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1.
Sci China Life Sci ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32382980

RESUMO

Spinal cord injury (SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues (aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of aSCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein 2-, 5-hydroxytryptamine-, choline acetyltransferase- and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in aSCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.

2.
Comput Methods Programs Biomed ; 194: 105487, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32473514

RESUMO

Monte Carlo (MC)-based simulation is the most precise method in scatter correction for Cone-beam CT (CBCT). Nonetheless, the existing MC methods cannot be fully applied in clinical due to its low efficiency. The traditional MC simulations perform calculations via a particle-by-particle scheme, which leads to high computation costs because abundant photons do not reach the X-ray detector in transport. The conventional approaches cannot control where the particle ends. Hence, it unavoidably waste lots of time in transporting numerous photons that have no contribution to the signal at the detector, yielding a low computational efficiency. To solve the problem, an innovative GPU-based Metropolis MC (gMMC) method was proposed. Compared with the traditional ones, the Metropolis based algorithm utilizes a path-by-path sampling method. The method can automatically control each particle path and eventually accelerate the convergence. In this paper, we firstly take planning CT image as prior information because of its precise CT value, and utilize gMMC to estimate scatter signal. Then the scatter signals are removed from the raw CBCT projections. Afterwards, FDK reconstruction is performed to obtain the corrected image,some accelerating strategies including reducing photon history number, pixels sampling, projection angles sampling and reconstructed image down-sampling achieve adaptive fast CBCT image reconstruction. For having high computational efficiency, we implemented the whole workflow on a 4-GPU workstation. In order to verify the feasibility of the the method, the experiment of several cases are conducted including simulation, phantom, and real patient cases. Results indicate that the image contrast becomes better, the scatter artifacts are eliminated. The maximum error (emax), the minimum error (emin), the 95th percentile error (e95%), average error (¯e) are reduced from 264, 56, 14 and 21 HU to 28, 10, 3 and 7 HU in full-fan case, and from 387, 5, 19 and 95 HU to 39, 2, 2 and 6 HU in the half-fan case. In terms of computation time, the MC simulation time of all cases is within 2.5 seconds, and the total time is within 15 seconds.

3.
Medicine (Baltimore) ; 99(17): e19938, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332675

RESUMO

The pathophysiology of alcohol use disorder (AUD) is not totally clear. The aim of this study was to investigate the serum levels of brain-derived neurotrophic factor (BDNF) and oxidative stress markers in AUD patients during alcohol detoxification. Evaluation of changes in BDNF, glutathione peroxidase (GPX), catalase, superoxide dismutase, thiobarbituric acid reactive substances, 8-hydroxy 2'-deoxyguanosine, PCC and S100B were carried out.14 AUD inpatients and 20 healthy control subjects were recruited for this study. The serum BDNF, S100B and oxidative stress markers were measured with assay kits.Serum levels of catalase, GPX, PCC and 8-hydroxy 2'-deoxyguanosine were significantly higher in the AUD group subjects than in the controls (P < .05). However, BDNF levels were lower in the AUD group than in the controls (P < .05). After alcohol detoxification treatment, the GPX levels in the AUD group dropped (P < .05) and the BDNF levels rose (P < .05).The results suggest that serum BDNF and GPX levels might be state biomarkers for AUD patients undergoing alcohol detoxification.


Assuntos
Alcoolismo/sangue , Alcoolismo/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/análise , Glutationa Peroxidase/análise , Inativação Metabólica/fisiologia , Adulto , Alcoolismo/fisiopatologia , Biomarcadores/análise , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Feminino , Glutationa Peroxidase/sangue , Humanos , Inativação Metabólica/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade
4.
Emerg Infect Dis ; 26(3): 437-445, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32091361

RESUMO

CaliciNet China, a network of provincial, county, and city laboratories coordinated by the Chinese Centers for Disease Control and Prevention, was launched in October 2016 to monitor the epidemiology and genotype distribution of norovirus outbreaks in China. During October 2016-September 2018, a total of 556 norovirus outbreaks were reported, and positive fecal samples from 470 (84.5%) outbreaks were genotyped. Most of these outbreaks were associated with person-to-person transmission (95.1%), occurred in childcare centers or schools (78.2%), and were reported during November-March of each year (63.5%). During the 2-year study period, 81.2% of all norovirus outbreaks were typed as GII.2[P16]. In China, most norovirus outbreaks are reported by childcare centers or schools; GII.2[P16] is the predominant genotype. Ongoing surveillance by CaliciNet China will provide information about the evolving norovirus genotype distribution and outbreak characteristics important for the development of effective interventions, including vaccines.

