Metal-Free Regioselective Hydrophosphorodithioation of Spirovinylcyclopropyl Oxindoles: Rapid Access to Allyl Dialkylphosphorodithioates.

Phosphorodithioates are important substructures due to their great use in bioactive compounds and functional materials. A metal-free 1,5-addition of spirovinylcyclopropyl oxindoles have been developed by choosing P4S10 and alcohol as nucleophiles through the regioselective ring-opening of spirovinylcyclopropyl oxindoles. This method provides access to allylic organothiophosphates with high efficiency, wide functional group tolerance, good chemo- and regioselectivity, and E-selectivity. 1,3-Addition products were also prepared in high yield. Furthermore, the resulting organothiophosphates could be readily transformed into other allylic derivatives.

Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells.

BACKGROUND: DPP8 and DPP9 have been demonstrated to play important roles in multiple diseases. Evidence for increased gene expression of DPP8 and DPP9 in tubulointerstitium was found to be associated with the decline of kidney function in chronic kidney disease (CKD) patients, which was observed in the Nephroseq human database. To examine the role of DPP8 and DPP9 in the tubulointerstitial injury, we determined the efficacy of DPP8 and DPP9 on epithelial-to-mesenchymal transition (EMT) and tubulointerstitial fibrosis (TIF) as well as the underlying mechanisms. METHODS: We conducted the immunofluorescence of DPP8 and DPP9 in kidney biopsy specimens of CKD patients, established unilateral ureteral obstruction (UUO) animal model, treated with TC-E5007 (a specific inhibitor of both DPP8 and DPP9) or Saxagliptin (positive control) or saline, and HK-2 cells model. RESULTS: We observed the significantly increased expression of DPP8 and DPP9 in the renal proximal tubule epithelial cells of CKD patients compared to the healthy control subjects. DPP8/DPP9 inhibitor TC-E5007 could significantly attenuate the EMT and extracellular matrix (ECM) synthesis in UUO mice, all these effects were mediated via interfering with the TGF-ß1/Smad signaling. TC-E5007 treatment also presented reduced renal inflammation and improved renal function in the UUO mice compared to the placebo-treated UUO group. Furthermore, the siRNA for DPP8 and DPP9, and TC-E5007 treatment decreased EMT- and ECM-related proteins in TGF-ß1-treated HK-2 cells respectively, which could be reversed significantly by transduction with lentivirus-DPP8 and lentivirus-DPP9. CONCLUSION: These data obtained provide evidence that the DPP8 and DPP9 could be potential therapeutic targets against TIF.

Management of large renal stones with super-mini percutaneous nephrolithotomy: an international multicentre comparative study.

OBJECTIVES: To comparatively evaluate the clinical outcomes of super-mini percutaneous nephrolithotomy (SMP) and mini-percutaneous nephrolithotomy (Miniperc) for treating urinary tract calculi of >2 cm. PATIENTS AND METHODS: An international multicentre, retrospective cohort study was conducted at 20 tertiary care hospitals across five countries (China, the Philippines, Qatar, UK, and Kuwait) between April 2016 and May 2019. SMP and Miniperc were performed in 3525 patients with renal calculi with diameters of >2 cm. The primary endpoint was the stone-free rate (SFR). The secondary outcomes included: blood loss, operating time, postoperative pain scores, auxiliary procedures, complications, tubeless rate, and hospital stay. Propensity score matching analysis was used to balance the selection bias between the two groups. RESULTS: In all, 2012 and 1513 patients underwent SMP and Miniperc, respectively. After matching, 1380 patients from each group were included for further analysis. Overall, there was no significant difference in the mean operating time or SFR between the two groups. However, the hospital stay and postoperative pain score were significantly in favour of SMP (both P < 0.001). The tubeless rate was significantly higher in the SMP group (72.6% vs 57.8%, P < 0.001). Postoperative fever was much more common in the Miniperc group (12.0% vs 8.4%, P = 0.002). When the patients were further classified into three subgroups based on stones diameters (2-3, 3-4, and >4 cm). The advantages of SMP were most obvious in the 2-3 cm stone group and diminished as the size of the stone increased, with longer operating time in the latter two subgroups. Compared with Miniperc, the SFR of SMP was comparable for 3-4 cm stones, but lower for >4 cm stones. There was no statistical difference in blood transfusions and renal embolisations between the two groups. CONCLUSIONS: Our data showed that SMP is an ideal treatment option for stones of <4 cm and is more efficacious for stones of 2-3 cm, with lesser postoperative fever, blood loss, and pain compared to Miniperc. SMP was less effective for stones of >4 cm, with a prolonged operating time.

