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1.
Biochem Pharmacol ; : 114907, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007523

RESUMO

Phosphorylation of proteins is one of the most extensively investigated post-translational protein modifications. Threonine, serine and tyrosine in proteins are the most commonly phosphorylated amino acids. Dysregulated cancer-related signaling pathways due to aberrant phosphorylation status of the key protein(s) in these pathways exist in most malignancies. Intensive studies in the recent decade have implicated long non-coding RNAs (lncRNAs) in the precise regulation of protein phosphorylation in cancers. In this review, we systematically delve into recent advance that underlines the multidimensional role of lncRNAs in modulating protein phosphorylation, regulating cancerous signaling and impacting prognosis of gastrointestinal (GI) cancers including hepatocellular carcinoma, colorectal cancer, gastric cancer, esophageal cancer, and pancreatic cancer. LncRNAs regulate protein phosphorylation via directly binding to the target protein(s), interacting with the partner protein(s) of the target protein(s) or lncRNAs-encoded small peptides. Although there are still extensive studies on disclosing the intricate interactions between lncRNAs and proteins and their impacts on protein phosphorylation, we believe that targeting lncRNAs controlling phosphorylation of key protein(s) in cancerous signaling pathways might provide novel paths for precision therapeutics of GI cancers in the future.

2.
Ecotoxicol Environ Saf ; 229: 113093, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34942419

RESUMO

Polycyclic musks (PMs) have drawn increased attention in recent years because of their persistence, bioaccumulation and toxicity. As two typical PMs contaminants, tonalide (AHTN) and galaxolide (HHCB) are widely detected in sediment worldwide. Acute and chronic toxicity data of AHTN and HHCB to freshwater and seawater organisms in water and sediments are collected and screened. The predicted no effect concentrations (PNECsediment) for AHTN and HHCB is derived according to the equilibrium partitioning method recommended by the EU technical guidance document (TGD) and the species sensitivity distribution (SSD) method based on the measured sediment toxicity data. The concentration levels of AHTN and HHCB are investigated and evaluated in freshwater and seawater sediments. Results show the difference between native and non-native freshwater species is not statistically significant. AHTN is more toxic to freshwater and seawater organisms than HHCB, and seawater organisms are more sensitive to 2 musks than freshwater organisms. The chronic PNECsediment values of AHTN and HHCB are 194.48 and 416.47 ng/g in freshwater sediment, 88.93 and 128.34 ng/g in seawater sediment respectively. The AHTN and HHCB linear correlation analysis exhibited a strong positive linear correlation in both domestic (R2=0.9054) and foreign (R2 = 0.9645) sediment. Preliminary risk assessment shows that the risks posed by AHTN and HHCB in sediment based on individual or combined concentrations of two musks are at medium to high levels in some regions. Further risk assessment results indicate that, for HHCB, 1.72% of foreign freshwater sediment may pose an ecological risk to 5% species; for AHTN, 8.06% of foreign freshwater sediment and 1.02% of domestic freshwater sediment may pose an ecological risk to 5% species, and 5.86% of seawater sediment may pose an ecological risk to 5% species. The above results indicate that there are some negligible risks in domestic and foreign sediments posed by these two musks, we should continue to pay attention to the toxic effects and pollution level of both musks in environment.


Assuntos
Poluentes Químicos da Água , Benzopiranos , Medição de Risco , Tetra-Hidronaftalenos/análise , Tetra-Hidronaftalenos/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
3.
Int J Biol Macromol ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34890635

RESUMO

Non-derivatizing, high-efficiency and low-toxicity solvents are important for studying the dissolution behavior and potential applications of starch. In this study, we investigated the starch dissolution mechanism and molecular conformation in KOH/thiourea aqueous solutions and compared these with KOH/urea and KOH aqueous solutions. Solubility analysis revealed that the KOH/thiourea solution demonstrates a better ability to dissolve corn starch than KOH/urea and KOH solutions. Rheological behavior and dynamic and static light scattering indicated that starch is stable in KOH/thiourea solution and exists as a regular star structure. Fourier transform infrared spectroscopy, 13C NMR, and molecular dynamics simulations indicated that hydrated K+ and OH- destroy the strong starch hydrogen bond interactions; thiourea hydrate self-assembles into a shell surrounding the starch-KOH complex through interaction with KOH, whereas there is no direct strong interaction between urea and KOH. Therefore, adding thiourea to a KOH solution can promote dissolution and prevent self-aggregation of the starch chain.

