The potential mechanism of treating IC/BPS with hyperbaric oxygen by reducing vascular endothelial growth inhibitor and hypoxia-inducible factor-1α.

Background/aim: To investigate the roles of vascular endothelial growth inhibitor (VEGI) and hypoxia-inducible factor-1α (HIF-1α) in the treatment of refractory interstitial cystitis/bladder pain syndrome (IC/BPS) with hyperbaric oxygen (HBO). Materials and methods: A total of 38 patients were included. They were assessed before and 6 months after HBO treatment. Three-day voiding diaries were recorded, and O'leary-Sant scores, visual analog scale (VAS) scores, quality of life (QoL) scores, pelvic pain, and urgency/frequency (PUF) scores were evaluated. Bladder capacity was assessed by cystoscopy. Bladder mucosa was collected for Western blot, qRT-PCR, and immunofluorescence staining to compare the expression of VEGI and HIF-1α before and after treatment. Results: Compared with before treatment, patients showed significant improvements in 24-h voiding frequency (15.32 ± 5.38 times), nocturia (3.71 ± 1.80 times), O'leary-Sant score (20.45 ± 5.62 points), VAS score (41.76 ± 17.88 points), QoL score (3.03 ± 1.44 points), and PUF score (19.95 ± 6.46 points) after treatment (p < 0.05). There was no significant difference in bladder capacity before and after treatment (p ≥ 0.05). The expression levels of VEGI and HIF-1α protein and mRNA were significantly decreased 6 months after treatment compared with before treatment. Immunofluorescence staining results showed that the double positive expression of VEGI and HIF-1α protein in bladder tissue of IC/BPS patients after HBO treatment quantitatively decreased significantly. Conclusion: This study identified a possible mechanism by which VEGI and HIF-1α expression decreased after HBO treatment due to hypoxia reversal, which improved symptoms in IC/BPS patients.

Pilot-scale production of a highly efficacious and stable monoglycosylated influenza split virus vaccine.

The yearly epidemics and unpredictable outbreaks of influenza have raisedserious concernsglobally and led to prioritizing the development of an effective vaccine toprotectagainst newly emerging variants. Previously, we demonstrated that monoglycosylated influenza virus vaccines derived from A/California/7/2009 or an updated A/Brisbane/02/2018 (IVR-190) vaccine strain recommended by WHO are superior to fully glycosylated vaccines and could broadly protect against past and new coming H1N1 variants. However, whether such a monoglycosylated virus vaccine can be mass-produced to meet clinical demands and stable enough to provide consistent efficacy against H1N1 viruses remains unclear. Herein, we developed a platform for the pilot-scale production of the monoglycosylated split virus vaccine from the IVR-190 strain (IVR-190mg) with a robust and cost-effective manufacturing process. The critical parameters of inoculum dose, concentration of kifunensine, and optimized Endo H treatment process were comprehensively investigated. Several aims for preclinical studies of IVR-190mg were achieved, including [i] the execution of three engineering batch runs to validate lot-to-lot consistency, [ii] the establishment of IVR-190mg specifications to meet the acceptance criteria of a conventional influenza vaccine, [iii] an investigation of the stability profile of IVR-190mg, and completion of a safety evaluation by conducting an animal toxicology study. The toxicology study under GLP guidance found no systemic toxicity after rabbits were vaccinated with IVR-190mg. The serological data showed that IVR-190mg is highly immunogenic and effective in inducing a cross-strain protective level of antibody immune responses, including hemagglutination-inhibition titers, viral neutralization activity, and broad HA- and NA-inhibiting antibody titers against past and new H1N1 viruses. In conclusion, this study provides efficacy and safety profiles of IVR-190mg for further clinical study and shows that this vaccine without a glycan shield has great potential to be safe and protective against H1N1 variants.