Extracellular vesicles of carcinoma-associated fibroblasts creates a pre-metastatic niche in the lung through activating fibroblasts.

OBJECTIVES: Carcinoma-associated fibroblasts (CAFs) have been known to promote cancer progression by modifying the primary tumor microenvironment. We aimed to elucidate the intercellular communication between CAFs and secondary organs in salivary adenoid cystic carcinoma (SACC) metastasis. METHODS: Pre-metastatic and metastatic animal models of SACC were established using extracellular vesicles (EVs) from CAFs and SACC cells. Lung fibroblasts (LFs) were treated with EVs and their transcriptomic alterations were identified by RNA sequencing. ITRAQ were performed to analyze EV cargos. TC I-15 was used to inhibit EV uptake by LFs and SACC lung metastasis in vivo. RESULTS: Here, we show that CAF EVs induced lung pre-metastatic niche formation in mice and consequently increased SACC lung metastasis. The pre-metastatic niche induced by CAF EVs was different from that induced by SACC EVs. CAF EVs presented a great ability for matrix remodeling and periostin is a potential biomarker characterizing the CAF EV-induced pre-metastatic niche. We found that lung fibroblast activation promoted by CAF EVs was a critical event at the pre-metastatic niche. Integrin α2ß1 mediated CAF EV uptake by lung fibroblasts, and its blockage by TC I-15 prevented lung pre-metastatic niche formation and subsequent metastasis. Plasma EV integrin ß1 was considerably upregulated in the mice bearing xenografts with high risk of lung metastasis. CONCLUSIONS: We demonstrated that CAF EVs participated in the pre-metastatic niche formation in the lung. Plasma EV integrin ß1 might be a promising biomarker to predict SACC metastasis at an early stage. An integrated strategy targeting both tumor and stromal cells is necessary to prevent SACC metastasis.

Prevalence and prognostic value of FBXO11 expression in patients with clear cell renal cell carcinoma.

BACKGROUND: FBXO11, a member of the F-box protein family, regulates the cell-cycle by promoting the degradation of Bcl-6 and p53. This protein has been implicated in the progression of several cancers, including renal cell carcinoma (RCC). The aim of this study was to determine the prognostic role of FBXO11 in the clinical outcome of RCC patients. METHODS: FBXO11 mRNA expression was analysed in normal and RCC tissue microarrays of the Oncomine database. In addition, the in situ expression levels of stromal FBXO11 protein were assessed in primary RCC tissues from 227 patients (training and validation cohorts) using immunohistochemistry (IHC). Kaplan Meier and Cox regression analyses were used to determine the association between FBXO11 expression and cliniopathological factors. A nomogram was established using the significant prognostic factors to predict overall survival (OS) of RCC patients after one, three and 5 years. RESULTS: In the Oncomine database, FBXO11 mRNA levels were lower in normal tissues than in cancer tissues, including clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), hereditary ccRCC, non-hereditary ccRCC, VHL mutant ccRCC and VHL wild-type ccRCC. In addition, FBXO11 expression was also significantly higher in metastatic kidney cancer than in primary cancer. Immunohistochemical analysis reported that 57.3% (86 of 150) of the training cohort and 57.1% (44 of 77) of the validation cohort were scored as having high FBXO11 staining density. FBXO11 expression was significantly associated with Fuhrman grade (p = 0.003), UISS score (p = 0.021) and age (p = 0.048) in the training cohort. Furthermore, Kaplan-Meier survival analysis showed that higher FBXO11 levels, T stage, UISS scores and SSIGN score were associated with poor OS in ccRCC patients. Multivariate Cox analysis demonstrated that higher FBXO11 levels and higher UISS score were independent prognostic indicators for OS. Nomogram, calibration plots, AUC values and the C-index showed that the predictive accuracy of conventional prognostic models, including UISS score and SSIGN score, was improved when FBXO11 expression was added. CONCLUSIONS: FBXO11 expression was closely related to RCC malignancy and poor prognosis, indicating its potential as a prognostic marker as well as a therapeutic target for RCC.

MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor PDCD4 and promotes cell transformation, proliferation, and metastasis in renal cell carcinoma.

OBJECTIVES: MiR-21 induces neoplastic transformation, cell proliferation, and metastasis and downregulates programmed cell death4 (PDCD4) in some cancers. The aim of this study was to investigate the roles and interactions of PDCD4 and miR-21 in human renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 32 paired tumor and normal tissue specimens from RCC patients as well as three renal cancer cell lines (786-O, A498, caki-1) and one normal epithelial kidney cell line (HK-2) were studied. The expression levels of PDCD4 (protein and mRNA) and miR-21 were examined by Western blot analysis and by qRT-PCR and luciferase reporter assays. Furthermore, we transfected 786-O cells with pre-miR-21 (mimics) and anti-miR-21 (inhibitor) and then again analyzed the expression of PDCD4 protein and mRNA, and determined cell proliferation and transformation capabilities by EDU and soft agar colony formation assay. RESULTS: MiR-21 expression was significantly upregulated in RCC, metastatic RCC specimens and renal cancer cell lines (A498, 786-O, caki-1) compared to normal non-metastatic RCC specimens and HK-2 cells (P<0.05). In contrast, PDCD4 protein expression significantly decreased (P<0.05), whereas PDCD4 mRNA expression remained unaltered (P>0.05). Moreover, we observed a significant reduction in PDCD4 protein levels in miR-21mimic-transfected cells, but a significant increase in miR-21inhibitor-transfected cells (P<0.05), whereas PDCD4 mRNA was practically unaltered (P>0.05). Furthermore, miR-21mimic-transfected cells exhibited increased cell proliferation and transformation capacity according to EDU analysis and soft agar formation assay, whereas miR-21inhibitor-transfected cells exhibited the opposite phenomenon(P<0.05). CONCLUSIONS: MiR-21 not only promoted cancer cell hyperplasia and contributed to tumor cell transformation and metastasis, but also post-transcriptionally downregulated PDCD4 protein expression. PDCD4 and miR-21 expression levels potentially play an important role in renal cell cancer.

Harnessing Atomically Dispersed Cobalt for the Reductive Catalytic Fractionation of Lignocellulose.

The reductive catalytic fractionation (RCF) of lignocellulose, considering lignin valorization at design time, has demonstrated the entire utilization of all lignocellulose components; however, such processes always require catalysts based on precious metals or high-loaded nonprecious metals. Herein, the study develops an ultra-low loaded, atomically dispersed cobalt catalyst, which displays an exceptional performance in the RCF of lignocellulose. An approximately theoretical maximum yield of phenolic monomers (48.3 wt.%) from lignin is realized, rivaling precious metal catalysts. High selectivity toward 4-propyl-substituted guaiacol/syringol facilitates their purification and follows syntheses of highly adhesive polyesters. Lignin nanoparticles (LNPs) are generated by simple treatment of the obtained phenolic dimers and oligomers. RCF-resulted carbohydrate pulp are more obedient to enzymatic hydrolysis. Experimental studies on lignin model compounds reveal the concerted cleavage of Cα-O and Cß-O pathway for the rupture of ß-O-4 structure. Overall, the approach involves valorizing products derived from lignin biopolymer, providing the opportunity for the comprehensive utilization of all components within lignocellulose.

Recent development and future application of biodegradable ureteral stents.

