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1.
J Cancer ; 15(17): 5622-5635, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39308683

RESUMO

Purpose: Breast cancer poses a huge threat to the lives and health of women worldwide. However, drug resistance makes the treatment of breast cancer challenging. This study aims to investigate the effect of miR-141-3p on paclitaxel resistance and its underlying mechanisms in breast cancer. Methods: Using bioinformatics analysis and qRT-PCR to explore the potential molecule miR-141-3p. Specific binding of miR-141-3p to Keap1 was determined by using a dual luciferase reporter assay. qRT-PCR and Western blot were utilized to observe the expression of miR-141-3p, Keap1, Nrf2, SLC7A11 and GPX4. GSH/GSSG content, MDA content and JC-1 assays were used to observe the ferroptosis levels of breast cancer cells. CCK-8 assay was used to observe the cell viability of breast cancer cells. Tumor subcutaneous transplantation experiment was used to understand the effect of miR-141-3p on paclitaxel resistance in breast cancer in vivo. Results: In the present study, miR-141-3p was found to be highly expressed and associated with poor prognosis in breast cancer. miR-141-3p inhibited Keap1 expression, promoted Nrf2 expression, and facilitated paclitaxel resistance in breast cancer cells. Inhibition of miR-141-3p promoted Keap1 expression, inhibited Nrf2 and its downstream SLC7A11-GSH-GPX4 signaling pathway, as well as promoted ferroptosis in cancer cells, and inhibited paclitaxel and RSL3 resistance. ML385 blocks the effect of miR-141-3p on paclitaxel resistance and ferroptosis resistance in breast cancer cells. In vivo, miR-141-3p mimics promoted paclitaxel resistance, whereas miR-141-3p inhibitors inhibited paclitaxel resistance in breast cancer cells. Conclusion: This work revealed that modulation of the Keap1-Nrf2 signaling pathway by miR-141-3p promoted paclitaxel resistance via regulating ferroptosis in breast cancer cells.

2.
Food Res Int ; 193: 114855, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39160046

RESUMO

Pepper (Capsicum spp.) is an important fruit vegetable worldwide, and it is a rich dietary source of minerals for human being. Yet, the spatio-temporal distribution of pepper fruit mineral composition and the factors influencing such variations at global scale remain unknown. A global meta-analysis of 140 publications providing 649, 562, 690, 811 datapoints was conducted to quantify and evaluate the nutritional quality, comprising potassium (K), magnesium (Mg), iron (Fe) and zinc (Zn), of pepper fruits and its influencing variables. The analysis showed that the global average of K, Mg, Fe and Zn content in pepper fruits was 20-25 g kg-1, 1-1.5 g kg-1, 80-100 mg kg-1, and 20-40 mg kg-1, respectively. There had been a downward trend in pepper fruit nutritional quality over the last decade, especially for Fe and Zn. And, the concentration of all these four nutrients were at lower levels in less developed regions, especially in Africa. Our results showed that the vegetable "green pepper" contains more K, Mg, Fe and Zn than the "hot pepper" used as spice. The concentration of K, Mg, Fe and Zn were increased with fruit yield but that of Fe and Zn were decreased with increase in single fruit weight. Nutritional quality was optimal at mean annual temperature of 10 ℃ - 20 ℃, and was adversely affected when mean annual precipitation was < 500 mm. Pepper fruits produced at pH 6.5-7.5 had higher fruit K concentration while acidic soils (pH<6.5) favored higher Fe and Zn concentrations. The higher soil organic matter (SOM) generally improved the nutritional quality of the pepper. Our results suggest that systematic selection of superior varieties and soil amelioration (adjusting pH and SOM) of the soil-crop system are needed to achieve higher nutritional quality of pepper fruit.


