New Contributions to Asarum Powder on Immunology Related Toxicity Effects in Lung

Objective. Asarum is widely used in clinical practice of Chinese medicine in the treatment of respiratory diseases. Many toxic ingredients (safrole, etc.) had been found in Asarum that show multiple visceral toxicities. In this study, we performed systematic investigation of expression profiles of genes to take a new insight into unclear mechanism of Asarum toxicities in lung. Methods. mRNAs were extracted from lungs of rats after intragastric administration with/without Asarum powders, and microarray assays were applied to investigate gene expression profiles. Differentially expressed genes with significance were selected to carry out GO analysis. Subsequently, quantitative PCRs were performed to verify the differential expression of Tmprss6, Prkag3, Nptx2, Antxr11, Klk11, Rag2, Olr77, Cd7, Il20, LOC69, C6, Ccl20, LOC68, and Cd163 in lung. Changes of Ampk, Bcl2, Caspase 3, Il1, Il20, Matriptase2, Nfκb, Nptx2, and Rag2 in the lung on protein level were verified by western blotting and immunohistochemistry. Results. Compared with control group, the estimated organ coefficients were relatively increased in Asarum group. Results of GO analysis showed that a group of immune related genes in lung were expressed abnormally. The result of PCRs showed that Ccl20 was downregulated rather than other upregulated genes in the Asarum group. Western blotting and immunohistochemistry images showed that Asarum can upregulate the expression of Ampk, Caspase 3, Il1, Il20, Matriptase2, Nfκb, and Rag2 and downregulate the expression of Bcl2 in lung. Conclusion. Our data suggest that expressions of immune related genes in lung were selectively altered by Asarum. Therefore, inflammatory response was active, by regulating Caspase 3, Il1, Il20, Matriptase2, Nfκb, Rag2, Tmprss6, Prkag3, Nptx2, Antxr1, Klk11, Olr77, Cd7, LOC69, C6, LOC68, Cd163, Ampk, Bcl2, and Ccl20. Our study indicated that inflammatory factors take effect in lung toxicity caused by Asarum, which provides a new insight into molecular mechanism of Asarum toxicities in lung.

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Genomic profiles and predictive biological networks in oxidant-induced atherogenesis

Physiological Genomics ◽

10.1152/physiolgenomics.00006.2003 ◽

2003 ◽

Vol 13 (3) ◽

pp. 263-275 ◽

Cited By ~ 22

Author(s):

C. D. Johnson ◽

Y. Balagurunathan ◽

K. P. Lu ◽

M. Tadesse ◽

M. H. Falahatpisheh ◽

...

Keyword(s):

Oxidative Stress ◽

Biological Networks ◽

Expression Profiles ◽

Redox Homeostasis ◽

Gene Expression Profiles ◽

Antioxidant Treatment ◽

Chemical Treatments ◽

Polycyclic Aromatic ◽

Immune Related Genes ◽

Insight Into

Atherogenic stimuli trigger complex responses in vascular smooth muscle cells (VSMCs) that culminate in activation/repression of overlapping signal transduction cascades involving oxidative stress. In the case of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon present in tobacco smoke, the atherogenic response involves interference with redox homeostasis by oxidative intermediates of BaP metabolism. The present studies were conducted to define genomic profiles and predictive gene biological networks associated with the atherogenic response of murine (aortic) VSMCs to BaP. A combined oxidant-antioxidant treatment regimen was used to identify redox-sensitive targets during the early course of the atherogenic response. Gene expression profiles were defined using cDNA microarrays coupled to analysis of variance and several clustering methodologies. A predictor algorithm was then applied to gain insight into critical gene-gene interactions during atherogenesis. Supervised and nonsupervised analyses identified clones highly regulated by BaP, unaffected by antioxidant, and neutralized by combined chemical treatments. Lymphocyte antigen-6 complex, histocompatibility class I component factors, secreted phosphoprotein, and several interferon-inducible proteins were identified as novel redox-regulated targets of BaP. Predictor analysis confirmed these relationships and identified immune-related genes as critical molecular targets of BaP. Redox-dependent patterns of gene deregulation indicate that oxidative stress plays a prominent role during the early stages of BaP-induced atherogenesis.

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Lateral rectus muscle differentiation potential in paralytic esotropia patients

BMC Ophthalmology ◽

10.1186/s12886-021-01994-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qing Xia ◽

Xiangtian Ling ◽

Zhonghao Wang ◽

Tao Shen ◽

Minghao Chen ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Rectus Muscle ◽

Lateral Rectus ◽

Control Group ◽

Differentiation Potential ◽

Partial Restoration ◽

Reverse Transcription Pcr ◽

Lateral Rectus Muscle

Abstract Purpose and background Recently, we found that maximal medial rectus recession and lateral rectus resection in patients with complete lateral rectus paralysis resulted in a partial restoration of abduction. In an attempt to understand some of the mechanisms involved with this effect we examined gene expression profiles of lateral recti from these patients, with our focus being directed to genes related to myogenesis. Materials and methods Lateral recti resected from patients with complete lateral rectus paralysis and those from concomitant esotropia (controls) were collected. Differences in gene expression profiles between these two groups were examined using microarray analysis and quantitative Reverse-transcription PCR (qRT-PCR). Results A total of 3056 differentially expressed genes (DEGs) were identified between these two groups. Within the paralytic esotropia group, 2081 genes were up-regulated and 975 down-regulated. The results of RT-PCR revealed that PAX7, MYOG, PITX1, SIX1 and SIX4 showed higher levels of expression, while that of MYOD a lower level of expression within the paralytic esotropia group as compared with that in the control group (p < 0.05). Conclusion The decreased expression of MYOD in the paralytic esotropia group suggested that extraocular muscle satellite cell (EOMSCs) differentiation processes were inhibited. Whereas the high expression levels of PAX7, SIX1/4 and MYOG, suggested that the EOMSCs were showing an effective potential for differentiation. The stimulation resulting from muscle surgery may induce EOMSCs to differentiate and thus restore abduction function.

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Dienogest exerts its anti-endometriotic effect throughthe direct suppression of matrix metallopeptidases

10.21203/rs.3.rs-84809/v1 ◽

2020 ◽

Author(s):

Hiroshi Honda ◽

Norihisa Nishimichi ◽

Michinori Yamashita ◽

Yumiko Akimoto ◽

Hirotoshi Tanimoto ◽

...

Keyword(s):

Expression Profiles ◽

Group Versus ◽

Gene Expression Profiles ◽

High Specificity ◽

Reproductive Age ◽

Control Group ◽

Canonical Pathways ◽

Hormonal Therapies ◽

And Control ◽

Direct Suppression

Abstract Background: Endometriosis, which affects up to 10% women of reproductive age, is defined by the presence of ectopic endometrial tissue outside the uterus. The current key drug of hormonal therapies for endometriosis is dienogest, which is a progestin with high specificity for the progesterone receptor. Although many findings about the anti-endometriotic effect of dienogest on endometriosis have been reported, the precise mechanisms of dienogest's anti-endometriotic effect remain unknown. Methods: To investigate the direct anti-endometriotic effect of dienogest on endometriotic cells, we determined and compared the genome-wide gene expression profiles of endometriotic stromal cells treated with dienogest (Dienogest group) and those not treated with dienogest (Control group) and then performed a pathway analysis using these data. To test the microarray data, we performed real-time RT-PCRs for matrix metallopeptidase (MMP)-1, MMP-3, MMP-10, and TIMP-4.Results: Six-hundred forty-seven genes were revealed to be differentially expressed between the Dienogest and Control groups. Of them, 314 genes were upregulated and 333 genes were downregulated in the Dienogest group compared to the Control group. We identified 20 canonical pathways that are significantly distinct in the Dienogest group versus the Control group. Among the 20 canonical pathways, MMPs including MMP-1, -3, and -10 were found to be the most involved genes. Conclusions: Our results suggest that dienogest may exert its anti-endometriotic effect through the direct suppression of MMPs.

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Identification and Validation of a Predictive Immune-related Genes Signature for the Prognosis of Cholangiocarcinoma

10.21203/rs.3.rs-59448/v1 ◽

2020 ◽

Author(s):

Rui Zhang ◽

Chen Chen ◽

Qi Li ◽

Jialu Fu ◽

Dong Zhang ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

High Risk ◽

Risk Score ◽

Risk Model ◽

Predictive Accuracy ◽

Expression Profiles ◽

Gene Expression Profiles ◽

The Cancer Genome Atlas ◽

Immune Related Genes

Abstract Background: Immune-related genes (IRGs) play a crucial role in the initiation and progression of cholangiocarcinoma (CCA). However, immune signatures have rarely been used to predict prognosis of CCA. The aim of this study was to construct a novel model for CCA to predict survival based on IRGs expression data.Methods: The gene expression profiles and clinical data of CCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were integrated to establish and validate prognostic IRG signatures. Differentially expressed immune-related genes were screened. Univariate and multivariate Cox analysis were performed to identify prognostic IRGs, and the risk model that predicts outcomes was constructed. Furthermore, receiver operating characteristic (ROC) and Kaplan-Meier curve were plotted to examine predictive accuracy of the model, and a nomogram was constructed based on IRGs signature, combining with other clinical characteristics. Finally, CIBERSORT was used to analyze the association of immune cells infiltration with risk score.Results: We identified that 223 IRGs were signiﬁcantly dysregulated in patients with CCA, among which five IRGs (AVPR1B, CST4, TDGF1, RAET1E and IL9R) were identified as robust indicators for overall survival (OS), and a prognostic model was built based on the IRGs signature. Meanwhile, patients with high risk had worse OS in training and validation cohort, and the area under the ROC was 0.898 and 0.846, respectively. Nomogram demonstrated that immune risk score contributed much more points than other clinicopathological variables, with a C-index of 0.819 (95% CI, 0.727-0.911). Finally, we found that IRGs signature was positively correlated with the proportion of CD8+ T cells, neurophils and T gamma delta, while negatively with that of CD4+ memory resting T cells.Conclusions: We established and validated an effective five IRGs-based prediction model for CCA, which could accurately classify patients into groups with low and high risk of poor prognosis.

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Pathway-focused gene expression profiles and immunohistochemistry detection identify contrasting association of caspase 3 (CASP3) expression with prognosis in pediatric classical Hodgkin lymphoma

Hematological Oncology ◽

10.1002/hon.2523 ◽

2018 ◽

Vol 36 (4) ◽

pp. 663-670 ◽

Cited By ~ 4

Author(s):

Gabriela Vera-Lozada ◽

Priscilla Segges ◽

Claudio Gustavo Stefanoff ◽

Mário Henrique M. Barros ◽

Gerald Niedobitek ◽

...

Keyword(s):

Gene Expression ◽

Hodgkin Lymphoma ◽

Caspase 3 ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Classical Hodgkin Lymphoma

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

Journal of Diabetes Research ◽

10.1155/2020/6542346 ◽

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.

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PCA-based unsupervised feature extraction for gene expression analysis of COVID-19 patients

Scientific Reports ◽

10.1038/s41598-021-95698-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kota Fujisawa ◽

Mamoru Shimo ◽

Y.-H. Taguchi ◽

Shinya Ikematsu ◽

Ryota Miyata

Keyword(s):

Gene Expression ◽

Feature Extraction ◽

Target Genes ◽

Gene Selection ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Principal Component ◽

Data Set ◽

Immune Related Genes ◽

Unsupervised Feature Extraction

AbstractCoronavirus disease 2019 (COVID-19) is raging worldwide. This potentially fatal infectious disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the complete mechanism of COVID-19 is not well understood. Therefore, we analyzed gene expression profiles of COVID-19 patients to identify disease-related genes through an innovative machine learning method that enables a data-driven strategy for gene selection from a data set with a small number of samples and many candidates. Principal-component-analysis-based unsupervised feature extraction (PCAUFE) was applied to the RNA expression profiles of 16 COVID-19 patients and 18 healthy control subjects. The results identified 123 genes as critical for COVID-19 progression from 60,683 candidate probes, including immune-related genes. The 123 genes were enriched in binding sites for transcription factors NFKB1 and RELA, which are involved in various biological phenomena such as immune response and cell survival: the primary mediator of canonical nuclear factor-kappa B (NF-κB) activity is the heterodimer RelA-p50. The genes were also enriched in histone modification H3K36me3, and they largely overlapped the target genes of NFKB1 and RELA. We found that the overlapping genes were downregulated in COVID-19 patients. These results suggest that canonical NF-κB activity was suppressed by H3K36me3 in COVID-19 patient blood.

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Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women

International Journal of Molecular Sciences ◽

10.3390/ijms21010295 ◽

2019 ◽

Vol 21 (1) ◽

pp. 295

Author(s):

Rebeca González-Fernández ◽

Rita Martín-Ramírez ◽

Deborah Rotoli ◽

Jairo Hernández ◽

Frederick Naftolin ◽

...

Keyword(s):

Gene Expression ◽

Protein Localization ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Cellular Protein ◽

Control Group ◽

Poor Responders ◽

Male Factor ◽

Expression Levels ◽

Genes Expression

Sirtuins are a family of deacetylases that modify structural proteins, metabolic enzymes, and histones to change cellular protein localization and function. In mammals, there are seven sirtuins involved in processes like oxidative stress or metabolic homeostasis associated with aging, degeneration or cancer. We studied gene expression of sirtuins by qRT-PCR in human mural granulosa-lutein cells (hGL) from IVF patients in different infertility diagnostic groups and in oocyte donors (OD; control group). Study 1: sirtuins genes’ expression levels and correlations with age and IVF parameters in women with no ovarian factor. We found significantly higher expression levels of SIRT1, SIRT2 and SIRT5 in patients ≥40 years old than in OD and in women between 27 and 39 years old with tubal or male factor, and no ovarian factor (NOF). Only SIRT2, SIRT5 and SIRT7 expression correlated with age. Study 2: sirtuin genes’ expression in women poor responders (PR), endometriosis (EM) and polycystic ovarian syndrome. Compared to NOF controls, we found higher SIRT2 gene expression in all diagnostic groups while SIRT3, SIRT5, SIRT6 and SIRT7 expression were higher only in PR. Related to clinical parameters SIRT1, SIRT6 and SIRT7 correlate positively with FSH and LH doses administered in EM patients. The number of mature oocytes retrieved in PR is positively correlated with the expression levels of SIRT3, SIRT4 and SIRT5. These data suggest that cellular physiopathology in PR’s follicle may be associated with cumulative DNA damage, indicating that further studies are necessary.

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Classical Cancer Biology: Misconceptions and Limitations

10.1101/121053 ◽

2017 ◽

Author(s):

Abicumaran Uthamacumaran

Keyword(s):

Cancer Cells ◽

Cancer Biology ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Transformed Cells ◽

Epigenetic Landscape ◽

Normal Cells ◽

Cancer Models ◽

Stem Cell Division ◽

Insight Into

Cancer is the co-evolution of cancer cells and their turbulent microenvironment, characterized by dynamical hyper-chaotic gene expression profiles. However, cancers should not be viewed as the result of random mutations and malfunctioning information processing systems. Rather, it is the selective advantages conferred by adaptive evolution of cellular biosystems. Although on a systemic scale, cancer is defined as a disease, on a cellular basis they outperform healthy (non-transformed cells) in terms of survival and reproductive success. Their enhanced longevity pathways, metastatic invasion, extended telomeres, dynamical morphogenesis, regenerative stem cell division and environment-specific metabolic cascades indicate they are adaptive evolutionary cell states that have surpassed the boundaries normal cells are confined to. Therefore, the paper presents a brief summary of currently existing classical cancer models in the field of mathematical biology and the misconceptions of cancer epimetabolomes to further advance cancer research beyond its current limits. Through an insight into the mathematical behaviors of cancer cells, a quantum adaptive epigenetic landscape is proposed to explain the selective evolutionary dominance of cancer cells.

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