Clinical and Molecular Evaluation of Warming and Tonic Herb Treatment for Sibling Patients of a Typical Kidney-yang Deficiency Family

It is essential to explore the molecular therapeutic effect of warm and tonic herb treatment for individuals with typical kidney-yang deficiency. In this report, we have identified members of a family with a history of suffering from cold and kidney-yang deficiency syndromes. First, we have employed the accumulated scores of the 40-items clinical scoring indicators for kidney-yang deficiency and cold syndromes to clinically assess the presence or absence of the deficiency for 15 family members. We then proceeded to compare the gene expression profiles of RNA isolated from blood samples, prior to and post-herbal treatment, of a sibling (brother and younger sister) that are suffering from the deficiency using cDNA microarrays with 18816 genes. Following treatments with the warming and tonic herb, the accumulated clinical scores obtained from the 40-items clinical scoring indicators were compared to those obtained pre-treatment. It was observed that the accumulated clinical scores were reduced by 1/3 for the brother and 2/3 for his younger sister following the treatments. Furthermore, we have demonstrated that the level of gene expression for a total of 33 genes at pre-treatment was modulated after treatments with the warming and tonic herb and correlated well with the clinical improvements of their syndromes. These results suggest that the combination of gene profiling and the accumulated clinical scores obtained from the 40-items clinical scoring indicators may provide an accurate clinical assessment and a way to monitor the therapeutic efficacy of the warming and tonic herb treatment.

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Assessment of gene expression profiles of peripheral blood mononuclear cells from patients with a history of carbamazepine hypersensitivity

The Lancet ◽

10.1016/s0140-6736(17)30500-7 ◽

2017 ◽

Vol 389 ◽

pp. S104

Author(s):

Vincent Yip ◽

Eunice Zhang ◽

Kim Clarke ◽

Ben Francis ◽

Lucille Rainbow ◽

...

Keyword(s):

Gene Expression ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

History Of

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Role of homeobox pathway in prostate carcinogenesis.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.126 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 126-126

Author(s):

James Lin Chen ◽

Kristen Otto ◽

Donald Vander Griend

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Seminal Vesicle ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Protein Network ◽

Gene Profiling ◽

Normal Prostate ◽

Survival Difference

126 Background: Identifying aberrant activity of developmental pathways in prostate cancer provides therapeutic opportunities. To this end, despite a shared embryonic origin and similarities to prostate cancer in histology and androgen dependence, seminal vesicle cancer is exceptionally rare. Genomic pathway analyses of their critical developmental differences may reveal uncharacterized oncogenic pathways. Previous attempts to do so have used whole tissue preparations. We hypothesized that careful gene profiling of pure primary epithelial cultures from normal prostate and seminal vesicles would reduce confounding noise during analysis and provide more robust pathway prioritization. Methods: Paired normal prostate and seminal vesicle epithelium cultures were created from three de-identified patients. Derived gene expression profiles were grouped into cancer biomodules using a protein-protein network algorithm to analyze their relationship to known oncogenes. Each resultant biomodule was assayed for its prognostic ability in independent Kaplan-Meier analyses of prostate cancer patients for time to recurrence and overall survival. Protein products from prioritized biomodule genes were then evaluated in vitro. Results: Gene expression profiling and protein network prioritization resulted in three cancer biomodules. Survival analysis revealed that the embryonic developmental biomodule centered on homeobox genes Meis1, Meis2 and Pbx1 to have clinical import. This homeobox biomodule detected a survival difference in a set of active surveillance patients (n=172, p=0.05) and identified men who were more likely to recur biochemically post-prostatectomy (n=78, p=0.02). We analyzed in vitro protein expression of Meis1, Meis2, Pbx1 and confirmed decreased gene expression in independent datasets of prostate cancer versus normal tissue. Conclusions: The Meis1/Meis2/Pbx1 biomodule may explain key differences in seminal vesicle and normal prostate epithelium development. In contrast to other cancers, Meis1, Meis2, and Pbx1 may play a tumor suppressor role in prostate cancer. Thus deregulation of this biomodule may be critical in prostate cancer oncogenesis.

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Abstract 149: Regulation of Pathogen-Associated Molecular Pattern Recognition by the Apo A-I Mimetic Peptide 4F

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a149 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Geeta Datta ◽

David K Crossman ◽

Lesley E Smythies ◽

M N Palgunachari ◽

Manjula Chaddha ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Responses ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Rna Isolation ◽

