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2.
Shock ; 61(6): 951-960, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38598838

RESUMO

ABSTRACT: Objectives: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). Methods: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines. Identification of target proteins was conducted through western blotting. Histological alterations and apoptosis were scrutinized using hematoxylin-eosin staining and TUNEL staining, respectively. The ultrastructure of the endoplasmic reticulum was observed via transmission electron microscopy. Results: Puerarin significantly protected mice from LPS-induced ALI, reducing lung interstitial width, neutrophil and lymphocyte infiltration, pulmonary interstitial and alveolar edema, and lung apoptosis. Puerarin treatment also markedly attenuated levels of TNF-α and IL-1ß in both alveolar lavage fluid and serum. Furthermore, puerarin significantly attenuated LPS-induced increases in Mst1, GRP78, CHOP, and Caspase12 protein expression and blunted LPS-induced decrease in ZO-1 protein expression in lung tissues. Puerarin obviously reduced endoplasmic reticulum expansion and vesiculation. Similarly, puerarin significantly mitigated the LPS-induced reduction in HUVEC cell viability and ZO-1 expression. Puerarin also attenuated LPS-induced increase in apoptosis, TNF-α and IL-1ß, FD40 flux, and Mst1, GRP78, CHOP, and Caspase12 expression in HUVEC cells. Nevertheless, the inhibitory impact of puerarin on vascular endothelial cell injury, lung injury, and endoplasmic reticulum stress (ERS) was diminished by Mst1 overexpression. Conclusion: These findings demonstrated that the Mst1/ERS signaling pathway played a pivotal role in the development of LPS-induced vascular endothelial cell dysfunction and ALI. Puerarin exhibited the ability to attenuate LPS-induced vascular endothelial cell dysfunction and ALI by inhibiting the Mst1/ERS signaling pathway.


Assuntos
Lesão Pulmonar Aguda , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Isoflavonas , Transdução de Sinais , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Animais , Camundongos , Transdução de Sinais/efeitos dos fármacos , Masculino , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Fator de Crescimento de Hepatócito/metabolismo , Lipopolissacarídeos/toxicidade , Proteínas Proto-Oncogênicas/metabolismo , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
3.
Biochem Genet ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345758

RESUMO

In the present study, we aimed to explore the effect and underlying mechanism of metformin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). A total of 24 BALB/C mice were randomly divided into four groups: control group, LPS group and metformin group (50 or 100 mg/kg). The histological changes and cell apoptosis in kidney tissues were detected by hematoxylin-eosin staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling assay, respectively. Enzyme-linked immunosorbent assay was applied to determine serum levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), creatinine (Cre), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). Western blotting analysis were carried out to confirm the expressions of monocyte chemotactic protein-inducible protein 1 (MCPIP1), silent information regulator sirtuin 1 (SIRT1), and NF-κB p65 (acetyl K310). Compared with the control group, the mice in LPS group had glomerular capillary dilatation, renal interstitial edema, tubular cell damage and apoptosis. The serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1ß in LPS group were significantly higher than those in control group. Moreover, LPS also elevated the expressions of MCPIP1 and NF-κB p65 (acetyl K310) but decreased the expression of SIRT1 in kidney tissues. However, metformin distinctly decreased LPS-induced renal dysfunction, the serum levels of BUN, KIM-1, Cre, TNF-α, and IL-1ß. In addition, metformin markedly increased the expressions of MCPIP1 and SIRT1 but decreased the expression of NF-κB p65 (acetyl K310) in kidney tissues. Metformin prevented LPS-induced AKI by up-regulating the MCPIP1/SIRT1 signaling pathway and subsequently inhibiting NF-κB-mediated inflammation response.

