Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 194
Filtrar
1.
Cancer Immunol Immunother ; 73(11): 220, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235609

RESUMEN

BACKGROUND: The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking. METHODS: ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing. RESULTS: A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival. CONCLUSION: This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.


Asunto(s)
Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Humanos , Masculino , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/genética , Adulto , Pronóstico
2.
Sensors (Basel) ; 24(17)2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39275395

RESUMEN

Wearable flexible strain sensors require different performance depending on the application scenario. However, developing strain sensors based solely on experiments is time-consuming and often produces suboptimal results. This study utilized sensor knowledge to reduce knowledge redundancy and explore designs. A framework combining knowledge graphs and graph representational learning methods was proposed to identify targeted performance, decipher hidden information, and discover new designs. Unlike process-parameter-based machine learning methods, it used the relationship as semantic features to improve prediction precision (up to 0.81). Based on the proposed framework, a strain sensor was designed and tested, demonstrating a wide strain range (300%) and closely matching predicted performance. This predicted sensor performance outperforms similar materials. Overall, the present work is favorable to design constraints and paves the way for the long-awaited implementation of text-mining-based knowledge management for sensor systems, which will facilitate the intelligent sensor design process.

3.
Cell Rep Med ; 5(9): 101710, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39232496

RESUMEN

Claudin18.2 has been recently recognized as a potential therapeutic target for gastric/gastroesophageal junction or pancreatic cancer. Here, we develop a Claudin18.2-directed antibody-drug conjugate (ADC), CMG901, with a potent microtubule-targeting agent MMAE (monomethyl auristatin E) and evaluate its preclinical profiles. In vitro studies show that CMG901 binds specifically to Claudin18.2 on the cell surface and kills tumor cells through direct cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and bystander killing activity. In vivo pharmacological studies show significant antitumor activity in patient-derived xenograft (PDX) models. Toxicity studies show that the major adverse effects related to CMG901 are reversible hematopoietic changes attributed to MMAE. The highest non-severely toxic dose (HNSTD) is 6 mg/kg in cynomolgus monkeys and 10 mg/kg in rats once every 3 weeks. CMG901's favorable preclinical profile supports its entry into the human clinical study. CMG901 is currently under phase 3 investigation in patients with advanced gastric/gastroesophageal junction adenocarcinoma expressing Claudin18.2 (NCT06346392).


Asunto(s)
Claudinas , Inmunoconjugados , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Línea Celular Tumoral , Claudinas/metabolismo , Ratas , Ratones , Macaca fascicularis , Femenino , Oligopéptidos/farmacología , Oligopéptidos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Masculino , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos
4.
Adv Sci (Weinh) ; : e2401013, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39234824

RESUMEN

Both the transforming growth factor beta (TGF-ß) signaling pathway and N6-methyladenosine (m6A) modification for mRNA play an important role in hepatocellular carcinoma (HCC) progression. However, the relationship between TGF-ß and m6A in hepatocellular carcinoma (HCC) remains unclear. Here, it is found that TGF-ß can promote the liquid phase separation of METTL3, which further leads to the reduction of mRNA stability of ITIH1. As a secreted protein, ITIH1 can act as a ligand of integrin α5ß1 to antagonize fibronectin, induce the inhibition of focal adhesion kinase signaling pathway, and inhibit the progression of HCC. In the preclinical model (mouse model, patient-derived organoid, patient-derived xenografts), purified recombinant ITIH1 (r-ITIH1) protein can be targeted for HCC. More importantly, r-ITIH1 can play a synergistic role in targeting HCC with TGF-ß inhibitor. The downstream ITIH1 regulatory mechanism of TGF-ß and m6A modification is revealed, and ITIH1 can be translational as a potential target for HCC.

