Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid ...diseases and to observe methylation changes after treatment for these conditions.
A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3
T and CD19
B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction.
Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases.
Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.
Diallyl trisulfide (DATS), derived from garlic, is a well‐known hydrogen sulfide (H2S) donor. H2S has recently emerged as a novel gasotransmitter involved in the regulation of cancer progression. The ...present study demonstrated that DATS along with other two H2S donors, NaHS and GYY4137, significantly inhibited papillary thyroid carcinoma KTC‐1 cells growth. DATS treatment triggered a rapid H2S generation within 5 min in KTC‐1 cells. Iodoacetamide, a potent thiol blocker reagent, partially rescued the cell membrane damage and ultimate cell death induced by DATS, indicating H2S contributed to the apoptosis‐inducing efficacy of DATS on thyroid cancer cells. Specifically, DATS treatment significantly upregulated the expression and enzymatic activity of cystathionine gamma‐lyase (CTH), one of H2S‐producing enzymes, which was responsible for endogenous H2S generation. After DATS treatment, H2S quickly permeated cell membranes and activated NF‐κΒ/p65 signaling pathway in KTC‐1 cells. Nuclear translocated NF‐κB bound to the promoter of CTH to enhance its transcription. These evidences proved that exogenous H2S elevated CTH expression. CTH, in turn, catalytically generated a much higher level of endogenous H2S. This positive feedback sustained excess H2S production, which resulted in PTC cells growth inhibition. These findings may shed light on the development of novel H2S‐based antitumor agents.
Radioactive iodine (RAI) is commonly used to treat differentiated thyroid cancer (DTC). A major challenge is the dedifferentiation of DTC with the loss of radioiodine uptake. Patients with distant ...metastases have persistent or recurrent disease and develop resistance to RAI therapy due to tumor dedifferentiation. Hence, tumor redifferentiation to restore sensitivity to RAI therapy is considered a promising strategy to overcome RAI resistance. In the present study, curcumin, a natural polyphenolic compound, was found to re-induce cell differentiation and increase the expression of thyroid-specific transcription factors, TTF-1, TTF-2 and transcriptional factor paired box 8 (PAX8), and iodide-metabolizing proteins, including thyroid stimulating hormone receptor (TSHR), thyroid peroxidase (TPO) and sodium iodide symporter (NIS) in dedifferentiated thyroid cancer cell lines, BCPAP and KTC-1. Importantly, curcumin enhanced NIS glycosylation and its membrane trafficking, resulting in a significant improvement of radioiodine uptake
. Additionally, AKT knockdown phenocopied the restoration of thyroid-specific gene expression; however, ectopic expressed AKT inhibited curcumin-induced up-regulation of NIS protein, demonstrating that curcumin might improve radioiodine sensitivity
the inhibition of the PI3K-AKT-mTOR signaling pathway. Our study demonstrates that curcumin could represent a promising adjunctive therapy for restoring iodide avidity and improve radioiodine therapeutic efficacy in patients with RAI-refractory thyroid carcinoma.
Due to dedifferentiation of tumor cells, manifested by a decreased expression of iodide-handling genes in thyrocytes, some thyroid carcinomas lose their capability for radioiodine concentration and ...gradually develop radioactive iodine (RAI) resistance. This work aimed to investigate the role of tumor microenvironment (TME) in the process of tumor cell dedifferentiation.
Bioinformatic analyses and subsequent immunohistochemistry (IHC) and western blot assays were performed in papillary thyroid carcinoma (PTC) and matched normal tissue. ELISA was used to assess the secretion of cytokines under the stimulation of pharmacological endoplasmic reticulum (ER) stress inducer.
Higher levels of pro-inflammatory cytokines, interleukin 6 (IL-6) and (C-X-C motif chemokine ligand 8 (CXCL8), were found in thyroid cancer tissues compared with matched normal tissues. ER stress, induced by stressful environmental stimuli, such as nutrient deprivation and hypoxia, occurred in thyroid tumors. Classic ER stress inducers, thapsigargin (Tg) and tunicamycin (Tm), promoted the expression of IL6 and CXCL8 in thyroid cancer cells at mRNA and protein levels. Of note, rIL-6 and rCXCL8 promoted the dedifferentiation of thyroid cancer cells or even non-transformed cells in an autocrine/paracrine manner, weakening radioiodine uptake ability of thyroid cancer cells. Intriguingly, sorafenib, a multiple kinase inhibitor (MKI), could potently suppress not only ER stress-induced but also basal expressions of IL-6 and CXCL8 in thyroid cancer cells.
The inflammatory TME could regulate cell dedifferentiation, leading to loss of thyroid-specific gene expressions, through reciprocal interaction between thyroid tumor cells and follicular cells. Our study provides a new perspective on the mechanisms of how inflammatory TME affects DTC dedifferentiation.
Capsaicin (CAP) is a well‐known anti‐cancer agent. Recently, we reported capsaicin‐induced apoptosis in anaplastic thyroid cancer (ATC) cells. It is well accepted that the generation of cancer stem ...cells (CSCs) is responsible for the dedifferentiation of ATC, the most lethal subtype of thyroid cancer with highly dedifferentiation status. Whether CAP inhibited the ATC growth through targeting CSCs needed further investigation. In the present study, CAP was found to induce autophagy in ATC cells through TRPV1 activation and subsequent calcium influx. Meanwhile, CAP dose‐dependently decreased the sphere formation capacity of ATC cells. The stemness‐inhibitory effect of CAP was further by extreme limiting dilution analysis (ELDA). CAP significantly decreased the protein level of OCT4A in both 8505C and FRO cells. Furthermore, CAP‐induced OCT4A degradation was reversed by autophagy inhibitors 3‐MA and chloroquine, BAPTA‐AM and capsazepine, but not proteasome inhibitor MG132. Collectively, our study firstly showed CAP suppressed the stemness of ATC cells partially via calcium‐dependent autophagic degradation of OCT4A. Our study lent credence to the feasible application of capsaicin in limiting ATC stemness.
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•A PVP hierarchical nanofiber membrane was prepared via BiI3 sublimation.•Porous laser-induced graphene electrodes were created by engraving PI films.•The capacitive pressure sensor ...exhibits enhanced sensitivity and detection range.•A shooting posture recognition system was developed utilizing a CNN algorithm.•The sensor contributes to wearable health devices and human–computer interaction.
The development of a highly sensitive and wide-range flexible pressure sensor is great significant to realize the practical applications in human–computer interaction, health monitoring, and motion detection. Here, a dielectric layer of nano-cracked polyvinyl pyrrolidone (PVP) hierarchical nanofiber membrane (HNM) was fabricated by sublimating BiI3 from an electrospun BiI3/PVP composite nanofiber membrane (NM) via one-step annealing process. The upper and lower electrodes of porous laser-induced graphene (LIG) were produced through the engraving process on polyimide (PI) substrates. Subsequently, a flexible capacitive pressure sensor was constructed by assembling the middle PVP HNM dielectric layer with upper and lower LIG electrodes, which demonstrates enhanced sensitivity and detection range for motion posture recognition. Experimental results indicate that compared with traditional PVP NM-based pressure sensor, the assembled sensor in this work exhibits 22 times higher sensitivity (at 2–100 kPa) and 4 times wider detection range (0–200 kPa). Additionally, the sensor boasts a fast response/recovery time of 29/41 ms, an exceptionally low detection limit of 2.7 Pa, and an outstanding stability of 3000 cycles. With the aid of a convolutional neural network (CNN) algorithm, a shooting posture recognition system was developed by multiple sensors to accurately identify (accuracy: 93.89 %) and guide the shooting postures of basketball players.
In this work, a novel waxberry-like C@CoS2 composite was fabricated by a two-step hydrothermal method and used for peroxymonosulfate (PMS) activation. The unique morphology was beneficial to provide ...a large number of active sites. The C@CoS2 composite exhibited high performance on phenol degradation with the kinetic constant of 0.2795 min−1, which was 6–7 times that of simple CoS2 (0.0421 min−1) under the optimal conditions of C@CoS2 composite dose 0.3 g/L, PMS concentration 2.5 mM, 30 °C and initial pH= 7. The Cl− and NO3− had a slight inhibition on phenol degradation, while the HCO3− had a quick boost on phenol degradation. After five cycles, the phenol removal rate could still reach 90 % in the C@CoS2/PMS system. The sulfate radical ( SO4•−) and singlet oxygen (1O2) were identified to be the main active oxygen species (ROS) by radical quenching experiments and the electron paramagnetic resonance (EPR) measurements. The results of electrochemical impedance spectroscopy (EIS) indicated that the carbon spheres enhanced the conductivity of the composite, thus accelerating the electrons transport from Co(Ⅱ) to PMS, and the X-ray photoelectron spectroscopy (XPS) results proved that the S species in the CoS2 promoted the conversion cycle of Co(Ⅲ)/Co(Ⅱ) by donating electrons, resulting in the rapid PMS activation. This work is expected to provide a new strategy for establishing cobalt-based catalysts with high performance in the field of SO4•−-based advanced oxidation processes (AOPs).
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•A novel waxberry-like C@CoS2 composite was fabricated by a two-step hydrothermal method and used for PMS activation.•Carbon spheres as a great carrier improved the dispersion and conductivity of CoS2.•Co (III)/Co (II) cycle was enhanced by electrons transfer from S2-/Sn2-, further accelerating PMS activation.•The combination of SO4•−and 1O2 in C@CoS2/PMS dominated phenol degradation.
