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BACKGROUND: Previous research has focused on the association between immune cells and the development of benign prostatic hyperplasia (BPH). Nevertheless, the causal relationships in this context remain uncertain. METHODS: This study employed a comprehensive and systematic two-sample Mendelian randomization (MR) analysis to determine the causal relationships between immunophenotypes and BPH. We examined the causal associations between 731 immunophenotypes and the risk of BPH by utilizing publicly available genetic data. Integrated sensitivity analyses were performed to validate the robustness, assess heterogeneity, and examine horizontal pleiotropy in the results. RESULTS: We discovered that 38 immunophenotypes have a causal effect on BPH. Subsequently, four of these immunophenotypes underwent verification using weighted median, weighted mode, and inverse variance weighted (IVW) algorithms, which included CD19 on CD24+ CD27+, CD19 on naive-mature B cell, HLA DR on CD14- CD16+ and HLA DR+ T cell%lymphocyte. Furthermore, BPH exhibited a significant association with three immunophenotypes: CD19 on IgD+ CD38dim (ß = -0.152, 95% CI = 0.746-0.989, P = 0.034), CD19 on IgD+ (ß = -0.167, 95% CI = 0.737-0.973, P = 0.019), and CD19 on naive-mature B cell (ß = -0.166, 95% CI = 0.737-0.972, P = 0.018). CONCLUSIONS: Our study provides valuable insights for future clinical investigations by establishing a significant association between immune cells and BPH.
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Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/genética , Análise da Randomização Mendeliana , Proteínas Adaptadoras de Transdução de Sinal , Algoritmos , Antígenos HLA-DRRESUMO
The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases.
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Sinalização do Cálcio , Hibernação , Miócitos Cardíacos/metabolismo , Animais , Caveolinas/genética , Caveolinas/metabolismo , Células Cultivadas , Acoplamento Excitação-Contração , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Nucleares/sangue , Proteínas Nucleares/metabolismo , Sciuridae , Transativadores/sangue , Transativadores/metabolismoRESUMO
PD1/PDL1 pathway plays a critical role in cancer immune responses. The immune checkpoint inhibitors of PD1/PDL1 have been well explored and developed for immunotherapies of solid tumors. Recently, various monoclonal antibodies targeting the PD1/PDL1 pathway have emerged and achieved remarkable success in clinical trials. However, challenges with these monoclonal antibodies have appeared during cancer therapies, including predictors of response, patient selection, and innate resistance. Thus, a competitive antagonist of native PD1/PDL1, with smaller size and lower side-effect, is required for future cancer therapies. In this study, we utilized a protein evolution system of phage-assisted continuous evolution (PACE) to evolve PD1 continuously. Our results indicated that the newly evolved PD1 bound to PDL1 with higher affinity. The interactome analysis further suggested that these evolved PD1s exhibited higher specificity with PDL1. Therefore, these evolved PD1s may be applied as a new tool for tumor immunotherapy.
