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1.
Proc Natl Acad Sci U S A ; 120(9): e2219952120, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36802416

RESUMO

Social behavior starts with dynamic approach prior to the final consummation. The flexible processes ensure mutual feedback across social brains to transmit signals. However, how the brain responds to the initial social stimuli precisely to elicit timed behaviors remains elusive. Here, by using real-time calcium recording, we identify the abnormalities of EphB2 mutant with autism-associated Q858X mutation in processing long-range approach and accurate activity of prefrontal cortex (dmPFC). The EphB2-dependent dmPFC activation precedes the behavioral onset and is actively associated with subsequent social action with the partner. Furthermore, we find that partner dmPFC activity is responsive coordinately to the approaching WT mouse rather than Q858X mutant mouse, and the social defects caused by the mutation are rescued by synchro-optogenetic activation in dmPFC of paired social partners. These results thus reveal that EphB2 sustains neuronal activation in the dmPFC that is essential for the proactive modulation of social approach to initial social interaction.


Assuntos
Córtex Pré-Frontal , Receptor EphB2 , Comportamento Social , Animais , Camundongos , Encéfalo , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Receptor EphB2/genética , Receptor EphB2/fisiologia
2.
Crit Rev Eukaryot Gene Expr ; 34(3): 73-82, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305290

RESUMO

Gestational diabetes mellitus (GDM) complicated with preeclampsia can lead to polyhydramnios, ketosis. Herein, we explored that CPEB4 in cancer progression of preeclampsia and its underlying mechanism. All the serum samples were collected from patients with preeclampsia. These was the induction of CPEB4 in patients with preeclampsia. The serum of CPEB4 mRNA expression was positive correlation with Proteinuria, systolic blood pressure and diastolic blood pressure in patients. The serum of CPEB4 mRNA expression was also negative correlation with body weight of infant in patients. The serum of CPEB4 mRNA expression also was negative correlation with GPX4 level and GSH activity level in patients. The serum of CPEB4 mRNA expression was positive correlation with iron content in patients. CPEB4 gene inhibited trophoblast cell proliferation. CPEB4 gene promoted trophoblast cell ferroptosis by mitochondrial damage. CPEB4 gene induced PFKFB3 expression by the inhibition of PFKFB3 Ubiquitination. PFKFB3 inhibitor reduced the effects of CPEB4 on cell proliferation and ferroptosis of trophoblast cell. Taken together, the CPEB4 promoted trophoblast cell ferroptosis through mitochondrial damage by the induction of PFKFB3 expression, CPEB4 as an represents a potential therapeutic strategy for the treatment of preeclampsia or various types of GDM.


Assuntos
Diabetes Gestacional , Ferroptose , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Regulação para Baixo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Ferroptose/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , RNA Mensageiro , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo
3.
Epidemiol Infect ; 152: e31, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329110

RESUMO

Wastewater-based epidemiology (WBE) has proven to be a powerful tool for the population-level monitoring of pathogens, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For assessment, several wastewater sampling regimes and methods of viral concentration have been investigated, mainly targeting SARS-CoV-2. However, the use of passive samplers in near-source environments for a range of viruses in wastewater is still under-investigated. To address this, near-source passive samples were taken at four locations targeting student hall of residence. These were chosen as an exemplar due to their high population density and perceived risk of disease transmission. Viruses investigated were SARS-CoV-2 and its variants of concern (VOCs), influenza viruses, and enteroviruses. Sampling was conducted either in the morning, where passive samplers were in place overnight (17 h) and during the day, with exposure of 7 h. We demonstrated the usefulness of near-source passive sampling for the detection of VOCs using quantitative polymerase chain reaction (qPCR) and next-generation sequencing (NGS). Furthermore, several outbreaks of influenza A and sporadic outbreaks of enteroviruses (some associated with enterovirus D68 and coxsackieviruses) were identified among the resident student population, providing evidence of the usefulness of near-source, in-sewer sampling for monitoring the health of high population density communities.


