Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Immunol Rev ; 308(1): 123-148, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35373371

RESUMEN

Pregnant women infected with pathogenic respiratory viruses, such as influenza A viruses (IAV) and coronaviruses, are at higher risk for mortality, hospitalization, preterm birth, and stillbirth. Several factors are likely to contribute to the susceptibility of pregnant individuals to severe lung disease including changes in pulmonary physiology, immune defenses, and effector functions of some immune cells. Pregnancy is also a physiologic state characterized by higher levels of multiple hormones that may impact the effector functions of immune cells, such as progesterone, estrogen, human chorionic gonadotropin, prolactin, and relaxin. Each of these hormones acts to support a tolerogenic immune state of pregnancy, which helps prevent fetal rejection, but may also contribute to an impaired antiviral response. In this review, we address the unique role of adaptive and innate immune cells in the control of pathogenic respiratory viruses and how pregnancy and specific hormones can impact their effector actions. We highlight viruses with sex-specific differences in infection outcomes and why pregnancy hormones may contribute to fetal protection but aid the virus at the expense of the mother's health.


Asunto(s)
Infecciones por Coronavirus , Virus de la Influenza A , Nacimiento Prematuro , Femenino , Hormonas , Humanos , Recién Nacido , Pulmón , Masculino , Embarazo
2.
Angew Chem Int Ed Engl ; 63(11): e202319605, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38217331

RESUMEN

Modifying redox potential of substrates and intermediates to balance pairs of redox steps are important stages for multistep photosynthesis but faced marked challenges. Through co-clathration of iridium photosensitizer and imine substrate within one packet of a metal-organic capsule to shift the redox potentials of substrate, herein, we reported a multiphoton enzymatic strategy for the generation of heterocycles by intramolecular C-X hydrogen evolution cross-couplings. The cage facilitated a pre-equilibrium substrate-involving clathrate that cathodic shifts the oxidation potential of the substrate-dye-host ternary complex and configuration inversion of substrate via spatial constraints in the confined space. The new two photon excitation strategy enabled the precise control of the multistep electron transfer between each pair (photosensitizer, substrate and the capsule), endowing the catalytic system proceeding smoothly with an enzymatic fashion. Three kinds of 2-subsituted (-OH, -NH2 , and -SH) imines and N-aryl enamines all give the corresponding cyclization products efficiently under visible light irradiation, demonstrating the promising of the microenvironment driven thermodynamic activation in the host-dye-substrate ternary for synergistic combination of multistep photocatalytic transformations.

3.
BMC Endocr Disord ; 23(1): 113, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37208644

RESUMEN

BACKGROUND: Recurrent and metastatic thyroid cancer is more invasive and can transform to dedifferentiated thyroid cancer, thus leading to a severe decline in the 10-year survival. The thyroid-stimulating hormone receptor (TSHR) plays an important role in differentiation process. We aim to find a therapeutic target in redifferentiation strategies for thyroid cancer. METHODS: Our study integrated the differentially expressed genes acquired from the Gene Expression Omnibus database by comparing TSHR expression levels in the Cancer Genome Atlas database. We conducted functional enrichment analysis and verified the expression of these genes by RT-PCR in 68 pairs of thyroid tumor and paratumor tissues. Artificial intelligence-enabled virtual screening was combined with the VirtualFlow platform for deep docking. RESULTS: We identified five genes (KCNJ16, SLC26A4, TG, TPO, and SYT1) as potential cancer treatment targets. TSHR and KCNJ16 were downregulated in the thyroid tumor tissues, compared with paired normal tissues. In addition, KCNJ16 was lower in the vascular/capsular invasion group. Enrichment analyses revealed that KCNJ16 may play a significant role in cell growth and differentiation. The inward rectifier potassium channel 5.1 (Kir5.1, encoded by KCNJ16) emerged as an interesting target in thyroid cancer. Artificial intelligence-facilitated molecular docking identified Z2087256678_2, Z2211139111_1, Z2211139111_2, and PV-000592319198_1 (-7.3 kcal/mol) as the most potent commercially available molecular targeting Kir5.1. CONCLUSION: This study may provide greater insights into the differentiation features associated with TSHR expression in thyroid cancer, and Kir5.1 may be a potential therapeutic target in the redifferentiation strategies for recurrent and metastatic thyroid cancer.


