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1.
Clin Genet ; 97(1): 25-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31432497

RESUMO

DNA mismatch repair (MMR) status was considered to be a potential prognostic factor for colorectal cancer (CRC) but with conflicting reports, and varied in terms of TNM stages. Its relationship with prognosis in stage II-III CRC had not yet been systematically established. Therefore, we retrieved eligible studies published through May 2019, and screened out 51 studies that reported survival data (overall survival [OS] and/or disease-free survival [DFS]) in 28 331 CRC patients at stage II-III, totally 16.4% of whom were characterized as deficient MMR (dMMR). Significant associations of dMMR status were observed with longer OS (Hazard Ratio [HR] = 0.74, 95% CI: 0.68-0.82; P < .001), as well as DFS (HR = 0.67, 95% CI: 0.59-0.75, P < .001). However, dMMR patients received no statistically significant benefit from fluoropyrimidine-based treatment for either OS (HR = 0.84, 95%CI: 0.60-1.17; P = .31) or DFS (HR = 0.83, 95%CI: 0.60-1.15; P = .27), compared with that in proficient MMR (pMMR) patients for both OS (HR = 0.55, 95% CI: 0.43-0.71; P < .001) and DFS (HR = 0.60, 95% CI: 0.50-0.73; P < .001). Our analysis indicate that dMMR CRC patients at stage II-III had higher OS and DFS than pMMR ones, and fluoropyrimidine-based chemotherapy could improve survival in pMMR patients rather than dMMR ones.

2.
World J Microbiol Biotechnol ; 35(10): 153, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31576426

RESUMO

Karst caves, considering to be the "arks" of biodiversity, often contain high levels of endemism. In the present study, the actinobacterial community in Shuanghe Cave, the longest cave in Asia, was analyzed for the first-time using culture-dependent and -independent (16S rRNA amplicon sequencing) approaches. The amplicon sequencing analysis revealed a broad taxonomic diversity in Shuanghe Cave, including 19 phyla (predominantly Actinobacteria) and 264 different genera. While the culture-dependent method got the unrepresentative but supplemental result, a total of 239 actinomycetes were isolated and were identified to seven genera based on culture features and 16S rRNA tests. Among the three habitats (soil, rock soil, and bat guano), the dominant phyla did not differ significantly, while the dominant genus community varied among different habitats, and the richness in soil and rock soil samples was higher than that in bat guano. Furthermore, 16 isolate strains showed antimicrobial activity, especially, the strain S142 (Streptomyces badius) and S761 (Actinoplanes friuliensis) exhibited the most promising activity against various pathogens. Overall, this work showed the abundant bacterial diversity and the antimicrobial potential of the isolates from the Shuanghe Cave.


Assuntos
Actinobacteria/isolamento & purificação , Cavernas/microbiologia , Actinobacteria/classificação , Actinobacteria/genética , Actinobacteria/crescimento & desenvolvimento , Animais , Ásia , Biodiversidade , Quirópteros/microbiologia , DNA Bacteriano/genética , Ecossistema , Sedimentos Geológicos/microbiologia , Filogenia , RNA Ribossômico 16S/genética , Microbiologia do Solo
3.
J Affect Disord ; 256: 594-603, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31299440

RESUMO

BACKGROUND: Asthma is associated with multiple psychiatric comorbidities. However, the relationship between asthma and suicidality has not be well established. METHODS: According to the PRISMA guidelines, protocol of the study was registered in the PROSPERO database (CRD42019123150). A systematic search of the PubMed, Embase and PsycINFO databases was performed for relevant studies published from its inception to January 25, 2019. Studies that reported the risk of suicidal ideation, attempts and mortality in asthmatics compared with non-asthmatics were included. A random-effects model was used to synthesize the estimates and the quality of the included studies was assessed under the Newcastle-Ottawa Scale. RESULTS: Twenty-eight studies including 2,759,841 asthmatic patients and 16,290,362 non-asthmatic controls were pooled and analyzed in the current study. The pooled data showed that asthmatic patients had increased risk of exhibiting suicidal ideation (OR, 1.52; 95%CI, 1.37-1.70), suicide attempts (OR, 1.60; 95%CI, 1.33-1.92) and suicide mortality (OR, 1.31; 95%CI, 1.11-1.55) compared to non-asthmatic controls. Noticeably, adolescent asthmatic patients had a more than 2-fold risk of suicide mortality compared to non-asthmatic controls (OR, 2.14; 95%CI, 1.61-2.83). LIMITATIONS: The limitations of the present study were variability in study designs and various measures of asthma and suicidality, which possibly contribute to notable heterogeneity. CONCLUSIONS: Patients with asthma have a significantly increased risk of suicidal ideation, suicide attempts and suicide mortality. Clinical physicians should pay more attention to the increased risk of suicidality in asthmatics, screen for these suicidal thoughts and behaviors, and make appropriate mental health referrals when necessary.

4.
Neural Plast ; 2019: 5765284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31097956

RESUMO

Adult neurogenesis in the hippocampal dentate gyrus (DG) modulates cognition and behavior in mammals, while motherhood is associated with cognitive and behavioral changes essential for the care of the young. In mice and rats, hippocampal neurogenesis is reported to be reduced or unchanged during pregnancy, with few data available from other species. In guinea pigs, pregnancy lasts ~9 weeks; we set to explore if hippocampal neurogenesis is altered in these animals, relative to gestational stages. Time-pregnant primigravidas (3-5 months old) and age-matched nonpregnant females were examined, with neurogenic potential evaluated via immunolabeling of Ki67, Sp8, doublecortin (DCX), and neuron-specific nuclear antigen (NeuN) combined with bromodeoxyuridine (BrdU) birth-dating. Relative to control, subgranular Ki67, Sp8, and DCX-immunoreactive (+) cells tended to increase from early gestation to postpartum and peaked at the late gestational stage. In BrdU pulse-chasing experiments in nonpregnant females surviving for different time points (2-120 days), BrdU+ cells in the DG colocalized with DCX partially from 2 to 42 days (most frequently at 14-30 days) and with NeuN increasingly from 14 to 120 days. In pregnant females that received BrdU at early, middle, and late gestational stages and survived for 42 days, the density of BrdU+ cells in the DG was mostly high in the late gestational group. The rates of BrdU/DCX and BrdU/NeuN colocalization were similar among these groups and comparable to those among the corresponding control group. Together, the findings suggest that pregnancy promotes maternal hippocampal neurogenesis in guinea pigs, at least among primigravidas.


Assuntos
Giro Denteado/fisiologia , Neurogênese , Neurônios/fisiologia , Gravidez , Animais , Diferenciação Celular , Feminino , Cobaias , Células-Tronco Neurais/fisiologia
5.
Cancer Manag Res ; 11: 2425-2439, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30988640

RESUMO

Purpose: Large-scale studies have revealed that appropriate antiangiogenic treatment enables the recovery of the normal structure and function of solid tumor vessels. Epigallocatechin-3-gallate (EGCG), a natural extract of green tea, has multiple effects on angiogenesis. However, normalization of blood vessels due to natural ingredients has not yet been reported. Therefore, we examined the microvasculature, microenvironment, and efficacy of EGCG combined with chemotherapy in a xenograft model. Methods: We treated A549 cell (human lung adenocarcinoma cell line) xenograft-bearing nude mice with EGCG in vivo. CD31, αSMA, and collagen IV were labeled and detected using quantum-dot double-labeled immunofluorescence to measure microvessel density, microvessel pericyte-coverage index, and collagen IV expression. Vessel-perfusion function was determined by lectin injection, permeability by Evans blue extravasation, interstitial fluid pressure using the wick-in-needle technique, and hypoxia levels using a polarographic electrode and immunohistochemical pimonidazole labeling. Cisplatin concentration in tumor tissue was detected using graphite-furnace atomic absorption spectrophotometry. Xenograft mice were randomized into five groups: treated with saline, cisplatin, EGCG, EGCG + cisplatin on day 1, or EGCG + cisplatin during the vascular normalization window. Tumor-growth delay and tumor-suppression rate were measured to evaluate tumor growth. Results: EGCG treatment in vivo caused temporary changes, including transient depression of microvessel density, microvessel pericyte-coverage index, and collagen IV expression, transient elevation of vessel perfusion and permeability, and decreased interstitial fluid pressure and hypoxia. During vascular normalization, pretreatment with EGCG increased cisplatin concentration in tumor tissue compared with treatment with cisplatin only. Tumor-growth delay after treatment in the five groups during the vascular normalization window was 6.3±1.51, 7.5±1.57, 8.3±1.79, 12.1±1.35, and 15.4±1.99 days, indicating synergistic EGCG-cisplatin effects, especially during the vascular normalization window (P<0.01). Conclusion: EGCG-induced vascular normalization in human lung adenocarcinoma may be a novel modality for enhancing chemotherapy effects.

6.
Proc Natl Acad Sci U S A ; 116(14): 6908-6913, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30877258

RESUMO

Rapid phenotypic changes in traits of adaptive significance are crucial for organisms to thrive in changing environments. How such phenotypic variation is achieved rapidly, despite limited genetic variation in species that experience a genetic bottleneck is unknown. Capsella rubella, an annual and inbreeding forb (Brassicaceae), is a great system for studying this basic question. Its distribution is wider than those of its congeneric species, despite an extreme genetic bottleneck event that severely diminished its genetic variation. Here, we demonstrate that transposable elements (TEs) are an important source of genetic variation that could account for its high phenotypic diversity. TEs are (i) highly enriched in C. rubella compared with its outcrossing sister species Capsella grandiflora, and (ii) 4.2% of polymorphic TEs in C. rubella are associated with variation in the expression levels of their adjacent genes. Furthermore, we show that frequent TE insertions at FLOWERING LOCUS C (FLC) in natural populations of C. rubella could explain 12.5% of the natural variation in flowering time, a key life history trait correlated with fitness and adaptation. In particular, we show that a recent TE insertion at the 3' UTR of FLC affects mRNA stability, which results in reducing its steady-state expression levels, to promote the onset of flowering. Our results highlight that TE insertions can drive rapid phenotypic variation, which could potentially help with adaptation to changing environments in a species with limited standing genetic variation.


Assuntos
Adaptação Fisiológica , Capsella , Elementos de DNA Transponíveis , Loci Gênicos , Variação Genética , Fenótipo , Capsella/genética , Capsella/metabolismo , Proteínas de Domínio MADS/biossíntese , Proteínas de Domínio MADS/genética , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Plantas/genética , RNA de Plantas/metabolismo
7.
Front Neuroanat ; 13: 31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30914927

RESUMO

Sortilin is a member of the vacuolar protein sorting 10 protein (VPS10P) domain receptor family, which carries out signal transduction and protein transport in cells. Sortilin serves as the third, G-protein uncoupled, receptor of neurotensin that can modulate various brain functions. More recent data indicate an involvement of sortilin in mood disorders, dementia and Alzheimer-type neuropathology. However, data regarding the normal pattern of regional and cellular expression of sortilin in the human brain are not available to date. Using postmortem adult human brains free of neuropathology, the current study determined sortilin immunoreactivity (IR) across the entire brain. Sortilin IR was broadly present in the cerebrum and subcortical structures, localizing to neurons in the somatodendritic compartment, but not to glial cells. In the cerebrum, sortilin IR exhibited differential regional and laminar patterns, with pyramidal, multipolar and polymorphic neurons in cortical layers II-VI, hippocampal formation and amygdaloid complex more distinctly labeled relative to GABAergic interneurons. In the striatum and thalamus, numerous small-to-medium sized neurons showed light IR, with a small group of large sized neurons heavily labeled. In the midbrain and brainstem, sortilin IR was distinct in neurons at the relay centers of descending and ascending neuroanatomical pathways. Dopaminergic neurons in the substantia nigra, cholinergic neurons in the basal nuclei of Meynert and noradrenergic neurons in the locus coeruleus co-expressed strong sortilin IR in double immunofluorescence. In comparison, sortilin IR was weak in the olfactory bulb and cerebellar cortex, with the mitral and Purkinje cells barely visualized. A quantitative analysis was carried out in the lateral, basolateral, and basomedial nuclei of the amygdaloid complex, as well as cortical layers II-VI, which established a positive correlation between the somal size and the intensity of sortilin IR among labeled neurons. Together, the present study demonstrates a predominantly neuronal expression of sortilin in the human brain with substantial regional and cell-type variability. The enriched expression of sortilin in pyramidal, dopaminergic, noradrenergic and cholinergic neurons suggests that this protein may be particularly required for signal transduction, protein trafficking and metabolic homeostasis in populations of relatively large-sized projective neurons.

8.
Am J Med Sci ; 357(4): 289-295, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30638601

RESUMO

BACKGROUND: Severe pneumonia is responsible for great mortality and morbidity worldwide, and early-applied effective anti-infective therapy can improve the prognosis of patients. However, identification of infectious agents in severe pneumonia remains a major challenge so far. In this study, the potential utility of transmission electron microscopy (TEM) in detecting nonbacterial pathogens in patients with severe pneumonia was retrospectively evaluated. MATERIALS AND METHODS: A total of 106 patients diagnosed with severe pneumonia at our hospital from September 2015 to December 2017 were included, and their baseline clinical characteristics were collected. Nonbacterial infectious agents detected by TEM in bronchoalveolar lavage fluid (BALF) and serological tests were summarized. The detection rates were further compared between TEM and serological tests. RESULTS: BALF examination under the transmission electron microscope revealed 24 viruses, 16 mycoplasmas, 18 chlamydia, 2 fungi and 74 bacteria in 99 samples, among which 61 samples were mixed infections. The combined use of serological tests and TEM significantly improved the detection rate of nonbacterial infectious agents in patients with severe pneumonia. CONCLUSIONS: Our data support that implementation of TEM could improve the sensitivity for detecting viruses, atypical pathogens and mixed infections in BALF from patient of severe pneumonia. Therefore, TEM may be used as an auxiliary diagnostic method of other microbiological tests in severe pneumonia.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Microscopia Eletrônica de Transmissão/métodos , Micoses/diagnóstico , Pneumonia/diagnóstico , Viroses/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido da Lavagem Broncoalveolar/virologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Pneumonia/microbiologia , Pneumonia/virologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Viroses/virologia , Adulto Jovem
9.
Int J Biol Macromol ; 124: 360-367, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30448499

RESUMO

In the present study, the pharmacological effects of oligosaccharides from Cistanche deserticola extract on inflammation, oxidative stress, and apoptosis in male albino rats with spinal cord injury were investigated. Lipid peroxidation, GSH, catalase, superoxide dismutase, acetylcholine esterase, GPx, ROS, and nitric acid were significantly altered in the rats with spinal cord injury. The mRNA expression levels of IL-6, TNF-α, cyclooxygenase-2, iNOS, p53, caspase-3, bax, and pro-NGF were reduced by >20% following extract supplementation. Protein expression levels of caspase-3 and pro-NGF were also reduced by >20%. The number of p53 positive cells was 1, 79, 54, 33, and 19 in groups GI-GV, respectively, and the corresponding numbers of caspase-3 positive cells were 2, 87, 51, 23, and 14. Based on the present results, the use of oligosaccharides from Cistanche deserticola extract was effective against inflammation, oxidative stress, and apoptosis in spinal cord injury male albino rats.


Assuntos
Inflamação/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Extratos Vegetais/administração & dosagem , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Apoptose/efeitos dos fármacos , Caspase 3/genética , Cistanche/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/etiologia , Inflamação/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Oligossacarídeos/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , RNA Mensageiro/genética , Ratos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/patologia
11.
J Phys Condens Matter ; 30(45): 455601, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30251965

RESUMO

Surface potassium dosing has been proven to be an effective method in tuning the electron doping and enhancing the superconducting transition temperatures in both iron chalcogenides and electron doped iron pnictides. However, it is not clear how surface potassium dosing affects the hole doping and superconductivity in hole doped Fe-based superconductors. Here we performed K-dosing on Ba0.5K0.5Fe2As2, a prototypical hole-doped iron pnictide compound, and explored the electronic structure by in situ angle-resolved photoemission spectroscopy measurements. Starting from the slightly over-doped Ba0.5K0.5Fe2As2, surface K-dosing effectively reduces the hole concentration towards optimal doping and enhances the superconductivity. Intriguingly, the enhancement of superconductivity does not slow down at optimal doping, and the gap further increases with K dosing even when the carrier doping effect is saturated. Meanwhile, the quasiparticle coherence of the inner hole pockets is enhanced by higher K dosing. Our results uncover a novel scattering-reduction effect of K-dosing in Ba1-x K x Fe2As2, which collaborates with the carrier doping effect and enhances superconductivity.

12.
Sci Adv ; 4(9): eaat8355, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30225369

RESUMO

Semiconductors are essential materials that affect our everyday life in the modern world. Two-dimensional semiconductors with high mobility and moderate bandgap are particularly attractive today because of their potential application in fast, low-power, and ultrasmall/thin electronic devices. We investigate the electronic structures of a new layered air-stable oxide semiconductor, Bi2O2Se, with ultrahigh mobility (~2.8 × 105 cm2/V⋅s at 2.0 K) and moderate bandgap (~0.8 eV). Combining angle-resolved photoemission spectroscopy and scanning tunneling microscopy, we mapped out the complete band structures of Bi2O2Se with key parameters (for example, effective mass, Fermi velocity, and bandgap). The unusual spatial uniformity of the bandgap without undesired in-gap states on the sample surface with up to ~50% defects makes Bi2O2Se an ideal semiconductor for future electronic applications. In addition, the structural compatibility between Bi2O2Se and interesting perovskite oxides (for example, cuprate high-transition temperature superconductors and commonly used substrate material SrTiO3) further makes heterostructures between Bi2O2Se and these oxides possible platforms for realizing novel physical phenomena, such as topological superconductivity, Josephson junction field-effect transistor, new superconducting optoelectronics, and novel lasers.

13.
Clin Lab ; 64(7): 1177-1182, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30146830

RESUMO

BACKGROUND: The current study aims to evaluate the expression pattern changes of miR-199-3p in diabetic nephropathy (DN) patients and explore whether it could be used as a potential biomarker. METHODS: Real time PCR analysis was performed to examine the level of miR-199-3p in normoalbuminuria group (diabetes mellitus [DM]), microalbuminuria group (DNE), macroalbuminuria group (DNC), and healthy controls. ROC analysis was carried out to determine whether urine miR-199-3p could be used as a potential biomarker. Dual luciferase reporter assay was used to identify the target gene of miR-199-3p. RESULTS: Here we showed novel data that urine miR-199-3p was significantly decreased in the diabetes patients compared to healthy controls. Meanwhile, urine miR-199-3p was lowest in DNC group, lower in DNE group, but was relatively higher in DM group. Additionally, urine miR-199-3p level positively correlated with UAE level in both DNE group and DNC group. ROC analysis showed that the urine miR-199-3p may be used to differentiate DNE and DNC subjects from healthy controls and DM group. Besides, miR-199-3p could significantly suppress the relative luciferase activity of pmirGLO-ZEB1, indicating ZEB1 was a target gene of miR-199-3p. CONCLUSIONS: In summary, for the first time, we showed novel data that decreased urinary miR-199-3p could screen DN patients from DM patients and healthy controls, which may be a non-invasive biomarker for DN patients.


Assuntos
Biomarcadores/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , MicroRNAs/urina , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Idoso , Albuminúria/diagnóstico , Albuminúria/urina , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/diagnóstico , Feminino , Células HEK293 , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
14.
Hum Cell ; 31(4): 282-291, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30097922

RESUMO

Obesity is associated with increased risks of diverse diseases; brown adipose tissue (BAT) can increase energy expenditure and protect against obesity by increasing the decomposition of white adipose tissue (WAT) to enhance the non-coupled oxidative phosphorylation of fatty acid in adipocytes and contributes to weight loss. However, BAT is abundant in only small rodents and newborn humans, but not in adults. PRDM16 is a key factor that induces the differentiation of skeletal muscle precursors to brown adipocytes and simultaneously inhibits myogenic differentiation. In the present study, we set insulin-induced skeletal muscle satellite cells (SMSCs) adipogenic differentiation model, as confirmed by the contents of adipogenic markers PRDM16, UCP1 and PGC1α and myogenic markers MyoD1 and MyoG. We selected miR-499 as candidate miRNA, which might regulate PRDM16 to affect SMSCs adipogenic differentiation. Possibly through directly binding to PRDM16 3'-UTR, miR-499 negatively regulated PRDM16 expression and hindered SMSCs adipogenic differentiation by reducing adipogenic markers PRDM16, UCP1 and PGC1α and increasing myogenic markers MyoD1 and MyoG. PRDM16 overexpression could partially reverse the effect of miR-499 on the above markers and SMSCs adipogenic differentiation. Taken together, miR-499/PRDM16 axis can affect the balance between SMSC myogenic and adipogenic differentiation, targeting miR-499 to rescue PRDM16 expression, thus promoting SMSCs adipogenic differentiation may be a promising strategy for obesity treatment.


Assuntos
Adipócitos Marrons/fisiologia , Adipogenia/genética , Diferenciação Celular/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/genética , MicroRNAs/fisiologia , Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Regiões 3' não Traduzidas/fisiologia , Animais , Células Cultivadas , Camundongos , Terapia de Alvo Molecular , Obesidade/etiologia , Obesidade/terapia
15.
Biomed Chromatogr ; 32(12): e4364, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30119143

RESUMO

Posaconazole (PCZ) is a triazole antifungal agent with an extended spectrum of antifungal activity. It is approved for the prophylaxis of invasive fungal infections in patients with neutropenia or in hematopoietic stem cell transplant recipients undergoing high-dose immunosuppressive therapy for graft-vs-host disease, and for the treatment of fungal infections. However, its pharmacological effects are severely limited owing to its poor solubility and low bioavailability. In order to solve these problems, a sulfobutyl ether-ß-cyclodextrin compound was used to prepare an intramuscular injection to improve the bioavailability of posaconazole. The extracorporeal dissolution rate of posaconazole was markedly improved by this inclusion complex with >90% being released within 5 min, and the in vivo pharmacokinetics were studied using a HPLC/MS/MS method for quantifying posaconazole and the posaconazole-sulfobutyl ether-ß-cyclodextrin inclusion complex in rat blood. Posaconazole and an internal standard, itraconazole, were extracted by protein precipitation using acetonitrile. The concentration range of posaconazole was 0.05-4.0 µg/mL with good linearity (r = 0.9980), the peak concentrations of pure posaconazole and the inclusion complex were 0.565 ± 0.102 µg/mL and 1.12 ± 0.091 µg/mL, the values for AUC0-t were 12.2 ± 2.5 and 19.9 ± 2.5 µg h/mL, and the values for AUC0-∞ were 16.4 ± 3.2 and 25.0 ± 3.5 µg h/mL, respectively. The main pharmacokinetics parameters showed significant differences (P < 0.01). Compared with pure posaconazole, the posaconazole-sulfobutyl ether-ß-cyclodextrin inclusion complex markedly improved the bioavailability of posaconazole.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Triazóis/análise , beta-Ciclodextrinas/química , Animais , Antifúngicos/análise , Antifúngicos/sangue , Antifúngicos/química , Antifúngicos/farmacocinética , Disponibilidade Biológica , Estabilidade de Medicamentos , Feminino , Limite de Detecção , Modelos Lineares , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Solubilidade , Triazóis/sangue , Triazóis/química , Triazóis/farmacocinética , beta-Ciclodextrinas/farmacocinética
16.
Cancer Manag Res ; 10: 1927-1934, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30013399

RESUMO

Background: Tumor cell dissemination after needle biopsy has been reported in a variety of malignancies, including non-small-cell lung cancer (NSCLC). However, there is little clinical evidence in regard to whether preoperative biopsy increases the risk of recurrence in completely resected NSCLC. Patients and methods: A total of 322 patients diagnosed as pathological stage I NSCLC using intraoperative biopsy (IOB) (control group), preoperative percutaneous needle biopsy (PNB) or bronchoscopic biopsy were included in this study. Baseline characteristics were collected and compared. The disease-free survival (DFS) of patients was analyzed using Kaplan-Meier method. Subgroup analysis and Cox regression were performed to evaluate the effect of preoperative biopsy on recurrence risk with adjustment for potential confounders. Results: Among these patients, 202 (63%) underwent IOB, 66 (20%) underwent PNB, and 54 (17%) underwent bronchoscopic biopsy. DFS of patients who had preoperative PNB or bronchoscopic biopsy was similar to those who had IOB (P=0.514 and 0.869). Neither preoperative PNB nor transbronchial biopsy significantly affected recurrence incidence across all the relevant subgroups. Furthermore, multivariate analysis showed that preoperative biopsy was not associated with increased recurrence risk in NSCLC patients with adjustment for confounders, while squamous cell carcinoma and adjuvant chemotherapy were associated with prolonged DFS. Conclusion: Neither preoperative PNB nor bronchoscopic biopsy increased the recurrence risk in patients with resected stage I NSCLC, indicating that these procedures could be safely used for diagnosis of early-stage NSCLC.

17.
Am J Med Sci ; 356(1): 79-83, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30049332

RESUMO

Solitary laryngeal neurofibromas are exceedingly rare with only 14 cases reported in the previous literature. Herein, we reported a case of solitary laryngeal neurofibroma and reviewed all the published cases of this disease on the clinical manifestations and management options. Patients with solitary laryngeal neurofibromas can present with a variety of respiratory symptoms. Immunohistochemical examination of tumor specimen is critical for pathologic diagnosis and complete surgical resection is the optimal therapy. Endoscopic microsurgeries followed by CO2 laser management of the surgical border may be effective on preventing recurrence. Depending on the location, size and invasiveness of the lesions, the management and prognosis vary among patients. Long-term follow-up is highlighted owing to the possibility of recurrence during a long period of time after surgery.


Assuntos
Neoplasias Laríngeas , Laringoscopia , Terapia a Laser , Recidiva Local de Neoplasia , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Neurofibroma/diagnóstico , Neurofibroma/metabolismo , Neurofibroma/cirurgia
18.
J Thorac Dis ; 10(3): 1614-1621, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29707313

RESUMO

Background: Acinetobacter baumannii (A. baumannii) is one of the most troublesome opportunistic pathogens associated with hospital-acquired pneumonia (HAP). It is important to be able to discriminate A. baumannii colonization from infection in its early stages so that effective antibiotics can be promptly applied. Recent studies have reported that the secretion of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is markedly upregulated in pneumonia and sepsis, but the expression pattern of sTREM-1 in A. baumannii colonization and infection in the lung has not been explored. Methods: C57BL/6J male mice were intraperitoneally injected with 1% streptozotocin for 5 consecutive days to establish diabetic models. Subsequently, aerosol inhalation of A. baumannii suspension was performed in these mice to induce pulmonary colonization or infection with saline as vehicle control. Mice were sacrificed and lung tissue was harvested on days 0, 1, 3, 5 and 7 after exposure. Pharyngeal swab culture, lung homogenate culture, and H&E staining of lung tissue were performed to assess the severity of infectious inflammation. sTREM-1 expressions in serum and lung supernatants, serum procalcitonin (PCT) and C-reactive protein (CRP) concentrations were measured by ELISA. Results: A. baumannii colonization and infection models were verified by pharyngeal swab culture, lung homogenate culture, and H&E staining. While sTREM-1 concentrations in mice with A. baumannii colonization remained unchanged in serum and lung supernatants, sTREM-1 expression levels in infected animals were significantly upregulated. In addition, serum sTREM-1 concentration was positively correlated with serum levels of PCT and CRP. Conclusions: Dynamic secretion of sTREM-1 is associated with the development of A. baumannii infection in the lung. Therefore, sTREM-1 expression level may be a promising biomarker for discriminating A. baumannii infection from colonization.

19.
Exp Ther Med ; 15(6): 4643-4650, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29805481

RESUMO

Cimetidine is widely used for the treatment of digestive tract ulcers, but it induces testis injury. To explore the mechanisms underlying cimetidine-induced toxicity towards the testis, the effects of oral cimetidine on the reproductive system of male rats were assessed. Cimetidine was orally administered to male rats at 20, 40 or 120 mg/kg/day for 9 weeks. The rats were then euthanized, and serum, testis, epididymis, prostate gland, seminal vesicle, preputial gland, levator ani muscle and sphincter ani samples were collected. Sperm parameters were obtained by computer-assisted sperm analysis. Serum hormone levels were measured by ELISA. Protein expression levels were detected by immunohistochemistry. Apoptosis was assessed with the DeadEnd™ Colorimetric Apoptosis Detection System. The results indicated that the sperm average path velocity, straight line velocity and curvilinear velocity were significantly decreased in the 120 mg/kg cimetidine group compared with the control group, while luteinizing hormone and testosterone levels were significantly higher compared with the control group. Testicular lesions were observed by histopathology in the 120 mg/kg cimetidine group. The amounts of cells positive for cyclooxygenase-2 (COX-2) and nuclear factor κB (NF-κB) were increased in the 120 mg/kg cimetidine group compared with the control group. The amounts of cells positive for iNOS were increased in all cimetidine treatment groups. In addition, apoptotic cells were significantly more abundant in the 120 mg/kg cimetidine group compared with the control group, as indicated by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling. Overall, 9 weeks of oral cimetidine induced pathological changes in the testicles and hormone secretion disorder in rats. COX-2, iNOS and NF-κB upregulation and induction of apoptosis may be associated with the reproductive toxicity caused by cimetidine.

20.
Nat Med ; 24(6): 814-822, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29785025

RESUMO

Beige adipocytes have recently been shown to regulate energy dissipation when activated and help organisms defend against hypothermia and obesity. Prior reports indicate that beige-like adipocytes exist in adult humans and that they may present novel opportunities to curb the global epidemic in obesity and metabolic illnesses. In an effort to identify unique features of activated beige adipocytes, we found that expression of the cholinergic receptor nicotinic alpha 2 subunit (Chrna2) was induced in subcutaneous fat during the activation of these cells and that acetylcholine-producing immune cells within this tissue regulated this signaling pathway via paracrine mechanisms. CHRNA2 functioned selectively in uncoupling protein 1 (Ucp1)-positive beige adipocytes, increasing thermogenesis through a cAMP- and protein kinase A-dependent pathway. Furthermore, this signaling via CHRNA2 was conserved and present in human subcutaneous adipocytes. Inactivation of Chrna2 in mice compromised the cold-induced thermogenic response selectively in subcutaneous fat and exacerbated high-fat diet-induced obesity and associated metabolic disorders, indicating that even partial loss of beige fat regulation in vivo had detrimental consequences. Our results reveal a beige-selective immune-adipose interaction mediated through CHRNA2 and identify a novel function of nicotinic acetylcholine receptors in energy metabolism. These findings may lead to identification of therapeutic targets to counteract human obesity.


Assuntos
Adipócitos Bege/imunologia , Comunicação Celular , Receptores Nicotínicos/metabolismo , Transdução de Sinais , Acetilcolina/metabolismo , Animais , Dieta Hiperlipídica , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Obesidade/patologia , Gordura Subcutânea/imunologia , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
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