The value of preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and red blood cell distribution width in predicting positive surgical margin after laparoscopic radical prostatectomy.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignant tumors in men, and laparoscopic radical prostatectomy (LRP) is commonly used to treat localized and advanced PCa. Positive surgical margin (PSM) is one of the most frequent problems faced by surgeons. AIMS: This study aimed to explore the value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) in predicting PSM after LRP. METHODS AND RESULTS: Three hundred and twenty patients with PCa were admitted and underwent LRP in Beijing Chaoyang Hospital from January 2017 to June 2023. Patients were randomly divided into a training set (225 cases) and a validation set (95 cases) in a 7:3 ratio. NLR, PLR, and RDW were significantly higher in the PSM group than in the negative surgical margins (NSM) group. In addition, the NLR, PLR, and RDW values correlated with clinical T stage, Gleason score, and seminal vesicle invasion in the PSM group. In training set, ROC curve analysis revealed that the optimal cutoff values of NLR, PLR, and RDW for predicting postoperative PSM in PCa were 2.31, 115.40, and 12.85%, respectively. Multivariate Logistic regression analysis showed NLR and RDW were the clinical independent predictors. The area under the curve (AUC, 0.770, 95% CI 0.709-0.831) for postoperative PSM was the highest when a combination of the three parameters was used, with sensitivity and specificity of 62.5% and 85.2%, respectively. In validation set, the AUC values for NLR, PLR, RDW and the three markers combined were 0.708, 0.675, 0.723, and 0.780, respectively. Correlation analysis showed that in the PSM group, NLR was positively correlated with PLR and RDW, and PLR was positively correlated with RDW. By contrast, in the NSM group, a positive association was only found between NLR and PLR. CONCLUSIONS: Higher preoperative NLR, PLR, and RDW values were associated with postoperative PSM. Additionally, the three markers combined may be useful to predict PSM.

Comparison of Air-charged Catheter and Water-filled Catheter in Female Urethral Pressure Profile.

OBJECTIVE: To compared the maximum urethral pressure (Pura@max) and functional urethral length (FUL) obtained with water-filled catheters and air-charged catheters during female urethral pressure profile (UPP) in a retrospective study. PATIENTS AND METHODS: One hundred and five female patients were enrolled in our investigation. At Beijing Chao-Yang Hospital, patients who had lower urinary tract dysfunction underwent UPP using a modified UPP equipment. In one UPP, both a water-filled catheter (WFC) and an air-charged catheter (ACC) were employed simultaneously. The paired t test was used to compare the differences between the two systems. Bias and correlations between the two systems were analyzed according to the American Clinical and Laboratory Standardization Institute (CLSI) EP9-A3 recommendations. RESULTS: There were 105 female participants in this study. The patients were 55.5 ± 14.2years old on average. By using the ACC and WFC systems, the mean FUL was determined to be 39.7 ± 16.2 mm and 33.9 ± 13.9 mm, respectively. The FUL findings of two systems differed significantly from one another (P < .01), and a linear fit with R2 = 0.94 indicates a strong linear correlation. The findings of the maximum urethral pressure (Pura@max) measurements made by the ACC and WFC systems, respectively, were 134.3 ± 39.1cmH2O and 99.2 ± 27.6cmH2O, are substantially different (P < .01), and the linear fit R2 = 0.67. The Pura@max of two systems did not linearly correlate with one another. CONCLUSION: For UPP, ACCs often provide higher readings than WFCs, and there is a significant difference in the readings between the two systems. The pressure values derived from the two systems do not correlate, although the FUL does have a significant linear correlation. Results from the ACC and WFC cannot be used interchangeably.

Monoglycosylated SARS-CoV-2 receptor binding domain fused with HAstem-scaffolded protein vaccine confers broad protective immunity against SARS-CoV-2 and influenza viruses.

The SARS-CoV-2 and influenza pandemics have posed a devastating threat to global public health. The best strategy for preventing the further spread of these respiratory viruses worldwide is to administer a vaccine capable of targeting both viruses. Here, we show that a novel monoglycosylated vaccine designed based on the influenza virus HAstem conserved domain fused with the SARS-CoV-2 spike-RBD domain (HSSRmg) can present proper antigenicity that elicits sufficient neutralization efficacy against various SARS-CoV-2 variants while simultaneously providing broad protection against H1N1 viruses in mice. Compared with the fully glycosylated HSSR (HSSRfg), HSSRmg induced higher ELISA titers targeting HAstem and spike-RBD and exhibited significantly enhanced neutralization activity against the Wuhan pseudovirus. The enhanced immune responses raised by JR300-adjuvanted HSSRmg compared to HSSRmg alone include more anti-HAstem and anti-spike-RBD antibodies that provide cross-protection against H1N1 challenges and cross-neutralization of SARS-CoV-2 pseudoviruses. Furthermore, the enhanced immune response raised by JR300-adjuvanted-HSSRmg skews toward a more balanced Th1/Th2 response than that raised by HSSRmg alone. Notably, HSSRmg elicited more plasma B cells and memory B cells, and higher IL-4 and IFN-γ cytokine immune responses than spike (S-2P) in mice with preexisting influenza-specific immunity, suggesting that B-cell activation most likely occurs through CD4+ T-cell stimulation. This study demonstrated that HSSRmg produced using a monoglycosylation process and combined with the JR300 adjuvant elicits superior cross-strain immune responses against SARS-CoV-2 and influenza viruses in mice compared with S-2P. JR300-adjuvanted HSSRmg has great potential as a coronavirus-influenza vaccine that provides dual protection against SARS-CoV-2 and influenza infections.

