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1.
Ecotoxicol Environ Saf ; 231: 113159, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35032728

RESUMO

Desiccation is a common stress experienced by crabs during aquaculture and transportation. In China, the crustacean, Chinese mitten crab (Eriocheir sinensis), is economically important. However, little is known about the molecular pathways underlying physiological stress. Here, by using untargeted gas chromatography-mass spectrometry metabolomics, we investigated the metabolic responses of the gills of E. sinensis subjected to air-exposure stress by six biological replicates of the control group (CG) and the air-exposure stress group (AG). Metabolomic analysis identified 43 differential metabolites in the AG versus the CG that could be potential biomarkers of desiccation stress. In addition, integrated analysis of key metabolic pathways revealed the involvement of histidine metabolism; glycine, serine and threonine metabolism; the pentose phosphate pathway; the citrate cycle (TCA cycle); and nicotinate and nicotinamide metabolism. These findings indicated the special physiological responses to air-exposure stresses in this species.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34985725

RESUMO

BACKGROUND AND OBJECTIVES: Methotrexate (MTX) is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, its toxicity and efficacy varied greatly among individuals, and they could be predicted by its pharmacokinetics. Many population pharmacokinetic models have been published to describe MTX pharmacokinetics. The objective of this systematic review was to summarize and discuss covariates with significant influence on MTX pharmacokinetics. METHODS: We searched PubMed and EMBASE databases from their inception to April 2021 for population pharmacokinetic of MTX. The articles were screened by inclusion and exclusion criteria. The characteristics of studies and information for model construction and validation were extracted, summarized and discussed. RESULTS: Thirty-five articles were included. The two-compartment model well described the pharmacokinetic behavior of MTX. For inter-individual variability, an exponential distribution error model was usually used for high-dose MTX population pharmacokinetic models, while a proportional distribution error model was used for low-dose MTX population pharmacokinetic models. Proportional and combined proportional and additive error models were used to describe residual error. Renal function was an independent indicator of MTX clearance. Body weight, age, gene polymorphisms (SLCO1B1, ABCC2, ABCB1, ABCG2 and MTHFR) and co-medications (proton pump inhibitors, non-steroidal anti-inflammatory drug, dexamethasone, vancomycin, penicillin and salicylic acid) could influence MTX clearance. Body weight, body surface area, age and dosage regimen have significant influence on MTX central compartment volume. Internal bootstrap test, external validation and visual predictive check were used to evaluate model predictive ability. CONCLUSIONS: Various covariates could affect MTX pharmacokinetics, and their relationships have been summarized and discussed. This review will be helpful for researchers to develop their own population pharmacokinetic models and select appropriate models for individualized therapy of MTX.

3.
Biomed Mater ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35026740

RESUMO

The design of bone scaffolds is predominately aimed to well reproduce the natural bony environment by imitating the architecture/composition of host bone. Such biomimetic biomaterials are gaining increasing attention and acknowledged quite promising for bone tissue engineering. Herein, novel biomimetic bone scaffolds containing decellularized small intestinal submucosa matrix (SIS-ECM) and Sr2+/Fe3+co-doped hydroxyapatite (SrFeHA) are fabricated for the first time by the sophisticated self-assembled mineralization procedure, followed by cross-linking and lyophilization post-treatments. The results indicate the constructed SIS/SrFeHA scaffolds are characterized by highly porous structures, rough microsurface and improved mechanical strength, as well as efficient releasing of bioactive Sr2+/Fe3+and ECM components. These favorable physico-chemical properties endow SIS/SrFeHA scaffolds with an architectural/componential biomimetic bony environment which appears to be highly beneficial for inducing angiogenesis/osteogenesis both in vitro and in vivo. In particular, the cellular functionality and bioactivity of endotheliocytes/osteoblasts are significantly enhanced by SIS/SrFeHA scaffolds, and the cranial defects model further verifies the potent ability of SIS/SrFeHA to accelerate in vivo vascularization and bone regeneration following implantation. In this view these results highlight the considerable angiogenesis/osteogenesis potential of biomimetic porous SIS/SrFeHA scaffolds for inducing bone regeneration and thus may afford a new promising alternative for bone tissue engineering.

