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1.
Biomacromolecules ; 25(2): 838-852, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38164823

RESUMEN

Nowadays, wearable devices derived from flexible conductive hydrogels have attracted enormous attention. Nevertheless, the utilization of conductive hydrogels in practical applications under extreme conditions remains a significant challenge. Herein, a series of inorganic salt-ion-enhanced conductive hydrogels (HPE-LiCl) consisting of hydroxyethyl cellulose, hydroxyethyl acrylate, lithium chloride, and ethylene glycol/water binary solvent were fabricated via a facile one-pot method. Apart from outstanding self-adhesion, high stretchability, and remarkable fatigue resistance, the HPE-LiCl hydrogels possessed especially excellent antifreezing and long-lasting moisture performances, which could maintain satisfactory flexibility and electric conductivity over extended periods of time, even in challenging conditions such as extremely low temperatures (as low as -40 °C) and high temperatures (as high as 80 °C). Consequently, the HPE-LiCl-based sensor could timely and accurately monitor various human motion signals even in adverse environments and after long-term storage. Hence, this work presents a facile strategy for the design of long-term reliable hydrogels as smart strain sensors, especially used in extreme environments.


Asunto(s)
Celulosa , Frío , Humanos , Conductividad Eléctrica , Hidrogeles , Iones
2.
Cancer Cell Int ; 21(1): 380, 2021 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-34273985

RESUMEN

BACKGROUND: Our previous study shows that LINC01278 inhibits the malignant proliferation and invasion of papillary thyroid carcinoma (PTC) cells by regulating the miR-376c-3p/DNM3 axis. However, the regulation mechanism of LINC01278 expression in PTC cells is still unclear. METHODS: The luciferase reporter and ChIP assays were used to confirm the binding of LEF-1 to the putative promoter site of LINC01278 gene. The RNA immunoprecipitation and RNA pulldown were used to determine the enrichment of LINC01278 in ß-catenin protein. The proteasome inhibitors (MG132) was used for detecting the ß-catenin ubiquitination-proteasome degradation. Wnt/ß-catenin specific agonists (LiCI), inhibitors (WiKI4) and TOP/FOP-flash reporter assay were used for detecting the activation of Wnt/ß-catenin signal. Western blot was used to detected the expression of target proteins. RESULTS: The online PROMO algorithm determines a putative LEF-1 binding site on LINC01278 promoter, the LEF-1 binds to the putative promoter site of LINC01278 gene, and ß-catenin enhances the binding of LEF-1 to the LINC01278 gene promoter. Furthermore, LINC01278 negatively regulated the protein accumulation of ß-catenin in the cytoplasm, into nucleus, and ultimately inhibited the transcription of downstream target genes activated by Wnt/ß-catenin signal. The results of RNA immunoprecipitation and RNA pulldown proved the direct binding of LINC01278 to ß-catenin protein. In addition, the combination of LINC01278 and ß-catenin promotes the ß-catenin ubiquitination-proteasome degradation. CONCLUSION: In summary, we found the transcriptional activation of LINC01278 by the ß-catenin/LEF-1 transcription factor, and the negative feedback regulation of LINC01278 onß-catenin signal.

