ABSTRACT
Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.
Subject(s)
Fluorescent Dyes , Glioblastoma , Mitochondria , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Humans , Glioblastoma/diagnostic imaging , Glioblastoma/pathology , Mitochondria/metabolism , Viscosity , Cell Line, Tumor , Animals , Mice , Mice, Nude , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Optical ImagingABSTRACT
Due to changes in lifestyle, diet structure, and aging worldwide, the incidence of metabolic syndromes such as hyperlipidemia, hypertension, diabetes, and obesity is increasing. Metabolic syndrome is considered to be closely related to cardiovascular disease and severely affects human health. In recent years, researchers have revealed that the gut microbiota, through its own or interacting metabolites, has a positive role in regulating metabolic syndrome. Therefore, the gut microbiota has been a new "organ" for the treatment of metabolic syndrome. The role has not been clarified, and more research is necessary to prove the specific role of specific strains. Probiotics are also believed to regulate metabolic syndromes by regulating the gut microbiota and are expected to become a new preparation for treating metabolic syndromes. This review focuses on the regulation of lipid metabolism disorders by the gut microbiota through the effects of bile acids (BA), short-chain fatty acids (SCFAs), bile salt hydrolase (BSH), and genes such as ABCG5 and ABCG8, FXR, NPC1L, and LDL-R.
ABSTRACT
OBJECTIVE: To study the extraction system of hirudin emulsion liquid membrane with the Poecilobdella manillensis as raw material, di-(2-ethylhexyl) phosphate (D2EHPA) as carrier, Span 80 as emulsifier, octane and D2EHPA mixed to constitute membrane solution, diluted HCl solutions as internal aqueous phase. METHOD: Using the orthogonal experiment to optimize the extraction conditions of hirudin reference substance such as membrane phase, internal aqueous phase volume ratio (MIPVR), external aqueous phase pH, internal aqueous phase pH, mobile carrier concentration and so on, and then using hirudin crude extracts to do purifying experiment, and gaining experimental samples. RESULT: The optimal conditions of hirudin extraction were as follows: MIPVR 10: 3, internal aqueous phase pH 2.6, external aqueous phase pH 3.4, the mass fraction of carrier D2EHPA 2%. In the optimal extraction conditions, when the initial concentration of hirudin was one anti-thrombin activity units (ATU) x mL(-1), ATU recovery rate of the reference substance was 83.06%. In the purifying experiment of crude extracts, ATU recovery rate was 82.99%, and the specific activity of sample was 3 289.48 the ATU x mg(-1). Discontinuous polyacrylamide gel electrophoresis and spectral scanning, the results showed that the purity and reference substance were considerable. CONCLUSION: The method of preparation hirudin was relatively simple, the purity of the experimental samples and ATU recovery were both high.