An Integrated Extraction-Purification Process for Raspberry Leaf Polyphenols and Their In Vitro Activities.

To improve the utilization value of raspberry leaves, the extraction and purification conditions of phenolic compounds from raspberry leaves were optimized, and the contents of phenolic compounds and the biological activities of extracts were studied. After steam explosion pretreatment at 115 °C for 15 min, raspberry leaf extract with a total phenolic content (TPC) of 136.30~140.51 mg GAE/g was obtained via homogenization and ultrasound-assisted extraction. In addition, the adsorption relationship between raspberry leaf polyphenols and middle polar XDA-6 macroporous resin was best described by the Langmuir model, and tended to be monolayer adsorption. Its adsorption kinetics best resembled the pseudo second-order kinetic model, and it was speculated that this was influenced by multiple factors. According to the optimal integrated extraction-purification process, the TPC of the extracts increased to 738.98 mg GAE/g after one application of purification and 905.27 mg GAE/g after two applications of purification. Moreover, the latter case showed the highest antioxidant activity and α-glucosidase inhibition activity, and the content of the most typical compound, quercetin-3-glucuronide, reached 199.69 mg/g. SE has a double-edged effect, and is more conducive to the release of active substances as a pre-treatment method. This study provides a theoretical basis for the efficient use of raspberry leaves, further improving their medicinal and economic value.

Case Report: Analysis of four cases of metastatic bladder masses after radical prostatectomy.

Objective: The aim of this study is to investigate the clinical characteristics and diagnostic and therapeutic methods of bladder metastasis after radical prostatectomy and to improve its diagnosis and treatment. Methods: The clinical data of four patients with bladder metastasis after radical prostatectomy were retrospectively analyzed from January 2011 to December 2021. Three cases suffered from intermittent gross hematuria, and only one case was found to have an elevated prostate-specific antigen (PSA) value. Transurethral resection of bladder tumor was performed in four cases, in which one case also underwent resection of urethral mass. Three cases received endocrine therapy, one of which added intravesical instillation and radiation therapy. Another case received chemotherapy based on comprehensive treatment. Results: According to the pathological and immunohistochemical results, three cases were acinar adenocarcinoma of the prostate with Gleason score of 9, and all cases were PSA positive and negative for cytokeratin 7 (CK7) and GATA binding protein 3 (GATA-3). One case was small cell neuroendocrine carcinoma of the prostate and was positive for chromogranin A (CGA), synaptophysin (SYN), and cluster of differentiation 56 (CD56). During the follow-up period of 4 to 13 months, one case was lost to follow-up and three cases were alive. Conclusion: Bladder metastasis after radical prostatectomy is rare, and pathology combined with immunohistochemistry is the gold standard for its diagnosis. Pathological type determines its treatment. Systemic treatment is essential, and local treatment is the most palliative means. Early diagnosis and treatment is significant for better prognosis.

Pilot-scale production of inactivated monoglycosylated split H1N1 influenza virus vaccine provides cross-strain protection against influenza viruses.

