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3.
Endocrine ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32180116

RESUMO

PURPOSE: There is an increasing agreement that acromegaly caused by growth hormone (GH) cell adenoma has two distinct subtypes: densely granulated (DG) and sparsely granulated (SG). We hypothesized that differential molecular signatures may explain their behavior. METHODS: Total transcriptome sequencing was performed on ten DG and seven SG adenomas. The differentially expressed RNAs were identified by bioinformatic analyses, and a candidate RNA was verified by quantitative real-time PCR. Immunohistochemical staining was also performed to detect the protein expression of the candidate. Clinical parameters were correlated with protein expression. Subsequently, cell proliferation, colony formation, and cell cycle progression were analyzed after knockdown of the candidate in pituitary GH3 cells. Activation of the cAMP pathway was assessed by ELISA and Western blot. RESULTS: We confirmed that there were obvious differentially expressed genes between the subtypes. Through gene profiling, we discovered that an orphan adhesion G protein-coupled receptor, GPR64, was overexpressed in more aggressive SG adenomas. Noticeably, GPR64 knockdown significantly inhibited the proliferation of GH3 tumor cells and decreased colony formation. The knockdown also induced cell cycle arrest in GH3 tumor cells. Further studies revealed that GPR64 knockdown decreased cAMP levels and the ratios of p-CREB/CREB, indicating that it suppressed the cAMP/CREB pathway. CONCLUSIONS: Our results indicated that GPR64 may promote aggressiveness in SG-type GH cell adenomas and that it is a key factor regulating the cAMP pathway to promote aggressiveness of GH cell adenomas.

4.
Microvasc Res ; 130: 103990, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32088162

RESUMO

BACKGROUND: Assessment of the coronary microcirculation remains challenging. OBJECTIVE: we explored the feasibility of evaluating the coronary microvasculature in rats with myocardial infarction (MI) using a three-dimensional visualization technique. METHODS: Animals were divided into the sham operation group (S), MI 45 min group (M45), and MI 180 min group (M180). Opened microvessels were labelled with the fluorescent dye DiI (1, 1'-dioctadecyl-3, 3, 3'3'-tetramethylindo carbocyanine perchlorate) using a heart perfusion method. The microvascular distribution and opening status were observed under laser scanning confocal microscopy, which was adjusted to facilitate evaluation of subjects around 6 to 20 µm. RESULTS: Microvascular vessels (6-20 µm) were successfully labelled by DiI. Intact and clear three-dimensional microvascular structures were observed in myocardium of sham rats and remote non-infarct myocardial tissue of MI rats, while there was almost no microvascular structure in the infarct area of the M45 group, and only a small amount of microvascular visualization was visualized in the infarct area of the M180 group. The microvascular area and microvascular density in M45 group and M180 group in the infarct border zone were significantly lower than corresponding area in S group. CONCLUSION: Three-dimensional visualization of opened coronary microvascular vessels is feasible in DiI-labelled myocardium in this rat MI model. This novel technique might be useful for defining the underlying mechanisms of coronary microvascular diseases and observe the efficacy of various therapy strategies on coronary microvessels.

5.
Infect Dis Ther ; 9(1): 165-174, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32096145

RESUMO

INTRODUCTION: Electronic bronchoscopy is invasive and may cause pain. This study aimed to explore the clinical value of virtual bronchoscopic navigation (VBN) in the diagnosis of benign central airway stenosis (CAS) secondary to tracheobronchial tuberculosis (TBT). METHODS: Sixty-eight patients with benign CAS caused by TBT were recruited between July 2015 and December 2017. The location, length and diameter of stenoses were independently determined by VBN and electronic bronchoscopy (EOB), and the sensitivity and specificity of VBN in identifying stenosis were assessed with EOB as the gold standard. RESULTS: In 68 patients with TBT, the overall coincidence between EOB and VBN in the identification of stenosis was 100%. A total of 188 sites were selected from the central airway, and the stenosis was graded into 0%, ≤ 25%, 26-50%, 51-75%, 76-90% and > 90%. The sensitivity of VBN in determining the degree of stenosis was 98.45%, 100.00%, 100.00%, 100.00%, 84.62% and 0.00%, respectively; the specificity was 91.53%, 96.07%, 97.09%, 97.08%, 97.14% and 97.30%, respectively; the accuracy rate was 96.28%, 96.28%, 97.34%, 97.34%, 96.28% and 95.7%, respectively. The length of airway stenosis on EOB was divided into < 10 mm, 10-30 mm, 30-50 mm and > 50 mm. There was no significant difference in the length of airway stenosis between VBN and EOB (t = 0.083, P = 0.936; t = 1.340, P = 0.199; t = 1.297, P = 0.216; t = 2.186, P = 0.081). In three patients who received stent placement, VBN was able to accurately assess the postoperative expansion. CONCLUSION: VBN is helpful for the diagnosis of TBT-induced CBS and may provide important information on the location, length, diameter and cross-sectional area of stenosis for further EOB examination and interventional therapy. VBN is recommended for patients with TBT and those with contradictions to bronchoscopy, as well as for regular follow-up of stable TBT, because it reduces the incidence of injury, avoids repeat operations and shortens treatment time.

6.
Thorac Cancer ; 11(3): 748-753, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989777

RESUMO

BACKGROUND: The ProCore 25-gauge needle is a novel specifically designed puncture needle for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which may improve the puncture efficiency of the procedure while ensuring the diagnostic rate. The aim of the present study was to evaluate the diagnostic accuracy, mRNA yield, and complication rate of 25-gauge needles compared to those of 22-gauge needles in the evaluation of mediastinal and hilar lymphadenopathy. METHODS: A total of 39 patients undergoing EBUS-TBNA at our institution were evaluated. All the procedures were performed by an experienced endoscopist formally trained in interventional pulmonology. Both the traditional 22-gauge and ProCore 25-gauge needles were used at each lymph node station. For all specimens obtained via EBUS-TBNA, 50 µL was used to extract mRNA and detect the RNA concentration, whereas the other part was sent to the pathological evaluation. χ2 test and t-test were performed to determine the differences between the two types of the needles. A P-value of <0.05 was considered significant. RESULTS: A total of 88 lymph nodes were punctured by the two needles separately. The diagnostic accuracy for each puncture between the two needles did not show any significant difference (P > 0.05). No serious procedure-related complications were reported. In addition, the mRNA concentration did not differ between the two types of needles (P > 0.05). CONCLUSION: The ProCore 25-gauge needle gained a similar diagnostic yield with less puncture time and frequency compared with the 22-gauge needle.

7.
Acta Diabetol ; 57(2): 141-150, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31367992

RESUMO

AIMS: Present study observed the impact of blood glucose control on sympathetic and vagus functional status in type 2 diabetes mellitus (DM) patients through observing the association between glycosylated hemoglobin (HbA1c) level and sympathetic and vagus functional status detected by heart rate recovery (HRR) and heart rate variability (HRV) assessments. METHODS: Consecutive hospitalized DM patients were divided into well glycemic control group (HbA1c < 7.0%, group WGC, n = 100) and poor glycemic control group (HbA1c ≥ 7.0%, group PGC, n = 100), 100 hospitalized patients without DM served as control group (group C). All subjects underwent blood biochemistry test, treadmill exercise testing and 24-h Holter monitoring. RESULTS: HRR and HRV parameters were significantly lower in group WGC and PGC than in group C. Standard deviation of NN intervals (SDNN), standard deviation of all 5-min average NN intervals (SDANN), very low frequency (VLF) values were significantly lower in group PGC than in group WGC. HbA1c level was negatively correlated with HRR1, SDNN, SDANN, VLF, low frequency and high frequency. Logistic regression analysis showed that lower SDNN, SDANN and VLF values were risk factors for high HbA1c levels in DM patients after adjusting for gender, age and beta-blocker use in the model 1, and for gender, age, beta-blocker use, coronary artery disease and hypertension in the model 2. CONCLUSIONS: Present results indicate that sympathetic and vagal functional status are impaired independent of HbA1c level, while poor glycemic control is related to more significant neurocardiac dysfunction in DM patients.

8.
J Clin Neurosci ; 71: 26-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31859176

RESUMO

An increased serum phosphate (P) level is common in acromegaly patients, however, the relationships among P, growth hormone (GH), insulin-like growth factor 1 (IGF-1) and disease status remain unknown. To reveal these relationships, we examined the association of P with comprehensive clinical data. We measured the serum P, calcium, GH, oral glucose tolerance test-GH (OGTT-GH), IGF-1, and insulin-like growth factor binding protein-3 (IGBP-3) levels in 103 acromegaly patients. SAGIT® was used to assess the disease status comprehensively. Spearman's rank correlation coefficient was obtained to evaluate the associations among the above parameters. Stepwise multiple linear regression analysis was performed to investigate factors independently associated factors with the SAGIT scores. The area under the receiver operating characteristic curve (AUCROC) was used to evaluate the efficacy of the percentage change in the serum phosphate level in predicting remission in patients with postoperatively discordant GH and IGF-1 levels. Hyperphosphatemia was found in 68.9% of patients at baseline. The serum P level was higher in the non-remission group, but no correlation was found between hyperphosphatemia and remission. We revealed a significant correlation between the P level and SAGIT® score in patients both preoperatively (r = 0.659, p = 0.000) and 1-year postoperatively without remission patients (r = 0.534, p = 0.027). All biochemical levels decreased significantly postoperatively, and the GH and OGTT-GH levels achieved early stability (1 month); however, the P, IGF-1 and IGBP-3 levels showed a gradual decline. A percentage change in P of -8.12% is recommended as a cut-off value for predicting remission in patients with postoperatively discordant GH and IGF-1 levels. As a metabolic product which affected by the GH/IGF-1 axis, serum P appears to more closely reflect the comprehensive disease status in acromegaly. When the GH and IGF-1 levels are discordant during follow-up, perioperative change in the P level may be a potential predictor of remission.

9.
Ann Transl Med ; 7(20): 567, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807548

RESUMO

Background: In the absence of a positive sputum bacteriological result, pathological and bacteriological examinations of lung lesion biopsies are important methods to confirm bacteriological-negative tuberculosis. Endobronchial ultrasonography with guide sheath (EBUS-GS) and electromagnetic navigation bronchoscopy (ENB) are two new endobronchial diagnostic techniques, the combination of which has greatly facilitated the diagnosis of peripheral pulmonary lesions and is an especially useful, minimally invasive, effective diagnostic method for bacteriologically-negative tuberculosis cases. Methods: A total of 78 patients were included in this study with suspected pulmonary tuberculosis based on clinical manifestations, laboratory tests, and imaging studies. The patients underwent a high-resolution chest CT scan before bronchoscopy, A method was selected (EBUS-GS alone, or EBUS-GS + ENB) based on the lesion site and the level and angle of the bronchus involved. After the lesion was found, a puncture needle, biopsy forceps, and brushing forceps were used to collect a tissue sample. Results: Forty-four patients were diagnosed with tuberculosis; 1, nontuberculous Mycobacteria (NTM) lung disease; 15, lung cancer; 15, pulmonary infection; 1, allergic bronchopulmonary aspergillosis (ABPA); and 2, pneumoconiosis. A total of 25 patients of TB (56.8%) were successfully diagnosed with EBUS-GS plus ENB. Among the patients with confirmed diagnosis, 9 were diagnosed with pathological examination; 4, genetic analysis; 11, positive smear; and 14, positive culture. Conclusions: The introduction of EBUS and ENB in China has provided a new direction for the diagnosis of atypical bacteriological-negative tuberculosis, as the techniques are less invasive and less expensive than thoracoscopy.

10.
Ann Transl Med ; 7(20): 586, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807567

RESUMO

Background: Acute variceal bleeding is one of the critical complications in patients with liver cirrhosis. Severe renal vasoconstriction in consequence of low peripheral vascular resistance triggers the reduction of glomerular filtration rate (GFR), and thus induces acute kidney injury (AKI)/hepato-renal syndrome (HRS). Terlipressin and octreotide have been used in the management of cirrhotic patients with variceal bleeding. Also, terlipressin has been recommended as the international first-line pharmacological therapy for the treatment of HRS. In addition, the use of renal functional magnetic resonance imaging (fMRI) has become increasingly prevalent in research and clinical applications. However, the renal function-protective effect of terlipressin and octreotide and the value of fMRI in monitoring renal function remains unclear in patients with cirrhosis undergoing acute variceal bleeding. Methods: This is a multicenter, randomized controlled trial (RCT). Participants will be 1:1 assigned randomly into either terlipressin or octreotide groups. Sixty participants with clinically and/or pathologically diagnosed cirrhosis and active gastroesophageal variceal bleeding (GVB) will be recruited in several sites in China. Participants will receive either the treatment of terlipressin or octreotide after assigned into each group. The primary end point for the trial is the renal function. The secondary end points are (I) renal perfusion; (II) renal blood oxygenation; (III) failure to control bleeding; (IV) intra-hospital rebleeding; (V) intra-hospital mortality; (VI) adverse events (AE); (VII) overall survival. Statistical analysis including multivariate Cox regression, Kaplan-Meier analysis with log-rank test, etc. will be conducted. Discussion: The study will provide new insight into the protection of renal function in the process of the treatment of variceal bleeding in patients with cirrhosis. Trial registration number: NCT04028323.

11.
Theranostics ; 9(24): 7140-7155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695758

RESUMO

Rationale: Peri-prosthetic osteolysis (PPO) is mainly induced by wear particles and represents the leading cause of implant failure and revision surgery. Previous studies have identified mitigation of wear particle-induced inflammation and bone resorption as the main approaches to treat PPO. Recently, wear particle-induced reduction of bone formation around the prosthesis was identified as a major factor in the development of PPO. Acetyl-11-keto-ß-boswellic acid (AKBA), a derivative of frankincense, has been shown to play a potential role in bone metabolism. However, whether AKBA enhances bone formation in wear particle-induced osteolysis remains unknown. In this study, we examined whether AKBA attenuates titanium particle-induced osteogenic reduction. Methods: Titanium particles were used to induce osteolysis in murine calvaria, and micro-CT and histological analyses were used to evaluate the results. Mouse osteoblast cells, MC3T3-E1 were co-cultured with titanium particles to determine their effect on osteoblast formation in vitro. Results: We demonstrated that AKBA treatment significantly inhibited titanium particle-induced osteogenic inhibition by enhancing osteogenesis both in vivo and in vitro. AKBA treatment also enhanced the phosphorylation of GSK-3ß, decreased the degradation of ß-catenin, and increased the translocation of ß-catenin from the cytoplasm to the nucleus. Taken together, these results showed that AKBA treatment attenuated titanium-induced osteogenic inhibition by activating the GSK-3ß/ß-catenin signaling pathway. Conclusion: These findings suggest that AKBA is a promising new target in the prevention and treatment of PPO.

12.
Research (Wash D C) ; 2019: 5385763, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31549068

RESUMO

Topological valley-contrasting physics has attracted great attention in exploring the use of the valley degree of freedom as a promising carrier of information. Recently, this concept has been extended to acoustic systems to obtain nonbackscattering sound propagations. However, previous demonstrations are limited by the cut-off frequency of 2D waveguides and lattice-scale size restrictions since the topological edge states originate from Bragg interference. Here we engineer topologically valley-projected edge states in the form of spoof surface acoustic waves that confine along the surface of a subwavelength honeycomb lattice composed of 330-mL soda cans. The inversion symmetry is broken through injecting a certain amount of water into one of the two cans in each unit cell, which gaps the Dirac cone and ultimately leads to the topological valley-Hall phase transition. Dual-frequency ranges of the valley-projected edge states below the sound line are observed, which originate from the first-order and second-order resonances, respectively. These results have the potential to enable promising routes to design integrated acoustic devices based on valley-contrasting physics.

13.
Clin Respir J ; 13(12): 765-772, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31487103

RESUMO

INTRODUCTION: Peripheral pulmonary lesions (PPL) are difficult to diagnose. We analysed the diagnostic values and risks of endobronchial ultrasonography with a guide sheath (EBUS-GS) and computed tomography-guided transthoracic needle aspiration (CT-TTNA) in diagnosing PPL. METHODS: We collected 250 cases received EBUS-GS examination, and 279 cases received CT-TTNA examination. We analysed the diagnosis results and the complications of each operation and determined the relevant indications. RESULTS: Biopsy was successful in 239 cases (95.6%) using EBUS-GS and in 279 cases (100%) using CT-TTNA. Lesions were smaller than or equal to 30 mm for biopsy using EBUS-GS in 60.7% of the cases. The distances of lesions from the chest wall were greater than 80 mm for EBUS-GS examination in 89.1% of the cases. The diagnostic rate of EBUS-GS was 78.2%, including 41.8% (100 cases) malignant diseases. EBUS-GS is a highly safe method. The distances of lesions from the chest wall were no greater than 80 mm for CT-TTNA examination in 90.0% of the cases. The diagnosis rate using CT-TTNA was 94.6%, including 90.0% (251 cases) malignant diseases. For CT-TTNA, there is a high chance of complications such as pneumothorax and intrapulmonary hemorrhage. CONCLUSION: EBUS-GS and CT-TTNA each have their own limitations. EBUS-GS has a slightly lower diagnostic rate but higher safety, while CT-TTNA has a higher diagnostic rate but requires attention to complications. For lesions 80 mm more from the chest wall, we recommend EBUS-GS. For lesions 80 mm from or closer to the chest wall, we recommend CT-TTNA.

14.
ACS Appl Mater Interfaces ; 11(40): 36333-36346, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31535550

RESUMO

Cell-based delivery platforms have received great interest in recent years and have been indicated as a promising strategy for cancer immunotherapy. Despite their wide applications in the clinical and preclinical stages, their concomitant viability and efficacy remain major issues. Herein, a strategy for harnessing regulatory T (Treg) cells is developed as an actively targeting drug-delivery system to transport drug-loaded liposomes to the desired tumor sites via conjugating liposomes on the surface of Treg cells. Under the guidance of tumor-oriented chemokines, liposome-anchored Treg cells can be leveraged to migrate and infiltrate the acidic tumor microenvironment, where pH-sensitive liposomes release the loaded cargos [comprising interleukin-2, programmed cell death ligand 1 antibody (PD-L1), and imiquimod], provoke dramatic dendritic cell maturation, block the PD-1/PD-L1 immune-checkpoint, elevate the frequency of infiltrating CD8+ effector T cells, and collectively contribute to potent inhibition of in situ and metastatic tumors. Here, the findings suggest a potential approach that offers a simple, robust, and safe insight into the tuning of Treg cells as an encouraging vector for augmenting cancer immunotherapy.


Assuntos
Lipossomos/química , Neoplasias/imunologia , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/imunologia , Animais , Quimiotaxia , Citotoxicidade Imunológica , Concentração de Íons de Hidrogênio , Imunoterapia , Neoplasias Pulmonares/secundário , Camundongos Endogâmicos C57BL , Neoplasias/patologia , Distribuição Tecidual
15.
J Cancer ; 10(17): 3975-3984, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417642

RESUMO

Lung adenocarcinoma (LAD) is the most common type of lung cancer with a high possibility of tumor relapse and metastasis. ENKUR (Enkurin) was originally identified as a potential regulator or effector of TRPC channels that directly binds to several TRPC proteins and the p85 subunit of PI3K. However, the role of ENKUR in cancer development has remained unclear. In this study we analyzed the expression profile of ENKUR mRNA in clinical LAD samples and examined ENKUR mRNA expression and ENKUR protein level in LAD cells. Significant down-regulated ENKUR expression was observed in clinical tumor tissues of LAD as well as in human LAD cells. To evaluate the effects of aberrant ENKUR expression on cellular biology of LAD cells in vitro and tumor growth in vivo, ENKUR-overexpressed and -silenced LAD cell lines were constructed using lentiviral vectors. Our results showed that overexpression of ENKUR in LAD cells inhibited cell proliferation, migration and invasion, while silencing of ENKUR led to the opposite effects. Silencing of ENKUR in LAD cells also promoted tumorigenesis in nude mice model and caused epithelial to mesenchymal transition (EMT). Furthermore, using western blot and co-immunoprecipitation analyses, we demonstrated that ENKUR interacts with PI3K directly and is possibly involved in the PI3K/Akt and MAPK/ERK signaling pathways.

16.
J Cardiovasc Pharmacol ; 74(1): 13-19, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31274838

RESUMO

We recently showed that ticagrelor reduced myocardial ischemia-reperfusion injury (IRI) and downregulated galectin-3 in the ischemic myocardium. This study tested the hypothesis that ticagrelor could reduce IRI through the NF-κB pathway. Rats were randomly divided into sham-operated group, placebo group (gastric administration of saline after IRI), ticagrelor group (gastric administration of ticagrelor after left anterior descending artery ligation), dextran sodium sulfate (DSS) group (DSS was added to drinking water 7 days before IRI), and DSS + ticagrelor group (DSS was added to drinking water 7 days before IRI and gastric administration of ticagrelor after left anterior descending artery ligation). Ticagrelor significantly reduced the infarct size and plasma cTnI at 3 and 7 days after IRI, significantly downregulated protein and mRNA expressions of NF-κB and galectin-3, and mRNA expressions of IL-6 and TNF-α in the ischemic area at 24 hours, 3 and 7 days after IRI. Ticagrelor also significantly decreased plasma high-sensitivity C-reactive protein and NT-proBNP levels at 24 hours and 3 days after IRI. Furthermore, pretreatment with DSS blocked the beneficial effects of ticagrelor. Our study indicates that the cardioprotective effect of ticagrelor might be partly mediated by inhibiting the NF-κB pathway in this rat model of IRI.

17.
Am J Transl Res ; 11(5): 2775-2783, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217853

RESUMO

Accumulation of advanced glycation end-products (AGEs) increases inflammation and triggers processes involved in the pathogenesis of osteoarthritis (OA). As a major debilitating age-related disease, it is imperative that novel therapies for OA be sought. In the present study, we investigated the effects of the selective dipeptidyl peptidase IV (DPP-4) inhibitor sitagliptin in human primary chondrocytes exposed to insult by AGEs to elucidate the potential role of sitagliptin in the treatment of OA. Our findings show that inhibition of DPP-4 by sitagliptin could reduce oxidative stress, increase cell viability and prevent degradation of type II collagen and aggrecan by matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) induced by AGEs in human primary chondrocytes. Mechanistically, we found that sitagliptin inhibited AGEs-induced nuclear translocation of p65 protein and drastically decreased the luciferase activity of NF-κB. These findings indicate that sitagliptin may have potential as a novel therapeutic option for the treatment and prevention of OA.

18.
Respir Res ; 20(1): 97, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118045

RESUMO

BACKGROUND: We recently showed that intravenous sodium nitroprusside treatment (SNP) could relieve the pulmonary vasospasm of pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions in a rabbit massive pulmonary embolism (MPE) model associated with shock. The present study explored the potential role of cardiopulmonary sympathetic activity on the pathogenesis and the impact of vasodilators on cardiopulmonary sympathetic activity in this model. METHODS: Rabbits were randomly divided into sham operation group (S group, n = 8), model group (M, equal volume of saline intravenously, n = 11), SNP group (3.5 µg/kg/min intravenously, n = 10) and diltiazem group (DLZ, 6.0 µg/kg/min intravenously, n = 10). RESULTS: MPE resulted in reduced mean arterial pressure and increased mean pulmonary arterial pressure as well as reduced PaO2 in the M, SNP and DLZ groups. Tyrosine hydroxylase (TH), neuropeptide Y (NPY) and endothelin-1 (ET-1) expression levels were significantly increased, while nitric oxide (NO) levels were reduced in both PE and non-PE regions in the M group. Both SNP and DLZ decreased mean pulmonary arterial pressure, reversed shock status, downregulated the expression of TH, NPY and ET-1, and increased NO levels in PE and non-PE regions. CONCLUSION: Present results indicate that upregulation of the sympathetic medium transmitters TH and NPY in whole lung tissues serves one of the pathological features of MPE. The vasodilators SNP and DLZ could relieve pulmonary vasospasm in both embolization and non-embolization regions and reverse circulatory shock, thereby indirectly downregulating the sympathetic activation of the whole lung tissues and breaking a vicious cycle related to sympathetic activation in this model.


Assuntos
Neuropeptídeo Y/biossíntese , Embolia Pulmonar/metabolismo , Choque/metabolismo , Tirosina 3-Mono-Oxigenase/biossíntese , Vasodilatadores/uso terapêutico , Animais , Embolia Pulmonar/tratamento farmacológico , Coelhos , Distribuição Aleatória , Choque/tratamento farmacológico , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Vasodilatadores/farmacologia
19.
Technol Cancer Res Treat ; 18: 1533033819841433, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30947633

RESUMO

Colorectal cancer is one of the most prevalent malignancies worldwide. ENKUR is a transient receptor potential canonical-binding protein that acts as a potential regulator or effector of transient receptor potential canonical channels. It also directly interacts with the p85 regulatory subunit of phosphoinositide 3-kinase. However, the role of ENKUR in colorectal cancer remains unclear. In the present study, the expression profiles of ENKUR in the The Cancer Genome Atlas and ONCOMINE databases were analyzed. Significant downregulation of ENKUR was observed in clinical tumor samples of various cancer types, including colorectal cancer. Decreased ENKUR messenger RNA expression and ENKUR protein level were detected in 6 human colorectal cancer cell lines. Silencing of ENKUR in colorectal cancer cells led to enhanced cell proliferation, migration, and invasion, while the opposite effects were achieved in ENKUR-overexpressing cells. Furthermore, ENKUR-underexpressing cells exhibited increased activity of phosphoinositide 3-kinase /Akt signaling pathway. Downregulation of the epithelial marker, E-cadherin, and upregulation of the mesenchymal markers, vimentin and N-cadherin, were detected in ENKUR-underexpressing cells, suggesting the induction of epithelial-mesenchymal transition. In conclusion, the present study demonstrates that ENKUR may be responsible for alterations in the proliferative, migratory, and invasive potential of colorectal cancer cells through possible involvement in the phosphoinositide 3-kinase /Akt signaling pathway.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/patologia , Proteínas de Ligação a Calmodulina/metabolismo , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Proteínas de Ligação a Calmodulina/genética , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Células Tumorais Cultivadas
20.
World Neurosurg ; 128: e334-e339, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31028986

RESUMO

BACKGROUND: The cerebellomesencephalic vein (CMV) was frequently sacrificed in surgery approached via the supracerebellar infratentorial (SCIT) route for resecting pineal region tumors, which resulted in potential risk of neurologic deficit. Preserving the CMV in the SCIT approach could enhance the safety and effectiveness of this natural corridor surgery. The aim of this article was to identify the probability and safety of preserving the CMV through the application of neuroendoscopy in the SCIT approach. METHODS: Clinical data of patients who underwent pineal region tumor resection through a purely endoscopic SCIT approach were retrospectively analyzed, focusing on surgical techniques and clinical outcomes. RESULTS: The study included 8 patients with pineal region tumors. The CMV was preserved intact in all patients. Total tumor removal was achieved in 7 of 8 patients. In 1 patient with 2 tumors in the pineal region and roof of the third ventricle, the tumor in the pineal region was resected completely, followed by subsequent chemotherapy combined with radiotherapy, after which the other tumor disappeared totally. All patients recovered normally with uneventful postoperative outcomes. CONCLUSIONS: The advantage of close observation and panoramic view provided by neuroendoscopy combined with meticulous manipulation improved the ability to preserve the CMV in resecting pineal region tumors via the SCIT approach. The neuroendoscopic technique enhances the safety and efficacy of the SCIT approach.


Assuntos
Neoplasias Encefálicas/cirurgia , Neuroendoscopia/métodos , Glândula Pineal/cirurgia , Pinealoma/cirurgia , Terceiro Ventrículo/cirurgia , Adulto , Neoplasias Encefálicas/complicações , Cerebelo/irrigação sanguínea , Criança , Germinoma/complicações , Germinoma/cirurgia , Glioblastoma/complicações , Glioblastoma/cirurgia , Cefaleia/etiologia , Humanos , Masculino , Mesencéfalo/irrigação sanguínea , Pessoa de Meia-Idade , Neurocitoma/complicações , Neurocitoma/cirurgia , Tratamentos com Preservação do Órgão , Pinealoma/complicações , Estudos Retrospectivos , Teratoma/complicações , Teratoma/cirurgia , Ventriculostomia , Adulto Jovem
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