Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 61
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Neuroendocrinol ; 31(7): e12763, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31251830

RESUMO

Ghrelin is a gut hormone that signals to the hypothalamus to stimulate growth hormone release, increase food intake and promote fat deposition. The ghrelin receptor, also known as growth hormone secretagogue receptor (GHS-R), is highly expressed in the brain, with the highest expression in agouti-related peptide (AgRP) neurones in the hypothalamus. Compelling evidence indicates that ghrelin serves as a survival hormone with respect to maintaining blood glucose and body weight during nutritional deficiencies. Recent studies have demonstrated that AgRP neurones are involved in metabolic and behavioural adaptation to an energy deficit to improve survival. In the present study, we used a neuronal subtype-specific GHS-R knockout mouse (AgRP-Cre;Ghsrf/f ) to investigate the role of GHS-R in hypothalamic AgRP neurones in metabolic and behavioural adaptation to hypocaloric restricted feeding. We subjected the mice to a restricted feeding regimen of 40% mild calorie restriction (CR), with one-quarter of food allotment given in the beginning of the light cycle and three-quarters given at the beginning of the dark cycle, to mimic normal mouse intake pattern. The CR-fed AgRP-Cre;Ghsrf/f mice exhibited reductions in body weight, fat mass and blood glucose. Metabolic profiling of these CR-fed AgRP-Cre;Ghsrf/f mice showed a trend toward reduced basal metabolic rate, significantly reduced core body temperature and a decreased expression of thermogenic genes in brown adipose tissue. This suggests a metabolic reset to a lower threshold. Significantly increased physical activity, a trend toward increased food anticipatory behaviour and altered fuel preferences were also observed in these mice. In addition, these CR-fed AgRP-Cre;Ghsrf/f mice exhibited a decreased counter-regulatory response, showing impaired hepatic glucose production. Lastly, hypothalamic gene expression in AgRP-Cre;Ghsrf/f mice revealed increased AgRP expression and a decreased expression of genes in ß-oxidation pathways. In summary, our data suggest that GHS-R in AgRP neurones is a key component of the neurocircuitry involved in metabolic adaptation to calorie restriction.

2.
Int J Mol Sci ; 20(11)2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31212704

RESUMO

Lysophosphatidic acid (LPA) is a bioactive phospholipid present in most tissues and body fluids. LPA acts through specific LPA receptors (LPAR1 to LPAR6) coupled with G protein. LPA binds to receptors and activates multiple cellular signaling pathways, subsequently exerting various biological functions, such as cell proliferation, migration, and apoptosis. LPA also induces cell damage through complex overlapping pathways, including the generation of reactive oxygen species, inflammatory cytokines, and fibrosis. Several reports indicate that the LPA-LPAR axis plays an important role in various diseases, including kidney disease, lung fibrosis, and cancer. Diabetic nephropathy (DN) is one of the most common diabetic complications and the main risk factor for chronic kidney diseases, which mostly progress to end-stage renal disease. There is also growing evidence indicating that the LPA-LPAR axis also plays an important role in inducing pathological alterations of cell structure and function in the kidneys. In this review, we will discuss key mediators or signaling pathways activated by LPA and summarize recent research findings associated with DN.