Asunto(s)
Canales de Potasio de Rectificación Interna , Neoplasias de la Tiroides , Humanos , Canales de Potasio de Rectificación Interna/genética , Simulación del Acoplamiento Molecular , Inteligencia Artificial , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Receptores de Tirotropina/metabolismo , Descubrimiento de Drogas
4.
J Environ Manage ; 211: 63-72, 2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29408084

RESUMEN

This study employed Box-Behnken design and response surface methodology to optimize activation parameters for the production of activated petroleum coke (APC) adsorbent from petroleum coke (PC) to achieve highest adsorption capacity for three model naphthenic acids. Activated petroleum coke (APC) adsorbent with a BET surface area of 1726 m2/g and total pore volume of 0.85 cc/g was produced at the optimum activation conditions (KOH/coke mass ratio) of 3.0, activation temperature 790 °C, and activation time 3.47 h). Effects of the activation parameters on the adsorption pefromances (adsortion capaciy and kinetics) were investigated. With the APC obtained at the optimum activation condition, the maximum adsorption capacity of 451, 362, and 320 (mg/g) was achieved for 2-naphthoic acid, diphenylacetic acid and cyclohexanepentanoic acid (CP), respectively. Although, generally APC adsorbents with a higher specific surface area and pore volume provide better adsorption capacity, the textural properties (surface areas and pore volume) are not the only parameters determining the APC adsorbents' adsorption capacity. Other parameters such as surface functionalities play effective roles on the adsorption capacity of the produced APC adsorbents for NAs. The KOH activation process, in particular the acid washing step, distinctly reduced the sulfur and metals contents in the raw PC, decreasing the leaching potential of metals from APC adsorbents during adsorption.


Asunto(s)
Ácidos Carboxílicos/aislamiento & purificación , Coque , Contaminantes Ambientales/aislamiento & purificación , Petróleo , Adsorción
5.
Pain Pract ; 18(5): 597-610, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29044905

RESUMEN

OBJECTIVE: This study aims to evaluate the efficacy and safety of parecoxib injection in pain relief after laparoscopic surgeries. METHODS: A comprehensive literature search based on 4 online databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane Collaboration's tool was applied to evaluate the methodological quality of included studies. A standardized data collection sheet was designed to extract data from included studies. RevMan version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark) was selected to perform meta-analysis. RESULTS: A total of 1,060 participants who were scheduled for gynecological laparoscopic surgery or laparoscopic cholecystectomy (LC) were enrolled in 12 selected RCTs. The methodological qualities of the studies were evaluated as moderate to high. The combined data showed that perioperative parecoxib injection could significantly reduce the proportion of patients who required adjuvant pain relieve after laparoscopic surgeries. Significantly lower pain scores in the parecoxib groups were observed, which proved that preoperative or intraoperative injection of 40 mg parecoxib was more effective than placebo for immediate pain relief after LC. But preoperative injection of 40 mg parecoxib showed no improvement compared with placebo in the management of immediate pain following gynecological laparoscopic surgery. The occurrence of adverse events showed no differences between perioperative parecoxib administration and placebo control. CONCLUSION: Perioperative parecoxib administration was effective in reducing the proportion of patients who required adjuvant pain relief after laparoscopic surgeries without significant adverse events compared with placebo. The effect of parecoxib injection on immediate pain relief remains in question. Future RCTs with larger sample sizes are encouraged.


Asunto(s)
Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Isoxazoles/uso terapéutico , Laparoscopía/efectos adversos , Manejo del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dinamarca , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
6.
Nutrients ; 16(5)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38474707

RESUMEN

Processed meat products are one of the most consumed pre-packaged foods in China. They are also group-1 carcinogens, whose consumption has proved to be positively associated with the risk of noncommunicable diseases (NCDs). The purpose of this study is to analyze the nutrient content on the food label of processed meat products based on the China Standardized Database for the Composition of Pre-packaged Food and the National Open Database of the UK and France. The Chilean front-of-pack warning label (FOPWL) and the Chinese Healthier Choice Logo were used to compare the nutrient content of processed meat products from the three countries. It was found that cured meat products have the highest median energy (483 kcal/100 g), total fat content (38.7 g/100 g), and sodium content (2076 mg/100 g) and dried meat products have the highest median protein content (30.2 g/100 g) and carbohydrate content (38.2 g/100 g). In addition, there were significant differences in energy content and contents of total fat, protein, and carbohydrate across different products of the three countries (p < 0.001). A large number of processed meat products currently collected did not meet the criteria of the Chilean FOPWL and the Chinese Healthier Choice Logo. This study provided information on the healthiness of Chinese processed meat products and provided data for improving food formulations for different categories of processed meat products.


