Developmental validation of the STRSeqTyper122 kit for massively parallel sequencing of forensic STRs.

Massively parallel sequencing allows for integrated genotyping of different types of forensic markers, which reduces DNA consumption, simplifies experimental processes, and provides additional sequence-based genetic information. The STRseqTyper122 kit genotypes 63 autosomal STRs, 16 X-STRs, 42 Y-STRs, and the Amelogenin locus. Amplicon sizes of 117 loci were below 300 bp. In this study, MiSeq FGx sequencing metrics for STRseqTyper122 were presented. The genotyping accuracy of this kit was examined by comparing to certified genotypes of NIST standard reference materials and results from five capillary electrophoresis-based kits. The sensitivity of STRseqTyper122 reached 125 pg, and > 80% of the loci were correctly called with 62.5 pg and 31.25 pg input genomic DNA. Repeatability, species specificity, and tolerance for DNA degradation and PCR inhibitors of this kit were also evaluated. STRseqTyper122 demonstrated reliable performance with routine case-work samples and provided a powerful tool for forensic applications.

Effect of azilsartan on myocardial remodeling after acute myocardial infarction.

PURPOSE: To investigate the effect of azilsartan on myocardial remodeling after acute myocardial infarction (AMI). METHODS: A total of 200 AMI patients under percutaneous coronary intervention (PCI) were selected from the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from Jan 2021 to Dec 2021. The subjects were randomly divided to take either azilsartan or benazepril. Serum C1q tumor necrosis factor-associated protein 1 (CTRP1) levels were detected in all subjects after admission, and the indices of left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) were measured by using echocardiography. At the follow-up of 6 months and 1 year after PCI, the differences in CTRP1 and echocardiogram indices between the two groups were compared, and the influencing factors of myocardial remodeling after acute myocardial infarction were analyzed. RESULTS: The levels of LVEDV and CTRP1 in all subjects at 6 months and 1 year after PCI were lower than those before discharge, and the LVEDV in the azilsartan group at 6 months and 1 year after PCI was lower than that in the benazepril group. An improvement in myocardial remodeling was obviously observed within 6 months after PCI, but the effect declined over time. CONCLUSIONS: Azilsartan can improve myocardial remodeling after acute myocardial infarction. CTRP1 may become an effective target for the prevention and treatment of myocardial remodeling after acute myocardial infarction.

Reduced expression of transmembrane protein 43 during cardiac hypertrophy leads to worsening heart failure in mice.

Transmembrane protein 43 (TMEM43), a member of the transmembrane protein subfamily, was found to be associated with arrhythmogenic right ventricular cardiomyopathy. However, its role in cardiac hypertrophy has not been elucidated. Here, we used a pressure overload-induced cardiac hypertrophy model to explore the role of TMEM43 in heart failure. Mice were subjected to aortic banding (AB) to induce cardiac hypertrophy. The mice were also randomly selected to receive injection of adeno-associated virus 9 (AAV9)-shTMEM43 to knockdown TMEM43 in cardiomyocytes or control AAV9 (ScRNA). Four weeks after AB, the mice were subjected to echocardiography to evaluate cardiac function. Neonatal rat cardiomyocytes (NRCMs) were stimulated with angiotensin II (AngII, 1 µM) and transfected with an adenovirus to over-express TMEM43. We found that TMEM43 was downregulated in mouse hearts and cardiomyocytes poststimulation. Mice with TMEM43 knockdown showed worsening heart failure accompanied by deteriorating cardiac function and exacerbated cardiac hypertrophy and fibrosis at 4 weeks post-AB. NRCMs over-expressing TMEM43 exhibited an ameliorated hypertrophic response. Moreover, we found that TMEM43 deficiency increased nuclear factor kappa B (NF-κB) activation in mouse hearts post-AB, while TMEM43 over-expression reduced NF-κB activation in cardiomyocytes upon AngII stimulation. Thus, we conclude that reduced expression of TMEM43 during cardiac hypertrophy leads to worsening heart failure in mice.

[Anti-inflammatory and analgesic potency of carboxyamidotriazole, a tumoristatic agent].

OBJECTIVE: To explore the potential anti-inflammatory and analgesic activities of carboxyamidotriazole (CAI). METHODS: A variety of animal models, including the croton oil-induced ear edema, the cotton-induced granuloma, the rat adjuvant-induced arthritis, were used to evaluate anti-inflammatory effect of CAI. Vascular endothelial growth factor (VEGF)--or histamine-stimulated local vascular permeability in mouse modulated by CAI was also determined. In addition, we assessed the effect of CAI on the levels of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-beta) at the site of inflammation and in sera. Moreover, antinociceptive effect of CAI on inflammatory pain was assessed using acetic acid-induced writhing model and the formalin test. RESULTS: CAI significantly inhibited acute and chronic phases of inflammation, reduced VEGF or histamine-induced vascular permeability, and showed marked inhibition of proinflammatory cytokines such as TNF-alpha and IL-1 beta. CAI also showed potential therapeutic effect on peripheral inflammatory pain. CONCLUSION: CAI is a promising anti-inflammatory and analgesic agent.