Glucose-responsive enzymatic biomimetic nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic anticancer therapy.

Photothermal therapy (PTT) combined with chemodynamic therapy (CDT) presents an appealing complementary anti-tumor strategy, wherein PTT accelerates the production of reactive oxygen species (ROS) in CDT and CDT eliminates residual tumor tissues that survive from PTT treatment. However, nanomaterials utilized in PTT/CDT are limited by non-specific damage to the entire organism. Herein, a glucose-responsive enzymatic Fe@HRP-ABTS/GOx nanodot is judiciously designed for tumor-specific PTT/CDT via a simple and clean protein-templated biomimetic mineralization synthesis. By oxidizing glucose in tumor cells, glucose oxidase (GOx) activates glucose-responsive tumor therapy and increases the concentration of H2O2 at the tumor site. More importantly, the self-supplied peroxide hydrogen (H2O2) can convert ABTS (2,2'-Hydrazine-bis(3-ethylbenzothiazoline-6-sulfonic acid) diamine salt) into oxidized ABTS (oxABTS) through horseradish peroxidase (HRP) catalysis for PTT and photoacoustic (PA) imaging. Furthermore, the Fe2+ arising from the reduction of Fe3+ by overexpressed GSH reacts with H2O2 to generate intensely reactive •OH through the Fenton reaction, concurrently depleting GSH and inducing efficient tumor CDT. The in vitro and in vivo experiments demonstrate superior cancer cell killing and tumor eradication effect of Fe@HRP-ABTS/GOx nanodot under near-infrared (NIR) laser irradiation. Collectively, the nanodots provide mutually reinforcing catalytic PTT/CDT anti-tumor strategies for treating liver cancer and potentially other malignancies. STATEMENT OF SIGNIFICANCE: Combinatorial antitumor therapy with nanomedicines presents great prospects for development. However, the limitation of non-specific damage to normal tissues hinders its further clinical application. In this work, we fabricated tumor-selective biomimetic Fe@HRP-ABTS/GOx nanodots for H2O2 self-supplied catalytic photothermal/chemodynamic therapy of tumors. The biomimetic synthesis strategy provides the nanodots with enzymatic activity in response to glucose to produce H2O2. The self-supplied H2O2 initiates photothermal therapy with oxidized ABTS and enhances chemodynamic therapy through simultaneous •OH generation and GSH depletion. Our work provides a new paradigm for developing tumor-selective catalytic nanomedicines and will guide further clinical translation of the enzymatic biomimetic synthesis strategy.

Birth month associates with risk of coronary artery disease and its complications: A propensity score matched analysis / El mes de nacimiento se asocia con el riesgo de padecer una arteriopatía coronaria y sus complicaciones: análisis mediante propensity score

Objective: Birth month and climate affect lifetime disease risk, while the underlying mechanisms remain largely elusive. It is vital to investigate the risks of coronary artery disease (CAD) and its complications in patients born in different months. Methods: A total of 12,263 patient medical records were reviewed from the BioBank of First Affiliated Hospital of Xinxiang Medical University, with 4729 records from patients with CAD (CAD group) and 7534 records from control patients without CAD (control group). Two groups of patients were matched by the propensity score matched method. Birth months were compared between two groups of patients. The relationships between birth month and the numbers of CAD and its complications were also investigated. Interestingly, we also explore the relationship between the birth seasons and the numbers of CAD and its complications. Results: Compared to control, CAD group had greater CAD risks for patients born in November (OR 1.390, 95% CI 1.090-1.772), December (OR 1.358, 95% CI 1.067-1.730), and February (OR 1.332, 95% CI 1.043-1.700) compared to those born in May. Compared to patients born in December, patients born in January to March and May to September had greater risk of heart failure (P<0.05). There was no difference in the incidence of myocardial infarction, conduction block, and atrial fibrillation across birth months (P>0.05). In terms of birth season, patients born in winter have greater CAD risk than those born in spring (OR 1.247, 95% CI 1.075-1.447). And there was no difference in the incidence of CAD complications across with birth seasons (P>0.05). Conclusions: There was a correlation between birth month and CAD. People born in November, December, and February had greater CAD risk, and people born in winter had greater CAD risk. Among CAD patients, those born in January to March and May to September had the greater risk of heart failure