5.
Health Secur ; 18(S1): S14-S22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32004129

RESUMO

Global spread of Zika virus in 2015 and 2016 highlighted the importance of surveillance to rapidly detect, report, and respond to emerging infections. We describe the lessons learned from the development and deployment of a web-based surveillance reporting system for Zika virus and other acute febrile illnesses (AFI) in Guangdong and Yunnan provinces, China. In less than 2 months, we customized the China Epidemiologic Dynamic Data Collection (EDDC) platform to collect, manage, and visualize data in close to real time. According to provincial and sentinel hospital staff requirements, the customized platform provided specific user authorization management, online/offline data collection, data quality control, and secure data transmission and protection and visualization tools. AFI case data and laboratory test results were entered through a web-based interface by hospital and provincial-level staff and saved on a China CDC server in Beijing. The dashboard visualized aggregate data by hospital, age, onset date, and laboratory test results. From June 2017 to December 2018, data from 768 patients with AFI were entered into the web-based surveillance system and visualized by hospital and provincial-level decision makers. Input from provincial and hospital staff was essential for developing the AFI case-reporting and feedback tools appropriate for specific settings and decision-making requirements. Web-based systems (eg, EDDC, data collection, and visualization tools that can be easily adapted to meet local surveillance needs) can help shorten time for system deployment, thereby strengthening global health security to rapidly detect and respond to emerging infections and outbreaks.

6.
J Immunother Cancer ; 8(1)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31959728

RESUMO

BACKGROUND: Immunotherapy has become an important treatment option for patients with advanced non-small cell lung cancer (NSCLC). At present, none of these existing biomarkers can effectively stratify true responders and there is an urgent need for identifying novel biomarkers. Exosomes derived from the serum of patients with cancer have been proven to be reliable markers for cancer diagnosis. Here, we explored the possibility of using plasma-derived exosomal microRNAs as potential biomarkers for optimal selection of patients with advanced EGFR / ALK negative NSCLC to immunotherapy. METHODS: From June 2017 to February 2019, 30 patients with advanced EGFR / ALK wild-type (WT) NSCLC who received PD-1/PD-L1 inhibitors were enrolled. The efficacy evaluation was conducted after every three cycles of treatment according to RECIST 1.1. Plasma samples of these patients were collected before the administration of PD-1/PD-L1 inhibitors as baseline, and after every three cycles if the patients achieved partial response (PR) or complete response. Plasma from seven healthy individuals was also collected as normal control. Exosomes were prepared by ultracentrifugation followed by total RNA extraction, and exosome-derived miRNAs were profiled using small RNA next-generation sequencing followed by differential expression analysis. RESULTS: In order to identify biomarker for better response, all five patients who achieved PR and four patients with progressive disease (PD) at efficacy evaluation were included for differential expression analysis. Based on unsupervised hierarchical clustering, exosomal miRNA expression profile was significantly altered in patients with NSCLC compared with normal controls with a total of 155 differentially expressed exosomal miRNAs. Interestingly, hsa-miR-320d, hsa-miR-320c, and hsa-miR-320b were identified significantly upregulated in the PD groups compared with the PR group at baseline before the treatment. In addition, we identified that hsa-miR-125b-5p, a T-cell suppressor, showed a trend of increased expression in the PD group at baseline and was significantly downregulated in the post-treatment plasma exosomes compared with pre-treatment samples of the PR patients. CONCLUSION: Patients with NSCLC represent unique plasma exosomal miRNA profiles. Hsa-miR-320d, hsa-miR-320c, and hsa-miR-320b were identified as potential biomarkers for predicting the efficacy of immunotherapy in advanced NSCLCs. When T-cell suppressor hsa-miR-125b-5p was downregulated during the treatment, the patients may obtain increased T-cell function and respond well to immunotherapy.

