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1.
Expert Rev Mol Med ; 26: e7, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602081

RESUMO

Trauma is a significant health issue that not only leads to immediate death in many cases but also causes severe complications, such as sepsis, thrombosis, haemorrhage, acute respiratory distress syndrome and traumatic brain injury, among trauma patients. Target protein identification technology is a vital technique in the field of biomedical research, enabling the study of biomolecular interactions, drug discovery and disease treatment. It plays a crucial role in identifying key protein targets associated with specific diseases or biological processes, facilitating further research, drug design and the development of treatment strategies. The application of target protein technology in biomarker detection enables the timely identification of newly emerging infections and complications in trauma patients, facilitating expeditious medical interventions and leading to reduced post-trauma mortality rates and improved patient prognoses. This review provides an overview of the current applications of target protein identification technology in trauma-related complications and provides a brief overview of the current target protein identification technology, with the aim of reducing post-trauma mortality, improving diagnostic efficiency and prognostic outcomes for patients.


Assuntos
Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/terapia , Hemorragia
2.
Neuroepidemiology ; : 1-18, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38870921

RESUMO

OBJECTIVE: This study aims to precisely determine the prevalence of mild cognitive impairment (MCI) in China, acknowledging its significance as a preclinical stage of dementia and a potential "intervention window." The acceleration of the aging process in China underscores the urgency of this research. METHODS: A comprehensive search was conducted across PubMed, Embase, Web of Science, CNKI, WFD, VIP, and CBM databases from their inception until March 1, 2023. The Agency for Healthcare Research and Quality (AHRQ) methodology checklist guided our quality assessment. A random-effects model meta-analysis was employed to synthesize the pooled prevalence data of MCI in China. RESULTS: Our analysis encompassed 139 studies, incorporating data from 393,525 individuals aged 40 years and above. The studies were predominantly rated as moderate-to-high quality. The overall prevalence of MCI was determined to be 19.6% (95% CI: 17.7-21.6%). Subgroup analyses indicated variations in prevalence: 20.8% (95% CI: 18.9-22.7%) for P-MCI compared to 16.2% (95% CI: 11.7-20.7%) for DSM criteria. Geographically, prevalence in Southern China (21.0%, 95% CI: 18.1-23.9%) exceeded that in Northern China (17.6%, 95% CI: 15.9-19.4%). Notably, prevalence in hospitals (61.7%, 95% CI: 27.8-95.7%) was significantly higher than in nursing homes (16.1%, 95% CI: 14.3-17.9%) and communities (25.3%, 95% CI: 17.4-33.2%), especially after the COVID-19 outbreak. CONCLUSION: The study confirms a 19.6% prevalence rate of MCI in China, influenced by factors such as sample sources, beginning year of survey, and regional differences. It highlights the need for targeted screening and resource allocation to subpopulations at risk, aiming to prevent the progression to dementia.

3.
Ecotoxicol Environ Saf ; 269: 115818, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38091676

RESUMO

A synthetic organic substance called bisphenol A (BPA) is used to make polyester, epoxy resin, polyacrylate, and polycarbonate plastic. BPA exposure on a regular basis has increased the risk of developing cancer. Recent research has shown that there is a strong link between BPA exposure and a number of malignancies. We want to investigate any connections between BPA and prostate cancer in this work. The scores of bisphenols in the prostate cancer cohort were obtained using the ssGSEA algorithm. The analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment was used to investigate probable pathways that are closely related to the genes tied to BPA. The BPA-based risk model was built using regression analysis. Additionally, the molecular docking method was employed to assess BPA's capacity to attach to important genes. Finally, we were able to successfully get the BPA cohort ratings for prostate cancer patients. Additionally, the KEGG enrichment study showed that of the malignancies linked to BPA, prostate cancer is the most highly enriched. In a group of men with prostate cancer, the BPA-related prognostic prediction model exhibits good predictive value. The BPA demonstrated strong and efficient binding to the androgen receptor, according to the molecular docking studies. According to cell proliferation and invasion experiments, exposing prostate cancer cells to BPA at a dosage of 10-7 uM could greatly enhance their ability to proliferate and invade.


