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DNA G-quadruplex(G4) is a guanine-rich single-stranded DNA sequence that spontaneously folds into a spherical four-stranded DNA secondary structure in oncogene promoter sequences and telomeres. G4s are highly associated with the occurrence and development of cancer and have emerged as promising anticancer targets. Natural products have long been important sources of anticancer drug development. In recent years, significant progress has been made in the discovery of natural drugs targeting DNA G4s, with many DNA G4s have been confirmed as promising targets of natural products, including MYC-G4, KRAS-G4, PDGFR-ß-G4, BCL-2-G4, VEGF-G4, and telomeric G4. This review summarizes the research progress in discovering natural small molecules that target DNA G4s and their binding mechanisms. It also discusses the opportunities of and challenges in developing drugs targeting DNA G4s. This review will serve as a valuable reference for the research on natural products, particularly in the development of novel antitumor medications.
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Produtos Biológicos , Quadruplex G , Quadruplex G/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Humanos , Animais , DNA/química , DNA/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Time-restricted eating (TRE) effectively improves healthspan, including controlling obesity and improving metabolic health. To date, few meta-analyses have been conducted to explore the effects of various protocols of TRE in participants with overweight/obesity. PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched up until October 15, 2022. Randomized and non-randomized clinical trials that investigated the effect of TRE on body weight, body composition and cardiometabolic parameters in participants with overweight/obesity were included. Mean differences of changes from the baseline were used for all analyses between the two groups. Prespecified subgroup analyses based on different protocols of TRE were performed. Twenty-three studies were included in the meta-analysis with 1867 participants. TRE interventions led to significant changes in body weight. When energy restriction strategies were conducted in both the TRE and control groups, the weight-loss effect of TRE remained significant. TRE with 4 â¼ 8h feeding window, morning or late eating strategies, led to reduction in body weight and fat mass for at least 8 wk. Hence TRE is a potential and effective approach for weight loss for participants with overweight/obesity. An 8h-TRE intervention with a morning eating strategy for at least eight weeks might be the optimum TRE intervention mode.
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Background: The current research on advanced glycosylation end products (AGEs) and cognitive function is limited. Objective: We aimed to investigate the relationship between multiple plasma AGEs and cognitive function and mild cognitive impairment (MCI). Methods: Baseline data from The Lifestyle and Healthy Aging of Chinese Square Dancer Study was used in this cross-sectional study. Ultra-high-performance liquid chromatography tandem mass spectrometry was used to determine plasma levels of carboxymethyl lysine (CML), carboxyethyl lysine (CEL), and methyl imidazolinone (MG-H1). Four cognitive tests were used to obtain the four cognitive domain scores and the composite z scores. The Petersen criteria were used to diagnose MCI. The data were analyzed by multivariable linear and logistic regression models. Results: This study included 1,018 participants (median age 61.0 years, 87.3% female). After multivariate adjustment, the ßs of the highest quartile of CML and CEL compared to the lowest quartile were -0.28 (-0.38, -0.17) and -0.13 (-0.23, -0.03), respectively, for the composite z score. For the four cognitive domains, CML was negatively correlated with memory, attention, and executive function, and CEL was negatively associated with memory and language function. In addition, higher CML was associated with a higher odds of MCI. MG-H1 was not associated with cognitive function. Conclusions: High plasma AGE levels were correlated with poorer cognitive function, particularly CML and CEL, higher levels of CML were also associated with higher odds of MCI. To clarify the effects of different AGEs on cognitive function and the underlying mechanisms, further longitudinal and experimental studies are needed.
