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1.
Crit Care Resusc ; 22(2): 126-132, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32389104

RESUMO

BACKGROUND: To determine the temporal trends of incidence and outcome based on different sources of sepsis using a nationwide administrative database. METHODS: From 2002 to 2012, the entire Taiwan's health insurance claims data of emergency-treated and hospital-treated sepsis were analysed for incidence and mortality trends. The information about patients with sepsis and sources of sepsis was identified using a set of validated International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) codes. The 30-day all-cause mortality was verified by linked death certificate database. RESULTS: A total of 1 259 578 episodes of sepsis were identified during the 11-year study period. Lower respiratory tract infection is the most common source of sepsis in patients, with the highest mortality rate. The incidence of genitourinary tract infection has the fastest growing rate. The sepsis mortality was declining at different rates for each source of sepsis. Co-infections in patients with sepsis are associated with higher mortality rate. CONCLUSION: The temporal trends of sepsis incidence and mortality varied among different sources of sepsis, with lower respiratory tract being the highest burden among patients with sepsis. Furthermore, sources of sepsis and the presence of co-infection are independent predictors of mortality. Our results support source-specific preventive and treatment strategies for future sepsis management.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Mortalidade Hospitalar/tendências , Sepse/etiologia , Feminino , Doenças Urogenitais Femininas/epidemiologia , Doenças Urogenitais Femininas/etiologia , Humanos , Incidência , Classificação Internacional de Doenças , Masculino , Doenças Urogenitais Masculinas/epidemiologia , Doenças Urogenitais Masculinas/etiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Sepse/epidemiologia , Sepse/mortalidade , Taiwan/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia
2.
Mater Sci Eng C Mater Biol Appl ; 109: 110368, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228920

RESUMO

Prolonged healing is a severe problem for elderly and diabetic patients. Impaired angiogenesis, stem cell differentiation, and migration have been shown to delay wound healing. The chemokine stromal cell-derived factor-1 (SDF-1) plays an essential role in recruiting cells to wound sites and is suggested to be a candidate for tissue engineering. In this study, chitosan (CHI) scaffolds were crosslinked with nontoxic genipin (Gp) and further heparinized for SDF-1 immobilization. Then, the structures were evaluated for their physicochemical properties (porosity, swelling ratio, and water vapor transmission rate (WVTR)). The interaction between SDF-1 and heparin could sustain SDF-1 release, which has been shown to enhance human umbilical vein endothelial cell (HUVEC) 2D/3D migration. The investigation of the wound-healing activity of the SDF-1-loaded CHI scaffolds revealed a better wound recovery rate in vivo in healthy and streptozotocin-induced diabetic Sprague-Dawley (SD) rats. The histological analysis illustrated that the local of SDF-1 treatment scaffold at the wound site enhanced neovascularization. The wounds treated with SDF-1 scaffolds also exhibited higher vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-ß) expression in Western blot assays. Based on the wound-healing activity and beneficial characteristics, the SDF-1-loaded CHI scaffold demonstrates potential as a material for treating skin wounds.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31817127

RESUMO

Background: Sarcopenia is critically associated with morbidity and mortality in the progression of Parkinson's disease (PD). However, analyses of clinical severity and brain changes, such as white matter (WM) alterations in PD patients with sarcopenia are limited. Further understanding of the factors associated with sarcopenia may provide a focused screen and potential for early intervention in PD patients. Methods: 52 PD patients and 19 healthy participants accepted dual-energy X-ray absorptiometry to measure the body composition. Using diffusion tensor imaging, the difference of WM integrity was measured between PD patients with sarcopenia (PDSa) and without sarcopenia (PDNSa). Multivariate analysis was performed to explore the relationships between clinical factors, WM integrity, and sarcopenia in PD patients. Results: 21 PD patients (40.4%) had sarcopenia. PDSa had a higher Unified Parkinson's Disease Rating Scale (UPDRS III) score, lower body mass index (BMI) and lower fat weight compared with the PDNSa. Additionally, PDSa patients exhibited lower fractional anisotropy accompanied by higher radial diffusivity and/or higher mean diffusivity in the fronto-striato-thalamic circuits, including bilateral cingulum, left superior longitudinal fasciculus, left genu of corpus callosum, and right anterior thalamic radiation, which participate in the executive function. In addition, decreased muscle mass was associated with worse WM integrity in these regions. Multiple linear regression analysis revealed that WM integrity in the left cingulum, right anterior thalamic radiation, together with gender (male) significantly predicted muscle mass in PD patients. Conclusions: WM alterations in the executive network, such as the fronto-striato-thalamic circuits, may indicate a risk factor for ongoing sarcopenia in PD patients. The effectiveness of using executive function to serve as a prodromal marker of sarcopenia in PD patients should be evaluated in future studies.


Assuntos
Função Executiva/fisiologia , Doença de Parkinson/epidemiologia , Sarcopenia/epidemiologia , Substância Branca/diagnóstico por imagem , Absorciometria de Fóton , Idoso , Índice de Massa Corporal , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Fatores de Risco , Sarcopenia/diagnóstico por imagem , Sarcopenia/patologia , Índice de Gravidade de Doença , Substância Branca/patologia
4.
J Biol Eng ; 13: 86, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754373

RESUMO

Background: Large gap healing is a difficult issue in the recovery of peripheral nerve injury. The present study provides in vivo trials of silicone rubber chambers filled with collagen containing IFN-γ or IL-4 to bridge a 15 mm sciatic nerve defect in rats. Fillings of NGF and normal saline were used as the positive and negative controls. Neuronal electrophysiology, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide and histology of the regenerated nerves were evaluated. Results: At the end of 6 weeks, animals from the groups of NGF and IL-4 had dramatic higher rates of successful regeneration (100 and 80%) across the wide gap as compared to the groups of IFN-γ and saline controls (30 and 40%). In addition, the NGF group had significantly higher NCV and shorter latency compared to IFN-γ group (P < 0.05). The IL-4 group recruited significantly more macrophages in the nerves as compared to the saline controls and the NGF-treated animals (P < 0.05). Conclusions: The current study demonstrated that NGF and IL-4 show potential growth-promoting capability for peripheral nerve regeneration. These fillings in the bridging conduits may modulate local inflammatory conditions affecting recovery of the nerves.

5.
Polymers (Basel) ; 11(10)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590259

RESUMO

The nervous system is the part of our body that plays critical roles in the coordination of actions and sensory information as well as communication between different body parts through electrical signal transmissions. Current studies have shown that patients are likely to experience a functional loss if they have to go through a nerve repair for >15 mm lesion. The ideal treatment methodology is autologous nerve transplant, but numerous problems lie in this treatment method, such as lack of harvesting sites. Therefore, researchers are attempting to fabricate alternatives for nerve regeneration, and nerve conduit is one of the potential alternatives for nerve regeneration. In this study, we fabricated polyurethane/polydopamine/extracellular matrix (PU/PDA/ECM) nerve conduits using digital light processing (DLP) technology and assessed for its physical properties, biodegradability, cytocompatibility, neural related growth factor, and proteins secretion and expression and its potential in allowing cellular adhesion and proliferation. It was reported that PU/PDA/ECM nerve conduits were more hydrophilic and allowed enhanced cellular adhesion, proliferation, expression, and secretion of neural-related proteins (collagen I and laminin) and also enhanced expression of neurogenic proteins, such as nestin and microtubule-associated protein 2 (MAP2). In addition, PU/PDA/ECM nerve conduits were reported to be non-cytotoxic, had sustained biodegradability, and had similar physical characteristics as PU conduits. Therefore, we believed that PU/PDA/ECM nerve conduits could be a potential candidate for future nerve-related research or clinical applications.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31569569

RESUMO

Background: To investigate the relationship between fat content and the cross-sectional area of psoas and thigh muscles, and clinical severity in patients with Parkinson's disease. Materials and Methods: Twenty-five patients and 20 age- and sex-matched normal controls were recruited. All subjects underwent MRI study to determine the fat content of the bilateral psoas and thigh muscles. Muscle quality was measured by grasp, walking speed, and cross-sectional area. All patients underwent clinical surveys to evaluate disease severity and frailty, and analyses of the correlations between muscle quality and disease severity were performed. Results: Compared with the controls, patients exhibited higher fatty content in the measured muscles. The higher fat infiltration of measured muscles was significantly correlated with increased disease severity and frailty in patients. The fat fraction of the bilateral medial compartment of the thigh was correlated with the Unified Parkinson Disease Rating Scale-I results and the fat fraction of the bilateral anterior compartment of the thigh was correlated with weakness and exhaustion in patients. Conclusions: Decreased quality in psoas and thigh muscles is prominent in Parkinson's disease which is further associated with disease severity and frailty. Awareness of the risk of sarcopenia and associated sequelae might improve patient care and outcomes.