3.
FASEB J ; 34(8): 10966-10983, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32592217

RESUMEN

Uterine leiomyomas (ULM) are a major public health issue contributing to high morbidity and poor pregnancy outcomes. However, its molecular pathogenesis is poorly understood. HMGA2-ULM is the second major subtype of human ULM and associates with large sizes, fast-growth, and high percentages of estrogen receptor α (ERα). As altered ERα expression plays a distinct role in ULM growth, here, we investigate a regulatory mechanism driving ULM growth via HMGA2 and ERα. We reveal a positive correlation of HMGA2 with ERα protein and demonstrate that HMGA2 promotes ULM cells proliferation via ERα. In addition, autophagy pathway and p62/SQSTM1 (a selective autophagy receptor) are found to participate in the regulation of HMGA2 and ERα. Moreover, HMGA2 suppresses the transcription of p62 by binding to its promoter, meanwhile, p62 interacts with ERα, and inhibition of p62 increases ERα expression and enhances cell viability in ULM, suggesting a novel mechanism of the HMGA2-p62-ERα axis in ULM proliferation. Notably, rapamycin, a familiar autophagy agonist, reduces ERα levels and the proliferation ability of ULM cells. This study demonstrates a causal role of the HMGA2-p62-ERα axis in preventing autophagy and increasing ERα expression in HMGA2-ULM. Therefore, blocking HMGA2-p62-ERα axis and targeting autophagy pathway establish a roadmap toward HMGA2-ULM medical treatment.


Asunto(s)
Proliferación Celular/fisiología , Receptor alfa de Estrógeno/genética , Proteína HMGA2/genética , Leiomioma/genética , Proteína Sequestosoma-1/genética , Neoplasias Uterinas/genética , Adulto , Autofagia/fisiología , Supervivencia Celular/genética , Células Cultivadas , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Células HEK293 , Humanos , Leiomioma/patología , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Transducción de Señal/genética , Transcripción Genética/genética , Neoplasias Uterinas/patología , Útero/patología
4.
Neurosurg Rev ; 44(2): 1119-1125, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32333283

RESUMEN

OBJECTIVE: To determine whether diabetes mellitus (DM) contributes to the drug resistance of carbamazepine (CBZ), we investigated the correlation between the blood glucose status and the CBZ resistance condition in patients with trigeminal neuralgia (TN). PATIENTS AND METHODS: A total of 155 TN patients treated with the CBZ monotherapy were selected at Shanghai General Hospital and Shanghai Xinhua Hospital from September 2018 to January 2020. Among them, 15 were diagnosed with DM. Patients' CBZ resistance levels were evaluated according to progression-free survival. We utilized ordered multiple classification logistic regression to determine the dominant factors leading to CBZ resistance. We analyzed the correlation between hemoglobin A1c (HbA1c) and progression-free survival using the Pearson correlation analysis. RESULTS: The regression analysis showed that DM was the only factor affecting CBZ resistance (p = 0.035; OR = 0.327; 95% CI, 0.115-0.926). Progression-free survival was 28.5 ± 21.2 months in the DM group and 66.0 ± 33.2 months in the non-DM group. The concentration of HbA1c in the blood was negatively correlated with progression-free survival (r = - 0.197; p = 0.014). CONCLUSIONS: This study shows that blood glucose status is a significant factor contributing to the CBZ resistance in the treatment of TN. The progression-free survival of patients is affected by the status of DM and blood HbAlc levels.


Asunto(s)
Carbamazepina/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Resistencia a Medicamentos/fisiología , Neuralgia del Trigémino/tratamiento farmacológico , Neuralgia del Trigémino/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos no Narcóticos/farmacología , Analgésicos no Narcóticos/uso terapéutico , Carbamazepina/farmacología , China/epidemiología , Estudios de Cohortes , Resistencia a Medicamentos/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neuralgia del Trigémino/diagnóstico
5.
J Cell Mol Med ; 24(1): 304-316, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31657132

