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Objective: To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD). Methods: This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results: A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm2 vs. (47.9±23.8) cm2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group (P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group (P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition (P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score (r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score (r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95%CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95%CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95%CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95%CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence (OR=6.616, 95%CI: 1.383-31.656, P=0.018; OR=5.548, 95%CI: 1.062-28.973, P=0.042). Conclusion: Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.
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Composição Corporal , Doença da Artéria Coronariana , Gordura Intra-Abdominal , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , Estudos Transversais , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/fisiopatologia , Gordura Intra-Abdominal/diagnóstico por imagem , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/complicações , Calcificação Vascular/fisiopatologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
Objective: To investigate the clinical effect of the radical resection with a proximal incisal edge length of 20-25 mm and 30-35 mm in Siewert type â ¡ advanced esophagogastric junction adenocarcinoma, to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm. Methods: A retrospective cohort study method was used. The clinical data of 166 patients with Siewert type â ¡ advanced esophagogastric junction adenocarcinoma who underwent total gastrectomy from January 2017 to August 2020 in the Department of Gastrointestinal Surgery, Heji Hospital Affiliated to Changzhi Medical College were retrospectively collected. According to the proximal incisal edge length, the patients were divided into two groups: the proximal incisal edge length of 20-25 mm group (69 cases) and 30-35 mm group (97 cases). The perioperative conditions and the 6-month follow-up after the operation were compared between the two groups. Results: There was no statistically significant difference in baseline information between the patients in the two groups (P>0.05). The operations of both groups were completed. The intraoperative operation time of the proximal incisal edge length of 20-25 mm group was shorter than that in the proximal incisal edge length of 30-35 mm group ((172±24)and(206±27)min, P<0.001). There were no significant differences in the amount of intraoperative blood loss, the treatment of the diaphragm during the operation and the positive rate of intraoperative freezing of the upper incisal edge between the patients in the two groups (all P>0.05). And there was no significant differences in the first exhaust time, gastric tube removal time, first feeding time and hospital stay after the operation of the two groups (all P>0.05). There was no significant differences in the incidence of anastomotic leakage, anastomotic stenosis, reflux esophagitis and intestinal obstruction after the operation between the patients in the two groups (all P>0.05). And there was no anastomotic leakage case among the 69 cases in the proximal incisal edge length of 20-25 mm group. Postoperative pathological treatment showed no significant differences in the vascular tumor thrombus and nerve infiltration between the two groups (both P>0.05). During the 6-month follow-up, there was no death or tumor recurrence in the two groups, and there was no significant difference in body weight loss at 6 months after the operation between the two groups (P=0.178). Conclusion: When radical resection of Siewert type â ¡ advanced esophagogastric junction adenocarcinoma is performed, it is feasible to shorten the minimum safe distance of the proximal incisal edge to 20-25 mm under the premise of ensuring R0 resection. The operation time is shortened. Due to the shortening the incisal edge distance, the anastomotic tension is decreased, and the incidence of postoperative anastomotic leakage is also reduced.
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica , Gastrectomia , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias Gástricas/cirurgiaRESUMO
China is the world's largest producer and user of dyes. The mass production and widespread use of disperse azo dyes led to environmental pollutions and potential human health risks. Azo dyes in environmental media (i.e., water, soil, air, and dust), food and clothing can enter the human body through multiple exposure routes, and some of them can be metabolized to produce more toxic metabolites, which can trigger toxic effects such as allergic reactions, tumor formation, and endocrine disruptions. This study systematically reviewed the production and use of azo dyes, environmental concentrations, human exposures, toxic effects and their underlying mechanisms, and regulations and standards. Meanwhile, the research trends of azo dyes were also discussed.
