Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.202
Filtrar
2.
Front Public Health ; 12: 1353415, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966699

RESUMO

Background: The protective effectiveness provided by naturally acquired immunity against SARS-CoV-2 reinfection remain controversial. Objective: To systematically evaluate the protective effect of natural immunity against subsequent SARS-CoV-2 infection with different variants. Methods: We searched for related studies published in seven databases before March 5, 2023. Eligible studies included in the analysis reported the risk of subsequent infection for groups with or without a prior SARS-CoV-2 infection. The primary outcome was the overall pooled incidence rate ratio (IRR) of SARS-CoV-2 reinfection/infection between the two groups. We also focused on the protective effectiveness of natural immunity against reinfection/infection with different SARS-CoV-2 variants. We used a random-effects model to pool the data, and obtained the bias-adjusted results using the trim-and-fill method. Meta-regression and subgroup analyses were conducted to explore the sources of heterogeneity. Sensitivity analysis was performed by excluding included studies one by one to evaluate the stability of the results. Results: We identified 40 eligible articles including more than 20 million individuals without the history of SARS-CoV-2 vaccination. The bias-adjusted efficacy of naturally acquired antibodies against reinfection was estimated at 65% (pooled IRR = 0.35, 95% CI = 0.26-0.47), with higher efficacy against symptomatic COVID-19 cases (pooled IRR = 0.15, 95% CI = 0.08-0.26) than asymptomatic infection (pooled IRR = 0.40, 95% CI = 0.29-0.54). Meta-regression revealed that SARS-CoV-2 variant was a statistically significant effect modifier, which explaining 46.40% of the variation in IRRs. For different SARS-CoV-2 variant, the pooled IRRs for the Alpha (pooled IRR = 0.11, 95% CI = 0.06-0.19), Delta (pooled IRR = 0.19, 95% CI = 0.15-0.24) and Omicron (pooled IRR = 0.61, 95% CI = 0.42-0.87) variant were higher and higher. In other subgroup analyses, the pooled IRRs of SARS-CoV-2 infection were statistically various in different countries, publication year and the inclusion end time of population, with a significant difference (p = 0.02, p < 0.010 and p < 0.010), respectively. The risk of subsequent infection in the seropositive population appeared to increase slowly over time. Despite the heterogeneity in included studies, sensitivity analyses showed stable results. Conclusion: Previous SARS-CoV-2 infection provides protection against pre-omicron reinfection, but less against omicron. Ongoing viral mutation requires attention and prevention strategies, such as vaccine catch-up, in conjunction with multiple factors.


Assuntos
COVID-19 , Reinfecção , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Imunidade Inata
3.
Sci Rep ; 14(1): 15516, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969651

RESUMO

The intelligent appearance quality classification method for Auricularia auricula is of great significance to promote this industry. This paper proposes an appearance quality classification method for Auricularia auricula based on the improved Faster Region-based Convolutional Neural Networks (improved Faster RCNN) framework. The original Faster RCNN is improved by establishing a multiscale feature fusion detection model to improve the accuracy and real-time performance of the model. The multiscale feature fusion detection model makes full use of shallow feature information to complete target detection. It fuses shallow features with rich detailed information with deep features rich in strong semantic information. Since the fusion algorithm directly uses the existing information of the feature extraction network, there is no additional calculation. The fused features contain more original detailed feature information. Therefore, the improved Faster RCNN can improve the final detection rate without sacrificing speed. By comparing with the original Faster RCNN model, the mean average precision (mAP) of the improved Faster RCNN is increased by 2.13%. The average precision (AP) of the first-level Auricularia auricula is almost unchanged at a high level. The AP of the second-level Auricularia auricula is increased by nearly 5%. And the third-level Auricularia auricula AP is increased by 1%. The improved Faster RCNN improves the frames per second from 6.81 of the original Faster RCNN to 13.5. Meanwhile, the influence of complex environment and image resolution on the Auricularia auricula detection is explored.


Assuntos
Aprendizado Profundo , Algoritmos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Humanos
4.
J Hum Genet ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982179

RESUMO

Endometriosis is a common gynecological disorder affecting around 10% of reproductive-age women. Although many hypotheses were proposed, genetic alteration has been considered as one of the key factors promoting pathogenesis. Due to racial/ethnic disparities in the process of hormone regulation and nutrition metabolism, a genome-wide association study (GWAS) with 2794 cases and 27,940 controls was conducted in a Taiwanese-Han population. Our study identified five significant susceptibility loci for endometriosis, and three of them, WNT4 (on the 1p36.12), RMND1 (6q25.1), and CCDC170 (6q25.1), have been previously associated with endometriosis across different populations, including European and Japanese descent cohorts. Other two including C5orf66/C5orf66-AS2 (5q31.1) and STN1 (10q24.33) are newly identified ones. Functional network analysis of potent risk genes revealed the involvement of cancer susceptibility and neurodevelopmental disorders in endometriosis development. In addition, long non-coding RNAs (lncRNAs) C5orf66 and C5orf66-AS2 can interact with many RNA-binding proteins (RBPs) which can influence RNA metabolic process, mRNA stabilization, and mRNA splicing, leading to dysregulation in tumor-promoting gene expression. Those findings support clinical observations of differences in the presentation of endometriosis in Taiwanese-Han population with higher risks of developing deeply infiltrating/invasive lesions and the associated malignancies.

5.
Int Immunopharmacol ; 138: 112623, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38991630

RESUMO

OBJECTIVE: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited. METHODS: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene. RESULTS: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa. CONCLUSIONS: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients.

6.
Foods ; 13(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38998648

RESUMO

(1) Background: Rapid on-site testing is an effective method for the detection of Escherichia coli O157: H7(E. coli O157: H7) in food ingredients and the environment. (2) Methods: In this study, we developed colorimetric loop-mediated isothermal amplification (LAMP) and immunochromatographic test strips (ICTs) for the rapid and visual detection of E. coli O157: H7. This study designed new specific LAMP primers for E. coli O157: H7 virulence island genes. After the LAMP amplification, the double-stranded DNA target sequence labeled with digoxin and fluorescein isothiocyanate (FITC) at both ends was bound to the anti-digoxin antibody on the gold nanoparticles. Subsequently, it was further bound to the anti-FITC antibody at the T line of the ICTs, forming a positive test result. Hydroxynaphthyl blue dye was directly added to the LAMP amplification product. A blue color indicated positive results, while a purple color indicated negative results. (3) Results: Two visualization methods showed high specificity for the target strains. The visualization tests had sensitivities of 5.7 CFU mL-1, and the detection limit of the Escherichia coli O157: H7 in artificially contaminated milk samples was 5.7 × 102 CFU mL-1, which was consistent with the results of the standard method (LAMP-electrophoresis method) used in commercial inspection. (4) Conclusions: Both methods could be useful in remote and under-resourced areas.

7.
Sci Bull (Beijing) ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38945747

RESUMO

Water has been detected in lunar regolith, with multiple sources identified through the analysis of individual grains. However, the primary origin of water in the bulk lunar regolith remains uncertain. This study presents spectroscopic analyses of water content in sealed Chang'e-5 samples. These samples were sieved into various size fractions (bulk, <45 µm, and 45-355 µm) inside a glovebox filled with high-purity nitrogen. Results indicate a higher water content in the fine fractions (∼87 ± 11.9 ppm) than in bulk soil (∼37 ± 4.8 ppm) and coarse fractions (∼11 ± 1.5 ppm). This suggests that water is predominantly concentrated in the outermost rims of the regolith grains, and thus exhibits dependence on the surface volume ratio (also known as surface correlation), indicating solar wind is a primary source of lunar surface water. Laboratory, in-situ, and orbital results bridge sample analysis and remote sensing, offering a cohesive understanding of lunar surface water characteristics as represented by Chang'e-5. The discovery provides statistical evidence for the origin of water in lunar soil and can be considered representative of the lunar surface conditions. The water enrichment of the finest fraction suggests the feasibility of employing size sorting of lunar soils as a potential technological approach for water resource extraction in future lunar research stations.

