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INTRODUCTION: Thalassemia represents a significant public health challenge globally. However, the global burden of thalassemia and the disparities associated with it remain poorly understood. Our study aims to uncover the long-term spatial and temporal trends in thalassemia at global, regional, and national levels, analyze the impacts of age, time periods, and birth cohorts, and pinpoint the global disparities in thalassemia burden. METHODS: We extracted data on the thalassemia burden from the Global Burden of Disease Study (GBD) 2019. We employed a joinpoint regression model to assess temporal trends in thalassemia burden and an age-period-cohort model to evaluate the effects of age, period, and cohort on thalassemia mortality. RESULTS: From 1990 to 2019, the number of thalassemia incident cases, prevalent cases, mortality cases, and disability-adjusted life years (DALYs) decreased by 20.9%, 3.1%, 38.6%, and 43.1%, respectively. Age-standardized rates of incidence, prevalence, mortality, and DALY declined across regions with high, high-middle, middle, and low-middle sociodemographic index (SDI), yet remained the highest in regions with low SDI and low-middle SDI as well as in Southeast Asia, peaking among children under five years of age. The global prevalence rate was higher in males than in females. The global mortality rate showed a consistent decrease with increasing age. CONCLUSION: The global burden of thalassemia has significantly declined, yet notable disparities exist in terms of gender, age groups, periods, birth cohorts, SDI regions, and GBD regions. Systemic interventions that include early screening, genetic counseling, premarital health examinations, and prenatal diagnosis should be prioritized in regions with low, and low-middle SDI, particularly in Southeast Asia. Future population-based studies should focus specifically on thalassemia subtypes and transfusion requirements, and national registries should enhance data capture through newborn screening.
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Carga Global de Enfermedades , Talasemia , Humanos , Talasemia/epidemiología , Talasemia/mortalidad , Carga Global de Enfermedades/tendencias , Masculino , Femenino , Niño , Preescolar , Adolescente , Prevalencia , Lactante , Incidencia , Adulto , Salud Global/estadística & datos numéricos , Adulto Joven , Recién Nacido , Años de Vida Ajustados por Discapacidad , Costo de Enfermedad , Tasa de SupervivenciaRESUMEN
The exploration of the physical attributes of the recently discovered orthocarbonate Sr3CO5 is significant for comprehending the carbon cycle and storage mechanisms within the Earth's interior. In this study, first-principles calculations are initially used to examine the structural phase transitions of Sr3CO5 polymorphs within the range of lower mantle pressures. The results suggest that Sr3CO5 with the Cmcm phase exhibits a minimal enthalpy between 8.3 and 30.3 GPa. As the pressure exceeds 30.3 GPa, the Cmcm phase undergoes a transition to the I4/mcm phase, while the experimentally observed Pnma phase remains metastable under our studied pressure. Furthermore, the structural data of SrO, SrCO3, and Sr3CO5 polymorphs are utilized to develop a deep learning potential model suitable for the Sr-C-O system, and the pressure-volume relationship and elastic constants calculated using the potential model are in line with the available results. Subsequently, the elastic properties of Cmcm and I4/mcm phases in Sr3CO5 at high temperature and pressure are calculated using the molecular dynamics method. The results indicate that the I4/mcm phase exhibits higher temperature sensitivity in terms of elastic moduli and wave velocities compared to the Cmcm phase. Finally, the thermodynamic properties of the Cmcm and I4/mcm phases are predicted in the range of 0-2000 K and 10-120 GPa, revealing that the heat capacity and bulk thermal expansion coefficient of both phases increase with temperature, with the constant volume heat capacity gradually approaching the Dulong-Petit limit as the temperature rises.
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The instability of ester bonds, low water solubility, and increased cytotoxicity of flavonoid glycoside esters significantly limit their application in the food industry. Therefore, the present study attempted to resolve these issues through liposome encapsulation. The results showed that baicalin butyl ester (BEC4) and octyl ester (BEC8) have higher encapsulation and loading efficiencies and lower leakage rate from liposomes than baicalin. FTIR results revealed the location of BEC4 and BEC8 in the hydrophobic layer of liposomes, which was different from baicalin. Additionally, liposome encapsulation improved the water solubility and stability of BEC4 and BEC8 in the digestive system and PBS but significantly reduced their cytotoxicity. Furthermore, the release rate of BEC4 and BEC8 from liposomes was lower than that of baicalin during gastrointestinal digestion. These results indicate that liposome encapsulation alleviated the negative effects of fatty chain introduction into flavonoid glycosides.
