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1.
Adv Exp Med Biol ; 1287: 1-7, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034022

RESUMO

The evolutionary conserved Notch pathway that first developed in metazoans and that was first discovered in fruit flies (Drosophila melanogaster) governs fundamental cell fate decisions and many other cellular key processes not only in embryonic development but also during initiation, promotion, and progression of cancer. On a first look, the Notch pathway appears remarkably simple, with its key feature representing a direct connection between an extracellular signal and transcriptional output without the need of a long chain of protein intermediaries as known from many other signaling pathways. However, on a second, closer look, this obvious simplicity exerts surprising complexity. There is no doubt that the enormous scientific progress in unraveling the functional mechanisms that underlie this complexity has recently greatly increased our knowledge about the role of Notch signaling for pathogenesis and progression of many types of cancer. Moreover, these new scientific findings have shown promise in opening new avenues for cancer prevention and therapy, although this goal is still challenging. Vol. III of the second edition of the book Notch Signaling in Embryology and Cancer, entitled Notch Signaling in Cancer, summarizes important recent developments in this fast-moving and fascinating field. Here, we give an introduction to this book and a short summary of the individual chapters that are written by leading scientists, covering the latest developments in this intriguing research area.


Assuntos
Neoplasias/prevenção & controle , Neoplasias/terapia , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Diferenciação Celular , Humanos , Neoplasias/patologia
2.
Adv Exp Med Biol ; 1287: 31-46, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034024

RESUMO

The endosomal pathway plays a pivotal role upon signal transduction in the Notch pathway. Recent work on lethal (2) giant discs (lgd) points to an additional critical role in avoiding uncontrolled ligand-independent signalling during trafficking of the Notch receptor through the endosomal pathway to the lysosome for degradation. In this chapter, we will outline the journey of Notch through the endosomal system and present an overview of the current knowledge about Lgd and its mammalian orthologs Lgd1/CC2D1b and Lgd2/CC2D1a. We will then discuss how Notch is activated in the absence of lgd function in Drosophila and ask whether there is evidence that a similar ligand-independent activation of the Notch pathway can also happen in mammals if the orthologs are inactivated.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Neoplasias/metabolismo , Receptores Notch/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais , Proteínas Supressoras de Tumor/metabolismo , Animais , Endossomos/metabolismo , Humanos
3.
Adv Exp Med Biol ; 1287: 105-122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034029

RESUMO

The NOTCH pathway is critical for the development of many cell types including the squamous epithelium lining of cutaneous and mucosal surfaces. In genetically engineered mouse models, Notch1 acts as one of the first steps to commit basal keratinocytes to terminally differentiate. Similarly, in human head and neck squamous cell cancers (HNSCCs), NOTCH1 is often lost consistent with its essential tumor-suppressive role for initiating keratinocyte differentiation. However, constitutive NOTCH1 activity in the epithelium results in expansion of the spinous keratinocyte layers and impaired terminal differentiation is consistent with the role of NOTCH1 as an oncogene in other cancers, especially in T-cell acute lymphoblastic leukemia. We have previously observed that NOTCH1 plays a dual role as both a tumor suppressor and oncogene, depending on the mutational context of the tumor. Namely, gain or loss or NOTCH1 activity promotes the development of human papillomavirus (HPV)-associated cancers. The additional HPV oncogenes likely disrupt the tumor-suppressive activities of NOTCH and enable the oncogenic pathways activated by NOTCH to promote tumor growth. In this review, we detail the role of NOTCH pathway in head and neck cancers with a focus on HPV-associated cancers.


Assuntos
Carcinogênese , Neoplasias Bucais/metabolismo , Neoplasias Bucais/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Humanos , Infecções por Papillomavirus/virologia
4.
Adv Exp Med Biol ; 1287: 123-154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034030

RESUMO

Since many decades, nonmelanoma skin cancer (NMSCs) is the most common malignancy worldwide. Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) are the major types of NMSCs, representing approximately 70% and 25% of these neoplasias, respectively. Because of their continuously rising incidence rates, NMSCs represent a constantly increasing global challenge for healthcare, although they are in most cases nonlethal and curable (e.g., by surgery). While at present, carcinogenesis of NMSC is still not fully understood, the relevance of genetic and molecular alterations in several pathways, including evolutionary highly conserved Notch signaling, has now been shown convincingly. The Notch pathway, which was first developed during evolution in metazoans and that was first discovered in fruit flies (Drosophila melanogaster), governs cell fate decisions and many other fundamental processes that are of high relevance not only for embryonic development, but also for initiation, promotion, and progression of cancer. Choosing NMSC as a model, we give in this review a brief overview on the interaction of Notch signaling with important oncogenic and tumor suppressor pathways and on its role for several hallmarks of carcinogenesis and cancer progression, including the regulation of cancer stem cells, tumor angiogenesis, and senescence.


