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1.
Proc Natl Acad Sci U S A ; 119(32): e2121225119, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35914143

RESUMEN

G protein-coupled receptor (GPCR) signaling is ubiquitous. As an archetype of this signaling motif, rod phototransduction has provided many fundamental, quantitative details, including a dogma that one active GPCR molecule activates a substantial number of downstream G protein/enzyme effector complexes. However, rod phototransduction is light-activated, whereas GPCR pathways are predominantly ligand-activated. Here, we report a detailed study of the ligand-triggered GPCR pathway in mammalian olfactory transduction, finding that an odorant-receptor molecule when (one-time) complexed with its most effective odorants produces on average much less than one downstream effector. Further experiments gave a nominal success probability of tentatively ∼10-4 (more conservatively, ∼10-2 to ∼10-5). This picture is potentially more generally representative of GPCR signaling than is rod phototransduction, constituting a paradigm shift.


Asunto(s)
Ligandos , Odorantes , Receptores Acoplados a Proteínas G , Receptores Odorantes , Transducción de Señal , Olfato , Animales , Fototransducción , Mamíferos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Odorantes/metabolismo , Células Fotorreceptoras Retinianas Bastones
2.
BMC Infect Dis ; 24(1): 691, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992583

RESUMEN

BACKGROUND: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions. CASE PRESENTATION: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 109/L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella. CONCLUSION: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis.


Asunto(s)
Varicela , Coinfección , Infecciones por Citomegalovirus , Citomegalovirus , Humanos , Masculino , Adulto , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/aislamiento & purificación , Varicela/tratamiento farmacológico , Varicela/complicaciones , Varicela/virología , Varicela/diagnóstico , Coinfección/virología , Coinfección/tratamiento farmacológico , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Hemorragia/virología , Hemorragia/etiología , Herpesvirus Humano 3/aislamiento & purificación , Activación Viral
3.
Proc Natl Acad Sci U S A ; 118(14)2021 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-33785600

RESUMEN

The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases.


Asunto(s)
Señalización del Calcio , Hibernación , Miocitos Cardíacos/metabolismo , Animales , Caveolinas/genética , Caveolinas/metabolismo , Células Cultivadas , Acoplamiento Excitación-Contracción , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Nucleares/sangre , Proteínas Nucleares/metabolismo , Sciuridae , Transactivadores/sangre , Transactivadores/metabolismo
4.
BMC Infect Dis ; 23(1): 53, 2023 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-36694122

RESUMEN

BACKGROUND: The effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on mortality was preliminarily explored through the comparison of ACEIs/ARBs with non-ACEIs/ARBs in patients with coronavirus disease 2019 (COVID-19). Reaching a conclusion on whether previous ACEI/ARB treatment should be continued in view of the different ACE2 levels in the comparison groups was not unimpeachable. Therefore, this study aimed to further elucidate the effect of ACEI/ARB continuation on hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) in the same patient population. METHODS: We searched PubMed, the Cochrane Library, Ovid, and Embase for relevant articles published between December 1, 2019 and April 30, 2022. Continuation of ACEI/ARB use after hospitalization due to COVID-19 was considered as an exposure and discontinuation of ACEI/ARB considered as a control. The primary outcome was hospital mortality, and the secondary outcomes included 30-day mortality, rate of ICU admission, IMV, and other clinical outcomes. RESULTS: Seven observational studies and four randomized controlled trials involving 2823 patients were included. The pooled hospital mortality in the continuation group (13.04%, 158/1212) was significantly lower than that (22.15%, 278/1255) in the discontinuation group (risk ratio [RR] = 0.45; 95% confidence interval [CI], 0.28-0.72; P = 0.001). Continuation of ACEI/ARB use was associated with lower rates of ICU admission (10.5% versus 16.2%, RR = 0.63; 95% CI 0.5-0.79; P < 0.0001) and IMV (8.2% versus 12.5%, RR = 0.62; 95% CI 0.46-0.83, P = 0.001). Nevertheless, the effect was mainly demonstrated in the observational study subgroup (P < 0.05). Continuing ACEI/ARB had no significant effect on 30-day mortality (P = 0.34), acute myocardial infarction (P = 0.08), heart failure (P = 0.82), and acute kidney injury after hospitalization (P = 0.98). CONCLUSION: Previous ACEI/ARB treatment could be continued since it was associated with lower hospital deaths, ICU admission, and IMV in patients with COVID-19, although the benefits of continuing use were mainly shown in observational studies. More evidence from multicenter RCTs are still needed to increase the robustness of the data. Trial registration PROSPERO (CRD42022341169). Registered 27 June 2022.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , COVID-19 , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Sistema Renina-Angiotensina , Antihipertensivos/uso terapéutico , Análisis de Regresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Observacionales como Asunto , Estudios Multicéntricos como Asunto
5.
World J Surg Oncol ; 21(1): 28, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36721235

RESUMEN

BACKGROUND AND OBJECTIVES: In patients with colorectal cancer and clinically suspected para-aortic lymph node metastasis, the survival benefit of para-aortic lymphadenectomy is unknown. We conducted a meta-analysis and systematic review to investigate it. METHODS: PubMed, Web of Science, and EMBASE were searched until January 2000 to April 2022 to identify studies reporting overall survivals, complication rates, and hazard ratios of prognostic factors in patients with colorectal cancer undergoing para-aortic lymphadenectomy, and those data were pooled. RESULTS: Twenty retrospective studies (1021 patients undergoing para-aortic lymphadenectomy) met the inclusion criteria. Meta-analysis indicates that participants undergoing para-aortic lymphadenectomy were associated with 5-year survival benefit, compared to those not receiving para-aortic lymphadenectomy (odds ratio = 3.73, 95% confidence interval: 2.05-6.78), but there was no significant difference in complication rate (odds ratio = 0.97, 95% confidence interval: 0.46-2.08). Further analysis of para-aortic lymphadenectomy group showed that 5-year survival of the positive group with pathologically para-aortic lymph node metastasis was lower than that of the negative group (odds ratio = 0.19, 95% confidence interval: 0.11-0.31). Moreover, complete resection (odds ratio = 5.26, 95% confidence interval: 2.02-13.69), para-aortic lymph node metastasis (≤4) (hazard ratio = 1.88, 95% confidence interval: 0.97-3.62), and medium-high differentiation (hazard ratio = 2.98, 95% confidence interval: 1.48-5.99) were protective factors for survival. Preoperative extra-retroperitoneal metastasis was associated with poorer relapse-free survival (hazard ratio = 1.85, 95% confidence interval: 1.10-3.10). CONCLUSION: Para-aortic lymphadenectomy had promising clinical efficacy in prolonging survival rather than complication rate in patients with colorectal cancer and clinically diagnostic para-aortic lymph node metastasis. Further prospective studies should be performed. TRIAL REGISTRATION: PROSPERO: CRD42022379276.


Asunto(s)
Neoplasias Colorrectales , Escisión del Ganglio Linfático , Humanos , Neoplasias Colorrectales/cirugía , Metástasis Linfática , Estudios Prospectivos , Estudios Retrospectivos
6.
J Transl Med ; 20(1): 218, 2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35562743

RESUMEN

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.


Asunto(s)
Células Acinares , Endorribonucleasas , Animales , Humanos , Ratones , Células Acinares/metabolismo , Ácido Araquidónico/metabolismo , Proteínas Portadoras/metabolismo , Endorribonucleasas/metabolismo , Fibrosis , Radioisótopos de Galio , Ratones Noqueados , Tomografía Computarizada por Tomografía de Emisión de Positrones , Proteínas Serina-Treonina Quinasas , Tripsina/metabolismo , Proteínas Supresoras de Tumor/metabolismo
7.
Respir Res ; 23(1): 328, 2022 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-36463140

RESUMEN

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.


Asunto(s)
Bronquiectasia , Humanos , Bronquiectasia/diagnóstico , Bronquiectasia/epidemiología , China/epidemiología , Estudios de Cohortes , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Estudios Prospectivos , Calidad de Vida , Sistema de Registros
8.
Transpl Int ; 35: 10265, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35221789

RESUMEN

Background: Accurate identification of pathogens is essential for the diagnosis and control of infections. We aimed to compare the diagnostic performance of metagenomic next-generation sequencing (mNGS) and conventional detection methods (CDM) in lung transplant recipients (LTRs). Methods: We retrospectively analyzed 107 LTRs with suspected infection of pulmonary, blood, central nervous system or chest wall between March 2018 and November 2020. Bronchoalveolar lavage fluid and other body fluids were subject to pathogen detection by both mNGS and CDM. Results: Of the 163 specimens, 84 (51.5%) tested positive for both mNGS and culture, 19 (11.7%) of which were completely consistent, 44 (27.0%) were partially congruent, and 21 (12.9%) were discordant (kappa = .215; p = .001). Compared with CDM, mNGS detected a higher diversity of pathogens. Moreover, the turn-around time was significantly shorter for mNGS compared with culture (2.7 ± .4 vs. 5.5 ± 1.6 days, p < .001). As an auxiliary method, treatment strategies were adjusted according to mNGS findings in 31 cases (29.0%), including eight patients with non-infectious diseases, who were finally cured. Conclusion: mNGS can identify pathogens with a shorter turn-around time and therefore provide a more accurate and timely diagnostic information to ascertaining pulmonary infections. mNGS might have a role in differentiating infectious from non-infectious lung diseases in LTRs.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Receptores de Trasplantes , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Pulmón , Estudios Retrospectivos , Sensibilidad y Especificidad
9.
Arch Virol ; 166(11): 3105-3116, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34482448

RESUMEN

Several outbreaks of duck hepatitis A virus type 1 (DHAV-1), which were characterized by yellow coloration and hemorrhage in pancreatic tissues, have occurred in China. The causative agent is called pancreatitis-associated DHAV-1. The mechanisms involved in pancreatitis-associated DHAV-1 infection are still unclear. Transcriptome analysis of duck pancreas infected with classical-type DHAV-1 and pancreatitis-associated DHAV-1 was carried out. Deep sequencing with Illumina-Solexa resulted in a total of 53.9 Gb of clean data from the cDNA library of the pancreas, and a total of 29,597 unigenes with an average length of 993.43 bp were generated by de novo sequence assembly. The expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase, which are involved in glycine, serine, and threonine metabolism pathways, were significantly downregulated in ducks infected with pancreatitis-associated DHAV-1 compared with those infected with classical-type DHAV-1. These findings provide information regarding differences in expression levels of metabolism-associated genes between ducks infected with pancreatitis-associated DHAV-1 and those infected with classical-type DHAV-1, indicating that intensive metabolism disorders may contribute to the different phenotypes of DHAV-1-infection.


Asunto(s)
Virus de la Hepatitis del Pato/patogenicidad , Hepatitis Viral Animal/virología , Interacciones Huésped-Patógeno/genética , Infecciones por Picornaviridae/veterinaria , Enfermedades de las Aves de Corral/virología , Aminoácidos/genética , Aminoácidos/metabolismo , Animales , Patos/virología , Expresión Génica , Hepatitis Viral Animal/genética , Hepatitis Viral Animal/metabolismo , Hepatitis Viral Animal/patología , Páncreas/citología , Páncreas/patología , Páncreas/virología , Pancreatitis/patología , Pancreatitis/virología , Infecciones por Picornaviridae/metabolismo , Infecciones por Picornaviridae/patología , Infecciones por Picornaviridae/virología , Enfermedades de las Aves de Corral/genética , Enfermedades de las Aves de Corral/metabolismo , Enfermedades de las Aves de Corral/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ARN
10.
Surg Endosc ; 35(3): 1126-1137, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32140860

RESUMEN

BACKGROUND AND AIMS: Previous studies have suggested that aggressive hydration with lactated ringer solution are one of the protective factors in preventing post endoscopic retrograde cholangiopancreatography (post-ERCP). We conducted a systematic review and meta-analysis to examine the efficacy aggressive hydration with lactated Ringer solution in preventing PEP. METHODS: All published and unpublished articles on aggressive hydration with lactated ringer solution in those underwent ERCP procedure for any reasons were screened for eligibility. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. This paper doesn't need the IRB approval. RESULTS: Seven RCTs met the inclusion criteria. Meta-analysis indicates that aggressive hydration with lactated Ringer solution were associated with lower PEP rate.[odds ratio (OR) 0.29; 95% confidence interval (CI) 0.18-0.48]; lower incidence of hyperamylasemia (OR 0.49; 95% CI 0.35, 0.69) and lower risk of pain (OR 0.28; 95% CI 0.10-0.81). The association between aggressive hydration with lactated Ringer solution and incidence of moderate severity PEP were unclear (OR 0.57; 95% CI 0.22, 1.45). Sensitivity analyses also showed that omitting 1 study from analysis of PEP rate could reduce the heterogeneity but did not change the conclusion of this meta-analysis. A cumulating meta-analysis was performed statistically which showed a stable result of overall incidence of PEP. CONCLUSIONS: Aggressive hydration with lactated Ringer solution was a protective factor in reducing the overall incidence of PEP, hyperamylasemia and risk of abdominal pain.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Pancreatitis/etiología , Pancreatitis/prevención & control , Lactato de Ringer/uso terapéutico , Dolor Abdominal/etiología , Dolor Abdominal/prevención & control , Humanos , Hiperamilasemia/prevención & control , Incidencia , Oportunidad Relativa , Pancreatitis/epidemiología , Sustancias Protectoras/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto
11.
Proc Natl Acad Sci U S A ; 115(21): 5570-5575, 2018 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-29735665

