Objective To investigate the kinectics characteristics of sulfation of apigenin mediated by SULTIA3.Methods After incubation of apigenin using in vitro SULT1A3 system, high-performance liquid chromatography was utilized to determine the sulfates of apigenin.Mass spectrum(MS) were employed to elucidate the structure of metabolite.The program GraphPad Prism 5 was used to perform the kinetic characterization of SULT1A3 catalyzed metabolism of apigenin.Results A liner calibration curve for the assay of apigenin was validated in the range of 0.15625 ~30 μM with the recoveries of at least 80% and intra-day and inter-day RSD of less than 15%.Metabolic product of apigenin and SULT1A3 in the incubated system was identified one monosulfate.The metabolic behavior of apigenin in SULT1A3 was followed substrate inhibition kinetics.Apparent kinetic parameters of metabolism of apigenin by SULT1A3, Kmwas(0.355 ±1.04) μM and Ksi was(23.62 ±0.06) μM,Vmax was(65.71 ±1.30) nmol/(min? mg),Vmax/Km was 185.10 mL/(min? mg).Conclusion SULT1A3 can mediate the binding of apigenin sulfonated reaction, and the character of enzymatic kinetics shows substrate inhibition.Sulfation of apigenin mediated by SULTIA3 may play an important role in phaseⅡmetabolic in vivo.

Since the first application of whole brain radiation therapy (WBRT) to brain metastases in 1950 s,it has been regarded as a standard treatment for brain metastases of non-small cell lung cancer (NSCLC).Recently,more accurate radiotherapy technique and more effective systemic therapy have been developed.Especially,the molecular targeted drugs are upgraded rapidly with stronger targeting capability and better permeability of the central nervous system.With the prolonged survival of patients,long-term damage to the nervous system induced by WBRT causes widespread concerns.This article will review the related controversies and research progress in the application of WBRT to NSCLC with brain metastases in modern integrated therapy.

Surgery,radiotherapy and chemotherapy are three traditional treatments for malignant tumors.With the development of medicine,immunotherapy has been gradually adopted as an emerging therapy of malignancies.Recent clinical studies have demonstrated that the combination of radiotherapy and immunotherapy can induce the abscopal effect and improve the prognosis of patients.Compared with the conventional radiotherapy,stereotactic radiotherapy has a larger single dose and higher accuracy,which is more likely to induce the bystander effect and anti-tumor response.The combination of stereotactic radiotherapy and immunotherapy has been proven to be a more promising therapy in certain clinical trials.However,not all types of tumors can benefit from such combined therapy in clinical practice.The optimal dose,fraction pattern and lesion of radiotherapy,immune enhancement and safety remain to be further clarified.In this article,the research progress,related controversies and future research direction of stereotactic radiotherapy combined with immunotherapy for malignancies were reviewed.

Betacoronavirus ; isolation & purification ; pathogenicity ; Bile Acids and Salts ; metabolism ; Bile Ducts, Intrahepatic ; pathology ; virology ; Cell Culture Techniques ; Coronavirus Infections ; complications ; pathology ; Cytokine Release Syndrome ; etiology ; physiopathology ; Cytopathogenic Effect, Viral ; Epithelial Cells ; enzymology ; pathology ; virology ; Humans ; Hyperbilirubinemia ; etiology ; Liver ; pathology ; Organoids ; pathology ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; analysis ; Pneumonia, Viral ; complications ; pathology ; Receptors, Virus ; analysis ; Serine Endopeptidases ; analysis ; Viral Load