Asunto(s)
Productos de la Carne , Nutrientes , Etiquetado de Alimentos , Valor Nutritivo , Carbohidratos
7.
Cancer Lett ; 597: 216995, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38851313

RESUMEN

Globally, breast cancer (BC) is the predominant malignancy with a significant death rate due to metastasis. The epithelial-mesenchymal transition (EMT) is a fundamental initiator for metastatic progression. Through advanced computational strategies, TCF19 was identified as a critical EMT-associated gene with diagnostic and prognostic significance in BC, based on a novel EMT score. Molecular details and the pro-EMT impact of the TCF19/miR-199a-5p/SP1/LOXL2 axis were explored in BC cell lines through in vitro validations, and the oncogenic and metastatic potential of TCF19 and LOXL2 were investigated using subcutaneous and tail-vein models. Additionally, BC-specific enrichment of TCF19 and LOXL2 was measured using a distribution landscape driven by diverse genomic analysis techniques. Molecular pathways revealed that TCF19-induced LOXL2 amplification facilitated migratory, invasive, and EMT activities of BC cells in vitro, and promoted the growth and metastatic establishment of xenografts in vivo. TCF19 decreases the expression of miR-199a-5p and alters the nuclear dynamics of SP1, modulating SP1's affinity for the LOXL2 promoter, leading to increased LOXL2 expression and more malignant characteristics in BC cells. These findings unveil a novel EMT-inducing pathway, the TCF19/miR-199a-5P/SP1/LOXL2 axis, highlighting the pivotal role of TCF19 and suggesting potential for novel therapeutic approaches for more focused BC interventions.


Asunto(s)
Aminoácido Oxidorreductasas , Neoplasias de la Mama , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , MicroARNs , Factor de Transcripción Sp1 , Humanos , Transición Epitelial-Mesenquimal/genética , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Factor de Transcripción Sp1/metabolismo , Factor de Transcripción Sp1/genética , Animales , Aminoácido Oxidorreductasas/genética , Aminoácido Oxidorreductasas/metabolismo , Ratones , Línea Celular Tumoral , Movimiento Celular , Metástasis de la Neoplasia , Transducción de Señal , Ratones Desnudos
8.
Cell Prolif ; 57(8): e13634, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38494923

RESUMEN

Differentiation of human embryonic stem cells (hESCs) into human embryonic stem cells-derived parathyroid-like cells (hESC-PT) has clinical significance in providing new therapies for congenital and acquired parathyroid insufficiency conditions. However, a highly reproducible, well-documented method for parathyroid differentiation remains unavailable. By imitating the natural process of parathyroid embryonic development, we proposed a new hypothesis about the in vitro differentiation of parathyroid-like cells. Transcriptome, differentiation marker protein detection and parathyroid hormone (PTH) secretion assays were performed after the completion of differentiation. To optimize the differentiation protocol and further improve the differentiation rate, we designed glial cells missing transcription factor 2 (GCM2) overexpression lentivirus transfection assays and constructed hESCs-derived parathyroid organoids. The new protocol enabled hESCs to differentiate into hESC-PT. HESC-PT cells expressed PTH, GCM2 and CaSR proteins, low extracellular calcium culture could stimulate hESC-PT cells to secrete PTH. hESC-PT cells overexpressing GCM2 protein secreted PTH earlier than their counterpart hESC-PT cells. Compared with the two-dimensional cell culture environment, hESCs-derived parathyroid organoids secreted more PTH. Both GCM2 lentiviral transfection and three-dimensional cultures could make hESC-PT cells functionally close to human parathyroid cells. Our study demonstrated that hESCs could differentiate into hESC-PT in vitro, which paves the road for applying the technology to treat hypoparathyroidism and introduces new approaches in the field of regenerative medicine.


