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1.
JMIR Form Res ; 8: e51977, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38788211

RESUMO

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.

2.
Front Bioeng Biotechnol ; 12: 1373130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572363

RESUMO

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.

3.
Adv Sci (Weinh) ; : e2310202, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38493491

RESUMO

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.

4.
Lab Chip ; 24(6): 1702-1714, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38321884

RESUMO

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.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Microfluídica , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Células-Tronco Neoplásicas/metabolismo , Técnicas de Cultura de Células , Antineoplásicos/metabolismo , Proliferação de Células , Linhagem Celular Tumoral
5.
Oncol Rep ; 51(2)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38131234

RESUMO

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].

6.
BMJ Open ; 13(7): e073503, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37433727

RESUMO

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.


Assuntos
Asma , Qualidade de Vida , Humanos , Adulto , Estudos de Viabilidade , Medicina Estatal , Asma/terapia , Atenção Primária à Saúde
7.
Cancer Med ; 12(4): 3931-3951, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36779496

RESUMO

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.


Assuntos
Carcinoma de Células em Anel de Sinete , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Masculino , Pessoa de Meia-Idade , Variações do Número de Cópias de DNA , Biologia Molecular , Mutação , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
8.
Asian J Androl ; 25(3): 366-374, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35915542

RESUMO

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.


Assuntos
COVID-19 , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/induzido quimicamente , Antagonistas de Androgênios/efeitos adversos , Androgênios/uso terapêutico , SARS-CoV-2
9.
J Org Chem ; 87(19): 12844-12853, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36166737

RESUMO

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.


Assuntos
Compostos Alílicos , Paládio , Compostos Alílicos/química , Catálise , Organotiofosfatos , Oxindóis , Paládio/química , Estereoisomerismo
10.
Mol Oncol ; 16(20): 3666-3688, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36052737

RESUMO

The genetic features of primary lymphoepithelioma-like carcinoma (LELC) of the upper urinary tract have not been systematically explored. In this study, tumor mutation profiling was performed using whole-genome sequencing in two patients with LELC of the renal pelvis. Novel candidate variants relevant to known disease genes were selected using rare-variant burden analysis. Subsequently, a population-based study was performed using the Surveillance, Epidemiology, and End Results (SEER), PubMed, MEDLINE, Embase, and Scopus databases to explore clinical features and prognostic risk factors. Immunohistochemical analysis revealed seven positive cytokeratin-associated markers in tumor cells and five positive lymphocyte-associated markers in and around the tumor area. Sub-sequently, we identified KDM6A as the susceptibility gene and LEPR as the driver gene by Sanger sequencing in case 2 of LELC of the renal pelvis. Three mutation sites of the existing targeted drugs were screened: CA9, a therapeutic target for zonisamide; ARVCF, a therapeutic target for bupropion; and PLOD3, a therapeutic target for vitamin C. In a population-based study, patients with primary LELC of the upper urinary tract had clinical outcomes similar to those of patients with primary upper urinary tract urothelial carcinoma (UUT-UC) before and after propensity score matching at 1 : 5. Focal subtype was an independent prognostic factor for the overall survival of patients with LELC of the upper urinary tract. The carcinogenesis of primary LELC may be due to different genetic variations, including single-nucleotide variants, insertion and deletions, structural variations, and repeat regions, which may provide the basis for clinical diagnosis and treatment. The prognosis of LELC in the upper urinary tract is similar to that of UUT-UC. We suggest that the focal subtype can serve as a prognostic factor for LELC of the upper urinary tract; however, further studies are required to confirm this.


Assuntos
Carcinoma de Células Escamosas , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Zonisamida , Bupropiona , Pelve Renal , Histona Desmetilases , Queratinas , Ácido Ascórbico , Nucleotídeos
11.
ChemSusChem ; 15(14): e202200646, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35548878

RESUMO

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.


Assuntos
Álcoois , Lignina , Biopolímeros , Lignina/química , Preparações Farmacêuticas
12.
Ther Adv Urol ; 14: 17562872221079473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422880

RESUMO

Objectives: The purpose of this study is to determine the therapeutic value of surgery in individuals with urinary bladder signet ring cell carcinoma (SRCC). Surgery has not been examined as a prognostic factor for urinary bladder cancer (SRCC). Materials and Methods: Using the Surveillance, Epidemiology, and End Results program (SEER), patients with urinary bladder SRCC who presented from 1975 to 2018 were included in a retrospective study. The effect of surgical therapy on cause-specific survival (CSS) and overall survival (OS) was examined using univariate and multivariate Cox regression models. We subdivided 595 patients with SRCC into 2 groups, as follows: 496 who underwent surgery; and 99 who did not undergo surgery. Results: Males had high predominance in all cases in both groups (p = 0.04). Moderate and poor differentiation (III-IV) were observed in the majority of patients who underwent surgery (77.2 vs 58.6, p ⩽ 0.001) and had no insurance (p ⩽ 0.001). By using KM, the OS and CSS of the surgery group were found to be significantly better than those of the non-surgery group (p = 0.001,%) after adjusting for the variables of age, race, sex, primary site, grade, stage, lymph node removal, chemotherapy record, radiotherapy record, insurance, and marital status in the multivariate Cox proportional hazard model (hazard ratio [HR]= 0. 592; 95% confidence interval [CI] = 0.449-0.782; p = 0.0001). In comparison with chemotherapy and radiation, which resulted in poorer survival rates, surgery considerably improved survival outcomes in urinary bladder SRCC. The nomogram prediction model was built with C-index values of 0.70 and 73 for OS and CSS prediction, respectively. AUC in OS values were 0.77, 0.76, and 0.74, whereas AUC in CSS were 0.83, 0.80, and 0.79 for the 1-, 3-, and 5-year survival nomograms, respectively. Conclusion: Surgery was a significant independent predictor of bladder SRCC survival. Patients who underwent surgery had higher CSS and OS than people who did not undergo surgery. Surgery also led to better survival than the combination of the different treatment modalities.

13.
Front Cell Infect Microbiol ; 11: 723781, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869053

RESUMO

Urinary stones and urinary tract infection (UTI) are the most common diseases in urology and they are characterized by high incidence and high recurrence rate in China. Previous studies have shown that urinary stones are closely associated with gut or urine microbiota. Calcium oxalate stones are the most common type of urinary stones. However, the profile of urinary tract microorganisms of calcium oxalate stones with UTI is not clear. In this research, we firstly found two novel clusters in patients with calcium oxalate stones (OA) that were associated with the WBC/HP (white blood cells per high-power field) level in urine. Two clusters in the OA group (OA1 and OA2) were distinguished by the key microbiota Firmicutes and Enterobacteriaceae. We found that Enterobacteriaceae enriched in OA1 cluster was positively correlated with several infection-related pathways and negatively correlated with a few antibiotics-related pathways. Meantime, some probiotics with higher abundance in OA2 cluster such as Bifidobacterium were positively correlated with antibiotics-related pathways, and some common pathogens with higher abundance in OA2 cluster such as Enterococcus were positively correlated with infection-related pathways. Therefore, we speculated that as a sub-type of OA disease, OA1 was caused by Enterobacteriaceae and the lack of probiotics compared with OA2 cluster. Moreover, we also sequenced urine samples of healthy individuals (CK), patients with UTI (I), patients with uric acid stones (UA), and patients with infection stones (IS). We identified the differentially abundant taxa among all groups. We hope the findings will be helpful for clinical treatment and diagnosis of urinary stones.


Assuntos
Microbiota , Cálculos Urinários , Infecções Urinárias , Cálcio , Oxalato de Cálcio , DNA Ribossômico/genética , Humanos
14.
Front Oncol ; 11: 633462, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34350107

RESUMO

Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa (P=0.175). Stratified analyses of sex showed that aspirin intake did not lead to a lower risk of BCa in female patients (P=0.063). However, the male population who regularly took aspirin had a lower incidence of BCa (OR=0.748, 95% CI= 0.584-0.958, P=0.021). Subgroup analyses stratified by smoking found a significant reduction in the risk of BCa in current smokers with aspirin intake (OR=0.522, 95% CI=0.342-0.797, P=0.002). In terms of prognosis of BCa, patients with a history of aspirin intake did not had a markedly longer OS or RFS than those with no history of aspirin intake by Kaplan-Meier curves. Stratified analysis by sex showed no correlation between aspirin intake and the recurrence or survival of BCa for either male or female patients. However, in people younger than 68, aspirin intake seemed to have prolonged effects for overall survival (HR=3.876; 95% CI=1.326-11.325, P=0.019). Then, we performed a meta-analysis and the combined results from 19 articles and our study involving more than 39524 BCa cases indicated that aspirin intake was not associated with the occurrence of BCa (P=0.671). Subgroup analysis by whether regular use of aspirin, by the mean duration of use of aspirin, by sex, by smoking exposure, by research region and by study type also supported the above results. In terms of the impact of aspirin intake on the prognosis of patients with BCa, 11 articles and our study involving 8825 BCa cases were eligible. The combined results showed that patients with aspirin intake did not have significantly influence on survival, recurrence, progression and metastasis than those without aspirin intake. On the whole, both our retrospective study and literature meta-analysis suggested a lack of a strong relevant association between the use of aspirin and the incidence or prognosis of BCa. Thus, additional long-term follow-up prospective research is warranted to clarify the association of aspirin with BCa incidence and prognosis.

15.
PLoS One ; 16(6): e0252865, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34111167

RESUMO

Apple scab caused by Venturia inaequalis is a serious disease of cultivated apple worldwide. In this study, we collected 132 V. inaequalis isolates from Shaanxi, Gansu, Xinjiang, and the U.K. and analyzed their genetic diversity by using 13 microsatellite markers. Cluster analysis based on population structure and genetic distances suggested high similarity among the four regions. Population differentiation values ranged from 0.044 to 0.155, indicating there is a high level of kinship among the four regions. All isolates could be divided into 5 lineages with a 0.76 similarity coefficient. Among the four regions, Shaanxi had only one lineage, Group II; Gansu had four lineages, Group I, Group II, Group IV, and Group V; Xinjiang had all five lineages, Group I, Group II, Group III, Group IV, and Group V; and the U.K. had three lineages, Group I, Group II and Group IV. High molecular variance was detected for populations in the four regions, with 91% of the variance occurring within the populations and 9% among the populations. Structure analysis there are three common ancestors of these four regions. The results of the present study shed light on the genetic diversity of V. inaequalis in Shaanxi, Gansu and Xinjiang, which will lead to the development of more effective management strategies and new resistant apple cultivars through molecular marker-assisted selection.


Assuntos
Fungos do Gênero Venturia/genética , Malus/microbiologia , Repetições de Microssatélites , China , DNA Fúngico/genética , Fungos do Gênero Venturia/classificação , Marcadores Genéticos , Variação Genética , Filogenia , Filogeografia , Doenças das Plantas/microbiologia , Reino Unido
16.
Pharmacol Res ; 169: 105630, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33932609

RESUMO

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.


Assuntos
Dipeptidases/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Túbulos Renais Proximais/metabolismo , Adamantano/análogos & derivados , Adamantano/farmacologia , Animais , Western Blotting , Estudos de Casos e Controles , Linhagem Celular , Dipeptidases/antagonistas & inibidores , Dipeptídeos/farmacologia , Dipeptidil Peptidases e Tripeptidil Peptidases/antagonistas & inibidores , Transição Epitelial-Mesenquimal , Fibrose , Imunofluorescência , Humanos , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia
17.
Medicine (Baltimore) ; 100(20): e25745, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011033

RESUMO

ABSTRACT: To analyze the efficacy and safety between bipolar transurethral enucleation of the prostate (BipoLEP) and bipolar transurethral resection of the prostate (B-TURP).One hundred twenty eight patients with benign prostatic hyperplasia were recruited and divided into group 1 (BipoLEP group, n = 72) and group 2 (B-TURP group, n = 56). The study period was from October 2016 to February 2019. All data parameters were prospectively collected and analyzed.In these 2 groups, there were no significant differences of the mean ages (71.88 ±â€Š6.54 years vs 73.05 ±â€Š7.05 years, P = .407), prostate volumes (99.14 ±â€Š9.5 mL vs 95.08 ±â€Š10.93 mL, P = .302) and the mean operation times (93.7 ±â€Š27.5 minutes vs 89.8 ±â€Š22.4 minutes, P = .065). In BipoLEP group, it had more prostate tissue resected (64.2 ±â€Š22.1 g vs 52.7 ±â€Š28.6 g, P = .018), less duration of continuous bladder irrigation (20.7 ±â€Š6.5 hours vs 29.6 ±â€Š8.3 hours, P = .044), shorter catheterization time (4.3 ±â€Š1.5 days vs 5.6 ±â€Š2.1 days, P = .032), shorter hospitalization stay (5.2 ±â€Š1.4 days vs 6.5 ±â€Š1.9 days, P = .031) and less complications (3 cases vs 9 cases, P = .021). There were significant improvements in 3-month postoperative parameters, including: post void residual urine, maximum flow rate, International Prostatic Symptoms Scale, and quality of life in each group (p < 0.01). However, there were no significant differences of preoperative and 3-month postoperative parameters, including: post void residual urine, maximum flow rate, International Prostatic Symptoms Scale, and quality of life between these 2 groups (P > .05).BipoLEP can produce a more radical prostatic resection with better safety profile and faster postoperative recovery. It may become a more favorable surgical alternative to the B-TURP, especially for the prostate larger than 80 g.


Assuntos
Complicações Pós-Operatórias/epidemiologia , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Retenção Urinária/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Cateterismo/estatística & dados numéricos , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Próstata/cirurgia , Qualidade de Vida , Irrigação Terapêutica/estatística & dados numéricos , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do Tratamento , Retenção Urinária/diagnóstico , Retenção Urinária/etiologia , Retenção Urinária/prevenção & controle , Urodinâmica
18.
Medicine (Baltimore) ; 100(7): e24799, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607841

RESUMO

BACKGROUND: The combination of Traditional Chinese medicine and Western medicine (TCM+WM) has been widely used in the treatment of glomerulosclerosis, but the results are still controversial. This study will assess the clinical efficacy of TCM+WM for glomerulosclerosis and provide evidence-based medical data via meta-analysis. METHOD: The MEDLINE, EMBASE, PubMed, Cochrane Central Registry of Controlled Trials, and multiple Chinese databases (Wan Fang, CNKI, and VIP) were searched for randomized controlled trials (RCT) that compared the effects of WM and TCM+WM. Review Manager 5.3 software was used for the meta-analysis of selected studies, and appropriate tests were performed to determine the quality, heterogeneity and sensitivity of these studies. RESULTS: Sixteen RCTs met the inclusion criteria and were selected for the analysis. Compared with the placebo or WM-treated glomerulosclerosis patients, TCM+WM intervention significantly improved renal function indices including 24-hour urine protein quantity (24 h U-Pro), serum creatinine (Scr), blood urea nitrogen (BUN), creatinine clearance (Ccr). In addition, the serum albumin (ALB), triglyceride (TG), and cholesterol (CHOL) levels were also significantly improved (P < .05) in patients receiving the combination therapy. Finally, the combination of TCM+WM reduced the indices of glomerulosclerosis more effectively compared with WM alone. CONCLUSION: The combination of TCM+WM can significantly improve the renal function and prognosis of patients with glomerulosclerosis.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Terapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
BJU Int ; 126(1): 168-176, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32279423

RESUMO

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.


Assuntos
Cálculos Renais/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nefrolitotomia Percutânea/métodos , Pontuação de Propensão , Feminino , Seguimentos , Humanos , Cálculos Renais/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia
20.
Int J Oncol ; 56(1): 178-192, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789394

RESUMO

Accumulating evidence has demonstrated that microRNAs are associated with malignant biological behaviour, including tumorigenesis, cancer progression and metastasis via the regulation of target gene expression. Our previous study demonstrated that programmed cell death protein 4 (PDCD4), which is a tumour suppressor gene, is a target of microRNA­21 (miR­21), which affects the proliferation and transformation capabilities of renal cell carcinoma (RCC) cells. However, the role of miR­21 in the molecular mechanism underlying the migration, invasion and angiogenesis of RCC remains poorly understood. The effects of miR­21 on the invasion, migration and angiogenesis of RCC cells was determined through meta­analysis and regulation of miR­21 expression in vitro. After searching several databases, 6 articles including a total of 473 patients met the eligibility criteria for this analysis. The combined results of the meta­analysis revealed that increased miR­21 expression was significantly associated with adverse prognosis in patients with RCC, with a pooled hazard ratio estimate of 1.740. In in vitro experiments, we demonstrated that a miR­21 inhibitor decreased the number of migrating and invading A498 and 786­O RCC cells, along with a decrease in PDCD4, c­Jun, matrix metalloproteinase (MMP)2 and MMP9 expression. Additionally, inhibition of miR­21 was revealed to reduce tube formation and tube junctions in the endothelial cell line HMEC­1 by affecting the expression of angiotensin­1 and vascular endothelial growth factor A, whereas PDCD4 small interfering RNA exerted opposite effects on the same cells. Overall, these findings, along with evidence­based molecular biology, demonstrated that miR­21 expression promoted the migration, invasion and angiogenic abilities of RCC cells by directly targeting the PDCD4/c­Jun signalling pathway. The results may help elucidate the molecular mechanism underlying the development and progression of RCC and provide a promising target for microRNA­based therapy.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/patologia , MicroRNAs/genética , Neovascularização Patológica/patologia , Proteínas de Ligação a RNA/metabolismo , Fator de Transcrição AP-1/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Proliferação de Células , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Prognóstico , Proteínas de Ligação a RNA/genética , Fator de Transcrição AP-1/genética , Células Tumorais Cultivadas
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