Currently, neoadjuvant chemotherapy is a standard therapeutic strategy for breast cancer, as it can provide timely and individualized chemo-sensitivity information and is beneficial for ...custom-designing subsequent treatment strategies. To accurately select candidates for neoadjuvant chemotherapy, the association between various immunohistochemical biomarkers of primary disease and tumor response to neoadjuvant chemotherapy has been investigated, and results have shown that certain pathological indicators evaluated after neoadjuvant chemotherapy are associated with long-term prognosis. The Food and Drug Administration (FDA) has recommended that complete pathological response can be used as a surrogate endpoint for neoadjuvant chemotherapy, which is related to better prognosis. Considering that residual tumor persists in the majority of patients after neoadjuvant chemotherapy, the value of various pathological indicators of residual disease in predicting the long-term outcomes is being extensively investigated. This review summarizes and compares various predictive and prognostic indicators for patients who have received neoadjuvant chemotherapy, and analyzes their efficacy in different breast cancer subtypes.
Objective:
A potential solution for islet transplantation and drug discovery vis-à-vis treating diabetes is the production of functional islets in a three-dimensional extracellular matrix. Although ...several scaffold materials have been reported as viable candidates, a clinically applicable one that is injectable and can maintain long-term functionality and survival of islet pancreatic beta-cells (β-cells) is far from being established.
Results:
In the current study, we evaluated a ready-to-use and injectable hydrogel’s impact on β-cells’ function and viability, both in vitro and in vivo. We found that β-cells in high concentration with hydrogels functionalized via Arg-Gly-Asp (RGD) demonstrated better viability and insulin secretory capacity in vitro. Moreover, it is a biocompatible hydrogel that can maintain β-cell proliferation and vascularization without stimulating inflammation after subcutaneous injection. Meanwhile, modifying the hydrogel with RGD can maintain β-cells’ secretion of insulin, regulating the blood glucose levels of mice with streptozotocin-induced diabetes.
Conclusions:
Thus, these preliminary results indicate that this RGD-modified hydrogel is a potential extracellular matrix for islet transplantation at extrahepatic sites, and they also provide a reference for future tissue engineering study.
Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract ...this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition.
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•Intracellular MH overcomes sorafenib resistance, unlike exogenous hyperthermia•Intracellular MH reverses sorafenib resistance via ROS-MEK-ERK pathway downregulation•MH enhances tumor sensitivity to sorafenib, suppressing growth and improving survival
Biomedical Engineering; Nanomedicine; Molecular biology; Biomaterials
Subway station projects are characterized by complex construction technology, complex site conditions, and being easily influenced by the surrounding environment; thus, construction safety accidents ...occur frequently. In order to improve the computing performance of the early risk warning system in subway station construction, a novel model based on least-squares support vector machines (LSSVM) optimized by quantum-behaved particle swarm optimization (QPSO) was proposed. First, early warning factors from five aspects (man, machine, management, material, and the environment) were selected based on accident causation theory and literature research. The data acquisition method of each risk factor was provided in detail. Then, the LSSVM with strong small sample analysis and nonlinear analysis abilities was chosen to give the early warning. To further ameliorate the early warning accuracy of the LSSVM, QPSO with a strong global retrieval ability was used to find the optimal calculation parameters of the LSSVM. Seventeen subway stations of Chengdu Metro Line 11 in China were picked as the empirical objects. The results demonstrated that the best regularization parameter was 1.742, and the best width parameter was 14.167. The number of misjudged samples of the proposed model was 1, and the early warning error rate was only 4.41%, which met the needs of engineering practice. Compared with the classic and latest methods, the proposed model was found to have a faster prediction speed and higher prediction accuracy.
Aims
Management of blood glucose fluctuation is essential for diabetes. Exercise is a key therapeutic strategy for diabetes patients, although little is known about determinants of glycemic response ...to exercise training. We aimed to investigate the effect of combined aerobic and resistance exercise training on blood glucose fluctuation in type 2 diabetes patients and explore the predictors of exercise‐induced glycemic response.
Materials and Methods
Fifty sedentary diabetes patients were randomly assigned to control or exercise group. Participants in the control group maintained sedentary lifestyle for 2 weeks, and those in the exercise group specifically performed combined exercise training for 1 week. All participants received dietary guidance based on a recommended diet chart. Glycemic fluctuation was measured by flash continuous glucose monitoring. Baseline fat and muscle distribution were accurately quantified through magnetic resonance imaging (MRI).
Results
Combined exercise training decreased SD of sensor glucose (SDSG, exercise‐pre vs exercise‐post, mean 1.35 vs 1.10 mmol/L, p = .006) and coefficient of variation (CV, mean 20.25 vs 17.20%, p = .027). No significant change was observed in the control group. Stepwise multiple linear regression showed that baseline MRI‐quantified fat and muscle distribution, including visceral fat area (β = −0.761, p = .001) and mid‐thigh muscle area (β = 0.450, p = .027), were significantly independent predictors of SDSG change in the exercise group, as well as CV change.
