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1.
Ann Surg Oncol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980585

RESUMO

BACKGROUND: Pelvic exenteration (PE) is often the only curative treatment option for selected locally advanced and locally recurrent colorectal cancer associated with significant morbidity. Open and laparoscopic approaches were accepted for this procedure. OBJECTIVE: This study aimed to examine the Chinese patient-reported outcomes (PROs) and health-related quality of life (HRQoL) after PE. METHODS: A total of 122 enrolled participants were asked to complete PROs at baseline and 1, 3, 6, 9 and 12 months after PE. PROs included seven symptoms from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The HRQoL was assessed using the Functional Assessment of Cancer Therapy-Colorectal (FACT-C). RESULTS: The overall postoperative complication rate was 41.0%. Patients experienced lower physical and functional well-being and FACT-C 1 month after surgery, then gradually recovered. The FACT-C score returned to baseline 9 months after surgery. Social and emotional well-being did not show signs of recovery until 6 months after the surgical procedure, and did not fully return to baseline until 12 months post-surgery. Symptom rates of insomnia, anxiety, discouragement, and sadness (composite score >0) did not improve significantly from baseline until 12 months after surgery. CONCLUSIONS: PE is a feasible treatment choice for locally advanced primary and recurrent colorectal cancer. Social, psychological, and emotional recovery in the Chinese population after PE tends to be slower compared with the physical condition.

4.
Adv Mater ; : e2405275, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38897213

RESUMO

The development of minimally invasive surgery has greatly advanced precision tumor surgery, but sometimes suffers from restricted visualization of the surgical field, especially during the removal of abdominal tumors. A 3-D inspection of tumors could be achieved by intravenously injecting tumor-selective fluorescent probes, whereas most of which are unable to instantly distinguish tumors via in situ spraying, which is urgently needed in the process of surgery in a convenient manner. In this study, we have designed an injectable and sprayable fluorescent nanoprobe, termed Poly-g-BAT, to realize rapid tumor imaging in freshly dissected human colorectal tumors and animal models. Mechanistically, the incorporation of γ-glutamyl group facilitates the rapid internalization of Poly-g-BAT, and these internalized nanoprobes can be subsequently activated by intracellular NAD(P)H: quinone oxidoreductase-1 to release near-infrared fluorophores. As a result, Poly-g-BAT can achieve a superior tumor-to-normal ratio (TNR) up to 12.3 and enable a fast visualization (3 min after in situ spraying) of tumor boundaries in the xenograft tumor models, Apcmin/+ mice models and fresh human tumor tissues. In addition, Poly-g-BAT is capable of identifying minimal premalignant lesions via intravenous injection. This article is protected by copyright. All rights reserved.

5.
Int J Mol Sci ; 25(12)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38928100

RESUMO

Rich biological information in sweat provides great potential for health monitoring and management. However, due to the complexity of sweat, the development of environmentally friendly green electronic products is of great significance to the construction of ecological civilization. This study utilized a simple combination of polystyrene sulfonate sodium (PSS) and filter paper (FP) to prepare cellulose materials coated with conductive polymers, developing an electrochemical sensor based on the modified materials. The mechanical and electrochemical properties of the fabricated PSS/FP membrane were optimized by adjusting the feeding dosage of PSS. The realized PSS/FP composite containing 7% PSS displayed good conductivity (9.1 × 10-2 S/m), reducing electric resistance by 99.2% compared with the original FP membrane (6.7 × 10-4 S/m). The stable current of the membrane in simulated sweat under different pH environments is highly correlated with the pH values. Additionally, when the membrane is exposed to simulated sweat with varying ion concentrations, the current signal changes in real time with the concentration variations. The response time averages around 0.3 s.


Assuntos
Celulose , Condutividade Elétrica , Poliestirenos , Suor , Suor/química , Celulose/química , Concentração de Íons de Hidrogênio , Poliestirenos/química , Polímeros/química , Humanos , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos
6.
Aging (Albany NY) ; 16(11): 9813-9823, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38848144

RESUMO

BACKGROUND: Glaucoma is an optic neurodegenerative disease. Retinal ganglion cells (RGCs) are the fundamental neurons in the trabecular meshwork, and their loss is the main pathological reason for glaucoma. The present study was to investigate mechanisms that regulate RGCs survival. METHODS: A mouse model of glaucoma was established by injecting hypertonic saline into the limbal veins. RGCs apoptosis was detected by using flow cytometry. Protein expressions in RGCs in response to DNA damage inducer cisplatin treatment were detected by immunofluorescence and western blot. The expressions of inflammatory cytokines were determined using ELISA and real-time PCR. RESULTS: In the hypertonic saline-injected mice, we found visual function was impaired followed by the increased expression of γH2AX and activation of cGAS-STING signaling. We found that DNA damage inducer cisplatin treatment incurred significant DNA damage, cell apoptosis, and inflammatory response. Mechanistically, cisplatin treatment triggered activation of the cGAS-STING signaling by disrupting mitochondrial function. Suppression of cGAS-STING ameliorated inflammation and protected visual function in glaucoma mice. CONCLUSIONS: The data demonstrated that cGAS-STING signaling is activated in the damaged retinal ganglion cells, which is associated with increased inflammatory responses, DNA damage, and mitochondrial dysfunction. Targeting the cGAS-STING signaling pathway represents a potential way to alleviate glaucoma-related visual function.


Assuntos
Dano ao DNA , Glaucoma , Proteínas de Membrana , Nucleotidiltransferases , Células Ganglionares da Retina , Transdução de Sinais , Animais , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Glaucoma/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
7.
Int J Food Sci Nutr ; : 1-13, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918932

RESUMO

Cow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health.

8.
Immunobiology ; 229(5): 152821, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38935988

RESUMO

BACKGROUND: As metastatic papillary thyroid carcinoma becomes increasingly challenging to treat, immunotherapy has emerged as a new research direction. Tumor-associated macrophages (TAMs) influence the occurrence, invasion, and metastasis of tumors. Apolipoprotein E (APOE) can regulate the polarization changes of macrophages and participate in the remodeling of the tumor microenvironment. However, the role of APOE in regulating the polarization and biological functions of TAMs in papillary thyroid carcinoma (PTC) remains unclear, as it acts as a dual biomarker. METHODS: We probed APOE expression in PTC tissues using immunohistochemical staining. A cell co-culture model was established where different APOE-expressing K1 cells were co-cultured with THP-1-derived M0 macrophages. An in-depth analysis of macrophage polarization behavior was performed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Subsequently, the impact of APOE-regulated macrophages on tumor cell behavior, especially proliferation, migration, and invasion, was evaluated utilizing IncuCyte ZOOM system, flow cytometry, colony formation, and scratch experiments. Finally, we used a xenograft model to confirm the effects of APOE on PTC tumorigenesis. RESULTS: Tumor dimensions, stage, and lymphatic metastases were significantly associated with increased APOE expression in PTC tissues. K1 cells were markedly limited in their proliferation, migration, and invasion abilities when APOE expression was silenced, a process mediated by the PI3K/Akt/NF-κB signaling axis. Moreover, APOE is a key facilitator of the enhancement of the anti-inflammatory cytokines IL-10 and TGF-ß1. In PTC cellular models, APOE contributed to the phenotypic shift of THP-1 derived macrophages towards an M2 phenotypic polarization, predominantly through the modulation of IL-10. Furthermore, in vivo studies involving athymic nude mice have demonstrated pivotal role of APOE in tumor progression and the induction of M2-like TAM polarization. CONCLUSION: Our results elucidated that APOE could promote the shift of TAMs from M0-type to M2-type polarization by regulating inflammatory factors expressions in K1 cell through the PI3K/Akt/NF-κB pathway. These findings are crucial for understanding the molecular mechanisms underlying PTC pathogenesis and for developing immunological drugs to treat this disease.

