Evaluation of the properties of whey protein films with modifications.

Whey protein concentrate (WPC) has been widely studied as a biodegradable bio-based packaging material in the food industry. In this study, different whey protein films were obtained through physical, chemical, enzymatic, and composite modifications. The molecular structure, micro-morphology, mechanical properties, barrier properties, and other characteristics of the films were evaluated. The results illustrated that the thickness of WPC with composite modification increased and the transmittance decreased, but the mechanical properties and barrier properties were more prominent. The WPC film prepared by physical modification combined with transglutaminase has the best film-forming effect, the tensile strength (TS) was 5.45 MPa, the elongation at break (EAB) was 25.19%, the WVP was 5.53 g·mm/m2 ·hr·kPa, and the Oxygen permeability (OP) was 1.83 meq/K, and its microstructure was and uniform. In addition, based on the the results of SDS-PAGE and Fourier transform infrared spectroscopy (FTIR), the intermolecular and intramolecular interactions of various modification methods on WPC were studied, thus contributing to analyze the properties of the film. This study provides theoretical basis and technical support for the industrial production of protein-based films.

Clinical Outcomes Of Using Nebulized Budesonide As The Initial Treatment For Acute Exacerbations Of Chronic Obstructive Pulmonary Disease: A Post-Hoc Analysis.

Purpose: The current guidelines recommend the use of systemic corticosteroids (SCS) as the optimal treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this real-world study was to evaluate whether nebulized budesonide (NBS) could also be used as an initial treatment for AECOPD. Patients and methods: AECOPD patients initially treated with NBS or SCS (oral/intravenous) were enrolled. A large-scale, long-term multicenter cohort study of AECOPD patients was performed to analyze outcomes for each treatment (NCT02051166). Results: Initial NBS and SCS treatment resulted in similar outcomes in terms of improvements in FEV1, PaO2, SaO2, and PaCO2. Disease severity affected outcome similarly in both groups. When the groups were stratified according to whether the initial treatment was subsequently intensified or reduced, more intubation was seen in the groups in which initial treatment was intensified. NBS escalation and SCS reduction groups spent more days in the hospital. The NBS escalation group was associated with the highest medical expenditure and a relatively higher rate of new-onset pneumonia. The NBS maintenance/reduction group showed the lowest mortality rate between groups. Stratification according to initial PaCO2 level showed more intubation in the groups with high initial PaCO2 concentrations. Conclusion: These results indicate that NBS may be used as an initial treatment in certain AECOPD patients, and further studies are needed to better define those most likely to benefit.

Mechanical properties of whey protein concentrate based film improved by the coexistence of nanocrystalline cellulose and transglutaminase.

Whey Protein Concentrate (WPC) has been researched as food packaging materials in recent years. However, WPC films own the drawbacks on the barrier ability to water vapor and mechanical properties. In the presented work, Transglutaminase (TGase) and different concentrations of nanocrystalline cellulose (NCC) (0-15% wt. of WPC) were incorporated into the WPC matrix to prepare WPC-NCC composite film, their transmittance, mechanical properties, water vapor permeability and microstructures were investigated and compared with that of WPC films. Results illustrated that NCC as fillers in the protein network blended with WPC markedly improved the mechanical properties. The tensile strength of composite film increased from 1.3 to 3.15 MPa as NCC increased to 15% wt. of WPC. Moreover, TGase took a promoted effect on mechanical properties. The composite film achieved a maximal elongation value of 86.7% when TGase was added at 9 U/g of WPC. SDS-PAGE confirmed that TGase positively facilitated the formation of the protein polymers. FTIR analysis observed conformational changes caused by TGase in the films and implied the interaction between WPC and NCC. Results suggest NCC and TGase have a synergy effect on mechanical properties of WPC based film, and TGase-crosslinked WPC-NCC composite film can be applied as an alternative packaging material.

Plastein reaction enhanced bile-acid binding capacity of soybean protein hydrolysates and whey protein hydrolysates.

Plastein reaction is a modification reaction that can improve the functional properties of protein hydrolysate. The product of the reaction is a thixotropic aggregation of peptides. This study investigated the formation condition of soybean-whey plastein and bile acid binding capacity of plastein. Soy protein and whey protein were hydrolyzed by pepsin. The mixture (1:1, w/w) of two hydrolysates was modified by pepsin again. After the reaction, the decrease in free amino groups and the turbidity of the modified hydrolysate were measured to obtain appropriate reaction condition. Results showed that the concentration of hydrolysates 40% (w/v), enzyme ratio of 2.0 KU/g protein, pH 5.0, 37 °C, reaction time of 3.0 h respectively, were showed maximum changes in protein hydrolysates. Tricine SDS-PAGE analysis under denaturing conditions revealed that whey protein was more sensitive to pepsin and yielded different polypeptides (PPs) of molecular weight ranged from 3.5-17 kDa. However, a high molecular weight PP was completely hydrolyzed while PPs of 14.2-26 kDa were partially digested after pepsin treatment. Native page analysis further revealed the presence of a high-molecular weight PP in crude and purified plastein product. The bile acid binding capacity was improved by the plastein reaction. The amount of binding sodium deoxycholate, sodium taurocholate, and sodium cholate were 0.75, 2.0 and 1.87 µmol/100 mg respectively.

Risk factors for mortality from pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis.

The number of patients with non-human immunodeficiency virus (HIV) related pneumocystis carinii pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We performed a meta-analysis to describe the clinical characteristics and factors associated with outcomes of PCP in HIV-negative patients. A total of 13 studies including 867 patients with non-HIV related PCP was included. The overall mortality for non-HIV patients with PCP was 30.6%. The most common underlying disorder for the development of PCP is hematological malignancies (29.1%), followed by autoimmune disease (20.1%), organ or bone marrow transplantation (14.0%), and solid tumors (6.0%). Risk factors associated with increased mortality rate including old age, female sex, longer time from onset of symptoms to diagnosis, respiratory failure, solid tumors, high lactate dehydrogenase, low serum albumin, bacterial, and aspergillus co-infection, etc (P < 0.05). Adjunctive corticosteroid and PCP prophylaxis was not shown to improve the outcome of PCP in non-HIV patients (P > 0.05). Our findings indicate that mortality in non-HIV patients with PCP is high. Improved knowledge about the prognostic factors may guide the early treatment.

Diagnostic MicroRNA Biomarker Discovery for Non-Small-Cell Lung Cancer Adenocarcinoma by Integrative Bioinformatics Analysis.

Lung cancer is the leading cause of cancer death and its incidence is ranked high in men and women worldwide. Non-small-cell lung cancer (NSCLC) adenocarcinoma is one of the most frequent histological subtypes of lung cancer. The aberration profile and the molecular mechanism driving its progression are the key for precision therapy of lung cancer, while the screening of biomarkers is essential to the precision early diagnosis and treatment of the cancer. In this work, we applied a bioinformatics method to analyze the dysregulated interaction network of microRNA-mRNA in NSCLC, based on both the gene expression data and the microRNA-gene regulation network. Considering the properties of the substructure and their biological functions, we identified the putative diagnostic biomarker microRNAs, some of which have been reported on the PubMed citations while the rest, that is, miR-204-5p, miR-567, miR-454-3p, miR-338-3p, and miR-139-5p, were predicted as the putative novel microRNA biomarker for the diagnosis of NSCLC adenocarcinoma. They were further validated by functional enrichment analysis of their target genes. These findings deserve further experimental validations for future clinical application.

DCLK1 is correlated with MET and ERK5 expression, and associated with prognosis in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive cancer for which more effective treatments are needed. In this study, strong to moderate staining of MET and ERK5 was detected in 67.1 and 48% of the analyzed 73 human mesothelioma tumors, and significant correlation of MET and ERK5 expression was identified (P<0.05). We evaluated the doublecortin-like kinase 1 (DCLK1) expression in human mesothelioma tumors. Our results showed that 50.7% of the immunohistochemistry analyzed human mesothelioma tumors have strong to moderate staining of DCLK1, and its expression is significantly correlated with MET or ERK5 expression (P<0.05). Also, the upregulation of DCLK1 is correlated with poor prognosis in MPM patients (P=0.0235). To investigate whether DCLK1 is downstream of MET/ERK5 signaling in human mesothelioma, the effect of DCLK1 expression was analyzed after treatments with either the MET inhibitor XL184 or the ERK5 inhibitor XMD8-92 in human mesothelioma cell lines. Our results showed that the MET inhibitor XL184 reduced the expression of phospho­ERK5 and DCLK1 expression in human mesothelioma cell lines. In addition, the ERK5 inhibitor XMD8-92 reduced the expression of phospho-ERK5 and DCLK1 expression in human mesothelioma cell lines. Furthermore, XML184 and XMD8-92 treatment impaired invasion and tumor sphere formation ability of H290 mesothelioma cells. These results suggest that DCLK1 is regulated by MET/ERK5 signaling in human mesothelioma, and the MET/ERK5/DCLK1 signaling cascade could be further developed into a promising therapeutic target against mesothelioma.

FOXP3+ associated with the pro-inflammatory regulatory T and T helper 17 effector cells in asthma patients.

Asthma is a chronic bronchial inflammation that results to reversible incidence of airway obstruction and shortness of breath. Under normal circumstances, the lung immune system is maintained in a state of controlled inflammation, where balance exists between protective immunity mediated by effector cells and tolerance mediated by cells with regulatory function. Therefore, the inflammation observed in asthma patients may be caused by an imbalance between regulatory T (Treg) cells (CD4-positive with high expression of CD25 surface markers) and forkhead box P3 (FOXP3)-positive pro-inflammatory T helper 17 (Th17) cells. The aim of the present study was to evaluate whether reduced Treg cells and increased Th17 cells could be observed in the peripheral blood samples of asthma patients. As important markers of Treg cells, the expression levels of FOXP3 and interleukin (IL)-17a were analyzed via reverse trancription-quantitative polymerase chain reaction. The results indicated that the levels of cytokines that promote Th17 cells, including IL-6, IL-23 and TGF-ß, were found to increase in the bronchoalveolar lavage fluid sample of asthma patients. However, the IL-10 level in the corresponding sample was much lower compared with that in control individuals. In conclusion, these results suggest that asthma associated with a reduced proportion of Treg and Th17 cells in the blood is characterized by the expression of pro-inflammatory cytokines that may be beneficial for the continuous generation of Th17 cells.

Predicting Diagnostic Gene Biomarkers for Non-Small-Cell Lung Cancer.

Lung cancer is the primary reason for death due to cancer worldwide, and non-small-cell lung cancer (NSCLC) is the most common subtype of lung cancer. Most patients die from complications of NSCLC due to poor diagnosis. In this paper, we aimed to predict gene biomarkers that may be of use for diagnosis of NSCLC by integrating differential gene expression analysis with functional association network analysis. We first constructed an NSCLC-specific functional association network by combining gene expression correlation with functional association. Then, we applied a network partition algorithm to divide the network into gene modules and identify the most NSCLC-specific gene modules based on their differential expression pattern in between normal and NSCLC samples. Finally, from these modules, we identified genes that exhibited the most impact on the expression of their functionally associated genes in between normal and NSCLC samples and predicted them as NSCLC biomarkers. Literature review of the top predicted gene biomarkers suggested that most of them were already considered critical for development of NSCLC.

Umeclidinium Plus Vilanterol Versus Placebo, Umeclidinium, or Vilanterol Monotherapies for Chronic Obstructive Pulmonary Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The role of umeclidinium plus vilanterol as a combination therapy for chronic obstructive pulmonary disease (COPD) has not yet been clearly defined. OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy and safety of umeclidinium plus vilanterol, in contrast to either monotherapy or placebo. METHODS: Systematic searches were conducted in Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and the Chinese Biomedical Literature Database (CBM). Randomized clinical trials pertaining to the treatment of COPD with the combination of umeclidinium and vilanterol, versus umeclidinium, vilanterol or placebo, were reviewed. Studies were pooled to mean differences (MDs), with 95 % confidence intervals (CIs). RESULTS: Six studies were included in our meta-analysis. The application of umeclidinium plus vilanterol compared with umeclidinium alone showed increases in trough forced expiratory volume in 1 s [FEV1] (MD 0.05 L, 95 % CI 0.04-0.07; p < 0.00001) and forced vital capacity [FVC] (MD 0.07 L, 95 % CI 0.04-0.10; p < 0.00001). Similarly, versus vilanterol alone, the application of umeclidinium plus vilanterol showed increases in trough FEV1 (MD 0.10, 95 % CI 0.08-0.12; p < 0.00001) and FVC (MD 0.16 L, 95 % CI 0.13-0.20; p < 0.00001). Compared with placebo, umeclidinium plus vilanterol also showed increases in trough FEV1 (MD 0.21 L, 95 % CI 0.19-0.22; p < 0.00001) and FVC (MD 0.31 L, 95 % CI 0.26-0.35; p < 0.00001). In addition, umeclidinium plus vilanterol has beneficial effects on dyspnea, albuterol use, and health-related quality of life compared with the other three groups. CONCLUSIONS: Compared with the other three groups, i.e. placebo, umeclidinium and vilanterol, umeclidinium plus vilanterol improves lung function and quality of life in patients with COPD, reduces the use of albuterol, and does not increase the incidence of adverse events and serious adverse events.

Characterization of whey protein-carboxymethylated chitosan composite films with and without transglutaminase treatment.

Edible composite packaging has the advantage of complementary functional properties over its each bio-components. However, reports on whey protein concentrates (WPC)-carboxymethylated chitosan (CMC) composite films have not yet been released. To investigate the preparation of WPC-CMC composite films and its functional properties, four types of WPC-CMC composite films were prepared with and without Transglutaminase (TGase) treatment by mixing WPC aqueous solutions (10%, w/v) with CMC aqueous solutions (3%, w/v) at WPC to CMC volume ratios of (100:0), (75:25), (50:50), and (25:75). SDS-PAGE confirmed that TGase catalyzed crosslinking of whey protein. Results revealed that CMC incorporation conferred a smooth and even surface microstructure on the films and markedly improved the transparency, water barrier properties, mechanical properties and solubility of the composite film. Furthermore, TGase resulted in an improvement in the water vapor barrier properties and mechanical properties of WPC-CMC (75:25 and 50:50, v/v) composite films, and there was no impairment of thermal stability of composite films. Therefore, TGase successfully facilitated the formation of WPC-CMC composite films with some improved functional properties. This offers potential applications as an alternative approach to the preparation of edible packaging films.

Rare case of primary pleural lymphoma presenting with pleural effusion.

Primary pleural lymphoma is rare and has been described in association with human immunodeficiency virus (HIV) infection or pyothorax. We report a rare case of primary pleural lymphoma in a 73-year-old man who presented with chest pain and no history of HIV infection or pyothorax. Chest imaging showed pleural thickening and pleural effusion. Thoracoscopic pleural biopsy was performed. Histopathological and immunohistochemical examinations conformed to that of a diffuse large B-cell lymphoma. Physicians should be aware of this rare location of primary lymphoma and implement thoracoscopy as soon as possible.

Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis.

The prognostic value of FoxP3(+) regulatory T cells (Tregs) in cancer remains controversial. We did a meta-analysis to assess the prognostic effect of FoxP3(+) Treg across different types of cancer and to investigate factors associated with variations in this effect. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched to identify eligible studies. In total, we analyzed 76 articles encompassing 17 types of cancer, and including 15,512 cancer cases. The overall pooled analysis including all types of cancer suggested FoxP3(+)Tregs had a significant negative effect on overall survival (OS) (OR 1.46, P < 0.001), but the prognostic effect varied greatly according to tumor site. High FoxP3(+) Tregs infiltration was significantly associated with shorter OS in the majority of solid tumors studied, including cervical, renal, melanomas, and breast cancers, et al; whereas, FoxP3(+) Tregs were associated with improved survival in colorectal, head and neck, and oesophageal cancers. The stratified analysis suggested the molecular subtype and tumor stage significantly influenced the prognostic value of FoxP3(+) Tregs in certain types of cancer. In conclusion, our meta-analysis suggests that the prognostic role of FoxP3(+) Tregs was highly influenced by tumor site, and was also correlated with the molecular subtype and tumor stage.

Effects of histone deacetylase inhibitor trichostatin A combined with cisplatin on apoptosis of A549 cell line.

BACKGROUND: Histone deacetylase (HDAC) inhibitors combined with other drugs for the treatment of malignant tumors are used more and more widely. In this study, we investigated the effect of trichostatin A (TSA), a HDAC inhibitor, in combination with cisplatin, a cytotoxic chemotherapy agent, on the apoptosis of lung cancer A549 cells. METHODS: A549 cells were treated with TSA alone, cisplatin alone or the two drugs combined. Cell viability and apoptosis were evaluated using a light microscope, methyl thiazolyl tetrazolium (MTT) (3-[4, 5-dimethylthiazol-2-yl] -2, 5-diphenyltetrazolium bromide) assay and Hochst33258 staining. Moreover, Western blot analysis was employed to examine the alterations of apoptosis protein: cellular Fas-associated death domain-like interleukin-1 ß converting enzyme inhibitory protein (cFLIP) and caspase-8 in A549 cells in response to the different exogenous stimuli. RESULTS: Compared with single-agent treatment, the co-treatment of A549 cells with TSA and cisplatin synergistically inhibited cell proliferation, induced apoptosis, and increased the inhibition rate. Treatment with TSA and cisplatin led to a significant decrease of cFLIP expression. Furthermore, the treatment of A549 cells with TSA and cisplatin resulted in a significant decrease of pro-caspase-8 and a significant increase of caspase-8. CONCLUSIONS: Synergistic anti-tumor effects are observed between cisplatin and TSA in lung cancer cells. The combination of TSA with cisplatin may be a more effective method in human lung cancer treatment.

Identification of Gene Biomarkers for Distinguishing Small-Cell Lung Cancer from Non-Small-Cell Lung Cancer Using a Network-Based Approach.

Lung cancer consists of two main subtypes: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) that are classified according to their physiological phenotypes. In this study, we have developed a network-based approach to identify molecular biomarkers that can distinguish SCLC from NSCLC. By identifying positive and negative coexpression gene pairs in normal lung tissues, SCLC, or NSCLC samples and using functional association information from the STRING network, we first construct a lung cancer-specific gene association network. From the network, we obtain gene modules in which genes are highly functionally associated with each other and are either positively or negatively coexpressed in the three conditions. Then, we identify gene modules that not only are differentially expressed between cancer and normal samples, but also show distinctive expression patterns between SCLC and NSCLC. Finally, we select genes inside those modules with discriminating coexpression patterns between the two lung cancer subtypes and predict them as candidate biomarkers that are of diagnostic use.

R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma.

OBJECTIVES: Mutations in the GJB2 gene encoding connexin 26 (Cx26) are major causes of hereditary deafness. This study aimed to characterize the mutation profiles of the GJB2 gene in a Chinese family with sensorineural hearing loss. METHODS: A Chinese family that included three individuals with sensorineural hearing loss and palmoplantar keratoderma underwent complete physical examinations, audiological examinations including pure tone audiometry and auditory brainstem response, skin pathological examination, and temporal CT scans. The entire coding region of GJB2, GJB3, GJB6, and the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN) were sequenced. Structural analysis was performed to detect the effects of mutation on the tertiary structure of Cx26. RESULTS: A dominant GJB2 mutation, c.224G>A (p.Arg75Gln, p.R75Q), was detected in the family. No other mutation was identified in GJB2, GJB3, GJB6, or the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN). Structural analysis revealed that the p.R75Q mutation likely affects the structural stability and permeation properties of the Cx26 gap junction channel. CONCLUSION: Our findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma.

Recipient-related clinical risk factors for primary graft dysfunction after lung transplantation: a systematic review and meta-analysis.

BACKGROUND: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Herein, we carried out a systematic review and meta-analysis of published literature to identify recipient-related clinical risk factors associated with PGD development. METHOD: A systematic search of electronic databases (PubMed, Embase, Web of Science, Cochrane CENTRAL, and Scopus) for studies published from 1970 to 2013 was performed. Cohort, case-control, or cross-sectional studies that examined recipient-related risk factors of PGD were included. The odds ratios (ORs) or mean differences (MDs) were calculated using random-effects models. RESULT: Thirteen studies involving 10042 recipients met final inclusion criteria. From the pooled analyses, female gender (OR 1.38, 95% CI 1.09 to 1.75), African American (OR 1.82, 95%CI 1.36 to 2.45), idiopathic pulmonary fibrosis (IPF) (OR 1.78, 95% CI 1.49 to 2.13), sarcoidosis (OR 4.25, 95% CI 1.09 to 16.52), primary pulmonary hypertension (PPH) (OR 3.73, 95%CI 2.16 to 6.46), elevated BMI (BMI≥25 kg/m2) (OR 1.83, 95% CI 1.26 to 2.64), and use of cardiopulmonary bypass (CPB) (OR 2.29, 95%CI 1.43 to 3.65) were significantly associated with increased risk of PGD. Age, cystic fibrosis, secondary pulmonary hypertension (SPH), intra-operative inhaled nitric oxide (NO), or lung transplant type (single or bilateral) were not significantly associated with PGD development (all P>0.05). Moreover, a nearly 4 fold increased risk of short-term mortality was observed in patients with PGD (OR 3.95, 95% CI 2.80 to 5.57). CONCLUSIONS: Our analysis identified several recipient related risk factors for development of PGD. The identification of higher-risk recipients and further research into the underlying mechanisms may lead to selective therapies aimed at reducing this reperfusion injury.

Primary choriocarcinoma in mediastinum with multiple lung metastases in a male patient: A case report and a review of the literature.

Primary choriocarcinoma is a rare malignant tumor, particularly in men. The tumor, mostly found in the gastrointestinal system and mediastinum, often metastasizes early with poor therapeutic effects and prognosis. Herein, we present a male patient with primary mediastinum choriocarcinoma and widespread lung metastases. The disease progressed rapidly with little therapeutic effect from chemotherapy. The patient died of this disease 75 days after initial symptom presentations. Literature review found only 41 cases of primary choriocarcinoma reported in the mediastinum. This case highlights the importance of keeping primary choriocarcinoma in the differentials for mediastinum tumors in young men. Sex hormone testing is helpful to confirm diagnosis. Early biopsy should be performed to confirm pathologic diagnose, and early surgery and chemotherapy should be considered to improve the cure rate of this disease.