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Cognição , Disfunção Cognitiva , Produtos Finais de Glicação Avançada , Lisina , Humanos , Feminino , Produtos Finais de Glicação Avançada/sangue , Masculino , Disfunção Cognitiva/sangue , Pessoa de Meia-Idade , Estudos Transversais , Cognição/fisiologia , Idoso , Lisina/análogos & derivados , Lisina/sangue , Testes Neuropsicológicos/estatística & dados numéricos , China/epidemiologiaRESUMO
OBJECTIVES: To investigate the association of serum saturated fatty acids (SFAs) and prevalent mild cognitive impairment (MCI) among middle-aged and elderly Chinese. METHODS: A total of 607 Chinese adults aged at least 45 years were included in the baseline survey of The Lifestyle and Healthy Aging of Chinese Square Dancer Study. Serum concentrations of individual SFAs including 6 even-chain SFAs (C14:0, C16:0, C18:0, C20:0, C22:0, and C24:0) and 4 odd-chain SFAs (C15:0, C17:0, C21:0, and C23:0), were quantified by Gas chromatography system with a mass spectrometer. According to Petersen's criteria, prevalent MCI was diagnosed by neurologists through uniformed neuropsychological tests, including trail-making test-part B (TMT-B), auditory verbal learning test (AVLT), digit symbol substitution test (DSST), and verbal fluency test (VFT). RESULTS: The median age was 62 years with an interquartile range of 57.0 to 67.0 years, and 86 (14.17%) participants were living with MCI. Higher levels of either even-chain or odd-chain individual SFAs were associated with the higher odds of MCI, and their odds ratios (ORs) and 95% confidence intervals (95%CIs) were 2.054 (1.012 to 4.171) for C14:0, 2.246 (1.061 to 4.755) for C16:0, 2.789 (1.321 to 5.886) for C18:0, and 2.329 (1.136 to 4.778) for C15:0, and 2.761 (1.310 to 5.820) for C17:0, respectively. CONCLUSIONS: The serum concentration of SFAs was positively related to the odds of MCI in middle-aged and elderly adults. Determining the link between SFAs profiles and MCI may inform a better understanding of the potential role of saturated fat intake on cognitive function.
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Elucidating the quality markers(Q-markers) of traditional Chinese medicines is essential for understanding the mechanisms of action and promoting the rational use of traditional Chinese medicines as well as for developing traditional Chinese medicine-derived drugs. Studies have shown that surface plasmon resonance(SPR) is promising in this field. This study proposed a method based on pull-down with SPR chips to predict the Q-markers of Angong Niuhuang pills(AGNHP). Firstly, 71 main chemical components of AGNHP were analyzed by UPLC-Q-TOF-MS, and then network pharmacology was employed to predict the potential targets of AGNHP against stroke. Secondly, the STAT3 protein chip was constructed, and the extract of AGNHP was recovered by pull-down of the SPR system for STAT3 ligand. The potential active ingredients were collected, enriched, and identified as coptisine, palmatine, epiberberine, berberine, worenine, demethyleneberberine, jatrorrhizine, tetrahydrocoptisine, baicalein, and baicalin methyl ester. Next, the affinity constants of the 10 active ingredients were determined as 44.7, 44, 58.1, 51.3, 39.7, 32.1, 49.2, 69.1, 19.7, and 24.9 µmol·L~(-1), respectively. The molecular docking results showed that the 10 compounds could compete for binding with STAT3. This is the first report that SPR combined with UPLC-Q-TOF-MS is reliable and feasible for determining the active ingredients of AGNHP at the molecular level from complex systems. STAT3 could be used as a potential target for the biological quality evaluation of AGNHP.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas , Ressonância de Plasmônio de Superfície , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Espectrometria de Massas/métodos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Controle de Qualidade , Humanos , Espectrometria de Massa com Cromatografia LíquidaRESUMO
Circadian clock plays a vital role in the pathological progression of cardiovascular disease (CVD). Our previous studies showed that acrolein, an environmental pollutant, promoted atherosclerosis by reducing CLOCK/BMAL1 and disturbing circadian rhythm. Whereas, intermittent fasting (IF), a diet pattern, was able to ameliorate acrolein-induced atherosclerosis. In vivo, mice were fed acrolein 3 mg/kg/day via drinking water and IF for 18h (0:00-18:00). We observed that IF decreased acrolein-accelerated the formation of aortic lesion in ApoE -/- mice. Up-regulation of NF-κB, IL-1ß and TNF-α levels were found in liver and heart tissue upon acrolein exposure, while was down-regulated by IF. Interestingly, IF treatment exhibited higher AMPK, p-AMPK and SIRT1and lower MAPK expression which was caused by acrolein. Besides, circadian genes Clock/ Bmal1 expression were suppressed and disturbed treated with acrolein, while were reversed by IF. Furthermore, consistent with that in vivo, short-term starvation as a fasting cell model in vitro could improve the disorders of CLOCK/BMAL1 and raised SIRT1 via regulating AMPK, as well as ROS-MAPK induced by acrolein. In conclusion, we demonstrated that IF repressed ROS-MAPK while activated AMPK to elevate the expression of circadian clock genes to ameliorate acrolein-induced atherogenesis, which shed a novel light to prevent cardiovascular diseases.
