ABSTRACT
The gut microbiota and its metabolites have become a hotspot of recent research. Trimethylamine N-oxide (TMAO) metabolized by the gut microbiota is closely related to many diseases such as cardiovascular disease, chronic kidney disease, type 2 diabetes, etc. Chronic kidney disease (CKD) is an important contributor to morbidity and mortality from non-communicable diseases. Recently, increasing focus has been put on the role of TMAO in the development and progress of chronic kidney disease. The level of TMAO in patients with chronic kidney disease is significantly increased, and a high level of TMAO deteriorates chronic kidney disease. This article describes the relationship between TMAO and chronic kidney disease and the research progress of drugs targeted TMAO, providing a reference for the development of anti-chronic kidney disease drugs targeted TMAO.
ABSTRACT
The human leukocyte antigen (HLA) molecules encoded within the human major histocompatibility complex are a group of highly conserved cell surface proteins, which are related to antigen recognition. HLA genes display a high degree of genetic polymorphism, which is the basis of individual differences in immunity. Specific HLA genotypes have been highly associated with typical adverse drug reactions. HLA-A*31:01 and HLA-B*15:02 are associated with carbamazepine-induced severe cutaneous adverse reactions, HLA-B*57:01 is related to abacavir-induced drug-induced hypersensitivity syndrome and flucloxacillin/pazopanib-induced drug-induced liver injury, while HLA-B*35:01 is a potential biomarker for predicting polygonum multiflorum-induced liver injury. It is not clear how small drug molecules to interact with HLA molecules and T cell receptors (TCR). There are four mechanistic hypotheses, including the hapten/prohapten theory, the pharmacological interaction concept, the altered peptide repertoire model, and the altered TCR repertoire model.
Subject(s)
Humans , Drug-Related Side Effects and Adverse Reactions/genetics , Genotype , HLA Antigens/genetics , Polymorphism, GeneticABSTRACT
Generic drugs account for more than 95% of the chemicals market in China, and their quality is directly related to the efficacy and safety of the people. The bioequivalence evaluation with pharmacokinetic parameters as the end point is the main content of the consistency evaluation of the quality and efficacy of generic drugs. Gut microbiota is considered to have an important influence on pharmacokinetics. This article reviewed the influence of gut microbiota on pharmacokinetics and analyzed its potential significance in the evaluation of the consistency of quality and efficacy of generic drugs.
ABSTRACT
Objective:To investigate the dynamic expression and spatial distribution of P2X7 receptor in pilocarpine-induced epileptic rat hippocampus.Methods:Status epilepticus (SE) model of rats was established by intraperitoneal injection with chloride lithium and pilocarpine.Rat brain tissue and hippocampus were collected at 1,3,7,14,28 days after SE.The protein expression of P2X7 receptor in rat hippocampus was detected by Western blot.The distribution of P2X7 receptor in hippocampal sub-region was analyzed by immunohistochemistry.Results:Bilateral forelimb clonus appeared at (33.9±12.3 min after intraperitoneal injection with pilocarpine.The protein expression of P2X7 receptor was increased at 1d after SE,while it was decreased gradually from 3 d to minimum at 7 d,then it was elevated continuously to 28 d.Among them,the expression of P2X7 receptor was increased significantly at 1,14 and 28 d post-SE (P＜0.05).Immunohistochemical staining showed that P2X7 receptor was detected in all areas.The expression pattern of P2X7 receptor in hippocampal DG and CA3 area was consistent with protein expression,but its expression in hippocampal CA1 area was not significantly changed after SE.Conclusion:The expression of P2X7 receptor in post-SE hippocampus is in a time-dependent manner and spatial specificity.P2X7 receptor might be involved in the development of chronic epilepsy.
