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1.
Eur J Med Res ; 29(1): 334, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38880878

RESUMO

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.


Assuntos
Cognição , Genótipo , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Doença de Parkinson/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Cognição/fisiologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Apolipoproteínas E/genética , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína E4/genética
2.
Ecotoxicol Environ Saf ; 278: 116336, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691883

RESUMO

Aflatoxin B1 (AFB1), a common mycotoxin, can occur in agricultural products. As a metabolite of AFB1, aflatoxin M1 (AFM1) mainly exist in dairy products. These two mycotoxins threaten human health, although it is unclear how they affect the function of the intestinal barrier. In this study, mice were exposed to AFB1 (0.3 mg/kg body b.w.) and AFM1(3.0 mg/kg b.w.) either individually or in combination for 28 days to explore the main differentially expressed proteins (DEPs) and the associated enriched pathways. These findings were preliminarily verified by the transcriptomic and proteomic analyses in differentiated Caco-2 cells. The results revealed that AFB1 and AFM1 exposure in mice disrupted the function of the intestinal barrier, and the combined toxicity was greater than that of each toxin alone. Further proteomic analysis in mice demonstrated that the mechanisms underlying these differences could be explained as follows: (i) lipid metabolism was enriched by AFB1-induced DEPs. (ii) protein export pathway was stimulated by AFM1-induced DEPs. (iii) cell metabolic ability was inhibited (as evidenced by changes in UDP-GT1, UDP-GT2, and Gatm6), apoptosis was induced (MAP4K3), and epithelial cell integrity was disrupted (Claudin7 and IQGAP2), resulting in more extensive intestinal damage after combined treatment. In conclusion, the hazardous impact of co-exposure to AFB1 and AFM1 from proteomic perspectives was demonstrated in the present study.


Assuntos
Aflatoxina B1 , Aflatoxina M1 , Proteômica , Aflatoxina M1/toxicidade , Aflatoxina B1/toxicidade , Animais , Camundongos , Células CACO-2 , Humanos , Masculino , Intestinos/efeitos dos fármacos , Intestinos/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo
3.
Int J Legal Med ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38802694

RESUMO

In forensic practice, determining the postmortem submersion interval (PMSI) and cause-of-death of cadavers in aquatic ecosystems has always been challenging task. Traditional approaches are not yet able to address these issues effectively and adequately. Our previous study proposed novel models to predict the PMSI and cause-of-death based on metabolites of blood from rats immersed in freshwater. However, with the advance of putrefaction, it is hardly to obtain blood samples beyond 3 days postmortem. To further assess the feasibility of PMSI estimation and drowning diagnosis in the later postmortem phase, gastrocnemius, the more degradation-resistant tissue, was collected from drowned rats and postmortem submersion model in freshwater immediately after death, and at 1 day, 3 days, 5 days, 7 days, and 10 days postmortem respectively. Then the samples were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the dynamic changes of the metabolites. A total of 924 metabolites were identified. Similar chronological changes of gastrocnemius metabolites were observed in the drowning and postmortem submersion groups. The difference in metabolic profiles between drowning and postmortem submersion groups was only evident in the initial 1 day postmortem, which was faded as the PMSI extension. Nineteen metabolites representing temporally-dynamic patterns were selected as biomarkers for PMSI estimation. A regression model was built based on these biomarkers with random forest algorithm, which yielded a mean absolute error (± SE) of 5.856 (± 1.296) h on validation samples from an independent experiment. These findings added to our knowledge of chronological changes in muscle metabolites from submerged vertebrate remains during decomposition, which provided a new perspective for PMSI estimation.

