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SCOPE: Cerebral ischemia-reperfusion (IR) injury stands as a prominent global contributor to disability and mortality. Nervonic acid (NA), a bioactive elongated monounsaturated fatty acid, holds pivotal significance in human physiological well-being. This research aims to explore the prophylactic effects and fundamental mechanisms of NA in a rat model of cerebral IR injury. METHODS AND RESULTS: Through the induction of middle cerebral artery occlusion, this study establishes a rat model of cerebral IR injury and comprehensively assesses the pharmacodynamic impacts of NA pretreatment. This evaluation involves behavioral analyses, histopathological examinations, and quantification of serum markers. Detailed mechanisms of nervonic acid's prophylactic effects are revealed through fecal metabolomics and 16S rRNA sequencing analyses. Our findings robustly support nervonic acid's capacity to ameliorate neurological impairments in rats afflicted with cerebral IR injury. Beyond its neurological benefits, NA demonstrates its potential by rectifying metabolic perturbations across diverse pathways, particularly those pertinent to unsaturated fatty acid metabolism. Additionally, NA emerges as a modulator of gut microbiota composition, notably by selectively enhancing vital genera like Lactobacillus. CONCLUSION: These comprehensive findings highlight the potential of incorporating NA as a functional component in dietary interventions aimed at targeting cerebral IR injury.
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Suplementos Dietéticos , Heces , Microbioma Gastrointestinal , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Heces/microbiología , Heces/química , Ratas , Infarto de la Arteria Cerebral Media , Isquemia Encefálica , Modelos Animales de EnfermedadRESUMEN
This study aims to investigate the effects of Gualou Xiebai Banxia Decoction(GXBD) on type 2 diabetes mellitus(T2DM) combined with acute myocardial infarction(AMI) in rats via chemerin/chemokine-like receptor 1(CMKLR1)/peroxisome proliferator-activated receptor α(PPARα) signaling pathway, and to explore the mechanism of GXBD in alleviating glucose and lipid metabolism disorders. The SD rats were randomized into control, model, positive control, and low-and high-dose GXBD groups. The rat model of T2DM was established by administration with high-fat emulsion(HFE) by gavage and intraperitoneal injection with streptozotocin, and then coronary artery ligation was performed to induce AMI. The control and model groups were administrated with the equal volume of normal saline, and other groups were administrated with corresponding drugs by gavage. Changes in relevant metabolic indicators were assessed by ELISA and biochemical assays, and the protein levels of chemerin, CMKLR1, and PPARα in the liver, abdominal fat, and heart were determined by Western blot. The results showed that GXBD alleviated the myocardial damage and reduced the levels of blood lipids, myocardial enzymes, and inflammatory cytokines, while it did not lead to significant changes in blood glucose. Compared with the model group, GXBD down-regulated the expression of chemerin in peripheral blood and up-regulated the expression of cyclic adenosine monophosphate(cAMP) and protein kinase A(PKA) in the liver. After treatment with GXBD, the protein levels of chemerin and CMKLR1 in the liver, abdominal fat, and heart were down-regulated, while the protein levels of PPARα in the liver and abdominal fat were up-regulated. In conclusion, GXBD significantly ameliorated the disorders of glycolipid metabolism in the T2DM-AMI model by regulating the chemerin/CMKLR1/PPARα signaling pathway to exert a protective effect on the damaged myocardium. This study provides a theoretical basis for further clinical study of GXBD against T2DM-AMI and is a manifestation of TCM treatment of phlegm and turbidity causing obstruction at the protein level.
