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Objective: Sarcopenia is a gradually advancing systemic disorder affecting skeletal muscles, primarily distinguished by diminished muscle mass and functional decline. As of present, a universally accepted diagnostic criterion for sarcopenia has yet to be established. From the perspective of the constitution theory in traditional Chinese medicine (TCM), the Yin-deficiency constitution is believed to have a significant correlation with the development of sarcopenia. The primary objective of this study was to examine the potential association between sarcopenia and Yin-deficiency constitution. Methods: The present study is a cross-sectional analysis. The Asian Working Group for Sarcopenia (AWGS) recommended a diagnostic criterion for sarcopenia. A total of 141 participants over 50 years of age were diagnosed with sarcopenia. To determine the constitution of each patient, classification and determination standards were used in traditional Chinese medicine. In this study, a combination of logistic regression and propensity score matching (PSM) was employed to analyze a dataset comprising 1,372 eligible observations. The diagnostic efficacy of the test in distinguishing sarcopenia was assessed through receiver operating characteristic (ROC) curve analysis. Results: The relationship between Yin-deficiency constitution and sarcopenia was examined using logistic regression analysis. In the crude model, the odds ratio (OR) was found to be 3.20 (95% confidence interval [CI]: 1.70-6.03). After adjusting for various confounding factors, including gender, sex, 6 m walking test/(m/s), SMI, and maximum grip strength/kg, the OR increased to 9.70 (95% CI: 3.20-69.38). The associations between seven other biased traditional Chinese medicine (TCM) constitutions and sarcopenia were not found to be statistically significant in the fully adjusted model. The propensity score matching (PSM) analysis yielded consistent results with the logistic regression analysis. Receiver operating characteristic (ROC) curve analysis showed that the AUC of the Yin-deficiency constitution combined with age and gender reached 0.707. Conclusion: Among the nine TCM constitutions examined, the Yin-deficiency constitution demonstrates an independent association with sarcopenia. Yin-deficiency constitution may serve as a potential risk factor for the development of sarcopenia. To establish a causal relationship, further experimental investigations are warranted. The diagnostic performance of sarcopenia is effectively demonstrated by the Yin-deficiency constitution combined with age and gender.
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Medicina Tradicional Chinesa , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Estudos Transversais , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Deficiência da Energia Yin/diagnóstico , Curva ROC , Idoso de 80 Anos ou maisRESUMO
After myocardial ischemia/reperfusion injury (MI/RI), endothelial cell injury causes impaired angiogenesis and obstruction of microcirculation, resulting in an inflammatory outburst that exacerbates the damage. Therefore, synergistic blood vessel repair and inflammation inhibition are effective therapeutic strategies. In this study, we developed a platelet membrane (PM)-encapsulated baicalin nanocrystalline (BA NC) nanoplatform with a high drug load, BA NC@PM, which co-target to endothelial cells and macrophages through the transmembrane proteins of the PM to promote angiogenesis and achieve anti-inflammatory effects. In vitro cell scratch assays and transwell assay manifested that BA NC@PM could promote endothelial cell migration, as well as increase mRNA expression of CD31 and VEGF in the heart after treatment of MI/RI mice, suggesting its favorable vascular repair function. In addition, the preparation significantly reduced the expression of pro-inflammatory factors and increased the expression of anti-inflammatory factors in plasma, promoting the polarization of macrophages. Our study highlights a strategy for enhancing the treatment of MI/RI by promoting angiogenesis and regulating macrophage polarization via the biomimetic BA NC@PM nanoplatform.
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Objective: Sarcopenia is a geriatric syndrome that occurs with age and is characterized by a gradual decline in muscle mass, power, and functionality. It serves as a prominent contributor to frailty, disability, and mortality among older individuals. Currently, no standardized global guidelines exist for the diagnosis of sarcopenia. This study aimed to establish the correlation between sarcopenia and the constitutions of traditional Chinese medicine (TCM), considering the connection between physical functioning and sarcopenia. Methods: A total of 1441 participants in this study were diagnosed with sarcopenia. The Asian Working Group for Sarcopenia (AWGS) proposed a sarcopenia definition algorithm. To determine the constitution of each participant, classification and determination standards were used in traditional Chinese medicine. This study evaluated the demographics, lifestyles, and self-reported medical history of individuals diagnosed with sarcopenia through a self-administered questionnaire. The constitution of the participants was determined using TCM classification and determination standards. Subsequently, we analyzed the results of univariate analysis and multivariate regression and constructed a receiver operating characteristic (ROC) curve. Results: Participants who were diagnosed with sarcopenia had substantially lower original Neutral constitution scores (P < 0.050). In comparison to those without sarcopenia, individuals with sarcopenia exhibited notably elevated original Qi-deficiency, Yang-deficiency, Yin-deficiency, Blood-stagnation, and Qi-stagnation scores in contrast to those in the healthy group (P < 0.050). The identified risk factors associated with sarcopenia included the following: Neutral (OR = 0.903), Qi-deficiency (in males, OR = 1.126), Yang-deficiency (OR = 1.062), Phlegm-dampness (in males, OR = 0.833), and Blood-stagnation (in females, OR = 1.089). The highest area under the curve (AUC) was observed for the original neutral constitution score, followed by the Yang-deficiency and blood-stagnation scores (0.644, 0.613, and 0.611, respectively). Additionally, the AUC for the combined original scores of all nine constitutions among males reached 0.778. Conclusions: In this cross-sectional study of older people with higher original Qi-deficiency, Yin deficiency, Yang-deficiency, Blood-stagnation, and Qi-stagnation were associated with sarcopenia. Notably, various TCM constitutions are significantly linked to sarcopenia. There was a significant occurrence of various body constitution types among individuals diagnosed with sarcopenia. The mixture of the nine original constitution scores exhibited good diagnostic performance for sarcopenia in males.
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Atherosclerosis (AS) is considered to be one of the major causes of cardiovascular disease. Its pathological microenvironment is characterised by increased production of reactive oxygen species, lipid oxides, and excessive inflammatory factors, which accumulate at the monolayer endothelial cells in the vascular wall to form AS plaques. Therefore, intervention in the pathological microenvironment would be beneficial in delaying AS. Researchers have designed biomimetic nanomedicines with excellent biocompatibility and the ability to avoid being cleared by the immune system through different therapeutic strategies to achieve better therapeutic effects for the characteristics of AS. Biomimetic nanomedicines can further enhance delivery efficiency and improve treatment efficacy due to their good biocompatibility and ability to evade clearance by the immune system. Biomimetic nanomedicines based on therapeutic strategies such as neutralising inflammatory factors, ROS scavengers, lipid clearance and integration of diagnosis and treatment are versatile approaches for effective treatment of AS. The review firstly summarises the targeting therapeutic strategy of biomimetic nanomedicine for AS in recent 5 years. Biomimetic nanomedicines using cell membranes, proteins, and extracellular vesicles as carriers have been developed for AS.
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Aterosclerose , Biomimética , Sistemas de Liberação de Medicamentos , Nanomedicina , Humanos , Aterosclerose/tratamento farmacológico , Nanomedicina/métodos , Biomimética/métodos , Sistemas de Liberação de Medicamentos/métodos , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/administração & dosagem , Espécies Reativas de Oxigênio/metabolismoRESUMO
Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy.
