ABSTRACT
ETHNIC PHARMACOLOGICAL RELEVANCE: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease (ESRD), which is a public health problem with a significant economic burden. Serious adverse effects, such as hypotension, hyperkalemia, and genitourinary infections, as well as increasing adverse cardiovascular events, limit the clinical application of available drugs. Plenty of randomized controlled trials(RCTs), meta-analysis(MAs) and systematic reviews(SRs) have demonstrated that many therapies that have been used for a long time in medical practice including Chinese patent medicines(CPMs), Chinese medicine prescriptions, and extracts are effective in alleviating DKD, but the mechanisms by which they work are still unknown. Currently, targeting inflammation is a central strategy in DKD drug development. In addition, many experimental studies have identified many Chinese medicine prescriptions, medicinal herbs and extracts that have the potential to alleviate DKD. And part of the mechanisms by which they work have been uncovered. AIM OF THIS REVIEW: This review aims to summarize therapies that have been proven effective by RCTs, MAs and SRs, including CPMs, Chinese medicine prescriptions, and extracts. This review also focuses on the efficiency and potential targets of Chinese medicine prescriptions, medicinal herbs and extracts discovered in experimental studies in improving immune inflammation in DKD. METHODS: We searched for relevant scientific articles in the following databases: PubMed, Google Scholar, and Web of Science. We summarized effective CPMs, Chinese medicine prescriptions, and extracts from RCTs, MAs and SRs. We elaborated the signaling pathways and molecular mechanisms by which Chinese medicine prescriptions, medicinal herbs and extracts alleviate inflammation in DKD according to different experimental studies. RESULTS: After overviewing plenty of RCTs with the low hierarchy of evidence and MAs and SRs with strong heterogeneity, we still found that CPMs, Chinese medicine prescriptions, and extracts exerted promising protective effects against DKD. However, there is insufficient evidence to prove the safety of Chinese medicines. As for experimental studies, Experiments in vitro and in vivo jointly demonstrated the efficacy of Chinese medicines(Chinese medicine prescriptions, medicinal herbs and extracts) in DKD treatment. Chinese medicines were able to regulate signaling pathways to improve inflammation in DKD, such as toll-like receptors, NLRP3 inflammasome, Nrf2 signaling pathway, AMPK signaling pathway, MAPK signaling pathway, JAK-STAT, and AGE/RAGE. CONCLUSION: Chinese medicines (Chinese medicine prescriptions, medicinal herbs and extracts) can improve inflammation in DKD. For drugs that are effective in RCTs, the underlying bioactive components or extracts should be identified and isolated. Attention should be given to their safety and pharmacokinetics. Acute, subacute, and subchronic toxicity studies should be designed to determine the magnitude and tolerability of side effects in humans or animals. For drugs that have been proven effective in experimental studies, RCTs should be designed to provide reliable evidence for clinical translation. In a word, Chinese medicines targeting immune inflammation in DKD are a promising direction.
ABSTRACT
Atherosclerosis (AS) is the main cause of death in individuals with cardiovascular and cerebrovascular diseases. A growing body of evidence suggests that oxidative stress plays an essential role in Atherosclerosis pathology. The aim of this study was to determine genetic mechanisms associated with Atherosclerosis and oxidative stress, as well as to construct a diagnostic model and to investigate its immune microenvironment. Seventeen oxidative stress-related genes were identified. A four-gene diagnostic model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm based on these 17 genes. The area under the Receiver Operating Characteristic (ROC) curve (AUC) was 0.967. Based on the GO analysis, cell-substrate adherens junction and focal adhesion were the most enriched terms. KEGG analysis revealed that these overlapping genes were enriched in pathways associated with Alzheimer's disease and Parkinson's disease, as well as with prion disease pathways and ribosomes. Immune cell infiltration correlation analysis showed that the immune cells with significant differences were CD4 memory activated T cells and follicular helper T cells in the GSE43292 dataset and CD4 naïve T cells and CD4 memory resting T cells in the GSE57691 dataset. We identified 17 hub genes that were closely associated with oxidative stress in AS and constructed a four-gene (aldehyde dehydrogenase six family member A1 (ALDH6A1), eukaryotic elongation factor 2 kinase (EEF2K), glutaredoxin (GLRX) and l-lactate dehydrogenase B (LDHB)) diagnostic model with good accuracy. The four-gene diagnostic model was also found to have good discriminatory efficacy for the immune cell infiltration microenvironment of AS. Overall, these findings provide valuable information and directions for future research into Atherosclerosis diagnosis and aid in the discovery of biological mechanisms underlying AS with oxidative stress.
