Morphometric and physiological characteristics of brown trout (Salmo trutta) from the Ponor River

This paper presents the data related to morphometric and physiological (hematological) characteristics of brown trout (Salmo trutta) from the Ponor River. This river rises near the village Podrašnica (municipality of Mrkonjić Grad), sinks above the ground and after a while, near the settlement of Krupa na Vrbasu, appears as a source of the Krupa River (tributary of the Vrbas River). Fish sampling was performed during the summer of 2015 and during this period 22 Salmo trutta units were caught (11 females and 11 males). On that occasion, several morphometric (total and standard body length) and hematological traits (Hct-hematocrit, Hb-hemoglobin and MCHC-mean corpuscular hemoglobin concentration), body mass and Fulton's condition factor were analyzed. The average value for total body length was 18.85 cm and for standard body length it was 16.85 cm; the mean value for body mass was 80.38 g, and for Fulton's condition factor 1.41. In case of hematological parameters, the average value for Hct was 0.39 l/l, Hb 70.62 g/l and MCHC 180.64 g/l erythrocytes. The estimated parameters can serve as indicators for the condition of these aquatic organisms, and indirectly, the state of their environment

Morphometric and Physiological Characteristics of Brown Trout (Salmo trutta) from the Ponor River

This paper presents the data related to morphometric and physiological (hematological) characteristics of brown trout (Salmo trutta) from the Ponor River. This river rises near the village Podrašnica (municipality of Mrkonjić Grad), sinks above the ground and after a while, near the settlement of Krupa na Vrbasu, appears as a source of the Krupa River (tributary of the Vrbas River). Fish sampling was performed during the summer of 2015 and during this period 22 Salmo trutta units were caught (11 females and 11 males). On that occasion, several morphometric (total and standard body length) and hematological traits (Hct-hematocrit, Hb-hemoglobin and MCHC - mean corpuscular hemoglobin concentration), body mass and Fulton’s condition factor were analyzed. The average value for total body length was 18.85 cm and for standard body length it was 16.85 cm; the mean value for body mass was 80.38 g, and for Fulton’s condition factor 1.41. In case of hematological parameters, the average value for Hct was 0.39 l/l, Hb 70.62 g/l and MCHC 180.64 g/l erythrocytes. The estimated parameters can serve as indicators for the condition of these aquatic organisms, and indirectly, the state of their environment

Bromodomain Protein Inhibitors Reorganize the Chromatin of Synovial Fibroblasts

Bromodomain- and extra-terminal domain (BET) proteins are epigenetic reader proteins that regulate transcription of their target genes by binding to acetylated histone side chains. Small molecule inhibitors, such as I-BET151, have anti-inflammatory properties in fibroblast-like synoviocytes (FLS) and in animal models of arthritis. Here, we investigated whether BET inhibition can also affect the levels of histone modifications, a novel mechanism underlying BET protein inhibition. On the one hand, FLSs were treated with I-BET151 (1 µM) for 24 h in absence and presence of TNF. On the other hand, FLSs were washed with PBS after 48 h of I-BET151 treatment, and the effects were measured 5 days after I-BET151 treatment or after an additional 24 h stimulation with TNF (5 d + 24 h). Mass spectrometry analysis indicated that I-BET151 induced profound changes in histone modifications, with a global reduction in acetylation on different histone side chains 5 days after treatment. We confirmed changes on acetylated histone side chains in independent samples by Western blotting. I-BET151 treatment reduced mean TNF-induced levels of total acetylated histone 3 (acH3), H3K18ac, and H3K27ac. In line with these changes, the TNF-induced expression of BET protein target genes was suppressed 5 d after I-BET151 treatment. Our data indicate that BET inhibitors not only prevent the reading of acetylated histones but directly influence overall chromatin organization, in particular after stimulation with TNF

Bromodomain Protein Inhibitors Reorganize the Chromatin of Synovial Fibroblasts.

Bromodomain- and extra-terminal domain (BET) proteins are epigenetic reader proteins that regulate transcription of their target genes by binding to acetylated histone side chains. Small molecule inhibitors, such as I-BET151, have anti-inflammatory properties in fibroblast-like synoviocytes (FLS) and in animal models of arthritis. Here, we investigated whether BET inhibition can also affect the levels of histone modifications, a novel mechanism underlying BET protein inhibition. On the one hand, FLSs were treated with I-BET151 (1 µM) for 24 h in absence and presence of TNF. On the other hand, FLSs were washed with PBS after 48 h of I-BET151 treatment, and the effects were measured 5 days after I-BET151 treatment or after an additional 24 h stimulation with TNF (5 d + 24 h). Mass spectrometry analysis indicated that I-BET151 induced profound changes in histone modifications, with a global reduction in acetylation on different histone side chains 5 days after treatment. We confirmed changes on acetylated histone side chains in independent samples by Western blotting. I-BET151 treatment reduced mean TNF-induced levels of total acetylated histone 3 (acH3), H3K18ac, and H3K27ac. In line with these changes, the TNF-induced expression of BET protein target genes was suppressed 5 d after I-BET151 treatment. Our data indicate that BET inhibitors not only prevent the reading of acetylated histones but directly influence overall chromatin organization, in particular after stimulation with TNF

Dietary Derived Propionate Regulates Pathogenic Fibroblast Function and Ameliorates Experimental Arthritis and Inflammatory Tissue Priming

Short-chain fatty acids are gut-bacteria-derived metabolites that execute important regulatory functions on adaptive immune responses, yet their influence on inflammation driven by innate immunity remains understudied. Here, we show that propionate treatment in drinking water or upon local application into the joint reduced experimental arthritis and lowered inflammatory tissue priming mediated by synovial fibroblasts. On a cellular level, incubation of synovial fibroblasts with propionate or a physiological mixture of short-chain fatty acids interfered with production of inflammatory mediators and migration and induced immune-regulatory fibroblast senescence. Our study suggests that propionate mediates its alleviating effect on arthritis by direct abrogation of local arthritogenic fibroblast function

Reset of inflammatory priming of joint tissue and reduction of the severity of arthritis flares by bromodomain inhibition

OBJECTIVE: We have recently shown that priming of synovial fibroblasts (SFs) drives arthritis flares. Pathogenic priming of SFs is essentially mediated by epigenetic reprogramming. Bromodomain and extra-terminal motif (BET) proteins translate epigenetic changes into transcription. Here we used a BET inhibitor to target inflammatory tissue priming and reduce flare severity in experimental arthritis. METHODS: BALB/c mice were treated intraperitoneally or locally into the paw with I-BET151, which blocks interaction of BET proteins with acetylated histones. Effect of I-BET151 on acute arthritis and/or inflammatory tissue priming was assessed in a model of repeated injections of monosodium urate crystals or zymosan into the paw. I-BET151 was given either from before arthritis induction, at peak inflammation, or after healing of the first arthritis bout. Transcriptomic (RNA-Seq), epigenomic (ATAC-Seq) and functional analysis (invasion, cytokine production, migration, senescence, metabolic flux) was performed on murine and human SFs treated with I-BET151 in vitro or in vivo. RESULTS: Systemic I-BET151 administration did not affect acute inflammation but abolished inflammatory tissue priming and diminished flare severity in both preventive and therapeutic treatment settings. I-BET151 was also effective when applied locally in the joint. BET inhibition also inhibited osteoclast differentiation, while macrophage activation in the joint was not affected. Flare reduction after BET inhibition was mediated, at least in part, by rolling back the primed transcriptional, metabolic and pathogenic phenotype of SFs. CONCLUSION: Inflammatory tissue priming is dependent on transcriptional regulation by BET proteins, which makes them promising therapeutic targets for preventing arthritis flares in previously affected joints