Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
1.
J Am Chem Soc ; 146(21): 14685-14696, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38717074

RESUMEN

The exploration of new polymer materials required the development of efficient, economic, robust, and scalable synthetic routes, taking energy consumption, environmental benefit, and sustainability into overall consideration. Herein, through retro-polymerization analysis of functional aromatic polythioureas, a multicomponent reaction of elemental sulfur, CH2Cl2, and aromatic amines was designed with the assistance of fluoride, and efficient, economic, and robust multicomponent polymerizations (MCPs) of these three abundantly available cheap monomers, elemental sulfur, CH2Cl2, and aromatic diamines, were developed to realize scalable conversion directly from sulfur to a series of functional aromatic polythioureas with high molecular weights (Mn up to 50,800 g/mol) in excellent yields (up to 98%). The synergistic cooperation of the strong and selective coordination of thiourea with gold ions and the redox property of aromatic polythiourea enable in situ reduction of Au3+ to elemental gold under a normal bench condition. Furthermore, the functional aromatic polythiourea could be chemically recycled through aminolysis with NH3·H2O to afford a diamine monomer in 83% isolated yield. The development of elemental sulfur-based MCP has brought the opportunity to access cost-effective and sustainable sulfur-containing functional polymer materials, which is anticipated to provide a solution for the utilization of sulfur waste and making profitable polymer materials.

2.
Nutr Cancer ; : 1-9, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39252461

RESUMEN

Given the consistent detection of Epstein-Barr virus (EBV) in prostate tissues and the clinical evidence suggesting its involvement in prostate cancer (PCa), the potential association between EBV infection and PCa warrants further investigation. This study aimed to assess the causal relationship between EBV infection and PCa using Mendelian randomization (MR). We utilized data from a publicly available genome-wide association study (GWAS) on PCa, alongside data on five serum anti-EBV virus-related antibodies. Our findings indicate a potential causal link between serum EBV EA-D antibody levels and an increased risk of PCa. These results highlight the need for additional research to elucidate the mechanisms by which EBV may contribute to the progression of PCa, potentially offering new insights into its pathogenesis and therapeutic targets.

3.
Langenbecks Arch Surg ; 408(1): 305, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37566144

RESUMEN

BACKGROUND AND AIMS: The use of sutures to strengthen the anastomosis after rectal cancer surgery to reduce the possibility of anastomotic leakage has been debated. The aim of this systematic review and meta-analysis was to investigate the influence of intraoperative anastomotic reinforcing sutures on anastomotic leakage of double-stapling anastomosis for laparoscopic rectal cancer surgery. METHODS: A systematic search of PubMed, Embase, Web of Science, and Cochrane databases was performed to identify literature examining anastomotic leak as the primary outcome to compare studies of laparoscopic surgery for rectal cancer using the double-stapling anastomosis technique with or without intraoperative anastomotic reinforcement with sutures. RESULTS: A total of 1122 rectal cancer patients from 5 nonrandomized studies were included in the research. In the combined trial, intraoperative anastomotic reinforcement sutures significantly reduced the incidence of anastomotic leakage in patients who underwent laparoscopic rectal cancer surgery (OR, 0.32; 95% CI, 0.19-0.55; p < 0.0001). With or without intraoperative anastomotic reinforcing sutures, the incidence of postoperative reoperation for anastomotic leak did not differ substantially (OR, 0.32; 95% CI, 0.08-1.21, p = 0.09). Moreover, the surgery was prolonged due to anastomotic reinforcement with sutures (OR, 6.64; 95% CI, - 6.18 to 19.47, p = 0.31). CONCLUSIONS: Intraoperative anastomotic reinforcement with sutures may be associated with a lower incidence of anastomotic leakage. The amount of research evidence is limited because most of the studies analyzed did not include patients with factors such as neoadjuvant therapy or prophylactic stomas. Therefore, additional multicenter randomized controlled studies with larger size samples are needed to support the validity of the approach.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Humanos , Fuga Anastomótica/etiología , Factores de Riesgo , Anastomosis Quirúrgica/métodos , Laparoscopía/métodos , Neoplasias del Recto/cirugía , Suturas/efectos adversos , Estudios Multicéntricos como Asunto
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(2): 136-140, 2020 Feb.
Artículo en Zh | MEDLINE | ID: mdl-32051080

RESUMEN

OBJECTIVE: To study the effect of low-dose dopamine adjuvant therapy on inflammatory factors and prognosis in preterm infants with necrotizing enterocolitis (NEC). METHODS: A total of 100 preterm infants with NEC from June 2017 to June 2019 were enrolled and divided into a dopamine treatment group and a conventional treatment group using a random number table, with 50 infants in each group. The infants in the conventional treatment group were given symptomatic treatment, and those in the dopamine treatment group were given low-dose dopamine adjuvant therapy in addition to the conventional treatment. ELISA was used to measure the levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8). The two groups were compared in terms of time to relief of clinical symptoms, fasting time, treatment outcome, prognosis, and adverse reactions. RESULTS: Both groups had significant reductions in the levels of CRP, TNF-α, and IL-8 after treatment, and the dopamine treatment group had significantly lower levels of these markers than the conventional treatment group after treatment (P<0.05). Compared with the conventional treatment group, the dopamine treatment group had significantly shorter time to defecation improvement, time to relief of abdominal distension and diarrhea, and fasting time (P<0.05), a significantly higher response rate (P<0.05), and a significantly lower surgery rate (P<0.05). There were no significant differences in the mortality rate and incidence of adverse events between the two groups (P>0.05). CONCLUSIONS: Low-dose dopamine adjuvant therapy can effectively improve the levels of inflammatory factors and clinical symptoms in preterm infants with NEC and has good safety, and therefore, it holds promise for clinical application.


Asunto(s)
Enterocolitis Necrotizante , Enfermedades del Recién Nacido , Dopamina , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Pronóstico
5.
World J Urol ; 37(6): 1197-1204, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30251051

RESUMEN

PURPOSE: Our study aimed to investigate the clinical significance of urinary neutrophil gelatinase-associated lipocalin (NGAL) as an effective real-time monitoring biomarker of renal function in patients with obstructive ureteral calculi presenting renal colic. METHODS: A cohort of 89 first-visit patients with renal colic caused by unilateral ureteral calculi were retrospectively reviewed. 46 of which received double-J ureteral stent placement (group 1) and the remaining 43 treated conservatively with analgesics and hydration (group 2) when diagnosed. Urinary NGAL (uNGAL) values in the baseline, 2 h and 1 day after treatments were recorded. The variation of this parameter over time and the association with patients' characteristics were analyzed. RESULTS: uNGAL levels decreased as time went by for patients receiving double-J ureteral stent placement (47.23 ± 28.32 ng/mL for baseline, 40.73 ± 21.86 ng/mL for 2 h and 34.67 ± 18.00 ng/mL for 1 day after operation; p = 0.0363). Nevertheless, for those treating conservatively, the levels emerged a mild increase (50.63 ± 32.30 ng/mL, 56.00 ± 32.01 ng/mL and 60.63 ± 34.08 ng/mL, correspondingly; p = 0.3708). By analyzing the association between uNGAL variation and patients' characteristics of group 1, operation duration showed the best correlation coefficient (Pearson r = 0.6106, r2 = 0.3728, p < 0.0001). CONCLUSIONS: uNGAL can be used as a biomarker to monitor the renal function effectively when serum creatinine (sCr) was within normal limits. And double-J ureteral stent can be considered as a protective factor to renal function in patients with obstructive ureteral calculi presenting renal colic.


Asunto(s)
Lipocalina 2/orina , Cálculos Ureterales/orina , Obstrucción Ureteral/orina , Biomarcadores/orina , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Cólico Renal/etiología , Cólico Renal/orina , Estudios Retrospectivos , Cálculos Ureterales/complicaciones , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/etiología
6.
Aging Male ; 21(4): 231-237, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29316842

RESUMEN

BACKGROUND: Enzalutamide, a novel androgen receptor (AR) signaling inhibitor, has been widely used to increase survival in patients with castration-resistant prostate cancer. However, resistance to enzalutamide invariably develops. METHODS: To understand the underlying mechanisms of resistance to enzalutamide, we performed integrative analysis on multiple transcriptome datasets to identify those genes constantly up- or down-regulated in response to enzalutamide treatment. RESULTS: There were 703 and 581 differentially expressed genes derived from enzalutamide-sensitive and -resistant cell lines, respectively. Functional enrichment analysis on these genes demonstrated that biological processes of cell proliferation and ubiquitin mediated proteolysis pathway are specifically disturbed in sensitive cell lines but not resistant ones. Such divergence explained why enzalutamide ineffective for resistant prostate cancer. CONCLUSIONS: Taken together, the present study revealed a set of critical genes, which can provide etiologic clues as to enzalutamide-resistant prostate cancer and guide novel therapeutic approaches.