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Antígeno B7-H1/metabolismo , Evolução Molecular Direcionada/métodos , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/química , Antígeno B7-H1/genética , Sítios de Ligação , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica/efeitos dos fármacos , Genes Reporter , Células HEK293 , Humanos , Luciferases/genética , Luciferases/metabolismo , Modelos Moleculares , Mutagênese Sítio-Dirigida/métodos , Mutagênicos/farmacologia , Biblioteca de Peptídeos , Plasmídeos/química , Plasmídeos/metabolismo , Receptor de Morte Celular Programada 1/química , Receptor de Morte Celular Programada 1/genética , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
BACKGROUND: Sleep is an essential health behavior, and sleep difficulties are strongly associated with adolescent health, potentially leading to more severe sleep disorders. The beneficial effects of physical activity (PA) in alleviating sleep difficulties have been well-documented. Numerous investigations reveal influence in moderate to high-intensity physical activity (PA) positively influences sleep quality. Despite these findings, a gap in the literature exists, particularly regarding the association between frequency of vigorous-intensity physical activity (VPA) and sleep difficulties. AIM: This study aims to bridge the knowledge gap by exploring the link between sleep difficulty and frequency of VPA among adolescents. Insights are derived from analyzing data accumulated from the Health Behavior in School-aged Children (HBSC) project. METHODS: The analysis in this study utilized cross-sectional data from the HBSC (2017/2018). The study sample comprised a total of 171,233 respondents aged 11, 13, and 15 years, with males representing 51.1% of sample. Measurement instruments included a self-administered questionnaire, providing direct insight into sleep difficulty and frequency of VPA levels. Statistical analysis on the associaiton between frequency of VPA and sleep difficulties was conducted using Generalized Linear Models. RESULTS: 50.0% of adolescents reported no sleep difficulties, while 12.3% experienced sleep issues daily. Additionally, 17.1% of adolescents engaged in frequency of VPA on a daily basis, while 6.4% never participated in such activities. daily VPA was associated with fewer sleep difficulties (OR = 1.07 [1.00, 1.15]), 4-6 times a week (OR = 1.08 [1.01, 1.15]), and 2-3 times a week (OR = 1.08 [1.02, 1.16]). However, no significant association was found between sleep difficulties and frequency of VPA in girls. Furthermore, a negative association was observed between sleep difficulties and all frequencies of VPA (p < 0.05) in 11-year-old adolescents. For 13-year-olds, daily VPA was significantly associated with fewer sleep difficulties (OR = 1.10 [1.02, 1.19]), 4-6 times a week (OR = 1.15 [1.07, 1.24]), 2-3 times a week (OR = 1.19 [1.10, 1.27]), and once a week (OR = 1.13 [1.05, 1.22]). However, no significant association was found between sleep difficulties and frequency of VPA in 15-year-old adolescents. CONCLUSION: More participations in VPA would be an effective approach to reduce sleep difficulties in adolescents. Insights gleaned from this research illustrate a discernible link between sleep difficulty and frequency of VPA, particularly notable in male and 13-year-old participants. It is also imperative to underscore the variability in the connection between sleep difficulty and frequency of VPA, distinctly influenced by factors such as gender and age. Consequently, tailoring sleep intervention methodologies to align with the specific needs dictated by these variables emerges as a pivotal recommendation.
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Exercício Físico , Transtornos do Sono-Vigília , Feminino , Criança , Humanos , Masculino , Adolescente , Estudos Transversais , Comportamentos Relacionados com a Saúde , Inquéritos e Questionários , Transtornos do Sono-Vigília/epidemiologiaRESUMO
Quantum machine learning has made remarkable progress in many important tasks. However, the gate complexity of the initial state preparation is seldom considered in lots of quantum machine learning algorithms, making them non-end-to-end. Herein, we propose a quantum algorithm for the node embedding problem that maps a node graph's topological structure to embedding vectors. The resulting quantum embedding state can be used as an input for other quantum machine learning algorithms. With O ( log ( N ) ) qubits to store the information of N nodes, our algorithm will not lose quantum advantage for the subsequent quantum information processing. Moreover, owing to the use of a parameterized quantum circuit with O ( poly ( log ( N ) ) ) depth, the resulting state can serve as an efficient quantum database. In addition, we explored the measurement complexity of the quantum node embedding algorithm, which is the main issue in training parameters, and extended the algorithm to capture high-order neighborhood information between nodes. Finally, we experimentally demonstrated our algorithm on an nuclear magnetic resonance quantum processor to solve a graph model.