Assuntos
Infecções por Enterovirus , Águas Residuárias , Humanos , Universidades , Surtos de Doenças , Antígenos Virais , SARS-CoV-2 , RNA Viral
4.
J Public Health (Oxf) ; 46(1): 144-150, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-37934971

RESUMO

BACKGROUND: The population of unpaid carers in Wales increased to record. There is no systematic approach to record unpaid caring status, resulting in limited quantitative evidence on unpaid carers' health. The aim of this study is to: (i) create an e-cohort of unpaid carers by linking routinely collected health and administrative datasets in Wales, UK. (ii) investigate whether long-term health conditions and multimorbidity are more prevalent amongst unpaid carers than non-carers. METHODS: Unpaid carers were identified by linking primary care dataset, National Survey for Wales data with demographic characteristics in the Secure Anonymise Information Linkage Databank. The clinical codes identified in Cambridge Multimorbidity Score were used to explore the prevalence of long-term health conditions. RESULTS: A total of 91 220 unpaid carers in Wales were identified between 1 January 2010 and 1 March 2022. Unpaid carers were found at higher risk of managing 35 of 37 long-term health conditions and multimorbidity than non-carers, exacerbated amongst younger age groups and deprived communities. CONCLUSIONS: The creation of the first e-cohort of unpaid carers in Wales provides opportunities to perform rapid analysis to systematically understand health needs and evaluate initiatives in future. To better support unpaid carers, flexible approaches focusing on early identification and prevention is crucial.


Assuntos
Cuidadores , Projetos de Pesquisa , Humanos , País de Gales/epidemiologia , Armazenamento e Recuperação da Informação
5.
Lancet ; 400 Suppl 1: S25, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36929968

RESUMO

BACKGROUND: Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention. METHODS: BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models. FINDINGS: Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60·4% vs 62·7%; p<0·001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard. INTERPRETATION: Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening. FUNDING: Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.


Assuntos
COVID-19 , Pandemias , Masculino , Humanos , País de Gales/epidemiologia , Medicina Estatal , Estudos Retrospectivos , Programas de Rastreamento/métodos , COVID-19/epidemiologia
6.
Plant Physiol ; 188(3): 1496-1506, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-34893909

RESUMO

Tanshinone ⅡA (TⅡA), a diterpene quinone with a furan ring, is a bioactive compound found in the medicinal herb redroot sage (Salvia miltiorrhiza Bunge), in which both furan and dihydrofuran analogs are present in abundance. Progress has been made recently in elucidating the tanshinone biosynthetic pathway, including heterocyclization of the dihydrofuran D-ring by cytochrome P450s; however, dehydrogenation of dihydrofuran to furan, a key step of furan ring formation, remains uncharacterized. Here, by differential transcriptome mining, we identified six 2-oxoglutarate-dependent dioxygenase (2-ODD) genes whose expressions corresponded to tanshinone biosynthesis. We showed that Sm2-ODD14 acts as a dehydrogenase catalyzing the furan ring aromatization. In vitro Sm2-ODD14 converted cryptotanshinone to TⅡA and thus was designated TⅡA synthase (SmTⅡAS). Furthermore, SmTⅡAS showed a strict substrate specificity, and repression of SmTⅡAS expression in hairy root by RNAi led to increased accumulation of total dihydrofuran-tanshinones and decreased production of furan-tanshinones. We conclude that SmTⅡAS controls the metabolite flux from dihydrofuran- to furan-tanshinones, which influences medicinal properties of S. miltiorrhiza.


Assuntos
Dioxigenases/genética , Dioxigenases/metabolismo , Diterpenos/metabolismo , Furanos/metabolismo , Plantas Medicinais/metabolismo , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Vias Biossintéticas , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Raízes de Plantas/metabolismo
7.
Opt Lett ; 48(7): 1674-1677, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37221738

RESUMO

An ultra-sensitive sensor, based on two Fabry-Perot interferometers (FPIs), has been realized for temperature and pressure sensing. A polydimethylsiloxane (PDMS)-based FPI1 was used as a sensing cavity, and a closed capillary-based FPI2 was used as a reference cavity for its insensitivity to both temperature and pressure. The two FPIs were connected in series to obtain a cascaded FPIs sensor, showing a clear spectral envelope. The temperature and pressure sensitivities of the proposed sensor reach up to 16.51 nm/°C and 100.18 nm/MPa, which are 25.4 and 21.6 times, respectively, larger than these of the PDMS-based FPI1, showing a great Vernier effect.