4.
Angew Chem Int Ed Engl ; 63(17): e202400424, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38433094

RESUMO

Halide superionic conductors (SICs) are drawing significant research attention for their potential applications in all-solid-state batteries. A key challenge in developing such SICs is to explore and design halide structural frameworks that enable rapid ion movement. In this work, we show that the close-packed anion frameworks shared by traditional halide ionic conductors face intrinsic limitations in fast ion conduction, regardless of structural regulation. Beyond the close-packed anion frameworks, we identify that the non-close-packed anion frameworks have great potential to achieve superionic conductivity. Notably, we unravel that the non-close-packed UCl3-type framework exhibit superionic conductivity for a diverse range of carrier ions, including Li+, Na+, K+, and Ag+, which are validated through both ab initio molecular dynamics simulations and experimental measurements. We elucidate that the remarkable ionic conductivity observed in the UCl3-type framework structure stems from its significantly more distorted site and larger diffusion channel than its close-packed counterparts. By employing the non-close-packed anion framework as the key feature for high-throughput computational screening, we also identify LiGaCl3 as a promising candidate for halide SICs. These discoveries provide crucial insights for the exploration and design of novel halide SICs.

5.
J Chem Phys ; 160(11)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38501473

RESUMO

We establish a theoretical model to analyze the photoassociative spectroscopy of 85Rb 133Cs molecules in the (3)3Σ+ state. The vibrational energy, spin-spin coupling constant, and hyperfine interaction constant of the (3)3Σ+ state are determined based on nine observed vibrational levels. Consequently, the Rydberg-Klein-Rees potential energy curve of the (3)3Σ+ state is obtained and compared with the ab initial potential energy curve. Our model can be adopted to analyze the photoassociative spectroscopy of other heteronuclear alkali-metal diatomic molecules in the (3)3Σ+ state.

6.
Alcohol ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38387693

RESUMO

OBJECTIVES: Alcohol consumption is not uncommon among people with HIV (PWH) and may exacerbate HIV-induced intestinal damage, and further lead to dysbiosis and increased intestinal permeability. This study aimed to determine the changes in the faecal microbiota and its association with alcohol consumption in HIV-infected patients. METHODS: A cross-sectional survey was conducted between November 2021 and May 2022, and 93 participants were recruited. To investigate the alterations of alcohol misuse on fecal microbiology in HIV-infected individuals, we performed 16s rDNA gene sequencing on fecal samples from the low to moderate drinking (n=21) and non-drinking (n=72) groups. RESULTS: Comparison between groups using alpha and beta diversity showed that the diversity of stool microbiota in the low to moderate drinkinge group did not differ from that of the non-drinking group (all P>0.05). The Linear discriminant Analysis effect size (LEfSe) algorithm was to determine the bacterial taxa associated with alcohol consumption, and the results showed altered fecal bacterial composition in HIV-infected patients who consumed alcohol, with Coprobacillus, Pseudobutyrivibrio and Peptostreptococcaceae enriched, and Pasteurellaceae and Xanthomonadaceae were depleted. In addition, by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional microbiome features were also found to be altered in the low to moderate drinking group, showing a reduction in metabolic pathways (P=0.036) and cardiovascular disease pathway (P=0.006). CONCLUSION: Low to moderate drinking will change the composition, metabolism and cardiovascular disease pathway of the gut microbiota of HIV-infected patients.

7.
Am J Gastroenterol ; 119(4): 655-661, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37975609

RESUMO

INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. TRAIL REGISTRATION NUMBER: ChiCTR2300070100.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Pirróis , Sulfonamidas , Humanos , Amoxicilina/uso terapêutico , Bismuto/uso terapêutico , Bismuto/efeitos adversos , Antibacterianos , Infecções por Helicobacter/tratamento farmacológico , Estudos Prospectivos , Quimioterapia Combinada , Adesão à Medicação , Resultado do Tratamento , Inibidores da Bomba de Prótons/efeitos adversos
9.
Fa Yi Xue Za Zhi ; 39(5): 441-446, 2023 Oct 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38006262