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Despite advancements in medical care, the management of bone injuries remains one of the most significant challenges in the fields of medicine and sports medicine globally. Bone tissue damage is often associated with aging, reduced quality of life, and various conditions such as trauma, cancer, and infection. While bone tissue possesses the natural capacity for self-repair and regeneration, severe damage may render conventional treatments ineffective, and bone grafting may be limited due to secondary surgical procedures and potential disease transmission. In such cases, bone tissue engineering has emerged as a viable approach, utilizing cells, scaffolds, and growth factors to repair damaged bone tissue. This research shows a comprehensive review of the current literature on the most important and effective methods and materials for improving the treatment of these injuries. Commonly employed cell types include osteogenic cells, embryonic stem cells, and mesenchymal cells, while scaffolds play a crucial role in bone tissue regeneration. To create an effective bone scaffold, a thorough understanding of bone structure, material selection, and examination of scaffold fabrication techniques from inception to the present day is necessary. By gaining insights into these three key components, the ability to design and construct appropriate bone scaffolds can be achieved. Bone tissue engineering scaffolds are evaluated based on factors such as strength, porosity, cell adhesion, biocompatibility, and biodegradability. This article examines the diverse categories of bone scaffolds, the materials and techniques used in their fabrication, as well as the associated merits and drawbacks of these approaches. Furthermore, the review explores the utilization of various scaffold types in bone tissue engineering applications.
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Traumatismos em Atletas , Doenças Ósseas , Osso e Ossos , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Humanos , Alicerces Teciduais/química , Doenças Ósseas/terapia , Osso e Ossos/lesões , Traumatismos em Atletas/terapia , Animais , Regeneração ÓsseaRESUMO
BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder for which effective therapies are currently lacking. Studies suggest that increasing physical activity (PA) and reducing leisure sedentary behavior (LSB) mitigate the progression of HD, but their causal relationship with the age at onset (AAO) of HD remains uncertain. To investigate this, we conducted the Two-sample Mendelian Randomization (MR). METHODS: Exposure were retrieved from the UK BioBank's (UKB) Genome-Wide Association Study (GWAS). PA included accelerometer-based average PA, vigorous PA, self-reported moderate-to-vigorous PA (MVPA), and light do-it-yourself activity. LSB included television (TV) time, computer time, and driving time. Outcome came from the GWAS of the GEM-HD Consortium. We applied several MR methods such as inverse variance weighted (IVW), MR-Egger regression, weighted median (WM) for sensitivity analysis. RESULTS: Increases in light PA (ß = 8.53 years, 95 % CI = 10.64 to 44.09, P = 0.001) and accelerometer-based vigorous PA (ß = 5.18, 95 % CI = 0.92 to 9.43, P = 0.017) delayed AAO of HD, while longer TV time was associated with earlier AAO of HD (ß = -2.88 years, 95 % CI = -4.99 to -0.77, P = 0.007). However, other PA and LSB phenotypes did not significantly affect AAO of HD. CONCLUSION: The study revealed a unidirectional causality between PA, LSB and the AAO of HD. Increasing PA and reducing TV time delay HD onset. Therefore, we recommend increasing physical activity and reducing sedentary behavior to delay the occurrence of motor symptoms for premanifest HD individuals.
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Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFß1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFß1 suppression. Overall, TGFß1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process.
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Fator 9 de Crescimento de Fibroblastos , Fibrose , MicroRNAs , Inibidores da Fosfodiesterase 5 , Hiperplasia Prostática , Tadalafila , Masculino , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Tadalafila/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Humanos , Fator 9 de Crescimento de Fibroblastos/metabolismo , Fator 9 de Crescimento de Fibroblastos/genética , Próstata/efeitos dos fármacos , Próstata/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Proliferação de Células/efeitos dos fármacosRESUMO
Abscisic acid (ABA)-based chemically induced proximity (CIP) is primarily mediated by the interaction of the ABA receptor pyrabactin resistance 1-like 1 (PYL1) and the 2C-type protein phosphatase ABI1, which confers ABA-induced proximity to their fusion proteins, and offers precise temporal control of a wide array of biological processes. However, broad application of ABA-based CIP has been limited by ABA response intensity. In this study, we demonstrated that ABA-induced interaction between another ABA receptor pyrabactin resistance 1 (PYR1) and ABI1 exhibited higher ABA response intensity than that between PYL1 and ABI1 in HEK293T cells. We engineered PYR1-ABI1 and PYL1-ABI1 into ABA-induced transcriptional activation tools in mammalian cells by integration with CRISPR/dCas9 and found that the tool based on PYR1-ABI1 demonstrated better ABA response intensity than that based on PYL1-ABI1 for both exogenous and endogenous genes in mammalian cells. We further achieved ABA-induced RNA m6A modification installation and erasure by combining ABA-induced PYR1-ABI1 interaction with CRISPR/dCas13, successfully inhibiting tumor cell proliferation. We subsequently improved the interaction of PYR1-ABI1 through phage-assisted continuous evolution (PACE), successfully generating a PYR1 mutant (PYR1m) whose interaction with ABI1 exhibited a higher ABA response intensity than that of the wild-type. In addition, we tested the transcriptional activation tool based on PYRm-ABI1 and found that it also showed a higher ABA response intensity than that of the wild type. These results demonstrate that we have developed a novel ABA-based CIP and further improved upon it using PACE, providing a new approach for the modification of other CIP systems.
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Parallel tidal channel systems, characterized by commonly cross-shore orientation and regular spacing, represent a distinct class of tidal channel networks in coastal environments worldwide. Intriguingly, these cross-shore oriented channel systems can develop in environments dominated by alongshore tidal currents, for which the mechanisms remain elusive. Here, we combine remote sensing imagery analysis and morphodynamic simulations to demonstrate that the deflection of alongshore tidal currents at transitions in bed elevation determines the characteristic orientation of the parallel tidal channels. Numerical results reveal that sharp changes in bed elevation lead to nearly 90-degree intersection angles, while smoother transitions in bed profiles result in less perpendicular channel alignments. These findings shed light on the potential manipulation of tidal channel patterns in coastal wetlands, thus equipping coastal managers with a broader range of strategies for the sustainable management of these vital ecosystems in the face of climate change and sea level rise.
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Molecular markers for predicting oral cancer development in premalignant oral leukoplakia (OL) are urgently needed. The objective of this study was to examine the expression patterns of cancer stem cell markers ALDH1 and CD133 in samples from patients with OL, and determine their prognostic values for subsequent development of oral cancer. Immunohistochemistry for ALDH1 and CD133 was performed in samples from a cohort of 141 patients with biopsy-proven OL who received a mean follow-up of 5.5 years. Patient clinicopathologic and follow-up data were analyzed. Expression of ALDH1 and CD133 was observed in 54 (38.3%) and 32 (22.7%) of 141 patients with OL, respectively. Kaplan-Meier analysis showed that 48.1% patients with ALDH1-positivity developed oral cancer compared with 12.6% those with ALDH1-negativity (p < 0.001). Meanwhile, 59.4% patients with CD133-positivity developed oral cancer compared with 16.5% those with CD133-negativity (p < 0.001). Multivariate analysis revealed that ALDH1 and CD133 expression was associated with 4.17-fold [95% confidence interval (CI), 1.96-8.90; p < 0.001] and 2.86-fold (95% CI, 1.48-5.55; p = 0.002) increased risk of OL transformation, respectively. Collectively, these data demonstrated for the first time that the expression of ALDH1 and CD133 correlated with malignant transformation in a large series of patients with OL who received a long-term follow-up, which suggests that they may serve as predictors to identify OL with a high risk of oral cancer development.
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Antígenos CD/metabolismo , Transformação Celular Neoplásica , Glicoproteínas/metabolismo , Isoenzimas/metabolismo , Leucoplasia Oral/metabolismo , Neoplasias Bucais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Peptídeos/metabolismo , Retinal Desidrogenase/metabolismo , Antígeno AC133 , Adulto , Idoso , Família Aldeído Desidrogenase 1 , Biomarcadores Tumorais/metabolismo , Transformação Celular Neoplásica/metabolismo , Estudos de Coortes , Feminino , Humanos , Leucoplasia Oral/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Phospholipase C-γ1 (PLCγ1) is required for cellular migration during tumor progression and invasion of oral squamous cell carcinoma (OSCC) cells. The objective of the current study was to determine immunoexpression pattern of PLCγ1 in oral potentially malignant lesions (OPLs) and evaluate PLCγ1 usefulness as a biomarker for predicting clinical behavior in the carcinogenesis of OPL. METHODS: In a retrospective follow-up study, the expression pattern of PLCγ1 protein was determined using immunohistochemistry in samples from 68 patients, including untransformed cases (n = 38) and malignant-transformed cases (n = 30). The corresponding post-malignant lesions (OSCCs) were also performed. RESULTS: We observed that elevated expression of PLCγ1 in 40 of 68 (59%) general OPLs and 23 of 30 (77%) OSCCs compared with that in normal oral mucosa. Kaplan-Meier analysis revealed that patients with PLCγ1 positivity had a significantly higher incidence of OSCC than those with PLCγ1 negativity. Cox regression analysis revealed that PLCγ1 expression patterns were significantly associated with increased risk of malignant progression. In addition, the correlation between PLCγ1 expression in pre-malignant OPL and that in post-malignant OSCC was significant (P = 0.004). CONCLUSION: These data indicate that PLCγ1 expression in OPL correlated with oral cancer progression, and PLCγ1 may serve as a useful marker for the identification of high-risk OPL into OSCC.
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Carcinoma de Células Escamosas/metabolismo , Transformação Celular Neoplásica/metabolismo , Neoplasias Bucais/metabolismo , Invasividade Neoplásica/patologia , Fosfolipase C gama/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Receptores ErbB/fisiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/metabolismo , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Transdução de Sinais , Células Tumorais CultivadasRESUMO
BACKGROUND: Oral erythroplakia (OE) is a notoriously aggressive oral pre-malignant lesion with a high tendency to oral cancer development, but its biological behavior is largely unknown. The objective of this study was to determine the expression of cancer stem cell markers ALDH1 and Bmi1 in OE and their correlation with malignant transformation of OE. METHODS: In a retrospective case-control study, expression patterns of ALDH1 and Bmi1 were determined using immunohistochemistry in samples from 34 patients with OE, including patients with untransformed lesions (n=17) and patients with malignant transformed lesions (n=17). RESULTS: ALDH1 and Bmi1 expression was observed in 19 (55.9%) and 20 (58.8%) of 34 patients with OE, respectively. Multivariate analysis revealed that ALDH1 expression was significantly associated with increased risk of transformation (P<0.05), but Bmi1 expression was not a significant marker (P > 0.05). Notably, the coexpression of both ALDH1 and Bmi1 was a strong indicator associated with 8.56-fold (95% confidence interval [CI], 1.74-42.17; P<0.01) for malignant transformation. Point prevalence analysis revealed that 78.6% (95% CI, 54.0-100) of the patient with coexpression of both ALDH1 and Bmi1 developed oral cancer. CONCLUSION: Our data indicated that the expression patterns of ALDH1 and Bmi1 in OE were associated with malignant transformation, suggesting that they may be valuable predictors for evaluating the risk of oral cancer.