3.
J Cachexia Sarcopenia Muscle ; 10(4): 903-918, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31020810

RESUMO

BACKGROUND: Skeletal muscle atrophy is defined as a reduction of muscle mass caused by excessive protein degradation. However, the development of therapeutic interventions is still in an early stage. Although glucagon-like peptide-1 receptor (GLP-1R) agonists, such as exendin-4 (Ex-4) and dulaglutide, are widely used for the treatment of diabetes, their effects on muscle pathology are unknown. In this study, we investigated the therapeutic potential of GLP-1R agonist for muscle wasting and the mechanisms involved. METHODS: Mouse C2C12 myotubes were used to evaluate the in vitro effects of Ex-4 in the presence or absence of dexamethasone (Dex) on the regulation of the expression of muscle atrophic factors and the underlying mechanisms using various pharmacological inhibitors. In addition, we investigated the in vivo therapeutic effect of Ex-4 in a Dex-induced mouse muscle atrophy model (20 mg/kg/day i.p.) followed by injection of Ex-4 (100 ng/day i.p.) for 12 days and chronic kidney disease (CKD)-induced muscle atrophy model. Furthermore, we evaluated the effect of a long-acting GLP-1R agonist by treatment of dulaglutide (1 mg/kg/week s.c.) for 3 weeks, in DBA/2J-mdx mice, a Duchenne muscular dystrophy model. RESULTS: Ex-4 suppressed the expression of myostatin (MSTN) and muscle atrophic factors such as F-box only protein 32 (atrogin-1) and muscle RING-finger protein-1 (MuRF-1) in Dex-treated C2C12 myotubes. The suppression effect was via protein kinase A and protein kinase B signalling pathways through GLP-1R. In addition, Ex-4 treatment inhibited glucocorticoid receptor (GR) translocation by up-regulating the proteins of GR inhibitory complexes. In a Dex-induced muscle atrophy model, Ex-4 ameliorated muscle atrophy by suppressing muscle atrophic factors and enhancing myogenic factors (MyoG and MyoD), leading to increased muscle mass and function. In the CKD muscle atrophy model, Ex-4 also increased muscle mass, myofiber size, and muscle function. In addition, treatment with a long-acting GLP-1R agonist, dulaglutide, recovered muscle mass and function in DBA/2J-mdx mice. CONCLUSIONS: GLP-1R agonists ameliorate muscle wasting by suppressing MSTN and muscle atrophic factors and enhancing myogenic factors through GLP-1R-mediated signalling pathways. These novel findings suggest that activating GLP-1R signalling may be useful for the treatment of atrophy-related muscular diseases.

4.
Biochim Biophys Acta Mol Basis Dis ; 1865(6): 1332-1340, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30763641

RESUMO

Diabetic nephropathy (DN) is one of the major long-term complications of diabetes. Lysophosphatidic acid (LPA) signaling has been implicated in renal fibrosis. In our previous study, we found that the LPA receptor 1/3 (LPAR1/3) antagonist, ki16425, protected against DN in diabetic db/db mice. Here, we investigated the effects of a specific pharmacological inhibitor of LPA receptor 1 (LPA1), AM095, on DN in streptozotocin (STZ)-induced diabetic mice to exclude a possible contribution of LPAR3 inhibition. AM095 treatment significantly reduced albuminuria and the albumin to creatinine ratio and significantly decreased the glomerular volume and tuft area in the treated group compared with the STZ-vehicle group. In the kidney of STZ-induced diabetic mice, the expression of LPAR1 mRNA and protein was positively correlated with oxidative stress. AM095 treatment inhibited LPA-induced reactive oxygen species production and NADPH oxidase expression as well as LPA-induced toll like receptor 4 (TLR4) expression in mesangial cells and in the kidney of STZ-induced diabetic mice. In addition, AM095 treatment suppressed LPA-induced pro-inflammatory cytokines and fibrotic factors expression through downregulation of phosphorylated NFκBp65 and c-Jun N-terminal kinases (JNK) in vitro and in the kidney of STZ-induced diabetic mice. Pharmacological or siRNA inhibition of TLR4 and NADPH oxidase mimicked the effects of AM095 in vitro. In conclusion, AM095 is effective in preventing the pathogenesis of DN by inhibiting TLR4/NF-κB and the NADPH oxidase system, consequently inhibiting the inflammatory signaling cascade in renal tissue of diabetic mice, suggesting that LPAR1 antagonism might provide a potential therapeutic target for DN.

