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1.
Eur J Med Chem ; 275: 116638, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38950489

RESUMO

The cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway promotes antitumor immune responses by sensing cytosolic DNA fragments leaked from nucleus and mitochondria. Herein, we designed a highly charged ruthenium photosensitizer (Ru1) with a ß-carboline alkaloid derivative as the ligand for photo-activating of the cGAS-STING pathway. Due to the formation of multiple non-covalent intermolecular interactions, Ru1 can self-assemble into carrier-free nanoparticles (NPs). By incorporating the triphenylphosphine substituents, Ru1 can target and photo-damage mitochondrial DNA (mtDNA) to cause the cytoplasmic DNA leakage to activate the cGAS-STING pathway. Finally, Ru1 NPs show potent antitumor effects and elicit intense immune responses in vivo. In conclusion, we report the first self-assembling mtDNA-targeted photosensitizer, which can effectively activate the cGAS-STING pathway, thus providing innovations for the design of new photo-immunotherapeutic agents.

2.
Cell Death Dis ; 15(6): 460, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942760

RESUMO

Lung cancer stands as the leading cause of mortality among all types of tumors, with over 40% of cases being lung adenocarcinoma (LUAD). Family with sequence similarity 83 member A (FAM83A) emerges as a notable focus due to its frequent overexpression in LUAD. Despite this, the precise role of FAM83A remains elusive. This study addresses this gap by unveiling the crucial involvement of FAM83A in maintaining the cancer stem cell-like (CSC-like) phenotype of LUAD. Through a global proteomics analysis, the study identifies human epidermal growth factor receptor 2 (HER2 or ErbB2) as a crucial target of FAM83A. Mechanistically, FAM83A facilitated ErbB2 expression at the posttranslational modification level via the E3 ubiquitin ligase STUB1 (STIP1-homologous U-Box containing protein 1). More importantly, the interaction between FAM83A and ErbB2 at Arg241 promotes calcineurin (CALN)-mediated dephosphorylation of ErbB2, followed by inhibition of STUB1-mediated ubiquitin-proteasomal ErbB2 degradation. The maintenance of the CSC-like phenotype by FAM83A, achieved through the posttranslational regulation of ErbB2, offers valuable insights for identifying potential therapeutic targets for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas de Neoplasias , Células-Tronco Neoplásicas , Fenótipo , Receptor ErbB-2 , Humanos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Animais , Camundongos , Linhagem Celular Tumoral , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética
3.
J Am Heart Assoc ; 13(13): e034805, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38934866

RESUMO

BACKGROUND: The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. METHODS AND RESULTS: Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming. CONCLUSIONS: This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.


Assuntos
Proliferação de Células , Quinase 1 do Ponto de Checagem , Modelos Animais de Doenças , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Animais , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/genética , Quinase 1 do Ponto de Checagem/metabolismo , Quinase 1 do Ponto de Checagem/genética , Humanos , Piruvato Quinase/metabolismo , Piruvato Quinase/genética , Células HEK293 , Suínos , Reprogramação Celular , Proteínas de Ligação a Hormônio da Tireoide , Regeneração , Ligação Proteica , Sus scrofa , Remodelação Ventricular/fisiologia , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Metabolismo Energético/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Reprogramação Metabólica
4.
J Med Virol ; 96(6): e29724, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837426

RESUMO

Although the burden of the human immunodeficiency virus (HIV) in the Asia-Pacific region is increasingly severe, comprehensive evidence of the burden of HIV is scarce. We aimed to report the burden of HIV in people aged 15-79 years from 1990 to 2019 using data from the Global Burden of Disease Study (GBD) 2019. We analyzed rates of age-standardized disability-adjusted life years (ASDR), age-standardized mortality (ASMR), and age-standardized incidence (ASIR) in our age-period-cohort analysis by sociodemographic index (SDI). According to HIV reports in 2019 from 29 countries in the Asia-Pacific region, the low SDI group in Papua New Guinea had the highest ASDR, ASMR, and ASIR. From 1990 to 2019, the ASDR, ASIR, and ASMR of persons with acquired immune deficiency syndrome (AIDS) increased in 21 (72%) of the 29 countries in the Asia-Pacific region. During the same period, the disability-adjusted life years (DALYs) of AIDS patients in the low SDI group in the region grew the fastest, particularly in Nepal. The incidence of HIV among individuals aged 20-30 years in the low-middle SDI group was higher than that of those in the other age groups. In 2019, unsafe sex was the main cause of HIV-related ASDR in the region's 29 countries, followed by drug use. The severity of the burden of HIV/AIDS in the Asia-Pacific region is increasing, especially among low SDI groups. Specific public health policies should be formulated based on the socioeconomic development level of each country to alleviate the burden of HIV/AIDS.