9.
Nat Metab ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937659

RESUMO

The low-carbohydrate ketogenic diet (KD) has long been practiced for weight loss, but the underlying mechanisms remain elusive. Gut microbiota and metabolites have been suggested to mediate the metabolic changes caused by KD consumption, although the particular gut microbes or metabolites involved are unclear. Here, we show that KD consumption enhances serum levels of taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA) in mice to decrease body weight and fasting glucose levels. Mechanistically, KD feeding decreases the abundance of a bile salt hydrolase (BSH)-coding gut bacterium, Lactobacillus murinus ASF361. The reduction of L. murinus ASF361 or inhibition of BSH activity increases the circulating levels of TDCA and TUDCA, thereby reducing energy absorption by inhibiting intestinal carbonic anhydrase 1 expression, which leads to weight loss. TDCA and TUDCA treatments have been found to protect against obesity and its complications in multiple mouse models. Additionally, the associations among the abovementioned bile acids, microbial BSH and metabolic traits were consistently observed both in an observational study of healthy human participants (n = 416) and in a low-carbohydrate KD interventional study of participants who were either overweight or with obesity (n = 25). In summary, we uncover a unique host-gut microbiota metabolic interaction mechanism for KD consumption to decrease body weight and fasting glucose levels. Our findings support TDCA and TUDCA as two promising drug candidates for obesity and its complications in addition to a KD.

10.
BJOG ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38924674

RESUMO

OBJECTIVE: This study aimed to investigate the incidence, risk factors and trends for vaginal cancer. DESIGN: Retrospective observational design. SETTING: Data were collected from multiple sources, including the Global Cancer Observatory, Cancer Incidence in Five Continents Plus, Global Burden of Disease, World Bank and the United Nations. POPULATION: Individuals diagnosed with vaginal cancer. METHODS: The study collected data on vaginal cancer from the specified sources. The age-standardised rate (ASR) of vaginal cancer was calculated for different regions and age groups. Multivariable and univariable linear regression analyses were performed to examine the associations between risk factors and the incidence of vaginal cancer. Trend analysis was conducted using joinpoint regression analysis, and the average annual percentage change (AAPC) was calculated to quantify the temporal trend. MAIN OUTCOME MEASURES: The main outcome measures of the study were the incidence of vaginal cancer, risk factors associated with the disease and the trend of its incidence over time. RESULTS: There were 17 908 newly reported cases of vaginal cancer (ASR = 0.36, 95% CI 0.30-0.44) in 2020, with the highest ASRs reported in South-Central Asia and Southern Africa. Risk factors associated with a higher incidence of vaginal cancer included a higher prevalence of unsafe sex and human immunodeficiency virus (HIV) infection. The temporal trend showed an overall rising incidence globally, with Iceland (AAPC = 29.56, 95% CI 12.12-49.71), Chile (AAPC = 22.83, 95% CI 13.20-33.27), Bahrain (AAPC = 22.05, 95% CI 10.83-34.40) and the UK (AAPC = 1.40, 95% CI 0.41-2.39) demonstrating the most significant rising trends. CONCLUSIONS: The significant regional disparities and risk factors associated with vaginal cancer underscore the necessity for targeted interventions and education, particularly in regions with a lower human development index (HDI) and a higher prevalence of human papillomavirus (HPV) infection. The increasing incidence trend emphasises the need for enhanced HPV vaccination rates to prevent the development of vaginal cancer.

11.
Front Neurol ; 15: 1375383, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694772

RESUMO

Background: Postoperative delirium (POD) is a common postoperative neurological complication that can lead to a variety of postoperative complications. At present, the pathogenesis of POD is unclear. This study aims to explore the relationship between serum prealbumin and serum albumin and POD and whether serum prealbumin and serum albumin influence POD through POD core pathology. Objective: We enrolled 500 Chinese Han patients between September 2020 to January 2023. We analyzed the risk and protective factors of POD using the multivariate logistic regression. We also assessed the predictive power of serum prealbumin, serum albumin, and both in combination with CSF POD biomarkers. We used Stata MP16.0. to examine whether the association between serum prealbumin and serum albumin and POD was mediated by CSF POD biomarkers, and conducted an internal validation study to verify the accuracy of the combination of serum prealbumin + serum albumin + CSF POD biomarkers for predicting POD. The model was visualized using ROC curve and decision curve analysis (DCA). DynNom and Shiny packages were used to create an online calculator. Ten patients who had POD occurring from February 2023 to October 2023 were selected for internal verification. Results: Finally, a total of 364 patients were included in our study. Levels of serum prealbumin, serum albumin in the POD group were lower than those in the NPOD group. The lever of serum prealbumin, serum albumin were protective factors for POD. The relationship between serum prealbumin, serum albumin and POD was partially mediated by T-tau (12.28%) and P-tau (20.61%). The model combining serum prealbumin and serum albumin and POD biomarkers exhibited a relatively better discriminatory ability to predict POD. DCA also showed that the combination of serum prealbumin and serum albumin and POD biomarkers brought high predictive benefits to patients. The dynamic online calculator can accurately predict the occurrence of POD in the internal validation study. Conclusion: Preoperative low serum prealbumin and serum albumin levels were the preoperative risk factors for POD, which is partly mediated by T-tau and P-tau. The model combining serum prealbumin and serum albumin and CSF POD biomarkers can accurately predict the occurrence of POD. Clinical trial registration: http://www.clinicaltrials.gov, identifier ChiCTR2000033439.

13.
Brain Behav ; 14(5): e3512, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747874

RESUMO

OBJECTIVE: Our study aimed to investigate the correlation between intraoperative hypothermia and postoperative delirium (POD) in patients undergoing general anesthesia for gastrointestinal surgery. METHODS: The study comprised 750 participants from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study database, which ultimately screened 510 individuals in the final analysis. Preoperative cognitive function was evaluated using the Mini-Mental State Examination (MMSE). The occurrence of POD was determined using the Confusion Assessment Method, and the severity of POD was evaluated using the Memorial Delirium Assessment Scale. Logistic regression was employed to scrutinize the association between intraoperative hypothermia and the incidence of POD, and the sensitivity analysis was conducted by introducing adjusted confounding variables. Decision curves and a nomogram model were utilized to assess the predictive efficacy of intraoperative hypothermia for POD. Mediation analysis involving 10,000 bootstrapped iterations was employed to appraise the suggested mediating effect of numeric rating scale (NRS) scores at 24 and 48 h post-surgeries. The receiver-operating characteristic (ROC) was utilized to evaluate the effectiveness of intraoperative hypothermia in predicting POD. RESULTS: In the PNDRFAP study, the occurrence of POD was notably higher in the intraoperative hypothermia group (62.2%) compared to the intraoperative normal body temperature group (9.8%), with an overall POD incidence of 17.6%. Logistic regression analysis, adjusted for various confounding factors (age [40-90], gender, education, MMSE, smoking history, drinking history, hypertension, diabetes, and the presence of cardiovascular heart disease), demonstrated that intraoperative hypothermia significantly increased the risk of POD (OR = 4.879, 95% CI = 3.020-7.882, p < .001). Mediation analyses revealed that the relationship between intraoperative hypothermia and POD was partially mediated by NRS 24 h after surgery, accounting for 14.09% of the association (p = .002). The area under the curve of the ROC curve was 0.685, which confirmed that intraoperative hypothermia could predict POD occurrence to a certain extent. Decision curve and nomogram analyses, conducted using the R package, further substantiated the predictive efficacy of intraoperative hypothermia on POD. CONCLUSION: Intraoperative hypothermia may increase the risk of POD, and this association may be partially mediated by NRS scores 24 h after surgery.