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Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Infarto del Miocardio , Ratas , Animales , PPAR alfa/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ratas Sprague-Dawley , Transducción de Señal , Infarto del Miocardio/tratamiento farmacológico , QuimiocinasRESUMEN
Near-infrared-II fluorescence imaging (NIR-II FI) has become a powerful imaging technique for disease diagnosis owing to its superiorities, including high sensitivity, high spatial resolution, deep imaging depth, and low background interference. Despite the widespread application of conjugated polymer nanoparticles (CPNs) for NIR-II FI, most of the developed CPNs have quite low NIR-II fluorescence quantum yields based on the energy gap law, which makes high-sensitivity and high-resolution imaging toward deep lesions still a huge challenge. This work proposes a nanoengineering strategy to modulate the size of CPNs aimed at optimizing their NIR-II fluorescence performance for improved NIR-II phototheranostics. By adjusting the initial concentration of the synthesized conjugated polymer, a series of CPNs with different particle sizes are successfully prepared via a nanoprecipitation approach. Results show that the NIR-II fluorescence brightness of CPNs gradually amplifies with decreasing particle size, and the optimal CPNs, NP0.2, demonstrate up to a 2.05-fold fluorescence enhancement compared with the counterpart nanoparticles. With the merits of reliable biocompatibility, high photostability, and efficient light-heat conversion, the optimal NP0.2 has been successfully employed for NIR-II FI-guided photothermal therapy both in vitro and in vivo. Our work highlights an effective strategy of nanoengineering to improve the NIR-II performance of CPNs, advancing the development of NIR-II FI in life sciences.
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Nanopartículas , Terapia Fototérmica , Polímeros , Nanopartículas/uso terapéutico , Imagen Óptica/métodos , Fototerapia , Línea Celular TumoralRESUMEN
In this study, a new polysaccharide (PSPJ) with specific molecular weight and monosaccharide compositions was isolated and purified from the water extract of Panacis Japonici Rhizoma (PJR). 16S rRNA analysis and untargeted metabolomic analysis were used to assess PSPJ's efficacy in averting non-alcoholic fatty liver disease (NAFLD). This study indicated that PSPJ significantly reduced liver fat accumulation, the increase in blood lipids and ALT caused by HFD, indicating that PSPJ can prevent NAFLD. We demonstrated through cell experiments that PSPJ does not directly affect liver cells. The gut microbiota disorder and alterations in short-chain fatty acids (SCFAs) induced by the high-fat diet (HFD) were ameliorated by PSPJ, as evidenced by the analysis of 16S rRNA. In particular, supplementing PSPJ reduced the abundance of Turicibacter, Dubosiella, and Staphylococcus, and increased the abundance of Bacteroides, Blautia, and Lactobacillus. Untargeted metabolomic analysis shows that PSPJ improves liver metabolic disorders by regulating arachidonic acid metabolism, carbohydrate digestion and absorption, fatty acid biosynthesis, fatty acid metabolism and retinol metabolism. The findings of our investigation indicate that PSPJ has the potential to modulate liver metabolism through alterations in the composition of intestinal bacteria, hence preventing NAFLD.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Panax , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Panax/metabolismo , Hígado/metabolismo , Ácidos Grasos Volátiles/metabolismo , Polisacáridos/farmacología , Polisacáridos/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
Artemisia argyi H.Lév. & Vaniot essential oil (AAEO) has shown pharmacological effects such as anti-inflammation, antioxidant, and anti-tumor properties. However, the protective effect of AAEO on lipopolysaccharide (LPS)-induced liver injury and its potential protective mechanism are still unclear. In this study, we used ultra-performance liquid chromatography tandem mass spectrometry metabolomics techniques to investigate the changes in liver tissue metabolites in mice exposed to LPS with or without AAEO treatment for 14 days. The biochemical results showed that compared with the control group, AAEO significantly reduced the levels of liver functional enzymes, suggesting a significant improvement in liver injury. In addition, the 18 differential metabolites identified by metabolomics were mainly involved in the reprogramming of arachidonic acid metabolism, tryptophan metabolism, and purine metabolism. AAEO could significantly inhibit the expression of COX-2, IDO1, and NF-κB; enhance the body's anti-inflammatory ability; and alleviate liver injury. In summary, our study identified the protective mechanism of AAEO on LPS-induced liver injury at the level of small molecular metabolites, providing a potential liver protective agent for the treatment of LPS-induced liver injury.