Assuntos
Fenóis , Neoplasias da Próstata , Receptores Androgênicos , Masculino , Humanos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Simulação de Acoplamento Molecular , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Compostos Benzidrílicos/toxicidade , Proliferação de Células
4.
Molecules ; 28(22)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38005394

RESUMO

Two previously undescribed pyrrolizine alkaloids, named phenopyrrolizins A and B (1 and 2), were obtained from the fermentation broth of marine-derived Micromonospora sp. HU138. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR spectra as well as HRESIMS data. The structure of 1 was confirmed by single-crystal diffraction analysis and its racemization mechanism was proposed. The antifungal activity assay showed that 2 could inhibit the mycelial growth of Botrytis cinerea with the inhibitory rates of 18.9% and 35.9% at 20 µg/disc and 40 µg/disc, respectively.


Assuntos
Actinobacteria , Alcaloides , Micromonospora , Actinomyces , Micromonospora/química , Alcaloides/farmacologia , Alcaloides/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular
5.
Cancer Control ; 29: 10732748221129451, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36283420

RESUMO

OBJECTIVE: Evidence shows that gene mutation is a significant proportion of genetic factors associated with prostate cancer. The DNA damage response (DDR) is a signal cascade network that aims to maintain genomic integrity in cells. This comprehensive study was performed to determine the link between different DNA damage response gene mutations and prostate cancer. MATERIALS AND METHODS: A systematic literature search was performed using PubMed, Web of Science, and Embase. Papers published up to February 1, 2022 were retrieved. The DDR gene mutations associated with prostate cancer were identified by referring to relevant research and review articles. Data of prostate cancer patients from multiple PCa cohorts were obtained from cBioPortal. The OR or HR and 95% CIs were calculated using both fixed-effects models (FEMs) and random-effects models (REMs). RESULTS: Seventy-four studies were included in this research, and the frequency of 13 DDR genes was examined. Through the analysis of 33 articles that focused on the risk estimates of DDR genes between normal people and PCa patients, DDR genes were found to be more common in prostate cancer patients (OR = 3.6293 95% CI [2.4992; 5.2705]). Also, patients in the mutated group had a worse OS and DFS outcome than those in the unmutated group (P < .05). Of the 13 DDR genes, the frequency of 9 DDR genes in prostate cancer was less than 1%, and despite differences in race, BRCA2 was the potential gene with the highest frequency (REM Frequency = .0400, 95% CI .0324 - .0541). The findings suggest that mutations in genes such as ATR, BLM, and MLH1 in PCa patients may increase the sensitivity of Olaparib, a PARP inhibitor. CONCLUSION: These results demonstrate that mutation in any DDR pathway results in a poor prognosis for PCa patients. Furthermore, mutations in ATR, BLM, and MLH1 or the expression of POLR2L, PMS1, FANCE, and other genes significantly influence Olaparib sensitivity, which may be underlying therapeutic targets in the future.


Assuntos
Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Humanos , Masculino , Dano ao DNA , Reparo do DNA/genética , Mutação , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Prognóstico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética
6.
Phys Chem Chem Phys ; 24(38): 23910-23918, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36165573

RESUMO

A two-dimensional (2D) multifunctional material, which couples multiple physical properties together, is both fundamentally intriguing and practically appealing. Here, based on first-principles calculations and tight-binding (TB) model analysis, the possibility of regulating the valley-contrasting physics and nontrivial topological properties via ferroelectricity is investigated in monolayer AsCH2OH. Reversible electric polarization is accessible via the rotation operation on the ligand. The broken inversion symmetry and the spin-orbit coupling (SOC) would lead to valley spin splitting, spin-valley coupling and valley-contrasting Berry curvature. More importantly, the reversal of electric polarization can realize the nonvolatile control of valley-dependent properties. Besides, the nontrivial topological state is confirmed in the monolayer AsCH2OH, which is robust against the rotation operation on the ligand. The magnitude of polarization, valley spin splitting and bulk band gap can be effectively modulated by the biaxial strain. The H-terminated SiC is demonstrated to be an appropriate candidate for encapsulating monolayer AsCH2OH, without affecting its exotic properties. These findings provide insights into the fundamental physics for the coupling of the valley-contrasting phenomenon, topological properties and ferroelectricity, and open avenues for exploiting innovative device applications.