4.
ACS Appl Mater Interfaces ; 14(1): 2326-2334, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34958562

RESUMO

Ultrathin two-dimensional (2D) metal-organic framework (MOF) nanosheets (MOFNs) comprise an emerging family of attractive materials with excellent potential for use in different catalytic, electrochemical, and sensing applications owing to their striking features such as ultrathin thickness, a large surface area, and highly ordered network structures. However, to the best of our knowledge, the ligand-cluster units activated through exfoliation into the MOFNs have rarely been realized, which is indeed crucial for surface-enhanced Raman scattering (SERS) analysis. Herein, we emphasize that the activated ligand-cluster units are based on the accessible coordination sites at the exposed cluster nodes accompanied by a complete excitation of the ligand-cluster units under incident photons, which make MOFNs highly effective SERS substrates, significantly outperforming their bulk counterparts. The SERS enhancement of MOFNs is further illustrated by an efficient integration of the inherent ligand-cluster charge-transfer (LCCT) transitions in MOFNs into interfacial charge-transfer processes through an "L"-type charge-transfer (CT) pathway, as further evidenced by an ultrahigh degree (0.98) of CT contributed to the SERS enhancement. This study provides an efficient strategy of exfoliating MOFs into ultrathin nanosheets for the design of highly efficient MOF-based SERS substrates.

5.
J Org Chem ; 87(1): 231-242, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34941259

RESUMO

Amides are important functional synthons that have been widely used in the construction of peptides, natural products, and drugs. The C-N bond cleavage provides the direct method for amide conversion. However, amides, especially secondary amides, tend to be chemically inert due to the resonance of the amide bond. Here, we describe an efficient Pd-catalyzed transamidation and decarbonylation of multiamide structure molecules through C-N bond cleavage with excellent chemoselectivity. The transamidation of secondary amides and the decarbonylation of phthalimide provide meaningful tools for the modification of amino acid derivatives. Moreover, further transformations of azidation and C(sp3)-H monoarylation emphasized the potential utility of this selective C-N bond cleavage method.

6.
Food Chem ; 369: 130920, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461518

RESUMO

Chinese traditional fermented baijiu is a famous alcoholic beverage with unique flavor. Despite its consumption for millennia, the flavor mystery behind baijiu is still unclear. Studies indicate that esters are the most important flavor substances, and bring health benefits. However, the aroma contribution and formation mechanism of esters still need to be clarified to reveal the flavor profile of baijiu. This review systematically summarizes all the 510 esters and finds 9 ethyl esters contribute greatly to the flavor of baijiu. The 508 different microbial species that have been identified affect the synthesis of esters through fatty acid and amino acid metabolism. The determination of minimum functional microbial groups and the analysis of their metabolic characteristics are crucial to reveal the mechanism of formation of baijiu flavor, and ensure the reproducible formation of flavor substances.


Assuntos
Ésteres , Aromatizantes , China , Fermentação , Aromatizantes/análise , Odorantes/análise , Paladar
7.
Mol Plant ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34883279

RESUMO

Achieving sufficient food with finite resources and leaving lesser impact on the environment to feed the growing global population has always been a great challenge. Here we review the concept and practices of Green Super Rice (GSR) that has led to a paradigm shift in the goals of crop genetic improvement and models of food production for promoting sustainable agriculture. The momentous achievements and global deliveries of GSR have been fueled through the integration of abundant genetic resources, functional gene discoveries, innovative breeding techniques with precise gene and whole-genome selections, and efficient agronomic management for promoting resource-saving and environment-friendly crop production systems. We also provide perspectives of new horizons in future genomic breeding technologies towards delivering green and nutritious crop varieties to further enhance the development of green agriculture to better nourish the world population.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34909662

