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1.
Nucleic Acids Res ; 52(6): 3291-3309, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38165050

RESUMO

The mechanisms by which the relatively conserved spliceosome manages the enormously large number of splicing events that occur in humans (∼200 000 versus ∼300 in yeast) are poorly understood. Here, we show deposition of one RNA modification-N2-methylguanosine (m2G) on the G72 of U6 snRNA (the catalytic center of the spliceosome) promotes efficient pre-mRNA splicing activity in human cells. This modification was identified to be conserved among vertebrates. Further, THUMPD2 was demonstrated as the methyltransferase responsible for U6 m2G72 by explicitly recognizing the U6-specific sequences and structural elements. The knock-out of THUMPD2 eliminated U6 m2G72 and impaired the pre-mRNA splicing activity, resulting in thousands of changed alternative splicing events of endogenous pre-mRNAs in human cells. Notably, the aberrantly spliced pre-mRNA population elicited the nonsense-mediated mRNA decay pathway. We further show that THUMPD2 was associated with age-related macular degeneration and retinal function. Our study thus demonstrates how an RNA epigenetic modification of the major spliceosome regulates global pre-mRNA splicing and impacts physiology and disease.


Assuntos
Precursores de RNA , Splicing de RNA , Proteínas de Ligação a RNA , Degeneração Retiniana , Animais , Humanos , Metilação , Conformação de Ácido Nucleico , Degeneração Retiniana/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Splicing de RNA/genética , RNA Nuclear Pequeno/metabolismo , Saccharomyces cerevisiae/genética , Spliceossomos/genética , Spliceossomos/metabolismo
2.
Dig Dis Sci ; 69(7): 2559-2566, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38662161

RESUMO

BACKGROUND: Gastrointestinal tumors bleeding remains a significantly clinical challenge due to its resistance to conventional endoscopic hemostasis methods. While the efficacy of endoscopic tissue adhesives (ETA) in variceal bleeding has been established, its role in gastrointestinal tumor bleeding (GITB) remains ambiguous. AIMS: This study aims to assess the feasibility and effectiveness of ETA in the treatment of GITB. METHODS: The study enrolled 30 patients with GITB who underwent hemostasis through Histoacryl® tissue glue injection. Hemostasis success rates, ETA-related adverse events, and re-bleeding rates were evaluated. RESULTS: ETA application achieved successful hemostasis at all tumor bleeding sites, with immediate hemostasis observed in all 30 (100.0%) patients. Among the initially hemostasis cases, 5 patients (17.0%) experienced re-bleeding within 30 days, and the 60 day re-bleeding rate was 20.0% (6/30). Expect for one case of vascular embolism, no adverse events related with ETA application were reported. The 6 month survival was 93%. CONCLUSION: ETA demonstrated excellent immediate hemostasis success rate in GITB cases and showed promising outcomes in prevention re-bleeding.


Assuntos
Hemorragia Gastrointestinal , Neoplasias Gastrointestinais , Hemostase Endoscópica , Adesivos Teciduais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adesivos Teciduais/uso terapêutico , Adesivos Teciduais/administração & dosagem , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Neoplasias Gastrointestinais/complicações , Hemostase Endoscópica/métodos , Adulto , Resultado do Tratamento , Embucrilato/administração & dosagem , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Estudos Retrospectivos
3.
BMC Palliat Care ; 23(1): 155, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902684

RESUMO

OBJECTIVE: Explore the feasibility of a mobile health(mHealth) and virtual reality (VR) based nutrition-exercise-psychology integrated rehabilitation model in Chinese cancer patients. METHODS: We recruited cancer patients in the Oncology department of the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from October 2022 to April 2023. The rehabilitation program was provided by a team of medical oncologists, dietitians, psychotherapists, and oncology specialist nurses. Participants received standard anti-cancer therapy and integrated intervention including hospitalized group-based exercise classes, at-home physical activity prescription, behavior change education, oral nutrition supplements, and psychological counseling. An effective intervention course includes two consecutive hospitalization and two periods of home-based rehabilitation (8 weeks). Access the feasibility as well as changes in aspects of physical, nutritional, and psychological status. RESULTS: At the cutoff date of April 2023, the recruitment rate was 75% (123/165). 11.4%patients were lost to follow-up, and 3.25% withdrew halfway. Respectively, the completion rate of nutrition, exercise, and psychology were 85%,55%, and 63%. Nutrition interventions show the highest compliance. The parameters in nutrition, psychology, muscle mass, and quality of life after the rehabilitation showed significant improvements (P < .05). There was no significant statistical difference (P > .05) in handgrip strength and 6-minute walking speed. CONCLUSION: It is feasible to conduct mHealth and VR-based nutrition-exercise-psychology integrated rehabilitation model in Chinese cancer patients. A larger multi-center trial is warranted in the future. TRIAL REGISTRATION: ChiCTR2200065748 Registered 14 November 2022.


