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1.
Heliyon ; 10(17): e37230, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39286117

RESUMEN

Background: SZ-685C, an anthracycline compound derived from the mangrove endophytic fungus Halorosellinia sp. (No. 1403) collected from the South China Sea, has shown strong anticancer activities. Non-functioning pituitary adenomas (NFPAs) are a type of tumor that can be challenging to manage clinically and have a significant unmet medical need. Our research has found that SZ-685C showed an inhibitory effect on the viability, migration ability, and proliferation ability of a human non-functioning pituitary tumor-derived folliculostellate (PDFS) cell line. Methods: SZ-685C was prepared and purified from the mangrove endophytic fungus No. 1403. PDFS cells were exposed to SZ-685C, and the effect of SZ-685C on PDFS cells was evaluated. RNA sequencing was used to analyze the miRNA expression profile in PDFS cells of the control group and SZ-685C-treated group. Quantitative polymerase chain reaction (qPCR) was performed to verify the expression of selected miR-340-3p. The effects of SZ-685C on PDFS cells after overexpression of miR-340-3p were evaluated. Dual-luciferase reporter assays showed PPP1CB is a direct target of miR-340-3p. Finally, the action pathway of the selected miR-340-3p was predicted and evaluated through bioinformatics analysis. Results: SZ-685C reduced cell viability in PDFS cells, accompanied by inhibition of migration ability and proliferation ability. The IC50 value for 24 h is 9.144 ± 0.991 µM, and for 48 h is 4.635 ± 0.551 µM. SZ-685C increased the protein levels of Beclin 1, the ratio of LC3-II to LC3-I, and LAMP-1, and down-regulated p62. MiRNA sequencing and further validation showed that miR-340-3p significantly decreased in PDFS cells treated with SZ-685C. After overexpression of miR-340-3p, the inhibition of viability, migration ability, proliferation ability, and autophagy-promoting effect of SZ-685C on PDFS cells were weakened. SZ-685C caused a decrease in PPP1CB expression and activation of the ERK pathway in PDFS cells, and this trend was reversed after overexpression of miR-340-3p. Conclusions: SZ-685C downregulates the expression of miR-340-3p in PDFS cells, thereby reducing the expression of PPP1CB and activating the ERK pathway to promote autophagic cell death, leading to inhibition of PDFS cell growth.

2.
Langmuir ; 40(37): 19316-19323, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39217623

RESUMEN

The oxygen level in the tumor microenvironment (TME) plays a critical role in regulating cell fates such as proliferation, migration, apoptosis, and so forth. To better elucidate how hypoxia affects tumor cell behaviors, a series of microfluidic strategies have been utilized to generate an oxygen gradient covering both hypoxia and normoxia conditions. However, in most studies, some chemicals are introduced into microfluidic chips, causing the potential of their poor biocompatibility. The common oxygen gradient with linear variation does not allow the effects of specific oxygen concentrations on tumor cells to be analyzed accurately. In this paper, based on the physical method of gas diffusion, a microfluidic device integrated with an oxygen gradient generator is proposed for investigating effects of different hypoxia levels on responses of tumor cells. This device consists of three layers, i.e., upper layer, thin film layer, and bottom layer. The upper layer is used for introducing the initial gas and generating an oxygen gradient in the form of gas. The bottom layer is used for introducing cells and culture medium. The thin film layer separates the former two layers, allowing the gas to diffuse from the top to the bottom through it. The oxygen gradient in the bottom layer is finally generated in the form of dissolved oxygen. The device is fabricated using microfabrication technology. The effects of structural and working parameters of the device on the oxygen gradient are evaluated by finite element simulation. The oxygen gradient in cell culture channels is characterized by using oxygen-sensitive fluorescence materials. The proliferation and morphology of HeLa cells under specific oxygen levels are compared after culturing for 48 h. The oxygen gradient with a ladder-like distribution demonstrates that this microfluidic device can provide a prospective experimental platform for in vitro cell studies and revelation of the mechanism of tumor metastasis associated with a specific hypoxic microenvironment.


