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PURPOSE: This research aims to use a data-driven analytical method to compare the effectiveness of High-Intensity Focused Ultrasound (HIFU) partial gland ablation with Robot-Assisted Radical Prostatectomy (RARP) for treating localized prostate cancer, evaluating variations in treatment results. METHODS: We performed a systematic review of the literature, covering key databases including the Cochrane Library, PubMed, EMBASE, Web of Science, and Google Scholar, with the latest information updated until August 2024. We utilized Stata 18 for data analysis, computing weighted mean differences (WMDs) for continuous data and odds ratios (ORs) for categorical data, with all results reported alongside 95% confidence intervals (CIs). Additionally, the studies included were evaluated using the Newcastle-Ottawa Scale (NOS). RESULTS: This meta-analysis incorporated data from three paired studies, encompassing a total of 1,503 patients. Patients treated with HIFU experienced a shorter hospital stay (WMD = -2.78, 95%CI -5.14,-0.43; p = 0.02) compared to those who received RARP. Additionally, evaluations at 3 and 12 months post-surgery revealed that the HIFU group exhibited better recovery in urinary continence and sexual function than the RARP group. However, there were no notable disparities in complication rates (OR = 1.48, 95%CI 0.92,2.40; p = 0.110) and the requirement for salvage therapy (OR = 2.92, 95%CI 0.60,14.33; p = 0.186) between the two treatment methods. CONCLUSION: In conclusion, this meta-analysis appears to suggest potential benefits of HIFU partial gland ablation in possibly reducing the length of hospital stays and seems to indicate that it might be associated with improved recovery in terms of urinary incontinence and sexual function, particularly during the early to mid-term postoperative period. Although the differences in complication rates and the requirement for salvage therapy between the two surgical methods were not statistically significant, the findings provided by this analysis are instrumental in guiding clinical decision-making.
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Ultrasonido Enfocado de Alta Intensidad de Ablación , Prostatectomía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Humanos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Masculino , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Resultado del Tratamiento , Tiempo de Internación/estadística & datos numéricos , Medicina Basada en la Evidencia , Próstata/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Incontinencia Urinaria/etiologíaRESUMEN
Evaluating the risk factors for the conversion from robotic-assisted partial nephrectomy (RAPN) to radical nephrectomy (RN). Through a comprehensive database search encompassing PubMed, Web of Science, Embase, and the Cochrane Library, we identified pertinent English-language research published by June 2024. We utilized the NOS scale for quality assessment. The aggregate effect was quantified via the odds ratio (OR), alongside a 95% confidence interval (CI). Sensitivity analyses were conducted using both fixed-effects and random-effects models to evaluate reliability. The meta-analytical process was facilitated by the Stata 18 software suite. Our meta-analysis encompassed a total of 8 retrospective studies and 3 prospective studies, totaling 4056 patients. We found that increasing patient age (OR: 1.04; 95% CI 1.00-1.08; P = 0.005), higher American Society of Anesthesiologists (ASA) scores (3 or above) (OR: 2.74; 95% CI 1.52-4.93; P = 0.001), elevated R.E.N.A.L. scores (7 or above) (OR: 2.49; 95% CI 1.57-3.95; P < 0.001), and the use of off-clamp RAPN (OR: 7.21; 95% CI 2.60-19.93; P < 0.001) significantly raised the odds of surgical conversion. On the other hand, male sex (OR: 1.04; 95% CI 0.67-1.62; P = 0.858), the side of the tumor (OR: 0.97; 95% CI 0.48-1.95; P = 0.936), tumor size (OR: 3.43; 95% CI 0.57-20.55; P = 0.177), body mass index (BMI) (OR: 1.03; 95% CI 0.96-1.11; P = 0.426), clinical stage (OR: 3.78; 95% CI 0.46-30.70; P = 0.214), and the use of single-port RAPN (OR: 0.54; 95% CI 0.16-1.78; P = 0.31) did not show a statistically significant link to an increased conversion risk. This meta-analysis elucidates the critical risk factors for the conversion from robotic-assisted partial nephrectomy to radical nephrectomy, providing significant guidance for preoperative risk assessment and clinical decision-making. However, our findings necessitate validation through studies with larger sample sizes.