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Biomarcadores Tumorais/análise , Eritroplasia/patologia , Isoenzimas/análise , Neoplasias Bucais/patologia , Células-Tronco Neoplásicas/patologia , Complexo Repressor Polycomb 1/análise , Retinal Desidrogenase/análise , Dedos de Zinco/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Família Aldeído Desidrogenase 1 , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Transformação Celular Neoplásica/patologia , Estudos de Coortes , Feminino , Seguimentos , Previsões , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , FumarRESUMO
The design of the probes is based on bioluminescence imaging, which has been widely adopted in studies of many important biological processes. Traditional Chinese Medicine (TCM) fitness could improve the state of health of adults' intestinal flora. The research aims at analyzing the impact of TCM fitness on the intestinal probiotics (Bifidobacterium, Lactobacillus) and opportunistic pathogen (Enterococcus, Enterobacteriaceae) by the noninvasive imaging. In accordance with the searching results, the researchers have found that TCM fitness has a significant impact on improving Bifidobacterium (SDM = 1.55; P = 0.02) and Lactobacillus (SDM = 1.26; P <0.01), while the impact could not be seen on Enterococcus (SDM = 0.29;P = 0.68) and Enterobacteriaceae (SDM = 0.05;P = 0.94). And there is no significant difference between the two interventions of Tai Chi and Fitness Qigong. The results of the present review show that TCM fitness could significantly better the probiotics of intestinal flora while the influence on opportunistic pathogen needs to be further investigated with the precise and reasonable proof of scientific studies.The findings suggest that TCM fitness can be used as an effective intervention, and there is no significant difference between the two interventions on the improvement of the intestinal flora. The using of optical tool based on ultrasensitive bioluminescent imaging may lead to better precision medicine treatments in the future.
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Microbioma Gastrointestinal , Qigong , Tai Chi Chuan , Medicina Tradicional Chinesa/métodosRESUMO
BACKGROUND: Cancer-associated fibroblasts (CAFs) are an essential component of the tumor immune microenvironment that are involved in extracellular matrix (ECM) remodeling. We aim to investigate the characteristics of CAFs in prostate cancer and develop a biochemical recurrence (BCR)-related CAF signature for predicting the prognosis of PCa patients. METHODS: The bulk RNA-seq and relevant clinical information were obtained from the TCGA and GEO databases, respectively. The infiltration scores of CAFs in prostate cancer patients were calculated using the MCP counter and EPIC algorithms. The single-cell RNA sequencing (scRNA-seq) was downloaded from the GEO database. Subsequently, univariate Cox regression analysis was employed to identify prognostic genes associated with CAFs. We identified two subtypes (C1 and C2) of prostate cancer that were associated with CAFs via non-negative matrix factorization (NMF) clustering. In addition, the BCR-related CAF signatures were constructed using Lasso regression analysis. Finally, a nomogram model was established based on the risk score and clinical characteristics of the patients. RESULTS: Initially, we found that patients with high CAF infiltration scores had shorter biochemical recurrence-free survival (BCRFS) times. Subsequently, CAFs in four pairs of tumors and paracancerous tissues were identified. We discovered 253 significantly differentially expressed genes, of which 13 had prognostic significance. Using NMF clustering, we divided PCa patients into C1 and C2 subgroups, with the C1 subgroup having a worse prognosis and substantially enriched cell cycle, homologous recombination, and mismatch repair pathways. Furthermore, a BCR-related CAFs signature was established. Multivariate COX regression analysis confirmed that the BCR-related CAFs signature was an independent prognostic factor for BCR in PCa. In addition, the nomogram was based on the clinical characteristics and risk scores of the patient and demonstrated high accuracy and reliability for predicting BCR. Lastly, our findings indicate that the risk score may be a useful tool for predicting PCa patients' sensitivity to immunotherapy and drug treatment. CONCLUSION: NMF clustering based on CAF-related genes revealed distinct TME immune characteristics between groups. The BCR-related CAF signature accurately predicted prognosis and immunotherapy response in prostate cancer patients, offering a promising new approach to cancer treatment.
