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BACKGROUND: The purpose of this study is to employ a competing risk model based on the Surveillance, Epidemiology, and End Results (SEER) database to identify prognostic factors for elderly individuals with sigmoid colon adenocarcinoma (SCA) and compare them with the classic Cox proportional hazards model. METHODS: We extracted data from elderly patients diagnosed with SCA registered in the SEER database between 2010 and 2015. Univariate analysis was conducted using cumulative incidence functions and Gray's test, while multivariate analysis was performed using both the Fine-Gray and Cox proportional hazards models. RESULTS: Among the 10,712 eligible elderly patients diagnosed with SCA, 5595 individuals passed away: 2987 due to sigmoid colon adenocarcinoma and 2608 from other causes. The results of one-way Gray's test showed that age, race, marital status, AJCC stage, differentiation grade, tumor size, surgical status, liver metastasis status, lung metastasis status, brain metastasis status, radiotherapy status, and chemotherapy status all affected the prognosis of SCA (P < .05). Multivariate analysis showed that sex, age, race, marital status, and surgical status affected the prognosis of SCA (P < .05). Multifactorial Fine-Gray analysis revealed that key factors influencing the prognosis of SCA patients include age, race, marital status, AJCC stage, grade classification, surgical status, tumor size, liver metastasis, lung metastasis, and chemotherapy status (P < .05). CONCLUSION: Data from the SEER database were used to more accurately estimate CIFs for sigmoid colon adenocarcinoma-specific mortality and prognostic factors using competing risk models.
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Adenocarcinoma , Programa de VERF , Neoplasias del Colon Sigmoide , Humanos , Masculino , Femenino , Anciano , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Pronóstico , Neoplasias del Colon Sigmoide/patología , Neoplasias del Colon Sigmoide/mortalidad , Medición de Riesgo/métodos , Anciano de 80 o más Años , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
Acute lung injury (ALI), a common clinical type of critical illness, is an acute hypoxic respiratory insufficiency caused by the damage of alveolar epithelial cells and capillary endothelial cells. In a previous study, we reported a novel lncRNA, lncRNA PFI, which could protect against pulmonary fibrosis in pulmonary fibroblasts. The present study demonstrated that lncRNA PFI was downregulated in alveolar epithelial cell of mice injury lung tissues, and further investigated the role of lncRNA PFI in regulating inflammation-induced alveolar epithelial cell apoptosis. Overexpression of lncRNA PFI could partially abrogated bleomycin induced type II AECs injured. Subsequently, bioinformatic prediction revealed that lncRNA PFI might directly bind to miR-328-3p, and further AGO-2 RNA binding protein immunoprecipitation (RIP) assay confirmed their binding relationship. Furthermore, miR-328-3p promoted apoptosis in MLE-12 cells by limiting the activation of the Creb1, a protein correlated with cell apoptosis, whereas AMO-328-3p ablated the pro-apoptosis effect of silencing lncRNA PFI in MLE-12 cells. While miR-328-3p could also ablate the function of lncRNA PFI in bleomycin treated human lung epithelial cells. Enhanced expression of lncRNA PFI reversed the LPS-induced lung injury in mice. Overall, these data reveal that lncRNA PFI mitigated acute lung injury through miR-328-3p/Creb1 pathway in alveolar epithelial cells.
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Lesión Pulmonar Aguda , MicroARNs , ARN Largo no Codificante , Síndrome de Dificultad Respiratoria , Humanos , Ratones , Animales , Células Epiteliales Alveolares/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células Endoteliales/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/metabolismo , Apoptosis/genética , Síndrome de Dificultad Respiratoria/metabolismo , Lipopolisacáridos/efectos adversos , Bleomicina/farmacologíaRESUMEN
BACKGROUND: SARC-F questionnaire is a simple and convenient tool for sarcopenia screening, and SARC-CalF is a modified version of it. The developments of their Chinese versions are warranted for the clinical use for Chinese population. This study aimed to culturally adapt the SARC-F questionnaire into Chinese using standardized methods, validate the reliability and diagnostic accuracy of the Chinese version SARC-F and SARC-CalF against five sarcopenia diagnosis criteria, and determine optimal cut-off values for clinical practice in Chinese population. METHODS: The translation and cross-cultural adaptation of SARC-F into Chinese were conducted following the methodological report from European Union Geriatric Medicine Society Sarcopenia Special Interest Group. The Chinese version of SARC-F was validated through a diagnostic test, using diagnostic criteria of sarcopenia recommended by the revised 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) consensus, Asian Working Group for Sarcopenia (AWGS2019) consensus, the International Working Group on Sarcopenia (IWGS), the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium and the Sarcopenia Definition and Outcomes Consortium (SDOC). Additional analysis was done against the criteria of severe sarcopenia according to the revised EWGSOP2 and AWGS2019. RESULTS: The Chinese version of SARC-F was well translated and demonstrated good reliability and acceptability. The diagnostic test included 1859 community-dwelling older individuals from two medical centers. Against five different definitions of sarcopenia, the Chinese version of SARC-F showed reasonable diagnostic accuracy for sarcopenia screening (AUC 0.614-0.821), and was demonstrated low sensitivity (13.7-37.9%) but high specificity (94.8-97.7%) with a cut-off value of ≥ 4. SARC-CalF significantly enhanced the diagnostic accuracy of SARC-F when using definitions of EWGSOP2, AWGS2019 and IWGS (all P ≤ 0.001). A score of ≥ 2 for SARC-F and ≥ 7 for SARC-CalF were established as optimal cut-off points for identifying older individuals as at risk of sarcopenia in Chinese population. CONCLUSIONS: The Chinese version SARC-F is of reasonable reliability and validity for sarcopenia screening. Despite its low sensitivity, it proves to be a useful tool to identify severe cases in community taking advantage of its simplicity. SARC-CalF appears to be a more suitable screening tool for clinical use in detecting sarcopenia.
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Sarcopenia , Traducciones , Humanos , Sarcopenia/diagnóstico , Anciano , Masculino , Femenino , China/epidemiología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Anciano de 80 o más Años , Tamizaje Masivo/métodos , Evaluación Geriátrica/métodos , Persona de Mediana EdadRESUMEN
As the global incidence of diabetes rises and diagnoses among younger patients increase, transplant centers worldwide are encountering more organ donors with diabetes. This study examined 80 donors and 160 recipients, including 30 donors with diabetes (DD) and their 60 recipients (DDR). The control group comprised 50 non-diabetic donors (ND) and 100 recipients (NDR). We analyzed clinical, biochemical, and pathological data for both diabetic and control groups, using logistic regression to identify risk factors for delayed graft function (DGF) after kidney transplantation. Results showed that pre-procurement blood urea nitrogen levels were significantly higher in DD [18.20 ± 10.63 vs. 10.86 ± 6.92, p = 0.002] compared to ND. Renal pathological damage in DD was notably more severe, likely contributing to the higher DGF incidence in DDR compared to NDR. Although DDR had poorer renal function during the first three months post-transplant, both groups showed similar renal function thereafter. No significant differences were observed in 1-year or 3-year mortality rates or graft failure rates between DDR and NDR. Notably, according to the Renal Pathology Society (RPS) grading system, kidneys from diabetic donors with a grade > IIb are associated with significantly lower postoperative survival rates. Recipient gender [OR: 5.452 (1.330-22.353), p = 0.013] and pre-transplant PRA positivity [OR: 34.879 (7.698-158.030), p < 0.001] were identified as independent predictors of DGF in DDR. In conclusion, transplant centers may consider utilizing kidneys from diabetic donors, provided they are evaluated pathologically, without adversely impacting recipient survival and graft failure rates.
