Zika virus transmission via breast milk in suckling mice.

OBJECTIVES: Infectious Zika viral particles were detected in human milk; however, whether they can be transmitted via breastfeeding remains unknown, so our objective was to clarify this. METHODS: Here, in a natural breastfeeding model, wild-type (C57Bl/6; WT) or interferon α/ß (IFNα/ß) receptor-deficient (A129; KO) murine dams on day 1 post-delivery were infected with Zika virus (ZIKV) intraperitoneally, and the neonates were suckled. In a novel artificial feeding model, WT suckling mice at 1 day old were fed with ZIKV alone or ZIKV and human breast milk mixtures. Thereafter, the virus distribution, clinical progression and neuropathology in the WT or KO neonates were characterized to evaluate the risk of ZIKV transmission through breast milk. RESULTS: In natural breastfeeding, viral RNAs (8/8) and infectious viral particles (7/8) were extensively present in the mammary glands of KO dams. All tested KO neonates (5/5), and none of WT neonates (0/9), were infected with ZIKV. In artificial feeding, 100% of the WT neonates (two groups, 12/12 and 16/16) were infected and developed some signs of neurodegeneration. ZIKV tended to seed and accumulate in the lungs and were subsequently disseminated to other tissues in both 16 naturally suckled and 19 artificially fed infected neonates. As human breast milk was mixed with ZIKV and fed to WT neonates, 45% individuals (9/20) were infected; in the infected neonates, the viral spread to the brain was delayed, and the clinical outcomes were alleviated. CONCLUSIONS: These results demonstrated that suckling mice can be infected with ZIKV through suckling, and breast milk has potential antiviral activity, inhibiting ZIKV infection.

Propionate alleviates high-fat diet-induced lipid dysmetabolism by modulating gut microbiota in mice.

AIMS: The aims were to examine whether oral sodium propionate supplementation regulate lipid metabolism through modulating gut microbiota. METHODS AND RESULTS: ICR male mice (26·98 ± 0·30 g) were randomly assigned to three groups (n = 10) and fed control diet (Con), high-fat diet (HFD) and HFD plus propionate (Pro) respectively. In this study, we found that HFD increased the weight of final body, inguinal white adipose tissues (iWAT), epididymal white adipose tissue (eWAT) and perirenal white adipose tissue (pWAT), as well as the adipocyte mean area of iWAT and eWAT in mice (P < 0·05), whereas sodium propionate treatment reduced the weight of iWAT and pWAT as well as adipocyte mean area of iWAT in mice fed a HFD (P < 0·05). Moreover, in the iWAT, the mRNA expression of lipogenesis genes, including peroxisome proliferator activated receptor γ, acetyl-CoA carboxylase and carnitine palmitoyl transferase-1ß, was upregulated by HFD challenge (P < 0·05), and the elevation of these genes was nearly reversed to the level of control diet-fed mice by sodium propionate treatment. Meanwhile, sodium propionate treatment increased the hormone-sensitive lipase mRNA expression in the iWAT of HFD-fed mice (P < 0·05). High-throughput pyrosequencing of the 16S rRNA demonstrated that sodium propionate treatment significantly recovered the gut microbiota dysbiosis in HFD-fed mice, including the richness and diversity of microbiota and the ratio of Firmicutes to Bacteroidetes. Furthermore, the HFD-induced reductions in colonic levels of butyrate and valerate were reversed by sodium propionate treatment, which also normalized the serum LPS level seen in HFD-fed mice to the levels of the control diet-fed mice. CONCLUSIONS: Collectively, these results indicated that sodium propionate treatment could improve lipid metabolism in HFD-fed mice, and the potential mechanisms might be via regulating gut microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: We demonstrated for the first time that oral sodium propionate significantly improved HFD-induced dysbiosis of gut microbiota, indicating that the mitigative effect of propionate for HFD-induced lipid dysmetabolism might be mediated by gut microbiota in mice.

[Serum levels of periostin and their influencing factors in the beta-lactam antibiotic enterprise workers].

Objective: To observe serum levels of periostin, ECP, IgE in the antibiotic enterprise workers, and study the role of periostin, ECP, IgE in the development of allergic inflammation. Methods: 90 cases with asthma or rhinitis were enrolled as disease group, another 117 workers exposed to 7-ACA、6-APA dust without suffering from allergic illness, are chosen as group of dust exposed, and 192 healthy workers who didn't contact dust were chosen as control group. Questionnaires were used to learn their basic information.Lung function was determined with a portable spirometer.The expression levels of periostin、ECP and IgE in serum were measured by enzyme-linked immuno sorbent assay. Results: The exposure group and disease group had significantly lower forced vital capacity (FVC) , forced expiratory volume in 1 second (FEV(l.0)) , and FEV(l.0)/FVC ratio than the control group (P<0.05) . The disease group had significantly higher eosinophil than the control group (P<0.05) . Compared with the control group, the exposure group, the disease group, asthma subgroup, rhinitis subgroup of serum periostin and IgE increased, the differences are statistically significant (P<0.05) . Serum levels of ECP in the workers of asthma subgroup were significantly higher than that in control group (P<0.05) . Serum expression levels of periostin were positively correlated with IgE, ECP in workers (P<0.001) , serum levels of periostin were negatively correlated with FEV(1.0) in workers (P<0.05) . Multiple logistics regression analysis found that exposure to 7-ACA or 6-APA (OR=3.09, 95%CI: 1.83-5.21) , age>47years (OR=2.53, 95%CI: 1.22-5.26) , higher ECP (OR=1.04, 95%CI: 1.01-1.06) were risk factors for increased serum periostin level. Conclusion: Occupational exposure to 7-ACA or 6-APA can result in higher serum periostin level, exposure to 7-ACA or 6-APA, age>47 years, higher ECP are risk factors for increased serum periostin level.

Protein phosphatase-1 regulates Akt1 signal transduction pathway to control gene expression, cell survival and differentiation.

AKT pathway has a critical role in mediating signaling transductions for cell proliferation, differentiation and survival. Previous studies have shown that AKT activation is achieved through a series of phosphorylation steps: first, AKT is phosphorylated at Thr-450 by JNK kinases to prime its activation; then, phosphoinositide-dependent kinase 1 phosphorylates AKT at Thr-308 to expose the Ser-473 residue; and finally, AKT is phosphorylated at Ser-473 by several kinases (PKD2 and others) to achieve its full activation. For its inactivation, the PH-domain containing phosphatases dephosphorylate AKT at Ser-473, and protein serine/threonine phosphatase-2A (PP-2A) dephosphorylates it at Thr-308. However, it remains unknown regarding which phosphatase dephosphorylates AKT at Thr-450 during its inactivation. In this study, we present both in vitro and in vivo evidence to show that protein serine/threonine phosphatase-1 (PP-1) is a major phosphatase that directly dephosphorylates AKT to modulate its activation. First, purified PP-1 directly dephosphorylates AKT in vitro. Second, immunoprecipitation and immunocolocalization showed that PP-1 interacts with AKT. Third, stable knock down of PP-1alpha or PP-1beta but not PP-1gamma, PP-2Aalpha or PP-2Abeta by shRNA leads to enhanced phosphorylation of AKT at Thr-450. Finally, overexpression of PP-1alpha or PP-1beta but not PP-1gamma, PP-2Aalpha or PP-2Abeta results in attenuated phosphorylation of AKT at Thr-450. Moreover, our results also show that dephosphorylation of AKT by PP-1 significantly modulates its functions in regulating the expression of downstream genes, promoting cell survival and modulating differentiation. These results show that PP-1 acts as a major phosphatase to dephosphorylate AKT at Thr-450 and thus modulate its functions.

Percutaneous probe reduction of frontal fractures of the humeral capitellum.

Nine frontal fractures of the humeral capitellum treated by percutaneous probe reduction are reported. Most of the fractures were percutaneously reduced with a Steinmann pin inserted along the lateral border of the biceps tendon. To prevent redisplacement of the fragment, the elbow joint was first flexed more than 90 degrees with plaster immobilization for two weeks. The favorable results obtained with this method are due to reduced surgical trauma to local tissues and good reduction of the fracture. The percutaneous probe reduction should be considered for frontal fracture of the humeral capitellum before open reduction is performed.