Follicular Epithelial Cells Research Articles

Establishment of a CaCC-based Cell Model and Method for High-throughput Screening of M3 Receptor Drugs.

Muscarinic acetylcholine receptor subtype 3 (M3 receptor) is a G Protein-Coupled Receptor (GPCR) that mediates many important physiological functions. Currently, most M3 receptor drugs also have high affinity for other subtypes of muscarinic acetylcholine receptors (mAChRs) and produce the risk of side effects. Therefore, in order to find M3 receptor drugs with high specificity, high activity and low side effects, we established a cell model and method for efficient and sensitive screening of M3 receptor based on calcium-activated chloride channels (CaCCs), and this method is also suitable for the screening of other GPCR drugs. This screening model consists of Fischer rat thyroid follicular epithelial (FRT) cells that endogenously express M3 receptors, CaCCs, and the indicator YFP-H148Q/I152L. We verified that the model can sensitively detect changes in intracellular Ca2+ concentration using fluorescence quenching kinetics experiments, confirmed the screening function of the model by applying available M3 receptor drugs, and also evaluated the good performance of the model in high-throughput screening.

Different Expression of Thyroid-Specific Proteins in Thyroid Cancer Cells between 2-Dimensional (2D) and 3-Dimensional (3D) Culture Environment.

The two-dimensional (2D) monolayer culture as a conventional method has been widely applied in molecular biology fields, but it has limited capability to recapitulate real cell environments, being prone to misinterpretation with poor prediction of in vivo behavior. Recently, the three-dimensional (3D) spheroid culture has been studied extensively. Spheroids are self-assembled cell aggregates that have biomimicry capabilities. The behavior of thyroid cancer under the 3D spheroid culture environment has been studied; however, there are no reports regarding differences in the degree of thyroid cancer cell differentiation under 2D and 3D culture conditions. This study investigated the expression of thyroid differentiation proteins related to iodide-metabolizing mechanisms in thyroid cancer cells under different culture conditions. Four thyroid cancer cell lines and one thyroid follicular epithelial cell line were grown in adherent 2D cell culture and 3D spheroid culture with agarose-coated plates. We observed changes in proliferation, hypoxia, extracellular matrix (ECM), cytoskeleton, thyroid-specific proteins, and thyroid transcription factors. All cell lines were successfully established in the spheroid following cell aggregation. Proliferation considerably decreased, while hypoxia-inducible factor 1-α(HIF1-α) was promoted in 3D spheroids; moreover, 3D spheroids with thyroid cancers showed diminished thyroid differentiation markers, but thyroid follicular epithelial cells revealed either a maintenance or weak decline of protein expression. We verified that the 3D spheroid culture environment can be similar to in vivo conditions because of its alterations in numerous cellular and functional activities, including morphology, cellular proliferation, viability, hypoxia, ECM, cytoskeleton, and thyroid differentiation, compared to the conventional 2D monolayer culture environment. An in vitro experimental study using 3D spheroid culture is ideal for the faster discovery of new drugs.

PSAT335 Histopathological changes of the thyroid may be subtle yet important in Amiodarone induced thyrotoxicosis (AIT).

Abstract Background Amiodarone is an effective antiarrhythmic for several cardiac arrhythmias. Due to its high iodine content and long half-life with direct toxic effects on the thyroid gland, it is known to cause a spectrum of thyroid dysfunction. AIT type 1, a form of iodine-induced hyperthyroidism, and AIT type 2, a drug induced destructive thyroiditis, pose a diagnostic and therapeutic challenge. Since the physical and psychological consequences of long-term therapy with either condition are too large to ignore, it is crucial to differentiate between the two types. Histopathologic findings in AIT includes disrupted follicles filled with desquamated vacuolated epithelial cells, foamy macrophages, scattered lymphocytes, involution changes and fibrosis. However, these changes may be subtle in patients who have been treated with long term high dose steroids, but helpful in establishing either AIT 1 or 2. Case A 56-year-old man with a history of cardiomyopathy with an ejection fraction of 30% and atrial flutter treated previously with six months of amiodarone, presented for a routine appointment found to be in atrial flutter with rapid ventricular rate. The patient was off amiodarone therapy for ∼ 6 months prior to current presentation. The patient was referred to the ER where initial vital signs were remarkable for heart rate in the 140s. Exam was remarkable for mild tremor of the outstretched bilateral hands. Labs were remarkable for TSH of 0.01 ulU/ml (0.27-4.20), Free T4 of 2.2 ng/dl (0.93-1.70), Free T3 of 5.9 pg/ml(2.3-4.2). Thyroid ultrasonography revealed a heterogeneously enlarged thyroid gland with no increased vascularity, and 2.4 cm isthmus nodule of a TI-RAD-3. Thyroid stimulating immunoglobulins (TSI) of 96 (<140%), and thyroid peroxidase (TPO) of 2IU/ml (<9). Thyroid radioactive iodine uptake (RAIU) revealed a severely decreased uptake in the setting of amiodarone use. Mixed AIT was suspected and patient was placed on titrated dose of Methimazole (MMI) and Prednisone. Approximately three weeks later, patient was discharged on MMI 40 mg TID and Prednisone 60 mg daily. He had a close outpatient follow up with further titration of prednisone to 80 mg daily. Due to prolonged nature of disease, he was subsequently referred for total thyroidectomy. Histological examination revealed subtle changes including desquamated follicular epithelial cells and intrafollicular foamy macrophages. The thyroid architecture was maintained and no inflammatory infiltrates of fibrosis were noted. These findings are consistent with AIT type 2. Conclusion AIT is a challenging diagnosis, and in medically refractory cases, total thyroidectomy is a curative option. The pathological findings in a patients treated with prolonged steroids may dampen inflammation of AIT2, and therefore careful histologic examination and monitoring of inflammatory markers may help to consolidate diagnosis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Amiodarone-drove XBP1s aggravates endoplasmic reticulum stress and apoptosis in Hashimoto’s thyroiditis through regulating LINC00842/miR-214/FASL axis

Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disease, that eventually lead to hypothyroidism. XBP1s is an endoplasmic reticulum stress related protein and participates in the pathogenesis of several diseases. Nevertheless, the potential role of XBP1s in amiodarone (AMIO)-treated HT patients remains unknown. In this study, AMIO aggravated the endoplasmic reticulum stress responses in HT patients and thyroid epithelial follicular cells. Moreover, MTT assay and flow cytometry analysis revealed that knockdown of XBP1s suppressed AMIO-induced thyroid epithelial follicular cells apoptosis. Mechanically, the Chromatin Immunoprecipitation (ChIP) and luciferase activity assay proved that XBP1s enhanced LINC00842 expression in HT patients and thyroid epithelial follicular cells via binding to LINC00842 promoter. LINC00842 functioned as a miR-214 sponge in HT patients and thyroid epithelial follicular cells. Besides, LINC00842 up-regulated Fas ligand (FASL) expression via inhibition of miR-214. In rescue experiments, overexpression of FASL reversed shXBP1s-induced suppression of cell apoptosis in AMIO-treated thyroid epithelial follicular cells. These findings concluded that AMIO-drove XBP1s aggravated endoplasmic reticulum stress and apoptosis in HT via modulating LINC00842/miR-214/FASL axis, providing a new sight for the therapeutic strategy of AMIO-induced HT.

CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment

Anaplastic thyroid carcinoma (ATC) is an extremely malignant type of endocrine cancer frequently accompanied by extrathyroidal extension or metastasis through mechanisms that remain elusive. We screened for the CREB3 transcription-factor family in a large cohort, consisting of four microarray datasets. This revealed that CREB3L1 was specifically up regulated in ATC tissues and negatively associated with overall survival of patients with thyroid cancer. Consistently, high expression of CREB3L1 was negatively correlated with progression-free survival in an independent cohort. CREB3L1 knockdown dramatically attenuated invasion of ATC cells, whereas overexpression of CREB3L1 facilitated the invasion of papillary thyroid carcinoma (PTC) cells. Loss of CREB3L1 inhibited metastasis and tumor growth of ATC xenografts in zebrafish and nude mouse model. Single-cell RNA-sequencing analysis revealed that CREB3L1 expression gradually increased during the neoplastic progression of a thyroid follicular epithelial cell to an ATC cell, accompanied by the activation of the extracellular matrix (ECM) signaling. CREB3L1 knockdown significantly decreased the expression of collagen subtypes in ATC cells and the fibrillar collagen in xenografts. Due to the loss of CREB3L1, ATC cells were unable to activate alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs). After CREB3L1 knockdown, the presence of CAFs inhibited the growth of ATC spheroids and the metastasis of ATC cells. Further cytokine array screening showed that ATC cells activated α-SMA-positive CAFs through CREB3L1-mediated IL-1α production. Moreover, KPNA2 mediated the nuclear translocation of CREB3L1, thus allowing it to activate downstream ECM signaling. These results demonstrate that CREB3L1 maintains the CAF-like property of ATC cells by activating the ECM signaling, which remodels the tumor stromal microenvironment and drives the malignancy of ATC.Graphical

BRAF gene mutation and papillary thyroid carcinoma

Nowadays, Thyroid carcinoma (TC) is the most common malignant tumor of endocrine system, accounting for about 1% of the malignant tumors in the whole body, ranking first in the head and neck malignant tumors. Papillary thyroid carcinoma (PTC) is a malignant tumor originated from thyroid follicular epithelial cells, which is the most common pathological type in TC. V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a molecular biological marker for the diagnosis and prognosis of PTC and a target gene for the treatment of PTC. Its gene mutation is a hot point in the TC research field. The most common gene mutation is BRAF V600E mutation and it is a molecular marker in PTC. With the deep-going of its research, contradictions and controversies about the relationship between BRAF V600E and PTC gradually emerge. Many molecular targeted drugs targeting BRAF gene are also being continuously researched and some achievements have been made. This review mainly expounds the relationship between BRAF V600E and clinicopathological features, analyzes and expounds the controversial parts currently as well as show the research status of molecular targeted drugs.

Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration.

For a group of cells to migrate together, each cell must couple the polarity of its migratory machinery with that of the other cells in the cohort. Although collective cell migrations are common in animal development, little is known about how protrusions are coherently polarized among groups of migrating epithelial cells. We address this problem in the collective migration of the follicular epithelial cells in Drosophila melanogaster. In this epithelium, the cadherin Fat2 localizes to the trailing edge of each cell and promotes the formation of F-actin-rich protrusions at the leading edge of the cell behind. We show that Fat2 performs this function by acting in trans to concentrate the activity of the WASP family verprolin homolog regulatory complex (WAVE complex) at one long-lived region along each cell's leading edge. Without Fat2, the WAVE complex distribution expands around the cell perimeter and fluctuates over time, and protrusive activity is reduced and unpolarized. We further show that Fat2's influence is very local, with sub-micron-scale puncta of Fat2 enriching the WAVE complex in corresponding puncta just across the leading-trailing cell-cell interface. These findings demonstrate that a trans interaction between Fat2 and the WAVE complex creates stable regions of protrusive activity in each cell and aligns the cells' protrusions across the epithelium for directionally persistent collective migration.

Assessment of tissue expression of matrix metalloproteinase-9 level in patients with vitiligo and its relation to disease pattern, activity, and severity

Background Vitiligo is a common acquired depigmentary disorder characterized by milky-white cutaneous macules devoid of identifiable functional melanocytes of unknown origin. Several hypotheses have been advanced to explain the link between matrix metalloproteinase-9 (MMP-9) and vitiligo. Aim We aimed to compare the tissue expression of MMP-9 in vitiligo lesions with that of healthy controls. Patients and methods A case–control study was performed to evaluate MMP-9 levels by punch biopsies using an immunohistochemistry technique in lesional and nonlesional tissues of the same patient with vitiligo and in comparison with healthy controls. The study included 20 patients (10 patients with vitiligo and 10 healthy controls). Patients included were 18 years of age and older of both sexes, any duration, and any subtype. Results MMP-9 expression was found to be lower in the lesional skin of patients with vitiligo at the basal cell layer, follicular epithelium, and stromal cell layer when compared with nonlesional skin of the same patient with vitiligo and matched control individuals. Conclusion Tissue MMP-9 imbalance has a role in the etiopathogenesis of vitiligo. The low MMP-9 tissue expression may not facilitate the migration of melanoblasts. Tissue MMP-9 is a significant predictor of severity of vitiligo.

Effects of life cycle exposure to polystyrene microplastics on medaka fish (Oryzias latipes)

The number of published studies evaluating the effects of microplastics (MPs) in fish has increased in the last decade. However, of the available studies, few have explored the long-term effects of MPs on fish growth and reproduction and have resorted to MPs in the form of μm-sized beads/microspheres. In this study, 6-10 day-old post-hatch medaka (Oryzias latipes) fish were exposed to 50 (i.e. 1X) and 500 (i.e. 10X) μg of heterogeneously sized and irregularly shaped virgin polystyrene (PS) MP particles (200-μm range)/L for 150 days. These concentrations corresponded to respective daily mean values of 247 and 3087 particles/L administered through the diet. The PS MPs dietary exposure resulted in body burdens of 114 and 440 particles/g fish on day 50, and of 78 and 173 particles/g fish on day 100 since the respective exposures to the 1X and the 10X treatments started. The biometric analyses found no incidence of PS MPs ingestion on overall fish growth and development. The histological survey in the 10X group did not reveal alterations in gills or in the digestive tract. Mild alterations in other organs were seen and included increased fluid material in the peritoneal cavity, glomerular and tubular alterations in kidneys, and differences in the diameter of the thyroid follicles and thickness of the follicular epithelial cells. The initial days of the reproductive phase revealed MP-related differences in the number of gravid females, fecundity, and fertilization rates. Overall, these values reverted to normal rates throughout the succeeding days. No significant effects of PS MPs exposure were evidenced on offspring success. The 150-day PS MPs dietary exposure used in this study provided clues of histological effects and a reproduction delay. However, it did not seem to compromise overall growth/thriving and the ongoing reproduction.

Positron Emission Tomography Radiopharmaceuticals in Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC), arising from thyroid follicular epithelial cells, is the most common type of thyroid cancer. Despite the well-known utilization of radioiodine treatment in DTC, i.e., iodine-131, radioiodine imaging in DTC is typically performed with iodine-123 and iodine-131, with the current hybrid scanner performing single photon emission tomography/computed tomography (SPECT/CT). Positron emission tomography/computed tomography (PET/CT) provides superior visualization and quantification of functions at the molecular level; thus, lesion assessment can be improved compared to that of SPECT/CT. Various types of cancer, including radioiodine-refractory DTC, can be detected by 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), the most well-known and widely used PET radiopharmaceutical. Several other PET radiopharmaceuticals have been developed, although some are limited in availability despite their potential clinical utilizations. This article aims to summarize PET radiopharmaceuticals in DTC, focusing on molecular pathways and applications.

Bone Marrow Mesenchymal Stem Cells (BMSCs) Promote the Metastasis of Thyroid Papillary Cancer by Inhibiting Poly-Pyrimidine Tract Binding Protein 1 (PTBP1)

We aimed to explore the mechanism underlying the role of bone marrow mesenchymal stem cells (BMSCs) in the invasion of papillary thyroid cancer (PTC) cells. BMSCs were co-cultured with PTC cells WRO or normal thyroid follicular epithelial cells T3TD followed by analysis of cell migration and proliferation by Transwell assay and MTT assay. Cells were transfected with shRNA or overexpression of PTBP1, followed by measuring cell proliferation and invasion and PTBP1 expression by RT-qPCR and Western blot. Co-cultivation with MSC promoted the malignant transformation of WRO, inhibited the RNA-binding protein PTBP1 and activation of GS3Kβ/Akt. In addition, silencing of PTBP1 accelerated cell invason and induced overexpression of EMT proteins, while overexpression of PTBP1 inhibited cell proliferation and migration. In conclusion, BMSCs might promote PTC invasion and metastasis by inhibiting PTBP1 expression, providing a novel insight into the treatment of PTC.

The Effect of Early Life Exposure to Triclosan on Thyroid Follicles and Hormone Levels in Zebrafish.

Triclosan (TCS) is an antimicrobial chemical widely used in personal care products. Most of the TCS component is discharged and enters the aquatic ecosystem after usage. TCS has a similar structure as thyroid hormones that are synthesized by thyroid follicular epithelial cells, thus TCS has a potential endocrine disrupting effect. It is still not clear how the different levels of the environmental TCS would affect early development in vivo. This study examines the effects of TCS on thyroid hormone secretion and the early development of zebrafish. The fertilized zebrafish eggs were exposed to TCS at 0 (control), 3, 30, 100, 300, and 900 ng/mL, and the hatching rate and the larvae mortality were inspected within the first 14 days. The total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) were measured at 7, 14, and 120 days post-fertilization (dpf). The histopathological examinations of thyroid follicles were conducted at 120 dpf. TCS exposure at 30-300 ng/mL reduced the hatching rate of larvae to 34.5% to 28.2 % in the first 48 hours and 93.8 .7 % to 86.8 % at 72 h. Extremely high TCS exposure (900 ng/mL) strongly inhibited the hatching rate, and all the larvae died within 1 day. Exposure to TCS from 3 to 300 ng/mL reduced the thyroid hormones production. The mean TT3 and FT3 levels of zebrafish decreased in 300 ng/mL TCS at 14 dpf (300 ng/mL TCS vs. control : TT3 , 0.19 ± 0.08 vs. 0.39 ± 0.06; FT3, 19.21 ± 3.13 vs. 28.53 ± 1.98 pg/mg), and the FT4 decreased at 120 dpf ( 0.09 ± 0.04 vs. 0.20 ± 0.14 pg/mg). At 120 dpf , in the 300 ng/mL TCS exposure group, the nuclear area and the height of thyroid follicular epithelial cells became greater, and the follicle cell layer got thicker. This happened along with follicle hyperplasia, nuclear hypertrophy, and angiogenesis in the thyroid. Our study demonstrated that early life exposure to high TCS levels reduces the rate and speed of embryos hatching, and induces the histopathological change of thyroid follicle, and decreases the TT3, FT3, and FT4 production in zebrafish.

Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß.

Simple SummaryPBDEs have been reported to have endocrine-disrupting and tumour-promoting activity; however, the effects of BDE209 (the highest brominated PBDEs) on the thyroid and the underlying mechanisms are unclear. In this study, we found that long-term exposure to BDE209 could cause chronic toxicity and potential tumourigenesis by inhibiting the expression and function of TRß, which induces the proliferation of thyroid tissue and the oncogenesis of thyroid carcinoma. These findings emphasize the damaging effects that exposure to BDE209 has on human thyroid and papillary thyroid carcinoma.Polybrominated diphenyl ethers (PBDEs) have been reported to possess endocrine-disrupting and tumour-promoting activity. However, the effects of long-term exposure to decabromodiphenyl ether (BDE209) on thyroid tumourigenesis of papillary thyroid carcinoma (PTC) and the underlying mechanisms remain poorly defined. In this study, functional assays in vitro and mouse models in vivo were used to evaluate the toxic effects of long-term exposure to environmental concentrations of BDE209 on the pathogenesis and progression of PTC. MTS, EdU and colony-forming assays confirmed the chronic toxicity of BDE209 on the proliferation of human normal follicular epithelial cell line (Nthy-ori 3-1) and PTC-derived cell lines (TPC-1 and BCPAP). Wound and Transwell assays showed that BDE209 exacerbated the aggressiveness of PTC cells. BDE209 significantly promoted cell proliferation during the S and G2/M phases of the cell cycle. Mechanistically, BDE209 altered the thyroid system by acting as a competitive inhibitor of thyroid receptor beta (TRß) expression and function, which was further proven by public databases and RNA-seq bioinformation analysis. Taken together, these results demonstrated that BDE209 has chronic toxicity and potential tumourigenic effects on the thyroid by inhibiting TRß.

