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1.
Aging (Albany NY) ; 132021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780352

RESUMO

BACKGROUND: Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are thought to underlie the progression of coronavirus disease 2019 (COVID-19). We sought to further characterize host antiviral and cytokine gene expression in COVID-19 patients based on illness severity. METHODS: In this case-control study, we retrospectively analyzed 46 recovered COVID-19 patients and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We assessed changes in antiviral gene expression between healthy controls and patients with mild/moderate (MM) and severe/critical (SC) disease. RESULTS: We found that type I interferon signaling (IFNA2, TLR8, IFNA1, IFNAR1, TLR9, IRF7, ISG15, APOBEC3G, and MX1) and genes encoding proinflammatory cytokines (IL12B, IL15, IL6, IL12A and IL1B) and chemokines (CXCL9, CXCL11 and CXCL10) were upregulated in patients with MM and SC disease. Moreover, we found that IFNA1, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), and Fas-associated protein with death domain (FADD) were significantly downregulated (P < 0.05) in the SC group compared to the MM group. We also observed that microRNA (miR)-155 and miR-130a levels were markedly higher in the MM group compared to the SC group. CONCLUSION: COVID-19 is associated with the activation of host antiviral genes. Induction of the IFN system appears to be particularly important in controlling SARS-CoV-2 infection, as decreased expression of IFNA1, APOBEC3G and FADD genes in SC patients, relative to MM patients, may be associated with disease progression.

2.
Br J Cancer ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742144

RESUMO

BACKGROUND: Lactate dehydrogenase (LDH) is a critical metabolic enzyme. LDH A (LDHA) overexpression is a hallmark of aggressive malignancies and has been linked to tumour initiation, reprogramming and progression in multiple tumour types. However, successful LDHA inhibition strategies have not materialised in the translational and clinical space. We sought to develop a rational strategy for LDHA suppression in the context of solid tumour treatment. METHODS: We utilised a doxycycline-inducible short hairpin RNA (shRNA) system to generate LDHA suppression. Lactate and LDH activity levels were measured biochemically and kinetically using hyperpolarised 13C-pyruvate nuclear magnetic resonance spectroscopy. We evaluated effects of LDHA suppression on cellular proliferation and clonogenic survival, as well as on tumour growth, in orthotopic models of anaplastic thyroid carcinoma (ATC) and head and neck squamous cell carcinoma (HNSCC), alone or in combination with radiation. RESULTS: shRNA suppression of LDHA generated a time-dependent decrease in LDH activity with transient shifts in intracellular lactate levels, a decrease in carbon flux from pyruvate into lactate and compensatory shifts in metabolic flux in glycolysis and the Krebs cycle. LDHA suppression decreased cellular proliferation and temporarily stunted tumour growth in ATC and HNSCC xenografts but did not by itself result in tumour cure, owing to the maintenance of residual viable cells. Only when chronic LDHA suppression was combined with radiation was a functional cure achieved. CONCLUSIONS: Successful targeting of LDHA requires exquisite dose and temporal control without significant concomitant off-target toxicity. Combinatorial strategies with conventional radiation are feasible as long as the suppression is targeted, prolonged and non-toxic.