Assuntos
Estudos de Viabilidade , Neoplasias , Telemedicina , Realidade Virtual , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Neoplasias/psicologia , Neoplasias/reabilitação , Neoplasias/complicações , Estudos Prospectivos , Adulto , Idoso , Exercício Físico/psicologia , Terapia por Exercício/métodos , Terapia por Exercício/normas , Terapia por Exercício/psicologia , China
4.
Sensors (Basel) ; 24(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38793891

RESUMO

In response to the numerous challenges faced by traditional human pose recognition methods in practical applications, such as dense targets, severe edge occlusion, limited application scenarios, complex backgrounds, and poor recognition accuracy when targets are occluded, this paper proposes a YOLO-Pose algorithm for human pose estimation. The specific improvements are divided into four parts. Firstly, in the Backbone section of the YOLO-Pose model, lightweight GhostNet modules are introduced to reduce the model's parameter count and computational requirements, making it suitable for deployment on unmanned aerial vehicles (UAVs). Secondly, the ACmix attention mechanism is integrated into the Neck section to improve detection speed during object judgment and localization. Furthermore, in the Head section, key points are optimized using coordinate attention mechanisms, significantly enhancing key point localization accuracy. Lastly, the paper improves the loss function and confidence function to enhance the model's robustness. Experimental results demonstrate that the improved model achieves a 95.58% improvement in mAP50 and a 69.54% improvement in mAP50-95 compared to the original model, with a reduction of 14.6 M parameters. The model achieves a detection speed of 19.9 ms per image, optimized by 30% and 39.5% compared to the original model. Comparisons with other algorithms such as Faster R-CNN, SSD, YOLOv4, and YOLOv7 demonstrate varying degrees of performance improvement.


Assuntos
Algoritmos , Postura , Humanos , Postura/fisiologia , Dispositivos Aéreos não Tripulados , Processamento de Imagem Assistida por Computador/métodos
5.
Anal Chem ; 95(28): 10625-10633, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37424077

RESUMO

A growing number of studies have shown that tumor cells secrete extracellular vesicles (EVs) containing programmed death-ligand 1 (PD-L1) protein. These vesicles can travel to lymph nodes and remotely inactivate T cells, thereby evading immune system attack. Therefore, the simultaneous detection of PD-L1 protein expression in cells and EVs is of great significance in guiding immunotherapy. Herein, we developed a method based on qPCR for the simultaneous detection of PD-L1 protein and mRNA in EVs and their parental cells (PREC-qPCR assay). Lipid probes immobilized on magnetic beads were used to capture EVs directly from samples. For RNA assay, EVs were directly broken by heating and quantified with qPCR. As to protein assay, EVs were recognized and bound with specific probes (such as aptamers), which were used as templates in subsequent qPCR analysis. This method was used to analyze EVs of patient-derived tumor clusters (PTCs) and plasma samples from patients and healthy volunteers. The results revealed that the expression of exosomal PD-L1 in PTCs was correlated with tumor types and significantly higher in plasma-derived EVs from tumor patients than that of healthy individuals. When extended to cells and PD-L1 mRNAs, the results showed that the expression of PD-L1 protein was consistent with mRNA in cancer cell lines, while PTCs demonstrated significant heterogeneity. This comprehensive detection of PD-L1 at four levels (cell, EVs, protein, and mRNA) is believed to enhance our understanding of the relationship among PD-L1, tumors, and the immune system and to provide a promising tool for predicting the benefits of immunotherapy.


