Human serum metabolomic analysis reveals progression for high blood pressure in type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is one of the most ordinary metabolic disorders and manifests as a high blood sugar level; 80%-90% of patients with T2DM will develop high blood pressure (HBP), which exacerbates irreversible organ damage. Understanding the metabolic basis of HBP is essential to facilitating early diagnosis and prompt treatments of diabetic complications. RESEARCH DESIGN AND METHODS: 34 patients who originally had T2DM and then developed HBP within 1 year were selected from physical examination participants. Using ultrahigh-performance liquid chromatography quadrupole time-of-flight metabolomic analysis, we compared the metabolomic profile of patients with 30 healthy controls. The results showed a clear discrimination in metabolomic profiles between T2DM and T2DM+HBP when employing orthogonal projection to latent structure with discriminant analysis with electrospray ionization modes. RESULTS: Eight differential metabolites changed significantly during disease progression, among which L-isoleucine, L-glutamic acid, pyroglutamic acid and linoleic acid decreased, while sphinganine, Cer(d18:0/16:0), Cer(d18:0/18:0), and citric acid increased. These metabolites are associated with the γ-glutamyl cycle, tricarboxylic acid cycle, and ceramide metabolism. CONCLUSIONS: These novel serum biomarkers may improve the management of T2DM and HBP complications, thus reducing the use of incorrect medical care.

Synergistic effects of anti-MRSA herbal extracts combined with antibiotics.

MRSA is a super drug-resistant bacterium. Developing new drug or therapeutic strategies against MRSA is urgently needed. Increasing evidence has shown that herbal extracts and antibiotics can have synergistic effects against MRSA. This review focuses on commonly used antibiotics combined with herbal extracts against MRSA and the corresponding mechanisms. Through systematic analysis, we found that herbal extracts combined with antibiotics, such as ß-lactams, quinolones, aminoglycosides, tetracyclines and glycopeptides, could greatly enhance the antibacterial effects of the antibiotics, reduce the dosage and toxic side effects, and reverse MRSA resistance. Therefore, we conclude that herbal extracts combined with antibiotics may be a promising strategy to combat MRSA. This review provides a novel idea for overcoming antibiotic resistance.

A pilot study to identify the longitudinal serum metabolite profiles to predict the development of hyperuricemia in essential hypertension.

BACKGROUND: Essential hypertension (EHT) is the most prevalent chronic medical condition and a major risk factor for cardiovascular morbidity and mortality. EHT often progresses and combines with hyperuricemia (HU) in clinical cases, which increases organ damage in patients with EHT. We compared serum metabolites in EHT patients with EHT + HU patients and to find metabolic markers and related pathways in the progression of EHT to EHT + HU. METHODS: A longitudinal study was carried out in 35 patients (initially EHT and EHT + HU one year later). With 10 metabolites in EHT + HU identified as potential biomarkers, linoleic acid metabolism, sphingolipid metabolism, steroid hormone biosynthesis, starch and sucrose metabolism and purine metabolism interacted with EHT + HU. RESULTS: Distinct changes in the metabolomics profile of sera were observed among healthy controls (HC), EHT and EHT + HU groups. Uric acid (UA), L-lactic acid, and quinolinic acid may play important roles in the progression from EHT to EHT + HU. They were mainly involved in pyruvate metabolism, purine metabolism and nicotinate and nicotinamide metabolism pathways. CONCLUSIONS: The continuous elevation of L-lactic acid and quinolinic acid might be useful for understanding the mechanisms of pathogenesis in EHT + HU and provide prospects for preventing the development of EHT and HU.

Low Level Antibodies Against Alpha-Tropomyosin Are Associated With Increased Risk of Coronary Heart Disease.