7.
Low Urin Tract Symptoms ; 12(1): 41-46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31430060

RESUMO

OBJECTIVES: Detrusor underactivity (DU) is a common but poorly understood clinical problem. The diagnosis and treatment are difficult and full of uncertainties. There are many overlaps between DU and bladder outlet obstruction (BOO) in men. Prostatic surgery might improve voiding efficiency (VE). This study aims to investigate effectiveness and predictors of voiding function recovery after prostate surgery in patients with DU. METHODS: Male patients with DU and small total prostate volume (TPV, <40 mL) who had undergone transurethral prostate surgery were retrospectively reviewed over the past two decades. Video-urodynamic studies were performed before and after the operation. The urodynamic parameters were recorded, and change of VE was used to determine treatment outcome. A postoperative VE of ≥50% was considered successful. RESULTS: A total of 48 patients were included, with a mean age of 74.4 ± 10.0 years. The mean follow-up period was 24.9 ± 30.5 months. At the most recent follow-up, 29 (60.4%) patients had positive results. Among them, 21 (72.4%) patients recovered within 1 month, and only one recovered later than 6 months after the operation. After surgery, the maximum flow rate, voided volume, postvoid residual urine, and VE all showed improvement. Patients with successful outcome had a higher baseline detrusor pressure (p = .029) and greater maximum flow rate (p = .034) than the nonrecovery group. The age and other parameters were not significantly different between recovery and nonrecovery group. CONCLUSIONS: Patients with DU and small TPV might also benefit from prostatic surgery if they had a higher detrusor pressure and maximum flow rate at baseline.

8.
Int J Mol Sci ; 20(24)2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31847115

RESUMO

Various animal studies have shown beneficial effects of hypercapnia in lung injury. However, in patients with acute respiratory distress syndrome (ARDS), there is controversial information regarding the effect of hypercapnia on outcomes. The duration of carbon dioxide inhalation may be the key to the protective effect of hypercapnia. We investigated the effect of pre-treatment with inhaled carbon dioxide on lipopolysaccharide (LPS)-induced lung injury in mice. C57BL/6 mice were randomly divided into a control group or an LPS group. Each LPS group received intratracheal LPS (2 mg/kg); the LPS groups were exposed to hypercapnia (5% carbon dioxide) for 10 min or 60 min before LPS. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. LPS significantly increased the ratio of lung weight to body weight; concentrations of BALF protein, tumor necrosis factor-α, and CXCL2; protein carbonyls; neutrophil infiltration; and lung injury score. LPS induced the degradation of the inhibitor of nuclear factor-κB-α (IκB-α) and nuclear translocation of NF-κB. LPS increased the surface protein expression of toll-like receptor 4 (TLR4). Pre-treatment with inhaled carbon dioxide for 10 min, but not for 60 min, inhibited LPS-induced pulmonary edema, inflammation, oxidative stress, lung injury, and TLR4 surface expression, and, accordingly, reduced NF-κB signaling. In summary, our data demonstrated that pre-treatment with 10-min carbon dioxide inhalation can ameliorate LPS-induced lung injury. The protective effect may be associated with down-regulation of the surface expression of TLR4 in the lungs.


Assuntos
Lesão Pulmonar Aguda , Dióxido de Carbono/farmacologia , Regulação para Baixo/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Síndrome do Desconforto Respiratório do Adulto , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/biossíntese , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Masculino , Camundongos , Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/metabolismo , Síndrome do Desconforto Respiratório do Adulto/patologia
9.
High Alt Med Biol ; 20(3): 293-302, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31329475

RESUMO

Background: This study aimed to explore the effects of netrin-1 on hypobaric hypoxia-induced lung injury in mice. Methods: We exposed 6-8-week-old C57BL/6 mice to hypobaric stress at 340 mmHg for 30 minutes followed by 260 mmHg for different periods (6, 12, 18, and 24 hours) to observe the severity of lung injury (O2 concentration, 21%; 54.6 mmHg). The wet/dry weight ratio and protein leakage from the mouse lung were used to determine the suitable exposure time. Netrin-1 was injected into the tail vein of mice before 18-hour decompression. Inflammatory cytokines, lung injury scores, and activity of nuclear factor κB were evaluated. The expression of apoptosis-related proteins was also examined. Results: Protein concentration in the bronchoalveolar lavage fluid was significantly higher in the 18-hour group (p < 0.05). Pulmonary pathology revealed neutrophil infiltration, alveolar septum thickening, and tissue edema. Injury score and macrophage inflammatory protein 2 levels were also increased. Intrinsic apoptosis pathway was activated. Hypoxia decreased the expression of Bcl2 protein, the number of active caspase-3-stained cells, and UNC5HB receptors. Pretreatment with netrin-1 reduced protein leakage, inhibited neutrophil migration, lowered the injury score, attenuated apoptosis, and increased UNC5HB receptor expression. Conclusion: Netrin-1 dampens hypobaric hypoxia-induced lung injury by inhibiting neutrophil migration and attenuating apoptosis.

10.
Cancer Chemother Pharmacol ; 84(2): 415-425, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31250154

RESUMO

PURPOSE: Glioblastoma is the most malignant glioma tumors with inevitable relapse and resistance to chemotherapy; however, the mechanisms driving chemoresistance remain to be fully elucidated. This study is to explore the molecular and cellular mechanisms involving in the chemoresistance of glioblastoma. METHODS: The expression of musashi (MSI) RNA-binding protein in the tumor tissues and cells of glioblastoma was measured. The effects of MSI2 in epithelial-to-mesenchymal transition (EMT), resistance to temozolomide (TMZ), tumor cell invasion, migration, and proliferation and associated signaling were evaluated. RESULTS: High MSI2 expression was observed in the glioblastoma tissues. Silencing or overexpression of MSI2 significantly affected tumor cells invasion, migration, and proliferation. Silencing of MSI2 expression significantly inhibited O6-methylguanine-DNA methyltransferase (MGMT) expression and tumor growth, and reversed resistance to TMZ in xenograft tumor models. MSI2 expression regulated EMT through activating the transcription factors Snail and the TGFß R1/SMAD3 signaling. CONCLUSIONS: Our study demonstrated a positive feedback loop of MSI2-TGFß/SMAD3 signaling which activates the EMT and MGMT which may contribute to chemoresistance in glioblastoma. This study also highlights that MSI2 could be a new target for the therapy of glioblastoma.


Assuntos
Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioblastoma/genética , Proteínas de Ligação a RNA/genética , Proteína Smad3/genética , Animais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/patologia , Humanos , Camundongos , Transdução de Sinais
11.
Front Pharmacol ; 10: 583, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178737

RESUMO

Background: Increasing evidence suggests that Fbxo3 signaling has an important impact on the pathophysiology of the inflammatory process. Fbxo3 protein inhibition has reduced cytokine-driven inflammation and improved disease severity in animal model of Pseudomonas-induced lung injury. However, it remains unclear whether inhibition of Fbxo3 protein provides protection in acute lung injury induced by ischemia-reperfusion (I/R). In this study, we investigated the protective effects of BC-1215 administration, a Fbxo3 inhibitor, on acute lung injury induced by I/R in rats. Methods: Lung I/R injury was induced by ischemia (40 min) followed by reperfusion (60 min). The rats were randomly assigned into one of six experimental groups (n = 6 rats/group): the control group, control + BC-1215 (Fbxo3 inhibitor, 0.5 mg/kg) group, I/R group, or I/R + BC-1215 (0.1, 0.25, 0.5 mg/kg) groups. The effects of BC-1215 on human alveolar epithelial cells subjected to hypoxia-reoxygenation (H/R) were also examined. Results: BC-1215 significantly attenuated I/R-induced lung edema, indicated by a reduced vascular filtration coefficient, wet/dry weight ratio, lung injury scores, and protein levels in bronchoalveolar lavage fluid (BALF). Oxidative stress and the level of inflammatory cytokines in BALF were also significantly reduced following administration of BC-1215. Additionally, BC-1215 mitigated I/R-stimulated apoptosis, NF-κB, and mitogen-activated protein kinase activation in the injured lung tissue. BC-1215 increased Fbxl2 protein expression and suppressed Fbxo3 and TNFR associated factor (TRAF)1-6 protein expression. BC-1215 also inhibited IL-8 production and NF-κB activation in vitro in experiments with alveolar epithelial cells exposed to H/R. Conclusions: Our findings demonstrated that Fbxo3 inhibition may represent a novel therapeutic approach for I/R-induced lung injury, with beneficial effects due to destabilizing TRAF proteins.

12.
Glob Chang Biol ; 25(10): 3485-3493, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31220383

RESUMO

Global climate change can significantly influence oceanic phytoplankton dynamics, and thus biogeochemical cycles and marine food webs. However, associative explanations based on the correlation between chlorophyll-a concentration (Chl-a) and climatic indices is inadequate to describe the mechanism of the connection between climate change, large-scale atmospheric dynamics, and phytoplankton variability. Here, by analyzing multiple satellite observations of Chl-a and atmospheric conditions from National Center for Environmental Prediction/National Center for Atmospheric Research reanalysis datasets, we show that high-latitude atmospheric blocking events over Alaska are the primary drivers of the recent decline of Chl-a in the eastern North Pacific transition zone. These blocking events were associated with the persistence of large-scale atmosphere pressure fields that decreased westerly winds and southward Ekman transport over the subarctic ocean gyre. Reduced southward Ekman transport leads to reductions in nutrient availability to phytoplankton in the transition zone. The findings describe a previously unidentified climatic factor that contributed to the recent decline of phytoplankton in this region and propose a mechanism of the top-down teleconnection between the high-latitude atmospheric circulation anomalies and the subtropical oceanic primary productivity. The results also highlight the importance of understanding teleconnection among atmosphere-ocean interactions as a means to anticipate future climate change impacts on oceanic primary production.


Assuntos
Mudança Climática , Fitoplâncton , Alaska , Cadeia Alimentar , Oceanos e Mares
13.
Viruses ; 11(4)2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30979014

RESUMO

We conducted a retrospective analysis of norovirus outbreaks reported to the National Public Health Emergency Event Surveillance System (PHEESS) in China from January 1, 2014 to December 31, 2017. We reviewed all acute gastroenteritis outbreaks (n = 692) submitted to PHEESS to identify the frequency, seasonality, geographic distribution, setting, and transmission mode of outbreaks due to norovirus. A total of 616 norovirus outbreaks resulting in 30,848 cases were reported. Among these outbreaks, 571 (93%) occurred in school settings including 239 (39%) in primary schools, 136 (22%) in childcare facilities, and 121 (20%) in secondary schools. The majority of outbreaks (63%) were due to person-to-person transmission, followed by multiple modes of transmission (11%), foodborne (5%) and waterborne (3%) transmission. These findings highlight the importance of improving hand hygiene and environmental disinfection in high-risk settings. Developing a standard and quantitative outbreak reporting structure could improve the usefulness of PHEESS for monitoring norovirus outbreaks.


Assuntos
Infecções por Caliciviridae/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Gastroenterite/epidemiologia , Doença Aguda , Infecções por Caliciviridae/transmissão , China/epidemiologia , Monitoramento Epidemiológico , Gastroenterite/etiologia , Humanos , Norovirus , Estudos Retrospectivos , Estações do Ano
14.
J Neurotrauma ; 36(15): 2316-2324, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30801232

RESUMO

Spinal cord injury (SCI) repair is one of the most desirable but extremely challenging clinical problems. Developing suitable animal models and validating the therapeutic interventions in these models is the prerequisite for SCI repair improvement. Non-human primates, closer to humans than other species, are considered to be ideal models for translating laboratory discoveries into human clinical trials. In this study, the acute thoracic (T9) complete transection model in rhesus monkeys was established to evaluate the effects of linear-ordered collagen scaffold (LOCS) and LOCS combined with collagen binding neurotrophin-3 (CBD-NT3), which has been demonstrated to promote axonal regrowth and functional restoration in rodent models. After 10 months post-surgery, the grafted groups dramatically reduced cystic cavity formation and chondroitin sulfate proteoglycans (CSPGs) deposition and facilitated the ingrowth of axonal fibers at the lesion site. Further, the grafted groups displayed more regenerated fibers, exhibiting remyelination and synapse formation. Notably, the LOCS+CBD-NT3 group showed significant locomotor and electrophysiological recovery compared with the Control and LOCS groups. Therefore, LOCS+CBD-NT3 transplantation represents an effective strategy to promote spinal cord repair in non-human primates. More importantly, this complete transection model in non-human primate will contribute to effectively evaluating the potential interventions and accelerating clinical transformation in the future.

15.
Int Immunopharmacol ; 68: 17-29, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30599444

RESUMO

Previous studies demonstrated that triptolide (PG490) has many anti-inflammatory and immunosuppressive effects. However, little is known about the effect of PG490-88 (a water-soluble derivative of triptolide) on ischemia/reperfusion (I/R)-induced acute lung injury. We assessed the effects of PG490-88 on I/R-induced acute lung injury in rats and on hypoxia/reoxygenation (H/R) in a line of murine epithelial cells. Isolated perfused rat lungs were subjected to 40 min of ischemia, followed by 60 min of reperfusion to induce I/R injury. Induction of I/R led to lung edema, elevated pulmonary arterial pressure, histological evidence of lung inflammation, oxidative stress, and increased levels of TNF-α and CINC-1 in bronchoalveolar lavage fluid. PG490-88 significantly suppressed all of these responses. Additionally, induction of I/R reduced the expression of claudin-4, occludin, and ZO-1, and increased apoptosis in lung tissue. PG490-88 also significantly suppressed these effects. I/R reduced the levels of IκB-α and MKP-1, and increased the levels of nuclear NF-κB and mitogen-activated protein kinase in lung tissue, and PG490-88 suppressed these effects. In vitro studies using mouse lung alveolar epithelial cells indicated that H/R increased the levels of phosphorylated p65 and MIP-2, but decreased the level of IκB-α. PG490-88 also suppressed these effects. In I/R damaged lungs, PG490-88 suppresses the inflammatory response, disruption of tight junction structure, and apoptosis. PG490-88 has the potential as a prophylactic agent to prevent I/R-induced lung injury.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Diterpenos/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/fisiopatologia , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Pressão Arterial/efeitos dos fármacos , Linhagem Celular , Diterpenos/farmacologia , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos
16.
Int Urogynecol J ; 30(5): 761-766, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30083942

RESUMO

INTRODUCTION AND HYPOTHESIS: The suburethral sling procedure has been widely used as the first-line treatment for stress urinary incontinence (SUI) in women. Although the success rate is high, difficult urination and urine retention can occur in a small portion of patients. A transvaginal sling incision can solve this problem but recurrent SUI may occur. This study investigated the long-term outcomes of women who underwent the pubovaginal sling (PVS) procedure and subsequent transvaginal sling incision for urethral obstruction. METHODS: We retrospectively reviewed the voiding conditions of women who underwent transvaginal sling incision owing to bladder outlet obstruction after the PVS procedure over the past two decades. Urodynamic study was performed before and after each operation. The patients' Global Impression of Improvement (PGI-I) and quality of life index (QoL-I) due to urinary symptoms were used for outcome evaluation. RESULTS: Among 405 women who underwent PVS procedure, 14 (3.5%) underwent subsequent transvaginal sling incision. The main symptoms were severe dysuria, followed by urinary retention or severe wound discomfort. The average interval between the two operations was 147.6 ± 353.6 days (range 3~1,344). The mean follow-up time after sling incision was 91.1 ± 50.7 months. At follow-up, 12 patients (85.7%) could maintain urinary continence whereas 2 had urgency incontinence. Ten patients (71.4%) were satisfied with their quality of life postoperatively. CONCLUSIONS: Transvaginal sling incision is effective for urethral obstruction after PVS procedure. Voiding dysfunction after PVS could be resolved via sling incision. Most patients could maintain urinary continence and reported good satisfaction.