4.
Sci Rep ; 13(1): 543, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631556

RESUMO

To analyze alterations of the liver appearance during the hepatobiliary phase of individuals with type 2 diabetes who are receiving gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI). Fifty-seven individuals who received Gd-EOB-DTPA-enhanced MRI and had normal liver and renal function but did not have (control group) or have type 2 diabetes (observation group) were retrospectively included in this study. The liver enhancement ratio (LER) and contrast between liver parenchyma and portal vein (LPC) were calculated from hepatobiliary phase images. Utilizing liver to kidney signal intensity, signs of the biliary system, and signs of the portal vein, a functional liver imaging score (FLIS) was calculated. Wilcoxon rank-sum test was used to assess the between-group differences in LER, LPC, and FLIS. FLIS constituent ratios between the two groups were tested using the χ2 test. The effectiveness of LER, LPC, and FLIS for identifying type 2 diabetes was assessed by receiver operating characteristic curves (ROCs). The interobserver consistency of FLIS was evaluated using the intraclass correlation coefficients. The observation group's LER and LPC were lower than the control group. The constituent ratio of the FLIS score (liver to kidney signal intensity, p = 0.011) showed a significant between-group difference. According to ROCs, LER and LPC were associated with the identification of type 2 diabetes. LER = 0.54 and LPC = 1.46 were the optimal cutoff for identifying type 2 diabetes, respectively. FLIS demonstrated excellent inter-reader agreement. The relative signal intensity of the liver during the hepatobiliary phase is decreased in patients with type 2 diabetes. This should be considered when individuals with type 2 diabetes undergo Gd-EOB-DTPA-enhanced MRI to avoid misdiagnoses, such as small hepatocellular carcinoma or abnormal liver function.


Assuntos
Diabetes Mellitus Tipo 2 , Fígado , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/patologia , Gadolínio DTPA , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
5.
Cell Biol Toxicol ; 39(5): 2331-2343, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35639300

RESUMO

Loss of expression or protein kinase B (Akt1)-mediated post-translational modification of the RNA binding protein Poly r(C) binding protein 1 (PCBP1) is closely related to metastatic advancement of breast cancer. However, the role of PCBP1 in tumorigenesis is not completely defined. Using a xenograft orthotopic model of breast tumorigenesis (4T1-Pcbp1-/-), we show here that PCBP1 knockdown-induced tumorigenesis is inhibited by activation of the WNT signaling via treating with the glycogen synthase kinase 3 beta inhibitor TWS119, but not the Akt2/Akt3 inhibitor GSK690693. Mass cytometry-based evaluation of the tumor microenvironment (TME) revealed significantly more regulatory T cells (Tregs) and significantly less cytotoxic T cells in 4T1-Pcbp1-/-mice treated with saline control in comparison to mice treated with TWS119. Infiltrating cytotoxic T cells were phenotypically and functionally exhausted. Treatment with TWS119 resulted in rescue of cytotoxic T cell function and inhibition of suppressor activity of Tregs. Using cytotoxic T cells isolated from healthy donors, we show that TWS119-induced WNT signaling-mediated inhibition of cytotoxic T cell expansion is reliant on expression of PCBP1. In conclusion, decreased PCBP1 expression favors breast tumorigenesis by potentiating skewing of tumor infiltrating T cells towards Tregs, thereby effectively suppressing anti-tumor immunity.


Assuntos
Neoplasias da Mama , Via de Sinalização Wnt , Animais , Feminino , Humanos , Camundongos , Carcinogênese , Transformação Celular Neoplásica , Proteínas de Ligação a DNA , Proteínas de Ligação a RNA/genética , Microambiente Tumoral
6.
Ann Noninvasive Electrocardiol ; 28(2): e13025, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36479729

RESUMO

Congenital left ventricular diverticulum (CL.koVD) refers to a localized cystic protrusion of the ventricular wall that interacts with the heart cavities through a narrow channel and is a rare heart malformation. In recent years, many cases of this disease involving infants and children have been reported, while few cases involving adults have been described. The case of an adult with CLVD who underwent successful surgery was retrospectively evaluated. The echocardiography examination indicated that the apical myocardium of the left ventricle was thin and bulging outward and that the contractile movement was significantly reduced. During the surgery, it was observed that the left ventricle was enlarged, and a left ventricular diverticulum structure was observed on the left side of the apex. A bovine pericardial patch of the corresponding size was used to continuously suture and repair the internal orifice of the diverticulum. The postoperative pathology revealed that the resected sample was composed of full myocardial tissue. This report focused on the imaging characteristics of left ventricular diverticula to improve the understanding of CLVD. With its simple, economical, and noninvasive characteristics, echocardiography presents the best option for diagnosing a ventricular diverticulum.


Assuntos
Divertículo , Cardiopatias Congênitas , Lactente , Criança , Humanos , Adulto , Animais , Bovinos , Estudos Retrospectivos , Eletrocardiografia , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Divertículo/diagnóstico por imagem , Divertículo/cirurgia
7.
J Transl Med ; 20(1): 276, 2022 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-35717238

RESUMO

BACKGROUND: Patients with triple-negative breast cancer (TNBC) are better responders to neoadjuvant chemotherapy; however, they are poor in the durability of response with decreased overall and progression-free survival. METHODS: Given that significant improvements have been reported with PD-L1-PD-1 blockade in different cancers, we evaluated the in vitro and in vivo effectiveness of Tomivosertib (eFT-508), an anthracycline, adriamycin, and MNK1/2 inhibitor, which has been previously shown to inhibit translation of PD-L1 in mice model of liver cancer, alone or in combination using BC cell lines and an orthotopic xenograft mice model using the TNBC cell line MDA-MB-231. RESULTS: Within the context of The Cancer Genome Atlas (TCGA) dataset, expression of CD274 mRNA, which encodes programmed death-ligand 1 (PD-L1), was found to be significantly overexpressed in TNBC patients compared to patients with HER2 + or luminal breast cancer (BC). Even within TNBC sub-types, CD274 expression was significantly higher in the immune modulatory subtype (TNBC-IM). BC cells exhibited high IC50 = 0.85 ± 0.07 nM with Adriamycin and significantly lower IC50 = 0.23 ± 0.04 nM with eFT-508 (P < 0.01). Combination treatment showed in vitro synergism on chemosensitivity. Combination therapy also exhibited a synergistic effect on inhibition of tumor growth and lung colonization in vivo. Mass cytometry-based evaluation of the tumor microenvironment revealed significant attenuation of both PD-L1 and PD-L2 following mono- or combination therapy with eFT-508. CONCLUSIONS: Treatment with eFT-508 restored effector and cytotoxic function of tumor-infiltrating CD8 + T cells in mice. The remarkable efficacy observed both in vitro and in vivo, and clinical synergism with adriamycin, highlights the potential of eFT-508 as an alternative, yet more efficacious, therapeutic option for patients with TNBC.


Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Animais , Antígeno B7-H1/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Camundongos , Piridinas , Pirimidinas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Microambiente Tumoral
8.
J Cancer Res Ther ; 17(5): 1269-1274, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34850777

RESUMO

OBJECTIVES: The objective of the study was to assess the clinical efficacy of computed tomography (CT)-guided cryoablation as a means to treat adrenal metastasis (AM) secondary to lung cancer. MATERIALS AND METHODS: This study was a single-center retrospective study that analyzed 39 consecutive patients with AM secondary to lung cancer who underwent CT-guided cryoablation in our center. The rates of complete ablation, local recurrence, local recurrence-free survival (RFS), and overall survival (OS) were analyzed. RESULTS: The rates of primary and secondary complete ablation were 94.9% and 100%, respectively, and none of the patients suffered from a hypertensive crisis associated with the treatment. Over the follow-up period, 20.5% of the patients experienced local recurrence, and the median RFS duration was 26 months. The cumulative 1-, 3-, and 5-year local RFS rates in this study were 84.6%, 51.3%, and 5.9%, respectively. Extra-adrenal gland metastases were detected in five patients. Over the course of follow-up, 26 patients died. The mean OS duration was 34 months with cumulative 1-, 3-, and 5-year OS rates of 89.7%, 53.4%, and 8.3%, respectively. Advanced age (P = 0.001), primary adenocarcinoma (P = 0.006), other primary lung cancers (P = 0.038), and primary Stage III lung cancers (P = 0.007) were all found to be independent predictive factors of poor OS in these patients. CONCLUSION: CT-guided cryoablation can be safely and effectively used to control AM secondary to lung cancer, and patients with AM secondary to lung squamous cell carcinoma may be best suited for this form of treatment.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Ablação por Cateter/mortalidade , Criocirurgia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Segunda Neoplasia Primária/cirurgia , Cirurgia Assistida por Computador/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Segunda Neoplasia Primária/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos
10.
J Cardiothorac Surg ; 16(1): 263, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34537071

RESUMO

BACKGROUND: Fatal pericardial tamponade caused by aortic or atrial perforation due to erosion of atrial septal occluders has been reported previously, but the timing of erosion is uncertain, and the process is also unclear. CASE PRESENTATION: We present a case of a 5-year-old boy with erosion of the aorta and atrium by the occluder not leading to perforation or pericardial tamponade because of early detection and timely surgery. A small amount of pericardial effusion may be the only manifestation of early erosion. This case firstly revealed the early process of device erosion in children. CONCLUSIONS: An absent aortic rim may be a higher risk factor for erosion than oversized device for a child, and it is wise to choose a relatively small occluder or change to surgery. This may be helpful for preventing and treating serious complications caused by erosion of the occluder.


Assuntos
Tamponamento Cardíaco , Traumatismos Cardíacos , Comunicação Interatrial , Dispositivo para Oclusão Septal , Cateterismo Cardíaco/efeitos adversos , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/etiologia , Criança , Pré-Escolar , Comunicação Interatrial/cirurgia , Humanos , Masculino , Dispositivo para Oclusão Septal/efeitos adversos , Resultado do Tratamento
12.
Orthop Surg ; 13(2): 501-505, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33570256

RESUMO

OBJECTIVES: To explore the trend of changes in the serum prealbumin (PA) level in patients with spinal tuberculosis during the perioperative period and its relationship with postoperative incision complications. METHODS: A retrospective study was performed by enrolling 162 patients (82 men and 80 women) with spinal tuberculosis who had been admitted to the Tianjin Haihe Hospital from June 2013 to June 2017. The included patients were then assigned to the elderly group (≥65 years of age, n = 35) and the non-elderly group (<65 years of age, n = 127). The chemotherapy regimen was 3HREZ/9HRE, in combination with nutritional support for 3-4 weeks, as well as one-stage debridement and (or) bone graft fusion and internal fixation. The serum PA levels of patients with spinal tuberculosis at admission, prior to surgery, and at 2 and 4 weeks after surgery were collected, and incision healing and sinus formation were observed for 3 months. Changes in serum PA levels of all patients at different time points were observed using one-way analysis of variance. Pairwise comparison at different time points was performed using the least significant difference method and comparison of serum PA levels between different groups at the same time points was subjected to t-test. The χ2 -test was used for comparison of the incidence of incision complications between different groups and between different subgroups based on different PA levels. RESULTS: There was a gradual increased trend in the PA level from admission to 4 weeks after surgery in all patients [(0.14 ± 0.03) g/L < (0.16 ± 0.04)g/L < (0.22 ± 0.04) g/L < (0.25 ± 0.04) g/L]. The increase in the non-elderly group was higher than that in the elderly group (P < 0.01). Furthermore, the incidence of incision complications in the elderly group was higher than in the non-elderly group (14.29% > 1.78%, P < 0.01). The serum PA level was graded in accordance with NRS2002. There were 88 patients with preoperative grade 0-1 serum PA level (≥0.16g/L) who had no incision complications. The incidence of incision complications in patients with grade 3 serum PA level (<0.10 g/L, 9 patients) was higher than in patients with grade 2 (0.100-0.159 g/L, 66 patients) (44.44% > 6.06%, P < 0.01). CONCLUSION: Changes in serum PA level in patients with spinal tuberculosis during the perioperative period are consistent with the trend of inflammation control and nutrition improvement, and are correlated with the incidence of incision complications after surgery. The relationship between the changes and the timing of surgery is worthy of future research.