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Compostos Azo , Corantes , Compostos Azo/toxicidade , China , Corantes/toxicidade , HumanosRESUMO
Osteoporosis is a disease characterized by low bone mass, most commonly caused by an increase in bone resorption that is not matched by sufficient bone formation. The most common complications of postmenopausal osteoporosis are bone-related defects and fractures. Fracture healing is a multifactorial bone regeneration process, influenced by both biological and mechanical factors related to age, osteoporosis and stability of the osteosynthesis. During the treatment of bone defects in osteoporotic conditions, imbalanced bone remodeling is the leading cause for implant failure. To overcome these problems, ethyl-2,5-dihydroxybenzoate (E-2,5-DHB), a drug that promotes bone formation and inhibits bone resorption, was used. E-2,5-DHB-incorporating titanium (Ti) implants using poly(lactic-co-glycolic acid) (PLGA) coating for local delivery of E-2,5-DHB were developed and the effects on bone healing of femoral defects were evaluated in an osteoporotic model. The release of E-2,5-DHB resulted in decreased bone resorption and increased bone formation around the implant. Thus, it was confirmed that, in the osteoporotic model, bone healing was increased and implant fixation was enhanced. These results suggested that E-2,5-DHB-coated Ti implants have great potential as an ultimate local drug delivery system for bone tissue scaffolds.
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Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Gentisatos/farmacologia , Osteoporose/fisiopatologia , Impressão Tridimensional , Próteses e Implantes , Animais , Densidade Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Modelos Animais de Doenças , Feminino , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/diagnóstico por imagem , Osteoporose/patologia , Ovariectomia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Titânio/farmacologia , Cicatrização/efeitos dos fármacosAssuntos
COVID-19 , Dermatologia , Telemedicina , Hospitais , Humanos , Pandemias , Encaminhamento e ConsultaRESUMO
Objective: Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) . Methods: Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients. Results: In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion: BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.
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Anticorpos Biespecíficos , Imunoterapia Adotiva , Humanos , Masculino , Adulto , Feminino , Anticorpos Biespecíficos/administração & dosagem , Pessoa de Meia-Idade , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Estudos Retrospectivos , Adulto Jovem , Idoso , Resultado do Tratamento , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
BACKGROUND AND OBJECTIVES: Previous literature showed a high risk of recurrence following surgical treatment in patients with gastrointestinal stromal tumours (GISTs). However, little is known about the patient- and treatment characteristics of local recurrences (LRs) in GIST patients. Therefore, this study aimed to better understand patterns of LR in surgically treated localised GIST and to describe treatment options based on our Dutch GIST Registry (DGR). METHODS: Data of primary surgically treated localised GIST between January 2009 until July 2021 were retrospectively retrieved from the DGR. RESULTS: Of 1452 patients registered in the DGR, 912 patients were included in this study. Only 3.8% (35/912) of patients developed LR, including 20 patients with LR only and 15 patients with simultaneous LR and distant metastases (DM). Median time to LR was 30 (interquartile range 8-53) months from date of surgery. Eleven percent (100/912) of patients developed only DM. A total of 2.3% (6/259) of patients treated with adjuvant treatment developed an LR during adjuvant therapy. Seventy percent of patients with LR only (14/20) were treated with surgery (85.7% R0), which was mostly combined with systemic treatment. CONCLUSIONS: Patients with primary surgically treated localised GIST have a limited risk of developing recurrence. Fifteen percent developed recurrence, of which one quarter developed an LR. Therefore, less intensified follow-up schedules could be considered, especially during treatment with adjuvant imatinib. In patients with LR only, potentially curative treatment strategies, including surgical (re-)resection, are often possible as treatment for LR.