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Funcionamiento Retardado del Injerto , Supervivencia de Injerto , Trasplante de Riñón , Complicaciones Posoperatorias , Donantes de Tejidos , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Funcionamiento Retardado del Injerto/epidemiología , Funcionamiento Retardado del Injerto/etiología , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Diabetes Mellitus/epidemiología , Estudios Retrospectivos , Riñón/fisiopatología , Riñón/patología , Tasa de Supervivencia , Modelos Logísticos , IncidenciaRESUMEN
BACKGROUND AND OBJECTIVES: Sarcopenia has garnered extensive attention in clinical practice since its high prevalence and significant impact on clinical outcomes. Multiple organizations have published guidance documents on sarcopenia, offering evidence-based recommendations for clinical practice and/or research. We aimed to appraise the methodological quality of the included documents and synthesize available recommendations for the screening, diagnosis, and intervention of sarcopenia. METHODS AND STUDY DESIGN: We conducted a search on PubMed, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, guideline database, and guideline organizations and professional societies websites for clinical practices, consensus statements and position papers in terms of sarcopenia, muscle atrophy or muscle loss published before April 17, 2023. The AGREE II instrument was used by three independent reviewers to assess the methodological quality of these documents. RESULTS: Thirty-six guidance documents published between 2010 and 2023 were included. Seven documents fulfilled ≥ 50% of all the AGREE II domains. Seven underwent a Delphi process and six graded the strength of the recommendations. The process of screening (n=21), early diagnosis of sarcopenia (n=12), diagnosis of sarcopenia and severe sarcopenia (n=10), and management (n=21) were increasingly recommended. SARC-F (n=14) was the most recommended screening tool, and the assessment of muscle function was considered the first step in diagnosing sarcopenia. The management strategy for both age-related and disease-related sarcopenia mainly focused on exercise and nutrition intervention. CONCLUSIONS: The guidance documents have provided referential recommendations that have great guiding significance. But the inconsistency in recommendations and variation in methodological rigour suggests that high-quality evidence is lacking yet.
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Fuerza Muscular , Músculo Esquelético , Sarcopenia , Sarcopenia/diagnóstico , Sarcopenia/terapia , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND AND OBJECTIVES: It is recommended by Asian Working Group for Sarcopenia to early identify people at risk for sarcopenia using simple screening tools like SARC-F. The modified version SARC-F+EBM showed higher diagnostic performance. However, this cut-off value of body mass index (BMI) remained uncertain to be used in Chinese population. In this study, we used appropriate BMI recommended for Chinese older population and further modified SARC-F+EBM by combining calf circumference. METHODS AND STUDY DESIGN: Diagnostic tests were performed and the receiver operating characteristics analyses were conducted between the SARC-F, SARC-F+EBM (cut-off of BMI: ≤ 21 kg/m2), SARC-F+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2), SARC-CalF and SARC-CalF+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2) in 1660 community-dwelling participants aged ≥ 65 years from China. RESULTS: The participants had an average age of 71.7±5.1 years, of which 56.8% were women. All the modified models could enhance the areas under the receiver operating characteristic curve (AUC) of original SARC-F (all p<0.001). The SARC-F+EBM (CN) also showed a significantly higher sensitivity of 47.4% (p<0.001) and an AUC of 0.809 (p=0.005) than SARC-F+EBM. SARC-CalF+EBM (CN) was validated to be of great diagnostic value of the highest AUC of 0.88 among these sarcopenia screening tools, including SARC-F, SARC-CalF and SARC-F+EBM (CN) (all p<0.001). Using this study population as a reference, the optimal cut-off value of SARC-CalF+EBM (CN) is ≥12 points, with a sensitivity of 79.3% and a specificity of 80.7%. CONCLUSIONS: The SARC-F+EBM (CN) and SARC-CalF+EBM (CN) could enhance the diagnostic performance of SARC-F and SARC-F+EBM and are suitable sarcopenia screening tools for Chinese population.
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Sarcopenia , Humanos , Femenino , Anciano , Masculino , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Tamizaje Masivo/métodos , Curva ROC , Vida Independiente , China/epidemiología , Evaluación Geriátrica/métodos , Encuestas y CuestionariosRESUMEN
Since the discovery of apoptosis signal-regulated kinase 1 (ASK1), the signal transduction mechanism and pathophysiological process involved in its regulation have been continuously revealed. Many previous studies have identified that ASK1 is involved and plays a critical role in the development of diseases affecting the nervous, cardiac, renal, and other systems. As a mitogen-activated protein kinase (MAPK) kinase kinase, ASK1 mediates apoptosis, necrosis, inflammation, and other pathological processes by activating its downstream c-Jun N-terminal kinase (JNK)/p38 MAPK. Owing to the important role of ASK1, an increasing number of studies in recent years have focused on its status in liver-related diseases. In this paper, we review the mechanisms and targets of ASK1 in liver-related diseases to emphasize its important role in the development of liver disease.