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Artemisia , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Aceites Volátiles , Ratones , Animales , Artemisia/química , Aceites Volátiles/farmacología , Lipopolisacáridos/efectos adversos , Espectrometría de Masas en Tándem , Cromatografía Líquida con Espectrometría de Masas , MetabolómicaRESUMEN
Previous longitudinal studies have documented bidirectional associations between parental psychological control and children's externalizing problems over months or years. However, most studies have only examined these associations at the between-family level, and there is a lack of intensive longitudinal data (ILD) on psychological control and children's externalizing problems. Thus, this daily diary study examined the bidirectional associations between parental psychological control and externalizing problems among Chinese children. Further, we explored whether between-family mindful parenting linked to the mean levels and daily fluctuations of parental psychological control and children's externalizing problems. The sample included 71 parents of children between 7 to 13 years old (50.7% male; Mage = 9.92, SD = 1.46). Our findings indicate that at the within-family level, higher parental psychological control than usual predicted increases in externalizing problems among children reported by parents the next day, but not vice versa. Furthermore, between-family mindful parenting was negatively associated with the mean levels of psychological control and children's externalizing problems, as well as with fewer fluctuations of parental psychological control. This study contributes to the understanding of the within-family associations between parental psychological control and children's externalizing problems on a daily basis. Finally, we discuss implications for prevention and intervention programs targeting negative parenting and child externalizing problems.
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Relaciones Padres-Hijo , Responsabilidad Parental , Adolescente , Niño , Femenino , Humanos , Masculino , China , Responsabilidad Parental/psicología , Padres , Pueblos del Este de AsiaRESUMEN
Nervonic acid is a natural component of breast milk and is frequently used as a food additive due to its excellent neuroprotective effects. Although it has been reported that nervonic acid may play a role in the recovery of human cognitive impairment, its specific mechanism of action is still unclear. In this study, the results of serum biochemical indexes showed that nervonic acid improved inflammation and reduced amyloid ß peptide (Aß) deposition and tau protein phosphorylation in Alzheimer's disease (AD) rats. Subsequently, we further used a metabolomics approach to investigate the potential mechanism of action of nervonic acid in the treatment of AD. The results of serum and urine metabolomics study showed that the intervention of nervonic acid significantly reversed the metabolic profile disorder in AD rats. A total of 52 metabolites were identified. They mainly involved linoleic acid metabolism, alpha-linolenic acid metabolism, phenylalanine metabolism and arachidonic acid metabolism, and all these metabolic pathways were associated with the emergence of inflammation in vivo. It suggests that the therapeutic effect of nervonic acid on AD is likely to be produced by ameliorating inflammation. The results obtained in this study provide new insights into the mechanism of nervonic acid treatment of AD and lay a foundation for the clinical application of nervonic acid in the treatment of Alzheimer's disease.
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Enfermedad de Alzheimer , Medicamentos Herbarios Chinos , Ácidos Grasos Monoinsaturados , Humanos , Ratas , Animales , Péptidos beta-Amiloides/metabolismo , Cromatografía Líquida de Alta Presión , Ratas Sprague-Dawley , Medicamentos Herbarios Chinos/farmacología , Metabolómica/métodos , Inflamación/tratamiento farmacológico , BiomarcadoresRESUMEN
Subcellular organelle mitochondria are becoming a key player and a driver of cancer. Mitochondrial targeting phototheranostics has attracted increasing attention for precise cancer therapy. However, those phototheranostic systems still face great challenges, including complex and multiple components, light scattering, and insufficient therapeutic efficacy. Herein, a molecular fluorophore IR-TPP-1100 was tactfully designed by molecular engineering for mitochondria-targeted fluorescence imaging-guided phototherapy in the second near-infrared window (NIR-II). IR-TPP-1100 not only exhibited prominent photophysical properties and high photothermal conversion efficiency but also achieved excellent mitochondria-targeting ability. The mitochondria-targeting IR-TPP-1100 enabled NIR-II fluorescence and photoacoustic dual-modality imaging of mitochondria at the organism level. Moreover, it integrated photothermal and photodynamic therapy, obtaining remarkable tumor therapeutic efficacy by inducing mitochondrial apoptosis. These results indicate that IR-TPP-1100 has great potential for precise cancer therapy and provides a promising strategy for developing mitochondria-targeting NIR-II phototheranostic agents.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fototerapia/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Mitocondrias , Nanomedicina Teranóstica/métodos , Línea Celular TumoralRESUMEN