RESUMEN

The role of long non-coding RNAs (lncRNAs) in thyroid carcinoma (TC), the most frequent endocrine malignancy, has been extensively examined. This study investigated effect of interaction among lncRNA TNRC6C-AS1, serine/threonine-protein kinase 4 (STK4) and Hippo signalling pathway on TC. Initially, lncRNA TNRC6C-AS1 expression in TC tissues was detected. To explore roles of lncRNA TNRC6C-AS1, STK4 and Hippo signalling pathway in TC progression, their expressions were altered. Interaction between lncRNA TNRC6C-AS1 and STK4, STK4 promoter methylation, or Hippo signalling pathway was verified. After that, a series of experiments were employed to evaluate in vitro ability of apoptosis, proliferation and autophagy of TC cells and in vivo tumorigenicity, and tumour growth of TC cells. lncRNA TNRC6C-AS1 was highly expressed while STK4 was poorly expressed in TC tissues. LncRNA TNRC6C-AS1 promoted the STK4 methylation and down-regulated STK4 expression, which further activated the Hippo signalling pathway. STK4 silencing was observed to promote the proliferation ability of TC cells, inhibit the apoptosis and autophagy abilities, as well as enhance the tumorigenicity and tumour growth. Moreover, the in vitro proliferation ability as well as the in vivo tumorigenicity and tumour growth of TC cells were inhibited after the blockade of Hippo signalling pathway, while the apoptosis and autophagy abilities were promoted. The results demonstrate that the lncRNA TNRC6C-AS1 increases STK4 promoter methylation to down-regulate STK4 expression, thereby promoting the development of TC through activation of Hippo signalling pathway. It highlights that lncRNA TNRC6C-AS1 may be a novel therapeutic target for the treatment of TC.


Asunto(s)
Apoptosis/genética , Autofagia/genética , Metilación de ADN/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Secuencia de Bases , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Vía de Señalización Hippo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Modelos Biológicos , Proteínas Serina-Treonina Quinasas/genética , ARN Largo no Codificante/genética , Transducción de Señal
6.
Neuroendocrinology ; 110(6): 477-488, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31597135

RESUMEN

Cabergoline is a dopamine agonist that has been used as the first-line treatment option for prolactin-secreting pituitary adenomas for several decades. It not only suppresses hormone production from these prolactinomas, but also causes tumour shrinkage. Recent studies revealed some novel mechanisms by which cabergoline suppresses tumour cell proliferation and induces cell death. In this article, we review the most recent findings in cabergoline studies, focusing on its anti-tumour function. These studies suggest the potential broader clinical use of cabergoline in the treatment of other tumours such as breast cancer, pancreatic neuroendocrine tumours, and lung cancer.


Asunto(s)
Antineoplásicos/farmacología , Cabergolina/farmacología , Agonistas de Dopamina/farmacología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/tratamiento farmacológico , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactinoma/tratamiento farmacológico , Humanos
7.
Macromol Rapid Commun ; 39(1)2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28791749

RESUMEN

A well-defined amphiphilic triblock copolymer, poly[(ethylene glycol)methyl ether]-block-poly(N,N-dimethylamino ethyl methacrylate-co-2,2,2-trifluoroethyl methacrylate)-block-poly(4-(4-methoxy-phenylazo)phenoxy methacrylate) (PEG-b-P(DMAEMA-co-TFEMA)-b-PMEPPMA), is successfully synthesized by stepwise atom transfer radical polymerization. Owing to its amphiphilic nature, PEG-b-P(DMAEMA-co-TFEMA)-b-PMEPPMA can self-assemble into vesicles in aqueous solution and exhibits a reversible triple-responsive behavior toward CO2 , O2 , and light stimuli. More importantly, such vesicles can exhibit a controlled "breathing" behavior via external stimuli due to their suitable chemical structure and stimuli responsiveness. Consequently, these vesicles can be employed as nanocarriers for rate-tunable controlled release via adjustment of their membrane permeability by a single stimulus or various stimuli combinations.


Asunto(s)
Dióxido de Carbono/química , Luz , Oxígeno/química , Polímeros/síntesis química , Estructura Molecular , Polimerizacion , Polímeros/química
8.
Surg Innov ; 24(1): 29-34, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27634477