3.
Theranostics ; 11(10): 4790-4808, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754028

RESUMO

Rationale: Doxorubicin is a widely used anticancer drug. However, its major side effect, cardiotoxicity, results from cardiomyocyte loss that causes left ventricle (LV) wall thinning, chronic LV dysfunction and heart failure. Cardiomyocyte number expansion by thyroid hormone (T3) during preadolescence is suppressed by the developmental induction of an ERK1/2-specific dual specificity phosphatase 5 (DUSP5). Here, we sought to determine if a brief course of combined DUSP5 suppression plus T3 therapy replaces cardiomyocytes lost due to preexisting doxorubicin injury and reverses heart failure. Methods: We used in vivo-jetPEI to deliver DUSP5 or scrambled siRNA to ~5-week-old C57BL6 mice followed by 5 daily injections of T3 (2 ng/µg body weight). Genetic lineage tracing using Myh6-MerCreMer::Rosa26fs-Confetti mice and direct cardiomyocyte number counting, along with cell cycle inhibition (danusertib), was used to test if this treatment leads to de novo cardiomyocyte generation and improves LV contractile function. Three doses of doxorubicin (20 µg/g) given at 2-weekly intervals, starting at 5-weeks of age in C57BL6 mice, caused severe heart failure, as evident by a decrease in LV ejection fraction. Mice with an ~40 percentage point decrease in LVEF post-doxorubicin injury were randomized to receive either DUSP5 siRNA plus T3, or scrambled siRNA plus vehicle for T3. Age-matched mice without doxorubicin injury served as controls. Results: In uninjured adult mice, transient therapy with DUSP5 siRNA and T3 increases cardiomyocyte numbers, which is required for the associated increase in LV contractile function, since both are blocked by danusertib. In mice with chronic doxorubicin injury, DUSP5 siRNA plus T3 therapy rebuilds LV muscle by increasing cardiomyocyte numbers, which reverses LV dysfunction and prevents progressive chamber dilatation. Conclusion: RNA therapies are showing great potential. Importantly, a GMP compliant in vivo-jetPEI system for delivery of siRNA is already in use in humans, as is T3. Given these considerations, our findings provide a potentially highly translatable strategy for addressing doxorubicin cardiomyopathy, a currently untreatable condition.

4.
J Mater Chem B ; 9(12): 2802-2815, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33710247

RESUMO

Over the past decades, the morbidity and mortality caused by pathogen invasion remain stubbornly high even though medical care has increasingly improved worldwide. Besides, impacted by the ever-growing multidrug-resistant bacterial strains, the crisis owing to the abuse and misuse of antibiotics has been further exacerbated. Among the wide range of antibacterial strategies, polymeric antibacterial materials with diversified synthetic strategies exhibit unique advantages (e.g., their flexible structural design, processability and recyclability, tuneable platform construction, and safety) for extensive antibacterial fields as compared to low molecular weight organic or inorganic antibacterial materials. In this review, polymeric antibacterial materials are summarized in terms of four structure styles and the most representative material platforms to achieve specific antibacterial applications. The superiority and defects exhibited by various polymeric antibacterial materials are elucidated, and the design of various platforms to elevate their efficacy is also described. Moreover, the application scope of polymeric antibacterial materials is summarized with regard to tissue engineering, personal protection, and environmental security. In the last section, the subsequent challenges and direction of polymeric antibacterial materials are discussed. It is highly expected that this critical review will present an insight into the prospective development of antibacterial functional materials.

5.
J Alzheimers Dis ; 80(1): 321-330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33523005

RESUMO

BACKGROUND: Increasing evidence supports an important role of vascular risk in cognitive decline and dementia. OBJECTIVE: This study aimed to examine whether vascular risk was associated with cognitive decline, cerebral hypometabolism, and clinical progression in cognitively intact elders. METHODS: Vascular risk was assessed by the Framingham Heart Study general Cardiovascular disease (FHS-CVD) risk score. The cross-sectional and longitudinal associations of FHS-CVD risk score with cognition and brain glucose metabolism were explored using multivariate linear regression and linear mixed effects models, respectively. The risk of clinical progression conversion was assessed using Kaplan-Meier survival curves and multivariate Cox proportional hazard models. RESULTS: A total of 491 cognitively intact elders were included from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants with high FHS-CVD risk scores had lower baseline Mini-Mental State Examination (MMSE) (p = 0.009), executive function (EF) (p < 0.001), memory function (MEM) (p < 0.001) scores, and F18-fluorodeoxyglucose positron emission tomography (FDG-PET) uptake (p < 0.001) than those with low FHS-CVD risk scores. In longitudinal analyses, individuals with higher FHS-CVD risk scores had greater longitudinal declines in MMSE (p = 0.043), EF (p = 0.029) scores, and FDG-PET uptake (p = 0.035). Besides, individuals with a higher vascular risk had an increased risk of clinical progression (p = 0.004). CONCLUSION: These findings indicated effects of vascular risk on cognitive decline, cerebral hypometabolism, and clinical progression. Early detection and management of vascular risk factors might be useful in the prevention of dementia.

6.
Dev Psychobiol ; 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33615462

RESUMO

Father-infant and mother-infant (one-year-olds) adrenocortical attunement was explored during the Strange Situation Procedure (SSP) among 125 father-infant and 141 mother-infant dyads. Cortisol was assessed at baseline (T1), 20 (T2), and 40 minutes (T3) after the first parent-infant separation. Initial correlations indicated significant associations between father-infant and mother-infant cortisol at each time. Cortisol interdependence was further explored using Actor-Partner Interdependence Models. There was no evidence supporting cortisol interdependence based on within-time residual correlations between parent-infant cortisol, once stability and cross-lagged paths were controlled. Infant cortisol at T2 predicted T3 cortisol for fathers and mothers resulting in a series of follow-up exploratory analyses to examine mediating processes which revealed that infant distress during the SSP predicted infant T2 cortisol, which, in turn, predicted infant negativity during the 15-min mother-infant teaching task that followed the SSP. Among father-infant dyads, infant T2 cortisol predicted infant negativity during father-infant interaction, with infants expressing more negativity having less sensitive fathers. Findings provide little support of parent-infant adrenocortical attunement across either father-infant or mother-infant dyads during the SSP, but preliminary evidence indicates infant distress as a potential mediator. Future research may want to focus on affective and behavioral processes that underlie the concept of parent-infant adrenocortical attunement.

7.
Transl Psychiatry ; 11(1): 89, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531457

RESUMO

The bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer's disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aß42 (p = 0.0008), as well as increased p-tau/Aß42 (p = 0.0001) and t-tau/Aß42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aß42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

8.
Sci Rep ; 11(1): 2266, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33500544

RESUMO

WD40 domain-containing proteins constitute one of the most abundant protein families in all higher plants and play vital roles in the regulation of plant growth and developmental processes. To date, WD40 protein members have been identified in several plant species, but no report is available on the WD40 protein family in mango (Mangifera indica L.). In this study, a total of 315 WD40 protein members were identified in mango and further divided into 11 subgroups according to the phylogenetic tree. Here, we reported mango TRANSPARENT TESTA GLABRA 1 (MiTTG1) protein as a novel factor that functions in the regulation of Arabidopsis root growth and development. Bimolecular fluorescence complementation (BiFC) assay in tobacco leaves revealed that MiTTG1 protein physically interacts with MiMYB0, MiTT8 and MibHLH1, implying the formation of a new ternary regulatory complex (MYB-bHLH-WD40) in mango. Furthermore, the MiTTG1 transgenic lines were more adapted to abiotic stresses (mannitol, salt and drought stress) in terms of promoted root hairs and root lengths. Together, our findings indicated that MiTTG1 functions as a novel factor to modulate protein-protein interactions and enhance the plants abilities to adjust different abiotic stress responses.

9.
Alzheimers Res Ther ; 13(1): 15, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419465

RESUMO

BACKGROUND: Genome-wide association studies have identified more than 30 Alzheimer's disease (AD) risk genes, although the detailed mechanism through which all these genes are associated with AD pathogenesis remains unknown. We comprehensively evaluate the roles of the variants in top 30 non-APOE AD risk genes, based on whether these variants were associated with altered mRNA transcript levels, as well as brain amyloidosis, tauopathy, and neurodegeneration. METHODS: Human brain gene expression data were obtained from the UK Brain Expression Consortium (UKBEC), while other data used in our study were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We examined the association of AD risk allele carrier status with the levels of gene expression in blood and brain regions and tested the association with brain amyloidosis, tauopathy, and neurodegeneration at baseline, using a multivariable linear regression model. Next, we analyzed the longitudinal effects of these variants on the change rates of pathology using a mixed effect model. RESULTS: Altogether, 27 variants were detected to be associated with the altered expression of 21 nearby genes in blood and brain regions. Eleven variants (especially novel variants in ADAM10, IGHV1-68, and SLC24A4/RIN3) were associated with brain amyloidosis, 7 variants (especially in INPP5D, PTK2B) with brain tauopathy, and 8 variants (especially in ECHDC3, HS3ST1) with brain neurodegeneration. Variants in ADAMTS1, BZRAP1-AS1, CELF1, CD2AP, and SLC24A4/RIN3 participated in more than one cerebral pathological process. CONCLUSIONS: Genetic variants might play functional roles and suggest potential mechanisms in AD pathogenesis, which opens doors to uncover novel targets for AD treatment.

10.
J Hazard Mater ; 404(Pt B): 124044, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059153

RESUMO

Bauxite mine tailings can be used as the reserve resources of aluminium and lithium. In this study, a less energy consumption treatment method for extracting aluminium and lithium from bauxite mine tailings has been proposed, which used mixed acid to leach aluminium and lithium from tailings directly, avoided roasting for reducing energy consumption, and obtained effective results.The minerals in the tailings are kaolinite, diaspore, boehmite, anatase and illite, among others. The minerals have fine dissemination sizes and low liberation. Under the leaching conditions of Al and Li of an acid concentration of 60%, a liquid-solid ratio of 4 mL/g, a reaction temperature of 100 °C and a reaction time of 3 h, the highest leaching rates of Al and Li are 88.64% and 96.35%, respectively. In the leaching process, phosphoric acid reacts with Al and Li in the strong acidic environment provided by sulphuric acid to produce heteropoly acids or heteropoly acid salts that dissolve in the solution.

11.
Mol Cancer Ther ; 20(3): 500-511, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33361272

RESUMO

Immune-checkpoint inhibitors and adoptive tumor-infiltrating lymphocyte (TIL) therapies have profoundly improved the survival of patients with melanoma. However, a majority of patients do not respond to these agents, and many responders experience disease relapse. Although numerous innovative treatments are being explored to offset the limitations of these agents, novel therapeutic combinations with immunotherapies have the potential to improve patient responses. In this study, we evaluated the antimelanoma activity of immunotherapy combinations with Telaglenastat (CB-839), a potent glutaminase inhibitor (GLSi) that has favorable systemic tolerance. In in vitro TIL:tumor coculture studies, CB-839 treatment improved the cytotoxic activity of autologous TILs on patient-derived melanoma cells. CB-839 treatment decreased the conversion of glutamine to alpha-ketoglutarate (αKGA) more potently in tumor cells versus TILs in these cocultures. These results suggest that CB-839 may improve immune function in a tumor microenvironment by differentially altering tumor and immune cell metabolism. In vivo CB-839 treatment activated melanoma antigen-specific T cells and improved their tumor killing activity in an immune-competent mouse model of adoptive T-cell therapy. Additionally, the combination of CB-839 with anti-PD1 or anti-CTLA4 antibodies increased tumor infiltration by effector T cells and improved the antitumor activity of these checkpoint inhibitors in a high mutation burden mouse melanoma model. Responsiveness to these treatments was also accompanied by an increase of interferon gamma (IFNγ)-associated gene expression in the tumors. Together, these results provide a strong rationale for combining CB-839 with immune therapies to improve efficacy of these treatments against melanoma.

12.
Sci Rep ; 10(1): 21918, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318551

RESUMO

Cardiomyocytes of newborn mice proliferate after injury or exposure to growth factors. However, these responses are diminished after postnatal day-6 (P6), representing a barrier to building new cardiac muscle in adults. We have previously shown that exogenous thyroid hormone (T3) stimulates cardiomyocyte proliferation in P2 cardiomyocytes, by activating insulin-like growth factor-1 receptor (IGF-1R)-mediated ERK1/2 signaling. But whether exogenous T3 functions as a mitogen in post-P6 murine hearts is not known. Here, we show that exogenous T3 increases the cardiomyocyte endowment of P8 hearts, but the proliferative response is confined to cardiomyocytes of the left ventricular (LV) apex. Exogenous T3 stimulates proliferative ERK1/2 signaling in apical cardiomyocytes, but not in those of the LV base, which is inhibited by expression of the nuclear phospho-ERK1/2-specific dual-specificity phosphatase, DUSP5. Developmentally, between P7 and P14, DUSP5 expression increases in the myocardium from the LV base to its apex; after this period, it is uniformly expressed throughout the LV. In young adult hearts, exogenous T3 increases cardiomyocyte numbers after DUSP5 depletion, which might be useful for eliciting cardiac regeneration.

13.
Haematologica ; Online ahead of print2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33353284

RESUMO

MCL-1 and BCL-2 are both frequently overexpressed in acute myeloid leukemia and critical for the survival of acute myeloid leukemia cells and acute myeloid leukemia stem cells. MCL-1 is a key factor in venetoclax resistance. Using genetic and pharmacological approaches, we discovered that MCL-1 regulates leukemia cell bioenergetics and carbohydrate metabolisms, including the TCA cycle, glycolysis and pentose phosphate pathway and modulates cell adhesion proteins and leukemia-stromal interactions. Inhibition of MCL-1 sensitizes to BCL-2 inhibition in acute myeloid leukemia cells and acute myeloid leukemia stem/progenitor cells, including those with intrinsic and acquired resistance to venetoclax through cooperative release of pro-apoptotic BIM, BAX, and BAK from binding to anti-apoptotic BCL-2 proteins and inhibition of cell metabolism and key stromal microenvironmental mechanisms. The combined inhibition of MCL-1 by MCL-1 inhibitor AZD5991 or CDK9 inhibitor AZD4573 and BCL-2 by venetoclax greatly extended survival of mice bearing patient-derived xenografts established from an acute myeloid leukemia patient who acquired resistance to venetoclax/decitabine. These results demonstrate that co-targeting MCL-1 and BCL-2 improves the efficacy of and overcomes preexisting and acquired resistance to BCL-2 inhibition. Activation of metabolomic pathways and leukemia-stroma interactions are newly discovered functions of MCL-1 in acute myeloid leukemia, which are independent from canonical regulation of apoptosis by MCL-1. Our data provide new mechanisms of synergy and rationale for co-targeting MCL-1 and BCL-2 clinically in patients with acute myeloid leukemia and potentially other cancers.

15.
Sci Rep ; 10(1): 20017, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208758

RESUMO

Polyphenols based bioactive compounds from vegetables and fruits are known for impressive antioxidant activity. Ingestion of these antioxidants may promote human health against cardiovascular diseases and cancer. Mango is a popular tropical fruit with special taste, high nutritional value and health-enhancing metabolites. The aim was to investigate the diversity of phytochemicals between two mango cultivars of china at three stages of fruit maturity. We used ESI-QTRAP-MS/MS approach to characterize comprehensively the metabolome of two mango cultivars named Hongguifei (HGF) and Tainong (TN). HPLC was used to quantify selected catechin based phenolic compounds. Moreover, real-time qPCR was used to study the expression profiles of two key genes (ANR and LAR) involved in proanthocyanidin biosynthesis from catechins and derivatives. A total of 651 metabolites were identified, which include at least 257 phenolic compounds. Higher number of metabolites were differentially modulated in peel as compared to pulp. Overall, the relative quantities of amino acids, carbohydrates, organic acids, and other metabolites were increased in the pulp of TN cultivar. While the contents of phenolic compounds were relatively higher in HGF cultivar. Moreover, HPLC based quantification of catechin and derivatives exhibited cultivar specific variations. The ANR and LAR genes exhibited an opposite expression profile in both cultivars. Current study is the first report of numerous metabolites including catechin-based derivatives in mango fruit. These findings open novel possibilities for the use of mango as a source of bioactive compounds.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1578-1584, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067957

RESUMO

OBJECTIVE: To investigate the potential mechanisms of miR-224 affecting the proliferation and invasion of diffuse large B-cell lymphoma (DLBCL) cells. METHODS: The blood samples of 76 DLBCL patients(DLBCL group) diagnosed at the First Affiliated Hospital of Kunming Medical University from June 2011 to December 2017, and 41 healthy persons of physical examination (normal control group) as well as human lymphatic endothelial cells (HELC) and DLBCL cell lines HBL1, OCI-LY10, OCI-LY8, OCI-LY19 were collected. The expression of miR-224 and PIK3CD mRNA was measured by RT-qPCR. The proliferation of HBL1 cells was detected by CCK-8 method and colony formation test. The invasion ability of HBL1 cells was detected by Transwell test. Dual-luciferase reporter gene assay was used to verify the relationship between miR-224 and PIK3CD. The expression of PIK3CD protein was measured by Western blot. RESULTS: The expression of miR-224 in blood of DLBCL patients was very significantly lower than that in normal control group (P<0.01). The overexpression of miR-224 significantly decreased proliferation and invasion of HBL1 cells (all P<0.01). PIK3CD was a target gene of miR-224. Knockdown of PIK3CD significantly suppressed the proliferation and invasion of HBL1 cells (all P<0.01). CONCLUSION: MiR-224 plays a key role in the progression of DLBCL, and the proliferation and invasion of HBL1 cells can be suppressed by targeted inhibition of PIK3CD.


Assuntos
Linfoma Difuso de Grandes Células B , MicroRNAs , Linhagem Celular Tumoral , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases/genética , Células Endoteliais , Humanos , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1115-1119, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051427

RESUMO

Roof plate specific spondins (Rspos) are important activators of the Wnt signaling pathway discovered recently. Rspos include four secreted proteins: Rspo1, Rspo2, Rspo3, and Rspo4.They are mainly involved in the regulation of cell proliferation and differentiation via regulating the canonical Wnt/ß-catenin signaling pathway.The physiological functions of Rspos include regulating sex selection, limb development, organ formation and development. Rspos are involved in the pathogenesis of some malignant tumors, and the roles of Rspos vary in different types of tumors.


Assuntos
Neoplasias , Trombospondinas , Proliferação de Células , Sistema Digestório , Humanos , Via de Sinalização Wnt
19.
Ann Clin Transl Neurol ; 7(10): 1766-1778, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910550

RESUMO

OBJECTIVE: To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), or their ratio (ApoB/A1) were associated with early changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology in elderly adults with subjective cognitive decline (SCD). METHODS: This study included 507 objective cognitive normal participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database including 288 cognitive normal participants (CN) and 219 SCD. Multiple linear regression models were used to examine the associations of apolipoproteins with CSF AD biomarkers. RESULTS: Compared with control group, SCD participants with significant AD biological characteristics had lower ApoB levels (P = 0.0461). In total participants, lower level of serum ApoB was associated with decreases in CSF Aß42 (P = 0.0015) and Aß42/40 (P = 0.0081) as well as increases in CSF p-tau/Aß42 (P < 0.0001) and t-tau/Aß42 (P = 0.0013), independent of APOEɛ4 status. In further subgroup analysis, these associations were more significant in SCD participants (ApoB × Diagnose: P < 0.05). In addition, lower levels of ApoB were also found associated with increases in p-tau in the SCD subgroup (P = 0.0263). Furthermore, these protective associations were more significant in the overweight participants (ApoB × weight: P < 0.05). Results showed no association between ApoA1 and CSF biomarkers. INTERPRETATION: This study is the first to find protective associations of serum ApoB with CSF AD core biomarkers, especially in SCD individuals. It indicated that ApoB may be a potential biomarker for preclinical AD and may play different roles in different stages of AD.

20.
Alzheimers Dement (Amst) ; 12(1): e12041, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32995461

RESUMO

Introduction: We sought lipid-metabolic biomarkers involved in the processes underlying cognitive decline and detected them in association with Alzheimer's disease (AD) phenotypes. Methods: A least absolute shrinkage and selection operator logistic regression model was used to select lipids that best classified cognitive decline defined by a fast-annual rate of cognition. Lipid summary scores were constructed as predictors of cognitive decline by using this model. Multivariable-adjusted models tested the associations of risk score with AD phenotypes. Results: A model incorporating 17 selected lipids showed good discrimination and calibration. The lipid risk score was positively associated with the baseline Alzheimer Disease Assessment Scale-13-item cognitive subscale (ADAS-Cog13) score and cerebrospinal tau protein level, and predicted cognitive diagnoses. Additional results showing that individuals with increased lipid risk scores had rapid change rates of ADAS-Cog13 and brain atrophy further corroborated the predictive role of lipids. Discussion: A panel of blood lipids instead of individual lipid molecules could better diagnose and predict cognitive decline.

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