Assuntos
Reação em Cadeia da Polimerase em Tempo Real , Humanos , Neoplasias/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , RNA Mensageiro/análise , RNA Mensageiro/genética , Vesículas Extracelulares/genética , Linhagem Celular Tumoral
6.
Appl Opt ; 62(13): 3416-3421, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132842

RESUMO

In this study, the time-spatial evolution of single-pulse femtosecond laser-induced plasma in sapphire is studied by using femtosecond time-resolved pump-probe shadowgraphy. Laser-induced sapphire damage occurred when the pump light energy was increased to 20 µJ. Based on its shadowgraphy image, the threshold electron density can be estimated to be about 2.48×1020 c m -3. The evolution law of the transient peak electron density and its spatial position as femtosecond laser propagation in sapphire were researched. The transitions from single-focus to multi-focus as the laser focus shifted from the surface to a deeper part were observed from the transient shadowgraphy images. The focal point distance in multi-focus increased as the focal depth increased. The distributions of femtosecond laser-induced free electron plasma and the final microstructure were consistent with each other.

7.
Nucleic Acids Res ; 49(20): 11900-11919, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34669960

RESUMO

Post-transcriptional modifications affect tRNA biology and are closely associated with human diseases. However, progress on the functional analysis of tRNA modifications in metazoans has been slow because of the difficulty in identifying modifying enzymes. For example, the biogenesis and function of the prevalent N2-methylguanosine (m2G) at the sixth position of tRNAs in eukaryotes has long remained enigmatic. Herein, using a reverse genetics approach coupled with RNA-mass spectrometry, we identified that THUMP domain-containing protein 3 (THUMPD3) is responsible for tRNA: m2G6 formation in human cells. However, THUMPD3 alone could not modify tRNAs. Instead, multifunctional methyltransferase subunit TRM112-like protein (TRMT112) interacts with THUMPD3 to activate its methyltransferase activity. In the in vitro enzymatic assay system, THUMPD3-TRMT112 could methylate all the 26 tested G6-containing human cytoplasmic tRNAs by recognizing the characteristic 3'-CCA of mature tRNAs. We also showed that m2G7 of tRNATrp was introduced by THUMPD3-TRMT112. Furthermore, THUMPD3 is widely expressed in mouse tissues, with an extremely high level in the testis. THUMPD3-knockout cells exhibited impaired global protein synthesis and reduced growth. Our data highlight the significance of the tRNA: m2G6/7 modification and pave a way for further studies of the role of m2G in sperm tRNA derived fragments.


Assuntos
Metiltransferases/metabolismo , RNA de Transferência/metabolismo , Proteínas de Ligação a RNA/metabolismo , tRNA Metiltransferases/metabolismo , Células HEK293 , Células HeLa , Humanos , Metilação , Metiltransferases/genética , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/genética , Especificidade por Substrato , tRNA Metiltransferases/genética
8.
Med Sci Monit ; 24: 7625-7632, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30359340

RESUMO

BACKGROUND Liver cancer is the third leading cause of tumor-related deaths worldwide. Stomatin-like protein 2 (STOML2) is obviously upregulated in various tumors. In this study, we explored the potential roles and mechanisms of si-STOML2 in the migration and invasion of human hepatoma LM3 cells. MATERIAL AND METHODS The expression levels of STOML2 in tissues and cells were separately analyzed with quantitative real-time PCR (qRT-PCR) and Western blotting. The viability, migration, and invasion of cells were assessed by cell counting kit-8 (CCK-8), wound healing, and transwell analysis, respectively. The mRNA and protein levels of various factors were separately measured using qRT-PCR and Western blotting. Correlation analysis between the expression of STOML2 and the clinicopathological features of liver cancer patients was evaluated using the chi-square test. RESULTS Surprisingly, our results showed that STOML2 was upregulated in liver cancer tissue and cells, and this upregulation was linked to tumor size, histologic grade, and metastasis, but was not associated with sex, age, or TNM stage. The knockdown of STOML2 significantly repressed the viability, migration, and invasion of LM3 cells. We also observed that silencing STOML2 markedly downregulated the expression levels of matrix metalloproteinase-2 (MMP-2), MMP-9, metastatic tumor antigen 1 (MTA1), and nuclear factor kappa B (NF-κB), and upregulated levels of E-cadherin, tissue inhibitor of metalloproteinases 2 (TIMP2), and the inhibitor of kappa B (IκB). CONCLUSIONS STOML2 has a vital role in the progression of liver cancer. STOML2 silencing in LM3 cells obviously repressed the abilities of migration and invasion via suppressing the NF-κB pathway.