Asunto(s)
Diferenciación Celular , Células Madre Embrionarias Humanas , Organoides , Glándulas Paratiroides , Hormona Paratiroidea , Factores de Transcripción , Humanos , Organoides/citología , Organoides/metabolismo , Células Madre Embrionarias Humanas/citología , Células Madre Embrionarias Humanas/metabolismo , Glándulas Paratiroides/citología , Glándulas Paratiroides/metabolismo , Hormona Paratiroidea/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Células Cultivadas , Técnicas de Cultivo de Célula/métodos , Proteínas Nucleares
9.
J Int Med Res ; 52(7): 3000605241259669, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39053452

RESUMEN

Parathyroid carcinoma (PC) is a rare and aggressive endocrine malignancy with limited treatment options. Current treatments such as chemotherapy and radiotherapy have demonstrated limited efficacy. Here, we report the case of a male patient who presented with symptoms including polydipsia, polyuria, and joint pain. Further examination revealed a neck lump, hypercalcemia, and hyperparathyroidism, leading to a diagnosis of PC after en bloc surgery. Seven months later, the patient developed local recurrence and lung metastases, which were resected via left lateral neck dissection and thoracoscopic wedge resection. A 422-gene panel test revealed the presence of epidermal growth factor receptor (EGFR) p.L858R (c. T2573G) mutation, which may sensitize the EGFR-tyrosine kinase inhibitor response, and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) p.E545KV (c. G1633A) mutation. After multidisciplinary treatment discussions, the patient was treated with the multi-target tyrosine kinase inhibitor, anlotinib, resulting in survival benefits for 19 months. This case highlights the potential of targeted therapy in terms of long-term survival in patients with distant metastatic PC, as well as the importance of precision therapy guided by genome sequencing to identify potential therapeutic targets.


Asunto(s)
Receptores ErbB , Mutación , Neoplasias de las Paratiroides , Humanos , Masculino , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Neoplasias de las Paratiroides/genética , Neoplasias de las Paratiroides/patología , Persona de Mediana Edad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología
10.
Heliyon ; 9(7): e17821, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37455957

RESUMEN

Given the problem of considerable livestock and poultry pollution and the differentiation of the regional agricultural layout in China, the combination of planting and breeding (CPB) forms an agricultural co-agglomeration to recycle manure waste into croplands to reduce livestock and poultry pollution. This study aims to evaluate CPB co-agglomeration and empirically examine its effects on livestock and poultry pollution. Based on provincial data from 1997 to 2020 in China, this study constructed three indicators to evaluate CPB co-agglomeration, summarized its temporal and spatial characteristics, and conducted a spatial analysis using the Spatial Lag Model (SLM) to empirically investigate its effect on livestock and poultry pollution. The results showed that: first, from 1997 to 2020, the overall level of CPB co-agglomeration in China declined and the region with higher CPB co-agglomeration level transferred from the central provinces to the west provinces. Second, livestock and poultry pollution in most provinces had significantly positive spatial correlations with adjacent regions. The co-agglomeration of CPB had a significantly positive effect on reducing livestock and poultry pollution; however, the effect had no significant spatial spillover. Third, the breeding industry agglomeration and the moderate expansion of breeding industry scale significantly reduced pollution. These findings provide a reference for reducing livestock and poultry pollution by promoting CPB co-agglomeration to establish a waste recycling system. Optimizing the layout of the planting and breeding industry helps achieve the goal of long-term sustainable development of the breeding industry.

11.
Dalton Trans ; 52(26): 8857-8863, 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37350344

RESUMEN

In this research, we synthesized CdS nanoparticle-doped metal-organic frameworks (CdS@DUT-52) with different contents using a solvothermal method. CdS@DUT-52 possesses strong light absorption ability and effective electron-hole separation properties, which was proved by performing UV-vis spectroscopy and photoelectrochemical testing. It was used to trigger the photooxidation of amines, sulfides, and alcohols to produce the corresponding imines, sulfoxides, and aldehydes in the presence of air or oxygen, exhibiting considerable yields of products under visible light irradiation compared with a single component.

