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Self-assembled peptide and polysaccharide nanogels are excellent candidates for bioactive delivery vectors. However, there are still significant challenges in the application of nanogels as delivery tools for bioactive elements. This study aims to deliver, and control the release of a hydrophobic bioactive flavonoid hesperidin. Using the self-assembling peptide (SAP) Fmoc-FRGDF, extracellular matrix mimicking nanofibrils were fabricated, which were decorated and bolstered with immunomodulatory polysaccharide strands of fucoidan and infused with hesperidin. The mechanical properties, secondary structure, and microscopic morphologies of the composite hydrogels were characterized using rheometer, FTIR, XRD, and TEM, etc. The encapsulation efficiency (EE) and release behavior of hesperidin were determined. Coassembly of the SAP with fucoidan improved the mechanical properties (from 9.54 Pa of Fmoc-FRGDF hydrogel to 7735 Pa of coassembly hydrogel at 6 mg/mL fucoidan concentration), formed thicker nanofibril bundles at 4 and 6 mg/mL fucoidan concentration, improved the EE of hesperidin from 72.86 % of Fmoc-FRGDF hydrogel to over 90 % of coassembly hydrogels, and showed effectively controlled release of hesperidin in vitro. Intriguingly, the first order kinetic model predicted an enhanced hydrogel retention and release of hesperidin. This study revealed a new approach for bioengineered nanogels that could be used to stabilize and release hydrophobic payloads., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Aims: Serum calcium abnormality is associated with adverse cardiovascular outcomes, but the effects of serum calcium level on stroke outcomes remain unknown. We aimed to assess the relationship between serum calcium level and 1-year outcomes in patients with acute ischemic stroke and transient ischemic attack., Methods: We included 9375 stroke patients from the China National Stroke Registry III for analysis. Participants were divided into 4 groups according to albumin corrected-calcium quartiles. Composite end point comprised recurrent stroke, myocardial infarction, other ischemic vascular events, and all-cause mortality. Multivariable Cox or logistic regression was used to evaluate the independent association of albumin corrected-calcium with all-cause mortality, recurrent stroke, composite end point, and poor functional outcome (modified Rankin Scale score ≥3)., Results: Compared with the lowest calcium quartile (<2.16 mmol/L), the adjusted hazard ratio (95% CI) of the top quartile (≥2.31 mmol/L) was 1.56 (1.11-2.18) for all-cause mortality, 1.06 (0.87-1.28) for recurrent stroke and 1.08 (0.90-1.01) for composite end point, and the adjusted odds ratio for poor functional outcome was 1.18 (0.96-1.44). The addition of serum calcium to conventional risk factors improved risk prediction of all-cause mortality, leading to a small but significant increase in C-statistics and reclassification with non-significant integrated discrimination improvement (C-statistics, p = 0.02; net reclassification index 11.8%, p = 0.038; integrated discrimination improvement 0.08%, p = 0.42)., Conclusions: High serum calcium levels at baseline were associated with all-cause mortality at 1-year after ischemic stroke, suggesting that serum calcium may be a potential prognostic biomarker and therapeutic target for ischemic stroke., (Copyright © 2021. Published by Elsevier B.V.)

Background: Health-related quality of life and utility scores of patients with breast cancer and precancerous lesions are sparse in China. This study aimed to derive utility scores of patients with breast cancer and precancer in China., Material and Methods: An interviewer-administered cross-sectional survey was conducted in 12 provinces across China from 2013 to 2014. The three-level EuroQol-5-Dimension instrument was used to evaluate quality of life, and utility scores were generated using the Chinese value set. Univariate and multivariate analyses were performed to explore the determinants of utility scores., Results: In total, 2626 breast cancer and 471 precancer patients were included. Mean age was 49.1 for breast cancer and 41.4 years for precancer (p < 0.001). Among the five dimensions, pain/discomfort was the most reported problem, 53.9% in breast cancer and 29.3% in precancer patients. Mean (95% CI) utility scores for breast cancer and precancer patients were estimated as 0.887 (0.875-0.899) and 0.781 (0.774-0.788), and the scores of breast cancer at stage-I, stage-II, stage-III and stage-IV were 0.789 (0.774-0.805), 0.793 (0.783-0.802), 0.774 (0.759-0.788) and 0.686 (0.654-0.717), respectively. Mean (95% CI) visual analogue scale scores for breast cancer and precancer were 75.6 (74.0-77.3) and 72.8 (72.3-73.3). Multiple regression showed advanced clinical stage, lower educational level, lower household income, surgery treatment, and undergoing treatment were independently associated with lower utility scores for breast cancer patients., Conclusion: The utility scores deteriorate with the severity of breast neoplasms. Detailed utility scores of breast cancer and precancer are fundamental for further cost-utility analysis in China., (Copyright © 2018. Published by Elsevier Ltd.)

Our previous study successfully identified that the novel isatin derivative (E)-methyl 3-(1-(4-methoxybenzyl)-2,3-dioxoindolin-5-yl) acrylate (HKL 2H) acts as an anticancer agent at an inhibitory concentration (IC50) level of 3nM. In this study, the molecular mechanism how HKL 2H induces cytotoxic activity in the human chronic myelogenous leukemia K562 cells was investigated. Flow cytometric analysis showed that the cells were arrested in the G2/M phase and accumulated subsequently in the sub-G1 phase in the presence of HKL 2H. HKL 2H treatment down-regulated the expressions of CDK1 and cyclin B but up-regulated the level of phosphorylated CDK1. Annexin-V staining and the classic DNA ladder studies showed that HKL 2H induced the apoptosis of K562 cells. Our study further showed that HKL 2H treatment caused the dissipation of mitochondrial membrane potential, activated caspase-3 and lowered the Bcl-2/Bax ratio in K562 cells, suggesting that the HKL 2H-causing programmed cell death of K562 cells was caused via the mitochondrial apoptotic pathway. Taken together, our data demonstrated that HKL 2H, a 5-(2-carboxyethenyl) isatin derivative, notably induces G2/M cell cycle arrest and mitochondrial-mediated apoptosis in K562 cells, indicating that this compound could be a promising anticancer candidate for further investigation., (Copyright © 2014 Elsevier Inc. All rights reserved.)