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Ésteres , Flavonoides , Liposomas , Flavonoides/química , Flavonoides/farmacología , Flavonoides/administración & dosificación , Liposomas/química , Humanos , Ésteres/química , Solubilidad , Supervivencia Celular/efectos de los fármacos , Composición de MedicamentosRESUMEN
Baicalin, a phenolic glycoside with good lipid-lowering activity, has poor intestinal absorption due to low lipophilicity. In this study, six ester derivatives of baicalin, named BECn (n = 2, 3, 4, 6, 8, and 10) based on their fatty chain lengths, were synthesized by whole-cell catalyzed esterification to improve lipophilicity, and the intestinal absorption and lipid-lowering activity of the synthesized esters were investigated using cell models in vitro. BEC2, BEC3, and BEC4 exhibited higher Papp values than baicalin in Caco-2 cell monolayers. The lipid-lowering activity of the three esters was stronger than baicalin in the cell models of hepatic steatosis, adipocytes and foam macrophages, and was attributed to their higher intracellular accumulation and stronger direct activation of the carnitine palmitoyltransferase 1A. Moreover, these esters were easily hydrolyzed by carboxylesterase and were unstable at pH 7.4, which significantly weakened their absorption and lipid-lowering activity. This study laid the foundation for industrial production and practical application of BAI esters.
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Ésteres , Lípidos , Células CACO-2 , Catálisis , Esterificación , Ésteres/farmacología , Flavonoides , HumanosRESUMEN
Normally, there are multiple microRNAs involved in the pathogenesis of liver fibrosis. In our work, we aimed at identifying the role of miR-34c in the hepatic stellate cell (HSC) activation and liver fibrosis and its potential mechanism. Our results have shown that during natural activation of HSC, the level of miR-34c was increased significantly whereas acyl-CoA synthetase long-chain family member-1(ACSL1), which is a key enzyme can affect fatty acid(FA) synthesis, was decreased. A double fluorescence reporter assay further confirmed that ACSL1 is a direct target gene of miR-34c. Moreover, the inhibition of miR-34C can attenuate the synthesis of collagen in HSC-T6. In our rescue assay, ACSL1 expression was 1.49-fold higher compared to normal control cells which were transfected with the miR-34c inhibitor in a stable low expression ACSL1 cell line. While at the same time, α-SMA and Col1α expression decreased by 18.22% and 2.58%, respectively. Moreover, we performed an in vivo model using dimethylnitrosamine (DMN) in conjunction with the miR-34c agomir, combined with the treatment of DMN and the miR-34c agomir can increase liver fibrosis. Meanwhile, the degree of hepatic fibrosis was increased and lipid droplets reduced dramatically in rats and HSC-T6 cell treated with miR-34c mimics alone compared to untreated groups. Our results indicate that miR-34c plays an essential role in liver fibrosis by targeting ACSL1 closely associated with lipid droplets, and it might be used as a potential therapeutic target.
