6 Paths of ERK5 signaling pathway regulate hepatocyte proliferation in rat liver regeneration

165-172Generally, extra-cellular-signal-regulated kinase 5 (ERK5) signaling pathway regulates many physiological activities, such as cell proliferation and cell differentiation. However, little is known about how ERK5 signaling pathway composed of 15 paths participates in regulating hepatocyte proliferation during liver regeneration (LR). In this study, to explore the influence ERK5 signaling pathway upon hepatocytes at gene transcription level, rat genome 230 2.0 array was used to detect expression changes of 75 related genes in isolated hepatocytes from rat regenerating liver. Bioinformatics and systems biology methods were applied to analyze the precise role of ERK5 signaling pathway in regulating hepatocyte proliferation during LR. Results showed that 62 genes were contained in the array and 22 genes were significantly changed. It was found that 6 paths were related to hepatocyte proliferation during rat LR. Among them, paths 3, 6 and 13 of ERK5 signaling pathway modulated cell cycle progression by decreasing the negative influence on ERK5 and paths 3, 4, 8 and 9 by reinforcing the positive influence on ERK5. In summary, the study shows that 22 genes and 6 paths of ERK5 signaling pathway participate in regulating proliferation of hepatocytes in rat LR

The Metabolic Effects of Oats Intake in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

The present study aimed to comprehensively assess if oats intake is beneficial for diabetic patients. The literature search was conducted in PubMed database up to 23 August 2015. Fourteen controlled trials and two uncontrolled observational studies were included. Compared with the controls, oats intake significantly reduced the concentrations of glycosylated hemoglobin A1c (HbA1c) (MD, −0.42%; 95% CI, −0.61% to −0.23%), fasting blood glucose (FBG) (MD, −0.39 mmol/L; 95% CI, −0.58 to −0.19 mmol/L), total cholesterol (TC) (MD, −0.49 mmol/L; 95% CI, −0.86 to −0.12 mmol/L), low-density lipoprotein cholesterol (LDL-C) (MD, −0.29 mmol/L; 95% CI, −0.48 to −0.09 mmol/L). Oatmeal significantly reduced the acute postprandial glucose and insulin responses compared with the control meal. The present study has revealed a beneficial effect of oats intake on glucose control and lipid profiles in type 2 diabetic patients. Further investigations of oats intake in patients with type 1 diabetes and the safety of oats consumption are required

Design and preliminary application of affinity peptide based on the structure of the porcine circovirus type II Capsid (PCV2 Cap)

Background Affinity peptides, as a core part of affinity chromatography, play an important role in the purification of target molecules. Methods Here we describe the use of molecular docking technology for virtual screening of affinity peptides that specifically recognize the PCV2 Cap protein for the first time. Thirteen candidate peptides with high scores were obtained and then further characterized. Experimentally, the affinity and sensitivity of the peptides studied were identified by ELISA and LSPR, respectively. In order to investigate the purification effect of a selected peptide (L11) for the recombinant PCV2 Cap protein, it was coupled to NHS agarose magnetic beads as an affinity adsorbent (NaMB-L11); and the ligand density of the affinity adsorbent and pH value in the purification of the recombinant PCV2 Cap protein were optimized. Results Our data showed that the peptide L11- DYWWQSWE has the smallest KD = 103 nM with higher specificity for PCV2 Cap protein recognition. The NaMB-L11 affinity adsorbent yielded a purified Cap sample with 98% purity at 90% recovery in a single step. Conclusion Based on the structure, we obtained a high affinity peptide L11 binding to the PCV2 Cap protein by molecular docking technology. It not only provides a theoretical basis for the design of PCV2 Cap affinity peptide, but a new method for the purification of the PCV2 Cap protein

Double-layered N-S1 protein nanoparticle immunization elicits robust cellular immune and broad antibody responses against SARS-CoV-2

Abstract Background The COVID-19 pandemic is a persistent global threat to public health. As for the emerging variants of SARS-CoV-2, it is necessary to develop vaccines that can induce broader immune responses, particularly vaccines with weak cellular immunity. Methods In this study, we generated a double-layered N-S1 protein nanoparticle (N-S1 PNp) that was formed by desolvating N protein into a protein nanoparticle as the core and crosslinking S1 protein onto the core surface against SARS-CoV-2. Results Vaccination with N-S1 PNp elicited robust humoral and vigorous cellular immune responses specific to SARS-CoV-2 in mice. Compared to soluble protein groups, the N-S1 PNp induced a higher level of humoral response, as evidenced by the ability of S1-specific antibodies to block hACE2 receptor binding and neutralize pseudovirus. Critically, N-S1 PNp induced Th1-biased, long-lasting, and cross-neutralizing antibodies, which neutralized the variants of SARS-CoV-2 with minimal loss of activity. N-S1 PNp induced strong responses of CD4+ and CD8+ T cells, mDCs, Tfh cells, and GCs B cells in spleens. Conclusions These results demonstrate that N-S1 PNp vaccination is a practical approach for promoting protection, which has the potential to counteract the waning immune responses against SARS-CoV-2 variants and confer broad efficacy against future new variants. This study provides a new idea for the design of next-generation SARS-CoV-2 vaccines based on the B and T cells response coordination. Graphical Abstract Steps involved in the preparation of double-layered N-S1 protein nanoparticle vaccines and experimental design performed in combating virus infection. After intramuscular immunization of mice, the double-layered N-S1 protein nanovaccine could effectively promote the maturation of antigen-presenting and mature dendritic cells, robust broad-spectrum neutralizing antibody production, cytokines secretion, robust mDC, Tfh cell, and GCs B cell responses induction, T-cell memory formation and durable antibody responses, and unique global transcriptome characteristics, thus achieving a robust cellular immunity and broad antibody responses against SARS-CoV-2 based on the B and T cells response coordinatio

Body Composition-Specific Asthma Phenotypes: Clinical Implications

Background: Previous studies have indicated the limitations of body mass index for defining disease phenotypes. The description of asthma phenotypes based on body composition (BC) has not been largely reported. Objective: To identify and characterize phenotypes based on BC parameters in patients with asthma. Methods: A study with two prospective observational cohorts analyzing adult patients with stable asthma (n = 541 for training and n = 179 for validation) was conducted. A body composition analysis was performed for the included patients. A cluster analysis was conducted by applying a 2-step process with stepwise discriminant analysis. Logistic regression models were used to evaluate the association between identified phenotypes and asthma exacerbations (AEs). The same algorithm for cluster analysis in the independent validation set was used to perform an external validation. Results: Three clusters had significantly different characteristics associated with asthma outcomes. An external validation identified the similarity of the participants in training and the validation set. In the training set, cluster Training (T) 1 (29.4%) was “patients with undernutrition”, cluster T2 (18.9%) was “intermediate level of nutrition with psychological dysfunction”, and cluster T3 (51.8%) was “patients with good nutrition”. Cluster T3 had a decreased risk of moderate-to-severe and severe AEs in the following year compared with the other two clusters. The most important BC-specific factors contributing to being accurately assigned to one of these three clusters were skeletal muscle mass and visceral fat area. Conclusion: We defined three distinct clusters of asthma patients, which had distinct clinical features and asthma outcomes. Our data reinforced the importance of evaluating BC to determining nutritional status in clinical practice

Reduced Skeletal Muscle Mass Is Associated with an Increased Risk of Asthma Control and Exacerbation

Background: Skeletal muscle mass (SMM) has been suggested to be associated with multiple health-related outcomes. However, the potential influence of SMM on asthma has not been largely explored. Objective: To study the association between SMM and clinical features of asthma, including asthma control and exacerbation, and to construct a model based on SMM to predict the risk of asthma exacerbation (AEx). Methods: In this prospective cohort study, we consecutively recruited patients with asthma (n = 334), classified as the SMM Normal group (n = 223), SMM Low group (n = 88), and SMM High group (n = 23). We investigated the association between SMM and clinical asthma characteristics and explored the association between SMM and asthma control and AEx within a 12-month follow-up period. Based on SMM, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort (n = 157). Results: Compared with the SMM Normal group, SMM Low group exhibited more airway obstruction and worse asthma control, while SMM High group had a reduced eosinophil percentage in induced sputum. Furthermore, SMM Low group was at a significantly increased risk of moderate-to-severe exacerbation compared with the SMM Normal group (relative risk adjusted 2.02 [95% confidence interval (CI), 1.35–2.68]; p = 0.002). In addition, a model involving SMM was developed which predicted AEx (area under the curve: 0.750, 95% CI: 0.691–0.810). Conclusions: Low SMM was an independent risk factor for future AEx. Furthermore, a model involving SMM for predicting the risk of AEx in patients with asthma indicated that assessment of SMM has potential clinical implications for asthma management