Asunto(s)
Antineoplásicos/farmacología , Resistencia a Antineoplásicos/genética , Perfilación de la Expresión Génica , Expresión Génica/efectos de los fármacos , Feniltiohidantoína/análogos & derivados , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Antineoplásicos/uso terapéutico , Benzamidas , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Masculino , Nitrilos , Feniltiohidantoína/farmacología , Feniltiohidantoína/uso terapéutico , Transducción de Señal/genética , Insuficiencia del Tratamiento
7.
Phys Chem Chem Phys ; 20(42): 26995-27002, 2018 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-30328434

RESUMEN

A series of Ce3+/Tb3+ doped Li3Sc2(PO4)3 phosphors has been obtained using high temperature solid state reactions. Density functional theory (DFT) calculations using the CASTEP module have given an insight into the bandgap and electronic structures of the hosts. The phase formation and the crystal structure of the prepared samples were verified using X-ray diffraction and Rietveld structure refinement analysis. Samples singly doped with Ce3+ ions had an intense emission centered at 350 nm under UV light irradiation, while samples singly doped with Tb3+ ions exhibited a typical green emission under 230 nm irradiation. Efficient Ce3+→Tb3+ energy transfer can cause the Li3Sc2(PO4)3:Ce3+,Tb3+ samples to have an intense green emission at very low Tb3+ concentrations under 285 nm excitation, making Li3Sc2(PO4)3:Ce3+,Tb3+ an efficient UV-excited green phosphor. The mechanism and critical distance for Ce3+→Tb3+ energy transfer in the phosphor were determined by detailed luminescence decay curve analysis utilizing the I-H model. Moreover, a WLED device was fabricated using our prepared green phosphor.

8.
Kidney Blood Press Res ; 43(1): 152-161, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29444515

RESUMEN

BACKGROUND/AIMS: Mesenchymal stromal cells (MSCs) participate in the tissue-specific repair of many different organs, especially the kidney. Their effects are primarily mediated by the paracrine release of factors including extracellular vesicles (EVs), which are composed of micro-vesicles and exosomes. The corresponding microRNAs (miRNAs) of EVs are considered important for their biological functions. METHODS: MSCs were cultured from the human umbilical cord, and EVs were isolated from the medium. The expression levels of miRNAs in MSCs and EVs were determined by microarray analysis, and gene ontology (GO) was used to analyze the functions of their target genes. RESULTS: MSCs and EVs had similar miRNA expression profiles, with the exception of a small number of selectively enriched miRNAs. GO analysis indicated that, unlike MSCs, the target genes of EV-enriched miRNAs were associated with calcium channel regulation and cell junction activities, which may indicate that MSC and EVs have different regulatory properties. Angiogenesis, oxidative stress, and inflammatory signaling pathways related to the repair of renal injury were also analyzed, and EV-enriched miRNAs targeted genes associated with oxidative stress, T cell activation, and Toll-like receptor signaling. The miRNAs enriched in both MSCs and EVs targeted different genes in signaling pathways regulating angiogenesis and chemokine release. CONCLUSION: MSCs and their EVs shared similar miRNA component, and some selectively enriched miRNAs observed in MSCs and EVs may affect different target genes through some specific signaling pathways.


Asunto(s)
Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/metabolismo , MicroARNs/análisis , Ontología de Genes , Humanos , Transducción de Señal , Análisis de Matrices Tisulares , Cordón Umbilical/citología
9.
BMC Urol ; 18(1): 64, 2018 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-30041630