8.
Appl Opt ; 62(2): 275-283, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36630225

RESUMO

In this paper, an enhanced Vernier effect temperature sensor based on two parallel Fabry-Perot interferometers (FPIs) is proposed and demonstrated experimentally. Among them, F P I 1 is composed of a single-mode fiber (SMF), a quartz capillary, and AB glue filled in the capillary. F P I 2 is formed by filling a capillary with polyimide (PI) solution and inserting two-segment SMF from both sides of the capillary. Since AB glue and PI have good thermal sensitivity, F P I 1 and F P I 2 are highly sensitive to temperature. Due to their different structures, the temperature sensitivity of F P I 1 is negative, and that of F P I 2 is positive. When F P I 1 and F P I 2 with similar free spectral range are connected in parallel, they will act as reference cavities for each other, resulting in an enhanced Vernier effect, which enlarges the sensitivity of the sensor more. In the temperature range of 40°C-58°C, the temperature sensitivity of the sensor is as high as -13.09n m/∘ C, and the fitting coefficient is 0.9974. The experimental results show that in the enhanced Vernier effect sensor structure, only two FPIs with opposite temperature sensitivity are required, which does not increase the difficulty and cost of sensor manufacturing. In addition, the sensor has good stability and repeatability.

9.
BMC Public Health ; 23(1): 546, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949447

RESUMO

BACKGROUND: Response to the early stages of the COVID-19 pandemic resulted in the temporary disruption of cancer screening in the UK, and strong public messaging to stay safe and to protect NHS capacity. Following reintroduction in services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who may benefit from tailored interventions. METHODS: Records within the BSW were linked to electronic health records (EHR) and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank. Ethnic group was obtained from a linked data method available within SAIL. We examined uptake for the first 3 months of invitations (August to October) following the reintroduction of BSW programme in 2020, compared to the same period in the preceding 3 years. Uptake was measured across a 6 month follow-up period. Logistic models were conducted to analyse variations in uptake by sex, age group, income deprivation quintile, urban/rural location, ethnic group, and clinically extremely vulnerable (CEV) status in each period; and to compare uptake within sociodemographic groups between different periods. RESULTS: Uptake during August to October 2020 (period 2020/21; 60.4%) declined compared to the same period in 2019/20 (62.7%) but remained above the 60% Welsh standard. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Compared to the pre-pandemic period in 2019/20, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most income deprived group. Uptake continues to be lower in males, younger individuals, people living in the most income deprived areas and those of Asian and unknown ethnic backgrounds. CONCLUSION: Our findings are encouraging with overall uptake achieving the 60% Welsh standard during the first three months after the programme restarted in 2020 despite the disruption. Inequalities did not worsen after the programme resumed activities but variations in CRC screening in Wales associated with sex, age, deprivation and ethnic group remain. This needs to be considered in targeting strategies to improve uptake and informed choice in CRC screening to avoid exacerbating disparities in CRC outcomes as screening services recover from the pandemic.


Assuntos
COVID-19 , Neoplasias Colorretais , Masculino , Humanos , Pandemias/prevenção & controle , País de Gales/epidemiologia , Detecção Precoce de Câncer/métodos , COVID-19/diagnóstico , COVID-19/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Fatores Socioeconômicos
10.
Euro Surveill ; 28(39)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37768558

RESUMO

Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.