RESUMO

Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2), together with its suppressive binding partner Kelch-like ECH-associated protein 1 (Keap1), regulates cellular antioxidant response and drug metabolism. The roles of Nrf2/Keap1 signaling in the pathology of many diseases have been extensively investigated, and small molecules targeting Nrf2/Keap1 signaling have been developed to prevent or treat diseases such as multiple sclerosis, chronic kidney disease and cancer. Notably, Nrf2 plays dual roles in cancer development and treatment. Activation of Nrf2/Keap1 signaling in cancer cells has been reported to promote cancer progression and result in therapy resistance. Since cancer patients are often suffering comorbidities of other chronic diseases, anticancer drugs could be co-administrated with other drugs and herbs. Nrf2/Keap1 signaling modulators, especially activators, are common in drugs, herbs and dietary ingredients, even they are developed for other targets. Therefore, drug-drug or herb-drug interactions due to modulation of Nrf2/Keap1 signaling should be considered in cancer therapies. Here we briefly summarize basic biochemistry and physiology functions of Nrf2/Keap1 signaling, Nrf2/Keap1 signaling modulators that cancer patients could be exposed to, and anticancer drugs that are sensitive to Nrf2/Keap1 signaling, aiming to call attention to the potential drug-drug or herb-drug interactions between anticancer drugs and these Nrf2/Keap1 signaling modulators.

9.
J Biosci ; 462021.
Artigo em Inglês | MEDLINE | ID: mdl-34911832

RESUMO

The aim of this study is to investigate the effect and mechanism of 17 ß-estradiol (E2) on oxidative stress in the osteoblasts. An oxidative stress-induced damage model was established using H2O2 in MC3T3-E1 cells, and H2O2-induced cells were treated with E2. The results indicated that E2 attenuated oxidative stress in H2O2- induced MC3T3-E1 cells. In addition, H2O2 upregulated the expression of miR-320-3p and downregulated that of RUNX2, but these changes were counteracted by E2. Thereafter, we verified the interactive relationship between miR-320-3p and RUNX2. Then, H2O2-induced MC3T3-E1 cells were transfected with miR-320-3p mimics or inhibitors and treated with E2. The results indicated that miR-320-3p inhibition suppressed H2O2- induced inflammation, apoptosis, and oxidative stress and promoted the osteogenic differentiation of MC3T3- E1 cells by regulating RUNX2, ALP, and OCN, and this effect was further strengthened by E2. In conclusion, the findings suggest that E2 alleviates oxidative damage in osteoblasts by regulating the miR-320/RUNX2 signaling.

10.
Front Oncol ; 11: 754353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722307

RESUMO

Prostate cancer (PCa) has become the most frequently occurring cancer among western men according to the latest report, and patients' prognosis is often poor in the event of tumor progression, therefore, many researches are devoted to exploring the molecular mechanism of PCa metastasis. MicroRNAs (miRNA) have proved to play an important role in this process. In present study, by combining clinical samples with public databases, we found that miR-629-5p increased to varying degrees in primary localized PCa tissues and metastatic PCa tissues compared with adjacent normal tissues, and bioinformatics analysis suggested that high level of miR-629-5p was related to poor prognosis. Functionally, miR-629-5p drove PCa cell proliferation, migration and invasion in vitro, and promoted growth of PCa cells in vivo. Moreover, A-kinase Anchor Protein 13 (AKAP13) was screened as a direct target of miR-629-5p, that expression was negatively correlated with the malignant phenotype of tumor cells. In the end, through verification in clinical specimens, we found that AKAP13 could be independently used as a clinical prognostic indicator. Overall, the present study indicates that miR-629-5p plays an oncogenic role in PCa by targeting AKAP13, which provides a new idea for clinical diagnosis and treatment of complex refractory PCa.

11.
Front Plant Sci ; 12: 748125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777427

RESUMO

The petiole-lamina relationship is central to the functional tradeoff between photosynthetic efficiency and the support/protection cost. Understanding environmental gradients in the relationship and its underlying mechanisms remains a critical challenge for ecologists. We investigated the possible scaling of the petiole-lamina relationships in three dimensions, i.e., petiole length (PL) vs. lamina length (LL), petiole cross sectional area (PCA) vs. lamina area (LA), and petiole mass (PM) vs. lamina mass (LM), for 325 Qinghai-Tibetan woody species, and examined their relation to leaf form, altitude, climate, and vegetation types. Both crossspecies analysis and meta-analysis showed significantly isometric, negatively allometric, and positively allometric scaling of the petiole-lamina relationships in the length, area, and mass dimensions, respectively, reflecting an equal, slower, and faster variation in the petiole than in the lamina in these trait dimensions. Along altitudinal gradients, the effect size of the petiole-lamina relationship decreased in the length and mass dimensions but increased in the area dimension, suggesting the importance of enhancing leaf light-interception and nutrient transport efficiency in the warm zones in petiole development, but enhancing leaf support/protection in the cold zones. The significant additional influences of LA, LM, and LA were observed on the PL-LL, PCA-LA, and PM-LM relationships, respectively, implying that the single-dimension petiole trait is affected simultaneously by multidimensional lamina traits. Relative to simple-leaved species, the presence of petiolule in compound-leaved species can increase both leaf light interception and static gravity loads or dynamic drag forces on the petiole, leading to lower dependence of PL variation on LL variation, but higher biomass allocation to the petiole. Our study highlights the need for multidimension analyses of the petiole-lamina relationships and illustrates the importance of plant functional tradeoffs and the change in the tradeoffs along environmental gradients in determining the relationships.

12.
J Affect Disord ; 295: 1079-1086, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706417

RESUMO

BACKGROUND: It is well known that the thalamus is not a unitary and homogeneous entity but a complex and highly connected archeocortical structure. Although many neuroimaging studies have reported alterations in the thalamus in major depressive disorder (MDD), the structural alterations in thalamic subfields remain unclear. This study aimed to investigate changes in gray matter volume (GMV) in thalamic subfields in MDD patients. METHODS: The present study included structural images of 848 MDD patients and 794 age-matched normal controls (NC) from 17 study sites of the REST-meta-MDD consortium. We performed voxel-based morphometric analyses to calculate the GMV in the entire thalamus and its subfields using three different automated anatomical labeling atlases and subsequently compared the differences between first-episode drug-naïve major depressive disorder (FEDN), recurrent major depressive disorder (RMDD), and NC groups. We also evaluated the relationships between thalamic GMV and clinical symptoms in MDD patients. RESULTS: Compared to NC, the FEDN patients showed increased GMV in thalamic subfields but not in the entire thalamus, while RMDD patients showed no significant alterations in GMV in the entire thalamus and its subfields. Moreover, the mean GMV in the right anterior thalamus and left anteroventral thalamus in RMDD patients were mildly positively correlated with the Hamilton Anxiety Rating Scale scores. LIMITATIONS: The main limitations are a single-modal analysis based on T1-weighted MR images and a cross-sectional design. CONCLUSIONS: Our findings suggest that FEDN and RMDD patients show heterogeneous alterations across thalamic subfields, which may help us understand the pathophysiological mechanisms of MDD.


Assuntos
Transtorno Depressivo Maior , Estudos Transversais , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tálamo/diagnóstico por imagem
13.
Sci Rep ; 11(1): 18104, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518565

RESUMO

The aim of this study was to assess the analgesic efficacy of QLB versus controls in women undergoing cesarean section (CS). We systematically searched Cochrane Library, PUBMED, EMBASE, VIP, WANFANG, and China National Knowledge Infrastructure. Trials were eligible if parturients received QLB during CS. GRADE system was used to assess the certainty of evidence and Trial sequential analyses (TSA) were performed to determine whether the results are supported by sufficient data. Thirteen studies involving 1269 patients were included. Compared to controls, QLB significantly reduced the cumulative postoperative intravenous opioid consumption (in milligram morphine equivalents) at 24 h (MD, - 11.51 mg; 95% CI - 17.05 to - 5.96) and 48 h (MD, - 15.87 mg; 95% CI - 26.36 to - 5.38), supported by sufficient data confirmed by TSA. The postoperative pain scores were significantly reduced by QLB at 4 h, 6 h, 12 h, 24 h, and 48 h postoperatively by QLB compared with control. Moreover, the time to first request for rescue analgesic and the incidence of PONV were also significantly reduced by QLB. The quality of evidence of most results were low and moderate assessed by GRADE.

