Association of congenital iodine deficiency syndrome and differentiated thyroid cancer: a Mendelian randomization study.

BACKGROUND: The effect of iodine deficiency, especially during the fetal period, on thyroid cancer risk remains unclear. The evidence from observational studies is controversial because of the inevitable confounding factors. We studied the causal effect of congenital iodine deficiency on differentiated thyroid cancer (DTC) based on Mendelian randomization (MR). METHODS: Two-Sample MR analysis was performed using data from published genome-wide association studies, including congenital iodine deficiency syndrome (CIDS) (353 cases, 187,684 controls) and DTC (649 cases, 431 controls) data. RESULTS: There was a causal relationship between CIDS and DTC (P < 0.05), with CIDS increasing the DTC risk by 37.4% (OR = 1.374, 95%CI = 1.110-1.700). Heterogeneity tests and tests of multiple validities indicated that the results were solid and reliable (all P < 0.05). CONCLUSIONS: Fetal iodine deficiency increases the risk of DTC, so future clinical studies should focus on the effect of iodine supplementation during pregnancy to reduce the risk of thyroid cancer in the offspring.

Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. METHODS: High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. RESULTS: Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. CONCLUSIONS: These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.

Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection.

Nuclear receptor corepressor 1 (NCOR1) and NCOR2 (also known as SMRT) regulate gene expression by activating histone deacetylase 3 through their deacetylase activation domain (DAD). We show that mice with DAD knock-in mutations have memory deficits, reduced anxiety levels, and reduced social interactions. Mice with NCOR1 and NORC2 depletion specifically in GABAergic neurons (NS-V mice) recapitulated the memory deficits and had reduced GABAA receptor subunit α2 (GABRA2) expression in lateral hypothalamus GABAergic (LHGABA) neurons. This was associated with LHGABA neuron hyperexcitability and impaired hippocampal long-term potentiation, through a monosynaptic LHGABA to CA3GABA projection. Optogenetic activation of this projection caused memory deficits, whereas targeted manipulation of LHGABA or CA3GABA neuron activity reversed memory deficits in NS-V mice. We describe de novo variants in NCOR1, NCOR2 or HDAC3 in patients with intellectual disability or neurodevelopmental disorders. These findings identify a hypothalamus-hippocampus projection that may link endocrine signals with synaptic plasticity through NCOR-mediated regulation of GABA signaling.

Dual-Directional Immunomodulatory Effects of Corbrin Capsule on Autoimmune Thyroid Diseases.

Purpose. To investigate the effects of Corbrin Capsule (CS-C-Q80), a drug derived from Cordyceps sinensis (Berk.) Sacc., on autoimmune thyroid diseases (AITD). Methods. 44 Patients with Graves's disease (GD) and 56 patients with Hashimoto's thyroiditis (HT) were randomly assigned to treatment group (GD-Tx and HT-Tx) or control group (GD-Ct and HT-Ct). The control groups were given methimazole or levothyroxine only while the treatment groups were given Corbrin Capsule (2.0 g tid) besides the same conventional prescriptions as control groups. Thyroid hormones, thyroid antibodies, and T lymphocyte subsets were quantified at baseline and 24 weeks posttreatment. Results. Significant drop of serum anti-TPO-Ab levels was observed in both GD-Tx and HT-Tx groups. Before treatment, GD patients had higher helper T cells compared to cytotoxic T cells, while HT patients suffered from a nearly inverted proportion of helper T/cytotoxic T cells. There was a significant drop of the helper T/cytotoxic T cells ratio in GD-Tx to the median of the normal ranges after Corbrin treatment for 24 weeks, while that in HT-Tx was elevated. Conclusion. Corbrin Capsule could restore the balance between helper T and cytotoxic T cells in both GD and HT patients with dual-directional immunomodulatory effects. And it could significantly reduce the autoantibody levels in both GD and HT.