Metabolic Reprogramming in Thyroid Cancer Ju, Sang-Hyeon; Song, Minchul; Lim, Joung Youl ...
Endocrinology and metabolism,
06/2024, Letnik:
39, Številka:
3
Journal Article
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Thyroid cancer is a common endocrine malignancy with increasing incidence globally. Although most cases can be treated effectively, some cases are more aggressive and have a higher risk of mortality. ...Inhibiting RET and BRAF kinases has emerged as a potential therapeutic strategy for the treatment of thyroid cancer, particularly in cases of advanced or aggressive disease. However, the development of resistance mechanisms may limit the efficacy of these kinase inhibitors. Therefore, developing precise strategies to target thyroid cancer cell metabolism and overcome resistance is a critical area of research for advancing thyroid cancer treatment. In the field of cancer therapeutics, researchers have explored combinatorial strategies involving dual metabolic inhibition and metabolic inhibitors in combination with targeted therapy, chemotherapy, and immunotherapy to overcome the challenge of metabolic plasticity. This review highlights the need for new therapeutic approaches for thyroid cancer and discusses promising metabolic inhibitors targeting thyroid cancer. It also discusses the challenges posed by metabolic plasticity in the development of effective strategies for targeting cancer cell metabolism and explores the potential advantages of combined metabolic targeting.
This article presents a novel monolithic transformer (TF) structure, which is designed to improve TF efficiency by enhancing the quality factor of the metal trace. When the number of thick metal ...layers is limited in semiconductor technology, it is necessary to use thin metals that have lower quality factors to form the TF coil, which degrades TF efficiency. To overcome this limitation, supplementary walls of metal and a via are connected along both sides of the thin metal to form a U‐shaped metal trace, which in turn improves the quality factor and TF efficiency. The proposed structure does not require additional metal layers, other than the metal layers used in the TF configuration. Thus, the proposed structure is widely applicable to all semiconductor technologies, including those that provide only a small number of metal layers. To assess and validate this proposed structure, we fabricated a set of TFs including conventional structures using gallium arsenide (GaAs) technology, which is the most widely used technology in mobile power amplifier (PA) fabrication. The proposed structure was successfully demonstrated to effectively improve the TF efficiency by as much as 8.6% and 6.5% in comparison to a conventional planar structure and a stacked structure, respectively.
Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to β-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell ...senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers.
In this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication.
The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (T
) significantly decreased after intervention in the rosuvastatin/ezetimibe group (-4.5 ± 14.1% and -1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193,
=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538,
=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (
=0.314) or LDL-C (
=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (
=0.011), but not in the rosuvastatin group (
=0.339).
We observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.
The infarcted heart undergoes irreversible pathological remodeling after reperfusion involving left ventricle dilation and excessive inflammatory reactions in the infarcted heart, frequently leading ...to fatal functional damage. Extensive attempts have been made to attenuate pathological remodeling in infarcted hearts using cardiac patches and anti-inflammatory drug delivery. In this study, we developed a paintable and adhesive hydrogel patch using dextran-aldehyde (dex-ald) and gelatin, incorporating the anti-inflammatory protein, ANGPTL4, into the hydrogel for sustained release directly to the infarcted heart to alleviate inflammation. We optimized the material composition, including polymer concentration and molecular weight, to achieve a paintable, adhesive hydrogel using 10% gelatin and 5% dex-ald, which displayed in-situ gel formation within 135 s, cardiac tissue-like modulus (40.5 kPa), suitable tissue adhesiveness (4.3 kPa), and excellent mechanical stability. ANGPTL4 was continuously released from the gelatin/dex-ald hydrogel without substantial burst release. The gelatin/dex-ald hydrogel could be conveniently painted onto the beating heart and degraded in vivo. Moreover, in vivo studies using animal models of acute myocardial infarction revealed that our hydrogel cardiac patch containing ANGPTL4 significantly improved heart tissue repair, evaluated by echocardiography and histological evaluation. The heart tissues treated with ANGPTL4-loaded hydrogel patches exhibited increased vascularization, reduced inflammatory macrophages, and structural maturation of cardiac cells. Our novel hydrogel system, which allows for facile paintability, appropriate tissue adhesiveness, and sustained release of anti-inflammatory drugs, will serve as an effective platform for the repair of various tissues, including heart, muscle, and cartilage.
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•A paintable and adhesive hydrogel patch was developed using dextran-aldehyde (dex-ald) and gelatin.•The gelatin/dex-ald hydrogel exhibits biodegradability, tissue adhesiveness, and cardiac tissue-like elasticity.•The gelatin/dex-ald hydrogel with the anti-inflammatory protein, ANGPTL4, continuously released to the infarcted heart.•The drug-loaded hydrogel cardiac patch significantly improved heart regeneration.
Skin fibrosis occurs in a variety of human diseases but the current anti-fibrosis treatments are not sufficient. One major cause of fibrotic diseases shared across diverse organ fibrosis is ...uncontrolled overexpression of the connective tissue growth factor (CTGF, also known as CCN2). Here, we examine the anti-fibrotic activity of RNAi therapy utilizing siRNA against CTGF with a new drug delivery system (DDS), 'DegradaBALL', which is based on porous nanoparticles, for durable CTGF gene silencing. DegradaBALL is a modular DDS having many favorable properties for RNA delivery such as effective intracellular uptake, convenient drug loading, biocompatibility, sustained release profile and biodegradability. DegradaBALL loaded with siCTGF, named 'LEM-S401', showed highly durable and effective CTGF gene-silencing in TGF-β induced lung fibrosis and skin fibrosis model cells, A549 and HaCaT, respectively. In addition, LEM-S401 induced knockdown of collagen types I and III, which are excess extracellular matrix components in fibrotic skin in addition to CTGF in the mouse wound healing model. Most importantly, we showed that LEM-S401 effectively inhibited the formation of hypertrophic scars in wound-associated dermal fibrosis mouse models, during both the epidermis recovery and tissue remodeling process. Our findings suggest that LEM-S401 could be a highly potent therapeutic option for skin fibrotic diseases.
LEM-S401, siRNA against CTGF with DegradaBALL, could be a highly potent RNAi therapeutics for skin fibrotic diseases by inducing long lasting knockdown of CTGF with lower dosage and fewer injections.
Rhodium nanoparticles are promising transition metal nanocatalysts for electrochemical and synthetic organic chemistry applications. However, notwithstanding their potential, to date, Rh ...nanoparticles have not been utilized for biological applications; there has been no cytotoxicity study of Rh reported in the literature. In this regard, the absence of a facile and controllable synthetic strategy of Rh nanostructures with various sizes and morphologies might be responsible for the lack of progress in this field. Herein, we have developed a synthetic strategy for Rh nanostructures with controllable morphology through an inverse-directional galvanic replacement reaction. Three types of Rh-based nanostructuresnanoshells, nanoframes, and porous nanoplateswere successfully synthesized. A plausible synthetic mechanism based on thermodynamic considerations has also been proposed. The cytotoxicity, surface functionalization, and photothermal therapeutic effect of manufactured Rh nanostructures were systematically investigated to reveal their potential for in vitro and in vivo biological applications. Considering the comparable behavior of porous Rh nanoplates to that of gold nanostructures that are widely used in nanomedicine, the present study introduces Rh-based nanostructures into the field of biological research.
Shellfish are exoskeleton-bearing aquatic invertebrates that consume various organic and inorganic substances floating in seawater through filter feeding. Heavy metals are known as absorbed and ...accumulated in seawater. Some of the toxic heavy metals are highly accumulated in seawater, and exposure to them can cause a variety of risks to the human body. Since Koreans like to eat seafood, they are more likely to be exposed to contaminated seafood with heavy metals. In this study, nine types of heavy metals were analyzed on ten different shellfish species in the coastal area of South Korea. The risk assessment was also done on shellfish in which heavy metals were detected. Zinc (Zn) and copper (Cu) were identified at an average of 56.7 mg/kg (6.70 to 466 mg/kg) and 13.2 mg/kg (0.064 to 143 mg/kg), respectively. Lead (Pb) average of 0.208 mg/kg (0.000750 to 1.02 mg/kg), cadmium (Cd) average of 0.454 mg/kg (0.0388 to 1.56 mg/ kg) and mercury (Hg) average of 0.0266 mg/kg (0.00548 to 0.174 mg/kg) were identified. Additionally, arsenic (As), chromium (Cr), nickel (Ni), and silver (Ag) were also identified as average concentrations of 4.02 (0.460 to 15.0 mg/kg), 0.167 (< limit of quantification LOQ to 0.820 mg/kg), 0.281 (< LOQ to 1.46 mg/kg), and 0.158 mg/kg (< LOQ to 1.15 mg/kg). The result indicates that the monitoring results of heavy metals in most shellfish satisfied the Korean standard. However, Pb and Cd have exceeded some foreign standards, such as the United States and the EU. The permissible human exposure calculated using the heavy metal intake and detection amount was lower than the Joint FAO/WHO Expert Committee on Food Additives human safety standard, and the risk of heavy metals from shellfish consumption was at an acceptable level.
In this paper, we study cognitive radio (CR) networks that consist of multiple secondary TV band device (TVBD) station-user pairs and one primary digital TV (DTV) station-user pair, where each ...terminal has a single antenna. Specifically, we consider spectrum sharing (SS)-based secondary TVBD networks to effectively utilize limited spectrum resources in the presence of cochannel primary DTV interference. We first present an opportunistic single secondary network selection scheme to maximize the mutual information over all secondary TVBD networks under the constraint of the availability of the primary DTV service. Then, the performance bound of CR networks with the secondary network selection is obtained through the derivation of an exact and closed-form outage probability. It is shown that the derived outage probability is given as a function of transmission power, channel coefficients, and target rates of both the primary DTV network and the secondary TVBD networks.
A major challenge for developing rechargeable Mg-ion batteries (MIB) is the lack of suitable electrolytes. We report herein dialkyl sulfones as non-Grignard and Lewis acid-free MIB electrolytes. In ...particular, a dipropyl sulfone (DPSO)/tetrahydrofuran (THF) (1/1, v/v) solution with MgCl2 salt exhibits high ionic conductivity (1.1 mS cm–1 at 30 °C), Mg cycling efficiency (>90%), and anodic stability (ca. 3.0 V vs Mg). As evidenced by single crystal X-ray diffraction analysis, a novel Mg(DPSO)62+ cation complex balanced by two MgCl3(THF)− anions is identified in the DPSO/THF solution. The DPSO/THF electrolyte also enables excellent cycle performance (>300 cycles) of a Chevrel phase Mo6S8 cathode and displays a decent compatibility with an organic cathode (3,4,9,10-perylenetetracarboxylic dianhydride, PTCDA). Along with the superior electrochemical properties of the DPSO/THF electrolyte, its innate chemical stability and eco-friendly nature make it a promising MIB electrolyte.
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