RESUMO
The cell cycle consists of successive events that lead to the generation of new cells. The cell cycle is regulated by different cyclins, cyclin-dependent kinases (CDKs) and their inhibitors, such as p27Kip1. At the nuclear level, p27Kip1 has the ability to control the evolution of different phases of the cell cycle and oppose cell cycle progression by binding to CDKs. In the cytoplasm, diverse functions have been described for p27Kip1, including microtubule remodeling, axonal transport and phagocytosis. In Alzheimer's disease (AD), alterations to cycle events and a purported increase in neurogenesis have been described in the early disease process before significant pathological changes could be detected. However, most neurons cannot progress to complete their cell division and undergo apoptotic cell death. Increased levels of both the p27Kip1 levels and phosphorylation status have been described in AD. Increased levels of Aß42, tau hyperphosphorylation or even altered insulin signals could lead to alterations in p27Kip1 post-transcriptional modifications, causing a disbalance between the levels and functions of p27Kip1 in the cytoplasm and nucleus, thus inducing an aberrant cell cycle re-entry and alteration of extra cell cycle functions. Further studies are needed to completely understand the role of p27Kip1 in AD and the therapeutic opportunities associated with the modulation of this target.
Assuntos
Doença de Alzheimer/patologia , Ciclo Celular , Inibidor de Quinase Dependente de Ciclina p27/química , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Processamento de Proteína Pós-Traducional , Doença de Alzheimer/metabolismo , Animais , HumanosRESUMO
Major depressive disorder (MDD) seriously threatens human health. BRICS, known as an acronym for "Brazil, Russia, India, China, and South Africa," were also actively carrying out researches on MDD. This study aimed to conduct a bibliometric study of research on MDD conducted by the BRICS. By searching in the Web of Science and using the software Vosviewer and Citespace as analysis tools, this study analyzed the cooperation network at the country, institution, author-specific levels, the research hotspots and trends from BRICS between 2003-2022. A total of 10,911 articles were finally included. Our findings showed that researches on MDD from BRICS rapidly increased during the past two decades. China and India have shown explosive growth, while South Africa has the largest average "Usage Count" and "Time Cited". The current cooperation partners of the BRICS were mainly high-income countries and other developing countries with similar cultures, languages, and geographical locations. Institutions in high-income countries served as the main bridges for BRICS cooperation, while at the author level, some core authors in the BRICS countries serve as centers. China showed a flexible model in domestic partnership, but institutions and authors in the other four countries have gathered to cooperate within the group. BRICS research on MDD mainly focused on cognitive science, brain science, epidemiology, and disease mechanisms. The keywords"gut microbiota", "network analysis," "machine learning" and "sleep quality" showed explosive growth and might become research hotspots in the near future. This bibliometric analysis provided a science knowledge graph and references for other researchers.
Assuntos
Transtorno Depressivo Maior , Humanos , Encéfalo , Bibliometria , Brasil , ChinaRESUMO
Background: Garcinia cambogia is widely used as a weight-loss supplement, and it is reported to be negatively associated with metabolic diseases including insulin resistance (IR), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and dyslipidemia. Objective: This study aimed to investigate the effect of G. cambogia water extract (GE) on high-fat diet (HFD)-induced obesity, IR, and hepatic lipid accumulation. Design: C57BL/6 male mice were fed HFD with or without GE, GED and GEP for 16 weeks, and the mice were subjected to insulin tolerance tests and liver histological analysis. The hydroxycitric acid (HCA) levels of GE, GED, and GEP were measured by high-performance liquid chromatography. Results: The results showed that GE significantly reduced HFD-induced body weight gain (P < 0.001), alleviated IR (P < 0.01), reduced serum total cholesterol (TC) (P < 0.001), and attenuated HFD-induced hepatic lipid accumulation. To investigate the constituent that was responsible for these effects, we separated GE into the component that dissolved in ethanol (GED) and the component that was precipitated by ethanol (GEP). Further mouse experiments showed that both GED and GEP were effective, but GED (which was used at a dose of 4 g/L) was more effective than GEP (which was used at a lower dose of 1 g/L). The HCA levels in GED and GEP were similar, although less than in GE. HCA may be the effective component in GE. Conclusion: This study provides evidence that G. cambogia can be used as a natural supplement to alleviate IR and hepatic lipid accumulation.
RESUMO
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease. AD is the main cause of dementia worldwide and aging is the main risk factor for developing the illness. AD classical diagnostic criteria rely on clinical data. However, the development of a biological definition of AD using biomarkers that reflect the underling neuropathology is needed. Content: The aim of this review is to describe the main outcomes when measuring classical and novel biomarkers in biological fluids or neuroimaging. Summary: Nowadays, there are three classical biomarkers for the diagnosis of AD: Aß42, t-Tau and p-Tau. The diagnostic use of cerebrospinal fluid biomarkers is limited due to invasive collection by lumbar puncture with potential side effects. Plasma/serum measurements are the gold standard in clinics, because they are minimally invasive and, in consequence, easily collected and processed. The two main proteins implicated in the pathological process, Aß and Tau, can be visualized using neuroimaging techniques, such as positron emission tomography. Outlook: As it is currently accepted that AD starts decades before clinical symptoms could be diagnosed, the opportunity to detect biological alterations prior to clinical symptoms would allow early diagnosis or even perhaps change treatment possibilities.