RESUMEN

The study assessed the role of an activated carbon nanoparticle lymphatic tracer in reducing unintentional damage to the parathyroid glands during thyroidectomy for papillary thyroid non-microcarcinoma diagnosed intraoperatively by cryosections. A total of 103 patients with papillary thyroid non-microcarcinomas diagnosed by intraoperative cryosection were randomly assigned to receive routine radical thyroidectomy or radical thyroidectomy following administration of activated carbon nanoparticle lymphatic tracer to the contralateral thyroid, at the department of Thyroid Surgery, Sun Yat-sen Memorial Hospital (Guangzhou, China), between January 2012 and May 2013. The success of level VI lymphadenectomy and postoperative parathyroid function were compared. Administration of the activated carbon nanoparticle lymphatic tracer did not affect the frequency of recovered lymph nodes containing metastases; however, it did significantly reduce the incidence of permanent and transient hypoparathyroidism from 2 to 0 and 18 to 6, and reduced the mean recovery time for transient hypoparathyroidism from 57.0 days to 22.3 days. Administration of activated carbon nanoparticles to the contralateral thyroid after intraoperative cryosections did not contribute to lymphadenectomy for papillary thyroid non-microcarcinoma, but significantly protected parathyroid functions. This approach could decrease the morbidity of radical thyroidectomy and the occurrence of hypoparathyroidism.


Asunto(s)
Carbono , Carcinoma Papilar/cirugía , Hipoparatiroidismo/prevención & control , Nanopartículas , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Adulto , Carcinoma Papilar/patología , Femenino , Humanos , Hipoparatiroidismo/etiología , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Glándulas Paratiroides , Neoplasias de la Tiroides/patología , Tiroidectomía/efectos adversos
9.
Carbohydr Polym ; 332: 121932, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38431422

RESUMEN

Conductive hydrogel-based sensors offer diverse applications in artificial intelligence, wearable electronic devices and character recognition management. However, it remains a significant challenge to maintain their satisfactory performances under extreme climatic conditions. Herein, a stretchable, self-adhesive, self-healing and environmentally stable conductive hydrogel was developed through free radical polymerization of hydroxyethyl acrylate (HEA) and poly(ethylene glycol) methacrylate (PEG) as the skeleton, followed by the incorporation of polyaniline-coated cellulose nanocrystal (CNC@PANI) as the conductive and reinforced nanofiller. Encouragingly, the as-prepared hydrogel (CHP) exhibited decent mechanical strength, satisfactory self-adhesion, prominent self-healing property (95.04 % after 60 s), excellent anti-freezing performance (below -60 °C) and outstanding moisture retention. The assembled sensor derived from CHP hydrogel possessed a low detection limit (0.5 % strain), high strain sensitivity (GF = 1.68) and fast response time (96 ms). Remarkably, even in harsh environmental temperatures from -60 °C to 80 °C, it reliably detected subtle and large-scale human motion for a long-term process (>10,000 cycles), manifesting its exceptional environmental tolerance. More interestingly, this hydrogel-based sensor could be assembled into a "writing board" for accurate handwritten numeral recognition. Therefore, the as-obtained multifunctional hydrogel could be a promising material applied in human motion detection and character recognition platforms even in harsh surroundings.

10.
J Hazard Mater ; 469: 134101, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38522196

RESUMEN

CO2-responsive materials have emerged as promising adsorbents for the remediation of refractory organic dyes-contaminated wastewater without the formation of byproducts or causing secondary pollution. However, realizing the simultaneous adsorption-separation or complete removal of both anionic and cationic dyes, as well as achieving deeper insights into their adsorption mechanism, still remains a challenge for most reported CO2-responsive materials. Herein, a novel type of urchin-like CO2-responsive Fe3O4 microspheres (U-Fe3O4 @P) has been successfully fabricated to enable ultrafast, selective, and reversible adsorption of anionic dyes by utilizing CO2 as a triggering gas. Meanwhile, the CO2-responsive U-Fe3O4 @P microspheres exhibit the capability to initiate Fenton degradation of non-adsorbable cationic dyes. Our findings reveal exceptionally rapid adsorption equilibrium, achieved within a mere 5 min, and an outstanding maximum adsorption capacity of 561.2 mg g-1 for anionic dye methyl orange upon CO2 stimulation. Moreover, 99.8% of cationic dye methylene blue can be effectively degraded through the Fenton reaction. Furthermore, the long-term unresolved interaction mechanism of organic dyes with CO2-responsive materials is deciphered through a comprehensive experimental and theoretical study by density functional theory. This work provides a novel paradigm and guidance for designing next-generation eco-friendly CO2-responsive materials for highly efficient purification of complex dye-contaminated wastewater in environmental engineering.