Assuntos
Capsicum , Frutas , Valor Nutritivo , Capsicum/química , Frutas/química , Minerais/análise , Análise Espaço-Temporal , Potássio/análise , Magnésio/análise , Zinco/análise , Ferro/análise
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125026, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39216145

RESUMO

Raman spectroscopy has emerged as a crucial mineral analysis technique in planetary surface exploration missions. Nonetheless, the inherently low Raman scattering efficiency of planetary silicate materials makes it challenging to extract enough Raman information. Theoretical and experimental studies of the remote Raman scattering properties of planetary materials are also urgent requirements for future lunar and planetary explorations. Here, Shandong University Remote Raman Spectrometer (SDU-RRS) was developed to demonstrate the feasibility of lunar remote Raman technology and conduct preliminary research on remote Raman scattering properties. SDU-RRS utilizes a pulsed 532 nm laser, a non-focal Cassegrain telescope, a volume phase holographic grating, an intensified charge-coupled device, and the time-gating technique to detect weak-signal silicate minerals. The spectral resolution obtained with atomic emission lamps was <4.91 cm-1, and the wavelength accuracy was <1 cm-1, across the spectral range of 241-2430 cm-1. SDU-RRS can detect natural augite within a feldspar-olivine-augite matrix at a concentration of 20 % at ∼1 m under ambient lighting conditions. A series of experiments were conducted to evaluate the influence of measurement conditions and physical matrix effects on acquired Raman signals, either qualitatively or quantitatively, on geological materials. The study indicates that the transmission of Raman-scattered light conforms to Lambert's cosine law, and a linear correlation exists between Raman intensity and laser power. The study also evaluated the impact of grain size, surface roughness, porosity, and shadow-hiding effects. Reducing grain size decreases Raman intensity and broadens Raman spectra. These characteristics are essential for achieving definitive mineralogical information from granular materials by remote Raman spectroscopy in lunar and planetary explorations.

4.
J Cyst Fibros ; 23(4): 716-724, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39060183

RESUMO

Cystic fibrosis (CF) is a single-gene disorder that affects the lung, digestive system, and other organs. Mutations in the CF transmembrane conductance regulator (CFTR) gene are classified into several classes based on their pathogenic mechanism and clinical severity. The distinct and heterogeneous clinical behavior of each CF class and the respective CFTR mutations have made the development of a durable therapy for all CF patients extremely challenging. While the FDA-approved drug elexacaftor/tezacaftor/ivacaftor (Trikafta) benefits CF patients carrying at least one F508del mutation in CFTR, it's not effective for many CF patients carrying a variety of other CFTR mutations. To establish a better understanding of CF pathophysiology and aid the development of novel therapeutics for different classes of CF patients, we have created four CF-mutation-specific cell models that recapitulate respectively four distinct CF classes and disease phenotypes, as confirmed by sequencing, CFTR mRNA and protein quantification. The channel function of each cell model was first validated using a well-established FLIPR (Fluorescent Imaging Plate Reader) membrane potential assay and then assessed by the YFP-based functional assay. Integrated with a halide-sensitive fluorescent reporter, these CF cell models can be used for high-throughput drug screening, as demonstrated by a proof-of-concept study using Trikafta. These cell models have the potential to advance CFTR mutation-specific therapies thus addressing the unmet needs of CF patients with rare mutations.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Avaliação Pré-Clínica de Medicamentos , Ensaios de Triagem em Larga Escala , Fibrose Cística/genética , Fibrose Cística/tratamento farmacológico , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Ensaios de Triagem em Larga Escala/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Aminofenóis/uso terapêutico , Aminofenóis/farmacologia , Mutação , Benzodioxóis/uso terapêutico , Benzodioxóis/farmacologia , Indóis/uso terapêutico , Indóis/farmacologia , Quinolonas/farmacologia , Quinolonas/uso terapêutico
5.
Mol Med Rep ; 30(1)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38785160

RESUMO

Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis­associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.


Assuntos
Ferroptose , Transdução de Sinais , Acidente Vascular Cerebral , Ferroptose/efeitos dos fármacos , Humanos , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Terapia de Alvo Molecular , Medicina Tradicional Chinesa/métodos
6.
BMC Cancer ; 24(1): 611, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773399

RESUMO

RNA interactomes and their diversified functionalities have recently benefited from critical methodological advances leading to a paradigm shift from a conventional conception on the regulatory roles of RNA in pathogenesis. However, the dynamic RNA interactomes in adenoma-carcinoma sequence of human CRC remain unexplored. The coexistence of adenoma, cancer, and normal tissues in colorectal cancer (CRC) patients provides an appropriate model to address this issue. Here, we adopted an RNA in situ conformation sequencing technology for mapping RNA-RNA interactions in CRC patients. We observed large-scale paired RNA counts and identified some unique RNA complexes including multiple partners RNAs, single partner RNAs, non-overlapping single partner RNAs. We focused on the antisense RNA OIP5-AS1 and found that OIP5-AS1 could sponge different miRNA to regulate the production of metabolites including pyruvate, alanine and lactic acid. Our findings provide novel perspectives in CRC pathogenesis and suggest metabolic reprogramming of pyruvate for the early diagnosis and treatment of CRC.


Assuntos
Adenoma , Neoplasias Colorretais , MicroRNAs , Ácido Pirúvico , RNA Longo não Codificante , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Ácido Pirúvico/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Reprogramação Metabólica
7.
J Hazard Mater ; 470: 134214, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38603908

RESUMO

Fe(II) regeneration is decisive for highly efficient H2O2-based Fenton-like processes, but the role of cobalt-containing reactive sites in promoting Fe(II) regeneration was overlooked. Herein, a single atom Co-N-C catalyst was employed in Fe(II)/H2O2 system to promote the degradation of diverse organic contaminants. The EPR and quenching experiments indicated Co-N-C significantly enhanced the generation of superoxide species, and accelerated hydroxyl radical generation for pollutant degradation. The electrochemical and surface composition analyses demonstrated the enhanced H2O2 activation and Fe(III)/Fe(II) recycling on the catalyst. Furthermore, in-situ Raman characterization with shell-isolated gold nanoparticles was employed to visualize the interfacial reactive intermediates and their time-resolved interaction. The accumulation of interfacial CoOOH* was confirmed when Co-N-C activated H2O2 alone, but it rapidly transformed into FeOOH* upon Fe(II) addition. Besides, the temporal variation of OOH* intermediates and the relative intensity of Co(III)-O and Co(IV)=O peaks depicted the dynamic interaction of reactive intermediates along the H2O2 consumption. With this basis, we proposed a mechanism of interfacial OOH* mediated Fe(II) regeneration, which overcame the kinetical limitation of Fe(II)/H2O2 system. Therefore, this study provided a primary effort to elucidate the overlooked role of interfacial CoOOH* in the Fenton-like processes, which may inspire the design of more efficient catalysts.

8.
Eur J Pharmacol ; 972: 176553, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38574838

RESUMO

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.


Assuntos
Benzamidas , Ferroptose , Microglia , Fator 2 Relacionado a NF-E2 , Pirróis , Traumatismo por Reperfusão , Animais , Ferroptose/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/efeitos dos fármacos , Modelos Animais de Doenças , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Linhagem Celular , Transporte Ativo do Núcleo Celular/efeitos dos fármacos
9.
Insects ; 15(3)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38535368

RESUMO

Erannis jacobsoni Djak (Lepidoptera, Geometridae) is a leaf-feeding pest unique to Mongolia. Outbreaks of this pest can cause larch needles to shed slowly from the top until they die, leading to a serious imbalance in the forest ecosystem. In this work, to address the need for the low-cost, fast, and effective identification of this pest, we used field survey indicators and UAV images of larch forests in Binder, Khentii, Mongolia, a typical site of Erannis jacobsoni Djak pest outbreaks, as the base data, calculated relevant multispectral and red-green-blue (RGB) features, used a successive projections algorithm (SPA) to extract features that are sensitive to the level of pest damage, and constructed a recognition model of Erannis jacobsoni Djak pest damage by combining patterns in the RGB vegetation indices and texture features (RGBVI&TF) with the help of random forest (RF) and convolutional neural network (CNN) algorithms. The results were compared and evaluated with multispectral vegetation indices (MSVI) to explore the potential of UAV RGB images in identifying needle pests. The results show that the sensitive features extracted based on SPA can adequately capture the changes in the forest appearance parameters such as the leaf loss rate and the colour of the larch canopy under pest damage conditions and can be used as effective input variables for the model. The RGBVI&TF-RF440 and RGBVI&TF-CNN740 models have the best performance, with their overall accuracy reaching more than 85%, which is a significant improvement compared with that of the RGBVI model, and their accuracy is similar to that of the MSVI model. This low-cost and high-efficiency method can excel in the identification of Erannis jacobsoni Djak-infested regions in small areas and can provide an important experimental theoretical basis for subsequent large-scale forest pest monitoring with a high spatiotemporal resolution.

10.
J Cardiovasc Aging ; 4(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38464671

RESUMO

Introduction: Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model. Aim: The purpose of this study was to assess whether adeno-associated virus type-9 (AAV9)-mediated somatic genome editing could prevent ventricular arrhythmias by removal of the mutant allele in mice that are heterozygous for Ryr2 variant p.Arg176Gln (R176Q/+). Methods and Results: Guide RNA and SaCas9 were delivered using AAV9 vectors injected subcutaneously in 10-day-old mice. At 6 weeks after injection, R176Q/+ mice had a 100% reduction in ventricular arrhythmias compared to controls. When aged to 12 months, injected R176Q/+ mice maintained a 100% reduction in arrhythmia induction. Deep RNA sequencing revealed the formation of insertions/deletions at the target site with minimal off-target editing on the wild-type allele. Consequently, CRISPR/SaCas9 editing resulted in a 45% reduction of total Ryr2 mRNA and a 38% reduction in RyR2 protein. Genome editing was well tolerated based on serial echocardiography, revealing unaltered cardiac function and structure up to 12 months after AAV9 injection. Conclusion: Taken together, AAV9-mediated CRISPR/Cas9 genome editing could efficiently disrupt the mutant Ryr2 allele, preventing lethal arrhythmias while preserving normal cardiac function in the R176Q/+ mouse model of CPVT.

11.
Mol Ther Methods Clin Dev ; 32(1): 101208, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38414825

RESUMO

Wiskott-Aldrich syndrome (WAS) is a severe X-linked primary immunodeficiency resulting from a diversity of mutations distributed across all 12 exons of the WAS gene. WAS encodes a hematopoietic-specific and developmentally regulated cytoplasmic protein (WASp). The objective of this study was to develop a gene correction strategy potentially applicable to most WAS patients by employing nuclease-mediated, site-specific integration of a corrective WAS gene sequence into the endogenous WAS chromosomal locus. In this study, we demonstrate the ability to target the integration of WAS2-12-containing constructs into intron 1 of the endogenous WAS gene of primary CD34+ hematopoietic stem and progenitor cells (HSPCs), as well as WASp-deficient B cell lines and WASp-deficient primary T cells. This intron 1 targeted integration (TI) approach proved to be quite efficient and restored WASp expression in treated cells. Furthermore, TI restored WASp-dependent function to WAS patient T cells. Edited CD34+ HSPCs exhibited the capacity for multipotent differentiation to various hematopoietic lineages in vitro and in transplanted immunodeficient mice. This methodology offers a potential editing approach for treatment of WAS using patient's CD34+ cells.

12.
Mol Med Rep ; 29(3)2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38275110

RESUMO

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD­like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL­1ß and IL­18, as well as gasdermin­D­mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3­mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Piroptose , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo
14.
J Orthop Surg Res ; 18(1): 878, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980499

RESUMO

BACKGROUND: Total hip arthroplasty (THA) performed using the direct anterior approach (DAA) has demonstrated favourable early-, mid-, and long-term outcomes. However, the traditional femoral release technique remains technically demanding and is associated with challenges and a heightened risk of complications. This study aimed to compare the clinical outcomes of patients who underwent THA with DAA performed using either the femoral-release-first (FRF) or the traditional approach (TA) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 106 patients between 2018 and 2019. The patients were categorised into two groups: FRF (44 hips) and TA (69 hips). RESULTS: The FRF group showed a reduced operative time, haemoglobin (Hb) drop, postoperative hospital stay, and more optimal acetabular cup anteversion angles. Furthermore, during the first 2 months postoperatively, the FRF group demonstrated superior visual analogue scale, Harris Hip, and Oxford Hip scores. In the TA group, two hips experienced greater trochanter fractures, and one experienced delayed incision healing. CONCLUSIONS: Compared with the TA, employing the FRF strategy during THA with DAA resulted in improved outcomes within the first 2 months postoperatively and comparable functional recovery beyond this period. The FRF method exhibited advantages such as favourable acetabular exposure and alignment and a reduced risk of complications. Therefore, the FRF strategy may be a favourable option.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Articulação do Quadril/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Fêmur/cirurgia
15.
Opt Lett ; 48(20): 5419-5422, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37831882

RESUMO

We propose what we believe to be a new kind of diffractive phase element, i.e., vortex phase plate (VPP) with phase singularities along the azimuth direction. Phase function of the proposed VPP is given analytically. Axial intensity oscillations of propagating Bessel beams are ideally suppressed by using the proposed VPP. Compared with the traditional amplitude mask, the proposed VPP takes such advantages as a simpler fabrication procedure and a lower cost.

16.
Biomed Environ Sci ; 36(9): 862-868, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37803898

RESUMO

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Bioensaio , Ciclo Celular
17.
Fitoterapia ; 170: 105661, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37648030

RESUMO

Ormosia hosiei Hemsl. et Wils (Fabaceae family) is an arbor species endemic to China. The seeds of O. hosiei have been used as traditional Chinese medicine to treat hernia, abdominal pain, blood stasis and amenorrhea. Cytisine-like and angustifoline type alkaloids were main components identified from this plant. In our research on the bioactive alkaloids from the promising Chinese medicinal plants, four new angustifoline type alkaloids (1-4) and a new cytisine-like alkaloid (5), named hosimosine A-E, together with 13 known analogues (6-18) were isolated from the seeds of O. hosiei. Their structures were elucidated by the extensive spectroscopic methods, especially the interpretation of NMR spectra and specific rotations, along with the methods of NMR and ECD calculation. Compounds 1-4 were identified as two pairs of epimers, whose relative configurations were deduced from density functional theory (DFT) calculations of NMR chemical shifts and DP4+ analysis, and absolute configurations were determined by comparison of their experimental and theoretical ECD spectra. Compound 5 displayed two sets of NMR data caused by the existence of tautomeric forms. Compounds 14, 17 and 18 were determined to be enantiomers of literature compounds. Some of the isolates exhibited moderate cytotoxic effects against HepG2, A2780 and MCF-7 cells.


Assuntos
Alcaloides , Fabaceae , Neoplasias Ovarianas , Humanos , Feminino , Estrutura Molecular , Linhagem Celular Tumoral , Alcaloides/farmacologia , Alcaloides/química , Sementes
18.
bioRxiv ; 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37546995

RESUMO

Homology Directed Repair (HDR)-based genome editing is an approach that could permanently correct a broad range of genetic diseases. However, its utility is limited by inefficient and imprecise DNA repair mechanisms in terminally differentiated tissues. Here, we tested "Repair Drive", a novel method for improving targeted gene insertion in the liver by selectively expanding correctly repaired hepatocytes in vivo. Our system consists of transient conditioning of the liver by knocking down an essential gene, and delivery of an untargetable version of the essential gene in cis with a therapeutic transgene. We show that Repair Drive dramatically increases the percentage of correctly targeted hepatocytes, up to 25%. This resulted in a five-fold increased expression of a therapeutic transgene. Repair Drive was well-tolerated and did not induce toxicity or tumorigenesis in long term follow up. This approach will broaden the range of liver diseases that can be treated with somatic genome editing.

19.
J Environ Public Health ; 2023: 1564614, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457596

RESUMO

The sustainable development of the urban environmental landscape is a process that integrates resource utilization, ecological benefit, economy, and society and involves elements of culture, society, politics, economy, and individual residents. Citizen participation is increasingly important for the urban landscape design, and therefore, urban environmental landscape studies must be evaluated objectively by the public to ensure both sustainable development and social justice. In this study, the Tao Sichuan Creative Industry Park (the former "Universe Porcelain Factory") in Jingdezhen, Jiangxi province, China, was taken as example, and the implemented landscape reconstruction was evaluated. The analytical hierarchy process was used to collect both expert and public opinions regarding the cultural landscape; then, the weight coefficient of the value index layer of the industrial heritage park was obtained. A comparison of the two groups (experts and the public) showed that the experts do not exactly agree with the perspective of the public: experts prefer the artistic value far more than any other factors, while the public prefers the artistic value, social value, and economic value. Each group prefers different values of the landscape, suggesting that environmental justice should not be biased toward one of these perspectives. Finally, a design optimization principle is proposed according to the results of this study. This principle strengthens the sustainable development concept in the landscape reconstruction of industrial heritage parks, and suggestions are provided for optimizing the allocation of urban public landscape resources.


Assuntos
Conservação dos Recursos Naturais , Desenvolvimento Sustentável , China , Opinião Pública , Indústrias
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