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1.
Health Res Policy Syst ; 20(1): 142, 2022 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-36585666

RESUMEN

BACKGROUND: Many countries have an inefficient vaccination system, which hinders global exit from the COVID-19 pandemic. It is vital to summarize COVID-19 vaccination practices in countries with high vaccination coverage and provide implications for other countries. This study aimed to investigate China's COVID-19 vaccination system and to summarize its implementation experience from a health system perspective. METHODS: We conducted key informant interviews in five representative cities of China in late 2021. Guided by the health systems framework proposed by WHO, we developed our interview guidelines which included seven building blocks-leadership and governance, health workforce, vaccination service delivery, vaccination mobilization and communication, financing, access to vaccines, and information systems. Semi-structured interviews and COVID-19 vaccination policy documents were collected and coded using a thematic analysis approach. RESULTS: A total of 61 participants (nine vaccination programme directors of the local Center for Disease Control and Prevention, four government staff and 48 vaccination service workers) were interviewed. We found that China adopted a whole-of-society approach with adequate government engagement and linked health and non-health sectors to promote COVID-19 vaccination. Key measures included the collaboration of multiple systems and departments from a governance perspective, allocating sufficient health workers and resources, large-scale vaccination mobilization and communication, expansion of vaccine financing channels, localized production and digital information systems. With the vaccination system strengthening, the two-doses vaccination coverage reached 89.5% for the total population but relatively lower coverage for older adults as of July 2022. CONCLUSIONS: Our study highlights the importance of a government-led whole-of-society approach to promote mass vaccination. The low vaccination coverage among older adults should be paid the greatest attention to. The experiences and lessons from China may serve as a reference for other countries.


Asunto(s)
COVID-19 , Vacunas , Humanos , Anciano , Vacunas contra la COVID-19 , Pandemias , COVID-19/prevención & control , Vacunación , China
2.
Molecules ; 27(6)2022 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-35335379

RESUMEN

Our team discovered a moderate SphK1 inhibitor, SAMS10 (IC50 = 9.8 µM), which was screened by computer-assisted screening. In this study, we developed a series of novel diaryl derivatives with improved antiproliferative activities by modifying the structure of the lead compound SAMS10. A total of 50 new compounds were synthesized. Among these compounds, the most potent compound, named CHJ04022Rb, has significant anticancer activity in melanoma A375 cell line (IC50 = 2.95 µM). Further underlying mechanism studies indicated that CHJ04022R exhibited inhibition effect against PI3K/NF-κB signaling pathways, inhibited the migration of A375 cells, promoted apoptosis and exerted antiproliferative effect by inducing G2/M phase arrest in A375 cells. Furthermore, acute toxicity experiment indicated CHJ04022R exhibited good safety in vivo. Additionally, it showed a dose-dependent inhibitory effect on the growth of xenograft tumor in nude mice. Therefore, CHJ04022R may be a potential candidate for the treatment of melanoma.


Asunto(s)
Antineoplásicos , Animales , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular , Humanos , Ratones , Ratones Desnudos , Relación Estructura-Actividad
3.
Dig Dis Sci ; 66(12): 4251-4262, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33528684

RESUMEN

BACKGROUND: Whether 7,8-dihydroxyflavone (7,8-DHF), a tyrosine kinase receptor B (TrkB) agonist, modulates colonic smooth muscle motility and/or alleviates constipation has not yet been studied. AIMS: Here, we aimed to determine how 7,8-DHF influences carbachol (CCh)-stimulated contraction of colonic strips and the in vivo effect of 7,8-DHF on constipation. METHODS: Muscle strips were isolated from rat colons for recording contractile tension and performing western blotting. Constipation was induced in rats with loperamide. RESULTS: Although it specifically activated TrkB, 7,8-DHF applied alone neither activated PLCγ1 in the colonic strips nor induced colonic strip contraction. However, 7,8-DHF enhanced CCh-stimulated PLCγ1 activation and strip contraction. The PLCγ1 antagonist U73122 suppressed both CCh-stimulated and 7,8-DHF-enhanced/CCh-stimulated contraction. While clarifying the underlying mechanism, we revealed that 7,8-DHF augmented muscarinic M3 receptor expression in the colonic strips. The M3-selective antagonist tarafenacin specifically inhibited the 7,8-DHF-enhanced/CCh-stimulated contraction of the colonic strips. Since 7,8-DHF increased Akt phosphorylation, and LY294002 (an antagonist of PI3K upstream of Akt) dramatically inhibited both 7,8-DHF-augmented M3 expression and 7,8-DHF-enhanced/CCh-stimulated contractions, we assumed that 7,8-DHF/TrkB/Akt was associated with the modulation of M3 expression in the colonic strips. ANA-12, a specific TrkB antagonist, not only inhibited TrkB activation by 7,8-DHF but also suppressed 7,8-DHF-enhanced cholinergic contraction, 7,8-DHF/CCh-mediated activation of PLCγ1/Akt, and M3 overexpression in colonic strips. In vivo 7,8-DHF, also by promoting intestinal motility and M3 expression, significantly alleviated loperamide-induced functional constipation in rats. CONCLUSIONS: Our results suggest that 7,8-DHF regulates colonic motility possibly via a TrkB/Akt/M3 pathway and may be applicable for alleviating constipation.