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Coenzima A Ligasas/genética , Células Estrelladas Hepáticas/patología , Cirrosis Hepática Experimental/genética , Hígado/patología , MicroARNs/metabolismo , Animales , Coenzima A Ligasas/metabolismo , Colágeno/biosíntesis , Dimetilnitrosamina/administración & dosificación , Dimetilnitrosamina/toxicidad , Células Estrelladas Hepáticas/efectos de los fármacos , Humanos , Gotas Lipídicas/metabolismo , Metabolismo de los Lípidos/genética , Hígado/citología , Hígado/efectos de los fármacos , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/patología , MicroARNs/agonistas , MicroARNs/antagonistas & inhibidores , RatasRESUMEN
INTRODUCTION AND AIMS: Choline-metabolizing genetic variation may interact with choline intake on fetal programming and pregnancy outcome. This case-control study aims to explore the association of maternal choline consumption and phosphatidylethanolamine N-methyltransferase (PEMT) gene polymorphism rs7946 with preterm birth risk. METHODS: 145 Han Chinese women with preterm delivery and 157 Han Chinese women with term delivery were recruited in Shanghai. Dietary choline intake during pregnancy was assessed using a validated food frequency questionnaire. Additionally, DNA samples were genotyped for PEMT rs7946 (G5465A) with plasma homocysteine (Hcy) levels measured. RESULTS: Compared with the lowest quartile of choline intake, women within the highest consumption quartile had adjusted odds ratio (aOR) for preterm birth of 0.48 (95% confidence interval, CI [0.24, 0.95]). There was a significant interaction between maternal choline intake and PEMT rs7946 (p for interaction = 0.04), where the AA genotype carriers who consumed the energy-adjusted choline <255.01 mg/day had aOR for preterm birth of 3.75 (95% CI [1.24, 11.35]), compared to those with GG genotype and choline intake >255.01 mg/day during pregnancy. Additionally, the greatest elevated plasma Hcy was found in the cases with AA genotype and choline consumption <255.01 mg/day (p < 0.001). CONCLUSION: The AA genotype of PEMT rs7946 may be associated with increased preterm birth in these Han Chinese women with low choline intake during pregnancy.
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Colina/análisis , Fenómenos Fisiologicos Nutricionales Maternos/genética , Fosfatidiletanolamina N-Metiltransferasa/genética , Resultado del Embarazo/genética , Nacimiento Prematuro/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Dieta/estadística & datos numéricos , Encuestas sobre Dietas , Ingestión de Alimentos/genética , Femenino , Genotipo , Humanos , Polimorfismo Genético/efectos de los fármacos , EmbarazoRESUMEN
Diabetes mellitus (DM) is a principal health problem with increasing incidence worldwide. It can be associated with various systemic diseases. Long non-coding RNA (lncRNA), a member of non-coding RNA has been newly linked with various human diseases. Recent evidence from animal experiments has shown that the incidence and development of type 2 diabetes are contributed by the atypical expression of lncRNA in which the biomarker with capable clinical potential was lncRNA NONRATT021972. In this review, we demonstrated the numerous functions of NONRATT021972 in different diabetes-related diseases including diabetic neuropathy, diabetic cardiac autonomic neuropathy, myocardial ischemia, and hepatic glucokinase dysfunction. The emerging evidence shows that the role of NONRATT021972 in diabetic-related disease is novel and therapeutic. These results direct us to conclude that NONRATT021972 is a potential diagnostic and future targeted therapy for diabetes-associated diseases.
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Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Neuropatías Diabéticas/genética , Isquemia Miocárdica/genética , ARN Largo no Codificante/metabolismo , Animales , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/epidemiología , Regulación de la Expresión Génica , Glucógeno Sintasa Quinasa 3/deficiencia , Humanos , Incidencia , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiología , RatasRESUMEN
OBJECTIVE: To discover the expression pattern and potential underlying mechanism of the caspase recruitment domain-containing protein 9 (CARD9) in oral squamous cell carcinoma (OSCC). METHODS: Caspase recruitment domain-containing protein 9 expression was detected by qRT-PCR and Western blot in OSCC tissues and cells, and OSCC (CGHNC9 and OECM-1) cell lines were divided into control, NC siRNA, and CARD9 siRNA groups. Then, MTT, flow cytometry, wound-healing, and Transwell assays were carried out to determine the changes in cellular biological characteristics. Immunoblot assay was performed for the expressions of NF-κB pathway. Finally, we constructed the xenograft models in nude mice to validate the in vivo effect of CARD9 siRNA on OSCC cell growth. RESULTS: Caspase recruitment domain-containing protein 9 was upregulated in both OSCC tissues and cells, exhibiting a close relation with major clinicopathological features of OSCC patients. Transfection of CARD9 siRNA inhibited the proliferation, migration, and invasion of OSCC cells with the enhanced cell apoptosis, and meanwhile, CARD9, p-p65/p65, p-IKKα/IKKα, and p-IkBα/IkBα were downregulated. The tumor formation assay on nude mice also suggested that CARD9 siRNA might block the in vivo growth of OSCC cells. CONCLUSION: Caspase recruitment domain-containing protein 9 suppression results in the upregulation of NF-κB pathway with suppressed proliferation, migration, and invasion of OSCC cells and facilitates the apoptosis.
