Fermentation of tomato juice improves \u3cem\u3ein vitro\u3c/em\u3e bioaccessibility of lycopene

The impact of fermentation (Saccharomyces cerevisiae ATCC 9763) on the bioaccessibility of lycopene in a model tomato juice was examined. The physicochemical and structural properties of the tomato tissue were determined after fermentation and the bioaccessibility of lycopene was monitored using a simulated gastrointestinal tract. A lycopene concentration of 45.1 mg/100 g was obtained under optimal fermentation conditions. The cell walls of the tomato cells were hydrolyzed and disrupted by fermentation. Cell disruption decreased the pectin content and reduced the tissue fragment size, thereby reducing gravitational separation and facilitating lycopene release. The lycopene bioaccessibility in the tomato juices increased in the following order: unfermented (8.5%) \u3c fermented (11.4%) \u3c unfermented-emulsified (13.6%) \u3c fermented-emulsified (22.7%). These effects were attributed to a combination of greater tomato tissue disruption and enhanced mixed micelle formation. Our results may be useful for the development of functional foods and beverages with improved health benefits

Seroprevalence of Bartonella in Eastern China and analysis of risk factors

<p>Abstract</p> <p>Background</p> <p><it>Bartonella </it>infections are emerging in the Zhejiang Province of China. However, there has been no effort to date to explore the epidemiology of these infections in this region, nor to identify risk factors associated with exposure to <it>Bartonella</it>. The aim of this study was to investigate the seroprevalence of <it>Bartonella </it>in both patients bitten by dogs and blood donors (for control) in Eastern China, and to identify risk factors associated with exposure to <it>Bartonella</it>. As no previous data for this region have been published, this study will provide baseline data useful for <it>Bartonella </it>infection surveillance, control, and prevention.</p> <p>Methods</p> <p>Blood samples were collected from industrial rabies clinic attendees and blood donors living in eight areas of the Zhejiang Province of China, between December 2005 and November 2006. An indirect immunofluorescent antibody test was used to determine the presence of <it>Bartonella </it>in these samples. Risk factors associated with <it>Bartonella </it>exposure were explored using Chi-square tests and logistic regression analysis of epidemiological data relating to the study's participants.</p> <p>Results</p> <p><it>Bartonella </it>antibodies were detected in 19.60% (109/556) of blood samples. Seroprevalence varied among the eight areas surveys, ranging from over 32% in Hangzhou to only 2% in Jiangshan (X²= 28.22, P < 0.001). We detected a significantly higher prevalence of <it>Bartonella </it>antibodies in people who had been bitten by dogs than in blood donors (X²= 13.86, P < 0.001). Seroprevalence of <it>Bartonella </it>was similar among males (18.61%, n = 317) and females (20.92%, n = 239).</p> <p>Conclusions</p> <p><it>Bartonella </it>antibodies were encountered in people living across Zhejiang Province and the seropositivity rate among those exposed to dog bites was significantly higher than that among blood donors, indicating that dog bites may be a risk factor for <it>Bartonella </it>infection.</p

Mesenchymal Stem Cell in the Intervertebral Disc

Degeneration of the intervertebral disc (IVD) is a major spinal disorder that causes back pain. Nucleus pulposus (NP) in the central of IVD dehydrates and become more fibrous in the IVD degeneration. NP cells undergo apoptosis with the degeneration of extracellular matrix (ECM) components. To replenish the NP cells and core ECM, bone marrow mesenchymal stromal cells (BMSCs) have been highlighted in the regeneration of IVD degeneration. BMSCs differentiate into NP-like cells with the secretion of ECM components, which may not only replenish the number of NP cells but also stimulate NP reconstruction. This further maintains tissue homeostasis. Up to date, the disc progenitor cells (DPCs) have been identified with the characteristics of multidifferentiation and stem cell phenotype. These cells are involved in the IVD diseases and show regenerative potentials. However, the differences between the BMSCs and DPCs remain elusive, in particular, the cellular connection in vivo. As such, this chapter will discuss the findings of the two cell types and propose a novel concept in the understanding of the biology of IVD

Dual adversarial models with cross-coordination consistency constraint for domain adaption in brain tumor segmentation

The brain tumor segmentation task with different domains remains a major challenge because tumors of different grades and severities may show different distributions, limiting the ability of a single segmentation model to label such tumors. Semi-supervised models (e.g., mean teacher) are strong unsupervised domain-adaptation learners. However, one of the main drawbacks of using a mean teacher is that given a large number of iterations, the teacher model weights converge to those of the student model, and any biased and unstable predictions are carried over to the student. In this article, we proposed a novel unsupervised domain-adaptation framework for the brain tumor segmentation task, which uses dual student and adversarial training techniques to effectively tackle domain shift with MR images. In this study, the adversarial strategy and consistency constraint for each student can align the feature representation on the source and target domains. Furthermore, we introduced the cross-coordination constraint for the target domain data to constrain the models to produce more confident predictions. We validated our framework on the cross-subtype and cross-modality tasks in brain tumor segmentation and achieved better performance than the current unsupervised domain-adaptation and semi-supervised frameworks

Strategies targeting endoplasmic reticulum stress to improve Parkinson’s disease

Parkinson’s disease (PD) is a common neurodegenerative disorder with motor symptoms, which is caused by the progressive death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Accumulating evidence shows that endoplasmic reticulum (ER) stress occurring in the SNpc DA neurons is an early event in the development of PD. ER stress triggers the activation of unfolded protein response (UPR) to reduce stress and restore ER function. However, excessive and continuous ER stress and UPR exacerbate the risk of DA neuron death through crosstalk with other PD events. Thus, ER stress is considered a promising therapeutic target for the treatment of PD. Various strategies targeting ER stress through the modulation of UPR signaling, the increase of ER’s protein folding ability, and the enhancement of protein degradation are developed to alleviate neuronal death in PD models. In this review, we summarize the pathological role of ER stress in PD and update the strategies targeting ER stress to improve ER protein homeostasis and PD-related events

A modified Ranson score to predict disease severity, organ failure, pancreatic necrosis, and pancreatic infection in patients with acute pancreatitis

BackgroundAlthough there are several scoring systems currently used to predict the severity of acute pancreatitis, each of them has limitations. Determine the accuracy of a modified Ranson score in predicting disease severity and prognosis in patients with acute pancreatitis (AP).MethodsAP patients admitted or transferred to our institution were allocated to a modeling group (n = 304) or a validation group (n = 192). A modified Ranson score was determined by excluding the fluid sequestration parameter and including the modified computed tomography severity index (CTSI). The diagnostic performance of the modified Ranson score was compared with the Ranson score, modified CTSI, and bedside index of severity in acute pancreatitis (BISAP) score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection.ResultsThe modified Ranson score had significantly better accuracy that the Ranson score in predicting all four outcome measures in the modeling group and in the validation group (all p &lt; 0.05). For the modeling group the modified Ranson score had the best accuracy for predicting disease severity and organ failure, and second-best accuracy for predicting pancreatic necrosis and pancreatic infection. For the verification group, it had the best accuracy for predicting organ failure, second-best accuracy for predicting disease severity and pancreatic necrosis, and third-best accuracy for predicting pancreatic infection.ConclusionThe modified Ranson score provided better accuracy than the Ranson score in predicting disease severity, organ failure, pancreatic necrosis and pancreatic infection. Relative to the other scoring systems, the modified Ranson system was superior in predicting organ failure

miRNA Expression Profile of Saliva in Subjects of Yang Deficiency Constitution and Yin Deficiency Constitution

Background/Aims: Based on the theory of constitution in Traditional Chinese Medicine (TCM), the Chinese Han population has been classified into nine constitutions. Of these, Yang deficiency constitution mainly exhibit cold intolerance while Yin deficiency constitution mainly exhibit heat intolerance. Some studies have been carried out to explore the modern genetic and biological basis of such constitution classification, but more remains to be done. MicroRNA (miRNA) serves as post-transcriptional regulators of gene expression and may play a role in the classification process. Here, we examined miRNA expression profile of saliva to further improve the comprehensiveness of constitution classification. Methods: Saliva was collected from Chinese Han individuals with Yang deficiency, Yin deficiency and Balanced constitutions (n=5 each), and miRNA expression profile was determined using the Human miRNA OneArray®v7. Based on 1.5 Fold change, means log2|Ratio|≥0.585 and P-value&#x3c; 0.05, differentially expressed miRNA was screened. Target genes were predicted using DIANA-TarBasev7.0 and analysis of KEGG pathway was carried out using DIANA-mirPathv.3. Results: We found that 81 and 98 differentially expressed miRNAs were screened in Yang deficiency and Yin deficiency constitution, respectively. Among them, 16 miRNAs were identical and the others were unique. In addition, the target genes that are regulated by the unique miRNAs were significantly enriched in 27 and 20 signaling pathways in Yang deficiency and Yin deficiency constitution, respectively. Thyroid hormone signaling pathway is present in both constitutions. These unique miRNAs that regulated target genes of thyroid hormone signaling pathway may be associated with cold intolerance or heat intolerance. Conclusion: The results of our study show that Yang deficiency and Yin deficiency constitutions exhibit systematic differences in miRNA expression profile. Moreover, the distinct characteristics of TCM constitution may be explained, in part, by differentially expressed miRNAs

SIK2 inhibition enhances PARP inhibitor activity synergistically in ovarian and triple-negative breast cancers

Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) have had an increasing role in the treatment of ovarian and breast cancers. PARP inhibitors are selectively active in cells with homologous recombination DNA repair deficiency caused by mutations in BRCA1/2 and other DNA repair pathway genes. Cancers with homologous recombination DNA repair proficiency respond poorly to PARP inhibitors. Cancers that initially respond to PARP inhibitors eventually develop drug resistance. We have identified salt-inducible kinase 2 (SIK2) inhibitors, ARN3236 and ARN3261, which decreased DNA double-strand break (DSB) repair functions and produced synthetic lethality with multiple PARP inhibitors in both homologous recombination DNA repair deficiency and proficiency cancer cells. SIK2 is required for centrosome splitting and PI3K activation and regulates cancer cell proliferation, metastasis, and sensitivity to chemotherapy. Here, we showed that SIK2 inhibitors sensitized ovarian and triple-negative breast cancer (TNBC) cells and xenografts to PARP inhibitors. SIK2 inhibitors decreased PARP enzyme activity and phosphorylation of class-IIa histone deacetylases (HDAC4/5/7). Furthermore, SIK2 inhibitors abolished class-IIa HDAC4/5/7–associated transcriptional activity of myocyte enhancer factor-2D (MEF2D), decreasing MEF2D binding to regulatory regions with high chromatin accessibility in FANCD2, EXO1, and XRCC4 genes, resulting in repression of their functions in the DNA DSB repair pathway. The combination of PARP inhibitors and SIK2 inhibitors provides a therapeutic strategy to enhance PARP inhibitor sensitivity for ovarian cancer and TNBC

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN