In mammals, embryonic development are highly regulated morphogenetic processes that are tightly controlled by genetic elements. Failure of any one of these processes can result in embryonic malformation. The lysyl oxidase (LOX) family genes are closely related to human diseases. In this study, we investigated the essential role of lysyl oxidase-like 3 (LOXL3), a member of the LOX family, in embryonic development. Mice lacking LOXL3 exhibited perinatal lethality, and the deletion of the Loxl3 gene led to impaired development of the palate shelves, abnormalities in the cartilage primordia of the thoracic vertebrae and mild alveolar shrinkage. We found that the obvious decrease of collagen cross-links in palate and spine that was induced by the lack of LOXL3 resulted in cleft palate and spinal deformity. Thus, we provide critical in vivo evidence that LOXL3 is indispensable for mouse palatogenesis and vertebral column development. The Loxl3 gene may be a candidate disease gene resulting in cleft palate and spinal deformity.

BackgroundPlatelet aggregation mediated by inflammation played a critical role in the development of coronary heart diseases (CHD). Our previous clinical researches showed that Th17 cells and their characteristic cytokine IL-17A were associated with the plaque destabilization in patients with acute coronary syndrome (ACS). However, the potent effect of IL-17A on platelets-induced atherothrombosis remains unknown.Methods and ResultsIn this study, we detected the plasma IL-17A levels and platelet aggregation in patients with stable angina (SA), unstable angina (UA), acute myocardial infarction (AMI) and chest pain syndrome (CPS). In addition, the markers of platelet activation (CD62P/PAC-1) and the mitogen-activated protein kinases (MAPKs) pathway were detected in platelets from ACS patients. We found that plasma IL-17A levels and platelet aggregation in patients with ACS (UA and AMI) were significantly higher than patients with SA and CPS, and the plasma IL-17A levels were positively correlated with the platelet aggregation (R = 0.47, P<0.01). In addition, in patients with ACS, the platelet aggregation, CD62P/PAC-1 and the phosphorylation of ERK2 signaling pathway were obviously elevated in platelets pre-stimulated with IL-17A in vitro. Furthermore, the specific inhibitor of ERK2 could attenuate platelet aggregation and activation triggered by IL-17A.ConclusionOur experiment firstly proved that IL-17A could promote platelet function in patients with ACS via activating platelets ERK2 signaling pathway and may provide a novel target for antiplatelet therapies in CHD.

Psychological stress is associated with a systemic inflammatory response. It is unclear, however, whether psychological stress contributes to vascular inflammation. Here, we examined the effects of unpredictable chronic mild stress (UCMS) on vascular inflammation in rabbits. One hundred rabbits were randomly divided into control and stress groups. UCMS was induced by a set of defined adverse conditions applied in a shuffled order for 4, 8, 12, or 16 weeks, and rabbits were killed 24 h after the end of the UCMS protocol. Expression of different inflammatory molecules was analyzed by real-time polymerase chain reaction, immunohistochemistry, or enzyme-linked immunosorbent assay. UCMS resulted in depression-like behaviors, decreased body weight gain, and hypertension with no significant effects on serum lipids. Aortic mRNA and protein expression for tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor, and expression of intercellular adhesion molecule-1 (ICAM-1) protein were increased. UCMS increased circulating concentrations of corticosterone, TNF-α, and CRP throughout. Moreover, stress downregulated the expression of endothelial nitric oxide synthase. At 16 weeks of UCMS, macrophage infiltration and lipid accumulation in the subendothelial space were detected in the aorta. In cultured murine vascular smooth muscle cells, treatment with serum from stressed rabbits significantly increased phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and upregulated expression of MCP-1 and ICAM-1 mRNAs, in which the effect was blunted by a TNF-α neutralizing antibody or p38 and JNK inhibitors. Our results indicate that chronic psychological stress induces vascular inflammation via TNF-α and p38/JNK pathways, which may contribute to the development of atherosclerosis.

We conducted the present study to investigate the effects of the different loading doses of dexmedetomidine hydrochloride in the prevention of adverse reactions after combined spinal-epidural anesthesia. A total of 200 patients that were admitted to the Department of Obstetrics at the Second Affiliated Hospital of Xi'an Jiaotong University hospital and treated with cesarean section through the use of combined spinal-epidural anesthesia from December, 2014 to June, 2016, were randomly divided into 4 groups. The therapeutic regimens of patients were shown as follows: group A was administered an intravenous pump of 10 ml/l physiological saline in surgery until the end of the delivery. group B was administered 0.2 µg/kg dexmedetomidine. group C was administered 0.4 µg/kg dexmedetomidine. group D was administered 0.6 µg/kg dexmedetomidine. The anesthesia plane was adjusted to the level below the T10 plane. After the onset of anesthesia, participants of each group were treated with an intravenous pump of dexmedetomidine at loading dose. After intravenous pumping for 10 min in each group during the surgery, patients were administered with an intraoperative maintenance dose of 0.2 µg/kg/h until the end of the delivery. The heart rate (HR), mean arterial pressure (MAP), Narcotrend index (NI), Ramsay sedation score and the incidence of adverse reactions at each time-point of the start of drug administration (T0), 10 min (T2), 30 min (T3), 60 min (T4), 90 min (T5) and the end of surgery (T6) were recorded. Within 24 h post-delivery, the degree of amnesia from using dexmedetomidine until the end of the delivery were followed up. Compared to group A and T0, the HRs of participants at T3-6 in groups B and C were decreased. The MAP at T1 in group D was increased. In groups B and C, the NIs were significantly decreased at T2-6, the Ramsay scores were increased at T3-6, and the differences were statistically significant (P<0.05). The follow-up within 24 h after delivery showed that the degree of anterograde amnesia from groups B to D was significantly higher than group A, with statistically significant difference (P<0.05). A combined spinal-epidural anesthesia with 0.6 µg/kg loading dose of dexmedetomidine, by intravenous pumping within 10 min before cesarean section, can achieve a satisfied sedative effect at 30 min after administration. It maintains the characteristics of intraoperative hemodynamic stability and less adverse reactions. Therefore, it is of great significance to improve the quality of cesarean section delivery.

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