11.
Chin Neurosurg J ; 10(1): 1, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167418

RESUMEN

BACKGROUND: Trigeminal neuralgia (TN) is a common cause of craniofacial pain. The retrosigmoid approach is usually used to treat TN, but no cases of endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) were used to undergo operation for TN. CASE PRESENTATION: Two patients were presented with severe facial pain and preliminary diagnosis was TN. Preoperative magnetic resonance imaging revealed that a superior cerebellar artery (SCA) compressed the trigeminal nerve in case 1, and a tumor located in the petrous apex extending into the Meckel's cave compressed the trigeminal nerve in case 2. Operations were achieved through the EF-SCITA. The pain was totally relieved with no postsurgical complications in both cases. CONCLUSIONS: We present the first two case reports of EF-SCITA to relieve classical and secondary TN successfully. The EF-SCITA can be a promising approach for treating TN.

12.
Cancers (Basel) ; 16(4)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38398117

RESUMEN

Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients' medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.

13.
Neuro Oncol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38989697

RESUMEN

BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.

14.
Acta Neuropathol Commun ; 12(1): 61, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637883

RESUMEN

We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Hipofisarias , Humanos , Panobinostat/farmacología , Panobinostat/uso terapéutico , Factor 2 Relacionado con NF-E2/genética , Tumores Neuroendocrinos/tratamiento farmacológico , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Transducción de Señal
15.
Genome Med ; 16(1): 60, 2024 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658971

RESUMEN

BACKGROUND: Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood. METHODS: The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis. RESULTS: The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1+, C1Q+, and GPNMB+ showed enhanced contact with tumor cells expressing NR5A1 + , TBX19+, and POU1F1+, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1+ macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis. CONCLUSIONS: In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.


Asunto(s)
Macrófagos , Tumores Neuroendocrinos , Neoplasias Hipofisarias , Análisis de la Célula Individual , Transcriptoma , Microambiente Tumoral , Humanos , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/inmunología , Tumores Neuroendocrinos/metabolismo , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/inmunología , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/metabolismo , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Animales , Ratones , Macrófagos/metabolismo , Macrófagos/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Fenotipo , Apoptosis/genética , Linaje de la Célula/genética
16.
Macromol Rapid Commun ; 34(14): 1118-33, 2013 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-23723041

RESUMEN

This Review focuses on the recent progress in the area of CO2 -responsive polymers and provides detailed descriptions of these existing examples. CO2 -responsive polymers can be categorized into three types based on their CO2 -responsive groups: amidine, amine, and carboxyl groups. Compared with traditional temperature, pH, or light stimuli-responsive polymers, CO2 -responsive polymers provide the advantage to use CO2 as a "green" trigger as well as to capture CO2 directly from air. In addition, the current challenges of CO2 -responsive polymers are discussed and the different solution methods are compared. Noteworthy, CO2 -responsive polymers are considered to have a prosperous future in various scientific areas.


Asunto(s)
Amidinas/síntesis química , Aminas/síntesis química , Dióxido de Carbono/química , Nanotubos de Carbono/química , Polímeros/síntesis química , Acrilamidas/química , Técnicas Biosensibles/métodos , Sistemas de Liberación de Medicamentos/métodos , Colorantes Fluorescentes , Geles , Concentración de Iones de Hidrógeno , Pirenos/química , Temperatura
17.
Carbohydr Polym ; 321: 121265, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37739494