Assuntos
Proteínas Sanguíneas/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Adulto , Idoso , Proteínas Sanguíneas/genética , Caderinas/genética , Caderinas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/fisiologia , Feminino , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/genética , Pessoa de Meia-Idade , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Invasividade Neoplásica , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Transativadores , Ativação Transcricional
9.
Sci Rep ; 14(1): 5443, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443440

RESUMO

Due to the alternating loads on pumping units and the integration of new energy sources, multisource DC microgrid pumping unit well groups experience increased fluctuations in voltage and power as well as superimposed peak and valley values. This work presents a distributed control strategy for pumping unit well groups on a multisource DC microgrid based on the weighted moving average algorithm. A centralized control program is implanted in the RTU of the single-well controller of each pumping unit, and communication with each well is realized via SCADA and multicast communication, resulting in a distributed well group system. The real-time power values of the pumping well group are calculated by grouping the power values, and each group is weighted using the total power fluctuation threshold of the well group as the control target. Then, a weighted moving average algorithm is used to predict the next power value and form a table of predicted real-time power spectra. According to the power values in the community power spectrum table, the inverter frequency is proportionally adjusted downwards to reach the power peak before deceleration; after the power peak is crossed, the frequency is increased in the same way to reach the power valley before acceleration. Finally, the peak and valley power values of the bus system level off and further learn to reach the set impulse; ultimately, a stable impulse is formed. In laboratory testing and field application in the Shengli Oilfield XIN-11 block, the group control software module effectively suppressed the active power peak and valley values and voltage fluctuations of the bus system, the active power fluctuation rate range decreased by more than 70%, and the DC bus voltage fluctuation range decreased by more than 80%; moreover, the active power decreased by approximately 6% without additional hardware costs.

10.
Diabetes Metab ; 50(2): 101523, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38341132

RESUMO

AIMS: Identifying physiological factors that could reduce pregnant women's risk for developing gestational diabetes mellitus (GDM) is crucial for early prevention and intervention. We aimed to examine whether higher serum levels of total bilirubin (TBIL) were associated with a decreased risk of GDM. METHODS: We conducted a retrospective cohort study in a tertiary care hospital in Shanghai, China. A total of 92,885 pregnant women were included. Serum TBIL levels were determined during the first antenatal visit before 24 weeks of gestation and GDM was diagnosed with a 75-g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. RESULTS: A total of 13,037 GDM cases were identified, a prevalence of 14.0 % (13,037/92,885). These women had a higher median TBIL concentration 7.9 versus 7.6 mmol/l (P < 0.001). For the 91,051 women with TBIL within the physiologically normal range (≤ 17.1 µmol/l), a one interquartile range increase in TBIL (3.4 µmol/l) was associated with a decreased risk of GDM: adjusted odds ratio (OR)=0.89 [95 % CI 0.87;0.92]. For these women, the adjusted ORs for GDM across TBIL quartiles were: 0.92 [0.88;0.97] for the second, 0.85 [0.81;0.90] for the third, and 0.78 [0.74;0.83] for the fourth quartile in comparison with the first quartile. CONCLUSION: Our study demonstrated that elevated serum TBIL levels were associated with decreased risk of GDM and supported its potential role in the prevention and early intervention of GDM.


Assuntos
Diabetes Gestacional , Gravidez , Feminino , Humanos , Gestantes , Glicemia , Estudos Retrospectivos , Fatores de Proteção , China/epidemiologia , Bilirrubina , Fatores de Risco
11.
Int J Biol Macromol ; 264(Pt 2): 130821, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484816

RESUMO

Cellulose nanofibers (CNF) based films are promising packaging materials, but the lack of special functions (especially UV-shielding property) usually restrict their further applications. In this work, MXene was incorporated into the CNF film by a direct solvent volatilization induced film forming method to study its UV-shielding property for the first time, which avoided the using of a vacuum filtration equipment. The composite films containing glycerin could be folded repeatedly without breaking, showing good flexibility. The structure and properties of MXene/CNF composite films (CMF) were characterized systematically. The results showed that MXene distributed uniformly in the CNF film matrix and there was strong hydrogen bonding interaction between CNF and MXene. The tensile strength and Young's modulus of the composite films could reach 117.5 MPa and 2.23 GPa, which was 54.1 % and 59.2 % higher than those of pure CNF film, respectively. With the increase of MXene content, both the UVA and UVB shielding percentages increased significantly from 17.2 % and 25.5 % to 100.0 %, showing excellent UV-shielding property. Moreover, CMF exhibited a low oxygen permeability (OP) value of 0.39 cc µm d-1 m-2 kPa-1, a low water vapor permeability (WVP) value of 5.13 × 10-11 g-1s-1Pa-1 and a high antibacterial rate against E. coli (94.1 % at 24 h), showing potential application in the packaging field.


Assuntos
Celulose , Nanofibras , Nitritos , Elementos de Transição , Celulose/química , Nanofibras/química , Escherichia coli , Embalagem de Produtos
12.
Front Immunol ; 15: 1448485, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39253086

RESUMO

Background: ß-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. We aimed to evaluate the efficacy and safety of ß-glucan plus immunotherapy and chemotherapy in the first-line treatment of advanced gastric adenocarcinoma. Methods: This is a phase IB, prospective, single-arm, investigator-initiated trail. Advanced gastric adenocarcinoma patients received ß-glucan, camrelizumab, oxaliplatin, oral S-1 every 3 weeks. The curative effect was evaluated every 2 cycles. The primary endpoints were objective response rate (ORR) and safety, with secondary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). The exploratory endpoint explored biomarkers of response to treatment efficacy. Results: A total of 30 patients had been enrolled, including 20 (66.7%) males and all patients with an ECOG PS score of ≥1. The ORR was 60%, the mPFS was 10.4 months (95% confidence interval [CI], 9.52-11.27), the mOS was 14.0 months (95% CI, 11.09-16.91). A total of 19 patients (63.3%) had TRAEs, with 9 patients (30%) with grade ≥ 3. The most common TRAEs were nausea (53.3%). After 2 cycles of treatment, the levels of IL-2, IFN-γ and CD4+ T cells significantly increased (P < 0.05). Furthermore, biomarker analysis indicated that patient with better response and longer OS exhibited lower GZMA expression at baseline serum. Conclusions: This preliminary study demonstrates that ß-glucan plus camrelizumab and SOX chemotherapy offers favorable efficacy and a manageable safety profile in patients with advanced gastric adenocarcinoma, and further studies are needed to verify its efficacy and safety. Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR2100044088.


Assuntos
Adenocarcinoma , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Oxaliplatina , Neoplasias Gástricas , beta-Glucanas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Masculino , Pessoa de Meia-Idade , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , beta-Glucanas/uso terapêutico , beta-Glucanas/administração & dosagem , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Ácido Oxônico/efeitos adversos , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Tegafur/efeitos adversos , Combinação de Medicamentos , Estudos Prospectivos , Resultado do Tratamento
13.
Sci Rep ; 14(1): 10554, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719903

RESUMO

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 µmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.


Assuntos
Ferro , Sarcopenia , Transferrina , Humanos , Sarcopenia/sangue , Masculino , Feminino , Ferro/sangue , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Transferrina/metabolismo , Transferrina/análise , Índice de Massa Corporal , Força da Mão , Fatores de Risco , Músculo Esquelético/metabolismo , Modelos Logísticos , Idoso de 80 Anos ou mais
14.
DNA Cell Biol ; 43(5): 258-266, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513057

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers globally. Circular RNAs (circRNAs) have been implicated in the development of HCC. Previous studies have confirmed that circ-EIF3I plays an important role in the progress of lung cancer. Nevertheless, the biological functions of circ-EIF3I and the underlying mechanisms by which they regulate HCC progression remain unclear. In this study, the regulatory mechanism and targets were studied with bioinformatics analysis, luciferase reporting analysis, transwell migration, Cell Counting Kit-8, and 5-Ethynyl-2'-deoxyuridine analysis. In addition, in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circ-EIF3I in HCC. The result shows that the circ-EIF3I expression was increased in HCC cell line, which means that circ-EIF3I plays a role in the progression of HCC. Downregulation of circ-EIF3I suppressed HCC cells' proliferation and migration in both in vivo and in vitro experiments. Bioinformatics and luciferase report analysis confirmed that both miR-361-3p and Dual-specificity phosphatase 2 (DUSP2) were the downstream target of circ-EIF3I. The overexpression of DUSP2 or inhibition of miR-361-3p restored HCC cells' proliferation and migration ability after silence circ-EIF3I. Taken together, our study found that downregulation of circ-EIF3I suppressed the progression of HCC through miR-361-3p/DUSP2 Axis.


Assuntos
Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs , RNA Circular , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Animais , Camundongos , Linhagem Celular Tumoral , Progressão da Doença , Camundongos Nus , Camundongos Endogâmicos BALB C
15.
Cancer Biomark ; 41(1): 1-24, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39240627

RESUMO

Glioma is the most common primary tumor of the central nervous system (CNS). Glioblastoma (GBM) is incurable with current treatment strategies. Additionally, the treatment of recurrent GBM (rGBM) is often referred to as terminal treatment, necessitating hospice-level care and management. The presence of the blood-brain barrier (BBB) gives GBM a more challenging or "cold" tumor microenvironment (TME) than that of other cancers and gloma stem cells (GSCs) play an important role in the TME remodeling, occurrence, development and recurrence of giloma. In this review, our primary focus will be on discussing the following topics: niche-associated GSCs and macrophages, new theories regarding GSC and TME involving pyroptosis and ferroptosis in GBM, metabolic adaptations of GSCs, the influence of the cold environment in GBM on immunotherapy, potential strategies to transform the cold GBM TME into a hot one, and the advancement of GBM immunotherapy and GBM models.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Células-Tronco Neoplásicas , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Glioblastoma/imunologia , Glioblastoma/patologia , Glioblastoma/terapia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Imunoterapia/métodos , Animais , Barreira Hematoencefálica/metabolismo
16.
Phytomedicine ; 112: 154716, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36805484

RESUMO

BACKGROUND: Berberine has been widely used for the adjuvant therapy of several cardiovascular diseases (CVDs). However, evidence for its efficacy remains controversial. PURPOSE: This study aimed to evaluate the efficacy and safety of berberine in CVDs. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We searched ten electronic databases for articles from inception to December 23, 2022. RCTs comparing berberine alone or combined with statins versus statins or routine for CVDs were included. Meta-analysis was performed according to the Cochrane Handbook. RESULTS: Forty-four RCTs were included with 4606 patients. There were no differences between berberine alone and routine or statins in improving total cholesterol (TC) (SMD, 0.43; 95% CI, -0.39 to 1.24; p = 0.30; I2 = 95%), triglyceride (TG) (SMD, -0.14; 95% CI, -0.49 to 0.21; p = 0.44; I2 = 76%), low-density lipoprotein cholesterol (LDL-C) (SMD, 0.69; 95% CI, -0.23 to 1.60; p = 0.14; I2 = 96%), high-density lipoprotein cholesterol (HDL-C) (SMD, 0.55; 95% CI, -0.48 to 1.57; p = 0.30; I2 = 96%), and Crouse score levels. Berberine alone significantly reduced National Institute of Health Stroke Scale (NIHSS) score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intima-media thickness (IMT) levels than routine therapy. Berberine plus statins significantly reduced TC, TG, LDL-C, NIHSS score, hs-CRP, TNF-α, IMT, Crouse score, and number of unstable plaques levels than routine or statins. However, no differences were found between groups in improving HDL-C and IL-6 levels. There were no significant differences between groups in the incidence of adverse reactions. CONCLUSION: This study suggests that berberine may be a promising alternative for CVDs with no serious adverse reactions. However, our results may be limited by the quality of existing research. High-quality RCTs are needed to provide more convinced evidence.


Assuntos
Berberina , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Berberina/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , LDL-Colesterol , Proteína C-Reativa , Fator de Necrose Tumoral alfa , Interleucina-6 , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos , HDL-Colesterol
17.
Health Data Sci ; 3: 0098, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38487200

RESUMO

Importance: Drug-likeness of a compound is an overall assessment of its potential to succeed in clinical trials, and is essential for economizing research expenditures by filtering compounds with unfavorable properties and poor development potential. To this end, a robust drug-likeness prediction method is indispensable. Various approaches, including discriminative rules, statistical models, and machine learning models, have been developed to predict drug-likeness based on physiochemical properties and structural features. Notably, recent advancements in novel deep learning techniques have significantly advanced drug-likeness prediction, especially in classification performance. Highlights: In this review, we addressed the evolving landscape of drug-likeness prediction, with emphasis on methods employing novel deep learning techniques, and highlighted the current challenges in drug-likeness prediction, specifically regarding the aspects of generalization and interpretability. Moreover, we explored potential remedies and outlined promising avenues for future research. Conclusion: Despite the hurdles of generalization and interpretability, novel deep learning techniques have great potential in drug-likeness prediction and are worthy of further research efforts.

18.
J Neurointerv Surg ; 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37463767

RESUMO

OBJECTIVE: To introduce a novel endovascular recanalization method and to investigate its success rate, periprocedural complications, and early outcomes in patients with chronic internal carotid artery occlusion (CICAO). As this novel technique was designed to treat CICAO with a full coaxial system, we named it the COCO technique. METHODS: Data from consecutive patients with symptomatic CICAO who underwent endovascular recanalization in our institution were retrospectively reviewed. The COCO technique allows extracranial angioplasty and stenting with occasional intracranial angioplasty and stenting as needed to be performed in a coaxial fashion. Patients' demographic and clinical information, morphologic characteristics, procedural results, complications, and follow-up outcomes were recorded. RESULTS: Forty-nine patients were enrolled in this study. The technical success rate was 89.8% (44/49). Four patients experienced intraoperative complications, two patients had a slight subarachnoid hemorrhage, and two patients had asymptomatic dissection. Distal embolization or carotid-cavernous arteriovenous fistula was not detected. In addition, three patients developed hemorrhagic complications and three developed postoperative ischemic complications. All these patients improved after conservative treatment and subsequent rehabilitation. During the median 6 (3-6) months of follow-up, one patient died of severe pneumonia and two patients experienced recurrent ischemic events. In patients with successful recanalization, modified Rankin Scale scores were lower at the 3-month follow-up than at baseline (1 (0-2) vs 2 (1-2), P=0.04). Restenosis was observed in six (15.8%) patients. CONCLUSIONS: Our study showed that the COCO technique is effective and safe for endovascular recanalization in patients with CICAO and has low periprocedural complications and favorable functional outcomes.

19.
Medicine (Baltimore) ; 102(43): e35491, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37904433

RESUMO

Clinical outcomes of colon adenocarcinoma (COAD) exhibit heterogeneity among different patients, highlighting the need for novel prognostic biomarkers. Kinesin superfamily members have been shown to play a crucial role in tumors and can predict cancer diagnosis and prognosis. However, the role of kinesin family member C2 (KIFC2) in tumors, particularly its prognostic value in COAD, remains poorly understood. Our bioinformatics analysis of the cancer genome atlas and GEO databases revealed significantly higher expression of KIFC2 in COAD, correlating with a worse prognosis in the cancer genome atlas-COAD and GSE17536 cohorts. Additionally, differentially expressed genes in COAD were enriched in immune-related pathways, and patients with higher KIFC2 expression showed fewer activated CD4 + T cells. These findings suggest KIFC2 as a potential prognostic biomarker for COAD, warranting further validation in clinical studies.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/genética , Cinesinas/genética , Prognóstico , Adenocarcinoma/genética , Biomarcadores
20.
PeerJ ; 11: e14913, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36908815

RESUMO

Background: Hippocampus impairment is a common condition encountered in the clinical diagnosis and treatment of traumatic brain injury (TBI). Several studies have investigated this phenomenon. However, its molecular mechanism remains unclear. Methods: In this study, Illumina RNA-seq technology was used to determine the gene expression profile in mice hippocampus after TBI. We then conducted bioinformatics analysis to identify the altered gene expression signatures and mechanisms related to TBI-induced pathology in the hippocampus. Real-time quantitative polymerase chain reaction and western blot were adopted to verify the sequencing results. Results: The controlled cortical impact was adopted as the TBI model. Hippocampal specimens were removed for sequencing. Bioinformatics analysis identified 27 upregulated and 17 downregulated differentially expressed genes (DEGs) in post-TBI mouse models. Potential biological functions of the genes were determined via Gene Set Enrichment Analysis (GSEA)-based Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, which suggested a series of functional changes in the nervous system. Specifically, the nucleoporin 62 (Nup62) DEG was discussed and verified. Gene ontology biological process enriched analysis suggests that the cell division was upregulated significantly. The present study may be helpful for the treatment of impaired hippocampus after TBI in the future.


Assuntos
Lesões Encefálicas Traumáticas , Perfilação da Expressão Gênica , Animais , Camundongos , Lesões Encefálicas Traumáticas/genética , Divisão Celular , Perfilação da Expressão Gênica/métodos , Hipocampo/metabolismo , RNA-Seq
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