Project description:Introduction Iodine-131 (131I) is frequently used in nuclear medicine. Unbound or released 131I accumulate in the thyroid gland and may be detrimental to normal thyroid function. The aim of the present study was to identify biomarkers for 131I exposure in rat thyroid tissue and to assess the effect on thyroid function. Methods Thirty six male Sprague Dawley rats were i.v. injected with 150 µl saline solution containing 9.0, 88, 170, 260, 340, 760, 1300, or 4700 kBq (group A-H) 131I, or mock-treated with 150 µl saline solution only, and killed at 24 h after injection. Total RNA was extracted from individual thyroid tissue samples thyroids and mRNA levels were determined with the Agilent microarray platform. Results Estimated absorbed doses in treatment groups A-H was 0.0058, 0.057, 0.11, 0.17, 0.22, 0.5 Gy, 0.8 Gy, and 3 Gy. Totally, 429 transcripts were identified with a fold change fold change ⥠1.5 and adjusted p-value ⤠0.01. A trend with downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified, but only statistically significant after 0.0058 and 0.22 Gy. Three transcripts coding for isoform 1 of the DBP protein showed a pattern with monotonous decrease in downregulation with absorbed dose between 0.0058-0.22 Gy. Changes in Dbp expression were not statistically significant between 0.5-3 Gy. However, a trend with downregulation at 0.5 and 0.8 Gy and upregulation and 3 Gy was identified. Previously, 131I (0.85-17 Gy) and 211At (0.023-32 Gy) exposure resulted in upregulation of Dbp in mice thyroid tissue 24 h after administrations. Additionally, a monotonous decrease in Dbp downregulation has been identified of in mouse kidney tissue at 8 and 12 months after 177Lu-octreotate administrations. Conclusion Conclusively, the Dbp gene is a promising candidate biomarker gene for exposure to 131I and possibly other internal radiation emitters. Further studies should be performed to establish how Dbp expression vary with dose-rate, absorbed dose, time after administration, different radiation qualities, and the function of Dbp. Total RNA was isolated from fresh-frozen individual thyroid tissue samples (Sprague Dawley rats). Each sample was run once. Four rats received the same treatment. Control samples (from non-irradiated rats) are included.
Project description:Introduction Iodine-131 (131I) is frequently used in nuclear medicine. Unbound or released 131I accumulate in the thyroid gland and may be detrimental to normal thyroid function. The aim of the present study was to identify biomarkers for 131I exposure in rat thyroid tissue and to assess the effect on thyroid function. Methods Thirty six male Sprague Dawley rats were i.v. injected with 150 µl saline solution containing 9.0, 88, 170, 260, 340, 760, 1300, or 4700 kBq (group A-H) 131I, or mock-treated with 150 µl saline solution only, and killed at 24 h after injection. Total RNA was extracted from individual thyroid tissue samples thyroids and mRNA levels were determined with the Agilent microarray platform. Results Estimated absorbed doses in treatment groups A-H was 0.0058, 0.057, 0.11, 0.17, 0.22, 0.5 Gy, 0.8 Gy, and 3 Gy. Totally, 429 transcripts were identified with a fold change fold change ≥ 1.5 and adjusted p-value ≤ 0.01. A trend with downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified, but only statistically significant after 0.0058 and 0.22 Gy. Three transcripts coding for isoform 1 of the DBP protein showed a pattern with monotonous decrease in downregulation with absorbed dose between 0.0058-0.22 Gy. Changes in Dbp expression were not statistically significant between 0.5-3 Gy. However, a trend with downregulation at 0.5 and 0.8 Gy and upregulation and 3 Gy was identified. Previously, 131I (0.85-17 Gy) and 211At (0.023-32 Gy) exposure resulted in upregulation of Dbp in mice thyroid tissue 24 h after administrations. Additionally, a monotonous decrease in Dbp downregulation has been identified of in mouse kidney tissue at 8 and 12 months after 177Lu-octreotate administrations. Conclusion Conclusively, the Dbp gene is a promising candidate biomarker gene for exposure to 131I and possibly other internal radiation emitters. Further studies should be performed to establish how Dbp expression vary with dose-rate, absorbed dose, time after administration, different radiation qualities, and the function of Dbp.
Project description:Analysis of LBNF1 rat testes from controls, containing both somatic and all germ cell types and from irradiated rats in which all cells germ cells except type A spermatgogonia are eliminated. Results provide insight into distinguishing germ and somatic cell genes and identification of somatic cell genes that are upregulated after irradiation.
Project description:Knee osteoarthritis (KOA), as a degenerative multifactorial disease, affects the quality of life and mental health of patients, and also brings a huge socioeconomic burden. Treating synovitis have shown promise as anti-inflammatory therapeutics in mitigating OA symptoms and disease progression. Here, by analysing synovial single-cell sequencing (scRNA-seq) data from KOA, we found that synovial fibroblasts (FLS) in OA synovium showed a distinct pro-inflammatory phenotype. We collected synovial tissue from patients with clinical OA as well as from healthy donors, and histological examination was consistent with findings in scRNA-seq. Inspired by recent cross-tissue fibroblast lineage studies, we identified by sequencing that healthy FLS in synovial tissues share transcriptome-level similarities with dermal fibroblasts (DFb). Subsequently, we revealed the local as well as systemic distribution of intra-articular injected DFbs by constructing/extracting two types of rat fibroblasts (luciferase DFbs as well as GFP DFbs). The results demonstrate that DFbs can be locally retained in the synovium for up to three weeks following targeted engrafting on it. And intra-articular injection does not result in DFbs migration to vital organs or the occurrence of histological changes in these organs. A rat model of KOA was constructed by anterior cruciate ligament transection (ACLT) in order to study the therapeutic effect of DFbs on KOA. After injection, the rats showed improvement in painful gait. In addition, histological as well as imaging results showed reduced synovitis and improvement in articular cartilage. Finally we verified the protective effect of DFbs on cytokine-stimulated chondrocytes in a co-culture system.