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BACKGROUND: A significant number of coronavirus disease 2019 (COVID-19) survivors are experiencing long COVID, with symptoms lasting beyond three months. While diverse long COVID symptoms are established, there are gaps in understanding its long-term trends, intensity, and risk factors, requiring further investigation. AIMS: This study aimed to investigate the long COVID characteristics and associated factors by following COVID-19 survivors for one year post-infection and comparing them with healthy counterparts. MAIN METHODS: In this longitudinal, correlational study, COVID-19 survivors diagnosed between November 2021 and February 2023 were monitored every three months for a year. Participants aged ≥18 years who had reported a positive COVID-19 test were recruited via social media and healthcare provider referrals. KEY FINDINGS: Out of 182 survivors who initially agreed to participate, 176 completed the study. The mean age was 47.56 years (SD = 16.2), and 51.1 % were female. There was a clinically significant decline in cognitive function and health-related quality of life over time, with symptoms like shortness of breath, reduced physical fitness, and increased health concerns. Those with severe acute COVID-19 symptoms experienced greater cognitive and physical declines and more shortness of breath a year later. Lower financial status was linked to poorer health-related quality of life and increased health concerns. SIGNIFICANCE: A year post-infection, COVID-19's impact on cognitive function and health-related quality of life remains significant, affecting individuals and communities. Survivors with severe initial symptoms and economic disadvantages need more attention. Future research should identify additional predictors of severe long COVID.
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COVID-19 , Qualidade de Vida , Sobreviventes , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , COVID-19/complicações , Feminino , Masculino , Estudos Longitudinais , Pessoa de Meia-Idade , Adulto , SARS-CoV-2 , Idoso , Síndrome de COVID-19 Pós-Aguda , Fatores de Risco , Estudos de Coortes , Dispneia/fisiopatologiaRESUMO
Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.
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Mutação , Neoplasias Pancreáticas , Prolina , Proteínas Proto-Oncogênicas p21(ras) , Pirrolina Carboxilato Redutases , delta-1-Pirrolina-5-Carboxilato Redutase , Animais , Humanos , Camundongos , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/genética , Linhagem Celular Tumoral , Proliferação de Células , Ferritinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Oxirredutases , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , Prolina/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Pirrolina Carboxilato Redutases/metabolismo , Pirrolina Carboxilato Redutases/genéticaRESUMO
Breast density is an independent risk factor for breast cancer, although variability exists in measurements. This study sought to evaluate the agreement between radiologists and automated breast density assessment software and assess the impact of breast density measures on breast cancer risk estimates using the Breast Cancer Surveillance Consortium (BCSC) model (v.2). A retrospective database search identified women who had undergone mammography between December 2021 and June 2022. The Breast Imaging Reporting and Data System (BI-RADS) breast composition index assigned by a radiologist (R) was recorded and analyzed using three commercially available software programs (S1, S2, and S3). The agreement rate and Cohen's kappa (κ) were used to evaluate inter-rater agreements concerning breast density measures. The 5-year risk of invasive breast cancer in women was calculated using the BCSC model (v.2) with breast density inputs from various density estimation methods. Absolute differences in risk between various density measurements were evaluated. Overall, 1,949 women (mean age, 53.2 years) were included. The inter-rater agreement between R, S1, and S2 was 75.0-75.6%, while that between S3 and the others was 60.2%-63.3%. Kappa was substantial between R, S1, and S2 (0.66-0.68), and moderate (0.49-0.50) between S3 and the others. S3 placed fewer women in mammographic density d (14.9%) than R, S1, and S2 (40.5%-44.0%). In BCSC risk assessment (v.2), S3 assessed fewer women with a high 5-year risk of invasive breast cancer than the other methods, resulting in an absolute difference of 0% between R, S1, and S2 in 75.0%-75.6% of cases, whereas the difference between S3 and the other methods occurs in 60.2%-63.3% of cases. Breast density assessment using various methods showed moderate-to-substantial agreement, potentially affecting risk assessments. Precise and consistent breast density measurements may lead to personalized and effective strategies for breast cancer prevention.