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Fibroblastos Associados a Câncer , Neoplasias da Próstata , Masculino , Humanos , Reprodutibilidade dos Testes , Prognóstico , Neoplasias da Próstata/genética , RNA-Seq , Microambiente Tumoral/genéticaRESUMO
Sepsis often causes organ dysfunction and is manifested in increased endothelial cell permeability in blood vessels. Early-stage inflammation is accompanied by metabolic changes, but it is unclear how the metabolic alterations in the endothelial cells following lipopolysaccharide (LPS) stimulation affect endothelial cell function. In this study, the effects of 1 µg/ml of LPS on the metabolism of human umbilical vein endothelial cells (HUVECs) were investigated, and the metabolic changes after LPS stimulation were explained from the perspective of mRNA expression, chromatin openness and metabolic flux. We found changes in the central metabolism of endothelial cells after LPS stimulation, such as enhanced glycolysis function, decreased mitochondrial membrane potential, and increased production of reactive oxygen species (ROS). Sphingolipid metabolic pathways change at the transcriptome level, and sphingosine-1-phosphatase 2 (SGPP2) was upregulated in LPS-stimulated endothelial cells and zebrafish models. Overexpression of SGPP2 improved cell barrier function, enhanced mitochondrial respiration capacity, but also produced oxidative respiration chain uncoupling. In addition, SGPP2 overexpression inhibited the degradation of HIF-1α protein. The molecular and biochemical processes identified in this study are not only beneficial for understanding the metabolic-related mechanisms of LPS-induced endothelial injury, but also for the discovery of general therapeutic targets for inflammation and inflammation-related diseases.
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Fenômenos Bioquímicos , Lipopolissacarídeos , Animais , Humanos , Células Endoteliais da Veia Umbilical Humana , Inflamação/genética , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
Heat shock transcription factors (Hsf) are pivotal as essential transcription factors. They function as direct transcriptional activators of genes regulated by thermal stress and are closely associated with various abiotic stresses. Asparagus (Asparagus officinalis) is a vegetable of considerable economic and nutritional significance, abundant in essential vitamins, minerals, and dietary fiber. Nevertheless, asparagus is sensitive to environmental stresses, and specific abiotic stresses harm its yield and quality. In this context, Hsf members have been discerned through the reference genome, and a comprehensive analysis encompassing physical and chemical attributes, evolutionary aspects, motifs, gene structure, cis-acting elements, collinearity, and expression patterns under abiotic stresses has been conducted. The findings identified 18 members, categorized into five distinct subgroups. Members within each subgroup exhibited analogous motifs, gene structures, and cis-acting elements. Collinearity analysis unveiled a noteworthy pattern, revealing that Hsf members within asparagus shared one, two, and three pairs with counterparts in Arabidopsis, Oryza sativa, and Glycine max, respectively.Furthermore, members displayed tissue-specific expression during the seedling stage, with roots emerging as viable target tissue. Notably, the expression levels of certain members underwent modification under the influence of abiotic stresses. This study establishes a foundational framework for understanding Hsf members and offers valuable insights into the potential application of molecular breeding in the context of asparagus cultivation.
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Asparagus , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Asparagus/genética , Asparagus/metabolismo , Verduras/metabolismo , Estresse Fisiológico/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/metabolismo , Filogenia , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: Although oral leukoplakia (OL) is the best-known potentially malignant disorder, the risk of OL malignant transformation is difficult to assess. ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1 are stem cell markers that have been found to be associated with head and neck tumorigenesis. The objective of the current study was to evaluate the usefulness of ABCG2 and BMI-1 in predicting OL transformation. METHODS: In a retrospective cohort of 135 patients with OL from the study institution who had a mean follow-up of 5.5 years, 32 developed cancer between 1985 and 2008. The expression of ABCG2 and BMI-1 was determined using immunohistochemistry in samples from these patients, and included untransformed OL (n = 103) and malignant-transformed OL (n = 32). The association between protein expression and clinicopathological parameters and transformation was analyzed. RESULTS: Expression of ABCG2 and BMI-1 was observed in 58 (43.0%) and 44 (32.6%) of 135 patients, respectively. The correlation between ABCG2 and BMI-1 expression was significant (P = .024). Kaplan-Meier analysis revealed that 37.9% of patients with ABCG2 positivity developed cancer compared with 13.0% of patients with ABCG2 negativity (P = .014, log-rank test). Approximately 40.9% of patients with BMI-1 positivity developed cancer compared with 15.4% of patients with BMI-1 negativity (P = .029, log-rank test). Multivariate analysis revealed that ABCG2 and BMI-1 expression was associated with a 3.24-fold (95% confidence interval [95% CI], 1.31-7.98; P = .011) and 4.03-fold (95% CI, 1.59-10.26; P = .003) increased the risk of transformation, respectively. CONCLUSIONS: ABCG2 and BMI-1 expression was found to be associated with the development of oral cancer in a large cohort of patients with OL for whom long-term follow-up was available, which suggests that ABCG2 and BMI-1 may be used as predictors of OL transformation.
Assuntos
Transportadores de Cassetes de Ligação de ATP/fisiologia , Transformação Celular Neoplásica , Leucoplasia Oral/patologia , Proteínas de Neoplasias/fisiologia , Proteínas Nucleares/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Proteínas Repressoras/fisiologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/análise , Adulto , Idoso , Feminino , Seguimentos , Humanos , Leucoplasia Oral/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Proteínas Nucleares/análise , Complexo Repressor Polycomb 1 , Proteínas Proto-Oncogênicas/análise , Proteínas Repressoras/análise , Estudos RetrospectivosRESUMO
BACKGROUND: Oral verrucous hyperplasia (VH) and verrucous carcinoma (VC) are two clinicopathologically distinctive oral verrucous lesions. The objective of this study was to investigate the clinicopathological features of the two verrucous lesions and estimate their relationship from China. METHODS: Retrospective review of two series of patients with histologically confirmed VH (n = 121) and VC (n = 56) between 1996 and 2009 in our hospital were conducted. RESULTS: The average age of VH was 58.5 years (ratio male:female = 1.37) with the tongue being the predominant site. The average age of VC was 64.3 years (ratio male:female = 1.15) with the lower lip being the predominant site. Multivariate analysis revealed that the elderly patient with verrucous lesion (≥60 years) was associated with 3.06-fold (P = 0.007) increased carcinoma risk compared with the non-elderly patient. The lesion located on lower lip was associated with 13.54-fold (P < 0.001) increased carcinoma risk compared with other sites. CONCLUSION: Clinicopathological features of VH and VC in China were elucidated. Elderly patient with oral verrucous lesion located on the lower lip correlates with higher risk of carcinoma.
Assuntos
Carcinoma Verrucoso/epidemiologia , Mucosa Bucal/patologia , Neoplasias Bucais/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , China/epidemiologia , Epitélio/patologia , Feminino , Humanos , Hiperplasia , Leucoplasia Oral/epidemiologia , Neoplasias Labiais/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Neoplasias da Língua/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To investigate the epidemiological and clinical characteristics of a relatively large cohort of patients with oral lichen planus (OLP) from eastern China. STUDY DESIGN: A total of 518 patients with histologically confirmed OLP in a long-term follow-up period (6 months-21.5 years) were retrospectively reviewed in our clinic. RESULTS: Of the 518 patients, 353 females and 165 males were identified. The average age at diagnosis was 46.3 years (range 9-81 years) with the buccal mucosa being the most common site (87.8%). At initial presentation, white lichen and red lichen was seen in 52.3% and 47.7% patients, respectively. Of these, 5 (0.96%) patients previously diagnosed clinically and histopathologically as OLP developed oral cancer. All of them were the females with no a history of smoking or alcohol use. CONCLUSIONS: Clinical features of eastern Chinese OLP patients were elucidated. Notably, approximately 1% of OLP developed into cancer, which provides further evidence of potentially malignant nature of OLP.