RESUMEN

BACKGROUND: The current research aims to evaluate the risk factors of urethrocutaneous fistula after hypospadias surgery among the youth in China. METHODS: One hundred twenty hypospadias patients were enrolled in our study. All of them were defined as Tanner 4 or 5. The information collected from the participants include age, urethral operation history, urinary comorbidities before operation, urine test before operation, body temperature before and after operation, type of surgical repair, chordee degree, urethral defect length and whether received vesicostomy after surgery or not. Independent t test, chi-square test and multivariate logistic regression were performed to evaluate the risk factor of urethrocutaneous fistula. RESULTS: Among the enrolled patients, 39 patients (32.5%) developed urethrocutaneous fistula after hypospadias repair. Our result showed significant association between the group with urethrocutaneous fistula and the group without urethrocutaneous fistula with respect to age, pyuria before operation, urethral defect length and the urethral operation history. The following logistic regression showed that urethral defect length and the urethral operation history were the risk factors of urethrocutaneous fistula. CONCLUSIONS: Urethral defect length and urethral operation history should be taken into consideration before undergoing hypospadias surgery since our study discovered that the risk of developing urethrocutaneous fistula after hypospadias repair is associated with urethral defect length and urethral operation history. Age, surgical procedure, type of surgical repair, chordee degree and other factors were not obviously related to the development of urethrocutaneous fistula.


Asunto(s)
Fístula Cutánea/epidemiología , Hipospadias/cirugía , Complicaciones Posoperatorias/epidemiología , Enfermedades Uretrales/epidemiología , Fístula Urinaria/epidemiología , Procedimientos Quirúrgicos Urológicos Masculinos/efectos adversos , Adolescente , Adulto , Niño , China/epidemiología , Fístula Cutánea/etiología , Humanos , Incidencia , Masculino , Estudios Retrospectivos , Factores de Riesgo , Enfermedades Uretrales/etiología , Fístula Urinaria/etiología , Adulto Joven
10.
Aging Male ; 20(4): 250-256, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28787260

RESUMEN

BACKGROUND: The etiology of benign prostatic hyperplasia (BPH) has not been well established. The preferred medical treatment for many men with symptomatic benign prostatic hyperplasia is either an α-adrenergic receptor antagonist (α-blocker), or a 5α-reductase inhibitor. Single nucleotide polymorphism (SNP) is a powerful tool for successful implementation of individualized treatment. METHODS: Eighteen SNPs associated with drug efficacy in a Chinese population were genotyped in 790 BPH cases (330 aggressive and 460 non-aggressive BPH cases) and 1008 controls. All BPH patients were treated with α-adrenergic blockers for at least 9 months. We tested the associations between tagging single nucleotide polymorphism and BPH risk/aggressiveness, clinical characteristics at baseline, including the International Prostate Symptom Score (IPSS) and total prostate volume, and changes in clinical characteristics after treatment. RESULTS: There were nine SNPs associated with BPH risk, clinical progression and therapeutic effect. (1) There were nine tSNPs been chosen in CYP3A4, CYP3A5 and RANBP3L genes. (2) The SNP, rs16902947 in RANBP3L at 5p13.2 (p = .01), was significantly associated with BPH. (3) We found two SNPs, rs16902947 in RANBP3L at 5p13.2 (p = .0388) and rs4646437 in CYP3A4 at 7q21.1 (p = .0325), associated with drug effect. (4) Allele "G" for rs16902947 was found to be risk alleles for BPH risk (OR= 2.357, 95%CI 1.01-1.48). The "A" allele of rs4646437 was associated with lower IPSS at baseline (ß= -0.4232, p= .03255). CONCLUSIONS: rs16902947, rs16902947 and rs4646437 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.


Asunto(s)
Inhibidores de 5-alfa-Reductasa/uso terapéutico , Antagonistas Adrenérgicos alfa/uso terapéutico , Próstata/efectos de los fármacos , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/genética , Anciano , Estudios de Casos y Controles , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Próstata/patología
11.
World J Urol ; 32(2): 329-33, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22885658

RESUMEN

PURPOSE: To evaluate elastography using a bi-plane transducer for localizing prostate cancer (PCa) in patients scheduled for radical prostatectomy (RP), in comparison with step section pathological analysis. METHODS: Fifty-six consecutive PCa patients underwent real-time elastography examination with a bi-plane transducer before RP. Transverse elastographic images were obtained from the apex to the base by slightly compressing and releasing the prostate tissue using the probe. The diagnostic performance of elastography was evaluated in correlation with step section RP histopathology. RESULTS: In 56 PCa patients, gray-scale ultrasonography detected at least one lesion in 36 patients, whereas elastography detected at least one lesion in 53 patients (P = 0.001). The overall sensitivity, specificity and accuracy of elastography in depicting tumor lesions were 67.6, 89.5 and 82.7 %, respectively. The detection rate of a PCa lesion with elastography was best in the left posterior region, followed by the right posterior region. Elastography was more sensitive in detecting PCa lesions with higher Gleason scores, diameter >5 mm and extracapsular extension. CONCLUSIONS: The additional use of elastography with the bi-plane transducer can improve PCa detection rate by providing more information about tissue stiffness within the prostate gland.