Assuntos
Carcinogênese , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica , Receptores Notch/metabolismo , Transdução de Sinais , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Animais , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Cutâneas/irrigação sanguínea
5.
GM Crops Food ; 12(1): 115-124, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33084486

RESUMO

Transgenic crops that produce Bacillus thuringiensis (Bt) toxins are effective tools for controlling lepidopteran pests. However, the degree of susceptibility to Bt toxins differs among various pest species due to relatively narrow spectrum and high selectivity of such toxins. Bt corn hybrids for Chinese market were designed to target Asian corn borer Ostrinia furnacalis (Guenée), while their efficacy against other lepidopteran pests are not well defined, such as Conogethes punctiferalis (Guenée), Helicoverpa armigera (Hübner), Agrotis ypsilon (Rottemberg), and Mythimna separata (Walker), which are also important lepidopteran pests on corn in the Huang-Huai-Hai Summer Corn Region of China. To determine what type of Bt corn is suitable for this region, the efficacy of five Bt toxins, i.e., Cry1Ab, Cry1Ac, Cry1F, Cry2Ab, and Vip3A, to these five lepidopteran species was evaluated in laboratory. Both O. furnacalis and C. punctiferalis showed similar high susceptibility to all five Bt toxins. A. ypsilon and M. separate were less sensitive to Cry1Ab and Cry1Ac than the other species. H. armigera, A. ypsilon and M. separate were less sensitive to Cry1F than O. furnacalis and C. punctiferalis. H. armigera was more sensitive to Cry2Ab than other tested species. All five species were equally sensitive to Vip3A, though their LC50s were all relatively higher. These findings suggest that the first generation Bt corn expressing single Cry1 toxin should not be the first choice because of the potential risk of control failure or less efficacy against H. armigera, A. ypsilon or M. separate. The second-generation Bt corn expressing Cry1 and Cry2 toxins, or the third generation Bt corn expressing Cry1, Cry2 and Vip3A toxins might produce better protection of corn in the Huang-Huai-Hai Summer Corn Region of China.


Assuntos
Bacillus thuringiensis , Animais , Bacillus thuringiensis/genética , China , Produtos Agrícolas , Fatores de Transcrição , Zea mays/genética
6.
GM Crops Food ; 12(1): 47-56, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32862762

RESUMO

The sugarcane (Saccharum X officinarum) is one of the most important crops used to produce sugar and raw material for biofuel in the world. One of the main causes for sucrose content and yield losses is the attack by insect. In this investigation, cry1Ac gene was introduced into sugarcane variety GT54-9(C9) using the Agrobacterium tumefaciens transformation method for transgenic sugarcane production presenting insect-resistance. The A. tumefaciens strain GV1303 including pARTcry1Ac vector was used for the production of transformed sugarcane. The Bacillus thuringiensis cry gene were successfully used to produce transgenic plants used for the improvement of both agronomic efficiency and product quality by acquiring insect resistance. PCR and Southern hybridization techniques were used to confirm the cry1Ac gene incorporation into sugarcane genome. Transformation percentage was 22.2% using PCR analysis with specific primers for cry1Ac and npt-II (Neomycin phosphotransferase) genes. The expression of cry1Ac gene was determined using reverse transcriptase polymerase chain reaction (RT-PCR), QuickStix test, and insect bioassays. Bioassays for transformed sugarcane plants showed high level of toxicity to Sesamia cretica giving 100% mortality of the larvae. Sugarcane insect resistance was improved significantly by using cry1Ac gene transformation.