OBJECTIVE: Natural autoantibodies have been implicated to play a key role in the pathogenesis of coronary heart disease (CHD) because they augment autoimmune activation. The aim of this study was to identify novel specific autoantibodies of CHD, and analyze the relationship between their levels and CHD risk indicators. APPROACH AND RESULTS: First, clinical data and sera from CHD patients were collected. Then, one protein microarray containing 37 proteins that represent candidate autoantigens was developed. The arrays were used to profile autoantibodies in randomly selected sera from 35 samples (20 CHD patients, and 15 healthy controls). After that, microarray data were analyzed and autoantibodies for CHD were screened out. Then, ELISA detection was conducted to validate the differentiable autoantibodies using larger numbers of serum samples (131 CHD patients, and 131 healthy controls). Finally, the associations of antibodies with CHD risk indicator parameters were assessed. Inter-group comparison by microarray indicated that three CHD novel autoantibodies, including glucose-6-phosphate isomerase (G6PI), alpha-tropomyosin (TPM1), and heterogeneous nuclear ribonucleoprotein D-like (HnRNPDL), were significantly (P < 0.05) increased when compared with the healthy controls. Moreover, a significant increase of IgG autoantibodies for these three autoantigens was confirmed in CHD patients by ELISA (P < 0.0001). The correction analysis revealed a negative correlation of anti-TPM1 antibody levels and total cholesterol (P = 0.0034), and low-density lipoprotein cholesterol (P = 0.0086), respectively. CONCLUSION: G6PI, TPM1, and HnRNPDL were CHD natural autoantigens, and serum anti-TPM1 antibody could be used as a potential marker to predict the risk for CHD patients.

Effect of Andrographolide and Its Analogs on Bacterial Infection: A Review.

Bacterial infections remain the leading cause of death in children, the elderly, and immunocompromised patients. Andrographolide (AG), the main active component of the herb Andrographis paniculata, has been used for many years for anti-inflammatory and antibacterial infections. AG has an antibacterial effect on a wide variety of bacteria, which is reflected in the inhibition of bacterial pathogenic factors and the regulation of immunity to downregulate infectious inflammation caused by bacteria. In the current climate of frequently occurring antibiotic resistance, AG might be considered a promising lead for new antibacterial drug development. This review outlines the therapeutic potential of AG and its analogs in combating various bacterial infections, focusing on the mechanisms of action.

Identification of Characteristic Autoantibodies Associated With Deficiency Pattern in Traditional Chinese Medicine of Rheumatoid Arthritis Using Protein Chips.

Background: Rheumatoid arthritis (RA) is an autoimmune disease. Based on traditional Chinese medicine (TCM) theory, deficiency pattern (DP) which leads to specific treatment principles in clinical management is a crucial pattern diagnosis among RA patients, and autoantibodies have potential implications in TCM pattern classification. The purpose of this study was to identify specific RA DP-associated autoantibodies. Methods: RA DP patients, RA nondeficiency pattern (NDP) patients and healthy controls (HCs) were recruited for this study. Then, clinical data and sera from all subjects were collected. After that, the sera were probed with protein chips, which were constructed by known RA related autoantigens, to screen for DP-associated candidate autoantibodies. Lastly, candidate autoantibodies were validated via enzyme-linked immunosorbent assay (ELISA) and function was evaluated by network analysis. Results: Protein chips results showed that RA patients have higher levels of anti-vascular endothelial growth factor (VEGF) A165 antibodies than HC (P < 0.005); anti-VEGFA165 antibodies levels of patients with RA DP were lower than patients with RA NDP (P < 0.05). The results of the ELISA also showed statistically significant differences in anti-VEGFA165 antibodies between the RA and HC group (P < 0.0001); and there were statistically significant differences in anti-VEGFA165 antibodies between the RA DP and RA NDP group (P < 0.05). Network analysis results suggested IL-6 signaling pathway has a significant effect on VEGFA165 in RA patients. Conclusion: Autoantibodies identification in RA using protein chips help in understanding DP in TCM. Discovery of anti-VEGFA165 antibodies may provide the possibility for clinical precision treatment.