Ureteral stenting is a common clinical procedure for the treatment of upper urinary tract disorders, including conditions such as urinary tract infections, tumors, stones, and inflammation. Maintaining normal renal function by preventing and treating ureteral obstruction is the primary goal of this procedure. However, the use of ureteral stents is associated with adverse effects, including surface crusting, bacterial adhesion, and lower urinary tract symptoms (LUTS) after implantation. Recognizing the need to reduce the complications associated with permanent ureteral stent placement, there is a growing interest among both physicians and patients in the use of biodegradable ureteral stents (BUS). The evolution of stent materials and the exploration of different stent coatings have given these devices different roles tailored to different clinical needs, including anticolithic, antibacterial, antitumor, antinociceptive, and others. This review examines recent advances in BUS within the last 5 years, providing an in-depth analysis of their characteristics and performance. In addition, we present prospective insights into the future applications of BUS in clinical settings.

Web Application to Enable Online Social Interactions in a Parkinson Disease Risk Cohort: Feasibility Study and Social Network Analysis.

BACKGROUND: There is evidence that social interaction has an inverse association with the development of neurodegenerative diseases. PREDICT-Parkinson Disease (PREDICT-PD) is an online UK cohort study that stratifies participants for risk of future Parkinson disease (PD). OBJECTIVE: This study aims to explore the methodological approach and feasibility of assessing the digital social characteristics of people at risk of developing PD and their social capital within the PREDICT-PD platform, making hypotheses about the relationship between web-based social engagement and potential predictive risk indicators of PD. METHODS: A web-based application was built to enable social interaction through the PREDICT-PD portal. Feedback from existing members of the cohort was sought and informed the design of the pilot. Dedicated staff used weekly engagement activities, consisting of PD-related research, facts, and queries, to stimulate discussion. Data were collected by the hosting platform. We examined the pattern of connections generated over time through the cumulative number of posts and replies and ego networks using social network analysis. We used network metrics to describe the bonding, bridging, and linking of social capital among participants on the platform. Relevant demographic data and Parkinson risk scores (expressed as an odd 1:x) were analyzed using descriptive statistics. Regression analysis was conducted to estimate the relationship between risk scores (after log transformation) and network measures. RESULTS: Overall, 219 participants took part in a 4-month pilot forum embedded in the study website. In it, 200 people (n=80, 40% male and n=113, 57% female) connected in a large group, where most pairs of users could reach one another either directly or indirectly through other users. A total of 59% (20/34) of discussions were spontaneously started by participants. Participation was asynchronous, with some individuals acting as "brokers" between groups of discussions. As more participants joined the forum and connected to one another through online posts, distinct groups of connected users started to emerge. This pilot showed that a forum application within the cohort web platform was feasible and acceptable and fostered digital social interaction. Matching participants' web-based social engagement with previously collected data at individual level in the PREDICT-PD study was feasible, showing potential for future analyses correlating online network characteristics with the risk of PD over time, as well as testing digital social engagement as an intervention to modify the risk of developing neurodegenerative diseases. CONCLUSIONS: The results from the pilot suggest that an online forum can serve as an intervention to enhance social connectedness and investigate whether patterns of online engagement can impact the risk of developing PD through long-term follow-up. This highlights the potential of leveraging online platforms to study the role of social capital in moderating PD risk and underscores the feasibility of such approaches in future research or interventions.

Selective expansion of renal cancer stem cells using microfluidic single-cell culture arrays for anticancer drug testing.