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Neoplasias Renales , Nefrectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Nefrectomía/métodos , Neoplasias Renales/cirugía , Factores de Riesgo , Masculino , Femenino , Factores de EdadRESUMEN
Assessing the perioperative, oncological, and functional results of robotic-assisted radical prostatectomy (RARP) versus three-dimensional laparoscopic radical prostatectomy (3D LRP), a comprehensive exploration of the Cochrane Library, PubMed, EMBASE, and Web of Science databases was carried out until July 2024. The combined results were evaluated by utilizing the weighted mean differences (WMDs) and odds ratios (ORs) through the application of Stata version 18, where data were gathered and scrutinized. In addition, sensitivity analyses were performed to ensure the robustness of our findings. In the meta-analysis we conducted, four studies were incorporated in total, which comprised two randomized controlled trials, one study that was retrospective and another that was prospective. The findings revealed that RARP was associated with a significantly reduced estimated blood loss (EBL) (WMD - 31.04, 95%CI - 54.57, - 7.51; p = 0.01) compared to 3D LRP. Nonetheless, there were no notable statistical variances seen between the two groups regarding operative time (OT), nerve-sparing rates, positive surgical margin (PSM) rates, biochemical recurrence (BCR) rates, or the restoration of urinary continence and potency 3 or 6 months after the surgery. In conclusion, our comprehensive meta-analysis has offered a detailed contrast between the results of RARP and 3D LRP in the treatment of prostate cancer. The findings highlight a considerable decrease in projected blood loss linked with RARP, yet no notable variances were detected between the two methods regarding other perioperative, oncological, and functional results.
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Pérdida de Sangre Quirúrgica , Laparoscopía , Prostatectomía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Laparoscopía/métodos , Márgenes de Escisión , Tempo Operativo , Prostatectomía/efectos adversos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del Tratamiento , Incontinencia Urinaria/etiología , Incontinencia Urinaria/prevención & controlRESUMEN
Chronic pain, as a social public health problem, has a serious impact on the quality of patients' life. Currently, the main drugs used to treat chronic pain are opioids, antipyretic, and nonsteroidal anti-inflammatory drugs (NSAIDs). But the obvious side effects limit their use, so it is urgent to find new therapeutic targets. Postsynaptic density (PSD)-95 protein plays an important role in the occurrence and development of chronic pain. The over-expression of the PSD-95 protein and its interaction with other proteins are closely related to the chronic pain. Besides, the PSD-95-related drugs that inhibit the expression of PSD-95 as well as the interaction with other protein have been proved to treat chronic pain significantly. In conclusion, although more deep studies are needed in the future, these studies indicate that PSD-95 and the related proteins, such as NMDA receptor (NMDAR) subunit 2B (GluN2B), AMPA receptor (AMPAR), calmodulin-dependent protein kinase II (CaMKII), 5-hydroxytryptamine 2A receptor (5-HT2AR), and neuronal nitric oxide synthase (nNOS), are the promising therapeutic targets for chronic pain.
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The traditional preparation method of ratiometric probes faces challenges such as cumbersome preparation and low sensitivity. Thus, there is an urgent need to provide a simple method of preparing a highly sensitive ratiometric probe. Here, Eu3+-doped zinc-based organic framework (Eu/Zn-MOF) was prepared through hydrothermal method for the detection of tetracycline analogs (TCs). Under the same excitation conditions, the probe can simultaneously display valuable fluorescence and second-order scattering signals. The developed probe enabled specific identification and fast detection (1 min) of TCs, including tetracycline, oxytetracycline, doxycycline, and chlortetracycline. The linear detection ranges of tetracycline, oxytetracycline, doxycycline and chlortetracycline were respectively 100 nM - 200 µM, 100 nM - 200 µM, 98 nM - 195 µM, and 97 nM - 291 µM, and the corresponding detection limits were respectively 15.79 nM, 20.83 nM, 15.31 nM, and 28.30 nM. The developed sensor was successfully applied to detect TCs in real samples, and the recovery rate was from 92.54 % to 109.69 % and the relative standard deviation was from 0.04 % to 2.97 %. Moreover, the heterometallic Eu/Zn-MOF was designed as a ratiometric neuron for Boolean logic computing and information encryption based on the specific identification of TCs. As a proof of concept, molecular steganography was successfully employed to encode, store, and conceal information by transforming the specific identification patterns of Eu/Zn-MOF into binary strings. This study is anticipated to advance the application of metal-organic frameworks in logic detection and information security, and bridging the gap between molecular sensors and the realm of information.
