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1.
Artigo em Inglês | MEDLINE | ID: mdl-32418133

RESUMO

BACKGROUND: With technical improvement, accumulating lesions could be resected using endoscopic endonasal surgery. However, cerebrospinal fluid leakage is still a concern. Intraoperative dural defect reconstruction is critical. METHOD: We developed a new knotting technique for dural closure during endoscopic skull base surgery. We presented a step-by-step description of the fascia lata inlay and autologous dural patch intermittent suturing method following cross-reinforcing principles and emphasized the key points of the novel intranasal knotting technique. CONCLUSION: The new intranasal knotting and suturing technique is a feasible method to close the dura and to prevent cerebrospinal fluid leakage.

2.
Neurosci Bull ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32436179

RESUMO

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.

3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(2): 145-149, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32274996

RESUMO

OBJECTIVE: To clarify the distribution and composition of drug-resistant genes of carbapenem-resistant Klebsiella pneumoniae (CRKP) in Qingdao City and to provide rationale for clinical application of antibacterial treatment by screening for carbapenemase phenotype and detecting resistance genes of CRKP. METHODS: Fifty-four clinically isolated non-repeating CRKP from five Third Grade and Class A Hospitals in Qingdao City from October 2016 to September 2019 were collected. Kirby-Bauer method was used for drug sensitivity tests of commonly used antibacterial drugs; modified Hodge test was used for carbapenemase phenotypic screening; and polymerase chain reaction (PCR) was used to amplify blaKPC-2, blaNDM-1, blaOXA-48, blaIMP, blaVIM target genes. The amplified products were subjected to agarose gel electrophoresis. RESULTS: Drug susceptibility tests showed that CRKP had the lowest resistance rate to amikacin (35.2%), followed by compound sinomine (53.7%), gentamicin (55.6%), levofloxacin (75.9%), and imipenem-cilastatin (88.9%); piperacillin-tazobactam, meropenem, cefotaxime, and cefoperazone-sulbactam were all higher than 90%. There were 43 positive strains in the modified Hodge test (the positive rate was 79.63%) and 11 negative strains. A total of 40 strains with carbapenemase resistance were detected by PCR resistance gene detection. The detection rate of target drug-resistant genes was 74.07%. Among them, 35 strains carry the KPC-2 gene, 7 strains carry the OXA-48 gene, 4 strains carry the NDM-1 gene, and 1 strain carries the IMP gene. All strains carrying the OXA-48 gene also carried the KPC-2 gene, which was not detected. Strains carrying the VIM gene were identified, and the remaining 14 strains did not detect the target carbapenem gene. CONCLUSIONS: The carbapenem-producing genes carried by CRKP in five hospitals in Qingdao City are mainly KPC-2, followed by OXA-48 and NDM-1.

4.
Int J Stem Cells ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32323514

RESUMO

Background and Objectives: The effective use of MSCs for the treatment of some B cell-mediated immune diseases is quite limited. The main reason is that the immunomodulatory effects of mesenchymal stem cells (MSCs) on B cells are unclear, and their underlying mechanisms have not been fully explored. Methods and Results: By co-culturing B cells with MSCs without (MSC/CTLsh) or with suppressor of cytokine signaling 1 (SOCS1) knockdown (MSC/SOCS1sh), we found that MSCs inhibited B cell proliferation, activation and terminal differentiation. Remarkably, the highest inhibition of B cell proliferation was observed in MSC/SOCS1sh co-culture. Besides, MSC/SOCS1sh reversed the inhibitory effect of MSCs in the last stage of B cell differentiation. However, MSC/SOCS1sh had no effect on inhibiting B cell activation by MSCs. We also showed that IgA+ B cell production was significantly higher in MSC/SOCS1sh than in MSC/CTLsh, although no difference was observed when both MSCs co-cultures were compared to isolated B cells. In addition, MSCs increased PGE2 production after TNF-α/IFN-γ stimulation, with the highest increase observed in MSC/SOCS1sh co-culture. Conclusions: Our results highlighted the role of SOCS1 as an important new mediator in the regulation of B cell function by MSCs. Therefore, these data may help to develop new treatments for B cell-mediated immune diseases.

5.
Zhongguo Zhong Yao Za Zhi ; 45(5): 997-1003, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237438

RESUMO

To investigate the characteristics of the cold and heat properties of each resolution component of Açaí and the material basis of cooling by observing the effect of resolution components, such as Açaí oil, alcohol extract and water extract, on the neurotransmitter, endocrine hormone and immune factor level in mice with deficiency-heat and deficiency-cold syndrome. KM male mice were randomly divided into 12 groups, namely blank group, deficiency-heat model group, deficiency-heat+Açaí group, deficiency-heat+Açaí oil group, deficiency-heat+Açaí alcohol extract group, deficiency-heat+Açaí water extract group, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Açaí group, deficiency-cold+Açaí oil group, deficiency-cold+Açaí alcohol extract group, and deficiency-cold+Açaí water extract group. The mice in deficiency-heat group were given with thyroid tablet solution(160 mg·kg~(-1)), and the mice in deficiency-cold group were given with hydrocortisone solution(25 mg·kg~(-1)) by intragastric administration every afternoon for 14 days. The mice in each administration group received corresponding drug. The neurotransmitter, endocrine hormone and immune factor levels in the mice were measured after the experiment. The Açaí alcohol extract, consistent with the Açaí powder, showed a regulatory effect on the deficiency-heat model mice; Açaí oil and its water extract were consistent with Cinna-momi Cortex, showing a regulatory effect on the deficiency-cold model mice. In this study, on the basis of proving that Açaí was was cool in property, it also revealed that alcohol extract of Açaí was cool while oil and water extract were warm in property based on the effect of Açaí on neuro-endocrine-immune network. The results suggested that the medicine property of Açaí was the result of the comprehensive action of the resolution components with different properties, and the alcohol extract of Açaí was proved as the material basis of Açaí cold medicine by using the methods of homogeneous comparison and heterogeneous disproval.

6.
Brain Res ; 1739: 146823, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32272097

RESUMO

Cerebral venous infarction (CVI) caused by the injury of cortical bridging veins (CBVs), is one of the most serious complications following neurosurgical craniotomy. Different from cerebral artery infarction, this CVI pathological process is more complicated, accompanied by acute venous hypertension, brain edema, cerebral ischemia and hemorrhage in the veins bridged brain area. Therefore, a reliable and stable small animal model is particularly important for the pathological study of CVI induced by surgical CBV interruption (CBVi). A mouse model established by cutting off the right CBVs from bregma to lambda with microsurgical technique is used for the assessment of the pathological process. Adult male mice underwent craniotomy after transection of the parietal skin under anesthesia. The right CBVs were exposed by removing the right skull along the right lateral edge of the sagittal sinus (forming a 4 mm × 3 mm bone window from bregma to lambda) with a drill under the operating microscope. Following the final inspection of the cerebral veins, the CBVs (30% one, 60% two, 10% none) were sacrificed using bipolar coagulation technique. Intracranial pressure (ICP) monitoring, motor function examination, brain edema assessment and brain histopathological observation after perfusion were performed at different time points (6 h, 12 h, 24 h, and 48 h) in the postoperative mice. Cerebral hemisphere swelling, midline shift and subcortical petechial hemorrhage were found on histological sections 6 h after CBVs dissection. The change of ICP was consistent with cerebral edema and peaked at 12 h after surgery, as well as the disruption of the blood-brain barrier assessed by Evans Blue staining. Tissue necrosis, nerve cell loss and monocytes infiltration were also dynamically increased in the postoperative hemispheric cortex. Behavioral tests showed obvious somato- and forelimb-motor dysfunction, and severe somatosensory disorder on the operative mice at 12 h, which were substantially recovered at 48 h. Our study provided a novel mouse model of CVI caused by surgical CBVi that was close to clinical practice, and preliminarily confirmed its pathological process. This model might become an important tool to study the clinical pathology and the molecular mechanism of nerve injury following CVI.

7.
Exp Neurol ; 329: 113302, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32275928

RESUMO

The effects of current treatment strategies for ischemic stroke are weakened by ischemia-reperfusion (I/R) injury. Effective treatments targeting I/R injury are still insufficient. Adiponectin (APN), a fat-derived hormone, has a wide range of antioxidative and anti-inflammatory effects. However, the application of APN to the central nervous system is restricted by its limited blood-brain barrier permeability. Therefore, an adiponectin peptide (APNp) was chemically synthesized on the basis of the functional area in the APN structure. The present study was carried out to explore the effect and the underlying mechanism of APNp on I/R injury. A transient middle cerebral artery occlusion (tMCAO) model with C57BL/6 J mice was used, and an in vitro oxygen-glucose deprivation and reintroduction (OGD-R) model with primary astrocytes was induced. The results showed that APNp decreased the cerebral infarction volume, alleviated brain edema, improved neurological function and had antioxidative, anti-inflammatory, and antiapoptotic effects against cerebral I/R injury. In addition, APNp upregulated the phosphorylation of AMPK and GSK-3ß, promoted the nuclear translocation of Nrf2 and increased the expression of Trx1. The protective effect of APNp was abolished by compound C, a selective AMPK inhibitor, and PX-12, a selective Trx inhibitor. Moreover, APNp decreased the protein level of TXNIP and suppressed the activation of the NLRP3 inflammasome in astrocytes, which were also reversed by compound C and PX-12. These findings suggest that APNp, as a potential substitute for adiponectin, has a great potential for clinical application in the treatment of acute brain ischemia.

8.
Neural Regen Res ; 15(10): 1814-1820, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32246622

RESUMO

Current management for spinal cord injury aims to reduce secondary damage and recover sensation and movement. Acute spinal cord injury is often accompanied by spinal cord compartment syndrome. Decompression by durotomy and/or myelotomy attempts to relieve secondary damage by completelyrelieving the compression of the spinal cord, removing the necrotic tissue, decreasing edema, reducing hemorrhage, and improving blood circulation in the spinal cord. However, it is controversial whether durotomy and/or myelotomy after spinal cord injury are beneficial to neurological recovery. This review compares the clinical effects of durotomy with those of myelotomy in the treatment of spinal cord injury. We found that durotomy has been performed more than myelotomy in the clinic, and that durotomy may be safer and more effective than myelotomy. Durotomy performed in humans had positive effects on neurological function in 92.3% of studies in this review, while durotomy in animals had positive effects on neurological function in 83.3% of studies. Myelotomy procedures were effective in 80% of animal studies, but only one clinical study of myelotomy has reported positive results, of motor and sensory improvement, in humans. However, a number of new animal studies have reported that durotomy and myelotomy are ineffective for spinal cord injury. More clinical data, in the form of a randomized controlled study, are needed to understand the effectiveness of durotomy and myelotomy.

9.
Aging (Albany NY) ; 12(6): 4757-4777, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32209727

RESUMO

Non-small cell lung cancer (NSCLC), which consists mainly of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), are the leading cause of cancer deaths worldwide. In this study, we performed a comprehensive analysis of the tumor microenvironmental and genetic factors to identify prognostic biomarkers for NSCLC. We evaluated the immune and stromal scores of patients with LUAD and LUSC using data from The Cancer Genome Atlas database with the ESTIMATE algorithm. Based on these scores, the differentially expressed genes were obtained and immune-related prognostic genes were identified. Functional analysis and protein-protein interaction network further revealed the immune-related biological processes in which these genes participated. Additionally, 22 subsets of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment were analyzed with the CIBERSORT algorithm. Finally, we validated these valuable genes using an independent cohort from the Gene Expression Omnibus database. The associations of the immune and stromal scores with patients' clinical characteristics and prognosis were positive in LUAD but negative in LUSC and the correlations of TIICs with clinical characteristics were clarified. Several differentially expressed genes were identified to be potential immune-related prognostic genes. This study comprehensively analyzed the tumor microenvironment and presented immune-related prognostic biomarkers for NSCLC.

10.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(1): 72-77, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32148235

RESUMO

OBJECTIVE: To evaluate the nutritional status of patients in intensive care unit (ICU) by using nutritional risk screening 2002 scale (NRS2002), subjective general assessment (SGA) and critical illness nutritional risk score (NUTRIC), and to compare the characteristics and applicability of three scoring tools. METHODS: A cross-sectional survey was conducted. 315 patients admitted to the comprehensive ICU of Affiliated Qingdao Municipal Hospital of Qingdao University from April 2018 to July 2019 were enrolled. Basic information of patients was collected, and patients were divided into two groups with 65 years old as the standard to compare the nutritional status of patients among different genders and ages. The nutritional status of patients were assessed by NRS2002, SGA, and NUTRIC. Height, weight, body mass index (BMI), triceps skinfold thickness (TSF), upper arm circumference (AC), leg circumference (LC), and other related parameters of human nutrition were measured. Total protein (TP), albumin (Alb), prealbumin (PA), serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), total number of lymphocytes (LYM), hemoglobin (Hb), C-reactive protein (CRP) and other blood biochemical indicators were performed. Spearman rank correlation analysis was used to analyze the correlation between the three nutrition evaluation scales and other objective nutrition parameters. Binary multivariate Logistic regression analysis was used to evaluate the influencing factors of nutritional status with three scales of patients in ICU. RESULTS: Among 315 patients in ICU, 183 were male and 132 were female. There were 143 patients < 65 years old and 172 ≥ 65 years old. In male patients, the acute physiology and chronic health evaluation II (APACHE II) score, age and BUN of patients aged ≥ 65 years old were significantly increased, and the height, weight, BMI, TSF, AC, LC, Alb and PA were significantly lowered as compared with those aged < 65 years old, while the difference in other indicators was not statistically significant. In the female patients, the APACHE II score, age, SCr and BUN of the patients aged ≥ 65 years old were significantly increased, the height, Alb, PA and Hb were significantly decreased as compared with those aged < 65 years old, and the difference in other indicators was not statistically significant. The proportion of patients with nutritional risk evaluated by NRS2002 (NRS2002 score ≥ 3) was 87.62% (276/315). SGA showed that the proportion of malnourished patients (SGA was grade B or C) was 62.86% (198/315). NUTRIC showed 66.03% of patients (208/315) in high nutritional risk (NUTRIC score ≥ 5). Spearman rank correlation analysis showed that there were significant correlations among NRS2002, SGA and NUTRIC of patients in ICU (rNRS2002 with SGA = 0.522, rNRS2002 with NUTRIC = 0.392, rSGA with NUTRIC = 0.442, all P < 0.01). Among the three assessment tools, SGA had the best correlation with blood biochemical indicators and body measurements to assess nutritional status, followed by NRS2002, and NUTRIC had the worst correlation. Binary multivariate Logistic regression showed that APACHE II score, BMI, AC, BUN and TG were factors influencing NRS2002 assessment of nutritional status in ICU patients [odds ratio (OR) were 2.535, 0.404, 1.438, 0.858, and 2.391, respectively, all P < 0.05]; APACHE II score, age, weight, TP, BUN, LYM and CRP were influence factors of SGA for evaluating the malnutrition of patients in ICU (OR values were 1.074, 1.038, 0.921, 0.947, 1.077, 1.625 and 0.991, respectively, all P < 0.05); APACHE II score, age, LYM and CRP were the influence factors of NUTRIC assessment for malnutrition of patients in ICU (OR values were 1.159, 1.049, 0.715 and 0.995, respectively, all P < 0.05). CONCLUSIONS: The nutrition status of ICU patients evaluated by NRS2002, SGA and NUTRIC was simple and easy to operate, and the positive screening rate of NRS2002 was the highest, which was suitable for patients with mild conditions in ICU. SGA is the most valuable tool to evaluate the nutritional status of ICU patients. NUTRIC has a poor correlation with objective indicators reflecting nutritional status, while its indicators are objective and easy to obtain, which is suitable for ICU patients with critical condition and unclear consciousness. Nutritional assessment tools should be integrated with the patient's gender, age, anthropometric and biochemical indicators.


Assuntos
Unidades de Terapia Intensiva , Avaliação Nutricional , Estado Nutricional , APACHE , Idoso , Estudos Transversais , Feminino , Humanos , Masculino
11.
Artigo em Inglês | MEDLINE | ID: mdl-31897729

RESUMO

BACKGROUND: In light of the controversies regarding the surgical treatment of adult Chiari malformation type I (CM-I) with syringomyelia, a retrospective study was conducted to evaluate the safety and efficacy of tonsillectomy followed by modified reconstruction of the cisterna magna with or without craniectomy. METHODS: Between 2008 and 2017, 78 adult CM-I patients (36 males and 42 females, mean age 40.6 years old) with syringomyelia were treated with posterior fossa decompression (PFD) with tonsillectomy and modified reconstruction of the cisterna magna. Patients were divided into two study groups: group A (n = 40) underwent cranioplasty with replacement of the bone flap; group B (n = 38) underwent suboccipital craniectomy. Neurological outcomes were evaluated by traditional physician assessment (improved, unchanged, and worsened) and the Chicago Chiari Outcome Scale (CCOS). Syringomyelia outcomes were assessed radiologically. RESULTS: The procedure was successfully performed in all patients, and restoration of normal cerebrospinal fluid (CSF) flow was confirmed by intraoperative ultrasonography. The median postoperative follow-up was 20.3 months (range 18-60 months). Clinical improvement was evident in 66 (84.6%) patients, with no significant differences between the two groups (85.0% vs. 84.2%, P = 0.897). According to the CCOS, 36 patients (90.0%) in group A were labeled as "good" outcome, compared with that of 34 (86.8%) in group B (P = 0.734). Improvement of syringomyelia was also comparable between the groups, which was observed in 35 (87.5%) vs. 33 (86.8%) patients (P = 0.887). The postoperative overall (7.5% vs. 23.7%, P = 0.048) and CSF-related (2.5% vs. 18.4%, P = 0.027) complication rates were significantly lower in group A than group B. CONCLUSIONS: Tonsillectomy with modified reconstruction of the cisterna magna without craniectomy seems to be a safe and effective surgical option to treat adult CM-I patients with syringomyelia, though future well-powered prospective randomized studies are warranted to validate these findings.

12.
Biofactors ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898375

RESUMO

Little is known about the influence of central nesfatin-1 on lipid metabolism under diabetic conditions. The main objective of this study was to characterize the mechanisms by which central nesfatin-1 regulates lipid metabolism in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) and whether the sympathetic nervous system is involved. Male Kunming mice were fed high-fat diets (HFDs) and were treated twice with low-dose STZ (100 mg/kg, intraperitoneal [IP]) to generate the T2DM model. Pharmacological adrenergic blockage (phentolamine 10 mg/kg, propranolol 0.017 mmol) and surgical denervation of sympathetic nervous system of the hindlimb and inguinal fat were used to block nerve conduction to determine whether the effect of central nesfatin-1 required the hypothalamic-sympathetic nervous system axis. Plasma free fatty acid (FFA) and insulin levels were measured. AMP-activated protein kinase (AMPK) levels in skeletal muscle and hormone-sensitive lipase and adipose triglycerides lipase (HSL/ATGL) levels in white adipose tissue (WAT) were measured using western blot. mRNA expression of AMPK was measured. We found that there were significantly fewer NUCB2/nesfatin-1 immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) in T2DM mice. Central nesfatin-1 administration decreased levels of plasma FFA significantly and activated AMPK to enhance fatty-acid oxidation in skeletal muscle in T2DM mice. In addition, HSL and ATGL were significantly activated during triglyceride mobilization in WAT triggered by central nesfatin-1 administration. Adrenergic blockade and morphological denervation of the sciatic and femoral nerves reduced these changes. Taken together, these data suggest that central nesfatin-1 regulates peripheral lipid metabolism in type 2 diabetes via the sympathetic nervous system.

13.
Cell Prolif ; 53(2): e12759, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31922310

RESUMO

OBJECTIVE: Low levels of adiponectin (APN), a biomarker of diabetes mellitus, have been implicated in the poor outcome of intracerebral haemorrhage (ICH). Herein, we aimed to demonstrate the neuroprotective effects of a blood-brain barrier-permeable APN peptide (APNp) on ICH injury in diabetic mice and explore the underlying mechanisms. MATERIALS AND METHODS: Recombinant APNp was administrated intraperitoneally to mice with collagenase-induced ICH. Neurological deficits, brain water content and neural apoptosis were assessed. Western blotting, immunofluorescence staining, quantitative RT-PCR and transmission electron microscopy were used to determine the signalling pathways affected by APNp. RESULTS: Adiponectin peptide significantly alleviated neural apoptosis, neurological deficits and brain oedema following ICH in diabetic mice. Mechanistically, APNp promoted the restoration of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α related mitochondrial function and suppressed activating transcription factor 4 (ATF4)-CCAAT-enhancer-binding protein homologous protein (CHOP)-induced neural apoptosis. Furthermore, Smad3 signalling was found to play a regulatory role in this process by transcriptionally regulating the expression of PGC-1α and ATF4. APNp significantly suppressed the elevated phosphorylation and nuclear translocation of Smad3 after ICH in diabetic mice, while the protective effects of APNp on mitochondrial and ATF4-CHOP apoptosis pathways were counteracted when Smad3 was activated by exogenous transforming growth factor (TGF)-ß1 treatment. CONCLUSIONS: Our study provided the first evidence that APNp promoted neural survival following ICH injury in the diabetic setting and revealed a novel mechanism by which APNp suppressed mitochondrial and ATF4-CHOP apoptosis pathways in a Smad3 dependent manner.


Assuntos
Adiponectina/metabolismo , Apoptose/fisiologia , Hemorragia Cerebral/metabolismo , Diabetes Mellitus Experimental/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Fator 4 Ativador da Transcrição/metabolismo , Animais , Encéfalo/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transporte Proteico/fisiologia , Proteínas Recombinantes/metabolismo , Proteína Smad3/metabolismo , Fator de Transcrição CHOP/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
14.
AAPS PharmSciTech ; 21(2): 66, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932983

RESUMO

The purpose of this study was to investigate the potential of Bletilla striata polysaccharide (BSP, a natural glucomannan material) for the development of a gastroretentive drug delivery system for the first time. Novel BSP-based porous wafer was prepared for levofloxacin hydrochloride (LFH) delivery by combining floating, swelling, and mucoadhesion mechanisms. The influences of BSP and ethyl cellulose (EC) on drug release and mucoadhesive strength were studied by 32 factorial design. The optimized matrix was coated with polycaprolactone (PCL) electrospun membrane by electrospinning and heat treatment technology. The optimized formula (F6, coated) exhibited Q4 h of 41.20 ± 1.90%, Q8 h of 76.49 ± 1.69%, and mucoadhesive strength of 86.11 ± 1.33 gf, and its drug release profile most closely resembled the Korsmeyer-Peppas model with anomalous diffusion driving mechanism. F6 (coated) also presented excellent buoyancy, preferred swelling characteristic due to the porous structure formed by freeze-drying. Meanwhile, the internal morphology, physical state, drug-excipient compatibility, and thermal behavior were recorded. The negligible cytotoxicity of F6 (coated) was observed in human gastric epithelial cell cultures. In the in vitro antimicrobial experiment, the prepared wafer exhibited obvious bacterial inhibition zone, and due to its longer gastric retention, the wafer also performed a more effective Helicobacter pylori clearance than free LFH in vivo. Graphical abstract.


Assuntos
Sistemas de Liberação de Medicamentos , Mucosa Gástrica/metabolismo , Mananas/química , Orchidaceae/química , Poliésteres/química , Células Cultivadas , Celulose/análogos & derivados , Celulose/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos
15.
Kaohsiung J Med Sci ; 36(4): 265-273, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31889432

RESUMO

Wilms tumor (WT) is the most common solid childhood tumors all over the world. MicroRNAs (miRs) contribute to tumorigenesis of various cancers through targeting gene. The present study investigated the vital role of miR-194-5p and its underlying mechanism in the progression of WT. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) assay indicated downregulation of miR194-5p and upregulation of Crk, in WT tissues compared to adjacent normal tissues. Transfection with miR-194-5p mimics into nephroblastoma cells showed a significant decline in cell migration and invasion, which was detected by Transwell assay. Luciferase assay confirmed that Crk was a direct target gene of miR-194-5p. More important, the mesenchymal to epithelial transition (EMT) biomarkers containing E-cadherin, N-cadherin and Zeb1 were examined by Western blot, and revealed that miR-194-5p mimics decreased the levels of N-cadherin and Zeb1 but increased E-cadherin, which suggested that miR-194-5p inhibited EMT. Crk knockdown could reverse the increased nephroblastoma cell invasion, migration and EMT caused by miR-194-5p inhibitor. Interestingly, qRT-PCR and Western blot analysis showed that overexpression of miR-194-5p deactivated HGF/c-Met/Scr signaling pathway via targeting Crk. In conclusion, miR-194-5p inhibited nephroblastoma cell metastasis and EMT in the progression of WT by targeting Crk. Thus, miR-194-5p might be a potential target in WT particularly for the prevention of metastasis and EMT.

16.
Transl Stroke Res ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31902083

RESUMO

Intracerebral hemorrhage (ICH) is a life-threatening subtype of cerebral stroke with high morbidity and mortality; however, effective treatment for ICH is still lacking. Adiponectin (APN) is a a kind of fat-derived plasma protein with beneficial effects in cerebrovascular disorders. In this study, we aimed to investigate the protective effects of recombinant APN peptide (APNp) on brain injury after ICH in adult male C57BL/6J mice and further explored the underlying molecular mechanisms of these effects. APNp treatment exerted dose-dependent neuroprotective effects including improved neurological function, decreased brain edema, reduced neural apoptosis, and alleviated blood-brain barrier (BBB) disruption in ICH mice. We found the massive accumulation of APNp on reactive astrocytes around brain microvessels under hemorrhage conditions by immunofluorescence analysis. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that APNp significantly attenuated the inflammatory response and mitochondrial respiratory dysfunction in astrocytes. Further study revealed that this process was, at least in part, reliant on the inhibition of Drp1-mediated excessive mitochondrial fission. More specifically, APNp increased AMP-activated protein kinase (AMPK) activation-dependent Drp1 serine 637 (S637) phosphorylation, which inhibited the translocation of Drp1 to the mitochondrial membrane and reduced mitochondrial fragmentation and the production of mitochondrial superoxide, ultimately attenuating inflammatory brain injury induced by hemorrhage. In conclusion, we propose APNp as a potential therapeutic agent for ICH. We provide the first mechanistic evidence that APNp can modulate Drp1-mediated mitochondrial fission, which then contributes to alleviating astrocyte-derived inflammation.

17.
Clin Cancer Res ; 26(7): 1749-1762, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31900278

RESUMO

PURPOSE: Glioblastoma (GBM) is one of the most aggressive and lethal cancer types in humans. The standard treatment approach is surgery followed by chemoradiation. However, the molecular mechanisms of innate tumor radioresistance remain poorly understood. EXPERIMENTAL DESIGN: We tested the expression of Smoothened (Smo) in primary and recurrent GBM tissues and cells. Then, we determined radiation effectiveness against primary and recurrent GBM cells. Lastly, the functional role of Smo in GBM radioresistance was further confirmed by in vitro and in vivo experiments. RESULTS: We reported that Smo was significantly upregulated in recurrent GBM cell lines and tumor tissues following radiation treatment. Higher Smo expression indicated poor prognosis of GBM patients after radiation treatment. Smo had radioresistance effects in both GBM cells and human tumor xenografts. The mechanisms underlying these effects involved the attenuation of DNA damage repair caused by IR. Importantly, we found that the effect of Smo on radioresistance was mediated by Claspin polyubiquitination and proteasomal degradation, leading to the regulation of ATR-Chk1 signaling. Moreover, we found that Smo reduced Claspin polyubiquitination and proteasomal degradation by promoting USP3 transcription. Furthermore, we demonstrated that the Smo inhibitor GDC-0449 induced radiosensitivity to GBM. CONCLUSIONS: These data suggest that Smo confers radiation resistance in GBM by promoting USP3 transcription, leading to the activation of Claspin-dependent ATR-Chk1 signaling. These findings identify a potential mechanism of GBM resistance to radiation and suggest a potential therapeutic target for radiation resistance in GBM.

18.
World Neurosurg ; 136: e542-e552, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954884

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of an enhanced recovery after surgery (ERAS) program for intraspinal tumors in a single-institutional prospective randomized controlled trial. METHODS: A multimodal and multidisciplinary ERAS protocol for intraspinal tumor surgery was developed. A total of 94 enrolled patients were randomized into 2 groups: 48 were managed following the ERAS protocol (ERAS group), and 46 received conventional perioperative care (control group). The primary end point was postoperative length of stay (LOS). The secondary outcomes included postoperative pain score and pain medication use, urinary catheterization, ambulation, mortality, reoperation/readmission rates, complication rates, patient satisfaction, and overall cost. RESULTS: A significant reduction in LOS was achieved in patients undergoing ERAS protocol compared with the controls (5 vs. 8 days; P < 0.0001). Moreover, patients in the ERAS group had better postoperative pain scores (1.0 ± 1.3 vs. 1.9 ± 1.3; P = 0.007), decreased use of patient-controlled analgesia (4.2% vs. 19.6%; P = 0.020) and oral opioid (37.5% vs. 58.7%; P = 0.040), early urinary catheter removal (58.3% vs. 6.5%; P < 0.0001), greater ambulation (68.8% vs. 17.4%; P < 0.0001), and higher satisfaction scores (91.8 ± 4.4 vs. 88.2 ± 6.8; P = 0.022) than did the control group. There were no deaths or 30-day readmission/reoperation in both groups, nor did the postoperative complication rates differ between groups. CONCLUSIONS: The ERAS protocol for intraspinal tumor surgery seems to be feasible, effective, and safe in shortening postoperative LOS, improving postoperative pain control with reduced opioid use, and accelerating functional recovery without increasing rates of complications or reoperation/readmission. Adoption of spine ERAS programs could be encouraged in practice, although validation with larger-scale multicenter trials is warranted.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/etiologia , Satisfação do Paciente , Assistência Perioperatória/métodos , Estudos Prospectivos , Resultado do Tratamento
19.
J Cell Biochem ; 121(2): 1728-1735, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31609014

RESUMO

OBJECTIVE: To further explore the role of BCL-2 associated anthanogen-1 (BAG-1) in neuronal apoptosis and whether the effect of BAG-1 depends on heat shock protein 70 (HSP70). METHODS: RNA interference (RNAi) technology was used to inhibit the expression of BAG-1 in SH-SY5Y cells. Hypoxia-reoxygenation injury model in the SH-SY5Y cells was established. Cell Counting Kit-8 (CCK-8) was performed for cell viability. Annexin V-APC/7-AAD double-staining followed by flow cytometry was used to measure cell apoptosis. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were used to detect the messenger RNA (mRNA) and protein expression of genes, respectively. RESULTS: BAG-1 gene silencing decreased SH-SY5Y cell viability and promoted SH-SY5Y cell apoptosis after hypoxia-reoxygenation. However, the down-regulation of BAG-1 had no effect on the mRNA and protein expression of HSP70. CONCLUSION: BAG-1 could protect SH-SY5Y cells from the hypoxia-reoxygenation injury without affecting HSP70 expression.

20.
J Neurointerv Surg ; 12(1): 55-61, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31300535

RESUMO

BACKGROUND: The main surgical techniques for spontaneous basal ganglia hemorrhage include stereotactic aspiration, endoscopic aspiration, and craniotomy. However, credible evidence is still needed to validate the effect of these techniques. OBJECTIVE: To explore the long-term outcomes of the three surgical techniques in the treatment of spontaneous basal ganglia hemorrhage. METHODS: Five hundred and sixteen patients with spontaneous basal ganglia hemorrhage who received stereotactic aspiration, endoscopic aspiration, or craniotomy were reviewed retrospectively. Six-month mortality and the modified Rankin Scale score were the primary and secondary outcomes, respectively. A multivariate logistic regression model was used to assess the effects of different surgical techniques on patient outcomes. RESULTS: For the entire cohort, the 6-month mortality in the endoscopic aspiration group was significantly lower than that in the stereotactic aspiration group (odds ratio (OR) 4.280, 95% CI 2.186 to 8.380); the 6-month mortality in the endoscopic aspiration group was lower than that in the craniotomy group, but the difference was not significant (OR=1.930, 95% CI 0.835 to 4.465). A further subgroup analysis was stratified by hematoma volume. The mortality in the endoscopic aspiration group was significantly lower than in the stereotactic aspiration group in the medium (≥40-<80 mL) (OR=2.438, 95% CI 1.101 to 5.402) and large hematoma subgroup (≥80 mL) (OR=66.532, 95% CI 6.345 to 697.675). Compared with the endoscopic aspiration group, a trend towards increased mortality was observed in the large hematoma subgroup of the craniotomy group (OR=8.721, 95% CI 0.933 to 81.551). CONCLUSION: Endoscopic aspiration can decrease the 6-month mortality of spontaneous basal ganglia hemorrhage, especially in patients with a hematoma volume ≥40 mL.

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