Asunto(s)
Colon/efectos de los fármacos , Estreñimiento/tratamiento farmacológico , Defecación/efectos de los fármacos , Flavonas/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Agonistas Muscarínicos/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Animales , Colon/metabolismo , Colon/fisiopatología , Estreñimiento/inducido químicamente , Estreñimiento/fisiopatología , Modelos Animales de Enfermedad , Técnicas In Vitro , Loperamida , Músculo Liso/metabolismo , Músculo Liso/fisiopatología , Fosfolipasa C gamma/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor Muscarínico M3/agonistas , Receptor Muscarínico M3/metabolismo , Receptor trkB/agonistas , Receptor trkB/metabolismo , Transducción de Señal
4.
J Med Internet Res ; 23(4): e26518, 2021 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-33750739

RESUMEN

BACKGROUND: COVID-19 cases resurged worldwide in the second half of 2020. Not much is known about the changes in public responses to containment measures from the initial outbreak to resurgence. Monitoring public responses is crucial to inform policy measures to prepare for COVID-19 resurgence. OBJECTIVE: This study aimed to assess and compare public responses to containment measures during the initial outbreak and resurgence of COVID-19 in China. METHODS: We curated all COVID-19-related posts from Sina Weibo (China's version of Twitter) during the initial outbreak and resurgence of COVID-19 in Beijing, China. With a Python script, we constructed subsets of Weibo posts focusing on 3 containment measures: lockdown, the test-trace-isolate strategy, and suspension of gatherings. The Baidu open-source sentiment analysis model and latent Dirichlet allocation topic modeling, a widely used machine learning algorithm, were used to assess public engagement, sentiments, and frequently discussed topics on each containment measure. RESULTS: A total of 8,985,221 Weibo posts were curated. In China, the containment measures evolved from a complete lockdown for the general population during the initial outbreak to a more targeted response strategy for high-risk populations during COVID-19 resurgence. Between the initial outbreak and resurgence, the average daily proportion of Weibo posts with negative sentiments decreased from 57% to 47% for the lockdown, 56% to 51% for the test-trace-isolate strategy, and 55% to 48% for the suspension of gatherings. Among the top 3 frequently discussed topics on lockdown measures, discussions on containment measures accounted for approximately 32% in both periods, but those on the second-most frequently discussed topic shifted from the expression of negative emotions (11%) to its impacts on daily life or work (26%). The public expressed a high level of panic (21%) during the initial outbreak but almost no panic (1%) during resurgence. The more targeted test-trace-isolate measure received the most support (60%) among all 3 containment measures in the initial outbreak, and its support rate approached 90% during resurgence. CONCLUSIONS: Compared to the initial outbreak, the public expressed less engagement and less negative sentiments on containment measures and were more supportive toward containment measures during resurgence. Targeted test-trace-isolate strategies were more acceptable to the public. Our results indicate that when COVID-19 resurges, more targeted test-trace-isolate strategies for high-risk populations should be promoted to balance pandemic control and its impact on daily life and the economy.


Asunto(s)
COVID-19/epidemiología , Control de Enfermedades Transmisibles/métodos , Opinión Pública , Medios de Comunicación Sociales/estadística & datos numéricos , COVID-19/psicología , China/epidemiología , Brotes de Enfermedades , Humanos , Pandemias , SARS-CoV-2/aislamiento & purificación
5.
BMC Vet Res ; 16(1): 317, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32859190