7.
BMC Public Health ; 22(1): 336, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35177008

RESUMO

BACKGROUND: Metabolic syndrome has become a major health threat throughout the world, but there are few studies that focus on the effects of housework on human metabolism. This study explores the association between housework and metabolic markers and examines whether there are gender differences in the relationship of housework intensity on these markers. METHODS: We obtained data for 2,624 participants from the China Health and Nutrition Survey and used binary logistic regression to analyze the association between housework and metabolic markers (triglycerides, high- and low-density lipoprotein cholesterol, hemoglobin, blood glucose, cholesterol, and blood pressure). RESULTS: We observed no association between housework and metabolic markers for men. However, we find that women who engaged in housework had a higher risk of triglycerides than those who did not (OR=1.16, 95% CI: 1.16, 4.25). Compared with low-intensity, we also find that women who performed moderate- and high-housework intensity had a higher risk of triglycerides (moderate-intensity: OR=1.78, 95% CI: 1.14, 2.78; high-intensity: OR=1.91, 95% CI: 1.22, 2.98), MetS (OR=1.54, 95% CI: 0.98, 2.43; OR=1.68, 95% CI: 1.07, 2.66), pre-hypertension (OR=1.68, 95% CI: 1.08, 2.62; OR=1.63, 95% CI: 1.04, 2.55), and obesity (OR=1.65, 95% CI: 1.01, 2.70; OR=1.66, 95% CI: 1.01, 2.72). CONCLUSION: In women, we find that housework is positively associated with the metabolic markers, triglycerides, MetS, and pre-hypertension. However, we did not find evidence that this relationship exists in men, f or any biomarkers we considered. One possible explanation is that people who engage in high-intensity housework are more stressed and sleep less, which could be a mechanism by which housework becomes associated with metabolic disease.


Assuntos
Síndrome Metabólica , Pré-Hipertensão , Biomarcadores , Glicemia/metabolismo , China/epidemiologia , Colesterol , HDL-Colesterol , Feminino , Zeladoria , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco , Fatores Sexuais , Triglicerídeos
8.
Ecotoxicol Environ Saf ; 221: 112457, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34175827

RESUMO

Zearalenone (ZEA) is an oestrogen-like mycotoxin produced by Fusarium fungi, which has a considerable impact on human and animal health and results in substantial economic losses worldwide. This study aimed to demonstrate the reproductive injury induced by ZEA in rodents. We conducted a rigorous meta-analysis of the related literature via PubMed, Embase, and Web of Science. The scope of the study includes the following: development of reproductive organs, serum testosterone, oestradiol, and luteinizing hormone (LH) levels; parameters of Leydig cells; and parameters of semen. In total, 19 articles were reviewed. Compared with the control group, the increased relative epididymis weight, increased serum oestradiol level, and decreased LH levels in the prenatally exposed group were observed. In pubertal and adult rodents, the relative testicular weight, serum oestradiol level, Leydig cell number, and percentage of ST (+) Leydig cells decreased under ZEA exposure. In rodents at all ages, decreased serum testosterone level, sperm concentration, sperm motility rate, and increased serum deformity rate were observed in exposed groups compared with control groups. Although subgroup analysis failed to identify a clear dose-response relationship between ZEA exposure and reproductive system damage in male rodents, we still managed to confirm that zearalenone could decrease the serum testosterone level at the dosage of 50 mg/kg*day, 1.4 mg/kg*day, and 84 mg/kg*day, of prenatal, pubertal, and mature rodents respectively; pubertal zearalenone exposure impairs the quality and quantity of sperms of rodents at the dosage of 1.4 mg/kg*day and mature zearalenone exposure has the same effect at the dosage of 84 mg/kg*day. In conclusion, we found that ZEA exposure can cause considerable damage to the reproductive system of rodents of all ages. While the exact underlying mechanism of ZEA-induced toxicity in the reproductive system remains largely unknown, the theories of oestrogen-like effects and oxidative stress damage are promising.


