Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders.

HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS-INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS-INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS-INRs. In our study, to identify the typical HIV/AIDS-INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome-specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs-INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS-INRs.

Proteomic investigation and biomarker identification of lung and spleen deficiency syndrome in HIV/AIDS immunological nonresponders.

Background: Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) immunological nonresponders (HIV/AIDS-INRs) whose CD4+ cell counts do not rebound after highly active antiretroviral therapy (HAART) treatment usually experience severely impaired immune function and high mortality. Traditional Chinese medicine (TCM) has many advantages in the field of AIDS, especially its promotion of patients' immune reconstitution. Accurate differentiation of TCM syndromes is a prerequisite for guiding an effective TCM prescription. However, the objective and biological evidence for identification of the TCM syndromes in HIV/AIDS-INRs remains lacking. Lung and spleen deficiency (LSD) syndrome, a typical HIV/AIDS-INR syndrome, was examined on in this study. Methods: We first performed a proteomic study of LSD syndrome in INRs (INRs-LSD) using tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS) and screened them against the healthy and undocumented identifiable groups. The TCM syndrome-specific proteins were subsequently validated based on bioinformatics analysis and enzyme-linked immunosorbent assay (ELISA). Results: A total of 22 differentially expressed proteins (DEPs) were screened in INRs-LSD compared to the healthy group. Based on bioinformatic analysis, these DEPs were found to be mainly associated with the immunoglobin A (IgA)-generated intestinal immune network. In addition, we examined the TCM syndrome-specific proteins alpha-2-macroglobulin (A2M) and human selectin L (SELL) with ELISA and found that they were both upregulated, which was consistent with the proteomic screening results. Conclusions: A2M and SELL were finally identified as potential biomarkers for INRs-LSD, providing a scientific and biological basis for identifying typical TCM syndromes in HIV/AIDS-INRs and an opportunity to build a more effective TCM treatment system for HIV/AIDS-INRs.

Biological Differentiation of Dampness-Heat Syndromes in Chronic Hepatitis B: From Comparative MicroRNA Microarray Profiling to Biomarker Identification.

Increasing interest is aroused by traditional Chinese medicine (TCM) treatment of chronic hepatitis B (CHB) based on specific TCM syndrome. As the most common CHB syndromes, spleen-stomach dampness-heat (SSDH) syndrome and liver-gallbladder dampness-heat (LGDH) syndrome are still apt to be confused in TCM diagnosis, greatly hindering the stable exertion of TCM effectiveness. It is urgently needed to provide objective and biological evidences for differentiation and identification of the two significant syndromes. In this study, microRNA (miRNA) microarray analyses coupled with bioinformatics were employed for comparative miRNA profiling of SSDH and LGDH patients. It was found that the two syndromes had both the same and different significantly differentially expressed miRNAs (SDE-miRNAs). Commonness and specificity were also both found between their SDE-miRNA-based bioinformatics analyses, including Hierarchical Clustering, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and miRNA-GO/pathway networks. Furthermore, syndrome-specific SDE-miRNAs were identified as the potential biomarkers, including hsa-miR-1273g-3p and hsa-miR-4419b for SSDH as well as hsa-miR-129-1-3p and hsa-miR-129-2-3p for LGDH. All these laid biological and clinical bases for classification and diagnosis of the two significant CHB dampness-heat syndromes including SSDH and LGDH, providing more opportunities for better application of TCM efficacy and superiority in CHB treatment.