Assuntos
Saccharum/genética , Agrobacterium , Animais , Proteínas de Bactérias/genética , Endotoxinas , Proteínas Hemolisinas/genética , Plantas Geneticamente Modificadas
7.
GM Crops Food ; 12(1): 1-17, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32762312

RESUMO

A biophysical survey was conducted in 15 cotton-growing districts of Pakistan. Four hundred cotton growers were approached and inquired about the production technology of Bt cotton. Further, 25 strip tests using combo strips (Cry1Ac, Cry2Ab, Vip3Aa and Cp4, EPSPS gene) were performed at each farmer's field. Out of 10,000 total-tested samples, farmers claimed 9682 samples as Bt and 318 samples as non-Bt. After performing a strip test, 1009 and 87 samples were found false negative and false positive, respectively. Only 53 samples were found positive for Cry2Ab, 214 for EPSPS and none for Vip3Aa gene. Quantification of Cry endotoxin and bioassay studies were performed by taking leaves from upper, middle, and lower canopies, and fruiting parts at approximately 80 days after sowing from 89 varieties. Expression was highly variable among different canopies and fruiting parts. Moreover, Cry endotoxin expression and insect mortality varied significantly among varieties from 0.26 µg g-1 to 3.54 µg g-1 with mortality ranging from 28 to 97%, respectively. Highest Cry1Ac expression (3.54 µg g-1) and insect mortality (97%) were observed for variety FH-142 from DG Khan. Cry endotoxin expression varied significantly across various plant parts, i.e., IUB-13 variety from upper canopy documented 0.34 µg g-1 expression with 37% insect mortality in Layyah to 3.42 µg g-1 expression and 96% insect mortality from DG Khan. Lethal dose, LD95 (2.20 µg g-1) of Cry1Ac endotoxin was optimized for effective control of H. armigera. Our results provided evidence of practical resistance in H. armigera and way forward.


Assuntos
Proteínas Hemolisinas/genética , Mariposas , Animais , Proteínas de Bactérias/genética , Endotoxinas , Gossypium , Resistência a Inseticidas , Larva , Paquistão , Plantas Geneticamente Modificadas
8.
GM Crops Food ; 12(1): 18-24, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32787504

RESUMO

Since 1996 till 2018, the global area cultivated with GM crops has increased 113-fold, making biotech crops one of the fastest adopted crop technology in the past decades. In the European Union, only two countries still cultivate one available transgenic crop event on minor hectarage. Moreover, the number of notifications for confined field trials has dramatically dropped in the last decade. All these are happening while the EU legislation on GM crops has come under severe criticism. The percentage of EU citizens concerned about the presence of GMOs in the environment has decreased from 30% (in 2002) to 19% (in 2011), while the level of concern about the use of GM ingredients in food or drinks has decreased from 63% (in 2005) to 27% (in 2019). The steadily increasing acceptance of the EU citizens of GMOs in the environment and food, as it was recorded by Eurobarometers, should additionally ease the way and support a positive change of the legal framework that regulates the GM crops' testing and commercial cultivation in the EU.


Assuntos
Biotecnologia , Produtos Agrícolas/genética , Animais , Animais Geneticamente Modificados , União Europeia , Plantas Geneticamente Modificadas
9.
Rev. bioét. derecho ; (50): 19-35, nov. 2020.
Artigo em Espanhol | IBECS | ID: ibc-191344

RESUMO

La pandemia de COVID-19 tiene un origen zoonótico: fue transmitida de los animales a los humanos. Lo mismo ha sucedido con otras epidemias recientes (como las causadas por los virus SARS-CoV-1 y H7N9, entre otros). Estas epidemias surgieron en un contexto de explotación animal: el comercio de animales silvestres. Mucha gente ha pedido la prohibición total de la venta de animales silvestres en mercados. Sin embargo, la prohibición puede ser contraproducente y tener peores consecuencias tanto para los animales como para la salud pública. Este artículo argumenta en contra de una prohibición total y a favor de una regulación progresiva que tome en cuenta el bienestar de los animales, pero que tenga como finalidad última la desaparición del comercio de animales silvestres


The COVID-19 pandemic has a zoonotic origin: it was transmitted from animals to humans. The same has happened with other recent epidemics (such as those caused by the virus SARS-CoV-1 and H7N9, among others). These epidemics arose in a context of animal exploitation: the trade in wildlife. Many people have asked for a blanket ban of wildlife trade in wet markets. However, a blanket ban may be counterproductive and have worse consequences both for the animals and for public health. This paper argues against a blanket ban and argues for a progressive regulation that takes into account the welfare of animals, but that has as its final goal the disappearance of trade in wildlife


