Molecular mechanism of Tongmai Yangxin Pill intervention in elderly patients with coronary heart disease.

OBJECTIVE: The Tongmai Yangxin Pill (TMYX) is considered an effective treatment for coronary heart disease (CHD). However, its mechanism is unclear. This study aimed at exploring the molecular mechanisms and key genes of the TMYX in the treatment of CHD. MATERIALS AND METHODS: Differentially expressed genes (DEGs) in the GSE142008 dataset were screened with the R software, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Then, protein-protein interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes database. The correlation analysis between key genes was conducted, and gene expression was verified. RESULTS: A total of 1,614 DEGs were identified, including 1,591 upregulated and 23 downregulated genes. GO enrichment analysis revealed that 240 biological processes, 44 cellular components, and 23 molecular functions were significantly enriched for DEGs in elderly patients with CHD. Similarly, 36 KEGG terms were significantly enriched for DEGs. Ten key genes were screened, and after verification and analysis, seven key genes (RSL24D1, NMD3, DCAF13, WDR36, SDAD1, KRR1, and RPF1) were identified as significantly overexpressed. CONCLUSIONS: We identified seven key genes as candidate biomarkers for TMYX in the treatment of elderly patients with CHD; these results can serve as a theoretical basis for targeted therapy.

Increased risk of strontium ranelate-related SJS/TEN is associated with HLA.

UNLABELLED: Severe adverse drug reactions (ADR) of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in some patients receiving strontium ranelate have been reported, but the risk factors are unclear. We show that HLA-A*33:03 and B*58:01 are significantly associated with patients who developed SJS/TEN; and provide the first evidence that genetic risk factors are involved in strontium ranelate-associated SJS/TEN. INTRODUCTION: In this study, HLA as a genetic risk factor was assessed among osteoporotic patients prescribed with strontium ranelate that developed severe cutaneous adverse drug reactions (SCARs) compared with those who were tolerant. METHODS: Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) of patients was HLA typed using sequencing-based typing method to determine their HLA profiles. RESULTS: Osteoporotic patients who are currently on strontium ranelate were enrolled in the study (n = 76). Tolerant controls were defined as patients who received strontium ranelate for a minimum of 3 months (range 3 months to 8 years) with no reports of any cutaneous reactions as these reactions usually occur within the first 12 weeks after starting treatment. Retrospective cases of SJS/TEN were also identified (n = 5). The majority of the accrued samples were of Han Chinese descent: controls (n = 72) and cases (n = 4). All cases and controls were genotyped at four HLA genes, namely HLA-A, HLA-B, HLA-C, and HLA-DRB1. In comparing the samples of Han Chinese descent (72 controls and 4 cases), we found significant associations with HLA-A*33:03 (p = 0.002) and HLA-B*58:01 (p = 0.023). There was no significant association with any HLA-C or HLA-DRB1 alleles. CONCLUSIONS: This study reveals that the occurrence of SJS/TEN in Han Chinese patients receiving strontium ranelate is HLA associated. This has important clinical implications for understanding the underlying mechanisms for this ADR as well as evaluating the potential role of genetic pre-screening for osteoporotic patients who may be prescribed strontium ranelate.

Therapeutic effect of magnesium isoglycyrrhizinate in rats on lung injury induced by paraquat poisoning.

OBJECTIVE: The aim of this study was to investigate the effect of Magnesium Isoglycyrrhizinate (MgIG) on intercellular adhesion moledule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9) in rats with Paraquat (PQ) poisoning and its potential mechanism. MATERIALS AND METHODS: 30 male Sprague Dawley rats were randomly divided into five groups, including normal control group, poisoned control group, low-dose MgIG group, medium-dose MgIG group and high-dose MgIG group. Each group was treated with corresponding dose of MgIG once on daily basis by intraperitoneal injection 24 hours later, and the normal control group and poisoned control group were injected with physiological saline. All the animals were killed 14 days after poisoning, the contents of ICAM-1 and matrix MMP-9 were determined. HE staining and Masson staining were performed, the hydroxyproline (HYP) content in the lung tissue was also determined, and the expressions of ICAM-1 and MMP-9 were detected by immunohistochemical test. RESULTS: The contents of ICAM-1 and MMP-9 in the rat serum for all treatment groups were significantly decreased compared with those of the poisoned control group (p < 0.05, or < 0.01), and the expressions of the two proteins were significantly down-regulated, especially for the medium dose group. CONCLUSIONS: There is an improvement effect of ICAM-1 and MMP-9 in rats with Paraquat poisoning for the medium dose of MgIG, capable of slowing down the process of pulmonary fibrosis to certain extent.

Quantification of brain creatine concentration using PRESS sequence and LCModel: comparison with HPLC method.

To investigate the accuracy for quantification of brain total creatine (Cr) concentration using in vivo long echo time (TE) PRESS sequence with an external standard and LCModel. Ten swine and an external standard containing a detectable compounds of known concentration were studied by using 1.5 T GE Signa scanner and the standard head coil; the single-voxel proton magnetic resonance spectroscopy (1H-MRS) data was acquired from the 20-mm cubic VOI which was placed in the swine brain and external standard respectively by using the PRESS sequence with TE=135 msec, TR=1500 msec, and 128 scan averages. The quantification of Cr was accomplished by the linear combination of model spectra (LCModel). After MRS examination, each animal was sacrificed, and in vitro Cr concentration was analyzed by high performance liquid chromatography (HPLC). In the MRS group, the mean concentration of Cr was 9.37+/-0.137mmol/kg; in the HPLC group, the mean concentration of Cr was 8.905+/-0.126 mmol/kg. There were no statistically significant differences between two methods (P=0.491), which indicated that long TE PRESS sequence with an external standard can accurately detect the brain Cr concentration. The application of LCModel introduces more convenience for the MRS quantification.

Accuracy of noninvasive quantification of brain NAA concentrations using PRESS sequence: verification in a swine model with external standard.

The metabolite ratios had been employed in the field of MR spectroscopy (MRS) for a long period. The main drawback of metabolite ratio is that ratio results are not comparable with absolute metabolite concentration in vivo. The purpose of this study was to examine the accuracy of noninvasive quantification of brain N-acetylaspartate (NAA) concentrations using previously reported MR external standard method. Eight swine were scanned on a GE 1.5 T scanner with a standard head coil. The external standard method was utilized with a sphere filled with NAA, GABA, glutamine, glutamate, creatine, choline chloride, and myo-inositol. The position resolved spectroscopy (PRESS) sequence was used with TE=135 msec, TR=1500 msec, and 128 scan averages. The analysis of MRS was done with SAGE/IDL program. In vivo NAA concentration was obtained using the equation S=N * e(-TE/T2) * [1-e(-TR/T1). In vitro NAA concentration was measured by high performance liquid chromatography (HPLC). In the MRS group, the mean concentration of NAA was 10.03 plusmn 0.74 mmol/kg. In the HPLC group, the mean concentration of NAA was 9.22 plusmn 0.55 mmol/kg. There was no significant difference between the two groups (p = 0.46). However, slightly higher value was observed in the MRS group (7/8 swine), compared with HPLC group. The range of differences was between 0.02~2.05 mmol/kg. MRS external reference method could be more accurate than internal reference method. 1H MRS does not distinguish between N-acetyl resonance frequencies and other N-acetylated amino acids.