Lin Zou

β-arrestin2 mediates β-2 adrenergic receptor signaling inducing prostate cancer cell progression

The expression of the β-2 adrenergic receptor (β2AR), one of the stress-inducible receptors, has been reported to be closely correlated with malignant tumors. Prostate cancer is the most common non-cutaneous cancer among males, accompanied with increased castration levels and β2AR activation in patients. However, the role of β2AR activation in prostate cancer cells and its underlying mechanisms are not fully understood. Here, we found that β2AR activation promoted cell proliferation and cell migration through increasing cellular adenylyl cyclase (cAMP) levels and ERK1/2 activation in LNCaP and PC3 prostate cancer cells. Moreover, the scaffold protein β-arrestin2 was found to be involved in the β2AR-mediated activation of ERK1/2 and cell proliferation using stable overexpressing β-arrestin2 LNCaP (LNCaP-βArr2) cells. Furthermore, enhanced β-arrestin2/c-Src complex formation by β2AR activation was observed in LNCaP-βArr2 cells. In addition, the c-Src inhibitor could block this enhanced complex formation and suppressed cell proliferation. This study demonstrates that βArr2 is involved in prostate carcinogenesis induced by stress and provides potential therapeutic targets for cancer.

Investigation of Mycoplasma pneumoniae infection in pediatric population from 12,025 cases with respiratory infection☆

Although Mycoplasma pneumoniae (MP) is a major pathogen of primary atypical pneumonia in children, the clinical and laboratory characteristics of MP infection in large pediatric population are less reported. Here, we retrospectively analyzed 12,025 hospitalized children with respiratory infection by using serology and polymerase chain reaction (PCR) methods simultaneously. The results showed that 2433 (20.23%) children had MP infection, which mainly occurred in November to April. The presence of sore throat and pharyngitis was peculiar to MP infection. The positive percentage of MP-DNA was higher than that of MP-IgM in children aged <1 (P < 0.0001) and 1-3 years (P < 0.0001). Moreover, the positive rate of P1 gene, the key adhesion gene for MP infection, was higher in children with MP infection than in those with other pathogens (P < 0.0001). Our work provides the clinical information of children MP infection and highlights the superiority of PCR and potential usage of P1 as a diagnosis target for MP infection.

Elevated β-arrestin1 expression correlated with risk stratification in acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the main subtype of childhood leukemia. Risk stratification is pivotal for ALL prognosis and individualized therapy. The current factors for risk stratification include clinical and laboratory features, cytogenetic characteristics of the blast, early response to chemotherapy, and genetic factors. Analyses of gene expression are becoming increasingly important in ALL risk stratification. β-Arrestin1, a multifunctional scaffold protein mediating many intracellular signaling networks, has been shown to be involved in many tumors. However, little is known of β-arrestin1 in leukemia. In this study, we found that β-arrestin1 was significantly elevated in 155 newly diagnosed ALL patients, compared with 51 controls. Further analysis showed that β-arrestin1 expression was positively related with risk classification and white blood cell count in ALL. Moreover, expression of Notch1, an essential gene for developing hematological cells and T-ALL, was found to be negatively correlated with β-arrestin1 in ALL. In conclusion, β-arrestin1 may be a useful predictor of risk stratification and prognosis of ALL, and thus of potential use in the design of individualized therapy strategies.

WT1 mutations and single nucleotide polymorphism rs16754 analysis of patients with pediatric acute myeloid leukemia in a Chinese population

Abstract Acute myeloid leukemia (AML) is relatively rare in children. Somatic mutations including the single nucleotide polymorphism (SNP) rs16754 in Wilms tumor 1 gene (WT1) and their prognostic relevance in pediatric AML have not been studied in Chinese populations. We analyzed WT1 mutations and rs16754 genotypes in a cohort of 86 patients with de novo pediatric AML in a Chinese population. We detected WT1 mutations in approximately 20% of the patients. Most of the mutations identified were deletions and insertions clustered in exons 7 and 9. No differences were observed with respect to overall survival and relapse-free survival between patients with and without WT1 mutations. The analysis of rs16754 in WT1 exon 7 revealed G as the major allele. Patients with the rs16754GG genotype had improved overall survival (p =0.020) and relapse-free survival (p =0.025) compared with those with either rs16754GA or rs16754AA. Moreover, better overall survival (p =0.044) and relapse-free survival (p =0.068) were observed among patients with wild-type CEBPA with rs16754GG compared with those carrying rs16754GA/AA.

β-Arrestin1 promotes the self-renewal of the leukemia-initiating cell-enriched subpopulation in B-lineage acute lymphoblastic leukemia related to DNMT1 activity

The self-renewal ability of the leukemia initiating cell-enriched subpopulation is critical for leukemia initiation and maintenance. However, the regulation of leukemia initiating cells for the leukemia progression is poorly understood. In this study, we observed that β-Arrestin1, a multiple-function protein, is elevated in leukemia initiating cells-enriched fraction from B-lineage acute lymphoblastic leukemia patients. The loss of β-Arrestin1 in leukemia initiating cells-enriched fraction attenuates its self-renewal capacity both in vitro and in vivo. Further experiments showed that the mRNA expression level of β-Arrestin1 is negatively correlated with that of PTEN in leukemia initiating cells-enriched fraction. Moreover, DNA methylation of the PTEN promoter region, the activity and expression of DNMTs were enhanced in the leukemia initiating cells-enriched fraction. The inhibition of DNMT1 activity impaired the self-renewal and increased expression of PTEN of leukemia initiating cells-enriched fraction. In addition, depletion of β-Arrestin1 significantly decreased DNMT1 activity and PTEN methylation, and consistently increased PTEN expression in leukemia initiating cells-enriched fraction. Our study reveals a novel function of β-Arrestin1 in the regulation of the self-renewal of leukemia initiating cells-enriched fraction from B-lineage acute lymphoblastic leukemia patients related to DNMT1 activity, indicating that β-Arrestin1 is a potential therapeutic target in B-lineage acute lymphoblastic leukemia.

Therapeutic Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Acute Lung Injury Mice.

The incidence and mortality of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are still very high, but stem cells show some promise for its treatment. Here we found that intratracheal administration of human umbilical cord-mesenchymal stem cells (UC-MSCs) significantly improved survival and attenuated the lung inflammation in lipopolysaccharide (LPS)-induced ALI mice. We also used the proteins-chip and bioinformatics to analyze interactions between UC-MSCs treatment and immune-response alternations of ALI mice. Then we demonstrated that UC-MSCs could inhibit the inflammatory response of mouse macrophage in ALI mice, as well as enhance its IL-10 expression. We provide data to support the concept that the therapeutic capacity of UC-MSCs for ALI was primarily through paracrine secretion, particularly of prostaglandin-E2 (PGE2). Furthermore, we showed that UC-MSCs might secrete a panel of factors including GM-CSF, IL-6 and IL-13 to ameliorate ALI. Our study suggested that UC-MSCs could protect LPS-induced ALI model by immune regulation and paracrine factors, indicating that UC-MSCs should be a promising strategy for ALI/ARDS.

Epidemiology of 45,616 suspect cases of Hand, Foot and Mouth Disease in Chongqing, China, 2011–2015

Epidemiology and etiology of hand, foot, and mouth disease (HFMD) based on large sample size or evaluation of detection for more enterovirus serotypes are not well investigated in Chongqing of China. 45,616 suspect HFMD patients were prospectively enrolled among whom 21,615 were laboratory confirmed HFMD cases over a 5-year period (January 2011 to December 2015). Their epidemiological, clinical, and laboratory data were extracted and stratified by month, age, sex, disease severity, and enterovirus serotype. Subsequently 292 non-EV-A71/CV-A16 HFMD confirmed cases were randomly selected in three consecutive outbreaks to detect CV-A6 and CV-A10, using RT-PCR. Results showed that the HFMD epidemic peaked in early summer and autumn. The median age of onset was 2.45 years with a male-to-female ratio of 1.54:1, and with children under 5 years of age accounting for 92.54% of all confirmed cases. EV-A71 and CV-A16 infection accounted for only 36.05% (7793/21615) of total confirmed cases while EV-A71 accounted for 59.64% (232/389) of severe cases. Importantly, the proportion of EV-A71 infection generally increased with age which showed rapid growth in severe cases. CV-A6 and CV-A10 were tested positive in Chongqing, but CV-A6 had greater positive rates of 62.33% while CV-A10 had 4.79% in non-EV-A71/CV-A16 HFMD confirmed cases.

Determination of optimal cutoff value to accurately identify glucose-6-phosphate dehydrogenase-deficient heterozygous female neonates.

BACKGROUND Conventional screening tests to assess G6PD deficiency use a low cutoff value of 2.10 U/gHb which may not be adequate for detecting females with heterozygous deficiency. The aim of present study was to determine an appropriate cutoff value with increased sensitivity in identifying G6PD-deficient heterozygous females. METHODS G6PD activity analysis was performed on 51,747 neonates using semi-quantitative fluorescent spot test. Neonates suspected with G6PD deficiency were further analyzed using quantitatively enzymatic assay and for common G6PD mutations. The cutoff values of G6PD activity were estimated using the receiver operating characteristic curve. RESULTS Our results demonstrated that using 2.10 U/g Hb as a cutoff, the sensitivity of the assay to detect female neonates with G6PD heterozygous deficiency was 83.3%, as compared with 97.6% using 2.55 U/g Hb as a cutoff. The high cutoff identified 21% (8/38) of the female neonates with partial G6PD deficiency which were not detected with 2.10 U/g Hb. Our study found that high cutoffs, 2.35 and 2.55 U/g Hb, would increase assays sensitivity to identify male and female G6PD deficiency neonates, respectively. CONCLUSIONS We established a reliable cutoff value of G6PD activity with increased sensitivity in identifying female newborns with partial G6PD deficiency.

Vitamin A maintains the airway epithelium in a murine model of asthma by suppressing glucocorticoid‐induced leucine zipper

The effects of glucocorticoids (GCs) on the repair of the airway epithelium in asthma are controversial, and we previously reported that the GC dexamethasone (Dex) inhibits the repair of human airway epithelial cells and that this process is mediated by glucocorticoid‐induced leucine zipper (GILZ) through MAPK‐ERK signaling in vitro. Vitamin A (VA) is involved in the regulation of the MAPK‐ERK pathway but has not been widely supplied during asthma treatment. It is unclear whether VA attenuates the negative regulation of GILZ on the MAPK‐ERK pathway and maintains airway epithelium integrity during asthma treatment.

Daily prednisone treatment in duchenne muscular dystrophy in southwest china

In this study we aimed to determine the influence of daily prednisone treatment in Duchenne muscular dystrophy (DMD) by performing a prospective, randomized, placebo‐controlled trial in southwestern China.