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Biomarcadores de Tumor/metabolismo , Proteínas Adaptadoras de Señalización CARD/genética , Carcinoma de Células Escamosas/patología , Regulación hacia Abajo/fisiología , Neoplasias de la Boca/patología , Proteína p53 Supresora de Tumor/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Desnudos , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , FN-kappa BRESUMEN
OBJECTIVE: A strain of Aspergillus niger (A. niger), capable of releasing bound phenolic acids from wheat bran, was isolated. This strain was identified by gene sequence identification. The antioxidant and anti-inflammatory capacity of ferulic acid released from wheat bran by this A. niger strain (FA-WB) were evaluated. METHODS: Molecular identification techniques based on PCR analysis of specific genomic sequences were conducted; antioxidant ability was examined using oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA) assays, and erythrocyte hemolysis assays. RAW264.7 cells were used as a model to detect anti-inflammatory activity. RESULTS: The filamentous fungal isolate was identified to be A. niger. ORAC and CAA assay showed that FA-WB had better antioxidant activity than that of the ferulic acid standard. The erythrocyte hemolysis assay results suggested that FA-WB could attenuate AAPH-induced oxidative stress through inhibition of reactive oxy gen species (ROS) generation. FA-WB could significantly restore the AAPH-induced increase in intracellular antioxidant enzyme activities to normal levels as well as inhibit the intracellular malondialdehyde formation. TNF-a, IL-6, and NO levels indicated that FA-WB can inhibit the inflammation induced by lipopolysaccharide (LPS). CONCLUSION: Ferulic acid released from wheat bran by a new strain of A. niger had good anti-inflammatory activity and better antioxidant ability than standard ferulic acid.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Aspergillus niger/metabolismo , Ácidos Cumáricos/farmacología , Fibras de la Dieta/microbiología , Animales , Antiinflamatorios/metabolismo , Antioxidantes/metabolismo , Aspergillus niger/genética , Aspergillus niger/aislamiento & purificación , Ácidos Cumáricos/metabolismo , ADN de Hongos/análisis , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Fermentación , Células Hep G2 , Humanos , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Ratones , Células RAW 264.7 , Ovinos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: The 2016 President's Cancer Panel Connected Health report calls for thoroughly characterizing the team structures and processes involved in coordinating care for people with chronic conditions. We developed a multilevel care coordination framework by integrating existing frameworks from the teams and care coordination literatures, and used it to review evidence examining care coordination processes for patients with cancer, diabetes, cardiovascular disease, and combinations of these conditions. METHODS: We searched Pubmed/MedLINE, CINAHL Plus, Cochrane, PsycINFO (December 2009-June 2016), and references from previous reviews. Studies describing behavioral markers of coordination between ≥2 US health care providers caring for adults with cancer, chronic heart disease, diabetes, or populations with a combination of these conditions were included. Two investigators screened 4876 records and 180 full-text articles yielding 33 studies. One investigator abstracted data, a second checked abstractions for accuracy. RESULTS: Most studies identified information sharing or monitoring as key coordination processes. To execute these processes, most studies used a designated role (eg, coordinator), objects and representations (eg, survivorship plans), plans and rules (eg, protocols), or routines (eg, meetings). Few examined the integrating conditions. None statistically examined coordination processes or integrating conditions as mediators of relationships between specific coordination mechanisms and patient outcomes. LIMITATIONS: Restricted to United States, English-language studies; heterogeneity in methods and outcomes. CONCLUSIONS: Limited research unpacks relationships between care coordination mechanisms, coordination processes, integrating conditions, and patient outcomes suggested by existing theory. The proposed framework offers an organizer for examining behaviors and conditions underlying effective care coordination.
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Continuidad de la Atención al Paciente , Conducta Cooperativa , Personal de Salud , Humanos , Difusión de la Información/métodos , Enfermedades no Transmisibles/terapiaRESUMEN
BACKGROUND: Flavonoid glycosides have many beneficial effects on health, but these bioactivities tend to decrease after oral administration owing to their poor lipophilicity. In this study, a facile whole-cell-based method was developed for selective preparation of monoester or diester of troxerutin, a flavonoid derivative. In addition, the bioavailabilities and antioxidant properties of troxerutin and its acylated derivatives were also investigated in cells. RESULTS: Pseudomonas aeruginosa and Pseudomonas stutzeri cells showed high catalytic efficiency (substrate conversion > 90%) and different preferences for troxerutin, resulting in the production of its monoester (TME) and diester (TDE), respectively. The logP values of troxerutin, TME, and TDE were - 2.04 ± 0.10, - 0.75 ± 0.08, and 1.51 ± 0.05 and their Papp values were 0.34 × 10-6 ± 0.05, 0.99 × 10-6 ± 0.12, and 1.54 × 10-6 ± 0.17 cm/s, respectively. The results of hydroxyl radical, ABTS, and ORAC assays indicated that the antiradical activities of acylated derivatives did not exceed that of troxerutin, but showed higher inhibition effects upon 2,2'-azobis(2-amidinopropane) dihydrochloride-induced erythrocyte hemolysis than that of troxerutin (P < 0.05). CONCLUSION: A facile and efficient whole-cell biocatalysis method was developed to synthesize troxerutin-acylated derivatives, markedly enhancing the bioavailability and antioxidant activities of troxerutin in cells. Additionally, the mechanism underlying the observed difference in the antioxidant activities of troxerutin and its esters was ascribed to both their free radical scavenging abilities and distribution on the cell membrane surface.
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Anticoagulantes/síntesis química , Antioxidantes/metabolismo , Hidroxietilrutósido/análogos & derivados , Anticoagulantes/uso terapéutico , Disponibilidad Biológica , Humanos , Hidroxietilrutósido/síntesis química , Hidroxietilrutósido/uso terapéuticoRESUMEN
Aging is a complex phenomenon, where damage accumulation, increasing deregulation of biological pathways, and loss of cellular homeostasis lead to the decline of organismal functions over time. Interestingly, aging is not entirely a stochastic process and progressing at a constant rate, but it is subject to extensive regulation, in the hands of an elaborate and highly interconnected signaling network. This network can integrate a variety of aging-regulatory stimuli, i.e. fertility, nutrient availability, or diverse stresses, and relay them via signaling cascades into gene regulatory events - mostly of genes that confer stress resistance and thus help protect from damage accumulation and homeostasis loss. Transcription factors have long been perceived as the pivotal nodes in this network. Yet, it is well known that the epigenome substantially influences eukaryotic gene regulation, too. A growing body of work has recently underscored the importance of the epigenome also during aging, where it not only undergoes drastic age-dependent changes but also actively influences the aging process. In this review, we introduce the major signaling pathways that regulate age-related decline and discuss the synergy between transcriptional regulation and the epigenetic landscape.