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BACKGROUND & AIMS: Aquatic food is rich in nutrients which benefit the human brain and cognitive health; however, concerns about heavy metal accumulation in aquatic food remain. This study evaluated the associations between aquatic food consumption, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) intake, and blood mercury levels with cognition in middle-aged and older adults. METHODS: This cross-sectional study used baseline data from the Lifestyle and Healthy Aging of Chinese Square Dancer Study. Aquatic food consumption and LC n-3 PUFAs intake were obtained from a food frequency questionnaire. Blood mercury levels were measured using inductively coupled plasma mass spectrometry. A composite z-score was developed to represent global cognition by averaging the z-scores for each cognitive domain. Participants with mild cognitive impairment (MCI) were diagnosed according to Petersen's criteria. Multivariate linear and logistic regression models were used to examine the association between the exposure factors and cognitive performance including cognitive scores and MCI. RESULTS: Of 2621 middle-aged and older adults, the mean (SD) age was 63.71 (5.15) years, and 85.73% were females. Compared with the lowest quartile, those in the highest quartile for aquatic food consumption were associated with higher composite z-scores (ß = 0.156, 95% CI: 0.088-0.225) and lower MCI odds (OR = 0.598, 95% CI: 0.425-0.841). A similar positive relationship between LC n-3 PUFAs intake and composite z-score and an inverse association between LC n-3 PUFAs intake and MCI were also observed. In addition, the participants in the highest quartile for blood mercury levels had higher composite z-scores than those in the lowest quartile. CONCLUSIONS: In this cross-sectional study, higher aquatic food consumption, LC n-3 PUFAs intake, and blood mercury levels were related to better cognitive function. Further studies in Chinese populations are required to confirm these findings.
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Cognição , Disfunção Cognitiva , Ácidos Graxos Ômega-3 , Mercúrio , Humanos , Feminino , Masculino , Mercúrio/sangue , Estudos Transversais , Pessoa de Meia-Idade , Ácidos Graxos Ômega-3/sangue , Cognição/efeitos dos fármacos , Cognição/fisiologia , Idoso , China , Disfunção Cognitiva/sangue , Alimentos Marinhos , Dieta/estatística & dados numéricos , Dieta/métodosRESUMO
Iron is an essential micronutrient that is necessary for proper cognitive function. However, the dose-response relationship between body iron status and cognitive function remains unclear. The objective of this study was to investigate the association between serum ferritin concentrations, an indicator of body iron status, and cognitive function in older adults. Based on the National Health and Nutrition Examination Survey (NHANES) 1999 -2002 in the United States, nationally representative data was collected from 2,567 adults aged 60 years and older who had objectively measured serum ferritin levels and cognitive performance. High ferritin levels were defined as a serum ferritin level >200 ng/mL in women and >300 ng/mL in men. Low ferritin levels were defined as a serum ferritin level <30 ng/mL. The digit symbol substitution test (DSST) was employed to assess cognitive function. Multivariable logistic regression analyses with survey weights were performed after the DSST was dichotomized at the median score. The weighted prevalence of adults with normal, low, and high serum ferritin levels were 73.98%, 9.12%, and 16.91%, respectively. A U-shaped association between serum ferritin concentrations and cognitive task performance was observed. After adjusting for demographic, socioeconomic, lifestyle, and C-reactive protein factors, the odds ratio (95% confidence intervals) for lower cognitive performance was 1.39 (1.11, 1.74) in adults with high ferritin levels and 1.38 (0.86, 2.22) in adults with low ferritin levels, compared with those with normal ferritin levels. The association between serum ferritin levels and lower cognitive performance was stronger in adults aged 60 to 69 years old than those aged 70 years and older. In conclusion, in a nationally representative sample of older adults in the United States, a high serum ferritin level was significantly associated with worse cognitive task performance. Thus, the relationship between low serum ferritin concentrations and cognitive task performance warrants further investigation.
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OBJECTIVES: Previous studies suggested protective associations of vegetables and fruits (VF) intake with cognitive function, but evidence on specific types of VF was insufficient. METHODS: The current study included 4066 participants from 1997 to 2006 in the China Health and Nutrition Survey (CHNS) and 6170 participants from 2013 to 2020 in the Health and Retirement Study (HRS). Dietary intake (using 3-day 24-h dietary recalls in CHNS and food frequency questionnaire in HRS) and cognitive function (using the Telephone Interview for Cognitive Status-Modified, TICS-m) were measured. Linear mixed-effects models were used to estimate the beta coefficients (ß) and the 95% confidence intervals (CI) to evaluate the association of VF with cognitive function (z-score) and its decline. RESULTS: Highest intake of total VF was associated with better cognitive function and slower cognitive decline. Differences in cognitive function z-score between the highest and lowest tertiles of VF consumption were 0.039 (95% CI: 0.002, 0.076) for CHNS and 0.063 (95% CI: 0.026, 0.100) for HRS. The corresponding differences in annual cognitive decline were 0.011 (95% CI: 0.002, 0.021) and 0.012 (95% CI: 0.003, 0.020) units respectively. Vegetables and fruits showed independent associations with cognitive function and its decline. In specific VF subgroups, when comparing the highest to the lowest tertile intake, cruciferous vegetables (ß = 0.058, 95% CI: 0.017, 0.100 in CHNS and ß = 0.067, 95% CI: 0.032, 0.101 in HRS) and green leafy vegetables (ß = 0.036, 95% CI: -0.001, 0.073 in CHNS and ß = 0.082, 95% CI: 0.046, 0.117 in HRS) was associated with better cognitive function in both cohorts. Similarly, higher intake of dark-colored vegetables (ß = 0.019, 95% CI: 0.008, 0.030 for red/yellow vegetables in CHNS and ß = 0.004, 95% CI: 0.001, 0.007 for green leafy vegetables in HRS) were associated with slower cognitive decline in subsequent years. Moreover, rigorous sensitivity analyses confirmed the stability of the results. CONCLUSIONS: Our findings support the potential beneficial roles of VF, especially cruciferous vegetables, green leafy vegetables, and red/yellow vegetables, in maintaining cognitive function and slowing cognitive decline in middle-aged and older adults.
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Cognição , Disfunção Cognitiva , Dieta , Frutas , Verduras , Humanos , Feminino , Masculino , Cognição/fisiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Idoso , China , Dieta/estatística & dados numéricos , Inquéritos NutricionaisRESUMO
As a notorious phytopathogenic virus, the tobacco mosaic virus (TMV) severely reduced the quality of crops worldwide and caused critical constraints on agricultural production. The development of novel virucides is a persuasive strategy to address this predicament. Herein, a series of novel bisamide-decorated benzotriazole derivatives were elaborately prepared and screened. Biological tests implied that the optimized compound 7d possessed the most brilliant antiviral inactive profile (EC50 = 157.6 µg/mL) and apparently surpassed that of commercial ribavirin (EC50 = 442.1 µg/mL) 2.8-fold. The preliminary antiviral mechanism was elaborately investigated via transmission electron microscopy, microscale thermophoresis (MST) determination, RT-qPCR, and Western blot analysis. The results showed that compound 7d blocked the assembly of TMV by binding with coat protein (Kd = 0.7 µM) and suppressed TMV coat protein gene expression and biosynthesis process. Computational simulations indicated that 7d displayed strong H-bonds and pi interactions with TMV coat protein, affording a lower binding energy (ΔGbind = -17.8 kcal/mol) compared with Ribavirin (ΔGbind = -10.7 kcal/mol). Overall, current results present a valuable perception of bisamide decorated benzotriazole derivatives with appreciably virustatic competence and should be profoundly developed as virucidal candidates in agrochemical.