9.
Yi Chuan ; 46(6): 452-465, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38886149

RESUMO

LIN28A and its homolog LIN28B are highly conserved RNA-binding proteins that play important roles in early embryonic development, somatic cell reprogramming, metabolism and tumorigenesis. LIN28A/B are highly expressed in a variety of malignant tumors such as breast cancer. They play important roles in the initiation, maintenance, and metastasis of tumors and are associated with poor prognosis. Previous studies have shown that the main regulatory mechanisms of LIN28A/B include let-7s dependent ways and let-7s independent ways, such as directly targeting mRNA. In this review, we summarize the function and molecular regulatory mechanisms of LIN28A/B in malignant tumors such as liver cancer, breast cancer and colorectal cancer, in order to provide references for further exploring the function and mechanism of LIN28A/B and their possible roles in clinical applications.


Assuntos
Neoplasias , Proteínas de Ligação a RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Progressão da Doença , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética
10.
Inorg Chem ; 63(27): 12469-12474, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38912662

RESUMO

Two Mn(II)-bridged Silverton-type {UMo12O42}-based polyoxomolybdates with different three-dimensional structures, Na6(H2O)12[Mn(UMo12O42)] (NaMn) and (NH4)2[K2Na6(µ4-O)2(H2O)1.2Mn(UMo12O42)]·4.6H2O (KMn), were hydrothermally synthesized and further characterized, demonstrating a feasible strategy for the assembly of Silverton-type polyoxomolybdates. Additionally, NaMn is demonstrated to be a good heterogeneous catalyst in the condensation cyclization reaction of hydrazines and 1,3-diketones, and a range of valuable pyrazoles were produced in up to 99% yield.

11.
Int Immunopharmacol ; 137: 112485, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38878487

RESUMO

Circular RNAs (circRNAs) are gaining attention for their involvement in immune escape and immunotherapy sensitivity regulation. CircZNF609 is a well-known oncogene in various solid tumours. Our previous research revealed its role in reducing the chemosensitivity of bladder cancer (BCa) to cisplatin. However, the underlying role of circZNF609 in BCa immune escape and immunotherapy sensitivity remains unknown. We conducted BCa cells-CD8 + T cells co-culture assays, cell line-derived xenograft and patient-derived xenograft mouse models with human immune reconstitution to further confirm the role of circZNF609 in BCa immune escape and immunotherapy sensitivity. Overexpression of circZNF609 promoted BCa immune escape in vitro and in vivo. Mechanistically, circZNF609 was bound to IGF2BP2, enhancing its interaction with the 3'-untranslated region of CD36. This increased the stability of the CD36 mRNA, leading to enhanced fatty acid uptake by BCa cells and fatty acid depletion within the tumour microenvironment. Additionally, the nuclear export of circZNF609 was regulated by DDX39B. CircZNF609 promoted immune escape and suppressed BCa immunotherapy sensitivity by regulating the newly identified circZNF609/IGF2BP2/CD36 cascade. Therefore, circZNF609 holds potential as both a biomarker and therapeutic target in BCa immunotherapy.


Assuntos
Ácidos Graxos , Imunoterapia , RNA Circular , Proteínas de Ligação a RNA , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Humanos , Animais , RNA Circular/genética , RNA Circular/metabolismo , Linhagem Celular Tumoral , Camundongos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Imunoterapia/métodos , Ácidos Graxos/metabolismo , Evasão Tumoral , Microambiente Tumoral/imunologia , Transdução de Sinais , Regulação Neoplásica da Expressão Gênica , Ensaios Antitumorais Modelo de Xenoenxerto , Linfócitos T CD8-Positivos/imunologia , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Masculino , Feminino , Antígenos CD36
12.
Biomed Opt Express ; 15(6): 3859-3868, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38867779

RESUMO

The fiber surface plasmon resonance (SPR) sensor used for the detection of active ingredients in traditional Chinese medicine has the problems of low sensitivity and difficult specific recognition. This paper proposed a wave type fiber SPR sensor, which reduced the mode of transmitted light through a periodic wave structure and caused concentrated and total reflection of the transmitted beam at the interface between the bent peak cladding and the air. A 50 nm gold film was coated on the surface of the cladding in the wave structure area to form the SPR sensing area. By controlling the width and height of the wave structure to control the total reflection angle of the transmitted light, i.e., the SPR incidence angle, the sensitivity of the fiber SPR sensor was effectively improved to 4972 nm/RIU. Furthermore, HSP90AA protein was modified on the gold film of the sensor to achieve specific detection of hyperoside. The longest single detection time was only 3 minutes, and the detection sensitivity was 0.53 nm/(µg/ml), with a detection limit as low as 0.68µg/ml, which is comparable to liquid chromatography. The proposed wave type fiber SPR sensor is fast in production and has high structural mechanical strength, providing a new approach for the rapid, highly sensitive, and specific detection of active ingredients in traditional Chinese medicine.

13.
Opt Express ; 32(9): 15882-15892, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38859228

RESUMO

To achieve a fiber strain sensor with a large detection range and high sensitivity, this paper proposes a wave structured fiber SPR strain sensor. When subjected to axial strain, the wave structured fiber is stretched axially, increasing the stretchability of the sensor and achieving a large detection range strain sensing. Meanwhile, axial strain reduces the longitudinal amplitude of the fiber wave structure, effectively changing the total reflection angle of the transmitted beam at the peak and valley (SPR incidence angle) to achieve high sensitivity SPR strain sensing. The experiment indicates that the strain detection range of the sensor can reach 0-1800µÎµ, with a maximum strain sensitivity of 36.25pm/µÎµ. The wave structured fiber SPR strain sensor designed in this article provides a new approach to improve the range and sensitivity of strain detection.

14.
Opt Express ; 32(8): 13783-13796, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859339

RESUMO

The conical fiber SPR sensor is easy to manufacture and has been used in biochemical detection research, but it has the problem of structural fragility. This article proposes a spiral cone fiber SPR sensor, which introduces a spiral structure on the 76µm fiber coarse cone, achieving good coupling of the core mode into the cladding mode, and improving the physical strength and practicality of the cone-shaped fiber SPR sensor. By modifying the target protein on the surface of the sensor gold film, specific detection of ginsenoside Rg1, an active ingredient of traditional Chinese medicine ginseng, was achieved. The detection sensitivity was 0.138 nm/(µm/ml) and the detection limit was 0.22µm/ml. The proposed spiral cone fiber SPR sensor provides a new scheme for the specific detection of active ingredients in traditional Chinese medicine, which is structurally stable and physically strong.


Assuntos
Ginsenosídeos , Ressonância de Plasmônio de Superfície , Ginsenosídeos/análise , Ressonância de Plasmônio de Superfície/métodos , Técnicas Biossensoriais/instrumentação , Desenho de Equipamento , Tecnologia de Fibra Óptica/instrumentação , Limite de Detecção
15.
Nanotechnology ; 35(36)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38865988

RESUMO

Reactive oxygen species (ROS) play important roles in regulating various physiological functions in the human body, however, excessive ROS can cause serious damage to the human body, considering the various limitations of natural enzymes as scavengers of ROS in the body, the development of better materials for the scavenging of ROS is of great significance to the biomedical field, and nanozymes, as a kind of nanomaterials which can show the activity of natural enzymes. Have a good potential for the development in the area of ROS scavenging. Metal-organic frameworks (MOFs), which are porous crystalline materials with a periodic network structure composed of metal nodes and organic ligands, have been developed with a variety of active nanozymes including catalase-like, superoxide dismutase-like, and glutathione peroxidase-like enzymes due to the adjustability of active sites, structural diversity, excellent biocompatibility, and they have shown a wide range of applications and prospects. In the present review, we first introduce three representative natural enzymes for ROS scavenging in the human body, methods for the detection of relevant enzyme-like activities and mechanisms of enzyme-like clearance are discussed, meanwhile, we systematically summarize the progress of the research on MOF-based nanozymes, including the design strategy, mechanism of action, and medical application, etc. Finally, the current challenges of MOF-based nanozymes are summarized, and the future development direction is anticipated. We hope that this review can contribute to the research of MOF-based nanozymes in the medical field related to the scavenging of ROS.


Assuntos
Estruturas Metalorgânicas , Espécies Reativas de Oxigênio , Estruturas Metalorgânicas/química , Espécies Reativas de Oxigênio/metabolismo , Humanos , Sequestradores de Radicais Livres/química , Nanoestruturas/química , Catalase/química , Catalase/metabolismo , Animais , Superóxido Dismutase/metabolismo , Superóxido Dismutase/química
16.
Eur J Ophthalmol ; : 11206721241259798, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856976

RESUMO

PURPOSE: The report presents a modified surgical technique wherein the perfluorocarbon liquid (PFCL)-assisted drainage of subretinal fluid (SRF) through the choroid was combined with partial-thickness sclerectomy (PTS) and punch sclerostomy as a treatment for bullous central serous chorioretinopathy (bCSCR) in a nanophthalmic eye. METHODS: The developed surgical approach is herein discussed together with a corresponding surgical video. Briefly, two 5 × 4 mm half-thickness sclerectomies and a punch sclerostomy (diameter: 2 mm) to the choroid were performed in the inferior quadrants. Following vitrectomy, SRF was drained through the exposed choroid in the region where the punch sclerostomy was performed, whereafter PFCL was instilled into the vitreous cavity. RESULTS: The complete resolution of SRF accumulation was evident at one-week post-surgery, with no evidence of recurrence over an 18-month follow-up period. No abnormal fluorescent leakage or choroidal vasodilation were evident via fundus fluorescein angiography and indocyanine green angiography examination at the patient's final follow-up visit. CONCLUSION: PFCL-assisted SRF drainage through the choroid combined with PTS and punch sclerostomy may represent a viable approach to treating patients with bCSCR and nanophthalmic eyes, providing a rapid and long-lasting means of eliminating SRF accumulation.

17.
Mil Med Res ; 11(1): 36, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863031

RESUMO

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.


Assuntos
Elementos Facilitadores Genéticos , Neoplasias , Locos de Características Quantitativas , Humanos , Elementos Facilitadores Genéticos/genética , Neoplasias/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Neoplasias Colorretais/genética , Estudos de Casos e Controles , RNA/genética , China , RNAs Intensificadores
18.
Ann Surg Oncol ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824192

RESUMO

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

19.
Alzheimers Dement ; 20(6): 4212-4233, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38753870

RESUMO

BACKGROUND: Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown. METHODS: We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches. RESULTS: Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aß) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and normalized lysosomal cathepsins, primarily cathepsin Z, to restore lysosomal function in AD, indicating the critical role of cathepsins in UA-induced therapeutic effects on AD. CONCLUSIONS: Our study highlights the importance of lysosomal dysfunction in AD etiology and points to the high translational potential of UA. HIGHLIGHTS: Long-term urolithin A (UA) treatment improved learning, memory, and olfactory function in Alzheimer's disease (AD) mice. UA restored lysosomal functions in part by regulating cathepsin Z (Ctsz) protein. UA modulates immune responses and AD-specific pathophysiological pathways.


Assuntos
Doença de Alzheimer , Cumarínicos , Modelos Animais de Doenças , Lisossomos , Camundongos Transgênicos , Mitofagia , Doença de Alzheimer/tratamento farmacológico , Animais , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Camundongos , Mitofagia/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Cognição/efeitos dos fármacos
20.
Int J Immunopathol Pharmacol ; 38: 3946320241240706, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38712735

RESUMO

Introduction: Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. Methods: Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. Results: We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. Conclusion: Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy.


Assuntos
Transportador de Cobre 1 , Neoplasias da Bexiga Urinária , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Transportador de Cobre 1/genética , Transportador de Cobre 1/metabolismo , Progressão da Doença , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Mutação , Prognóstico , Regiões Promotoras Genéticas , Regulação para Cima , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA