The Expression and Role of microRNA-133a in Plasma of Patients with Kawasaki Disease.

Kawasaki disease (KD)), also known as mucocutaneous lymph node syndrome (MCLS), is an autoimmune and systemic vasculitis syndrome. Its etiology and pathogenesis are still unclear. microRNAs (miRNA), a novel class of small non-coding RNAs, regulate the expression of multiple protein-encoding genes at the post-transcriptional level. We intend to study the change of miRNA-133a in the plasma of patients with KD, explore the role of miRNA-133a on HUVEC and define the pathogenesis of vascular dysfunction in KD. miRNA-133a expression and the mRNA and protein expression of protein phosphatase 2 catalytic subunit alpha (PPP2CA) were assessed by RT-qPCR and Western blot, respectively. The PPP2CA mRNA 3'UTR was predicted to be the potential target of miRNA-133a by using the miRNA databases and verified by the luciferase assay. The plasmids of miRNA-133a mimics and inhibitors were transfected into HUVEC cells. The plasma soluble vascular endothelial cadherin (sVE-cadherin, the excised extracellular part of VE-cadherin) levels were investigated by ELISA. The results suggested that miRNA-133a was increased by 3.8 times in the acute KD group and by 2.7 times in the convalescent KD group compared with the control group (both P = .000). PPP2CA is the target gene of miRNA-133a and its expression was inhibited by miRNA-133a acting on PPP2CA mRNA 3'UTR (P = .013). The plasma sVE-cadherin levels in the acute KD groups were increased compared with the control group (P = .024). The ROC curve analysis showed that the expression of miRNA-133a segregate acute KD patients from convalescent KD patients and healthy children. Our results suggest that miRNA-133a might be a new biomarker for KD.

Single-nucleotide Polymorphism rs17860041 A/C in the Promoter of the PPIA Gene is Associated with Susceptibility to Kawasaki Disease in Chinese Children.

Background: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. Cyclophilin A (CypA), also known as PPIA, has been identified to play a vital role in the pathogenesis of cardiovascular or inflammatory diseases. However, no studies have examined the relationship between single-nucleotide polymorphisms (SNPs) in the peptidylprolyl isomerase A (PPIA) and the development of KD and KD with or without coronary artery lesions (CALs). Objective: The present study was conducted to evaluate whether PPIA SNPs are associated with susceptibility to KD or CALs in KD. Methods: Three PPIA SNPs were genotyped in 101 KD patients and 105 healthy controls from a Chinese population. The allele and genotype frequencies were compared between the case and control groups, as well as in KD patients with and without CALs. Results: The data revealed a significant difference in the genotype and allele frequencies of rs17860041 A/C between KD patients and normal controls. Compared to the rs17860041 CC genotype, the AC genotype demonstrated a consistently beneficial roles in reducing the KD incidence. Furthermore, the allele frequency of C in the KD group was higher than that in the control group (P < .05). Haplotype analysis for PPIA polymorphisms (rs10951772 A/G, rs17860041 A/C, and rs4720485 A/T) also confirmed this association in KD patients and normal controls. Conclusion: A PPIA promoter SNP (rs17860041 A/C) confers susceptibility to KD in Chinese children and was identified as an important marker of KD in this study.

Spectrum of Ankyrin Mutations in Hereditary Spherocytosis: A Case Report and Review of the Literature.

BACKGROUND/AIMS: Hereditary spherocytosis (HS) is a common pediatric hemolytic anemia caused by congenital red blood cell defects. HS due to ankyrin 1 (ANK1) mutations is the most common type. We explored an ANK1 mutation from an HS patient and reviewed the literature. METHODS: We detected the mutation in a Chinese family in which 2 members were diagnosed with HS by next-generation sequencing. The proband was diagnosed with HS in the newborn period, based on clinical manifestations, laboratory data, and family history. The mutation spectrum of the ANK1 gene was summarized based on 85 patients diagnosed with HS carrying ANK1 mutations, and the ANK1 mutation spectrum was summarized and analyzed. RESULTS: We identified a novel mutation affecting ANK1 gene splicing (a splicing mutation) in both the patient and her mother, which is a substitution of T>G 2 nt after exon 25 in intron 26. The study expands our knowledge of the ANK1 gene mutation spectrum, providing a molecular basis for HS. CONCLUSION: A novel ANK1 mutation (NM_000037.3, c.2960+2T>G, intron 26) that is potentially associated with HS was identified. To date, 80 ANK1 mutations have been reported to be associated with HS in humans.

Study on Pharmacokinetic Interactions Between HS-10234 and Emtricitabine in Healthy Subjects: An Open-Label, Two-Sequence, Self-Controlled Phase I Trial.

INTRODUCTION: HS-10234, a novel prodrug of tenofovir (TFV), functions by inhibiting nucleotide reverse transcriptase against retroviral infections including hepatitis B virus and human immunodeficiency virus (HIV). As it is a possible substitute for TFV co-administration with emtricitabine, determining the drug-drug interactions (DDI) between HS-10234 and emtricitabine therapy will be helpful for researchers to design and conduct future phase II/III studies and merits careful examination in the era of evolving new combination antiretroviral therapy regimens. METHODS: We conducted an open-label, two-sequence, two-period, self-controlled phase I trial that enrolled 36 healthy volunteers randomized into two groups (group 1 and group 2). Eighteen subjects in group 1 were orally administered HS-10234 at a 25-mg daily dose for 7 days during period 1 (D1-D7) followed by co-administration of emtricitabine at a 200-mg dose once daily (QD) for 7 additional days during period 2 (D8-D14). Participants in group 2 were orally administered emtricitabine 200 mg QD for 7 days during period 1 (D1-D7) and then co-administered HS-10234 25 mg QD for 7 additional days during period 2 (D8-D14). Pharmacokinetics (PK) of HS-10234 and emtricitabine were characterized when administered alone and in combination. The concentrations of HS-10234 and its metabolites TFV and emtricitabine were determined using high performance liquid chromatography-mass spectrometry (HPLC-MS)/MS. Peripheral blood monocyte cells (PBMCs) were isolated for detection of intracellular concentrations of HS-10234's active metabolite, intracellular tenofovir diphosphate (TFV-DP) pre-dose and 2, 4, 8, 12 and 24 h post-dose on D7 and D14 in group 1. WinNonlin software was used to calculate PK parameters. RESULTS: After multiple-dose administration of HS-10234 with emtricitabine, the AUC0-tau of HS-10234 and TFV-DP was 1.327- and 1.403-fold higher than that with HS-10234 administration alone. The Cmax and AUC0-tau were increased 1.120- and 1.077-fold compared to emtricitabine administration alone. Co-administration of HS-10234 with oral emtricitabine was well tolerated. No serious adverse events were observed. CONCLUSIONS: Although a slightly increased steady-state PK exposure of HS-10234 and TFV-DP was observed with co-administration of oral HS-10234 with emtricitabine, these changes were not considered clinically relevant. Thus, dose adjustments are not recommended for HS-10234 combination with emtricitabine. TRIAL REGISTRATION: NCT04477096, July 20, 2020.

Growth and photoelectrochemical properties of ordered CuInS2 nanorod arrays.

CuInS(2) nanorod array structures are synthesized via a template-free and non-vacuum route for the first time. The obtained CuInS(2) thin films show promising conversion efficiency in a two-electrode photoelectrochemical cell.

Synthesis of hexagonal structured wurtzite and chalcopyrite CuInS2 via a simple solution route.

Wurtzite semiconductor CuInS2 [CIS] has been reported in recent years. As a kind of metastable structure, it is a great challenge to synthesize pure wurtzite CIS at low temperature. In this paper, via a simple and quick solution route, we synthesize both wurtzite- and chalcopyrite-structure CIS. Well-controlled wurtzite CIS hexagonal plates are obtained when an appropriate agent is added. The influence of the used agent triethanolamine [TEA] has also been studied, and it turns out that without TEA, chalcopyrite CIS with a kind of rare morphology is formed through this method.