12.
Chem Commun (Camb) ; 59(75): 11220-11223, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37655546

RESUMEN

By incorporating tetrakis(4-carboxyphenyl)porphyrin and bis(3,5-dicarboxyphenyl)pyridine into one single metal-organic framework (MOF), a multifunctional mixed-ligand Zn-MIX with large pores was obtained. Under visible-light irradiation, Zn-MIX exhibits high photocatalytic activity for the oxidation of amines and sulfides.

13.
Nutrients ; 15(23)2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-38068721

RESUMEN

Sodium intake from pre-packaged foods is increasing in China and is well above the WHO recommendation of 5 g per day. The purpose of this study is to analyze the sodium content of pre-packaged foods collected by the National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention (NINH, China CDC) in 20 provinces of China from 2017 to 2022. The proportion of pre-packaged foods that meet or exceed the low-sodium, medium-sodium, and high-sodium classifications were analyzed. The proportion of pre-packaged foods that meet and do not meet the WHO global sodium benchmarks and the difference in sodium content between these foods was also calculated. High-sodium foods include sauces, dips, and dressings (3896 mg/100 g), convenience foods (1578 mg/100 g), processed fish products (1470 mg/100 g), processed meat products (1323 mg/100 g), processed poultry products (1240 mg/100 g), snack foods (750 mg/100 g), processed egg products (741 mg/100 g), and fine dried noodles (602 mg/100 g). A large number of pre-packaged foods currently collected in China have a sodium content above sodium benchmarks. This study provided data to support the assessment of sodium intake from pre-packaged foods in the Chinese population and the implementation of comprehensive salt reduction strategies.


Asunto(s)
Sodio en la Dieta , Sodio , Sodio/análisis , Cloruro de Sodio Dietético , Etiquetado de Alimentos , Comida Rápida , Análisis de los Alimentos
14.
Neurosci Biobehav Rev ; 153: 105390, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37708918

RESUMEN

Infections and inflammation during pregnancy or early life can alter child neurodevelopment and increase the risk for structural brain abnormalities and mental health disorders. There is strong evidence that TORCH infections (i.e., Treponema pallidum, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes virus) alter fetal neurodevelopment across multiple developmental domains and contribute to motor and cognitive disabilities. However, the impact of a broader range of viral and bacterial infections on fetal development and disability is less well understood. We performed a literature review of human studies to identify gaps in the link between maternal infections, inflammation, and several neurodevelopmental domains. We found strong and moderate evidence respectively for a higher risk of motor and cognitive delays and disabilities in offspring exposed to a range of non-TORCH pathogens during fetal life. In contrast, there is little evidence for an increased risk of language and sensory disabilities. While guidelines for TORCH infection prevention during pregnancy are common, further consideration for prevention of non-TORCH infections during pregnancy for fetal neuroprotection may be warranted.


Asunto(s)
Trastornos Mentales , Complicaciones Infecciosas del Embarazo , Toxoplasma , Femenino , Humanos , Embarazo , Citomegalovirus , Inflamación , Complicaciones Infecciosas del Embarazo/microbiología , Recién Nacido
15.
Chem Commun (Camb) ; 58(6): 807-810, 2022 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-34928273

RESUMEN

Two dye-loaded metal-organic capsules constructed with different spatial sizes and functional groups simulated the enzymatic substrate activation for hydrogenation of nitroarenes with the kinetics obeying the Michaelis-Menten mechanism.