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Ribavirina , Vírus do Mosaico do Tabaco , Triazóis , Relação Estrutura-Atividade , Ribavirina/farmacologia , Antivirais/farmacologia , Antivirais/química , Desenho de FármacosRESUMO
OBJECTIVES: The objective of this study was to examine the association between dietary diversity and sleep quality among Chinese middle-aged and older adults. METHODS: The Lifestyle and Healthy Aging of Chinese Square Dancer Study is a prospective, community-based cohort study that enrolled participants aged 45 years and above from 2020 to 2021. Using the semiquantitative food frequency questionnaire to investigate the diets of study participants, and using the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Dietary diversity was assessed using two scoring methods covering ten food groups and 66 food items, respectively: the dietary diversity score (DDS) and the food variety score (FVS). The higher scores of DDS and FVS indicated greater dietary diversity and higher dietary quality. Logistic regression analysis explored the associations between these scores and sleep quality. RESULTS: A total of 2409 individuals with completed information on PSQI and FFQ were included in this study, of whom 767 (31.8%) had poor sleep quality. Participants with higher DDS were associated with an 18% lower odds of poor sleep quality compared to those with low DDS (OR = 0.82, 95% CI, 0.68-0.98). Participants in the highest quartile of the FVS had a 32% lower odds of poor sleep quality than those in the lowest quartile (OR = 0.68, 95% CI, 0.52-0.89). CONCLUSIONS: There was a positive correlation between higher FVS and DDS with better sleep quality. Therefore, ensuring a diverse diet may be beneficial for maintaining good sleep quality among middle-aged and older adults.
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Dieta , Qualidade do Sono , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , China , Estudos Prospectivos , Dieta/estatística & dados numéricos , Estudos de Coortes , Inquéritos e Questionários , População do Leste AsiáticoRESUMO
BACKGROUND: Studies regarding the validity of the food frequency questionnaire (FFQ) and the food composition table (FCT) are limited in Asian countries. We aimed to evaluate the validity of a 64-item FFQ and different methods of constructing the FFQ FCTs for assessing dietary intakes of foods and nutrients among adults in eastern China. METHODS: A total of 2325 participants (aged 56.2 ± 14.9 years, 51.6% female) from nine cities in Zhejiang province who completed a 64-item FFQ and 3-day 24-hour dietary recalls (24HRs) in 2015 were included. Eight FFQ FCTs were generated covering food items and specific weights estimated using professional knowledge, representative 24HRs data, or the Chinese FCT (CFCT). Energy-adjusted intakes of foods and nutrients were estimated by residual and energy density methods. Spearman correlation coefficients (SCCs) of intakes of 14 food groups and 17 nutrients between FFQ and 24HRs were calculated to evaluate the overall validity of FFQ. RESULTS: The average intakes of most food groups and nutrients assessed with FFQ were higher than those assessed using the 24HRs. For the food groups, the averaged energy-adjusted (residual method) SCC between FFQ and 24HRs was 0.27, ranging from 0.14 (starch-rich beans) to 0.49 (aquatic products). For nutrient assessment, the weighted FCT (WFCT) performs the best, and the averaged energy-adjusted (residual method) SCC was 0.26, ranging from 0.16 (iron) to 0.37 (potassium). Similar correlations with 24HRs were observed when using other FFQ FCT in the calculation of nutrient intakes. CONCLUSION: The 64-item Chinese FFQ and the WFCT were reasonably valid to assess the dietary intakes of certain foods and nutrients among adults in eastern China.
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Dieta , Alimentos , Adulto , Humanos , Feminino , Masculino , Inquéritos e Questionários , Ingestão de Energia , Ingestão de Alimentos , China , Reprodutibilidade dos Testes , Inquéritos sobre DietasRESUMO
BACKGROUND: Little is known regarding the association of interviewer-reported cognitive problems (ICP) with age-related cognitive decline. We aimed to investigate the independent associations of ICP and the combined associations of ICP and self-reported cognitive problems (SCP) with subsequent cognitive decline and dementia in two prospective cohort studies. METHODS: We included 10,976 Chinese (age = 57.7 ± 8.7) and 40,499 European (age = 64.6 ± 9.4) adults without dementia from the China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Ageing, and Retirement in Europe (SHARE). Self-rated memory (5-point scale) and interviewer-rated frequencies of asking for clarification (6-point scale) were used to define SCP and ICP (dichotomized). Outcomes included objective cognitive test scores (z-score transformation) and incident dementia. Generalized estimating equation models were performed to evaluate mean differences in objective cognitive decline. Logistic and Cox regression models were used to estimate the relative risk of dementia. Results from two cohorts were pooled using the random-effects models. RESULTS: ICP was associated with faster cognitive decline in CHARLS (ßCHARLS = -0.025 [-0.044, -0.006] z-score/year). ICP and SCP were also independently associated with higher risk of dementia in two cohorts (pooled relative risk for SCP = 1.73 [1.30, 2.29]; pooled relative risk for ICP = 1.40 [1.10, 1.79]). In the joint analysis, participants with coexistence of SCP and ICP had the fastest cognitive decline (ßCHARLS = -0.051 [-0.080, -0.021]; ßSHARE = -0.024 [-0.043, -0.004]; pooled ß = -0.035 [-0.061, -0.009] z-score/year) and highest risk of dementia (ORCHARLS = 1.77 [1.42, 2.20]; HRSHARE = 2.94 [2.42, 3.59]; pooled relative risk = 2.29 [1.38, 3.77]). CONCLUSIONS: The study suggested that interviewer-reported cognitive problems may be early indicators of cognitive decline and dementia in middle-aged and older adults. A combination of self- and interviewer-reported cognitive problems showed the strongest associations with cognitive decline and dementia.
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Disfunção Cognitiva , Demência , Pessoa de Meia-Idade , Humanos , Idoso , Estudos Prospectivos , Demência/epidemiologia , Demência/psicologia , Estudos Longitudinais , Disfunção Cognitiva/epidemiologia , CogniçãoRESUMO
OBJECTIVE: The study's objective was to explore whether early time-restricted eating (eTRE) and late time-restricted eating (lTRE) have different impacts on intrahepatic fat and metabolic health among patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This is an 8-week, randomized, parallel-arm, open-label trial. Forty eligible patients were randomly assigned to eTRE (eating between 8:00 a.m. and 4:00 p.m.) or lTRE (eating between 12:00 p.m. and 8:00 p.m.). The primary outcome was the change of intrahepatic fat measured by magnetic resonance image-derived proton density fat fraction. Secondary outcomes included changes in weight, body composition, liver function, and cardiometabolic factors. RESULTS: Forty participants who underwent randomization completed the trial (mean age: 38.25 years). The eTRE group had a -3.24% absolute reduction of intrahepatic fat (95% CI: -4.55% to -1.92%) and there was a -3.51% absolute reduction for the lTRE group (95% CI: -5.10% to -1.92%). Changes in intrahepatic fat were not statistically different between the two groups. Both the eTRE and lTRE groups had similar and significant reductions in weight, visceral fat, subcutaneous fat, liver enzymes, and glucose regulatory indicators. CONCLUSIONS: Among patients with NAFLD, both eTRE and lTRE induced significant reductions in intrahepatic fat and improvements in body composition, liver function, and metabolic health with similar magnitude. These findings suggest that eTRE and lTRE are comparable and feasible strategies for NAFLD management.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Adulto , Hepatopatia Gordurosa não Alcoólica/complicações , Imageamento por Ressonância Magnética , Composição Corporal , Fígado/metabolismoRESUMO
BACKGROUND: Naturally occurring alkaloids are particularly suitable for use as pesticide precursors and further modifications due to their cost-effectiveness, unique mechanism of action, tolerable degradation, and environmental friendliness. The famous tobacco mosaic virus (TMV) is a persistent plant pathogenic virus that can parasitize many plants and severely reduce crop production. To treat TMV disease, TMV helicase acts as a crucial target by hydrolyzing adenosine triphosphate (ATP) to provide energy for double-stranded RNA unwinding. RESULTS: To seek novel framework alkaloid leads targeting TMV helicase, this work successfully established an efficient screening platform for TMV helicase inhibitors based on natural alkaloids. In vivo activity screening, enzyme activity detection, and binding assays showed that Rutaecarpine from Evodia rutaecarpa (Juss.) Benth exhibited excellent TMV helicase inhibitory properties [dissociation constant (Kd ) = 1.1 µm, half maximal inhibitory concentration (IC50 ) = 227.24 µm] and excellent anti-TMV ability. Molecular docking and dynamic simulations depicted that Rutaecarpine could stably bind in active pockets of helicase with low binding energy (ΔGbind = -17.8 kcal/mol) driven by hydrogen bonding and hydrophobic interactions. CONCLUSION: Given Rutaecarpine's laudable bioactivity and structural modifiability, it can serve as a privileged building block for further pesticide discovery.
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Alcaloides , Alcaloides Indólicos , Praguicidas , Quinazolinonas , Vírus do Mosaico do Tabaco , Viroses , Simulação de Acoplamento Molecular , Nicotiana , Doenças das Plantas/prevenção & controleRESUMO
OBJECTIVE: The intestine is responsible for approximately one-third of uric acid (UA) excretion. The effect of commensal Enterococcus faecalis (E. faecalis), one of the most colonized bacteria in the gut, on UA excretion in the intestine remains to be investigated. The aim of this study was to evaluate the effect of commensal E. faecalis on UA metabolism and gut microbiota. METHODS: The 16S rRNA gene sequencing was used to examine the species of Enterococcus in mouse fecal content. E. faecalis strain was isolated from mouse feces and identified to be E. faecalis W5. The hyperuricemia (HUA) animal model was established with yeast-rich forage and 250 mg·kg-1 ·day-1 potassium oxonate. Oral administration of E. faecalis W5 was given for 20 days, serving as the Efa group. RESULTS: Disrupted intestinal barrier, activated proinflammatory response and low UA excretion in the intestine were found in HUA mice. After E. faecalis W5 treatment, the gut barrier was restored and serum UA level was decreased. Additionally, fecal and intestinal UA levels were elevated, intestinal urate transporter ABCG2 and purine metabolism were upregulated. Moreover, short-chain fatty acid levels were increased, and intestinal inflammation was ameliorated. CONCLUSIONS: Commensal E. faecalis W5 ameliorated HUA through reversing the impaired gut barrier, promoting intestinal UA secretion by regulating ABCG2 expression, and decreasing intestinal UA synthesis by regulating purine metabolism. The results may provide the potential for developing treatments for HUA through the intestine.
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Microbioma Gastrointestinal , Hiperuricemia , Camundongos , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Enterococcus faecalis , RNA Ribossômico 16S , PurinasRESUMO
In the protracted "arms race" between host and plant pathogenic bacteria, host organisms have evolved powerful weapons known as host defense peptides (HDPs). However, natural HDPs are not suitable for large-scale applications; therefore, researchers have chosen to develop bespoke small-molecule functional mimics. Phenothiazine derivatives were developed as functional HDPs mimics, owing to their broad biological activity and high lipophilicity. The phenothiazine analogues designed in this study exhibited excellent in vitro bioactivity against the three Gram-negative bacteria Xanthomonas oryzae pv oryzae, Xanthomonas axonopodis pv citri, and Pseudomonas syringae pv actinidiae, with optimal EC50 values of 0.80, 0.31, and 1.91 µg/mL, respectively. Preliminary evidence suggests that compound C2 may act on bacterial cell membranes and interact with bacterial Deoxyribonucleic acid in the groove binding mode. In vivo trials showed that compound C2 was highly effective against rice leaf blight (51.97-56.69%), with activity superior to those of bismerthiazol (40.7-43.4%) and thiodiazole copper (30.2-37.1%). Our study provides strong evidence to support the development of phenothiazine derivatives into pesticide candidates.
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Background: The evidence concerning dietary diversity and cognitive function remains insufficient. Objective: To investigate the association of dietary diversity score (DDS) with mild cognitive impairment (MCI) and cognitive performance in different domains. Methods: Data from The Lifestyle and Healthy Aging of Chinese Square Dancer Study was used in this study. DDS was constructed based on the intake frequencies of 9 food groups assessed by a validated food frequency questionnaire. MCI was diagnosed by Petersen's criteria. A neuropsychological test battery was used to assess the performance on cognitive domains, and test scores were standardized to Z scores. Multiple linear regression models and logistic regression models were used to estimate the ß and odds ratios and their 95% CIs, respectively. Results: Among 1,982 participants, the mean (SD) age was 63.37 (5.00) years, 1,778 (89.71%) were women, and 279 (14.08%) had MCI. Compared to the DDS quartile (0, 6], the multivariable-adjusted odds ratios (95% CI) were 0.74 (0.48, 1.15) for DDS quartile (6, 7], 0.65 (0.43, 0.97) for DDS quartile (7, 8], and 0.55 (0.37, 0.84) for DDS quartile (8, 9]. Furthermore, higher DDS was positively associated with better performance of cognitive domains, including global cognitive function (ß=â0.20, 95% CI: 0.12, 0.30), episodic memory (ß=â0.21, 95% CI: 0.07, 0.35), attention (ß=â0.15, 95% CI: 0.03, 0.26), language fluency (ß=â0.24, 95% CI: 0.10, 0.38), and executive function (ß=â- 0.24, 95% CI: - 0.38, - 0.10). Conclusions: This study indicated that higher DDS was associated with better cognitive function among middle-aged and older Chinese people.
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In the work, zein-yeast carboxymethyl glucan (ZY) particles were fabricated by a novel ultrasonic assisted anti-solvent precipitation (ASP) method, which was a good delivery system for resveratrol. The particle size and zeta-potential of ZY samples were detected by Zetasizer Pro analyzer, they gradually increased as the mass ratio of zein and yeast carboxymethyl glucan (YCG) changed from 10:1 to 10:5. The intermolecular interactions were investigated by zeta-potentiometric analyzer, Fourier transform infrared spectroscopy and fluorescence spectroscopy. Electrostatic interaction, hydrogen bonding and hydrophobic effects between zein and YCG molecules were identified as the main driving forces in the formation of ZY particles. The optimized ZY (10:3) binary particles were used as delivery system for encapsulating and protecting resveratrol. They had high encapsulation efficiency (85.4 %) and loading capacity (6.1 %), and increased the retention rate of resveratrol by 2.10 and 1.21 folds after exposure to light and heat conditions, effectively protect resveratrol against light and thermal degradation. These particles also delayed the release of resveratrol in simulated gastrointestinal digestion, which might improve its oral bioavailability. In conclusion, ZY binary particles could be regarded as a useful and promising delivery vehicle, which might contribute to the application of hydrophobic bioactive ingredients in functional foods.
Assuntos
Nanopartículas , Zeína , Glucanos , Saccharomyces cerevisiae , Zeína/química , Resveratrol , Nanopartículas/química , Tamanho da PartículaRESUMO
Plant proteins are high-quality dietary components of food products. With the growing interest in sustainable and healthy food alternatives, plant proteins have gained significant attention as viable substitutes for animal-based proteins. Understanding the diversity of protein sources derived from plants, novel processing technology, and multiple applications is crucial for developing nutritious and sustainable plant protein-based products. This Review summarizes the natural sources of traditional and emerging plant proteins. The classifications, processing technologies, and applications of plant protein-based products in the food industry are explicitly elucidated. Moreover, the advantages and disadvantages of plant protein-based food products are revealed. Strategies such as protein fortification and complementation to overcome these shortcomings are critically discussed. We also demonstrate several issues that need to be addressed in future development.