5.
Exp Hematol Oncol ; 13(1): 91, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39223632

RESUMEN

Although immune checkpoint-based cancer immunotherapy has shown significant efficacy in various cancers, resistance still limits its therapeutic effects. Ubiquitination modification is a mechanism that adds different types of ubiquitin chains to proteins, mediating protein degradation or altering their function, thereby affecting cellular signal transduction. Increasing evidence suggests that ubiquitination modification plays a crucial role in regulating the mechanisms of resistance to cancer immunotherapy. Drugs targeting ubiquitination modification pathways have been shown to inhibit tumor progression or enhance the efficacy of cancer immunotherapy. This review elaborates on the mechanisms by which tumor cells, immune cells, and the tumor microenvironment mediate resistance to cancer immunotherapy and the details of how ubiquitination modification regulates these mechanisms, providing a foundation for enhancing the efficacy of cancer immunotherapy by intervening in ubiquitination modification.

6.
Int J Nanomedicine ; 19: 7775-7797, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099795

RESUMEN

Purpose: The present study aimed to develop a lipid nanoplatform, denoted as "BAL-PTX-LN", co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs. Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining. Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 µg/mL vs 31.722 µg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration. Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications.


Asunto(s)
Neoplasias Pulmonares , Paclitaxel , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacología , Paclitaxel/administración & dosificación , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Humanos , Flavonoides/química , Flavonoides/farmacología , Flavonoides/farmacocinética , Flavonoides/administración & dosificación , Tamaño de la Partícula , Nanopartículas/química , Ratones , Liposomas/química , Liposomas/farmacocinética , Células A549 , Lípidos/química , Masculino , Ratones Endogámicos BALB C , Línea Celular Tumoral , Liberación de Fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacocinética , Ratones Desnudos , Hemólisis/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Antineoplásicos/administración & dosificación
7.
Mol Genet Metab Rep ; 40: 101123, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39185018

RESUMEN

Aim: To analyze the clinical phenotype and genetic etiology of three cases of glutaric aciduria type 1 (GA1) in Chinese children. Methods: We performed genetic and metabolic testing using tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), followed by trio whole-exome sequencing (trio-WES) and Sanger sequencing. A literature review on glutaric aciduria type 1 (GA1) in Chinese patients was also conducted. Results: Sequencing results showed each case had compound heterozygous variants in GCDH(NM_000159.4): c.214C > G (p.Arg72Gly) and c.411C > G (p.Tyr137Term) (Case 1), c.214C > G (p.Arg72Gly) and c.1204C > T (p.Arg402Trp) (Case 2), and c.1228G > T (p.Val410Leu) and c.395G > A (p.Arg132Gln) (Case 3). These variants were inherited from their respective parents. Notably, the c.214C > G variant found in two children was a novel variant not previously reported. A review of the literature revealed that, clinically, the majority of patients experienced onset in infancy and early childhood (82%). Additionally, 38.36% were diagnosed through newborn screening, with the primary reasons for the initial visit being delayed development (32.43%) and infections (21.61%). The most common clinical manifestations included increased head circumference (77.19%) and motor developmental delay (65.15%). Biochemically, patients exhibited significant elevations in C5DC (98.51%) and C5DC/C8 (94.87%) in blood, as well as GA (94.37%) and 3OHGA (69.39%) in urine. Radiographically, patients showed a high prevalence of abnormalities in cranial MRI (86.15%) and EEG (73.33%). Genetically, 67 distinct GCDH gene variants were identified among 73 patients, with missense variants being the most prevalent type (73.97%). The most frequent variant was c.1244-2 A > C, observed in 17.12% of cases. Additionally, the majority of variant sites were located in exons 11 (25.37%) and 6 (22.39%). Conclusion: GCDH variants were identified as the causative factors in the three children. The discovery of the novel variant (c.214C > G) expands the spectrum of pathogenic GCDH variants. These findings facilitate the diagnosis and treatment of affected children and provide a basis for genetic counseling and prenatal diagnosis for their families.

