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1.
Neurol Sci ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683084

RESUMO

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a group of antibody-mediated inflammatory demyelinating central nervous system diseases. T lymphocytes participate in NMOSD pathogenesis, with regulatory T cells (Treg) being the core in maintaining immune homeostasis. Studies have revealed that different Treg subsets play different roles in autoimmune diseases. The distribution of LAP+ or GARP+ Treg subsets in NMOSD may help us deeply understand their immune mechanism. METHODS: This study reviewed 22 NMOSD patients and 20 normal controls. Flow cytometric analysis was utilized to detect subsets of Treg cells expressing Foxp3, Helios, LAP, or GARP in peripheral blood. ELISA was used to detect plasma TGF-ß1 and IL-10. In addition, changes in the proportion of Treg cell subsets before and after glucocorticoid treatment in 10 patients were analyzed. RESULTS: Compared with healthy controls, LAP and GARP expressions were significantly downregulated in the peripheral blood of NMOSD patients. TGF-ß1 expression in NMOSD patients was lower and was positively correlated with the ratio of CD4+GARP+ Treg cells. After treatment with glucocorticoid, LAP and GARP expressions in the peripheral blood of NMOSD patients were upregulated. CONCLUSIONS: The proportion of Treg cells expressing LAP and GARP is downregulated, implying that Treg cells with the best inhibitory function are insufficient to maintain autoimmune homeostasis in NMOSD patients. Upregulation of Treg cells expressing LAP and GARP in NMOSD patients may be one of the mechanisms of glucocorticoid treatment.

2.
Physiol Plant ; : e13853, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36628625

RESUMO

The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 palys a role in regulating plant growth under abiotic conditions.

3.
Phytomedicine ; 109: 154580, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610132

RESUMO

BACKGROUND: Flavonoids and saponins are important bioactive compounds that have attracted wide research interests. This review aims to summarise the state of the art of the pharmacology, toxicology and clinical efficacy of these compounds. METHODS: Data were retrieved from PubMed, Cochrane Library, Web of Science, Proquest, CNKI, Chongqing VIP, Wanfang, NPASS and HIT 2.0 databases. Meta-analysis and systematic reviews were evaluated following the PRISMA guideline. Statistical analyses were conducted using SPSS23.0. RESULTS: Rising research trends on flavonoids and saponins were observed since the 1990s and the 2000s, respectively. Studies on pharmacological targets and activities of flavonoids and saponins represent an important area of research advances over the past decade, and these important resources have been documented in open-access specialised databases and can be retrieved with ease. The rising research on flavonoids and saponins can be attributed, at least in part, to their links with some highly investigated fields of research, e.g., oxidative stress, inflammation and cancer; i.e., 6.88% and 3.03% of publications on oxidative stress cited by PubMed in 1990 - 2021 involved flavonoids and saponins, respectively, significantly higher than the percentage involving alkaloids (1.88%). The effects of flavonoids concern chronic venous insufficiency, cervical lesions, diabetes, rhinitis, dermatopathy, prostatitis, menopausal symptoms, angina pectoris, male pattern hair loss, lymphocytic leukaemia, gastrointestinal diseases and traumatic cerebral infarction, etc, while those of saponins may have impact on venous oedema in chronic deep vein incompetence, erectile dysfunction, acute impact injuries and systemic lupus erythematosus, etc. The volume of in vitro research appears way higher than in vivo and clinical studies, with only 10 meta-analyses and systematic reviews (involving 290 interventional and observational studies), and 36 clinical studies on flavonoids and saponins. Data are sorely needed on pharmacokinetics, in vitro pan-assay interferences, purity of tested compounds, interactions in complex herbal extracts, real impact of anti-oxidative strategies, and mid- and long-term toxicities. To fill these important gaps, further investigations are warranted. On the other hand, drug interactions may cause adverse effects but might also be useful for synergism, with the goals of enhancing effects or of detoxifying. Furthermore, the interactions between phytochemicals and the intestinal microbiota are worth investigating as the field may present a promising potential for novel drug development.