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Vías Clínicas , Hepatopatías , Humanos , Transducción de Señal/fisiología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Apoptosis/fisiología , Quinasas Quinasa Quinasa PAM/metabolismoRESUMEN
Although high gravity brewing technology has been widely used for beer industries due to its economic benefits, yeast cells are subjected to multiple environmental stresses throughout the fermentation process. Eleven bioactive dipeptides (LH, HH, AY, LY, IY, AH, PW, TY, HL, VY, FC) were selected to evaluate their effects on cell proliferation, cell membrane defense system, antioxidant defense system and intracellular protective agents of lager yeast against ethanol-oxidation cross-stress. Results showed that the multiple stresses tolerance and fermentation performance of lager yeast were enhanced by bioactive dipeptides. Cell membrane integrity was improved by bioactive dipeptides through altering the structure of macromolecular compounds of the cell membrane. Intracellular reactive oxygen species (ROS) accumulation was significantly decreased by bioactive dipeptides, especially for FC, decreasing by 33.1%, compared with the control. The decrease of ROS was closely related to the increase of mitochondrial membrane potential, intracellular antioxidant enzyme activities including superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), and glycerol level. In addition, bioactive dipeptides could regulate the expression of key genes (GPD1, OLE1, SOD2, PEX11, CTT1, HSP12) to enhance the multilevel defense systems under ethanol-oxidation cross-stress. Therefore, bioactive dipeptides should be potentially efficient and feasible bioactive ingredients to improve the multiple stresses tolerance of lager yeast during high gravity fermentation.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/metabolismo , Fermentación , Etanol/metabolismo , Cerveza , Peroxinas/metabolismo , Proteínas de la Membrana , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
NCOA7 is a nuclear receptor coactivator that is downregulated in a variety of cancers. However, the expression and prognostic significance of NCOA7 in clear cell renal cell carcinoma (ccRCC) remain unknown. The expression of NCOA7 in ccRCC tissues was analyzed using bioinformatics analysis, Western blotting, and immunohistochemistry. Kaplan-Meier analysis, the receiver operating characteristic (ROC) curve, and clinicopathological correlation analysis were used to assess the predictive power of NCOA7. Overexpression function tests were conducted in cells and mouse models to clarify the function and mechanism of NCOA7 in inhibiting the progression of ccRCC. NCOA7 expression was downregulated in all three subtypes of renal cell carcinoma, and only had significant prognostic value for patients with ccRCC. NCOA7 overexpression inhibited the proliferation, invasion, and metastasis of ccRCC cells in vivo and in vitro. Mechanistically, NCOA7 inhibited the MAPK/ERK pathway to regulate epithelial-mesenchymal transformation (EMT) and apoptosis, thereby inhibiting the progression of ccRCC. NCOA7 inhibits tumor growth and metastasis of ccRCC through the MAPK/ERK pathway, thus indicating its potential as a prognostic marker and therapeutic target for ccRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Animales , Ratones , Carcinoma , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Sistema de Señalización de MAP Quinasas , Transducción de Señal , HumanosRESUMEN
Iron walnut (Juglans sigillata Dode) is a native species in southwestern China that exhibits variation in both fruit morphology and shell thickness. However, the underlying molecular processes controlling hardened endocarp development in walnut has not yet been reported. Here, we generated transcriptional profiles of iron walnut endocarp at three developmental stages using "Dapao", the most common commercial variety. Using pairwise comparisons between these three stages, a total of 8555 non-redundant differentially expressed genes (DEGs) were identified, and more than one-half of the total DEGs exhibited significant differential expression in stage I as compared with stage II or stage III, suggesting that the first stage may ultimately determine the final characteristics of the mature walnut shell. Furthermore, in the clustering analysis of the above DEGs, 3682, 2349, and 2388 genes exhibited the highest expression in stages I, II, and III, respectively. GO enrichment analysis demonstrated that the major transcriptional variation among the three developmental stages was caused by differences in cell growth, plant hormones, metabolic process, and phenylpropanoid metabolism. Namely, using the tissue-specific expression analysis and a gene co-expression network, we identified MADS-box transcription factor JsiFBP2 and bHLH transcription factor JsibHLH94 as candidate regulators of endocarp formation in the early stage, and JsiNAC56 and JsiMYB78 might play key roles in regulating the lignification process of endocarp in the late stage. This study provides useful information for further research to dissect the molecular mechanisms governing the shell formation and development of iron walnut.
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Juglans , Transcriptoma , Hierro/metabolismo , Nueces , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las PlantasRESUMEN
We have developed a new solution-phase chemical reduction method for the synthesis of poly(vinyl alcohol) coated copper nanoparticles in aqueous solution. Copper nitrate is used as the precursor, sodium hypophosphite as the reducing agent, and poly(vinyl alcohol) as the coating agent. The synthesis of copper nanoparticles could be completed within several hours and the copper nanoparticles in powder form could be stored within one week in ambient condition. In Ar atmosphere, the complete thermal decomposition temperature of coated layer was lower than 450 °C. The antioxidative properties of poly(vinyl alcohol) coated copper nanoparticles were evaluated compared to that of polyvinylpyrrolidone coated copper nanoparticles.
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Actin filament-associated protein-120kD (AFAP-120) is an alternatively spliced isoform of actin filament-associated protein-110kD (AFAP-110) and contains an additional neuronal insert (NINS) fragment in addition to identical domains to the AFAP-110. Unlike AFAP-110 widely expressed in tissues, AFAP-120 is specifically expressed in the nervous system and plays a role in organizing dynamic actin structures during neuronal differentiation. However, anti-AFAP-120 antibody is still commercially unavailable, and this may hinder the function research for AFAP-120. In this study, we simultaneously used the ABCpred online server and the BepiPred 1.0 server to predict B-cell epitopes in the exclusive NINS sequence of human AFAP-120 protein, and found that a 16aa-peptide sequence was the consensus epitope predicted by both tools. This peptide was chemically synthesized and used as an immunogen to develop polyclonal antibody against AFAP-120 (anti-AFAP-120). The sensitivity and specificity of anti-AFAP-120 were analyzed with immunoblotting, immunoprecipitation, and immunofluorescence assays. Our results indicated that anti-AFAP-120 could react with over-expressed and endogenous human AFAP-120 protein under denatured condition, but not with human AFAP-110 protein. Moreover, native human AFAP-120 protein could also be recognized by the anti-AFAP-120 antibody. These results suggested that the prepared anit-AFAP-120 antibody would be a useful tool for studying the biochemical and biological functions of AFAP-120.
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Anticuerpos/inmunología , Proteínas de Microfilamentos/inmunología , Fosfoproteínas/metabolismo , Animales , Afinidad de Anticuerpos , Células COS , Línea Celular Tumoral , Chlorocebus aethiops , Epítopos/inmunología , Células HEK293 , Humanos , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/inmunologíaRESUMEN
Three luminescent polymorphs based on a new copper(I) complex Cu(2-QBO)(PPh3)PF6 (1, PPh3 = triphenylphosphine, 2-QBO = 2-(2'-quinolyl)benzoxazole) have been synthesized and characterized by FT-IR, UV-vis, elemental analyses, and single-crystal X-ray diffraction analyses. Each polymorph can reversibly convert from one to another through appropriate procedures. Interestingly, such interconversion can be distinguished by their intrinsic crystal morphologies and colors (namely α, dark yellow plate, ß, orange block, γ, light yellow needle) as well as photoluminescent (PL) properties. X-ray crystal structure analyses of these three polymorphs show three different supramolecular structures from 1D to 3D, which are expected to be responsible for the formation of three different crystal morphologies such as needle, plate, and block. Combination of the experimental data with DFT calculations on these three polymorphs reveals that the polymorphic interconversion is triggered by the conformation isomerization of the 2-QBO ligand and can be successfully controlled by the polarity of the process solvents (affecting the molecular dipole moment) and thermodynamics (affecting the molecular total energy). It is also found that the different crystal colors of polymorphs and their PL properties are derived from different θ values (dihedral angle between benzoxazolyl and quinolyl group of the 2-QBO ligand) and P-Cu-P angles based on TD-DFT calculations. Moreover, an interesting phase interconversion between γ and ß has also been found under different temperature, and this result is consistent with the DFT calculations in which the total energy of ß is larger than that of γ. This polymorphism provides a good model to study the relationship between the structure and the physical properties in luminescent copper(I) complexes as well as some profound insights into their PL properties.
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The basic theory of high power green laser equipment for prostate hyperplasia therapy and the components of the system developed are introduced. Considering the requirements of the clinical therapy, the working process of the high power green laser apparatus are designed and the laser with stable output at 120 W is achieved. The controlling hardware and application software are developed, and the safety step is designed. The high power green laser apparatus manufactured with characteristics of stable output, multifunctional and friendly interface provides a choices of prostate hyperplasia therapy for using nationalization instrument.
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Terapia por Láser , Hiperplasia Prostática/terapia , Humanos , Rayos Láser , Masculino , Seguridad del Paciente , Programas InformáticosRESUMEN
The potential of potassium chloride (KCl) to be used as a substitute for sodium chloride (NaCl) was studied by monitoring the effects of salt treatment on thermal behavior, aggregation kinetics, rheological properties, and protein conformational changes. The results show that the addition of KCl can improve solubility, reduce turbidity and particle size, and positively influence rheological parameters such as apparent viscosity, consistency coefficient (K value), and fluidity index (n). These changes indicate delayed thermal denaturation. In addition, KCl decreased the content of ß-sheet and random coil structures and increased the content of α-helix and ß-turn structures. The optimal results were obtained with 2% KCl addition, leading to an increase in Tp up to 85.09 °C. The correlation results showed that Tp was positively correlated with solubility, α-helix and ß-turn but negatively correlated with ΔH, turbidity, ß-sheet and random coil. Overall, compared to NaCl, 2% KCl is more effective in delaying the thermal aggregation of LWE, and these findings lay a solid theoretical foundation for the study of sodium substitutes in heat-resistant liquid egg products.
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BACKGROUND: The incidence of clear cell renal cell carcinoma (ccRCC) is increasing annually. While the cure rate and prognosis of early ccRCC are promising, the 5-year survival rate of patients with metastatic ccRCC is below 12%. Autophagy disfunction is closely related to infection, cancer, neurodegeneration and aging. Nevertheless, there has been limited exploration of the association between autophagy and ccRCC through bioinformatics analysis. METHODS: A novel risk model of autophagy-related genes (ARGs) was constructed to predict the prognosis of patients with ccRCC and guide the individualized treatment to some extent. Relevant data samples were obtained from the TCGA database, and ccRCC-related ARGs were identified by Pearson correlation analysis, leading to the establishment of a risk model covering 10 ccRCC-related ARGs. Many indicators were used to assess the accuracy of the risk model. RESULTS: Receiver operating characteristic (ROC) curve analysis showed that the risk model had high accuracy, indicating that the risk model could predict the prognosis of ccRCC patients. Moreover, the findings revealed significant differences about immune and metabolic features in low- and high-risk groups. The study also found that BAG1 within the risk model was closely related to the prognosis of ccRCC and an independent risk factor. In vitro and in vivo experiments validated for the first time that BAG1 could suppress the proliferation, migration, and invasion of ccRCC. CONCLUSION: The construction of ARGs risk model, can well predict the prognosis of ccRCC patients, and provide guidance for individual therapy to patients. It was also found that BAG1 has significant prognostic value for ccRCC patients and acts as a tumor suppressor gene in ccRCC. These findings have crucial implications for the prognosis and treatment of ccRCC patients.
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Autofagia , Carcinoma de Células Renales , Proliferación Celular , Proteínas de Unión al ADN , Neoplasias Renales , Factores de Transcripción , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/mortalidad , Humanos , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Pronóstico , Autofagia/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Animales , Masculino , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Femenino , Proliferación Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Ratones , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Movimiento Celular/genética , Ratones DesnudosRESUMEN
Hepatic ischemia/reperfusion injury (HIRI) represents a prevalent pathophysiological process that imposes a substantial economic burden in clinical practice, especially in liver surgery. Sentrin-specific protease 1 (SENP1) is a crucial enzyme involved in the regulation of SUMOylation, and is related to various diseases. However, the role of SENP1 in HIRI remains unexplored. Here, we confirmed that SENP1 actively participated in modulating the oxidative damage induced by HIRI. Notably, SENP1 functioned by maintaining mitochondrial homeostasis. Further mechanistic exploration indicated that the protective mitochondrial protein sirtuin-3 (Sirt3) was inactivated by SUMOylation during HIRI, which was reversed by SENP1. Overexpression of SENP1 could restore mitochondrial function, mitigate oxidative stress and attenuated apoptosis through recovering the expression of Sirt3 during HIRI. Nevertheless, 3-TYP, an inhibitor of Sirt3, could eliminate the therapeutic effects brought by overexpression of SENP1. In conclusion, our findings demonstrated that SENP1 mediated the deSUMOylation of Sirt3 and maintained mitochondrial homeostasis, thus alleviating HIRI induced oxidative damage. SENP1 might be a promising therapeutic target for HIRI.
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Hepatopatías , Daño por Reperfusión , Sirtuina 3 , Humanos , Sirtuina 3/genética , Sirtuina 3/metabolismo , Transducción de Señal , Hepatopatías/genética , Hepatopatías/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Reperfusión , Isquemia/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genética , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/metabolismoRESUMEN
Background: Previous studies revealed that vitamin K might help maintain muscle homeostasis, but this association has received little attention. We aimed to explore the associations of vitamin K intake with skeletal muscle mass and strength. Methods: We included cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES, 2011-2018). Vitamin K intake was assessed via 24-h recall. Covariate-adjusted multiple linear regression and restricted cubic splines were used to evaluate the associations of dietary vitamin K intake with skeletal muscle mass and strength, measured by dual-energy X-ray absorptiometry and handgrip dynamometer, respectively. Results: Dietary vitamin K intake was positively associated with skeletal muscle mass in males (ß = 0.05747, p = 0.0204) but not in females. We also revealed a positive association between dietary vitamin K intake and handgrip strength within the range of 0-59.871 µg/d (P nonlinear = 0.049). However, beyond this threshold, increasing vitamin K intake did not cause additional handgrip strength improvements. Conclusion: We provided evidence for a positive relationship between dietary vitamin K intake and skeletal muscle mass in males. Moreover, our study revealed a nonlinear relationship between dietary vitamin K intake and handgrip strength, highlighting an optimal intake range.
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During liver ischemia-reperfusion injury, existing mechanisms involved oxidative stress, calcium overload, and the activation of inflammatory responses involve mitochondrial injury. Mitochondrial autophagy, a process that maintains the normal physiological activity of mitochondria, promotes cellular metabolism, improves cellular function, and facilitates organelle renewal. Mitochondrial autophagy is involved in oxidative stress and apoptosis, of which the PINK1-Parkin pathway is a major regulatory pathway, and the deletion of PINK1 and Parkin increases mitochondrial damage, reactive oxygen species production, and inflammatory response, playing an important role in mitochondrial quality regulation. In addition, proper mitochondrial permeability translational cycle regulation can help maintain mitochondrial stability and mitigate hepatocyte death during ischemia-reperfusion injury. This mechanism is also closely related to oxidative stress, calcium overload, and the aforementioned autophagy pathway, all of which leads to the augmentation of the mitochondrial membrane permeability transition pore opening and cause apoptosis. Moreover, the release of mitochondrial DNA (mtDNA) due to oxidative stress further aggravates mitochondrial function impairment. Mitochondrial fission and fusion are non-negligible processes required to maintain the dynamic renewal of mitochondria and are essential to the dynamic stability of these organelles. The Bcl-2 protein family also plays an important regulatory role in the mitochondrial apoptosis signaling pathway. A series of complex mechanisms work together to cause hepatic ischemia-reperfusion injury (HIRI). This article reviews the role of mitochondria in HIRI, hoping to provide new therapeutic clues for alleviating HIRI in clinical practice.
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AIM: To evaluate the association between frailty and postoperative delirium (POD) in elderly cardiac surgery patients. METHODS: A retrospective study was conducted of older patients admitted to the intensive care unit after cardiac surgery at a tertiary academic medical center in Boston from 2008 to 2019. Frailty was measured using the Modified Frailty Index (MFI), which categorized patients into frail (MFI ≥3) and non-frail (MFI = 0-2) groups. Delirium was identified using the confusion assessment method for the intensive care unit and nursing notes. Logistic regression models were used to examine the association between frailty and POD, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Of the 2080 patients included (median age approximately 74 years, 30.9% female), 614 were frail and 1466 were non-frail. The incidence of delirium was significantly higher in the frail group (29.2% vs. 16.4%, p < 0.05). After adjustment for age, sex, race, marital status, Acute Physiology Score III (APSIII), sequential organ failure assessment (SOFA), albumin, creatinine, hemoglobin, white blood cell count, type of surgery, alcohol use, smoking, cerebrovascular disease, use of benzodiazepines, and mechanical ventilation, multivariate logistic regression indicated a significantly increased risk of delirium in frail patients (adjusted OR: 1.61, 95% CI: 1.23-2.10, p < 0.001, E-value: 1.85). CONCLUSIONS: Frailty is an independent risk factor for POD in older patients after cardiac surgery. Further research should focus on frailty assessment and tailored interventions to improve outcomes.