scholarly journals Correlation Network Analysis Reveals Relationships between MicroRNAs, Transcription FactorT-bet, and Deregulated Cytokine/Chemokine-Receptor Network in Pulmonary Sarcoidosis

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Tereza Dyskova ◽  
Regina Fillerova ◽  
Tomas Novosad ◽  
Milos Kudelka ◽  
Monika Zurkova ◽  
...  

Sarcoidosis is an inflammatory granulomatous disease with unknown etiology driven by cytokines and chemokines. There is limited information regarding the regulation of cytokine/chemokine-receptor network in bronchoalveolar lavage (BAL) cells in pulmonary sarcoidosis, suggesting contribution of miRNAs and transcription factors. We therefore investigated gene expression of 25 inflammation-related miRNAs, 27 cytokines/chemokines/receptors, and a Th1-transcription factorT-betin unseparated BAL cells obtained from 48 sarcoidosis patients and 14 control subjects using quantitative RT-PCR. We then examined both miRNA-mRNA expressions to enrich relevant relationships. This first study on miRNAs in sarcoid BAL cells detected deregulation ofmiR-146a,miR-150,miR-202,miR-204, andmiR-222expression comparing to controls. Subanalysis revealed higher number ofmiR-155,let-7ctranscripts in progressing (n=20) comparing to regressing (n=28) disease as assessed by 2-year follow-up. Correlation network analysis revealed relationships between microRNAs, transcription factorT-bet, and deregulated cytokine/chemokine-receptor network in sarcoid BAL cells. Furthermore,T-betshowed more pronounced regulatory capability to sarcoidosis-associated cytokines/chemokines/receptors than miRNAs, which may function rather as “fine-tuners” of cytokine/chemokine expression. Our correlation network study implies contribution of both microRNAs and Th1-transcription factorT-betto the regulation of cytokine/chemokine-receptor network in BAL cells in sarcoidosis. Functional studies are needed to confirm biological relevance of the obtained relationships.

Respiration ◽  
2021 ◽  
pp. 1-9
Author(s):  
Elad Guber ◽  
Ori Wand ◽  
Gali Epstein Shochet ◽  
Ayal Romem ◽  
David Shitrit

<b><i>Background:</i></b> Sarcoidosis is a heterogeneous multisystemic disorder of unknown etiology. Dyspnea and fatigue are two of the most common and debilitating symptoms experienced by subjects with sarcoidosis. There is limited evidence regarding the short- and long-term impact of pulmonary rehabilitation (PR) on exercise capacity and fatigue in these individuals. <b><i>Objective:</i></b> To evaluate the benefit of PR in subjects with pulmonary sarcoidosis at different severity stages and to review the current literature about PR in sarcoidosis. <b><i>Methods:</i></b> PR included a 12-week training program of a twice-weekly 90-min workouts. Fifty-two subjects with stable pulmonary sarcoidosis were recruited. Maximal exercise capacity, defined as VO<sub>2</sub>max, was measured using the cardiopulmonary exercise test (CPET). Pulmonary function tests, 6-min walking distance (6MWD), St. George’s Respiratory Questionnaire (SGRQ), and the modified Medical Research Council (mMRC) and Hospital Anxiety and Depression Scale (HADS) questionnaires were given before and after PR and following 6 months (follow-up). <b><i>Results:</i></b> The PR program significantly increased the VO<sub>2</sub>max (1.8 ± 2.3 mL/kg/min, <i>p</i> = 0.002), following 12 weeks. mMRC and SGRQ scores were also improved (−0.3 ± 0.8, <i>p</i> = 0.03, and −3.87 ± 10.4, <i>p</i> = 0.03, respectively). The impact of PR on VO<sub>2</sub>max was more pronounced in subjects with pulmonary parenchymal involvement. The increase in VO<sub>2</sub>max correlated with initial disease severity (indicated by FEV1/FVC, <i>p</i> = 0.01). Subjects with FEV1/FVC &#x3c;70% showed greater improvement in 6MWD. 6MWD also improved in those with a transfer coefficient of the lung for CO (KCO) above 80% predicted (<i>p</i> &#x3c; 0.05). At 6-month follow-up, the VO<sub>2</sub>max, 6MWD, and SGRQ scores remained stable, thus suggesting lasting effects of PR. <b><i>Conclusion:</i></b> PR is a promising complementary therapeutic intervention for subjects with sarcoidosis. Further study is needed to validate these findings.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xueling Li ◽  
Yudou Cheng ◽  
Meng Wang ◽  
Sujuan Cui ◽  
Junfeng Guan

Abstract Background Flesh is prone to accumulate more anthocyanin in postharvest ‘Friar’ plum (Prunus salicina Lindl.) fruit stored at an intermediate temperature. However, little is known about the molecular mechanism of anthocyanin accumulation regulated by storage temperature in postharvest plum fruit. Results To reveal the potential molecular regulation mechanism of anthocyanin accumulation in postharvest ‘Friar’ plum fruit stored at different temperatures (0 °C, 10 °C and 25 °C), the fruit quality, metabolite profile and transcriptome of its flesh were investigated. Compared to the plum fruit stored at 0 °C and 25 °C, the fruit stored at 10 °C showed lower fruit firmness after 14 days and reduced the soluble solids content after 21 days of storage. The metabolite analysis indicated that the fruit stored at 10 °C had higher contents of anthocyanins (pelargonidin-3-O-glucoside, cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside and quercetin-3-O-rutinose), quercetin and sucrose in the flesh. According to the results of weighted gene coexpression correlation network analysis (WGCNA), the turquoise module was positively correlated with the content of anthocyanin components, and flavanone 3-hydroxylase (F3H) and chalcone synthase (CHS) were considered hub genes. Moreover, MYB family transcription factor APL (APL), MYB10 transcription factor (MYB10), ethylene-responsive transcription factor WIN1 (WIN1), basic leucine zipper 43-like (bZIP43) and transcription factor bHLH111-like isoform X2 (bHLH111) were closely related to these hub genes. Further qRT–PCR analysis verified that these transcription factors were specifically more highly expressed in plum flesh stored at 10 °C, and their expression profiles were significantly positively correlated with the structural genes of anthocyanin synthesis as well as the content of anthocyanin components. In addition, the sucrose biosynthesis-associated gene sucrose synthase (SS) was upregulated at 10 °C, which was also closely related to the anthocyanin content of plum fruit stored at 10 °C. Conclusions The present results suggest that the transcription factors APL, MYB10, WIN1, bZIP43 and bHLH111 may participate in the accumulation of anthocyanin in ‘Friar’ plum flesh during intermediate storage temperatures by regulating the expression of anthocyanin biosynthetic structural genes. In addition, the SS gene may play a role in anthocyanin accumulation in plum flesh by regulating sucrose biosynthesis.


2021 ◽  
Author(s):  
Olga Basso ◽  
Sydney K Willis ◽  
Elizabeth E Hatch ◽  
Ellen M Mikkelsen ◽  
Kenneth J Rothman ◽  
...  

Abstract STUDY QUESTION Do daughters of older mothers have lower fecundability? SUMMARY ANSWER In this cohort study of North American pregnancy planners, there was virtually no association between maternal age ≥35 years and daughters’ fecundability. WHAT IS KNOWN ALREADY Despite suggestive evidence that daughters of older mothers may have lower fertility, only three retrospective studies have examined the association between maternal age and daughter’s fecundability. STUDY DESIGN, SIZE, DURATION Prospective cohort study of 6689 pregnancy planners enrolled between March 2016 and January 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Pregnancy Study Online (PRESTO) is an ongoing pre-conception cohort study of pregnancy planners (age, 21-45 years) from the USA and Canada. We estimated fecundability ratios (FR) for maternal age at the participant’s birth using multivariable proportional probabilities regression models. MAIN RESULTS AND THE ROLE OF CHANCE Daughters of mothers ≥30 years were less likely to have previous pregnancies (or pregnancy attempts) or risk factors for infertility, although they were more likely to report that their mother had experienced problems conceiving. The proportion of participants with prior unplanned pregnancies, a birth before age 21, ≥3 cycles of attempt at study entry or no follow-up was greater among daughters of mothers &lt;25 years. Compared with maternal age 25–29 years, FRs (95% CI) for maternal age &lt;20, 20–24, 30–34, and ≥35 were 0.72 (0.61, 0.84), 0.92 (0.85, 1.00), 1.08 (1.00, 1.17), and 1.00 (0.89, 1.12), respectively. LIMITATIONS, REASONS FOR CAUTION Although the examined covariates did not meaningfully affect the associations, we had limited information on the participants’ mother. Differences by maternal age in reproductive history, infertility risk factors and loss to follow-up suggest that selection bias may partly explain our results. WIDER IMPLICATIONS OF THE FINDINGS Our finding that maternal age 35 years or older was not associated with daughter’s fecundability is reassuring, considering the trend towards delayed childbirth. However, having been born to a young mother may be a marker of low fecundability among pregnancy planners. STUDY FUNDING/COMPETING INTEREST(S) PRESTO was funded by NICHD Grants (R21-HD072326 and R01-HD086742) and has received in-kind donations from Swiss Precision Diagnostics, FertilityFriend.com, Kindara.com, and Sandstone Diagnostics. Dr Wise is a fibroid consultant for AbbVie, Inc. TRIAL REGISTRATION NUMBER n/a


2021 ◽  
pp. 1-11
Author(s):  
Xuewei Wang ◽  
Hai Bui ◽  
Prashanthi Vemuri ◽  
Jonathan Graff-Radford ◽  
Clifford R. Jack Jr ◽  
...  

Background: Lipid alterations contribute to Alzheimer’s disease (AD) pathogenesis. Lipidomics studies could help systematically characterize such alterations and identify potential biomarkers. Objective: To identify lipids associated with mild cognitive impairment and amyloid-β deposition, and to examine lipid correlation patterns within phenotype groups Methods: Eighty plasma lipids were measured using mass spectrometry for 1,255 non-demented participants enrolled in the Mayo Clinic Study of Aging. Individual lipids associated with mild cognitive impairment (MCI) were first identified. Correlation network analysis was then performed to identify lipid species with stable correlations across conditions. Finally, differential correlation network analysis was used to determine lipids with altered correlations between phenotype groups, specifically cognitively unimpaired versus MCI, and with elevated brain amyloid versus without. Results: Seven lipids were associated with MCI after adjustment for age, sex, and APOE4. Lipid correlation network analysis revealed that lipids from a few species correlated well with each other, demonstrated by subnetworks of these lipids. 177 lipid pairs differently correlated between cognitively unimpaired and MCI patients, whereas 337 pairs of lipids exhibited altered correlation between patients with and without elevated brain amyloid. In particular, 51 lipid pairs showed correlation alterations by both cognitive status and brain amyloid. Interestingly, the lipids central to the network of these 51 lipid pairs were not significantly associated with either MCI or amyloid, suggesting network-based approaches could provide biological insights complementary to traditional association analyses. Conclusion: Our attempt to characterize the alterations of lipids at network-level provides additional insights beyond individual lipids, as shown by differential correlations in our study.


2011 ◽  
Vol 36 (2) ◽  
pp. 123-126 ◽  
Author(s):  
Marcio Guelmann ◽  
Joseph Shapira ◽  
Daniela Silva ◽  
Anna Fuks

Objective: The goal of this manuscript was to review the existing literature in regards to esthetic options to restore pulpotomized primary molars. Study design: A pubmed literature search has been performed and all relevant studies were assessed. Results: Two laboratory, 3 restrospective and 4 prospective clinical studies were found, reviewed and analyzed. Conclusions: Based on the limited information available, we concluded that tooth colored and bonded restorations showed promising results as alternative materials to replace stainless steel crowns after pulpotomies in primary molars. Hybrid composites tend to perform better than compomers. Resin modified glass ionomer cements demonstrated excellent marginal seal and retention. More long-term follow up studies are necessary until more definitive recommendations can be made.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nan-Hui Zhang ◽  
Yi-Chun Cheng ◽  
Ran Luo ◽  
Chun-Xiu Zhang ◽  
Shu-Wang Ge ◽  
...  

Abstract Background Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Despite abundant data on that many COVID-19 patients also displayed kidney disease, there is limited information available about the recovery of kidney disease after discharge. Methods Retrospective and prospective cohort study to patients with new-onset kidney disease during the COVID-19 hospitalization, admitted between January 28 to February 26, 2020. The median follow-up was 4 months after discharge. The follow-up patients were divided into the recovery group and non-recovery group. Descriptive statistics and between-groups comparison were used. Results In total, 143 discharged patients with new-onset kidney disease during the COVID-19 hospitalization were included. Patients had a median age was 64 (IQR, 51–70) years, and 59.4% of patients were men. During 4-months median follow-up, 91% (130 of 143) patients recovered from kidney disease, and 9% (13 of 143) patients haven’t recovered. The median age of patients in the non-recovery group was 72 years, which was significantly higher than the median age of 62 years in the recovery group. Discharge serum creatinine was significantly higher in the non-recovery group than in the recovery group. Conclusions Most of the new-onset kidney diseases during hospitalization of COVID-19 patients recovered 4 months after discharge. We recommend that COVID-19 patients with new-onset kidney disease be followed after discharge to assess kidney recovery, especially elderly patients or patients with high discharge creatinine.


2021 ◽  
pp. jim-2020-001659
Author(s):  
Amir Mousapasandi ◽  
Cristan Herbert ◽  
Paul Thomas

Sarcoidosis is a systemic granulomatous disease of unknown etiology and pathogenesis with a heterogeneous clinical presentation. In the appropriate clinical and radiological context and with the exclusion of other diagnoses, the disease is characterized by the pathological presence of non-caseating epithelioid cell granulomas. Sarcoidosis is postulated to be a multifactorial disease caused by chronic antigenic stimulation. The immunopathogenesis of sarcoidosis encompasses a complex interaction between the host, genetic factors and postulated environmental and infectious triggers, which result in granuloma development.The exact pathogenesis of the disease has yet to be elucidated, but some of the inflammatory pathways that play a key role in disease progression and outcomes are becoming apparent, and these may form the logical basis for selecting potential biomarkers.Biomarkers are biological molecules that are altered pathologically. To date, there exists no single reliable biomarker for the evaluation of sarcoidosis, either diagnostically or prognostically but new candidates are emerging. A diagnosis of sarcoidosis ideally requires a biopsy confirming non-caseating granulomas, but the likelihood of progression that requires intervention remains unpredictable. These challenging aspects could be potentially resolved by incorporating biomarkers into clinical practice for both diagnosis and monitoring disease activity.This review outlines the current knowledge on sarcoidosis with an emphasis on pulmonary sarcoidosis, and delineates the understanding surrounding the implication of biomarkers for the clinical evaluation of sarcoidosis.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Amir Schricker ◽  
Tina Baykaner ◽  
Junaid Zaman ◽  
Gautam Lalani ◽  
Kenneth Hopper ◽  
...  

Introduction: Targets for the ablation of atrial fibrillation (AF) are debated. In particular, recent studies questioning fractionated electrograms and lines has increased focus on AF substrates of rotors and focal impulses. These AF sources are seen in both atria, but have unknown etiology. We hypothesized that differential remodeling between the right atrium (RA), whose structural changes are largely undefined, and left atrium (LA) influence the distribution of AF sources and the outcomes from AF source ablation. Methods: In 60 patients at AF ablation (62±10 years, 60% persistent, 5% long-standing persistent), we compared size differences between RA and LA to the number of sources in each chamber and outcomes from AF source-guide ablation. We studied if a 64-pole basket differentially fit the LA or RA, judged by deformation of its splines by the atria (fig. A, B) over multiple cardiac cycles on fluoroscopy. Ablation targeted sources in both atria and was followed by PVI, with follow-up per guidelines. Results: Using baskets in both atria, 205 sources (LA 138; RA 67) were identified and ablated. Notably, the same basket in each patient was dynamically deformed by RA in 51 (85%) of cases but in the LA in only 39 (65%), indicating greater LA remodeling. The number of AF sources was higher in the presence of basket deformation of RA (n=174) than LA (n=130). LA deformation correlated with LVEF (p=0.05). Freedom from AF at 1 year was reduced in patients with no basket deformation (i.e. dilation) in LA (p=0.07) or RA (p=0.06). Notably, single procedure AF freedom was substantially lower in patients with differential remodeling (deformation in only 1 chamber) of 84% vs. 60% (fig C). Conclusions: Structural atrial remodeling influences the number of electrical rotors and focal sources in each chamber. A mismatch between right and left atrial remodeling predicts lower success from rotor ablation. These data also provide novel clinical indices of effective basket positioning.


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