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Europio , Estructuras Metalorgánicas , Espectrometría de Fluorescencia , Zinc , Estructuras Metalorgánicas/química , Europio/química , Zinc/química , Zinc/análisis , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Tetraciclinas/análisis , Límite de Detección , Antibacterianos/análisis , Tetraciclina/análisis , FluorescenciaRESUMEN
Somatic mutation phasing informs our understanding of cancer-related events, like driver mutations. We generated linked-read whole genome sequencing data for 23 samples across disease stages from 14 multiple myeloma (MM) patients and systematically assigned somatic mutations to haplotypes using linked-reads. Here, we report the reconstructed cancer haplotypes and phase blocks from several MM samples and show how phase block length can be extended by integrating samples from the same individual. We also uncover phasing information in genes frequently mutated in MM, including DIS3, HIST1H1E, KRAS, NRAS, and TP53, phasing 79.4% of 20,705 high-confidence somatic mutations. In some cases, this enabled us to interpret clonal evolution models at higher resolution using pairs of phased somatic mutations. For example, our analysis of one patient suggested that two NRAS hotspot mutations occurred on the same haplotype but were independent events in different subclones. Given sufficient tumor purity and data quality, our framework illustrates how haplotype-aware analysis of somatic mutations in cancer can be beneficial for some cancer cases.
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Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.
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Neoplasias Encefálicas , Glioma , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Transducción de Señal , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Glioma/genética , Glioma/patología , Glioma/metabolismo , Mutación , Proteómica/métodos , Procesamiento Proteico-Postraduccional , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/metabolismo , Fosforilación , Clasificación del Tumor , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismoRESUMEN
A very simple and atom-economical method for the synthesis of vicinal trifluoromethyl thioethers via DBN-catalyzed hydrothiolation of α-(trifluoromethyl)styrenes with thiols was reported. The reaction proceeded smoothly under mild reaction conditions and provided the ß-CF3-thioethers in moderate to good yields in an anti-Markovnikov manner. Furthermore, this method features several remarkable advantages, such as the use of a catalytic amount of DBN, broad substrate scope, excellent functional group compatibility, and easy scalability.
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Insects detect and discriminate a diverse array of chemicals using odorant receptors (ORs), which are ligand-gated ion channels comprising a divergent odorant-sensing OR and a conserved odorant receptor co-receptor (Orco). In this work, we report structures of the ApOR5-Orco heterocomplex from the pea aphid Acyrthosiphon pisum alone and bound to its known activating ligand, geranyl acetate. In these structures, three ApOrco subunits serve as scaffold components that cannot bind the ligand and remain relatively unchanged. Upon ligand binding, the pore-forming helix S7b of ApOR5 shifts outward from the central pore axis, causing an asymmetrical pore opening for ion influx. Our study provides insights into odorant recognition and channel gating of the OR-Orco heterocomplex and offers structural resources to support development of innovative insecticides and repellents for pest control.
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Acetatos , Áfidos , Proteínas de Insectos , Receptores Odorantes , Receptores Odorantes/química , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Animales , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Áfidos/química , Acetatos/química , Acetatos/metabolismo , Ligandos , Terpenos/química , Terpenos/metabolismo , Odorantes/análisis , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Activación del Canal Iónico , Microscopía por Crioelectrón , Monoterpenos AcíclicosRESUMEN
Sex pheromones play crucial role in mating behavior of moths, involving intricate recognition mechanisms. While insect chemical biology has extensively studied type I pheromones, type II pheromones remain largely unexplored. This study focused on Helicoverpa armigera, a representative species of noctuid moth, aiming to reassess its sex pheromone composition. Our research unveiled two previously unidentified candidate type II sex pheromones-3Z,6Z,9Z-21:H and 3Z,6Z,9Z-23:H-in H. armigera. Furthermore, we identified HarmOR11 as an orphan pheromone receptor of 3Z,6Z,9Z-21:H. Through AlphaFold2 structural prediction, molecular docking, and molecular dynamics simulations, we elucidated the structural basis and key residues governing the sensory nuances of both type I and type II pheromone receptors, particularly HarmOR11 and HarmOR13. This study not only reveals the presence and recognition of candidate type II pheromones in a noctuid moth, but also establishes a comprehensive structural framework for PRs, contributing to the understanding of connections between evolutionary adaptations and the emergence of new pheromone types.
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Mariposas Nocturnas , Receptores de Feromonas , Atractivos Sexuales , Animales , Atractivos Sexuales/metabolismo , Atractivos Sexuales/química , Mariposas Nocturnas/metabolismo , Mariposas Nocturnas/fisiología , Receptores de Feromonas/metabolismo , Receptores de Feromonas/genética , Masculino , Proteínas de Insectos/metabolismo , Proteínas de Insectos/química , Femenino , Simulación del Acoplamiento Molecular , Secuencia de Aminoácidos , Filogenia , Simulación de Dinámica Molecular , Conducta Sexual Animal/fisiologíaRESUMEN
Objective: The incidence of perioperative neurocognitive disorders (PND) is high, especially after cardiac surgeries, and the underlying mechanisms remain elusive. Here, we conducted a prospective observational study to observe serum proteomics differences in PND patients after cardiac valve replacement surgery. Methods: Two hundred and twenty-six patients who underwent cardiac valve surgery were included. They were categorized based on scoring into non-PND group (group non-P) and PND group (group P'). The risk factors associated with PND were analyzed. These patients were further divided into group C and group P by propensity score matching (PSM) to investigate the serum proteome related to the PND by serum proteomics. Results: The postoperative 6-week incidence of PND was 16.8%. Risk factors for PND include age, chronic illness, sufentanil dosage, and time of cardiopulmonary bypass (CPB). Proteomics identified 31 down-regulated proteins and six up-regulated proteins. Finally, GSTO1, IDH1, CAT, and PFN1 were found to be associated with PND. Conclusion: The occurrence of PND can impact some oxidative stress proteins. This study provided data for future studies about PND to general anaesthesia and surgeries.
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Implantación de Prótesis de Válvulas Cardíacas , Proteómica , Humanos , Masculino , Estudios Prospectivos , Femenino , Proteómica/métodos , Persona de Mediana Edad , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Factores de Riesgo , Disfunción Cognitiva/sangre , Disfunción Cognitiva/etiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/diagnóstico , Anciano , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Cognitivas Postoperatorias/epidemiología , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/sangre , Complicaciones Cognitivas Postoperatorias/diagnóstico , Incidencia , Puntaje de Propensión , AdultoRESUMEN
A novel two-step synthesis of ß-trifluoromethyl primary amines from readily available α-(trifluoromethyl)styrenes and phthalimide is developed. The first step involves a hydroamination between α-(trifluoromethyl)styrenes and phthalimide (PhthNH) with the assistance of a base. Next, the hydrazinolysis of the resulting N-(ß-trifluoromethyl-ß-arylethyl)phthalimides with hydrazine hydrate affords the desired N-(ß-trifluoromethyl-ß-arylethyl)amines.
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Neuroinflammation induced by engulfment of synapses by phagocytic microglia plays a crucial role in neuropathic pain. Stauntonia chinensis is extracted from Stauntonia chinensis DC, which has been used as a traditional Chinese medicine to control trigeminal neuralgia or sciatica. However, the specific anti-neuralgia mechanism of Stauntonia chinensis is unknown. In this study, the analgesic effect of Stauntonia chinensis injection (SCI) in mice with neuropathic pain and the possible mechanisms are explored. We find that a local injection of 0.1 mL Stauntonia chinensis for 14 days can considerably relieve mechanical hyperalgesia and thermal hyperalgesia in mice with sciatic chronic constriction injury (CCI). Immunofluorescence staining shows that SCI reduces neuroinflammation in the spinal cord of CCI mice. RNA sequencing reveals that the expression of postsynaptic density protein 95 (PSD-95), a postsynaptic scaffold protein, is downregulated in the spinal cord of CCI mice, but upregulated after SCI administration. Immunofluorescence experiments also demonstrate that SCI administration reverses microglia proliferation and PSD-95 downregulation in CCI mice. These data suggest that SCI relieves neuropathic pain by increasing the expression of PSD-95 and reducing the proliferation of phagocytic microglia.
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The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions. Complement proteins C1q, C3, C5, as well as their cleavage products C3a and C5a, along with the associated receptors C3aR, CR3, and C5aR, are believed to have significant implications in the comorbid mechanism. The primary potential mechanisms encompass the involvement of the complement cascade C1q/C3-CR3 in the activation of microglia and synaptic pruning in the amygdala and hippocampus, the role of complement cascade C3/C3a-C3aR in the interaction between astrocytes and microglia, leading to synaptic pruning, and the C3a-C3aR axis and C5a-C5aR axis to trigger inflammation within the central nervous system. We focus on studies on the role of the complement system in the comorbid mechanisms of chronic pain and depression.
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BACKGROUND: Ecosystems are brimming with myriad compounds, including some at very low concentrations that are indispensable for insect survival and reproduction. Screening strategies for identifying active compounds are typically based on bioassay-guided approaches. RESULTS: Here, we selected two candidate odorant receptors from a major pest of cruciferous plants-the diamondback moth Plutella xylostella-as targets to screen for active semiochemicals. One of these ORs, PxylOR16, exhibited a specific, sensitive response to heptanal, with both larvae and adult P. xylostella displaying heptanal avoidance behavior. Gene knockout studies based on CRISPR/Cas9 experimentally confirmed that PxylOR16 mediates this avoidance. Intriguingly, rather than being involved in P. xylostella-host plant interaction, we discovered that P. xylostella recognizes heptanal from the cuticular volatiles of the parasitoid wasp Cotesia vestalis, possibly to avoid parasitization. CONCLUSIONS: Our study thus showcases how the deorphanization of odorant receptors can drive discoveries about their complex functions in mediating insect survival. We also demonstrate that the use of odorant receptors as a screening platform could be efficient in identifying new behavioral regulators for application in pest management.
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Aldehídos , Mariposas Nocturnas , Receptores Odorantes , Avispas , Animales , Ecosistema , LarvaRESUMEN
BACKGROUND: The study aimed to investigate the diagnostic value of lupus-related pattern recognition receptors (PRRs) genes in peripheral blood mononuclear cells (PBMCs) and monocytes (MONs) for lupus nephritis (LN). METHODS: PBMCs were isolated from a cohort with 37 LN patients and 39 healthy controls (HCs), and MONs were derived from another cohort with 70 LN patients and 66 HCs. Q-PCR was used to measure the mRNA levels of CGAS, IFNB1, AIM2, IL1Β, NLRC4, NLRP3, NLRP12 and ZBP1 in the PBMCs and MONs. The Mann-Whitney U test was used to compare the data in LN patients and HCs. Eleven GEO datasets of SLE/LN were used to perform differentially expressed genes (DEGs) analysis to these PRR genes. Receiver operating characteristic (ROC) curve analysis was employed to assess the performance of individual genes or the disease prediction model established by combining multiple genes in LN diagnosis. Spearman correlation method was done to analyze the correlation between these PRRs and other clinical characteristics. RESULTS: The mRNA levels of five genes (AIM2, NLRC4, IL1B, NLRP12 and ZBP1) in PBMCs, and seven genes (CGAS, IFNB1, AIM2, IL1B, NLRP3, NLRP12 and ZBP1) in MONs of LN patients were significantly higher than those of HCs (P < 0.05). DEGs analysis based on the GEO datasets showed that ZBP1, AIM2 and IL1B were significantly increased in several datasets. The ROC curve analysis indicated that the area under curve (AUC) of the LN prediction models derived from PBMCs or MONs were 0.82 or 0.91 respectively. In addition, the expression levels of these PRRs were correlated with other clinical features in LN patients, including Anti-Sm, ESR, serum Cr, and C3. CONCLUSION: Our study suggests that these lupus-related PRRs might be served as potential biomarkers of LN.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/genética , Nefritis Lúpica/metabolismo , Leucocitos Mononucleares/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Monocitos/metabolismo , Biomarcadores , ARN Mensajero/genética , Nucleotidiltransferasas , Curva ROCRESUMEN
Introduction: Circular RNA (circRNAs) are a type of non-coding RNA (ncRNAs) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic kidney disease (DKD), owing to their stability and enrichment in exosomes. However, the role of circRNAs in exosomes of tubular epithelial cells in DKD development has not been fully elucidated. Methods: In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. The small interfering RNAs (siRNA) and plasmid overexpression were used to validate functions of differentially expressed circRNAs. Results: We found that exosome concentration was higher in HG-stimulated HK-2 cells than in controls. A total of 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of the HG group. In parallel with the microarray data, the qPCR results showed that the expression of circ_0009885, circ_0043753, and circ_0011760 increased, and the expression of circ_0032872, circ_0004716, and circ_0009445 decreased in the HG group. Rescue experiments showed that the effects of high glucose on regulation of CCL2, IL6, fibronetin, n cadherin, e cadherin and epcam expression can be reversed by inhibiting or overexpressing these circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses indicated that circRNA parental genes are associated with glucose metabolism, lipid metabolism, and inflammatory processes, which are important in DKD development. Further analysis of circRNA/miRNA interactions indicated that 152 differentially expressed circRNAs with fold change (FC) ≥1.5 could be paired with 43 differentially expressed miRNAs, which are associated with diabetes or DKD. Discussion: Our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers, and may play a critical role in the progression of DKD.
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The successful mating of the hoverfly and the search for prey aphids are of great significance for biological control and are usually mediated by chemical cues. The odorant receptor co-receptor (Orco) genes play a crucial role in the process of insect odor perception. However, the function of Orco in the mating and prey-seeking behaviors of the hoverfly remains relatively unexplored. In this study, we characterized the Orco gene from the hoverfly, Eupeodes corollae, a natural enemy insect. We used the CRISPR/Cas9 technique to knock out the Orco gene of E. corollae, and the EcorOrco-/- homozygous mutant was verified by the genotype analysis. Fluorescence in situ hybridization showed that the antennal ORN of EcorOrco-/- mutant lack Orco staining. Electroantennogram (EAG) results showed that the adult mutant almost lost the electrophysiological response to 15 odorants from three types. The two-way choice assay and the glass Y-tube olfactometer indicated that both the larvae and adults of hoverflies lost their behavioral preference to the aphid alarm pheromone (E)-ß-farnesene (EBF). In addition, the mating assay results showed a significant decrease in the mating rate of males following the knock out of the EcorOrco gene. Although the mating of females was not affected, the amount of eggs being laid and the hatching rate of the eggs were significantly reduced. These results indicated that the EcorOrco gene was not only involved in the detection of semiochemicals in hoverflies but also plays a pivotal role in the development of eggs. In conclusion, our results expand the comprehension of the chemoreceptive mechanisms in the hoverflies and offers valuable insights for the advancement of more sophisticated pest management strategies.
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Dípteros , Receptores Odorantes , Animales , Femenino , Masculino , Odorantes , Receptores Odorantes/genética , Hibridación Fluorescente in Situ , Dípteros/genética , Insectos/genética , Feromonas , Mutagénesis , Proteínas de Insectos/genéticaRESUMEN
Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.
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Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias , Humanos , Hipoxia de la Célula , Núcleo Celular , Cromatina/genética , Cromatina/metabolismo , Elementos de Facilitación Genéticos/genética , Epigénesis Genética/genética , Transición Epitelial-Mesenquimal , Estrógenos/metabolismo , Perfilación de la Expresión Génica , Proteínas Activadoras de GTPasa/metabolismo , Metástasis de la Neoplasia , Neoplasias/clasificación , Neoplasias/genética , Neoplasias/patología , Secuencias Reguladoras de Ácidos Nucleicos/genética , Análisis de la Célula Individual , Factores de Transcripción/metabolismoRESUMEN
Chemotherapy is one of the main treatments for hematologic malignancies. However, chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxic reactions in chemotherapy, and the occurrence of CIPN affects patients' quality of life and can cause interruption of chemotherapy in severe cases, thus reducing the efficacy of chemotherapy. We currently summarize the existing CIPN animal models, including the characteristics of several common animal models such as bortezomib-induced peripheral neuropathy, vincristine-induced peripheral neuropathy, and oxaliplatin-induced peripheral neuropathy. It was found that CIPN may lead to behavioral, histopathological, and neurophysiological changes inducing peripheral neuropathy. However, the mechanism of CIPN has not been fully elucidated, especially the prevention and treatment protocols need to be improved. Therefore, this review article summarizes the progress of research on CIPN animal models and the possible mechanisms and treatment of CIPN.