RESUMEN

In mammalian olfactory transduction, odorants activate a cAMP-mediated signaling pathway that leads to the opening of cyclic nucleotide-gated (CNG), nonselective cation channels and depolarization. The Ca2+ influx through open CNG channels triggers an inward current through Ca2+-activated Cl channels (ANO2), which is expected to produce signal amplification. However, a study on an Ano2-/- mouse line reported no elevation in the behavioral threshold of odorant detection compared with wild type (WT). Subsequent studies by others on the same Ano2-/- line, nonetheless, found subtle defects in olfactory behavior and some abnormal axonal projections from the olfactory receptor neurons (ORNs) to the olfactory bulb. As such, the question regarding signal amplification by the Cl current in WT mouse remains unsettled. Recently, with suction-pipette recording, we have successfully separated in frog ORNs the CNG and Cl currents during olfactory transduction and found the Cl current to predominate in the response down to the threshold of action-potential signaling to the brain. For better comparison with the mouse data by others, we have now carried out similar current-separation experiments on mouse ORNs. We found that the Cl current clearly also predominated in the mouse olfactory response at signaling threshold, accounting for ∼80% of the response. In the absence of the Cl current, we expect the threshold stimulus to increase by approximately sevenfold.


Asunto(s)
Anoctaminas/fisiología , Encéfalo/fisiología , Calcio/farmacología , Cloruros/metabolismo , Canales Catiónicos Regulados por Nucleótidos Cíclicos/fisiología , Neuronas Receptoras Olfatorias/fisiología , Animales , Encéfalo/citología , AMP Cíclico/farmacología , Canales Catiónicos Regulados por Nucleótidos Cíclicos/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Ratones , Ratones Noqueados , Neuronas Receptoras Olfatorias/citología , Neuronas Receptoras Olfatorias/efectos de los fármacos , Técnicas de Placa-Clamp , Transducción de Señal/efectos de los fármacos , Olfato/efectos de los fármacos
12.
Int J Mol Sci ; 21(6)2020 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-32235811

RESUMEN

Vitamin D is associated with cardiovascular health through activating the vitamin D receptor that targets genes related to cardiovascular disease (CVD). The human cardiac microvascular endothelial cells (HCMECs) were used to develop mechanically and TGF-ß1-induced fibrosis models, and the rat was used as the isoproterenol (ISO)-induced fibrosis model. The rats were injected with ISO for the first five days, followed by vitamin D injection for the consecutive three weeks before being sacrificed on the fourth week. Results showed that mechanical stretching reduced endothelial cell marker CD31 and VE-cadherin protein expressions, as well as increased α-smooth muscle actin (α-SMA) and fibronectin (FN). The transforming growth factor-ß1 (TGF-ß1) reduced CD31, and increased α-SMA and FN protein expression levels. Vitamin D presence led to higher protein expression of CD31, and lower protein expressions of α-SMA and FN compared to the control in the TGF-ß1-induced fibrosis model. Additionally, protein expression of VE-cadherin was increased and fibroblast-specific protein-1 (FSP1) was decreased after vitamin D treatment in the ISO-induced fibrosis rat. In conclusion, vitamin D slightly inhibited fibrosis development in cell and animal models. Based on this study, the beneficial effect of vitamin D may be insignificant; however, further investigation of vitamin D's effect in the long-term is required in the future.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Endotelio/efectos de los fármacos , Corazón/efectos de los fármacos , Miocardio/patología , Vitamina D/uso terapéutico , Vitaminas/uso terapéutico , Animales , Biomarcadores/análisis , Enfermedades Cardiovasculares/patología , Línea Celular , Modelos Animales de Enfermedad , Endotelio/patología , Fibrosis , Humanos , Masculino , Ratas , Ratas Endogámicas WKY
13.
Cancer Sci ; 110(3): 997-1011, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30618098

RESUMEN

The catalytic subunit p110δ of phosphoinositide 3-kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small-interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of ß-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3ß (GSK-3ß) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD-mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of ß-catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with ß-catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK-3ß/ß-catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.


Asunto(s)
Proliferación Celular/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Neoplasias Colorrectales/genética , Glucógeno Sintasa Quinasa 3 beta/genética , Invasividad Neoplásica/genética , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal/genética , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica/genética , Células HCT116 , Células HT29 , Humanos , Invasividad Neoplásica/patología , ARN Interferente Pequeño/genética , beta Catenina/genética
14.
Proc Natl Acad Sci U S A ; 113(40): 11078-11087, 2016 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-27647918

RESUMEN

Olfactory transduction in vertebrate olfactory receptor neurons (ORNs) involves primarily a cAMP-signaling cascade that leads to the opening of cyclic-nucleotide-gated (CNG), nonselective cation channels. The consequent Ca2+ influx triggers adaptation but also signal amplification, the latter by opening a Ca2+-activated Cl channel (ANO2) to elicit, unusually, an inward Cl current. Hence the olfactory response has inward CNG and Cl components that are in rapid succession and not easily separable. We report here success in quantitatively separating these two currents with respect to amplitude and time course over a broad range of odorant strengths. Importantly, we found that the Cl current is the predominant component throughout the olfactory dose-response relation, down to the threshold of signaling to the brain. This observation is very surprising given a recent report by others that the olfactory-signal amplification effected by the Ca2+-activated Cl current does not influence the behavioral olfactory threshold in mice.


Asunto(s)
Calcio/metabolismo , Canales Catiónicos Regulados por Nucleótidos Cíclicos/metabolismo , Neuronas Receptoras Olfatorias/metabolismo , Olfato/fisiología , Animales , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Cloruros/metabolismo , AMP Cíclico/metabolismo , Canales Catiónicos Regulados por Nucleótidos Cíclicos/genética , Ratones , Odorantes/análisis , Neuronas Receptoras Olfatorias/fisiología , Transducción de Señal , Olfato/genética
15.
Zhongguo Zhong Yao Za Zhi ; 44(20): 4405-4411, 2019 Oct.
Artículo en Zh | MEDLINE | ID: mdl-31872625

RESUMEN

The application of chemical fingerprint to evaluate the quality of traditional Chinese medicine has been widely accepted and used in many countries. However,only by analyzing the type and content of its chemical components to evaluate the quality of traditional Chinese medicines,the gold standard of quality evaluation by evaluating pharmacodynamic effects is ignored. The study of Chinese medicinal spectrum-effect relationships combining the chemical composition with the pharmacodynamic activity of traditional Chinese medicine,which can evaluate the quality of traditional Chinese medicine from more comprehensive and different angles,has been applied in many fields of traditional Chinese medicine research. This paper mainly summarizes the research methods of the Chinese medicinal spectrum-effect relationships and its application in the field of traditional Chinese medicine study,and provides reference for the research,development and application of the Chinese medicinal spectrum-effect relationships.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Registros , Proyectos de Investigación
16.
Virol J ; 15(1): 175, 2018 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-30428893