8.
Expert Opin Drug Saf ; : 1-10, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39158402

RESUMEN

BACKGROUND: As synthesis technology advances, novel and efficient derivatives of tetracyclines are found. Three new antibiotics were approved within the past 18 years, and represent a new era in the use of tetracyclines. To gain further insight into adverse events linked to tetracyclines and better protect pediatric patients, ongoing monitoring of safety data is crucial. METHODS: The FAERS data from the first quarter of 2004 to the third quarter of 2023 in the AERSMine were extracted to conduct disproportionality analysis. The association between five tetracyclines and adverse events was evaluated using reporting odds ratio, and their risk factors were explored by multivariate logistic regression analysis. RESULTS: Our study showed that thyroid gland disorders had the strongest signal in children. Patients aged 12-18 and treatment with minocycline are risk factors for thyroid adverse events (12-18: OR = 10.727 [7.113-16.177], p < 0.0001; minocycline: OR = 17.025 [10.475-27.678], p < 0.0001). Second-generation tetracycline and third-generation tetracycline ADR patterns differed. Blood fibrinogen decreased and hypofibrinogenaemia was primarily reported with tigecycline and eravacycline. CONCLUSION: This study provided basic evidence for further research on tetracyclines-related adverse events. However, the safety of third-generation tetracycline in children requires additional validation through a large-scale prospective study.

9.
Cell ; 187(18): 4877-4889.e15, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39094568

RESUMEN

Innate immune responses to microbial pathogens are regulated by intracellular receptors known as nucleotide-binding leucine-rich repeat receptors (NLRs) in both the plant and animal kingdoms. Across plant innate immune systems, "helper" NLRs (hNLRs) work in coordination with "sensor" NLRs (sNLRs) to modulate disease resistance signaling pathways. Activation mechanisms of hNLRs based on structures are unknown. Our research reveals that the hNLR, known as NLR required for cell death 4 (NRC4), assembles into a hexameric resistosome upon activation by the sNLR Bs2 and the pathogenic effector AvrBs2. This conformational change triggers immune responses by facilitating the influx of calcium ions (Ca2+) into the cytosol. The activation mimic alleles of NRC2, NRC3, or NRC4 alone did not induce Ca2+ influx and cell death in animal cells, suggesting that unknown plant-specific factors regulate NRCs' activation in plants. These findings significantly advance our understanding of the regulatory mechanisms governing plant immune responses.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Calcio , Arabidopsis/inmunología , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/química , Calcio/metabolismo , Resistencia a la Enfermedad , Inmunidad Innata , Proteínas NLR/metabolismo , Inmunidad de la Planta , Receptores Inmunológicos/metabolismo
10.
J Microbiol Biotechnol ; 34(9): 1-7, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39187451

RESUMEN

Effective isolation and sensitive detection of Pseudomonas aeruginosa (P. aeruginosa) is crucial for the early diagnosis and prognosis of various diseases, such as urinary tract infections. However, efficient isolation and simultaneous detection of P. aeruginosa remains a huge challenge. Herein, we depict a novel fluorescence assay for sensitive, enzyme-free detection of P. aeruginosa by integrating DNAzyme cascade-induced DNA tweezers and magnetic nanoparticles (MNPs)-based separation. The capture probe@MNPs is capable of accurately identifying target bacteria and transporting the bacteria signal to nucleic acid signals. Based on the DNAzyme cascade-induced DNA tweezers, the nucleic acid signals are extensively amplified, endowing the method with a high sensitivity and a low detection limit of 1 cfu/mL. In addition, the method also exhibits a wide detection of six orders of magnitudes. The proposed method could be extended to other bacteria detection by simply changing the aptamer sequence. Taking the merit of the high sensitivity, greatly minimized detection time (less than 1.5 h), enzyme-free characteristics, and stability, the proposed method could be potentially applied to diagnosing and preventing diseases caused by pathogenic bacteria.

11.
Gastroenterol Rep (Oxf) ; 12: goae067, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39027914

RESUMEN

Background: Gastric cancer brain metastasis (GCBM) represents a rare but highly aggressive malignancy. Metastatic cancer cells are highly heterogeneous and differentially remodels brain vasculature and immune microenvironments, which affects the treatment effectiveness and patient outcome. This study aimed to investigate the spatial interactions among different cell components, especially the vasculature system and the brain microenvironment of GCBM patients. Methods: We used digital spatial profiling to examine 140 regions composing tumor, immune, and brain tissues from three GCBM patients. Transcriptomic data with spatial information were analyzed for tissue areas related to different blood recruitment strategies. For validation, independent analysis of patient bulk transcriptomic data and in vivo single-cell transcriptomic data were performed. Results: Angiogenesis and blood vessel co-option co-existed within the same GCBM lesion. Tumors with high epithelial-mesenchymal transition and an enhanced transcriptomic gene signature composed of CTNNB1, SPARC, VIM, SMAD3, SMAD4, TGFB1, TGFB2, and TGFB3 were more prone to adopt blood vessel co-option than angiogenesis. Enriched macrophage infiltration, angiogenic chemokines, and NAMPT were found in angiogenic areas, while increased T cells, T cell activating cytokines, and reduced NAMPT were found in vessel co-option regions. Spatially, angiogenesis was enriched at the tumor edge, which showed higher DMBT1 expression than the tumor center. Conclusions: This study mapped the orchestrated spatial characteristics of tumor and immunological compositions that support the conventional and atypical vascularization strategies in GCBM. Our data provided molecular insights for more effective combinations of anti-vascular and immune therapies.

12.
Sensors (Basel) ; 24(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38894466

RESUMEN

Strain sensors that can rapidly and efficiently detect strain distribution and magnitude are crucial for structural health monitoring and human-computer interactions. However, traditional electrical and optical strain sensors make access to structural health information challenging because data conversion is required, and they have intricate, delicate designs. Drawing inspiration from the moisture-responsive coloration of beetle wing sheaths, we propose using Ecoflex as a flexible substrate. This substrate is coated with a Fabry-Perot (F-P) optical structure, comprising a "reflective layer/stretchable interference cavity/reflective layer", creating a dynamic color-changing visual strain sensor. Upon the application of external stress, the flexible interference chamber of the sensor stretches and contracts, prompting a blue-shift in the structural reflection curve and displaying varying colors that correlate with the applied strain. The innovative flexible sensor can be attached to complex-shaped components, enabling the visual detection of structural integrity. This biomimetic visual strain sensor holds significant promise for real-time structural health monitoring applications.

13.
Adv Sci (Weinh) ; 11(28): e2401377, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38760901

RESUMEN

Tumor-associated chronic inflammation severely restricts the efficacy of immunotherapy in cold tumors. Here, a programmable release hydrogel-based engineering scaffold with multi-stimulation and reactive oxygen species (ROS)-response (PHOENIX) is demonstrated to break the chronic inflammatory balance in cold tumors to induce potent immunity. PHOENIX can undergo programmable release of resiquimod and anti-OX40 under ROS. Resiquimod is first released, leading to antigen-presenting cell maturation and the transformation of myeloid-derived suppressor cells and M2 macrophages into an antitumor immune phenotype. Subsequently, anti-OX40 is transported into the tumor microenvironment, leading to effector T-cell activation and inhibition of Treg function. PHOENIX consequently breaks the chronic inflammation in the tumor microenvironment and leads to a potent immune response. In mice bearing subcutaneous triple-negative breast cancer and metastasis models, PHOENIX effectively inhibited 80% and 60% of tumor growth, respectively. Moreover, PHOENIX protected 100% of the mice against TNBC tumor rechallenge by electing a robust long-term antigen-specific immune response. An excellent inhibition and prolonged survival in PHOENIX-treated mice with colorectal cancer and melanoma is also observed. This work presents a potent therapeutic scaffold to improve immunotherapy efficiency, representing a generalizable and facile regimen for cold tumors.


Asunto(s)
Modelos Animales de Enfermedad , Inmunoterapia , Inflamación , Animales , Ratones , Inmunoterapia/métodos , Inflamación/inmunología , Femenino , Microambiente Tumoral/inmunología , Hidrogeles/química , Imidazoles , Línea Celular Tumoral , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/terapia
14.
Asia Pac J Clin Nutr ; 33(2): 184-193, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38794978

