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1.
Infect Immun ; : e0002424, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700335

RESUMO

Cryptococcus deneoformans is a yeast-type fungus that causes fatal meningoencephalitis in immunocompromised patients and evades phagocytic cell elimination through an escape mechanism. Memory T (Tm) cells play a central role in preventing the reactivation of this fungal pathogen. Among these cells, tissue-resident memory T (TRM) cells quickly respond to locally invaded pathogens. This study analyzes the kinetics of effector T (Teff) cells and Tm cells in the lungs after cryptococcal infection. Emphasis is placed on the kinetics and cytokine expression of TRM cells in the early phase of infection. CD4+ Tm cells exhibited a rapid increase by day 3, peaked at day 7, and then either maintained their levels or exhibited a slight decrease until day 56. In contrast, CD8+ Tm cells reached their peak on day 3 and thereafter decreased up to day 56 post-infection. These Tm cells were predominantly composed of CD69+ TRM cells and CD69+ CD103+ TRM cells. Disruption of the CARD9 gene resulted in reduced accumulation of these TRM cells and diminished interferon (IFN) -γ expression in TRM cells. TRM cells were derived from T cells with T cell receptors non-specific to ovalbumin in OT-II mice during cryptococcal infection. In addition, TRM cells exhibited varied behavior in different tissues. These results underscore the importance of T cells, which produce IFN-γ in the lungs during the early stage of infection, in providing early protection against cryptococcal infection through CARD9 signaling.

3.
Infect Drug Resist ; 17: 1551-1559, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660055

RESUMO

Hypervirulent Klebsiella pneumoniae (hvKP) has emerged as a novel variant of K. pneumoniae, exhibiting distinct phenotypic and genotypic characteristics that confer increased virulence and pathogenicity. It is not only responsible for nosocomial infections but also community-acquired infections, including liver abscesses, endophthalmitis, and meningitis, leading to significant morbidity and mortality. HvKP has been reported all over the world, but it is mainly prevalent in Asia Pacific, especially China. Moreover, hvKP can acquire carbapenemase genes resulting in the emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP), which possesses both high virulence and drug resistance capabilities. Consequently, CR-hvKP poses substantial challenges to infection control and presents serious threats to global public health. In this paper, we provide a comprehensive summary of the epidemiological characteristics, virulence factors, and mechanisms underlying carbapenem resistance in hvKP strains with the aim of offering valuable insights for practical prevention strategies as well as future research.

4.
World J Urol ; 42(1): 89, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376590

RESUMO

PURPOSE: To investigate the effect of the postural drainage lithotripsy system developed by our experimental team on the vital signs of patient with urinary stones during the stone removal process. METHODS: Four groups of 15 subjects (0°, 10°, 40°, and 70°) were subjected to different angles of head-down tilt to measure middle cerebral artery blood flow velocity (MCAv), cerebrovascular conductance coefficient (CVCi), intracranial pressure (nICP), heart rate (HR), and mean arterial blood pressure (MAP). RESULTS: As the angle of HDT changed, MCAv values, nICP values, CVCi values, HR values, and MAP values changed significantly (all P ≤ 0.001), and the difference was statistically significant. During 10°HDT, despite a slight increase in nICP, the other measurements remained stable. During 40°HDT, only the MCAv values did not change significantly, whereas the rest of the measures were significantly altered. During 70°HDT, all indicators changed significantly. CONCLUSIONS: The significant alterations in cerebral blood flow, intracranial pressure, and hemodynamics induced during the treatment of renal residual fragments with postural drainage should be used with caution in individuals with cerebrovascular accidents. CHINA CLINICAL TRIALS REGISTRY: ChiCTR2300070671; Registration date: 2023-04-18.


Assuntos
Pressão Intracraniana , Litotripsia , Humanos , Pressão Sanguínea , Frequência Cardíaca , Drenagem Postural , Circulação Cerebrovascular
5.
Int Urol Nephrol ; 56(6): 1869-1877, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38214779

