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BACKGROUND: The Triglyceride Glucose-Body Mass Index (TyG-BMI) has been established as a robust indicator of insulin resistance (IR), reflecting metabolic health across various populations. In general, lower TyG-BMI values are often associated with better metabolic health outcomes and a reduced risk of adverse health events in non-critically ill populations. Previous studies have highlighted a significant negative association between TyG-BMI and all-cause mortality (ACM) among critically ill atrial fibrillation patients. Given the high prevalence and severe outcomes associated with stroke, understanding how TyG-BMI at the time of ICU admission correlates with ACM in critically ill stroke patients becomes imperative. This study aims to assess the correlation between TyG-BMI and ACM in this specific patient cohort, exploring how traditional associations between TyG-BMI and metabolic health may differ in the context of acute, life-threatening illness. METHODS: Patient data were retrieved by accessing the Medical Information Mart for Intensive Care IV (MIMIC-IV 2.2) database, categorizing patients into three groups on the basis of TyG-BMI tertiles. The study evaluated both primary and secondary outcomes: the primary outcomes included the 90-day, 180-day, and 1-year ACM, while secondary outcomes encompassed ICU, in-hospital, and 30-day ACM. Our study employed the Kaplan-Meier (K-M) curve method for outcome comparison across the groups while utilizing multivariate Cox proportional-hazards regression models and restricted cubic splines (RCS) to explore TyG-BMI association with these outcomes. Additionally, interaction and subgroup analyses were performed, focusing on different mortality time points. RESULTS: Among a cohort of 1707 individuals diagnosed with stroke, the average age was 68 years (interquartile range [IQR]: 58-78 years), with 946 (55.42%) of the participants being male. The analysis of K-M curves suggested that patients having a lower TyG-BMI level faced a heightened risk of long-term ACM, whereas the short-term ACM exhibited no statistically significant differences across the three TyG-BMI groups. Furthermore, Cox proportional-hazards regression analysis validated a statistically significant increased risk of long-term ACM among patients belonging to the lowest TyG-BMI tertile. Additionally, RCS analysis results demonstrated L-shaped correlations between the TyG-BMI index and both short- and long-term ACM. These findings underscore the TyG-BMI predictive value for long-term mortality in stroke patients, highlighting a nuanced relationship that varies over different time frames. The results revealed no interactions between TyG-BMI and the stratified variables, with the exception of age. CONCLUSION: In our study, lower TyG-BMI levels in critically ill stroke patients are significantly related to a higher risk of long-term ACM within the context of the United States. This finding suggests the potential of TyG-BMI as a marker for stratifying long-term risk in this patient population. However, it's crucial to note that this association was not observed for short-term ACM, indicating that the utility of TyG-BMI may be more pronounced in long-term outcome prediction. Additionally, our conclusion that TyG-BMI could serve as a reliable indicator for managing and stratifying stroke patients over the long term is preliminary. To confirm our findings and assess the universal applicability of TyG-BMI as a prognostic tool, it is crucial to conduct rigorously designed research across various populations.
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Biomarcadores , Glicemia , Índice de Massa Corporal , Estado Terminal , Bases de Dados Factuais , Unidades de Terapia Intensiva , Acidente Vascular Cerebral , Triglicerídeos , Humanos , Masculino , Idoso , Feminino , Glicemia/metabolismo , Fatores de Tempo , Pessoa de Meia-Idade , Medição de Risco , Triglicerídeos/sangue , Fatores de Risco , Biomarcadores/sangue , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Prognóstico , Estado Terminal/mortalidade , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Resistência à Insulina , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Hemorrhagic stroke (HS), including non-traumatic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), constitutes a substantial proportion of cerebrovascular incidents, accounting for around 30% of stroke cases. The triglyceride-glucose index (TyG-i) represents a precise insulin resistance (IR) indicator, a crucial metabolic disturbance. Existing literature has demonstrated an association between TyG-i and all-cause mortality (ACM) among individuals suffering from ischemic stroke (IS). Yet, the TyG-i prognostic implications for severe HS patients necessitating intensive care unit (ICU) admission are not clearly understood. Considering the notably elevated mortality and morbidity associated with HS relative to IS, investigating this association is warranted. Our primary aim was to investigate TyG-i and ACM association among critically ill HS patients within an ICU context. METHODS: Herein, patients with severe HS were identified by accessing the Medical Information Mart for Intensive Care-IV (MIMIC-IV, version 2.2) database, using the International Classification of Diseases (ICD)-9/10 as diagnostic guidelines. Subsequently, we stratified the subjects into quartiles, relying on their TyG-i scores. Moreover, we measured mortality at ICU, in-hospital, 30 days, 90 days, and 1 year as the outcomes. Cox proportional hazards regression analysis and restricted cubic splines (RCS) were deployed for elucidating the relation between the TyG-i and ACM while utilizing the Kaplan-Meier (K-M) method to estimate survival curves. The findings' robustness was assessed by conducting subgroup analysis and interaction tests employing likelihood ratio tests. RESULTS: The analysis included 1475 patients, with a male predominance of 54.4%. Observed mortality rates in the ICU, hospital, 30 days, 90 days, and 1 year were 7.3%, 10.9%, 13.8%, 19.7%, and 27.3%, respectively. Multivariate Cox regression analysis results manifested that heightened TyG-i was significantly related to ACM at 30 days (adjusted hazard ratio [aHR]: 1.32; 95% confidence interval [CI]: 1.05-1.67; P = 0.020), 90 days (aHR: 1.27; 95% CI: 1.04-1.55; P = 0.019), and 1 year (aHR: 1.22; 95% CI: 1.03-1.44; P = 0.023). The results of RCS analysis demonstrated a progressive elevation in ACM risk with rising TyG-i levels. Interaction tests found no significant effect modification in this relationship. CONCLUSION: In summary, TyG-i exhibits a significant correlation with ACM among patients enduring critical illness due to HS. This correlation underscores the probable utility of TyG-i as a prognostic tool for stratifying HS patients according to their risk of mortality. Applying TyG-i in clinical settings could enhance therapeutic decision-making and the management of disease trajectories. Additionally, this investigation augments existing research on the linkage between the TyG-i and IS, elucidating the TyG-i's role in predicting mortality across diverse stroke categories.
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Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Estado Terminal , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Glucose , Triglicerídeos , Glicemia , Fatores de Risco , BiomarcadoresRESUMO
Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI). Recently, ferroptosis was reported to be crucial for AKI pathogenesis. Our previous studies indicated antioxidant tetramethylpyrazine (TMP) prevent CIN in vivo. However, whether ferroptosis is involved in TMP nephroprotective mechanism against CIN is unclear. In the present study, we investigated the role of renal tubular epithelial cell ferroptosis in TMP reno-protective effect against CIN and the molecular mechanisms by which TMP regulates ferroptosis. Classical contrast-medium, Iohexol, was used to construct CIN models in rats and HK-2 cells. Results showed that tubular cell injury was accompanied by ferroptosis both in vivo and in vitro, including the typical features of ferroptosis, Fe2+ accumulation, lipid peroxidation and decreased glutathione peroxidase 4 (GPX4). Ferroptosis inhibition by classic inhibitors Fer-1 and DFO promoted cell viability and reduced intracellular ROS production. Additionally, TMP significantly inhibited renal dysfunction, reduced AKI biomarkers, prevented ROS production, inhibited renal Fe2+ accumulation and increased GPX4 expression. Expressions of various proteins associated with iron ion metabolism, including transferrin receptor (TFRC), divalent metal transporter 1, iron-responsive element binding protein 2, ferritin heavy chain 1, ferroportin 1, and heat shock factor binding protein 1, were examined using mechanistic analyses. Among these, TFRC changes were the most significant after TMP pretreatment. Results of siRNA knockdown and plasmid overexpression of TFRC indicated that TFRC is essential for TMP to alleviate ferroptosis and reduce LDH release, Fe2+ accumulation and intracellular ROS. Our findings provide crucial insights about the potential of TMP in treating AKI associated with ferroptosis.
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Injúria Renal Aguda , Ferroptose , Pirazinas , Animais , Ratos , Espécies Reativas de Oxigênio , Células Epiteliais , Receptores da Transferrina/genética , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controleRESUMO
BACKGROUND: Heterocyclic amines (HAs) and N-nitrosamines (NAs) are formed easily during the thermal processing of food, and epidemiological studies have demonstrated that consuming HAs and NAs increases the risk of cancer. However, there are few studies on the application of back propagation artificial neural network (BP-ANN) models to simultaneously predict the content of HAs and NAs in sausages. This study aimed to investigate the effects of cooking time and temperature, smoking time and temperature, and fat-to-lean ratio on the formation of HAs and NAs in smoked sausages, and to predict their total content based on the BP-ANN model. RESULTS: With an increase in processing time, processing temperature and fat ratio, the content of HAs and NAs in smoked sausages increased significantly, while the content of HA precursors and nitrite residues decreased significantly. The optimal network topology of the BP-ANN model was 5-11-2, the correlation coefficient values for training, validation, testing and all datasets were 0.99228, 0.99785, 0.99520 and 0.99369, respectively, and the mean squared error value of the best validation performance was 0.11326. The bias factor and the accuracy factor were within acceptable limits, and the predicted values approximated the true values, indicating that the model has good predictive performance. CONCLUSION: The contents of HAs and NAs in smoked sausages were significantly influenced by the cooking conditions, smoking conditions and fat ratio. The BP-ANN model has high application value in predicting the contents of HAs and NAs in sausages, which provides a theoretical basis for the suppression of carcinogen formation. © 2024 Society of Chemical Industry.
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Nitrosaminas , Nitrosaminas/análise , Fumaça , Aminas , Redes Neurais de Computação , CarcinógenosRESUMO
BACKGROUND: Complex phosphates (CP) can improve the physicochemical properties and gelation properties of myofibrillar fibrous protein (MP) in mixed meat products, but an excessive intake of phosphates over a long period of time is harmful to health. The present study investigated the effects of partial or complete substitution of CP with sodium bicarbonate (SB) on the physicochemical properties and gel properties of beef-pork-chicken mixed myofibrillar protein (BPC-MP), aiming to evaluate the feasibility of this method in reducing the amount of phosphate in mixed meat products. RESULTS: Under the optimal substitution conditions, the turbidity of BPC-MP was reduced by 37.8%, the net negative potential was increased by 28.9% and the modulus of elasticity (G') was increased. The tertiary structure indexes of protein (including fluorescence intensity, surface hydrophobicity and active thiol content) were significantly changed, whereas the α-helix and ß-turn angle contents in the secondary structure of protein were significantly increased. In addition, the water retention ability and strength of gel were also improved, which were increased by 20.7% and 42.6%, respectively. The results of scanning electron microscopy showed that the SB substitution group had a more compact and ordered microstructure. CONCLUSION: The results showed that partial substitution of CP with SB reduced the amount of phosphate added to BPC-MP and had a positive effect on the physicochemical and gel properties of BPC-MP. © 2024 Society of Chemical Industry.
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Galinhas , Géis , Proteínas Musculares , Miofibrilas , Fosfatos , Bicarbonato de Sódio , Animais , Bovinos , Fosfatos/química , Géis/química , Miofibrilas/química , Proteínas Musculares/química , Bicarbonato de Sódio/química , Suínos , Produtos da Carne/análise , Interações Hidrofóbicas e Hidrofílicas , Agregados Proteicos , Conformação ProteicaRESUMO
Objective: This investigation aimed to delineate the association between the advanced lung cancer inflammation index (ALI) and all-cause mortality (ACM) in individuals experiencing acute ischemic stroke (AIS). Methods: Drawing on information from the Medical Information Mart for Intensive Care (MIMIC)-IV database, release 2.2, covering the years 2012 to 2019, this research assessed the advanced lung cancer inflammation index (ALI) by factoring in body mass index (BMI), serum albumin levels (ALB), and the neutrophil-to-lymphocyte ratio (NLR). Patients with AIS were identified using codes from the International Classification of Diseases (ICD). To address potential confounding factors, a 1:1 propensity score matching (PSM) method was utilized. The investigation identified the pivotal ALI level impacting patient survival using maximally selected rank statistics. It then examined the effects on short- and long-term ACM through multivariate Cox proportional hazards regression models and Kaplan-Meier (K-M) survival analysis. Additionally, restricted cubic spline (RCS) methods were applied to delve into the linear or nonlinear nature of the relationship between ALI and ACM, with further insights gained from interaction and subgroup analyses. Results: The cohort comprised 838 AIS patients. Post-PSM, analysis involved 199 matched patient pairs. Adjusted Cox proportional hazard models indicated a significant association of low ALI (<10.38) with increased in-hospital ACM, both before (HR: 1.98; 95% CI: 1.36-2.88; p < 0.001) and after PSM (HR: 2.16; 95% CI: 1.32-3.52; p = 0.002). Associations of low ALI with elevated risk were consistent across ICU, 30 days, 90 days, and 1 year ACM pre- and post-PSM. Subsequent RCS analysis post-PSM underscored a negative nonlinear relationship between ALI and ACM over both short and long terms, without significant interaction effects across different subgroups for ACM. Conclusion: In this retrospective cohort study, by utilizing a nationally representative sample of United States patients with AIS, our analysis elucidates a negative correlation between the ALI and ACM in individuals with AIS, underscoring the utility of ALI as a novel, efficacious, and accessible inflammatory biomarker for prognosticating ACM. These results carry profound implications for public health policy and practice. A deeper comprehension of these associations can empower public health practitioners and researchers to devise more targeted interventions and policies, aimed specifically at catering to the distinct needs of the AIS patient population, thereby enhancing their health outcomes. The further research in other races/ethnicity is urgent, particularly before applying these findings in clinical practice.
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The ability of spices (bay leaf, star anise, and red pepper) and their characteristic phenolic compounds (quercetin, kaempferol, and capsaicin) to inhibit Heterocyclic aromatic amines (HAAs) in roasted beef patties were compared. Density functional theory (DFT) was used to reveal phenolic compounds interacting with HAAs-related intermediates and free radicals to explore possible inhibitory mechanisms for HAAs. 3 % red chili and 0.03 % capsaicin reduced the total HAAs content by 57.09 % and 68.79 %, respectively. DFT demonstrated that this was due to the stronger interaction between capsaicin and the ß-carboline HAAs intermediate (Ebind = -32.95 kcal/mol). The interaction between quercetin and phenylacetaldehyde was found to be the strongest (Ebind = -17.47 kcal/mol). Additionally, DFT indicated that capsaicin reduced the carbonyl content by transferring hydrogen atoms (HAT) to eliminate HO·, HOO·, and carbon-centered alkyl radicals. This study provided a reference for the development of DFT in the control of HAAs.
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Aminas , Culinária , Teoria da Densidade Funcional , Compostos Heterocíclicos , Fenóis , Aminas/química , Bovinos , Compostos Heterocíclicos/química , Animais , Fenóis/análise , Capsaicina/química , Capsaicina/farmacologia , Capsaicina/análogos & derivados , Capsicum/química , Escatol/análise , Especiarias/análise , Carne Vermelha/análise , Produtos da Carne/análise , Temperatura Alta , Quercetina/análogos & derivados , Quercetina/análise , Quercetina/farmacologiaRESUMO
Background: Uropathogenic Escherichia coli (UPEC) activates innate immune response upon invading the urinary tract, whereas UPEC can also enter bladder epithelial cells (BECs) through interactions with fusiform vesicles on cell surfaces and subsequently escape from the vesicles into the cytoplasm to establish intracellular bacterial communities, finally evading the host immune system and leading to recurrent urinary tract infection (RUTI). Tailin Fang II (TLF-II) is a Chinese herbal formulation composed of botanicals that has been clinically proven to be effective in treating urinary tract infection (UTI). However, the underlying therapeutic mechanisms remain poorly understood. Methods: Network pharmacology analysis of TLF-II was conducted. Female Balb/C mice were transurethrally inoculated with UPEC CFT073 strain to establish the UTI mouse model. Levofloxacin was used as a positive control. Mice were randomly divided into four groups: negative control, UTI, TLF-II, and levofloxacin. Histopathological changes in bladder tissues were assessed by evaluating the bladder organ index and performing hematoxylin-eosin staining. The bacterial load in the bladder tissue and urine sample of mice was quantified. Activation of the TLR4-NF-κB pathway was investigated through immunohistochemistry and western blotting. The urinary levels of interleukin (IL)-1ß and IL-6 and urine leukocyte counts were monitored. We also determined the protein expressions of markers associated with fusiform vesicles, Rab27b and Galectin-3, and levels of the phosphate transporter protein SLC20A1. Subsequently, the co-localization of Rab27b and SLC20A1 with CFT073 was examined using confocal fluorescence microscopy. Results: Data of network pharmacology analysis suggested that TLF-II could against UTI through multiple targets and pathways associated with innate immunity and inflammation. Additionally, TLF-II significantly attenuated UPEC-induced bladder injury and reduced the bladder bacterial load. Meanwhile, TLF-II inhibited the expression of TLR4 and NF-κB on BECs and decreased the urine levels of IL-1ß and IL-6 and urine leukocyte counts. TLF-II reduced SLC20A1 and Galectin-3 expressions and increased Rab27b expression. The co-localization of SLC20A1 and Rab27b with CFT073 was significantly reduced in the TLF-II group. Conclusion: Collectively, innate immunity and bacterial escape from fusiform vesicles play important roles in UPEC-induced bladder infections. Our findings suggest that TLF-II combats UPEC-induced bladder infections by effectively mitigating bladder inflammation and preventing bacterial escape from fusiform vesicles into the cytoplasm. The findings suggest that TLF-II is a promising option for treating UTI and reducing its recurrence.