RESUMEN

BACKGROUND AND OBJECTIVES: This study aimed to assess the associations of maternal iron status and placental iron transport proteins expression with the risk of pre-eclampsia (PE) in Chinese pregnant women. METHODS AND STUDY DESIGN: A total of 94 subjects with PE and 112 healthy pregnant women were enrolled. Fasting blood samples were collected to detect maternal iron status. The placenta samples were collected at delivery to detect the mRNA and protein expression of divalent metal transporter 1 (DMT1) and ferroportin-1 (FPN1). Logistic analysis was used to explore the associations of maternal iron status with PE risk. The associations of placental iron transport proteins with maternal iron status were explored. RESULTS: After adjusting for covariates, dietary total iron, non-heme iron intake and serum hepcidin were negatively associated with PE, with adjusted ORs (95%CIs) were 0.40 (0.17, 0.91), 0.42 (0.18, 0.94) and 0.02 (0.002, 0.13) for the highest versus lowest tertile, respectively. For the highest tertile versus lowest tertile, serum iron (4.08 (1.58, 10.57)) and ferritin (5.61 (2.36, 13.31)) were positively associated with PE. The mRNA expressions and protein levels of DMT1 and FPN1 in placenta were up-regulated in the PE group (p < 0.05). The mRNA expressions of DMT1 and FPN1 in placenta showed a negative correlation with the serum hepcidin (r = -0.71, p < 0.001; r = -0.49, p < 0.05). CONCLUSIONS: In conclusion, the maternal iron status were closely associated with PE risk, placental DMT1 and FPN1 were upregulated in PE which may be a promising target for the prevention of PE.


Asunto(s)
Proteínas de Transporte de Catión , Hierro , Placenta , Preeclampsia , Humanos , Femenino , Embarazo , Preeclampsia/epidemiología , Preeclampsia/sangre , Estudios de Casos y Controles , Adulto , Hierro/sangre , Hierro/metabolismo , Placenta/metabolismo , Proteínas de Transporte de Catión/genética , Hepcidinas/sangre , Factores de Riesgo , China/epidemiología , Estado Nutricional
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124415, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38733918

RESUMEN

SO2 derivatives play an important role in many metabolic processes, excessive ingestion of them can lead to serious complications of various diseases. In this work, a novel dual ratiometric NIR fluorescent probe XT-CHO based on ICT effect was synthesized for detecting SO2 derivative. In the design of the probe, the α, ß-unsaturated bond formed between benzopyran and coumarin was used as the reaction site for SO2, meanwhile, the extended π-conjugate system promoted maximum emission wavelength of the probe up to 708 nm. Notably, the probe exhibited high selectivity and sensitivity for detecting SO2, the limit of detection reached 2.13 nM and 58.5 nM in fluorescence spectra and UV-Vis absorption spectra, respectively. The reaction mechanism of SO2 and XT-CHO had been verified by 1H NMR, ESI-MS spectra and DFT calculation. Moreover, the probe was successfully applied in detecting endogenous and exogenous SO2 in living cells and proved possessed the mitochondrial targeted ability.


Asunto(s)
Colorantes Fluorescentes , Mitocondrias , Dióxido de Azufre , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Dióxido de Azufre/análisis , Humanos , Mitocondrias/química , Mitocondrias/metabolismo , Espectrometría de Fluorescencia , Células HeLa , Espectroscopía Infrarroja Corta/métodos , Cumarinas/química , Cumarinas/síntesis química , Límite de Detección , Teoría Funcional de la Densidad , Imagen Óptica
16.
MedComm (2020) ; 5(5): e535, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38741887

RESUMEN

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation-specific homologous factor (EHF), a member of the E26 transformation-specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma-associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor-associated macrophages (TAMs) through the C-C motif chemokine 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co-expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF-mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2-TAMs to inhibit EHF-driven CCA development.

17.
Mol Ther Nucleic Acids ; 35(2): 102203, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38737921

RESUMEN

[This corrects the article DOI: 10.1016/j.omtn.2017.07.005.].

18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(4): 467-472, 2024 Apr 10.
Artículo en Chino | MEDLINE | ID: mdl-38565514

RESUMEN

OBJECTIVE: To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD). METHODS: Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis. RESULTS: Both children were males and had manifested mainly with hypoglycemia. Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene, namely c.49G>C (p.Gly17Arg) and c.106-2A>G, which were inherited from his father and mother, respectively. Child 2 had harbored homozygous c.199-10T>G variants of the SLC25A20 gene, which were inherited from both of his parents. Among these, the c.106-2A>G and c.49G>C variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.49G>C (p.Gly17Arg), c.106-2A>G, and c.199-10T>G variants were classified as likely pathogenic (PM2_supporting+PP3+PM3_strong+PP4), pathogenic (PVS1+PM2_supporting+PM5+PP3), and pathogenic (PVS1+PM2_supporting+PP3+PP5), respectively. CONCLUSION: Combined with their clinical phenotype and genetic analysis, both children were diagnosed with CACTD. Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.