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Neoplasias da Mama , Nanopartículas , Fotoquimioterapia , Humanos , Feminino , Neoplasias da Mama/terapia , Verde de Indocianina/química , Fototerapia , Nanopartículas/química , Homeostase , Linhagem Celular TumoralRESUMO
Constituted by various heterogeneous cells, the tumor microenvironment (TME) is capable of promoting tumor proliferation, invasion, and metastasis through extensive crosstalk. The pivotal factor influencing the survival time of patients and their response to immunotherapy lies in the intratumoral immune environment. We obtained 112 differential genes related to T cell-mediated tumor killing in LUAD by employing bioinformatics analysis on the basis of the TCGA and TISIDB databases. Then the 6-gene prognostic risk score model (CA9, OIP5, TIMP1, SEC11C, FURIN, and TLR10) was constructed by conducting univariate LASSO as well as multivariate Cox regression analyses. The median risk score was taken as the threshold to classify the samples into two groups. Survival analysis revealed that the low-risk group exhibited a more favorable prognosis. Subsequently, the Cox regression analysis combined with clinical information (age, gender, and pathological stage) and the risk score of LUAD patients demonstrated the potential of this model as an independent prognostic factor. The nomogram established based on clinical information and a risk score in combination with the calibration curve indicated that this model had good predictive ability. Notable enrichment of the differential genes from the high- and low-risk groups was discovered in immune-associated processes or pathways, as shown by the GO and KEGG enrichment analyses. The combined use of single-sample gene enrichment analysis (ssGSEA) and immunophenoscore (IPS) demonstrated heightened immune infiltration and IPS scores in the low-risk group, indicating that immunotherapy was likely to show good efficacy in patients from this group. To sum up, the prognostic model of LUAD constructed based on T-cell-mediated cell killing-related genes was not only capable of screening the prognosis of LUAD patients but was also used for screening those LUAD patients with high sensitivity to immunotherapy. Our study offered novel insights into the clinical treatment and prognostic prediction of LUAD patients.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Linfócitos T , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/terapia , Apoptose , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Due to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it's urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon. RESULTS: In this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment. CONCLUSIONS: It's suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD.
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Curcumina , Emodina , Doenças Inflamatórias Intestinais , Humanos , Hidrogéis , Anti-Inflamatórios/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal , Inflamação , Alginatos , Curcumina/farmacologiaRESUMO
BACKGROUND: Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts. METHODS: We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models. RESULTS: The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749). CONCLUSIONS: The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population. TRIAL REGISTRATION: Chictr.org, ChiCTR 1800018895.
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Aprendizado Profundo , Sarcopenia , Humanos , Idoso , Sarcopenia/diagnóstico , Envelhecimento , Algoritmos , BiomarcadoresRESUMO
BACKGROUND: Sarcopenia is an age-related skeletal muscle disorder that involves a loss of muscle mass or strength and physiological function. Skeletal muscle deteriorates in both quantity and quality. The endocrine system is an important regulator of muscle metabolism. Therefore, we aimed to explore the relationship between biochemical markers and muscle mass in sarcopenia. METHODS: We used the AWGS 2014 as the diagnostic criteria for sarcopenia, considering both the loss in muscle mass, muscle strength and physical performance. A total of 2837 elderly female participants over 50 years of age from the West China Health and Aging Trend (WCHAT) study were included. Insulin, glucose, 25(OH)VD, procalcitonin, alanine aminotransferase, aspartate aminotransferase, total protein, prealbumin, albumin, thyroid-stimulating hormone, free triiodothyronine, free tetraiodothyronine, triglycerides, cholesterol, high-density lipoprotein, very low-density lipoprotein, cortisol, and follicle-stimulating hormone were measured. Based on the findings of univariate analysis, multivariate regression and receiver operating characteristic (ROC) curves were established. RESULTS: Participants with sarcopenia had significantly lower free triiodothyronine, insulin, total protein, albumin, prealbumin, albumin/prealbumin ratio (A/G), alanine aminotransferase, triglycerides, and very low-density lipoprotein concentrations (P < 0.05). Compared with those without sarcopenia, those with sarcopenia had significantly higher free tetraiodothyronine, cortisol, follicle-stimulating hormone (FSH), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT), and high-density lipoprotein concentrations (P < 0.05). Insulin (OR = 0.854), FSH (OR = 1.016), and the AST/ALT ratio (OR = 1.819) were independent risk factors for low muscle mass (P < 0.001). The AUC of insulin was the highest, followed by the AST/ALT ratio and FSH (0.691, 0.671, and 0.634, respectively), and the AUC of the mixture of the above three reached 0.736. CONCLUSION: In this cross-sectional study of elderly Chinese females aged over 50 years from the WCHAT, FSH, insulin, and AST/ALT ratio were associated with sarcopenia and risk factors for low muscle mass.