Assuntos
Complicações Pós-Operatórias/etiologia , Pré-Albumina/metabolismo , Ferida Cirúrgica , Tuberculose da Coluna Vertebral/cirurgia , Cicatrização , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Hum Cell ; 32(4): 504-514, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493246

RESUMO

The objective of this study was to examine the function of the long non-coding RNA (lncRNA) HOXA11-AS in hepatocellular carcinoma (HCC). In total, samples from liver tumor and surrounding normal liver tissues were collected from 66 cases of HCC patients. Normal liver cell line HL-7702 and HCC cell lines HepG2, Hep3B, MHCC-97H and BEL7402 were used. Cells were transfected with different small interference RNAs or vectors. Then, transwell assay, qRT-PCR, CHIP, RIP and Western blot experiments were performed. We found that the HOXA11-AS expression level was higher in HCC samples than surrounding normal liver tissues. And the higher expression level of HOXA11-AS in HCC patients indicated a lower 5-year survival rate. Knockdown of HOXA11-AS in HepG2 and Hep3B cells caused impaired cell invasion and migration abilities. Otherwise, upregulation of HOXA11-AS in MHCC-97H and BEL7402 cells displayed higher invasion and migration capabilities. We also demonstrated that HOXA11-AS could inhibit miR-124 expression by binding to EZH2. Furthermore, overexpression of miR-124 or knockdown EZH2 expression could reverse the HOXA11-AS-induced migration and invasion effects in HCC cells. In summary, the high HOXA11-AS expression in HCC patients is associated with the poor outcome. HOXA11-AS could inhibit miR-124 expression by binding to EZH2 and thus promoted the migration and invasion of HCC cells.


Assuntos
Carcinoma Hepatocelular/genética , Movimento Celular/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias Hepáticas/genética , MicroRNAs/genética , Linhagem Celular , Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Ligação Proteica
14.
J Cardiothorac Surg ; 14(1): 130, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272459

RESUMO

BACKGROUND: There are no unanimous reports on different layouts and classifications of multi-hole secundum atrial septal defects (MHASD) and subsequent standardized occlusion techniques. The MHASD can be isolated or cribriform with variable inter-defects distance. In this retrospective study, experience-based classification and two approaches-based occlusion results are presented. METHODS: We retrospectively collected and analyzed data of 150 MHASD patients from 1320 patients who underwent atrial septal defect occlusion in our institute. The MHASD patients were categorized into 4 types; type A, B, C and D and occluded under exclusive transesophageal echocardiographic guidance. According to different types, 122 patients were occluded using peratrial approach and 28 patients via percutaneous approach. In type A, single device implantation is performed to occlude the large hole and squeeze the small one. For type B single or double-device deployment was performed depending on an inter-defects distance. In type C and D, a patent foramen-ovale (PF) device was selectively positioned to the central defect to occlude the central defect and cover the peripheral ones. In peratrial approach, 8 patients underwent inter-defects septal puncture technique to achieve single-device occlusion. The intracardiac manipulation time, procedural time, double device deployment, redeployment rate, residual shunt, and proportions were analyzed between (and within peratrial technique) two techniques. RESULTS: Successful occlusion was achieved in all 150 patients. Single device occlusion was applied in 78/84 type A and 22/37 type B patients (p < 0.05). Double device occlusion was more applicable to type B than A patients (p < 0.01). Sixteen of 21 type C and all type D patients used PF device for a satisfactory occlusion. Redeployment of the device occurred frequently in type B patients than A (p < 0.01). The intracardiac manipulation time and procedural time were shorter in type A than B (p < 0.05). The intracardiac manipulation time was also shortened in type A peratrial than type A percutaneous group (p < 0.05). Complete occlusion rate for all patients at discharge was 70% and rose to 82% at 1 year follow up. CONCLUSIONS: The diverse layouts and classification of MHASDs can help to choose different techniques and proper devices of different kinds to achieve better occlusion results.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Comunicação Interatrial/classificação , Comunicação Interatrial/cirurgia , Dispositivo para Oclusão Septal , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos/instrumentação , Ecocardiografia Transesofagiana , Feminino , Seguimentos , Comunicação Interatrial/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Lab Chip ; 19(14): 2346-2355, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31232418

RESUMO

Nanoscale extracellular vesicles (nEVs) have recently demonstrated potential value in cancer diagnostics and treatment monitoring, but translation has been limited by technical challenges in nEV isolation. Thus, we have developed a one-step nEV isolation platform that utilizes nEV size-matched silica nanostructures and a surface-conjugated lipid nanoprobe with an integrated microfluidic mixer. The reported platform has 28.8% capture efficiency from pancreatic cancer plasma and can sufficiently enrich nEVs for simpler positive identification of point mutations, particularly KRAS, in nEV DNA from the plasma of pancreatic cancer patients.


Assuntos
Vesículas Extracelulares/química , Lipídeos/química , Nanoestruturas/química , Dióxido de Silício/química , Linhagem Celular Tumoral , Vesículas Extracelulares/patologia , Estudos de Viabilidade , Humanos , Dispositivos Lab-On-A-Chip , Mutação , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética
16.
Gene ; 697: 175-183, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-30772517

RESUMO

Ischemia reperfusion injury (IRI), a complex phenomenon often encountered in surgery, can lead to local and distant tissue destruction and sometimes even death. microRNA-203 (miR-203) has been reported to negatively regulate ischemia induced microglia activation with a feedback to myeloid differentiation primary-response gene 88 (MYD88). Accordingly, our study is to verify the effect of miR-203 and MYD88 on mice in IRI after total knee arthroplasty (TKA). After establishment of IRI mouse model, heart rate (HR) and mean arterial pressure (MAP) in mice were determined. The functional role of miR-203 in IRI was determined using ectopic expression, knockdown and reporter assay experiments. Levels of interferon γ (IFN-γ), interleukin 10 (IL-10), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected, and expression of miR-203, MYD88, toll-like receptor 4 (TLR4), Faslg, Cleaved-Caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) was evaluated. Initially, HR and MAP were decreased in IRI mice. Forced expression of miR-203 and silencing of MYD88 increased levels of SOD and IL-10 but decreased levels of MDA, CK, LDH, TNF-α, IL-6 and IFN-γ. Additionally, forced expression of miR-203 and silencing of MYD88 increased Bcl-2 expression but decreased MYD88, TLR4, Cleaved-Caspase-3, Falsg and Bax expression. MYD88, a target gene of miR-203, was decreased following miR-203 promotion, while the TLR signaling pathway inactivation occurred following MYD88 silencing. Generally, our study demonstrated the protective effects of miR-203 on mice with IRI after TKA through inhibiting TLR signaling pathway by negatively regulating MYD88.


Assuntos
Artroplastia do Joelho/efeitos adversos , MicroRNAs/antagonistas & inibidores , Fator 88 de Diferenciação Mieloide/antagonistas & inibidores , Traumatismo por Reperfusão/genética , Receptores Toll-Like/antagonistas & inibidores , Animais , Apoptose/fisiologia , Artroplastia do Joelho/métodos , Citocinas , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismo
17.
J Food Sci ; 83(10): 2612-2621, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30192013

RESUMO

We investigated the protective effects and possible mechanisms of Aplysin against alcohol-induced liver injury. Rats were given daily either alcohol only (alcohol model group; 8 to 12 mL/kg body weight), one of three doses of Aplysin (50, 100, or 150 mg/kg Aplysin) plus alcohol, or volume-matched saline. After 6 weeks, the effects of Aplysin were assessed in terms of changes in histology, biochemical indices, and DNA oxidative damage. Potential mechanisms were analyzed through measurements of lipid peroxidation, antioxidant defense systems, expression of cytochrome P450 2E1, and expression of apoptosis-related genes. We found that Aplysin significantly protected the liver against alcohol-induced oxidative injury, evidenced by improved hepatic histological structure, inhibited alcohol-induced elevation of serum biochemical indices, attenuated extents of hepatocellular DNA damage. At a mechanistic level, Aplysin alleviated alcohol-induced oxidative stress as illustrated by the revivification of erythrocyte membrane fluidity, the attenuation of glutathione depletion, the restoration of antioxidase activities, and reduced malondialdehyde overproduction. Furthermore, the mRNA levels of Bax, cytochrome c, and cytochrome P450 2E1 were significantly down-regulated, whereas those of Bcl-2 and caspase-9 and caspase-3 were markedly up-regulated. These findings suggest that Aplysin provides significant protection against alcohol-induced liver injury, possibly through alleviating oxidative damage and modulating endogenous apoptosis-related genes expression. PRACTICAL APPLICATION: Many natural components derived from alga have been used in the food, cosmetics, and biomedicine industries. Aplysin, a marine bromosesquiterpene, was extracted from the red alga Laurencia tristicha, which could effectively protect against alcohol-induced liver injury, might be a potential natural sources for preventing alcoholic liver damage.


Assuntos
Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Etanol/efeitos adversos , Hidrocarbonetos Bromados/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Antioxidantes/farmacologia , Caspase 3/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Dano ao DNA/efeitos dos fármacos , Membrana Eritrocítica/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Laurencia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Extratos Vegetais , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar
18.
Toxicol Lett ; 296: 163-172, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29908847

RESUMO

Roundup® is extensively used for weed control worldwide. Residues of this compound may lead to side effects of the male reproductive system. However, the toxic effects and mechanisms of Roundup® of male germ cells remain unclear. We aimed to investigate the apoptosis-inducing effects of Roundup® on mouse male germ cells and explore the role of a novel tumor suppressor XAF1 (X-linked inhibitor of apoptosis-associated factor 1) involved in this process. We demonstrated that Roundup® can impair spermatogenesis, decrease sperm motility and concentration, and increase the sperm deformity rate in mice. In addition, excessive apoptosis of germ cells accompanied by the overexpression of XAF1 occurred after Roundup® exposure both in vitro and in vivo. Furthermore, the low expression of XIAP (X-linked inhibitor of apoptosis) induced by Roundup® was inversely correlated with XAF1. Moreover, the knockdown of XAF1 attenuated germ cell apoptosis, improved XIAP expression and inhibited the activation of its downstream target proteins, caspase-3 and PARP, after Roundup® exposure. Taken together, our data indicated that XAF1 plays an important role in Roundup®-induced male germ cell apoptosis. The present study suggested that Roundup® exposure has potential negative implications on male reproductive health in mammals.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas F-Box/biossíntese , Células Germinativas/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas Reguladoras de Apoptose , Caspase 3/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glicina/toxicidade , Proteínas Inibidoras de Apoptose/biossíntese , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/ultraestrutura , Glifosato
19.
J Environ Pathol Toxicol Oncol ; 37(4): 341-350, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30806240

RESUMO

Cancer, the uncontrolled growth of cells, is a major disease that threatens the worldwide population. Among all cancer types, lung cancer has the highest morbidity rate, with a survival rate of less than 5%. Various studies have focused on discovering a potent anticancer drug that will increase the survival rate of lung cancer patients. Lutein (3,3'-dihydroxy-ß, ε-carotene), a carotenoid present in fruits and vegetables, is one such compound that possesses excellent antioxidant properties. The present study was designed to determine the anticancer effect of lutein against A549, a non-small-cell lung cancer cell line. The cytotoxic effect of lutein against lung cancer cells (A549 and HCC827) and normal cells (BEAS-2B) was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The Transwell assay was performed to detect the inhibitory potential of lutein against cell invasion and migration of A549 cells. The induction of apoptosis by lutein in A549 was analyzed by a double-staining technique using TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling) and DAPI (4',6-diamidino-2-phenylindole) staining assays to confirm the molecular mechanism exhibited by lutein to induce apoptosis through regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling molecules that are often deregulated in cancerous condition. The results show that lutein inhibits the PI3K/AKT signaling pathway and induces apoptosis in A549, which may therefore be used as a potent natural anticancer drug with no side effects to treat lung cancer.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Luteína/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Antineoplásicos/uso terapêutico , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular/efeitos dos fármacos , Humanos , Marcação In Situ das Extremidades Cortadas , Luteína/uso terapêutico , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-28966872

RESUMO

Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. The pathophysiological roles and clinical value of EVs are under intense investigation, yet most studies are limited by technical challenges in the isolation of nanoscale EVs (nEVs). Here, we report a lipid nanoprobe that enables spontaneous labelling and magnetic enrichment of nEVs in 15 minutes, with isolation efficiency and cargo composition similar to what can be achieved by the much slower and bulkier method of ultracentrifugation. We also show that the lipid nanoprobes, which allow for downstream analyses of nucleic acids and proteins, enabled the identification of EGFR and KRAS mutations following nEV isolation from blood plasma from non-small-cell lung-cancer patients. The efficiency and versatility of the lipid nanoprobe opens up opportunities in point-of-care cancer diagnostics.

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