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1.
Case Rep Womens Health ; 42: e00616, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38779129

RESUMO

Objective: This report summarizes the characteristics of a series of 8 recent (2020-2022) patients with abdominal wall endometriosis (AWE) who underwent laparoscopic surgery. The feasibility and advantages of laparoscopy in the treatment of AWE are set out. Methods: The clinical data of the 8 AWE patients were retrospectively analysed. Basic clinical characteristics, operation details and postoperative details were collected and analysed. Results: Laparoscopic treatment was successful in all 8 cases. The mean operation time was 212.13 ± 48.16 min, the mean estimated blood loss was 25.00 ± 11.18 ml, and the mean postoperative hospital stay was 5.25 ± 1.39 days. 7 of the patients were found to have concomitant pelvic endometriosis, and 1 patient was found to have concealed inguinal hernias during surgery. Concomitant laparoscopic surgery for pelvic lesions was performed, including electrocautery or lesion resection of the pelvic endometriosis lesions in 7 patients, uterine fibroidectomy in 2 patients, high ligation of the hernia sac in 1 patient and endometrial biopsy under hysteroscopy in 1 patient. Endometrial-like tissue was confirmed by postoperative pathological examination of resected AWE lesions in all patients. There were no intraoperative or postoperative complications. The mean follow-up time was 18.75 ± 3.96 months, and no recurrence of AWE was found. Conclusion: Laparoscopic surgery is a safe, effective and feasible treatment option for AWE patients and has the advantages of simultaneous diagnosis and treatment of other pelvic lesions.

2.
PeerJ ; 12: e17136, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590707

RESUMO

The germinations of three common buckwheat (Fagopyrum esculentum) varieties and two Tartary buckwheat (Fagopyrum tataricum) varieties seeds are known to be affected by high temperature. However, little is known about the physiological mechanism affecting germination and the effect of melatonin (MT) on buckwheat seed germination under high temperature. This work studied the effects of exogenous MT on buckwheat seed germination under high temperature. MT was sprayed. The parameters, including growth, and physiological factors, were examined. The results showed that exogenous MT significantly increased the germination rate (GR), germination potential (GP), radicle length (RL), and fresh weight (FW) of these buckwheat seeds under high-temperature stress and enhanced the content of osmotic adjustment substances and enzyme activity. Comprehensive analysis revealed that under high-temperature stress during germination, antioxidant enzymes play a predominant role, while osmotic adjustment substances work synergistically to reduce the extent of damage to the membrane structure, serving as the primary key indicators for studying high-temperature resistance. Consequently, our results showed that MT had a positive protective effect on buckwheat seeds exposed to high temperature stress, providing a theoretical basis for improving the ability to adapt to high temperature environments.


Assuntos
Fagopyrum , Melatonina , Germinação , Melatonina/farmacologia , Fagopyrum/química , Temperatura , Sementes/química
3.
Front Cell Dev Biol ; 12: 1331759, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650895

RESUMO

Background: Polyamine modification patterns in lung adenocarcinoma (LUAD) and their impact on prognosis, immune infiltration, and anti-tumor efficacy have not been systematically explored. Methods: Patients from The Cancer Genome Atlas (TCGA) were classified into subtypes according to polyamine metabolism-related genes using the consensus clustering method, and the survival outcomes and immune profile were compared. Meanwhile, the geneCluster was constructed according to the differentially expressed genes (DEGs) of the subtypes. Subsequently, the polyamine metabolism-related score (PMRS) system was established using the least absolute shrinkage and selection operator (LASSO) multivariate regression analysis in the TCGA training cohort (n = 245), which can be applied to characterize the prognosis. To verify the predictive performance of the PMRS, the internal cohort (n = 245) and the external cohort (n = 244) were recruited. The relationship between the PMRS and immune infiltration and antitumor responses was investigated. Results: Two distinct patterns (C1 and C2) were identified, in which the C1 subtype presented an adverse prognosis, high CD8+ T cell infiltration, tumor mutational burden (TMB), immune checkpoint, and low tumor immune dysfunction and exclusion (TIDE). Furthermore, two geneClusters were established, and similar findings were observed. The PMRS, including three genes (SMS, SMOX, and PSMC6), was then constructed to characterize the polyamine metabolic patterns, and the patients were divided into high- and low-PMRS groups. As confirmed by the validation cohort, the high-PMRS group possessed a poor prognosis. Moreover, external samples and immunohistochemistry confirmed that the three genes were highly expressed in tumor samples. Finally, immunotherapy and chemotherapy may be beneficial to the high-PMRS group based on the immunotherapy cohorts and low half-maximal inhibitory concentration (IC50) values. Conclusion: We identified distinct polyamine modification patterns and established a PMRS to provide new insights into the mechanism of polyamine action and improve the current anti-tumor strategy of LUAD.

4.
ACS Chem Biol ; 19(3): 654-659, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38331720

RESUMO

Extracellular soluble proteins are key agents in the development of various diseases. However, strategies to remove therapeutically relevant extracellular targets are still scarce. Here, we establish dendronized DNA chimera (DENTAC) as an efficient approach for targeted degradation of the extracellular protein of interest (ePOI). DENTAC consists of a DNA dendron against cell-surface scavenger receptors (SRs), a protein ligand, and a connecting linker, which harnesses SRs as a lysosome-trafficking receptor to mediate the lysosomal degradation of the ePOI. We interrogate and optimize structure-activity relationships of DENTAC. Using neutravidin as a model ePOI, we show that both branch number and DNA length in the DNA dendron are important determinants for efficient lysosomal delivery and degradation of the protein. We demonstrate three branches and 10 nucleotide-length polythymidine as the optimal DNA dendron components to construct DENTAC. We further exemplify the anticancer application of DENTAC by targeting matrix metalloproteinase-9 (MMP-9), where we find linker property as another factor important for DENTAC performance. We reveal that MMP-9-targeting DENTAC effectively restrain cancer cell proliferation, migration, and invasion. This study thus provides a potent strategy to delete extracellular proteins that are commonly difficult to target.


Assuntos
Dendrímeros , Metaloproteinase 9 da Matriz , Proteólise , Dendrímeros/farmacologia , Proliferação de Células , DNA
5.
ACS Omega ; 9(4): 4317-4323, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38313510

RESUMO

Benzo[a]pyrene (B[a]P) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) are widespread environmental pollutants and can destroy thyroid function. We assessed the biochemical changes in the thyroid tissue of rats exposed to B[a]P and BDE-47 using attenuated total reflection Fourier-transform infrared spectroscopy combined with support vector machine(SVM). After B[a]P and BDE-47 treatment in rats, the structure of thyroid follicles was destroyed and epithelial cells were necrotic, indicating that B[a]P and BDE-47 may lead to changes of the thyroid morphology of the rats. These damages are mainly related to C=O stretch vibrations of lipids (1743 cm-1), as well as the secondary structure of proteins [amide I (1645 cm-1) and amide II (1550 cm-1)], and carbohydrates [C-OH (1138 cm-1), C-O (1106 cm-1, 1049 cm-1, 991 cm-1), C-C (1106 cm-1) stretching] and collagen (phosphodiester stretching at 922 cm-1) vibration modes. When SVM was used for classification, there was a substantial separation between the control and the exposure groups (accuracy = 96%; sensitivity = 98%; specificity = 87%), and there was also a major separation between the exposed groups (accuracy = 93%; sensitivity = 94%; and specificity = 92%).