4.
Food Nutr Res ; 652021.
Artigo em Inglês | MEDLINE | ID: mdl-34908920

RESUMO

Background: Coronavirus disease 2019 (COVID-19) outbreak is progressing rapidly, and poses significant threats to public health. A number of clinical practice results showed that traditional Chinese medicine (TCM) plays a significant role for COVID-19 treatment. Objective: To explore the active components and molecular mechanism of semen armeniacae amarum treating COVID-19 by network pharmacology and molecular docking technology. Methods: The active components and potential targets of semen armeniacae amarum were retrieved from traditional Chinese medicine systems pharmacology (TCMSP) database. Coronavirus disease 2019-associated targets were collected in the GeneCards, TTD, OMIM and PubChem database. Compound target, compound-target pathway and medicine-ingredient-target disease networks were constructed by Cytoscape 3.8.0. Protein-protein interaction (PPI) networks were drawn using the STRING database and Cytoscape 3.8.0 software. David database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The main active components were verified by AutoDock Vina 1.1.2 software. A lipopolysaccharide (LPS)-induced lung inflammation model in Institute of Cancer Research (ICR) mice was constructed and treated with amygdalin to confirm effects of amygdalin on lung inflammation and its underlying mechanisms by western blot analyses and immunofluorescence. Results: The network analysis revealed that nine key, active components regulated eight targets (Proto-oncogene tyrosine-protein kinase SRC (SRC), interleukin 6 (IL6), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 3 (MAPK3), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), HRAS proto-oncogene (HRAS), caspase-3 (CASP3)). Gene ontology and KEGG enrichment analysis suggested that semen armeniacae amarum plays a role in COVID-19 by modulating 94 biological processes, 13 molecular functions, 15 cellular components and 80 potential pathways. Molecular docking indicated that amygdalin had better binding activity to key targets such as IL6, SRC, MAPK3, SARS coronavirus-2 3C-like protease (SARS-CoV-2 3CLpro) and SARS-CoV-2 angiotensin converting enzyme II (ACE2). Experimental validation revealed that the lung pathological injury and inflammatory injury were significantly increased in the model group and were improved in the amygdalin group. Conclusion: Amygdalin is a candidate compound for COVID-19 treatment by regulating IL6, SRC, MAPK1 EGFR and VEGFA to involve in PI3K-Akt signalling pathway, VEGF signalling pathway and MAPK signalling pathway. Meanwhile, amygdalin has a strong affinity for SARS-CoV-2 3CLpro and SARS-CoV-2 ACE2 and therefore prevents the virus transcription and dissemination.

5.
Pak J Med Sci ; 37(7): 1727-1733, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912386

RESUMO

Objectives: To investigate whether a combination of clinical risk factors, early pregnancy serum markers, and uterine artery pulsatility index (UTPI) can be used to predict twin preeclampsia (PE). Methods: This case control study included women with twin pregnancies who had undergone obstetrics treatments and gave birth at the Huzhou Maternity and Child Health Care Hospital from October 2018 to November 2020. Patients with PE comprised study group, and patients without PE comprised control group based on selection criteria and a 1:1 ratio. Statistical analysis was performed using clinical risk factors, early pregnancy serum markers, and UTPIs, and the area under the receiver operating curve (AUC. Sensitivity, and the specificity of different combinations of these variables were calculated to predict PE in women with twin pregnancy. Results: Logistic regression analysis revealed four independent predictors for the onset of PE during twin pregnancies: first delivery (OR, 7.51; P=0.045), conception method (OR, 7.11; P=0.036), ß-HCG level (per SD OR, 2.73; P=0.026), and UTPI (OR, 0.17; P=0.043). First-delivery and IVF pregnancy methods both lead to a 7-fold increase in the PE risk during twin pregnancies. Every one sigma (standard deviation) increase in the ß-HCG level led to a 2.73-fold increase in the PE risk. Every UTPI increment by 1.0 reduces the risk of PE by 83%. The prediction efficiencies were based on an AUC of 0.837, a sensitivity of 69%, and a specificity of 92% for the clinical risk factors; an AUC of 0.800, a sensitivity of 81%, and specificity of 78% for the ß-HCG level, and an AUC of 0.814, a sensitivity of 88%, and a specificity of 65% for the UTPI. AUC was 0.928, sensitivity 85%, and a specificity 88% after applying the three types of indicators together for prediction. Conclusions: By combining early pregnancy serum markers (ß-HCG), and UTPI, the predictive value for PE during twin pregnancy is improved together with its sensitivity and specificity.

6.
Pak J Med Sci ; 37(7): 1902-1907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912415

RESUMO

Objectives: To evaluate the clinical efficacy of immunotherapy combined with chemotherapy in patients with advanced gastric cancer and its effect on nutritional status and changes of peripheral blood T lymphocyte subsets. Methods: Sixty patients with locally advanced gastric cancer who were admitted by Affiliated Hospital of Hebei University from March 2020 to February 2021 were enrolled and randomly divided into two groups, with 30 cases in each group. The control group was treated with FOLFOX4 chemotherapy, while the experimental group was additively treated with cindilizumab on the basis of control group. The incidence of adverse reactions, clinical efficacy, improvement of nutritional and physical status, and changes in the levels of T lymphocyte subgroups in the two groups were compared and analyzed. Results: The total effective rate was 70% in the experimental group, which was better than 43.3% of the control group (p=0.04). The improvement rate of performance status (ECOG) score and nutritional indicators in the experimental group was significantly better than that in the control group (p<0.05). Moreover, the indicators of CD3+, CD4+, CD4+/CD8+ in the experimental group were significantly higher than those in the control group after treatment, with statistically significant differences (CD3+, p=0.01; CD4 +, p= 0.02; CD4+/CD8+, p=0.01). Conclusion: Immunotherapy combined with chemotherapy has a significant effect on locally advanced gastric cancer patients, with significant improvement in physical strength and nutritional status, significant improvement in T lymphocyte function, and no obvious adverse reactions. It is worth promoting in clinical application.

7.
Exp Ther Med ; 22(5): 1312, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630666

RESUMO

Alcoholic liver disease (ALD) is a worldwide health problem with limited therapeutic options, which is associated with gut-derived endotoxins, particularly lipopolysaccharide (LPS) and intestinal microbiota dysbiosis. Recently, probiotics, synbiotics and other food additive interventions have been shown to be effective in decreasing or preventing the progression of ALD. Bacillus subtilis (B. subtilis) and its metabolic products are widely used as food additives to maintain intestinal health, but the protective effects of B. subtilis against alcohol-induced liver injury are poorly understood. In the present study a chronic alcohol-induced liver injury model was constructed based on the Lieber-DeCarli diet and it aimed to determine whether dietary B. subtilis supplementation may alleviate alcohol-induced liver injury. Results revealed that prophylactic B. subtilis supplementation partially restored gut microbiota homeostasis and relieved alcohol-induced intestinal barrier injury, which significantly decreased the translocation of bacterial endotoxins to the blood. In addition, the decreased serum LPS alleviated hepatic inflammation via the toll-like receptor 4 pathway, resulting in improved hepatic structure and function. These results demonstrated that dietary B. subtilis supplementation imparts novel hepatoprotective functions by improving intestinal permeability and homeostasis.

8.
J Diabetes ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617682

RESUMO

BACKGROUND: We aimed to report pregnancy outcomes of women with type 1 diabetes (T1D) in China, on which data were sparse. METHODS: This is a nationwide retrospective study conducted in 11 general medical centers in 8 cities across China. We investigated the clinical data of all women who attended these centers with a singleton pregnancy and whose pregnancy ended between 1 January 2004 and 31 December 2014. Pregnancies of women with pregestational T1D were ascertained and compared with those of women without T1D. RESULTS: From over 300 000 pregnancies over the 11-year study period, we identified 265 singleton pregnancies of women with T1D. One maternal death was documented among 265 (0.37%) women with T1D and 83 among 318 486 (0.03%) women without T1D. Women with T1D suffered from higher rates of pregnancy loss (13.21% vs 2.92%, crude risk ratio [cRR] 5.08 [95% CI, 3.56-7.26]) and preeclampsia (17.74% vs 4.20%, cRR 4.94 [95% CI, 3.60-6.77]) compared with those without T1D. Infants of these women with T1D had elevated rates of neonatal death (5.65% vs 0.16%, cRR 37.36 [95% CI, 21.21-65.82]) and congenital malformation(s) (8.26% vs 3.53%, cRR 2.46 [95% CI, 1.54-3.93]) compared with those of women without T1D. No significant improvement in pregnancy outcomes in women with T1D was observed over the period 2004 to 2014. CONCLUSIONS: Pregnancy outcomes were persistently poor in women with T1D during 2004 to 2014 in China. Pregnancy care needs to be improved to reduce adverse pregnancy outcomes among Chinese women with T1D.

9.
J Breath Res ; 15(4)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34610588

RESUMO

Gastric cancer is a common malignancy, being the fifth most frequently diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide. Diagnosis of gastric cancer at the early stage is critical to effectively improve the survival rate. However, a substantial proportion of patients with gastric cancer in the early stages lack specific symptoms or are asymptomatic. Moreover, the imaging techniques currently used for gastric cancer screening, such as computed tomography and barium examination, are usually radioactive and have low sensitivity and specificity. Even though endoscopy has high accuracy for gastric cancer screening, its application is limited by the invasiveness of the technique. Breath analysis is an economic, effective, easy to perform, non-invasive detection method, and has no undesirable side effects on subjects. Extensive worldwide research has been conducted on breath volatile organic compounds (VOCs), which reveals its prospect as a potential method for gastric cancer detection. Many interesting results have been obtained and innovative methods have been introduced in this subject; hence, an extensive review would be beneficial. By providing a comprehensive list of breath VOCs identified by gastric cancer would promote further research in this field. This review summarizes the commonly used technologies for exhaled breath analysis, focusing on the application of analytical instruments in the detection of breath VOCs in gastric cancers, and the alterations in the profile of breath biomarkers in gastric cancer patients are discussed as well.

11.
Medicine (Baltimore) ; 100(40): e27396, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622844

RESUMO

BACKGROUND: Western medicine has played an essential role in treating poststroke insomnia (PSI) in China, and traditional Chinese medicine therapy based on Chinese characteristics is also effective. Combined with China's national conditions, we plan to conduct this systematic review and meta-analysis to compare the efficacy of integrated traditional Chinese medicine and Western medicine (INTEGRATED TCM and WM) therapy and Western medicine alone for PSI. METHODS: We will search the following 5 electronic databases: PubMed, Wanfang, Chinese biomedical literature database, the Chongqing VIP Chinese Science and Technology Periodical, and China national knowledge infrastructure. Randomized controlled trials that compared the efficacy of INTEGRATED TCM and WM with Western medicine alone in the treatment of PSI will be considered. Primary outcomes have Treatment effectiveness rate, and Pittsburgh sleep quality index. Secondary outcomes include traditional Chinese medicine syndrome score, Athens insomnia scale, the incidence of adverse reactions, and outcome follow-up. Based on the eligibility criteria, we will conduct literature screening and data extraction. The quality of the included literature will be evaluated using the Cochrane risk of bias tools. We will use Review Manager software (Version 5.3) for data synthesis and statistical analyses. If sources of heterogeneity exist, we will perform a subgroup analysis or sensitivity analysis. A funnel plot will be used to analyze publication bias. RESULTS: This study will provide evidence-based medicine evidence for treatment of PSI with INTEGRATED TCM and WM in terms of its efficacy. CONCLUSION: This systematic review aims to provide new options for INTEGRATED TCM and WM treatment of PSI in terms of its efficacy.


Assuntos
Medicina Tradicional Chinesa/métodos , Distúrbios do Início e da Manutenção do Sono/terapia , Acidente Vascular Cerebral/complicações , Humanos , Metanálise como Assunto , Distúrbios do Início e da Manutenção do Sono/etiologia , Revisões Sistemáticas como Assunto
12.
J Int Med Res ; 49(10): 3000605211039473, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34648414

RESUMO

OBJECTIVE: To investigate the potential correlation between the Arg188His (rs3218536) polymorphism of X-ray repair cross-complementing 2 (XRCC2) and colorectal cancer (CRC) risk, as the association remains unclear. METHODS: The CNKI, PubMed, EMBASE and Cochrane library databases were systematically searched for relevant studies published up to July 2021. Data were extracted from included studies, and analysed for pooled or subgroup odds ratios (ORs) with 95% confidence intervals (CIs) using STATA 12.0 software. RESULTS: Seven published studies were included. Pooled analysis revealed that the XRCC2 Arg188His polymorphism was associated with increased CRC risk (His versus Arg: OR 1.14, 95% CI 1.01, 1.29). Trial Sequential Analysis to test the power of the results showed that they were unreliable and the meta-analysis required additional studies. CONCLUSION: The current meta-analysis suggests that the XRCC2 Arg188His polymorphism may be a risk factor for CRC.


Assuntos
Neoplasias Colorretais , Complemento C2 , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Raios X
13.
Sci Rep ; 11(1): 21330, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716392

RESUMO

JAZ is a plant-specific protein family involved in the regulation of plant development, abiotic stresses, and responses to phytohormone treatments. In this study, we carried out a bioinformatics analysis of JAZ genes in turnip by determining the phylogenetic relationship, chromosomal location, gene structure and expression profiles analysis under stresses. The 36 JAZ genes were identified and classified into four subfamilies (ZML, JAZ, PPD and TIFY). The JAZ genes were located on 10 chromosomes. Two gene pairs were involved in tandem duplication events. We identified 44 collinear JAZ gene pairs in the turnip genome. Analysis of the Ka/Ks ratios indicated that the paralogs of the BrrJAZ family principally underwent purifying selection. Expression analysis suggested JAZ genes may be involved in the formation of turnip tuberous root, and they also participated in the response to ABA, SA, MeJA, salt stress and low-temperature stress. The results of this study provided valuable information for further exploration of the JAZ gene family in turnip.

14.
Theranostics ; 11(18): 8797-8812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522212

RESUMO

Rationale: Neprilysin (NEP) is a major endogenous catabolic enzyme of amyloid ß (Aß). Previous studies have suggested that increasing NEP expression in animal models of Alzheimer's disease had an ameliorative effect. However, the underlying signaling pathway that regulates NEP expression remains unclear. The aryl hydrocarbon receptor (AhR) is a ligand-activated cytoplasmic receptor and transcription factor. Recent studies have shown that AhR plays essential roles in the central nervous system (CNS), but its physiological and pathological roles in regulating NEP are not entirely known. Methods: Western blotting, immunofluorescence, quantitative RT-PCR and enzyme activity assay were used to verify the effects of AhR agonists on NEP in a cell model (N2a) and a mouse model (APP/PS1). Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to investigate the roles of AhR in regulating NEP transcription. Object recognition test and the Morris water maze task were performed to assess the cognitive capacity of the mice. Results: Activating AhR by the endogenous ligand L-Kynurenine (L-KN) or FICZ, or by the exogenous ligand diosmin or indole-3-carbinol (I3C) significantly increases NEP expression and enzyme activity in N2a cells and APP/PS1 mice. We also found that AhR is a direct transcription factor of NEP. Diosmin treatment effectively ameliorated the cognitive disorder and memory deficit of APP/PS1 transgenic mice. By knocking down AhR or using a small molecular inhibitor targeting AhR or NEP, we found that diosmin enhanced Aß degradation through activated AhR and increased NEP expression. Conclusions: These results indicate a novel pathway for regulating NEP expression in neurons and that AhR may be a potential therapeutic target for the treatment of Alzheimer's disease.

15.
Water Res ; 204: 117632, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34536686

RESUMO

The spatiotemporal variations, influencing factors and potential sources, as well as the ecological/health risks of polycyclic aromatic hydrocarbons (PAHs) were systematically investigated in seawater, sediment, and fish from Xiangshan Bay, China, one of the most important and oldest domestic marine aquaculture bases. The average concentrations of ΣPAHs in seawater, sediment and fish were 150 ± 70.0 ng/L, 276 ± 271 µg/kg (dry weight, dw), and 434 ± 151 µg/kg (dw), respectively. Naphthalene, phenanthrene, fluoranthene, benzo(b)fluoranthene and pyrene were the dominant contaminants in all samples. The highest PAH concentrations in the seawater and sediment samples occurred in the inner bay where the mariculture and industry are clustered. Seasonal differences were observed in the seawater samples but not in the sediment samples. Among all 15 fish species, large yellow croaker (Larimichthys crocea) (775 µg/kg (dw)), red drum (Sciaenops ocellatus) (749 µg/kg (dw)), and flathead grey mullet (Mugil cephalus) (637 µg/kg (dw)) had relatively high PAH accumulation concentrations in muscle tissue. According to the molecular diagnostic ratio method, the PAHs in seawater mainly originated from a mixed source of petroleum and combustion, whereas biomass/coal combustion sources were identified for sediment. The results obtained from the risk quotient (for seawater), sediment quality guidelines and toxic equivalence quotients (for seawater and sediment) methods showed that the ecological risks posed by PAHs were generally at a low to moderate level. Potentially toxic effects existed from PAH-contaminated fish consumption, and the resulting potential carcinogenic risk was also slightly higher than the recommended guidelines (10-6).


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Animais , Ecossistema , Monitoramento Ambiental , Sedimentos Geológicos , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Poluentes Químicos da Água/análise
16.
J Gastrointest Oncol ; 12(4): 1939-1943, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532140

RESUMO

Duodenal adenocarcinoma (DA) is a subtype of small bowel adenocarcinoma (SBA). Compared with gastrointestinal cancers such as colorectal cancer and gastric cancer, SBA is less common. For patients with advanced and metastatic DA, chemotherapies are usually extrapolated from colorectal cancer and gastric cancer but the therapeutic effects remain undefined. Herein, we reported a 50-year-old female patient whom was diagnosed as stage IV DA with metastasis to both lungs and retroperitoneal lymph nodes. The next generation sequencing (NGS) using a panel consisting of 168 cancer related genes revealed amplification of the HER2/ERBB2 gene which has been a well-recognized therapeutic target among various tumor types. The anti-HER2 targeted therapy trastuzumab was used in combination with XELOX (oxaliplatin and capecitabine) as the first line treatment. The patient achieved partial response (PR) and had progression-free survival (PFS) of six months. After progressive disease (PD), the patient started the second line treatment with trastuzumab and PD1 inhibitors and remained stable disease (SD) with PFS for three months. The use of trastuzumab in neoadjuvant and adjuvant settings have been reported in sporadic cases. To the best of our knowledge, it is the first report to use anti-HER2 therapy and PD-1 inhibition as systemic therapy for advanced DA patients.

17.
Proc Natl Acad Sci U S A ; 118(35)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34417345

RESUMO

Replicability takes on special meaning when researching phenomena that are embedded in space and time, including phenomena distributed on the surface and near surface of the Earth. Two principles, spatial dependence and spatial heterogeneity, are generally characteristic of such phenomena. Various practices have evolved in dealing with spatial heterogeneity, including the use of place-based models. We review the rapidly emerging applications of artificial intelligence to phenomena distributed in space and time and speculate on how the principle of spatial heterogeneity might be addressed. We introduce a concept of weak replicability and discuss possible approaches to its measurement.

18.
J Alzheimers Dis ; 83(2): 897-906, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334408

RESUMO

BACKGROUND: The global race-dependent association of Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. OBJECTIVE: This study aims to determine how race and APOE genotype affect the risks for AD. METHODS: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. RESULTS: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOEɛ4 was a risk factor for AD, whereas APOEɛ2 protected against it. The effects of APOEɛ4 and ɛ2 on AD risk were distinct in various races, and they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOEɛ4/ɛ4 and lower frequency of APOEɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. CONCLUSION: Our meta-analysis suggests that the association of APOE genotypes and AD differ among races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.

19.
Autophagy ; 17(11): 3887-3888, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34455934

RESUMO

For network rewiring and information storage in the brain, late phase long-term synaptic depression (L-LTD) requires the long-lasting reorganization of cellular resources. We found that activation of GRIN/NMDAR recruits transcription-dependent autophagy for synaptic turnover to support L-LTD. Activity-dependent CRTC1 synapto-nuclear translocation increases nuclear CRTC1 that competes with FXR for binding to CREB; this in turn enhances the direct binding between CRTC1-CREB and macroautophagy/autophagy gene promoters. Synergistic actions of CRTC1-CREB are preferentially turned on by LTD-inducing stimuli and switched off by genetic knockdown of CREB or CRTC1, or acutely activating FXR. Disrupted CRTC1-CREB signaling impairs activity-driven loss of surface GRIA/AMPARs and DLG4/PSD-95, and selectively prevents GRIN/NMDAR-dependent L-LTD, which are rescued by enhancing MTOR-regulated autophagy. These findings suggest a novel mechanism in L-LTD, in which brief synaptic activities recruit long-lasting autophagy through excitation-transcription coupling for ensuing synaptic remodeling.

20.
Ageing Res Rev ; 71: 101450, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34419673

RESUMO

BACKGROUND: Reduced cerebral blood flow (CBF) contributes to the pathophysiology of Alzheimer's disease (AD). However, it is unclear whether there is a spatial-temporal-specific pattern of changed CBF in AD progression. METHODS: We systematically screened literature databases for cross-sectional and longitudinal studies reporting resting CBF or CBF velocity (CBFv) among patients with AD, mild cognitive impairment (MCI), and healthy controls (HCs). Standardised mean differences (SMDs) for CBF and mean differences (MDs) for CBFv were calculated. Quality assessments, meta-analysis, subgroup analysis, and meta-regression were subsequently performed (PROSPERO: CRD42020207548). RESULTS: Overall, 244 studies comprising 13,644 participants and 60 regions were included. Compared with HCs, AD subjects had decreased resting CBF throughout the brain (SMD range: -1.87 to -0.32), especially within the posterior cingulate and temporal-parietal regions. However, MCI subjects presented decreased CBF in ten regions with modest effects (SMD range: -0.86 to -0.25), especially in the precuneus. We identified the decreased CBF in the temporal, parietal, and hippocampal regions was associated with the lower AD Mini-Mental State Examination scores. CONCLUSIONS: Our findings suggest that the spatial-temporal pattern of CBF decreased from the precuneus, posterior cingulate and temporal-parietal regions to broader areas with progression from HC to MCI to AD, supporting the incorporation of CBF into the AD research framework.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Circulação Cerebrovascular , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética
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