RESUMO

OBJECTIVE: Abdominal obesity, especially visceral fat, may have negative effects on the development and progression of prostate cancer (PCa). A body shape index (ABSI) can more accurately measure visceral fat accumulation. This study aimed to investigate the association between ABSI and PCa in US adults. METHODS: 11,013 participants were enrolled in the National Health and Nutrition Examination Survey from 2001 to 2018. Weighted multivariate logistic regression analyses were employed to explore the independent relationship between ABSI and PCa. Moreover, restricted cubic spline (RCS) analysis, subgroup analysis, and interaction tests were performed. RESULTS: ABSI was positively associated with the presence of PCa. When comparing the second, third, and fourth ABSI quartile to the lowest quartile, the adjusted odds ratios (95% confidence intervals) for PCa risk were 1.34 (0.77, 2.31), 1.75 (1.03, 3.00), and 1.91 (1.12, 3.27), respectively (p for trend = 0.011). The restricted cubic spline regression analysis did not reveal a non-linear correlation between ABSI and PCa (p for non-linearity = 0.076). Subgroup analysis showed a significant interaction effect in subgroups of different BMI (p for interaction = 0.01). CONCLUSIONS: Elevated ABSI is significantly associated with an increased risk of PCa, particularly among individuals who are under/normal weighted or obese.


Assuntos
Inquéritos Nutricionais , Neoplasias da Próstata , Humanos , Masculino , Estudos Transversais , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Idoso , Adulto , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/complicações
6.
BMC Pulm Med ; 23(1): 329, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37674193

RESUMO

BACKGROUND: The Corona Virus Disease 2019(COVID-19) pandemic has strained healthcare systems worldwide, necessitating the early prediction of patients requiring critical care. This study aimed to analyze the laboratory examination indicators, CT features, and prognostic risk factors in COVID-19 patients. METHODS: A retrospective study was conducted on 90 COVID-19 patients at the First Affiliated Hospital of Gannan Medical University between December 17, 2022, and March 17, 2023. Clinical data, laboratory examination results, and computed tomography (CT) imaging data were collected. Logistic multivariate regression analysis was performed to identify independent risk factors, and the predictive ability of each risk factor was assessed using the area under the receiver operating characteristic (ROC) curve. RESULTS: Multivariate logistic regression analysis revealed that comorbid diabetes (odds ratio [OR] = 526.875, 95%CI = 1.384-1960.84, P = 0.053), lymphocyte count reduction (OR = 8.773, 95%CI = 1.432-53.584, P = 0.064), elevated D-dimer level (OR = 362.426, 95%CI = 1.228-984.995, P = 0.023), and involvement of five lung lobes (OR = 0.926, 95%CI = 0.026-0.686, P = 0.025) were risk factors for progression to severe COVID-19. ROC curve analysis showed the highest predictive value for 5 lung lobes (AUC = 0.782). Oxygen saturation was positively correlated with normally aerated lung volume and the proportion of normally aerated lung volume (P < 0.05). CONCLUSIONS: The study demonstrated that comorbid diabetes, lymphocyte count reduction, elevated D-dimer levels, and involvement of the five lung lobes are significant risk factors for severe COVID-19. In CT lung volume quantification, normal aerated lung volume and the proportion of normal aerated lung volume correlated with blood oxygen saturation.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Cuidados Críticos , Progressão da Doença
7.
Infect Drug Resist ; 16: 1511-1519, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36945680

RESUMO

Background: The global prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a serious challenge for nosocomial infection and attracted worldwide attention. This study explored the drug resistance genes and molecular characteristics for CRKP, providing a reference for nosocomial prevention and control. Methods: A total of 42 CRKP isolates were collected from the First Affiliated Hospital of Gannan Medical University (Ganzhou, China) from January 2018 to February 2021. The drug resistance of CRKP was tested by the VitekII Compact system. Drug resistance gene expression was detected by poly-merase chain reaction (PCR), and molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Results: All the 42 CRKP isolates were multi-drug resistant. Among them, 35 isolates (83.3%) produced blaKPC-2 and 12 isolates (28.6%) produced blaNDM-1. The detection rate of blaIMP-4 and blaOXA-48 was 2.4% (1/42), respectively. Twelve isolates (28.6%) carried both blaKPC-2 and blaNDM-1, one isolate (2.4%) carried both blaKPC-2 and blaIMP-4, and one isolate (2.4%) carried blaKPC-2, blaNDM-1 and blaOXA-48. A variety of other extended-spectrum beta-lactamases (ESBLs) were also detected. All 42 isolates carried blaSHV and blaCTX-M-1, 27 isolates (64.3%) carried blaTEM and 12 isolates (28.6%) carried blaCTX-M-9. The MLST data classified the 42 CRKP isolates into 11 sequence types, mainly ST11, accounting for 61.9% (26/42), of which 92.3% of isolates (24/26) carrying blaKPC-2. The PFGE results demonstrated that the 42 CRKP isolates could be divided into 20 clusters A-T, with cluster A (26.2%, 11/42) and cluster H (21.4%, 9/42) dominating, which were all ST11. Conclusion: The CRKP isolates were severely multi-drug resistant, and the main resistant gene was blaKPC-2 production, carrying multiple ESBLs genes simultaneously. The MLST and PFGE revealed that the ST11-blaKPC-2 Klebsiella pneumoniae was the main clonotype. Our findings may offer help to antibiotics selection and nosocomial infection prevention and control.