6.
Int J Pharm ; 649: 123657, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38040398

RESUMO

Reactive oxygen species (ROS) can not only induce cellular oxidative stress, but also trigger antitumor immune response. However, single ROS generated therapy is usually not enough to induce efficient antitumor immune response. Furthermore, the adaptive antioxidant mechanisms coupled with overexpressed ROS can also decrease the antitumor capacity of ROS therapy. To circumvent this problem, we designed a synergistic strategy for inducing robust ROS based ICD effect by constructing a coloaded liposomes (PPA, Pyropheophorbide-alpha and SHK, shikonin) with Fe3+ gradient to simultaneously enhance ROS mediated oxidative stress and glutathione depletion. Interestingly, the coloaded liposome possesses an acid/GSH dual triggered release profile. More importantly, with the help of depleting GSH, LipoPS (coloaded liposome of SHK and PPA) can excite robust ROS and demonstrate synergistic antitumor efficacy with amplified ICD effect. Summarized, the established coloaded liposome LipoPS exhibits good therapeutic security and synergistic antitumor effect with strong antitumor immune activation, providing potential for further development.


Assuntos
Morte Celular Imunogênica , Lipossomos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Glutationa/metabolismo
7.
Sci China Life Sci ; 67(4): 698-710, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38151609

RESUMO

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets. c-Myc is hyperactivated in the majority of TNBC tissues, however, it has been considered an "undruggable" target due to its disordered structure. Herein, we developed an ultrasound-responsive spherical nucleic acid (SNA) against c-Myc and PD-L1 in TNBC. It is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA (siRNA) shell and a hydrophobic core made of a peptide nucleic acid (PNA)-based antisense oligonucleotide (ASO) and a sonosensitizer. We accomplished significant enrichment in the tumor by enhanced permeability and retention (EPR) effect, the controllable release of effective elements by ultrasound activation, and the combination of targeted therapy, immunotherapy and physiotherapy. Our study demonstrated significant anti-tumoral effects in vitro and in vivo. Mass cytometry showed an invigorated tumor microenvironment (TME) characterized by a significant alteration in the composition of tumor-associated macrophages (TAM) and decreased proportion of PD-1-positive (PD-1+) T effector cells after appropriate treatment of the ultrasound-responsive SNA (USNA). Further experiments verified that tumor-conditioned macrophages residing in the TME were transformed into the anti-tumoral population. Our finding offers a novel therapeutic strategy against the "undruggable" c-Myc, develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.


Assuntos
Ácidos Nucleicos , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antígeno B7-H1/genética , Receptor de Morte Celular Programada 1 , Macrófagos/patologia , Microambiente Tumoral , Linhagem Celular Tumoral
8.
BMJ Open ; 13(11): e076694, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37977876

RESUMO

OBJECTIVES: This study aimed to analyse trends in the prevalence and economic burden of hypertension and its socioeconomic disparities in rural southwestern China. DESIGN: Two repeated cross-sectional studies were conducted to collect interview and health examination data among individuals aged ≥35 years in rural Yunnan Province, China. SETTING: Three rural areas of Yunnan, China. PARTICIPANTS: We invited 8187 consenting participants in 2010-2011 and 7572 consenting participants in 2020-2021 to undergo interviews and health examinations. RESULTS: The standardised prevalence of hypertension significantly increased from 26.1% in 2011 to 40.4% in 2021 (p<0.01), and the per capita direct, indirect and disease economic burdens increased from US$1323, US$46 and US$1369 to US$2196, US$49 and US$2244, respectively. In addition to the indirect economic burden, the direct and disease economic burdens increased significantly. The prevalence of hypertension was higher in illiterate population, among participants with low annual household income per capita, and participants with good access to medical services than in their counterparts who had good education, high annual household income per capita and poor access to medical services (all p<0.05). Moreover, the prevalence of hypertension showed a downward trend with improvement in socioeconomic position (SEP) (p<0.05). The per capita direct and disease economic burdens increased most in participants with low SEP, but the per capita indirect economic burden increased most in participants with upper-middle SEP. CONCLUSIONS: The prevalence and economic burden of hypertension have visibly accelerated in rural Yunnan Province over the 10 years studied, and socioeconomic disparities have been found in the prevalence and economic burden of hypertension. These findings highlight that socioeconomic differentials should be tailored to address the timing of effective interventions for hypertension prevention and control and reduce the economic burden of hypertension in rural southwestern China.


