Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK

<p>Abstract</p> <p>Background</p> <p>Islet transplantation provides a promising cure for Type 1 diabetes; however it is limited by a shortage of pancreas donors. Bone marrow-derived multipotent mesenchymal stem cells (MSCs) offer renewable cells for generating insulin-producing cells (IPCs).</p> <p>Methods</p> <p>We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation.</p> <p>Results</p> <p>Here, we report adding extracellular matrix proteins (ECM) such as fibronectin (FN) or laminin (LAM) enhances pancreatic differentiation with increases in insulin and Glut2 gene expressions, proinsulin and insulin protein levels, and insulin release in response to elevated glucose concentration. Adding FN or LAM induced activation of Akt and ERK. Blocking Akt or ERK by adding LY294002 (PI3K specific inhibitor), PD98059 (MEK specific inhibitor) or knocking down Akt or ERK failed to abrogate FN or LAM-induced enhancement of IPC differentiation. Only blocking both of Akt and ERK or knocking down Akt and ERK inhibited the enhancement of IPC differentiation by adding ECM.</p> <p>Conclusions</p> <p>These data prove IPC differentiation by MSCs can be modulated by adding ECM, and these stimulatory effects were mediated through activation of Akt and ERK pathways.</p

Genomic Signatures of Human versus Avian Influenza A Viruses

Fifty-two species-associated amino acid residues were found between human and avian influenza viruses

Quantitative measures of functional outcomes and quality of life in patients with C5 palsy

AbstractBackgroundIt is generally understood that postoperative C5 palsy can occur with anterior or posterior decompression surgery, but functional measures of the palsy have not been well documented. This study aimed to investigate the incidence of C5 palsy in different surgical procedures, examine the correlations between muscle strength, upper extremity functional measures, and health-related quality of life, and to observe potential risk factors contributing to C5 palsy.MethodsOur investigation involved a retrospective study design. A total of 364 patients who underwent decompression surgery were indicated within the selected exclusion criteria. Additionally, 12 C5 palsy patients were recruited. The relationships between the manual muscle test (MMT), the action research arm test (ARAT), the Jebsen test of hand function (JTHF), and the European quality of life-5 dimensions (EQ-5D) were studied, and univariate analyses were performed to search possible risk factors and recovery investigation.ResultsThe data analyzed in the 12 cases and C5 palsy incidences (3.3%) were: 0.7% in anterior procedures (n = 2), 8.8% in posterior procedures (n = 6), and 36.4% in combined procedures (n = 4). Moderate-to-high correlations were observed between the ARAT, JTHF, EQ-5D visual analog scale scores, and MMT (r = 0.636–0.899). There were significant differences in patient age, etiology of cervical lesion, variable decompression procedures, and the number of decompression levels between the C5 palsy and non-C5 palsy groups. For female patients (p = 0.018) and number of decompression levels (p = 0.028), there were significant differences between the complete recovery and the incomplete recovery groups.ConclusionPatients undergoing combined anterior–posterior decompression surgery had the highest incidence of C5 palsy, and correlations between the ARAT, JTHF, EQ-5D visual analog scale clinical tools, and MMT scores supported these findings. Female status and lower decompression levels could also be predictive factors for complete recovery, although additional research is needed to substantiate these findings

The genome sequence of Salmonella enterica serovar Choleraesuis, a highly invasive and resistant zoonotic pathogen

Salmonella enterica serovar Choleraesuis (S.Choleraesuis), a highly invasive serovar among non-typhoidal Salmonella, usually causes sepsis or extra-intestinal focal infections in humans. S.Choleraesuis infections have now become particularly difficult to treat because of the emergence of resistance to multiple antimicrobial agents. The 4.7 Mb genome sequence of a multidrug-resistant S.Choleraesuis strain SC-B67 was determined. Genome wide comparison of three sequenced Salmonella genomes revealed that more deletion events occurred in S.Choleraesuis SC-B67 and S.Typhi CT18 relative to S.Typhimurium LT2. S.Choleraesuis has 151 pseudogenes, which, among the three Salmonella genomes, include the highest percentage of pseudogenes arising from the genes involved in bacterial chemotaxis signal-transduction pathways. Mutations in these genes may increase smooth swimming of the bacteria, potentially allowing more effective interactions with and invasion of host cells to occur. A key regulatory gene of TetR/AcrR family, acrR, was inactivated through the introduction of an internal stop codon resulting in overexpression of AcrAB that appears to be associated with ciprofloxacin resistance. While lateral gene transfer providing basic functions to allow niche expansion in the host and environment is maintained during the evolution of different serovars of Salmonella, genes providing little overall selective benefit may be lost rapidly. Our findings suggest that the formation of pseudogenes may provide a simple evolutionary pathway that complements gene acquisition to enhance virulence and antimicrobial resistance in S.Choleraesuis

Rhodiola crenulata extract for prevention of acute mountain sickness: a randomized, double-blind, placebo-controlled, crossover trial

BACKGROUND: Rhodiola crenulata (R. crenulata) is widely used to prevent acute mountain sickness in the Himalayan areas and in Tibet, but no scientific studies have previously examined its effectiveness. We conducted a randomized, double-blind, placebo-controlled crossover study to investigate its efficacy in acute mountain sickness prevention. METHODS: Healthy adult volunteers were randomized to 2 treatment sequences, receiving either 800 mg R. crenulata extract or placebo daily for 7 days before ascent and 2 days during mountaineering, before crossing over to the alternate treatment after a 3-month wash-out period. Participants ascended rapidly from 250 m to 3421 m on two separate occasions: December 2010 and April 2011. The primary outcome measure was the incidence of acute mountain sickness, as defined by a Lake Louise score ≥ 3, with headache and at least one of the symptoms of nausea or vomiting, fatigue, dizziness, or difficulty sleeping. RESULTS: One hundred and two participants completed the trial. There were no demographic differences between individuals taking Rhodiola-placebo and those taking placebo-Rhodiola. No significant differences in the incidence of acute mountain sickness were found between R. crenulata extract and placebo groups (all 60.8%; adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) = 0.69–1.52). The incidence of severe acute mountain sickness in Rhodiola extract vs. placebo groups was 35.3% vs. 29.4% (AOR = 1.42, 95% CI = 0.90–2.25). CONCLUSIONS: R. crenulata extract was not effective in reducing the incidence or severity of acute mountain sickness as compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT01536288

Serum repressing efflux pump CDR1 in Candida albicans

BACKGROUND: In the past decades, the prevalence of candidemia has increased significantly and drug resistance has also become a pressing problem. Overexpression of CDR1, an efflux pump, has been proposed as a major mechanism contributing to the drug resistance in Candida albicans. It has been demonstrated that biological fluids such as human serum can have profound effects on antifungal pharmacodynamics. The aim of this study is to understand the effects of serum in drug susceptibility via monitoring the activity of CDR1 promoter of C. albicans. RESULTS: The wild-type C. albicans cells (SC5314) but not the cdr1/cdr1 mutant cells became more susceptible to the antifungal drug when the medium contained serum. To understand the regulation of CDR1 in the presence of serum, we have constructed CDR1 promoter-Renilla luciferase (CDR1p-RLUC) reporter to monitor the activity of the CDR1 promoter in C. albicans. As expected, the expression of CDR1p-RLUC was induced by miconazole. Surprisingly, it was repressed by serum. Consistently, the level of CDR1 mRNA was also reduced in the presence of serum but not N-acetyl-D-glucosamine, a known inducer for germ tube formation. CONCLUSION: Our finding that the expression of CDR1 is repressed by serum raises the question as to how does CDR1 contribute to the drug resistance in C. albicans causing candidemia. This also suggests that it is important to re-assess the prediction of in vivo therapeutic outcome of candidemia based on the results of standard in vitro antifungal susceptibility testing, conducted in the absence of serum