16.
Life Sci ; 309: 120993, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36162484

RESUMEN

HEADING AIMS: Breast cancer is one of the most common malignant tumors with a high incidence and leading cancer-related death in women worldwide. MiR-205 plays a crucial role in breast cancer initiation and progression. Here, we identified the relationship between miR-205 and lymphoid specific helicase and confirmed the significance of the miR-205/lymphoid specific helicase (miR-205/HELLS) axis. MATERIALS AND METHODS: Data from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were analyzed to investigate the expression level of miR-205 and HELLS in breast cancer. The TargetScan, Starbase and miRWalk databases were used to predict the candidate target genes of miR-205. Proliferation and migration abilities were examined using cell counting kit-8 assay, colony formation assays, transwell assay and wound-healing assay. Dual-luciferase reporter assay was utilized to confirm the binding of miR-205 and HELLS. Quantitative RT-PCR, western blot assays or immunohistochemistry were conducted to detect the expression level of genes in breast cancer cells or tissues. Mice xenograft models were constructed to explore the function of miR-205 and HELLS in vivo. KEY FINDINGS: Overexpressed miR-205 alleviated cancer cell proliferation and migration and influenced patients' prognosis by negatively regulating the HELLS gene. Consistently, animal experiments revealed that both overexpressing miR-205 and knocking down HELLS exhibited significant tumor growth inhibition in vivo. SIGNIFICANCE: Our study demonstrated that miR-205 targets HELLS to regulate tumor progression. MiR-205 and HELLS could be considered a novel diagnosis and therapeutic molecular marker of breast cancer.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Humanos , Femenino , Ratones , Animales , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Movimiento Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Oncogenes , Neoplasias de la Mama/patología , Ensayos Antitumor por Modelo de Xenoinjerto
17.
J Clin Endocrinol Metab ; 107(4): 1110-1126, 2022 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-34751400

RESUMEN

BACKGROUND: Chimeric antigen receptor T cells (CAR-Ts) have demonstrated remarkable efficacy in hematological cancers but have not yet translated in treating solid tumors. The significant hurdles limiting CAR-T therapy were from a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present TSH receptor (TSHR) as a putative target for CAR-T therapy of differentiated thyroid cancer (DTC). METHODS: We undertook a large-scale screen on thyroid cancer tissues and multiple internal organs through bioinformatical analysis and immunohistochemistry to date TSHR expression. Using 3 previously described monoclonal antibodies, we generated 3 third-generation CAR-Ts. We tested anti-TSHR CAR-T in vitro activity by T-cell function and killing assay. Then we tested preclinical therapeutical efficacy in a xenograft mouse model of DTC and analyzed mice's physical conditions and histological abnormalities to evaluate anti-TSHR CAR-T's safety. RESULTS: TSHR is highly and homogeneously expressed on 90.8% (138/152) of papillary thyroid cancer, 89.2% (33/37) of follicular thyroid cancer, 78.2% (18/23) of cervical lymph node metastases, and 86.7% of radioactive iodine resistance diseases. We developed 3 novel anti-TSHR CAR-Ts from monoclonal antibodies M22, K1-18, and K1-70; all 3 CAR-Ts mediate significant antitumor activity in vitro. Among these, we demonstrate that K1-70 CAR-T can have therapeutical efficacy in vivo, and no apparent toxicity has been observed. CONCLUSION: TSHR is a latent target antigen of CAR-T therapy for DTC. Anti-TSHR CAR-T could represent a therapeutic option for patients with locoregional relapsed or distant metastases of thyroid cancer and should be tested in carefully designed clinical trials.


Asunto(s)
Receptores Quiméricos de Antígenos , Neoplasias de la Tiroides , Animales , Anticuerpos Monoclonales/uso terapéutico , Humanos , Radioisótopos de Yodo , Ratones , Receptores Quiméricos de Antígenos/uso terapéutico , Receptores de Tirotropina/metabolismo , Linfocitos T , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia
18.
Endocrinology ; 163(4)2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35213720

RESUMEN

Papillary thyroid cancer (PTC) remains the most common endocrine malignancy, despite marked achieves in recent decades, and the mechanisms underlying the pathogenesis and progression for PTC are incompletely elucidated. Accumulating evidence show that γ-glutamylcyclotransferase (GGCT), an enzyme participating in glutathione homeostasis and is elevated in multiple types of tumors, represents an attractive therapeutic target. Using bioinformatics, immunohistochemistry, qRT-PCR, and Western blot assays, we found that GGCT expression was upregulated in PTC and correlated with more aggressive clinicopathological characteristics and worse prognosis. GGCT knockdown inhibited the growth and metastasis ability of PTC cells both in vitro and in vivo and reduced the expression of mesenchymal markers (N-cadherin, CD44, MMP2, and MMP9) while increasing epithelial marker (E-cadherin) in PTC cells. We confirmed binding of microRNA-205-5p (miR-205-5p) on the 3'-UTR regions of GGCT by dual-luciferase reporter assay and RNA-RNA pull-down assay. Delivery of miR-205-5p reversed the pro-malignant capacity of GGCT both in vitro and in vivo. Lastly, we found that GGCT interacted with and stabilized CD44 in PTC cells by co-immunoprecipitation and immunohistochemistry assays. Our findings illustrate a novel signaling pathway, miR-205-5p/GGCT/CD44, that involves in the carcinogenesis and progression of PTC. Development of miR-205-mimics or GGCT inhibitors as potential therapeutics for PTC may have remarkable applications.


Asunto(s)
MicroARNs , Neoplasias de la Tiroides , Regiones no Traducidas 3' , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/patología , gamma-Glutamilciclotransferasa/genética , gamma-Glutamilciclotransferasa/metabolismo
19.
Oncol Lett ; 21(5): 368, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33777194

RESUMEN

Long non-coding RNAs (lncRNAs) may participate in biological regulatory mechanisms of tumors. The aim of the present study was to uncover the molecular mechanism of the lncRNA LINC00052 in the tumorigenesis of breast cancer (BC). LINC00052 expression in BC tissues and cell lines was detected by reverse transcription-quantitative PCR analysis. The Cell Counting Kit-8, proliferation, Transwell and wound healing assays were employed to confirm the effect of LINC00052 on cell proliferation, migration and invasion. The cell localization of LINC00052 was estimated by cytoplasmic nuclear separation assay. Finally, the potential regulatory mechanism of LINC00052 in BC was detected by western blot analysis. The expression levels of LINC00052 were found to be significantly higher in BC tissues compared with those in the adjacent normal tissues. Downregulation of LINC00052 expression in vitro significantly suppressed the proliferation, migration and invasion of BC cells. LINC00052 was mainly expressed in the cytoplasm and was considered to bind with microRNA (miR)-145-5p based on various databases. Notably, the high expression levels of LINC00052 led to the low expression levels of miR-145-5p and high expression levels of TGF-ß receptor II (TGFBR2). In conclusion, the findings of the present study demonstrated that LINC00052 may sponge miR-145-5p to upregulate TGFBR2 expression in order to promote the proliferation and metastasis of BC cells. Therefore, LINC00052 may be an effective potential target for the diagnosis and treatment of BC.

20.
Cancer Manag Res ; 13: 2009-2024, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33658859

RESUMEN

PURPOSE: Breast cancer (BC), with varying histopathology, biology and response to systemic treatment, is the second leading cause of cancer-related mortality. Previous studies have inferred that the expression of mitochondrial ribosomal proteins (MRPs) is possibly related to the occurrence/progression of BC. MRPL13 might be one of the potential MRP candidates that are involved in BC tumorigenesis, but its role in BC has rarely been reported. The purpose of the current study was to evaluate the prognostic significance of MRPL13, as well as to explore its potential biological functions in BC. MATERIALS AND METHODS: A series of bioinformatic and statistical methods were adopted to assess the MRPL13 expression profile, its relationship with clinicopathological characteristics, copy number variation (CNV), impact on clinical outcomes and relevant functions. All the results are analysed by 1097 BC patients collected from The Cancer Genome Atlas (TCGA) dataset and 52 clinical samples for immunohistochemistry (IHC) assay. RESULTS: The results demonstrated that the expression of MRPL13 in BC tissues was remarkably elevated than that in normal breast tissues. In addition, the Kaplan-Meier curves and Cox model indicated that patients with high MRPL13 expression were connected to a worse prognosis, heralding the independent prognostic value of this protein in BC. Moreover, an enrichment analysis showed that MRPL13 was mainly involved in cell cycle/division-related, RNA processing (degradation/splicing), MYC targets and the MTORC1 pathways. In addition, RNA interference (RNAi)-mediated MRPL13 silencing remarkedly inhibited proliferation and migration as well as the expression of EMT-related genes of BC cells in vitro. Mechanistically, attenuation of MRPL13 significantly suppressed the phosphorylation of AKT and mTOR, which could be partially abolished by 740Y-P (a PI3K agonist). CONCLUSION: Our results provide evidence for the first time that increased MRPL13 expression correlates with adverse clinicopathological variables and unfavorable clinical outcomes of BC patients. Knockdown of MRPL13 restrains the proliferation and migration potential and EMT process of BC through inhibiting PI3K/AKT/mTOR signaling pathway.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA