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1.
J Environ Sci (China) ; 149: 68-78, 2025 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39181678

RESUMEN

The presence of aluminum (Al3+) and fluoride (F-) ions in the environment can be harmful to ecosystems and human health, highlighting the need for accurate and efficient monitoring. In this paper, an innovative approach is presented that leverages the power of machine learning to enhance the accuracy and efficiency of fluorescence-based detection for sequential quantitative analysis of aluminum (Al3+) and fluoride (F-) ions in aqueous solutions. The proposed method involves the synthesis of sulfur-functionalized carbon dots (C-dots) as fluorescence probes, with fluorescence enhancement upon interaction with Al3+ ions, achieving a detection limit of 4.2 nmol/L. Subsequently, in the presence of F- ions, fluorescence is quenched, with a detection limit of 47.6 nmol/L. The fingerprints of fluorescence images are extracted using a cross-platform computer vision library in Python, followed by data preprocessing. Subsequently, the fingerprint data is subjected to cluster analysis using the K-means model from machine learning, and the average Silhouette Coefficient indicates excellent model performance. Finally, a regression analysis based on the principal component analysis method is employed to achieve more precise quantitative analysis of aluminum and fluoride ions. The results demonstrate that the developed model excels in terms of accuracy and sensitivity. This groundbreaking model not only showcases exceptional performance but also addresses the urgent need for effective environmental monitoring and risk assessment, making it a valuable tool for safeguarding our ecosystems and public health.


Asunto(s)
Aluminio , Monitoreo del Ambiente , Fluoruros , Aprendizaje Automático , Aluminio/análisis , Fluoruros/análisis , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Fluorescencia
2.
J Orthop Surg Res ; 19(1): 615, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39350218

RESUMEN

BACKGROUND: Low back pain has become a globally challenging health problem, and about 90% of cases are nonspecific. Due to the risks associated with opioid use and the limited effectiveness of drug treatment, acupuncture and other non-drug methods have become the first-line treatment for this disease. However, the best acupuncture method has not yet been determined. In this study, the effects of different acupuncture methods on chronic nonspecific low back pain (CNLBP) were compared by network meta-analysis, aiming at identifying the best option and providing a basis for precise treatment of CNLBP. METHODS: Clinical randomized controlled trials (RCTs) on acupuncture in the treatment of NSLBP were searched in eight databases including PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang Data and VIP from the inception of databases to January 21, 2024. The Cochrane risk-of-bias tool 2.0 (RoB 2.0) and Stata 15.0 (Stata Corp, College Station, Texas, USA) were used to evaluate the literature quality and meta-analysis, and the evidence quality was assessed based on GRADE guidelines. This systematic review was registered at the International Prospective Register of Systematic Reviews. RESULTS: A total of 27 articles were included, involving 2579 patients. The results of the network meta-analysis showed that the top three treatment schemes were warm needle acupuncture, intensive silver needle therapy and meridian-sinew theory-based treatment. In terms of relieving pain, the top three treatments were electrical warm needling, intensive silver needle therapy and warm needle acupuncture. In improving mobility, the top three were meridian-sinew theory-based treatment, routine acupuncture and electroacupuncture. CONCLUSION: For CNLBP patients, warm needle acupuncture, electrical warm needling and meridian-sinew theory-based treatment are mainly recommended. If patients have significant pain, electroacupuncture is strongly suggested. On the contrary, for patients with decreased joint mobility, meridian-sinew theory-based treatment is advocated.


Asunto(s)
Terapia por Acupuntura , Dolor Crónico , Dolor de la Región Lumbar , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Dolor de la Región Lumbar/terapia , Humanos , Terapia por Acupuntura/métodos , Dolor Crónico/terapia , Resultado del Tratamiento , Masculino , Femenino , Adulto , Persona de Mediana Edad
3.
Wei Sheng Yan Jiu ; 53(5): 740-745, 2024 Sep.
Artículo en Chino | MEDLINE | ID: mdl-39308105

RESUMEN

OBJECTIVE: To analyze the relationship between body mass index(BMI) and blood pressure among Tibetan primary and secondary school students in Lhasa City. METHODS: From August to October 2020, 1929 Tibetan students were selected from 12 primary and secondary schools in Lhasa City to conduct questionnaire surveys on demographic characteristics, smoking, drinking, living habits, and food consumption frequency, and physical examinations such as height, weight and blood pressure measurements. The association between BMI and blood pressure was analyzed with multivariate logistic regression model and linear regression model. RESULTS: A total of 843 boys(43.70%)and 1086 girls(56.30%)were surveyed, with an average age of(14.25±2.71) years old.925 people(47.95%)were in urban areas and 1004 people(52.05%)were in rural areas. There were 726 people(37.64%)inprimary school students, 692 people(35.87%)in junior high school, 363 people(18.82%)in high school, and 148 people(7.67%)in vocational high school. There were 541 people(28.05%)who were emaciated, 183 people(9.49%)who were overweight, and 87 people(4.51%)who were obese. The wasting, overweight and obesity rates of Tibetan primary and secondary school students were 28.05%, 9.49% and 4.51%, respectively. The high blood pressure rate was 8.76%. The BMI value of the high blood pressure group of students was higher than that of the students in the normal blood pressure group, and the difference was statistically significant(t=4.63, P<0.05). The result of the multi-factor logistic regression model showed that among the study subjects, the risk of high blood pressure, high systolic blood pressure, and high diastolic blood pressure were 3.07 times higher than those of people with normal BMI(95% CI 1.71-5.51, P<0.01), 2.83 times(95% CI 1.38-5.81, P<0.01), 4.19 times(95% CI 2.11-8.32, P<0.01). The risk of high blood pressure in overweight people was 1.17 times that of people with normal BMI(95% CI 1.04-2.84, P=0.04). The result of the linear regression model showed that mild wasting(ß=-2.41, 95% CI-3.95--0.87) and moderate to severe wasting(ß=-4.71, 95% CI-6.19--3.23) was negatively correlated with systolic blood pressure, while overweight(ß=2.56, 95% CI 0.88-4.24) and obesity(ß=5.55, 95% CI 3.20-7.91) were positively correlated with systolic blood pressure, moderate to severe wasting(ß=-2.46, 95% CI-3.88--1.04) was negatively correlated with diastolic blood pressure, and obesity(ß=3.42, 95% CI 1.16-5.68) was positively correlated with diastolic blood pressure. CONCLUSION: Obesity is positively correlated with blood pressure and high blood pressure among Tibetan primary and secondary school students.


Asunto(s)
Presión Sanguínea , Índice de Masa Corporal , Hipertensión , Estudiantes , Humanos , Masculino , Femenino , Tibet , Adolescente , Estudiantes/estadística & datos numéricos , Encuestas y Cuestionarios , Hipertensión/epidemiología , Sobrepeso/epidemiología , Instituciones Académicas , Niño , Obesidad/epidemiología , Modelos Logísticos
4.
Adv Sci (Weinh) ; : e2405997, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287090

RESUMEN

Radiotherapy is a curative arsenal for prostate cancer (PCa), but radioresistance seriously compromises its effectiveness. Dysregulated RNA splicing factors are extensively involved in tumor progression. Nonetheless, the role of splicing factors in radioresistance remains largely unexplored in PCa. Here, 23 splicing factors that are differentially expressed between PCa and adjacent normal tissues across multiple public PCa databases are identified. Among those genes, polypyrimidine tract binding protein 1 (PTBP1) is significantly upregulated in PCa and is positively associated with advanced clinicopathological features and poor prognosis. Gain- and loss-of-function experiments demonstrate that PTBP1 markedly reinforces genomic DNA stability to desensitize PCa cells to irradiation in vitro and in vivo. Mechanistically, PTBP1 interacts with the heterogeneous nuclear ribonucleoproteins (hnRNP) associated with lethal yellow protein homolog (RALY) and regulates exon 5 splicing of DNA methyltransferase 3b (DNMT3B) from DNMT3B-S to DNMT3B-L. Furthermore, upregulation of DNMT3B-L induces promoter methylation of dual-specificity phosphatase-2 (DUSP2) and subsequently inhibits DUSP2 expression, thereby increasing radioresistance in PCa. The findings highlight the role of splicing factors in inducing aberrant splicing events in response to radiotherapy and the potential role of PTBP1 and DNMT3B-L in reversing radioresistance in PCa.

5.
Nano Lett ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39315658

RESUMEN

Tumor-associated antigens (TAAs) are not exclusively expressed in cancer cells, inevitably causing the "on target, off tumor" effect of molecular recognition tools. To achieve precise recognition of cancer cells, by using protein tyrosine kinase 7 (PTK7) as a model TAA, a DNA molecular logic circuit Aisgc8 was rationally developed by arranging H+-binding i-motif, ATP-binding aptamer, and PTK7-targeting aptamer Sgc8c in a DNA sequence. Aisgc8 output the conformation of Sgc8c to recognize PTK7 on cells in a simulated tumor microenvironment characterized by weak acidity and abundant ATP, but not in a simulated physiological environment. Through in vitro and in vivo results, Aisgc8 demonstrated its ability to precisely recognize cancer cells and, as a result, displayed excellent performance in tumor imaging. Thus, our studies produced a simple and efficient strategy to construct DNA logic circuits, opening new possibilities to develop convenient and intelligent precision diagnostics by using DNA logic circuits.

6.
J Int Med Res ; 52(9): 3000605241266234, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39301802

RESUMEN

The coronavirus disease (COVID-19) SARS-CoV-2 virus epidemic continues to exhibit a sporadic onset trend due to the continuous variation of the novel coronavirus. However, the psychological impact of the pandemic persists. It is crucial to reflect on our experiences to better prepare for future large-scale infectious diseases. During outbreaks of infectious diseases, patients may still require orthopaedic surgery. It is crucial to prioritize the safety of medical staff and establish procedures to ensure their protection. However, with the implementation of a series of standardized operational protection procedures, orthopaedic surgeons can safely perform their duties without the risk of contracting COVID-19. There is no doubt that the orthopaedic occupational exposure protection process and perioperative management plan for global infectious diseases, such as COVID-19, require a standardized summarization process and a narrative review.


Asunto(s)
COVID-19 , Exposición Profesional , Atención Perioperativa , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/transmisión , Exposición Profesional/prevención & control , Exposición Profesional/efectos adversos , Atención Perioperativa/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Pandemias/prevención & control , Equipo de Protección Personal , Procedimientos Ortopédicos/efectos adversos , Control de Infecciones/métodos
7.
J Ovarian Res ; 17(1): 189, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39342320

RESUMEN

BACKGROUND: Ovarian granulosa cells (GCs) play crucial roles in follicular growth and development. Their normal function is influenced by various factors, including oxidative stress, which is a significant factor. Afamin protein is a vitamin E-specific binding protein that acts as a vitamin E carrier in follicular fluid. Although the mechanism of the protective effect of afamin on human ovarian GCs is still unclear, there is evidence it has an antioxidant effect in neuronal cells. METHODS: In this study, we investigated the protective effects of afamin proteins on testosterone propionate (TP)-induced ovarian GCs using a human ovarian tumor granulosa cell line (KGN). RESULTS: The results showed that afamin reduced TP-induced oxidative stress in KGN cells by decreasing the levels of oxidative damage markers, enhancing the activity of antioxidant enzymes, and exerting a protective effect on GCs. Supplementation with afamin repaired mitochondrial dysfunction by improving mitochondrial membrane potential damage and ATP levels. It counteracted TP-induced apoptosis by decreasing the activity of Caspase-3 and upregulating the expression of the anti-apoptotic gene (BCL-2) while downregulating the expression of the pro-apoptotic gene BCL-2-associated X protein (BAX). In addition, afamin regulated the expression of genes related to ovarian steroid hormone synthesis, ameliorating the endocrine dysfunction observed in TP-induced KGN cells. CONCLUSION: Therefore, Afamin proteins may serve as important complementary factors that protect GCs from other types of damage, such as oxidative stress, and may help improve ovarian follicle quality and female reproductive function.


Asunto(s)
Células de la Granulosa , Estrés Oxidativo , Femenino , Humanos , Estrés Oxidativo/efectos de los fármacos , Células de la Granulosa/metabolismo , Células de la Granulosa/efectos de los fármacos , Apoptosis/efectos de los fármacos , Antioxidantes/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Albúmina Sérica Humana , Proteínas Portadoras , Glicoproteínas
8.
Eur Spine J ; 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39343794

