ABSTRACT
Bacterial extracellular vesicles (BEVs) are nano-size particles secreted by bacteria that carry various bioactive components. These vesicles are thought to provide a new window into the mechanisms by which bacteria affect their hosts, but their fundamental proprieties within human remain poorly understood. Here, we developed a single-vesicle analytical platform that enabled BEV detection in complex biological samples of host. Using this platform, we found the presence of BEVs in the host circulation and they were mainly derived from gut microbes. We showed that the levels of circulating BEVs in humans significantly increased with aging due to an age-related increase in intestinal permeability. Significantly different levels of BEVs in blood were also found in patients with colorectal cancer and colitis. Together, our study provides new insights into circulating BEV biology and reveals their potential as a new class of biomarkers.
Subject(s)
Extracellular Vesicles , Humans , BacteriaABSTRACT
Typical endocrine disrupting chemicals, including BPA (Bisphenol A), E2 (17-ß-Estradiol) and PCB 72 (polychlorinated biphenyl 72), are commonly and widely present in the environment with good chemical stability that are difficult to decompose in vitro and in vivo. Most of the high-qualified antibodies are required as the key biomaterials to fabricate the immunosensor for capturing and detecting. As an ideal alternative, the short-chain oligonucleotides (aptamer) are essentially and effectively employed with the advantages of small size, chemical stability and high effectiveness for monitoring these environmental contaminants. However, the molecular interaction, acting site and mode are still not well understood. In this work, we explored the binding features of the aptamers with their targeting ligands. The molecular dynamics simulations were performed on the aptamer-ligand complex systems. The stability of each simulation system was evaluated based on its root-mean-square deviation. The affinities of these proposed ligands and the predicted binding sites are analyzed. According to the binding energy analysis, the affinities between ligands and aptamers and the stability of the systems are BPA > PCB 72 >E2. Trajectory analysis for these three complexes indicated that these three ligands were able to steadily bind with aptamers at docking site from 0 to 50 ns and contributed to alteration of conformation of aptamers.
Subject(s)
Aptamers, Nucleotide/chemistry , Endocrine Disruptors/chemistry , Benzhydryl Compounds/chemistry , Binding Sites , Estradiol/chemistry , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , Phenols/chemistry , Polychlorinated Biphenyls/chemistryABSTRACT
It has been suggested that renal denervation (RD) may attenuate left ventricular (LV) hypertrophy. However, the role that autophagy serves in this process is currently unclear. In the present study, utilizing a model of hypertensioninduced cardiac hypertrophy in spontaneous hypertensive rats, it was demonstrated that RD was significantly associated with a reduction in LV hypertrophy. Furthermore, a decrease in the myocardial mRNA of hypertrophyassociated genes was demonstrated in RD rats compared with sham controls. In addition, RD in hypertensioninduced LV hypertrophy rats was associated with the attenuation of cellular autophagic response over activation at a physiological level. This was indicated by a reduction in the expression of Beclin1, autophagy related 9A and microtubuleassociated protein 1A/1B-light chain 3 II/I in RD rats to physiological levels that are observed in control rats. Furthermore, the number of autophagosomes was restored to physiological levels in the cardiomyocytes of RD rats. The results of the current study suggest that RD may attenuate LV hypertrophy via the regulation of autophagic responses.
Subject(s)
Autophagy , Cardiomegaly/pathology , Denervation , Kidney/innervation , Animals , Blood Pressure , Cardiomegaly/physiopathology , Heart Ventricles/pathology , Kidney/pathology , Myocardium/metabolism , Myocardium/pathology , Myocardium/ultrastructure , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Inbred SHR , Rats, Inbred WKY , Vacuoles/metabolism , Vacuoles/ultrastructureABSTRACT
LC3B is a marker of autophagic activity, and growing evidence supports its importance in myocardial hypertrophy. Thus, regulating LC3B expression may provide an important avenue to inhibit autophagy and protect against or inhibit pathological myocardial hypertrophy. To address this question, we investigated the effects of altering LC3B mRNA expression and autophagic activity in the setting of cardiomyocyte hypertrophy. In an in vitro angiotensin II (Ang II)-induced cardiomyocyte hypertrophy model, LC3B mRNA and protein expression was increased and there was activation of cardiomyocyte autophagy, which was assessed by transmission electron microscopy and flow cytometry. LC3B cDNA transfection also resulted in an upregulation of autophagic activity, whereas downregulation of autophagic activity was observed with knockdown of LC3B expression. Induction of LC3B expression was shown to further exacerbate Ang II-stimulated cardiomyocyte hypertrophy, whereas inhibition of LC3B expression inhibited the Ang II-stimulated cardiomyocyte hypertrophy (as assessed through cardiomyocyte morphology and expression of ANP and ß-MHC). This study demonstrated that LC3B modulates the Ang II-induced cardiomyocyte hypertrophy in cultured neonatal rat ventricular cardiomyocytes.