5.
Exp Mol Med ; 51(2): 18, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770784

RESUMO

Mesangial cell proliferation has been identified as a major factor contributing to glomerulosclerosis, which is a typical symptom of diabetic nephropathy (DN). Lysophosphatidic acid (LPA) levels are increased in the glomerulus of the kidney in diabetic mice. LPA is a critical regulator that induces mesangial cell proliferation; however, its effect and molecular mechanisms remain unknown. The proportion of α-SMA+/PCNA+ cells was increased in the kidney cortex of db/db mice compared with control mice. Treatment with LPA concomitantly increased the proliferation of mouse mesangial cells (SV40 MES13) and the expression of cyclin D1 and CDK4. On the other hand, the expression of p27Kip1 was decreased. The expression of Krüppel-like factor 5 (KLF5) was upregulated in the kidney cortex of db/db mice and LPA-treated SV40 MES13 cells. RNAi-mediated silencing of KLF5 reversed these effects and inhibited the proliferation of LPA-treated cells. Mitogen-activated protein kinases (MAPKs) were activated, and the expression of early growth response 1 (Egr1) was subsequently increased in LPA-treated SV40 MES13 cells and the kidney cortex of db/db mice. Moreover, LPA significantly increased the activity of the Ras-related C3 botulinum toxin substrate (Rac1) GTPase in SV40 MES13 cells, and the dominant-negative form of Rac1 partially inhibited the phosphorylation of p38 and upregulation of Egr1 and KLF5 induced by LPA. LPA-induced hyperproliferation was attenuated by the inhibition of Rac1 activity. Based on these results, the Rac1/MAPK/KLF5 signaling pathway was one of the mechanisms by which LPA induced mesangial cell proliferation in DN models.


Assuntos
Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Lisofosfolipídeos/farmacologia , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Biomarcadores , Proliferação de Células , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Expressão Gênica , Masculino , Camundongos , Camundongos Transgênicos , Transdução de Sinais/efeitos dos fármacos
6.
Int J Mol Sci ; 19(10)2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30275401

RESUMO

Ghrelin via its receptor, the growth hormone secretagogue receptor (GHS-R), increases food intake and adiposity. The tissue-specific functions of GHS-R in peripheral tissues are mostly unknown. We previously reported that while GHS-R expression is very low in white and brown fat of young mice, expression increases during aging. To investigate whether GHS-R has cell-autonomous effects in adipose tissues, we generated aP2-Cre-mediated GHS-R knockdown mice (aP2-Cre/Ghsrf/f). We studied young (5⁻6 months) and old (15⁻17 months) aP2-Cre/Ghsrf/f mice and their age-matched controls. Interestingly, young aP2-Cre/Ghsrf/f mice had normal body weight but reduced fat; old mice showed pronounced reductions of both body weight and body fat. Calorimetry analysis revealed that aP2-Cre/Ghsrf/f mice had normal food intake and locomotor activity at both young and old age; but intriguingly, while energy expenditure was normal at young age, it was significantly increased at old age. Both young and old aP2-Cre/Ghsrf/f mice exhibited improved insulin sensitivity and glucose tolerance. Importantly, old aP2-Cre/Ghsrf/f mice maintained higher core body temperature at 4 °C, and showed higher expression of the thermogenic uncoupling protein 1 (UCP1) gene. The ex vivo studies further demonstrated that GHS-R deficient white adipocytes from old mice exhibit increased glucose uptake and lipolysis, promoting lipid mobilization. Despite the fact that the in vivo phenotypes of aP2-Cre/Ghsrf/f mice may not be exclusively determined by GHS-R knockdown in adipose tissues, our data support that GHS-R has cell-autonomous effects in adipocytes. The anabolic effect of GHS-R in adipocytes is more pronounced in aging, which likely contributes to age-associated obesity and insulin resistance.