8.
Drug Test Anal ; 15(1): 115-122, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35986510

RESUMO

The identification of new psychoactive substances (NPS) is an active and cutting-edge topic in forensic science. With the emergence of a large number of NPS, their timely identification to prevent spread can pose a challenge to clinical and forensic toxicology laboratories. Three emerging NPS had been identified in recently seized materials, including two synthetic cannabinoids [N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobutyl)-1H-indazole-3-carboxamide (4F-AB-BUTINACA) and N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-phenethyl-1H-indazole-3-carboxamide (AB-PHETINACA)] and a ketamine-like substance [2-(2-fluorophenyl)-2-(ethylamino) cyclohexan-1-one(2F-NENDCK)]. The three compounds were first identified by Fourier transform infrared spectrometry (FT-IR), gas chromatography-mass spectrometry (GC-MS), ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UHPLC-QTOF-MS), and nuclear magnetic resonance (NMR). These data may assist forensic analysts in analyzing the same substances or their homologous compounds.


Assuntos
Drogas Ilícitas , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Drogas Ilícitas/análise , Espectrometria de Massas/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Indazóis/análise
9.
Zhonghua Nan Ke Xue ; 29(9): 821-825, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-38639595

RESUMO

OBJECTIVE: Exploring the clinical efficacy, safety, and surgical techniques of two-way rendezvous and trenching method for transurethral holmium laser prostatectomy in the treatment of benign prostatic hyperplasia. METHODS: Retrospective analysis of clinical data on preoperative, intraoperative, and postoperative follow-up of 326 patients with benign prostatic hyperplasia who underwent two-way rendezvous and trenching method of transurethral holmium laser prostatectomy at the Urology Department of Wujin People's Hospital in Changzhou City from January 2020 to January 2023. RESULTS: Compared with preoperative measures, IPSS symptom score, quality of life (QoL) score, maximum urinary flow rate (Qmax), and residual urine volume (PVR) were significantly improved at 1, 6, and 12 months postoperatively (P<0.05). Thirty two patients with normal and regular sexual life pre-operation were observed. There were no significant changes in their IIEF-5 score and Erectile Hardness Scale (EHGS) score after surgery compared with pre-operation (P<0.05). There were 9 patients (28.12%) with retrograde ejaculation after surgery. CONCLUSION: The two-way rendezvous and trenching method of transurethral holmium laser prostatectomy is a safe and effective method for treating benign prostatic hyperplasia, with precise results, high safety, minimal trauma, and fast postoperative recovery.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Próstata , Hiperplasia Prostática/diagnóstico , Qualidade de Vida , Lasers de Estado Sólido/uso terapêutico , Estudos Retrospectivos , Ressecção Transuretral da Próstata/métodos , Resultado do Tratamento , Terapia a Laser/métodos , Hólmio
10.
Zhonghua Nan Ke Xue ; 29(10): 899-903, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38639659

RESUMO

OBJECTIVE: Comparison of clinical efficacy between transurethral holmium laser prostate enucleation (two-way rendezvous and trenching method) and transurethral plasma enucleation. METHODS: A total of 483 patients with benign prostatic hyperplasia who were admitted to our hospital from December 2019 to December 2022 were randomly divided into an observation group (245 cases) and a control group (238 cases) using a random number table method. The observation group underwent transurethral holmium laser prostatectomy, while the control group underwent transurethral plasma prostatectomy,evaluate the efficacy of two surgical methods. RESULT: The IPSS symptom score, quality of life (QOL) score, maximum urinary flow rate (Qmax), residual urine volume (PVR) and other indicators were significantly improved in both groups after 6 months of surgery compared to before (P<0.05), and there was no statistically significant difference between the two groups (P>0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group (P<0.05). There was no statistically significant difference in sexual function and retrograde ejaculation between the two groups of patients(P>0.05). CONCLUSION: Both surgical methods have good surgical efficacy, but compared with prostate plasma resection, holmium laser prostatectomy can reduce intraoperative bleeding in patients with BPH, effectively shorten catheter retention time, patient hospitalization time, and postoperative bladder flushing time, resulting in higher quality of life and safety.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Hiperplasia Prostática/complicações , Qualidade de Vida , Lasers de Estado Sólido/uso terapêutico , Ressecção Transuretral da Próstata/métodos , Próstata/cirurgia , Terapia a Laser/métodos , Resultado do Tratamento , Hólmio
11.
J Oncol ; 2022: 8699359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117850

RESUMO

Background: CircFBXW7 has been determined to be involved in various cancers; however, its role in nonsmall cell lung cancer (NSCLC) remains unclear. This study examined the function and potential mechanism of circFBXW7 in NSCLC. Methods: The structure of circFBXW7 was verified via RT-PCR and Sanger sequencing. The expression of circFBXW7 in NSCLC was determined by qRT-PCR. The effect of circFBXW7 overexpression on the proliferation, migration, and invasion of NSCLC cells was examined by CCK-8 and Transwell assays. Furthermore, a circFBXW7-miRNA network was established to explore their interaction. Predicted miRNA was determined by qRT-PCR. Moreover, the miRNA mimics were synthesized, wherein its effect on proliferation, migration, and invasion of NSCLC cells overexpressed circFBXW7 was assessed. Results: The circularity of circFBXW7 was verified. The expression of circFBXW7 was found to be downregulated in NSCLC cells compared with that in normal human lung epithelial BEAS-2B cells. Overexpression of circFBXW7 reduced cell proliferation, migration, and invasion. Furthermore, according to the circFBXW7-miRNA network prediction and qRT-PCR validation, miR-492 was identified to be the target of circFBXW7. The inhibitory effect of circFBXW7 overexpression on cell proliferation, migration, and invasion was reversed by miR-492 mimics. Conclusion: CircFBXW7 is downregulated in NSCLC. CircFBXW7 inhibits NSCLC cells proliferation, migration, and invasion by regulating miR-492.

12.
Emerg Med Int ; 2022: 7651215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844464

RESUMO

Objective: The aim of this study is to investigate the clinical effects of percutaneous nephrolithotomy and transurethral ureteroscopic lithotripsy in the treatment of incarcerated upper ureteral calculi. Methods: This study retrospectively reviewed 400 patients with incarcerated upper ureteral calculi admitted to the hospital from January 2016 to December 2021. Among them, 200 patients treated with percutaneous nephrolithotomy were included in the percutaneous group and 200 patients treated with transurethral ureteroscopic lithotripsy were included in the transurethral group. Perioperative indicators and stone clearance rates on day 7 and 1 month after operation and the reoperation rate were compared between the two groups. The incidence of postoperative complications was recorded. Results: The operation time and postoperative hospital stay of the percutaneous group were longer than those of the transurethral group (P < 0.05). There was no significant difference in intraoperative blood loss, 24 h postoperative pain score, stone clearance rates on day 3 and day 14 after operation, or the reoperation rate between the two groups (P > 0.05). Postoperative complications in the two groups were mainly grade I and II. The total incidence of complications in the percutaneous group was significantly lower than that in the transurethral group (P < 0.05). Conclusion: Both percutaneous nephrolithotomy and transurethral ureteroscopic lithotripsy are effective in the treatment of incarcerated upper ureteral calculi. The former can reduce the incidence of postoperative complications, but the operation time and postoperative hospital stay are longer.