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Insulina , Sarcopenia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Alanina Transaminase , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Pré-Albumina , Tri-Iodotironina , Hidrocortisona , Estudos Transversais , Aspartato Aminotransferases , Músculo Esquelético , Triglicerídeos , Albuminas , Lipoproteínas HDL , Hormônio Foliculoestimulante , Lipoproteínas LDLRESUMO
Anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) are promising therapies for esophageal cancer. Zinc finger protein 64 (ZFP64) is precited as a transcriptional factor for PD-1 and CTLA-4 and presents high expression in esophagus cancer by bioinformatics analysis. The present study was designed to validate these results and to further explore the role of ZFP64 in esophagus cancer tumorigenesis. An orthotopic xenograft mouse model was established. Effects of ZFP64 on tumor growth and weight were assessed. Immunohistochemical staining was performed to reveal the protein expression of ZFP64, PD-1, and CTLA-4. Gain-of-function assays were performed to evaluate the influences of ZFP64 on cancer cell malignant phenotypes. The results revealed that ZFP64 transcriptionally activates PD-1 and CTLA-4 to increase their expression. ZFP64 plays an oncogenic role in esophageal cancer by promoting cancer cell proliferation, migration, invasion, and repressing apoptosis. ZFP64 also promotes esophageal cancer xenograft tumor growth in mice. In conclusion, ZFP64 increases PD-1 and CTLA-4 expression by binding to their promoters and facilitates esophageal cancer tumorigenesis, indicating ZFP64 protein transcription factor as a potential antidrug target in esophageal cancer.
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Neoplasias Esofágicas , Receptor de Morte Celular Programada 1 , Animais , Antígeno CTLA-4/genética , Antígeno CTLA-4/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Humanos , Camundongos , Receptor de Morte Celular Programada 1/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
PURPOSE: The West China longevity and ageing procedure (WCLAP) cohort study aims to provide guidance for older adults in western China with the aim of improving quality of life, reducing the burden of family care, summarising the characteristics of longevity lifestyles, building a Chinese-longevity-population biobank and exploring the mechanisms underlying population ageing. PARTICIPANTS: Since the establishment of the WCLAP research baseline in 2018, a population of 1537 adults aged 80 years and above, living in the community, have been enrolled in the programme as research participants. Of these, 231 are aged 100 years and above. Participants are followed up every year. FINDING TO DATA: WCLAP data are collected in five hospital research subcentres strategically located adjacent to the national 'Longevity Townships' of Chengdu Ziyang, Leshan, Yibin and Pengshan. Data collection included a comprehensive assessment of the participant's health (including physical, psychological, social and common chronic disease assessments), instrumental tests (body composition and muscle percentage) and the collection of biomedical-biobank samples (include blood, urine, faeces, hair and urine). FUTURE PLANS: Through the annual cohort follow-up, survival-related information is collected at a group level. Analysis of biological samples facilitates biological characterisation at the microscopic level through proteomics, metabolomics, genomics and other techniques. Baseline data, group-level follow-up data and microbiological examination data are integrated together to provide an evaluation tool, exploring sarcopenia, disability, dementia, caregiver burden, ageing biomarkers and other influencing factors. TRIAL REGISTRATION NUMBERS: 2018-463; ChiCTR1900020754.
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Envelhecimento , Longevidade , Idoso de 80 Anos ou mais , China , Estudos de Coortes , HumanosRESUMO
[This corrects the article DOI: 10.3389/fendo.2021.785045.].
