ABSTRACT
Polysaccharide (PS) is one of the principal constituents in most traditional Chinese medicine. In recent years, the efficacy of PS has gradually become a popular aspect in fields of life science. Meanwhile, its pharmacokinetic research is still in its infancy. The classification, bioanalytical methods and pharmacokinetics of PS in recent years are summarized in this review. We hope to provide reference and guidance for researchers to study the pharmacokinetics of PS.
ABSTRACT
The three-dimensional (3D) conformation of chromatin is integral to the precise regulation of gene expression. The 3D genome and genomic variations in non-alcoholic fatty liver disease (NAFLD) are largely unknown, despite their key roles in cellular function and physiological processes. High-throughput chromosome conformation capture (Hi-C), Nanopore sequencing, and RNA-sequencing (RNA-seq) assays were performed on the liver of normal and NAFLD mice. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments, topologically associated domains (TADs), and chromatin loops by Hi-C, and whole genome sequencing identifying structural variations (SVs) and copy number variations (CNVs) by Nanopore sequencing. We identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements, between normal and NAFLD mice, and revealed gene dysregulation frequently accompanied by these variations. Candidate target genes were identified in NAFLD, impacted by genetic rearrangements and spatial organization disruption. Our data provide a high-resolution 3D genome interaction resource for NAFLD investigations, revealed the relationship among genetic rearrangements, spatial organization disruption, and gene regulation, and identified candidate genes associated with these variations implicated in the pathogenesis of NAFLD. The newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.
ABSTRACT
Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I (DHP-I), was developed. In present study, the potential roles of renal organic anion transporters (OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated and in rabbits. Our results indicated that imipenem and cilastatin were substrates of hOAT1 and hOAT3. Cilastatin inhibited hOAT1/3-mediated transport of imipenem with IC values comparable to the clinical concentration, suggesting the potential to cause a clinical drug-drug interaction (DDI). Moreover, imipenem exhibited hOAT1/3-dependent cytotoxicity, which was alleviated by cilastatin and probenecid. Furthermore, cilastatin and probenecid ameliorated imipenem-induced rabbit acute kidney injury, and reduced the renal secretion of imipenem. Cilastatin and probenecid inhibited intracellular accumulation of imipenem and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells. Renal OATs, besides DHP-I, was also the target of interaction between imipenem and cilastatin, and contributed to the nephrotoxicity of imipenem. This therefore gives in part the explanation about the mechanism by which cilastatin protected against imipenem-induced nephrotoxicity. Thus, OATs can potentially be used as a therapeutic target to avoid the renal adverse reaction of imipenem in clinic.
ABSTRACT
Microemulsions are promising drug delivery systems for the oral administration of poorly water-soluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized, especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.
ABSTRACT
Partial hepatectomy (PH) is an effective method for the treatment of various liver tumors,and liver regeneration dysfunction is one of the most serious complications.Therefore,liver regeneration (LR) after PH is particularly important.In this paper,we reviewed the molecular mechanisms of LR including cellular factors,growth factors,metabolism and related signaling pathways,and reviewed the research progresses of the traditional Chinese medicine (TCM) in promoting liver regeneration.The aim was to further clarify the mechanism of the occurrence and development of LR,and to provide valuable information for the development of drugs for treating liver regeneration disorders.
ABSTRACT
The abnormal accumulation of extracellular matrix (ECM) in liver is the main feature of hepatic fibrosis,and collagen is the most important component in ECM.Collagen plays an important role in the occurrence and development of liver fibrosis.Therefore,to find traditional Chinese medicine with significant effect on collagen metabolism has become a critical approach for the treatment of hepatic fibrosis.This review summarized the role of collagen metabolism in liver fibrosis,and the research progress in traditional Chinese medicines with anti-hepatic fibrosis effect by regulating collagen metabolism was explored as well.
ABSTRACT
Acute kidney injury (AKI), a common clinical dis-ease, is one complex pathophysiological process. In this review paper, the relationship and the molecular mechanisms of ische-mia-reperfusion, major surgery, rhabdomyolysis, pus sepsis and drug-induced renal toxicity associated with AKI were comprehen-sively reviewed. In addition, the prevention and treatment of AKI by Chinese medicine and the effective components were also reviewed. Therefore, our review aims to provide valuable infor-mation for treatment of AKI, and also for exploration of innova-tive new drugs.