RESUMEN

PURPOSE: To evaluate the clinical efficacy of surgery in Kummell's disease (KD) to help us select the optimum surgical strategy. METHODS: We included 67 KD patients who underwent Percutaneous vertebral plasty (PVP), Percutaneous kyphosis plasty (PKP), Percutaneous pedicle screw fixation (PPSF) or Posterior decompression osteotomy fixation (PDOF). The differences in imaging parameters and prognosis changes of pre-operation, post-operative and follow-up endpoint were analyzed. RESULTS: The incidence rate of KD was 10.02% (67/668) in vertebral compressibility fracture. 80.60% of patients underwent PVP/PKP, 14.93% underwent PPSF, and 4.47% underwent PDOF. The significant differences between the actual used surgical methods and the classification recommended surgical strategies could be found. In I type, there was no significant difference in total improvement of the radiography data and clinical efficacy between PVP and PKP. In II type, there was a significant correlation between opening and closing sign (OCS) and surgical choice. Compared with PPSF, the positive OCS patients who underwent PVP/PKP suffered a poor prognosis. PDOF is an effective surgical method for type III, but PVP could also achieve a good prognosis for patients with poor condition. CONCLUSION: The mainstream KD classification system has shortcomings, and completely following its treatment strategy may lead to poor prognosis. Compared to PKP, PVP is a better choice for type I patients. OCS is one of the important factors in surgical selection for type II patients. The Li's type III is mainly treated with PDOF but the overall condition of the body needs to be evaluated.

9.
Sci Rep ; 14(1): 22657, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39349519

RESUMEN

This study aims to objectively assess the effect of three surgical approaches for posterior uterine fibroid resection: transumbilical laparoendoscopic single-site surgery (LESS), vaginal natural orifice transluminal endoscopic surgery (vNOTES) in prone position (vNOTES-P), and vNOTES in the lithotomy position (vNOTES-L). A retrospective analysis was conducted on data pertaining to all patients who underwent vNOTES and LESS for single posterior fibroids at our institution from January 2023 to July 2023. Patients were categorized into three groups based on the surgical approach: vNOTES-P group (n = 30), vNOTES-L group (n = 17), and LESS group (n = 32). Comparative analysis was performed on the demographic characteristics and perioperative outcomes among the three groups of patients. All 79 patients underwent surgery without the need for conversion to laparotomy. There were no statistically significant differences among the LESS group, vNOTES-P group, and vNOTES-L group in terms of operative time, intraoperative blood loss, and perioperative complication rates. In the vNOTES-L group, two patients required conversion to LESS during surgery. Patients had faster return of bowel function (less time to flatus) in the vNOTES group compared to the LESS group (P < 0.05). However, three cases of postoperative infection occurred in the vNOTES group, while none were reported in the LESS group. Compared to LESS, vNOTES demonstrates significant advantages in alleviating postoperative pain, shortening time to passage of flatus, speeding recovery and enhancing cosmetic outcomes. Particularly, vNOTES-P for posterior uterine fibroid resection, as an emerging surgical approach, offers certain advantages in facilitating surgical maneuverability and reducing operative time, rendering it more suitable for posterior uterine fibroid resection.


Asunto(s)
Laparoscopía , Leiomioma , Neoplasias Uterinas , Humanos , Femenino , Leiomioma/cirugía , Leiomioma/patología , Laparoscopía/métodos , Adulto , Estudios Retrospectivos , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Persona de Mediana Edad , Tempo Operativo , Cirugía Endoscópica por Orificios Naturales/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pérdida de Sangre Quirúrgica/estadística & datos numéricos
10.
Curr Drug Targets ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39323343

RESUMEN

SERCA2, a P-type ATPase located on the endoplasmic reticulum of cells, plays an important role in maintaining calcium balance within cells by transporting calcium from the cytoplasm to the endoplasmic reticulum against its concentration gradient. A multitude of studies have demonstrated that the expression of SERCA2 is abnormal in a wide variety of tumor cells. Consequently, research exploring compounds that target SERCA2 may offer a promising avenue for the development of novel anti-tumor drugs. This review has summarized the anti-tumor compounds targeting SERCA2, including thapsigargin, dihydroartemisinin, curcumin, galangin, etc. These compounds interact with SERCA2 on the endoplasmic reticulum membrane, disrupting intracellular calcium ion homeostasis, leading to tumor cell apoptosis, autophagy and cell cycle arrest, ultimately producing anti-tumor effects. Additionally, several potential research directions for compounds targeting SERCA2 as clinical anti-cancer drugs have been proposed in the review. In summary, SERCA2 is a promising anti-tumor target for drug discovery and development.

11.
Artículo en Inglés | MEDLINE | ID: mdl-39303016

RESUMEN

Tumor necrosis factor-α (TNF-α) plays a causal role in the pathogenesis of ulcerative colitis (UC), and anti-TNF-α siRNA shows great promise in UC therapy. However, delivering siRNA with site-targeted stability and therapeutic efficacy is still challenging due to the complex and dynamic intestinal microenvironment. Here, based on the functional plant-derived ginger extracellular vesicles (EVs) and porous ZIF-8 nanoparticles, we propose a novel TNF-α siRNA delivery strategy (EVs@ZIF-8@siRNA) for UC targeted therapy. Ginger EVs show strong colon and macrophage targeting, as well as robust resistance to acidic degradation in the stomach. Moreover, 6-shogaol in ginger-derived EVs displays anti-inflammatory effects, which enhance the treatment efficiency by cooperation with TNF-α siRNA. In vitro experiments reveal that ZIF-8 nanoparticles have high TNF-α siRNA loading capacity and promote siRNA escape from cellular lysosomes. In vivo experiments show that the TNF-α level is reduced more significantly in colonic tissue than other nontargeted inflammation related factors, showing a good targeting of this composite nanoparticle. Furthermore, gut microbiota sequencing results demonstrate that the nanoparticles can promote intestinal barrier repair by regulating the intestinal microbial balance and restoring the intestinal health of UC mice. Therefore, the developed EVs@ZIF-8@siRNA nanoparticles may represent a novel colon-targeted oral drug, providing a promising therapeutic strategy for UC therapy.

12.
Nat Commun ; 15(1): 7824, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39242636

RESUMEN

Tumour detection with high selectivity and sensitivity is crucial for delineating tumour margins and identifying metastatic foci during image-guided surgery. Optical nanoprobes with preferential tumour accumulation is often limited by inefficient amplification of biological signals. Here, we report the design of a library of hydrophobic core-tunable ultra-pH-sensitive nanoprobes (HUNPs) for orthogonally amplifying tumour microenvironmental signals on multiple tumour models. We find that tuning the hydrophobicity of nanoparticle core composition with non-ionizable monomers can enhance cellular association of HUNPs by more than ten-fold, resulting in a high cellular internalization efficiency of HUNPs with up to 50% in tumours. Combining high tumour accumulation and high cell internalization efficiency, HUNPs show orthogonally amplified fluorescence signals, permitting the precise locating and delineating margins between malignant lesions and normal tissues with high contrast-to-noise ratio and resolution. Our study provides key strategies to design nanomedicines with high intracellular bioavailability for cancer detection, drug/gene delivery, and therapy.


Asunto(s)
Nanopartículas , Nanopartículas/química , Animales , Humanos , Línea Celular Tumoral , Ratones , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Imagen Óptica/métodos , Microambiente Tumoral , Femenino , Interacciones Hidrofóbicas e Hidrofílicas , Concentración de Iones de Hidrógeno , Ratones Desnudos , Colorantes Fluorescentes/química , Fluorescencia
13.
Medicine (Baltimore) ; 103(36): e39464, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252309

RESUMEN

To more accurately diagnose and treat patients with different subtypes of thyroid cancer, we constructed a diagnostic model related to the iodine metabolism of THCA subtypes. THCA expression profiles, corresponding clinicopathological information, and single-cell RNA-seq were downloaded from TCGA and GEO databases. Genes related to thyroid differentiation score were obtained by GSVA. Through logistic analyses, the diagnostic model was finally constructed. DCA curve, ROC curve, machine learning, and K-M analysis were used to verify the accuracy of the model. qRT-PCR was used to verify the expression of hub genes in vitro. There were 104 crossover genes between different TDS and THCA subtypes. Finally, 5 genes (ABAT, CHEK1, GPX3, NME5, and PRKCQ) that could independently predict the TDS subpopulation were obtained, and a diagnostic model was constructed. ROC, DCA, and RCS curves exhibited that the model has accurate prediction ability. K-M and subgroup analysis results showed that low model scores were strongly associated with poor PFI in THCA patients. The model score was significantly negatively correlated with T cell follicular helper. In addition, the diagnostic model was significantly negatively correlated with immune scores. Finally, the results of qRT-PCR corresponded with bioinformatics results. This diagnostic model has good diagnostic and prognostic value for THCA patients, and can be used as an independent prognostic indicator for THCA patients.