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Background: Controlling saturated fat and cholesterol intake is important for the prevention of cardiovascular diseases. Although the use of mobile diet-tracking apps has been increasing, the reliability of nutrition apps in tracking saturated fats and cholesterol across different nations remains underexplored. Objective: This study aimed to examine the reliability and consistency of nutrition apps focusing on saturated fat and cholesterol intake across different national contexts. The study focused on 3 key concerns: data omission, inconsistency (variability) of saturated fat and cholesterol values within an app, and the reliability of commercial apps across different national contexts. Methods: Nutrient data from 4 consumer-grade apps (COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!) and an academic app (Formosa FoodApp) were compared against 2 national reference databases (US Department of Agriculture [USDA]-Food and Nutrient Database for Dietary Studies [FNDDS] and Taiwan Food Composition Database [FCD]). Percentages of missing nutrients were recorded, and coefficients of variation were used to compute data inconsistencies. One-way ANOVAs were used to examine differences among apps, and paired 2-tailed t tests were used to compare the apps to national reference data. The reliability across different national contexts was investigated by comparing the Chinese and English versions of MyFitnessPal with the USDA-FNDDS and Taiwan FCD. Results: Across the 5 apps, 836 food codes from 42 items were analyzed. Four apps, including COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, significantly underestimated saturated fats, with errors ranging from -13.8% to -40.3% (all P<.05). All apps underestimated cholesterol, with errors ranging from -26.3% to -60.3% (all P<.05). COFIT omitted 47% of saturated fat data, and MyFitnessPal-Chinese missed 62% of cholesterol data. The coefficients of variation of beef, chicken, and seafood ranged from 78% to 145%, from 74% to 112%, and from 97% to 124% across MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, respectively, indicating a high variability in saturated fats across different food groups. Similarly, cholesterol variability was consistently high in dairy (71%-118%) and prepackaged foods (84%-118%) across all selected apps. When examining the reliability of MyFitnessPal across different national contexts, errors in MyFitnessPal were consistent across different national FCDs (USDA-FNDSS and Taiwan FCD). Regardless of the FCDs used as a reference, these errors persisted to be statistically significant, indicating that the app's core database is the source of the problems rather than just mismatches or variances in external FCDs. Conclusions: The findings reveal substantial inaccuracies and inconsistencies in diet-tracking apps' reporting of saturated fats and cholesterol. These issues raise concerns for the effectiveness of using consumer-grade nutrition apps in cardiovascular disease prevention across different national contexts and within the apps themselves.
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Doenças Cardiovasculares , Aplicativos Móveis , Humanos , Aplicativos Móveis/normas , Aplicativos Móveis/estatística & dados numéricos , Reprodutibilidade dos Testes , Doenças Cardiovasculares/prevenção & controle , TaiwanRESUMO
CASE: We present a unique case of a 45-year-old man with his right middle finger embedded with rings. Limited finger flexion was noted because of flexor tendon injury caused by the dorsal migration of the embedded ring through joint. The rings were removed under anesthesia, resulting in the resolution of swelling and recover of osseous structure. Follow-up examinations revealed no residual edema or numbness, indicating preserved neurovascularization, despite the dorsal migration of the ring. CONCLUSION: Our unique case reveals continuous finger ring migration without compromising neurovascular bundles, with review of 30 cases emphasizing the importance of psychiatric consultation. Timely intervention yielded nearly half of patients achieving full recovery.
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Articulações dos Dedos , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos dos Dedos/cirurgia , Migração de Corpo Estranho/diagnóstico por imagemRESUMO
Evidence suggests aerobic exercise has beneficial effects on cognitive performance in adults with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms might depend on mechanisms of exercise-mediated brain physiology. The study aims to investigate the effects of acute aerobic exercise on cortical excitability and cognitive performance, and the correlation between these phenomena in adults with ADHD. Twenty-six drug-naïve ADHD adults, and twenty-six age-, and gender-matched healthy controls were assessed with respect to cortical excitability and cognitive performance before and after acute aerobic exercise (a single session for 30 min) or a control intervention. The results show significantly enhanced intracortical facilitation (ICF) and decreased short intracortical inhibition (SICI) after aerobic exercise in healthy subjects. In contrast, SICI was significantly enhanced following acute aerobic exercise in ADHD. In ADHD, furthermore inhibitory control and motor learning were significantly improved after the acute aerobic exercise intervention. Alterations of SICI induced by aerobic exercise, and inhibitory control and motor learning improvement were significantly positively correlated in the ADHD group. Aerobic exercise had partially antagonistic effects in healthy controls, and ADHD patients. Furthermore, aerobic exercise-induced cognition-enhancing effects in ADHD depend on specific alterations of brain physiology, which differ from healthy humans.
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Transtorno do Deficit de Atenção com Hiperatividade , Cognição , Exercício Físico , Estimulação Magnética Transcraniana , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/reabilitação , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Masculino , Feminino , Exercício Físico/fisiologia , Adulto , Adulto Jovem , Cognição/fisiologia , Potencial Evocado Motor/fisiologia , Excitabilidade Cortical/fisiologia , EletromiografiaRESUMO
From power plants on land to bridges over the sea, safety-critical built environments require periodic inspections for detecting issues to avoid functional discontinuities of these installations. However, navigation paths in these environments are usually challenging as they often contain difficult-to-access spaces (near-millimetre and submillimetre-high gaps) and multiple domains (solid, liquid and even aerial). In this paper, we address these challenges by developing a class of Thin Soft Robots (TS-Robot: thickness, 1.7 mm) that can access narrow spaces and perform cross-domain multimodal locomotion. We adopted a dual-actuation sandwich structure with a tuneable Poisson's ratio tensioning mechanism for developing the TS-Robots driven by dielectric elastomers, providing them with two types of gaits (linear and undulating), remarkable output force ( ~ 41 times their weight) and speed (1.16 times Body Length/s and 13.06 times Body Thickness/s). Here, we demonstrated that TS-Robots can crawl, climb, swim and collaborate for transitioning between domains in environments with narrow entries.
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BACKGROUND: The inclusion of a connecting path in a porous implant can promote nutrient diffusion to cells and enhance bone ingrowth. Consequently, this study aimed to evaluate the biomechanical, radiographic, and histopathological performance of a novel 3D-printed porous suture anchor in a rabbit femur model. METHODS: Three test groups were formed based on the type of suture anchor (SA): Commercial SA (CSA, Group A, n = 20), custom solid SA (CSSA, Group B, n = 20), and custom porous SA (CPSA, Group C, n = 20). The SAs were implanted in the lateral femoral condyle of the right leg in each rabbit. The rabbits (New Zealand white rabbits, male, mean body weight of 2.8 ± 0.5 kg, age 8 months) underwent identical treatment and were randomized into experimental and control groups via computer-generated randomization. Five rabbits (10 femoral condyles) were euthanized at 0, 4, 8, and 12 weeks post-implantation for micro-CT, histological analysis, and biomechanical testing. RESULTS: At 12 weeks, the CPSA showed a higher BV/TV (median 0.7301, IQR 0.7276-0.7315) than the CSSA and CSA. The histological analysis showed mineralized osteocytes near the SA. At 4 weeks, new bone was observed around the CPSA and had penetrated its porous structure. By 12 weeks, there was no significant difference in ultimate failure load between the CSA and CPSA. CONCLUSIONS: We demonstrated that the innovative 3D-printed porous suture anchor exhibited comparable pullout strength to conventional threaded suture anchors at the 12-week postoperative time-point period. Furthermore, our porous anchor design enhanced new bone formation and facilitated bone growth into the implant structure, resulting in improved biomechanical stability.