RESUMEN

BACKGROUND: Few studies have analyzed influenza B virus lineages based on hemagglutinin A (HA) gene sequences in southern China. The present study analyzed the HA gene and the lineages of influenza B virus isolates from Guangzhou during 2016, and compared our results with the WHO-recommended vaccine strain. METHODS: Ninety patients with influenza B were recruited from the First Hospital of Guangzhou Medical University. Throat swab specimens of 72 patients had high viral loads. Among these 72 isolates, the HA1 domain of the HA gene in 43 randomly selected isolates was sequenced using reverse transcription-polymerase chain reaction (RT-PCR), and analyzed using MEGA 5.05. RESULTS: Eight of the 90 patients (8.9%) also had influenza A virus infections. Analysis of the 43 influenza B virus isolates indicated that 34 (79.1%) were from the Victoria lineage and 9 (20.9%) were from the Yamagata lineage. A comparison isolates in our Victoria lineage with the B/Brisbane/60/2008 strain indicated 12 mutation sites in the HA1 domain, 4 of which (I132V, N144D, C196S, and E198D) were in antigenic epitopes. A comparison of isolates in our Yamagata lineage with the B/Phuket/3073/2013 stain indicated 5 mutation sites in the HA1 domain, none of which was in an antigenic epitope. None of the isolates had a mutation in regions of the neuraminidase gene (NA) that are known to confer resistance to NA inhibitors. CONCLUSION: In Guangzhou during 2016, most influenza B virus isolates were from the Victoria lineage, in contrast to the vaccine strain recommended by the WHO for this period.


Asunto(s)
Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Virus de la Influenza B/genética , Mutación , Secuencia de Bases , China , Epítopos/genética , Variación Genética , Humanos , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/virología , Neuraminidasa/genética , Faringe/virología , Filogenia , ARN Viral/genética , Carga Viral , Proteínas Virales/genética
17.
BMC Gastroenterol ; 18(1): 143, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-30285639

RESUMEN

BACKGROUND: Pancreatic pseudocyst (PPC) is a common complication of acute and chronic pancreatitis. To our knowledge no study has systematically reported the risk factors for the formation, intervention and recurrence of PPC. Therefore, the present study aimed to investigate the potential risk factors for PPC, with regards to its formation, intervention and recurrence. METHODS: A database containing 5106 pancreatitis patients was retrospectively analyzed. As a result, a total of 4379 eligible patients were identified and divided into 2 groups: PPC group (group A, n = 759) and non-PPC group (group B, n = 3620). The PPC group was subdivided into 2 groups: intervention PPC (group C, n = 347) and resolution PPC (group D, n = 412). The differences in surgical complication and recurrence rates were compared among 347 PPC patients receiving different interventions, including surgical, endoscopic and percutaneous drainages. Furthermore, group C was subdivided into 2 groups: recurrent PPC (group E, n = 34) and non-recurrent PPC (group F, n = 313). All possible risk factors for PPC formation, intervention and recurrence were determined by multivariate regression analysis. RESULTS: In this study, PPC was developed in 17.3% (759/4379) of pancreatitis patients. The significant risk factors for PPC formation included alcoholic pancreatitis (OR, 6.332; 95% CI, 2.164-11.628; p = 0.031), chronic pancreatitis (CP) (OR, 5.822; 95% CI, 1.921-10.723; p = 0.006) and infected pancreatic necrosis (OR, 4.253; 95% CI, 3.574-7.339; p = 0.021). Meanwhile, the significant risk factors of PPC patients who received intervention were alcoholic pancreatitis (OR, 7.634; 95% CI, 2.125-13.558; p = 0.016), size over 6 cm (OR, 8.834; 95% CI, 2.017-16.649; p = 0.002) and CP (OR, 4.782; 95% CI, 1.897-10.173; p = 0.038). In addition, the recurrence rate in PPC patients treated with percutaneous drainage was found to be the highest (16.3%) among the three intervention groups. Furthermore, percutaneous drainage was the only risk factor of PPC recurrence (OR, 7.812; 95% CI, 3.109-23.072; p = 0.013) identified from this retrospective cohort study. CONCLUSIONS: Alcoholic pancreatitis and CP are the main risk factors for PPC formation and intervention, but not PPC recurrence. A higher recurrence rate is found in PPC patients treated with percutaneous drainage, as compared to endoscopic and surgical interventions.


Asunto(s)
Seudoquiste Pancreático/etiología , Pancreatitis/complicaciones , Enfermedad Aguda , Adulto , Anciano , China , Drenaje , Endoscopía del Sistema Digestivo , Femenino , Humanos , Infecciones/complicaciones , Masculino , Persona de Mediana Edad , Necrosis , Seudoquiste Pancreático/cirugía , Pancreatitis/patología , Pancreatitis Alcohólica/complicaciones , Pancreatitis Crónica/complicaciones , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria
18.
Biomarkers ; 22(3-4): 246-252, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27323660

RESUMEN

OBJECTIVE: To investigate the relationship between plasma myostatin levels and right ventricle (RV) dysfunction (RVD) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: The study recruited 84 patients with AECOPD. Plasma myostatin was analyzed and tricuspid annular plane systolic excursion (TAPSE) < 16 mm was used as the main indicator for RVD. RESULTS: Plasma myostatin levels were significantly higher in 47 patients with RVD than 37 ones without (P < 0.005). Multivariate regression analysis revealed that myostatin levels correlated significantly with TAPSE values and RV myocardial performance index (p < 0.001) among the study patients. CONCLUSION: Plasma myostatin is a potential biomarker for improving diagnosis of RVD in AECOPD.


Asunto(s)
Miostatina/sangre , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Disfunción Ventricular Derecha/diagnóstico , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Análisis Multivariante , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Válvula Tricúspide/fisiopatología , Disfunción Ventricular Derecha/sangre , Disfunción Ventricular Derecha/etiología
19.
Respiration ; 94(4): 366-374, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28738344

RESUMEN

BACKGROUND: It is difficult to differentiate between chronic obstructive pulmonary disease (COPD) and asthma in clinics; therefore, for diagnostic purposes, imaging-based measurements could be beneficial to differentiate between the two diseases. OBJECTIVES: We aim to analyze quantitative measurements of the lung and bronchial parameters that are provided by low-dose computed tomography (CT) to differentiate COPD and asthma from an imaging perspective. MATERIALS AND METHODS: 69 COPD patients, 52 asthma patients, and 20 healthy subjects were recruited to participate in CT imaging and pulmonary function tests (PFTs). Comparative analysis was performed to identify differences between COPD and asthma in CT measurements. PFT measurements enabled validation of the differentiation between COPD and asthma patients. RESULTS: There were significant differences among the COPD, asthma, and healthy control groups. The differences were more significant among the following: inspiratory emphysema index (EI)-950 (%), expiratory lung volume, expiratory mean lung density (MLD), and expiratory EI-950 (%) and EI-850 (%). The COPD group had a significantly higher EI-950 (%) than the asthma group (p = 0.008). There were significant differences among the three groups in lumen area (LA), wall area (WA), total area, and Pi10WA. The asthma group had significantly higher WA%/WV% than both the COPD (p = 0.002) and the control group (p = 0.012). There was high sensitivity in EI-950 (%), EI-850 (%) and expiratory MLD in the parenchyma and high sensitivity in LA and Pi10WA in small airways in the differential diagnosis of COPD and asthma. CONCLUSION: To aid the diagnosis, CT can provide quantitative measurements to differentiate between COPD and asthma patients.


Asunto(s)
Asma/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X , Adulto Joven
20.
Respirology ; 21(8): 1376-1383, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27321896

RESUMEN

While identifying the underlying aetiology is a key part of bronchiectasis management, the prevalence and impact of identifying the aetiologies on clinical management remain unclear. We aimed to determine the etiological spectrum of bronchiectasis, and how often etiological assessment could lead to the changes in patients' management. A comprehensive search was conducted using MEDLINE (via PubMed) and EMBASE for observational studies published before October 2015 reporting aetiologies in adults with bronchiectasis. Of the 8216 citations identified, 56 studies including 8608 adults with bronchiectasis were relevant for this systematic review. The crude prevalence for the identified aetiologies ranged from 18% to 95%, which possibly resulted from the differences in the geographic regions and diagnostic workup. Post-infective (29.9%), immunodeficiency (5%), chronic obstructive pulmonary disease (3.9%), connective tissue disease (3.8%), ciliary dysfunction (2.5%), allergic bronchopulmonary aspergillosis (2.6%) were the most common aetiologies. In 1577 patients (18.3%), identifying the aetiologies led to changes in patient's management. Aetiologies varied considerably among different geographic regions (P < 0.001). Intensive investigations of these aetiologies might help change patient's management and therefore should be incorporated into routine clinical practice.


Asunto(s)
Bronquiectasia , Adulto , Bronquiectasia/diagnóstico , Bronquiectasia/epidemiología , Bronquiectasia/etiología , Técnicas de Diagnóstico del Sistema Respiratorio , Manejo de la Enfermedad , Humanos , Estudios Observacionales como Asunto , Prevalencia
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