Deregulation of apoptosis mediators' p53 and bcl2 in lung tissue of COPD patients

Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis. However, studies in human subjects are limited

Rescuing Loading Induced Bone Formation at Senescence

The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential

The First Illumina-Based De Novo Transcriptome Sequencing and Analysis of Safflower Flowers

BACKGROUND: The safflower, Carthamus tinctorius L., is a worldwide oil crop, and its flowers, which have a high flavonoid content, are an important medicinal resource against cardiovascular disease in traditional medicine. Because the safflower has a large and complex genome, the development of its genomic resources has been delayed. Second-generation Illumina sequencing is now an efficient route for generating an enormous volume of sequences that can represent a large number of genes and their expression levels. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the genes and pathways that might control flavonoids and other secondary metabolites in the safflower, we used Illumina sequencing to perform a de novo assembly of the safflower tubular flower tissue transcriptome. We obtained a total of 4.69 Gb in clean nucleotides comprising 52,119,104 clean sequencing reads, 195,320 contigs, and 120,778 unigenes. Based on similarity searches with known proteins, we annotated 70,342 of the unigenes (about 58% of the identified unigenes) with cut-off E-values of 10(-5). In total, 21,943 of the safflower unigenes were found to have COG classifications, and BLAST2GO assigned 26,332 of the unigenes to 1,754 GO term annotations. In addition, we assigned 30,203 of the unigenes to 121 KEGG pathways. When we focused on genes identified as contributing to flavonoid biosynthesis and the biosynthesis of unsaturated fatty acids, which are important pathways that control flower and seed quality, respectively, we found that these genes were fairly well conserved in the safflower genome compared to those of other plants. CONCLUSIONS/SIGNIFICANCE: Our study provides abundant genomic data for Carthamus tinctorius L. and offers comprehensive sequence resources for studying the safflower. We believe that these transcriptome datasets will serve as an important public information platform to accelerate studies of the safflower genome, and may help us define the mechanisms of flower tissue-specific and secondary metabolism in this non-model plant

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of bovine ruminal epithelium

peer-reviewedCompensatory growth (CG) is utilised worldwide in beef production systems as a management approach to reduce feed costs. However the underlying biology regulating the expression of CG remains to be fully elucidated. The objective of this study was to examine the effect of dietary restriction and subsequent re-alimentation induced CG on the global gene expression profile of ruminal epithelial papillae. Holstein Friesian bulls (n = 60) were assigned to one of two groups: restricted feed allowance (RES; n = 30) for 125 days (Period 1) followed by ad libitum access to feed for 55 days (Period 2) or (ii) ad libitum access to feed throughout (ADLIB; n = 30). At the end of each period, 15 animals from each treatment were slaughtered and rumen papillae harvested. mRNA was isolated from all papillae samples collected. cDNA libraries were then prepared and sequenced. Resultant reads were subsequently analysed bioinformatically and differentially expressed genes (DEGs) are defined as having a Benjamini-Hochberg P value of <0.05. During re-alimentation in Period 2, RES animals displayed CG, growing at 1.8 times the rate of their ADLIB contemporary animals in Period 2 (P < 0.001). At the end of Period 1, 64 DEGs were identified between RES and ADLIB, with only one DEG identified at the end of Period 2. When analysed within RES treatment (RES, Period 2 v Period 1), 411 DEGs were evident. Genes identified as differentially expressed in response to both dietary restriction and subsequent CG included those involved in processes such as cellular interactions and transport, protein folding and gene expression, as well as immune response. This study provides an insight into the molecular mechanisms underlying the expression of CG in rumen papillae of cattle; however the results suggest that the role of the ruminal epithelium in supporting overall animal CG may have declined by day 55 of re-alimentation.SMW received financial assistance from Science Foundation Ireland (SFI) contract no 09/ RFP/GEN2447

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Dental caries in primary and permanent teeth in children's worldwide, 1995 to 2019: a systematic review and meta-analysis

Background: Early childhood caries (ECC) is a type of dental caries in the teeth of infants and children that is represented as one of the most prevalent dental problems in this period. Various studies have reported different types of prevalence of dental caries in primary and permanent teeth in children worldwide. However, there has been no comprehensive study to summarize the results of these studies in general, so this study aimed to determine the prevalence of dental caries in primary and permanent teeth in children in different continents of the world during a systematic review and meta-analysis. Methods: In this review study, articles were extracted by searching in the national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed, and Web of Science (ISI) between 1995 and December 2019. Random effects model was used for analysis and heterogeneity of studies was evaluated by using the I2 index. Data were analyzed by using the Comprehensive Meta-Analysis (Version 2) software. Findings: In this study, a total of 164 articles (81 articles on the prevalence of dental caries in primary teeth and 83 articles on the prevalence of dental caries in permanent teeth) were entered the meta-analysis. The prevalence of dental caries in primary teeth in children in the world with a sample size of 80,405 was 46.2% (95% CI: 41.6–50.8%), and the prevalence of dental caries in permanent teeth in children in the world with a sample size of 1,454,871 was 53.8% (95% CI: 50–57.5%). Regarding the heterogeneity on the basis of meta-regression analysis, there was a significant difference in the prevalence of dental caries in primary and permanent teeth in children in different continents of the world. With increasing the sample size and the year of study, dental caries in primary teeth increased and in permanent teeth decreased. Conclusion: The results of this study showed that the prevalence of primary and permanent dental caries in children in the world was found to be high. Therefore, appropriate strategies should be implemented to improve the aforementioned situation and to troubleshoot and monitor at all levels by providing feedback to hospitals