubble coalescence efficiency follows the Hofmeister series of anions in the electrolyte. This dependency yields very different types of H2 gas bubble evolution in different electrolytes, ranging from periodic detachment of a single H2 gas bubble in sulfuric acid to aperiodic detachment of small H2 gas bubbles in perchloric acid. Our results indicate that the solutal Marangoni convection, induced by the anion concentration gradient developing during the reaction, plays a critical role at practical current density conditions. The resulting Marangoni force on the H2 gas bubble and the bubble departure diameter therefore depend on how surface tension varies with concentration for different electrolytes. This insight provides new avenues for controlling bubble dynamics during electrochemical gas bubble formation.

N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation.

Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress.

Comparison of color Doppler ultrasonography and computed tomography angiography (CTA) and computed tomography venography (CTV) in the diagnosis of arteriovenous thrombosis after simultaneous pancreas-kidney transplantation: a retrospective diagnostic accuracy study.

Background: Simultaneous pancreas-kidney transplantation is an important treatment approach for diabetic renal insufficiency, but pancreatic arteriovenous thrombosis is among the early serious surgical complications that can lead to graft loss and even be fatal. Ultrasound is considered to be a safe and non-invasive approach, but it is often affected by intestinal gas interference and operator proficiency, partial thromboses may be easily missed. Computed tomography angiography (CTA) and computed tomography venography (CTV) are highly accurate but radiative, requiring the use of contrast agents. Methods: A total of 194 patients with end-stage diabetic nephropathy who underwent simultaneous pancreas-kidney transplantation from September 2016 to May 2021 were selected, among which 32 patients with highly suspected arteriovenous thrombosis were enrolled as the research subjects. All patients were examined by color Doppler ultrasonography, CTA and CTV. CTA and CTV are the gold standard for diagnostic imaging. The diagnostic value of color Doppler ultrasound, CTA and CTV in the diagnosis of pancreatic arteriovenous thrombosis was compared. and Kappa coefficient was used for consistency test. Results: Among the 32 patients with high clinical suspicion of transplanted pancreatic arteriovenous thrombosis after simultaneous pancreas-kidney transplantation, 9 patients were diagnosed by CTA/CTV and 10 patients were diagnosed by color Doppler ultrasonography, of which 2 cases were false positive and 1 case false negative. After transplantation, the normal diameter of the donor splenic vein was 3.96±0.16 mm. The difference in the diameter of the donor splenic vein between those with and without donor splenic vein thrombosis was statistically significant (P<0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of color Doppler ultrasound in the diagnosis of arteriovenous thrombosis were 88.9%, 91.3%, 90.6%, 80%, and 95.5%, respectively. There was no significant difference between color Doppler ultrasound diagnosis of arteriovenous thrombosis and CTA and CTV results (McNemar test P=1). The diagnosis of arteriovenous thrombosis by color Doppler ultrasonography was consistent with that of CTA and CTV (Kappa coefficient =0.776). Conclusions: Color Doppler ultrasonography has the advantages of safety and radiation-free, and can be used as the first choice for diagnosis of pancreatic arteriovenous thrombosis after simultaneous pancreas-kidney transplantation.

Ablation of Basic Leucine Zipper Transcription Factor ATF-Like Potentiates Estradiol to Induce Atopic Dermatitis.

Background: Atopic dermatitis (AD) is an inflammatory and immune skin disorder. Basic leucine zipper transcription factor ATF-like (BATF) plays a key role in regulating the differentiation and functions of lymphocytes. However, the mechanism underlying the transcriptional regulation of BATF on AD is still not well understood. Methods: BATF knockout (BATF-/-) and C57BL/6(B6) mice were used for the development of spontaneous dermatitis. 17ß-Estradiol was injected intraperitoneally to induce AD. The lesioned tail skin of the mice was stained with hematoxylin and eosin to analyze the pathological characteristics. Impaired skin barrier function was assessed by measuring the transepidermal water loss (TEWL). The skin epithelial barrier indicators and cytokine mRNA levels were quantified by real-time quantitative PCR. The total serum immunoglobulin E (IgE) levels were measured by enzyme-linked immunosorbent assay (ELISA). T lymphocytes were analyzed using flow cytometry. Results: Ablation of BATF led to the spontaneous development of AD only in female mice and not in male mice. BATF deletion led to elevated serum levels of IgE and increased infiltration of eosinophils, neutrophils, and lymphocytes and promoted cytokine production including IL-4, IL-22, IL-1ß, IFN-γ, and TNF-α in the lesioned tail skin of the mice. The mRNA expression levels of filaggrin and loricrin significantly decreased, while S100A8 and S100A9 increased in female BATF-/- mice. BATF-deficient female mice were found to increase proliferation and IL-5 production by skin-infiltrating CD4+ T cells which implies Th2 activation. Moreover, AD was successfully induced only in the estradiol-treated BATF-deficient male mice and not in WT male mice. Estradiol enhanced the allergic and immunological responses to dermatitis primarily by triggering Th2-type immune responses via enhanced serum IgE and inflammatory cytokine levels in the male BATF-/- mice. Conclusion: The study concluded that BATF potentiates estradiol to induce mouse atopic dermatitis via potentiating inflammatory cytokine releases and Th2-type immune responses and may have important clinical implications for patients with AD.

Ex vivo removal of stones in donor kidneys by pyelotomy prior to renal transplantation: a single-center case series.

Background: Donors with incidentally discovered asymptomatic renal stones was considered a relative contraindication to the kidney donation because of a potential increased morbidity risk for renal transplant recipients. Stone clearance from the donors should be done before donation to ensure safety of the recipient. This study aimed to observe the safety and efficacy of kidney transplantation from donors with nephrolithiasis who received pyelolithotomy before transplantation. Methods: Between January 2015 and March 2021, 14 deceased organ donors at The Second Affiliated Hospital of Guangzhou Medical University were found to have kidney stones during predonation evaluation. After donor kidney repair, all of the donor kidneys underwent ex vivo pyelolithotomy. Then the organs were transplanted to the right iliac fossa of 17 patients with end-stage renal failure. Data were analyzed for technical feasibility, intraoperative and postoperative complications, and stone clearance. Ultrasonography and urinal routine were followed at the 1-, 3-, and 6-month postoperatively. Results: The stones were successfully removed ex vivo by pyelotomy with an average time of 41.0±12.8 minutes. Seventeen recipients successfully underwent renal transplantation, and their renal function recovered well. Slight gross hematuria occurred in 12 cases after operation, and hematuria disappeared after conservative treatment. Ureteral stents were removed within two months after the procedure. There were no complications such as delayed recovery of renal function, acute rejection, ureteral necrosis, and urinary fistula. The serum creatinine of 17 patients 1 month after the operation was 136.8±26.7 µmol/L. None of the 17 patients included in the study suffered from stone recurrence or graft dysfunction in the follow-up period. Conclusions: Ex vivo removal of stones by pyelotomy was a technically feasible means of safely and efficiency rendering a stone-bearing donor kidney stone-free. The procedure obtained good early-middle outcomes in kidney transplantation and is therefore worthy of clinical application.

Effects of Long Noncoding RNA HOXA-AS2 on the Proliferation and Migration of Gallbladder Cancer Cells.

To explore the function and mechanism of lncRNA HOXA-AS2 in cancer-associated fibroblasts (CAFs)-derived exosomes in gallbladder cancer metastasis, and provide new research targets for the treatment of gallbladder cancer. At the same time, in order to clarify the early predictive value of lncRNA HOXA-AS2 for gallbladder cancer metastasis, and to provide a theoretical basis for clinical individualized treatment of gallbladder cancer. Methods. In our previous work, we used TCGA database analysis to find that lncRNA HOXA-AS2 was highly expressed in gallbladder cancer tissues compared with normal tissues. In this study, the expression levels of HOXA-AS2 in gallbladder cancer cell lines and control cells were first verified by QPCR and Western blot methods. Then, lentiviral tools were used to construct knockdown vectors (RNAi#1, RNAi#2) and negative control vectors targeting two different sites of HOXA-AS2, and the vectors were transfected into NOZ and OCUG-1 cells, respectively. Real-time PCR was used to detect knockdown efficiency. Then, the effects of silencing HOXA-AS2 on the proliferation, cell viability, cell migration, and invasion ability of gallbladder cancer cells were detected by MTT, plate cloning assay, Transwell migration chamber assay, and Transwell invasion chamber assay. Finally, the interaction between HOXA-AS2 and miR-6867 and the 3'UTR of YAP1 protein was detected by luciferase reporter gene. The results showed that the expression level of HOXA-AS2 in gallbladder cancer cell lines was higher than that in control cells. The expression of HOXA-AS2 in gallbladder carcinoma tissues was significantly higher than that in adjacent tissues (p < 0.05). After successful knockout of HOXA-AS2 by lentiviral transfection, the expression of HOXA-AS2 in gallbladder cancer cell lines was significantly decreased. Through cell proliferation and plate clone detection, it was found that silencing HOXA-AS2 inhibited cell proliferation and invasion. Through software prediction and fluorescein reporter gene detection, it was found that HOXA-AS2 has a binding site with miR-6867, and the two are negatively correlated, that is, the expression of miR-6867 is enhanced after the expression of HOXA-AS2 is downregulated. And the 3'UTR of YAP1 protein in the Hippo signaling pathway binds to miR-6867. Therefore, HOXA-AS2 may affect the expression of YAP1 protein by regulating miR-6867, thereby inhibiting the Hippo signaling pathway and promoting the proliferation and metastasis of gallbladder cancer cells. HOXA-AS2 is abnormally expressed in gallbladder cancer cells. HOXA-AS2 may promote the migration and invasion of gallbladder cancer cells by regulating the Hippo signaling pathway through miR-6867. HOXA-AS2 may serve as a potential diagnostic and therapeutic target for gallbladder cancer in clinic.