scholarly journals Vertebral osteomyelitis is characterised by increased RANK/OPG and RANKL/OPG expression ratios in vertebral bodies and intervertebral discs

2021 ◽  
Vol 42 ◽  
pp. 438-451
Author(s):  
S Lang ◽  
◽  
M Loibl ◽  
J Gläsner ◽  
M Simon ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Patterns ◽  
Vertebral Osteomyelitis ◽  
Intervertebral Discs ◽  
Infection Group ◽  
Expression Ratio ◽  
Fracture Group ◽  
Expression Of Genes ◽  
Tissue Degradation ◽  
Vertebral Bodies

Vertebral osteomyelitis (VO) is an infection of the spine mainly caused by bacterial pathogens. The pathogenesis leading to destruction of intervertebral discs (IVDs) and adjacent vertebral bodies (VBs) is poorly described. The present study aimed at investigating the connection between infection and bone/disc metabolism in VO patients. 14 patients with VO (infection group) and 14 patients with burst fractures of the spine (fracture group; control) were included prospectively. Tissue biopsies from affected IVDs and adjacent VBs were analysed by RT-qPCR for mRNA-expression levels of 18 target genes including chemokines, adipokines and genes involved in bone metabolism. Most importantly, the receptor activator of NF-κB/osteoprotegerin (RANK/OPG) expression ratio was drastically elevated in both VBs and IVDs of the infection group. In parallel, expression of genes of the prostaglandin-E2-dependent prostanoid system was induced. Such genes regulate tissue degradation processes via the triad OPG/RANK/RANKL as well as via the chemokines IL-8 and CCL-20, whose expression was also found to be increased upon infection. The gene expression of the adipokine leptin, which promotes inflammatory tissue degradation, was higher in IVD tissue of the infection group, whereas the transcription of omentin and resistin genes, whose functions are largely unknown in the context of infectious diseases, was lower in infected VBs. In summary, similar expression patterns of pro-inflammatory cytokines and pro-osteoclastogenic factors were identified in VBs and IVDs of patients suffering from VO. This suggests that common immuno-metabolic pathways are involved in the mechanisms leading to tissue degradation in VBs and IVDs during VO.

scholarly journals Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer

2021 ◽  
Author(s):  
Chun Yang ◽  
Stéphane Croteau ◽  
Pierre Hardy
Keyword(s):  
Histone Deacetylase ◽  
Posttranslational Modifications ◽  
Histone Deacetylases ◽  
Muscle Development ◽  
Target Genes ◽  
Human Cancer ◽  
Expression Patterns ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Pathogenesis

Abstract Background HDAC9 (histone deacetylase 9) belongs to the class IIa family of histone deacetylases. This enzyme can shuttle freely between the nucleus and cytoplasm and promotes tissue-specific transcriptional regulation by interacting with histone and non-histone substrates. HDAC9 plays an essential role in diverse physiological processes including cardiac muscle development, bone formation, adipocyte differentiation and innate immunity. HDAC9 inhibition or activation is therefore a promising avenue for therapeutic intervention in several diseases. HDAC9 overexpression is also common in cancer cells, where HDAC9 alters the expression and activity of numerous relevant proteins involved in carcinogenesis. Conclusions This review summarizes the most recent discoveries regarding HDAC9 as a crucial regulator of specific physiological systems and, more importantly, highlights the diverse spectrum of HDAC9-mediated posttranslational modifications and their contributions to cancer pathogenesis. HDAC9 is a potential novel therapeutic target, and the restoration of aberrant expression patterns observed among HDAC9 target genes and their related signaling pathways may provide opportunities to the design of novel anticancer therapeutic strategies.

A deep learning system for automated, multi-modality 2D segmentation of vertebral bodies and intervertebral discs

Bone ◽  
2021 ◽  
pp. 115972
Author(s):  
Abhinav Suri ◽  
Brandon C. Jones ◽  
Grace Ng ◽  
Nancy Anabaraonye ◽  
Patrick Beyrer ◽  
...  
Keyword(s):  
Deep Learning ◽  
Intervertebral Discs ◽  
Learning System ◽  
Vertebral Bodies

scholarly journals Genome-wide analysis of changes in miRNA and target gene expression reveals key roles in heterosis for Chinese cabbage biomass

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Peirong Li ◽  
Tongbing Su ◽  
Deshuang Zhang ◽  
Weihong Wang ◽  
Xiaoyun Xin ◽  
...  
Keyword(s):  
Chinese Cabbage ◽  
Leaf Development ◽  
Target Genes ◽  
Expression Patterns ◽  
Seedling Stage ◽  
Differentially Expressed ◽  
Small Rna Sequencing ◽  
Leaf Morphogenesis ◽  
Expression Levels ◽  
Parental Lines

AbstractHeterosis is a complex phenomenon in which hybrids show better phenotypic characteristics than their parents do. Chinese cabbage (Brassica rapa L. spp. pekinensis) is a popular leafy crop species, hybrids of which are widely used in commercial production; however, the molecular basis of heterosis for biomass of Chinese cabbage is poorly understood. We characterized heterosis in a Chinese cabbage F1 hybrid cultivar and its parental lines from the seedling stage to the heading stage; marked heterosis of leaf weight and biomass yield were observed. Small RNA sequencing revealed 63 and 50 differentially expressed microRNAs (DEMs) at the seedling and early-heading stages, respectively. The expression levels of the majority of miRNA clusters in the F1 hybrid were lower than the mid-parent values (MPVs). Using degradome sequencing, we identified 1,819 miRNA target genes. Gene ontology (GO) analyses demonstrated that the target genes of the MPV-DEMs and low parental expression level dominance (ELD) miRNAs were significantly enriched in leaf morphogenesis, leaf development, and leaf shaping. Transcriptome analysis revealed that the expression levels of photosynthesis and chlorophyll synthesis-related MPV-DEGs (differentially expressed genes) were significantly different in the F1 hybrid compared to the parental lines, resulting in increased photosynthesis capacity and chlorophyll content in the former. Furthermore, expression of genes known to regulate leaf development was also observed at the seedling stage. Arabidopsis plants overexpressing BrGRF4.2 and bra-miR396 presented increased and decreased leaf sizes, respectively. These results provide new insight into the regulation of target genes and miRNA expression patterns in leaf size and heterosis for biomass of B. rapa.

scholarly journals Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Junjie Cen ◽  
Yanping Liang ◽  
Yong Huang ◽  
Yihui Pan ◽  
Guannan Shu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Expression Patterns ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Proliferation And Metastasis

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

scholarly journals The Coordinated Upregulated Expression of Genes Involved in MEP, Chlorophyll, Carotenoid and Tocopherol Pathways, Mirrored the Corresponding Metabolite Contents in Rice Leaves during De-Etiolation

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1456
Author(s):  
Xin Jin ◽  
Can Baysal ◽  
Margit Drapal ◽  
Yanmin Sheng ◽  
Xin Huang ◽  
...  
Keyword(s):  
Higher Plants ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Isoprenoid Biosynthesis ◽  
Promoter Regions ◽  
Expression Of Genes ◽  
Coordinated Expression ◽  
Rice Leaves ◽  
Mechanistic Basis ◽  
Phosphate Synthase

Light is an essential regulator of many developmental processes in higher plants. We investigated the effect of 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 1/2 genes (OsHDR1/2) and isopentenyl diphosphate isomerase 1/2 genes (OsIPPI1/2) on the biosynthesis of chlorophylls, carotenoids, and phytosterols in 14-day-old etiolated rice (Oyza sativa L.) leaves during de-etiolation. However, little is known about the effect of isoprenoid biosynthesis genes on the corresponding metabolites during the de-etiolation of etiolated rice leaves. The results showed that the levels of α-tocopherol were significantly increased in de-etiolated rice leaves. Similar to 1-deoxy-D-xylulose-5-phosphate synthase 3 gene (OsDXS3), both OsDXS1 and OsDXS2 genes encode functional 1-deoxy-D-xylulose-5-phosphate synthase (DXS) activities. Their expression patterns and the synthesis of chlorophyll, carotenoid, and tocopherol metabolites suggested that OsDXS1 is responsible for the biosynthesis of plastidial isoprenoids in de-etiolated rice leaves. The expression analysis of isoprenoid biosynthesis genes revealed that the coordinated expression of the MEP (2-C-methyl-D-erythritol 4-phosphate) pathway, chlorophyll, carotenoid, and tocopherol pathway genes mirrored the changes in the levels of the corresponding metabolites during de-etiolation. The underpinning mechanistic basis of coordinated light-upregulated gene expression was elucidated during the de-etiolation process, specifically the role of light-responsive cis-regulatory motifs in the promoter region of these genes. In silico promoter analysis showed that the light-responsive cis-regulatory elements presented in all the promoter regions of each light-upregulated gene, providing an important link between observed phenotype during de-etiolation and the molecular machinery controlling expression of these genes.

scholarly journals Genetic and epigenetic concept of SARS-CoV-2 targets in different renal cancer subtypes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Dilara Fatma Akin-Bali ◽  
Rahşan Ilikci Sagkan
Keyword(s):  
Renal Cancer ◽  
Promoter Methylation ◽  
Target Genes ◽  
Expression Patterns ◽  
Rna Expression ◽  
Total Rate ◽  
Cancer Subtypes ◽  
Genetic Landscape ◽  
Healthy Control ◽  
Genetic Anomaly

AbstractObjectivesRecent advances in defining the genetic landscape of has shown the host cell- SARS-CoV-2 interaction via ACE2 protein and the presence of at least three additional virus invasion genes including TMPRSS2, FURIN, CD147/BSG. In current study, we investigated the mutation and m-RNA expression patterns of target genes by evaluating the associations between genetic and epigenetic mechanisms in the target genes and susceptibility of SARS-CoV-2 infection of renal cancer subtypes.MethodsWe investigated the mutation and m-RNA expression patterns of our target genes. The promoter methylation profiles of target genes were tested in the UALCAN database.ResultsThe total rate of carrying genetic anomaly in the target genes including was 1.6% and seven mutations, one of which had a pathogenic feature, were detected. The expression analysis results in renal cancer groups showed that while the KIRC and KIRP patients had a lower level of TMPRSS2 than the healthy control, their ACE2 level was high. KICH patients had a higher level of CD147/BSG expression than the healthy group. The promoter methylation levels of ACE2 in KIRC and KIRP were reduced.ConclusionsWe concluded that renal cancer patients may be more sensitive to SARS-CoV-2 infection, which may worsen the prognosis.

scholarly journals Minimally invasive debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis: a long‐term follow‐up study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jianbiao Xu ◽  
Leiming Zhang ◽  
Rongqiang Bu ◽  
Yankang Liu ◽  
Kai-Uwe Lewandrowski ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Clinical Manifestations ◽  
Operation Time ◽  
Intervertebral Discs ◽  
Intraoperative Ct ◽  
Long Term Follow Up ◽  
Invasive Method ◽  
Vertebral Bodies ◽  
Adjacent Segments

Abstract Background Spondylodiscitis is an unusual infectious disease, which usually originates as a pathogenic infection of intervertebral discs and then spreads to neighboring vertebral bodies. The objective of this study is to evaluate percutaneous debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis. Methods From January 2002 to May 2017, 23 patients with multilevel spondylodiscitis were treated with minimally invasive debridement and drainage procedures in our department. The clinical manifestations, evolution, and minimally invasive debridement and drainage treatment of this refractory vertebral infection were investigated. Results Of the enrolled patients, the operation time ranged from 30 minutes to 124 minutes every level with an average of 48 minutes. Intraoperative hemorrhage was minimal. The postoperative follow-up period ranged from 12 months to 6.5 years with an average of 3.7 years. There was no reactivation of infection in the treated vertebral segment during follow-up, but two patients with fungal spinal infection continued to progress by affecting adjacent segments prior to final resolution. According to the classification system of Macnab, one patient had a good outcome at the final follow-up, and the rest were excellent. Conclusions Minimally invasive percutaneous debridement and irrigation using intraoperative CT-Guide is an effective minimally invasive method for the treatment of multilevel spondylodiscitis.

scholarly journals The noncoding MIR100HG RNA enhances the autocrine function of transforming growth factor β signaling

Oncogene ◽  
2021 ◽  
Author(s):  
Panagiotis Papoutsoglou ◽  
Dorival Mendes Rodrigues-Junior ◽  
Anita Morén ◽  
Andrew Bergman ◽  
Fredrik Pontén ◽  
...  
Keyword(s):  
Growth Factor ◽  
Target Genes ◽  
Rna Binding ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tgfβ Signaling ◽  
Ribonucleoprotein Complexes ◽  
Expression Of Genes ◽  
Downstream Effectors ◽  
Human Carcinomas

AbstractActivation of the transforming growth factor β (TGFβ) pathway modulates the expression of genes involved in cell growth arrest, motility, and embryogenesis. An expression screen for long noncoding RNAs indicated that TGFβ induced mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) expression in diverse cancer types, thus confirming an earlier demonstration of TGFβ-mediated transcriptional induction of MIR100HG in pancreatic adenocarcinoma. MIR100HG depletion attenuated TGFβ signaling, expression of TGFβ-target genes, and TGFβ-mediated cell cycle arrest. Moreover, MIR100HG silencing inhibited both normal and cancer cell motility and enhanced the cytotoxicity of cytostatic drugs. MIR100HG overexpression had an inverse impact on TGFβ signaling responses. Screening for downstream effectors of MIR100HG identified the ligand TGFβ1. MIR100HG and TGFB1 mRNA formed ribonucleoprotein complexes with the RNA-binding protein HuR, promoting TGFβ1 cytokine secretion. In addition, TGFβ regulated let-7a-2–3p, miR-125b-5p, and miR-125b-1–3p expression, all encoded by MIR100HG intron-3. Certain intron-3 miRNAs may be involved in TGFβ/SMAD-mediated responses (let-7a-2–3p) and others (miR-100, miR-125b) in resistance to cytotoxic drugs mediated by MIR100HG. In support of a model whereby TGFβ induces MIR100HG, which then enhances TGFβ1 secretion, analysis of human carcinomas showed that MIR100HG expression correlated with expression of TGFB1 and its downstream extracellular target TGFBI. Thus, MIR100HG controls the magnitude of TGFβ signaling via TGFβ1 autoinduction and secretion in carcinomas.

scholarly journals Effect of Xenon Treatment on Gene Expression in Brain Tissue after Traumatic Brain Injury in Rats

2021 ◽  
Vol 11 (7) ◽  
pp. 889
Author(s):  
Anton D. Filev ◽  
Denis N. Silachev ◽  
Ivan A. Ryzhkov ◽  
Konstantin N. Lapin ◽  
Anastasiya S. Babkina ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Tissue ◽  
Target Genes ◽  
Neural Function ◽  
Stress Genes ◽  
Expression Of Genes ◽  
Delayed Recovery ◽  
The Brain ◽  
Lower Expression

The overactivation of inflammatory pathways and/or a deficiency of neuroplasticity may result in the delayed recovery of neural function in traumatic brain injury (TBI). A promising approach to protecting the brain tissue in TBI is xenon (Xe) treatment. However, xenon’s mechanisms of action remain poorly clarified. In this study, the early-onset expression of 91 target genes was investigated in the damaged and in the contralateral brain areas (sensorimotor cortex region) 6 and 24 h after injury in a TBI rat model. The expression of genes involved in inflammation, oxidation, antioxidation, neurogenesis and neuroplasticity, apoptosis, DNA repair, autophagy, and mitophagy was assessed. The animals inhaled a gas mixture containing xenon and oxygen (ϕXe = 70%; ϕO2 25–30% 60 min) 15–30 min after TBI. The data showed that, in the contralateral area, xenon treatment induced the expression of stress genes (Irf1, Hmox1, S100A8, and S100A9). In the damaged area, a trend towards lower expression of the inflammatory gene Irf1 was observed. Thus, our results suggest that xenon exerts a mild stressor effect in healthy brain tissue and has a tendency to decrease the inflammation following damage, which might contribute to reducing the damage and activating the early compensatory processes in the brain post-TBI.

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