Asunto(s)
Carnitina Aciltransferasas/deficiencia , Asesoramiento Genético , Genómica , Errores Innatos del Metabolismo Lipídico , Niño , Masculino , Femenino , Embarazo , Humanos , Linaje , Madres , Mutación , Proteínas de Transporte de Membrana
19.
RSC Adv ; 14(15): 10538-10545, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38567325

RESUMEN

Graphene-based (Gr-based) electrothermal heaters, due to their light weight, low electrical resistance, high thermal conductivity, and easy accessibility, have attracted widespread attention in the field of electrothermal heating. To achieve a high steady-state temperature in electrothermal heaters under low voltage, here we constructed a Gr-based film with low electrical resistance. Firstly, we employed non-toxic vitamin C to reduce silver nitrate for the in situ chemical deposition of silver nanoparticles (AgNPs) on the Gr surface. The SEM results confirmed that the AgNPs were uniformly deposited on the Gr surface. The synergistic interaction between AgNPs and Gr provided high-speed electrons transport paths for the film. On the other hand, we employed biodegradable lignocellulose fiber (LCF) as a dispersant and film-forming agent. The aromatic ring structure of LCF interacts with Gr via π-π interactions, aiding the dispersion of Gr in aqueous solutions. SEM results revealed that LCF permeated through the surfaces and interstices of the two-dimensional Gr sheets, providing mechanical support for the composite film. This approach enables the creation of freestanding Gr-AgNPs/LCF electrothermal composites. The resistivity and electrothermal results demonstrated that the obtained 20 wt% Gr-based composite film possessed low electrical resistance (5.4 Ω sq-1) and exhibited an outstanding saturated temperature of 214 °C under a very low input voltage of 7 V. The preparation method of this Gr-based composite film is simple, easy to operate, and environmentally friendly, providing a new reference for the preparation of eco-friendly and high-performance resistance heating electronics.

20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 306-311, 2024 Mar 10.
Artículo en Chino | MEDLINE | ID: mdl-38448019

RESUMEN

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency (OTCD) and MECP2 duplication syndrome. METHODS: A proband who was admitted to the Neonatal Intensive Care Unit of Gansu Provincial Maternal and Child Health Care Hospital on December 19, 2017 was selected as the study subject. High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were carried out for her pedigree, and short tandem repeat-based linkage analysis and chromosome copy number variation sequencing (CNV-seq) were used for the prenatal diagnosis. RESULTS: The proband, a 3-day-old female, was found to harbor heterozygous deletion of exons 7-9 of the OTC gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PVS1+PM2_Supporting+PP4). The proband was diagnosed with OTCD , which was in keeping with her acute encephalopathy and metabolic abnormalities (manifesting as hyperammonemia, decreased blood citrulline, and increased urine orotic acid). Prenatal diagnosis was carried out for the subsequent pregnancy. The fetus did not harbor the exons 7-9 deletion of the OTC gene, but was found to carry a duplication in Xq28 region (which encompassed the whole region of MECP2 duplication syndrome) and was positive for the SRY sequence. The same duplication was also found in the proband and her mother. Considering the possible existence of X-chromosome inactivation, the proband was diagnosed with two X-linked recessive disorders including OTCD and MECP2 duplication syndrome, and the fetus was determined as a male affected with the MECP2 duplication syndrome. CONCLUSION: Discoveries of the pathogenic variants underlying the OTCD and MECP2 duplication syndrome have enabled clinical intervention, treatment, genetic counseling and prenatal diagnosis for this pedigree.


Asunto(s)
Transferasas de Carboxilo y Carbamoilo , Discapacidad Intelectual Ligada al Cromosoma X , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa , Niño , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , China , Variaciones en el Número de Copia de ADN , Ornitina , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/diagnóstico , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/genética , Linaje , Diagnóstico Prenatal
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...