BACKGROUND: Firearm injury is a significant public health concern in the United States. METHODS: Data on fatal and nonfatal firearm injuries were obtained from a cohort of N = 7,473,650 members of Kaiser Permanente Southern California, a large integrated healthcare system between 2010 and 2020. Age-adjusted rates of combined fatal and nonfatal firearm injury per 100,000 members were calculated by year, with the 2010 US census as the reference population. Trends were evaluated using Poisson or negative binomial regression. RESULTS: There was an increasing trend in overall firearm injuries between 2010 and 2020 among adults in this large integrated healthcare system (p < .0001), primarily driven by non-self-inflicted firearm injuries (p < .0001). Self-inflicted injuries decreased during this time (p = .01). Injuries among youth showed no significant change. CONCLUSION: There was an increasing trend in firearm injuries between 2010 and 2020 among adults in this large integrated healthcare system, primarily driven by non-self-inflicted firearm injuries; however, self-inflicted injuries decreased during this time. Injuries among youth showed no significant change.
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Armas de Fuego , Heridas por Arma de Fuego , Adulto , Adolescente , Humanos , Estados Unidos , Heridas por Arma de Fuego/epidemiología , California/epidemiología , Distribución por Edad , Atención a la SaludRESUMEN
OBJECTIVE: To compare the clinical efficacy of acupuncture, Chinese medication and combination of acupuncture and medication in the treatment of dry eye complicated with computer vision syndrome (CVS). METHODS: A total of 152 patients with dry eye complicated with CVS were randomly divided into an acupuncture-medication group (38 cases, 1 case was removed), an acupuncture group (38 cases, 1 case dropped off), a Chinese medication group (38 cases, 1 case was removed), and a western medication group (38 cases, 1 case dropped off). In the western medication group, sodium hyaluronate eye drop combined with esculin and digitalis glycosides eye drop were used. In the acupuncture group, acupuncture was applied at bilateral Taiyang (EX-HN 5)ï¼ Cuanzhu (BL 2), Fengchi (GB 20), Qimen (LR 14) , and Hegu (LI 4) etc., once a day. In the Chinese medication group, Yiqi Congming decoction formula ganule was given orally, one dose a day. In the acupuncture-medication group, acupuncture combined with Yiqi Congming decoction formula granule were used. All groups were treated for 14 d. The non-invasive first tear film break-up time (NIBUT f), non-invasive average tear film break-up time (NIBUT av), tear meniscus height (TMH), ocular surface disease index (OSDI) score, and CVS symptom score were compared between the patients of each group before and after treatment. RESULTS: After treatment, the NIBUT f, NIBUT av, and TMH were increased compared with those before treatment in the patients of the 4 groups (P<0.01); the NIBUT f and NIBUT av in the acupuncture-medication group and the acupuncture group were higher than those in the Chinese medication group and the western medication group (P<0.05), and the TMH in the acupuncture-medication group and the Chinese medication group were higher than those in the acupuncture group and the western medication group (P<0.05). After treatment, the OSDI scores, the various scores and total scores of CVS (except for head symptom score in the western medication group) were decreased compared with those before treatment in the patients of the 4 groups (P<0.01). The OSDI score, total score, eye symptom score, and body symptom score of CVS in the acupuncture-medication group were lower than those in the acupuncture group, the Chinese medication group, and the western medication group (P<0.01, P<0.05), the head symptom score of the acupuncture-medication group was lower than that in the western medication group (P<0.05), and the CVS physical symptom scores and mental cognitive symptom scores of the acupuncture-medication group and the acupuncture group were lower than those in the Chinese medication group and the western medication group (P<0.05). CONCLUSION: Acupuncture has advantages in improving NIBUT f, NIBUT av, and CVS physical symptoms and cognitive symptoms, and the Chinese medication has advantage in improving TMH. The combination of acupuncture and Chinese medication has better effects compared with monotherapy.