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Background: Sarcopenia is an age-related and skeletal muscle disorder involving the loss of muscle mass or strength, and physiological function. Although the diagnostic indicators used in the different guidelines are for muscle mass, strength and physical performance, there are currently no uniform diagnostic criteria. Therefore, we aimed to explore the relationship between a series of biomarkers with sarcopenia in southwest China. Methods: We included 4302 patients from West China Health and Aging Trend (WCHAT) study. Sarcopenia was defined according to the Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. Thyroxineãalbuminãtotal proteinãprealbuminãalbumin to globulin ratio (A/G)ã25(OH)VDãfasting insulinãadrenal cortisolãtriglycerideãhigh-density lipoproteinãhemoglobin and aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) were measured. The receiver operating characteristic curves (ROC) were established to describe the predictive value for sarcopenia and we also used multivariate logistic regression analysis to identify risk factors of the disease. Results: In terms of protein state, patients with sarcopenia had lower value in total protein, albumin, prealbumin, A/G than the control (P<0.001). Patients had lower value in triglyceride but higher value in high-density lipoprotein compared with the healthy in the indicators of lipid metabolism (P<0.001). In the aspect of hormone state, patients had lower free triiodothyronine, fasting insulin but higher free tetraiodothyronine and adrenal cortisol than the healthy (P<0.001). The fasting insulin level (AUC=0.686) and the AST/ALT ratio (AUC=0.682) were the best predictors of sarcopenia among biomarkers. The diagnostic performance of fasting insulin combined with the AST/ALT ratio (AUC=0.720) is equal to multiple indicators (AUC=0.742). Conclusion: The fasting insulin combined with the AST/ALT ratio exhibits good diagnostic performance for sarcopenia.
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Envelhecimento/sangue , Laboratórios Clínicos/tendências , Sarcopenia/sangue , Sarcopenia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sarcopenia/diagnósticoRESUMO
ABSTRACT: It remains unknown whether dissecting the intrapulmonary lymph nodes (stations 13 and 14) when resecting peripheral non-small cell lung cancer (NSCLC) is necessary for accurate tumor node metastasis (TNM) staging. This study investigated intrapulmonary lymph node dissection (stations 13 and 14) on the pathological staging of peripheral NSCLC and the metastatic pattern of the lymph nodes.This retrospective study included patients with primary peripheral NSCLC who underwent radical dissection between January 2013 and December 2015. The clinical data of patients and examination results of intrapulmonary stations 12, 13, and 14 lymph nodes were analyzed.Of 3019 resected lymph nodes in a total of 234 patients (12.9/patient), 263 (8.7%) had metastasis. Ninety-nine patients had lymph node metastasis (42.3%): 40 (17.1%) were N1, 11 (4.7%) were N2, 48 (20.5%) were both N1 and N2, and 135 (57.7%) had no N1 or N2 metastasis. Sixteen (6.8%) patients had metastasis of stations 13 and/or 14. Metastasis in N1 positive patients of stations 10, 11, 12, 13, and 14 were 2.7%, 10.5%, 9.8%, 10.4%, and 8.5%, respectively. Missed detection without station 13 and 14 dissection was up to 6.8% (16/234).Dissection of stations 13 and 14 could be helpful for the identification of lymph node metastasis and for the accurate TNM staging of primary NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/diagnóstico , Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Estadiamento de Neoplasias , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Pine oil contains a high percentage of polyunsaturated fatty acids, which make it prone to oxidation. Luteolin (LUT) micro-nano particles with antioxidant properties can be used as stabilizers to form an edible oil-in-water Pickering emulsion to improve the oxidative stability of pine nut oil. RESULTS: Under optimal preparation conditions, the LUT micro-nano particles and pine nut oil account for about 0.44 and 90.9 g·kg-1 of the total mass of the emulsion, respectively. The LUT particles in the suspension have a mean particle size of about 479 nm, present a sheet-like structure with a cut surface of 30-50 nm, and can reduce the surface tension of deionized water. In the optimized Pickering emulsion, the emulsion droplets are approximately spherical and have a mean diameter of about 125.6 nm and uniform distribution. The optimized Pickering emulsion droplets can remain stable for up to 2 h in an environment where the pH levels are 7-8.5, ultraviolet B radiation (UVB) irradiation, of less than 5.0 g·kg-1 , and at a temperature of 80 °C. The stability of the emulsion in simulated digestive fluid changed minimally. In the first 7 days of the accelerated oxidation experiment, LUT micro-nano particles not only successfully protected the integrity of emulsion droplets but also fully inhibited the peroxidation of pine oil. CONCLUSION: The strong antioxidant properties of LUT micro-nano particles, and the dense protective layer they formed, stabilized the Pickering emulsion successfully. The particles also improved the oxidation stability of pine nut oil. © 2020 Society of Chemical Industry.