Asunto(s)
Oxígeno , Humanos , Oxígeno/química , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/instrumentación , Células HeLa , Microambiente Tumoral , Hipoxia de la Célula
3.
Neurosurg Rev ; 47(1): 499, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196456

RESUMEN

BACKGROUND: Percutaneous balloon compression (PBC) is an effective, low-cost, and simple treatment for primary trigeminal neuralgia (TN). However, PBC has poor efficacy and no better solution for the third branch (V3) of TN. METHODS: Clinical data of 52 patients with trigeminal neuralgia treated with PBC were retrospectively analyzed. Postoperative numbness of the patient was evaluated by facial numbness at the Barrow Neurological Institute (BNI-N). The main observation was the incidence of higher numbness in the V3 than in the other two branches or equally strong numbness in the three branches in the immediate postoperative period. RESULTS: The efficacy values in the pear-shaped balloon group at the first postoperative day (T1), the first month (T2), in the third month (T3), and the sixth month (T4) were 96.7%, 93.3%, 93.3%, and 90%, respectively, and 1 patient (3.3%) had recurrence. The efficacy value for the extracapsular capsule group was 95.5% at all times and there were no patients with recurrence within 6 months after surgery. In the immediate postoperative period, the effective compression rate of V3 in the pear-shaped balloon group was 43.3%, and 86.4% in the extracapsular capsule group (P = 0.020). At six months of follow-up, the effective compression rate of V3 was higher in the extracapsular capsule group than in the pear-shaped balloon group. CONCLUSIONS: The riveted structure of the extracapsular capsule can effectively compress V3, thus performing PBC with a balloon shaped as an extracapsular capsule is a new, effective, and safe treatment option for TN V3. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2300067313.


Asunto(s)
Neuralgia del Trigémino , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Nervio Trigémino/cirugía , Neuralgia del Trigémino/cirugía , Neuralgia del Trigémino/terapia , Estudios de Casos y Controles
4.
Front Pediatr ; 12: 1398182, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39091987

RESUMEN

Objective: While the pain threshold index (PTI) holds potential as a tool for monitoring analgesia-pain equilibrium, its precision in forecasting postoperative pain in children remains unconfirmed. This study's primary aim was to assess the PTI's predictive precision for postoperative pain. Methods: Children (aged 2-16 years) undergoing general surgery under general anesthesia were included. Within 5 min prior to the patient's emergence from surgery, data including PTI, wavelet index (WLI), heart rates (HR) and mean arterial pressure (MAP) were collected. Subsequently, a 15-min pain assessment was conducted following the patient's awakening. The accuracy of these indicators in discerning between mild and moderate to severe postoperative pain was evaluated through receiver operating characteristic (ROC) analysis. Results: The analysis encompassed data from 90 children. ROC analysis showed that PTI was slightly better than HR, MAP and WLI in predicting postoperative pain, but its predictive value was limited. The area under the curve (AUC) was 0.659 [0.537∼0.780] and the optimal threshold was 65[64-67]. Sensitivity and specificity were determined at 0.90 and 0.50, respectively. In a multivariable logistic regression model, a higher predictive accuracy was found for a multivariable predictor combining PTI values with gender, BMI, HR and MAP (AUC, 0.768; 95%CI, 0.669-0.866). Upon further scrutinizing the age groups, PTI's AUC was 0.796 for children aged 9-16, 0.656 for those aged 4-8, and 0.601 for younger individuals. Conclusions: PTI, when used alone, lacks acceptable accuracy in predicting postoperative pain in children aged 2 to 16 years. However, when combined with other factors, it shows improved predictive accuracy. Notably, PTI appears to be more accurate in older children.

5.
J Hazard Mater ; 477: 135388, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39094308

RESUMEN

Catalytic ozone (O3) decomposition is a promising technology for curbing indoor O3 pollution, whereas its application is limited by the stability and moisture resistance of heterogeneous catalysts. Ag-Hollandite is a capable solution, but its facile synthesis still lacks systematic investigation. In this study, Ag-Hollandite catalysts were prepared using AgMnO4 as the precursor by reflux (AMO-Re), hydrothermal (AMO-HT), and homogeneous (AMO-HR) methods, respectively. The as-prepared samples showed excellent stability under moisture conditions, with the optimal one maintaining an O3 conversion rate of 99.19 % after 100 h. In the characterization results, Ramsdellite (R-MnO2) was identified as an intermediate species in the synthesis. AMO-HR exhibits higher activity due to enhanced active site exposure and weakened adsorption towards *OO species, while reduced surface hydroxyl content was a crucial factor for moisture resistance. This study aims to contribute insights for preparing catalysts by a facile method.

6.
Drug Dev Res ; 85(6): e22251, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39188035

RESUMEN

Nonfunctioning pituitary adenoma (NFPA) is one of the major subtypes of pituitary adenomas (PA) and its primary treatment is surgical resection. However, normal surgery fails to remove lesions completely and there remains in lack of frontline treatment, so the development of new drugs for NFPA is no doubt urgent. Oridonin (ORI) has been reported to have antitumor effects on a variety of tumors, but whether it could exhibit the same effect on NFPA requires to be further investigated. The effects of ORI on pituitary-derived folliculostellate cell line (PDFS) cell viability, colony formation, proliferation ability, migration, and invasion were examined by Cell Counting Kit-8, colony formation assay, 5­Ethynyl­2'­deoxyuridine proliferation assay, wound-healing assay, and Transwell assay. The differentially expressed genes in the control and ORI-treated groups were screened by transcriptome sequencing analysis and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. Cell cycle analysis was performed to detect changes in cell cycle. Annexin V-fluorescein isothiocyanate/propidium iodide staining was performed to detect apoptosis in ORI-treated cells. Western blot assay was performed to detect Bax, Bcl-2, and cleaved Caspase-3 protein expression. ORI inhibited PDFS cell viability and significantly suppressed cell proliferation, migration, and invasion. GO and KEGG results showed that ORI was associated with signaling pathways such as cell cycle and apoptosis in PDFS cells. In addition, ORI blocked cells in G2/M phase and induced apoptosis in PDFS cells. ORI can trigger cell cycle disruption and apoptosis collaboratively in PDFS cells, making it a promising and effective agent for NFPA therapy.


Asunto(s)
Apoptosis , Proliferación Celular , Diterpenos de Tipo Kaurano , Neoplasias Hipofisarias , Diterpenos de Tipo Kaurano/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/patología , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Humanos , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Adenoma/tratamiento farmacológico , Adenoma/patología
7.
Microorganisms ; 12(8)2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39203419

RESUMEN

Soil nitrogen (N) mineralization typically governs the availability and movement of soil N. Understanding how factors, especially functional genes, affect N transformations is essential for the protection and restoration of forest ecosystems. To uncover the underlying mechanisms driving soil N mineralization, this study investigated the effects of edaphic environments, substrates, and soil microbial assemblages on net soil N mineralization in boreal forests. Field studies were conducted in five representative forests: Larix principis-rupprechtii forest (LF), Betula platyphylla forest (BF), mixed forest of Larix principis-rupprechtii and Betula platyphylla (MF), Picea asperata forest (SF), and Pinus sylvestris var. mongolica forest (MPF). Results showed that soil N mineralization rates (Rmin) differed significantly among forests, with the highest rate in BF (p < 0.05). Soil properties and microbial assemblages accounted for over 50% of the variability in N mineralization. This study indicated that soil environmental factors influenced N mineralization through their regulatory impact on microbial assemblages. Compared with microbial community assemblages (α-diversity, Shannon and Richness), functional genes assemblages were the most important indexes to regulate N mineralization. It was thus determined that microbial functional genes controlled N mineralization in boreal forests. This study clarified the mechanisms of N mineralization and provided a mechanistic understanding to enhance biogeochemical models for forecasting soil N availability, alongside aiding species diversity conservation and fragile ecosystem revitalization in boreal forests.

8.
Microorganisms ; 12(8)2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39203454

RESUMEN

The effects of environmental factors on phytoplankton are not simply positive or negative but complex and dependent on the combination of their concentrations in a fluctuating environment. Traditional statistical methods may miss some of the complex interactions between the environment and phytoplankton. In this study, the temporal-spatial fluctuations of phytoplankton diversity and abundance were investigated in a shallow temperate mountain river. The machine learning method classification and regression tree (CART) was used to explore the effects of environmental variables on the phytoplankton community. The results showed that both phytoplankton species diversity and abundance varied fiercely due to environmental fluctuation. Microcystis aeruginosa, Amphiprora sp., Anabaena oscillarioides, and Gymnodinium sp. were the dominant species. The CART analysis indicated that dissolved oxygen, oxidation-reduction potential, total nitrogen (TN), total phosphorus (TP), and water temperature (WT) explained 36.00%, 13.81%, 11.35%, 9.96%, and 8.80%, respectively, of phytoplankton diversity variance. Phytoplankton abundance was mainly affected by TN, WT, and TP, with variance explanations of 39.40%, 15.70%, and 14.09%, respectively. Most environmental factors had a complex influence on phytoplankton diversity and abundance: their effects were positive under some conditions but negative under other combinations. The results and methodology in this study are important in quantitatively understanding and exploring aquatic ecosystems.

9.
Food Chem ; 460(Pt 2): 140669, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39094346

RESUMEN

As vastly modified on secreted proteins, N-glycosylation is found on milk proteins and undergo dynamic changes during lactation, characterizing milk protein glycosylation would benefit the elucidation of glycosylation pattern differences between samples. However, their low abundance required specific enrichment. Herein, through rational design and controllable synthesis, we developed a novel multi-functional polymer for the isolation of protein glycosylation. It efficiently separated glycopeptides from complex background inferences with mutual efforts of hydrophilic interaction chromatography (HILIC), metal ion affinity and ion exchange. By fine-tuning Ca2+ as regulators of aldehyde hyaluronic acid (HA) conformation, the grafting density of HA was remarkably improved. Moreover, grafting Ti4+ further enhanced the enrichment performance. Application of this material to characterize bovine milk and colostrum proteins yields 479 and 611 intact glycopeptides, respectively. Comparative analysis unraveled the distinct glycosylation pattern as well the different distribution of glycoprotein abundances between the two samples, offering insights for functional food development.


Asunto(s)
Calostro , Interacciones Hidrofóbicas e Hidrofílicas , Leche , Polímeros , Polisacáridos , Animales , Bovinos , Calostro/química , Leche/química , Glicosilación , Polisacáridos/química , Polímeros/química , Femenino , Proteínas de la Leche/química , Glicoproteínas/química
10.
Cell Biol Toxicol ; 40(1): 65, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110292

RESUMEN

The primary aim of this research was to explore the functions of Wtap and Ythdf1 in regulating neuronal Lipocalin-2 (Lcn2) through m6A modification in traumatic brain injury (TBI). By employing transcriptome sequencing and enrichment analysis, we identified the Wtap/Ythdf1-mediated Lcn2 m6A modification pathway as crucial in TBI. In our in vitro experiments using primary cortical neurons, knockout of Wtap and Ythdf1 led to the inhibition of Lcn2 m6A modification, resulting in reduced neuronal death and inflammation. Furthermore, overexpression of Lcn2 in cortical neurons induced the activation of reactive astrocytes and M1-like microglial cells, causing neuronal apoptosis. In vivo experiments confirmed the activation of reactive astrocytes and microglial cells in TBI and importantly demonstrated that Wtap knockdown improved neuroinflammation and functional impairment. These findings underscore the significance of Wtap/Ythdf1-mediated Lcn2 regulation in TBI secondary injury and suggest potential therapeutic implications for combating TBI-induced neuroinflammation and neuronal damage.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Lipocalina 2 , Neuronas , Lesiones Traumáticas del Encéfalo/genética , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Lipocalina 2/metabolismo , Lipocalina 2/genética , Animales , Neuronas/metabolismo , Neuronas/patología , Ratones , Microglía/metabolismo , Microglía/patología , Astrocitos/metabolismo , Astrocitos/patología , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Masculino , Ratones Endogámicos C57BL , Apoptosis , Ratones Noqueados , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología
11.
FEBS J ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949993