Assuntos
Estresse Financeiro , Hipertensão , Humanos , Estudos Transversais , Disparidades Socioeconômicas em Saúde , Prevalência , China/epidemiologia , Hipertensão/epidemiologia , População Rural , Fatores Socioeconômicos
9.
J Plant Physiol ; 291: 154122, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37979433

RESUMO

Poplar, as a typical woody plant, is an ideal raw material for the production of lignocellulose biofuel. However, the longer life cycle is not conducive to the rapid identification of poplar genes. At present, protoplasts have been used for gene function identification and high-throughput analysis in many model plants. In this paper, a simplified and efficient protoplast isolation and transient expression system of Populus (Populus × xiaohei T. S. Hwang et Liang) is described. Firstly, we proposed an efficient enzyme hydrolysis method for isolating protoplasts from leaves of Populus × xiaohei. Secondly, we optimized the conditions of protoplast transformation mediated by PEG, and established an efficient transient expression system of protoplasts of Populus × xiaohei. Finally, the subcellular localization of three identified Dof transcription factors (PnDof19, PnDof20 and PnDof30) was also observed in the nucleus by using this scheme, which proved that the method was feasible. In general, this efficient method of protoplast isolation and transformation can be used for the study of protein subcellular localization and can be applied to other fields of molecular biology, such as protein interaction, gene activation and so on.


Assuntos
Populus , Populus/genética , Protoplastos/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas/genética , Fenótipo
11.
Polymers (Basel) ; 15(20)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37896309

RESUMO

Recently, material extrusion (MEX) 3D printing technology has attracted extensive attention. However, some high-performance thermoplastic polymer resins, such as polycarbonate (PC), cannot be processed by conventional MEX printing equipment due to poor processing performance. In order to develop new PC-based printing materials suitable for MEX, PC/poly(butylene adipate-co-terephthalate) (PBAT) blends were prepared using a simple polymer blending technique. It was found that the addition of PBAT component significantly improved processing performance of the PC, making the blends processable at 250 °C. More importantly, the PC was completely compatible with the PBAT, and the PBAT effectively reduced the Tg of the blends, endowing the blends with essential 3D printing performance. Furthermore, methyl methacrylate-butadiene-styrene terpolymer (MBS) was introduced into the PC/PBAT blends to improve toughness. SEM observations demonstrated that MBS particles, as stress concentration points, triggered shear yielding of polymer matrix and absorbed impact energy substantially. In addition, the MBS had little effect on the 3D printing performance of the blends. Thus, a PC/PBAT/MBS blend system with favorable comprehensive mechanical properties and 3D printing performance was achieved. This work can provide guidance for the development of novel MEX printing materials and is of great significance for expanding the variety of MEX printing materials.

12.
Endocrinol Metab (Seoul) ; 38(5): 504-521, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37749800

RESUMO

Maintenance of skeletal integrity requires the coordinated activity of multinucleated bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts form resorption lacunae on bone surfaces in response to cytokines by fusion of precursor cells. Osteoblasts are derived from mesenchymal precursors and lay down new bone in resorption lacunae during bone remodeling. Nuclear factorkappa B (NF-κB) signaling regulates osteoclast and osteoblast formation and is activated in osteoclast precursors in response to the essential osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL), which can also control osteoblast formation through RANK-RANKL reverse signaling in osteoblast precursors. RANKL and some pro-inflammatory cytokines, including tumor necrosis factor (TNF), activate NF-κB signaling to positively regulate osteoclast formation and functions. However, these cytokines also limit osteoclast and osteoblast formation through NF-κB signaling molecules, including TNF receptor-associated factors (TRAFs). TRAF6 mediates RANKL-induced osteoclast formation through canonical NF-κB signaling. In contrast, TRAF3 limits RANKL- and TNF-induced osteoclast formation, and it restricts transforming growth factor ß (TGFß)-induced inhibition of osteoblast formation in young and adult mice. During aging, neutrophils expressing TGFß and C-C chemokine receptor type 5 (CCR5) increase in bone marrow of mice in response to increased NF-κB-induced CC motif chemokine ligand 5 (CCL5) expression by mesenchymal progenitor cells and injection of these neutrophils into young mice decreased bone mass. TGFß causes degradation of TRAF3, resulting in decreased glycogen synthase kinase-3ß/ß-catenin-mediated osteoblast formation and age-related osteoporosis in mice. The CCR5 inhibitor, maraviroc, prevented accumulation of TGFß+/CCR5+ neutrophils in bone marrow and increased bone mass by inhibiting bone resorption and increasing bone formation in aged mice. This paper updates current understanding of how NF-κB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast and osteoblast formation and activation with a focus on the role of TRAF3 signaling, which can be targeted therapeutically to enhance bone mass.


Assuntos
NF-kappa B , Osteogênese , Camundongos , Animais , NF-kappa B/metabolismo , Fator 3 Associado a Receptor de TNF/metabolismo , Ligantes , Osteoclastos/metabolismo , Osteoclastos/patologia , Fator de Crescimento Transformador beta/metabolismo
14.
Crit Rev Oncol Hematol ; 191: 104136, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37716517

RESUMO

Small cell lung cancer (SCLC) is one of a pathological type of lung cancer, and it is characterized by invasiveness, high malignancy and refractoriness. The mortality rate of SCLC is significantly higher than other types of lung cancer, and the treatment options for SCLC patients are limited. Delta-like ligand 3 (DLL3) is a Notch signaling ligand that plays a role in regulating the proliferation, development and metastasis of SCLC cells. Mnay studies have shown that DLL3 is overexpressed on the surface of SCLC cells, suggesting that DLL3 is a potential target for SCLC patients. A series of drug trials targeting DLL3 are underway. The Phase III clinical trials of Rova-T, a drug targeting DLL3, have not yielded the expected results. However, other drugs that target DLL3, such as AMG119, AMG757 and DLL3-targeted NIR-PIT, bring new ideas for SCLC treatment. Overall, DLL3 remains a valuable target for SCLC.

15.
Front Plant Sci ; 14: 1250590, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37615020

RESUMO

Although rice has many pests, brown planthopper (BPH) in particular is known to cause substantial damage. The pyramiding application of BPH-resistance genes BPH14 and BPH15 has proven effective in enhancing rice defense against BPH. However, the molecular mechanisms underlying BPH14/BPH15-conferred resistance remain unexplained. In this investigation, we analyzed the transcriptomes of near isogenic lines (NILs) containing either BPH14 (B14), BPH15 (B15), or BPH14/BPH15 (B1415), as well as their recurrent parent (RP) 'Wushansimiao'. In total, we detected 14,492 differentially expressed genes (DEGs) across 12 mRNA profiles of resistant NILs and RP at different feeding stages. In the transcriptomic analysis, 531 DEGs appeared to be common among the resistant NILs compared to RP before and after BPH feeding. These common DEGs were enriched in defense response, phosphorylation, and salt stress response. In addition, 258 DEGs shared only in resistant NILs were obtained among the different feeding stages, which were enriched in oxidative stress response, karrikin response, and chloroplast organization. Considering the expression patterns and relevant research reports associated with these DEGs, 21 were chosen as BPH resistance candidates. In rice protoplasts, the candidate DEG OsPOX8.1 was confirmed to increase reactive oxygen species (ROS) accumulation by chemiluminescence measurement. Our results provide valuable information to further explore the defense mechanism of insect-resistant gene pyramiding lines and develop robust strategies for insect control.