Assuntos
Infecções por Enterovirus , Enterovirus , Miocardite , Recém-Nascido , Humanos , Criança , Miocardite/diagnóstico , Miocardite/complicações , Infecções por Enterovirus/complicações , Infecções por Enterovirus/diagnóstico , Enterovirus/genética , Enterovirus Humano B/genética , Saúde Pública
11.
J Med Virol ; 94(11): 5103-5111, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35819034

RESUMO

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative pathogen for the coronavirus disease 2019 (COVID-19) pandemic, has greatly stressed our healthcare system. In addition to severe respiratory and systematic symptoms, several comorbidities increase the risk of fatal disease outcomes, including chronic viral infections. Increasing cases of lytic reactivation of human herpesviruses in COVID-19 patients and vaccinated people have been reported recently. SARS-CoV2 coinfection, COVID-19 treatments, and vaccination may aggravate those herpesvirus-associated diseases by reactivating the viruses in latently infected host cells. In this review, we summarize recent clinical findings and limited mechanistic studies regarding the relationship between SARS-CoV-2 and different human herpesviruses that suggest an ongoing potential threat to human health in the postpandemic era.


Assuntos
COVID-19 , Herpesviridae , Humanos , Pandemias , RNA Viral , SARS-CoV-2
12.
J Public Health (Oxf) ; 44(4): 805-809, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34121112

RESUMO

BACKGROUND: Homelessness is an extreme form of social exclusion, with homeless people experiencing considerable social and health inequities. Estimates of morbidity and mortality amongst homeless populations is limited due to the lack of recording of housing status across health datasets. The aim of this study is to: (i) identify a homelessness e-cohort by linking routine health data in Wales, and (ii) explore whether a period of reported past homelessness, places this population at greater risk of morbidity and mortality. METHODS: Homelessness identified through linkage across primary, secondary care and substance misuse datasets in the Secure Anonymised Information Linkage (SAIL) Databank. Mortality was examined through linkage to the Office for National Statistics mortality data. RESULTS: E-cohort of 15 472 individuals with lived experience of homelessness identified. Of those, 21 individuals died between February and July 2020 involving coronavirus disease of 2019 (COVID-19). Those with lived experience of homelessness had increased mortality from many causes including accidents, liver diseases and suicides. CONCLUSION: Linking multiple routine datasets provides a more comprehensive dataset of a marginalized population, including individuals who are not included in government homeless statistics. Application of the cohort demonstrated that individuals with lived experience of homelessness have increased mortality involving COVID-19 and other causes. The underlying reasons, health needs and causes of death warrant further exploration.


Assuntos
COVID-19 , Pessoas Mal Alojadas , Suicídio , Humanos , País de Gales/epidemiologia , Problemas Sociais
13.
Acta Radiol ; 63(4): 536-544, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33745294

RESUMO

BACKGROUND: Most commonly used diffusion-weighted imaging (DWI) models include intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), stretched exponential model (SEM), and mono-exponential model (MEM). Previous studies of the four models were inconsistent on which model was more effective in distinguishing cervical cancer from normal cervical tissue. PURPOSE: To assess the performance of four DWI models in characterizing cervical cancer and normal cervical tissue. MATERIAL AND METHODS: Forty-seven women with suspected cervical carcinoma underwent DWI using eight b-values before treatment. Imaging parameters, calculated using IVIM, SEM, DKI, and MEM, were compared between cervical cancer and normal cervical tissue. The diagnostic performance of the models was evaluated using independent t-test, Mann-Whitney U test, receiver operating characteristic (ROC) curve analysis, and multivariate logistic regression analysis. RESULTS: All parameters except pseudo-diffusion coefficient (D*) differed significantly between cervical cancer and normal cervical tissue (P < 0.001). Through logistic regression analysis, all combined models showed a significant improvement in area under the ROC curve (AUC) compared to individual DWI parameters. The model with combined IVIM parameters had a larger AUC value compared to those of other combined models (P < 0.05). CONCLUSION: All four DWI models are useful for differentiating cervical cancer from normal cervical tissue and IVIM may be the optimal model.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Colo do Útero/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
Molecules ; 27(21)2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36364203

RESUMO

Fatigue seriously affects people's work efficiency and quality of life and has become a common health problem in modern societies around the world. The pathophysiology of fatigue is complex and not fully clear. To some degree, interactions between gut microbiota and host may be the cause of fatigue progression. Polyphenols such as tannin, tea polyphenols, curcumin, and soybean isoflavones relieve fatigue significantly. Studies have shown that the gut microbiota is able to convert these active compounds into more active metabolites through intestinal fermentation. However, the mechanism of anti-fatigue polyphenols is currently mainly analyzed from the perspective of antioxidant and anti-inflammatory effects, and changes in gut microbiota are rarely considered. This review focuses on gut microecology and systematically summarizes the latest theoretical and research findings on the interaction of gut microbiota, fatigue, and polyphenols. First, we outline the relationship between gut microbiota and fatigue, including changes in the gut microbiota during fatigue and how they interact with the host. Next, we describe the interactions between the gut microbiota and polyphenols in fatigue treatment (regulation of the gut microbiota by polyphenols and metabolism of polyphenols by the gut microbiota), and how the importance of potential active metabolites (such as urolithin) produced by the decomposition of polyphenols by gut microbiota is emerging. Based on the new perspective of gut microbiota, this review provides interesting insights into the mechanism of polyphenols in fatigue treatment and clarifies the potential of polyphenols as targets for anti-fatigue product development, aiming to provide a useful basis for further research and design.


Assuntos
Microbioma Gastrointestinal , Polifenóis , Humanos , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Polifenóis/metabolismo , Microbioma Gastrointestinal/fisiologia , Qualidade de Vida , Extratos Vegetais
15.
Metab Eng ; 68: 86-93, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34555495

RESUMO

Coenzyme Q (CoQ) is vital for energy metabolism in living organisms. In humans, CoQ10 deficiency causes diseases and must be replenished via diet; however, CoQ content in plant foods is primarily low. Here, we report the breeding of high CoQ10 tomato lines by expressing four enzymes with a fruit-specific promoter, which modifies the chloroplast chorismate pathway, enhances cytosolic isoprenoid biosynthesis, and up-regulates the first two reactions in mitochondrion that construct the CoQ10 polyisoprenoid tail. We show that, while the level of the aromatic precursor could be markedly elevated, head group prenylation is the key to increasing the final CoQ10 yield. In the HUCD lines expressing all four transgenes, the highest CoQ10 content (0.15 mg/g dry weight) shows a seven-fold increase from the wild-type level and reaches an extraordinarily rich CoQ10 food grade. Overviewing the changes in other terpenoids by transcriptome and metabolic analyses reveals variable contents of carotenoids and α-tocopherol in the HUCD lines. In addition to the enigmatic relations among different terpenoid pathways, high CoQ10 plants maintaining substantial levels of either vitamin can be selected. Our investigation paves the way for the development of CoQ10-enriched crops as dietary supplements.


Assuntos
Solanum lycopersicum , Ubiquinona , Carotenoides/metabolismo , Frutas/metabolismo , Humanos , Solanum lycopersicum/genética , Mitocôndrias , Ubiquinona/genética
16.
BMC Musculoskelet Disord ; 22(1): 809, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548056

RESUMO

BACKGROUND: The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang-(1-7)) axis has been shown to protect against the age-associated decline in skeletal muscle function. Here, we investigated the protective effects of ACE2 in mitigating the age-associated decline of skeletal muscle function and to identify the potential underlying molecular mechanisms. METHODS: We measured the expression levels of Ang-(1-7) in C57BL/6J mice of different ages and correlated these levels with measures of skeletal muscle function. We also investigated the expression of myocyte enhancer factor 2 A (MEF2A) in ACE2 knockout (ACE2KO) mice and its relationship with muscle function. We then treated aged ACE2KO mice for four weeks with Ang-(1-7) and characterized the levels of MEF2A and skeletal muscle function before and after treatment. We assessed the impact of Ang-(1-7) on the growth and differentiation of C2C12 cells in vitro and assessed changes in expression of the glucose transporter type 4 (Glut4). RESULTS: Aged mice showed reduced skeletal muscle function and levels of Ang-(1-7) expression in comparison to young and middle-aged mice. In ACE2KO mice, skeletal muscle function and MEF2A protein expression were significantly lower than in age-matched wild-type (WT) mice. After one month of Ang-(1-7) treatment, skeletal muscle function in the aged ACE2KO mice improved, while MEF2A protein expression was similar to that in the untreated group. In C2C12 cells, Ang-(1-7) was shown to promote along with the upregulated expression of Glut4. CONCLUSIONS: The ACE2/ Ang-(1-7) axis has a protective function in skeletal muscle and administration of exogenous Ang-(1-7) can delay the age-related decline in the function of skeletal muscle.


Assuntos
Angiotensina I , Fragmentos de Peptídeos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético
17.
J Virol ; 93(15)2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31118252

RESUMO

Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as host susceptibility factors. GII.13 and GII.21 huNoVs form a unique genetic lineage that emerged from mainstream GII NoVs via development of a new, nonconventional glycan binding site (GBS) that binds Lea antigen. This previous finding raised the question of whether the new GII.13/21 GBS really has such a narrow glycan binding spectrum. In this study, we provide solid phenotypic and structural evidence indicating that this new GBS recognizes a group of glycans with a common terminal ß-galactose (ß-Gal). First, we found that P domain proteins of GII.13/21 huNoVs circulating at different times bound three glycans sharing a common terminal ß-Gal, including Lec, lactose, and mucin core 2. Second, we solved the crystal structures of the GII.13 P dimers in complex with Lec and mucin core 2, which showed that ß-Gal is the major binding saccharide. Third, nonfat milk and lactose blocked the GII.13/21 P domain-glycan binding, which may explain the low prevalence of GII.13/21 viruses. Our data provide new insight into the host interactions and epidemiology of huNoVs, which would help in the control and prevention of NoV-associated diseases.IMPORTANCE Evidence from both phenotypic binding assay and structural study support the observed interactions of human noroviruses (huNoVs) with histo-blood group antigens (HBGAs) as receptors or attachment factors, affecting their host susceptibility. GII.13 and GII.21 genotypes form a unique genetic lineage that differs from the mainstream GII huNoVs in their unconventional glycan binding site. Unlike the previous findings that GII.13/21 genotypes recognize only Lea antigen, we found in this study that they can interact with a group of glycans with a common terminal ß-Gal, including Lec, lactose, and mucin core 2. However, this wide glycan binding spectrum in a unique binding mode of the GII.13/21 huNoVs appears not to increase their prevalence, probably due to the existence of decoy glycan receptors in human gastrointestinal tract limiting their infection. Our findings shed light on the host interaction and epidemiology of huNoVs, which would impact the strategy of huNoV control and prevention.


Assuntos
Antígeno CA-19-9/metabolismo , Galactose/metabolismo , Norovirus/fisiologia , Ligação Viral , Antígenos de Grupos Sanguíneos/metabolismo , Genótipo , Humanos , Norovirus/classificação , Norovirus/genética , Ligação Proteica
18.
Pharmacol Res ; 161: 105109, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32738494

RESUMO

Protocatechuic acid is a natural phenolic acid, which widely exists in our daily diet and herbs. It is also one of the main metabolites of complex polyphenols, such as anthocyanins and proanthocyanins. In recent years, a large number of studies on the pharmacological activities of protocatechuic acid have emerged. Protocatechuic acid has a wide range of pharmacological activities including antioxidant, anti-inflammatory, neuroprotective, antibacterial, antiviral, anticancer, antiosteoporotic, analgesia, antiaging activties; protection from metabolic syndrome; and preservation of liver, kidneys, and reproductive functions. Pharmacokinetic studies showed that the absorption and elimination rate of protocatechuic acid are faster, with glucuronidation and sulfation being the major metabolic pathways. However, protocatechuic acid displays a dual-directional regulatory effect on some pharmacological activities. When the concentration is very high, it can inhibit cell proliferation and reduce survival rate. This review aims to comprehensively summarize the pharmacology, pharmacokinetics, and toxicity of protocatechuic acid with emphasis on its pharmacological activities discovered in recent 5 years, so as to provide more up-to-date and thorough information for the preclinical and clinical research of protocatechuic acid in the future. Moreover, it is hoped that the clinical application of protocatechuic acid can be broadened, giving full play to its characteristics of rich sources, low toxicity and wide pharmacological activites.


Assuntos
Dieta , Hidroxibenzoatos/farmacologia , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Humanos , Hidroxibenzoatos/administração & dosagem , Hidroxibenzoatos/farmacocinética , Hidroxibenzoatos/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Extratos Vegetais/toxicidade
19.
Nanomedicine ; 20: 102020, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31125675

RESUMO

Local recurrence is common among patients with advanced cancer who have undergone surgery. Here, we developed a new surgical treatment for cancer based on a nanoparticle that loaded a near-infrared dye (IR780 iodide) and perfluorooctyl bromide into liposomes (NP-IR780). In an orthotopic breast cancer mouse model, NP-IR780 was demonstrated to have excellent tumor-targeting ability due to the selective tumor accumulation of IR780 iodide and the enhanced permeation and retention effect of the nanoparticle. With the excellent targeting ability, concurrent computed tomography and photoacoustic imaging were achieved for preoperative planning. In particular, NP-IR780 could serve as a tumor indicator for near-infrared fluorescence image-guided precise resection of lesions during surgery. Importantly, residual tumors could be ablated through intraoperative photothermal therapy without obvious recurrence. This work provides a theranostic strategy that significantly improved the survival of mice through pre/intraoperative image-guided tumor resection and subsequent photothermal therapy of residual lesions.


Assuntos
Hipertermia Induzida , Nanopartículas/química , Neoplasia Residual/terapia , Fototerapia , Espectroscopia de Luz Próxima ao Infravermelho , Cirurgia Assistida por Computador , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Indóis/química , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Metástase Neoplásica , Neoplasia Residual/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo
20.
J Anim Physiol Anim Nutr (Berl) ; 103(4): 1030-1038, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30702179

RESUMO

This study was to investigate the effects of Epigallocatechin-3-gallate (EGCG) on intestinal morphology, antioxidant capacity and anti-inflammatory response in heat-stressed broiler. A total of 192 2-week-old Arbour Acres broilers chickens were divided into four groups with six replicates per group and eight chickens per replicate: one thermoneutral control group (28°C, group TN), which was fed the basal diet; and three cyclic high-temperature groups (35°C from 7:00 to 19:00 hr; 28°C from 19:00 hr to 7:00 hr, heat stress group), which were fed the basal diet supplementation with EGCG 0 mg/kg (group HS0), 300 mg/kg (group HS300) and 600 mg/kg (group HS600). The gut morphology and intestinal mucosal oxidative stress indicators, as well as intestinal barrier-related gene expression, were analysed. The results showed that compared with group TN, heat stress reduced the villus height (VH), activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD)and catalase (CAT), increased the crypt depth (CD) and malondialdehyde (MDA)content at 21, 28 and 35 days (p < 0.05). After the heat-stressed broilers were supplemented with EGCG, VH, VH/CD (V/C), and the activities of GSH-Px, SOD and CAT were increased, and CD and MDA content were reduced compared with those in group HS0 without EGCG supplementation at 21, 28 and 35 days (p < 0.05). The EGCG supplementation promoted the gene expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), Claudin-1, Mucin 2 (Muc2) and alleviated the nuclear factor-kappa B (NF-κB) and lipopolysaccharide-induced tumour necrosis factor (LITAF) gene expression compared with group HS0 (p < 0.05). Moreover, intestinal morphology was strongly correlated with antioxidant ability and inflammatory response. In conclusion, EGCG alleviated the gut oxidative injury of heat-stressed broilers by enhancing antioxidant capacity and inhibiting inflammatory response.


Assuntos
Antioxidantes/metabolismo , Catequina/análogos & derivados , Galinhas , Transtornos de Estresse por Calor/veterinária , Intestino Delgado/anatomia & histologia , Intestino Delgado/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Catequina/administração & dosagem , Catequina/farmacologia , Transtornos de Estresse por Calor/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/patologia
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