Objetivo: El mes de nacimiento y el clima están relacionados con el riesgo de padecer una enfermedad crónica, aunque siguen desconociéndose en gran medida los mecanismos subyacentes. Resulta fundamental investigar los riesgos de padecer una arteriopatía coronaria (AC) y sus complicaciones en pacientes nacidos en distintos meses. Métodos: Se revisaron un total de 12.263 historias clínicas de pacientes extraídas del Biobanco del primer hospital afiliado de la Universidad Médica de Xinxiang, de las cuales 4.729 correspondían a pacientes con una AC (grupo con AC) y 7.534 correspondían a pacientes control sin una AC (grupo comparativo). Se emparejaron a 2 grupos de pacientes siguiendo el método de pareamiento por puntaje de propensión, y se compararon los meses de nacimiento de los pacientes de ambos grupos. También se investigó la relación existente entre el mes de nacimiento y el número de casos de AC y sus complicaciones. Resulta interesante destacar que también exploramos la relación existente entre las estaciones de nacimiento y el número de casos de AC y sus complicaciones. Resultados: En comparación con los pacientes del grupo comparativo, los pacientes del grupo con AC nacidos en noviembre (razón de posibilidades odds ratio [OR]: 1,390; intervalo de confianza [IC] del 95%: 1,090-1,772), diciembre (OR: 1,358; IC 95%: 1,067-1,730) y febrero (OR: 1,332; IC 95%: 1,043-1,700) presentaban un mayor riesgo de padecer una AC en comparación con los nacidos en mayo. En comparación con los pacientes nacidos en diciembre, los pacientes nacidos entre enero y marzo, y entre mayo y septiembre, presentaron un mayor riesgo de padecer una insuficiencia cardíaca (P<0,05). No se observaron diferencias en la incidencia de infarto de miocardio, bloqueo de la conducción y fibrilación auricular entre los distintos meses de nacimiento (P>0,05). En cuanto a la temporada de nacimiento, los pacientes nacidos en invierno presentaron un mayor riesgo de desarrollar una AC que los nacidos en primavera (OR: 1,247; IC 95%: 1,075-1,447). No se observaron diferencias en la incidencia de complicaciones de la AC entre las distintas temporadas de nacimiento (P>0,05). Conclusiones: Se observó una correlación entre el mes de nacimiento y la AC. Tanto las personas nacidas en los meses de noviembre, diciembre y febrero, como las nacidas en la temporada de invierno presentaron un mayor riesgo de padecer una AC. Entre los pacientes con AC, los nacidos entre enero y marzo, y entre mayo y septiembre, presentaron un mayor riesgo de padecer una insuficiencia cardíaca

Birth month associates with risk of coronary artery disease and its complications: A propensity score matched analysis.

OBJECTIVE: Birth month and climate affect lifetime disease risk, while the underlying mechanisms remain largely elusive. It is vital to investigate the risks of coronary artery disease (CAD) and its complications in patients born in different months. METHODS: A total of 12,263 patient medical records were reviewed from the BioBank of First Affiliated Hospital of Xinxiang Medical University, with 4729 records from patients with CAD (CAD group) and 7534 records from control patients without CAD (control group). Two groups of patients were matched by the propensity score matched method. Birth months were compared between two groups of patients. The relationships between birth month and the numbers of CAD and its complications were also investigated. Interestingly, we also explore the relationship between the birth seasons and the numbers of CAD and its complications. RESULTS: Compared to control, CAD group had greater CAD risks for patients born in November (OR 1.390, 95% CI 1.090-1.772), December (OR 1.358, 95% CI 1.067-1.730), and February (OR 1.332, 95% CI 1.043-1.700) compared to those born in May. Compared to patients born in December, patients born in January to March and May to September had greater risk of heart failure (P<0.05). There was no difference in the incidence of myocardial infarction, conduction block, and atrial fibrillation across birth months (P>0.05). In terms of birth season, patients born in winter have greater CAD risk than those born in spring (OR 1.247, 95% CI 1.075-1.447). And there was no difference in the incidence of CAD complications across with birth seasons (P>0.05). CONCLUSIONS: There was a correlation between birth month and CAD. People born in November, December, and February had greater CAD risk, and people born in winter had greater CAD risk. Among CAD patients, those born in January to March and May to September had the greater risk of heart failure.