Assuntos
Delírio , Hipotermia , Complicações Intraoperatórias , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hipotermia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Delírio/etiologia , Delírio/epidemiologia , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Anestesia Geral/efeitos adversos , Fatores de Risco , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Incidência , Adulto
14.
Cell Death Discov ; 10(1): 212, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697996

RESUMO

The escalating threat of bone-related diseases poses a significant challenge to human health. Mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs), as inherent cell-secreted natural products, have emerged as promising treatments for bone-related diseases. Leveraging outstanding features such as high biocompatibility, low immunogenicity, superior biological barrier penetration, and extended circulating half-life, MSC-EVs serve as potent carriers for microRNAs (miRNAs), long no-code RNAs (lncRNAs), and other biomolecules. These cargo molecules play pivotal roles in orchestrating bone metabolism and vascularity through diverse mechanisms, thereby contributing to the amelioration of bone diseases. Additionally, engineering modifications enhance the bone-targeting ability of MSC-EVs, mitigating systemic side effects and bolstering their clinical translational potential. This review comprehensively explores the mechanisms through which MSC-EVs regulate bone-related disease progression. It delves into the therapeutic potential of MSC-EVs as adept drug carriers, augmented by engineered modification strategies tailored for osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis, and osteosarcoma. In conclusion, the exceptional promise exhibited by MSC-EVs positions them as an excellent solution with considerable translational applications in clinical orthopedics.

15.
Heliyon ; 10(10): e30414, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38818170

RESUMO

Background: Postoperative delirium (POD) often occurs in elderly patients after surgery. We conducted two clinical studies to determine whether COVID-19 vaccination has a protective effect on POD and to explore the role of CSF biomarkers in this process. Methods: We conducted two clinical studies, Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) and Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE), in which patients more than or equal to 65 years old who have had elective non-cardiac surgery were enrolled. The preoperative cognitive status of patients were evaluated by Mini-Mental State Examination (MMSE) one day preoperatively. Confusion Assessment Method (CAM) was used to diagnose POD. We used the mediation model to analyze the relationship between CSF biomarkers, COVID-19 vaccination and POD, as well as Dynamic Nomogram to calculate the incidence of Non-Postoperative Delirium (NPOD). The main outcome of these studies was the incidence of POD during seven days postoperatively or before discharge, which was assessed by CAM. Results: In the final, 705 participants were enrolled in the PNDRFAP study, and 638 patients in the PNDABLE. In both studies, we found that the occurrence of POD was lower in patients who had injected COVID-19 vaccination before surgery compared with those without vaccination (PNDRFAP: 10.20 % [21/205] vs 25.80 % [129/500], P < 0.001; PNDABLE: 2.40 % [4/164] vs 34.60 % [164/474], P < 0.001). Mediation analysis showed that the protective effect of preoperative COVID-19 vaccine on POD was significantly mediated by CSF Aß42 (proportion = 17.56 %), T-tau (proportion = 19.64 %), Aß42/T-tau (proportion = 29.67 %), and Aß42/P-tau (proportion = 12.26 %). Conclusions: COVID-19 vaccine is a protective factor for POD in old patients, which is associated with CSF biomarkers.

16.
Inorg Chem ; 63(24): 11478-11486, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38819949

RESUMO

In the preparation of carbon dots (CDs), precursors are crucial, and abundant precursors endow CDs with various structures and fluorescence characteristics. Furan (FU) and its derivatives are considered excellent carbonization materials due to their π conjugated structures and active functional groups, such as hydroxyl and aldehyde groups. Herein, we prepare FU-derivative-based CDs by a solvothermal method and investigate the influences of the precursor structure on the fluorescence characteristics. Surprisingly, CDs prepared from 5-hydroxymethylfurfural (HMF) with both aldehyde and hydroxyl groups exhibit red-shifted fluorescence characteristics in the solid state. We postulate that this solid-state fluorescence characteristic is due to the enhancement of supramolecular cross-linking fluorescence between CDs. The unique precursor structure leads to carboxyl groups on the surface of HMF-CDs that are conducive to the hydrogen bond formation. As the concentration of CDs increases, the hydrogen bonding effect increases, leading to a red-shift in the fluorescence wavelength. Therefore, basically full-color CDs/poly(vinyl alcohol) (PVA) phosphor-based light-emitting diodes can be achieved by controlling the degree of supramolecular cross-linking of CDs in PVA. This research provides a new approach for the preparation of solid-state luminescent CDs.

17.
Shock ; 61(6): 942-950, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38664873

RESUMO

ABSTRACT: Background : Acute kidney injury (AKI) is a prevalent clinical syndrome with persistent kidney dysfunction. Renal ischemia/reperfusion (I/R) injury is a major cause of AKI. miR-208a-3p overexpression attenuated myocardial I/R injury. This study aims to investigate the role and mechanism of miR-208a-3p in I/R-induced AKI. Methods : AKI models were established using hypoxia/reoxygenation (H/R)-exposed tubule epithelial cell HK-2 and I/R-induced mice. The function and mechanism of miR-208a-3p were investigated by gain- or loss-of-function methods using real-time PCR, CCK-8, flow cytometry, ELISA, western blot, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, detection of Fe 2+ , reactive oxygen species, blood urea nitrogen and creatinine, and luciferase reporter assay. Results : miR-208a-3p expression was suppressed, while the expression of CELF2 and circular RNA ubiquinol-cytochrome c reductase core protein 2 (circUQCRC2) was increased in both AKI models. miR-208a-3p upregulation or circUQCRC2 silencing increased the viability, decreased the levels of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6), reduced apoptosis and contents of Fe 2+ and reactive oxygen species, elevated expression of GPX4 and SLC7A11, and reduced ACSL4 expression in H/R-stimulated HK-2 cells. In addition, miR-208a-3p improved kidney function by alleviating renal injury, apoptosis, inflammation, and ferroptosis in AKI mouse model. CELF2 was a target gene of miR-208a-3p, which was negatively modulated by circUQCRC2. Overexpression of CELF2 blocked the function of miR-208a-3p upregulation or circUQCRC2 silencing on H/R-treated HK-2 cells. Moreover, the effects of circUQCRC2 downregulation on H/R-injured cells were also reversed by miR-208a-3p inhibitor. Conclusions : miR-208a-3p regulated by circUQCRC2 could attenuate I/R-induced AKI by inhibiting CELF2-mediated tubular epithelial cell apoptosis, inflammation and ferroptosis. This study provides potential therapeutic targets for I/R-induced AKI.


Assuntos
Injúria Renal Aguda , Apoptose , Células Epiteliais , Ferroptose , Inflamação , MicroRNAs , Traumatismo por Reperfusão , Animais , Humanos , Masculino , Camundongos , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/etiologia , Proteínas CELF/metabolismo , Células Epiteliais/metabolismo , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/complicações , RNA Circular/genética , RNA Circular/metabolismo
18.
Nanoscale Adv ; 6(8): 1997-2001, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38633051

RESUMO

Herein, F-doped CDs with bright red SSF were synthesized by a solvothermal method using trifluoroethanol as the solvent and m-hydroxybenzaldehyde as the carbon source. Strong F-F interactions are vital for inducing crystallization, and solid luminescence is achieved by blocking the nonradiative energy dissipation pathways of crystalline organizations.

19.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167132, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38565386

RESUMO

The Epstein-Barr virus (EBV) is implicated in several cancers, including EBV-associated gastric cancer (EBVaGC). This study focuses on EBV-encoded BALF1 (BamH1 A fragment leftward reading frame 1), a key apoptosis regulator in EBV-related cancers, whose specific impact on EBVaGC was previously unknown. Our findings indicate that BALF1 overexpression in gastric cancer cells significantly enhances their proliferation, migration, and resistance to chemotherapy-induced apoptosis, confirming BALF1's oncogenic potential. A novel discovery is that BALF1 undergoes degradation via the ubiquitin-proteasome pathway. Through analysis of 69 deubiquitinating enzymes (DUBs), ovarian tumor protease (OTU) domain-containing protein 1 (OTUD1) emerged as a vital regulator for maintaining BALF1 protein stability. Furthermore, BALF1 was found to play a role in regulating the stability of the B-cell lymphoma-2 (Bcl-2) protein, increasing its levels through deubiquitination. This mechanism reveals BALF1's multifaceted oncogenic role in gastric cancer, as it contributes both directly and indirectly to cancer progression, particularly by stabilizing Bcl-2, known for its anti-apoptotic characteristics. These insights significantly deepen our understanding of EBV's involvement in the pathogenesis of gastric cancer. The elucidation of OTUD1's role in BALF1 regulation and its influence on Bcl-2 stabilization provide new avenues for therapeutic intervention in EBVaGC, bridging the gap between viral oncogenesis and cellular protein regulation and offering a more holistic view of gastric cancer development under the influence of EBV.


Assuntos
Apoptose , Proteínas Proto-Oncogênicas c-bcl-2 , Neoplasias Gástricas , Ubiquitinação , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Linhagem Celular Tumoral , Herpesvirus Humano 4/metabolismo , Herpesvirus Humano 4/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética , Proliferação de Células , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/genética , Estabilidade Proteica , Movimento Celular , Animais , Enzimas Desubiquitinantes/metabolismo , Enzimas Desubiquitinantes/genética , Proteínas Virais Reguladoras e Acessórias
20.
Lung Cancer ; 191: 107558, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569278

RESUMO

OBJECTIVES: Mediastinal neoplasms are typical but uncommon thoracic diseases with increasing incidence and unfavorable prognoses. A comprehensive understanding of their spatiotemporal distribution is essential for accurate diagnosis and timely treatment. However, previous studies are limited in scale and data coverage. Therefore, this study aims to elucidate the distribution of mediastinal lesions, offering valuable insights into this disease. MATERIALS AND METHODS: This multi-center, hospital-based observational study included 20 nationwide institutions. A retrospective search of electronic medical records from January 1st, 2009, to December 31st, 2020, was conducted, collecting sociodemographic data, computed tomography images, and pathologic diagnoses. Analysis focused on age, sex, time, location, and geographical region. Comparative assessments were made with global data from a multi-center database. RESULTS: Among 7,765 cases, thymomas (30.7%), benign mediastinal cysts (23.4%), and neurogenic tumors (10.0%) were predominant. Distribution varied across mediastinal compartments, with thymomas (39.6%), benign cysts (28.1%), and neurogenic tumors (51.9%) most prevalent in the prevascular, visceral, and paravertebral mediastinum, respectively. Age-specific variations were notable, with germ cell tumors prominent in patients under 18 and aged 18-29, while thymomas were more common in patients over 30. The composition of mediastinal lesions across different regions of China remained relatively consistent, but it differs from that of the global population. CONCLUSION: This study revealed significant heterogeneity in the spatiotemporal distribution of mediastinal neoplasms. These findings provide useful demographic data when considering the differential diagnosis of mediastinal lesions, and would be beneficial for tailoring disease prevention and control strategies.


Assuntos
Neoplasias do Mediastino , Humanos , Masculino , Feminino , Neoplasias do Mediastino/epidemiologia , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Adolescente , Adulto Jovem , Idoso , Criança , Análise Espaço-Temporal , Pré-Escolar , Tomografia Computadorizada por Raios X , Incidência
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