Assuntos
Estrogênios/toxicidade , Reprodução/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Masculino
9.
Ecotoxicol Environ Saf ; 223: 112589, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358932

RESUMO

In recent years, organophosphate ester flame retardants (OPFRs), which have been regarded as alternatives for brominated flame retardants (BFRs), have become widely used in building materials, textiles, and electric equipment. Elucidating the relationship between OPFRs and tumors holds great significance for the treatment and prevention of diseases. In this work, we found a new method for predicting the correlation between the interactive genes of OPFRs and tumors. Transcriptome profiles and OPFR information were obtained from The Cancer Genome Atlas and the Genotype-Tissue Expression, Comparative Toxicogenomics, and PharmMapper databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that interactive genes were mainly enriched in prostate cancer, steroid metabolic process, and steroid hormone regulation. Furthermore, protein-protein interaction network analysis revealed 33 biological hub genes. The operating characteristic curves and survival analysis showed the role of key genes in predicting the prognosis of prostate cancer. Gene target prediction and gene set variation analysis proved that OPFRs and their metabolites exert potential effects on prostate cancer. Colony formation assay showed that the cells with AR, mTOR and DDIT3 knockdown could remarkably mitigate the cell proliferation ability in both PC-3 and LNCap cells. Transwell assay demonstrated that the silencing of AR, mTOR and DDIT3 could significantly inhibit the cell invasion capacity of prostate cells. Triphenyl phosphate (TPP) significantly increase the cell proliferation ability and promote cell invasion capacity. AR, mTOR and DDIT3 in the PC-3 and LNCap cells were significantly upregulated with 10-6 M TPP treated.


Assuntos
Retardadores de Chama , Neoplasias da Próstata , Compreensão , Retardadores de Chama/toxicidade , Humanos , Masculino , Organofosfatos/toxicidade , Compostos Organofosforados , Neoplasias da Próstata/genética
10.
BMC Cancer ; 20(1): 1141, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33234125

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

11.
BMC Cancer ; 20(1): 1062, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148208

RESUMO

BACKGROUND: Extensive research has revealed that genes play a pivotal role in tumor development and growth. However, the underlying involvement of gene expression in gastric carcinoma (GC) remains to be investigated further. METHODS: In this study, we identified overlapping differentially expressed genes (DEGs) by comparing tumor tissue with adjacent normal tissue using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database. RESULTS: Our analysis identified 79 up-regulated and ten down-regulated genes. Functional enrichment analysis and prognosis analysis were conducted on the identified genes, and the fatty aldehyde dehydrogenase (FALDH) gene, ALDH3A2, was chosen for more detailed analysis. We performed Gene Set Enrichment Analysis (GSEA) and immunocorrelation analysis (infiltration, copy number alterations, and checkpoints) to elucidate the mechanisms of action of ALDH3A2 in depth. The immunohistochemical (IHC) result based on 140 paraffin-embedded human GC samples indicated that ALDH3A2 was over-expressed in low-grade GC cases and the OS of patients with low expression of ALDH3A2 was significantly shorter than those with high ALDH3A2 expression. In vitro results indicated that the expression of ALDH3A2 was negatively correlated with PDCD1, PDCD1LG2, and CTLA-4. CONCLUSION: We conclude that ALDH3A2 might be useful as a potential reference value for the relief and immunotherapy of GC, and also as an independent predictive marker for the prognosis of GC.


Assuntos
Adenocarcinoma/patologia , Aldeído Oxirredutases/metabolismo , Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Aldeído Oxirredutases/genética , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Transcriptoma
12.
J Environ Manage ; 157: 111-7, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25897505

RESUMO

A numerical model was employed to simulate the combustion process in a fixed porous bed of municipal solid waste (MSW). Mass, momentum, energy and species conservation equations of the waste bed were set up to describe the incineration process. The rate of moisture evaporation, volatile matter devolatilization, char combustion, NOx production, and reduction and dioxin formation were calculated and established according to the local thermal conditions and waste property characteristics. Changes in the bed volume during incineration were calculated according to the reaction rate of the process. The simulation results were compared with experimental data, which shows that the incineration process of waste in the fixed bed was reasonably simulated. The simulation results of weight loss and solid temperature in the bed agree with the experimental data, which shows that the waste combustion rate is nearly constant in the middle of the incineration process, and that moisture evaporation takes up most of the time for the overall incineration experiment. The emission of gas species from the bed surface is also agreeably simulated, with O2, CO2, and CO concentrations in flue gas agreeing with the experimental data. The simulation results benefit the understanding of the combustion process in the waste bed as well as the design of incinerator grates.


Assuntos
Dioxinas/química , Incineração/métodos , Modelos Teóricos , Eliminação de Resíduos , Resíduos Sólidos , Dióxido de Carbono/química , Monóxido de Carbono/química , Humanos , Oxigênio/química
13.
ACS Omega ; 9(13): 14997-15014, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38585075

RESUMO

Ammonia is considered to play an important role in replacing traditional fossil fuels in future energy systems. In the experimental study, CH4/NH3 flame was lit by applying a double-nozzle burner to gain insight into the structure, and the laminar diffusion flame structure, CH*/OH* intensity maximum, and flame size were analyzed by an ICCD camera. In addition, the extinction limit (lower limit) of the CH4/NH3 flame under different conditions was also studied. The results showed that with the increase of burner pitch, the two diffusion flames showed four states of merged flames, merging flames, inclining separated flames, and independent flames in turn. In the process of flame separation, the continuous pitch between merging flames was short. At this point, higher syngas flow could help increase the continuous pitch to keep merging form. The paper investigated the flame structure and found that the flame size would decrease when the NH3 content in the fuel was high. The flame stability also decreased with an increase of the NH3 content in the fuel. These findings provided experimental proof and a theoretical basis for future studies on the stability of CH4/NH3 co-firing.

14.
Toxicology ; 501: 153681, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38006928

RESUMO

Emerging flame retardants have been used to replace traditional flame retardants, but their potential impact on cancer, especially prostate cancer, is not well understood. Our study aimed to explore the link between flame retardants and prostate cancer, and identify potential carcinogenic mechanisms among populations exposed to emerging flame retardants. We screened flame retardant interacting genes differentially expressed in prostate cancer patients and identified hub genes by protein-protein interaction (PPI) analysis based on the STRING database. Univariate and multivariate Cox regression analyses were performed to construct risk models and identify flame retardant-related prognostic genes. We calculated the proportion of immune cell infiltration to explore the potential mechanism of the prognostic gene, and verified the target cell population of the prognostic gene in the single-cell transcriptome dataset. Our study revealed a significant link between emerging flame retardants and prostate cancer. We constructed a risk model with good predictive ability for prostate cancer prognosis using TCGA dataset, and identified six flame retardant-related prognostic genes validated in the GSE70769 dataset. We found that the expression of M2 macrophages was up-regulated in patients with high expression of prognostic genes, and the single-cell dataset confirmed the expression of prognostic genes in macrophages. Our study confirms the link between emerging flame retardants and prostate cancer, and highlights the role of immune-related pathways in the high-risk population exposed to these flame retardants.


Assuntos
Retardadores de Chama , Neoplasias da Próstata , Masculino , Humanos , Retardadores de Chama/toxicidade , Neoplasias da Próstata/genética
15.
Asian J Urol ; 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36776826

RESUMO

Objective: The novel coronavirus (severe acute respiratory syndrome coronavirus 2) has been spreading worldwide since December 2019, posing a serious danger to human health and socioeconomic development. A large number of clinical trials have revealed that coronavirus disease 2019 (COVID-19) results in multi-organ damage including the urogenital system. This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis. Methods: We used multiple publicly available databases to explore the expression patterns of ACE2, TMPRSS2, and CD147 (Basigin [BSG]) in major organs in the healthy and disease-specific populations, particularly the genitourinary organs. Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2, TMPRSS2, CD147, cytokine receptors, and cytokine interacting proteins in genitourinary organs, such as the bladder, kidney, prostate, and testis. Additionally, gene set enrichment analysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer. Results: The results revealed that ACE2, TMPRSS2, and CD147 were highly expressed in normal urogenital organs. Then, they were also highly expressed in multiple tumors and chronic kidney diseases. Additionally, ACE2, TMPRSS2, and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing. Cytokine receptors and cytokine interacting proteins, especially CCL2, JUN, and TIMP1, were commonly highly expressed in urogenital organs. Finally, gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK/STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19. Conclusion: Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives, which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.

16.
Front Oncol ; 13: 1207068, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37427103

RESUMO

Background: The association between clear cell renal cell carcinoma (ccRCC) and disulfidoptosis remains to be thoroughly investigated. Methods: We conducted multiple bioinformatics analyses, including prognostic analysis and cluster analysis, using R software. Additionally, we utilized Quantitative Real-time PCR to measure RNA levels of specific genes. The proliferation of ccRCC was assessed through CCK8 and colony formation assays, while the invasion and migration of ccRCC cells were evaluated using the transwell assay. Results: In this study, utilizing data from multiple ccRCC cohorts, we identified molecules that contribute to disulfidoptosis. We conducted a comprehensive investigation into the prognostic and immunological roles of these molecules. Among the disulfidoptosis-related metabolism genes (DMGs), LRPPRC, OXSM, GYS1, and SLC7A11 exhibited significant correlations with ccRCC patient prognosis. Based on our signature, patients in different groups displayed varying levels of immune infiltration and different mutation profiles. Furthermore, we classified patients into two clusters and identified multiple functional pathways that play important roles in the occurrence and development of ccRCC. Given its critical role in disulfidoptosis, we conducted further analysis on SLC7A11. Our results demonstrated that ccRCC cells with high expression of SLC7A11 exhibited a malignant phenotype. Conclusions: These findings enhanced our understanding of the underlying function of DMGs in ccRCC.

17.
Acta Biomater ; 155: 347-358, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36402295

RESUMO

Ureteral stricture disease (USD) is a common urologic condition. Patients with ureteral stricture disease may suffer from ipsilateral flank pain, nausea, urinary calculi, infection, and impaired renal function. The treatments of USD include surgery, followed by implantation of the ureteral stent to aid the drainage of the urine. The traditional ureteral stent may sometimes cause urological infection, encrustation, and discomfort. To decrease the complication of the ureteral stent, we modified the structure and material based on the traditional ureteral stent. The traditional nondegradable Double-J shape tubular ureteral stent was turned into the biodegradable mesh ureteral stent. The modified mesh ureteral stent and Double-J ureteral stent were inserted into the ureters of the USD animals, respectively. The results of the gross morphology, serology, urinalysis, histology, microstructure, et al. demonstrated that modified mesh ureteral stent has a favorable ability in supporting the ureter and has no effect on cell proliferation, migration, apoptosis, and cell cycle of the human uroepithelial cells. The mesh ureteral stent could relieve ureter obstruction and can be slowly biodegraded after 3-5 months of implantation without the need for a second surgery to remove the stent. Compared to the Double-J ureteral stent, the modified mesh ureteral stent has a lower rate of urinary tract infection and less encrustation. It is expected to be an alternative treatment approach for USD. However, due to the limited number of animals and clinical data, further study focused on the application value in clinical practice are essential. STATEMENT OF SIGNIFICANCE: This study demonstrates: 1. A modified biodegradable mesh ureteral stent; 2. Without the need for a second surgery to remove the stent; 3. A lower rate of urinary tract infection and less encrustation than a double-J ureteral stent; 4. An alternative treatment approach for USD.


Assuntos
Ureter , Obstrução Ureteral , Infecções Urinárias , Animais , Humanos , Ureter/cirurgia , Constrição Patológica/patologia , Telas Cirúrgicas/efeitos adversos , Obstrução Ureteral/cirurgia , Obstrução Ureteral/etiologia , Obstrução Ureteral/patologia , Stents/efeitos adversos , Infecções Urinárias/complicações , Infecções Urinárias/patologia
18.
BMJ Open ; 13(4): e072474, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041061

RESUMO

OBJECTIVE: To explore the associations between the consumption frequencies of alcohol, tea and sugar-sweetened beverages (SSBs) and the hypertension risk among Chinese adults. DESIGN: A longitudinal study of the effect of beverage consumption on hypertension risk. SETTING: Nine provinces in China, including Jiangsu, Hubei, Hunan, Guangxi, Guizhou, Liaoning, Heilongjiang, Shandong and Henan. PARTICIPANTS: The longitudinal data of the China Health and Nutrition Survey from 2004 to 2015 were used. A total of 4427 participants from 9 provinces were included at baseline. OUTCOME: First incidence of hypertension. RESULTS: During a mean follow-up of 8.7 years, 1478 participants developed hypertension. Alcohol consumption more than twice a week in young men (HR 1.86, 95% CI 1.09 to 3.18) or middle-aged men (HR 1.37, 95% CI 1.01 to 1.87) was associated with a higher hypertension risk. Middle-aged women who consumed tea frequently (HR 0.71, 95% CI 0.52 to 0.97), or young women who consumed SSBs less than once a week (HR 0.31, 95% CI 0.14 to 0.67) had a lower risk of hypertension. CONCLUSIONS: High-frequency alcohol consumption increased the risk of hypertension in men, and frequent tea consumption and low-frequency SSBs consumption were associated with lower risk of hypertension in women. Consumption frequency of beverages was also suggested to be considered in the prevention and control of hypertension.


Assuntos
Bebidas , Hipertensão , Pessoa de Meia-Idade , Masculino , Adulto , Humanos , Feminino , Estudos de Coortes , Estudos Longitudinais , China , Hipertensão/epidemiologia , Chá
19.
Eur J Med Res ; 28(1): 588, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38093375

RESUMO

Targeted therapy is pivotal in renal carcinoma treatment, and the dual-inhibitor NVP-BEZ235 has emerged as a promising candidate in preliminary studies. Its effectiveness against renal carcinoma and the mechanisms underlying potential resistance, however, warrant further exploration. This study aims to elucidate these aspects, enhancing our understanding of NVP-BEZ235's future clinical utility. To investigate resistance mechanisms, renal cancer cell lines were exposed to progressively increasing concentrations of NVP-BEZ235, leading to the development of stable resistance. These resistant cells underwent extensive RNA-sequencing analysis. We implemented gene interference techniques using plasmid vectors and lentivirus and conducted regular IC50 assessments. To pinpoint the role of LncRNAs, we utilized FISH and immunofluorescence staining assays, supplemented by RNA pull-down and RIP assays to delineate interactions between LncRNA and its RNA-binding protein (RBP). Further, Western blotting and qRT-PCR were employed to examine alterations in signaling pathways, with an animal model providing additional validation. Our results show a marked increase in the IC50 of NVP-BEZ235 in resistant cell lines compared to their parental counterparts. A significant revelation was the role of LncRNA-CHKB-AS1 in mediating drug resistance. We observed dysregulated expression of CHKB-AS1 in both clinical samples of clear cell renal cell carcinoma (ccRCC) and cell lines. In vivo experiments further substantiated our findings, showing that CHKB-AS1 overexpression significantly enhanced tumor growth and resistance to NVP-BEZ235 in a subcutaneous tumorigenesis model, as evidenced by increased tumor volume and weight, whereas CHKB-AS1 knockdown led to a marked reduction in these parameters. Critically, CHKB-AS1 was identified to interact with MAP4, a key regulator in the phosphorylation of the PI3k/Akt/mTOR pathway. This interaction contributes to a diminished antitumor effect of NVP-BEZ235, highlighting the intricate mechanism through which CHKB-AS1 modulates drug resistance pathways, potentially impacting therapeutic strategies against renal carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , RNA Longo não Codificante , Animais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Serina-Treonina Quinases TOR/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proliferação de Células , Proteínas Associadas aos Microtúbulos , Linhagem Celular Tumoral
20.
iScience ; 26(11): 108148, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37915611

RESUMO

O-GlcNAc transferase (OGT) acts in the development of various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we found that OGT was upregulated in ccRCC and this upregulation was associated with a worse survival. Moreover, OGT promoted the proliferation, clone formation, and invasion of VHL-mutated ccRCC cells. Mechanistically, OGT increased the protein level of hypoxia-inducible factor-2α (HIF-2α) (the main driver of the clear cell phenotype) by repressing ubiquitin‒proteasome system-mediated degradation. Interestingly, the OGT/HIF-2α axis conferred ccRCC a high sensitivity to ferroptosis. In conclusion, OGT promotes the progression of VHL-mutated ccRCC by inhibiting the degradation of HIF-2α, and agents that can modulate the OGT/HIF-2α axis may exert therapeutic effects on mutated VHL ccRCC.

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