Mimetic Peptide ◽

M1 Macrophage ◽

Vehicle Treatment ◽

Anti Inflammatory ◽

Pre Treatment

The apolipoprotein A-I (apoA-I) mimetic peptide 4F displays prominent anti-inflammatory properties, including the ability to reduce vascular macrophage content. Macrophages are a heterogenous group of cells that are represented by two principal phenotypes, the classically-activated M1 macrophage and an alternatively-activated M2 phenotype. We previously reported that apoA-I and 4F favor the differentiation of human monocytes to an anti-inflammatory phenotype similar to that displayed by M2 macrophages. Further, 4F treatment attenuated LPS-induced inflammatory responses in monocyte-derived macrophages (MDMs). In the current study, we investigated effects of 4F and vehicle on LPS-induced gene expression in human MDMs by microarray analysis. RNA isolation, labeling and hybridization were performed, and the transcriptional profile was examined using the Human Gene ST 1.0 Affymetrix chip. Analysis of MDM gene expression profiles revealed that 4F modulated mRNA expression for 1099 genes (± 2-fold change, p<0.05), of which 149 genes regulated inflammatory responses. LPS treatment of MDMs significantly up-regulated genes encoding Toll-like receptors (TLR1, 2, 4, 6, and 8) compared to vehicle treatment. These responses were attenuated by 4F treatment. MyD88, CD14, IRAK4, TRAF6, TRAF3, MALT1 and IKBKB, genes that modulate NF-κB activation and subsequent cytokine synthesis, were also reduced by 4F. Corroborating this, FACS analyses showed that pre-treatment of MDMs with 4F reduced the LPS-dependent phosphorylation of NF-κB by 70% compared to vehicle treatment. These 4F-induced responses were also associated with a reduction in TNF-α and IL-6 secretion. These data suggest that an important anti-inflammatory mechanism of 4F action may be to down-regulate genes involved in the TLR signaling pathway, thus attenuating the responsiveness of macrophages to LPS and other pathogen-associated molecular patterns (PAMPs).

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Cigarette smoke preparations, not moist snuff, impair expression of genes involved in immune signaling and cytolytic functions

Scientific Reports ◽

10.1038/s41598-019-48822-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Gang Liu ◽

Subhashini Arimilli ◽

Evan Savage ◽

G. L. Prasad

Keyword(s):

Gene Expression ◽

Immune Responses ◽

Cigarette Smoke ◽

Inflammatory Responses ◽

Expression Profiles ◽

Gene Expression Profiles ◽

High Dose ◽

Pre Treatment ◽

High Doses ◽

Higher Doses

Abstract Cigarette smoke-induced chronic inflammation is associated with compromised immune responses. To understand how tobacco products impact immune responses, we assessed transcriptomic profiles in peripheral blood mononuclear cells (PBMCs) pretreated with Whole Smoke-Conditioned Medium (WS-CM) or Smokeless Tobacco Extracts (STE), and stimulated with lipopolysaccharide, phorbol myristate and ionomycin (agonists). Gene expression profiles from PBMCs treated with low equi-nicotine units (0.3 μg/mL) of WS-CM and one high dose of STE (100 μg/mL) were similar to those from untreated controls. Cells treated with medium and high doses of WS-CM (1.0 and 3.0 μg/mL) exhibited significantly different gene expression profiles compared to the low WS-CM dose and STE. Pre-treatment with higher doses of WS-CM inhibited the expression of several pro-inflammatory genes (IFNγ, TNFα, and IL-2), while CSF1-R and IL17RA were upregulated. Pre-treatment with high doses of WS-CM abolished agonist-stimulated secretion of IFNγ, TNF and IL-2 proteins. Pathway analyses revealed that higher doses of WS-CM inhibited NF-ĸB signaling, immune cell differentiation and inflammatory responses, and increased apoptotic pathways. Our results show that pre-treatment of PBMCs with higher doses of WS-CM inhibits immune activation and effector cytokine expression and secretion, resulting in a reduced immune response, whereas STE exerted minimal effects.

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In Vivo Permanent Marking of Cells with RAG1 Activation History Demonstrates Only a Minor Contribution of the Lymphoid Pathway to Dendritic Cell Development.

Blood ◽

10.1182/blood.v108.11.1268.1268 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1268-1268

Author(s):

Yong Chong ◽

Shin-ichi Mizuno ◽

Hirokazu Shigematsu ◽

Yojiro Arinobu ◽

Tadafumi Iino ◽

...

Keyword(s):

Gene Expression ◽

Steady State ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Yellow Fluorescence Protein ◽

Developmental Program ◽

A Genome ◽

History Of ◽

A Minor

Abstract Dendritic cells (DCs) have been shown to arise from both myeloid and lymphoid pathways, by evaluating the in vivo reconstituting potential of myeloid- and lymphoid-committed progenitor populations. It has been suggested that these “myeloid” or “lymphoid” DCs may constitute independent DC compartments with different functions. However, evaluation of DC development after conventional adoptive transfer experiments may not correctly represent normal DC development including lineage contribution toward the formation of the DC pool. In order to accurately evaluate the distribution and the function of DCs originated from each lineage, it is ideal to mark their origin in vivo in steady-state hematopoiesis. By crossing RAG1-Cre knockin with yellow fluorescence protein (YFP)-floxed reporter lines, we developed a mouse line in which cells with a history of RAG activation should be permanently marked with YFP as a result of lymphoid commitment. The YFP expression started at the common lymphoid progenitor (CLP) stage (~35%), and the percentages of YFP+ cells progressively increased as they differentiate into mature lymphocytes. More than 99.5% of mature T and B cells were marked by YFP, while <0.5% of granulocyte/monocyte progenitors (GMPs) or granulocytes were YFP+, indicating that this system efficiently and exclusively marks cells of lymphoid origin. We found that only 4.1, 4.6, and 9.3% of DCs were YFP+ in the spleen, the lymph nodes, and the thymus, respectively. This is the formal evidence that the vast majority of DCs in steady-state hematopoiesis originate from stages that have committed to the myeloid lineage, even in the thymus. We then profiled the gene expression of the YFP+ and YFP- DCs at a genome wide level by DNA microarray analysis. Unexpectedly, the gene expression profiles of myeloid and lymphoid-derived DCs are virtually identical. These results collectively suggest that myeloid and lymphoid DCs might use a common developmental program that can be activated even after myeloid or lymphoid commitment. Thus, the DC developmental program is unique, which should be independent of either myeloid or lymphoid commitment program.

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