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Fêmur , Impressão Tridimensional , Âncoras de Sutura , Titânio , Animais , Coelhos , Fêmur/cirurgia , Fêmur/diagnóstico por imagem , Fêmur/patologia , Porosidade , Masculino , Fenômenos Biomecânicos , Microtomografia por Raio-XRESUMO
BACKGROUND: The inconsistent relationship between chemical exposure and estimated glomerular filtration rate (eGFR) has been examined in only a few studies. We investigated the association between paraben exposure and indicators of renal function in a total of 361 individuals recruiting from a representative study. METHOD: The levels of urinary parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), were measured using UPLC-MS/MS. The association between paraben exposure and indices of renal function was assessed using multiple logistic regression and Bayesian Kernel Machine Regression (BKMR). RESULTS: The median levels of urinary parabens in the adult group were significantly higher than those in the minor group, that is, 397 vs. 148â¯ng/mL for MeP, 38.8 vs. 13.6â¯ng/mL for EtP, 117 vs. 57.7â¯ng/mL for PrP, and 6.61 vs. 2.79â¯ng/mL for BuP (all P < 0.001). In the adult group, multivariate regression models confirmed a positive association between the albumin-to-creatinine ratio and urinary MeP (ß = 0.580) and a positive association of BUN (ß = 0.061) and a negative association of eGFR (ß = -0.051) with urinary EtP (all P < 0.001). In the adult group, compared with the lowest tertile group, the adjusted odds ratio in the third tertile (T3) of urinary EtP levels indicated a 3.08 times increased risk of eGFR abnormalities, followed by the second tertile (T2) with a 2.63 times increased risk. The generalized additive model (GAM) and BKMR models showed a non-linear correlation between urinary EtP levels and early CKD, as well as reduced eGFR. We observed a significant positive cumulative effect of urinary paraben on eGFR, and a significant positive single exposure effect of urinary EtP with eGFR abnormality. CONCLUSION: We found a significant association between exposure to EtP and an increased risk of high BUN levels and decreased eGFR.
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Taxa de Filtração Glomerular , Parabenos , Humanos , Parabenos/análise , Taxa de Filtração Glomerular/efeitos dos fármacos , Feminino , Masculino , Adulto , Taiwan , Pessoa de Meia-Idade , Idoso , Exposição Ambiental/estatística & dados numéricos , Adulto Jovem , Teorema de Bayes , Poluentes Ambientais/urinaRESUMO
Background Comparative performance between artificial intelligence (AI) and breast US for women with dense breasts undergoing screening mammography remains unclear. Purpose To compare the performance of mammography alone, mammography with AI, and mammography plus supplemental US for screening women with dense breasts, and to investigate the characteristics of the detected cancers. Materials and Methods A retrospective database search identified consecutive asymptomatic women (≥40 years of age) with dense breasts who underwent mammography plus supplemental whole-breast handheld US from January 2017 to December 2018 at a primary health care center. Sequential reading for mammography alone and mammography with the aid of an AI system was conducted by five breast radiologists, and their recall decisions were recorded. Results of the combined mammography and US examinations were collected from the database. A dedicated breast radiologist reviewed marks for mammography alone or with AI to confirm lesion identification. The reference standard was histologic examination and 1-year follow-up data. The cancer detection rate (CDR) per 1000 screening examinations, sensitivity, specificity, and abnormal interpretation rate (AIR) of mammography alone, mammography with AI, and mammography plus US were compared. Results Among 5707 asymptomatic women (mean age, 52.4 years ± 7.9 [SD]), 33 (0.6%) had cancer (median lesion size, 0.7 cm). Mammography with AI had a higher specificity (95.3% [95% CI: 94.7, 95.8], P = .003) and lower AIR (5.0% [95% CI: 4.5, 5.6], P = .004) than mammography alone (94.3% [95% CI: 93.6, 94.8] and 6.0% [95% CI: 5.4, 6.7], respectively). Mammography plus US had a higher CDR (5.6 vs 3.5 per 1000 examinations, P = .002) and sensitivity (97.0% vs 60.6%, P = .002) but lower specificity (77.6% vs 95.3%, P < .001) and higher AIR (22.9% vs 5.0%, P < .001) than mammography with AI. Supplemental US alone helped detect 12 cancers, mostly stage 0 and I (92%, 11 of 12). Conclusion Although AI improved the specificity of mammography interpretation, mammography plus supplemental US helped detect more node-negative early breast cancers that were undetected using mammography with AI. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Whitman and Destounis in this issue.
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Inteligência Artificial , Densidade da Mama , Neoplasias da Mama , Detecção Precoce de Câncer , Mamografia , Ultrassonografia Mamária , Humanos , Feminino , Mamografia/métodos , Neoplasias da Mama/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia Mamária/métodos , Detecção Precoce de Câncer/métodos , Adulto , Sensibilidade e Especificidade , Mama/diagnóstico por imagem , IdosoRESUMO
This study aims to investigate longitudinal associations between the dietary glycemic index (GI) and glycemic load (GL) and changes in glycemic and cardio-metabolic outcomes. A 28-month retrospective cohort study included 110 Vietnamese diabetic patients, collecting their dietary GI and GL values along with blood biochemical data from baseline 24-h dietary recall and medical records. Latent class growth modelling identified three distinct HbA1c trajectories during the follow-up period, with 51% of patients achieving good glycemic control. The adjusted linear mixed-effect model showed that 1 unit increase in logarithms in dietary GL was associated with a 0.14% increase in the log-HbA1c. Among poorly controlled diabetic patients, baseline GL values were positively correlated with increases in HbA1c; GI showed effects on changes in fasting plasma glucose and the triglyceride-glucose (TyG) index. No significant association was observed in patients with good glycemic control.
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Biomarcadores , Glicemia , Dieta , Hemoglobinas Glicadas , Índice Glicêmico , Carga Glicêmica , Humanos , Masculino , Feminino , Glicemia/metabolismo , Glicemia/análise , Hemoglobinas Glicadas/análise , Biomarcadores/sangue , Idoso , Vietnã , Estudos Retrospectivos , Pessoa de Meia-Idade , Estudos Longitudinais , Diabetes Mellitus Tipo 2/sangue , Triglicerídeos/sangue , Controle Glicêmico/métodosRESUMO
BACKGROUND: Recent studies indicated that bioactive lipids of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) predict unhealthy metabolic phenotypes, but results remain inconsistent. To fill this knowledge gap, we investigated whether essential trace elements affect PC-Lyso PC remodeling pathways and the risk of insulin resistance (IR). METHODS: Anthropometric and blood biochemical data (glucose, insulin, and lipoprotein-associated phospholipase A2 (Lp-PLA2)) were obtained from 99 adults. Blood essential/probably essential trace elements and lipid metabolites were respectively measured by inductively coupled plasma mass spectrometry (ICP-MS), and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). RESULT AND CONCLUSION: Except for LysoPC (O-18:0/0:0), an inverse V shape was observed between body weight and PC and LysoPC species. A Pearson correlation analysis showed that essential/probably-essential metals (Se, Cu, and Ni: r=-0.4â¼-0.7) were negatively correlated with PC metabolites but positively correlated with LysoPC (O-18:0/0:0) (Se, Cu, and Ni: r=0.85-0.64). Quantile-g computation showed that one quantile increase in essential metals was associated with a 2.16-fold increase in serum Lp-PLA2 (ß=2.16 (95â¯% confidence interval (CI): 0.34, 3.98), p=0.023), which are key enzymes involved in PC/Lyso PC metabolism. An interactive analysis showed that compared to those with the lowest levels (reference), individuals with the highest levels of serum PCs (pooled, M2) and the lowest essential/probably essential metals (M1) were associated with a healthier body composition and had a 76â¯% decreased risk of IR (odds ratio (OR)=0.24 (95â¯% CI: 0.06, 0.90), p<0.05). In contrast, increased exposure to LysoPC(O-18:0/0:0) (M2) and essential metals (M2) exhibited an 8.22-times highest risk of IR (OR= 8.22 (2.07, 32.57), p<0.05) as well as an altered body composition. In conclusion, overexposure to essential/probably essential trace elements may promote an unhealthy body weight and IR through modulating PC/LysoPC remodeling pathways.
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Composição Corporal , Resistência à Insulina , Fosfatidilcolinas , Oligoelementos , Humanos , Masculino , Fosfatidilcolinas/sangue , Fosfatidilcolinas/metabolismo , Feminino , Oligoelementos/sangue , Oligoelementos/metabolismo , Adulto , Pessoa de Meia-Idade , Lisofosfatidilcolinas/sangue , Lisofosfatidilcolinas/metabolismoRESUMO
PURPOSE OF REVIEW: Deficiencies in micronutrients persist as widespread global challenges, where supplementation remains a crucial therapeutic approach. This review aims to elucidate the intricate relationships between micronutrient supplementation - specifically iron, selenium (Se), and vitamin D (Vit D) - and gut microbiota composition, investigating their collective impact on host health and disease susceptibility. RECENT FINDINGS: Maintaining balanced iron levels is essential for gut microbiota equilibrium and host health, as both iron deficiency and excess disrupt gut bacterial balance, affecting colon health. Se supplementation can restore and improve the gut microbial balance, influencing health outcomes not only in the gut but also in areas such as neuroprotection in the brain, testicular health, and metabolic syndrome. Clinical and experimental models demonstrate that Vit D modulates the gut microbiome, enhancing anti-inflammatory effects, supporting metabolic health, and potentially reducing the risk of gut-related behavioral changes and diseases. SUMMARY: Findings of this review emphasize that balanced iron levels are essential for maintaining a healthy gut microbiota composition and underscore the beneficial effects of Se and Vit D in modulating the gut microbiome. The interactions between micronutrients and the gut microbiome are complex but may have a broad spectrum of health outcomes.
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Suplementos Nutricionais , Microbioma Gastrointestinal , Ferro , Micronutrientes , Selênio , Vitamina D , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Vitamina D/farmacologia , Vitamina D/administração & dosagem , Selênio/administração & dosagem , Selênio/farmacologia , Micronutrientes/farmacologia , AnimaisRESUMO
M2-like macrophages exhibit immunosuppressive activity and promote pancreatic cancer progression. Reactive oxygen species (ROS) affect macrophage polarization; however, the mechanism remains unclear. This study aimed to elucidate the underlying molecular basis and design a gene therapy to inhibit M2-like polarization. Microarray analysis and immunofluorescence staining were performed in M1-like and M2-like macrophages to ascertain the expression of CYBB, a major intracellular ROS source. Coculture assay and syngeneic orthotopic pancreatic cancer mice models were used to study the mechanism of M2-like skewing. Decoy oligodeoxynucleotides (ODNs) were designed to manipulate CYBB transcription to inhibit M2-like polarization and control tumor growth. Lipopolysaccharide treatment polarized U937 cells to M1-like macrophages in which CYBB expression was increased. In contrast, coculture with PANC-1 cells induced M2-like polarization in U937 cells with CYBB downregulation. High CD204 M2-like expression in combination with low CYBB expression was associated with the worst prognosis in patients with pancreatic cancer. STAT6 and HDAC2 in U937 cells were activated by cancer cell-derived IL4 after coculture and then bound to the CYBB promoter to repress CYBB expression, resulting in M2-like polarization. Diphenyleneiodonium, 8λ³-iodatricyclo[7.4.0.02,7]trideca-1(13),2,4,6,9,11-hexaen-8-ylium chloride that inhibits ROS production could block this action. Knockdown of STAT6 and HDAC2 also inhibited M2-like polarization and maintained the M1-like phenotype of U937 cells after coculture. Decoy ODNs interrupting the binding of STAT6 to the CYBB promoter counteracted M2-like polarization and tumor growth and triggered antitumor immunity in vivo. Gene therapy using STAT6-CYBB decoy ODNs can inhibit M2-like polarization, representing a potential therapeutic tool for pancreatic cancer.
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Macrófagos , Oligodesoxirribonucleotídeos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Camundongos , Oligodesoxirribonucleotídeos/farmacologia , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Terapia Genética/métodos , Linhagem Celular Tumoral , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Evasão Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Células U937RESUMO
Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.
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Regeneração Óssea , Liofilização , Gelatina , Ácido Hialurônico , Hidrogéis , Iridoides , Fibrina Rica em Plaquetas , Animais , Iridoides/química , Iridoides/farmacologia , Gelatina/química , Coelhos , Hidrogéis/química , Hidrogéis/farmacologia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Regeneração Óssea/efeitos dos fármacos , Fibrina Rica em Plaquetas/química , Engenharia Tecidual/métodos , Reagentes de Ligações Cruzadas/química , Alicerces Teciduais/química , Tíbia/efeitos dos fármacos , Tíbia/cirurgiaRESUMO
Introduction: Ever since the use of bisphenol A (BPA) has been restricted, concerns have been raised regarding the use of its substitutes, such as bisphenol S (BPS) and bisphenol F (BPF). Meanwhile, the EU European Food Safety Authority (EFSA) issued the new tolerable daily intake (TDI) after the latest re-risk assessment for BPA, which enforced the need for cumulative risk assessment in the population. This study was conducted to identify BPA and its substitute's exposure characteristics of the general Taiwanese population and estimate the cumulative risk of bisphenol exposure. Methods: Urine samples (N = 366 [adult, 271; minor, 95]) were collected from individuals who participated in the Taiwan Environmental Survey for Toxicants 2013. The samples were analyzed for BPA, BPS, and BPF through ultraperformance liquid chromatography-tandem mass spectrometry. Daily intake (DI) levels were calculated for each bisphenol. Hazard quotients (HQs) were calculated with the consideration of tolerable DI and a reference dose. Additionally, hazard index (HI; sum of HQs for each bisphenol) values were calculated. Results: Our study found that the median level of BPA was significantly higher in adults (9.63 µg/g creatinine) than in minors (6.63 µg/g creatinine) (p < 0.001). The DI of BPS was higher in female (0.69 ng/kg/day) than in male (0.49 ng/kg/day); however, the DIs of BPF and BPS were higher in boys (1.15 and 0.26 ng/kg/day, respectively) than in girls (0.57 and 0.20 ng/kg/day, respectively). Most HI values exceeded 1 (99% of the participants) after EFSA re-establish the TDI of BPA. Discussion: Our study revealed that the exposure profiles and risk of BPA and its substitute in Taiwanese varied by age and sex. Additionally, the exposure risk of BPA was deemed unacceptable in Taiwan according to new EFSA regulations, and food contamination could be the possible source of exposure. We suggest that the risk of exposure to BPA and its substitutes in most human biomonitoring studies should be reassessed based on new scientific evidence.
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Compostos Benzidrílicos , Exposição Ambiental , Fenóis , Sulfonas , Humanos , Fenóis/urina , Fenóis/análise , Fenóis/toxicidade , Compostos Benzidrílicos/urina , Compostos Benzidrílicos/toxicidade , Feminino , Masculino , Taiwan , Adulto , Medição de Risco , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Criança , Pessoa de Meia-Idade , Adolescente , Sulfonas/análise , Adulto Jovem , Idoso , Pré-Escolar , Espectrometria de Massas em Tandem , Monitoramento Ambiental , Inquéritos e Questionários , Poluentes Ambientais/análiseRESUMO
Previous studies have shown that aerobic exercise has beneficial effects on executive function in adolescents with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms could be partially due to aerobic exercise-induced cortical excitability modulation. The aim of this study was to explore the effects of acute aerobic exercise on executive functions and cortical excitability and the association between these phenomena in adolescents with ADHD. The study was conducted using a complete crossover design. Executive functions (inhibitory control, working memory, and planning) and cortical excitability were assessed in twenty-four drug-naïve adolescents with ADHD before and after acute aerobic exercise or a control intervention. Inhibitory control, working memory, and planning improved after acute aerobic exercise in adolescents with ADHD. Moreover, cortical excitability monitored by transcranial magnetic stimulation (TMS) decreased after intervention in this population. Additionally, improvements in inhibitory control and working memory performance were associated with enhanced cortical inhibition. The findings provide indirect preliminary evidence for the assumption that changes in cortical excitability induced by aerobic exercise partially contribute to improvements in executive function in adolescents with ADHD.
RESUMO
A systematic review and meta-analysis was conducted to evaluate the relative effectiveness of different dietary macronutrient patterns on changes in resting energy expenditure (REE) in relation to weight loss, categorized as minimal (<5%) and moderate to high (>5%). Changes in REE were assessed using a DerSimonian and Laird random-effects meta-analysis. A diet lower in carbohydrates (CHO) or higher in fat and protein was associated with smaller reductions in REE, with these trends being more pronounced among participants who experienced moderate to high weight loss. Adjusted meta-regression analysis indicated that, within the participants who experienced moderate to high weight loss, each 1% increase in CHO intake was associated with a reduction of 2.30 kcal/day in REE (95% CI: -4.11 to -0.47, p = 0.013). In contrast, a 1% increase in protein and fat intake was correlated with an increase in REE by 3.00 (95% confidence interval [CI] [1.02, 5.07], p = 0.003) and 0.5 (95% CI [-2.43, 3.41], p = 0.740) kcal/day, respectively. No significant associations were found among participants who experienced minimal weight loss. These findings indicate that, under a caloric deficit, the impact of dietary macronutrient composition on REE may vary depending on the degree of weight loss and individual metabolic responses.