Assuntos
Medicamentos de Ervas Chinesas , Saponinas , Humanos , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Etnofarmacologia , Flavonoides/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Metanálise como Assunto , Revisões Sistemáticas como Assunto
4.
Plant Physiol Biochem ; 196: 23-32, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36689830

RESUMO

Nitrogen (N) is an essential element that plays an important role in crop biomass accumulation and quality formation. Increased crop yield is relied on excessive application of fertilizers, which usually leads to environmental pollution and unsustainable development. Thus, identification and characterization of genes involved in promoting nitrogen use efficiency is of high priority in crop breeding. The activity of nitrate reductase (NR) plays a critical role in nitrogen metabolism. In model plant Arabidopsis, NITRATE REDUCTASE 2 (NIA2), one of the two NRs, is responsible for about 90% of the NR activity. In this study, MdNIA2 gene in apple (Malus domestica) genome was screened out and identified by using AtNIA2 as bait. Phylogenetic analysis revealed that MdNIA2 had the closest evolutionary relationship with MbNIA from Malus baccata. Ectopic expression of MdNIA2 in Arabidopsis elevated the nitrogen use efficiency and increased root hair elongation and formation, resulting in promoted plant growth. Furthermore, the overexpression of MdNIA2 improved salt and drought tolerance in transgenic Arabidopsis and improved the salt tolerance of transgenic apple callus, and MdNIA2-reagualted NO metabolism might contribute to the abiotic stress tolerance. Overall, our data indicate the critical role of MdNIA2 in regulating nitrogen utilization efficiency and abiotic stress responses.

5.
Int J Biol Macromol ; : 123227, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36646342

RESUMO

Eastern honeybee Apis cerana has important ecological value for the cold flowering loquat flower pollination in early winter in East Asia. However, the low-temperature adaptive pollination mechanism has not yet been revealed. One odorant-binding protein, OBP2, had been found that could bind to some plant volatiles with strong affinity before. In this study, by using competitive fluorescence binding assay, we first measured the ligand-binding profiles of recombinant OBP2 protein with 9 representative aroma chemical substances from loquat flowers. Thermodynamic results showed that three loquat volatiles, 4-Methoxybenzaldehyde, (E)-Ethyl cinnamate, and Methyl cinnamate, have the strongest binding affinity with OBP2 with the static process. And interestingly their binding affinity significantly increased at low temperature (285 K/12 °C) compared to high temperature (298 K/25 °C). In addition, site-directed mutagenesis results showed that Met55 and Lys51 may be the key amino acid sites in the electrostatic and hydrophobic interactions of OBP2 interacting with Methyl cinnamate, respectively. This study suggests that OBP2 is functionally similar and universal in binding to different flower volatiles at low temperatures. Our studies interpreted a novel olfactory mechanism of A. cerana sensing loquat floral volatiles in cold early winter, and enrich a theoretical molecular basis for the temperature-adaptive ecological mechanism of insects' pollination.

6.
J Hepatol ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36462680

RESUMO

BACKGROUND & AIMS: Alterations of multiple metabolites characterize distinct features of metabolic reprograming in hepatocellular carcinoma (HCC). However, most metabolites including propionyl-CoA (Pro-CoA) are illusive for their functions in metabolic reprograming and hepatocarcinogenesis. This study aims to dissect how Pro-CoA metabolism affects these processes. METHODS: TCGA data and HCC samples were used to analyze the ALDH6A1-mediated Pro-CoA metabolism and its correlation with HCC. Multiple metabolites were assayed by targeted mass spectrometry. The function of ALDH6A1-generated Pro-CoA was evaluated by HCC proliferation, migration, xenograft nude mouse model and primary liver cancer mouse models. Nontargeted metabolomic and targeted energy metabolomic analyses followed by multiple biochemical assays were performed to dissect the underlying mechanisms. RESULTS: Decreases in Pro-CoA and its derivative propionyl-L-carnitine (PLC) due to ALDH6A1 downregulation were tightly associated with HCC. Functionally, ALDH6A1-mediated Pro-CoA metabolism suppressed HCC proliferation and impaired hepatocarcinogenesis in mice. The aldehyde dehydrogenase activity was indispensable for the ALDH6A1 function while Pro-CoA carboxylases antagonized ALDH6A1 function by eliminating Pro-CoA. Mechanistically, ALDH6A1 caused a signature enrichment of central carbon metabolism in cancer and impaired energy metabolism: ALDH6A1-generated Pro-CoA suppressed citrate synthase (CS) activity that subsequently reduced TCA cycle flux, impaired mitochondrial respiration and membrane potential, and decreased ATP production. Moreover, Pro-CoA metabolism generated 2-methylcitric acid (MCA), which mimicked the inhibitory effect of Pro-CoA on CS and dampened mitochondrial respiration and HCC proliferation. CONCLUSIONS: Our study unveils novel features that the decline of ALDH6A1-mediated Pro-CoA metabolism contributes to metabolic remodeling and facilitates hepatocarcinogenesis. Pro-CoA, PLC and MCA may serve as novel metabolic biomarkers for diagnosis and therapy of HCC. Pro-CoA metabolism may provide potential targets for development of novel strategies against HCC. IMPACT AND IMPLICATIONS: Our study presents new insights on metabolic reprogramming and hepatocarcinogenesis attribute to the decline of ALDH6A1-mediated propionyl-CoA. These findings may enrich molecular and metabolic indicators for physicians to improve clinical practice. These biomarkers may potentially be used for diagnosis and serve as targets for the development of therapeutic strategies against HCC.

