RESUMO
The phosphatase and tensin congeners (Pten) gene affects cell growth, cell proliferation, and rearrangement of connections, and it is closely related to cellular senescence, but it remains unclear the role of muscle-Pten gene in exercise against age-related deterioration in skeletal muscle and mortality induced by a high-salt diet (HSD). In here, overexpression and knockdown of muscle Pten gene were constructed by building MhcGAL4 /PtenUAS-overexpression and MhcGAL4 /PtenUAS-RNAi system in flies, and flies were given exercise training and a HSD for 2 weeks. The results showed that muscle Pten knockdown significantly reduced the climbing speed, climbing endurance, GPX activity, and the expression of Pten, Sirt1, PGC-1α genes, and it significantly increased the expression of Akt and ROS level, and impaired myofibril and mitochondria of aged skeletal muscle. Pten knockdown prevented exercise from countering the HSD-induced age-related deterioration of skeletal muscle. Pten overexpression has the opposite effect on skeletal muscle aging when compared to it knockdown, and it promoted exercise against HSD-induced age-related deterioration of skeletal muscle. Pten overexpression significantly increased lifespan, but its knockdown significantly decreased lifespan of flies. Thus, current results confirmed that differential expression of muscle Pten gene played an important role in regulating skeletal muscle aging and lifespan, and it also affected the adaptability of aging skeletal muscle to physical exercise since it determined the activity of muscle Pten/Akt pathway and Pten/Sirt1/PGC-1α pathway.
Assuntos
Condicionamento Físico Animal , Sirtuína 1 , Animais , Sirtuína 1/metabolismo , Drosophila/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Condicionamento Físico Animal/fisiologia , Músculo Esquelético/metabolismo , Dieta , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismoRESUMO
Carbon isotope composition of tree-ring (δ13 CRing ) is a commonly used proxy for environmental change and ecophysiology. δ13 CRing reconstructions are based on a solid knowledge of isotope fractionations during formation of primary photosynthates (δ13 CP ), such as sucrose. However, δ13 CRing is not merely a record of δ13 CP . Isotope fractionation processes, which are not yet fully understood, modify δ13 CP during sucrose transport. We traced, how the environmental intra-seasonal δ13 CP signal changes from leaves to phloem, tree-ring and roots, for 7 year old Pinus sylvestris, using δ13 C analysis of individual carbohydrates, δ13 CRing laser ablation, leaf gas exchange and enzyme activity measurements. The intra-seasonal δ13 CP dynamics was clearly reflected by δ13 CRing , suggesting negligible impact of reserve use on δ13 CRing . However, δ13 CP became increasingly 13 C-enriched during down-stem transport, probably due to post-photosynthetic fractionations such as sink organ catabolism. In contrast, δ13 C of water-soluble carbohydrates, analysed for the same extracts, did not reflect the same isotope dynamics and fractionations as δ13 CP , but recorded intra-seasonal δ13 CP variability. The impact of environmental signals on δ13 CRing , and the 0.5 and 1.7 depletion in photosynthates compared ring organic matter and tree-ring cellulose, respectively, are useful pieces of information for studies exploiting δ13 CRing .
Assuntos
Terapia a Laser , Pinus sylvestris , Pinus , Árvores/metabolismo , Pinus sylvestris/metabolismo , Estações do Ano , Isótopos de Carbono/análise , Carboidratos/análise , Folhas de Planta/metabolismo , Sacarose/metabolismo , Pinus/metabolismoRESUMO
The timely identification of the high-risk groups for nosocomial infections (NIs) plays a vital role in its prevention and control. Therefore, it is crucial to investigate whether the ABO blood group is a risk factor for NI. In this study, patients with NI and non-infection were matched by the propensity score matching method and a logistic regression model was used to analyse the matched datasets. The study found that patients with the B&AB blood group were susceptible to Escherichia coli (OR = 1.783, p = 0.039); the A blood group were susceptible to Staphylococcus aureus (OR = 2.539, p = 0.019) and Pseudomonas aeruginosa (OR = 5.724, p = 0.003); the A&AB blood group were susceptible to Pseudomonas aeruginosa (OR = 4.061, p = 0.008); the AB blood group were vulnerable to urinary tract infection (OR = 13.672, p = 0.019); the B blood group were susceptible to skin and soft tissue infection (OR = 2.418, p = 0.016); and the B&AB blood group were vulnerable to deep incision infection (OR = 4.243, p = 0.043). Summarily, the patient's blood group is vital for identifying high-risk groups for NIs and developing targeted prevention and control measures for NIs.
Assuntos
Sistema ABO de Grupos Sanguíneos , Infecção Hospitalar , Humanos , Infecção Hospitalar/epidemiologia , Escherichia coli , Pseudomonas aeruginosa , Fatores de Risco , Staphylococcus aureusRESUMO
Gut microbiota balance and metabolites have become a potentially mechanism in maintaining health. The specific aim of this study was to compare the modulation of puerarin and puerarin acid esters on gut microbial composition and metabolites. Male mice were fed a control diet or diets supplemented with puerarin, puerarin propanoate ester, puerarin hexanoate ester, puerarin myristate ester for 24 h, respectively. The result revealed that puerarin acid esters with different chain lengths showed different activities to create more own impacted bacterial. Puerarin propanoate and puerarin hexanoate ester significantly improved the diversity of microbiota and promoted the relative abundance of beneficial gut microbiota such as Lactobacillus, Barnesiella, Clostridium IV, Prevotella. Additionally, the puerarin propanoate ester group showed the capacity to deliver specific propionic acid to the colon. But esters with medium-long chain lengths had more opportunity to alter gut microbiota for enhancing the short chain fatty acids production. As a whole, puerarin acid esters with different chain lengths supplements shaped different gut microbial and short chain fatty acids metabolism, which could improve human health.
Assuntos
Microbioma Gastrointestinal , Animais , Ésteres , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Isoflavonas , Camundongos , Propionatos , RatosRESUMO
BACKGROUND: Hand hygiene (HH) is the cornerstone of infection control, and the promotion of HH is the focus of the world. The study aims to compare the role of two different types of electronic hand hygiene monitoring systems (EHHMSs) in promoting HH of healthcare workers (HCWs) in the intensive care unit (ICU). METHODS: In a 16-bed ICU of a general tertiary hospital in Shenzhen, the research was divided into three stages with interrupted time series (ITS) design. In the first stage, the direct observation method was used to monitor and feed back the HH compliance rate of HCWs monthly. In the second stage, the type1 EHHMS was applied to monitor and feed back the individual number of HH events monthly. In the third stage, the type2 EHHMS with a function of instant reminder and feedback was employed, and the personal HH compliance rates were fed back monthly. Meanwhile, direct observation continued in the last two stages. RESULTS: In the second stage, The HH compliance rate increased. However, there was no significant difference in the trajectory of the rate compared with the first stage. In the first month of the third stage, the HH compliance rate increased by 12.324% immediately and then ascended by 1.242% over time. The number of HH events per bed day and HH products' consumption per bed day were consistent with the change of HH compliance rate observed. CONCLUSION: Monitoring and feedback can improve the HH of HCWs. The EHHMS, with the function of real-time reminders and feedback, has a more noticeable effect on promoting HH.
Assuntos
Equipamentos e Provisões Elétricas , Higiene das Mãos/métodos , Pessoal de Saúde , Promoção da Saúde/métodos , Controle de Infecções/métodos , Unidades de Terapia Intensiva , Adulto , China , Infecção Hospitalar/prevenção & controle , Retroalimentação , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Análise de Séries Temporais Interrompida , Masculino , Sistemas de Alerta , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Prevention and control (P&C) of Corona Virus Disease 2019 (COVID-19) is still a critical task in most countries and regions. However, there are many single evaluation indexes to assess the quality of COVID-19 P&C. It is necessary to synthesize the single evaluation indexes reasonably to obtain the overall evaluation results. METHODS: This study was divided into three steps. Step 1: In February 2020, the improved Delphi method was used to establish the quality evaluation indexes system for COVID-19 P&C. Step 2: in March 2020, the CRITIC method was used to adjust the Order Relation Analysis (G1) method to obtain the subjective and objective (S&O) combination weights. The comprehensive evaluation value was obtained using the weighted Efficacy Coefficient (EC) method, weighted TOPSIS method, weighted rank-sum ratio (RSR) method, and weighted Grey Relationship Analysis (GRA) method. Finally, the linear normalization method was used to synthesize the evaluation values of different evaluation methods. Step 3: From April 2020 to May 2021, this evaluation method was used to monitor and assess COVID-19 P&C quality in critical departments prospectively. The results were reported to the departments monthly. RESULT: A quality evaluation indexes system for COVID-19 P&C was established. Kendall's consistency test shows that the four evaluation method had good consistency (χ2 = 43.429, P<0.001, Kendall's consistency coefficient = 0.835). The Spearman correlation test showed that the correlation between the combined evaluation results and the original method was statistically significant(P < 0.001). According to the Mann-Kendall test, from March 2020 to May 2021, the mean value of COVID-19 P&C quality in all critical departments showed an upward trend (P < 0.01). CONCLUSIONS: The combined comprehensive evaluation method based on the S&O combined weight was more scientific and comprehensive than the single weighting and evaluation methods. In addition, monitoring and feedback of COVID-19 P&C quality were helpful for the improvement of P&C quality.