7.
Materials (Basel) ; 11(9)2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30213074

RESUMO

An irreversible thermochromic material based on manganese violet (MnNH4P2O7) is synthesized. The crystal phase, chemical composition, and morphology of the synthesized material are analyzed using X-ray diffraction, scanning electron microscopy coupled with energy-dispersive X-ray spectrometry, and Fourier-transform infrared spectroscopy. The absorption spectra of the synthesized material are obtained using a UV-Vis spectrometer, and the thermochromism exhibited by the powdered samples at high temperatures is also investigated. The as-synthesized manganese violet pigment consists of pure α-MnNH4P2O7 phase. In addition, the synthesized pigment largely consists of hexagonal crystals with a diameter of hundreds of nanometers. On heating, the pigment simultaneously loses H2O and NH3 in two successive steps at approximately 330⁻434.4 °C and 434.4⁻527 °C, which correspond to the formation of an intermediate phase and of Mn2P4O12, respectively. An overall mass loss of 14.22% is observed, which is consistent with the expected 13.79%. An irreversible color change from violet to white is observed after exposure of the synthesized manganese violet pigment at 400 °C for 30 min. This is attributed to the oxidation of ammonia to hydroxylamine, which then decomposes to nitrogen and water, or alternatively to the direct oxidation of ammonia to nitrogen. Furthermore, we demonstrate the potential application of synthesized manganese violet in the production of irreversible thermochromic paint by mixing with potassium silicate solution as a binder and deionized water as a solvent at a specific ratio. The thermochromic paint is then applied in fabrication of irreversible thermochromic sensors by coating it onto a steel plate surface. Finally, we show that manganese violet-based irreversible thermochromic sensors are able to detect temperatures around 400 °C by changing color from violet to white/milky.

8.
Acta Biomater ; 81: 231-241, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30240953

RESUMO

Direct delivery of proteins into cells has been considered an effective approach for treating the protein-related diseases. However, clinical use of proteins has still been limited due to their instability in the blood and poor membrane permeability. To achieve an efficient cellular delivery of the protein to target cells via a systemic administration, a multifunctional carrier system having desirable stability both in the blood stream and the cells, specific cell-targeting property and endosomal escape functions may be required. In this study, we prepared a catalytic nanoparticle containing an active enzyme by cross-tethering multiple superoxide dismutase (SOD) molecules with catechol-derivatized hyaluronic acid (HA). The permeable shell of hydrophilic HA chains effectively protects the enzyme from degradation in the blood after intravenous administration and provides an additional function for targeting hepatocytes expressing HA receptor (CD44). The structure and catalytic activity of the enzyme molecules in the nanoparticle were not significantly compromised in the nanoparticle. In addition, ultra-small calcium phosphate nanoparticles (USCaP, 2-5 nm) were crystalized and decorated on the surface of the nanoparticle for the efficient endosomal escape after cellular uptake. The SOD-containing nanoparticle fortified with USCaP was used for the treatment of acetaminophen (APAP)-induced fulminant hepatotoxicity and liver injury. The nanoparticle achieved the efficient hepatic cellular delivery of SOD via a systemic administration and resulted in efficient removal of reactive oxygen species (ROS) in the liver and remarkable improvement of APAP-induced hepatotoxicity and liver injury in animals. STATEMENT OF SIGNIFICANCE: Despite the enormous therapeutic potential, the intracellular delivery of proteins has been limited due to their poor membrane permeability and stability. In this study, we demonstrated an active enzyme-containing nanoparticle functionalized by hyaluronic acid and ultra-small size calcium phosphate nanoparticles (2-5 nm) for targeted cellular delivery of superoxide dismutase (SOD). The nanoparticle was designed to integrate all the essential functions, including serum stability, target specificity, and endosomal escape capability, for a systemic delivery of a therapeutic protein to the cells of the liver tissue. The intravenous administration of the nanoparticle efficiently removes reactive oxygen species (ROS) in the liver and remarkably improves the drug-induced hepatotoxicity and the progress of fulminant liver injury in an acetaminophen-overdose animal model.

9.
J Med Syst ; 42(10): 189, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30178422

RESUMO

False positive signals (FPSs) of continuous monitoring blood culture system (CMBCS) cause delayed reporting time and increased laboratory cost. This study aimed to analyze growth graphs digitally in order to identify specific patterns of FPSs and true positive signals (TPSs) and to find the method for improving positive predictive value (PPV) of FPS and TPS. 606 positive signal samples from the BACTEC FX (BD, USA) CMBCS with more than one hour of monitoring data after positive signal were selected, and were classified into FPS and TPS groups using the subculture results. The pattern of bacterial growth graph was analyzed in two steps: the signal stage recorded using the monitoring data until positive signal and the post-signal stage recorded using one additional hour of monitoring data gained after the positive signal. The growth graph before the positive signal consists of three periods; initial decline period, stable period, and steeping period. Signal stage analyzed initial decline period and stable period, and classified the graphs as standard, increasing, decreasing, irregular, or defective pattern, respectively. Then, all patterns were re-assigned as confirmed or suspicious pattern in the post-signal stage. Standard, increasing, and decreasing patterns with both initial decline period and stable period are typical patterns; irregular patterns lacking a smooth stable period and defective patterns without an initial decline period are false positive patterns. The false positive patterns have 77.2% of PPV for FPS. The confirmed patterns, showing a gradually increasing fluorescence level even after positive signal, have 97.0% of PPV for TPS.


Assuntos
Bactérias/isolamento & purificação , Hemocultura , Meios de Cultura , Reações Falso-Positivas , Monitorização Fisiológica , República da Coreia
10.
ACS Nano ; 12(10): 9702-9713, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30141896

RESUMO

Efficient delivery of tumor antigens and immunostimulatory adjuvants into lymph nodes is crucial for the maturation and activation of antigen-presenting cells (APCs), which subsequently induce adaptive antitumor immunity. A dissolving microneedle (MN) has been considered as an attractive method for transcutaneous immunization due to its superior ability to deliver vaccines through the stratum corneum in a minimally invasive manner. However, because dissolving MNs are mostly prepared using water-soluble sugars or polymers for their rapid dissolution in intradermal fluid after administration, they are often difficult to formulate with poorly water-soluble vaccine components. Here, we develop amphiphilic triblock copolymer-based dissolving MNs in situ that generate nanomicelles (NMCs) upon their dissolution after cutaneous application, which facilitate the efficient encapsulation of poorly water-soluble Toll-like receptor 7/8 agonist (R848) and the delivery of hydrophilic antigens. The sizes of NMCs range from 30 to 40 nm, which is suitable for the efficient delivery of R848 and antigens to lymph nodes and promotion of cellular uptake by APCs, minimizing systemic exposure of the R848. Application of MNs containing tumor model antigen (OVA) and R848 to the skin of EG7-OVA tumor-bearing mice induced a significant level of antigen-specific humoral and cellular immunity, resulting in significant antitumor activity.

11.
Drug Deliv ; 25(1): 1570-1578, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30044159

RESUMO

Paclitaxel (PTX) is used as a major antitumor agent for the treatment of recurrent and metastatic breast cancer. For the clinical application of PTX, it needs to be dissolved in an oil/detergent-based solvent due to its poor solubility in an aqueous medium. However, the formulation often causes undesirable complications including hypersensitivity reactions and limited tumor distribution, resulting in a lower dose-dependent antitumor effect. Herein, we introduce a facile and oil-free method to prepare albumin-based PTX nanoparticles for efficient systemic cancer therapy using a conjugate of human serum albumin (HSA) and poly(ethyleneglycol) (PEG). PTX were efficiently incorporated in the self-assembled HSA-PEG nanoparticles (HSA-PEG/PTX) using a simple film casting and re-hydration procedure without additional processes such as application of high pressure/shear or chemical crosslinking. The spherical HSA-PEG nanoparticle with a hydrodynamic diameter of ca. 280 nm mediates efficient cellular delivery, leading to comparable or even higher cytotoxicity in various breast cancer cells than that of the commercially available Abraxane®. When systemically administered in a mouse xenograft model for human breast cancer, the HSA-PEG-based nanoparticle formulation exhibited an extended systemic circulation for more than 96 h and enhanced intratumoral accumulation, resulting in a remarkable anticancer effect and prolonged survival of the animals.