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BACKGROUND: The incidence of liver fibrosis remains high due to the lack of effective therapies. Our previous work found that microRNA (miR)-34a expression was increased, while acy1-CoA synthetase long-chain family member1 (ACSL1) was decreased, in a dimethylnitrosamine (DNS)-induced hepatic fibrosis rat model. We hypothesized that miR-34a may play a role in the process of hepatic fibrosis by targeting ACSL1. MATERIAL AND METHODS: From days 2 to 14, cultured primary hepatic stellate cells (HSCs) underwent cell morphology, immunocytochemical staining, and quantitative reverse transcription PCR (RT-qPCR) for alpha smooth muscle actin (a-SMA), desmin, rno-miR-34a, and ACSL1 expression. Wild-type and mutant luciferase reporter plasmids were constructed according to the predicted miR-34a binding site on the 3'-untranslated region (UTR) of the ACSL1 mRNA and then transfected into HEK293 cells. rno-miR-34a was silenced in HSCs to confirm that rno-miR-34a negatively regulates ACSL1 expression. mRNA and protein expression of α-SMA, type I collagen, and desmin were assayed in miR-34a-silenced HSCs. RESULTS: HSCs were deemed quiescent during the first 3 days and activated after 10 days. rno-miR-34a expression increased, and ACSL1 expression decreased, from day 2 to 7 to 14. rno-miR-34a was shown to specifically bind to the 3'-UTR of ACSL1. miR-34a-silenced HSCs showed higher ACSL1and lower α-SMA, type I collagen, and desmin expression than that of matching negative controls and non-transfected cells. CONCLUSIONS: miR-34a appears to play an important role in the process of liver fibrosis by targeting ACSL1 and may show promise as a therapeutic molecular target for hepatic fibrosis.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Regulación de la Expresión Génica , Células Estrelladas Hepáticas/citología , MicroARNs/metabolismo , Regiones no Traducidas 3' , Actinas/metabolismo , Animales , Dimetilnitrosamina , Silenciador del Gen , Células HEK293 , Humanos , Inmunohistoquímica , Hígado/efectos de los fármacos , Hígado/patología , Cirrosis Hepática/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Saussurea laniceps is a traditional medicinal herb. In our previous study, a pectin polysaccharide, SLP-4, was isolated from the petals of S. laniceps. In this study, the immunomodulatory activity of SLP-4 was studied by analyzing its effects on macrophage (RAW 264.7 cells) polarization. The immunomodulatory activity assays indicated that SLP-4 could significantly enhance the pinocytic and phagocytic capacity and promote the expression and secretion of cytotoxic molecules (nitric oxide, increased by 6.4 times when the SLP-4 concentration was 800 µg/mL) and cytokines (tumor necrosis factor-α and interleukin-6 increased by 7.7 and 11.9 times, respectively) in original macrophage. The possible mechanism could be attributed to the activation of the mitogen-activated protein kinase and nuclear factor-κB signaling pathways through Toll-like receptors 2 and 4. Moreover, SLP-4 significantly induced M1 polarization of original macrophages and transferred macrophages from M2 to M1, but had little effect on the conversion of M1 macrophages into M2 phenotype. Overall, these results demonstrate the potential of SLP-4 as an attractive immunomodulating functional supplement.
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A novel yeast-mediated hydrogenation was developed for the synthesis of neohesperidin dihydrochalcone (NHDC) in high yields (over 83%). Moreover, whole-cell catalytic hydrolysis was also designed to hydrolyze NHDC into potential sweeteners, hesperetin dihydrochalcone-7-O-glucoside (HDC-G) and hesperetin dihydrochalcone (HDC). The biohydrogenation was further combined with whole-cell hydrolysis to achieve a one-pot two-step biosynthesis, utilizing yeast to hydrogenate CâC in the structure, while Aspergillus niger cells hydrolyze glycosides. The conversion of NHDC and the proportion of hydrolysis products could be controlled by adjusting the catalysts, the components of the reaction system, and the addition of glucose. Furthermore, yeast-mediated biotransformation demonstrated superior reaction stability and enhanced safety and employed more cost-effective catalysts compared to the traditional chemical hydrogenation of NHDC synthesis. This research not only provides a new route for NHDC production but also offers a safe and flexible one-pot cascade biosynthetic platform for the production of high-value compounds from citrus processing wastes.
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Chalconas , Hesperidina , Hesperidina/análogos & derivados , Saccharomyces cerevisiae , Hidrólisis , Saccharomyces cerevisiae/metabolismo , Estudios de Factibilidad , Hesperidina/química , BiotransformaciónRESUMEN
In this study, we developed a multi-site acylation strategy to improve the lipophilicity and cellular uptake of troxerutin, a natural flavonoid with many health-promoting bioactivities. By clarifying the acylation properties of troxerutin catalyzed by lipases from different sources, a series of troxerutin ester derivatives acylated at different sites was synthesized, including troxerutin dipropyl (TDP), tripropyl (TTP), tetrapropyl (TEP), dibutyl (TDB), monohexyl (TMH), monooctyl (TMO) and monodecyl (TMD) esters. Interestingly, the troxerutin esters acylated at multiple sites with shorter fatty chains (TDP, TTP and TEP) had similar lipophilicity to the mono-acylated esters bearing longer fatty chains (TMH, TMO and TMD, respectively) and meanwhile demonstrated surprisingly lower cytotoxicity than that of the long fatty-chain mono-esters. In particular, the multi-acylated esters with shorter fatty chains showed remarkably higher cellular uptake than the mono-esters with long fatty chains. In vitro gastrointestinal digestion suggested that the multi-acylated esters of troxerutin were more resistant to gastrointestinal degradation than the mono-esters. These results indicated that multi-site acylation with short fatty chains could be an effective alternative to introducing one-site mono-acylation for the modification of troxerutin and other flavonoid compounds.
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Hidroxietilrutósido , Lipasa , Acilación , Humanos , Hidroxietilrutósido/análogos & derivados , Hidroxietilrutósido/farmacología , Hidroxietilrutósido/química , Hidroxietilrutósido/metabolismo , Lipasa/metabolismo , Lipasa/química , AnimalesRESUMEN
AIMS: Caused by multiple risk factors, heavy burden of major depressive disorder (MDD) poses serious challenges to public health worldwide over the past 30 years. Yet the burden and attributable risk factors of MDD were not systematically known. We aimed to reveal the long-term spatio-temporal trends in the burden and attributable risk factors of MDD at global, regional and national levels during 1990-2019. METHODS: We obtained MDD and attributable risk factors data from Global Burden of Disease Study 2019. We used joinpoint regression model to assess the temporal trend in MDD burden, and age-period-cohort model to measure the effects of age, period and birth cohort on MDD incidence rate. We utilized population attributable fractions (PAFs) to estimate the specific proportions of MDD burden attributed to given risk factors. RESULTS: During 1990-2019, the global number of MDD incident cases, prevalent cases and disability-adjusted life years (DALYs) increased by 59.10%, 59.57% and 58.57%, respectively. Whereas the global age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR) and age-standardized DALYs rate (ASDR) of MDD decreased during 1990-2019. The ASIR, ASPR and ASDR in women were 1.62, 1.62 and 1.60 times as that in men in 2019, respectively. The highest age-specific incidence, prevalence and DALYs rate occurred at the age of 60-64 in women, and at the age of 75-84 in men, but the maximum increasing trends in these age-specific rates occurred at the age of 5-9. Population living during 2000-2004 had higher risk of MDD. MDD burden varied by socio-demographic index (SDI), regions and nations. In 2019, low-SDI region, Central sub-Saharan Africa and Uganda had the highest ASIR, ASPR and ASDR. The global PAFs of intimate partner violence (IPV), childhood sexual abuse (CSA) and bullying victimization (BV) were 8.43%, 5.46% and 4.86% in 2019, respectively. CONCLUSIONS: Over the past 30 years, the global ASIR, ASPR and ASDR of MDD had decreased trends, while the burden of MDD was still serious, and multiple disparities in MDD burden remarkably existed. Women, elderly and populations living during 2000-2004 and in low-SDI regions, had more severe burden of MDD. Children were more susceptible to MDD. Up to 18.75% of global MDD burden would be eliminated through early preventing against IPV, CSA and BV. Tailored strategies-and-measures in different regions and demographic groups based on findings in this studywould be urgently needed to eliminate the impacts of modifiable risk factors on MDD, and then mitigate the burden of MDD.
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Trastorno Depresivo Mayor , Carga Global de Enfermedades , Salud Global , Humanos , Trastorno Depresivo Mayor/epidemiología , Factores de Riesgo , Carga Global de Enfermedades/tendencias , Femenino , Masculino , Incidencia , Salud Global/estadística & datos numéricos , Adulto , Prevalencia , Persona de Mediana Edad , Análisis Espacio-Temporal , Anciano , Años de Vida Ajustados por Discapacidad/tendencias , Adulto Joven , Costo de Enfermedad , AdolescenteRESUMEN
AIM: To elucidate the relationship between macular sensitivity and time in range (TIR) obtained from continuous glucose monitoring (CGM) measures in diabetic patients with or without diabetic retinopathy (DR). METHODS: This was a cross-sectional study including 100 eyes of non-DR patients and 60 eyes of DR patients. An advanced microperimetry was used to quantitate the retinal mean sensitivity (MS) and fixation stability in central macula. TIR of 3.9-10.0 mmol/L was evaluated with CGM. Pearson coefficient analysis and multiple linear regression analysis were used to assess the correlation between TIR and retinal sensitivity. RESULTS: In a comparison of non-DR patients, significant differences (P<0.05) were found in HbA1c, TIR, coefficient of variation (CV), standard deviation of blood glucose (SDBG) and mean amplitude of glucose excursion (MAGE) values in DR patients. Besides, those DR patients had significantly poor best-corrected visual acuity (BCVA, logMAR, P=0.001). In terms of microperimetry parameters, retinal mean sensitivity (MS) and the percentages of fixation points located within 2° and 4° diameter circles were significantly decreased in the DR group (P<0.001, P<0.001, P=0.02, respectively). The bivariate contour ellipse area (BCEA) encompassing 68.2%, 95.4%, 99.6% of fixation points were all significantly increased in the DR group (P=0.01, P=0.006, P=0.01, respectively). Correlation analysis showed that MS were significantly correlated with HbA1c (P=0.01). TIR was positively correlated with MS (r=0.23, P=0.01). SDBG was negatively correlated with MS (r=-0.24, P=0.01) but there was no correlation between CV and MAGE with MS (P>0.05). A multivariable linear regression analysis was performed to prove that TIR and SDBG were both independent risk factors for MS reduction in the DR group. CONCLUSION: TIR is correlated with retinal MS reduction in DR patients, suggesting a useful option for evaluating DR progression.
RESUMEN
Ochratoxin A (OTA), a typical mycotoxin contaminant found in various agricultural products and foods, poses a serious threat to human health. In this study, an aptasensor based on a novel fluorescence probe comprising a G-rich DNA sequence (G43) and thioflavin T (ThT) was designed via hybridization chain reaction (HCR) for the ultrasensitive detection of OTA. G43 is a concatemer of G-quadruplex and G-triplex (a G-quadruplex-like structure with one G-quartet removed), which can drastically enhance the fluorescence intensity of ThT. For this strategy to work, the OTA aptamer is pro-locked in a hairpin structure, denoted "hairpin-locked aptamer" (HL-Apt). OTA binds to HL-Apt, opens the hairpin structure, releases the trigger sequence, and initiates the HCR reaction to form a long DNA duplex and numerous side chains. The side chains combine entirely with the complementary DNA and liberate the pro-locked G43 DNA, dramatically enhancing the intensity of the ThT fluorescence signal. The fluorescence intensity correlates linearly with the OTA concentration between 0.02 and 2.00 ng mL-1, and the method has a detection limit of 0.008 ng mL-1. The developed aptasensor was used to detect OTA in foodstuffs with satisfactory results.
Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Ocratoxinas , Humanos , Colorantes Fluorescentes/química , Ocratoxinas/análisis , Hibridación de Ácido Nucleico , ADN/genética , ADN/química , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Límite de DetecciónRESUMEN
Rapid eye movement (REM) sleep is the main sleep correlate of dreaming. Ponto-geniculo-occipital (PGO) waves are a signature of REM sleep. They represent the physiological mechanism of REM sleep that specifically limits the processing of external information. PGO waves look just like a message sent from the pons to the lateral geniculate nucleus of the visual thalamus, the occipital cortex, and other areas of the brain. The dedicated visual pathway of PGO waves can be interpreted by the brain as visual information, leading to the visual hallucinosis of dreams. PGO waves are considered to be both a reflection of REM sleep brain activity and causal to dreams due to their stimulation of the cortex. In this review, we summarize the role of PGO waves in potential neural circuits of two major theories, i.e., (1) dreams are generated by the activation of neural activity in the brainstem; (2) PGO waves signaling to the cortex. In addition, the potential physiological functions during REM sleep dreams, such as memory consolidation, unlearning, and brain development and plasticity and mood regulation, are discussed. It is hoped that our review will support and encourage research into the phenomenon of human PGO waves and their possible functions in dreaming.