The suboptimal prognosis associated with drug therapy for renal cancer can be attributed to the presence of stem-cell-like renal cancer cells. However, the limited number of these cells prevents conventional drug screening assays from effectively assessing the response of renal cancer stem cells to anti-cancer agents. To address this issue, the present study employed microfluidic single-cell culture arrays to expand renal cancer stem cells by exploiting the anti-apoptosis and self-renewal properties of tumor stem cells. A microfluidic chip with 18 000 hydrophilic microwells was designed and fabricated to establish the single-cell culture array. Over a 7 day culture, the large-scale single-cell culture yielded a limited quantity of single-cell-derived tumorspheres. The sphere formation rates for Caki-1, 786-O, and ACHN cells were determined to be 8.74 ± 0.53%, 12.02 ± 1.43%, and 4.98 ± 1.68%, respectively. The expanded cells exhibited stemness characteristics, as indicated by immunofluorescence, flow cytometry, serial passaging, and in vitro differentiation assays. Additionally, the comparative transcriptomic analysis showed significant differences in the gene expression patterns of the expanded cells compared to the differentiated renal cancer cells. The drug testing indicated that renal cancer stem cells exhibited reduced sensitivity towards the tyrosine kinase inhibitors sorafenib and sunitinib, compared to differentiated renal cancer cells. This reduced sensitivity can be attributed to the elevated expression levels of tyrosine kinase in renal cancer stem cells. This present study provides evidence that the utilization of microfluidic single-cell culture arrays for selective cell expansion can facilitate drug testing of renal cancer stem cells.

[Retracted] Isoquercitrin inhibits bladder cancer progression in vitro and in vivo by regulating the PI3K/Akt and PKC signaling pathways.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the agarose gel electrophoretic bands shown in Fig. 4A for PKC were strikingly similar to bands that had already appeared in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 36: 165­172, 2016; DOI: 10.3892/or.2016.4794].

Can tamsulosin facilitate expulsion of ureteral stones? A meta-analysis of randomized controlled trials.

OBJECTIVES: To determine the efficacy and safety of the adrenergic alpha-antagonist tamsulosin in facilitating ureteral stones expulsion. METHODS: A literature search was carried out using the PubMed database, Medline via Ovid, Embase and the Cochrane Library database to identify randomized controlled trials evaluating the efficiency of tamsulosin in the treatment of ureteral stones. Meta-analysis and forest plots were carried out by use of Review Manager version 5.1 software (Cochrane Collaboration). RESULTS: Compared with the control group, the tamsulosin group had an increase in expulsion rate of 51% and a decrease in expulsion time of 2.63 days. Furthermore, tamsulosin was found to reduce the risk of ureteral colic during treatment by 40% and also the risk of requirement of auxiliary procedures during follow up by 60%. In terms of safety, the tamsulosin group had a 117% increase in the incidence of side-effects compared with the control group, especially for incidence of dizziness. CONCLUSION: Tamsulosin facilitates the expulsion of ureteral calculi by providing a higher expulsion rate, a shorter expulsion time, a lower incidence of ureteral colic during treatment and a lower requirement of auxiliary procedures. However, the incidence of dizziness occurring during tamsulosin treatment is significantly higher in this setting.

[Effects of neoadjuvant chemotherapy on the prognostic mortality risk of invasive transitional bladder cancer: a meta-analysis].

OBJECTIVE: To systematically assess the effects of neoadjuvant chemotherapy on the prognostic risk of invasive transitional bladder cancer. METHODS: All known randomized controlled trials (RCTs) on neoadjuvant chemotherapy in the treatment of invasive transitional bladder cancer, published from the date of database building to September 2012, were retrieved from such databanks as Pubmed, CBMdisc, Embase and Cochrane. The data on 5-year survival rate of included studies were extracted for further heterogeneity exploration, subgroup analysis and statistical pooling with the RevMan 5.10 software. RESULTS: Fourteen subjects involving 2072 cases and 2086 controls were published from 1991 to 2012. The overall odds ratio of survival suggested a 21% relative reduction in mortality risk for neoadjuvant chemotherapy compared to that on control (OR = 0.79, 95%CI:0.70-0.90). In subgroup analysis according to different neoadjuvant chemotherapies, MCV (methotrexate, cisplatin and vinblastine) and MVAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapies showed significant benefit to overall survival with 28% and 25% reduction in risk of death respectively (OR = 0.72,95%CI:0.60-0.86, OR = 0.75,95%CI:0.59-0.96) . However, no significant difference existed in effects between C (cisplatin) chemotherapy, CM (cisplatin and methotrexate) chemotherapy and CD (cisplatin and docetaxel) chemotherapy and controls. In subgroup analysis according to local treatment of cystectomy or radiotherapy after neoadjuvant chemotherapy, the patients with cystectomy showed significant benefits in overall survival with 25% reduction in risk of death (OR = 0.75, 95%CI:0.65-0.87). However, the patients with radiotherapy or radiotherapy plus cystectomy showed no significant benefits in overall survival. CONCLUSIONS: MCV and MVAC neoadjuvant chemotherapies improve survival among patients with bladder cancer. And neoadjuvant chemotherapy has better long-term survival after cystectomy.