12.
J Clin Lab Anal ; 32(7): e22451, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29665075

RESUMO

BACKGROUND: Transferrin is the major plasma transport protein for iron. We aimed to investigate the characteristics of transferrin variant by carbohydrate-deficient transferrin (CDT) test using capillary zone electrophoresis. METHODS: We retrospectively analyzed the CDT tests of 2449 patients from March 2009 to May 2017 at a tertiary hospital in Korea. CDT was quantified using a Capillarys 2 system (Sebia, Lisses, France) by capillary zone electrophoresis. The characteristics of variant transferrin patterns using electropherogram of CDT tests were analyzed. RESULTS: Seventy-seven (3.1%) patients were classified as variant transferrin. Mean age of these patients was 51.8 years, and the male-to-female ratio was 3.5:1. The most common variants were the BC variants (n = 37), followed by the CD variants (n = 27), unclear patterns (n = 7), BD variants (n = 3), CC variants (n = 2), misclassification (n = 1). In the variant Tf group, the most common disease was alcoholic liver cirrhosis (n = 22, 28.6%), followed by the toxic effects of substances (n = 17, 22.1%), and mental and behavioral disorders attributable to alcohol (n = 11, 14.3%). Nonvariant group showed a predominance of the toxic substance effects (n = 880, 37.1%), a personal history of suicide attempts (n = 634, 26.7%), and mental and behavioral disorders due to alcohol (n = 336, 14.2%). CONCLUSION: We analyzed the basic characteristics of variant transferrin by CDT tests using capillary zone electrophoresis. The prevalence of variant transferrin was 3.1% of the study subjects. Male patients, alcohol abusers, and liver cirrhosis patients predominated in the variant transferrin population. Further prospective studies are warranted to elucidate variant transferrin in clinical practice.


Assuntos
Eletroforese Capilar/métodos , Transferrina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/sangue , Alcoolismo/epidemiologia , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/sangue , Isoformas de Proteínas/química , Estudos Retrospectivos , Transferrina/análise , Transferrina/química , Adulto Jovem
13.
Lab Med ; 49(3): 254-258, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29566170

RESUMO

Objective: To compare a manual squamous cell carcinoma antigen (SCCA) assay and an automated SCCA assay in a clinical setting. Methods: We included, in this study, a total of 158 specimens that had been tested using the manual SCCA assay. The CanAg SCC EIA assay and the Elecsys SCC were compared for their clinical settings. Results: Within-run and between-day coefficients of variation (CVs, %) were lower than 3%. Comparison of the manual and automated SCCA assays yielded good correlation. The correlation coefficient (R2) between the CanAg SCC EIA and Elecsys SCC assay results was 0.989 (P <.001) and the overall concordance rate was 94.3%. Conclusions: We report that the Elecsys SCC automated SCCA assay yielded performance comparable to that of the manual SCCA assay: the automated assay reduced the number of manual steps and test turnaround time.


Assuntos
Antígenos de Neoplasias/sangue , Automação Laboratorial/métodos , Biomarcadores Tumorais/sangue , Análise Química do Sangue , Técnicas Imunoenzimáticas/métodos , Medições Luminescentes/métodos , Serpinas/sangue , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Humanos , Modelos Lineares , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
J Clin Lab Anal ; 32(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28407318

RESUMO

BACKGROUND: Rapid influenza diagnostic tests (RIDTs) show variable sensitivities in clinical settings. We aimed to compare three digital RIDTs and one conventional RIDT. METHODS: We assessed 218 nasopharyngeal swabs from patients between neonates and 90 years old in 2016. Three digital RIDTs were BUDDI, Sofia Influenza A+B Fluorescence Immunoassay, Veritor System Flu A+B assay. One conventional test was the SD Bioline Influenza Ag A/B/A(H1N1/2009). All test results were compared with those from the Anyplex Flu A/B Typing Real-time Detection real-time PCR. The four RIDTs were tested with diluted solutions from the National Institute for Biological Standards and Control (NIBSC) to compare lower detection limit. Cross-reactivity of four RIDTs within other respiratory viruses was identified. RESULTS: For influenza A, BUDDI, Sofia, Veritor, and Bioline showed 87.7%, 94.5%, 87.7%, and 72.6% sensitivity, and 100%, 97.7%, 96.5%, and 100% specificity. For influenza B, BUDDI, Sofia, Veritor, and Bioline showed 81.7%, 91.7%, 81.7%, and 78.3% sensitivity, and 100%, 95.3%, 100%, and 100% specificity, respectively. Each RIDT could detect diluted NIBSC solution, according to the level of dilution and specific influenza subtypes. Cross-reactivity of four RIDTs with other respiratory viruses was not noted. CONCLUSIONS: Sofia showed the highest sensitivity for influenza A and B detection. BUDDI and Veritor showed higher detection sensitivity than a conventional RIDT for influenza A detection, but similar results for influenza B detection. Further study is needed to compare the test performance of RIDTs according to specific, prevalent influenza subtypes.