Asunto(s)
Adenocarcinoma/diagnóstico , Diagnóstico por Imagen de Elasticidad/métodos , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Anciano , Estudios de Cohortes , Diagnóstico por Imagen de Elasticidad/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Próstata/patología , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Sensibilidad y Especificidad , Transductores
12.
PLoS One ; 19(3): e0300931, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38512874

RESUMEN

A uniaxial compression test was conducted on sandstone specimens at various inclination angles to determine the energy evolution characteristics during deformation and damage. Based on the principle of minimum energy dissipation, an intrinsic model incorporating the damage threshold was developed to investigate the mechanical properties of sandstone at different inclination angles, and the energy damage evolution during deformation and damage. This study indicated that when the inclination angle of the structural surface remained below 40°, sandstone exhibited varying mechanical properties based on different inclination angles. The peak strain was positively correlated with the inclination angle, whereas the compressive strength and modulus of elasticity showed negative correlations. From an energy perspective, the deformation and damage of sandstone under external loading entail processes of energy input, accumulation, and dissipation. Moreover, higher inclination angles of the structural surface resulted in a smaller absorbed peak strain and a reduced proportion of dissipated energy relative to the energy input, thereby affecting the evolution of energy damage throughout the process. As the inclination angle of the structural surface increased, the absorbed total strain at the peak value decreased, whereas the proportion of the dissipated energy increased. Additionally, the damage threshold and critical value of the rock specimens increased with the inclination angle. The critical value, a composite index comprising the peak strain, compressive strength, and elastic modulus, also increased accordingly. These findings can offer a novel perspective for analyzing geological disasters triggered by fissure zones within underground rock formations.


Asunto(s)
Desastres , Salicilatos , Fuerza Compresiva , Módulo de Elasticidad , Elasticidad
13.
iScience ; 27(1): 108737, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38269099

RESUMEN

Lead (Pb(II)) contamination is common in liquid foods and can result from Pb(II) being present in the raw materials or during handling processes. However, due to the complexity of food matrices, there is limited data available concerning Pb(II) ion removal from food sources. This study focused on fabricating a PVA/PAA/DMTD electrospun nanofibrous membrane (ENFM) to efficiently and selectively remove Pb(II) ions from liquid foods. The PVA/PAA/DMTD ENFM had a maximum adsorption capacity of 138.3 mg/g for Pb(II) ions and demonstrated high selectivity toward the removal of Pb(II) ions. Negative values of the Gibbs free energy (ΔG°) showed that the spontaneous nature of the adsorption process was feasible at different temperatures. Moreover, it successfully removed Pb(II) ions from selected samples of commercially available drinks. Therefore, this adsorbent exhibits significant potential for removing Pb(II) ions from liquid food products, thereby reducing daily dietary exposure to Pb(II).

14.
World J Gastrointest Surg ; 16(2): 438-450, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38463372

RESUMEN

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a composite inflammatory biomarker, is associated with the prognosis in patients with colorectal tumors. However, whether the NLR can be used as a predictor of symptomatic postoperative anastomotic leakage (AL) in elderly patients with colon cancer is unclear. AIM: To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer. METHODS: Data from elderly colon cancer patients who underwent elective radical colectomy with anastomosis at three centers between 2018 and 2022 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the best predictive cutoff value for the NLR. Twenty-two covariates were matched using a 1:1 propensity score matching method, and univariate and multivariate logistic regression analyses were used to determine risk factors for the development of postoperative AL. RESULTS: Of the 577 patients included, 36 (6.2%) had symptomatic AL. The optimal cutoff value of the NLR for predicting AL was 2.66. After propensity score matching, the incidence of AL was significantly greater in the ≥ 2.66 NLR subgroup than in the < 2.66 NLR subgroup (11.5% vs 2.5%; P = 0.012). Univariate logistic regression analysis revealed statistically significant correlations between blood transfusion intraoperatively and within 2 d postoperatively, preoperative albumin concentration, preoperative prognostic nutritional index, and preoperative NLR and AL occurrence (P < 0.05); multivariate logistic regression analysis revealed that an NLR ≥ 2.66 [odds ratio (OR) = 5.51; 95% confidence interval (CI): 1.50-20.26; P = 0.010] and blood transfusion intraoperatively and within 2 d postoperatively (OR = 2.52; 95%CI: 0.88-7.25; P = 0.049) were risk factors for the occurrence of symptomatic AL. CONCLUSION: A preoperative NLR ≥ 2.66 and blood transfusion intraoperatively and within 2 d postoperatively are associated with a higher incidence of postoperative symptomatic AL in elderly patients with colon cancer. The preoperative NLR has predictive value for postoperative symptomatic AL after elective surgery in elderly patients with colon cancer.