[Clinical research on the correlations between type 2 diabetes mellitus and renal clear cell carcinoma].

OBJECTIVE: To investigate the relationship between renal clear cell carcinoma and type 2 diabetes mellitus (DM). METHODS: Two hundreds and sixty-four patients with renal clear cell carcinoma and four hundred controls who suffered from non-urinary system, non-neoplastic or non-hormone-related disorders, were enrolled from January 2008 to December 2012. The incidence of diabetes between the 2 groups and the relationship between renal clear cell carcinoma and duration of diabetes were compared, moreover, renal clear cell carcinoma patients with DM were compared with patients without DM for their clinical features, laboratory examinations and histological characteristics. RESULTS: The comparison of renal clear cell carcinoma group and control group: the incidence of DM in the two groups were 19.7% and 12.8% respectively, and the difference was significant (χ(2) = 5.86, P < 0.05, OR = 1.68). In the renal clear cell carcinoma group, the proportion of patients with DM diagnosed within 2-4 years was 4.92%, which were significant higher than those in the control group 1.70% (χ(2) = 5.49, P < 0.05, OR = 2.91). And men with diabetes had high occurrence risk 86% of renal clear cell carcinoma (OR = 1.86, 95%CI: 1.09-3.15). The comparison of diabetes patients subgroup and non-diabetic patients subgroup in renal clear cell carcinoma group: in respect of clinical features, greatest tumor diameter in the two subgroups were (4.9 ± 2.3) cm and (4.2 ± 2.1) cm respectively, and the difference was significant (t = 1.96, P < 0.05). However, there was no significant difference in terms of age, gender and cancer location between the two subgroups (P > 0.05). In respect of laboratory examinations, serum creatinine in the two subgroups were (72 ± 20) µmol/L and (65 ± 17) µmol/L, and the difference was significant (t = 2.34, P < 0.05); serum urea nitrogen in the 2 subgroups were (7.1 ± 2.1) mmol/L and (6.0 ± 1.5) mmol/L respectively, and the difference was significant too (t = 1.47, P < 0.05). In respect of histological characteristics, the proportion of well differentiated clear cell carcinoma were 80.8% and 81.1% respectively, and the difference was significant (χ(2) = 4.23, P < 0.05). The proportion of stage II were 25.0% and 27.8% respectively and the difference was significant (χ(2) = 4.08, P < 0.05). CONCLUSIONS: DM is closely related with renal clear cell carcinoma and DM may be a possible risk factor for the tumor. And for elderly patients with diabetes who appear waist discomfort or hematuria, a careful examination of kidney is important to make early diagnosis, give timely treatment and improve survival prognosis.

Molecular genetic and clinical characteristic analysis of primary signet ring cell carcinoma of urinary bladder identified by a novel OR2L5 mutation.