La pandèmia de la COVID-19 té un origen zoonòtic: es va transmetre dels animals als humans. El mateix ha passat amb altres epidèmies recents (com les causades pels virus SARS-CoV-1 I H7N9, entre d'altres). Aquestes epidèmies van sorgir en un context d'explotació animal: el comerç d'animals silvestres. Molta gent ha demanat la prohibició total de la venda d'animals silvestres en mercats. No obstant això, la prohibició pot ser contraproduent I tenir pitjors conseqüències tant per als animals com per a la salut pública. Aquest article argumenta en contra d'una prohibició total I a favor d'una regulació progressiva que tingui en compte el benestar dels animals, però que tingui com a finalitat última la desaparició del comerç d'animals silvestres


Assuntos
Humanos , Animais , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Pandemias , Zoonoses/epidemiologia , Animais Selvagens/virologia , Comércio/legislação & jurisprudência
10.
Rev. bioét. derecho ; (50): 425-438, nov. 2020.
Artigo em Espanhol | IBECS | ID: ibc-191366

RESUMO

La crisis sanitaria global que es la COVID-19 arroja al pensamiento hacia lugares incómodos. En el presente manuscrito sugiero que la filosofía pospandémica, de ahora en adelante, no puede ni podrá desentenderse del fenómeno de lo viviente, específicamente del viviente animal no humano. Precisamente, producto de la indiferencia de la cuestión animal, la filosofía ha creído por pretérita la tesis cartesiana del animal-máquina. Muy por el contrario, en este texto propongo que dicha comprensión del animal no tiene nada de arcaica, y que, provocada por el contexto pandémico, podría dar a lugar a lo que tentativamente es posible denominar "cartesianismo distópico". Ante esta consumación, cuya cristalización es el devenir (total) máquina del animal no humano, una bioética animal podría servir como vía para contravenir el cartesianismo distópico


The global health crisis that is the COVID-19 throws the thinking into uncomfortable places. In the present manuscript I suggest that post-pandemic philosophy, from now on, cannot and will not ignore the phenomenon of the living, specifically the living non-human animal. Precisely, as a result of the indifference of the animal question, philosophy has believed in the past the Cartesian thesis of the animal-machine. On the contrary, in this text we propose that such understanding of the animal is not archaic at all, and that, triggered by the pandemic context, could give rise to what can tentatively be called "dystopian Cartesianism". In front of this consummation, whose crystallization is the (total) machine becoming of the non-human animal, an animal bioethics could serve as a way to contravene the dystopian Cartesianism


La crisi sanitària global que és la COVID-19 llança el pensament cap a llocs incòmodes. En el present manuscrit suggereixo que la filosofia postpandèmica, d'ara endavant, no es pot ni es podrà desentendre del fenòmen del que és viu, específicament del vivent animal no humà. Precisament, producte de la indiferència de la qüestió animal, la filosofia ha cregut per pretèrita la tesi cartesiana de l'animal-màquina. Molt al contrari, en aquest text proposo que aquesta comprensió de l'animal no té res d'arcaica, I que, provocada pel context pandèmic, podria donar a lloc al que temptativament és possible anomenar "cartesianisme distòpic". Davant d'aquesta consumació, la cristal·lització del qual és l'esdevenir (total) màquina de l'animal no humà, una bioètica animal podria servir com a via per contravenir el cartesianisme distòpic


Assuntos
Humanos , Animais , Temas Bioéticos , Modelos Animais , Experimentação Animal/ética , Animais Domésticos , Infecções por Coronavirus , Pandemias , Comitês de Cuidado Animal
11.
Goiânia; s.n; out. 02, 2020. 1-24 p. ilus, tab, mapas, graf.(Boletim Epidemiológico Covid-19, 26).
Monografia em Português | Coleciona SUS, CONASS, SES-GO | ID: biblio-1121439

RESUMO

O Boletim Epidemiológico COVID-19 objetiva documentar e divulgar informações oficiais atualizadas da situação epidemiológica no Estado de Goiás-GO, Brasil. Resume que desde os primeiros registros na China em dezembro de 2019 até o dia 26 de setembro foram confirmados 32.730.945 casos de COVID-19 no mundo. Deste total, 991.224 evoluíram a óbito. Quando comparados o número de casos e óbitos confirmados desta semana epidemiológica (SE 39) com a semana anterior, houve aumento de 6,7% nos casos e 3,8% nos óbitos. Sintetiza que, no Brasil, neste mesmo intervalo de tempo, o aumento foi 4,2% e 3,5% no número de casos e óbitos, respectivamente. No país o primeiro caso foi confirmado no dia 26 de fevereiro e até 26 de setembro foram registrados 4.717.991 casos confirmados com 141.406 óbitos. Informa que o registro dos primeiros casos suspeitos em Goiás foi a partir de 04 de fevereiro e até 26 de setembro foram notificados à Vigilância Epidemiológica 595.334 casos de COVID-19. Infere que, nesta última semana epidemiológica (SE 39) houve a confirmação de 17.551 casos novos, representando um aumento nos casos de COVID-19 de 9,5%, superior ao aumento observado no Brasil 4,2%. No Estado, 202.528 (34,0%) foram confirmados sendo 196.210 (96,9%) por critério laboratorial, 4.408 (2,2%) pelo critério clínico-epidemiológico, 589 (0,3%) por critério clínico imagem e 802 (0,4%) pelo critério clínico, 148.086 (24,9%) foram descartados e 221.461 (37,2%) continuam como suspeitos


The COVID-19 Epidemiological Bulletin aims to document and disseminate updated official information on the epidemiological situation in the State of Goiás-GO, Brazil. It summarizes that since the first registrations in China in December 2019 until the 26th of September, 32,730,945 cases of COVID-19 have been confirmed worldwide. Of this total, 991,224 died. When comparing the number of confirmed cases and deaths of this epidemiological week (SE 39) with the previous week, there was an increase of 6.7% in cases and 3.8% in deaths. It synthesizes that, in Brazil, in this same time interval, the increase was 4.2% and 3.5% in the number of cases and deaths, respectively. In the country, the first case was confirmed on February 26 and until September 26, 4,717,991 confirmed cases were recorded, with 141,406 deaths. Informs that the record of the first suspected cases in Goiás was from February 4 and until September 26, 595,334 cases of COVID-19 were notified to the Epidemiological Surveillance. It infers that, in this last epidemiological week (SE 39), 17,551 new cases were confirmed, representing an increase in the cases of COVID-19 of 9.5%, higher than the increase observed in Brazil 4.2%. In the State, 202,528 (34.0%) were confirmed, 196,210 (96.9%) by laboratory criteria, 4,408 (2.2%) by clinical-epidemiological criteria, 589 (0.3%) by clinical image criteria and 802 (0.4%) by the clinical criterion, 148,086 (24.9%) were discarded and 221,461 (37.2%) remain as suspects


Assuntos
Humanos , Animais , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Pneumonia Viral/epidemiologia , Infecções por Coronavirus/epidemiologia , Betacoronavirus , Brasil/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Monitoramento Epidemiológico
12.
Artigo em Inglês | MEDLINE | ID: mdl-33036351

RESUMO

The new corona virus infection SARS-CoV2 which was later renamed COVID-19 is a pandemic affecting public health. The fear and the constraints imposed to control the pandemic may correspondingly influence leisure activities, such as birding, which is the practice of observing birds based on visual and acoustic cues. Birders are people who carry out birding observations around the globe and contribute to the massive data collection in citizen science projects. Contrasting to earlier COVID-19 studies, which have concentrated on clinical, pathological, and virological topics, this study focused on the behavioral changes of birders. A total of 4484 questionnaire survey responses from 97 countries were received. The questionnaire had an open-ended style. About 85% of respondents reported that COVID-19 has changed their birding behavior. The most significant change in birdwatchers' behavior was related to the geographic coverage of birding activities, which became more local. People focused mostly on yard birding. In total, 12% of respondents (n = 542 cases) reported having more time for birding, whereas 8% (n = 356 cases) reported having less time for birding. Social interactions decreased since respondents, especially older people, changed their birding behavior toward birding alone or with their spouse. Women reported more often than men that they changed to birding alone or with their spouse, and women also reported more often about canceled fieldtrips or society meetings. Respondents from higher developed countries reported that they spend currently more time for birding, especially for birding alone or with their spouse, and birding at local hotspots. Our study suggests that long lockdowns with strict regulations may severely impact on leisure activities. In addition, a temporal and spatial shift in birding due to the pandemic may influence data quality in citizen science projects. As nature-based recreation will be directed more toward nearby sites, environmental management resources and actions need to be directed to sites that are located near the users, e.g., in urban and suburban areas. The results can be applied with caution to other nature-based recreational activities.


Assuntos
Ciência do Cidadão , Infecções por Coronavirus/psicologia , Coronavirus , Atividades de Lazer , Pneumonia Viral/psicologia , Quarentena/psicologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Saúde Pública , Fatores Sexuais , Comportamento Social , Inquéritos e Questionários
14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1024-1034, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051415

RESUMO

OBJECTIVES: There is a significant increase of high-mobility group protein B1 (HMGB1) in plasma levels of patients with pulmonary hypertension, but the biological significance is still unclear. Anti-proliferative protein 1 (prohibitin 1, PHB1) is an important protein that maintains the homeostasis of vascular cells. This study aimed to investigate the effect of HMGB1 on pulmonary artery endothelial cells and the role of PHB1. METHODS: In vivo experiment: A rat model of pulmonary hypertension induced by monocrotaline (MCT) was constructed. The right ventricular systolic pressure (RVSP), and the weight ratio of right ventricle to left ventricle plus ventricular septum were used to evaluate the success of model. ELISA was used to detect the level of HMGB1 in rat's plasma. Western blotting was used to detect the level of PHB1 in rat's lung tissues. CD31 immunofluorescence was used to detect the integrity of pulmonary vascular endothelium. In vitro experiments: Pulmonary artery endothelial cell (PAEC) was incubated with HMGB1 to observe the effect of HMGB1 on PAEC injury. Overexpression and knockdown of PHB1 were conducted, and the role of PHB1 was investigated by detecting the levels of reative oxygen species and cytochrome c (cyto-c), and the activation of caspase-3. RESULTS: Compared with the control group, the level of HMGB1 in the plasma of rats with pulmonary hypertension was significantly increased (P<0.05), and the expression of PHB1 in the lung tissue was decreased accompanied with endothelial dysfunction (P<0.05); HMGB1 incubation damaged the pulmonary artery endothelium and down-regulated PHB1 expression (P<0.05), while overexpression of PHB1 reduced the PAEC damage and oxidative stress induced by HMGB1 (P<0.05). Meanwhile, PHB1 reduced HMGB1-induced cyto-c expression and caspase-3 cleavage by inhibiting oxidative stress (P<0.05). CONCLUSIONS: The down-regulation of PHB1 expression mediates HMGB1-induced PAEC injury, which is related to the induction of oxidative stress, the increase of cyto-c release, and the promotion of caspase-3 cleavage.


Assuntos
Proteína HMGB1 , Proteínas Repressoras , Animais , Células Endoteliais , Proteína HMGB1/genética , Humanos , Artéria Pulmonar , Ratos , Proteínas Repressoras/genética
15.
Proc Biol Sci ; 287(1931): 20201410, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-33043862

RESUMO

Joint friction has never previously been considered in the computation of mechanical and metabolic energy balance of human and animal (loco)motion, which heretofore included just muscle work to move the body centre of mass (external work) and body segments with respect to it. This happened mainly because, having been previously measured ex vivo, friction was considered to be almost negligible. Present evidences of in vivo damping of limb oscillations, motion captured and processed by a suited mathematical model, show that: (a) the time course is exponential, suggesting a viscous friction operated by the all biological tissues involved; (b) during the swing phase, upper limbs report a friction close to one-sixth of the lower limbs; (c) when lower limbs are loaded, in an upside-down body posture allowing to investigate the hip joint subjected to compressive forces as during the stance phase, friction is much higher and load dependent; and (d) the friction of the four limbs during locomotion leads to an additional internal work that is a remarkable fraction of the mechanical external work. These unprecedented results redefine the partitioning of the energy balance of locomotion, the internal work components, muscle and transmission efficiency, and potentially readjust the mechanical paradigm of the different gaits.


Assuntos
Extremidades , Articulações , Locomoção , Animais , Fricção , Humanos , Metabolismo , Estresse Mecânico
16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1035-1043, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051416

RESUMO

OBJECTIVES: Long non-coding RNAs (lncRNAs) were involved in the development and regulation of necrotizing enterocolitis (NEC) in premature infants. To investigate the changes of lncRNA expression profile in intestinal tissues of NEC for its possible mechanisms. METHODS: Intestinal samples were collected from 11 patients with NEC who needed surgery(the NEC group), and 7 from neonatal non-NEC patients with surgery (the Control group).LncRNA's changes in intestinal samples (3 in the Control group and 3 in the NEC group) were analyzed with high-throughput sequencing.Part of the remaining samples were detected by real-time polymerase chain reaction (real-time PCR), and the results were used to validate the results of high-throughput sequencing. Gene Ontology (GO) analysis and KEGG signaling pathway analysis were performed on differentially expressed genes. RESULTS: There were 5 257 different lncRNAs between the control group and the NEC group. The results of up-regulated lncRNAs (NONHSAG008675.3, NONHSAG020715.2, NONHSAG038187.2) and down-regulated lncRNA (NONHSAG028744.3) were confirmed to be consistent with the results of high-throughput sequencing. Expressions of DUOX2, IL-6, TNF, and SAA1 were up-regulated in intestinal tissues of NEC. GO analysis showed that the different lncRNAs were involved in regulation of stimulation, molecular junction and function, and signal transduction and transcription. KEGG analysis identified mainly biological pathways involved in inflammatory bowel disease, PI3K-Akt, NF-κB, etc. CONCLUSIONS: LncRNAs might be involved in the pathogenesis of NEC and the inflammation-related lncRNAs may be one of the key factors.


Assuntos
Enterocolite Necrosante , RNA Longo não Codificante , Animais , Oxidases Duais , Enterocolite Necrosante/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Intestinos , Fosfatidilinositol 3-Quinases , RNA Longo não Codificante/genética
17.
Oral Maxillofac Surg Clin North Am ; 32(4): 583-591, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33004149

RESUMO

Preprosthetic surgery remains a work horse of dentoalveolar surgery. Advances in rehabilitation of the edentulous mouth with the use of endosseous osseointegrating dental implants and dermal matrix substitutes have changed the narrative of traditional preprosthetic surgery while maintaining some fundamental principles. An outline of the basic techniques in preprosthetic dentoalveolar surgery is discussed in the setting of these technological and tissue engineering advances.


Assuntos
Implantação Dentária Endo-Óssea , Animais , Cavalos , Humanos
18.
Cells ; 9(10)2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998369

RESUMO

The vitamin K-dependent factors protein S (PROS1) and growth-arrest-specific gene 6 (GAS6) and their tyrosine kinase receptors TYRO3, AXL, and MERTK, the TAM subfamily of receptor tyrosine kinases (RTK), are key regulators of inflammation and vascular response to damage. TAM signaling, which has largely studied in the immune system and in cancer, has been involved in coagulation-related pathologies. Because of these established biological functions, the GAS6-PROS1/TAM system is postulated to play an important role in SARS-CoV-2 infection and progression complications. The participation of the TAM system in vascular function and pathology has been previously reported. However, in the context of COVID-19, the role of TAMs could provide new clues in virus-host interplay with important consequences in the way that we understand this pathology. From the viral mimicry used by SARS-CoV-2 to infect cells, to the immunothrombosis that is associated with respiratory failure in COVID-19 patients, TAM signaling seems to be involved at different stages of the disease. TAM targeting is becoming an interesting biomedical strategy, which is useful for COVID-19 treatment now, but also for other viral and inflammatory diseases in the future.


Assuntos
Infecções por Coronavirus/complicações , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pneumonia Viral/complicações , Proteína S/metabolismo , Trombose/etiologia , Imunidade Adaptativa , Animais , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Hemostasia , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Trombose/sangue , Trombose/imunologia , c-Mer Tirosina Quinase/metabolismo
19.
J Exp Med ; 217(12)2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33000129

RESUMO

Developing effective in vivo models for SARS-CoV-2 infection is crucial for mechanistic studies of COVID-19 disease progression. In this issue of JEM, Israelow et al. (https://doi.org/10.1084/jem.20201241) generate a model that supports SARS-CoV-2 infection in mice, which they use to characterize type I IFN-driven pulmonary inflammation.


Assuntos
Infecções por Coronavirus , Interferon Tipo I , Pandemias , Pneumonia Viral , Síndrome Respiratória Aguda Grave , Animais , Betacoronavirus , Camundongos
20.
Sci Rep ; 10(1): 16200, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004837

RESUMO

The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC50) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 103-, 104- and 103-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Digoxina/farmacologia , Ouabaína/farmacologia , Replicação Viral , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Animais , Betacoronavirus/fisiologia , Chlorocebus aethiops , Cloroquina/farmacologia , Concentração Inibidora 50 , Células Vero
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