RESUMEN

Cancer cells undergo metabolic adaptation to promote their survival and growth under energy stress conditions, yet the underlying mechanisms remain largely unclear. Here, we report that tripartite motif-containing protein 2 (TRIM2) is upregulated in response to glutamine deprivation by the transcription factor cyclic AMP-dependent transcription factor (ATF4). TRIM2 is shown to specifically interact with carnitine O-palmitoyltransferase 1 (CPT1A), a rate-limiting enzyme of fatty acid oxidation. Via this interaction, TRIM2 enhances the enzymatic activity of CPT1A, thereby regulating intracellular lipid levels and protecting cells from glutamine deprivation-induced apoptosis. Furthermore, TRIM2 is able to promote both in vitro cell proliferation and in vivo xenograft tumor growth via CPT1A. Together, these findings establish TRIM2 as an important regulator of the metabolic adaptation of cancer cells to glutamine deprivation and implicate TRIM2 as a potential therapeutic target for cancer.

12.
Int J Biol Sci ; 20(9): 3426-3441, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993572

RESUMEN

Background: Thyroid cancer (TC) is a common endocrine cancer with a favourable prognosis. However, poor patient prognosis due to TC dedifferentiation is becoming an urgent challenge. Recently, methyltransferase-like 3 (METTL3)-mediated N6 -methyladenosine (m6A) modification has been demonstrated to play an important role in the occurrence and progression of various cancers and a tumour suppressor role in TC. However, the mechanism of METTL3 in TC remains unclear. Methods: The correlation between METTL3 and prognosis in TC patients was evaluated by immunohistochemistry. Mettl3fl/flBrafV600ETPO-cre TC mouse models and RNA-seq were used to investigate the underlying molecular mechanism, which was further validated by in vitro experiments. The target gene of METTL3 was identified, and the complete m6A modification process was described. The phenomenon of low expression of METTL3 in TC was explained by identifying miRNAs that regulate METTL3. Results: We observed that METTL3 expression was negatively associated with tumour progression and poor prognosis in TC. Mechanistically, silencing METTL3 promoted the progression and dedifferentiation of papillary thyroid carcinoma (PTC) both in vivo and in vitro. Moreover, overexpressing METTL3 promoted the sensitivity of PTC and anaplastic thyroid cancer (ATC) cells to chemotherapeutic drugs and iodine-131 (131I) administration. Overall, the METTL3/PAX8/YTHDC1 axis has been revealed to play a pivotal role in repressing tumour occurrence, and is antagonized by miR-493-5p.


Asunto(s)
Diferenciación Celular , Metiltransferasas , Factor de Transcripción PAX8 , Neoplasias de la Tiroides , Animales , Femenino , Humanos , Masculino , Ratones , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Metiltransferasas/metabolismo , Metiltransferasas/genética , MicroARNs/metabolismo , MicroARNs/genética , Factor de Transcripción PAX8/metabolismo , Factor de Transcripción PAX8/genética , Pronóstico , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/genética
13.
Heliyon ; 10(12): e33221, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39005893

RESUMEN

Moxibustion has a long history of use as a traditional Chinese medicine therapy. Infrared radiation is an important and effective factor in moxibustion. Instead of the time-consuming and laborious process of holding moxa sticks in the hand, moxibustion devices are commonly used as moxibustion methods and tools in modern times. With the publication of the international standard of moxibustion devices (ISO18666:2021, Traditional Chinese Medicine - General requirements of moxibustion devices) published, moxibustion devices of various materials are now sold in the pharmacies and online stores. However, the influence of moxibustion devices on the therapeutic effect of moxibustion has not been studied. Therefore, this research was aimed to evaluate the infrared radiation of moxibustion devices, in order to select the moxibustion device that delivered infrared radiation closest to that of moxa stick combustion. The combination of combustion stability and infrared radiation intensity showed that cardboard tubes and silicone were better materials for moxibustion devices. In the mid-far infrared wave band, the moxibustion devices made from cardboard tubes and silica gels can better maintain the thermal effect generated by moxibustion and enable it to be more easily absorbed by the human body. The infrared radiation intensity of the cardboard moxibustion devices increased rapidly and steadily and could be maintained for the longest time. In conclusion, cardboard tubes are the better material for moxibustion devices with respect to infrared radiation.

15.
Angew Chem Int Ed Engl ; : e202411361, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39073279

RESUMEN

Perovskite light-emitting diodes (PeLEDs) that can be air-processed promises the development of displaying optoelectronic device, while is challenged by technical difficulty on both the active layer and hole transport layer (HTL) caused by the unavoidable humidity interference. Here, we propose and validate that, planting the polymer brush with tailored functional groups in inorganic HTL, provides unique bilateral embedded anchoring that is capable of simultaneously addressing the n phases crystallization rates in the active layer as well as the deteriorated particulate surface defects in HTL. Exemplified by zwitterionic polyethyleneimine-sulfonate (PEIS) in present study, its implanting in NiOx HTL offers abundant nuclei sites of amino and sulfonate groups that balance the growth rate of different n phases in quasi-2D perovskite films. Moreover, the PEIS effectively nailed the interfacial contact between perovskite and NiOx, and reduced the particulate surface defects in HTL, leading to the enhanced PLQY and stability of large-area blue perovskite film in ambient air. By virtue of these merits, present work achieves the first demonstration of the air-processed blue PeLEDs in large emitting area of 1.0 cm2 with peak external quantum efficiency (EQE) of 2.09 %, which is comparable to the similar pure-bromide blue PeLEDs fabricated in glovebox.

16.
J Med Chem ; 67(15): 13435-13445, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39078925

RESUMEN

Photodynamic therapy has been regarded as a noninvasive treatment for cancer with spatiotemporal control over drug activation. Bis-terpyridyl Ru(II) complexes exhibit a promising achiral structure but suffer from low photoreactivity due to deviation from the ideal octahedral geometry. Herein, we introduce the donor-acceptor-donor motif to construct a dinuclear bis-terpyridyl Ru(II) complex (Ru2). Ru2 exhibits superior light absorption properties compared with mononuclear complex Ru1. Importantly, upon 595 nm light excitation, Ru2 shows promising synergetic type I/II photosensitization and photocatalytic activity, while Ru1 is inactive. Anticancer mechanistic studies reflect that Ru2 induces intracellular redox imbalance and affects the biosynthetic and metabolic processes, leading to cell apoptosis. Overall, this work provides a simple strategy to rouse the PDT efficiency of bis-terpyridyl Ru(II) complexes.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Fotoquimioterapia , Fármacos Fotosensibilizantes , Rutenio , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Rutenio/química , Rutenio/farmacología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Estructura-Actividad
17.
Front Oncol ; 14: 1379420, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903715

RESUMEN

Background: Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated. Patients and methods: Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated. Results: AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%. Conclusion: AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.

18.
Anal Chem ; 96(26): 10506-10514, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38874382

RESUMEN

Dysregulation of protein core-fucosylation plays a pivotal role in the onset, progression, and immunosuppression of cancer. However, analyzing core-fucosylation, especially the accurate determination of the core-fucosylation (CF) site occupancy ratio, remains challenging. To address these problems, we developed a truncation strategy that efficiently converts intact glycopeptides with hundreds of different glycans into two truncated forms, i.e., a monosaccharide HexNAc and a disaccharide HexNAc+core-fucose. Further combination with data-independent analysis to form an integrated platform allowed the measurement of site-specific core-fucosylation abundances and the determination of the CF occupancy ratio with high reproducibility. Notably, three times CF sites were identified using this strategy compared to conventional methods based on intact glycopeptides. Application of this platform to characterize protein core-fucosylation in two breast cancer cell lines, i.e., MDA-MB-231 and MCF7, yields a total of 1615 unique glycosites and about 900 CF sites from one single LC-MS/MS analysis. Differential analysis unraveled the distinct glycosylation pattern for over 201 cell surface drug targets between breast cancer subtypes and provides insights into developing new therapeutic strategies to aid precision medicine. Given the robust performance of this platform, it would have broad application in discovering novel biomarkers based on the CF glycosylation pattern, investigating cancer mechanisms, as well as detecting new intervention targets.


Asunto(s)
Fucosa , Polisacáridos , Humanos , Polisacáridos/química , Polisacáridos/metabolismo , Polisacáridos/análisis , Fucosa/química , Fucosa/metabolismo , Glicosilación , Espectrometría de Masas en Tándem , Línea Celular Tumoral , Glicopéptidos/química , Glicopéptidos/análisis , Glicopéptidos/metabolismo
19.
Bioresour Technol ; 402: 130773, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701987

RESUMEN

This study explored the use of biochar to accelerate the establishment of anaerobic ammonium oxidation (anammox) reactors operating at 15 ± 1℃. Incorporating 10 g/L bamboo charcoal in S1 accelerated the start-up of anammox in 87 days, which was significantly shorter than 103 days in S0 (without biochar). After 140 days, S1 exhibited a 10.9 % increase in nitrogen removal efficiency due to a 28.9 % elevation in extracellular polymeric substances, bolstering anammox bacterial resilience. Predominant anammox bacteria (Cadidatus Brocadia and Cadidatus Jettenia) showed relative abundances of 3.19 % and 0.38 % in S1, respectively, which were significantly higher than 0.40 % and 0.05 % in S0. Biochar provides favorable habitats for the enrichment of anammox bacteria and accelerates the establishment of anammox at low temperatures. This finding holds promise for enhancing the efficiency of anammox in cold climates and advancing sustainable wastewater nitrogen removal.


Asunto(s)
Reactores Biológicos , Carbón Orgánico , Nitrógeno , Oxidación-Reducción , Carbón Orgánico/química , Frío , Anaerobiosis , Compuestos de Amonio/metabolismo , Bacterias/metabolismo , Purificación del Agua/métodos , Aguas Residuales/química
20.
Biomaterials ; 309: 122620, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38788456

RESUMEN

Photodynamic therapy (PDT) is a promising modality for cancer treatment. However, limited tissue penetration of external radiation and complicated tumor microenvironments (TMEs) restrict the antitumor efficiency of PDT. Herein, we report an energy-storing DNA-based hydrogel, which enables tumor-selective PDT without external radiation and regulates TMEs to achieve boosted PDT-mediated tumor immunotherapy. The system is constructed with two ultralong single-stranded DNA chains, which programmed partial complementary sequences and repeated G-quadruplex forming AS1411 aptamer for photosensitizer loading via hydrophobic interactions and π-π stacking. Then, energy-storing persistent luminescent nanoparticles are incorporated to sensitize PDT selectively at tumor site without external irradiation, generating tumor antigen to agitate antitumor immune response. The system catalytically generates O2 to alleviate hypoxia and releases inhibitors to reverse the IDO-related immunosuppression, synergistically remodeling the TMEs. In the mouse model of breast cancer, this hydrogel shows a remarkable tumor suppression rate of 78.3 %. Our study represents a new paradigm of photodynamic immunotherapy against cancer by combining laser-free fashion and TMEs remodeling.


Asunto(s)
ADN , Hidrogeles , Inmunoterapia , Fotoquimioterapia , Fármacos Fotosensibilizantes , Microambiente Tumoral , Animales , Fotoquimioterapia/métodos , Microambiente Tumoral/efectos de los fármacos , Hidrogeles/química , Inmunoterapia/métodos , Femenino , Ratones , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Ratones Endogámicos BALB C , Humanos , Línea Celular Tumoral , Rayos Láser
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