Asunto(s)
Yodo , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Biología Computacional/métodos , Femenino , Masculino , Aprendizaje Automático , Persona de Mediana Edad , Glándula Tiroides/patología , Glándula Tiroides/metabolismo , Curva ROC , Diferenciación Celular , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo
14.
bioRxiv ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39253432

RESUMEN

Background: Radiotherapy (RT) is the primary treatment for diffuse midline glioma (DMG), a lethal pediatric malignancy defined by histone H3 lysine 27-to-methionine (H3K27M) mutation. Based on the loss of H3K27 trimethylation producing broad epigenomic alterations, we hypothesized that H3K27M causes a functional double-strand break (DSB) repair defect that could be leveraged therapeutically with PARP inhibitor and RT for selective radiosensitization and antitumor immune responses. Methods: H3K27M isogenic DMG cells and orthotopic brainstem DMG tumors in immune deficient and syngeneic, immune competent mice were used to evaluate the efficacy and mechanisms of PARP1/2 inhibition by olaparib or PARP1 inhibition by AZD9574 with concurrent RT. Results: H3K27M mutation caused an HRR defect characterized by impaired RT-induced K63-linked polyubiquitination of histone H1 and inhibition of HRR protein recruitment. H3K27M DMG cells were selectively radiosensitized by olaparib in comparison to isogenic controls, and this effect translated to efficacy in H3K27M orthotopic brainstem tumors. Olaparib and RT induced an innate immune response and induction of NK cell (NKG2D) activating ligands leading to increased NK cell-mediated lysis of DMG tumor cells. In immunocompetent syngeneic orthotopic DMG tumors, either olaparib or AZD9574 in combination with RT enhanced intratumoral NK cell infiltration and activity in association with NK cell-mediated therapeutic responses and favorable activity of AZD9574. Conclusions: The HRR deficiency in H3K27M DMG can be therapeutically leveraged with PARP inhibitors to radiosensitize and induce an NK cell-mediated antitumor immune response selectively in H3K27M DMG, supporting the clinical investigation of best-in-class PARP inhibitors with RT in DMG patients. Key points: H3K27M DMG are HRR defective and selectively radiosensitized by PARP inhibitor.PARP inhibitor with RT enhances NKG2D ligand expression and NK cell-mediated lysis.NK cells are required for the therapeutic efficacy of PARP inhibitor and RT. Importance of the Study: Radiotherapy is the cornerstone of H3K27M-mutant diffuse midline glioma treatment, but almost all patients succumb to tumor recurrence with poor overall survival, underscoring the need for RT-based precision combination therapy. Here, we reveal HRR deficiency as an H3K27M-mediated vulnerability and identify a novel mechanism linking impaired RT-induced histone H1 polyubiquitination and the subsequent RNF168/BRCA1/RAD51 recruitment in H3K27M DMG. This model is supported by selective radiosensitization of H3K27M DMG by PARP inhibitor. Notably, the combination treatment results in NKG2D ligand expression that confers susceptibility to NK cell killing in H3K27M DMG. We also show that the novel brain penetrant, PARP1-selective inhibitor AZD9574 compares favorably to olaparib when combined with RT, prolonging survival in a syngeneic orthotopic model of H3K27M DMG. This study highlights the ability of PARP1 inhibition to radiosensitize and induce an NK cell-mediated antitumor immunity in H3K27M DMG and supports future clinical investigation.

15.
ACS Biomater Sci Eng ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39253844

RESUMEN

Photothermal therapy (PTT) provides a great prospect for noninvasive cancer therapy. However, it is still highly challenging to construct photothermal agents (PTAs) with the desired performances for imaging-guided PTT applications. Herein, a D-A-D-type naphthalene diamine (NDI)-based photothermal nano-PTAs NDS-BPN NP with near-infrared region (NIR) emission at 822 nm, aggregation-induced emission (AIE), high photothermal conversion efficiency (55.05%), and excellent photothermal stability is successfully designed and prepared through a simple two-step engineering method by using a new AIE molecule NDS-BPN and DSPE-PEG2000 as precursors. The prepared PTT nanoagents NDS-BPN NPs have been further applied for efficient photothermal ablation of cancer cells in vitro and also achieved the NIR fluorescent image-guided PTT tumor therapy in vivo with satisfactory results. We believe that this work provides an attractive NIR AIE NDI-based nano-PTA for the phototherapy of tumors as well as develops the construction strategy of NDI molecular-based photothermal nanoagents with desired performances for imaging-guided PTT.

16.
BMC Oral Health ; 24(1): 1051, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245715

RESUMEN

Dental implant restoration shows an effective method for the rehabilitation of missing teeth. The failure rate of periodontal implants in patients with chronic periodontitis is associated with periodontal flora, inflammation, and long-term periodontal bone resorption caused by chronic periodontitis. However, the therapeutic effects of dental implant restoration on inflammation in patients with chronic periodontitis have not addressed. The purpose of this study is to evaluate the risk indicators for inflammation, bone loss and implant failure in patients with chronic periodontitis. A total of 284 patients with dental implant restoration were recruited and divided into periodontally healthy patients (n = 128) and chronic periodontitis patients (n = 156). Periodontal indices including probing depth (PD), sulcus bleeding index (SBI), plaque index (PLI), gingival bleeding (GIL) and bleeding on probing (BOP) were compared in two groups. Inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) levels at baseline, 6 and 12 months after surgery, and the implant survival rate at 12 months after surgery, as well as the risk factors associated with failure of dental implant were also assessed. Outcomes demonstrated that patients in the chronic periodontitis group had higher values of periodontal indices than those in the periodontally healthy group. All inflammatory parameters in the chronic periodontitis group were higher than those in the periodontally healthy group and negatively associated with the chronic periodontal index (CPI) in chronic periodontitis patients. Chronic periodontitis patients had higher the prevalence of mucositis and peri-implantitis than patients with healthy periodontium. Implant diameter, length and design was associated with the risk of implant failure for chronic periodontitis patients receiving dental implant. The cumulative implant failure rate and incidence of implant fractures for chronic periodontitis patients at 12 months after surgery were 12.10% and 7.23% (p < 0.05), respectively, while were lower in the heathy periodontitis patients. Location, diameter, implant design, immediate loading and bone defect were risk indicators for bone loss for dental implant patients. The risk factors associated with failure of dental implant was higher in chronic periodontitis patients than patients in the periodontally healthy group (14.25% vs. 4.92%, p < 0.05). In conclusion, data in the current study indicate that inflammation is a risk indicator bone loss, implant fracture and implant failure in patients with chronic periodontitis.


Asunto(s)
Periodontitis Crónica , Implantes Dentales , Fracaso de la Restauración Dental , Índice Periodontal , Humanos , Periodontitis Crónica/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Factores de Riesgo , Implantes Dentales/efectos adversos , Adulto , Pérdida de Hueso Alveolar/etiología , Citocinas , Metaloproteinasa 9 de la Matriz , Interleucina-6/sangre
17.
ACS Macro Lett ; : 1233-1239, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258749

RESUMEN

Oxygen-independent alkyl radicals (R•) have demonstrated great promise in combating tumor hypoxia. Currently, Azo compounds have been the primary source of R•, suffering from external stimuli and decomposition during circulation. Herein, we developed a self-catalytic ATRP nanoinitiator that could generate R• via glutathione (GSH) reduction and thus selectively induce apoptosis of tumor cells. Specifically, a conjugation of laccase (possessing a copper(II) complex) and polymeric alkyl bromide, poly(iBBr), was fabricated to yield an ATRP nanoinitiator (Lac-P(iBBr)). After internalization by cells featured with overexpressed GSH, copper(II) in Lac-P(iBBr) was reduced to copper(I) by GSH, which abstracted the Br atom in poly(iBBr) to yield toxic R•. Moreover, GSH-depletion intensified the oxidative damage caused by R•. Efficient generation of R• by Lac-P(iBBr) could happen in lab flasks, living cells, and tumor-bearing mice without any external stimuli, as demonstrated by the radical product, as well as the consumption of GSH. Moreover, the self-catalytic ATRP nanoinitiator significantly induced cell apoptosis and suppressed tumor growth. Our study expands the chemical toolbox to manipulate cell fates.

18.
Adv Mater ; : e2409390, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39344856

RESUMEN

Electrochemical CO2 reduction reaction (CO2RR) offers a promising approach to close the carbon cycle and reduce reliance on fossil fuels. However, traditional decoupled CO2RR processes involve energy-intensive CO2 capture, conversion, and product separation, which increases operational costs. Here, we report the development of a bismuth-poly(ionic liquid) (Bi-PIL) hybrid catalyst that exhibits exceptional electrocatalytic performance for CO2 conversion to formate. The Bi-PIL catalyst achieves over 90% Faradaic efficiency for formate over a wide potential range, even at low 15% v/v CO2 concentrations typical of industrial flue gas. The biphenyl in PIL backbone affords hydrophobicity while maintaining high ionic conductivity, effectively mitigating the flooding issues. The PIL layer plays a crucial role as a CO2 concentrator and co-catalyst that accelerates the CO2RR kinetics. Furthermore, we demonstrate the potential of Bi-PIL catalysts in a solid-state electrolyte (SSE) electrolyzer for the continuous and direct production of pure formic acid solutions from flue gas. Techno-economic analysis suggests that this integrated process can produce formic acid at a significantly reduced cost compared to the traditional decoupled approaches. This work presents a promising strategy to overcome the challenges associated with low-concentration CO2 utilization and streamline the production of valuable liquid fuels and chemicals from CO2.

19.
Int J Mol Sci ; 25(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39273700

RESUMEN

Swietenia macrophylla fruit is a valuable and historically significant medicinal plant with anti-hypertension and anti-diabetes. We identified a toxic component, Febrifugin, from the edible part of the nut following zebrafish toxicity-guided isolation. Febrifugin is a mexicanolide-type limonoid compound. The toxic factor induced acute toxicity in zebrafish, including yolk sac edema and pericardial edema, reduced body length, decreased melanin deposition, and presented acute skeletal developmental issues. Further exploration of the acute toxicity mechanism through metabolomics revealed that Febrifugin caused significant changes in 13 metabolites in zebrafish larvae, which are involved in the pentose phosphate, tricarboxylic acid (TCA) cycle, and amino acid biosynthesis. The bioassay of oxidative stress capacity and qRT-PCR measurement showed that the compound significantly affected the h6pd gene in the pentose phosphate pathway and the mRNA expression of cs, idh3a, fh, and shda genes in the TCA cycle, leading to reactive oxygen species (ROS) accumulation and a notable decrease in glutathione (GSH) activity in zebrafish. These findings provide a basis for the rational use of S. macrophylla as a medicinal plant and raise awareness of the safety of medicinal plants.


Asunto(s)
Metabolómica , Pez Cebra , Animales , Pez Cebra/metabolismo , Metabolómica/métodos , Estrés Oxidativo/efectos de los fármacos , Meliaceae/química , Limoninas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Nueces/química , Larva/efectos de los fármacos , Larva/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Metaboloma , Plantas Medicinales/química , Ciclo del Ácido Cítrico/efectos de los fármacos , Glutatión/metabolismo
20.
Chin Med J (Engl) ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39261986

RESUMEN

BACKGROUND: Thyroid cancer (TC) is the most common malignancy of the endocrine system. This study aimed to assess the global distribution of TC incidence and mortality in 2022, as well as to predict the burden for the year 2050. METHODS: Data from the GLOBOCAN 2022 database were used to analyze the age-standardized incidence and mortality rates of TC by sex, age group (<55 years and ≥55 years), country, world region, and level of Human Development Index (HDI) for 185 countries. The predicted incidence and mortality burden for 2050 was calculated based on demographic projections. RESULTS: In 2022, an estimated 821,214 new TC cases and 47,507 TC-related deaths occurred worldwide. The age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were higher in women (ASIR: 13.60 per 100,000; ASMR: 0.53 per 100,000) than in men (ASIR: 4.60 per 100,000; ASMR: 0.35 per 100,000). The ASIR in high HDI countries was approximately ten times higher than that in low HDI countries for both sexes, with relatively similar ASMR across regions. Among 185 countries, China had the largest number of TC cases (accounting for 56.77% of total cases) and TC-related deaths (accounting for 24.35% of global TC-related deaths), with the highest ASIR in men (13.30 per 100,000). Worldwide, approximately 64.63% of TC cases occurred in populations under 55 years old, while nearly 82.99% of TC-related deaths occurred in populations aged 55 years and above. If the rates stay the same as in 2022, it is projected that approximately 1,100,000 new TC cases and 91,000 TC-related deaths will occur in 2050, indicating a 34.15% and 89.58% increase, respectively. CONCLUSIONS: TC is a highly frequent cancer worldwide with disparities across regions, genders, and age groups. Our results provide light on the worldwide TC disease burden and facilitate regionally customized prevention measures.

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