RESUMEN

BACKGROUND: The gram-negative Coxiella burnetii bacterium is the pathogen that causes Q fever. The bacterium is transmitted to animals via ticks, and manure, air, dead infected animals, etc. and can cause infection in domestic animals, wild animals, and humans. Xinjiang, the provincial-level administrative region with the largest land area in China, has many endemic tick species. The infection rate of C. burnetii in ticks in Xinjiang border areas has not been studied in detail. RESULTS: For the current study, 1507 ticks were collected from livestock at 22 sampling sites in ten border regions of the Xinjiang Uygur Autonomous region from 2018 to 2019. C. burnetii was detected in 205/348 (58.91%) Dermacentor nuttalli; in 110/146 (75.34%) D. pavlovskyi; in 66/80 (82.50%) D. silvarum; in 15/32 (46.90%) D. niveus; in 28/132 (21.21%) Hyalomma rufipes; in 24/25 (96.00%) H. anatolicum; in 219/312 (70.19%) H. asiaticum; in 252/338 (74.56%) Rhipicephalus sanguineus; and in 54/92 (58.70%) Haemaphysalis punctata. Among these samples, C. burnetii was detected in D. pavlovskyi for the first time. The infection rate of Rhipicephalus was 74.56% (252/338), which was the highest among the four tick genera sampled, whereas the infection rate of H. anatolicum was 96% (24/25), which was the highest among the nine tick species sampled. A sequence analysis indicated that 63 16S rRNA sequences could be found in four newly established genotypes: MT498683.1 (n = 18), MT498684.1 (n = 33), MT498685.1 (n = 6), and MT498686.1 (n = 6). CONCLUSIONS: This study indicates that MT498684.1 might represent the main C. burnetii genotype in the ticks in Xinjiang because it was detected in eight of the tick species studied. The high infection rate of C. burnetii detected in the ticks found in domestic animals may indicate a high likelihood of Q fever infection in both domestic animals and humans.


Asunto(s)
Coxiella burnetii/aislamiento & purificación , Ixodidae/microbiología , Fiebre Q/epidemiología , Animales , Vectores Arácnidos/microbiología , China/epidemiología , Coxiella burnetii/genética , Ganado/parasitología , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN
6.
Clin Exp Pharmacol Physiol ; 47(1): 67-75, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31313342

RESUMEN

It is known that 7,8-dihydroxyflavone (7,8-DHF), a synthetic agonist specific for TrkB, promotes intestinal cholinergic contraction. However, after intestinal ischaemia-reperfusion (IR) injury, how 7,8-DHF affects intestinal contractile dynamics is unknown. In this study, an IR injury model was prepared with rats subjected to 45 minutes clamping of the superior mesenteric artery. The IR injury decreased postoperative food intake and body weight, delayed defecation time, lowered intestinal propulsive rate and decreased cholinergic contraction of jejunal muscle strips, indicating the occurrence of injured jejunal contraction after IR. Feeding rats with 7,8-DHF improved these intestinal activities injured by IR, which exhibited the in vivo effect of 7,8-DHF. To explore its molecular mechanism, the expression and phosphorylation of TrkB, PLC γ1, Akt, and ERK1/2 in the jejunal strips were examined with western blots. The IR injury significantly decreased the expression and phosphorylation levels of all factors studied here. However, 7,8-DHF feeding specifically enhanced the phosphorylation of TrkB, PLC γ1 and Akt factors in both sham- and IR-operated rats, indicating that 7,8-DHF may have activated TrkB which then activated its downstream PLC γ1 and Akt. Finally, we found that 7,8-DHF augmented cholinergic receptor M3 expression somehow. These results imply a possibility that 7,8-DHF might be capable of alleviating the jejunal contractile damage caused by IR through activation of TrkB and augmentation of M3 expression.


Asunto(s)
Flavonas/farmacología , Yeyuno/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Animales , Yeyuno/metabolismo , Masculino , Contracción Muscular/efectos de los fármacos , Fosforilación/efectos de los fármacos , Ratas , Daño por Reperfusión/metabolismo , Transducción de Señal/efectos de los fármacos
7.
Exp Parasitol ; 217: 107955, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32649953

RESUMEN

Nicotiana tabacum, Stemona japonica, and Cnidium monnieri are common plants that are widely used for their anti-parasitic properties. The purpose of this study was to evaluate the acaricidal activity of extracts from these plants against the brown dog tick, Rhipicephalus sanguineus. A composition analysis of crude extracts by GC-MS was conducted to discover compounds with acaricidal effects. The toxicity of extraction against the engorged nymphs of R. sanguineus was evaluated by an immersion test. The results showed that the crude extracts of S. japonica and C. monnieri in varying ratios, concentrations, and from different extraction methods, had a killing effect on R. sanguineus. Lethality reached 76.67% ± 0.04410 when using a 1:1 extract of S. japonica:C. monnieri in 75% ethanol with ultrasonic extraction; the crude extract was determined at a concentration of 0.5 g/mL. GC-MS results showed that osthole and 5-hydroxymethylfurfural (5-HMF) are the main components of the extract. These results suggested that ultrasound-assisted extraction (UAE) extracts contained acaricidal components acting against R. sanguineus, which may result in the development of effective extracts of S. japonica and C. monnieri as a source of low-toxicity, plant-based, natural acaricidal drugs.