15.
Biomed Pharmacother ; 176: 116807, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38795644

RESUMEN

Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature. The study of autophagy represents a valuable field of research with significant clinical implications for identifying autophagy-related signals, pathways, mechanisms, and treatment options for MetS. Given the multifactorial etiology and various potential risk factors, it is imperative to explore the interplay between autophagy and gut microbiota in MetS more thoroughly. This will facilitate the elucidation of new mechanisms underlying the crosstalk among autophagy, gut microbiota, and MetS, thereby providing new insights into the diagnosis and treatment of MetS.


Asunto(s)
Autofagia , Microbioma Gastrointestinal , Resistencia a la Insulina , Síndrome Metabólico , Autofagia/fisiología , Microbioma Gastrointestinal/fisiología , Síndrome Metabólico/microbiología , Síndrome Metabólico/metabolismo , Humanos , Resistencia a la Insulina/fisiología , Animales , Transducción de Señal
16.
Cancer Lett ; 587: 216725, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38364963

RESUMEN

Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. STATEMENT OF SIGNIFICANCE: PAK1 drives ARSI cross-resistance in prostate cancer progression.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Receptores Androgénicos/metabolismo , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Detección Precoz del Cáncer , Recurrencia Local de Neoplasia/genética , Nitrilos/farmacología , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Quinasas p21 Activadas/genética , Quinasas p21 Activadas/metabolismo
17.
Cancer Lett ; 597: 217070, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38880227

RESUMEN

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance.


Asunto(s)
Benzamidas , Resistencia a Antineoplásicos , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata , Simportadores de Sodio-Bicarbonato , Animales , Humanos , Masculino , Ratones , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , FN-kappa B/metabolismo , FN-kappa B/genética , Feniltiohidantoína/farmacología , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/análogos & derivados , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba , Ensayos Antitumor por Modelo de Xenoinjerto , Simportadores de Sodio-Bicarbonato/genética
18.
J Hazard Mater ; 478: 135583, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39180998

RESUMEN

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), two prominent per- and polyfluoroalkyl substances (PFASs), are potentially harmful to many human organs. However, there only exist limited methods to mitigate their health hazards. The aim of this study is to combine a bioinformatics analysis with in vitro experiments to discover small molecules that can alleviate liver damage caused by PFOA/PFOS. We identified 192 and 82 key genes related to hepatocytes exposed to PFOA and PFOS, respectively. The functional enrichment analysis of key genes suggested cellular senescence may be important in PFOA/PFOS-induced hepatotoxicity. The in vitro models revealed that PFOA/PFOS led to hepatocyte senescence by increasing the activity of SA-ß-gal, inducing mitochondrial dysfunction, impacting cell cycle arrest, and elevating the expressions of p21, p53, IL-1ß, and SASP-related cytokines. The drug-target gene set enrichment analysis method was employed to compare the transcriptome data from the Gene Expression Omnibus database (GEO), Comparative Toxicogenomics Database (CTD), and the high-throughput experiment- and reference-guided database (HERB), and 21 traditional Chinese medicines (TCMs) were identified that may alleviate PFOA/PFOS-induced liver aging. The experimental results of co-exposure to PFOA/PFOS and TCMs showed that sanguinarine has particular promise in alleviating cellular senescence caused by PFOA/PFOS. Further investigations revealed that the mTOR-p53 signaling pathway was involved in PFOA/PFOS-mediated hepatic senescence and can be blocked using sanguinarine.


Asunto(s)
Ácidos Alcanesulfónicos , Caprilatos , Senescencia Celular , Fluorocarburos , Hepatocitos , Isoquinolinas , Fluorocarburos/toxicidad , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Senescencia Celular/efectos de los fármacos , Caprilatos/toxicidad , Humanos , Ácidos Alcanesulfónicos/toxicidad , Isoquinolinas/farmacología , Benzofenantridinas/farmacología , Biología Computacional , Animales , Células Hep G2 , Transducción de Señal/efectos de los fármacos
19.
World J Surg Oncol ; 11: 216, 2013 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-23987305

RESUMEN

BACKGROUND: Although nephron-sparing surgery has been reported not to affect total renal function, it is a non-negligible fact that functional damage of the operated kidney usually results, for various reasons. This study aimed to explore the effects of preoperative baseline characteristics, tumor characteristics, and function protection methods on postoperative renal damage. METHODS: This study was a retrospective review of 51 patients who underwent open nephron-sparing surgery. The mean age of the patients (39 men, 12 women) was 54.2 ± 13.9 years, range 32 to 71 years. The glomerular filtration rate (GFR) was measured preoperatively and 6th months after the operation. Univariate analysis was used to screen indicators with significant differences in different levels of renal function damage. All variables found to be significant on univariate analysis were entered into a multiple logistic regression model to predict risk factors for renal function damage. RESULTS: Univariate analysis showed that there was a significant difference in age, GFR of operated kidney, tumor diameter, tumor depth, and ischemic protection type between patients with little damage and those with heavy damage (P < 0.05). Forward stepwise logistic regression analysis suggested that age (odds ratio, 3.08; 95% confidence interval 1.78 to 7.04; P = 0.037), preoperative GFR of operated kidney (odds ratio, 0.51; 95% confidence interval 0.11 to 0.73; P = 0.033), and tumor diameter (odds ratio, 5.49; 95% confidence interval 2.14 to 7.88; P = 0.012) and depth (odds ratio, 5.82; 95% confidence interval 2.66 to 8.06; P = 0.010) were independent risk factors for postoperative renal function damage. CONCLUSIONS: Patients with older age, poor renal function, and large tumor diameter and depth might be at higher risk of renal function damage after nephron-sparing surgery.


Asunto(s)
Enfermedades Renales/diagnóstico , Neoplasias Renales/cirugía , Riñón/fisiopatología , Nefrectomía/efectos adversos , Nefronas/cirugía , Complicaciones Posoperatorias , Adulto , Anciano , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/etiología , Enfermedades Renales/fisiopatología , Pruebas de Función Renal , Neoplasias Renales/complicaciones , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tratamientos Conservadores del Órgano , Pronóstico , Estudios Retrospectivos
20.
Medicine (Baltimore) ; 102(47): e36226, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38013281

RESUMEN

This study aimed to develop and validate a nomogram for predicting the overall survival of cervical adenocarcinoma (CAC) patients using a large database comprising patients with different ethnicities. We enrolled primary CAC cases with complete clinicopathological and survival data from the Surveillance, Epidemiology, and End Results program during 2004 to 2015. For training set samples, this work applied the Cox regression model to obtain factors independently associated with patient prognosis, which could be incorporated in constructing the nomogram. Altogether 3096 qualified cases were enrolled, their survival ranged from 0 to 155 (median, 45.5) months. As revealed by multivariate regression, age, marital status, tumor size, grade, International Federation of Gynecology and Obstetrics (FIGO) classification, pelvic lymph node metastasis, surgery, and chemotherapy served as the factors to independently predict CAC (all P < .05). We later incorporated these factors for constructing the nomogram. According to the concordance index determined, this nomogram had superior discrimination over FIGO classification system (all P < .001). Based on calibration plot, the predicted value was consistent with actual measurement. As revealed by time-independent area under the curves, our constructed nomogram had superior 5-year overall survival over FIGO system. Additionally, according to decision curve analysis, our constructed nomogram showed high clinical usefulness as well as favorable discrimination. Our constructed nomogram attains favorable performances, indicating that it may be applied in predicting survival for CAC patients.


Asunto(s)
Adenocarcinoma , Neoplasias del Cuello Uterino , Femenino , Embarazo , Humanos , Nomogramas , Investigación , Calibración , Bases de Datos Factuales , Programa de VERF , Pronóstico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA