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1.
J Egypt Natl Canc Inst ; 36(1): 12, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38616231

ABSTRACT

BACKGROUND: Breast cancer is one of the most common cancers known among women. This study aimed to investigate the level of vitamin D receptor gene expression in two tumoral and healthy breast tissues in breast cancer patients and its association with prognostic factors. METHODS: This descriptive cross-sectional study was conducted in 2022 on 50 patients with high suspicion of breast cancer who were candidates for mastectomy and lumpectomy in a learning hospital. From the patients, two tissue samples were prepared, and there was a total of 100 samples. The samples were subjected to H/E staining and evaluated by a pathologist. The presence or absence of malignancy in each sample was confirmed by two pathologists, and HER2/ER/PR indices were determined. Descriptive and analytical statistical methods and SPSS version 22 software were used. RESULTS: The average age of the patients was 51.60 ± 11.22 years old, and the average tumor size was 3.17 ± 1.28. Most tumors were grade 2 (48%). The expression of HER2, ER, and PR was positive in 24, 64, and 54%, respectively. The largest number of cases were in stage 2A. The expression level of vitamin D receptor (VDR) gene in healthy tissue (2.08 ± 1.01) was higher than tumoral tissue (0.25 ± 1.38) (P = 0.001). In tumoral and healthy tissue, VDR expression was not significant according to tumor grade, HER2, ER, PR, LVI, LN, disease stage, age, and tumor size. CONCLUSIONS: The expression level of VDR in healthy tissue was significantly higher than tumoral tissue. However, there was no significant relationship between VDR and tumor grade, HER2, ER, PR, LVI, LN, disease stage, age, and tumor size.


Subject(s)
Breast Neoplasms , Humans , Female , Adult , Middle Aged , Breast Neoplasms/genetics , Receptors, Calcitriol/genetics , Cross-Sectional Studies , Prognosis , Mastectomy , Gene Expression
2.
Genome Biol ; 25(1): 96, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622747

ABSTRACT

We present a non-parametric statistical method called TDEseq that takes full advantage of smoothing splines basis functions to account for the dependence of multiple time points in scRNA-seq studies, and uses hierarchical structure linear additive mixed models to model the correlated cells within an individual. As a result, TDEseq demonstrates powerful performance in identifying four potential temporal expression patterns within a specific cell type. Extensive simulation studies and the analysis of four published scRNA-seq datasets show that TDEseq can produce well-calibrated p-values and up to 20% power gain over the existing methods for detecting temporal gene expression patterns.


Subject(s)
Gene Expression Profiling , Single-Cell Analysis , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , Gene Expression Profiling/methods , Computer Simulation , Gene Expression
3.
Mol Biol Rep ; 51(1): 524, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630344

ABSTRACT

BACKGROUND: Pterygium, characterized by the abnormal proliferation of epithelial cells, matrix remodeling, vascularization, and lesion migration, is a prevalent ocular surface disease involving the growth of fibrovascular tissue on the cornea. Despite the unclear underlying causes of pterygium, numerous investigations have indicated the involvement of cell death pathways in the regulation of cell cycle dynamics. Consequently, the objective of this study was to assess the expression levels of necroptosis markers in individuals diagnosed with pterygium, aiming to shed light on the potential role of necroptosis in the pathogenesis of this condition. METHODS: This study aimed to investigate the expression patterns of receptor-interacting serine/threonine kinase 3 (RIPK3) and receptor-interacting serine/threonine kinase 1 (RIPK1) genes in pterygium tissues. 41 patients undergoing pterygium excision surgery were recruited. Resected pterygium samples and normal conjunctival tissues were collected, and RIPK3 and RIPK1 mRNA levels were measured using quantitative real-time PCR. RESULTS: Our findings reveal that the expression of RIPK3 is significantly increased in samples obtained from individuals with pterygium. However, no significant alterations were observed in the expression of RIPK1 in these samples. Results showed significantly higher RIPK3 expression in pterygium tissues compared to controls. Moreover, increased RIPK3 levels correlated negatively with pterygium recurrence rates. CONCLUSIONS: These findings suggest RIPK3 may play a protective role against pterygium recurrence through necroptosis.


Subject(s)
Conjunctiva/abnormalities , Pterygium , Humans , Pterygium/genetics , Gene Expression/genetics , Serine , Receptor-Interacting Protein Serine-Threonine Kinases/genetics
4.
Int J Mol Sci ; 25(7)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38612480

ABSTRACT

The aim of this study was to investigate gene expression alterations associated with overall survival (OS) in glioblastoma (GBM). Using the Nanostring nCounter platform, we identified four genes (COL1A2, IGFBP3, NGFR, and WIF1) that achieved statistical significance when comparing GBM with non-neoplastic brain tissue. The four genes were included in a multivariate Cox Proportional Hazard model, along with age, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation, to create a unique glioblastoma prognostic index (GPI). The GPI score inversely correlated with survival: patient with a high GPI had a median OS of 7.5 months (18-month OS = 9.7%) whereas patients with a low GPI had a median OS of 20.1 months (18-month OS = 54.5%; log rank p-value = 0.004). The GPI score was then validated in 188 GBM patients from The Cancer Genome Atlas (TCGA) from a national data base; similarly, patients with a high GPI had a median OS of 10.5 months (18-month OS = 12.4%) versus 16.9 months (18-month OS = 41.5%) for low GPI (log rank p-value = 0.0003). We conclude that this novel mRNA-based prognostic index could be useful in classifying GBM patients into risk groups and refine prognosis estimates to better inform treatment decisions or stratification into clinical trials.


Subject(s)
Glioblastoma , Humans , Glioblastoma/genetics , Genes, Regulator , Databases, Factual , O(6)-Methylguanine-DNA Methyltransferase , Gene Expression
5.
Int J Mol Sci ; 25(7)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38612818

ABSTRACT

Many genomic, anatomical and functional differences exist between the medullary (MTAL) and the cortical thick ascending limb of the loop of Henle (CTAL), including a higher expression of claudin-10 (CLDN10) in the MTAL than in the CTAL. Therefore, we assessed to what extent the Cldn10 gene expression is a determinant of differential gene expression between MTAL and CTAL. RNAs extracted from CTAL and MTAL microdissected from wild type (WT) and Cldn10 knock out mice (cKO) were analyzed by RNAseq. Differential and enrichment analyses (GSEA) were performed with interactive R Shiny software. Between WT and cKO MTAL, 637 genes were differentially expressed, whereas only 76 were differentially expressed between WT and cKO CTAL. Gene expression patterns and GSEA analyses in all replicates showed that WT MTAL did not cluster with the other replicates; no hierarchical clustering could be found between WT CTAL, cKO CTAL and cKO MTAL. Compared to WT replicates, cKO replicates were enriched in Cldn16, Cldn19, Pth1r, (parathyroid hormone receptor type 1), Casr (calcium sensing receptor) and Vdr (Vitamin D Receptor) mRNA in both the cortex and medulla. Cldn10 is associated with gene expression patterns, including genes specifically involved in divalent cations reabsorption in the TAL.


Subject(s)
Adrenal Medulla , Extremities , Animals , Mice , Claudins/genetics , Mice, Knockout , Gene Expression
6.
Int J Mol Sci ; 25(7)2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38612913

ABSTRACT

Salt is frequently introduced in ecosystems, where it acts as a pollutant. This study examined how changes in salinity affect the survival and development of zebrafish from the two-cell to the blastocyst stage and from the blastocyst to the larval stage. Control zebrafish embryos were cultured in E3 medium containing 5 mM Sodium Chloride (NaCl), 0.17 mM Potassium Chloride (KCL), 0.33 mM Calcium Chloride (CaCl2), and 0.33 mM Magnesium Sulfade (MgSO4). Experiments were conducted using increasing concentrations of each individual salt at 5×, 10×, 50×, and 100× the concentration found in E3 medium. KCL, CaCl2, and MgSO4 did not result in lethal abnormalities and did not affect early embryo growth at any of the concentrations tested. Concentrations of 50× and 100× NaCl caused embryonic death in both stages of development. Concentrations of 5× and 10× NaCl resulted in uninflated swim bladders in 12% and 65% of larvae, compared to 4.2% of controls, and caused 1654 and 2628 genes to be differentially expressed in blastocysts, respectively. The ATM signaling pathway was affected, and the Sonic Hedgehog pathway genes Shh and Ptc1 implicated in swim bladder development were downregulated. Our findings suggest that increased NaCl concentrations may alter gene expression and cause developmental abnormalities in animals found in affected ecosystems.


Subject(s)
Hedgehog Proteins , Perciformes , Animals , Hedgehog Proteins/genetics , Sodium Chloride/pharmacology , Water , Zebrafish/genetics , Calcium Chloride , Ecosystem , Sodium Chloride, Dietary , Larva/genetics , Gene Expression
7.
Int J Mol Sci ; 25(7)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38612938

ABSTRACT

Glioblastoma multiforme (GBM) is a malignant tumor with a higher prevalence in men and a higher survival rate in transmenopausal women. It exhibits distinct areas influenced by changing environmental conditions. This study examines how these areas differ in the levels of estrogen receptors (ERs) which play an important role in the development and progression of many cancers, and whose expression levels are often correlated with patient survival. This study utilized two research models: an in vitro model employing the U87 cell line and a second model involving tumors resected from patients (including tumor core, enhancing tumor region, and peritumoral area). ER expression was assessed at both gene and protein levels, with the results validated using confocal microscopy and immunohistochemistry. Under hypoxic conditions, the U87 line displayed a decrease in ERß mRNA expression and an increase in ERα mRNA expression. In patient samples, ERß mRNA expression was lower in the tumor core compared to the enhancing tumor region (only in males when the study group was divided by sex). In addition, ERß protein expression was lower in the tumor core than in the peritumoral area (only in women when the study group was divided by sex). Immunohistochemical analysis indicated the highest ERß protein expression in the enhancing tumor area, followed by the peritumoral area, and the lowest in the tumor core. The findings suggest that ER expression may significantly influence the development of GBM, exhibiting variability under the influence of conditions present in different tumor areas.


Subject(s)
Glioblastoma , Male , Humans , Female , Glioblastoma/genetics , Estrogen Receptor beta/genetics , Gene Expression , Estrogens , RNA, Messenger/genetics
8.
Brief Bioinform ; 25(3)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38605638

ABSTRACT

Recent advances in single-cell RNA sequencing technology have eased analyses of signaling networks of cells. Recently, cell-cell interaction has been studied based on various link prediction approaches on graph-structured data. These approaches have assumptions about the likelihood of node interaction, thus showing high performance for only some specific networks. Subgraph-based methods have solved this problem and outperformed other approaches by extracting local subgraphs from a given network. In this work, we present a novel method, called Subgraph Embedding of Gene expression matrix for prediction of CEll-cell COmmunication (SEGCECO), which uses an attributed graph convolutional neural network to predict cell-cell communication from single-cell RNA-seq data. SEGCECO captures the latent and explicit attributes of undirected, attributed graphs constructed from the gene expression profile of individual cells. High-dimensional and sparse single-cell RNA-seq data make converting the data into a graphical format a daunting task. We successfully overcome this limitation by applying SoptSC, a similarity-based optimization method in which the cell-cell communication network is built using a cell-cell similarity matrix which is learned from gene expression data. We performed experiments on six datasets extracted from the human and mouse pancreas tissue. Our comparative analysis shows that SEGCECO outperforms latent feature-based approaches, and the state-of-the-art method for link prediction, WLNM, with 0.99 ROC and 99% prediction accuracy. The datasets can be found at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE84133 and the code is publicly available at Github https://github.com/sheenahora/SEGCECO and Code Ocean https://codeocean.com/capsule/8244724/tree.


Subject(s)
Cell Communication , Signal Transduction , Humans , Animals , Mice , Cell Communication/genetics , Learning , Neural Networks, Computer , Gene Expression
9.
Front Immunol ; 15: 1320444, 2024.
Article in English | MEDLINE | ID: mdl-38605949

ABSTRACT

Enhanced interferon α (IFNα) production has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We previously reported IFNα production by monocytes upon activation of the stimulator of IFN genes (STING) pathway was enhanced in patients with SLE. We investigated the mechanism of enhanced IFNα production in SLE monocytes. Monocytes enriched from the peripheral blood of SLE patients and healthy controls (HC) were stimulated with 2'3'-cyclic GAMP (2'3'-cGAMP), a ligand of STING. IFNα positive/negative cells were FACS-sorted for RNA-sequencing analysis. Gene expression in untreated and 2'3'-cGAMP-stimulated SLE and HC monocytes was quantified by real-time PCR. The effect of GATA binding protein 4 (GATA4) on IFNα production was investigated by overexpressing GATA4 in monocytic U937 cells by vector transfection. Chromatin immunoprecipitation was performed to identify GATA4 binding target genes in U937 cells stimulated with 2'3'-cGAMP. Differentially expressed gene analysis of cGAS-STING stimulated SLE and HC monocytes revealed the enrichment of gene sets related to cellular senescence in SLE. CDKN2A, a marker gene of cellular senescence, was upregulated in SLE monocytes at steady state, and its expression was further enhanced upon STING stimulation. GATA4 expression was upregulated in IFNα-positive SLE monocytes. Overexpression of GATA4 enhanced IFNα production in U937 cells. GATA4 bound to the enhancer region of IFIT family genes and promoted the expressions of IFIT1, IFIT2, and IFIT3, which promote type I IFN induction. SLE monocytes with accelerated cellular senescence produced high levels of IFNα related to GATA4 expression upon activation of the cGAS-STING pathway.


Subject(s)
Interferon Type I , Lupus Erythematosus, Systemic , Humans , Monocytes/metabolism , Gene Expression , Interferon Type I/metabolism , Interferon-alpha/metabolism , Nucleotidyltransferases/metabolism , Lupus Erythematosus, Systemic/metabolism , GATA4 Transcription Factor/genetics , GATA4 Transcription Factor/metabolism
10.
Mol Med Rep ; 29(6)2024 Jun.
Article in English | MEDLINE | ID: mdl-38606508

ABSTRACT

Genes are not randomly dispersed within the nuclear space, instead they occupy precise sites either with respect to the nuclear lamina as well as to each other. This observation stands at the basis of the today well accepted concept of nuclear territories where any chromosome shows reproducible spatial connections with a selection of others in a general picture that meets a functional criterion where genes that answer the same stimuli are grouped in the same sites. In fact, transcription is not visible widely dispersed throughout the nucleus but is gathered in several 'granules', called transcription factories that accommodates ~10 genes concurrently transcribed. This dynamic behavior of chromosomes is allowed by changes in chromatin plasticity that are governed by several classes of proteins that either modify its building or induce post­translational modifications in the protein component of nucleosomes, triggering formation of chromosome loops that modify the location of specific sites along the DNA strand. For example, transcription associated to nuclear receptors benefits of the generation of nuclear ROS that induce nicks following activation of the DNA repair apparatus that enhance helix unfolding and chromosome bridging. In the present review, the role that protocols facing elucidation of chromosome architecture are playing and will play in the near future were highlighted in order to investigate composition of the transcription factories assembled in response of a specific trigger: The estrogen­sensitive transcription was cited but the authors are convinced that the same portrait will be observed with a multitude of (if not all) other stimuli.


Subject(s)
Chromatin , Chromosomes , Chromatin/genetics , Chromosomes/genetics , Protein Processing, Post-Translational , Gene Expression
11.
Cells ; 13(7)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38607069

ABSTRACT

Despite being immune cells of the central nervous system (CNS), microglia contribute to CNS development, maturation, and homeostasis, and microglia dysfunction has been implicated in several neurological disorders. Recent advancements in single-cell studies have uncovered unique microglia-specific gene expression. However, there is a need for a simple yet elegant multiplexed approach to quantifying microglia gene expression. To address this, we have designed a NanoString nCounter technology-based murine microglia-specific custom codeset comprising 178 genes. We analyzed RNA extracted from ex vivo adult mouse microglia, primary mouse microglia, the BV2 microglia cell line, and mouse bone marrow monocytes using our custom panel. Our findings reveal a pattern where homeostatic genes exhibit heightened expression in adult microglia, followed by primary cells, and are absent in BV2 cells, while reactive markers are elevated in primary microglia and BV2 cells. Analysis of publicly available data sets for the genes present in the panel revealed that the panel could reliably reflect the changes in microglia gene expression in response to various factors. These findings highlight that the microglia panel used offers a swift and cost-effective means to assess microglial cells and can be used to study them in varying contexts, ranging from normal homeostasis to disease models.


Subject(s)
Microglia , Mice , Animals , Microglia/metabolism , Cell Line , Gene Expression
12.
Sci Rep ; 14(1): 8543, 2024 04 12.
Article in English | MEDLINE | ID: mdl-38609416

ABSTRACT

The development of an organism is orchestrated by the spatial and temporal expression of genes. Accurate visualisation of gene expression patterns in the context of the surrounding tissues offers a glimpse into the mechanisms that drive morphogenesis. We developed correlative light-sheet fluorescence microscopy and X-ray computed tomography approach to map gene expression patterns to the whole organism`s 3D anatomy. We show that this multimodal approach is applicable to gene expression visualized by protein-specific antibodies and fluorescence RNA in situ hybridisation offering a detailed understanding of individual phenotypic variations in model organisms. Furthermore, the approach offers a unique possibility to identify tissues together with their 3D cellular and molecular composition in anatomically less-defined in vitro models, such as organoids. We anticipate that the visual and quantitative insights into the 3D distribution of gene expression within tissue architecture, by multimodal approach developed here, will be equally valuable for reference atlases of model organisms development, as well as for comprehensive screens, and morphogenesis studies of in vitro models.


Subject(s)
Antibodies , Tomography, X-Ray Computed , In Situ Hybridization, Fluorescence , Microscopy, Fluorescence , Gene Expression
13.
Sci Rep ; 14(1): 8558, 2024 04 12.
Article in English | MEDLINE | ID: mdl-38609494

ABSTRACT

Glutamate (Glu) is important for memory and learning. Hence, Glu imbalance is speculated to affect autism spectrum disorder (ASD) pathophysiology. The action of Glu is mediated through receptors and we analyzed four metabotropic Glu receptors (mGluR/GRM) in Indo-Caucasoid families with ASD probands and controls. The trait scores of the ASD probands were assessed using the Childhood Autism Rating Scale2-ST. Peripheral blood was collected, genomic DNA isolated, and GRM5 rs905646, GRM6 rs762724 & rs2067011, and GRM7 rs3792452 were analyzed by PCR/RFLP or Taqman assay. Expression of mGluRs was measured in the peripheral blood by qPCR. Significantly higher frequencies of rs2067011 'A' allele/ AA' genotype were detected in the probands. rs905646 'A 'exhibited significantly higher parental transmission. Genetic variants showed independent as well as interactive effects in the probands. Receptor expression was down-regulated in the probands, especially in the presence of rs905646 'AA', rs762724 'TT', rs2067011 'GG', and rs3792452 'CC'. Trait scores were higher in the presence of rs762724 'T' and rs2067011 'G'. Therefore, in the presence of risk genetic variants, down-regulated mGluR expression may increase autistic trait scores. Since our investigation was confined to the peripheral system, in-depth exploration involving peripheral as well as central nervous systems may validate our observation.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Receptors, Metabotropic Glutamate , Humans , Child , Autistic Disorder/genetics , Autism Spectrum Disorder/genetics , Gene Expression , Glutamic Acid , Receptors, Metabotropic Glutamate/genetics
14.
BMC Med ; 22(1): 154, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609982

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. METHODS: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models. RESULTS: PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8+ T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy. CONCLUSIONS: PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.


Subject(s)
Apoptosis , Colorectal Neoplasms , Animals , Mice , Humans , CD8-Positive T-Lymphocytes , Disease Models, Animal , Gene Expression , Colorectal Neoplasms/genetics , Colorectal Neoplasms/radiotherapy , Guanine Nucleotide Exchange Factors
15.
Nucleus ; 15(1): 2339580, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38616309
16.
Sci Rep ; 14(1): 7726, 2024 04 02.
Article in English | MEDLINE | ID: mdl-38565619

ABSTRACT

Decidualization can be induced by culturing human endometrial stromal cells (ESCs) with several decidualization stimuli, such as cAMP, medroxyprogesterone acetate (MPA) or Estradiol (E2). However, it has been unclear how decidualized cells induced by different stimuli are different. We compared transcriptomes and cellular functions of decidualized ESCs induced by different stimuli (MPA, E2 + MPA, cAMP, and cAMP + MPA). We also investigated which decidualization stimulus induces a closer in vivo decidualization. Differentially expressed genes (DEGs) and altered cellular functions by each decidualization stimuli were identified by RNA-sequence and gene-ontology analysis. DEGs was about two times higher for stimuli that use cAMP (cAMP and cAMP + MPA) than for stimuli that did not use cAMP (MPA and E2 + MPA). cAMP-using stimuli altered the cellular functions including angiogenesis, inflammation, immune system, and embryo implantation whereas MPA-using stimuli (MPA, E2 + MPA, and cAMP + MPA) altered the cellular functions associated with insulin signaling. A public single-cell RNA-sequence data of the human endometrium was utilized to analyze in vivo decidualization. The altered cellular functions by in vivo decidualization were close to those observed by cAMP + MPA-induced decidualization. In conclusion, decidualized cells induced by different stimuli have different transcriptome and cellular functions. cAMP + MPA may induce a decidualization most closely to in vivo decidualization.


Subject(s)
Endometrium , Medroxyprogesterone Acetate , Female , Humans , Cells, Cultured , Endometrium/metabolism , Medroxyprogesterone Acetate/pharmacology , Stromal Cells/metabolism , Gene Expression , RNA/metabolism , Decidua/metabolism
17.
Eur J Med Res ; 29(1): 216, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38566246

ABSTRACT

BACKGROUND: Desmin is a major cytoskeletal protein considered ubiquitous in mature muscle fibers. However, we earlier reported that a subgroup of muscle fibers in the soft palate of healthy subjects and obstructive sleep apnea patients (OSA) lacked immunoexpression for desmin. This raised the question of whether these fibers also lack messenger ribonucleic acid (mRNA) for desmin and can be considered a novel fiber phenotype. Moreover, some fibers in the OSA patients had an abnormal distribution and aggregates of desmin. Thus, the aim of the study was to investigate if these desmin protein abnormalities are also reflected in the expression of desmin mRNA in an upper airway muscle of healthy subjects and OSA patients. METHODS: Muscle biopsies from the musculus uvulae in the soft palate were obtained from ten healthy male subjects and six male patients with OSA. Overnight sleep apnea registrations were done for all participants. Immunohistochemistry, in-situ hybridization, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) techniques were used to evaluate the presence of desmin protein and its mRNA. RESULTS: Our findings demonstrated that a group of muscle fibers lacked expression for desmin mRNA and desmin protein in healthy individuals and OSA patients (12.0 ± 5.6% vs. 23.1 ± 10.8%, p = 0.03). A subpopulation of these fibers displayed a weak subsarcolemmal rim of desmin accompanied by a few scattered mRNA dots in the cytoplasm. The muscles of OSA patients also differed from healthy subjects by exhibiting muscle fibers with reorganized or accumulated aggregates of desmin protein (14.5 ± 6.5%). In these abnormal fibers, the density of mRNA was generally low or concentrated in specific regions. The overall quantification of desmin mRNA by RT-qPCR was significantly upregulated in OSA patients compared to healthy subjects (p = 0.01). CONCLUSIONS: Our study shows evidence that muscle fibers in the human soft palate lack both mRNA and protein for desmin. This indicates a novel cytoskeletal structure and challenges the ubiquity of desmin in muscle fibers. Moreover, the observation of reorganized or accumulated aggregates of desmin mRNA and desmin protein in OSA patients suggests a disturbance in the transcription and translation process in the fibers of the patients.


Subject(s)
Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Humans , Male , Desmin/genetics , Sleep Apnea, Obstructive/genetics , RNA, Messenger/genetics , Gene Expression
18.
Front Cell Infect Microbiol ; 14: 1359766, 2024.
Article in English | MEDLINE | ID: mdl-38572321

ABSTRACT

Virus-induced genomic remodeling and altered gene expression contribute significantly to cancer development. Some oncogenic viruses such as Human papillomavirus (HPV) specifically trigger certain cancers by integrating into the host's DNA, disrupting gene regulation linked to cell growth and migration. The effect can be through direct integration of viral genomes into the host genome or through indirect modulation of host cell pathways/proteins by viral proteins. Viral proteins also disrupt key cellular processes like apoptosis and DNA repair by interacting with host molecules, affecting signaling pathways. These disruptions lead to mutation accumulation and tumorigenesis. This review focuses on recent studies exploring virus-mediated genomic structure, altered gene expression, and epigenetic modifications in tumorigenesis.


Subject(s)
Carcinogenesis , Cell Transformation, Neoplastic , Humans , Carcinogenesis/genetics , Viral Proteins , Genomics , Gene Expression
19.
Physiol Rep ; 12(7): e15995, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38561245

ABSTRACT

Exercise has different effects on different tissues in the body, the sum of which may determine the response to exercise and the health benefits. In the present study, we aimed to investigate whether physical training regulates transcriptional network communites common to both skeletal muscle (SM) and subcutaneous adipose tissue (SAT). Eight such shared transcriptional communities were found in both tissues. Eighteen young overweight adults voluntarily participated in 7 weeks of combined strength and endurance training (five training sessions per week). Biopsies were taken from SM and SAT before and after training. Five of the network communities were regulated by training in SM but showed no change in SAT. One community involved in insulin- AMPK signaling and glucose utilization was upregulated in SM but downregulated in SAT. This diverging exercise regulation was confirmed in two independent studies and was also associated with BMI and diabetes in an independent cohort. Thus, the current finding is consistent with the differential responses of different tissues and suggests that body composition may influence the observed individual whole-body metabolic response to exercise training and help explain the observed attenuated whole-body insulin sensitivity after exercise training, even if it has significant effects on the exercising muscle.


Subject(s)
Insulin Resistance , Obesity , Adult , Humans , Obesity/metabolism , Muscle, Skeletal/metabolism , Exercise/physiology , Subcutaneous Fat/metabolism , Insulin/metabolism , Insulin Resistance/physiology , Gene Expression , Adipose Tissue/metabolism
20.
BMC Plant Biol ; 24(1): 235, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38561649

ABSTRACT

Drought stress considered a key restrictive factor for a warm-season bermudagrass growth during summers in China. Genotypic variation against drought stress exists among bermudagrass (Cynodon sp.), but the selection of highly drought-tolerant germplasm is important for its growth in limited water regions and for future breeding. Our study aimed to investigate the most tolerant bermudagrass germplasm among thirteen, along latitude and longitudinal gradient under a well-watered and drought stress condition. Current study included high drought-resistant germplasm, "Tianshui" and "Linxiang", and drought-sensitive cultivars; "Zhengzhou" and "Cixian" under drought treatments along longitude and latitudinal gradients, respectively. Under water deficit conditions, the tolerant genotypes showed over-expression of a dehydrin gene cdDHN4, antioxidant genes Cu/ZnSOD and APX which leads to higher antioxidant activities to scavenge the excessive reactive oxygen species and minimizing the membrane damage. It helps in maintenance of cell membrane permeability and osmotic adjustment by producing organic osmolytes. Proline an osmolyte has the ability to keep osmotic water potential and water use efficiency high via stomatal conductance and maintain transpiration rate. It leads to optimum CO2 assimilation rate, high chlorophyll contents for photosynthesis and elongation of leaf mesophyll, palisade and thick spongy cells. Consequently, it results in elongation of leaf length, stolon and internode length; plant height and deep rooting system. The CdDHN4 gene highly expressed in "Tianshui" and "Youxian", Cu/ZnSOD gene in "Tianshui" and "Linxiang" and APX gene in "Shanxian" and "Linxiang". The genotypes "Zhongshan" and "Xiaochang" showed no gene expression under water deficit conditions. Our results indicate that turfgrass show morphological modifications firstly when subjected to drought stress; however the gene expression is directly associated and crucial for drought tolerance in bermudagrass. Hence, current research has provided excellent germplasm of drought tolerant bermudagrass for physiological and molecular study and future breeding.


Subject(s)
Antioxidants , Cynodon , Cynodon/physiology , Antioxidants/metabolism , Droughts , Plant Breeding , Photosynthesis/genetics , Water/metabolism , Gene Expression
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