RESUMO

OBJECTIVES: To evaluate the forensic application value of an age estimation model based on DNA methylation in eastern Chinese Han population, and to provide a theoretical basis for exploring age estimation models suitable for different detection platforms. METHODS: According to the 6 age-related methylation sites in the published blood DNA methylation age estimation models of Chinese Han population, the DNA methylation level of 48 samples was detected by pyrosequencing and next-generation sequencing (NGS). After submitting DNA methylation levels to the age estimation model, the DNA methylation ages were predicted and compared with their real ages. RESULTS: The 6 DNA methylation sites in both detection techniques were age-related, with an R2 of 0.85 and a median absolute deviation (MAD) of 4.81 years when using pyrosequencing;with an R2 of 0.84 and MAD of 4.41 years when using NGS. CONCLUSIONS: The blood DNA methylation age estimation model can be used under pyrosequencing and multi-purpose regional methylation enrichment sequencing technology based on NGS and it can accurately estimate the age.


Assuntos
Metilação de DNA , População do Leste Asiático , Humanos , Envelhecimento/genética , Ilhas de CpG , Genética Forense/métodos
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(10): 1016-1021, 2023 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-37905757

RESUMO

OBJECTIVES: To study the left heart structure and functional characteristics of term neonates with intrauterine growth restriction (IUGR). METHODS: This study included 86 term neonates with IUGR admitted to the Neonatal Ward of Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2022 as the IUGR group, as well as randomly selected 86 term neonates without IUGR born during the same period as the non-IUGR group. The clinical data and echocardiographic data were compared between the two groups. RESULTS: The analysis of left heart structure and function showed that compared with the non-IUGR group, the IUGR group had significantly lower left ventricular mass, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, end-diastolic interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume, left ventricular end-systolic volume, and stroke volume (P<0.05) and significantly higher ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness, proportion of neonates with a mitral peak E/A ratio of ≥1, and cardiac index (P<0.05). The Spearman correlation analysis suggested that stroke volume was positively correlated with birth weight and body surface area (rs=0.241 and 0.241 respectively; P<0.05) and that the ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness was negatively correlated with birth weight and body surface area (rs=-0.229 and -0.225 respectively; P<0.05). CONCLUSIONS: The left ventricular systolic function of neonates with IUGR is not significantly different from that of neonates without IUGR. However, the ventricular septum is thicker in neonates with IUGR. This change is negatively correlated with birth weight and body surface area. The left ventricular diastolic function may be impaired in neonates with IUGR.


Assuntos
Retardo do Crescimento Fetal , Coração , Humanos , Recém-Nascido , Peso ao Nascer , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Função Ventricular Esquerda
11.
Fa Yi Xue Za Zhi ; 39(1): 72-82, 2023 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37038859

RESUMO

With the improvement of DNA methylation detection techniques, studies on age-related methylation sites have found more age-specific ones across tissues, which improves the sensitivity and accuracy of age estimation. In addition, the establishment of various statistical models also provides a new direction for the age estimation of tissues from different sources. This review summarizes the related studies of age estimation based on DNA methylation from the aspects of detection technology, age-related cytosine phosphate guanine site and model selection in recent years.


Assuntos
Metilação de DNA , Genética Forense , Genética Forense/métodos , Ilhas de CpG , Medicina Legal
12.
J Agric Food Chem ; 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37017396

RESUMO

Tembotrione, a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, has been widely used in many types of plants. Tembotrione has been reported for its likelihood of causing injury and plant death to certain corn hybrids. Safeners are co-applied with herbicides to protect certain crops without compromising weed control efficacy. Alternatively, herbicide safeners may effectively improve herbicide selectivity. To address tembotrione-induced Zea mays injury, a series of novel ester-substituted cyclohexenone derivatives were designed using the fragment splicing method. In total, 35 title compounds were synthesized via acylation reactions. All the compounds were characterized using infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. The configuration of compound II-15 was confirmed using single-crystal X-ray diffraction. The bioactivity assay proved that tembotrione phytotoxicity to maize could be reduced by most title compounds. In particular, compound II-14 exhibited the highest activity against tembotrione. The molecular structure comparisons as well as absorption, distribution, metabolism, excretion, and toxicity predictions demonstrated that compound II-14 exhibited pharmacokinetic properties similar to those of the commercial safener isoxadifen-ethyl. The molecular docking model indicated that compound II-14 could prevent tembotrione from reaching or acting with Z. mays HPPD (PDB: 1SP8). Molecular dynamics simulations showed that compound II-14 maintained satisfactory stability with Z. mays HPPD. This research revealed that ester-substituted cyclohexenone derivatives can be developed as potential candidates for discovering novel herbicide safeners in the future.

13.
Cell Mol Life Sci ; 80(2): 50, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694058

RESUMO

The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.


Assuntos
Cardiomiopatias , Fibroblastos , Fibrose , Miofibroblastos , RNA Circular , Animais , Ratos , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Fibroblastos/metabolismo , Fibrose/genética , Fibrose/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Miofibroblastos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
14.
Sci Total Environ ; 854: 158777, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36115400

RESUMO

Aflatoxin M1 (AFM1) and ochratoxin A (OTA) are common mycotoxins in cereal foods and milk products, and may cause serious negative impacts on human health. The intestine is crucial for immune regulation as it protects host homeostatic health from external contaminants; however, the underlying mechanisms of AFM1 and OTA mediated intestinal immunotoxicity remain unclear. In this study, whole transcriptome analysis was used to characterize BALB/c mouse intestines exposed to individual and combined AFM1 and OTA [3.0 mg/kg body weight (BW)] for 28 days to screen for key intestinal immunotoxicity-related differentially expressed mRNAs (DEmRNAs), differentially expressed microRNAs (DEmiRNAs), differentially expressed long non-coding RNAs (DElncRNAs), and associated enriched signaling pathways. Functional validation was then conducted in intestinal differentiated Caco-2 cells using different inhibitor assays to verify the accuracy of transcriptome and the importance of the key screened regulatory factors. In vivo data revealed that AFM1 and OTA exposure disrupted the intestines and exerted intestinal immunosuppression effects. When compared with AFM1, OTA had stronger intestinal toxicity in combined treatments. Further analyses of competitive endogenous RNA (ceRNA) regulatory networks in mice showed that AFM1 and OTA mediated-intestinal immunosuppression was putatively explained as follows: (i) toxins affected DEmRNAs regarding transfer and transduction mechanisms between cells (Csf1, Csf1r, Cxcl10, Cx3cr1, and Irf1), which were regulated by key DEmiRNAs (miR-106-x, miR-107-y, and miR-124-y) and the DElncRNA Rian, and (ii) toxins inhibited transforming growth factor-ß-activated kinase 1 (TAK1)/I-kappaB kinase (IKK)/inhibitor of kappa Bα (IκBα)/p65 nuclear factor-κB (NF-κB) signaling phosphorylation levels, which was validated in differentiated Caco-2 cells using the TAK1 inhibitor (5Z-7-oxozeaenol). In conclusion, we evaluated the risk of co-exposure to AFM1 and OTA and associated health hazards from a whole transcriptome perspective.


Assuntos
Aflatoxina M1 , MicroRNAs , Humanos , Animais , Camundongos , Aflatoxina M1/toxicidade , Células CACO-2 , Intestinos , Perfilação da Expressão Gênica , Terapia de Imunossupressão
15.
Sci Rep ; 12(1): 21014, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470922

RESUMO

Partial bile duct ligation (pBDL) is considered a well-tolerated cholestatic model. Magnetic resonance imaging (MRI) is one of the most widely used tools in noninvasive imaging. However, no systematic studies have reported the possible effects of repeated MRI assessments in the pBDL model. Sixty BALB/C mice were investigated. MRI images of each mouse were recorded once every 2 weeks for 6 weeks after pBDL or sham surgery. The reproducibility of the pBDL model and the reliability of MRI were examined by behavioral, physiological, biochemical, and pathological parameters. The mice showed no alterations on behavioral and physiological tests (P > 0.05) at 2, 4, and 6 weeks after pBDL. Repeated general anesthesia did not result in any impairment after pBDL (P > 0.05). The behavioral and biochemical parameters were not affected by repeated MRIs or repeated contrast-enhanced MRIs (P > 0.05). Pathological staining showed the homogeneous formation of collagenous fiber in the pBDL mice and did not indicate any influence of repeated contrast-enhanced MRI on the number of inflammatory cells or fibrotic formation (P > 0.05). Thus, pBDL is a reproducible model with many advantages for animal welfare and scientific research. Additionally, MRI, as a safe tool for longitudinal evaluation and is well tolerated in mice with cholestasis.


Assuntos
Ductos Biliares , Colestase , Camundongos , Animais , Reprodutibilidade dos Testes , Camundongos Endogâmicos BALB C , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/cirurgia , Ductos Biliares/patologia , Colestase/diagnóstico por imagem , Colestase/patologia , Ligadura/métodos , Imageamento por Ressonância Magnética , Modelos Animais de Doenças , Fígado/patologia
16.
J Med Chem ; 65(19): 12979-13000, 2022 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-36112701

RESUMO

Lysine-specific demethylase 5B (KDM5B) has been recognized as a potential drug target for cardiovascular diseases. In this work, we first found that the KDM5B level was increased in mouse hearts after transverse aortic constriction (TAC) and in Ang II-induced activated cardiac fibroblasts. Structure-based design and further optimizations led to the discovery of highly potent pyrazole-based KDM5B inhibitor TK-129 (IC50 = 0.044 µM). TK-129 reduced Ang II-induced activation of cardiac fibroblasts in vitro, exhibited good PK profile (F = 42.37%), and reduced isoprenaline-induced myocardial remodeling and fibrosis in vivo. Mechanistically, we found that KDM5B up-regulation in cardiac fibroblast activation was associated with the activation of Wnt-related pathway. The protective effects of TK-129 were associated with its KDM5B inhibition and blocking KDM5B-related Wnt pathway activation. Taken together, TK-129 may represent a novel KDM5-targeting lead compound for cardiac remodeling and fibrosis.


Assuntos
Lisina , Miocárdio , Animais , Proteínas de Ligação a DNA/metabolismo , Fibrose , Isoproterenol , Histona Desmetilases com o Domínio Jumonji/metabolismo , Lisina/metabolismo , Camundongos , Miocárdio/metabolismo , Pirazóis/metabolismo , Pirazóis/farmacologia , Pirazóis/uso terapêutico
17.
Int J Legal Med ; 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175800

RESUMO

Post-mortem diagnosis of fatal hypothermia (FHT) is challenging in forensic practice because traditional morphological and biochemical methods lack specificity. Recent studies have reported that brown adipose tissue (BAT) is activated during cold-induced non-shivering thermogenesis in mammals, but BAT has not been used to diagnose FHT. The aim of this study was to identify novel biomarkers in BAT for FHT based on morphological changes and differential protein expression. Two FHT animal models were created by exposing mice to 4 or -20 °C at 50% humidity. Morphologically, the unilocular lipid droplet content was significantly increased in BAT of FHT model mice compared with that of control mice. Proteomics analysis revealed a total of 283 and 266 differentially expressed proteins (DEPs) between the 4 or -20 °C FHT subgroups and control group, respectively. In addition, 140 proteins were shared between the FHT subgroups. GO and KEGG analyses revealed that the shared DEPs were mainly enriched in pathways associated with metabolism, oxidative phosphorylation, and thermogenesis. Further screening (|log2FC| > 1.6, q-value (FDR) < 0.05) identified GMFB, KDM1A, DDX6, RAB1B, SHMT-1, CLPTM1, and LMF1 as candidate biomarkers of FHT. Subsequent validation experiments were performed in FHT model mice using classic immunohistochemistry and western blotting. RAB1B and GMFB expression was further verified in BAT specimens from human cases of FHT. The results demonstrate that BAT can be used as a target organ for FHT diagnosis employing RAB1B and GMFB as biological markers, thus providing a new strategy for the post-mortem diagnosis of FHT in forensic practice.