14.
Nat Commun ; 12(1): 5629, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561445

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease caused by a new type of SFTS virus (SFTSV). Here, a longitudinal sampling study is conducted to explore the differences in transcript levels after SFTSV infection, and to characterize the transcriptomic and epigenetic profiles of hospitalized patients. The results reveal significant changes in the mRNA expression of certain genes from onset to recovery. Moreover, m6A-seq reveals that certain genes related with immune regulation may be regulated by m6A. Besides the routine tests such as platelet counts, serum ALT and AST levels testing, distinct changes in myocardial enzymes, coagulation function, and inflammation are well correlated with the clinical data and sequencing data, suggesting that clinical practitioners should monitor the above indicators to track disease progression and guide personalized treatment. In this study, the transcript changes and RNA modification may lend a fresh perspective to our understanding of the SFTSV and play a significant role in the discovery of drugs for effective treatment of this disease.


Assuntos
Epigênese Genética , Epigenômica/métodos , Perfilação da Expressão Gênica/métodos , Febre Grave com Síndrome de Trombocitopenia/genética , Transcriptoma , Idoso , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Aspartato Aminotransferases/sangue , Creatinina/sangue , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Phlebovirus/efeitos dos fármacos , Phlebovirus/fisiologia , RNA-Seq/métodos , Amostragem , Febre Grave com Síndrome de Trombocitopenia/tratamento farmacológico , Febre Grave com Síndrome de Trombocitopenia/virologia
15.
Nano Lett ; 21(16): 6891-6897, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34355916

RESUMO

Inorganic electrochromic (EC) materials with vibrant multicolor change that are compatible with large-scale processing have been at the forefront of EC technology and are crucial in a wide range of applications, such as displays and camouflage. However, limited strategies are available to realize such inorganic materials, and challenges such as low color purity are yet to be overcome. Here, we demonstrate multilayered metal-dielectric metamaterials (MMDMs) as a new family of inorganics-based EC materials to achieve dynamic alternation among multicolors with high contrast and high color purity, which are structurally realized by significantly enhancing the confinement of the incident light in specific optical frequencies. This multilayer structure renders high reflectivity (75%), high quality factor (7.4), and a full width at half-maximum of 60 nm before coloration and presents a color gamut at least 40% wider than that of previously reported metamaterials after coloration, indicating good color quality.


Assuntos
Metais
16.
Curr Med Res Opin ; 37(11): 2001-2006, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34376068

RESUMO

BACKGROUND: Pharmacovigilance is a science that plays a significant role in reducing ADRs and helps predict adverse reactions to drugs in community. To safely use drugs in treatment and prevention of disease, adverse drug reaction has been paid more attention. OBJECTIVES: To evaluate the future needs of existing systems, the paper investigated the current state of pharmacovigilance and the reporting of ADR in Chinese hospitals. METHODS: This cross-sectional, questionnaire-based study involved 10,063 pharmacists, doctors, and nurses from primary, secondary, and tertiary hospitals in all 31 provinces of China. It was commissioned by the National Centre for ADR Monitoring of China and conducted in March 2020. Three areas were assessed: sociodemographic characteristics of participants, awareness of the pharmacovigilance system, and the current state of hospitals' reporting of ADRs. Chi-square tests were used to calculate P values. RESULTS: Health care professionals had heard the term "pharmacovigilance" previously (89.40%) and knew the reporting object (68.47%), content (65.94%), and range (64.83%) of pharmacovigilance. Most hospitals dispatched responsible professionals (87.64%) and departments (86.25%) to monitor ADR reporting. A total of 58.66% of tertiary medical, 45.25% of secondary, and 38.90% of primary hospitals extracted ADRs from a hospital information system. Moreover, 53.09% of tertiary medical, 38.93% of secondary, and 23.89% of primary hospitals had established a prescription automatic screening system to warn about risks for ADRs. Health care professionals' reports (99.92%) and patient feedback (77.99%) were included in most hospitals' ADR reporting. CONCLUSIONS: Chinese health care professionals generally have good awareness of pharmacovigilance, and pharmacovigilance is relatively more advanced in China compared to other developing countries.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos , China/epidemiologia , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Centros de Atenção Terciária
18.
Clin Exp Med ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427833

RESUMO

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the pathogenesis and progression of several cancers. However, the potential effect of MALAT1 in primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) has not been elucidated. This study aimed to explore the prognostic value of MALAT1 in patients with PGI-DLBCL. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of MALAT1 in 90 patients with PGI-DLBCL. MALAT1 was remarkably upregulated in PGI-DLBCL tissues compared to paired adjacent non-tumor tissues (P < 0.001), and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.838. MALAT1 expression was further increased in the non-germinal center B-cell-like (non-GCB), advanced stage (stages IIE-IV) and International Prognostic Index (IPI) score (3-5) groups (P = 0.01, P < 0.001 and P < 0.001, respectively). Furthermore, Kaplan-Meier analysis showed that elevated MALAT1 expression correlated with inferior overall survival (OS) and progression-free survival in PGI-DLBCL patients (P < 0.001 and P < 0.001, respectively), and our multivariate analysis results suggested that upregulation of MALAT1 and high IPI score (3-5) were two unfavorable prognostic factors for PGI-DLBCL. In conclusion, our results demonstrate that MALAT1 may serve as a novel prognostic biomarker and an ideal therapeutic target for patients with PGI-DLBCL.

19.
J Pharm Pharmacol ; 73(11): 1480-1490, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34254644

RESUMO

OBJECTIVES: This study aims to evaluate the association between polymorphisms of methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity in Chinese patients with primary central nervous system lymphoma. METHODS: Sixty-five patients in 411 treatment courses were enrolled and their toxicities were evaluated. The association between 30 candidate SNPs from 20 methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity was analysed by PLINK and logistic regression. KEY FINDINGS: TYMS 6 bp DI + II (rs151264360; OR, 0.41; 95% CI, 0.25-0.66; P = 0.00029), MTHFD1 1958 GA + AA (rs2236225; OR, 0.55; 95% CI, 0.33-0.91; P = 0.020) and CCND1 870 GA + GG (rs9344; OR, 0.42; 95% CI, 0.24-0.73; P = 0.0024) had less risk of hepatotoxicity compared with their homozygotes (DD, GG and AA, respectively), while ABCC2 intron 29 GA + GG (rs3740065; OR, 3.14; 95% CI, 1.89-5.20; P = 0.00001) was more prevalent in patients with hepatotoxicity than TT. CONCLUSIONS: TYMS 6 bp DI + II, MTHFD1 1958 GA + AA, CCND1 870 GA + GG genotypes were associated with a lower probability of hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy, and ABCC2 intron 29 GA + GG was correlated with increased risk of hepatotoxicity.

20.
J Am Heart Assoc ; 10(14): e020734, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34250817

RESUMO

Background Patients with hypertension and diabetes mellitus are susceptible to dementia, but regular therapy fails to reduce the risk of dementia. Glucagon-like peptide-1 receptor agonists have neuroprotective effects in experimental studies. We aimed to assess the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on cognitive function and whether its effect was associated with metabolic changes in patients with type 2 diabetes mellitus. Methods and Results Fifty patients with type 2 diabetes mellitus were recruited in this prospective study. All patients underwent cognitive assessment and brain activation monitoring by functional near-infrared spectroscopy. At 12 weeks, patients in the glucagon-like peptide-1 group acquired better scores in all cognitive tests and showed remarkable improvement in memory and attention (P=0.040) test compared with the control group after multivariable adjustment. Compared with the control group, liraglutide significantly increased activation of the dorsolateral prefrontal cortex and orbitofrontal cortex brain regions (P=0.0038). After liraglutide treatment, cognitive scores were significantly correlated with changes in these activating brain regions (P<0.05), but no correlation was observed between the changes in cognitive function and changes of body mass index, blood pressure, and glycemic levels. Conclusions We concluded that liraglutide improves cognitive decline in patients with type 2 diabetes mellitus. This beneficial effect is independent of its hypoglycemic effect and weight loss. The optimal intervention should be targeted to cognitive decline in the early stages of dementia. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT03707171.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Liraglutida/farmacologia , Metformina/uso terapêutico , Córtex Pré-Frontal/efeitos dos fármacos , Biomarcadores/metabolismo , Glicemia/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Prognóstico , Estudos Prospectivos
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