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Hepatology (Baltimore, Md.) Jul 2021HCV often causes chronic infection in liver, cirrhosis, and, in some instances, HCC. HCV encodes several factors' those impair host genes for establishment of chronic... (Observational Study)
Observational Study
BACKGROUND AND AIMS
HCV often causes chronic infection in liver, cirrhosis, and, in some instances, HCC. HCV encodes several factors' those impair host genes for establishment of chronic infection. The long noncoding RNAs (lncRNAs) display diverse effects on biological regulations. However, their role in virus replication and underlying diseases is poorly understood. In this study, we have shown that HCV exploits lncRNA long intergenic nonprotein-coding RNA, p53 induced transcript (Linc-Pint) in hepatocytes for enhancement of lipogenesis.
APPROACH AND RESULTS
We identified a lncRNA, Linc-Pint, which is significantly down-regulated in HCV-replicating hepatocytes and liver specimens from HCV infected patients. Using RNA pull-down proteomics, we identified serine/arginine protein specific kinase 2 (SRPK2) as an interacting partner of Linc-Pint. A subsequent study demonstrated that overexpression of Linc-Pint inhibits the expression of lipogenesis-related genes, such as fatty acid synthase and ATP-citrate lyase. We also observed that Linc-Pint significantly inhibits HCV replication. Furthermore, HCV-mediated enhanced lipogenesis can be controlled by exogenous Linc-Pint expression. Together, our results suggested that HCV-mediated down-regulation of Linc-Pint enhances lipogenesis favoring virus replication and liver disease progression.
CONCLUSIONS
We have shown that SRPK2 is a direct target of Linc-Pint and that depletion of SRPK2 inhibits lipogenesis. Our study contributes to the mechanistic understanding of the role of Linc-Pint in HCV-associated liver pathogenesis.
Topics: Biopsy; Cell Line; Disease Progression; Down-Regulation; Hepacivirus; Hepatitis C, Chronic; Hepatocytes; Host-Pathogen Interactions; Humans; Lipogenesis; Liver; Protein Serine-Threonine Kinases; RNA, Long Noncoding
PubMed: 33236406
DOI: 10.1002/hep.31656 -
Journal of Orthopaedic Surgery and... Aug 2023Lumbar disc herniation (LDH) is a complex spinal disease, with multiple genetic polymorphisms being related to its risk. Nevertheless, the role of LINC-PINT...
BACKGROUND
Lumbar disc herniation (LDH) is a complex spinal disease, with multiple genetic polymorphisms being related to its risk. Nevertheless, the role of LINC-PINT polymorphisms in LDH risk has remained unknown. Therefore, this study aimed to investigate the association between LINC-PINT polymorphisms and LDH risk.
METHODS
DNA was extracted from 504 LDH patients and 500 healthy controls. Three single nucleotide polymorphisms (SNPs) in LINC-PINT were selected and genotyped using Agena MassARRAY. We used logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) under multiple genetic models to evaluate the association between LINC-PINT polymorphisms and LDH risk. Haploview 4.2 and SNPStats software were used to evaluate the linkage strength of SNPs and the correlation between haplotypes and LDH risk. The impact of SNP-SNP interactions on LDH risk was analyzed using multi-factor dimensionality reduction (MDR).
RESULTS
Results showed that rs157916 (G vs. A: OR = 1.23, FDR-p = 0.029) and rs7801029 (G vs. C: OR = 1.39, FDR-p = 0.006; GG vs. CC: OR = 2.34, FDR-p = 0.038; recessive: OR = 2.13, FDR-p = 0.045; additive: OR = 1.39, FDR-p = 0.030) were associated with an increased risk of LDH. Furthermore, LINC-PINT rs157916 and rs780129 were found to be significantly associated with LDH risk in males. The "GGG" haplotype was associated with increased LDH risk (OR = 1.41, FDR-p = 0.006). MDR analysis indicated that the interaction between rs7801029 and rs16873842 was associated with an increased risk of LDH (OR = 1.47, p = 0.004). Additionally, there were significant differences in C-reactive protein levels among different genotypes of rs157916 and rs780129 (p < 0.05).
CONCLUSION
This study suggests that LINC-PINT gene polymorphisms (rs157916 and rs7801029) are considered risk factors for LDH in the Chinese Han population and provide a scientific basis for early screening, prevention, and diagnosis of LDH.
Topics: Humans; Male; Case-Control Studies; China; East Asian People; Gene Frequency; Genetic Predisposition to Disease; Intervertebral Disc Displacement; Lumbar Vertebrae; Polymorphism, Single Nucleotide; RNA, Long Noncoding
PubMed: 37553573
DOI: 10.1186/s13018-023-04052-5 -
Journal of the American Heart... Aug 2023Background Premature and early menopause are independently associated with greater risk of cardiovascular disease (CVD). However, mechanisms linking age of menopause...
Background Premature and early menopause are independently associated with greater risk of cardiovascular disease (CVD). However, mechanisms linking age of menopause with CVD remain poorly characterized. Methods and Results We measured 71 circulating CVD protein biomarkers in 1565 postmenopausal women enrolled in the FHS (Framingham Heart Study). We examined the association of early menopause with biomarkers and tested whether early menopause modified the association of biomarkers with incident cardiovascular outcomes (heart failure, major CVD, and all-cause death) using multivariable-adjusted linear regression and Cox models, respectively. Among 1565 postmenopausal women included (mean age 62 years), 395 (25%) had a history of early menopause. Of 71 biomarkers examined, we identified 7 biomarkers that were significantly associated with early menopause, of which 5 were higher in women with early menopause including adrenomedullin and resistin, and 2 were higher in women without early menopause including insulin growth factor-1 and CNTN1 (contactin-1) (Benjamini-Hochberg adjusted <0.1 for all). Early menopause also modified the association of specific biomarkers with incident cardiovascular outcomes including adrenomedullin (<0.05). Conclusions Early menopause is associated with circulating levels of CVD protein biomarkers and appears to modify the association between select biomarkers with incident cardiovascular outcomes. Identified biomarkers reflect several distinct biological pathways, including inflammation, adiposity, and neurohormonal regulation. Further investigation of these pathways may provide mechanistic insights into the pathogenesis, prevention, and treatment of early menopause-associated CVD.
Topics: Female; Humans; Middle Aged; Cardiovascular Diseases; Adrenomedullin; Menopause, Premature; Menopause; Biomarkers; Risk Factors
PubMed: 37548169
DOI: 10.1161/JAHA.122.028849 -
Biomedicine & Pharmacotherapy =... Nov 2021Cancer involves complex etiology factors, multiple stages, and intricate gene mutations. Long non-coding RNAs (lncRNAs) are implicated as molecular mechanisms underlying... (Review)
Review
Cancer involves complex etiology factors, multiple stages, and intricate gene mutations. Long non-coding RNAs (lncRNAs) are implicated as molecular mechanisms underlying human genomic activity in various physiologic and pathophysiologic conditions. However, the sophisticated modifications and regulatory processes linking lncRNAs to cancer initiation and progression have not yet been fully explored. Long intragenic non-coding RNA p53-induced transcript (LINC-PINT) is an lncRNA that functions as a tumor suppressor gene involved in various tumors and malignant activities. LINC-PINT is downregulated in nasopharyngeal cancer, renal carcinoma, non-small cell lung cancer, glioblastoma, thyroid cancer, retinoblastoma, ovarian cancer, breast cancer, esophageal squamous cell carcinoma, osteosarcoma, melanoma, and gastric cancer. Furthermore, decreased LINC-PINT expression predicts poor prognosis and advanced clinical tumor stages. Together, these studies indicate that LINC-PINT could serve as a diagnostic and prognostic indicator in cancer. The specific lncRNA regulatory mechanism of LINC-PINT may also be a novel target for cancer therapies.
Topics: Animals; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Prognosis; RNA, Long Noncoding; Signal Transduction
PubMed: 34474342
DOI: 10.1016/j.biopha.2021.112127 -
Journal of Dairy Science Dec 2017Ice cream has come a long way since the first snow cone was made. Innovations in a variety of areas over the past century have led to the development of highly... (Review)
Review
Ice cream has come a long way since the first snow cone was made. Innovations in a variety of areas over the past century have led to the development of highly sophisticated, automated manufacturing plants that churn out pint after pint of ice cream. Significant advances in fields such as mechanical refrigeration, chilling and freezing technologies, cleaning and sanitation, packaging, and ingredient functionality have shaped the industry. Advances in our understanding of the science of ice cream, particularly related to understanding the complex structures that need to be controlled to create a desirable product, have also enhanced product quality and shelf stability. Although significant advances have been made, there remain numerous opportunities for further advancement both scientifically and technologically.
Topics: Food Handling; History, 20th Century; History, 21st Century; Ice Cream; United States
PubMed: 29153152
DOI: 10.3168/jds.2017-13278 -
Cardiovascular Diabetology Aug 2023Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects....
Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis.
BACKGROUND
Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk.
METHODS
Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and ≥ 45-<60 versus ≥ 60 mL/min/1.73 m) or damage (urine albumin:creatinine ratio [UACR] ≥ 30-≤300 and > 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated.
RESULTS
Independently of treatment, participants with reduced kidney function (eGFR ≥ 45-<60 and < 45 mL/min/1.73 m: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30-≤300 and > 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [p] > 0.05). Semaglutide reduced HbA regardless of baseline eGFR and UACR (p>0.05); reductions in BW were affected by baseline eGFR (p<0.001) but not UACR (p>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup.
CONCLUSIONS
MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage.
TRIAL REGISTRATIONS
NCT01720446; NCT02692716.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Cardiovascular System; Kidney; Renal Insufficiency
PubMed: 37620807
DOI: 10.1186/s12933-023-01949-7 -
Foods (Basel, Switzerland) Jul 2020The beer production chain includes some crucial steps regarding processing, delivery, service, and consumption that can benefit from the implementation of IoT (Internet... (Review)
Review
The beer production chain includes some crucial steps regarding processing, delivery, service, and consumption that can benefit from the implementation of IoT (Internet of Things) based technologies. Large breweries implemented the use of sensors and digitization before smaller ones among which are craft breweries. Internet of Beer (IoB) technologies are becoming accessible to mid and small sized brewing companies. Therefore, the objective of this work is to review mainly low-cost IoB smart technologies that can be implemented from the mash to the final product and its service, to improve the brewing production, control, delivery, and final quality increasing profitability. The reviewed applications were retrieved both from the scientific databases and from the web. The work is structured in three macro areas such as beer processing, product logistics and traceability, and service. The results show a future trend characterized by a very fast increase in the use of IoB (also open source) systems to drive efficiency, productivity, quality, and safety. This will be done by real-time monitoring and a data-driven decision support system (DSS). Crucial aspects needing further investigation are data ownership and data standardization. The access price of IoB devices and software is destined for a significant decrease while their diversification on the market will grow leading to a massive future implementation within all the production levels.
PubMed: 32709156
DOI: 10.3390/foods9070950 -
Nucleic Acids Research Jul 2022Gliomas are one of the most common and lethal brain tumors among adults. One process that contributes to glioma progression and recurrence is the epithelial to...
Gliomas are one of the most common and lethal brain tumors among adults. One process that contributes to glioma progression and recurrence is the epithelial to mesenchymal transition (EMT). EMT is regulated by a set of defined transcription factors which tightly regulate this process, among them is the basic helix-loop-helix family member, TWIST1. Here we show that TWIST1 is methylated on lysine-33 at chromatin by SETD6, a methyltransferase with expression levels correlating with poor survival in glioma patients. RNA-seq analysis in U251 glioma cells suggested that both SETD6 and TWIST1 regulate cell adhesion and migration processes. We further show that TWIST1 methylation attenuates the expression of the long-non-coding RNA, LINC-PINT, thereby promoting EMT in glioma. Mechanistically, TWIST1 methylation represses the transcription of LINC-PINT by increasing the occupancy of EZH2 and the catalysis of the repressive H3K27me3 mark at the LINC-PINT locus. Under un-methylated conditions, TWIST1 dissociates from the LINC-PINT locus, allowing the expression of LINC-PINT which leads to increased cell adhesion and decreased cell migration. Together, our findings unravel a new mechanistic dimension for selective expression of LINC-PINT mediated by TWIST1 methylation.
Topics: Humans; Epithelial-Mesenchymal Transition; Nuclear Proteins; Protein Methyltransferases; Twist-Related Protein 1; Glioma; RNA, Long Noncoding; Cell Line, Tumor
PubMed: 35694846
DOI: 10.1093/nar/gkac485 -
Journal of the American Heart... Mar 2023Background In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) versus placebo) reduced cardiovascular death,... (Randomized Controlled Trial)
Randomized Controlled Trial
Background In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) versus placebo) reduced cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina requiring hospitalization, but was associated with increased atrial fibrillation/atrial flutter (AF) hospitalization (3.1% IPE versus 2.1% placebo; =0.004). Methods and Results We performed post hoc efficacy and safety analyses of patients with or without prior AF (before randomization) and with or without in-study time-varying AF hospitalization to assess relationships of IPE (versus placebo) and outcomes. In-study AF hospitalization event rates were higher in patients with prior AF (12.5% versus 6.3%, IPE versus placebo; =0.007) versus without prior AF (2.2% versus 1.6%, IPE versus placebo; =0.09). Serious bleeding rates trended higher in patients with (7.3% versus 6.0%, IPE versus placebo; =0.59) versus without prior AF (2.3% versus 1.7%, IPE versus placebo; =0.08). With IPE, serious bleeding trended higher regardless of prior AF (interaction value []=0.61) or postrandomization AF hospitalization (=0.66). Patients with prior AF (n=751, 9.2%) versus without prior AF (n=7428, 90.8%) had similar relative risk reductions of the primary composite and key secondary composite end points with IPE versus placebo (=0.37 and =0.55, respectively). Conclusions In REDUCE-IT, in-study AF hospitalization rates were higher in patients with prior AF especially in those randomized to IPE. Although serious bleeding trended higher in those randomized to IPE versus placebo over the course of the study, serious bleeding was not different regardless of prior AF or in-study AF hospitalization. Patients with prior AF or in-study AF hospitalization had consistent relative risk reductions across primary, key secondary, and stroke end points with IPE. Registration URL: https://clinicaltrials.gov/ct2/show/NCT01492361; Unique Identifier: NCT01492361.
Topics: Humans; Atrial Fibrillation; Risk Factors; Eicosapentaenoic Acid; Stroke; Treatment Outcome
PubMed: 36802845
DOI: 10.1161/JAHA.121.026756 -
Cancer Cell International Sep 2022Sonic Hedgehog (Shh) signaling cascade is one of the complex signaling pathways that control the accurately organized developmental processes in multicellular organisms.... (Review)
Review
Sonic Hedgehog (Shh) signaling cascade is one of the complex signaling pathways that control the accurately organized developmental processes in multicellular organisms. This pathway has fundamental roles in the tumor formation and induction of resistance to conventional therapies. Numerous non-coding RNAs (ncRNAs) have been found to interact with Shh pathway to induce several pathogenic processes, including malignant and non-malignant disorders. Many of the Shh-interacting ncRNAs are oncogenes whose expressions have been increased in diverse malignancies. A number of Shh-targeting miRNAs such as miR-26a, miR-1471, miR-129-5p, miR-361-3p, miR-26b-5p and miR-361-3p have been found to be down-regulated in tumor tissues. In addition to malignant conditions, Shh-interacting ncRNAs can affect tissue regeneration and development of neurodegenerative disorders. XIST, LOC101930370, lncRNA-Hh, circBCBM1, SNHG6, LINC-PINT, TUG1 and LINC01426 are among long non-coding RNAs/circular RNAs that interact with Shh pathway. Moreover, miR-424, miR-26a, miR-1471, miR-125a, miR-210, miR-130a-5p, miR-199b, miR-155, let-7, miR-30c, miR-326, miR-26b-5p, miR-9, miR-132, miR-146a and miR-425-5p are among Shh-interacting miRNAs. The current review summarizes the interactions between ncRNAs and Shh in these contexts.
PubMed: 36100906
DOI: 10.1186/s12935-022-02702-y