18.
Int J Biol Macromol ; 219: 876-885, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-35963349

RESUMO

In this study, three polysaccharides (BGPs: BGPs-Z21, BGPs-Z23, and BGPs-Z31) were successively extracted from barley (Hordeum vulgare L.) grasses (BG) at different growth stages, including seedling (Z21), tillering (Z23), and stem elongation (Z31). The effects of in vitro simulated saliva-gastrointestinal digestion on the physicochemical characteristics and biological activities of BGPs were investigated and compared. Results showed that the simulated saliva-gastrointestinal digestion had considerable influences on reducing sugar content, chemical components, monosaccharide constituents, and molecular weights of BGPs but hardly affected their preliminarily structural characteristics. Moreover, the antioxidant activities of BGPs were weakened after the simulated saliva-gastrointestinal digestion, but their bile acid-binding capacities were remarkably enhanced. The digested BGPs-Z31 by gastric juice possessed better antioxidant benefit, and bile acid-binding capacity (80.33 %) than other digested products. Overall, these results indicated that BGPs obtained from BG are valuable for functional foods as promising bioactive ingredients.


Assuntos
Hordeum , Antioxidantes/farmacologia , Ácidos e Sais Biliares , Digestão , Hordeum/química , Monossacarídeos , Poaceae , Polissacarídeos/química , Polissacarídeos/farmacologia
19.
Int J Biol Macromol ; 213: 923-933, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35654222

RESUMO

In this study, carboxylic curdlan (Cur-48) and negatively charged ferulic acid (FA)-grafted carboxylic curdlan (Cur-48-g-FA) were separately used to fabricate polyelectrolyte nanoparticles (PNPs: PNPs-CQ and PNPs-CFQ) with positively charged quaternized curdlan (Qcurd) for curcumin delivery. Results showed that curcumin-loaded PNPs-CQ and PNPs-CFQ had particle sizes of 338.1 and 301.3 nm, zeta potentials of -19.07 and -24.10 mV, and encapsulation efficiencies of 76.32% and 83.54%, respectively. Curcumin was properly encapsulated inside the two PNPs through electrostatic interactions and hydrogen bonds. Compared with free curcumin, entrapped curcumin in the two PNPs exhibited better redispersion performance, thermo- and photostability, and sustained release property. Furthermore, FA molecules surrounding the surface of PNPs-CFQ were conductive to the entrapped curcumin's particulate characteristics, stability, release behavior, and antioxidant potentials. Therefore, our findings indicated that PNPs formulated via Cur-48-g-FA and Qcurd can provide a novel delivery platform for encapsulation of hydrophobic nutrients, including curcumin, in functional foods.


Assuntos
Curcumina , Nanopartículas , Curcumina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Tamanho da Partícula , Polissacarídeos , beta-Glucanas
20.
Food Chem ; 394: 133470, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35716505

RESUMO

Among 26 sous-vide cooking conditions of scallop adductor muscle (SAM), 65 °C-5.5 h, 70 °C-1.5 h and 100 °C-5 min were selected by the differential scanning calorimetry analysis. After sous-vide cooking, the shear force, hardness, springiness, cohesiveness, chewiness and recoverability of SAM increased significantly compared to fresh sample. The cooking also changed the secondary structures of the proteins in SAM with the rising ß-sheet and descending α-helix, and the chemical interactions with the rising hydrophobic interactions and disulfide bonds but the descending ionic bonds and hydrogen bonds. These caused the longitudinal shrinkage and transverse aggregation of muscle fibers, and the aggregation and cross-linking between myofibrils which led to the squeeze of immobile water from myofibril network structure. This indicated that the denaturation, oxidation, aggregation and cross-linking of proteins caused by heat treatment changed the microstructure and water distribution, which contributed to the increased textural indicators of sous-vide cooked SAM.


Assuntos
Culinária , Pectinidae , Animais , Músculo Esquelético/química , Miofibrilas/química , Água/análise
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