Assuntos
Testes Diagnósticos de Rotina/métodos , Imunoensaio/métodos , Influenza Humana/diagnóstico , Virologia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Imunofluorescência , Humanos , Lactente , Recém-Nascido , Nasofaringe/virologia , Sensibilidade e Especificidade , Adulto Jovem
15.
BMC Complement Altern Med ; 17(1): 528, 2017 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-29228944

RESUMO

BACKGROUND: Acupuncture has been used as a common therapeutic tool in many disorders including anxiety and depression. Serotonin transporter (SERT) plays an important role in the pathology of anxiety and other mood disorders. The aim of this study was to evaluate the effects of acupuncture on lipopolysaccharide (LPS)-induced anxiety-like behaviors and SERT in the dorsal raphe nuclei (DRN). METHODS: Rats were given acupuncture at ST41 (Jiexi), LI11 (Quchi) or SI3 (Houxi) acupoint in LPS-treated rats. Anxiety-like behaviors of elevated plus maze (EPM) and open field test (OFT) were measured and expressions of SERT and/or c-Fos were also examined in the DRN using immunohistochemistry. RESULTS: The results showed that 1) acupuncture at ST41 acupoint, but neither LI11 nor SI3, significantly attenuated LPS-induced anxiety-like behaviors in EPM and OFT, 2) acupuncture at ST41 decreased SERT expression increased by LPS in the DRN. CONCLUSIONS: Our results suggest that acupuncture can ameliorate anxiety-like behaviors, possibly through regulation of SERT in the DRN.


Assuntos
Terapia por Acupuntura , Ansiedade/terapia , Comportamento Animal/fisiologia , Núcleo Dorsal da Rafe/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Animais , Ansiedade/induzido quimicamente , Modelos Animais de Doenças , Núcleo Dorsal da Rafe/química , Lipopolissacarídeos/efeitos adversos , Masculino , Ratos , Ratos Sprague-Dawley
16.
BMC Physiol ; 17(1): 8, 2017 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-29058611

RESUMO

BACKGROUND: Thermogenic impairment promotes obesity and insulin resistance. Adiponectin is an important regulator of energy homeostasis. While many beneficial metabolic effects of adiponectin resemble that of activated thermogenesis, the role of adiponectin in thermogenesis is not clear. In this study, we investigated the role of adiponectin in thermogenesis using adiponectin-null mice (Adipoq -/-). METHODS: Body composition was measured using EchoMRI. Metabolic parameters were determined by indirect calorimetry. Insulin sensitivity was evaluated by glucose- and insulin- tolerance tests. Core body temperature was measured by a TH-8 temperature monitoring system. Gene expression was assessed by real-time PCR and protein levels were analyzed by Western blotting and immunohistochemistry. The mitochondrial density of brown adipose tissue was quantified by calculating the ratio of mtDNA:total nuclear DNA. RESULTS: Under normal housing temperature of 24 °C and ad libitum feeding condition, the body weight, body composition, and metabolic profile of Adipoq -/- mice were unchanged. Under fasting condition, Adipoq -/- mice exhibited reduced energy expenditure. Conversely, under cold exposure, Adipoq -/- mice exhibited reduced body temperature, and the expression of thermogenic regulatory genes was significantly reduced in brown adipose tissue (BAT) and subcutaneous white adipose tissue (WAT). Moreover, we observed that mitochondrial content was reduced in BAT and subcutaneous WAT, and the expression of mitochondrial fusion genes was decreased in BAT of Adipoq -/- mice, suggesting that adiponectin ablation diminishes mitochondrial biogenesis and altered mitochondrial dynamics. Our study further revealed that adiponectin deletion suppresses adrenergic activation, and down-regulates ß3-adrenergic receptor, insulin signaling, and the AMPK-SIRT1 pathway in BAT. CONCLUSIONS: Our findings demonstrate that adiponectin is an essential regulator of thermogenesis, and adiponectin is required for maintaining body temperature under cold exposure.