Assuntos
Adiposidade/fisiologia , Composição Corporal , Fragilidade/fisiopatologia , Músculo Esquelético/fisiologia , Doença de Parkinson/fisiopatologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/fisiologia , Índice de Gravidade de Doença , Taiwan , Coxa da Perna
7.
J Clin Med ; 8(7)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269723

RESUMO

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). A dysfunctional TME promotes drug resistance, disease recurrence, and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within the TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins, and microRNAs. RESULTS: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Coculture of GAMs (and GAM-derived exosomes) and GBM cell lines increased GBM cells' resistance against temozolomide (TMZ) by upregulating the prosurvival gene programmed cell death protein 4 (PDCD4) and stemness markers SRY (sex determining region y)-box 2 (Sox2), signal transducer and activator of transcription 3 (STAT3), Nestin, and miR-21-5p and increasing the M2 cytokines interleukin 6 (IL-6) and transforming growth factor beta 1(TGF-ß1) secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed a markedly reduced ability to secret M2 cytokines and reduced miR-21-enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which the tumor suppressor PDCD4 was targeted. We subsequently established patient-derived xenograft (PDX) models where mice bore patient GBM and GAMs. Treatment with pacritinib and the combination of pacritinib and TMZ appeared to significantly reduce the tumorigenesis of GBM/GAM PDX mice as well as overcome TMZ resistance and M2 polarization of GAMs. CONCLUSION: In summation, we showed the potential of pacritinib alone or in combination with TMZ to suppress GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in clinical settings.

8.
Environ Toxicol ; 34(8): 921-927, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31066208

RESUMO

Hyperkalemia is often associated with cardiac dysfunction. In this study an earthworm extract (dilong) was prepared from dried Pheretima aspergillum powder and its effect against high-KCl challenge was determined in H9c2 cardiomyoblast cells. H9c2 cells pre-treated with dilong (31.25, 62.5, 125, and 250 mg/mL) for 24 hours, where challenged with different doses of KCl treatment for 3 hours to determine the protective mechanisms of dilong against cardiac fibrosis. High-KCl administration induced mitochondrial injury and elevated the levels of pro-apoptotic proteins. The mediators of fibrosis such as ERK, uPA, SP1, and CTGF were also found to be upregulated in high-KCl condition. However, dilong treatment enhanced IGF1R/PI3k/Akt activation which is associated with cell survival. In addition, dilong also reversed high-KCl induced cardiac fibrosis related events in H9c2 cells and displayed a strong cardio-protective effect. Therefore, dilong is a potential agent to overcome cardiac events associated with high-KCl toxicity.


Assuntos
Mitocôndrias Cardíacas/efeitos dos fármacos , Mioblastos Cardíacos/efeitos dos fármacos , Oligoquetos , Cloreto de Potássio/toxicidade , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular , Sobrevivência Celular , Fibrose , Mioblastos Cardíacos/patologia , Substâncias Protetoras/farmacologia
9.
Polymers (Basel) ; 11(2)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30960211

RESUMO

A poly(γ⁻glutamic acid)/ß⁻tricalcium phosphate (γ⁻PGA/ß⁻TCP) composite fibrous mat was fabricated using the electrospinning technique as a novel bone substitute. The mat was then cross-linked with cystamine in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide to improve its water-resistant ability. Scanning electron micrographs revealed that the γ⁻PGA/ß⁻TCP fibers had a uniform morphology with diameters ranging from 0.64 ± 0.07 µm to 1.65 ± 0.16 µm. The average diameter of the fibers increased with increasing cross-linking time. Moreover, increasing the cross-linking time and decreasing the γ⁻PGA/ß⁻TCP weight ratio decreased the swelling ratio and in vitro degradation rate of the composite fibrous mat. In vitro experiments with osteoblast-like MG-63 cells demonstrated that the mat with a γ⁻PGA/ß⁻TCP weight ratio of 20 and cross-linked time of 24 h had a higher alkaline phosphatase activity and better cell adhesion. Furthermore, the rat cranial bone defect was created and treated with the γ⁻PGA/ß⁻TCP composite fibrous mat to evaluate its potential in bone regeneration. After 8 weeks of implantation, micro computed tomography showed that the γ⁻PGA/ß⁻TCP composite fibrous mat promoted new bone growth. These observations suggest that the γ⁻PGA/ß⁻TCP composite fibrous mat has a potential application in bone tissue engineering.

10.
Medicine (Baltimore) ; 98(5): e14277, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702590

RESUMO

This study aimed to compare the differences in radiological outcomes and complications between single- and multilevel anterior cervical discectomy and fusion (ACDF) by using a polyetheretherketone (PEEK) cage-plate fusion system.Fifty-seven patients who underwent ACDF via the PEEK cage-plate fusion system were enrolled and subjected to ≥6 months of follow-up. The patients were divided into 4 groups according to different cage-plate implantation levels: 1-level group (n = 17), 2-level group (n = 24), 3-level group (n = 12), and 4-level group (n = 4). Fusion time, changes in segment and global lordotic angle, subsidence rate, and changes in disc and adjacent segmental disc height were subjected to radiological evaluation.The fusion period of multilevel ACDF was longer than that of single-level ACDF. The fusion period of the 3-level (4.09 ±â€Š0.94, P = .004) and 4-level (5.25 ±â€Š0.89, P = .004) group was also significantly longer than that of the 1-level group. The mean lordotic angle in all of the groups was changed in the immediate postoperative period and in the final follow-up. The cage subsidence rates were 11.76% (2/17) in the 1-level group, 20.83% (5/24) in the 2-level group, and 2/12 (16.67%) in the 3-level group. No subsidence occurred in the 4-level groups. Changes in the lower adjacent segmental disc height were significantly increased in multilevel ACDF compared with those in single-level ACDF.Despite the longer fusion time, the outcomes of the proposed system were even better with the greater number of treatment levels by using PEEK cage-plate fusion system. Changes in the lower adjacent segmental disc height should also prolong follow-up duration to investigate the symptomatic adjacent segment degeneration in multilevel ACDF.


Assuntos
Vértebras Cervicais/cirurgia , Discotomia/métodos , Fixadores Internos , Fusão Vertebral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Cetonas , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Fatores de Tempo
11.
Mater Sci Eng C Mater Biol Appl ; 96: 850-858, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30606599

RESUMO

This study examined the in vitro characteristics and in vivo wound healing effect of novel Lithospermi radix (LR) extract-containing bilayer scaffolds in a rat model. LR extract, which has been used as a traditional herbal medicine for treating skin wounds, was added to a biocompatible gelatin solution. After glutaraldehyde vapor was used to modify the surface of chitosan scaffolds, various ratios of mammalian gelatin and fish collagen (GF100, GF91 and GF82) were electrospun onto the chitosan scaffolds to manufacture bilayer scaffolds. The porous chitosan scaffolds with a high swelling ratio showed efficient exudate absorption ability. GF91 gelatin nanofibers electrospun at a constant flow rate at 0.1 mL/h and a voltage of 20 kV displayed the optimal characteristics required for cell attachment and skin tissue regeneration. Moreover, the LR extract was successfully released slowly from the GF91 nanofibers. The investigation of the wound-healing activity of the chitosan/gelatin (CGF) bilayer scaffolds revealed that CGF91L provided the highest wound recovery rate in vivo in Sprague-Dawley (SD) rats. Based on its wound-healing effect and beneficial characteristics, the novel LR extract-containing CGF91 bilayer scaffold demonstrates potential as a material for treating skin wounds.


Assuntos
Lithospermum/química , Nanofibras , Extratos Vegetais , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Animais , Linhagem Celular , Quitosana/química , Quitosana/farmacologia , Modelos Animais de Doenças , Implantes de Medicamento , Masculino , Camundongos , Nanofibras/química , Nanofibras/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologia
12.
Eur Radiol ; 29(5): 2659-2668, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30523452

RESUMO

INTRODUCTION: To investigate the structural changes of the brain that correlate with physical frailty and cognitive impairments in Parkinson's disease (PD) patients. METHODS: Sixty-one PD patients and 59 age- and sex-matched healthy controls were enrolled. For each participant, a frailty assessment using Fried's criteria and comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted, and structural brain MR images were acquired for voxel-based morphometric analysis. The neuropsychological testing includes various tests in these five domains: attention, executive, memory, speech and language, and visuospatial functions. Exploratory group-wise comparisons of gray matter volume (GMV) in the PD patients and controls were conducted. Voxel-wise multiple linear regression analyses were conducted for physical frailty-related and cognitive impairment-related GMV changes in the PD patients. Voxel-wise multiple linear regressions were also performed with the five cognitive domains separated using the same model. RESULTS: The PD patients exhibited diffuse GMV reductions in comparison to the controls. In the PD patients, physical frailty-related decreases in GMV were observed in the bilateral frontal and occipital cortices, while cognitive impairment-related decreases in GMV were observed in the bilateral frontal, occipital, and temporal cortices. These regions overlap in the lateral occipital cortex. After the five domains of cognitive functions were analyzed separately, physical frailty-related decreases in GMV still overlap in lateral occipital cortices with every domain of cognitive impairment-related decreases in GMV. CONCLUSION: Reduced GMV in the lateral occipital cortex is associated with cognitive impairment and physical frailty in PD patients. KEY POINTS: • Physical frailty in PD was associated with decreased GMV in the frontal and occipital cortices, while cognitive impairment was associated with decreased GMV in the frontal, temporal, and occipital cortices. • Physical frailty and cognitive impairment were both associated with decreased GMV in the lateral occipital cortex, which is part of the ventral object-based visual pathway. • Decreased GMV in the lateral occipital cortex may serve as a potential imaging biomarker for physical frailty and cognitive impairment in PD.


Assuntos
Disfunção Cognitiva/etiologia , Fragilidade/etiologia , Substância Cinzenta/patologia , Imagem por Ressonância Magnética/métodos , Lobo Occipital/patologia , Doença de Parkinson/complicações , Atenção , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Feminino , Fragilidade/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico
13.
Materials (Basel) ; 11(9)2018 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-30205596

RESUMO

Although autologous nerve grafting remains the gold standard treatment for peripheral nerve injuries, alternative methods such as development of nerve guidance conduits have since emerged and evolved to counter the many disadvantages of nerve grafting. However, the efficacy and viability of current nerve conduits remain unclear in clinical trials. Here, we focused on a novel decellularized extracellular matrix (dECM) and polydopamine (PDA)-coated 3D-printed poly(ε-caprolactone) (PCL)-based conduits, whereby the PDA surface modification acts as an attachment platform for further dECM attachment. We demonstrated that dECM/PDA-coated PCL conduits possessed higher mechanical properties when compared to human or animal nerves. Such modifications were proved to affect cell behaviors. Cellular behaviors and neuronal differentiation of Schwann cells were assessed to determine for the efficacies of the conduits. There were some cell-specific neuronal markers, such as Nestin, neuron-specific class III beta-tubulin (TUJ-1), and microtubule-associated protein 2 (MAP2) analyzed by enzyme-linked immunosorbent assay, and Nestin expressions were found to be 0.65-fold up-regulated, while TUJ1 expressions were 2.3-fold up-regulated and MAP2 expressions were 2.5-fold up-regulated when compared to Ctl. The methodology of PDA coating employed in this study can be used as a simple model to immobilize dECM onto PCL conduits, and the results showed that dECM/PDA-coated PCL conduits can as a practical and clinically viable tool for promoting regenerative outcomes in larger peripheral nerve defects.

14.
J Neuroinflammation ; 15(1): 281, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30257698

RESUMO

BACKGROUND: To identify the vulnerable areas associated with systemic oxidative stress and further disruption of these vulnerable areas by measuring the associated morphology and functional network alterations in Parkinson's disease (PD) patients with and without cognitive impairment. METHODS: This prospective study was approved by the institutional review board of KCGMH, and written informed consent was obtained. Between December 2010 and May 2015, 41 PD patients with different levels of cognitive functions and 29 healthy volunteers underwent peripheral blood sampling to quantify systemic oxidative stress, as well as T1W volumetric and resting state functional MRI (rs-fMRI) scans. Rs-fMRI was used to derive the healthy intrinsic connectivity patterns seeded by the vulnerable areas associated with any of the significant oxidative stress markers. The two groups were compared in terms of the functional connectivity correlation coefficient (fc-CC) and gray matter volume (GMV) of the network seeded by the vulnerable areas. RESULTS: The levels of oxidative stress markers, including leukocyte apoptosis and adhesion molecules, were significantly higher in the PD group. Using whole-brain VBM-based correlation analysis, the bilateral mesial temporal lobes (MTLs) were identified as the most vulnerable areas associated with lymphocyte apoptosis (P < 0.005). We found that the MTL network of healthy subjects resembled the PD-associated atrophy pattern. Furthermore, reduced fc-CC and GMV were further associated with the aggravated cognitive impairment. CONCLUSION: The MTLs are the vulnerable areas associated with peripheral lymphocyte infiltration, and disruptions of the MTL functional network in both architecture and functional connectivity might result in cognitive impairments in Parkinson's disease.


Assuntos
Transtornos Cognitivos/etiologia , Doenças Neurodegenerativas/etiologia , Estresse Oxidativo/fisiologia , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Lobo Temporal/patologia , Idoso , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Leucócitos/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/diagnóstico por imagem , Oxigênio/sangue , Doença de Parkinson/diagnóstico por imagem , Estudos Prospectivos , Estudos Retrospectivos , Lobo Temporal/diagnóstico por imagem
15.
Mater Sci Eng C Mater Biol Appl ; 91: 404-413, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30033271

RESUMO

This study proposes structural models of biodegradable vascular stents. One, two, or three plies of biodegradable polyvinyl alcohol (PVA) yarns are combined and twisted with twist factors of 2, 3, 4, 5, and 6 to form one-, two-, and three-ply PVA twisted yarns. The braided, warp-knitted, and weft-knitted PVA vascular stents are composed of PVA twisted yarns by using a braider, a warp knitting machine, and a weft knitting machine. The formation and mechanical properties of PVA vascular stents are evaluated, and the biological properties are examined in terms of biocompatibility through in vitro assay and subcutaneous embedding using in vivo assay. Test results indicate that the compression strength of PVA vascular stents is improved when using PVA twisted yarns containing a high number of plies and twist factor. Specifically, weft-knitted PVA vascular stents exhibit the optimal compression strength. PVA vascular stents treated with chemical cross-linking show weight loss lower than 3% after immersion in PBS solution for 30 days. Moreover, the antibacterial test and cell culture results suggest that PVA vascular stents are nontoxic and biocompatible. Subcutaneous embedding results show that PVA vascular stents retain intact formation when subcutaneously embedded in vivo for 28 days, indicating their good biological property. PVA vascular stents are suitable candidates for tissue engineering applications.


Assuntos
Materiais Biocompatíveis/química , Vasos Sanguíneos/fisiologia , Teste de Materiais/métodos , Fenômenos Mecânicos , Álcool de Polivinil/química , Stents , Animais , Antibacterianos/farmacologia , Linhagem Celular , Contagem de Colônia Microbiana , Escherichia coli/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Ratos , Staphylococcus aureus/efeitos dos fármacos , Tela Subcutânea/efeitos dos fármacos
16.
Int J Mol Sci ; 19(5)2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29701696

RESUMO

The process of autophagy in heart cells maintains homeostasis during cellular stress such as hypoxia by removing aggregated proteins and damaged organelles and thereby protects the heart during the times of starvation and ischemia. However, autophagy can lead to substantial cell death under certain circumstances. BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), a hypoxia-induced marker, has been shown to induce both autophagy and apoptosis. A BNIP3-docked organelle, e.g., mitochondria, also determines whether autophagy or apoptosis will take place. Estrogen (E2) and estrogen receptor (ER) alpha (ERα) have been shown to protect the heart against mitochondria-dependent apoptosis. The aim of the present study is to investigate the mechanisms by which ERα regulates BNIP3-induced apoptosis and autophagy, which is associated with hypoxic injury, in cardiomyoblast cells. An in vitro model to mimic hypoxic injury in the heart by engineering H9c2 cardiomyoblast cells to overexpress BNIP3 was established. Further, the effects of E2 and ERα in BNIP3-induced apoptosis and autophagy were determined in BNIP3 expressing H9c2 cells. Results from TUNEL assay and Immunoflourecense assay for LC3 puncta formation, respectively, revealed that ERα/E2 suppresses BNIP3-induced apoptosis and autophagy. The Western blot analysis showed ERα/E2 decreases the protein levels of caspase 3 (apoptotic marker), Atg5, and LC3-II (autophagic markers). Co-immunoprecipitation of BNIP3 and immunoblotting of Bcl-2 and Rheb showed that ERα reduced the interaction between BNIP3 and Bcl-2 or Rheb. The results confirm that ERα binds to BNIP3 causing a reduction in the levels of functional BNIP3 and thereby inhibits cellular apoptosis and autophagy. In addition, ERα attenuated the activity of the BNIP3 promoter by binding to SP-1 or NFκB sites.


Assuntos
Apoptose , Autofagia , Receptor alfa de Estrogênio/metabolismo , Estrogênios/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Mioblastos Cardíacos/metabolismo , Animais , Linhagem Celular , Ratos
17.
Am J Chin Med ; 46(1): 69-86, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29298514

RESUMO

Astragalus membranaceus (AM) is one of 50 fundamental herbs in traditional Chinese medicine. Previous studies have shown that AM extract can be a potential nerve growth-promoting factor, being beneficial for the growth of peripheral nerve axons. We further investigated the effects of AM extract on regeneration in a rat sciatic nerve transection model. Rats were divided into three groups ([Formula: see text]): normal saline (intraperitoneal) as the control, and 1.5[Formula: see text]g/kg or 3.0[Formula: see text]g/kg of AM extract (every other day for four weeks), respectively. We evaluated neuronal electrophysiology, neuronal connectivity, macrophage infiltration, expression levels and location of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors (NGFs) and immunoregulatory factors. In the high-dose AM group, neuronal electrophysiological function (measured by nerve conductive velocity and its latency) was significantly improved ([Formula: see text]). Expression levels of CGRP and macrophage density were also drastically enhanced ([Formula: see text]). Expression levels of fibroblast growth factor (FGF), NGF, platelet-derived growth factor (PDGF), transforming growth factor-[Formula: see text], interleukin-1 (IL-1), and interferon (IFN)-[Formula: see text] were reduced in the high-dose AM group ([Formula: see text]), while FGF, NGF, PDGF, IL-1, and IFN-[Formula: see text] were increased in the low-dose AM group ([Formula: see text]). These results suggest that AM can modulate local inflammatory conditions, enhance nerve regeneration, and potentially increase recovery of a severe peripheral nerve injury.


Assuntos
Astragalus propinquus/química , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Macrófagos/imunologia , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/imunologia , Nervos Periféricos/crescimento & desenvolvimento , Nervos Periféricos/fisiologia , Extratos Vegetais/farmacologia , Animais , Axônios/fisiologia , Relação Dose-Resposta a Droga , Fatores de Crescimento de Fibroblastos/metabolismo , Interferon gama/metabolismo , Interleucina-1/metabolismo , Fator de Crescimento Neural/metabolismo , Regeneração Nervosa/fisiologia , Condução Nervosa , Fator de Crescimento Derivado de Plaquetas/metabolismo , Ratos Sprague-Dawley , Estimulação Química
18.
J Cell Physiol ; 233(8): 5869-5876, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29226955

RESUMO

Systemic inflammation induced by bacterial infection is one of several causative agents for cardiovascular disorders in patients with periodontal disease. Experimental results indicate that miRNAs play important roles in systemic inflammation induced by endotoxins. Further evidence states that stem cell based therapy shows potential in the treatment of inflammatory responses induced by sepsis. This study investigates if stem cells show protective effects on cardiomyocyte damage induced by porphyromonas gingivalis-LPS (Pg-LPS) through regulating miRNAs. H9c2 cardiomyoblasts and neonatal rat cardiomyocytes (NRCMs) were damaged using Pg-LPS in this study. Pg-LPS damaged H9c2 or NRCMs were then rescued using adipose-derived stem cells (ADSC). The experimental results reveal that Pg-LPS treatment is capable of inducing TLR4/NFκB axis activation, cell death signaling and IGF1R/PI3 K/Akt axis suppression. miR181b was downregulated in Pg-LPS damaged H9c2/NRCMs. All markers were improved in H9c2/NRCMs cocultured with ADSC. miR181b mimic and inhibitor confirmed that miR181b plays a central role in regulating the cardio protective effect on Pg-LPS damaged H9c2/NRCMs cocultured with ADSC. miR181b acts as potential therapeutic marker in cardiomyopathy induced by Pg-LPS. Transplantation of adipose-derived stem cells show potential in the treatment of cardiomyopathy induced by porphyromonas gingivalis endotoxin via regulation of miR181b.


Assuntos
Cardiomiopatias/patologia , MicroRNAs/genética , Miócitos Cardíacos/patologia , Doenças Periodontais/patologia , Células-Tronco/metabolismo , Animais , Cardiotônicos , Linhagem Celular , Sobrevivência Celular , Inflamação/microbiologia , Inflamação/patologia , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Doenças Periodontais/microbiologia , Porphyromonas gingivalis , Ratos , Receptor 4 Toll-Like/metabolismo
19.
Sci Rep ; 7(1): 17489, 2017 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-29235541

RESUMO

In our previous study, we found that gelatin-based materials exhibit good conductivity and are non-cytotoxic. In this study, gelatin was cross-linked with bisvinyl sulfonemethyl (BVSM) to fabricate a biodegradable conduit for peripheral nerve repair. First, BVSM on the prepared conduit was characterized to determine its mechanical properties and contact angle. The maximum tensile strength and water contact angle of the gelatin-BVSM conduits were 23 ± 4.8 MPa and 74.7 ± 9°, which provided sufficient mechanical strength to resist muscular contraction; additionally, the surface was hydrophilic. Cytotoxicity and apoptosis assays using Schwann cells demonstrated that the gelatin-BVSM conduits are non-cytotoxic. Next, we examined the neuronal electrophysiology, animal behavior, neuronal connectivity, macrophage infiltration, calcitonin gene-related peptide localization and expression, as well as the expression levels of nerve regeneration-related proteins. The number of fluorogold-labelled cells and histological analysis of the gelatin-BVSM nerve conduits was similar to that observed with the clinical use of silicone rubber conduits after 8 weeks of repair. Therefore, our results demonstrate that gelatin-BVSM conduits are promising substrates for application as bioengineered grafts for nerve tissue regeneration.


Assuntos
Implantes Absorvíveis , Gelatina , Regeneração Tecidual Guiada , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/terapia , Sulfonas , Compostos de Vinila , Potenciais de Ação , Animais , Materiais Biocompatíveis , Sobrevivência Celular , Gelatina/química , Regeneração Tecidual Guiada/instrumentação , Macrófagos/patologia , Macrófagos/fisiologia , Masculino , Teste de Materiais , Camundongos Transgênicos , Músculo Esquelético/fisiopatologia , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Distribuição Aleatória , Ratos Sprague-Dawley , Células de Schwann/patologia , Células de Schwann/fisiologia , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Sulfonas/química , Compostos de Vinila/química
20.
Anesth Analg ; 125(5): 1549-1557, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28930937

RESUMO

BACKGROUND: Several clinical trials on hypertonic fluid administration have been completed, but the results have been inconclusive. The objective of this study is to summarize current evidence for treating hypovolemic patients with hypertonic solutions by performing a systematic review and meta-analysis. METHODS: Major electronic databases were searched from inception through June 2014. We included only randomized controlled trials involving hemorrhagic shock patients treated with hypertonic solutions. After screening 570 trials, 12 were eligible for the final analysis. Pooled effect estimates were calculated with a random effect model. RESULTS: The 12 studies included 6 trials comparing 7.5% hypertonic saline (HS) with 0.9% saline or Ringer's lactate solution and 11 trials comparing 7.5% hypertonic saline with dextran (HSD) with isotonic saline or Ringer's lactate. Overall, there were no statistically significant survival benefits for patients treated with HS (relative risk [RR], 0.96; 95% confidence interval [CI], 0.82-1.12) or HSD (RR, 0.92; 95% CI, 0.80-1.06). Treatment with hypertonic solutions was also not associated with increased complications (RR, 1.03; 95% CI, 0.78-1.36). Subgroup analysis on trauma patients in the prehospital or emergency department settings did not change these conclusions. There was no evidence of significant publication bias. Meta-regression analysis did not find any significant sources of heterogeneity. CONCLUSIONS: Current evidence does not reveal increased mortality when the administration of isotonic solutions is compared to HS or HSD in trauma patients with hemorrhagic shock. HS or HSD may be a viable alternative resuscitation fluid in the prehospital setting. Further studies are needed to determine the optimum volume and regimen of intravenous fluids for the treatment of trauma patients.


Assuntos
Dextranos/administração & dosagem , Hidratação/métodos , Hemodinâmica , Soluções Isotônicas/administração & dosagem , Solução Salina Hipertônica/administração & dosagem , Choque Hemorrágico/terapia , Cloreto de Sódio/administração & dosagem , Ensaios Clínicos como Assunto , Dextranos/efeitos adversos , Medicina Baseada em Evidências , Hidratação/efeitos adversos , Hidratação/mortalidade , Humanos , Infusões Intravenosas , Soluções Isotônicas/efeitos adversos , Razão de Chances , Lactato de Ringer , Fatores de Risco , Solução Salina Hipertônica/efeitos adversos , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/mortalidade , Choque Hemorrágico/fisiopatologia , Cloreto de Sódio/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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