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Antineoplásicos , Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Estudos de Coortes , Estudos Retrospectivos , Mesilato de Imatinib/uso terapêutico , Sistema de Registros , Recidiva Local de Neoplasia , Antineoplásicos/uso terapêuticoRESUMO
No consensus on standardized technique of enterostomy creation has been made meanwhile high heterogeneity of surgical procedure exists in 'stoma creation' chapters of textbooks or atlases of colorectal surgery. The present article reviews the anatomy of tendinous aponeurotic fibers which is crucial for abdominal wall tension and integrity. Through empirical practice we hypothesize a procedure of enterostomy creation basied on abdominal wall tension plus anchor suture for fascia fixation which could theoretically decrease short-term stoma complication rates and long-term parastomal hernia rates. Surgical techniques are as followed: (1) preoperative stoma site mark for de-functioning ileostomy should be positioned at the lateral border of rectus abdominis muscle (RAM) to decrease the difficulty of stoma reversal and for permanent colostomy should be placed overlying the RAM to promote adhesion; (2)Optimal circular removal or lineal opening of skin, and avoid dissection of subcutaneous tissue; (3) Lineal dissection of natural strong fascia (rectus sheath) at stoma site and blunt separation of muscular fibers. The tunnel of the fascia should be made with appropriate size without undue tension. To prevent the formation of dead space, additional suturing at fascia layer is unnecessary. (4) Anchor suture for fascia fixation at two ends of fascia opening could be considered to avoid delayed fascia disruption and parastomal hernia. (5) After pull-through of ileum or colon loop, 4-8 interrupted seromuscular sutures could be placed to attach loop to skin. For ileostomy, self-eversion of mucosa can be successful in vast majority of cases and a Brooke ileostomy is not necessary. The efficacy and safety of this procedure should be tested in future trials.
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Parede Abdominal , Enterostomia , Hérnia Incisional , Estomas Cirúrgicos , Humanos , Parede Abdominal/cirurgia , Estomas Cirúrgicos/efeitos adversos , FásciaRESUMO
Pulmonary SP-D is a defence lectin promoting clearance of viral infections. SP-D is recognized to bind the S protein of SARS-CoV and enhance phagocytosis. Moreover, systemic SP-D is widely used as a biomarker of alveolar integrity. We investigated the relation between plasma SP-D, SARS-type pneumonia and the SARS-specific IgG response. Sixteen patients with SARS, 19 patients with community-acquired pneumonia (CAP) (Streptococcus pneumonia) and 16 healthy control subjects were enrolled in the study. Plasma SP-D and anti-SARS-CoV N protein IgG were measured using ELISA. SP-D was significantly elevated in SARS-type pneumonia [median (95% CI), 453 (379-963) ng/ml versus controls 218 (160-362) ng/ml, P < 0.05] like in patients with CAP. SP-D significantly correlated with anti-SARS-CoV N protein IgG (r(2) = 0.5995, P = 0.02). The possible re-emergence of SARS or SARS-like infections suggests a need for minimal traumatic techniques for following the alveolar compartment, e.g. during testing of antivirals. We suggest that monitoring systemic SP-D may be useful in monitoring the alveolar integrity in SARS-type pneumonia. The significant correlation between plasma SP-D and anti-SARS-CoV-specific antibodies support the role for SP-D in interlinking innate and adaptive immune pathways.
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Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Proteínas do Nucleocapsídeo/imunologia , Proteína D Associada a Surfactante Pulmonar/sangue , Síndrome Respiratória Aguda Grave/imunologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Criança , Pré-Escolar , Proteínas do Nucleocapsídeo de Coronavírus , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologiaRESUMO
OBJECTIVE: The present study is aimed to investigate the regulatory effect of microRNA (miRNA or miR)-503 on endothelial functions, as well as the mechanism by which high glucose leads to injury of endothelial cells. MATERIALS AND METHODS: When reaching 80% confluency, human umbilical vein endothelial cells (HUVECs) were subjected to non-serum synchronization for 12 h, and medium of cells in high-glucose (HG) group was replaced by normal medium supplemented with 25 mmol/L D-glucose. HUVECs cultured in normal glucose (NG) medium were used as control. To overexpress miR-503, HUVECs were transfected with miR-503 mimics. To silence insulin-like growth factor-1 receptor (IGF-1R) mRNA, HUVECs were transfected with small interfering RNA (siRNA). To predict whether miR-503 targets IGF-1R, bioinformatics was performed. Quantitative Real-time polymerase chain reaction was used to determine miR-503 and IGF-1R mRNA expression, and Western blotting was employed to measure IGF-1R protein expression. Cell-Counting Kit 8 assay was used to determine HUVECs proliferation, while wound-healing assay was used to evaluate HUVECs migration. HUVECs apoptosis was investigated by measuring caspase 3 activity. RESULTS: Expression of IGF-1R in HUVECs in high glucose was decreased compared to that in normal glucose. miR-503 was predicted to target IGF-1R mRNA, and miR-503 expression in HUVECs in high glucose was higher than that in normal glucose. Overexpression of miR-503 inhibited the transcription and the translation of IGF-1R gene reducing migration, suppressed proliferation and promoted apoptosis. Transfection with IGF-1R siRNA decreased IGF-1R protein expression in HUVECs. Down-regulated IGF-1R expression reduced migration and proliferation, but promoted apoptosis of HUVECs. CONCLUSIONS: The present study demonstrates that miR-503 expression in HUVECs is elevated in high glucose condition. Also, miR-503 reduces migration and proliferation, but promotes apoptosis of HUVECs by inhibiting IGF-1R expression.
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Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glucose/farmacologia , MicroRNAs/metabolismo , Receptor IGF Tipo 1/metabolismo , Antagomirs/metabolismo , Movimento Celular , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/genética , Regulação para CimaRESUMO
OBJECTIVE: Transcriptional factor Gli1 in Hedgehog signal pathway facilitates epithelial mesenchymal transition (EMT) and is associated with invasion or proliferation of multiple tumor cells. The previous study showed the correlation between miR-132 down-regulation and glioma pathogenesis. We investigated the role of miR-132 in mediating Gli1 expression and in affecting proliferation or invasion of glioma cells. PATIENTS AND METHODS: Dual luciferase reporter gene assay was used to confirm the targeted regulation between miR-132 and Gli1. Tumor tissues at different pathological grades (grade II, III and IV) were collected from glioma patients, in parallel with brain tissues from contusion surgery. The expression of miR-132 and Gli1 was measured by RT-PCR. Glioma cell line U251 was treated with miR-132 or si-Gli1 followed by measuring the expression of Gli1, E-cadherin, Vimentin and Cyclin D1. In addition, flow cytometry and transwell assay were performed to evaluate cell invasion potency. RESULTS: Bioinformatics analysis showed the complementary binding sites between miR-132 and 3'-UTR of Gli1 mRNA. Transfection of miR-132 mimic significantly reduced luciferase activity, indicating the targeted regulatory relationship between miR-132 and Gli1 mRNA. Compared with control group, miR-132 expression was decreased and Gli1 level was elevated in glioma tissues, both of which were correlated with the pathological grade. Transfection of miR-132 mimic or si-Gli1 remarkably suppressed the expression of Gli1, Vimentin or Cyclin D1 in U251 cells, up-regulated E-cadherin expression, suppressed cell proliferation and invasion. CONCLUSIONS: Our data indicated that over-expression of miR-132 could inhibit proliferation or invasion of glioma cells via targeted inhibition of Gli1 expression.
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Neoplasias Encefálicas/patologia , Glioma/patologia , MicroRNAs/fisiologia , Proteína GLI1 em Dedos de Zinco/antagonistas & inibidores , Adulto , Idoso , Neoplasias Encefálicas/genética , Caderinas/genética , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteína GLI1 em Dedos de Zinco/genéticaRESUMO
OBJECTIVE: In this study, we tried to pool previous annotated genomic data to assess the association between ARAP3 expression and metastatic relapse (MR) risk in patients with breast cancer. Moreover, we also investigated the signaling pathways in which ARAP3 might be involved in breast cancer. MATERIALS AND METHODS: The raw microarray data (GDS5666) that compared gene transcriptional profiles of 4T1 derived lung-aggressive explant and primary tumor explant were reanalyzed to identify the dysregulated genes. ARAP3 mRNA expression, its association with MR-free survival and its co-upregulated genes in breast cancer, were studied by data mining in TCGA database and Breast Cancer Gene-Expression Miner Version 4.0 (bc-GenExMiner 4.0). RESULTS: ARAP3 is a significantly upregulated gene in the metastatic breast tumor cells. The ER- patients with high ARAP3 expression had significantly increased the risk of MR, regardless of the nodal status. Patients in ER-/Nm group with high ARAP3 expression had the highest risk of MR (HR: 1.25; 95%CI: 1.10-1.41, p<0.001). In patients with basal-like tumors, High ARAP3 level is associated with significantly worse MR-free survival (HR: 1.63, 95%CI: 1.22-2.19, p=0.001). ARAP3 might be closely related to the NOTCH4 and CDH5 signaling pathways in breast cancer. CONCLUSIONS: The expression level of ARAP3 might be a useful indicator of the metastatic likelihood of the basal-like breast tumors. ARAP3 might be involved in NOTCH4 and CDH5 related signaling pathways, but the underlying mechanism should be further studied.
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Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Biologia Computacional , Expressão Gênica , Humanos , Prognóstico , Transdução de SinaisRESUMO
OBJECTIVE: We investigated the involvement of miR-18a upregulation in autophagy regulation and paclitaxel (PTX) resistance in triple negative breast cancer (TNBC) cells. MATERIALS AND METHODS: PTX resistant MDA-MMB-231/PTX cells were generated using an intermittent, stepwise method. MiR-18a expression was assessed using qRT-PCR. The level of autophagy was assessed by Western blot analysis of LC3B expression and observation of LC3-GFP puncta formation under a fluorescence microscope. The effect of miR-18a mediated autophagy on PTX sensitivity was assessed by measuring IC50 and PTX induced cell apoptosis. RESULTS: MDA-MB-231/PTX cells had both higher miR-18a expression and basal autophagy than MDA-MB-231 cells. Enforced miR-18a overexpression directly led to increased autophagy in MDA-MB-231 cells, the effect of which was similar to that of rapamycin, a mTOR signaling inhibitor. Following Western blot analysis showed that miR-18a overexpression decreased the expression of p-mTOR and p-p70S6. Therefore, we infer that miR-18a increases autophagy level in MDA-MB-231 cells via inhibiting mTOR signaling pathway. Both drug sensitivity assay and flow cytometry analysis confirmed that the effect of miR-18a on increasing IC50 and decreasing PTX induced apoptosis in MDA-MB-231 cells could largely be abrogated by treatment with bafilomycin A1 (Baf. A1). CONCLUSIONS: MiR-18a upregulation results in enhanced autophagy via inhibiting mTOR signaling pathway in TNBC cells, which is a mechanism contributing to paclitaxel resistance.
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Autofagia/efeitos dos fármacos , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Regulação para Cima , Humanos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
This work aims to achieve deep insight into the phenomenon of phase transformation upon rapid cooling in metal systems and reveal the physical meaning of scatter in the time taken to reach crystallization. The total number of pure metals considered in this work accounts for 14. Taking pure copper as an example, the correlation between phase selection of crystal or glass and cooling rate was investigated using molecular dynamic simulations. The obtained results demonstrate that there exists a cooling rate region of 6.3 × 10(11)-16.6 × 10(11) K/s, in which crystalline fractions largely fluctuate along with cooling rates. Glass transformation in this cooling rate region is determined by atomic structure fluctuation, which is controlled by thermodynamic factors. According to the feature of bond-orientation order at different cooling rates, we propose two mechanisms of glass formation: (i) kinetic retardation of atom rearrangement or structural relaxation at a high cooling rate; and (ii) competition of icosahedral order against crystal order near the critical cooling rate.
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OBJECTIVES: This study was performed to determine whether there are differences in the operative, histopathologic, angiographic and clinical findings of isolated ostial stenosis between Oriental and western patients. BACKGROUND: Angiographic, clinical and histologic findings in isolated ostial stenosis have been reported in western but not in Oriental patients. METHODS: Six patients, all women (0.88% of a total of 684 patients who underwent coronary angiography between March 1989 and July 1991), were found to have isolated left main coronary ostial stenosis. We performed surgical ostial angioplasty with the autologous pericardial or saphenous venous patch and biopsy at the aortic arteriotomy site in four of the six patients. RESULTS: All six patients presented with severe angina (angina class III or IV) of short duration (mean +/- SD 6.2 +/- 6.2 months) and had a very low incidence of risk factors, although histopathologic examination showed typical atherosclerosis in four of the six patients. They were young to middle-aged women (mean 45 +/- 3 years) except for Patient 6 (62 years). Exercise duration was short and ST segment depression, accompanied by typical angina, was observed in many leads in the warm-up period or stage I. Despite the crucial location of the lesion, most patients had well preserved left ventricular function and normal wall motion. There was no angiographically definable collateral circulation from either ipsilateral or contralateral vessels except for grade I collateral circulation in Patient 5. Operative findings demonstrated mostly yellow atheroma in the aortic wall and left coronary ostium. Coronary angiography showed only ostial stenosis of the left coronary artery in all six patients, but operative findings documented atheromatous change in the left main coronary artery in two of the six. CONCLUSIONS: The clinical, angiographic, histopathologic and operative findings of Oriental patients were similar to those reported in western patients, but the incidence of isolated left main coronary ostial stenosis was higher in the Oriental group. Angiographically definable isolated coronary ostial stenosis may often not be true isolated ostial stenosis.
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Doença da Artéria Coronariana/etnologia , Cateterismo Cardíaco , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/patologia , Eletrocardiografia , Feminino , Humanos , Incidência , Coreia (Geográfico)/epidemiologia , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The utility of lentivirus as a gene delivery vector in the cochlea was evaluated in vitro and in vivo. Lentivirus transduction was assessed through expression analysis of a reporter gene, green fluorescent protein (GFP), integrated within the viral genome. In vitro characterization of lentivirus-GFP was assessed by infection of explants from cochleas of neonatal rat. The lentiviral vector transduced both spiral ganglion neurons (SGNs) and glial cells. In vivo characterization of lentivirus-GFP was assessed by directly infusing the vector into the guinea pig cochlea via an osmotic minipump. Sections of lentivirus-infused cochlea revealed a highly restricted fluorescence pattern limited to the periphery of the perilymphatic space. Transduction of SGNs and glial cells by lentivirus in vitro but not in vivo suggests limited dissemination of the viral vector from the perilymphatic space. The cellular and tissue architecture of the lentivirus-infused cochlea was intact and free of inflammation. Restricted transduction of cell types confined to the periphery of the perilymphatic space by the lentivirus is ideal for stable production of gene products secreted into the perilymph.
Assuntos
Cóclea/metabolismo , Técnicas de Transferência de Genes , Vetores Genéticos , Lentivirus/genética , Transgenes , Animais , Células Cultivadas , Cóclea/citologia , Imunofluorescência , Proteínas de Fluorescência Verde , Cobaias , Lentivirus/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Microscopia de Fluorescência , Neurônios/virologia , Técnicas de Cultura de Órgãos , Transdução GenéticaRESUMO
Septic shock is characterized by surges of tumor necrosis factor-alpha (TNF-alpha) along with myocardial dysfunction and systemic hypotension. TNF-alpha promotes the release of immunoreactive endothelin (ET). Because TNF-alpha is elevated in septic shock, we hypothesized that elevated levels of endothelin can contribute to cardiac dysfunction and hypotension. We infused live Pseudomonas aeruginosa into anesthetized, hemodynamically monitored young swine and measured ET and TNF-alpha. Septic swine developed systemic arterial hypotension and had significantly elevated TNF-alpha (4.15 +/- .41 U/ml at 1 h versus .40 +/- .13 U/ml at time zero) compared to control animals. ET levels were significantly elevated at 4 h (52.38 +/- 12.88 pg/ml vs. 10.45 +/- 1.82 pg/ml at time zero) and correlated negatively with the decline in cardiac output. We then passively immunized swine using anti TNF-alpha prior to the induction of sepsis to examine if TNF played a central role in the release ET. The anti TNF-alpha effectively removed circulating TNF-alpha bioactivity in septic animals. Anti-TNF-alpha-treated animals did not develop significant systemic arterial hypotension and had significant attenuation in endothelin (19.01 +/- 4.18 pg/ml at 4 h compared to 52.38 +/- 12.88 pg/ml in septic animals at 4 h) which correlated with preservation of cardiac output. TNF-alpha may cause cardiac dysfunction in sepsis syndrome through increased release of ET.