Assuntos
COVID-19 , Hospitais Gerais , Serviços de Saúde , Humanos , Estudos Prospectivos , SARS-CoV-2RESUMO
The Coronavirus Disease 2019 (COVID-19) highlights the importance of understanding and controlling the spread of the coronavirus between persons. We experimentally and numerically investigated an advanced engineering and environmental method on controlling the transmission of airborne SARS-CoV-2-laden aerosols in the breathing microenvironment between two persons during interactive breathing process by combining the limited space air stability and a ventilation method. Experiments were carried out in a full-scale ventilated room with different limited space air stability conditions, i.e., stable condition, neutral condition and unstable condition. Two real humans were involved to conducted normal breathing process in the room and the exhaled carbon dioxide was used as the surrogate of infectious airborne SARS-CoV-2-laden aerosols from respiratory activities. A correspondent numerical model was established to visualize the temperature field and contaminated field in the test room. Results show that the performance of a ventilation system on removing infectious airborne SARS-CoV-2-laden aerosols from the interpersonal breathing microenvironment is dependent on the limited space air stability conditions. Appropriate ventilation method should be implemented based on an evaluation of the air condition. It is recommended that total volume ventilation methods are suitable for unstable and neutral conditions and local ventilation methods are preferable for stable conditions. This study provides an insight into the transmission of airborne SARS-CoV-2-laden aerosols between persons in ventilated rooms with different limited space air stability conditions. Useful guidance has been provided to cope with COVID-19 in limited spaces.
Assuntos
COVID-19 , SARS-CoV-2 , Aerossóis , HumanosRESUMO
BACKGROUND: The prevalence of multiple nosocomial infections (MNIs) is on the rise, however, there remains a limited comprehension regarding the associated risk factors, cumulative risk, probability of occurrence, and impact on length of stay (LOS). METHOD: This multicenter study includes all hospitalized patients from 2020 to July 2023 in two sub-hospitals of a tertiary hospital in Guangming District, Shenzhen. The semi-Markov multi-state model (MSM) was utilized to analyze risk factors and cumulative risk of MNI, predict its occurrence probability, and calculate the extra LOS of nosocomial infection (NI). RESULTS: The risk factors for MNI include age, community infection at admission, surgery, and combined use of antibiotics. However, the cumulative risk of MNI is lower than that of single nosocomial infection (SNI). MNI is most likely to occur within 14 days after admission. Additionally, SNI prolongs LOS by an average of 7.48 days (95% Confidence Interval, CI: 6.06-8.68 days), while MNI prolongs LOS by an average of 15.94 days (95% CI: 14.03-18.17 days). Furthermore, the more sites of infection there are, the longer the extra LOS will be. CONCLUSION: The longer LOS and increased treatment difficulty of MNI result in a heavier disease burden for patients, necessitating targeted prevention and control measures.
Assuntos
Infecção Hospitalar , Tempo de Internação , Humanos , Infecção Hospitalar/epidemiologia , Tempo de Internação/estatística & dados numéricos , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Idoso , Adulto , Prevalência , Centros de Atenção Terciária , Antibacterianos/uso terapêuticoRESUMO
The inhibitory effects of cold plasma-activated water (PAW) on the formation of AGEs and methylimidazoles in cookies was examined. The results showed that different PAW (parameters: 50 W-50 s, 50 W-100 s, 50 W-150 s, 100 W-50 s, 100 W-100 s, and 100 W-150 s) reduced the contents of AGEs and methylimidazoles, in which the maximum inhibition rates were 47.38% and 40.17% for free and bound AGEs and 44.16% and 40.31% for free and bound methylimidazoles, respectively. Moreover, the mechanisms associated with the elimination of carbonyl intermediates and free radicals was determined by electron paramagnetic resonance (EPR) and high performance liquid chromatography-ultraviolet/visible absorption detector (HPLC-UV/Vis). The results showed the quenching of total free radicals, alkyl free radicals, and HO· by PAW, leading to the suppression of glyoxal and methylglyoxal intermediates. These findings support PAW as a promising agent to enhance the safety of cookies.
RESUMO
Western dietary patterns (WDP) and typical food groups may play a major role in the risk of behavioral health disorders. Nevertheless, the relationships between WDP, common food categories, and mental health disorders lack consistency and remain incompletely understood in relation to potential mechanisms. Therefore, the objective of the present study was conducted to synthesize available evidence linking WDP and typical food groups to these outcomes. Web of Science, PubMed, EMBASE, and MEDLINE were searched up to August 2023. Random effect meta-analyses were performed to obtain pooled odds ratio and the relative risk for the prevalence of outcomes and the incidence of outcomes, respectively. A total of 54 articles were included. WDP was associated with increased risk of both depression (1.19; 95% CI: 1.06-1.32) and depressive symptoms (1.20; 95% CI: 1.08-1.34). Except for high-fat dairy products, food groups are associated with an increased risk of anxiety, depression, and depressive symptoms. This review presents evidence to further understand the relationship between WDP, typical food groups, and the incidence of behavioral health disorders, and more randomized controlled trials and cohort studies are urgently required to confirm these findings and elucidate potential mechanisms.
Assuntos
Fenômenos Biológicos , Padrões Dietéticos , Humanos , Alimentos , Ansiedade/epidemiologia , Transtornos de AnsiedadeRESUMO
In the present study, citrus peels were extracted using various conventional and deep eutectic solvents (DESs). Compared to other citrus peel extracts, the DES extract based on choline chloride showed notably higher total phenolic and flavonoid content levels, along with superior antioxidant activity, among these extracts. Consequently, this study aimed to further investigate the inhibitory effects of the choline chloride based DES extract on the production of both free and bound heterocyclic amines (HAs) and advanced glycation end products (AGEs) in roast pork meat patties. The results indicated that the addition of choline chloride-based DES extracts, particularly the choline chloride-carbamide based DES extract, can effectively reduce the oxidation of lipids and proteins by quenching free radicals. This approach proves to be the most efficient in reducing the formation of both HAs and AGEs, leading to a significant reduction of 19.1-68.3% and 11.5-66.5% in free and protein-bound HAs, respectively. Moreover, the levels of free and protein-bound AGEs were reduced by 50.8-50.8% and 30.5-39.8%, respectively, compared to the control group. Furthermore, the major phenolics of citrus peel extract identified by UHPLC-MS were polymethoxylated flavonoids (PMFs) including hesperidin, isosinensetin, sinensetin, tetramethoxyflavone, tangeretin, and hexamethoxyflavone, which inferring that these compounds may be the main active ingredients responsible for the antioxidant activity and inhibition effects on the formation of HAs and AGEs. Further research is needed to explore the inhibitory effects and mechanisms of PMFs with different chemical structures on the formation of HAs and AGEs.
RESUMO
Light-based 3D bioprinting is now employed widely to fabricate geometrically complex constructs for various biomedical applications. However, the inherent light scattering defect creates significant challenges in patterning dilute hydrogels to form high-fidelity structures with fine-scale features. Herein, we introduce a photoinhibiting approach that can effectively suppress the light scattering effect via a mechanism of simultaneous photoabsorption and free-radical reaction. This biocompatible approach significantly improves the printing resolution (~1.2 - ~2.1 pixels depending on swelling) and shape fidelity (geometric error less than 5%), while minimising the costly trial-and-error procedures. The capability in patterning 3D complex constructs using different hydrogels is demonstrated by manufacturing various scaffolds featuring intricate multi-sized channels and thin-walled networks. Importantly, cellularised gyroid scaffolds (HepG2) are fabricated successfully, exhibiting high cell proliferation and functionality. The strategy established in this study promotes the printability and operability of light-based 3D bioprinting systems, allowing numerous new applications for tissue engineering.
Assuntos
Bioimpressão , Alicerces Teciduais , Alicerces Teciduais/química , Bioimpressão/métodos , Impressão Tridimensional , Engenharia Tecidual/métodos , Hidrogéis/químicaRESUMO
Different mechanisms for inhibiting tyrosinase can be exploited to avoid quality losses caused by the enzymatic browning of fruits and vegetables. Piceid (PI) and piceid 6â³-O- azelaic acid ester (PIA) are oxidized by tyrosinase; however, their oxidation products may have inhibitory effects on tyrosinase. This notion is because l-DOPA oxidation was inhibited after the pre-incubation of PI/PIA with tyrosinase, however, l-DOPA oxidation was not affected if this pre-incubation was not performed. Circular dichroism analysis indicated a conformational change in the secondary structure of tyrosinase after pre-incubation. Further, molecular docking and enzyme reaction kinetics assays were employed to reveal the mechanism underlying the effects of PI/PIA on tyrosinase in the absence of pre-incubation with tyrosinase. PI/PIA had anti-browning effects in the potato models. The increased rate of A420 in PI/PIA groups at 24 h were 281% and 279%, which were approximately 2.4- and 2.5-fold lower than that of control (668%).
Assuntos
Ésteres , Monofenol Mono-Oxigenase , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Glucosídeos , Cinética , Levodopa , Simulação de Acoplamento Molecular , EstilbenosRESUMO
A new Aspergillus niger whole-cell catalyst was cultured for the cascade hydrolysis of hesperidin (HES) to produce high-value hesperetin-7-O-glucoside (HG) and hesperetin with high conversion (above 90%). Moreover, the inducers used were shown to be useful for cell growth and to induce cells to produce specific enzymes. Remarkably, the type of inducers determined whether the cells can hydrolyze HES. The product composition was also controllable by adjusting different inducers. Transcriptome analysis suggested that both naringin-vs-blank group and saccharose-vs-blank group had obviously difference in gene expression. The naringin-vs-blank group was mainly up-regulated differentially expressed genes (DEGs), while saccharose-vs-blank group was mainly down-regulated DEGs. The Gene Ontology (GO) analysis showed that whether naringin or saccharose was added as an inducer would greatly affect the catalytic activity of cells. Furthermore, 3 genes related to rhamnosidase, 14 genes related to glucosidase and 5 genes related to hydrolase activity were found. These genes were not only involved in rhamnosidase and glucosidase activities, but also spliceosome and the sucrose and starch metabolic pathways. The quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that the results of transcriptome sequencing were reliable. This study gave a new approach to hydrolyze HES, and new perspectives to understand the mechanisms associated with the hydrolysis of whole-cell catalyst.
Assuntos
Citrus , Aspergillus , Aspergillus niger/genética , Flavonoides , Glucosidases , Hidrólise , Sacarose , TranscriptomaRESUMO
Background: Older individuals have been reported to suffer from cognitive disorders after surgery. Various types of surgical trauma have been used to establish postoperative cognitive dysfunction (POCD) animal models in preclinical studies. However, few comparative analyses of these animal models were conducted. Methods: Tibial surgery, abdominal surgery, and extended abdominal surgery were performed on aged ICR mice to establish POCD models. Behavioral tests included open field, novel object recognition, fear conditioning, and Morris water maze tests. The Z-score methodology was adopted to obtain a comprehensive and integrated memory performance profile. The changes in hippocampal neuroinflammation were analyzed by ELISA, PCR, and immunofluorescence. Results: In this study, we found that each type of non-cardiac surgical trauma has a different effects on locomotor activity. Tibial and extended abdominal surgeries led to more significant cognitive impairment than abdominal surgery. Inflammatory cytokines peaked on postoperative day 1 and decreased to control levels on days 3 and 7. Hippocampal neuroinflammation indicators between the three surgery types on postoperative day 1 had no statistical differences. Conclusion: Overall, the type and intensity of non-cardiac surgical trauma can affect cognitive behavioral outcomes and central inflammation. The shortcomings and emerging issues of POCD animal research methods need to be further studied and solved.
RESUMO
In this paper, an enzymatic route for synthesizing phenolic glycoside azelaic acid esters was successfully set up via lipase-catalyzed esterification and transesterification. Among the lipases tested, Candida antarctica lipase B (Novozyme 435) showed the highest activity in catalyzing esterification and Thermomyces lanuginosus (Lipozyme TLIM) gave the highest substrate conversion in catalyzing transesterification for the synthesis of ester. The addition of 4A molecular sieves into the reaction system is found to be an effective method for in situ absorption of the byproduct water and methanol, with which the substrate conversions of the enzymatic esterification and transesterification were 98.7 and 95.1%, respectively. Also, the main product ratios in transesterification were above 99.0% with lipozyme TLIM as a catalyst because the hydrolysis reaction was hindered. The results of the physical and biological properties indicate that all esters had higher Clogâ¯p values than their parent compounds. Also, the esters showed higher intracellular tyrosinase inhibitory and depigmentating activities than phenolic glycosides, azelaic acid (AA), and their physical mixtures due to their higher membrane penetration and tyrosinase inhibitory effects. In particular, piceid 6â³-O-azelaic acid ester (PIA) showed the strongest inhibitory effect against melanin production. Its inhibitory rate was 77.4% at a concentration of 0.25 mM, about 4.2 times higher than that of arbutin (18.5%).
Assuntos
Ésteres , Glicosídeos , Basidiomycota , Ácidos Dicarboxílicos , Esterificação , EurotialesRESUMO
BACKGROUND: This study sought to classify the level of quality of life in patients with moderate to severe hand trauma, and explore differences in their potential profile characteristics based on the Patient-Reported Outcomes Measurement Information System (PROMIS). METHODS: This was a survey research. A convenience sampling method was used to investigate 296 patients with moderate to severe hand trauma. A general information questionnaire (which was used to gather general demographic data and disease-related data) and PROMIS-57 were administered form November 2020 to May 2021. A latent profile analysis and Chi square test were conducted to analyze the data. RESULTS: Based on quality of life, patients with moderate to severe hand trauma were divided into the following 3 groups: (I) Group C1: the psychosocial-pain low-impact group (38.9%); (II) Group C2: the psychosocial-moderate-impact severe-pain group (43.9%); and (III) Group C3: the psychosocial-pain high-impact group (17.2%). There were significant differences in the distribution of age, educational level, marital status, occupation, monthly income, medical insurance type, family role, subsequent financial resources, cause of the injury, satisfaction with the appearance of the hand, degree of the injury, and impact of the injury on daily life among patients in the different groups (P<0.05). CONCLUSIONS: The quality of life in patients with moderate to severe hand trauma can be identified to provide precise care.
Assuntos
Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Dor , Inquéritos e QuestionáriosRESUMO
Tyrosinase is a key enzyme responsible for enzymatic browning of fruits and vegetables and skin disorders due to overproduction of melanin. Arbutin is an inhibitor of tyrosinase; however, its high polarity and weak transdermal absorption capacity limit its applications. In this paper, a green solvent system was developed to successfully synthesize arbutin esters with improved liposolubilities (Clog P values = 0.27-5.03). Among the obtained esters, arbutin undecenoate (AU) showed the strongest tyrosinase-inhibiting activity (15.6%), which was 9.0 times higher than that of arbutin. An enzyme kinetics study indicated that AU was a competitive inhibitor with reversible inhibition. The esters inhibited tyrosinase by making the secondary structure of tyrosinase looser and less stable; moreover, the interactions between tyrosinase and AU driven by metal interactions and hydrogen bonds also offered a mechanism for inhibition of AU on tyrosinase. In addition, AU (100 µM) reduced the melanin content of B16 mouse melanoma cells to 61.3% of the control group.
Assuntos
Arbutina , Ésteres , Animais , Arbutina/farmacologia , Catálise , Melaninas , Camundongos , Monofenol Mono-OxigenaseRESUMO
Acylation has become one of the most widely used methods to improve the lipid solubility and bioavailability of flavonoids. In this study, puerarin acid esters (PAES) with different chain lengths were synthesized via biocatalytic acylation. This was the first study to evaluate the digestion and transport profiles and immunocompetence of PAES. The relationship between the digestion and transport profiles and potential immunocompetence of the acylated derivatives in Caco-2 cell monolayers was also explored. Puerarin and PAES remained stable in gastric phases, whereas different degrees of hydrolysis of PAES were found in the intestine. PAES with less than 12 carbon chains were positively correlated with the degree of hydrolysis, while those with more than 12 carbon chains showed higher resistance to hydrolysis by the artificial human digestive juice. The apparent permeability coefficients of puerarin, puerarin acetate, puerarin propanoate, puerarin butyrate, puerarin hexanoate, puerarin octanate and puerarin laurate were 1.62 ± 0.09, 1.70 ± 0.15, 1.89 ± 0.19, 1.86 ± 0.18, 2.29 ± 0.12, 4.06 ± 1.01 and 2.32 ± 0.88 × 10-6 cm s-1, respectively, in Caco-2 cell monolayers. The results of the immune factor assays indicated that puerarin propanoate, puerarin hexanoate and puerarin myristate could significantly promote the secretion of IL-6, TNF-α and IL-10. These findings suggested that a better absorption could be predicted after oral intake using PAES. Meanwhile, the concentration of esters and their metabolites (puerarin) found in the digestion and transport profiles directly affected their potential immunocompetence.
Assuntos
Digestão , Imunocompetência/efeitos dos fármacos , Isoflavonas/química , Isoflavonas/farmacologia , Acilação , Disponibilidade Biológica , Células CACO-2 , Citocinas , Ácidos Graxos , Flavonoides , Humanos , Permeabilidade , SolubilidadeRESUMO
Background: Cancer patients may carry a worse prognosis with SARS-CoV-2 infection. Most of the previous studies described the outcomes of hospitalized cancer patients. We aimed to study the clinical factors differentiating patients requiring hospital care vs. home recovery, and the trajectory of their anti-cancer treatment. Methods: This study was conducted in a community cancer center in New York City. Eligible patients were those who had cancer history and were diagnosed of SARS-CoV-2 infection between March 1 and May 30, 2020, with confirmatory SARs-CoV-2 virus test or antibody test. Four groups were constructed: (A) hospitalized and survived, (B) hospitalized requiring intubation and/or deceased, (C) non-hospitalized, asymptomatic, with suspicious CT image findings, close exposure, or positive antibody test, and (D) non-hospitalized and symptomatic. Results: One hundred and six patients were included in the analysis. Thirty-five patients (33.0%) required hospitalization and 13 (12.3%) died. Thirty (28.3%) patients were asymptomatic and 41 (38.7%) were symptomatic and recovered at home. Comparing to patients who recovered at home, hospitalized patients were composed of older patients (median age 71 vs. 63 years old, p = 0.000299), more who received negative impact treatment (62.9 vs. 32.4%, p = 0.0036) that mostly represented myelosuppressive chemotherapy (45.7 vs. 23.9%, p = 0.0275), and more patients with poorer baseline performance status (PS ≥ 2 25.7 vs. 2.8%, p = 0.0007). Hypoxemia (35% in group A vs. 73.3% in group B, p = 0.0271) at presentation was significant to predict mortality in hospitalized patients. The median cumulative hospital stay for discharged patients was 16 days (range 5-60). The median duration of persistent positivity of SARS-CoV-2 RNA was 28 days (range 10-86). About 52.9% of patients who survived hospitalization and required anti-cancer treatment reinitiated therapy. Ninety-two percent of the asymptomatic patients and 51.7% of the symptomatic patients who recovered at home continued treatment on schedule and almost all reinitiated treatment after recovery. Conclusions: Cancer patients may have a more severe status of SARS-CoV-2 infection after receiving myelosuppressive chemotherapy. Avoidance should be considered in older patients with poor performance status. More than two thirds of patients exhibit minimal to moderate symptoms, and many of them can continue or restart their anti-cancer treatment upon recovery.