16.
Sci Rep ; 13(1): 12896, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37558719

RESUMO

Joshimath has received much attention for its massive ground subsidence at the beginning of the year. Rapid urbanization and its unique geographical location may have been one of the factors contributing to the occurrence of this geological disaster. In high mountain valley areas, the complex occurrence mechanism and diverse disaster patterns of geological hazards highlight the inadequacy of manual monitoring. To address this problem, the inversion of deformation of the Joshimath surface in multiple directions can be achieved by multidimensional InSAR techniques. Therefore, in this paper, the multidimensional SBAS-InSAR technique was used to process the lift-track Sentinel-1 data from 2020 to 2023 to obtain the two-dimensional vertical and horizontal deformation rates and time series characteristics of the Joshimath ground surface. To discover the causes of deformation and its correlation with anthropogenic activities and natural disasters by analyzing the spatial and temporal evolution of surface deformation. The results show that the area with the largest cumulative deformation is located in the northeastern part of the town, with a maximum cumulative subsidence of 271.2 mm and a cumulative horizontal movement of 336.5 mm. The spatial distribution of surface deformation is based on the lower part of the hill and develops towards the upper part of the hill, showing a trend of expansion from the bottom to the top. The temporal evolution is divided into two phases: gentle to rapid, and it is tentatively concluded that the decisive factor that caused the significant change in the rate of surface deformation and the early onset of the geological subsidence hazard was triggered by the 4.7 magnitude earthquake that struck near the town on 11 September 2021.

17.
J Trace Elem Med Biol ; 79: 127243, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37413925

RESUMO

BACKGROUND: Studies focused on independent effects of metals on small for gestational age, failing to account for potential interdependence among metals. METHODS: In this case-control study, we selected 187 pregnant women and 187 matched controls from the First Hospital of Shanxi Medical University. Determination of 12 elements in the venous blood of pregnant women before delivery by ICP-MS. Logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to estimate the overall effect and identify important mixture components that drive the associations with SGA. RESULTS: An increased risk of SGA was associated with As (OR= 1.06,95%CI: 1.01,1.12), Cd (OR= 1.24,95%CI: 1.04,1.47) and Pb (OR= 1.05,95%CI: 1.02,1.08), while Zn (OR= 0.58,95%CI: 0.45,0.76) and Mn (OR= 0.97,95%CI: 0.94,0.99) were protective factors for SGA. In the WQSR positive model, the mixture of heavy metals has a positive combined effect on SGA (OR= 1.74,95%CI: 1.15, 2.62), with Sb and Cd having the highest weights. The BKMR models confirmed that the metal mixture was associated with decreased risk of SGA when the concentration of 12 metals was between the 30th percentile and the 65th percentile, and Zn and Cd had the greatest independent effect. Zn and SGA may not be linearly correlated, higher Zn level may reduce the effect of Cd on the risk of SGA. CONCLUSIONS: Our study suggested that exposure to multiple metals was associated with risk of SGA, and the observed association with multiple metals was dominated by Zn, Cd. Sb exposure during pregnancy may also increase the risk of SGA.


Assuntos
Doenças do Recém-Nascido , Metais Pesados , Recém-Nascido , Humanos , Gravidez , Feminino , Cádmio , Idade Gestacional , Estudos de Casos e Controles , Teorema de Bayes , China
18.
J Am Chem Soc ; 145(30): 16642-16649, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37477624

RESUMO

Confining the protein degradation activity of proteolysis-targeting chimera (PROTAC) to cancer lesions ensures precision treatment. However, it still remains challenging to precisely control PROTAC function in tumor regions in vivo. We herein describe a near-infrared (NIR) photoactivatable nano-PROTAC (NAP) for remote-controllable proteolysis in tumor-bearing mice. NAP is formed by molecular self-assembly from an amphiphilic conjugate of PROTAC linked with an NIR photosensitizer through a singlet oxygen (1O2)-cleavable linker. The activity of PROTAC is initially silenced but can be remotely switched on upon NIR photoirradiation to generate 1O2 by the photosensitizer. We demonstrated that NAP enabled tumor-specific degradation of bromodomain-containing protein 4 (BRD4) in an NIR light-instructed manner. This in combination with photodynamic therapy (PDT) elicited an effective suppression of tumor growth. This work thus presents a novel approach for spatiotemporal control over targeted protein degradation by PROTAC.


Assuntos
Neoplasias , Fotoquimioterapia , Camundongos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Proteólise , Proteínas Nucleares , Fatores de Transcrição , Neoplasias/tratamento farmacológico
19.
Front Genet ; 14: 1206141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37351348

RESUMO

Background: Lung cancer has a high incidence and mortality rate worldwide. Vasculogenic mimicry (VM) is a specific modality of tumor angiogenesis that could potentially be a new target for tumor therapy. The purpose of this study was to explore the role of VM-related genes in assessing the prognosis and immune landscape of lung cancer. Methods: VM-related genes were obtained from previous studies, and the expression data and clinical data of lung adenocarcinoma (LUAD) patients were obtained from the TCGA database and GEO database. We performed enrichment analysis of 24 VM-related genes and screened hub genes by constructing a protein-protein interaction network and using Cytoscape software. Subsequently, we developed the VM score based on univariate Cox regression analysis and Lasso analysis and validated the VM score on the GSE72094 dataset. In addition, we constructed a nomogram based on the VM score in the TCGA cohort. Finally, we explored the correlation between the VM score and the tumor microenvironment, immune cell infiltration, immune checkpoints, and drug sensitivity. Results: Enrichment analysis revealed that VM-related genes were associated with the HIF signaling pathway and angiogenic pathway. We developed a VM score based on 3 genes (EPHA2, LAMC2 and LOXL2) in LUAD patients. Kaplan-Meier analysis showed that the VM score was associated with poor prognosis in LUAD patients. The receiver operating characteristic curve suggested that the VM score and nomogram are valid predictors for the overall survival of LUAD patients. The VM score was significantly correlated with immune cell infiltration, such as naïve B cells, neutrophils, and eosinophils, and there was a difference in the TME between the high VM score group and the low VM score group. LUAD patients in the high VM score group were more sensitive to antitumor drugs. Conclusion: In summary, the VM score developed in this study is a valuable indicator for evaluating the prognosis and immune landscape of LUAD patients. VM may be a potential target for antitumor therapy in lung cancer.

20.
AAPS PharmSciTech ; 24(5): 118, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37165275

RESUMO

To address the limitations of norcantharidin (NCTD) in clinical applications, including restricted tumor accumulation and intense irritation, we have developed a new derivative of NCTD with (S)-1-benzyl-3-pyrrolidinol, which can be actively loaded into liposomes to achieve drug encapsulation and sustained release properties by using pH gradient loading technique. Cytotoxicity tests against cancer cell lines (Hepa 1-6 and 4 T1 cells) have demonstrated that this derivative exhibits comparable activity to NCTD in vitro. The NCTD derivative can be efficiently loaded into liposomes with high encapsulation efficiency (98.7%) and high drug loading (32.86%). Tolerability and antitumor efficacy studies showed that the liposomal NCTD derivative was well tolerated at intravenous injection doses of 3 folds higher than the parent drug solution, while significantly improved anticancer activity in vivo was achieved. This liposomal nanodrug could become a potent and safe NCTD formulation alternative for cancer therapy.


Assuntos
Antineoplásicos , Nanopartículas , Lipossomos/química , Portadores de Fármacos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Nanopartículas/uso terapêutico , Nanopartículas/química , Linhagem Celular Tumoral
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