Derivation of thyroid progenitors from human induced pluripotent stem cells

Abstract Objective Despite the availability of synthetic thyroid hormone for therapeutic use, a significant number of patients with hypothyroidism do not feel well on replacement doses of thyroid hormones suggesting that better-individualized therapy is needed. For this reason, hypothyroidism resulting from congenital lack of functional thyrocytes, surgical tissue removal, or gland ablation, represents a particularly attractive endocrine disease target that may be conceivably cured by transplantation of long-lived functional thyroid progenitors or mature follicular epithelial cells. Methods To generate thyroid follicular progenitors from human induced pluripotent stem cells (hiPSCs), we sought to develop a directed differentiation approach by activating or inhibiting endogenous developmental signaling pathways previously identified in the mouse. To facilitate tracking and purification of candidate human thyroid progenitors, we engineered a hiPSC-line carrying a tdTomato reporter targeted to the PAX8 locus and a GFP reporter targeted to the NKX2-1 locus. Results We adapted our published in vitro differentiation protocol previously used to differentiate mouse PSCs into thyroid progenitors and observed tdTomato/GFP co-expressing cells first emerging from our hiPSC line by day 12 of culture and persisting for at least 2 months of further culture in thyroid maturation media, supplemented with TSH. Thus, we profiled all cells deriving from hiPSCs by single-cell RNA sequencing >6,000 cells captured on days 12 and 29 of in vitro differentiation. At day 12, tdTomato/GFP co-expression was observed in 12% of all cells and these cells appeared to be early thyroid follicular progenitors as they uniquely co-expressed the tetrad of thyroid lineage selective transcription factors, NKX2-1, PAX8, FOXE1, and HHEX. By day 29 tdTomato+/GFP+ cells represented 69% of all cells and had upregulated TG, TSHR, NIS and TPO expression in addition to the previously described four thyroid lineage markers, suggesting time-dependent differentiation and maturation of thyroid follicular epithelial cells. Conclusion Thus, we have employed a novel hiPSC line to optimize a protocol able to generate human thyroid progenitors and mature follicular epithelial cells, representing a purifiable source of human thyroid lineage cells whose functional and thyroid reconstituting potential can be tested in vivo in animal models of hypothyroidism.

Effects of cadmium exposure on thyroid gland and endochondral ossification in Rana zhenhaiensis

Discovery of elevated concentrations of cadmium in the natural environment has increased awareness because of their potential threats. Amphibians are negatively affected due to their moderate sensitivity to cadmium. Here, we conduct acute and subchronic toxicity tests to examine whether, and to what extent, cadmium exposure disturbs metamorphosis, growth, and kinetic ability of Rana zhenhaiensis. We set different concentration treatment groups for the subchronic toxicity test (0, 10, 40, 160 μg Cd L−1). Our findings demonstrate that cadmium exposure reduces growth parameters and the cumulative metamorphosis percent of R. zhenhaiensis. Decreases in follicular size and follicular epithelial cell thickness of thyroid gland are found in the treatment group. Further, subchronic exposure to cadmium decreases ossification ratio of hindlimbs in all treatment. Also, adverse effects of cadmium exposure on aquatic tadpoles can result in the reduced physical parameters and weak jumping ability in adult frogs. In this sense, our study suggests that cadmium adversely influences body condition and metamorphosis of R. zhenhaiensis, damages thyroid gland and impairs endochondral ossification. Meanwhile, we speculated that cadmium-damaged thyroid hormones inhibit skeletal development, resulting in the poor jumping ability, which probably leads to reduced survival of R. zhenhaiensis.

Poorly differentiated thyroid carcinoma: a clinician's perspective.

Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid carcinoma originating from follicular epithelial cells. No explicit consensus can be achieved to date due to sparse clinical data, potentially compromising the outcomes of patients. In this comprehensive review from a clinician’s perspective, the epidemiology and prognosis are described, diagnosis based on manifestations, pathology, and medical imaging are discussed, and both traditional and emerging therapeutics are addressed as well. Turin consensus remains the mainstay diagnostic criteria for PDTC, and individualized assessments are decisive for treatment option. The prognosis is optimal if complete resection is performed at early stage but dismal in nearly half of patients with locally advanced and/or distant metastatic diseases, in which adjuvant therapies such as 131I therapy, external beam radiation therapy, and chemotherapy should be incorporated. Emerging therapeutics including molecular targeted therapy, differentiation therapy, and immunotherapy deserve further investigations to improve the prognosis of PDTC patients with advanced disease.

TheLiTE™: A Screening Platform to Identify Compounds that Reinforce Tight Junctions.

Tight junctions (TJ) are formed by transmembrane and intracellular proteins that seal the intercellular space and control selective permeability of epithelia. Integrity of the epithelial barrier is central to tissue homeostasis and barrier dysfunction has been linked to many pathological conditions. TJ support the maintenance of cell polarity through interactions with the Par complex (Cdc42-Par-6-Par-3-aPKC) in which Par-6 is an adaptor and links the proteins of the complex together. Studies have shown that Par-6 overexpression delays the assembly of TJ proteins suggesting that Par-6 negatively regulates TJ assembly. Because restoring barrier integrity is of key therapeutic and prophylactic value, we focus on finding compounds that have epithelial barrier reinforcement properties; we developed a screening platform (theLiTE™) to identify compounds that modulate Par-6 expression in follicular epithelial cells from Par-6-GFP Drosophila melanogaster egg chambers. Hits identified were then tested whether they improve epithelial barrier function, using measurements of transepithelial electrical resistance (TEER) or dye efflux to evaluate paracellular permeability. We tested 2,400 compounds, found in total 10 hits. Here we present data on six of them: the first four hits allowed us to sequentially build confidence in theLiTE™ and two compounds that were shortlisted for further development (myricetin and quercetin). We selected quercetin due to its clinical and scientific validation as a compound that regulates TJ; food supplement formulated on the basis of this discovery is currently undergoing clinical evaluation in gastroesophageal reflux disease (GERD) sufferers.

Pathology and Occurrence of Swine Pox in an Organized Swine Farm-Bareilly, Uttar Pradesh

A swine pox outbreak occurred in April 2017 at Bareilly, Uttar Pradesh based organized swine production farm with roughly 200 animals. Twelve growing crossbred (Large White Yorkshire and local) animals were found to have skin lesions, which varied in size and were found on the face, ears, periorbital region, legs, ventral abdomen, inguinal region, dorsal and lateral sides, etc. The lesions ranged from papules and pustules that turned into crusty lesions that looked like brownish scabs. Microscopically, infected cells showed ballooning degeneration of epidermal and follicular epithelial cells, mild epidermal hyperplasia, nuclear vacuolation, and margination of chromatin. Multiple typical eosinophilic intracytoplasmic inclusion bodies were also seen in the epidermal cells, and inflammatory cells were infiltrating the dermis.

TRAb-IgM induced by Epstein-Barr virus reactivation does not have thyroid stimulating effect, but injures the thyroid follicular epithelial cells and releases thyroid antigens

TRAb-IgM induced by Epstein-Barr virus reactivation does not have thyroid stimulating effect, but injures the thyroid follicular epithelial cells and releases thyroid antigens

SJMHE1 protects against excessive iodine-induced pyroptosis in human thyroid follicular epithelial cells through a toll-like receptor 2-dependent pathway.

To elucidate the effect of Schistosoma japonicum peptide (SJMHE1) on pyroptosis in thyroid follicular epithelial cells (TFCs) induced by excessive iodine and the potential mechanism, the effects of SJMHE1 were investigated in NaI-treated Nthy-ori 3-1 cells; and the involvement of the ROS/MAPK/NF-κB signaling pathways in these effects was evaluated by employing CCK-8 assays, flow cytometry, ELISA, and Western blotting experiments. We found that SJMHE1 significantly reduced NLRP3, N-terminus of gasdermin D (GSDMD-N) and cleaved caspase-1 (C-caspase-1) expression, and decreased IL-1β secretion in TFCs. SJMHE1 also markedly reduced reactive oxygen species (ROS) production, and decreased the phosphorylation levels of MAPK and NF-κB pathway members. Moreover, blocking of the Toll-like receptor 2 significantly impaired SJMHE1-mediated protection from excessive iodine-induced pyroptosis in TFCs. Therefore, our results suggested a protective role of SJMHE1 in excessive iodine-induced pyroptosis in TFCs, which might be attributed to its suppression for ROS/MAPK/NF-κB signaling pathway by binding of SJMHE1 with TLR2.