Influenza epidemics and pandemics caused by newly emerging virus strains highlight an urgent need to develop a universal vaccine against viruses. Previously, a monoglycosylated X-181mg vaccine demonstrated that the HA possessing a single N-acetylglucosamine at each N-glycosylation site is superior to confer broader protection in mice than conventional vaccines. However, the greatest challenge in conducting clinical trials is the need to develop robust manufacturing processes capable of producing vaccines at the pilot scale with the desired stability, potency, and efficacy. Whether the monoglycosylated virus vaccine platform can be applied to the new vaccine strain in a timely manner and whether the mass-produced vaccine has the proper immunogenicity to induce cross-protective immunity remains unclear. Here, we show that a pilot-scale manufacturing process produced a monoglycosylated A/Brisbane/02/2018(H1N1) virus vaccine (IVR-190mg) with a single glycan at each glycosylation site of HA and NA. Compared with the fully glycosylated virus vaccine (IVR-190fg), the IVR-190mg provided broader cross-protection in mice against a wide range of H1N1 variants. The enhanced antibody responses induced by IVR-190mg immunization include higher hemagglutination-inhibition titers, higher neutralization activity, more anti-HA head domain, more anti-HA stem antibodies, higher neuraminidase activity inhibition titers, and notably, higher antibody-dependent cellular cytotoxicity. Additionally, the IVR-190mg also induced a more balanced Th1/Th2 response and elicited broader splenic CD4+ and CD8+ T-cell responses than IVR-190fg. This study demonstrated that IVR-190mg produced using a pilot-scale manufacturing process elicits comprehensive cross-strain immune responses that have great potential to substantially mitigate the need for yearly reformulation of strain-specific inactivated vaccines.

Investigation of the function of the novel tumor marker BEND5 in lung adenocarcinoma based on data mining and in vitro analysis.

Background: BEN domain-containing protein 5 (BEND5) belongs to the BEN family of structural domains, whose members can be found in several animal proteins. The characteristic ability of BEND5 to inhibit cell proliferation allows it to play a crucial role as a tumor suppressor gene in colorectal cancer. However, the function of BEND5 in lung adenocarcinoma (LUAD) has not been fully explored. Methods: The Cancer Genome Atlas (TCGA) database was used to extensively examine BEND5 dysregulation and its prognostic significance in pan-cancer data. Databases including TCGA, gene expression profiling interactive analysis (GEPIA), and STRING were used to perform analysis of the expression pattern and clinical significance of BEND5 in patients with LUAD, and the possible regulatory mechanisms responsible for the occurrence and progression of LUAD. To explore the relationship between BEND5 expression and tumor immunity in LUAD. Finally, transfection experiments using an in vitro model were performed to confirm BEND5 expression in LUAD cells while investigating its regulatory significance in tumor cell proliferation. Results: Significantly decreased BEND5 expression was observed in LUAD and in most other cancers. Further analysis of the Kyoto Encyclopedia of Genes and Genomes database revealed that the genes significantly linked to BEND5 were mainly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Also, BEND5 was found to be involved in tumor immunity in LUAD via its functional regulation of various tumor cell types, such as B cells and T cells. In vitro experimental results showed that BEND5 overexpression mediated LUAD cell inhibition and decreased the expression of cell cycle-related proteins. Further, BEND5 activated the PPAR signaling pathway, and knockdown of PPAR reversed the effect of BEND5 overexpression on LUAD cells. Conclusions: BEND5 expression is low in LUAD and may be associated with poor prognosis, and BEND5 overexpression inhibits LUAD cells via the PPAR signaling pathway. The dysregulation of BEND5 in LUAD, its prognostic significance, and its ability to function in vitro suggest that BEND5 could be a deciding factor in the progression of LUAD.

Downregulation of Linc00173 increases BCL2 mRNA stability via the miR-1275/PROCA1/ZFP36L2 axis and induces acquired cisplatin resistance of lung adenocarcinoma.

BACKGROUND: LINC00173 had been reported as a cisplatin (cis-diamminedichloroplatinum, DDP) chemotherapy-resistant inducer in small-cell lung cancer (SCLC) and lung squamous cell carcinoma (LUSC). This study aimed to display reverse data for LINC00173 as a DDP chemosensitivity-inducing factor in lung adenocarcinoma (LUAD). METHODS: LINC00173 was screened from the Gene Expression Omnibus database (GSE43493). The expression level of LINC00173 in LUAD tissues and cell lines was detected using in situ hybridization and quantitative reverse transcription-polymerase chain reaction. Colony formation, cell viability, half-maximal inhibitory concentration, flow cytometry, and xenograft mouse model were used to evaluate the role of LINC00173 in the chemosensitivity of LUAD to DDP. The mechanism of LINC00173 in DDP resistance by mediating miR-1275/PROCA1/ZFP36L2 axis to impair BCL2 mRNA stability was applied, and co-immunoprecipitation, chromatin immunoprecipitation, RNA antisense purification, RNA immunoprecipitation, and luciferase reporter assays were performed. RESULTS: LINC00173 downregulation in patients with DDP-resistant LUAD was correlated with poor prognosis. Further, LINC00173 expression was significantly reduced in DDP-resistant LUAD cells and DDP-treated human LUAD tissues. Suppressed LINC00173 expression in LUAD cells enhanced DDP chemoresistance in vivo and in vitro, while restored LINC00173 expression in DDP-resistant LUAD cells markedly regained chemosensitivity to DDP. Mechanistically, DDP-resistant LUAD cells activated PI3K/AKT signal and further elevated the c-Myc expression. The c-Myc, as an oncogenic transcriptional factor, bound to the promoter of LINC00173 and suppressed its expression. The reduced LINC00173 expression attenuated the adsorption of oncogenic miR-1275, downregulating the expression of miR-1275 target gene PROCA1. PROCA1 played a potential tumor-suppressive role inducing cell apoptosis and DDP chemosensitivity via recruiting ZFP36L2 to bind to the 3' untranslated region of BCL2, reducing the stability of BCL2 mRNA and thus activating the apoptotic signal. CONCLUSIONS: This study demonstrated a novel and critical role of LINC00173. It was transcriptionally repressed by DDP-activated PI3K/AKT/c-Myc signal in LUAD, promoting DDP-acquired chemotherapeutic resistance by regulating miR-1275 to suppress PROCA1/ZFP36L2-induced BCL2 degradation, which led to apoptotic signal reduction. These data were not consistent with the previously described role of LINC00173 in SCLC or LUSC, which suggested that LINC00173 could play fine-tuned DDP resistance roles in different pathological subtypes of lung cancer. This study demonstrated that the diminished expression of LINC00173 might serve as an indicator of DDP-acquired resistance in LUAD.

Profiles of self-compassion and psychological outcomes in cancer patients.

OBJECTIVES: The protective role of self-compassion in cancer patients' psychological outcomes has been confirmed. However, using a composite score of self-compassion, previous research could not clarify how distinct components of self-compassion may mutually interact. This study, using a person-centred approach, aimed to identify profiles of self-compassion in cancer patients and examined the associations of self-compassion profiles with sociodemographic and medical variables and psychological outcomes. METHODS: This cross-sectional study included 289 patients with heterogeneous cancer types recruited from two hospitals in Xi'an, China. Latent profile analysis was used to identify distinct profiles of self-compassion. The Bolck-Croon-Hagenaars approach was used to examine how these profiles related to sociodemographic and medical characteristics and psychological outcomes. RESULTS: Five profiles of self-compassion were identified: 'average self-compassion' (54%), 'high self-compassion' (19.4%), 'low self-compassion and low self-coldness' (11.4%), 'high self-compassion and high self-coldness' (8%), and 'average self-compassion and high self-coldness' (7.2%). Patients with the 'high self-compassion' profile tended to be older and report no cancer recurrence, and those with the 'low self-compassion and low self-coldness' profile tended to be female. Patients with the 'high self-compassion' profile reported the fewest depressive and anxiety symptoms while patients with the 'average self-compassion and high self-coldness' profile reported the most depressive and anxiety symptoms. CONCLUSIONS: The study revealed five self-compassion profiles in cancer patients, which had different psychological outcomes. Future longitudinal research should investigate the causality between self-compassion profiles and psychological outcomes.

Effects of different diets used to induce obesity/metabolic syndrome on bladder function in rats.

Preclinical and human studies on the relationship between obesity/metabolic syndrome (MetS) and lower urinary tract dysfunction (LUTD) are inconsistent. We compared the temporal effects of feeding four different diets used to induce obesity/MetS, including 60% fructose, 2% cholesterol +10% lard, 30% fructose + 20% lard, or 32.5% lard diet, up to 42 wk, on metabolic parameters and bladder function in male Sprague-Dawley rats. Rats fed a 30% fructose + 20% lard or 32.5% lard diet consumed less food (grams), but only the 32.5% lard diet group took in more calories. Feeding rats a 60% fructose or 30% fructose + 20% lard diet led to glucose intolerance and increased blood pressure. Higher body weight and increased cholesterol levels were observed in the rats maintained on a 2% cholesterol +10% lard diet, whereas exposure to a 32.5% lard diet affected most of the above parameters. Voiding behavior measurement showed that voiding frequency and the total voided volume were lower in the experimental diet groups except for the 30% fructose + 20% lard group. The mean voided volume was lower in the 30% fructose + 20% lard and 32.5% lard groups compared with the control group. Cystometric analysis revealed a decreased bladder capacity, mean voided volume, intermicturition interval, and compliance in the 32.5% lard diet group. In conclusion, experimental diets including 60% fructose, 30% fructose + 20% lard, or 2% cholesterol + 10% lard diet differently affected physiological and metabolic parameters and bladder function to a limited extent, while exposure to a 32.5% lard diet had a greater impact.

Study of mirabegron and solifenacin in the improvement of catheter-related bladder discomfort in patients undergoing transurethral resection: A case-control study.

BACKGROUND: The goal of this study was to see if using mirabegron, solifenacin, or placebo may help patients with transurethral resection avoid catheter-related bladder discomfort (CRBD). METHODS: Patients who underwent transurethral surgery and were given a catheter for 3 days after surgery were chosen for this study. The enrolled patients were separated into 3 groups: mirabegron (M), solifenacin (S), and a blank control group (C). All patients had their overactive bladder symptoms score (OABSS) and blood pressure checked before surgery. The CRBD, blood pressure, and heart rate were measured at 6, 24, 48, and 72 hours after surgery. The OABSS and side effects were documented on the 7th day. RESULTS: The 104 patients in this trial were randomized into 3 groups at random: M, S, and C. The ultimate follow-up was completed by 99 patients, including 33 in group M, 33 in group S, and 33 in group C. The OABSS, CRBD, and blood pressure in groups M and S were similar before and after surgery (P > .05). Groups M and S performed much better on the OABSS and CRBD than group C (P < .05). There were no significant differences in blood pressure between the 3 groups (P > .05). There were no significant differences in the occurrences of new onset dry mouth (P = .84) or constipation (P = .64) among the 3 groups. CONCLUSION: Mirabegron is comparable to solifenacin as an alternative for the prevention of CRBD, making it a viable option for CRBD prevention.

The Long-term Effects of Transurethral Bladder Neck Incision in the Treatment of Female Bladder Neck Obstruction.

PURPOSE: To investigate the long-term effects of transurethral bladder neck incision (TUBNI) for female primary bladder neck obstruction (PBNO). MATERIALS AND METHODS: We retrospectively reviewed seventy women diagnosed with bladder neck obstruction by video-urodynamic study (VUDS). TUBNI was performed for each patient, with incisions made at 2 different sites on the bladder neck. Postoperatively, patients were assessed by international prostate symptom score (IPSS), quality of life (QOL) and uroflowmetry. RESULTS: Follow-up data were available for 4-108 months (median 42 months) postoperatively. During follow-up, the IPSS, QOL, time to maximum uroflow rate, postvoid residual urine volume decreased significantly after TUBNI compared with preoperative [13.0 (10.0, 15.0) versus 3.0 (3.0, 8.0), P ＜ .001], [5.0 (5.0, 5.0) versus 2.0 (1.0, 3.0), P ＜ .001], [9.0 (5.0, 37.0) versus 6.1 (4.2, 8.7), P ＜ .001], [77.5 (23.5, 165.8) versus 0.0 (0.0, 30.0), P ＜ .001]. The maximum uroflow rate, average uroflow rate and the voided volume increased significantly compared with preoperative [7.0 (4.0, 10.3) versus 19.8 (12.8, 25.2), P ＜ .001], [3.0 (2.0, 5.0) versus 8.0 (4.9, 10.7), P ＜ .001] and [156.5 (85.0, 211.3) versus 261.3 (166.2, 345.6), P ＜ .001]. Several complications were identified after surgery, including bladder neck reobstruction, urethral stricture, and stress urinary incontinence, the corresponding number was 5 (7.1%), 7(10%) and 7(10%). Successful operation was achieved in 60/70 (85.7 %) patients. CONCLUSION: PBNO is a very rare yet easily treatable condition. VUDS is the primary diagnostic tool for the diagnosis of bladder neck obstruction in women, while TUBNI can effectively relieve obstruction symptoms and improve the quality of life for patients.

Preparation, physicochemical and application evaluation of raspberry anthocyanin and curcumin based on chitosan/starch/gelatin film.

Raspberry anthocyanin (RA) from Rubus idaeus L. (Rosaceae) and curcumin (Cur) from Curcuma longa L. (Zingiberaceae) can effectively improve the physicochemical properties of composite films, and as bioactive pigment components, they can impart pH-responsive properties to the film. In this study, RA and Cur were added to chitosan/starch/gelatin composite film (CSG) to prepare CSG-RA, CSG-Cur, CSG-RA/Cur82 and CSG-RA/Cur73 color films by solution casting method. The color films could change color under different pH conditions and had higher antioxidant activities using ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)) assay. The results from fourier transform infrared spectroscopy and scanning electron microscopy showed that RA and Cur were well dispersed in the CSG matrix and improved the structure of the composite films. The hydrophobic Cur increased the tensile strength from 6 Mpa (CSG) to 14 Mpa (CSG-Cur), but reduced the elongation at break from 55 % (CSG) to 40 % (CSG-Cur). These color films had a good fresh-keeping effect and freshness monitoring, in particular, CSG-RA/Cur73, had the better opacity, water solubility, thickness, moisture content and water vapor permeability than the other films. Briefly, binary pigment films had the potential to become a pH-sensitive indicator/packing film.

CBX4 contributes to HIV-1 latency by forming phase-separated nuclear bodies and SUMOylating EZH2.

The retrovirus HIV-1 integrates into the host genome and establishes a latent viral reservoir that escapes immune surveillance. Molecular mechanisms of HIV-1 latency have been studied extensively to achieve a cure for the acquired immunodeficiency syndrome (AIDS). Latency-reversing agents (LRAs) have been developed to reactivate and eliminate the latent reservoir by the immune system. To develop more promising LRAs, it is essential to evaluate new therapeutic targets. Here, we find that CBX4, a component of the Polycomb Repressive Complex 1 (PRC1), contributes to HIV-1 latency in seven latency models and primary CD4+ T cells. CBX4 forms nuclear bodies with liquid-liquid phase separation (LLPS) properties on the HIV-1 long terminal repeat (LTR) and recruits EZH2, the catalytic subunit of PRC2. CBX4 SUMOylates EZH2 utilizing its SUMO E3 ligase activity, thereby enhancing the H3K27 methyltransferase activity of EZH2. Our results indicate that CBX4 acts as a bridge between the repressor complexes PRC1 and PRC2 that act synergistically to maintain HIV-1 latency. Dissolution of phase-separated CBX4 bodies could be a potential intervention to reactivate latent HIV-1.

Enriched environment priors to TET1 hippocampal administration for regulating psychiatric behaviors via glial reactivity in chronic cerebral hypoperfusion models.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) has been gradually regarded as a common etiologic mechanism for cognitive and psychiatric disturbances. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) played an important role in adult hippocampal neurogenesis (AHN), neuronal circuits formation, cognition and psychiatric disorders. Enriched environment (EE) showed a beneficial effect on cognition and depression via effectively regulating AHN and glial reactivity. This study aimed to assess which strategy was feasible to improve cognition and psychiatric disturbances by comparing the TET1 hippocampal microinjection and EE in CCH models and to investigate the possible mechanisms. METHOD: CCH rats were established via permanent bilateral common carotid artery occlusion (2-VO). Rats were stereotaxically injected with the human catalytic domain of TET1 (hTET1) to overexpress the hTET1 in the hippocampus 10 days before 2-VO. 3 days after 2-VO, rats were subjected to standard environment or EE with free access to food and water. Behavioral tests were used to appraise depression and cognition before sacrifice. Epigenetic molecules, adult neurogenesis, synaptic proteins expression, and glial activation were analyzed using immunofluorescent staining, qRT-PCR and western blot. RESULTS: In the present study, we found both EE and genetical treatment with overexpressing hTET1 were sufficient for stimulating AHN. However, promoting ANH could not deal with the cognitive dysfunction and depressive-like behaviors in CCH rats. Notably, a healthy local brain environment with elevated BDNF and astrocytes was conducive to improving cognitive dysfunction. Meanwhile, astrocytes were involved in the cognitive regulating process of neurons, presynaptic function and microglia. In general, we held that depressive disturbances were determined by BDNF levels, neuronal and presynaptic function, as well as glial activation containing astrocytes and microglia. To further support this point, we investigated severe depressive symptoms that were strongly correlated with the activation of astroglia and microglia. Importantly, causal mediation analysis showed significant mediation by the presence of reactive glial cells in the relation between neural plasticity and depressive symptoms. Finally, we showed EE performed better than hTET1 treatment for cognitive deficits and depression. EE with less glial reactivity was much more resistant to depression, while hTET1 with more glial activation was more vulnerable to depressive disorders. CONCLUSIONS: EE was likely to be superior to TET1 hippocampal administration for cognition and psychiatric behaviors in CCH rats. Furthermore, a healthy local brain environment with elevated BDNF and astrocytes was conducive to improving cognitive dysfunction. More glial activation, and more vulnerable to depressive disorders. These results were important for our understanding of disease mechanisms and provided valuable tools for the overall management of CCH patients.

Phytochemicals and anti-tyrosinase activities of Paeonia ostii leaves and roots.

Tree peony (sect. Moutan) is a kind of Traditional Chinese Medicine and ornamental plant, which has been widely cultivated and utilized for thousands of years. To further study the active components of Paeonia ostii (Moutan, Fengdan), six fractions (soluble free (F), soluble esterification, soluble glycosylation, insoluble bound, insoluble esterification and insoluble glycosylation) were extracted from the leaves and roots by alkaline and acid treatment for the first time. Twenty-one typical compounds were identified and quantified by HPLC-MS. The results showed that total phenolic content (TPC) in peony roots (PR) and peony leaves (PL) were as high as 125.48 and 280.38 mg GAE·g-1 dw, which maximizes the extraction efficiency of phenolic compounds, especially leaves, compared with the conventional method. PR-F and PL-F had the highest TPC, antioxidant and anti-tyrosinase activities. Paeoniflorin was the main compounds in PL and PR. It and pentagalloylglucose (PGG) almost reached the anti-tyrosinase level of kojic acid, but they showed different inhibitory mechanisms by molecular docking. On the whole, PR-F, PL-F, PGG and paeoniflorin might be potential for skin whitening products.

The small molecule chemical compound cinobufotalin attenuates resistance to DDP by inducing ENKUR expression to suppress MYH9-mediated c-Myc deubiquitination in lung adenocarcinoma.

The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to ß-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.

Chemically synthesized cinobufagin suppresses nasopharyngeal carcinoma metastasis by inducing ENKUR to stabilize p53 expression.

Clinically, the metastasis of tumor cells is the key factor of death in patients with cancer. In this study, we used a model of metastatic nasopharyngeal carcinoma (NPC) to explore the effects of a new chemical, cinobufagin (CB), combined with cisplatin (DDP). We observed that chemically synthesized CB strongly decreased the metastasis of NPC. Furthermore, a better therapeutic effect was shown when CB was combined with DDP. Molecular analysis revealed that CB induced ENKUR expression by deregulating the PI3K/AKT pathway and suppressing c-Jun, an oncogenic transcriptional factor that binds to the ENKUR promoter and negatively modulated its expression in NPC. ENKUR as a tumor suppressor binds to MYH9 and decreases its expression by recruiting ß-catenin via its enkurin domain to prevent its nuclear accumulation, which therefore suppresses c-Jun-induced MYH9 expression. Subsequently, downregulated MYH9 reduces the enlistment of E3 ligase UBE3A and thus decreases the UBE3A-mediated ubiquitination degradation of p53, a key tumor suppressor that decreases epithelial-mesenchymal transition (EMT). Clinical sample analysis demonstrated that the ENKUR expression level was significantly reduced in NPC tissues. Its decreased expression substantially promoted clinical progression and reflected poor prognosis for patients with NPC. This study demonstrated that CB induced ENKUR to repress the ß-catenin/c-Jun/MYH9 signal and thus decreased UBE3A-mediated p53 ubiquitination degradation. As a result, the EMT signal was inactivated to suppress NPC metastasis.