Asunto(s)
Cnidium/química , Extractos Vegetales/farmacología , Rhipicephalus sanguineus/efectos de los fármacos , Stemonaceae/química , Control de Ácaros y Garrapatas/métodos , Animales , Bioensayo , Cumarinas/análisis , Cumarinas/farmacología , Furaldehído/análogos & derivados , Furaldehído/análisis , Furaldehído/farmacología , Cromatografía de Gases y Espectrometría de Masas , Muda/efectos de los fármacos , Ninfa/efectos de los fármacos , Extractos Vegetales/química , Conejos , Nicotiana/química
8.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1863(3): 299-312, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29277655

RESUMEN

The TMEM16A-mediated Ca2+-activated Cl- current drives several important physiological functions. Membrane lipids regulate ion channels and transporters but their influence on members of the TMEM16 family is poorly understood. Here we have studied the regulation of TMEM16A by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), cholesterol, and fatty acids using patch clamp, biochemistry and fluorescence microscopy. We found that depletion of membrane PI(4,5)P2 causes a decline in TMEM16A current that is independent of cytoskeleton, but is partially prevented by removing intracellular Ca2+. On the other hand, supplying PI(4,5)P2 to inside-out patches attenuated channel rundown and/or partially rescued activity after channel rundown. Also, depletion (with methyl-ß-cyclodextrin M-ßCD) or restoration (with M-ßCD+cholesterol) of membrane cholesterol slows down the current decay observed after reduction of PI(4,5)P2. Neither depletion nor restoration of cholesterol change PI(4,5)P2 content. However, M-ßCD alone transiently increases TMEM16A activity and dampens rundown whereas M-ßCD+cholesterol increases channel rundown. Thus, PI(4,5)P2 is required for TMEM16A function while cholesterol directly and indirectly via a PI(4,5)P2-independent mechanism regulate channel function. Stearic, arachidonic, oleic, docosahexaenoic, and eicosapentaenoic fatty acids as well as methyl stearate inhibit TMEM16A in a dose- and voltage-dependent manner. Phosphatidylserine, a phospholipid whose hydrocarbon tails contain stearic and oleic acids also inhibits TMEM16A. Finally, we show that TMEM16A remains in the plasma membrane after treatment with M-ßCD, M-ßCD+cholesterol, oleic, or docosahexaenoic acids. Thus, we propose that lipids and fatty acids regulate TMEM16A channels through a membrane-delimited protein-lipid interaction.


Asunto(s)
Anoctamina-1/metabolismo , Señalización del Calcio/fisiología , Membrana Celular/metabolismo , Colesterol/metabolismo , Ácidos Grasos/metabolismo , Proteínas de Neoplasias/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Anoctamina-1/genética , Calcio/metabolismo , Membrana Celular/genética , Colesterol/genética , Ácidos Grasos/genética , Células HEK293 , Humanos , Proteínas de Neoplasias/genética , Fosfatidilinositol 4,5-Difosfato/genética
9.
Clin Exp Pharmacol Physiol ; 45(11): 1170-1180, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29927500

RESUMEN

Although 7,8-dihydroxyflavone (7,8-DHF), a synthetic agonist specific for tyrosine kinase receptor B (TrkB), has been reported to promote intestinal dynamics, its effect on gastric dynamics has not been studied as yet. In this study, we explored how 7,8-DHF affected the carbachol (CCh)-induced contraction of rat gastric muscle by way of measuring the contractile tension of muscular strips. We found that although 7,8-DHF did not directly cause contraction of gastric muscle, it enhanced CCh-induced, instead of substance P- or high K+ -induced, contraction. The enhancing role of 7,8-DHF was partially blocked by ANA-12, a blocker specific for TrkB the activation of which in the gastric strips was evidenced by its phosphorylation. Although 7,8-DHF alone did not activate : phospholipase C (PLC)-γ in gastric muscle, CCh did, and importantly, the combined treatment with CCh + 7,8-DHF activated more PLC-γ. U73122, an antagonist to PLC-γ blocked both the CCh-induced and the 7,8-DHF-enhanced/CCh-induced contraction by ~30%. To pursue how 7,8-DHF could augment CCh-activated PLC-γ phosphorylation, we first examined the effect of 7,8-DHF on the expression of muscarinic receptors in gastric muscle and found that 7,8-DHF specifically increased M3 but not M2 receptor expression possibly through TrkB/Akt (protein kinase B) pathway because the Akt antagonist, LY294002 significantly suppressed the 7,8-DHF-augmemted M3 expression and completely blocked the 7,8-DHF-enhanced cholinergic contraction. Supporting the result, Akt phosphorylation in the gastric muscle was enhanced by 7,8-DHF treatment. The in vivo experiment showed that orally fed 7,8-DHF increased gastric emptying rate. The results imply a possibility that 7,8-DHF may be developed into a drug in the future for enhancing gastric dynamics.


Asunto(s)
Acetilcolina/metabolismo , Flavonas/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Receptor Muscarínico M3/metabolismo , Estómago/fisiología , Animales , Vaciamiento Gástrico/efectos de los fármacos , Masculino , Músculo Liso/fisiología , Ratas , Receptor trkB/metabolismo , Estómago/efectos de los fármacos
10.
Environ Monit Assess ; 189(8): 390, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28699119

RESUMEN

Atmospheric particulate matter (PM) from multinatural and anthropogenic sources poses serious risk to human health and contaminates soil and water resources as it settles back to ground environment and ecosystem. In this study, dust deposition flux (DDF), pollution load index (PLI) of heavy metals, enrichment factor (EF), and settling flux (SF) of eighteen chemical elements were investigated in comparison with crustal composition to assess the influence of anthropogenic emission on PM in major northern Chinese cities. The annual DDF in Lanzhou, Huhhot, Beijing, Zhengzhou, and Harbin was 134.7, 240.6, 103.7, 124.7, and 196.7 g m-2, respectively. The annual EF of Zn in Harbin, Cd in Lanzhou, and Cd in Beijing was 736.4, 248.6, and 166.3, respectively. Most of the inspected elements were enriched during winter in Lanzhou. Annual PLI showed that deposited dust in Beijing had the highest concentration of heavy metals. Seasonal PLI exhibited obvious changes in different cities. The annual SF of crustal elements was 1-5 orders higher than that of heavy metals. The highest annual SF of elements was identified mainly in Lanzhou and Huhhot. Sulfur, cadmium, copper, lead, and zinc in the dustfall of most urban areas were from human activities. Fossil fuel burning, metal smelting, mining, construction, and vehicle exhaust are the major sources of enriched elements in dustfall in urban areas of northern China. Toxic pollutants with dustfall are widespread and persistent, which deserves public concern in future sustainable development.


Asunto(s)
Contaminantes Atmosféricos/análisis , Polvo/análisis , Monitoreo del Ambiente , Contaminación del Aire/estadística & datos numéricos , Atmósfera/química , Beijing , China , Ciudades , Cobre , Humanos , Metales Pesados/análisis , Material Particulado/análisis , Estaciones del Año , Suelo/química , Emisiones de Vehículos/análisis
11.
J Cell Mol Med ; 20(3): 450-8, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26648569

RESUMEN

Arpin (Arp2/3 complex inhibitor), a novel protein found in 2013, plays a pivotal role in cell motility and migration. However, the precise role of Arpin in cancer is unclear. This study investigated the expression of Arpin in breast cancer and evaluated its correlation with the characteristics of clinical pathology and prognosis of breast cancer patients. Immunohistochemistry (IHC) for Arpin protein was performed on formalin-fixed, paraffin-embedded 176 breast cancer tissues and 43 normal breast tissues while qRT-PCR for Arpin mRNA with 104 paired tumour and paratumoural tissues from breast cancer patients respectively. The association of Arpin expression with clinical pathological features and survival was assessed in a retrospective cohort analysis of patients. The results showed that the expression of Arpin protein in cancer tissues was lower compared to that in normal breast and the expression of Arpin mRNA was also lower in cancer tissues than that in the matched paratumoural tissues. Among the 176 breast cancer patients, the lower expression of Arpin was significantly associated with advanced tumour, nodes and metastasis system stage, and the reduced Arpin expression was strongly associated with axillary lymph node metastasis using univariate and multivariate logistic regression analysis [odds ratio: 3.242; 95% confidence interval (CI): 1.526, 6.888; P < 0.05]. Furthermore, Arpin expression was an independent risk factor for recurrence-free survival (HR: 0.373; 95% CI: 0.171, 0.813; P < 0.05). As Arpin expression was first examined in human breast cancer tissues with qRT-PCR and IHC, our results suggest that Arpin downregulation may contribute to the initiation and development of breast cancer metastasis. Therefore, as a potential predictive marker, Arpin deserves future studies.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Proteínas Portadoras/metabolismo , Ganglios Linfáticos/metabolismo , Axila , Biomarcadores de Tumor/genética , Neoplasias de la Mama/mortalidad , Proteínas Portadoras/genética , Supervivencia sin Enfermedad , Femenino , Expresión Génica , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Metástasis Linfática , Glándulas Mamarias Humanas/metabolismo , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo
12.
J Mol Cell Cardiol ; 82: 22-32, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25739000

RESUMEN

Calcium-activated chloride channels (CaCCs) have been implicated in hypertension; however, the mechanism underlying their involvement is unknown. The aim of this study was to determine whether the CaCC ANO1 is involved in the pathogenesis of spontaneous hypertension. Arterial ANO1 expression and the effects on blood pressure (BP) of inhibiting ANO1 with an ANO1 inhibitor, T16(Ainh)-A01, and in vivo RNAi, were examined in spontaneously hypertensive rats (SHRs). Knockdown of ANO1 by siRNA prevented hypertensive development, and attenuation of ANO1 channel activity reduced BP in SHRs. Angiotensin II upregulated ANO1 expression in primary cultures of vascular smooth muscle cells (VSMCs). The protein level and activity of cellular ANO1 positively correlated with VSMC proliferation. Our data indicate an important role of increased ANO1 expression and activity in inducing hypertension in SHRs. It may mediate angiotensin II-dependent vascular remodeling. Our results increase the mechanistic understanding of hypertension and suggest ANO1 as a possible therapeutic target for hypertension.


Asunto(s)
Canales de Cloruro/genética , Expresión Génica , Ratas Endogámicas SHR/genética , Angiotensina II/farmacología , Animales , Anoctamina-1 , Arterias/efectos de los fármacos , Arterias/metabolismo , Presión Sanguínea/efectos de los fármacos , Proliferación Celular , Canales de Cloruro/antagonistas & inhibidores , Canales de Cloruro/metabolismo , Modelos Animales de Enfermedad , Acoplamiento Excitación-Contracción/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Glicosilación , Masculino , Modelos Biológicos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Ratas , Ratas Endogámicas SHR/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo , Transducción de Señal/efectos de los fármacos
13.
Circ Res ; 110(7): 990-9, 2012 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-22394518

RESUMEN

RATIONALE: Ca2+ -activated Cl channels play pivotal roles in the cardiovascular system. They regulate vascular smooth muscle tone and participate in cardiac action potential repolarization in some species. Ca2+ -activated Cl channels were recently discovered to be encoded by members of the anoctamin (Ano, also called Tmem16) superfamily, but the mechanisms of Ano1 gating by Ca2+ remain enigmatic. OBJECTIVE: The objective was to identify regions of Ano1 involved in channel gating by Ca2+. METHODS AND RESULTS: The Ca2+ sensitivity of Ano1 was estimated from rates of current activation, and deactivation in excised patches rapidly switched between zero and high Ca2+ on the cytoplasmic side. Mutation of glutamates E702 and E705 dramatically altered Ca2+ sensitivity. E702 and E705 are predicted to be in an extracellular loop, but antigenic epitopes introduced into this loop are not accessible to extracellular antibodies, suggesting this loop is intracellular. Cytoplasmically applied membrane-impermeant sulfhydryl reagents alter the Ca2+ sensitivity of Ano1 E702C and E705C as expected if E702 and E705 are intracellular. Substituted cysteine accessibility mutagenesis of the putative re-entrant loop suggests that E702 and E705 are located adjacent to the Cl conduction pathway. CONCLUSIONS: We propose an alternative model of Ano1 topology based on mutagenesis, epitope accessibility, and cysteine-scanning accessibility. These data contradict the popular re-entrant loop model by showing that the putative fourth extracellular loop (ECL 4) is intracellular and may contain a Ca2+ binding site. These studies provide new perspectives on regulation of Ano1 by Ca2+.


Asunto(s)
Calcio/fisiología , Canales de Cloruro/fisiología , Activación del Canal Iónico/fisiología , Riñón/fisiología , Animales , Anoctamina-1 , Canales de Cloruro/análisis , Canales de Cloruro/genética , Cisteína/análisis , Epítopos/genética , Glutamatos/análisis , Células HEK293 , Humanos , Riñón/citología , Mutación/genética , Técnicas de Placa-Clamp , Transducción de Señal/fisiología , Transfección
14.
China CDC Wkly ; 6(15): 318-323, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38736995

RESUMEN

What is already known about this topic?: The significant disparities in global coronavirus disease 2019 (COVID-19) vaccine coverage hamper the pace of epidemic control. There is a need to better understand the factors contributing to disparities in COVID-19 vaccination rates across countries. What is added by this report?: This report revealed significant associations between vaccination coverage and various country-level indicators. Better pandemic preparedness, higher levels of trust, and a lower proportion of young population aged 0-14 were strongly correlated with higher COVID-19 vaccination coverage. What are the implications for public health practices?: Our findings emphasize the need for enhanced pandemic preparedness and governance, coupled with building trust in government and healthcare systems. It also needs to address the hesitancy of vaccinating children and adolescents aged 0-14 as the vaccination campaign progresses.

15.
J Membr Biol ; 246(2): 177-82, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23124946

RESUMEN

Bestrophin 3 (Best3), a member of the bestrophin Cl(-) channel family, is a candidate of cGMP-sensitive, Ca(2+)-activated Cl(-) channel in vascular smooth muscle cells. The Best3 channel was recently found to play an important role in vasomotion. However, the mechanism for its activation has not been clarified. In previous studies, we found that a Best3 C-terminal sequence (amino acids 353-404) was associated with the cellular membrane. The sequence includes an autoinhibitory domain ((356)IPSFLGS(362)) and a downstream basic residue domain (amino acids 384-397). In this study, we found that the sequence (368-383) between the two domains is actually a determinant for Best3 C-terminal membrane associability. Deletion of the sequence almost abolished the membrane association but did not activate the Best3 channel. Treatment of Best3-expressing HEK293 cells with the PI3Kα inhibitor IV (a Best3 activator) could not abolish but weakened the Best3 membrane association. The result supports the assumption that the positively charged basic residues in the Best3 C terminus are likely associated with the membranous negatively charged phospholipids, which plays a role in the regulation of Best3 activation. But the relationship between membrane associability and Best3 activation seems more complicated than expected.


Asunto(s)
Canales de Cloruro/metabolismo , Proteínas Musculares/metabolismo , Bestrofinas , Línea Celular , Canales de Cloruro/genética , Electrofisiología , Humanos , Proteínas Musculares/genética , Solubilidad
16.
Am J Physiol Cell Physiol ; 302(3): C482-93, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-22075693

RESUMEN

Ca(2+)-activated Cl(-) channels (CaCCs) participate in numerous physiological functions such as neuronal excitability, sensory transduction, and transepithelial fluid transport. Recently, it was shown that heterologously expressed anoctamins ANO1 and ANO2 generate currents that resemble native CaCCs. The anoctamin family (also called Tmem16) consists of 10 members, but it is not known whether all members of the family are CaCCs. Expression of ANOs 3-7 in HEK293 cells did not generate Cl(-) currents activated by intracellular Ca(2+), as determined by whole cell patch clamp electrophysiology. With the use of confocal imaging, only ANO1 and ANO2 traffic to the plasma membrane when expressed heterologously. Furthermore, endogenously expressed ANO7 in the human prostate is predominantly intracellular. We took a chimeric approach to identify regions critical for channel trafficking and function. However, none of the chimeras of ANO1 and ANO5/7 that we made trafficked to the plasma membrane. Our results suggest that intracellular anoctamins may be endoplasmic reticulum proteins, although it remains unknown whether these family members are CaCCs. Determining the role of anoctamin family members in ion transport will be critical to understanding their functions in physiology and disease.


Asunto(s)
Canales de Cloruro/metabolismo , Retículo Endoplásmico/fisiología , Proteínas de la Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Animales , Anoctamina-1 , Anoctaminas , Transporte Biológico/fisiología , Células COS , Línea Celular , Membrana Celular/metabolismo , Quimera , Canales de Cloruro/biosíntesis , Canales de Cloruro/genética , Chlorocebus aethiops , Células HEK293 , Humanos , Masculino , Proteínas de la Membrana/genética , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Técnicas de Placa-Clamp , Próstata/metabolismo , Proteínas Recombinantes de Fusión/metabolismo
17.
Commun Med (Lond) ; 2: 113, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36101704

RESUMEN

Background: The COVID-19 pandemic exit strategies depend on widespread acceptance of COVID-19 vaccines. We aim to estimate the global acceptance and uptake of COVID-19 vaccination, and their variations across populations, countries, time, and sociodemographic subgroups. Methods: We searched four peer-reviewed databases (PubMed, EMBASE, Web of Science, and EBSCO) for papers published in English from December 1, 2019 to February 27, 2022. This review included original survey studies which investigated acceptance or uptake of COVID-19 vaccination, and study quality was assessed using the Appraisal tool for Cross-Sectional Studies. We reported the pooled acceptance or uptake rates and 95% confidence interval (CI) using meta-analysis with a random-effects model. Results: Among 15690 identified studies, 519 articles with 7,990,117 participants are eligible for meta-analysis. The global acceptance and uptake rate of COVID-19 vaccination are 67.8% (95% CI: 67.1-68.6) and 42.3% (95% CI: 38.2-46.5), respectively. Among all population groups, pregnant/breastfeeding women have the lowest acceptance (54.0%, 46.3-61.7) and uptake rates (7.3%, 1.7-12.8). The acceptance rate varies across countries, ranging from 35.9% (34.3-37.5) to 86.9% (81.4-92.5) for adults, and the lowest acceptance is found in Russia, Ghana, Jordan, Lebanon, and Syria (below 50%). The acceptance rate declines globally in 2020, then recovers from December 2020 to June 2021, and further drops in late 2021. Females, those aged < 60 years old, Black individuals, those with lower education or income have the lower acceptance than their counterparts. There are large gaps (around 20%) between acceptance and uptake rates for populations with low education or income. Conclusion: COVID-19 vaccine acceptance needs to be improved globally. Continuous vaccine acceptance monitoring is necessary to inform public health decision making.

19.
Vaccines (Basel) ; 9(11)2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34835258

RESUMEN

BACKGROUND: Following the COVID-19 pandemic, global interest in influenza vaccines and pneumonia vaccines has increased significantly. We aimed to examine public interest in and actual market circulation of influenza and pneumonia vaccines before and after the initial outbreak of COVID-19 and estimate the coverage and determinants of influenza and pneumonia vaccination uptake following the COVID-19 pandemic. METHODS: We obtained search volume data for vaccines using the Baidu search index and collected the numbers of vaccines issued from the National Institutes for Food and Drug Control. We also conducted a cross-sectional survey among 3346 adult residents to evaluate the coverage and determinants of influenza and pneumonia vaccination uptake in the Yangtze River delta, China, from 29 January to 4 February 2021. RESULTS: Public searches and the number of vaccines issued for the influenza vaccines and pneumonia vaccines obviously increased after the initial outbreak of COVID-19. In the total sample, 12.5% were vaccinated against influenza, and 21.5% had at least one family member vaccinated against pneumonia. A minority of participants perceived that they were highly or very highly susceptible to influenza (15.9%) and COVID-19 (6.7%). A range of socio-economic factors and perceived susceptibility to COVID-19 were associated with influenza and pneumonia vaccination uptake. CONCLUSIONS: Public interest in and issued volumes of influenza and pneumonia vaccines increased nationally following the COVID-19 pandemic. Perceptions of high susceptibility to COVID-19 were associated with the uptake of the influenza and pneumonia vaccines. Targeted interventions were needed to improve vaccination coverage.

20.
Front Vet Sci ; 8: 675457, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34239911

RESUMEN

Bartonella are gram-negative intracellular bacteria; certain species of Bartonella can cause diseases in mammals and humans. Ticks play a major role in the transmission of Bartonella. Xinjiang is the largest province in China according to land area and has one-third of the tick species in China; the infection rate of Bartonella in ticks in the Xinjiang border areas has not been studied in detail. Therefore, this study investigated tick infections by Bartonella in Xinjiang border areas, and the purpose of the study was to fill in gaps in information regarding the genetic diversity of tick infections by Bartonella in Xinjiang. We tested 1,549 tick samples from domestic animals (sheep and cattle) for Bartonella using ribC-PCR. Positive samples from the ribC-PCR assay for Bartonella spp. were further subjected to PCR assays targeting the ITS, rpoB and gltA genes followed by phylogenetic analyses. Bartonella DNA was detected in 2.19% (34/1,549) of tick samples, and the ITS, rpoB and gltA genes of ribC gene-positive samples were amplified to identify nine samples of Bartonella melophagi. In this study, molecular analysis was used to assess the presence and genetic diversity of B. melophagi in ticks collected from sheep and cattle from Xinjiang, China. This study provides new information on the presence and identity of B. melophagi in ticks from sheep and cattle.

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