Assuntos
Slings Suburetrais/efeitos adversos , Obstrução Uretral/cirurgia , Incontinência Urinária por Estresse/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , Resultado do Tratamento , Obstrução Uretral/etiologia , Retenção Urinária/etiologia , Retenção Urinária/cirurgia
17.
Low Urin Tract Symptoms ; 11(2): O42-O47, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29265766

RESUMO

OBJECTIVE: Interstitial cystitis (IC), also known as bladder pain syndrome (BPS), is a debilitating chronic disease. There are few treatment options for IC/BPS refractory to current medical therapy. This study investigated the clinical efficacy of intravesical injections of platelet-rich plasma (PRP) in IC/BPS. METHODS: Fifteen patients with IC/BPS received 4 intravesical injections, at 1-monthly intervals, of 12 mL PRP extracted from 50 mL of the patient's whole blood, followed by cystoscopic hydrodistention. The primary endpoint was the change in O'Leary-Sant symptom (OSS) index from baseline to 1 month after the 4th PRP injection. Secondary endpoints were changes in pain (measured using a visual analog scale [VAS]), daily frequency, nocturia, functional bladder capacity (FBC), maximum flow rate, voided volume, post-void residual (PVR) volume, and global response assessment (GRA). Urinary cytokine levels were measured at baseline and 1 month after the 1st PRP treatment. RESULTS: Of the 15 women in the study, 13 completed the 4 injections and follow-up visits (mean [± SD] age 52.9 ± 12.1 years). The OSS index and VAS pain score decreased significantly and FBC and GRA increased after the 1st PRP injection and lasted until the final endpoint. There was no change in PVR after repeated PRP injections, and all patients were free of urinary tract infections and difficulty urinating. Urinary interleukin (IL)-2 and IL-8 concentrations increased significantly after the 1st PRP injection. In patients with reductions in the VAS pain score ≥1, urinary IL-8 and vascular endothelial growth factor increased. In patients without reductions in the VAS pain score, IL-6 concentrations increased after PRP injection. CONCLUSIONS: Repeated intravesical PRP injections are well tolerated and appear to be safe and effective in medically refractive IC/BPS, providing significant symptom improvement.


Assuntos
Cistite Intersticial/terapia , Plasma Rico em Plaquetas , Administração Intravesical , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento
18.
J Infect ; 78(1): 66-74, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30017609

RESUMO

BACKGROUND: Rotavirus is a leading cause of morbidity and mortality in young children worldwide. In China, the universal immunization of children with the rotavirus vaccine has not been introduced, and the two globally distributed vaccines (RotaTeq and Rotarix) are not licensed in the country. We aim to determine the prevalence and strain diversity of rotavirus in children with diarrhea aged ≤ five years across China. MATERIALS AND METHODS: Sentinel-based surveillance of acute diarrhea was conducted at 213 participating hospitals in China from January 1, 2009, through December 31, 2015. Group A rotavirus (RVA) was tested by using enzyme-linked immunosorbent assays, and G- and P-genotype of RVA were tested by RT-PCR methods. RESULTS: Of 33,616 children with diarrhea, 10,089 (30%) were positive for RVA; RVA-associated diarrhea was identified in 2247 (39.5%, n = 2247/5685) inpatients and 7842 (28.1%, n = 7842/27931) outpatients. Children living in low-middle-income regions suffered from the highest burden of rotavirus, with 40.7% of diarrhea cases attributed to rotavirus infection, followed by 31.3% in upper-middle-income and 11.2% in high-income regions. The majority of children (88.9%, n = 8976/10089) who tested positive for RVA were children aged ≤ 2 years. The seasonal peak of RVA was in the winter. Among all 2533 RVA strains genotyped, five strain combinations, G9P[8], G3P[8], G1P[8], G2P[4] and G3P[4], contributed to 71.3% (1807/2533) of the RVA-associated diarrhea cases. The predominant strain of RVA has rapidly evolved from G3P[8] and G1P[8] to G9P[8] in the recent years, with the proportion of G9P[8] having increased remarkably from 3.4% in 2009 to 60.9% in 2015. CONCLUSIONS: The burden of diarrhea attributed to rotavirus is high in China, highlighting the potential value of vaccination. The rapid shift of RVA strains highlights the importance of conducting rotavirus surveillance to ensure that currently marketed vaccines provide protective efficacy against the circulating strains.


Assuntos
Diarreia/epidemiologia , Diarreia/virologia , Infecções por Rotavirus/epidemiologia , Rotavirus/genética , Doença Aguda , Pré-Escolar , China/epidemiologia , Fezes/virologia , Feminino , Variação Genética , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Filogenia , Prevalência , Rotavirus/classificação , Vigilância de Evento Sentinela
19.
PLoS One ; 13(11): e0207540, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30475834

RESUMO

Mutations in the small heat shock proteins α-crystallins have been linked to autosomal dominant cataracts in humans. Extensive studies in vitro have revealed a spectrum of alterations to the structure and function of these proteins including shifts in the size of the oligomer, modulation of subunit exchange and modification of their affinity to client proteins. Although mouse models of these mutants were instrumental in identifying changes in cellular proliferation and lens development, a direct comparative analysis of their effects on lens proteostasis has not been performed. Here, we have transgenically expressed cataract-linked mutants of αA- and αB-crystallin in the zebrafish lens to dissect the underlying molecular changes that contribute to the loss of lens optical properties. Zebrafish lines expressing these mutants displayed a range of morphological lens defects. Phenotype penetrance and severity were dependent on the mutation even in fish lines lacking endogenous α-crystallin. The mechanistic origins of these differences were investigated by the transgenic co-expression of a destabilized human γD-crystallin mutant. We found that the R49C but not the R116C mutant of αA-crystallin drove aggregation of γD-crystallin, although both mutants have similar affinity to client proteins in vitro. Our working model attributes these differences to the propensity of R49C, located in the buried N-terminal domain of αA-crystallin, to disulfide crosslinking as previously demonstrated in vitro. Our findings complement and extend previous work in mouse models and emphasize the need of investigating chaperone/client protein interactions in appropriate cellular context.


Assuntos
Animais Geneticamente Modificados , Catarata , Cristalinas , Modelos Animais de Doenças , Mutação , Peixe-Zebra , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/metabolismo , Catarata/genética , Catarata/metabolismo , Cristalinas/genética , Humanos , Camundongos , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/patologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , gama-Cristalinas/biossíntese , gama-Cristalinas/genética
20.
Front Immunol ; 9: 2049, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271405

RESUMO

Background: The expression of Na-K-2Cl cotransporter 1 (NKCC1) in the alveolar epithelium is responsible for fluid homeostasis in acute lung injury (ALI). Increasing evidence suggests that NKCC1 is associated with inflammation in ALI. We hypothesized that inhibiting NKCC1 would attenuate ALI after ischemia-reperfusion (IR) by modulating pathways that are mediated by tumor necrosis-associated factor 6 (TRAF6). Methods: IR-ALI was induced by producing 30 min of ischemia followed by 90 min of reperfusion in situ in an isolated and perfused rat lung model. The rats were randomly allotted into four groups comprising two control groups and two IR groups with and without bumetanide. Alveolar fluid clearance (AFC) was measured for each group. Mouse alveolar MLE-12 cells were cultured in control and hypoxia-reoxygenation (HR) conditions with or without bumetanide. Flow cytometry and transwell monolayer permeability assay were carried out for each group. Results: Bumetanide attenuated the activation of p-NKCC1 and lung edema after IR. In the HR model, bumetanide decreased the cellular volume and increased the transwell permeability. In contrast, bumetanide increased the expression of epithelial sodium channel (ENaC) via p38 mitogen-activated protein kinase (p38 MAPK), which attenuated the reduction of AFC after IR. Bumetanide also modulated lung inflammation via nuclear factor-κB (NF-κB). TRAF6, which is upstream of p38 MAPK and NF-κB, was attenuated by bumetanide after IR and HR. Conclusions: Inhibition of NKCC1 by bumetanide reciprocally modulated epithelial p38 MAPK and NF-κB via TRAF6 in IR-ALI. This interaction attenuated the reduction of AFC via upregulating ENaC expression and reduced lung inflammation.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Hipóxia/imunologia , Pulmão/patologia , Traumatismo por Reperfusão/metabolismo , Mucosa Respiratória/fisiologia , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Lesão Pulmonar Aguda/imunologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Bumetanida/administração & dosagem , Bumetanida/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Pulmão/imunologia , Masculino , Camundongos , NF-kappa B/metabolismo , Pneumonia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/imunologia , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/metabolismo
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