To get a better understanding of the genetic basis of primary signet ring cell carcinoma (SRCC) of the bladder, which is highly rare and not yet explored. First, by using immunohistochemistry to find histological pathological characteristics. Second, a massively parallel whole-exome sequencing (WES) was performed on a 58-year-old male patient who had painless macroscopic hematuria and was pathologically diagnosed with primary SRCC of the bladder, followed by comparing with genes of ordinary urothelial cancer (UC) from TCGA. Furthermore, a population-based analysis using the SEER database was performed to investigate the prognosis (SRCC vs. UC). We identified 63 copy number variations (CNVs) with gain counts and 181 CNVs with loss counts. Totally 4515 mutations were discovered in C > T with a success rate of greater than 89%. The most frequently mutated pathway was RTK-RAS which has 85 genes involved in carcinogenic signaling. Final screening on predisposing genes is performed after filtering based on ACMG. Moreover, several driver genes, including NBN, KCTD18, SPATA13, ANKRD36, OR2L5, MALRD1, and LSMEM1, were detected. Sanger sequencing of germline DNA revealed the presence of a mutant base A/G of OR2L5 in the sequence, which was discovered for the first time in primary SRCC of the bladder. Furthermore, the immunohistochemical profile showed that primary SRCC of the bladder were positive for CK7, CK20, GATA-3, and expression of CK(AE1/AE2), EMA, and Ki67. In the SEER-based study, the patients with primary SRCC of the bladder got a worse prognosis compared to those with UC with median months overall survival (OS) 14 vs. 41, respectively, P = 0001, even after adjusting the variables in the Cox regression model, the SRCC of the bladder showed worse survival HR = 1.119, 95% CI = (1.081-1.328), P = 0.0001. These results imply that suppression of potential driver mutations may be a viable adjuvant treatment approach for primary SRCC in the bladder in place of standard chemotherapy, a possibility that warrants further clinical investigation.

Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer.

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

Non-randomised feasibility study testing a primary care intervention to promote engagement in an online health community for adults with troublesome asthma: protocol.

INTRODUCTION: In the UK, approximately 4.3 million adults have asthma, with one-third experiencing poor asthma control, affecting their quality of life, and increasing their healthcare use. Interventions promoting emotional/behavioural self-management can improve asthma control and reduce comorbidities and mortality. Integration of online peer support into primary care services to foster self-management is a novel strategy. We aim to co-design and evaluate an intervention for primary care clinicians to promote engagement with an asthma online health community (OHC). Our protocol describes a 'survey leading to a trial' design as part of a mixed-methods, non-randomised feasibility study to test the feasibility and acceptability of the intervention. METHODS AND ANALYSIS: Adults on the asthma registers of six London general practices (~3000 patients) will be invited to an online survey, via text messages. The survey will collect data on attitudes towards seeking online peer support, asthma control, anxiety, depression, quality of life, information on the network of people providing support with asthma and demographics. Regression analyses of the survey data will identify correlates/predictors of attitudes/receptiveness towards online peer support. Patients with troublesome asthma, who (in the survey) expressed interest in online peer support, will be invited to receive the intervention, aiming to reach a recruitment target of 50 patients. Intervention will involve a one-off, face-to-face consultation with a practice clinician to introduce online peer support, sign patients up to an established asthma OHC, and encourage OHC engagement. Outcome measures will be collected at baseline and 3 months post intervention and analysed with primary care and OHC engagement data. Recruitment, intervention uptake, retention, collection of outcomes, and OHC engagement will be assessed. Interviews with clinicians and patients will explore experiences of the intervention. ETHICS AND DISSEMINATION: Ethical approval was obtained from a National Health Service Research Ethics Committee (reference: 22/NE/0182). Written consent will be obtained before intervention receipt and interview participation. Findings will be shared via dissemination to general practices, conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05829265.

Livin regulates prostate cancer cell invasion by impacting the NF-κB signaling pathway and the expression of FN and CXCR4.

Prostate cancer (PCa) has the second highest mortality rate of all tumor-related diseases for males in Western countries, and the incidence of PCa in China is increasing. Previous studies have proven that inhibitor of apoptosis proteins (IAPs) can regulate tumor cell invasion and metastasis. Livin is the most recently identified IAP. Our previous study showed that Livin might play an important role in the initiation of human PCa and that Livin-α might promote cell proliferation by regulating the G1-S cell cycle transition. However, whether Livin, as an IAP, can regulate the invasive ability of PCa cells remains unknown. In this study, we found that the expression of Livin was higher in metastatic PCa tissues than in nonmetastatic tissues and that the expression of Livin was downregulated/upregulated by small interfering RNA/vector, which could inhibit/promote PC-3/LNCaP cell invasion. This action was related to the impact of Livin on nuclear factor-κB (NF-κB) and its downstream signaling pathway, including FN and CXCR4. Together, our findings suggested that Livin might regulate tumor cell invasion in PCa directly, and that Livin might be an ideal candidate for preventing tumor cell invasion.