Assuntos
Adiponectina/fisiologia , Temperatura Baixa , Termogênese , Adiponectina/genética , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Comportamento Animal , DNA Mitocondrial/metabolismo , Meio Ambiente , Jejum , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Fisiológico
18.
Int J Mol Sci ; 18(4)2017 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-28420089

RESUMO

Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in Agouti-Related Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron-specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice by activating non-shivering thermogenesis. To further decipher the specific neuronal circuits mediating the metabolic effects of GHS-R, we generated AgRP neuron-specific GHS-R knockout mice (AgRP-Cre;Ghsrf/f). Our data showed that GHS-R in AgRP neurons is required for ghrelin's stimulatory effects on growth hormone secretion, acute food intake and adiposity, but not for long-term total food intake. Importantly, deletion of GHS-R in AgRP neurons attenuated diet-induced obesity (DIO) and enhanced cold-resistance in mice fed high fat diet (HFD). The HFD-fed knockout mice showed increased energy expenditure, and exhibited enhanced thermogenic activation in both brown and subcutaneous fat; this implies that GHS-R suppression in AgRP neurons enhances sympathetic outflow. In summary, our results suggest that AgRP neurons are key site for GHS-R mediated thermogenesis, and demonstrate that GHS-R in AgRP neurons plays crucial roles in governing energy utilization and pathogenesis of DIO.


Assuntos
Proteína Relacionada com Agouti/metabolismo , Neurônios/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Fragmentos de Peptídeos/metabolismo , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Termogênese , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Metabolismo Energético , Comportamento Alimentar , Deleção de Genes , Hormônio do Crescimento/metabolismo , Homeostase , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Knockout , Modelos Biológicos
20.
Diabetes ; 65(8): 2169-78, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27207529

RESUMO

Ghrelin signaling has major effects on energy and glucose homeostasis, but it is unknown whether ghrelin's functions are centrally and/or peripherally mediated. The ghrelin receptor, growth hormone secretagogue receptor (GHS-R), is highly expressed in the brain and detectable in some peripheral tissues. To understand the roles of neuronal GHS-R, we generated a mouse line where Ghsr gene is deleted in all neurons using synapsin 1 (Syn1)-Cre driver. Our data showed that neuronal Ghsr deletion abolishes ghrelin-induced spontaneous food intake but has no effect on total energy intake. Remarkably, neuronal Ghsr deletion almost completely prevented diet-induced obesity (DIO) and significantly improved insulin sensitivity. The neuronal Ghsr-deleted mice also showed improved metabolic flexibility, indicative of better adaption to different fuels. In addition, gene expression analysis suggested that hypothalamus and/or midbrain might be the sites that mediate the effects of GHS-R in thermogenesis and physical activity, respectively. Collectively, our results indicate that neuronal GHS-R is a crucial regulator of energy metabolism and a key mediator of DIO. Neuronal Ghsr deletion protects against DIO by regulating energy expenditure, not by energy intake. These novel findings suggest that suppressing central ghrelin signaling may serve as a unique antiobesity strategy.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Neurônios/metabolismo , Obesidade/metabolismo , Obesidade/prevenção & controle , Receptores de Grelina/metabolismo , Animais , Encéfalo/metabolismo , Calorimetria Indireta , Ingestão de Alimentos/genética , Ingestão de Alimentos/fisiologia , Metabolismo Energético/genética , Metabolismo Energético/fisiologia , Feminino , Teste de Tolerância a Glucose , Hipotálamo/metabolismo , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Masculino , Camundongos , Camundongos Mutantes , Obesidade/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Grelina/genética , Sinapsinas/genética , Sinapsinas/metabolismo , Termogênese/genética , Termogênese/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA