Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.812
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-38563722

RESUMO

OBJECTIVE: The mechanism of asymmetric dimethylarginine (ADMA) in thrombosis in patients with nonvalvular atrial fibrillation (NVAF) is still unclear. Our aim was to investigate the relationship between ADMA and indicators of prethrombotic state in NVAF patients and to analyze the predictive role of ADMA in NVAF thrombosis. METHODS: A total of 192 NVAF patients were continuously selected from January 2023 to October 2023. Plasma ADMA levels were measured by high-performance liquid chromatography. P-selectin (P-sel), von Willebrand factor (vWF), D-dimer (D-D), and plasminogen activator inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) levels were measured by the nitrate reductase assay for plasma nitrite/nitrate, then the Griess method (Shanghai Hailian Biotechnology Co., Shanghai, China) was used to calculate plasma NO levels. RESULTS: In our study, ADMA levels were significantly elevated and positively correlated with P-sel, vWF, D-D, and PAI-1, whereas NO levels were significantly negatively correlated with these prethrombotic factors in NVAF. Furthermore, multifactorial logistic regression analysis showed that ADMA and LA diameter were independent predictors of high thrombosis risk (CHA2DS2-VASc ≥2 score) in patients with NVAF. CONCLUSIONS: Our findings suggested that ADMA correlated with the prethrombotic state in NVAF and that reduction of ADMA levels in NVAF patients may be a novel therapeutic strategy for thrombosis risk reduction.

2.
J Investig Med ; : 10815589241248073, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594222

RESUMO

OBJECTIVE: The aim of this study was to evaluate the clinical features, pathological characteristics and prognosis in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies-associated glomerulonephritis (AAGN) with renal arteritis. METHODS: The study involved 97 children from five pediatric clinical centers with MPO-AAGN who exhibited distinct clinical features. The patients were divided into AAGN-A+ and AAGN-A-, based on the presence or absence of arteritis, and the disparities in clinical, histopathological characteristics, and prognosis between the two groups were evaluated. RESULT: In contrast to the AAGN-A- group, the children in the AAGN-A+ group exhibited more pronounced clinical symptoms and renal pathological injury. Arteritis positively moderately correlated with the serum creatinine (Scr), IL-6 (interleukin-6), urinary neutrophil gelatinase-associated lipocalin (NGAL), negatively moderately correlated with serum complement C3. The renal survival rate in the AAGN-A+ group was significantly poorer than AAGN-A- group (χ2=4.278, P=0.039). Arteritis showed a good predictive value for end-stage kidney disease (ESKD), and C3 deposition and arteritis were independent risk factors for the development of ESKD in children with MPO-AAGN. CONCLUSION: Arteritis is a significant pathological change observed in children with MPO-AAGN, and the formation of arteritis may be related to the inflammatory response and activation of the complement system.

3.
BMC Infect Dis ; 24(1): 413, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641791

RESUMO

Considering that neutralizing antibody levels induced by two doses of the inactivated vaccine decreased over time and had fallen to low levels by 6 months, and homologous and heterologous booster immunization programs have been implemented in adults in China. The booster immunization of recombinant COVID-19 vaccine (ZF2001) after priming with inactivated vaccine in healthy children and adolescents has not been reported. We performed an open-labeled, single-arm clinical trial to evaluate the safety and immunogenicity of heterologous booster immunization with ZF2001 after priming with inactivated vaccine among 240 population aged 3-17 years in China. The primary outcome was immunogenicity, including geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates of SARS-CoV-2 neutralizing antibodies against prototype SARS-CoV-2 and Omicron BA.2 variant at 14 days after vaccination booster. On day 14 post-booster, a third dose booster of the ZF2001 provided a substantial increase in antibody responses in minors, and the overall occurrence rate of adverse reactions after heterologous vaccination was low and all adverse reactions were mild or moderate. The results showed that the ZF2001 heterologous booster had high immunogenicity and good safety profile in children and adolescents, and can elicit a certain level of neutralizing antibodies against Omicron.Trial registration NCT05895110 (Retrospectively registered, First posted in ClinicalTrials.gov date: 08/06/2023).


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas de Subunidades , Adulto , Criança , Humanos , Adolescente , Vacinas contra COVID-19/efeitos adversos , Vacinas de Produtos Inativados/efeitos adversos , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Imunogenicidade da Vacina
4.
J Colloid Interface Sci ; 665: 846-854, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38564948

RESUMO

The unique superconductivity and charge density wave transition characteristics of NbSe2 make it worthy of exploring its electrochemical performance and potential applications in the field of batteries. Herein, the bulk NbSe2 was successfully exfoliated into few-layered NbSe2 nanostructures by wet grinding exfoliation approach, which solved the issues of its long activation period and poor cycle stability. The strong Nb-Se bond in the plane and weak van der Waals force between the adjacent layers could render the fast Na+ diffusion, provide abundant reaction sites and multi-directional migration paths, thus accelerate the ionic conductivity. The theoretical calculations verified the high Na+ adsorption tendency between the NbSe2 interlayers stemming from the continuous region of charge accumulation. Thanks to the unique electronic and two-dimensional few-layered structures, the exfoliated NbSe2 exhibited a high cyclic stability with a capacity of 502 mA h g-1 over 2800 cycles at 10 A/g. In addition, the reaction mechanism was studied by in-situ X-ray diffraction and other tests, indicating a reaction mechanism containing of simultaneous intercalation (NbSe2↔NaxNbSe2↔NaNbSe2↔Na1+xNbSe2) and conversion processes in NbSe2. This parallelly running mechanism not only alleviates the volume change but also ensures a high specific capacity. Additionally, different lattice planes of the NaNbSe2 intermediate in the intercalation process experience varying degrees of contraction and expanding in d-spacing due to the influence of Coulombic force.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38652615

RESUMO

Negative flips are errors introduced in a classification system when a legacy model is updated. Existing methods to reduce the negative flip rate (NFR) either do so at the expense of overall accuracy by forcing a new model to imitate the old models, or use ensembles, which multiply inference cost prohibitively. We analyze the role of ensembles in reducing NFR and observe that they remove negative flips that are typically not close to the decision boundary, but often exhibit large deviations in the distance among their logits. Based on the observation, we present a method, called Ensemble Logit Difference Inhibition (ELODI), to train a classification system that achieves paragon performance in both error rate and NFR, at the inference cost of a single model. The method distills a homogeneous ensemble to a single student model which is used to update the classification system. ELODI also introduces a generalized distillation objective, Logit Difference Inhibition (LDI), which only penalizes the logit difference of a subset of classes with the highest logit values. On multiple image classification benchmarks, model updates with ELODI demonstrate superior accuracy retention and NFR reduction.

7.
J Am Chem Soc ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652868

RESUMO

Lithium (Li) metal solid-state batteries feature high energy density and improved safety and thus are recognized as promising alternatives to traditional Li-ion batteries. In practice, using Li metal anodes remains challenging because of the lack of a superionic solid electrolyte that has good stability against reduction decomposition at the anode side. Here, we propose a new electrolyte design with an antistructure (compared to conventional inorganic structures) to achieve intrinsic thermodynamic stability with a Li metal anode. Li-rich antifluorite solid electrolytes are designed and synthesized, which give a high ionic conductivity of 2.1 × 10-4 S cm-1 at room temperature with three-dimensional fast Li-ion transport pathways and demonstrate high stability in Li-Li symmetric batteries. Reversible full cells with a Li metal anode and LiCoO2 cathode are also presented, showing the potential of Li-rich antifluorites as Li metal-compatible solid electrolytes for high-energy-density solid-state batteries.

8.
Oncol Lett ; 27(6): 262, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38646496

RESUMO

MicroRNAs (miRNAs/miRs) have abnormal expression in numerous tumors and are closely related to tumor development and resistance to radiotherapy and chemotherapy. However, there are few studies assessing the role and mechanism of miRNA in chordoma. The sequencing data of three pairs of chordoma and notochord tissues from the GSE56183 dataset were analyzed in the present study. Cell proliferation was assessed in vitro using Cell Counting Kit-8. Bioinformatics analysis and the dual luciferase reporter assay were used to evaluate the regulatory relationship between miR-1224 and chromobox 3 (CBX3) in chordoma. The results demonstrated that miR-1224 had a significantly lower expression level in chordoma tissues and cell lines. Overexpression of miR-1224 inhibited proliferation in the chordoma cells, while the knockdown of miR-1224 promoted proliferation of the chordoma cells. Bioinformatics analysis and the dual luciferase reporter assay confirmed that CBX3 was a direct target gene of miR-1224 and that miR-1224 induced the proliferation of chordoma cells through the inhibition of CBX3. In summary, miR-1224 reduced the proliferation of chordoma cells through inhibition of CBX3, which provides a theoretical basis for selecting a novel therapeutic target for chordoma.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 355-364, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660836

RESUMO

OBJECTIVE: To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia (AML). METHODS: High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center, the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML. The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML. The expression of IGF2BP3 in two anthracycline-resistant cell lines (HL60/ADR, K562/ADR) was detected by RT-qPCR and Western blot, and the expression difference of IGF2BP3 was compared with that in sensitive cells (HL60, K562). The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML, and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis. RESULTS: In the bone marrow primary leukemia cells of 27 AML patients in our center, the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients (P =0.0343). The expression of IGF2BP3 in leukemia patients with extramedullary infiltration (EMI) was significantly higher than that in AML patients without extramedullary infiltration (P =0.0049). Compared with healthy subjects (n=20), IGF2BP3 expression in AML patients (n=26) was higher (P =0.0009). The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines (HL60/ADR, K562/ADR) was significantly higher than that in the sensitive cell lines (K562/ADR vs K562,P =0.0430; HL60/ADR vs HL60, P =0.7369). Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells (P < 0.001). qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive (P =0.002). High expression of IGF2BP3 was associated with poor prognosis in AML (P < 0.05) in 3 large sample cohorts of AML patients. Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival (EFS, HR=1.887, P =0.024) and overall survival (OS, HR=1.619, P =0.016). CONCLUSION: The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML, suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.


Assuntos
Leucemia Mieloide Aguda , Proteínas de Ligação a RNA , Humanos , Leucemia Mieloide Aguda/genética , Prognóstico , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Expressão Gênica , Células HL-60 , Células K562 , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral
10.
Adv Sci (Weinh) ; : e2400101, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647267

RESUMO

Hydrogen-bonded organic frameworks (HOFs) are emerging porous materials that show high structural flexibility, mild synthetic conditions, good solution processability, easy healing and regeneration, and good recyclability. Although these properties give them many potential multifunctional applications, their frameworks are unstable due to the presence of only weak and reversible hydrogen bonds. In this work, the development history and synthesis methods of HOFs are reviewed, and categorize their structural design concepts and strategies to improve their stability. More importantly, due to the significant potential of the latest HOF-related research for addressing energy and environmental issues, this work discusses the latest advances in the methods of energy storage and conversion, energy substance generation and isolation, environmental detection and isolation, degradation and transformation, and biological applications. Furthermore, a discussion of the coupling orientation of HOF in the cross-cutting fields of energy and environment is presented for the first time. Finally, current challenges, opportunities, and strategies for the development of HOFs to advance their energy and environmental applications are discussed.

11.
Methods ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38518843

RESUMO

The process of virtual screening relies heavily on the databases, but it is disadvantageous to conduct virtual screening based on commercial databases with patent-protected compounds, high compound toxicity and side effects. Therefore, this paper utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells to learn the properties of drug compounds in the DrugBank, aiming to obtain a new and virtual screening compounds database with drug-like properties. Ultimately, a compounds database consisting of 26,316 compounds is obtained by this method. To evaluate the potential of this compounds database, a series of tests are performed, including chemical space, ADME properties, compound fragmentation, and synthesizability analysis. As a result, it is proved that the database is equipped with good drug-like properties and a relatively new backbone, its potential in virtual screening is further tested. Finally, a series of seedling compounds with completely new backbones are obtained through docking and binding free energy calculations.

12.
Environ Sci Pollut Res Int ; 31(17): 25589-25599, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38478308

RESUMO

Pentachlorophenol (PCP), a persistent organic pollutant, has been banned in many countries, but it is still used in China as a wood preservative, molluscicide, or reagent for fish-pond cleaning, which may pose risks to the ecosystem and humans. However, data on the occurrence of PCP in the environment are scarce in the recent decade. The Yangtze River was regarded as a priority area of PCP pollution according to previous documents. This study aimed to examine the spatial distribution of PCP in the Yangtze River water, the differences in dry and wet seasons, the ecological risk for aquatic organisms, and its removal efficiency in tap water treatment plants. The river water samples (n = 144) were collected from the upper, middle, and lower reaches across ten provinces (or municipalities) in December 2020 and June 2021, respectively. PCP was detected in 88.9% of all the samples, ranging from

Assuntos
Pentaclorofenol , Poluentes Químicos da Água , Humanos , Animais , Pentaclorofenol/análise , Ecossistema , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Rios , Cidades , China , Medição de Risco , Organismos Aquáticos
13.
Mar Pollut Bull ; 201: 116235, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508122

RESUMO

Marine oil pollution is one of the major global environmental pollution problems. Marine microalgae are the foundation of the marine food chain, providing the main primary productivity of the ocean. They not only maintain the energy flow and material cycle of the entire marine ecosystem, but also play an important role in regulating global climate change. Exploring the impact of petroleum pollutants on marine microalgae is extremely important for studying marine environmental pollution. This review first introduced the sources, compositions, and forms of petroleum pollutants and their migration and transformation processes in the ocean. Then, the toxic effects of petroleum pollutants on marine microalgae were summarized. The growth of marine microalgae showed low-concentration promotion and high-concentration inhibition. The population growth and interspecific relationships of marine microalga was changed and the photosynthesis of marine microalgae was influenced. Finally, potential research directions and suggestions for marine microalgae in the future were proposed.


Assuntos
Poluentes Ambientais , Microalgas , Petróleo , Poluentes Químicos da Água , Petróleo/toxicidade , Ecossistema , Poluentes Químicos da Água/toxicidade
14.
J Hazard Mater ; 469: 133760, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38522206

RESUMO

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.


Assuntos
Água Potável , Neoplasias da Bexiga Urinária , Poluentes Químicos da Água , Humanos , Trialometanos/toxicidade , Trialometanos/análise , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/epidemiologia , Efeitos Psicossociais da Doença , Medição de Risco , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise
15.
Int J Biol Macromol ; 264(Pt 1): 130576, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38442828

RESUMO

An exopolysaccharide, designated F1, was purified from the fermented milk by Lacticaseibacillus rhamnosus strain B6 (CGMCC No. 13310). F1, with the weight average molecular weight of 1.577 × 106 Da, is consisted of rhamnose, glucose and galactose in a molar ratio of 3.7:1.5: 1. The backbone included 1,3-linked Rha, 1,2,3-linked Rha, 1,2-linked Glc and 1,3-linked Glc residues, with the branching point located at O2 position of 1,2,3-linked Rha residue, and the branch chain composed of terminal linked galactose residue with a pyruvate substituent. F1 could significantly stimulate the phagocytic activity and TNF-α expression in RAW 264.7 macrophages in a dose-dependent manner, and the release of NO at 200 µg/mL as well. F1 at 200 µg/mL could stimulate the expression of the pro-inflammatory cytokine encoding genes including TNF-α and iNOS, but with a negligible upregulating effect on the mRNA expression of IL-10. F1 could up-regulate the expression of NF-κBp65 and skew macrophage polarization towards M1 phenotype. These results suggest F1 elicit an immunomodulatory effect through the NF-κB signaling pathway.


Assuntos
Lacticaseibacillus rhamnosus , Fator de Necrose Tumoral alfa/genética , Galactose , Macrófagos , NF-kappa B
16.
World J Psychiatry ; 14(2): 225-233, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38464777

RESUMO

Depression is a common mental health disorder. With current depression detection methods, specialized physicians often engage in conversations and physiological examinations based on standardized scales as auxiliary measures for depression assessment. Non-biological markers-typically classified as verbal or non-verbal and deemed crucial evaluation criteria for depression-have not been effectively utilized. Specialized physicians usually require extensive training and experience to capture changes in these features. Advancements in deep learning technology have provided technical support for capturing non-biological markers. Several researchers have proposed automatic depression estimation (ADE) systems based on sounds and videos to assist physicians in capturing these features and conducting depression screening. This article summarizes commonly used public datasets and recent research on audio- and video-based ADE based on three perspectives: Datasets, deficiencies in existing research, and future development directions.

17.
Cancer Gene Ther ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480975

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

18.
Chin Med J (Engl) ; 137(6): 729-736, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38433332

RESUMO

BACKGROUND: Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA. METHODS: The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 + ) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. RESULTS: The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10 -unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10 -unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. CONCLUSIONS: This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.


Assuntos
Infecções por HIV , HIV-1 , Humanos , HIV-1/genética , DNA Viral/genética , DNA Viral/uso terapêutico , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase , Infecções por HIV/tratamento farmacológico , Reação em Cadeia da Polimerase em Tempo Real
19.
Theriogenology ; 218: 163-173, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38330860

RESUMO

Cumulus cells surrounding oocytes furnish nutritional support crucial for oocyte maturation in vitro, and thereby enhance oocyte quality significantly. Our previous studies affirmed the role of SIRT2 in regulation of mitochondrial function in sheep granulosa cells. However, the effect of SIRT2 action on mitophagy in these cells remain unclear. Here, RNA-seq was used to scrutinize pathways where differentially expressed genes (DEGs) are enriched following SIRT2 knockdown in cumulus cells. Prior to SIRT2 knock down, cumulus cells were treated with the mitophagy inhibitor Mdivi-1. Potential mechanisms by which SIRT2 affects apoptosis via mitophagy were explored. Results indicated that DEGs after SIRT2 knockdown were enriched in various pathways including mitochondria, mitophagy, and apoptosis. The expression levels of CASP3/CASP9 were significantly increased after mitophagy activation (P < 0.01), whereas inhibition of mitophagy had no effect on apoptosis (P > 0.05). Pretreatment of cumulus cells with Mdivi-1 prior to SIRT2 knockdown significantly reduced the expression of mitophagy-related genes, the number of autolysosomes, the expression of CASP3/CASP9, and the levels of Ca2+ and cytochrome C (P < 0.05). In addition, an improvement in mitochondrial morphology and increases in ATP levels and mitochondrial DNA (mtDNA) copy numbers were observed. Interestingly, double knockdown of SIRT2 and MAPK15 was found to reverse increased mitophagy and apoptosis activity caused by SIRT2 knockdown. Our findings indicate that SIRT2 modulate apoptosis in cumulus cells by regulating mitophagy, with MAPK15 likely playing a pivotal role in this process.


Assuntos
Células do Cúmulo , Mitofagia , Feminino , Animais , Ovinos/genética , Mitofagia/genética , Células do Cúmulo/fisiologia , Caspase 3/metabolismo , Sirtuína 2/metabolismo , Oócitos/fisiologia , Apoptose , DNA Mitocondrial
20.
J Cell Mol Med ; 28(4): e18113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332530

RESUMO

The resistance to anoikis plays a critical role in the metastatic progression of various types of malignancies, including gastric cancer (GC). Nevertheless, the precise mechanism behind anoikis resistance is not fully understood. Here, our primary focus was to examine the function and underlying molecular mechanism of Integrin beta-like 1 (ITGBL1) in the modulation of anoikis resistance and metastasis in GC. The findings of our investigation have demonstrated that the overexpression of ITGBL1 significantly augmented the resistance of GC cells to anoikis and promoted their metastatic potential, while knockdown of ITGBL1 had a suppressive effect on both cellular processes in vitro and in vivo. Mechanistically, we proved that ITGBL1 has a role in enhancing the resistance of GC cells to anoikis and promoting metastasis through the AKT/Fibulin-2 (FBLN2) axis. The inhibition of AKT/FBLN2 signalling was able to reverse the impact of ITGBL1 on the resistance of GC cells to anoikis and their metastatic capability. Moreover, the expression levels of ITGBL1 were found to be significantly elevated in the cancerous tissues of patients diagnosed with GC, and there was a strong correlation observed between high expression levels of ITGBL1 and worse prognosis among individuals diagnosed with GC. Significantly, it was revealed that within our cohort of GC patients, individuals exhibiting elevated ITGBL1 expression and diminished FBLN2 expression experienced the worst prognosis. In conclusion, the findings of our study indicate that ITGBL1 may serve as a possible modulator of resistance to anoikis and the metastatic process in GC.


Assuntos
Anoikis , Proteínas de Ligação ao Cálcio , Neoplasias Gástricas , Humanos , Anoikis/genética , Neoplasias Gástricas/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas da Matriz Extracelular , Linhagem Celular Tumoral , Metástase Neoplásica , Integrina beta1/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...