[Expressions of E-cadherin and alpha-catenin in benign, malignant and metastatic prostate tumors].

OBJECTIVE: To investigate the expressions of E-cadherin (E-cd) and alpha-catenin (alpha-cat) proteins in benign and malignant prostate tumors, and determine whether they could be used as molecular markers for the prognosis of prostate cancer (PCa). METHODS: We detected the expressions of E-cd and alpha-cat in the prostatic tissues from 45 cases of PCa and 10 cases of benign prostatic hyperplasia (BPH) by immunohistochemical Elivision staining, and analyzed the relationships of E-cd and alpha-cat expressions with the PCa stage, PCa grade, preoperative PSA, results of endocrine therapy and prognosis. RESULTS: The E-cd protein was abnormally expressed in 86.7% of the PCa and 10.0% of the PSA patients, and the E-cd expression was significantly lower in the former than in the latter (P < 0.05). The abnormal expressions of E-cd in the PCa patients with metastasis, non-metastasis, Gleason score < or = 7 and > 7 were 85.0, 87.5, 100.0 and 86.7%, respectively, with no significant between-group differences (P > 0.05), those in the PCa patients with PSA < or = 10 and > 10 microg/L were 40.0 and 97.1%, respectively, significantly higher in the former than in the latter (P < 0.05), and those in the PCa patients with and without response to endocrine therapy were 93.8 and 72.7%, respectively, with no significant differences between the two groups (P > 0.05). The alpha-cat protein was abnormally expressed in 93.3% of the PCa and 30.0% of the BPH patients, respectively, and the alpha-cat expression was significantly lower in the former than in the latter (P < 0.05). The abnormal alpha-cat expressions in the PCa patients with metastasis, non-metastasis, Gleason score > 7 and < or = 7 were 90.0, 100.0, 90.0 and 100.0%, respectively, with no significant between-group differences (P > 0.05), those in the PCa patients with PSA < or = 10 and > 10 microg/L were 40.0 and 94.3%, respectively, significantly higher in the former than in the latter (P < 0.05), and those in the PCa patients with and without response to endocrine therapy were 100.0 and 81.8%, respectively, with no significant differences between the two groups (P > 0.05). CONCLUSION: The expressions of E-cd and alpha-cat are significantly lower in PCa than in BPH, and they are not associated with cancerous metastasis, but negatively correlated with the PSA level in PCa patients.

Sustainable Production of Bioactive Molecules from C-Lignin-Derived Propenylcatechol.

Catechyl lignin (C-lignin) is a naturally occurring linear homogeneous biopolymer composed solely of caffeyl alcohol subunits with cleavable benzodioxane linkages. The inherent structural features of propenylcatechol, a direct depolymerized product of castor seed coats C-lignin, render it a sustainable and promising platform for the synthesis of bioactive molecules. Herein, diversified transformations of propenylcatechol, including C=C bond difunctionalization, ß-modification, ß,γ-rearrangement, and γ-methyl derivatization, were reported based on known or developed methods. A series of functional molecular skeletons involved in the current synthetic routes for the preparation of pharmaceuticals and bioactive molecules were obtained. Starting from castor seed coats, annuloline (natural product) and CC-5079 (antitumor) were synthesized using facile and inexpensive reagents in only four- and five-sequence reactions, respectively, thereby demonstrating a superior step-efficiency to that of reported synthetic routes. Almost all atoms in the C-lignin biopolymer were incorporated into the final products owing to the intrinsic structures of naturally occurring C-lignin. Bioactive molecules produced from C-lignin integrate a low-carbon footprint with high-quality and economical manufacture of pharmaceuticals.