Alopecia areata (AA) is a prevalent disease associated with major emotional distress, and lacks effective, safe therapeutics for patients with extensive hair loss. This is the first report of hair regrowth with specific cytokine antagonism, in three patients with extensive hair loss ranging from 40% scalp involvement to alopecia universalis. Ustekinumab, an IL-12/23p40 antagonist that is highly effective in psoriasis, showed impressive ability to induce hair regrowth, coupled with suppression of inflammatory pathways and upregulation of hair keratins. Our report suggests that extensive AA is reversible using targeted treatments, opening the door for specific cytokine antagonism for this debilitating disease.
Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism.
Sex, Specimen part, Disease stage, Subject, Time
View SamplesPotassium is one of the essential macronutrients required for plant growth and development. It plays a major role in different physiological processes like cell elongation, stomatal movement, turgor regulation, osmotic adjustment, and signal transduction by acting as a major osmolyte and component of the ionic environment in the cytosol and subcellular organelles.
Gene expression analysis of rice seedling under potassium deprivation reveals major changes in metabolism and signaling components.
Specimen part, Treatment, Time
View SamplesKeloids are scars that extend beyond original wounds and are resistant to treatment. In order to improve understanding of the molecular basis of keloid scarring, we have assessed the genomic profiles of keloid fibroblasts and keratinocytes.
Keloid-derived keratinocytes exhibit an abnormal gene expression profile consistent with a distinct causal role in keloid pathology.
Sex, Age, Specimen part, Race
View SamplesThe goal of the experiment: To characterize the dynamic gene expression profile of engineered human skin in vitro and after grafting, and compare with expression profile of uninjured human skin.
Engineered human skin substitutes undergo large-scale genomic reprogramming and normal skin-like maturation after transplantation to athymic mice.
Specimen part
View SamplesHepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was also conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell.
Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus.
No sample metadata fields
View SamplesDysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream inflammatory gene synthesis in older adults remains poorly understood. Highly-purified human platelets and monocytes were isolated from healthy younger (age<45, n=37) and older (age60, n=30) adults and incubated together under autologous and non-autologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging. Basal IL-8 and MCP-1 synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous platelets, monocytes from older adults synthesized greater IL-8 (415 vs. 92 ng/mL, p<0.0001) and MCP-1 (867150 vs. 21636 ng/mL, p<0.0001) than younger adults. Non-autologous experiments demonstrated that platelets from older adults were sufficient for upregulating inflammatory gene synthesis by monocytes. Using RNA-seq followed by validation via RT-PCR and immunoblot, we discovered that granzyme A (GrmA), a serine protease not previously identified in human platelets, is increased in aging (~9-fold vs. younger adults, p<0.05) and governs increased IL-8 and MCP-1 synthesis through TLR4 and caspase-1. Inhibiting GrmA reduced the excessive IL-8 and MCP-1 synthesis in older adults to levels similar to younger adults. In summary, human aging is associated with changes in the platelet transcriptome and proteome. GrmA is present and bioactive in human platelets, is higher in older adults, and controls inflammatory gene synthesis by monocytes. Alterations in the platelet molecular signature and downstream signaling to monocytes may contribute to dysregulated inflammatory syndromes and adverse outcomes in older adults.
Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging.
Sex, Age, Specimen part, Disease
View SamplesUFH-001 cells, a newly isolated breast cancer line, have an STR profile that is most similar to that of the control MCF10A cells. Yet, the UFH-001 line is tumor forming with a triple negative phenotype. These cells have a unique transcriptome profile associated numerous breast cancer marker genes.
Selective inhibition of carbonic anhydrase IX over carbonic anhydrase XII in breast cancer cells using benzene sulfonamides: Disconnect between activity and growth inhibition.
Specimen part, Cell line
View SamplesCytoplasmic DNA triggers the activation of the innate immune system. While downstream signaling components have been characterized, the DNA sensing components remain largely elusive. We performed a systematic proteomics screen for proteins that associate with DNA, traversed to a screen for IFN--induced transcripts. We identified DSIRE (DNA sensor for the IL-1 response, previously called AIM2) as a candidate cytoplasmic sensor. DSIRE showed a marked selectivity for double-stranded DNA. DSIRE can recruit the inflammasome adaptor ASC and gets redistributed to ASC speckles upon coexpression of ASC. RNAi-mediated reduction of DSIRE expression led to an impairment in IL-1 maturation. Reconstitution of unresponsive cells with DSIRE, ASC, caspase 1 and IL-1 showed that DSIRE is sufficient for inflammasome activation. Overall, our data strongly suggest that DSIRE is a cytoplasmic DNA sensor for the inflammasome.
An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome.
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View SamplesThe goal of the experiment was to determine the transcriptional expression profile of zebrafish thrombocytes in order to enable comparison with mouse and human platelets. Overall design: Thrombocyte isolation from Tg(cd41:EGFP) zebrafish peripheral blood was performed using a novel monoclonal antibody (3H9) to Cd41
Sorting zebrafish thrombocyte lineage cells with a Cd41 monoclonal antibody enriches hematopoietic stem cell activity.
No sample metadata fields
View SamplesThe study was aimed at identifying genes directly or indirectly regulated by miR-205 in the prostate. To this purpose, DU145 prostate cancer cells, which express miR-205 at very low levels, were transfected with miR-205 synthetic precursor and consequent alterations of gene expression analyzed using a microarray approach.
miR-205 Exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cepsilon.
No sample metadata fields
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