scholarly journals Attenuated Oxidative Stress following Acute Exhaustive Swimming Exercise Was Accompanied with Modified Gene Expression Profiles of Apoptosis in the Skeletal Muscle of Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yi Sun ◽  
Di Cui ◽  
Zhe Zhang ◽  
Tan Zhang ◽  
Jun Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Swimming Exercise ◽  
Sod Activity ◽  
Time Points ◽  
Long Duration ◽  
Protein Expressions ◽  
Oxidative Stress Level

Purpose. The purpose of the present study was to investigate the effect of acute exhaustive swimming exercise on apoptosis in the skeletal muscle of mice.Method. C57BL/6 mice were averagely divided into seven groups. One group was used as control (C), while the remaining six groups went through one-time exhaustive swimming exercise and were terminated at 0 h, 2 h, 6 h, 12 h, 24 h, and 48 h upon completion of exercise.Result. ABTS was significantly lowered at 12 h and 48 h after exercise. The MDA level was significantly decreased at any time points sampled following exercise. Total SOD activity was significantly decreased at 6 h, 12 h, 24 h, and 48 h after exercise. Neither mRNA of Bax nor Bax/Bcl-2 ratio was significantly altered by exercise. mRNA of Bcl-2 was significantly decreased since 6 h after exercise. mRNA and protein expressions of PGC-1αwere significantly increased at different time points following exercise.Conclusion. Cellular oxidative stress level was decreased following low intensity, long duration acute exhaustive swimming exercise in mice, and the enzymatic antioxidant capacity was compromised. Apoptosis of the skeletal muscle was inhibited, which could partially be explained by the enhanced level of PGC-1α.

scholarly journals Bayesian approach for predicting responses to therapy from high-dimensional time-course gene expression profiles

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Arika Fukushima ◽  
Masahiro Sugimoto ◽  
Satoru Hiwa ◽  
Tomoyuki Hiroyasu
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Response To Therapy ◽  
Hcv Infection ◽  
Entire Treatment Period ◽  
Time Points ◽  
Time Course Data ◽  
Conventional Methods

Abstract Background Historical and updated information provided by time-course data collected during an entire treatment period proves to be more useful than information provided by single-point data. Accurate predictions made using time-course data on multiple biomarkers that indicate a patient’s response to therapy contribute positively to the decision-making process associated with designing effective treatment programs for various diseases. Therefore, the development of prediction methods incorporating time-course data on multiple markers is necessary. Results We proposed new methods that may be used for prediction and gene selection via time-course gene expression profiles. Our prediction method consolidated multiple probabilities calculated using gene expression profiles collected over a series of time points to predict therapy response. Using two data sets collected from patients with hepatitis C virus (HCV) infection and multiple sclerosis (MS), we performed numerical experiments that predicted response to therapy and evaluated their accuracies. Our methods were more accurate than conventional methods and successfully selected genes, the functions of which were associated with the pathology of HCV infection and MS. Conclusions The proposed method accurately predicted response to therapy using data at multiple time points. It showed higher accuracies at early time points compared to those of conventional methods. Furthermore, this method successfully selected genes that were directly associated with diseases.

scholarly journals Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma

2020 ◽  
Vol 318 (3) ◽  
pp. G419-G427 ◽  
Author(s):  
Tatsuhide Nabeshima ◽  
Shin Hamada ◽  
Keiko Taguchi ◽  
Yu Tanaka ◽  
Ryotaro Matsumoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Progression ◽  
Stress Responses ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Related Factor ◽  
Loss Of Function ◽  
P53 Expression ◽  
Nrf2 Activation

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/ p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/ p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad upregulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/ p53 expressing livers, accompanied by upregulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma. NEW & NOTEWORTHY The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response in cancer cells. Addition of the liver-specific Keap1 deletion to mice harboring mutant K-ras and p53 accelerated cholangiocarcinoma formation, together with the hallmarks of Nrf2 activation. This process involved the expansion of Sox9-positive cells, indicating increased differentiation toward the cholangiocyte phenotype.

scholarly journals Analyses of the pericyte transcriptome in ischemic skeletal muscles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuan-chi Teng ◽  
Alfredo Leonardo Porfírio-Sousa ◽  
Giulia Magri Ribeiro ◽  
Marcela Corso Arend ◽  
Lindolfo da Silva Meirelles ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Limb Ischemia ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Arterial Disease ◽  
The Body ◽  
Time Points

Abstract Background Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions. Methods In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing. Results Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells. Conclusions Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies.

PSIV-6 Differential gene expression of fibro/adipogenic progenitors between Wagyu and Brahman cattle: A possible contribution to their different meat quality

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 301-301
Author(s):  
Chaoyang Li ◽  
Qianglin Liu ◽  
Matt Welborn ◽  
Leshan Wang ◽  
Yuxia Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Meat Quality ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cattle Breed ◽  
Intramuscular Fat ◽  
Brahman Cattle ◽  
Differential Gene ◽  
The Difference

Abstract The amount of intramuscular fat directly influences the meat quality. However, significant differences in the ability to accumulate intramuscular fat are present among different beef cattle breeds. While Wagyu, a cattle breed that originated from Japan, is renowned for abundant intramuscular fat, Brahman cattle generally have very little intramuscular fat accumulation and produce tougher meat. We identified that bovine intramuscular fat is derived from a group of bipotent progenitor cells named fibro/adipogenic progenitors (FAPs) which also give rise to fibroblasts. Thus, the variation in intramuscular fat development between Wagyu and Brahman is likely attributed to the difference in FAPs between these two breeds. In order to understand the gene expression difference between FAPs of the two breeds, single-cell RNA-seq was performed using total single-nucleated cells isolated from the longissimus muscle of young purebred Wagyu, purebred Brahman, and Wagyu-Brahman cross cattle. FAPs constitute the largest single-nucleated cell population in both Wagyu and Brahman skeletal muscle. Multiple subpopulations of FAPs with different gene expression profiles were identified, suggesting that FAP is a heterogeneous population. A unique FAP cluster expressing lower levels of fibrillar collagen and extracellular remodeling enzyme genes but higher levels of select proadipogenic genes was identified exclusively in Wagyu skeletal muscle, which likely contributes to the robust intramuscular adipogenic efficiency of Wagyu FAPs. In conclusion, the difference in the cellular composition and gene expression of FAPs between Wagyu and Brahman cattle likely contribute to their distinct meat quality.

scholarly journals Analysis of gene expression profiles in insulin-sensitive tissues from pre-diabetic and diabetic Zucker diabetic fatty rats

2005 ◽  
Vol 34 (2) ◽  
pp. 299-315 ◽  
Author(s):  
Young Ho Suh ◽  
Younyoung Kim ◽  
Jeong Hyun Bang ◽  
Kyoung Suk Choi ◽  
June Woo Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats

Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age- and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating > 1.3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats at 12 weeks of age, expression of lipogenic genes was decreased in liver but increased in skeletal muscle of 12 week old diabetic ZDF rats. These results suggest that impairment of hepatic lipogenesis accompanied with the reduced lipogenesis of adipose tissue may contribute to development of diabetes in ZDF rats by increasing lipogenesis in skeletal muscle. Moreover, expression of antioxidant defense genes was decreased in the liver of 12-week old diabetic ZDF rats as well as in the adipose tissue of ZDF rats both at 6 and 12 weeks of age. Cytochrome P450 (CYP) genes were also significantly reduced in 12 week old diabetic liver of ZDF rats. Genes involved in glucose utilization were downregulated in skeletal muscle of diabetic ZDF rats, and the hepatic gluconeogenic gene was upregulated in diabetic ZDF rats. Genes commonly expressed in all three tissue types were also observed. These profilings might provide better fundamental understanding of insulin resistance and development of type 2 diabetes.

scholarly journals Exploring the Mechanism of Skeletal Muscle in a Tacrolimus-Induced Posttransplantation Diabetes Mellitus Model on Gene Expression Profiles

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Chenlei Zheng ◽  
Cheng Wang ◽  
Tan Zhang ◽  
Ding Li ◽  
Xiao-feng Ni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Muscle Development ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Enrichment Analysis ◽  
Quadriceps Muscle ◽  
Control Group ◽  
Bioinformatics Analyses

Objective. Posttransplantation diabetes mellitus (PTDM) is a known complication of transplantation that affects the prognosis. Tacrolimus (Tac or FK506) is a widely used immunosuppressant that has been reported to be a risk factor for PTDM and to further induce complications in heart and skeletal muscles, but the mechanism is still largely unknown. In our preliminary experiments, we found that after Tac treatment, blood glucose increased, and the weight of skeletal muscle declined. Here, we hypothesize that tacrolimus can induce PTDM and influence the atrophy of skeletal muscle. Methods. We designed preliminary experiments to establish a tacrolimus-induced PTDM model. Gene expression profiles in quadriceps muscle from this rat model were characterized by oligonucleotide microarrays. Then, differences in gene expression profiles in muscle from PTDM rats that received tacrolimus and control subjects were analyzed by using GeneSpring GX 11.0 software (Agilent). Functional annotation and enrichment analysis of differentially expressed genes (DEGs) helped us identify clues for the side effects of tacrolimus. Results. Our experiments found that the quadriceps in tacrolimus-induced PTDM group were smaller than those in the control group. The study identified 275 DEGs that may be responsible for insulin resistance and the progression of PTDM, including 86 upregulated genes and 199 downregulated genes. GO and KEGG functional analysis of the DEGs showed a significant correlation between PTDM and muscle development. PPI network analysis screened eight hub genes and found that they were related to troponin and tropomyosin. Conclusions. This study explored the molecular mechanism of muscle atrophy in a tacrolimus-induced PTDM model by bioinformatics analyses. We identified 275 DEGs and identified significant biomarkers for predicting the development and progression of tacrolimus-induced PTDM.

scholarly journals Effect of Sulforaphane and 5-Aza-2’-Deoxycytidine on Melanoma Cell Growth

Medicines ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 71 ◽  
Author(s):  
Tung-chin Chiang ◽  
Brian Koss ◽  
L. Joseph Su ◽  
Charity L. Washam ◽  
Stephanie D. Byrum ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Growth ◽  
Gene Transcription ◽  
Melanoma Cell ◽  
Dna Methyltransferase ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Epigenetic Modifications ◽  
Driving Mechanism ◽  
Epigenetic Drug

Background: UV exposure-induced oxidative stress is implicated as a driving mechanism for melanoma. Increased oxidative stress results in DNA damage and epigenetic dysregulation. Accordingly, we explored whether a low dose of the antioxidant sulforaphane (SFN) in combination with the epigenetic drug 5-aza-2’-deoxycytidine (DAC) could slow melanoma cell growth. SFN is a natural bioactivated product of the cruciferous family, while DAC is a DNA methyltransferase inhibitor. Methods: Melanoma cell growth characteristics, gene transcription profiles, and histone epigenetic modifications were measured after single and combination treatments with SFN and DAC. Results: We detected melanoma cell growth inhibition and specific changes in gene expression profiles upon combinational treatments with SFN and DAC, while no significant alterations in histone epigenetic modifications were observed. Dysregulated gene transcription of a key immunoregulator cytokine—C-C motif ligand 5 (CCL-5)—was validated. Conclusions: These results indicate a potential combinatorial effect of a dietary antioxidant and an FDA-approved epigenetic drug in controlling melanoma cell growth.

Gene expression profiles and protein balance in skeletal muscle of burned children after β-adrenergic blockade

2003 ◽  
Vol 285 (4) ◽  
pp. E783-E789 ◽  
Author(s):  
David N. Herndon ◽  
Mohan R. K. Dasu ◽  
Robert R. Wolfe ◽  
Robert E. Barrow
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Stable Isotope ◽  
Expression Profiles ◽  
Total Body Surface Area ◽  
Muscle Metabolism ◽  
Gene Expression Profiles ◽  
Adrenergic Blockade ◽  
Protein Balance ◽  
Gene And Protein Expression

Propranolol, a nonselective β-blocker, has been shown effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and lipolysis. This study investigates the effect of propranolol on gene and protein expression changes in skeletal muscle of burned children by use of high-density oligonucleotide arrays to establish the genetic profiles and stable isotope technique to quantitate protein synthesis. Thirty-seven children (mean age 9.7 ± 1.1 yr) were randomized into groups to receive placebo ( n = 23) or propranolol ( n = 14) titrated to reduce heart rate by 15%. Children had >40% total body surface area burns (mean 43 ± 5.6%). Protein net balance was determined by stable-isotope infusion technique. Total RNA from muscle biopsies was isolated, labeled, and cRNA hybridized to the HG-U95Av2 Affymetrix array. Mean net balance of protein synthesis and breakdown was –14.3 ± 12.9 nmol · min–1 · 100 ml leg volume–1 for placebo and +69.3 ± 34.9 nmol · min–1 · 100 ml leg volume–1 in the propranolol-treated children ( P = 0.012). Comparison of 12,000 genes in burned children receiving placebo showed increased expression of two genes with time, whereas children receiving propranolol showed increased expression of nine genes with a decrease in five genes. We conclude that burned children receiving propranolol showed a significant upregulation in genes involved in muscle metabolism and downregulation of an important enzyme involved in gluconeogenesis and insulin resistance compared with burned children receiving placebo. The upregulation of genes involved in muscle metabolism correlates well with the increase in net protein balance across the leg.

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