13.
Cancer Gene Ther ; 29(11): 1636-1647, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35650393

RESUMO

Megakaryocytes (MK) are mainly derived from bone marrow and are mainly involved in platelet production. Studies have shown that MK derived from bone marrow may have immune function, and that MK from peripheral blood are associated with prostate cancer. Single-cell transcriptome sequencing can help us better understand the heterogeneity and potential function of MK cell populations in bone marrow (BM), peripheral Blood (PB), and cord blood (CB) of healthy and diseased people.We integrated more than 1.2 million single-cell transcriptome data from 132 samples of PB, BM, and CB from healthy individuals and patients from different dataset. We examined the MK (including MK and product of MK) by single-cell RNA sequencing data analysis methods and identification of MK-related protein expression by the Human Protein atlas. We investigate the relationship between the MK subtype and Non-Small Cell Lung Cancer (NSCLC) in 77 non-cancer and 402 NSCLC. We found that MK were widely distributed and the amount of MK in peripheral blood was more than that in bone marrow and there were specificity MK subtypes in peripheral blood. We found classical MK1 with typical MK characteristics and non-classical MK2 closely related to immunity which was the most common subtype in bone marrow and cord blood. Classical MK1 was closely related to Non-Small Cell Lung Cancer (NSCLC) and can be used as a diagnostic marker. MK2 may have potential adaptive immune function and play a role in tumor NSCLC and autoimmune diseases Systemic Lupus Erythematosus. MK have 14 subtypes and are widely distributed in PB, CB, and BM. MK subtypes are closely related to immunity and have potential to be a diagnostic indicator of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Megacariócitos/patologia , Sangue Fetal , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Medula Óssea , Células da Medula Óssea/patologia , Neoplasias Pulmonares/patologia , Análise de Sequência de RNA
14.
World J Urol ; 40(2): 585-591, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34687345

RESUMO

PURPOSE: We developed a Postural Drainage Lithotripsy System (PDLS) that uses the patient's computed tomography urography (CTU) data to reconstruct the three-dimensional figure of the renal pelvis, provides an individualized inversion and overturning angle and uses gravity to remove residual fragments (RFs). The purpose of this study was to investigate PDLS in the treatment of renal RFs. METHODS: A stone with a diameter of 4.0 mm was placed in the upper, middle, and lower calyx of the renal model. A total of 60 trials were applied to 20 renal models. The movement trajectory, passage rate, and postural drainage angle of calculi during the treatment of PDLS were observed. RESULTS: All of the stones in 60 trials were observed to move during treatment, and 53/60 (88%) were relocated successfully to the renal pelvis. The passage rate of the upper calyx was 14/20 (70%), that of the middle calyx was 20/20 (100%), and that of the lower calyx was 19/20 (95%). CONCLUSIONS: PDLS can provide individualized inversion and reversal angles and remove stones from the renal model. More clinical trials are needed to verify the above view and evaluate its efficacy.


Assuntos
Cálculos Renais , Litotripsia , Humanos , Cálculos Renais/terapia , Cálices Renais , Pelve Renal , Software , Resultado do Tratamento
15.
Infect Immun ; 89(10): e0033021, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34251289

RESUMO

The cell walls and capsules of Cryptococcus neoformans, a yeast-type fungal pathogen, are rich in polysaccharides. Dectin-2 is a C-type lectin receptor (CLR) that recognizes high-mannose polysaccharides. Previously, we demonstrated that Dectin-2 is involved in cytokine production by bone marrow-derived dendritic cells (BM-DCs) in response to stimulation with C. neoformans. In the present study, we analyzed the role of Dectin-2 in the phagocytosis of C. neoformans by BM-DCs. The engulfment of this fungus by BM-DCs was significantly decreased in mice lacking Dectin-2 (Dectin-2 knockout [Dectin-2KO]) or caspase recruitment domain-containing protein 9 (CARD9KO), a common adapter molecule that delivers signals triggered by CLRs, compared to wild-type (WT) mice. Phagocytosis was likewise inhibited, to a similar degree, by the inhibition of Syk, a signaling molecule involved in CLR-triggered activation. A PI3K inhibitor, in contrast, completely abrogated the phagocytosis of C. neoformans. Actin polymerization, i.e., conformational changes in cytoskeletons detected at sites of contact with C. neoformans, was also decreased in BM-DCs of Dectin-2KO and CARD9KO mice. Finally, the engulfment of C. neoformans by macrophages was significantly decreased in the lungs of Dectin-2KO mice compared to WT mice. These results suggest that Dectin-2 may play an important role in the actin polymerization and phagocytosis of C. neoformans by DCs, possibly through signaling via CARD9 and a signaling pathway mediated by Syk and PI3K.