Conclusions
Combined exercise training improved blood glucose fluctuation in diabetes patients. Baseline fat and muscle distribution were significant factors that influence glycemic response to exercise, providing new insights into personalized exercise intervention for diabetes.
Highlights
Combined exercise training improved blood glucose fluctuation in diabetes patients.
Baseline fat and muscle distribution were significant factors that influence glycemic response to exercise.
The Mode I fracture of a dual-crosslink hydrogel under creep and constant stretch rate loading is investigated experimentally. The hydrogel network contains both permanent, or chemical, bonds and ...transient, or physical bonds that are constantly breaking and reforming. The resulting material is highly viscoelastic and capable of deforming to large strains prior to failure. Finite element and asymptotic analyses of the crack tip stress fields are used to calculate a stress intensity factor like crack tip parameter. Using this parameter in a kinetic model of failure in which the rate of bond breaking depends exponentially on the stress level, results from creep fracture tests are used to develop a fracture criterion that is then applied to predict failure under constant stretch rate loading conditions.
The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine ...model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21fl/flFOXP3Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21fl/flFOXP3Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.
Introduction
Type 2 diabetes patients have abdominal obesity and low thigh circumference. Previous studies have mainly focused on the role of exercise in reducing body weight and fat mass, improving ...glucose and lipid metabolism, with a lack of evaluation on the loss of muscle mass, diabetes complications, energy metabolism, and brain health. Moreover, whether the potential physiological benefit of exercise for diabetes mellitus is related to the modulation of the microbiota-gut-brain axis remains unclear. Multi-omics approaches and multidimensional evaluations may help systematically and comprehensively correlate physical exercise and the metabolic benefits.
Methods and Analysis
This study is a randomized controlled clinical trial. A total of 100 sedentary patients with type 2 diabetes will be allocated to either an exercise or a control group in a 1:1 ratio. Participants in the exercise group will receive a 16-week combined aerobic and resistance exercise training, while those in the control group will maintain their sedentary lifestyle unchanged. Additionally, all participants will receive a diet administration to control the confounding effects of diet. The primary outcome will be the change in body fat mass measured using bioelectrical impedance analysis. The secondary outcomes will include body fat mass change rate (%), and changes in anthropometric indicators (body weight, waist, hip, and thigh circumference), clinical biochemical indicators (glycated hemoglobin, blood glucose, insulin sensitivity, blood lipid, liver enzyme, and renal function), brain health (appetite, mood, and cognitive function), immunologic function, metagenomics, metabolomics, energy expenditure, cardiopulmonary fitness, exercise-related indicators, fatty liver, cytokines (fibroblast growth factor 21, fibroblast growth factor 19, adiponectin, fatty acid-binding protein 4, and lipocalin 2), vascular endothelial function, autonomic nervous function, and glucose fluctuation.
Discussion
This study will evaluate the effect of a 16-week combined aerobic and resistance exercise regimen on patients with diabetes. The results will provide a comprehensive evaluation of the physiological effects of exercise, and reveal the role of the microbiota-gut-brain axis in exercise-induced metabolic benefits to diabetes.
Clinical Trial Registration
http://www.chictr.org.cn/searchproj.aspx
, identifier ChiCTR2100046148.
IntroductionObesity is a complex and multifactorial disease that has affected many adolescents in recent decades. Clinical practice guidelines recommend exercise as the key treatment option for ...adolescents with overweight and obesity. However, the effects of virtual reality (VR) exercise on the physical and brain health of adolescents with overweight and obese remain unclear. This study aims to evaluate the effects of physical and VR exercises on physical and brain outcomes and explore the differences in benefits between them. Moreover, we will apply a multiomics analysis to investigate the mechanism underlying the effects of physical and VR exercises on adolescents with overweight and obesity.Methods and analysisThis randomised controlled clinical trial will include 220 adolescents with overweight and obesity aged between 11 and 17 years. The participants will be randomised into five groups after screening. Participants in the exercise groups will perform an exercise programme by adding physical or VR table tennis or soccer classes to routine physical education classes in schools three times a week for 8 weeks. Participants in the control group will maintain their usual physical activity. The primary outcome will be the change in body fat mass measured using bioelectrical impedance analysis. The secondary outcomes will include changes in other physical health-related parameters, brain health-related parameters and multiomics variables.Ethics and disseminationThis study was approved by the Ethics Committee of Shanghai Sixth People’s Hospital and registered in the Chinese Clinical Trial Registry. Dissemination of the findings will include peer-reviewed publications, conference presentations and media releases.Trial registration numberChiCTR2300068786.
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