Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most critical causes of healthcare-related or community-related infections. Resistance to most β-lactam antibiotics makes MRSA a big threat to clinical treatment. Utilization of low efficiency antibiotics such as vancomycin and teicoplanin makes new choices for therapies. Recently, much researchhas shed light on relevance between genetic mutations of MRSA and clinical characteristics such as antibiotic resistance, and virulence. These findings could contribute to development of novel antibiotics and vaccines.
In China, the epidemiological and socioeconomic status of the migrant population suggests that the vulnerable population should be prioritized for tuberculosis (TB) control. A face-to-face interview using a structured questionnaire was performed on a total of 314 smear-positive pulmonary TB patients among the migrant population of 12 randomly selected counties in Shandong Province, China. From the results, the cases of patient delay of diagnosis accounted for 40.8%, and the completion rate of Direct Observation Therapy, Short-course (DOTS) was as low as 67.2%. There were 47.1% missed cases in the first diagnosis. Factors affecting detection and treatment were present in their socioeconomic status, working style, and the accessibility to related TB care. The findings indicated that migrant TB patients suffer delayed diagnosis, a low case detection rate and a low completion DOTS rate. Improvement of migrants' working conditions and accessibility to specialized TB care is essential and is expected to lead to better case detection and treatment completion.
Influenza has long been considered a serious global health threat. The highly pathogenic avian influenza A virus (IAV) H5N1, particularly the currently identified IAV/H7N9 in humans in China, illustrates that influenza is still a significant public health problem. Due to the high mortality of H5N1, development of safe and effective vaccines against divergent strains of H5N1 influenza virus, especially the one capable of inducing both strong systemic and local immune responses in the vaccinated targets, is a challenge of immediate importance. In the present study, we designed two recombinant proteins containing highly conserved hemagglutinin (HA) residues 81-122 of H5N1 fused with Fc of human IgG (HA-81-122-Fc) and/or foldon (Fd) trimeric motif (HA-81-122-Fdc), and identified their immunogenicity in vaccinated mice. We found that HA-81-122-Fc and HA-81-122-Fdc proteins formed high molecular weight dimer and oligomer, respectively, and induced potent IgG antibodies in vaccinated mouse sera and lung wash. Stronger IgG1 (Th2-associated) and IgG2 (Th1-associated) antibody responses could be raised in the sera of mice following last vaccination of HA-81-122-Fdc than those raised by HA-81-122-Fc vaccination. Importantly, HA-81-122-Fdc is able to elicit high titers of IgA antibodies in vaccinated mouse lung wash and sera through the parenteral immunization pathway. Our data demonstrated that the recombinant protein containing highly conserved HA residues 81-122 of H5N1 fused with Fd and Fc could induce strong local mucosal and systemic humoral immune responses in the vaccinated animals, revealing the possibility of developing an effective Fc-mediated mucosal influenza vaccine.
The hyperglycemic response is an important prognostic factor for survival after hemorrhage. In this study, we investigated the effects of glucose administration during volume resuscitation from hemmorhagic shock in fasted rats under sevoflurane anesthesia on hemodynamics, acid/base-balance and glucose metabolism. Hemorrhagic shock was induced in rats by withdrawing 25 mL/kg of blood. For volume resuscitation, rats in groupDextran[saline] and group-Dextran[glucose] underwent infusion therapy using 10% dextran-40 dissolved in physiological saline and 10% dextran-40 dissolved in 5% glucose, respectively. Arterial blood was sampled just before blood withdrawal, immediately after blood withdrawal, immediately after volume resuscitation and at 30 min after volume resuscitation for arterial gas analyses and measurement of plasma insulin levels. After volume resuscitation, group-Dextran[glucose] showed similar arterial blood pressure, significantly lower heart rate, similar arterial PO2 and similar hematocrit in comparison with group-Dextran[saline], suggesting that there was no particular difference in oxygen demand/supply-balance between the two groups. After volume resuscitation, group-Dextran[glucose] showed significantly higher arterial pH, similar arterial PCO2, significantly higher bicarbonate levels and significantly higher base excess in comparison with group-Dextran[saline], suggesting that metabolic acidosis is a cause of the difference in acid/base-balance between the two groups. After volume resuscitation, group-Dextran[glucose] showed significantly higher glucose levels, significantly higher insulin levels and significantly lower lactate levels in comparison with group-Dextran[saline]. At 30 min after volume resuscitation, base excess correlated significantly with lactate levels. These results suggest that glucose administration during volume resuscitation using dextran-40 from hemorrhagic shock ameliorates acid/base-imbalance associated with hyperlactatemia in fasted rats under sevoflurane anesthesia.
Matrix vesicles (MVs) involved in the initiation of mineralization by deposition of hydroxyapatite (HA) in their lumen are released by the budding of mineralization-competent cells during skeletogenesis and bone development. To identify additional mineralization-related proteins, MVs were isolated from non-stimulated and stimulated Saos-2 cells in culture via an ExoquickTM approach and the corresponding proteomes were identified and quantified with label-free quantitative proteome technology. The isolated MVs were confirmed by electron microscopy, alkaline phosphatase activity (ALP), biomarkers, and mineral formation analyses. Label-free quantitative proteome analysis revealed that 19 calcium binding proteins (CaBPs), including Grp94, calnexin, calreticulin, calmodulin, and S100A4/A10, were up-regulated in MVs of Saos-2 cells upon stimulation of mineralization. This result provides new clues to study the mechanism of the initiation of MV-mediated mineralization.
Using a meta-analysis on gene expression data of hepatocellular carcinomas (HCC) from the Oncomine database, we identified that the Notch3 gene ranked as the highest up-regulated Notch pathway member in HCC tissues compared with normal liver tissues. We further detected the expression of Notch3 in 95 cases of HCC samples by immunohistochemistry, and evaluated its clinicopathological and prognostic significance. We confirmed that Notch3 is overexpressed in HCC tissues compared with normal liver tissues, and a high expression level of Notch3 was significantly associated with bigger tumor size (p = 0.014), multiple tumors (p = 0.026), late tumor-node-metastasis (TNM) stage (p < 0.01) and shorter overall survival (p = 0.002). Furthermore, high Notch3 expression emerged as a significant independent prognostic factor in multivariate analysis. In conclusion, we identified a positive association between Notch3 expression with more aggressive traits and shorter survival in HCC. Our findings suggest that Notch3 might be an important regulator in the development of HCC, and a potential therapeutic target for patients with HCC.
A research project involving sheets of retinal pigment epithelium constructed from iPS cells derived from patients with age-related maculopathy is one step closer to being approved for clinical trials by the Japanese Government. Now is the time to make therapies using iPS cells clinically available.