7.
Front Oncol ; 12: 1039930, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568176

RESUMO

Background: As increasing experimental evidence suggests that iron metabolism play crucial roles in cancer and non-cancer conditions, there is a lack of data on serum soluble transferrin receptor (sTfR), a promising marker representing unmet cellular iron demands, between cancer risk from epidemiological studies. Here, we aimed to evaluate the predictive value of sTfR and cancer prevalence. Materials and methods: We analyzed on 5,480 adult participants from 2015 to 2018 National Health and Nutrition Examination Survey (NHANES). Spearman correlation analysis was performed to investigate the correlations between sTfR and other characteristics. To identify the associations between sTfR and the prevalence of cancers, stratified multivariable logistic regression models, subgroup and sensitivity analyses were also performed. Results: In tertile analyses, participants in the highest level of sTfR were significantly associated with increased prevalence of total cancers [odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.15-2.02] as compared with those at the lowest tertile. Each unit increment in ln-transformed sTfR concentration was shown to be associated with 39% increased risks of total cancers. Similar associations were found in males rather than females. Further subgroup and sensitivity analyses indicated that, in continuous and tertile analyses, sTfR was more closely associated with male- and female-specific cancers of prostate and testis (2.35: 1.03-5.40; 2.03: 1.00-4.09; respectively), and breast, cervix, ovary and uterus (1.92: 1.11-3.35; 1.66: 1.02-2.69; respectively). Conclusions: Our findings suggested that elevated level of sTfR was associated with the prevalence of cancers, especially in sex-specific cancers. In order to better determine them, further research in humans will be required.

8.
Front Pharmacol ; 13: 986765, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523499

RESUMO

Gastric, liver, and colorectal cancers belong to gastrointestinal (GI) cancers, one of the most threatening diseases in the world. The tonics class in Chinese medicines plays a critical role in antigastrointestinal cancer as adjuvants. However, it is a challenge to study the effects and underlying mechanisms of tonics due to their multiple components and multiple targets; OMICs were introduced to facilitate the investigation of the complex mixture of tonics. In this review, the online databases PubMed, ProQuest, Web of Knowledge, China National Knowledge Infrastructure (CNKI), Chongqing VIP, and Wanfang were retrieved from 1 January 2011 to 31 May 2022, in an aim to summarize and discuss the research progress of the effects and, especially, the underlying mechanisms of tonics for antigastrointestinal cancers via OMICs. The results showed that through the combination of OMICs and other technologies, tonics have been used for gastrointestinal cancer by targeting cancer hallmarks, enhancing body resistance to carcinogenesis, enhancing therapeutic effects, and/or decreasing side effects. In conclusion, tonics may play a promising role in gastric, liver, and colorectal cancers as adjuvants and can be well investigated via the combination of OMICs and other technologies, which deserves further study.

9.
Front Med (Lausanne) ; 9: 1002325, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530914

RESUMO

Background: Gallbladder and biliary diseases are common gastrointestinal conditions associated with huge socioeconomic costs and are considered risk factors for cardiovascular diseases and digestive system cancers. The prevalence and incidence of gallbladder and biliary diseases have not received enough attention from 1990 to 2019. Several non-communicable diseases were associated with the incidence of gallbladder and biliary diseases. It is necessary to clarify the change in the incidence and disability burden of gallbladder and biliary diseases worldwide. Methods: Data on high body mass index (BMI)-related disease burden and incidence, years of life lost prematurely, and years lived with disability (YLDs) due to gallbladder and biliary diseases were obtained from the Global Burden of Disease 2019. The estimated annual percentage change was calculated to qualify the gallbladder and biliary disease burden change. Results: The global age-standardized incidence rate has increased from 585.35 per 100,000 (95% UI: 506.05-679.86) in 1990 to 634.32 per 100,000 (95% UI: 540.21-742.93) in 2019. And the increase in incidence was positively correlated with rising high BMI-related summary exposure value. The high BMI-related YLDs of gallbladder and biliary diseases have increased worldwide over time. Globally, the 25-49 age group suffered a rapid rise in incidence and high BMI attributable to the YLDs rate of gallbladder and biliary diseases. Conclusion: The global incidence and high BMI-related YLDs of gallbladder and biliary diseases remain prominent to increase over the past 30 years. Notably, the incidence and high BMI-related YLDs among people aged 25-49 years have rapidly increased over time. Therefore, high BMI should be emphasized in strategic priorities for controlling gallbladder and biliary diseases.

10.
Phytochemistry ; 207: 113567, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36549383

RESUMO

Chlorine-containing guaianolide sesquiterpenoids are rare natural compounds that are mainly derived from plants of the Asteraceae family. Our previous investigations on the whole plant of Achillea millefolium L. resulted in the discovery of two chlorine-containing guaianolide sesquiterpenoids. In the present study, a LC‒MS tracking strategy based on the characteristic isotropic peak of atomic chlorine was employed to isolate nine undescribed chlorine-containing guaianolide sesquiterpenoids, Millefolactons B1-B9, from A. millefolium L.. The structures of these compounds were elucidated by spectroscopic data analysis, and the corresponding absolute configurations were determined by single-crystal X-ray crystallography and ECD data analysis. Millefolactons B2-B7 displayed inhibitory activities against LPS-induced NO release in BV-2 microglial cells.

11.
Front Microbiol ; 13: 1041521, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406446

RESUMO

In oceanic oxygen minimum zones (OMZs), the abundances of aerobic organisms significantly decrease and energy shifts from higher trophic levels to microorganisms, while the microbial communities become critical drivers of marine biogeochemical cycling activities. However, little is known of the microbial ecology of the Andaman Sea and eastern Bay of Bengal (BoB) OMZs. In the present study, a total of 131 samples which from the Andaman Sea and eastern BoB epipelagic waters were analyzed. The microbial community distribution patterns across oxygen gradients, including oxygenic zones (OZs, dissolved oxygen [DO] ≥ 2 mg/L), oxygen limited zones (OLZs, 0.7 mg/L < DO < 2 mg/L), and OMZs (DO ≤ 0.7 mg/L), were investigated. Mantel tests and Spearman's correlation analysis revealed that DO was the most important driver of microbial community structures among several environmental factors. Microbial diversity, richness, and evenness were highest in the OLZs and lowest in the OZs. The microbial community compositions of OZ and OMZ waters were significantly different. Random forest analysis revealed 24 bioindicator taxa that differentiated OZ, OLZ, and OMZ water communities. These bioindicator taxa included Burkholderiaceae, HOC36, SAR11 Clade IV, Thioglobaceae, Nitrospinaceae, SAR86, and UBA10353. Further, co-occurrence network analysis revealed that SAR202, AEGEAN-169, UBA10353, SAR406, and Rhodobacteraceae were keystone taxa among the entire interaction network of the microbial communities. Functional prediction further indicated that the relative abundances of microbial populations involved in nitrogen and sulfur cycling were higher in OMZs. Several microbial taxa, including the Thioglobaceae, Nitrospinaceae, SAR202, SAR406, WPS-2, UBA10353, and Woeseiaceae, may be involved in nitrogen and/or sulfur cycling, while also contributing to oxygen consumption in these waters. This study consequently provides new insights into the microbial community structures and potentially important taxa that contribute to oxygen consumption in the Andaman Sea and eastern BoB OMZ.

12.
BMC Neurol ; 22(1): 430, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380277

RESUMO

BACKGROUND: The aim of the study was to determine whether the combination of Glasgow Coma Scale (GCS) and Pupil responses score (GCSP) with arterial lactate level would be an index to predict the short term prognosis in patients with traumatic brain injury (TBI). METHODS: A retrospective study was performed enrolling all TBI patients admitted to intensive care unit (ICU) from 2019 to 2020. The demographics, clinical characteristics, and arterial lactate concentration were recorded. The GCSP and arterial blood analysis (ABG) with lactate was tested as soon as the patient was admitted to ICU. The Glasgow Outcome Scale (GOS) after discharge was regarded as the clinical outcome. A new index named GCSP-L was the combination of GCSP and lactate concentration. GCSP-L was the GCSP score (range 1-15) plus the lactate score (range 0-2). The lactate score was defined based on different lactate concentrations. If lactate was below 2 mmol/L, lactate score was 0, which above 5 mmol/L was 2 and between 2 and 5 mmol/L, the score was 1. As the range of GCSP was 1-15, the range of the GCSP-L was 1 to 17. The area under receiver operating characteristic curve (AUC) was calculated to evaluate the predictive ability of GCSP, lactate and GCSP-L. Statistical significance was set when p value < 0.05. RESULTS: A total of 192 TBI patients were included in the study. Based on GCSP, mild, moderate, and severe TBI were 13.02, 14.06 and 72.92%, respectively. There were 103 (53.65%) patients with the lactate concentration below 2 mmol/L (1.23 ± 0.37 mmol/l), 63 (32.81%) of the range from 2 to 5 (3.04 ± 2.43 mmol/l) and 26 (13.54%) were above 5 mmol/l (7.70 ± 2.43 mmol/l). The AUC was 0.866 (95% CI 0.827-0.904) for GCSP-L, 0.812 (95% CI 0.765-0.858) for GCSP and 0.629 (95% CI 0.570-0.0.688) for lactate. The AUC of GCSP-L was higher than the other two, GCSP and lactate alone. CONCLUSIONS: The combination of GCSP and lactate concentration can be used to predict the short term prognosis in TBI patients.


Assuntos
Lesões Encefálicas Traumáticas , Humanos , Escala de Coma de Glasgow , Estudos Retrospectivos , Lesões Encefálicas Traumáticas/diagnóstico , Prognóstico , Ácido Láctico
13.
J Mol Med (Berl) ; 100(12): 1721-1739, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36396746

RESUMO

Metabolic cardiomyopathy is an emerging cause of heart failure in patients with obesity, insulin resistance, and diabetes. It is characterized by impaired myocardial metabolic flexibility, intramyocardial triglyceride accumulation, and lipotoxic damage in association with structural and functional alterations of the heart, unrelated to hypertension, coronary artery disease, and other cardiovascular diseases. Oxidative stress plays an important role in the development and progression of metabolic cardiomyopathy. Mitochondria are the most significant sources of reactive oxygen species (ROS) in cardiomyocytes. Disturbances in myocardial substrate metabolism induce mitochondrial adaptation and dysfunction, manifested as a mismatch between mitochondrial fatty acid oxidation and the electron transport chain (ETC) activity, which facilitates ROS production within the ETC components. In addition, non-ETC sources of mitochondrial ROS, such as ß-oxidation of fatty acids, may also produce a considerable quantity of ROS in metabolic cardiomyopathy. Augmented ROS production in cardiomyocytes can induce a variety of effects, including the programming of myocardial energy substrate metabolism, modulation of metabolic inflammation, redox modification of ion channels and transporters, and cardiomyocyte apoptosis, ultimately leading to the structural and functional alterations of the heart. Based on the above mechanistic views, the present review summarizes the current understanding of the mechanisms underlying metabolic cardiomyopathy, focusing on the role of oxidative stress.


Assuntos
Cardiomiopatias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Cardiomiopatias/etiologia , Estresse Oxidativo , Metabolismo Energético , Miocárdio/metabolismo
14.
PeerJ ; 10: e14373, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36411834

RESUMO

The antitumor drug doxorubicin is widely used in clinical practice. However, the low yield and high cost of this drug highlight the urgent need for cost-effective processes to rapidly manufacture antitumor drugs at scale. In the biosynthesis pathway, the multi-functional cytochrome P450 enzyme DoxA catalyzes the last three steps of hydroxylation. The final conversion of daunorubicin to doxorubicin is the rate-limiting step. In our work, the DoxA has been expressed with the ferredoxin reductase FDR2 and the ferredoxin FDX1 and purified to homogeneous. The reduced carbon monoxide difference spectroscopy, heme concentration, and enzymatic characteristic were characterized. These studies suggest an approach for engineering Streptomyces P450s with functional expression for mechanistic and structural studies.

15.
BMJ Open ; 12(11): e064064, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351728

RESUMO

INTRODUCTION: Spontaneous hyperventilation (SHV) is common in aneurysmal subarachnoid haemorrhage (aSAH). The reduction in arterial partial pressure of carbon dioxide (PaCO2) may change the brain physiology, such as haemodynamics, oxygenation, metabolism and may lead to secondary brain injury. However, how to correct SHV safely and effectively in patients with aSAH has not been well investigated. The aim of this study is to investigate the efficacy and safety of remifentanil dose titration to correct hyperventilation in aSAH, as well as the effect of changes in PaCO2 on cerebral blood flow (CBF). METHODS AND ANALYSIS: This study is a prospective, single-centre, physiological study in patients with aSAH. The patients who were mechanically ventilated and who meet with SHV (tachypnoea combined with PaCO2 <35 mm Hg and pH >7.45) will be enrolled. The remifentanil will be titrated to correct the SHV. The predetermined initial dose of remifentanil is 0.02 µg/kg/min and will be maintained for 30 min, and PaCO2 and CBF will be measured. After that, the dose of remifentanil will be sequentially increased to 0.04, 0.06, and 0.08 µg/kg/min, and the measurements for PaCO2 and CBF will be repeated 30 min after each dose adjustment and will be compared with their baseline values. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University (KY 2021-006-02) and has been registered at ClinicalTrials.gov. The results of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04940273.


Assuntos
Hemorragia Subaracnóidea , Humanos , Dióxido de Carbono , Circulação Cerebrovascular/fisiologia , Hiperventilação , Estudos Prospectivos , Remifentanil , Hemorragia Subaracnóidea/complicações
16.
Front Nutr ; 9: 1019615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352906

RESUMO

Background and aims: Overweight or obesity is one of the most prevalent health burdens in companion pets and predisposes subjects to multiple comorbidities and reduced longevity. Dietary management and sufficient exercise are effective options for weight loss but challenged by modern lifestyle and calorie control-triggered malnutrition. Therefore, this study aimed to develop a formulated obesity control diet characterized by protein- and fiber-rich diet and supplemented with astaxanthin. We systemically evaluated global influences of the designed weight-loss diet on metabolic homeostasis in an obese beagle model. Materials and methods: Beagles were induced for obesity by a 24-week HFD treatment and then included into weight-loss programs. Briefly, obese beagles were randomly assigned to two groups that were fed with a formulated weight-loss diet or control diet, respectively. Body weight and body condition scoring (BCS) were analyzed biweekly. Computed tomography (CT), nuclear magnetic resonance imaging (MRI) measurements, and blood and adipose tissue biopsies were collected at 0 and 8 weeks. Plasma lipids and adipocyte size were also measured after 8 weeks of weight-loss diet feeding. The global influence of the formulated diet on the whole spectrum of gene panels were examined by adipose RNA assays. Results: Twenty-four weeks of continuous HFD feeding significantly induced obesity in beagles, as evidenced by increased body weight, BCS, abdominal fat mass, and serum lipid levels. The obese and metabolic condition of the modeled canine were effectively improved by an 8-week weight-loss diet administration. Importantly, we did not observe any side effects during the weight loss duration. Transcriptional analysis of adipose tissues further supported that a weight-loss diet significantly increased energy metabolism-related pathways and decreased lipid synthesis-related pathways. Conclusion: The prescribed weight-loss diet exhibited profound benefits in canine weight management with well safety and palatability. These findings support effective strategies of nutritional management and supplementation approaches for weight control in companion animals.

17.
Front Cardiovasc Med ; 9: 941917, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330016

RESUMO

Background: Rheumatic heart disease (RHD) remains the leading cause of preventable death and disability in children and young adults, killing an estimated 320,000 individuals worldwide yearly. Materials and methods: We utilized the Bayesian age-period cohort (BAPC) model to project the change in disease burden from 2020 to 2030 using the data from the Global Burden of Disease (GBD) Study 2019. Then we described the projected epidemiological characteristics of RHD by region, sex, and age. Results: The global age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) of RHD increased from 1990 to 2019, and ASPR will increase to 559.88 per 100,000 population by 2030. The global age-standardized mortality rate (ASMR) of RHD will continue declining, while the projected death cases will increase. Furthermore, ASPR and cases of RHD-associated HF will continue rising, and there will be 2,922,840 heart failure (HF) cases in 2030 globally. Female subjects will still be the dominant population compared to male subjects, and the ASPR of RHD and the ASPR of RHD-associated HF in female subjects will continue to increase from 2020 to 2030. Young people will have the highest ASPR of RHD among all age groups globally, while the elderly will bear a greater death and HF burden. Conclusion: In the following decade, the RHD burden will remain severe. There are large variations in the trend of RHD burden by region, sex, and age. Targeted and effective strategies are needed for the management of RHD, particularly in female subjects and young people in developing regions.

18.
J Agric Food Chem ; 70(45): 14439-14447, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36317964

RESUMO

The purpose of this study was to determine the key odor-active compounds contributing to the off-flavor of aged pasteurized yogurt (APY) using sensory-directed flavor analysis. Additionally, different extraction methods were compared to determine their effects on the volatile compounds, including dynamic headspace sampling (DHS), solid-phase microextraction, and stir bar sorptive extraction, and DHS was found to be suitable for this study. The results showed that comprehensive two-dimensional gas chromatography-olfactometry-mass spectrometry analysis (GC × GC-O-MS) had more advantages in separating and identifying the volatile compounds than the traditional GC-O-MS. A total of 17 odor-active compounds were determined in the fresh pasteurized yogurt and APY samples by DHS coupled with GC × GC-O-MS. The dynamic headspace dilution analysis demonstrated that 2-heptanone and hexanal were the most vital components in APY with the highest flavor dilution factor. Furthermore, the spiking and omission experimental results revealed that the odor-active compounds, such as 2-heptanone, butanoic acid, pentanoic acid, hexanal, and (E)-2-heptenal, were the key odor-active off-flavor contributors in APY. Therefore, these compounds could be used as potential indicators to determine the freshness of pasteurized yogurt.


Assuntos
Odorantes , Compostos Orgânicos Voláteis , Odorantes/análise , Iogurte/análise , Paladar , Olfatometria/métodos , Compostos Orgânicos Voláteis/química
19.
J Ethnopharmacol ; 303: 115945, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36435407

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Polygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro. However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo. AIM OF THE STUDY: In this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats. MATERIALS AND METHODS: Quality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O-ß-D-glycoside (EMG), physcion-1-O-ß-D-glycoside (PHG) and chrysophanol-8-O-ß-D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS. RESULTS: The quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, Cmax (239.90 ± 146.71 vs. 898.46 ± 291.62, P < 0.001), Tmax (0.26 ± 0.15 vs. 12.55 ± 1.33, P < 0.001), AUC0-t (1575.09 ± 570.46 vs. 12154.96 ± 5394.25, P < 0.001), and AUC0-∞ (4742.51 ± 1837.62 vs. 37131.34 ± 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of Vd (380.75 ± 217.74 vs. 11.75 ± 7.35, P < 0.001), T1/2 (10.81 ± 1.99 vs. 6.65 ± 2.76, P < 0.05) and CL (19.30 ± 7.82 vs. 2.78 ± 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 ± 5.98 vs. 43.29 ± 4.16 and 26.72 ± 4.03 vs. 43.40 ± 14.19, respectively. P < 0.05) dominantly due to RH and PH. CONCLUSION: In conclusion, compared with treatment of EM alone, the AUC0-t value of EM in HSWE was decreased with different ways in rats. PH shortened Tmax, and increased Vd and CL. While AE prolonged T1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer.

20.
J Asian Nat Prod Res ; : 1-9, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36272136

RESUMO

Two new compounds verboncin A (1) and verboncin B (4) and 14 known compounds (2-3 and 5-16) were isolated from Verbena bonariensis, and these 14 compounds were first obtained from this plant. Their chemical structures were established by one and two-dimensional NMR and HRESIMS analysis and the results were compared with literature values. The absolute configuration of 1 was determined by calculating electronic circular dichroism (ECD). The cytotoxicity of some of the compounds against MCF-7, HCT-116, MDA-MB-231, and SW620 human cancer cell lines were evaluated, in which compound 4 showed negligible cytotoxic activity with an IC50 value of 68.08 ± 0.35 µM against the MCF-7 cell line.

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