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Luteolina/química , Pinus/química , Óleos de Plantas/química , Emulsões/química , Nozes/química , Oxirredução , Tamanho da PartículaRESUMO
There are many kinds of biological activities of resveratrol itself, but its clinical application is limited by its poor solubility in water and low bioavailability. Therefore, we have prepared glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles (GL-HSA-RESNPs). The purpose of this study was to investigate the bioavailability, pharmacokinetics and tissue distribution of resveratrol in rats after single-dose tail vein injection administration of GL-HSA-RESNPs. A sensitive and reliable high performance liquid chromatography (HPLC) method was established to verify the content of resveratrol in rat plasma and organs. The Cmax value after GL-HSA-RESNPs administration was significantly higher than that of resveratrol suspension (933 ± 76.64 ng/mL vs. 618 ± 42.54 ng/mL, p < .01). The Tmax value obtained after GL-HSA-RESNPs administration was significantly shorter than that after resveratrol suspension administration (0.17 ± 0.01 h vs. 0.25 ± 0.01 h, p < .001). The bioavailability of GL-HSA-RESNPs was 4.25 times higher than that of the pure resveratrol. The concentration of resveratrol in the main organs of rats treated with the GL-HSA-RESNPs was higher than that in rats treated with the pure resveratrol. Rats treated with GL-HSA-RESNPs had the highest concentration of resveratrol in their liver. It is indicated that GL-HSA-RESNPs is a promising liver-targeted delivery system that improves the in vivo bioavailability of resveratrol.
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Portadores de Fármacos/química , Ácido Glicirrízico/química , Nanopartículas/química , Resveratrol/farmacocinética , Albumina Sérica Humana/química , Animais , Feminino , Masculino , Taxa de Depuração Metabólica , Ratos , Resveratrol/administração & dosagem , Resveratrol/efeitos adversos , Solubilidade , Distribuição TecidualRESUMO
BACKGROUND: Lutein ester (LE) is an important carotenoid fatty acid ester. It is a form in which lutein is present in nature and is produced by free non-esterification and fatty acid esterification. LE is one of the safe sources of lutein. Increasing lutein intake can prevent and treat age-related macular degeneration. In addition, it can effectively inhibit gastric cancer, breast cancer, and esophageal cancer. However, the poor aqueous solubility of LE has impeded its clinical applications. OBJECTIVE: The objective of this study was to prepare lutein ester nanoparticles (LE-NPs) by liquid antisolvent precipitation techniques to improve the bioavailability of LE in vivo and improve eye delivery efficiency. MATERIALS AND METHODS: The physical characterization of LE-NPs was performed, and their in vitro dissolution rate, in vitro antioxidant capacity, in vivo bioavailability, tissue distribution, and ocular pharmacokinetics were studied and evaluated. RESULTS: The LE freeze-dried powder obtained under the optimal conditions possessed a particle size of ~164.1±4.3 nm. The physical characterization analysis indicated the amorphous form of LE-NPs. In addition, the solubility and dissolution rate of LE-NPs in artificial gastric juice were 12.75 and 9.65 times that of the raw LE, respectively. The bioavailability of LE-NPs increased by 1.41 times compared with that of the raw LE. The antioxidant capacity of LE-NPs was also superior to the raw LE. The concentration of lutein in the main organs of rats treated with the LE-NPs was higher than that in rats treated with the raw LE. The bioavailability of LE-NPs in rat eyeballs was found to be 2.34 times that of the original drug. CONCLUSION: LE-NPs have potential application as a new oral pharmaceutical formulation and could be a promising eye-targeted drug delivery system.
Assuntos
Precipitação Química , Sistemas de Liberação de Medicamentos/métodos , Ésteres/administração & dosagem , Luteína/administração & dosagem , Solventes/química , Administração Oftálmica , Administração Oral , Animais , Antioxidantes/farmacologia , Disponibilidade Biológica , Ésteres/química , Ésteres/farmacocinética , Luteína/química , Luteína/farmacocinética , Camundongos , Nanopartículas/administração & dosagem , Tamanho da Partícula , Ratos Sprague-Dawley , Solubilidade , Distribuição TecidualRESUMO
Binding and uptake of triglyceride-rich lipoproteins (TRLs) in mice depend on heparan sulfate and the hepatic proteoglycan, syndecan-1 (SDC1). Alteration of glucosamine N-sulfation by deletion of glucosamine N-deacetylase-N-sulfotransferase 1 (Ndst1) and 2-O-sulfation of uronic acids by deletion of uronyl 2-O-sulfotransferase (Hs2st) led to diminished lipoprotein metabolism, whereas inactivation of glucosaminyl 6-O-sulfotransferase 1 (Hs6st1), which encodes one of the three 6-O-sulfotransferases, had little effect on lipoprotein binding. However, other studies have suggested that 6-O-sulfation may be important for TRL binding and uptake. In order to explain these discrepant findings, we used CRISPR/Cas9 gene editing to create a library of mutants in the human hepatoma cell line, Hep3B. Inactivation of EXT1 encoding the heparan sulfate copolymerase, NDST1 and HS2ST dramatically reduced binding of TRLs. Inactivation of HS6ST1 had no effect, but deletion of HS6ST2 reduced TRL binding. Compounding mutations in HS6ST1 and HS6ST2 did not exacerbate this effect indicating that HS6ST2 is the dominant 6-O-sulfotransferase and that binding of TRLs indeed depends on 6-O-sulfation of glucosamine residues. Uptake studies showed that TRL internalization was also affected in 6-O-sulfation deficient cells. Interestingly, genetic deletion of SDC1 only marginally impacted binding of TRLs but reduced TRL uptake to the same extent as treating the cells with heparin lyases. These findings confirm that SDC1 is the dominant endocytic proteoglycan receptor for TRLs in human Hep3B cells and that binding and uptake of TRLs depend on SDC1 and N- and 2-O-sulfation as well as 6-O-sulfation of heparan sulfate chains catalyzed by HS6ST2.
Assuntos
Lipoproteínas/metabolismo , Mutação com Perda de Função , N-Acetilglucosaminiltransferases/metabolismo , Sulfotransferases/metabolismo , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Células Cultivadas , Hepatócitos/metabolismo , Humanos , Lipoproteínas/química , N-Acetilglucosaminiltransferases/genética , Ligação Proteica , Sulfotransferases/genética , Sindecana-1/genética , Sindecana-1/metabolismo , Triglicerídeos/química , Triglicerídeos/metabolismoRESUMO
In this study, a novel mesoporous silica nanoparticles drug carrier contributes to improving the solubility, dissolution, and the oral bioavailability of apigenin (AP). The apigenin of solid dispersion of mesoporous silica nanoparticles (AP-MSN) was prepared by physical absorption method and also, in-vitro drug release and in-vivo bioavailability performance were evaluated. Based on its solubility, the AP-MSN solid dispersion was prepared at the weight ratio of 1:1 to obtain the optimum solubility. The loading efficiency (LE), encapsulation efficiency (EE), and solubility of AP-MSN solid dispersion were 29.71%, 42.27%, and 25.11 µg/mL, respectively. SEM, TEM, BET, FTIR, XRD, DSC, and TG were also carried out. These results demonstrated that AP was good absorbed into the pores of MSN through physical absorption effect of MSN. The DMF residues of AP-MSN solid dispersion meet the ICH requirements. It was vital that the AP-MSN solid dispersion behaved well in-vitro and the accumulative release of AP-MSN solid dispersion was 2.37 times higher than that of raw AP. In-vivo study, the AP area under curve0-t was 8.32 times higher for the AP-MSN solid dispersion than that of raw AP, which indicated that the bioavailability of AP-MSN solid dispersion was greatly improved. Therefore, the prepared AP-MSN solid dispersion presents potential as a novel oral therapeutic agent formulation for clinical application.