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Terapia por Acupuntura , Síndromes de Ojo Seco , Humanos , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/etiología , Computadores , Resultado del Tratamiento , Puntos de Acupuntura , Soluciones OftálmicasRESUMEN
BACKGROUND: Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear. SETTING: Retrospective analyses of electronic health record data from 3 US integrated health care systems. METHODS: Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART. RESULTS: Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58). CONCLUSIONS: Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.
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Fármacos Anti-VIH , Fracturas Óseas , Infecciones por VIH , Humanos , Adulto , Persona de Mediana Edad , Tenofovir/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Estudios Retrospectivos , Estudios de Cohortes , Fracturas Óseas/etiología , Fracturas Óseas/inducido químicamente , Fármacos Anti-VIH/efectos adversosRESUMEN
BACKGROUND: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D3 supplementation (1 month) on physical performance in Chinese university students in winter. METHODS: One hundred and seventeen eligible subjects with 25(OH)D (19.2 ± 7.8 ng/mL) were randomly assigned to either vitamin D3 supplement (N = 56; 1000 IU/day) or the control (N = 61) group for 1 month. Pre- and post-measurements included: 1) serum levels of 25(OH)D; 2) musculoskeletal and pulmonary function [vertical jump height (VJH) and right handgrip strength (RHS), forced vital capacity (FVC), and forced expiratory volume at 1s (FEV1)]; 3) bone turnover markers [parathyroid hormone (PTH), n-terminal osteocalcin (N-MID), and calcium]; 4) hemoglobin-related parameters [hemoglobin (Hb), hematocrit (HCT), red blood cells (RBC), and red cell distribution width (RDW)]; 5) lipid parameters [total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)]; 6) Fatigue-related indicators [serum creatine kinase (CK), lactate dehydrogenase (LDH), and total testosterone (T)]. In addition, aerobic capacity was assessed by measuring maximal oxygen uptake (VO2max) at baseline. RESULTS: During wintertime, supplementation with 1000 IU/d of vitamin D3 significantly increased serum 25(OH)D levels (from 18.85 ± 7.04 to 26.98 ± 5.88 ng/mL, p < 0.05), accompanied by a decrease of PTH (p < 0.05). However, vitamin D3 supplementation did not significantly impact the physical performance, serum lipid parameters, and bone turnover markers of students. Furthermore, 25(OH)D was found to be positively correlated with VJH and negatively correlated with PTH and TC at the beginning and end of the study (p < 0.05). In addition, the multiple linear regression analysis showed that 25(OH)D combined with athletic, gender, height, weight, Hb, and FVC could account for 84.0% of the VO2max value. CONCLUSIONS: The study demonstrated that one-month of 1000 IU/d of vitamin D3 supplementation during the winter had beneficial effects on 25(OH)D status and PTH. However, vitamin D3 intervention was not sufficient to improve physical performance. Furthermore, 25(OH)D levels combined with athletic, Hb and FVC could be a predictor of VO2max.
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Colecalciferol , Fuerza de la Mano , Humanos , Universidades , Vitamina D , Rendimiento Físico Funcional , HDL-ColesterolRESUMEN
To elucidate the molecular mechanisms underlying the differential metabolism of albino (white), green, and purple pericarp coloration, biochemical profiling and transcriptome sequencing analyses were performed on three different tea pericarps, Zhongbaiyihao (Camellia sinensis L. var. Zhongbai), Jinxuan (Camellia sinensis L. var. Jinxuan), and Baitangziya (Camellia sinensis L. var. Baitang). Results of biochemical analysis revealed that low chlorophyll content and low chlorophyll/carotene ratio may be the biochemical basis for albino characteristics in the 'Zhongbaiyihao' pericarp. The differentially expressed genes (DEGs) involved in anthocyanin biosynthesis, including DFR, F3'5'H, CCoAOMT, and 4-coumaroyl-CoA, were highly expressed in the purple 'Baitangziya' pericarp. In the chlorophyll synthesis of white pericarp, GUN5 (Genome Uncoupled 5) and 8-vinyl-reductase both showed high expression levels compared to the green one, which indicated that albino 'Zhongbaiyihao' pericarp had a higher chlorophyll synthesis capacity than 'Jinxuan'. Meanwhile, chlorophyllase (CLH, CSS0004684) was lower in 'Baitang' than in 'Jinxuan' and 'Zhongbaiyihao' pericarp. Among the differentially expressed transcription factors, MYB59, WRKY41-like2 (CS ng17509), bHLH62 like1 (CS ng6804), and bHLH62-like3 (CSS0039948) were downregulated in Jinxuan pericarp, suggesting that transcription factors played a role in regulating tea pericarp coloration. These findings provide a better understanding of the molecular mechanisms and theoretical basis for utilizing functional components of tea pericarp.