Assuntos
Criptococose/microbiologia , Cryptococcus neoformans/patogenicidade , Células Dendríticas/metabolismo , Lectinas Tipo C/metabolismo , Fagocitose/fisiologia , Animais , Células da Medula Óssea/metabolismo , Células da Medula Óssea/microbiologia , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Criptococose/metabolismo , Citocinas/metabolismo , Células Dendríticas/microbiologia , Feminino , Pulmão/metabolismo , Pulmão/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfatidilinositol 3-Quinases/metabolismo
16.
Drug Des Devel Ther ; 15: 233-243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505158

RESUMO

BACKGROUND: Reineckia carnea is commonly used to treat cough, pneumonia and other diseases in China. In our previous study, it was found that the ethanol extracts of Reineckia carnea have a strong inhibitory effect on the proliferation of human lung cancer A549 cells. Here, we isolated gracillin from ethanol extracts for the first time. PURPOSE: Clarify the antiproliferation effect of gracillin on A549 cells and further explore its mechanisms via the mitochondrial pathway. METHODS: Gracillin was isolated and purified by silica gel, D-101 macroporous resin and preparative RP-HPLC, then identified by NMR and HR-MS. The inhibitory effects of gracillin on the proliferation of A549 cells were detected by the MTS method. Its mechanisms were further explored by flow cytometry and Western blot. RESULTS: A steroid saponin, gracillin, was isolated and identified from Reineckia carnea for the first time. In a concentration-dependent and time-dependent manner, gracillin significantly inhibited the proliferation of A549 cells with an IC50 value at 2.54 µmol/L and induced morphological changes. The results of flow cytometry analysis showed that the apoptosis rate of A549 cells was significantly increased (p < 0.05), and the cells proportion was obviously arrested in S phase. The concentration of intracellular calcium was raised (p < 0.01), and the mitochondrial membrane potential was greatly decreased (p < 0.01). In addition, the expression levels of Bax, caspase-3, cleaved caspase-3, and cytochrome C were dramatically up-regulated while Bcl-2 was down-regulated (p < 0.05) in A549 cells. CONCLUSION: This study confirmed that gracillin has a significant antiproliferative effect on A549 cells. Gracillin could induce the apoptosis of A549 cells through the mitochondrial pathway, which might be associated with regulation of the concentration of intracellular calcium, the mitochondrial membrane potential and the expression levels of Bax, Bcl-2, caspase-3, cleaved caspase-3, and cytochrome C.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Liliaceae/química , Mitocôndrias/efeitos dos fármacos , Espirostanos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Mitocôndrias/metabolismo , Espirostanos/química , Espirostanos/isolamento & purificação
17.
J Cancer ; 11(17): 5150-5161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742462

RESUMO

ACTL10 is a member of the actin family; however, despite previous studies suggesting that certain proteins in this family may be related to the pathogenesis of leukemia, to the best of our knowledge, no studies to date have demonstrated any association between ACTAL10 and leukemia. Thus, the present study aimed to determine the association between ACTL10 expression levels, DNA methylation levels and the clinical prognosis in cytogenic normal acute myeloid leukemia (CN-AML). Data from seventy-five patients with CN-AML and patients with AML treated with chemotherapy or allogeneic hematopoietic stem cell transplantation were obtained from The Cancer Genome Atlas (TCGA) dataset and were used to analyze the clinical prognosis of ACTL10 RNA expression levels and DNA methylation levels. In addition, the study also investigated the combined clinical prognosis of ACTL10 RNA expression levels and ACTL10 DNA methylation levels in 74 patients with CN-AML from the TCGA dataset. ACTL10 RNA expression levels were observed to be highly expressed in patients with CD34+/CD38+ AML (P<0.01). Both ACTL10 RNA expression levels and DNA methylation were found to be independent prognostic factors for patients with CN-AML; patients with CN-AML in the ACTL10 RNA-high expression group had an increased EFS (P=0.0016) and OS (P=0.014) and patients in ACTL10 DNA methylation-low group also demonstrated a long EFS (P<0.0001) and OS (P=0.004). Notably, integrating ACTL10 RNA expression levels and ACTL10 DNA methylation levels could more accurately predict the prognosis of patients with CN-AML (EFS and OS, P<0.0001). In conclusion, the findings of the present study suggested that the high RNA expression levels and low DNA methylation levels of ACTL10 may predict a good prognosis in patients with CN-AML.

18.
J Cancer ; 11(3): 619-629, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31942185

RESUMO

Background: Multiple myeloma (MM) is one of the most common incurable malignancies in malignant plasma cell disease. EPB41L4A is a target gene for the Wnt/ß-catenin pathway, which is closely related to the survival of multiple myeloma cells. However, there is currently no research report on the prognostic significance of the EPB41L4A gene in MM. Methods: We studied the biological significance and prognostic significance of EPB41L4A expression in MM by integrating 1956 MM samples from 7 datasets, and explored the relationship between EPB41L4A expression and MM ISS stage, molecular type, therapeutic response and survival. Results: We found that the expression level of EPB41L4A is inversely proportional to the copy number of 1q21 (P = 3.4e-13). EPB41L4A was low expressed in MAF, MMSET and proliferating molecular typing patients (P <= 0.001). High expression of EPB41L4A can predict good survival in MM (EFS: P < 0.0001; OS: P < 0.0001). We found that patients with relapsed MM had lower expression levels of EPB41L4A than those without recurrence (P = 0.0039). We also found that EPB41L4A can predict the prognosis of MM patients may be related to DNA replication. These results indicate that the initial expression level of EPB41L4A can predict the prognosis of MM patients. Conclusions: We found that the high expression of EPB41L4A predicts good survival level in MM.

19.
Cancer Gene Ther ; 27(1-2): 22-29, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30622325

RESUMO

Plasma cell myeloma (PCM) secretes monoclonal immunoglobulin (Ig) by clonal plasma cells of abnormal proliferation in the bone marrow. As PCM is incurable, it is necessary to find new biomarkers to predict the prognosis and recurrence of PCM. The relationship between cancer and RBBP8 has not been fully studied. The role of RBBP8 in tumorigenesis remains inconsistent. We described the expression of RBBP8 in the gene expression profile of 1930 PCM samples (1878 PCM patients) from seven independent data sets. We analyzed the relationship between RBBP8 and survival prognosis, recurrence, and treatment response in patients with PCM, and the biological significance of RBBP8 in PCM. The gene expression level of RBBP8 was significantly related to the International staging system (ISS) grade of PCM (P = 0.0012). RBBP8 expression in different molecular subtypes was different (P < 2.2e-16). High RBBP8 expression is associated with poor survival in PCM (P < 0.0001). High expression of RBBP8 indicates that PCM patients are more likely to relapse (P = 0.0078). The biological significance of RBBP8 in PCM is related to the cell cycle (P < 0.05). High RBBP8 expression predicts poorer survival and more likely relapse in PCM. RBBP8 plays an important role in the cell cycle of PCM. RBBP8 can be considered an independent prognostic factor for PCM. RBBP8 can be used as a potential biomarker for assessing the prognosis of PCM patients.


Assuntos
Biomarcadores Tumorais/genética , Endodesoxirribonucleases/genética , Regulação Neoplásica da Expressão Gênica , Mieloma Múltiplo/genética , Recidiva Local de Neoplasia/epidemiologia , Idoso , Biomarcadores Tumorais/análise , Medula Óssea/patologia , Carcinogênese/genética , Ciclo Celular/genética , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Endodesoxirribonucleases/análise , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Gradação de Tumores , Recidiva Local de Neoplasia/genética , Análise de Sequência com Séries de Oligonucleotídeos , Plasmócitos/patologia
20.
Tumori ; 106(2): 133-138, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31451070

RESUMO

OBJECTIVE: This study aimed to investigate the relationship between obesity and pathologic features and biochemical recurrence in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP) after neoadjuvant hormonal therapy (NHT). METHODS: A total of 422 consecutive patients with clinically localized PCa who received NHT before RP were retrospectively analyzed. Unconditional multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) regarding probability. A receiver operating characteristic (ROC) curve was used to assess the efficacy of the predictive variables. Castration resistance free survival curves were obtained using the Kaplan-Meier method, and were compared using the log-rank test. RESULTS: Being overweight was associated with an increased risk of positive margins (OR 2.281; 95% CI 1.292-4.028) after adjusting for potential confounders. The area under the ROC curve for overweight patients was larger than that for patients in the normal weight range. There was no significant difference between the overweight and normal weight groups regarding castration resistance free survival. CONCLUSIONS: Being overweight was associated with positive margins in patients with PCa undergoing RP after NHT.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Terapia Neoadjuvante , Obesidade/epidemiologia , Neoplasias da Próstata/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/cirurgia , Prognóstico , Antígeno Prostático Específico/genética , Prostatectomia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
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