RESUMEN
BACKGROUND: Radiofrequency ablation (RFA) effectively reduces volume and improves symptoms of benign, non-functioning thyroid nodules (NFTNs). Given RFA's unclear impact on thyroid function, we examined post-RFA trends in thyroid hormones and antibodies. METHODS: A retrospective cross-sectional analysis was conducted of patients treated at Columbia University with RFA for benign NFTNs between August 2019 and July 2023. Thyroid function tests were recorded pre-RFA and repeated 3, 6, and 12 months post-RFA. RESULTS: We analyzed 185 patients with 243 benign NFTNs who underwent RFA. Volume reduction ratio increased post-RFA. Mean TSH increased to 2.4 mlU/L (p â= â0.005) at 3 months post-RFA and decreased to 1.8 mlU/L (p â= â0.551) by 12 months post-RFA. Tg and TPO antibody levels peaked at 6 months post-RFA (103.1 IU/mL, p â= â0.868 and 66.6 IU/mL, p â= â0.523, respectively). CONCLUSIONS: With expected volume reduction post-RFA, we observed transient relative hypothyroidism as well as transient increases in thyroid antibodies, with normalization of these changes within 12 months.
RESUMEN
Renal olfactory receptor 1393 (Olfr1393) is an understudied sensory receptor that contributes to glucose handling in the proximal tubule. Our previous studies have indicated that this receptor may serve as a regulator of the sodium glucose co-transporters (SGLTs) and contributes to the development of glucose intolerance and hyperfiltration in the setting of diet-induced obesity. We hypothesized that Olfr1393 may have a similar function in Type 1 Diabetes. Using Olfr1393 wildtype (WT) and knockout (KO) mice along with streptozotocin (STZ) to induce pancreatic ß-cell depletion, we tracked the development and progression of diabetes over 12 weeks. Here we report that diabetic male Olfr1393 KO mice have a significant improvement in hyperglycemia and glucose tolerance, despite remaining susceptible to STZ. We also confirm that Olfr1393 localizes to the renal proximal tubule, and have uncovered additional expression within the glomerulus. Collectively, these data indicate that loss of renal Olfr1393 affords protection from STZ-induced type 1 diabetes and may be a general regulator of glucose handling in both health and disease.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Hiperglucemia/metabolismo , Receptores Odorantes/metabolismo , Animales , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 1/genética , Prueba de Tolerancia a la Glucosa , Homeostasis , Hiperglucemia/genética , Masculino , Ratones Noqueados , Neuronas Receptoras Olfatorias/metabolismo , Receptores Odorantes/genéticaRESUMEN
Sensory receptors, including olfactory receptors (ORs), taste receptors (TRs), and opsins (Opns) have recently been found in a variety of non-sensory tissues where they have distinct physiological functions. As G protein-coupled receptors (GPCRs), these proteins can serve as important chemosensors by sensing and interpreting chemical cues in the environment. We reasoned that the liver, the largest metabolic organ in the body, is primed to take advantage of some of these sensory receptors in order to sense and regulate blood content and metabolism. In this study, we report the expression of novel hepatic sensory receptors - including 7 ORs, 6 bitter TRs, and 1 Opn - identified through a systematic molecular biology screening approach. We further determined that several of these receptors are expressed within hepatocytes, the parenchymal cells of the liver. Finally, we uncovered several agonists of the previously orphaned hepatic ORs. These compounds fall under two classes: methylpyrazines and monoterpenes. In particular, the latter chemicals are plant and fungal-derived compounds with known hepatic protective effects. Collectively, this study sheds light on the chemosensory functions of the liver and unveils potentially important regulators of hepatic homeostasis.
RESUMEN
RecQ helicases are a family of proteins involved in maintaining genome integrity with functions in DNA repair, recombination, and replication. The human RecQ helicase family consists of five helicases: BLM, WRN, RECQL, RECQL4, and RECQL5. Inherited mutations in RecQ helicases result in Bloom Syndrome (BLM mutation), Werner Syndrome (WRN mutation), Rothmund-Thomson Syndrome (RECQL4 mutation), and other genetic diseases, including cancer. The RecQ helicase family is evolutionarily conserved, as Drosophila melanogaster have three family members: DmBlm, DmRecQL4, and DmRecQL5 and DmWRNexo, which contains a conserved exonuclease domain. DmBlm has functional similarities to human BLM (hBLM) as mutants demonstrate increased sensitivity to ionizing radiation (IR) and a decrease in DNA double-strand break (DSB) repair. To determine the extent of functional conservation of RecQ helicases, hBLM was expressed in Drosophila using the GAL4 > UASp system to determine if GAL4 > UASp::hBLM can rescue DmBlm mutant sensitivity to IR. hBLM was able to rescue female DmBlm mutant sensitivity to IR, supporting functional conservation. This functional conservation is specific to BLM, as human GAL4 > UASp::RECQL was not able to rescue DmBlm mutant sensitivity to IR. These results demonstrate the conserved role of BLM in maintaining the genome while reinforcing the applicability of using Drosophila as a model system to study Bloom Syndrome.