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Camellia sinensis , Camellia sinensis/genética , Clorofila , Perfilación de la Expresión Génica , Té/genética , Factores de TranscripciónRESUMEN
The demand for foods and beverages with therapeutic and functional features has increased as a result of rising consumer awareness of health and wellness. In natural, plants are abundant, widespread, and inexpensive, in addition to being rich in bioactive components that are beneficial to health. The bioactive substances contained in plants include polyphenols, polysaccharides, flavonoids, aromatics, aliphatics, terpenoids, etc., which have rich active functions and application potential for plant-based beverages. In this review, various existing extraction processes and their advantages and disadvantages are introduced. The antioxidant, anti-inflammatory, intestinal flora regulation, metabolism regulation, and nerve protection effects of plant beverages are described. The biotoxicity and sensory properties of plant-based beverages are also summarized. With the diversification of the food industry and commerce, plant-based beverages may become a promising new category of health functional foods in our daily lives.
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Bebidas , Fenómenos Fisiológicos de la Nutrición , Antioxidantes , Alimentos Funcionales , Extractos VegetalesRESUMEN
PURPOSE: This study validated incident and recurrent ischemic stroke identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) hospital discharge diagnosis codes. METHODS: Using electronic health records (EHR) of adults (≥18 years) receiving care from Kaiser Permanente Southern California with ICD-10 hospital discharge diagnosis codes of ischemic stroke (I63.x, G46.3, and G46.4) between October 2015 and September 2020, we identified 75 patients with both incident and recurrent stroke events (total 150 cases). Two neurologists independently evaluated validity of ICD-10 codes through chart reviews. RESULTS: The positive predictive value (PPV, 95% CI) for incident stroke was 93% (95% CI: 88%, 99%) and the PPV for recurrent stroke was 72% (95% CI: 62%, 82%). The PPV for recurrent stroke improved after applying a gap of 20 days (PPV of 75%; 95% CI: 63%, 87%) or removing hospital admissions related to stroke-related procedures (PPV of 78%; 95% CI: 68%, 88%). CONCLUSION: The ICD-10 hospital discharge diagnosis codes for ischemic stroke showed a high PPV for incident cases, while the PPV for recurrent cases were less optimal. Algorithms to improve the accuracy of ICD-10 codes for recurrent ischemic stroke may be necessary.
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Prestación Integrada de Atención de Salud , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adulto , Humanos , Clasificación Internacional de Enfermedades , Alta del Paciente , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Valor Predictivo de las Pruebas , HospitalesRESUMEN
OBJECTIVE: Traditional Chinese medicines (TCM) play an indispensable role during the pandemic of coronavirus disease 2019 (COVID-19), with an increasing number of randomized controlled trials (RCTs) designed and performed to evaluate the efficacy and safety of TCM for COVID-19. This study aimed to critically appraise the quality of currently available RCTs of TCM for COVID-19. METHODS: RCTs of TCM for COVID-19 were searched from three databases by two investigators and selected according to pre-established inclusion and exclusion criteria. General information of included studies was presented by applying descriptive statistics. The methodological and reporting quality of eligible RCTs was critically evaluated based on the risk of bias assessment tool 2 (RoB2) and CONSORT Extension for TCM (CONSORT-CHM Formulas 2017), respectively. The differences of risks and main general information were compared between RCTs published in English and Chinese journals. Microsoft Excel 2019 and SPSS were used for the statistical analysis. A result with p < 0.05 was considered statistically significant. RESULTS: This study finally included 64 RCTs with a total of 10858 participants investigating TCM for COVID-19. All 64 RCTs were evaluated as moderate-to-low RoB including 27 RCTs with high bias, 26 RCTs with some concerns, and 11 with low bias. Results of reporting quality appraisal by CONSORT-CHM Formulas 2017 showed that 61 (95%) RCTs reported more than 18 (50%) items, and 14 (22%) RCTs reported more than 26 (70%) items among all 38 items. Forty-two RCTs were approved by ethics committees and 47 RCTs reported the informed consent information. Twenty-five RCTs and 39 RCTs provided information on trial registration and funding resources, respectively. The quality of 44 RCTs published in Chinese was significantly worse than that of 20 RCTs published in English, especially in the following considerations including the overall RoB, ethics approved, informed consent, trial register, and reporting quality with CONSORT-CHM Formulas 2017. CONCLUSION: The overall quality of RCTs investigating TCM for COVID-19 was appraised as moderate-to-high that was substandard and needs to be continuously improved, especially for RCTs published in Chinese, in the future.
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COVID-19 , Medicamentos Herbarios Chinos , Humanos , Bases de Datos Factuales , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
ACT001 is a novel sesquiterpene lactone derivative that has been shown to have significant antitumor and anti-inflammatory effects. However, the effect of ACT001 on nonalcoholic steatohepatitis (NASH) is unknown. Methionine and choline deficient (MCD) diet induced NASH model in C57BL/6J mice. Steatosis, inflammation and fibrosis-related indices of serum and liver tissues were detected by fully automated biochemical analyzer, enzyme-linked immunosorbent assay (ELISA) kit, flow cytometry, hematoxylin and eosin (H&E), Masson and immunohistochemical staining. The results showed that ACT001 reduced serum lipid and inflammatory factor levels, attenuated hepatic steatosis, inflammation and fibrosis, and inhibited hepatic oxidative stress and activation of NOD-like receptor protein 3 (NLRP3) inflammatory vesicles in NASH mice. In addition, 381 differentially expressed proteins (DEPs), including 162 up-regulated and 219 down-regulated proteins, were identified in the MCD group and ACT001 high-dose group using isotope labeling relative and absolute quantification (iTRAQ) technique analysis. Among these DEPs, five proteins associated with NAFLD were selected for real-time fluorescence quantitative PCR (RT-qPCR) validation, and the results were consistent with proteomics. In conclusion, ACT001 has a therapeutic effect on NASH, and the results of proteomic analysis will provide new ideas for the mechanism study of ACT001 for NASH treatment.
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Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/patología , Marcaje Isotópico , Proteómica , Ratones Endogámicos C57BL , Hígado/metabolismo , Cirrosis Hepática/patología , Inflamación/patología , Colina/metabolismo , Metionina/metabolismo , Modelos Animales de EnfermedadRESUMEN
IMPORTANCE: Limited evidence supports kidney dysfunction as an indication for parathyroidectomy in asymptomatic primary hyperparathyroidism (PHPT). OBJECTIVE: To investigate the natural history of kidney function in PHPT and whether parathyroidectomy alters renal outcomes. DESIGN: Matched control study. SETTING: A vertically integrated health care system serving 4.6 million patients in Southern California. PARTICIPANTS: 6058 subjects with PHPT and 16 388 matched controls, studied from 2000 to 2016. EXPOSURES: Biochemically confirmed PHPT with varying serum calcium levels. MAIN OUTCOMES: Estimated glomerular filtration rate (eGFR) trajectories were compared over 10 years, with cases subdivided by severity of hypercalcemia: serum calcium 2.62-2.74â mmol/L (10.5-11â mg/dL), 2.75-2.87 (11.1-11.5), 2.88-2.99 (11.6-12), and >2.99 (>12). Interrupted time series analysis was conducted among propensity-score-matched PHPT patients with and without parathyroidectomy to compare eGFR trajectories postoperatively. RESULTS: Modest rates of eGFR decline were observed in PHPT patients with serum calcium 2.62-2.74 mmol/L (−1.0 mL/min/1.73 m2/year) and 2.75-2.87 mmol/L (−1.1 mL/min/1.73 m2/year), comprising 56% and 28% of cases, respectively. Compared with the control rate of −1.0 mL/min/1.73 m2/year, accelerated rates of eGFR decline were observed in patients with serum calcium 2.88-2.99 mmol/L (−1.5 mL/min/1.73 m2/year, P < .001) and >2.99 mmol/L (−2.1 mL/min/1.73 m2/year, P < .001), comprising 9% and 7% of cases, respectively. In the propensity scorematched population, patients with serum calcium >2.87 mmol/L exhibited mitigation of eGFR decline after parathyroidectomy (−2.0 [95% CI: −2.6 to −1.5] to −0.9 [95% CI: −1.5 to 0.4] mL/min/1.73 m2/year). CONCLUSIONS AND RELEVANCE: Compared with matched controls, accelerated eGFR decline was observed in the minority of PHPT patients with serum calcium >2.87â mmol/L (11.5â mg/dL). Parathyroidectomy was associated with mitigation of eGFR decline in patients with serum calcium >2.87â mmol/L.
Asunto(s)
Hipercalcemia , Hiperparatiroidismo Primario , Humanos , Hiperparatiroidismo Primario/cirugía , Calcio , Paratiroidectomía , Riñón , Hipercalcemia/complicaciones , Hormona ParatiroideaRESUMEN
Allergic rhinitis (AR) is a common allergic disease characterized by nasal congestion, rhinorrhoea, and sneezing. Cineole, a monoterpenoid compound widely present in various volatile oils, has a wide range of pharmacological activities and is of interest in allergic airway diseases for its anti-inflammatory and anti-mucus production abilities. However, the protective effects of cineole in mice with allergic rhinitis and its mechanisms have not been well investigated. In this study, the protective effect of cineole against ovalbumin-induced (OVA-induced) allergic rhinitis and its molecular mechanism is investigated by metabolomic analysis based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). OVA combined with aluminum hydroxide adjuvant is used to sensitize and establish the allergic rhinitis (AR) mouse model. The mice are randomly divided into groups of control, AR, cineole (30 mg/kg), and budesonide (38.83 µg/kg). The pharmacodynamic results show that cineole significantly reduces the levels of Th2-type cytokines and OVA-specific IgE (OVA-sIgE) in AR mice, improves nasal mucosal tissue damage and alleviates nasal symptoms compared to the untreated AR group. Metabolomic results show that arachidonic acid (AA) metabolism and tryptophan (Trp) metabolism are reprogrammed on the basis of 27 significantly altered metabolites. Further studies show that cineole inhibits the biosynthesis of pro-inflammatory lipid mediators leukotrienes (LTs) and prostaglandins (PGs) in mice by inhibiting the activity of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) in the arachidonic acid metabolic (AA metabolic) pathway. It also inhibits the production of Th2 cytokines and inflammatory cell infiltration, thereby alleviating symptoms such as nasal congestion and nasal leakage. These results reveal the action and molecular mechanism of cineole in alleviating AR and provide a theoretical basis for the clinical application of cineole in treating AR.
Asunto(s)
Prostaglandinas , Rinitis Alérgica , Ratones , Animales , Eucaliptol/uso terapéutico , Prostaglandinas/efectos adversos , Ácido Araquidónico , Cromatografía Liquida , Inmunoglobulina E , Espectrometría de Masas en Tándem , Rinitis Alérgica/inducido químicamente , Rinitis Alérgica/tratamiento farmacológico , Citocinas , Leucotrienos/efectos adversos , Metabolómica , Ovalbúmina , Modelos Animales de Enfermedad , Ratones Endogámicos BALB CRESUMEN
The environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography-mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up-regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA-induced hepatotoxicity by reversing the occurrence of ferroptosis.