RESUMEN

A Fe-pillared montmorillonite (Fe-MMT) functionalized bio-based foam (Fe-MMT@CS/G) was developed by using chitosan (CS) and gelatin (G) as the matrix for high-efficiency elimination of organic pollutants through the integration of adsorption and Fenton degradation. The results showed that the mechanical properties of as-obtained foam were strengthened by the addition of certain amounts of Fe-MMT. Interestingly, Fe-MMT@CS/G displayed efficient adsorption ability for charged pollutants under a wide range of pH. The adsorption processes of methyl blue (MB), methylene blue (MEB) and tetracycline hydrochloride (TCH) on Fe-MMT@CS/G were well described by the Freundlich isotherm model and pseudo-second-order kinetic model. The maximum adsorption capacities were 2208.24 mg/g for MB, 1167.52 mg/g for MEB, and 806.31 mg/g for TCH. Electrostatic interactions, hydrogen bonding and van der Waals forces probably involved the adsorption process. As expected, this foam could exhibit better removal properties toward both charged and uncharged organic pollutants through the addition of H2O2 to trigger the Fenton degradation reaction. For non-adsorbable and uncharged bisphenol A (BPA), the removal efficiency was dramatically increased from 1.20 % to 92.77 % after Fenton degradation. Additionally, it presented outstanding recyclability. These results suggest that Fe-MMT@CS/G foam is a sustainable and efficient green material for the alleviation of water pollution.

18.
ACS Appl Mater Interfaces ; 15(31): 37867-37883, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37522905

RESUMEN

The complex wastewater containing water-soluble dyes and water-insoluble oils has given rise to significant environmental concerns that demand urgent remediation. Herein, a novel "smart" multifunctional sponge (ZIF-8@PMS) stepwise decorated with ZIF-8 nanoparticles and CO2-responsive copolymer (poly(2-(diethylamino) ethyl methacrylate-co-3-(trimethoxysilyl)propyl acrylate-co-stearyl methacrylate) was successfully prepared for CO2 controllable oil/water separation and dyes removal. The results revealed that the sponge coated with CO2-responsive copolymer for three cycles (ZIF-8@PMS-3) exhibited optimal comprehensive properties. The ZIF-8@PMS-3 had excellent compressive-resilient characteristics and chemical stability. As expected, it displayed tunable wettability and charged state under the regulation of CO2. Based on these features, ZIF-8@PMS-3 presented highly efficient removal of oil and dyes, even for the dye-containing oil/water emulsions, via a synergistic combination of adsorption and separation methods. The adsorption capacity for oil and various organic solvents ranged from 21.3 to 50 g g-1. The maximum adsorption capacities toward anionic dyes: methyl orange with 1205.89 mg g-1 and methyl blue with 880.00 mg g-1 in the presence of CO2 through electrostatic interaction. In the absence of CO2, it achieved maximum adsorption capacities for cationic dyes, including malachite green with 1246.15 mg g-1 and rhodamine B with 203 mg g-1, primarily driven by π-π interactions. According to distinct adsorption mechanisms, ZIF-8@PMS-3 could selectively adsorb either anionic or cationic dyes by exploiting CO2 as a trigger. Furthermore, the separation efficiencies for both types of oil/water emulsions surpassed 99.9%, with respective fluxes of 1566.99 L m-2 h-1 (water-in-oil emulsion) and 310.37 L m-2 h-1 (oil-in-water emulsion). Additionally, the as-prepared sponges exhibited remarkable antibacterial properties and exceptional recyclability. Therefore, the ZIF-8@PMS-3 holds substantial promise for potential applications in practical industrial wastewater treatment.

19.
Front Endocrinol (Lausanne) ; 14: 1149997, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37534217

RESUMEN

Background: Pituitary neuroendocrine tumors (PitNETs), which originate from the pituitary gland, account for 10%-15% of all intracranial neoplasms. Recent studies have indicated that enhancer RNAs (eRNAs) exert regulatory effects on tumor growth. However, the mechanisms underlying the eRNA-mediated tumorigenesis of PitNETs have not been elucidated. Methods: Normal pituitary and PitNETs tissues were used to identify the differentially expressed eRNAs (DEEs). Immune gene sets and hallmarks of cancer gene sets were quantified based on single sample gene set enrichment analysis (ssGSEA) algorithm using GSVA. The perspective of immune cells among all samples was calculated by the CIBERSORT algorithm. Moreover, the regulatory network composed of key DEEs, target genes of eRNAs, hallmarks of cancer gene sets, differentially expressed TF, immune cells and immune gene sets were constructed by Pearson correlation analysis. Small molecular anti-PitNETs drugs were explored by CMap analysis and the accuracy of the study was verified by in vitro and in vivo experiments, ATAC-seq and ChIP-seq. Results: In this study, data of 134 PitNETs and 107 non-tumorous pituitary samples were retrieved from a public database to identify differentially expressed genes. In total, 1128 differentially expressed eRNAs (DEEs) (494 upregulated eRNAs and 634 downregulated eRNAs) were identified. Next, the correlation of DEEs with cancer-related and immune-related gene signatures was examined to establish a co-expression regulatory network comprising 18 DEEs, 50 potential target genes of DEEs, 5 cancer hallmark gene sets, 2 differentially expressed transcription factors, 4 immune cell types, and 4 immune gene sets. Based on this network, the following four therapeutics for PitNETs were identified using Connectivity Map analysis: ciclopirox, bepridil, clomipramine, and alexidine. The growth-inhibitory effects of these therapeutics were validated using in vitro experiments. Ciclopirox exerted potential growth-inhibitory effects on PitNETs. Among the DEEs, GNLY, HOXB7, MRPL33, PRDM16, TCF7, and ZNF26 were determined to be potential diagnostic and therapeutic biomarkers for PitNETs. Conclusion: This study illustrated the significant influence of eRNAs on the occurrence and development of PitNETs. By constructing the co-expression regulation network, GNLY, HOXB6, MRPL33, PRDM16, TCF7, and ZNF26 were identified as relatively significant DEEs which were considered as the novel biomarkers of diagnosis and treatment of PitNETs. This study demonstrated the roles of eRNAs in the occurrence and development of PitNETs and revealed that ciclopirox was a potential therapeutic for pituitary adenomas.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Ciclopirox , ARN/genética , Factores de Transcripción/genética , Hipófisis/patología , Proteínas de Homeodominio
20.
Endocrine ; 80(2): 419-424, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36689171

RESUMEN

PURPOSE: The dopamine agonists (DA) have been used widely to treat prolactinomas. However, it is difficult to predict whether the patient will be responsive to DA treatment. METHODS: We aimed to investigate whether the in vivo expression of DRD2 based on 18F-fallypride PET/MR could predict the therapeutic effect of DA on prolactinomas. Seven patients with prolactinomas completed 18F-fallypride PET/MR. Among them, three patients underwent surgery and further tumor immunohistochemistry. Imaging findings and immunohistochemical staining were compared with treatment outcomes. RESULTS: 18F-fallypride PET/MR was visually positive in 7 of 7 patients, and DRD2 target specificity could be confirmed by immunohistochemical staining. A significantly lower tracer standard uptake value (SUV) could be detected in the resistant patients (n = 3) than in the sensitive patients (n = 4; SUVmean, 4.67 ± 1.32 vs. 13.57 ± 2.42, p < 0.05). DRD2 expression determined by 18F-fallypride PET/MR corresponded with the DA treatment response. CONCLUSION: 18F-fallypride PET/MR may be a promising technique for predicting DA response in patients with prolactinoma.


Asunto(s)
Neoplasias Hipofisarias , Prolactinoma , Humanos , Prolactinoma/diagnóstico por imagen , Prolactinoma/tratamiento farmacológico , Agonistas de Dopamina/uso terapéutico , Proyectos Piloto , Receptores de Dopamina D2/metabolismo , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/metabolismo , Tomografía de Emisión de Positrones
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