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1.
Medicine (Baltimore) ; 103(18): e37524, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701298

RESUMO

PURPOSE: There is still controversy regarding the safety and efficacy of cold knife visual internal urethrotomy and laser incisions for the treatment of urethral stricture. This study aims to compare the results of postoperative long-term and short-term maximum urinary flow rates (Qmax), surgical time, postoperative complications, and 1-year recurrence rates between the cold knife and laser surgery. METHODS: We searched databases including Embase, PubMed, Cochrane, and Clinical Trials.gov to identify relevant literature published in English up to September 2023. We used Stata to compare various parameters. This study is registered in PROSPERO (CRD42023471634). Nine comparative experiments were conducted, involving a total of 659 participants. RESULTS: The laser group showed significantly better results compared to the cold knife group in terms of postoperative 12-month maximum urinary flow rate (mean differences [MD] 2.131; 95% [1.015, 3.249], P < .0001), postoperative bleeding (RR 0.277, 95% [0.079, 0.977], P = .046), and 1-year recurrence rate (RR 0.667, 95% [0.456, 0.976], P = .037). However, there were no significant differences in postoperative 6-month and 3-month Qmax, surgical time, urethral leakage complications, overall complications, and Visual Analog Scale (VAS) scores. CONCLUSION: The current study results suggest that laser urethral incision has greater advantages in the long-term (12 months), 1-year recurrence rate, and bleeding complications compared to cold knife urethral incision in the treatment of urethral stricture (<2 cm). Therefore, laser urethral incision may be a better choice for patients with urethral stricture.


Assuntos
Terapia a Laser , Uretra , Estreitamento Uretral , Estreitamento Uretral/cirurgia , Humanos , Terapia a Laser/métodos , Terapia a Laser/efeitos adversos , Uretra/cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Masculino , Recidiva , Duração da Cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
2.
Phytomedicine ; 129: 155598, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38608596

RESUMO

BACKGROUND: Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. OBJECTIVE: Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. METHODS: Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. RESULTS: Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. CONCLUSION: The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.

3.
J Agric Food Chem ; 72(13): 7291-7298, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38507714

RESUMO

Bacillus thuringiensis (Bt) is widely used to produce biological pesticides. However, its persistence is limited because of ultraviolet (UV) rays. In our previous study, we found that exogenous intermediates of the urea cycle were beneficial to Bt for survival under UV stress. To further explore the effect of the urea cycle on the resistance mechanism of Bt, the rocF/argG gene, encoding arginase and argininosuccinate synthase, respectively, were knocked out and recovered in this study. After the target genes were removed, respectively, the urea cycle in the tested Bt was inhibited to varying degrees. The UV stress test showed that the urea cycle disorder could reduce the resistance of Bt under UV stress. Meanwhile, the antioxidant enzyme activities of Bt were also decreased to varying degrees due to the knockout of the target genes. All of these results revealed that the urea cycle can metabolically regulate the stress resistance of Bt.


Assuntos
Bacillus thuringiensis , Bacillus thuringiensis/genética , Ureia , Proteínas de Bactérias/genética , Proteínas de Bactérias/farmacologia , Endotoxinas/farmacologia
4.
J Food Sci ; 89(3): 1485-1497, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38317483

RESUMO

To recognize the key ester-related volatile compounds, 5 types of peaches including 54 late-ripening peach materials were examined by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry and E-nose. Here, a large number of esters were identified to be released by ripe peach fruits and were mainly characterized by fruity, green, and fatty notes. The variety and content of esters had greatly changed within or between cultivars, indicating that the fruit volatiles were highly differentiated depending on the specific genotypes and cultivation conditions. The ester types showed that fatty acid-derived C6 alcohols and methyl-/ethyl- short-chain alcohol were the main ester precursors, which were more likely to be utilized and well selected by alcohol acyltransferases, whereas the preference of acyl donors was not observed. The common peach type, which exhibited a unique volatile profile, displayed broader diversity and more abundant characteristics in ester-related volatiles than the other four types. A total of 19 key esters were identified as the main components and the content of most esters showed no significant difference among different peach types. Some key esters had even been enriched in nectarines. Moreover, the multiple discriminant analysis revealed a possible relationship between peach types and the domestication of the peach evolution. This study investigated ester-related volatiles released by different types of peach fruits and can be further used to evaluate the peach qualities, providing an important reference for peach breeding and processing.


Assuntos
Prunus persica , Compostos Orgânicos Voláteis , Ésteres/análise , Compostos Orgânicos Voláteis/análise , Melhoramento Vegetal , Frutas/química , Álcoois Graxos/análise , Etanol/análise
5.
BMC Cancer ; 24(1): 261, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402385

RESUMO

BACKGROUND: Increasing evidence indicates that gut microbiota are closely related to prostate cancer. This study aims to assess the gut microbiota composition in patients with prostate cancer compared to healthy participants, thereby advancing understanding of gut microbiota's role in prostate cancer. METHODS: A systematic search was conducted across PubMed, Web of Science, and Embase databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS), and pertinent data were analyzed. The kappa score assessed interrater agreement. RESULTS: This study encompassed seven research papers, involving 250 prostate cancer patients and 192 controls. The kappa was 0.93. Meta-analysis results showed that alpha-diversity of gut microbiota in prostate cancer patients was significantly lower than in the control group. In terms of gut microbiota abundance, the ratio of Proteobacteria, Bacteroidia, Clostridia, Bacteroidales, Clostridiales, Prevotellaceae, Lachnospiraceae, Prevotella, Escherichia-Shigella, Faecalibacterium, and Bacteroides was higher in prostate cancer patients. Conversely, the abundance ratio of Actinobacteria, Bacteroidetes, Firmicutes, Selenomonadales, Veillonella, and Megasphaera was higher in the control group. CONCLUSION: Our study reveals differences in alpha-diversity and abundance of gut microbiota between patients with prostate cancer and controls, indicating gut microbiota dysbiosis in those with prostate cancer. However, given the limited quality and quantity of selected studies, further research is necessary to validate these findings.


Assuntos
Microbioma Gastrointestinal , Neoplasias da Próstata , Masculino , Humanos , Bactérias , Disbiose/microbiologia
6.
Front Pharmacol ; 14: 1290990, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074136

RESUMO

Background: Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment selection challenges due to limited therapeutic options. This study aimed to comprehensively assess the efficacy of multiple treatment regimens for mCRPC through a network meta-analysis (NMA) of randomized controlled trials (RCTs). Methods: A systematically comprehensive search for randomized controlled trials (RCTs) was performed in Pubmed, Cochrane Library, Embase, and Web of Science databases. The network meta-analysis was employed to compare the overall survival (OS), progression-free survival (PFS), and radiographic progression-free survival (rPFS) among different interventions at specific time points. This study was prospectively registered with PROSPERO (CRD42023422823). Results: A total of 29 RCTs, involving 12,706 patients and investigating 16 interventions, were included in the analysis. Chempretarget ((capivasertib or cabozantinib) + docetaxel + prednisone)) and PARP (Olaparib or rucaparib) inhibitors emerged as interventions that significantly improved survival outcomes compared to first-line treatment in mCRPC patients. Chempretarget demonstrated superior overall survival starting from the 12th month, while PARP inhibitors showed a clear advantage in progression-free survival within the 3-18 months range. Notably, chempre ((Docetaxel or Cabazitaxel) + prednisone) exhibited favorable performance in radiographic progression-free survival during the 3-18 month period. Conclusion: Our findings underscore the efficacy of chempretarget, PARP inhibitors, and chempre in enhancing survival outcomes for mCRPC patients. Further head-to-head comparisons are warranted to validate these results. These findings carry important implications for treatment decision-making in mCRPC and may guide the development of more effective therapeutic strategies.

7.
Front Microbiol ; 14: 1308412, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075860

RESUMO

Introduction: Licorice (Glycyrrhiza uralensis Fisch.) is a widely recognized significant form of medicine in China, with a long-standing history and extensive usage. It is considered the oldest and most prevalent herbal medicine in China. Currently, the licorice market is confronted with the primary challenges of mixed genotypes, inconsistent quality, and inadequate glycyrrhizic acid content. Methods: We conducted field experiments to investigate the impact of various cultivation locations on the growth characteristics, active ingredients, rhizospheric soil physicochemical properties and fungal communities of licorice that ten different genotypes. Results: The findings indicated significant variations in these parameters across ten different genotypes of licorice originating from two distinct production regions. The growth characteristics of licorice were primarily influenced by genotype, whereas the active ingredients of licorice were mainly influenced by environmental factors and soil physicochemical properties. Furthermore, the rhizospheric soil physicochemical properties of licorice plants were more influenced by environmental factors than genotypes. Additionally, the distribution of rhizospheric soil fungi in licorice plants of the same genotype exhibited significant variations across different cultivation areas. The utilization of structural equation model synthesis reveals variations in the quantity and strength of pathways that influence the growth characteristics, active ingredients, and rhizospheric soil microbial community of licorice across different cultivation regions. Discussion: Based on the main results, according to its growth characteristics and active ingredients, Z009 proved to be the most suitable genotype for cultivation in Jingtai. From a perspective centered on the active ingredient, Z010 proved to be the most optimal genotype for licorice cultivation in both production areas. Our study aims to enhance the understanding of the ecological adaptability of various genotypes of licorice resources and to identify appropriate licorice genotypes for specific cultivation regions. This research holds significant practical implications for enhancing the yield and quality of licorice, thereby improving its overall development.

8.
Front Immunol ; 14: 1280007, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143760

RESUMO

Background: Anaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment. Case presentation: The adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023. Conclusion: Taken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment. Trial registration number: NCT04767308.


Assuntos
Linfoma Anaplásico de Células Grandes , Receptores de Antígenos Quiméricos , Adolescente , Humanos , Diagnóstico Diferencial , Linfoma Anaplásico de Células Grandes/terapia , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores Proteína Tirosina Quinases/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/uso terapêutico , Linfócitos T/patologia
9.
J Immunother Cancer ; 11(11)2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38016717

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is an advanced and effective immunotherapy for relapsed or refractory B-cell malignancies. High expansion of CAR T cells in vivo and durable antitumor activity indicate a persistent therapeutic response. However, this treatment is linked to a high frequency of adverse events, such as cytokine release syndrome (CRS), which affects its efficacy and can even be life-threatening. At present, a variety of markers associated with clinical response and treatment toxicity after CAR T cells infusion have been reported. Although these biomarkers can act as effective indicators reflecting CAR T cells expansion as well as CRS, they fail to predict the expansion rate of CAR T cells. Hence, further investigation is urgent to find a new biomarker to fill this void. METHODS: We analyzed the association between the absolute neutrophil count (ANC) and CAR expansion and CRS in 45 patients with B-cell malignancies from two clinical trials. We proposed that ANC could be a practical biomarker for CAR T cells expansion and CRS, and conducted a feasibility analysis on its predictive ability. RESULTS: In this study, 17 B-cell hematological malignancy patients with anti-B-cell maturation antigen CAR-treated and 28 with CAR19/22 T-cell-treated were enrolled and divided into an ANC-absence group and an ANC-presence group. The results showed that ANC absence correlated positively with CAR expansion and the expansion rate. The ANC can be used as a predictive marker for CAR T cells expansion. Moreover, the patients with ANC absence experienced a more severe CRS, and ANC performed a predictive ability for CRS. In addition, the peak serum concentration of several cytokines involved in CRS was higher in patients with ANC absence. CONCLUSION: Thus, we suggest ANC as an evaluative and predictive biomarker for CAR expansion and CRS during CAR T cell therapy, which can help to maximize clinical efficacy, reduce treatment-related toxicity and prolong survival.


Assuntos
Neoplasias , Receptores de Antígenos de Linfócitos T , Humanos , Receptores de Antígenos de Linfócitos T/genética , Síndrome da Liberação de Citocina , Neutrófilos , Linfócitos T , Biomarcadores
10.
BMC Urol ; 23(1): 171, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875837

RESUMO

BACKGROUND: The advantages and disadvantages of retrograde intrarenal surgery (RIRS) and minimally invasive percutaneous nephrolithotomy (mPCNL) for treatment of upper urinary tract calculi have not been conclusively determined. METHODS: In this meta-analysis, We comprehensively evaluated the performance of the two surgical approaches in treatment of upper urinary calculi. We searched the Pubmed, Embase, Cochrane and Web of science databases for randomized controlled trial (RCT) articles on RIRS and mPCNL upto December 2022. Data were extracted by two independent reviewers and subjected to the meta-analysis using the Stata 15.1 software (StataSE, USA). RESULTS: A total of 18 eligible RCTs involving 1733 patients were included in this study. The meta-analysis revealed that mPCNL of 1-2 cm or 2-3 cm stones had a higher stone clearance rate (RR:1.08, 95%CI (1.03, 1.14), p = 0.002) and shorter operation time (WMD : -10.85 min, 95%CI (-16.76, -4.94), p<0.001). However, it was associated with more hospital stay time (WMD :1.01 day, 95%CI(0.53, 1.5), p<0.001), hemoglobin drops (WMD :0.27 g/dl, 95%CI (0.14, 0.41), p<0.001), blood transfusion rate (RR:5.04, 95%CI(1.62, 15.65), p = 0.005), pain visual analogue score (WMD:0.75, 95%CI (0.04, 1.46), p = 0.037), hospital costs (SMD :-0.97, 95%CI (-1.19, -0.76), p<0.001) and major complications (RR:1.89, 95%CI(1.01, 3.53), p = 0.045). CONCLUSION: Therefore, in terms of surgical effects and operation time, mPCNL is superior to RIRS, but is inferior with regards to other perioperative parameters. These factors should be fully considered in clinical decision making.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Cálculos Urinários , Sistema Urinário , Humanos , Nefrolitotomia Percutânea/efeitos adversos , Cálculos Renais/cirurgia , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Cálculos Urinários/cirurgia
11.
Front Oncol ; 13: 1233125, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37817773

RESUMO

Background: Panurothelial carcinoma is a rare and aggressive malignancy that requires effective treatment strategies to enhance patient outcomes. Methods: We conducted a systematic search of English publications in databases including PubMed, Embase, Cochrane Library, and Web of Science up to May 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale (NOS) and the Methodological Quality and Synthesis of Case Series and Case Reports tool. Data statistics and analysis were performed using Stata 15.1 software (StataSE, USA). Results: Six studies involving 339 patients were included in the analysis. Meta-analysis revealed that Simultaneous Radical Cystectomy and Nephroureterectomy had 2-year and 5-year overall survival rates of 68% (95% CI 60%-76%, I2 = 12.4%, P < 0.001) and 44% (95% CI 36%-53%, I2 = 0, P < 0.001), respectively. The 2-year and 5-year progression-free survival rates were 91% (95% CI 86%-95%, I2 = 95%, P < 0.001) and 65% (95% CI 58%-73%, I2 = 91.5%, P < 0.001), respectively. The 2-year and 5-year cancer-specific survival rates were 73% (95% CI 66%-81%, I2 = 16.7%, P < 0.001) and 57% (95% CI 49%-66%, I2 = 0, P < 0.001), respectively. Additionally, the incidence of minor complications was 19% (95% CI 15%-23%, P < 0.01), major complications was 49% (95% CI 34%-63%, P < 0.01), and the intraoperative blood transfusion rate was 53% (95% CI 44%-61%, P < 0.01). Conclusions: Simultaneous radical cystectomy and nephroureterectomy represent feasible approaches for the treatment of Panurothelial carcinoma. Nonetheless, a comprehensive assessment of the surgical risks and benefits is imperative, and larger-scale prospective cohort studies are required to validate therapeutic efficacy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023426401.

12.
J Robot Surg ; 17(6): 2633-2646, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37731152

RESUMO

To compare perioperative outcomes between Holmium laser enucleation of the prostate (HoLEP) and robotic-assisted simple pasta-ectomy (RASP)for large-volume benign prostatic hyperplasia(> 80 ml). In August 2023, we undertook a comprehensive search of major global databases including PubMed, Embase, and Google Scholar, focusing solely on articles written in English. Studies that were merely reviews or protocols without any specific published data were omitted. Furthermore, articles that comprised conference abstracts or content not pertinent to our subject of study were also disregarded. To calculate the inverse variances and 95% confidence intervals (CIs) for categorical variables' mean differences, we employed the Cochran-Mantel-Haenszel approach along with random-effects models. The findings were denoted in the form of odds ratios (ORs) and 95% CIs. A p-value less than 0.05 was deemed to indicate statistical significance. Our finalized meta-analysis incorporated six articles, including one randomized controlled trial (RCT) and five cohort studies. These studies accounted for a total of 1218 patients, 944 of whom underwent Holmium Laser Enucleation of the Prostate (HoLEP) and 274 who underwent Robotic-Assisted Simple Prostatectomy (RASP). The pooled analysis from these six papers demonstrated that compared to RASP, HoLEP had a shorter hospital stay, shorter catheterization duration, and a lower blood transfusion rate. Moreover, HoLEP patients exhibited a smaller reduction in postoperative hemoglobin levels. Statistically, there were no significant differences between the two procedures regarding operative time, postoperative PSA, the weight of prostate specimens, IPSS, Qmax, PVR, QoL, and postoperative complications. (HoLEP) and (RASP) are both effective and safe procedures for treating large-volume benign prostatic hyperplasia. HoLEP, with its benefits of shorter catheterization and hospitalization duration, lesser decline in postoperative hemoglobin, and reduced blood transfusion needs, stands as a preferred choice for treating extensive prostate enlargement. However, further validation through more high-quality clinical randomized trials is required.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Procedimentos Cirúrgicos Robóticos , Ressecção Transuretral da Próstata , Humanos , Masculino , Hemoglobinas , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Lasers de Estado Sólido/efeitos adversos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Túlio/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Resultado do Tratamento
13.
Steroids ; 199: 109290, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37549776

RESUMO

In this study, we synthesized androsta-4,14-diene-3,16-dione, 12ß-hydroxyandrosta-4,14-diene-3,16-dione, and other 3,16-androstenedione derivatives from commercially available dehydroepiandrosterone as a starting material in 9-13 steps with high yields. The bioactivity of the obtained compounds was evaluated. Compounds 14a and 23a were shown to have high antitumor activity against acute lymphoblastic leukemia cell lines Nalm-6 and BALL-1, respectively. Network pharmacology analysis showed that the anti-leukemia activity of compounds 14a and 23a might be related to the JAK2, ABL1 protein, and PI3K/Akt signaling pathways. The molecular docking of compounds 14a and 23a identified possible active sites, with the lowest docking scores for PTGS2 and MAPK14, respectively. In addition, the absorption, distribution, metabolism, and excretion prediction results revealed the drug-likeness of the two compounds. Therefore, compounds 14a and 23a should be considered anti-leukemia candidates in future studies.


Assuntos
Androstenodiona , Fosfatidilinositol 3-Quinases , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais
14.
J Neuroinflammation ; 20(1): 178, 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516843

RESUMO

BACKGROUND: Brain microglia and macrophages (Mi/MΦ) can shift to a harmful or advantageous phenotype following an ischemic stroke. Identification of key molecules that regulate the transformation of resting Mi/MΦ could aid in the development of innovative therapies for ischemic stroke. The transcription factor signal transducer and activator of transduction 1 (STAT1) has been found to contribute to acute neuronal death (in the first 24 h) following ischemic stroke, but its effects on Mi/MΦ and influence on long-term stroke outcomes have yet to be determined. METHODS: We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1 driven by Cx3cr1CreER. Expression of STAT1 was examined in the brain by flow cytometry and RNA sequencing after ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The impact of STAT1 mKO on neuronal cell death, Mi/MΦ phenotype, and brain inflammation profiles were examined 3-5 days after MCAO. Neurological deficits and the integrity of gray and white matter were assessed for 5 weeks after MCAO by various neurobehavioral tests and immunohistochemistry. RESULTS: STAT1 was activated in Mi/MΦ at the subacute stage (3 days) after MCAO. Selective deletion of STAT1 in Mi/MΦ did not alter neuronal cell death or infarct size at 24 h after MCAO, but attenuated Mi/MΦ release of high mobility group box 1 and increased arginase 1-producing Mi/MΦ 3d after MCAO, suggesting boosted inflammation-resolving responses of Mi/MΦ. As a result, STAT1 mKO mice had mitigated brain inflammation at the subacute stage after MCAO and less white matter injury in the long term. Importantly, STAT1 mKO was sufficient to improve functional recovery for at least 5 weeks after MCAO in both male and female mice. CONCLUSIONS: Mi/MΦ-targeted STAT1 KO does not provide immediate neuroprotection but augments inflammation-resolving actions of Mi/MΦ, thereby facilitating long-term functional recovery after stroke. STAT1 is, therefore, a promising therapeutic target to harness beneficial Mi/MΦ responses and improve long-term outcomes after ischemic stroke.


Assuntos
Encefalite , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Feminino , Masculino , Camundongos , Inflamação , Macrófagos , Microglia
15.
Clin Genitourin Cancer ; 21(5): 594-601.e2, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37482524

RESUMO

BACKGROUND: The potential cardiovascular adverse events associated with new-generation androgen receptor pathway inhibitors (ARPI) in the treatment of prostate cancer remain unclear. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to new-generation ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We analyzed reports of cardiovascular adverse events associated with drug therapy for prostate cancer submitted to FAERS between January 2014 and December 2022. Three primary new-generation ARPIs were identified: abiraterone acetate, enzalutamide, and apalutamide. Our primary composite endpoint was the PV of MACE caused by ARPIs in the treatment of prostate cancer, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. RESULTS: A total of 278,031 suspected drug-adverse event pairs related to drug treatment in patients with prostate cancer were identified, of which 10,861 reports were cardiovascular events, including 5800 reports of MACE and 5061 reports of other cardiovascular events. The majority of these cardiovascular adverse event reports came from the United States (36.6%) and were mostly older men (age 76.0 ± 8.6 years). Compared with enzalutamide, the constituent ratio of MACE caused by abiraterone acetate and apalutamide was significantly increased, but the incidence of severe MACE decreased significantly. The PV signal regarding MACE was detected in abiraterone acetate and apalutamide but not in enzalutamide. CONCLUSION: Abiraterone acetate and apalutamide presumably are associated with a higher risk of MACE than enzalutamide in new-generation ARPI for prostate cancer. More extensive prospective studies and more extended follow-up periods need to confirm this further.

16.
Front Oncol ; 13: 1202587, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37434978

RESUMO

Objectives: The perioperative, functional, and oncological outcomes of patients with solitary small renal tumors (SRMs) treated with ablation (AT) or partial nephrectomy (PN) remain controversial. The aim of this study was to compare the outcomes of these two surgical techniques. Methods: In April 2023, we conducted a literature search in several widely used databases worldwide, including PubMed, Embase, and Google Scholar. Review Manager was used to compare various parameters. The study was registered with PROSPERO (CRD42022377157). Results: Our final meta-analysis included 13 cohort studies with a total of 2,107 patients. Compared to partial nephrectomy (PN), ablation (AT) had shorter hospital stays (WMD -2.37 days, 95% CI -3.05 to -1.69; p < 0.00001), shorter operating times (WMD -57.06 min, 95% CI -88.92 to -25.19; p = 0.0004), less postoperative creatinine increases (WMD -0.17 mg/dL, 95% CI -0.29 to -0.05; p = 0.006), less postoperative glomerular filtration rate decreases (WMD -9.84 mL/min/1.73 m2, 95% CI -14.25 to -5.44; p < 0.0001), less postoperative new-onset chronic kidney disease (OR 0.33, 95% CI 0.16 to 0.71; p = 0.005), and less intraoperative blood loss (WMD -285.92 ml, 95% CI -428.44 to -143.40; p < 0.0001). The transfusion rate was lower in the ablation group (OR 0.17, 95% CI 0.06 to 0.51; p = 0.001). The risk of local recurrence was higher in the ablation group (OR 2.96, 95% CI 1.27 to 6.89; p = 0.01), while the risk of distant metastasis was higher in the partial nephrectomy group (OR 2.81, 95% CI 1.28 to 6.18; p = 0.01). The intraoperative and postoperative complication rates were lower in the ablation group (OR 0.23, 95% CI 0.08 to 0.62; p = 0.004 and OR 0.21, 95% CI 0.11 to 0.38; p < 0.00001, respectively). However, overall survival, postoperative dialysis rate, and tumor-specific survival were not different between the two groups. Conclusions: Our data suggest that ablation and partial nephrectomy are equally safe and effective in the treatment of small solitary kidney tumors and are better options for patients with poor preoperative physical condition or poor renal function.

17.
BMC Urol ; 23(1): 113, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420203

RESUMO

OBJECTIVES: Comparing stone-free rates and associated outcome measures between two surgical modalities of lithotripsy fragmentation and removal or spontaneous passage of dust during retrograde intrarenal surgery (RIRS). METHODS: In March 2023, we conducted a literature search in several widely used databases worldwide, including PubMed, Embase, and Google Scholar. We only considered English articles and excluded pediatric patients. Reviews and protocols without any published data were excluded. We also excluded articles with conference abstracts and irrelevant content. We used the Cochran-Mantel-Haenszel method and random-effects models to assess inverse variances and 95% confidence intervals (CIs) for mean differences in categorical variables. The results were reported as odds ratios (ORs) and 95% CIs. Statistical significance was set at p < 0.05. RESULTS: Our final meta-analysis included nine articles, comprising two randomized controlled trials (RCTs) and seven cohort studies. The total number of patients included in these studies was 1326, and all studies used holmium laser lithotripsy. The pooled analysis of the dust and fragmentation groups showed that the fragmentation group had a higher stone-free rate (OR 0.6; 95% CI 0.41 - 0.89; p = 0.01); the dust group had a shorter operative time (WMD - 11.6 min; 95% CI - 19.56 - -3.63; p = 0.004); and the dust group had a higher retreatment rate (OR 2.03; 95% CI 1.31 - 3.13; p = 0.001). There was no statistically significant difference between the two groups in terms of length of hospital stay, overall complications, or postoperative fever. CONCLUSIONS: Our results showed that both procedures could be safely and effectively used for upper ureteral and renal calculi lithotripsy, the dust group had potential advantages over the fragmentation group in terms of the operation time, and the fragmentation group had certain advantages in terms of stone-free rate and retreatment rate.


Assuntos
Cálculos Renais , Litotripsia a Laser , Litotripsia , Nefrolitotomia Percutânea , Humanos , Cálculos Renais/cirurgia , Rim/cirurgia , Resultado do Tratamento
18.
Front Oncol ; 13: 1161544, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091146

RESUMO

Background: The nerve-sparing (NS) effect of robot-assisted radical prostatectomy (RARP) on patients with a high-risk prostate cancer remains unclear. The objective of this study was to compare the urinary continence, erectile function and oncology outcomes of the nerve-sparing and non-nerve-sparing (NNS) group during RARP surgeries. Methods: We systematically searched databases including PubMed, Embase, Cochrane Library and Web of Science to identify relevant studies published in English up to December 2022. Newcastle-Ottawa Scale (NOS) was used as a quality evaluation tool to evaluate the quality of the literature parameters involved, including urinary continence, erectile function and oncologic outcomes, which were compared using the Stata 15.1 software (StataSE, USA). Results: A total of 8 cohort studies involving 2499 patients were included. A meta-analysis of results showed that the NS group was beneficial to the recovery of urinary continence (RR 0.46, 95%CI 0.22, 0.96; p=0.045<0.05) and erectile function (RR 0.32, 95%CI 0.16, 0.63; p=0.001<0.05) 12 months after surgeries, which showed a better oncological outcome (RR 1.31, 95%CI 1.01, 1.69; p=0.01<0.05). Conclusions: The current study results indicate that intraoperative NS during RARP is beneficial to long-term postoperative functional recovery and tumor prognosis of patients with high-risk prostate cancers. Due to interstudy interferences, the results should be interpreted with caution. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022384647.

19.
Front Oncol ; 13: 1092734, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36874080

RESUMO

Background: The effect of perioperative blood transfusion (PBT) on postoperative survival in RCC patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) remains controversial. Two meta-analyses in 2018 and 2019 reported the postoperative mortality of PBT patients with RCC, but they did not investigate the effect on the survival of patients. We performed a systematic review and meta-analysis of relevant literature to demonstrate whether PBT affected postoperative survival in RCC patients who received nephrectomy. Methods: Pubmed, Web of Science, Cochrane, and Embase databases were searched. Studies comparing RCC patients with or without PBT following either RN or PN were included in this analysis. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included literature, and hazard ratios (HRs) of overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), as well as 95% confidence intervals, were considered as effect sizes. All data were processed using Stata 15.1. Results: Ten retrospective studies involving 19,240 patients were included in this analysis, with the publication dates ranging from 2014 to 2022. Evidence revealed that PBT was significantly associated with the decline of OS (HR, 2.62; 95%CI: 1,98-3.46), RFS (HR, 2.55; 95%CI: 1.74-3.75), and CSS (HR, 3.15; 95%CI: 2.3-4.31) values. There was high heterogeneity among the study results due to the retrospective nature and the low quality of the included studies. Subgroup analysis findings suggested that the heterogeneity of this study might be caused by different tumor stages in the included articles. Evidence implied that PBT had no significant influence on RFS and CSS with or without robotic assistance, but it was still linked to worse OS (combined HR; 2.54 95% CI: 1.18, 5.47). Furthermore, the subgroup analysis with intraoperative blood loss lower than 800 ML revealed that PBT had no substantial impact on OS and CSS of postoperative RCC patients, whereas it was correlated with poor RFS (1.42, 95% CI: 1.02-1.97). Conclusions: RCC patients undergoing PBT after nephrectomy had poorer survival. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363106.

20.
Nutrients ; 15(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36986059

RESUMO

Fuzhuan brick tea (FBT), a distinctive Chinese dark tea with the predominant fungus of Eurotium cristatum, offered significant health benefits to Chinese people. In the current study, the in vivo bioactivities of E. cristatum (SXHBTBU1934) fermented green tea and spores of E. cristatum fermented on wheat were investigated, respectively. The methanol extract of fermented green tea and spore of E. cristatum both showed potent lipid-lowering activity in the blood of a high-fat diet induced hyperlipidemia model in golden hamsters and significantly reduced the accumulation of fat granules in the liver. These results indicated that the key active components were produced by E. cristatum. Chemical investigations suggested similar components in the two extracts and led to the identification of a new alkaloid, namely variecolorin P (1), along with four known structurally related compounds, (-)-neoechinulin A (2), neoechinulin D (3), variecolorin G (4), and echinulin (5). The structure of the new alkaloid was elucidated by HRESIMS, 1H, 13C, and 2D NMR analysis. The lipid-lowering activity of these compounds was evaluated using an oleic acid-induced HepG2 cell line model. Compound 1 significantly reduced the lipid accumulation in the HepG2 cell line with an IC50 value of 0.127 µM.


Assuntos
Alcaloides , Camellia sinensis , Animais , Cricetinae , Humanos , Chá/química , Mesocricetus , Metanol , Esporos Fúngicos , Camellia sinensis/química , Extratos Vegetais/farmacologia , Lipídeos
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