Assuntos
Carga Global da Doença , Infecções por HIV , Humanos , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Infecções por HIV/epidemiologia , Infecções por HIV/mortalidade , Masculino , Feminino , Idoso , Carga Global da Doença/tendências , Ásia/epidemiologia , Estudos de Coortes , Incidência , Anos de Vida Ajustados por Deficiência , Efeitos Psicossociais da Doença
5.
J Inflamm Res ; 17: 3753-3770, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882183

RESUMO

Background: Osteoarthritis (OA) is a major cause of human disability. Despite receiving treatment, patients with the middle and late stage of OA have poor survival outcomes. Therefore, within the framework of predictive, preventive, and personalized medicine (PPPM/3PM), early personalized diagnosis of OA is particularly prominent. PPPM aims to accurately identify disease by integrating multiple omic techniques; however, the efficiency of currently available methods and biomarkers in predicting and diagnosing OA should be improved. Disulfidptosis, a novel programmed cell death mechanism and appeared in particular metabolic status, plays a mysterious characteristic in the occurrence and development of OA, which warrants further investigation. Methods: In this study, we integrated three public datasets from the Gene Expression Omnibus (GEO) database, including 26 OA samples and 20 normal samples. Via a series of bioinformatic analysis and machine learning, we identified the diagnostic biomarkers and several subtypes of OA. Moreover, the expression of these biomarkers were verified in our in-house cohort and the single cell dataset. Results: Three significant regulators of disulfidptosis (NCKAP1, OXSM, and SLC3A2) were identified through differential expression analysis and machine learning. And a nomogram constructed based on these three regulators exhibited ideal efficiency in predicting early- and late-stage OA. Furthermore, based on the expression of three regulators, we identified two disulfidptosis-related subtypes of OA with different infiltration of immune cells and personalized expression level of immune checkpoints. Notably, the expression of the three regulators was demonstrated in a single-cell RNA profile and verified in the synovial tissue in our in-house cohort including 6 OA patients and 6 normal people. Finally, an efficient disulfidptosis-mediated diagnostic model was constructed for OA, with the AUC value of 97.6923% in the training set and 93.3333% and 100% in two validation sets. Conclusion: Overall, with regard to PPPM, this study provided novel insights into the role of disulfidptosis regulators in the personalized diagnosis and treatment of OA.

7.
PLoS One ; 19(6): e0305903, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913698

RESUMO

BACKGROUND: Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion (QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification. METHODS: The candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding "herb-compound-target" network of QFHXD. The protein-protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments. RESULTS: A total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1ß, STAT3, MMP-9, and TGF-ß1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-ß1/Smad2/3. CONCLUSIONS: QFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-ß1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.


Assuntos
Medicamentos de Ervas Chinesas , Farmacologia em Rede , Mapas de Interação de Proteínas , Fibrose Pulmonar , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Ratos , Masculino , Mapas de Interação de Proteínas/efeitos dos fármacos , Bleomicina , Fator de Crescimento Transformador beta1/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Humanos , COVID-19/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Tratamento Farmacológico da COVID-19
8.
Cancer Med ; 13(10): e7303, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38800967

RESUMO

Osteosarcoma (OS) is a prevalent bone solid malignancy that primarily affects adolescents, particularly boys aged 14-19. This aggressive form of cancer often leads to deadly lung cancer due to its high migration ability. Experimental evidence suggests that programmed cell death (PCD) plays a crucial role in the development of osteosarcoma. Various forms of PCD, including apoptosis, ferroptosis, autophagy, necroptosis, and pyroptosis, contribute significantly to the progression of osteosarcoma. Additionally, different signaling pathways such as STAT3/c-Myc signal pathway, JNK signl pathway, PI3k/AKT/mTOR signal pathway, WNT/ß-catenin signal pathway, and RhoA signal pathway can influence the development of osteosarcoma by regulating PCD in osteosarcoma cell. Therefore, targeting PCD and the associated signaling pathways could offer a promising therapeutic approach for treating osteosarcoma.


Assuntos
Apoptose , Neoplasias Ósseas , Osteossarcoma , Transdução de Sinais , Osteossarcoma/patologia , Osteossarcoma/terapia , Osteossarcoma/metabolismo , Humanos , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Neoplasias Ósseas/metabolismo , Autofagia , Ferroptose , Necroptose , Animais
9.
Exp Gerontol ; 192: 112460, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772192

RESUMO

OBJECTIVE: Knee Osteoarthritis (KOA) is a debilitating degenerative joint ailment afflicting millions of patients. Numerous studies have assessed the efficacy of mesenchymal stem cells (MSCs) derived from various sources for KOA treatment, yet direct comparisons are scarce and inconsistent. Furthermore, network meta-analysis (NMA) conclusions require updating, while the safety of MSCs therapy remains contentious. This study evaluates therapeutic approaches involving MSCs from different sources in patients with KOA through randomized controlled trials (RCTs) and cohort studies. The objective is to compare the effectiveness and safety of MSCs strategies from various sources for KOA treatment. METHODS: A systematic literature review was conducted to identify RCTs and cohort studies comparing different sources of MSCs in KOA patients. A randomized effects network meta-analysis was used to concurrently evaluate both direct and indirect comparisons across all protocols. RESULTS: The NMA included 16 RCTS and reported 1005 participants. Adipose-derived mesenchymal stem cells (AD-MSCs) were the most effective treatment, showing significant improvements in the Visual Analogue Scale (VAS), the Short Form 36 (SF-36 scale), the International Knee Literature Committee Knee Evaluation Scale (IKDC subjective scores), and the Knee Injury and OA Outcome Score (KOOS). The probabilities are P = 85.3, P = 70.5, P = 88 and P = 87, respectively. Compared with placebo, AD-MSCs resulted in a VAS Score (SMD 0.97; 95%CI 0.37, 1.57), IKDC subjective scores (SMD -0.71; 95%CI -1.20, -0.21) was significantly reduced. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) showed significant improvements in the University of Western Ontario and McMaster University OA (WOMAC) (P = 91.4). Compared with placebo, UC-MSCs had a higher WOMAC Score (SMD 1.65; 95%CI 0.27, 3.03) and ranked first. Compared with MSCs, placebo emerged as the safer option (P = 74.9), with a notable reduction in AEs associated with HA treatment (RR 0.77; 95%CI 0.61, 0.97). AD-MSCs were found to have the least favorable impact on AEs with a probability of P = 13.3. CONCLUSIONS: This network meta-analysis established that MSCs offer pain relief and enhance various knee scores in KOA patients compared to conventional treatment. It also identifies other therapeutic avenues warranting further exploration through high-quality studies. Nonetheless, it underscores the necessity to emphasize the potential complications and safety concerns associated with MSCs.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Metanálise em Rede , Osteoartrite do Joelho , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite do Joelho/terapia , Resultado do Tratamento
10.
Nutrients ; 16(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794748

RESUMO

The high prevalence of constipation after fracture surgery brings intolerable discomfort to patients on the one hand, and affects post-surgery nutrient absorption on the other hand, resulting in poor prognosis. Given the acknowledged probiotic properties of Lactobacillus rhamnosus, 100 fracture patients with post-surgery constipation were centrally enrolled and administered orally with L. rhamnosus JYLR-127 to assess the efficacy of probiotic-adjuvant therapy in alleviating post-fracture constipation symptoms. The results showed that L. rhamnosus JYLR-127 improved fecal properties, promoted gastrointestinal recovery, and relieved constipation symptoms, which were mainly achieved by elevating Firmicutes (p < 0.01) and descending Bacteroidetes (p < 0.001), hence remodeling the disrupted intestinal microecology. In addition, blood routine presented a decrease in C-reactive protein levels (p < 0.05) and an increase in platelet counts (p < 0.05) after probiotic supplementation, prompting the feasibility of L. rhamnosus JYLR-127 in anti-inflammation, anti-infection and hemorrhagic tendency prevention after fracture surgery. Our study to apply probiotics in ameliorating constipation after fracture surgery is expected to bless the bothered patients, and provide broader application scenarios for L. rhamnosus preparations.


Assuntos
Constipação Intestinal , Fraturas Ósseas , Lacticaseibacillus rhamnosus , Complicações Pós-Operatórias , Probióticos , Humanos , Constipação Intestinal/terapia , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Método Simples-Cego , Fraturas Ósseas/cirurgia , Fraturas Ósseas/complicações , Adulto , Microbioma Gastrointestinal , Fezes/microbiologia , Idoso , Resultado do Tratamento
11.
World J Gastrointest Oncol ; 16(4): 1180-1191, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660654

RESUMO

Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

12.
Sci Rep ; 14(1): 9496, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664484

RESUMO

Disposable bamboo chopsticks (DBCs) are difficult to recycle, which inevitably cause secondary pollution. Based on energy and environmental issues, we propose a facile strategy to fabricate floatable photocatalyst (fPC) coated onto DBCs, which can be flexibly used in water purification. The photocatalyst of titania and titanium carbide on bamboo (TiO2/TiC@b) was successfully constructed from TiC-Ti powders and DBCs using a coating technique followed heat treatment in carbon powder, and the fPC exhibited excellent photocatalytic activity under visible light irradation. The analysis results indicate that rutile TiO2 forms on TiC during heat treatment, achieving a low-density material with an average value of approximately 0.5233 g/cm3. The coatings of TiO2/TiC on the bamboo are firm and uniform, with a particle size of about 20-50 nm. XPS results show that a large amount of oxygen vacancies is generated, due to the reaction atmosphere of more carbon and less oxygen, further favoring to narrowing the band gap of TiO2. Furthermore, TiO2 formed on residual TiC would induce the formation of a heterojunction, which effectively inhibits the photogenerated electron-hole recombination via the charge transfer effect. Notably, the degradation of dye Rhodamine B (Rh.B) is 62.4% within 3 h, while a previous adsorption of 36.0% for 1 h. The excellent photocatalytic performance of TiO2/TiC@b can be attributed to the enhanced reaction at the water/air interface due to the reduced light loss in water, improved visible-light response, increased accessible area and charge transfer effect. Our findings show that the proposed strategy achieves a simple, low-cost, and mass-producible method to fabricate fPC onto the used DBCs, which is expected to applied in multiple fields, especially in waste recycling and water treatment.

13.
Int J Mol Sci ; 25(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38674003

RESUMO

A novel photocatalytic nanomaterial, Ho2YSbO7, was successfully synthesized for the first time using the solvothermal synthesis technique. In addition, a Ho2YSbO7/Bi2MoO6 heterojunction photocatalyst (HBHP) was prepared via the hydrothermal fabrication technique. Extensive characterizations of the synthesized samples were conducted using various instruments, such as an X-ray diffractometer, a Fourier transform infrared spectrometer, a Raman spectrometer, a UV-visible spectrophotometer, an X-ray photoelectron spectrometer, and a transmission electron microscope, as well as X-ray energy dispersive spectroscopy, photoluminescence spectroscopy, a photocurrent test, electrochemical impedance spectroscopy, ultraviolet photoelectron spectroscopy, and electron paramagnetic resonance. The photocatalytic activity of the HBHP was evaluated for the degradation of diuron (DRN) and the mineralization of total organic carbon (TOC) under visible light exposure for 152 min. Remarkable removal efficiencies were achieved, with 99.78% for DRN and 97.19% for TOC. Comparative analysis demonstrated that the HBHP exhibited markedly higher removal efficiencies for DRN compared to Ho2YSbO7, Bi2MoO6, or N-doped TiO2 photocatalyst, with removal efficiencies 1.13 times, 1.21 times, or 2.95 times higher, respectively. Similarly, the HBHP demonstrated significantly higher removal efficiencies for TOC compared to Ho2YSbO7, Bi2MoO6, or N-doped TiO2 photocatalyst, with removal efficiencies 1.17 times, 1.25 times, or 3.39 times higher, respectively. Furthermore, the HBHP demonstrated excellent stability and reusability. The mechanisms which could enhance the photocatalytic activity remarkably and the involvement of the major active species were comprehensively discussed, with superoxide radicals identified as the primary active species, followed by hydroxyl radicals and holes. The results of this study contribute to the advancement of efficient heterostructural materials and offer valuable insights into the development of sustainable remediation strategies for addressing DRN contamination.


Assuntos
Bismuto , Diurona , Luz , Molibdênio , Fotólise , Bismuto/química , Catálise , Molibdênio/química , Diurona/química , Poluentes Químicos da Água/química
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 72-81, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38433635

RESUMO

Circular RNAs(CircRNAs)are a class of non-coding RNAs with a covalently closed-loop structure,high stability,and tissue specificity,with the production mechanisms different from linear RNAs.Recent studies have discovered that some CircRNAs can encode proteins via cap-independent translation mechanisms such as internal ribosome entry site,N6-methyladenosine,and rolling loop translation.The encoded proteins regulate homologous linear proteins or downstream signaling pathways via protein bait or other mechanisms,thereby exerting biological functions.Studies have shown that CircRNAs play a role in various diseases,especially in tumor progression,proliferation,invasion,and metastasis and immune regulation.Therefore,by elucidating the expression and roles of proteins encoded by CircRNAs in tumorigenesis and development,this paper is expected to provide new tumor markers and potential targets for tumor diagnosis and treatment.


Assuntos
Neoplasias Gastrointestinais , RNA Circular , Humanos , Neoplasias Gastrointestinais/genética , Adenosina , Biomarcadores Tumorais
15.
J Biol Chem ; 300(4): 107208, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38521502

RESUMO

Transforming growth factor-ß (TGF-ß) and Hippo signaling are two critical pathways engaged in cancer progression by regulating both oncogenes and tumor suppressors, yet how the two pathways coordinately exert their functions in the development of hepatocellular carcinoma (HCC) remains elusive. In this study, we firstly conducted an integrated analysis of public liver cancer databases and our experimental TGF-ß target genes, identifying CYR61 as a pivotal candidate gene relating to HCC development. The expression of CYR61 is downregulated in clinical HCC tissues and cell lines than that in the normal counterparts. Evidence revealed that CYR61 is a direct target gene of TGF-ß in liver cancer cells. In addition, TGF-ß-stimulated Smad2/3 and the Hippo pathway downstream effectors YAP and TEAD4 can form a protein complex on the promoter of CYR61, thereby activating the promoter activity and stimulating CYR61 gene transcription in a collaborative manner. Functionally, depletion of CYR61 enhanced TGF-ß- or YAP-mediated growth and migration of liver cancer cells. Consistently, ectopic expression of CYR61 was capable of impeding TGF-ß- or YAP-induced malignant transformation of HCC cells in vitro and attenuating HCC xenograft growth in nude mice. Finally, transcriptomic analysis indicates that CYR61 can elicit an antitumor program in liver cancer cells. Together, these results add new evidence for the crosstalk between TGF-ß and Hippo signaling and unveil an important tumor suppressor function of CYR61 in liver cancer.


Assuntos
Carcinoma Hepatocelular , Proteína Rica em Cisteína 61 , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Fator de Crescimento Transformador beta , Proteínas de Sinalização YAP , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular , Proteína Rica em Cisteína 61/metabolismo , Proteína Rica em Cisteína 61/genética , Mineração de Dados , Regulação Neoplásica da Expressão Gênica/genética , Via de Sinalização Hippo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Camundongos Nus , Regiões Promotoras Genéticas , Transdução de Sinais/genética , Proteína Smad2/metabolismo , Proteína Smad2/genética , Proteína Smad3/metabolismo , Proteína Smad3/genética , Fatores de Transcrição de Domínio TEA/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Regulação para Cima , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética
18.
Micromachines (Basel) ; 15(3)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38542595

RESUMO

A challenge remains in achieving adequate surface roughness of SLM fabricated interior channels, which is crucial for fuel delivery in the space industry. This study investigated the surface roughness of interior fine flow channels (1 mm diameter) embedded in SLM fabricated TC4 alloy space components. A machine learning approach identified layer thickness as a significant factor affecting interior channel surface roughness, with an importance score of 1.184, followed by scan speed and laser power with scores of 0.758 and 0.512, respectively. The roughness resulted from thin layer thickness of 20 µm, predominantly formed through powder adherence, while from thicker layer of 50 µm, the roughness was mainly due to the stair step effect. Slow scan speeds increased melt pools solidification time at roof overhangs, causing molten metal to sag under gravity. Higher laser power increased melt pools temperature and led to dross formation at roof overhangs. Smaller hatch spaces increased roughness due to overlapping of melt tracks, while larger hatch spaces reduced surface roughness but led to decreased part density. The surface roughness was recorded at 34 µm for roof areas and 26.15 µm for floor areas. These findings contribute to potential adoption of TC4 alloy components in the space industry.

19.
PLoS One ; 19(1): e0295311, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38206913

RESUMO

Moderate rising of house prices are beneficial to the economic development. However, over high house prices worsen the economic distortions and thus hinder the development of the real economy. We use the stochastic frontier models to calculate the fundamental value in the housing in Chinese large and medium cities, and then obtain indexes which could measure the house prices' deviations from the fundamental value. With the macroeconomic data in the city-level, this paper empirically investigates the effects of the house prices' deviations on macro-economic variables like consumption, investment and output. The study reveals that the housing bubble exists in most Chinese cities, and first-tier cities fare the worst. House prices over the fundamental value, which could increase the scale of real estate investment, bring adverse impacts on GDP, as it causes declining civilian consumption and discourages real economy's investment and production. The encouragement and the discouragement on macroeconomy caused by house prices' deviation from its basic value take turns to play a key role in the process of China' eco-nomic growth. In the early stage of China's economic growth, the encouragement effect predominates. As urbanization and industrialization gradually upgrade to a higher level, the discouragement effect takes charge.


Assuntos
Habitação , Urbanização , Cidades , China , Investimentos em Saúde , Desenvolvimento Econômico
20.
Neurologist ; 29(4): 233-237, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38251319

RESUMO

OBJECTIVE: To study the correlation between risk factors, degree of vascular restenosis, and inflammatory factors after interventional treatment for stroke. METHODS: The clinical data of 96 stroke patients who received interventional therapy in our hospital from April 2020 to June 2021 were selected for retrospective study, and the postoperative follow-up was 1 year. Univariate and multivariate regression were used to analyze identified factors associated with interventional stroke efficacy. At the same time, the value of inflammatory factor levels in predicting vascular restenosis after interventional stroke was analyzed. RESULTS: According to our findings, several risk factors, including body mass index ≥ 25.51 kg/m 2 , smoking, drinking, hypertension, and diabetes, were identified as contributors to poor postoperative efficacy following stroke intervention ( P <0.05). Furthermore, a notable association was observed between the severity of vascular stenosis ( P <0.001) and the levels of interleukin 6, interleukin 2, TNF-α, and C-reactive protein. The combined assessment of these serum inflammatory factors exhibited excellent predictive capability for postoperative vascular restenosis and stenosis severity, yielding a sensitivity of 84.30%, a specificity of 81.20%, and an area under the curve of 0.882. CONCLUSIONS: Obesity, smoking, alcohol consumption, hypertension, and diabetes have been found to be associated with suboptimal outcomes following interventional treatment for stroke. The assessment of preoperative levels of inflammatory factors holds promise in predicting the likelihood of postoperative restenosis to a certain degree.


Assuntos
Acidente Vascular Cerebral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão/complicações , Inflamação/sangue , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Acidente Vascular Cerebral/etiologia
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