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1.
Sci Rep ; 14(1): 12234, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38806556

ABSTRACT

Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and development. However, the expression of P4Hs in head and neck cancer (HNSC) as well as its relationship with prognosis and tumor immunity infiltration has not yet been analyzed. We investigated the transcriptional expression, survival data, and immune infiltration of P4Hs in patients with HNSC from multiple databases. P4H1-3 expression was significantly higher in HNSC tumor tissues than in normal tissues. Moreover, P4HA1 and P4HA2 were associated with tumor stage, patient prognosis, and immune cell infiltration. P4HA3 was related to patient prognosis and immune cell infiltration. Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes.


Subject(s)
Biomarkers, Tumor , Head and Neck Neoplasms , Immunotherapy , Procollagen-Proline Dioxygenase , Humans , Biomarkers, Tumor/metabolism , Prognosis , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/diagnosis , Immunotherapy/methods , Procollagen-Proline Dioxygenase/metabolism , Procollagen-Proline Dioxygenase/genetics , Gene Expression Regulation, Neoplastic , Female , Male , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/mortality
2.
Sci Adv ; 10(16): eadl0263, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38640246

ABSTRACT

The in situ generation of H2O2 in cells in response to external stimulation has exceptional advantages in modulating intracellular Ca2+ dynamics, including high controllability and biological safety, but has been rarely explored. Here, we develop photocatalyst-based metal-organic frameworks (DCSA-MOFs) to modulate Ca2+ responses in cells, multicellular spheroids, and organs. By virtue of the efficient photocatalytic oxygen reduction to H2O2 without sacrificial agents, photoexcited DCSA-MOFs can rapidly trigger Ca2+ outflow from the endoplasmic reticulum with single-cell precision in a repeatable and controllable manner, enabling the propagation of intercellular Ca2+ waves (ICW) over long distances in two-dimensional and three-dimensional cell cultures. After photoexcitation, ICWs induced by DCSA-MOFs can activate neural activities in the optical tectum of tadpoles and thighs of spinal frogs, eliciting the corresponding motor behaviors. Our study offers a versatile optical nongenetic modulation technique that enables remote, repeatable, and controlled manipulation of cellular and animal behaviors.


Subject(s)
Calcium Signaling , Hydrogen Peroxide , Animals , Hydrogen Peroxide/metabolism , Gap Junctions/metabolism , Endoplasmic Reticulum , Behavior, Animal
3.
J Colloid Interface Sci ; 659: 31-39, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38157724

ABSTRACT

Rational construction of efficient carbon-supported rare earth cerium nanoclusters as oxygen reduction reaction (ORR) is of great significance to promote the practical application of zinc-air batteries (ZABs). Herein, N doped conductive carbon black anchored CeO2 nanoclusters (CeO2 Clusters/NC) for the ORR is reported. The volatile cerium species vaporized by CeO2 nanoclusters at high temperatures are captured by nitrogen-rich carbon carriers to form highly dispersed Ce-Nx active sites. Benefiting from the coupling effect between oxygen vacancies-enriched CeO2 nanoclusters and highly dispersed Ce-Nx sites, the prepared 2CeO2 Clusters/NC catalyst possesses an ORR half-wave potential of 0.88 V, superior electrochemical stability, and better methanol tolerance compared to commercial Pt/C catalysts. Moreover, the 2CeO2 Clusters/NC involved liquid ZABs show excellent energy efficiency, superior stability, and a high energy density of 982 Wh kg-1 at 10 mA cm-2.

4.
Cell Biosci ; 13(1): 226, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38102663

ABSTRACT

In multicellular organisms, regulatory cell death is a crucial aspect of growth and development. Ferroptosis, which was postulated roughly ten years ago, is a mode of cell death that differs from apoptosis, autophagy, and pyrodeath. This distinct pattern of cell death is triggered by an imbalance between oxidants and antioxidants and strongly associated with the metabolism of iron, lipids, amino acids, and glutathione. A growing body of research has implicated ferroptosis in the incidence and progression of many organ traumas and degenerative diseases. Recently, ferroptosis has gained attention as a crucial regulatory mechanism underlying the initiation and development of a variety of cardiovascular diseases, including myocardial ischemia/reperfusion injury, cardiomyopathy, arrhythmia, chemotherapy, and Corona Virus-2-induced cardiac injury. Pharmacological therapies that inhibit ferroptosis have great potential for the management of cardiovascular disorders. This review discusses the prevalence and regulatory mechanisms of ferroptosis, effect of ferroptosis on the immune system, significance of ferroptosis in cardiovascular diseases, and potential therapeutic value of regulating ferroptosis in a variety of heart diseases.

5.
Int J Mol Sci ; 24(17)2023 Sep 02.
Article in English | MEDLINE | ID: mdl-37686400

ABSTRACT

In the vertebrate brain, sensory experience plays a crucial role in shaping thalamocortical connections for visual processing. However, it is still not clear how visual experience influences tissue homeostasis and neurogenesis in the developing thalamus. Here, we reported that the majority of SOX2-positive cells in the thalamus are differentiated neurons that receive visual inputs as early as stage 47 Xenopus. Visual deprivation (VD) for 2 days shifts the neurogenic balance toward proliferation at the expense of differentiation, which is accompanied by a reduction in nuclear-accumulated ß-catenin in SOX2-positive neurons. The knockdown of ß-catenin decreases the expression of SOX2 and increases the number of progenitor cells. Coimmunoprecipitation studies reveal the evolutionary conservation of strong interactions between ß-catenin and SOX2. These findings indicate that ß-catenin interacts with SOX2 to maintain homeostatic neurogenesis during thalamus development.


Subject(s)
Biological Evolution , beta Catenin , Animals , Homeostasis , Thalamus , Xenopus laevis
6.
Int J Biol Sci ; 19(10): 2999-3014, 2023.
Article in English | MEDLINE | ID: mdl-37416765

ABSTRACT

Our previous studies have confirmed that transforming growth factor-ß (TGF-ß) plays an important role in tumor metastasis, and the serum deprivation protein response (SDPR) is a potential downstream target of TGF-ß. However, the role and mechanism of SDPR in gastric cancer are still unclear. We performed gene microarray, bioinformation analysis, combined with in vivo and in vitro experimental verification, we identified that SDPR is significantly downregulated in gastric cancer, and participates in TGF-ß-mediated tumour metastasis. Mechanically, SDPR interacts with extracellular signal-regulated kinase (ERK) and inhibits fatty acid metabolism key gene Carnitine palmitoyl transferase 1A (CPT1A) at transcriptional level by supressing ERK/PPAR pathway. Our findings suggest that the TGF-ß/SDPR/CPT1A axis play an important role in the fatty acid oxidation of gastric cancer, and provides a new insight into the crosstalk of tumour microenvironments and metabolism reprogramming and suggest that strategies to intervene the fatty acid metabolism may therapy gastric cancer metastasis.


Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/metabolism , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Cell Line, Tumor , Lipid Metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Fatty Acids/metabolism , Tumor Microenvironment
7.
Int J Mol Sci ; 24(12)2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37373466

ABSTRACT

Oligodendrocytes generate myelin sheaths vital for the formation, health, and function of the central nervous system. Mounting evidence suggests that receptor tyrosine kinases (RTKs) are crucial for oligodendrocyte differentiation and myelination in the CNS. It was recently reported that discoidin domain receptor 1 (Ddr1), a collagen-activated RTK, is expressed in oligodendrocyte lineage. However, its specific expression stage and functional role in oligodendrocyte development in the CNS remain to be determined. In this study, we report that Ddr1 is selectively upregulated in newly differentiated oligodendrocytes in the early postnatal CNS and regulates oligodendrocyte differentiation and myelination. Ddr1 knock-out mice of both sexes displayed compromised axonal myelination and apparent motor dysfunction. Ddr1 deficiency alerted the ERK pathway, but not the AKT pathway in the CNS. In addition, Ddr1 function is important for myelin repair after lysolecithin-induced demyelination. Taken together, the current study described, for the first time, the role of Ddr1 in myelin development and repair in the CNS, providing a novel molecule target for the treatment of demyelinating diseases.


Subject(s)
Discoidin Domain Receptor 1 , Myelin Sheath , Oligodendroglia , Animals , Female , Male , Mice , Cell Differentiation , Central Nervous System , Discoidin Domain Receptor 1/genetics , Discoidin Domain Receptor 1/metabolism , Mice, Knockout , Myelin Sheath/metabolism , Neurogenesis , Oligodendroglia/metabolism , Receptor Protein-Tyrosine Kinases/metabolism
8.
Front Endocrinol (Lausanne) ; 14: 1095604, 2023.
Article in English | MEDLINE | ID: mdl-37223020

ABSTRACT

Introduction: Zinc finger and SCAN domain-containing protein 18 (ZSCAN18) has been investigated as a putative biomarker of multiple human cancers. However, the expression profile, epigenetic modification, prognostic value, transcription regulation, and molecular mechanism of ZSCAN18 in breast cancer (BC) remain unknown. Methods: In the study, we present an integrated analysis of ZSCAN18 in BC based on public omics datasets with the use of multiple bioinformatics tools. Genes potentially regulated through restoration of ZSCAN18 expression in MDA-MB-231 cells were investigated to identify pathways associated with BC. Results: We observed that ZSCAN18 was downregulated in BC and mRNA expression was significantly correlated with clinicopathological parameters. Low expression of ZSCAN18 was found in the HER2-positive and TNBC subtypes. High expression of ZSCAN18 was associated with good prognosis. As compared to normal tissues, the extent of ZSCAN18 DNA methylation was greater with fewer genetic alterations in BC tissues. ZSCAN18 was identified as a transcription factor that might be involved in intracellular molecular and metabolic processes. Low ZSCAN18 expression was associated with the cell cycle and glycolysis signaling pathway. Overexpression of ZSCAN18 inhibited mRNA expression of genes associated with the Wnt/ß-catenin and glycolysis signaling pathways, including CTNNB1, BCL9, TSC1, and PFKP. ZSCAN18 expression was negatively correlated with infiltrating B cells and dendritic cells (DCs), as determined by the TIMER web server and reference to the TISIDB. ZSCAN18 DNA methylation was positively correlated with activated B cells, activated CD8+ and CD4+ T cells, macrophages, neutrophils, and activated DCs. Moreover, five ZSCAN18-related hub genes (KDM6B, KAT6A, KMT2D, KDM1A, and HSPBP1) were identified. ZSCAN18, ZNF396, and PGBD1 were identified as components of a physical complex. Conclusion: ZSCAN18 is a potential tumor suppressor in BC, as expression is modified by DNA methylation and associated with patient survival. In addition, ZSCAN18 plays important roles in transcription regulation, the glycolysis signaling pathway, and the tumor immune microenvironment.


Subject(s)
Breast Neoplasms , Zinc Fingers , Female , Humans , Adaptor Proteins, Signal Transducing , Biomarkers , Breast Neoplasms/genetics , DNA Methylation , Histone Acetyltransferases , Histone Demethylases , Jumonji Domain-Containing Histone Demethylases , RNA, Messenger , Tumor Microenvironment
9.
Cell Biosci ; 13(1): 86, 2023 May 13.
Article in English | MEDLINE | ID: mdl-37179344

ABSTRACT

Stress granules (SGs) are non-enveloped structures formed primarily via protein and RNA aggregation under various stress conditions, including hypoxia and viral infection, as well as oxidative, osmotic, and heat-shock stress. SGs assembly is a highly conserved cellular strategy to reduce stress-related damage and promote cell survival. At present, the composition and dynamics of SGs are well understood; however, data on the functions and related mechanisms of SGs are limited. In recent years, SGs have continued to attract attention as emerging players in cancer research. Intriguingly, SGs regulate the biological behavior of tumors by participating in various tumor-associated signaling pathways, including cell proliferation, apoptosis, invasion and metastasis, chemotherapy resistance, radiotherapy resistance, and immune escape. This review discusses the roles and mechanisms of SGs in tumors and suggests novel directions for cancer treatment.

10.
Molecules ; 28(7)2023 Apr 03.
Article in English | MEDLINE | ID: mdl-37049946

ABSTRACT

Ag/TiO2/muscovite (ATM) composites were prepared by the sol-gel method and the effects of Ag modification on the structure and photocatalytic performance were investigated. The photocatalysts were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller surface area (BET), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectra (FTIR), photoluminescence spectra (PL) and ultraviolet-visible diffuse reflectance spectra (DRS). The photocatalytic activity of the obtained composites was evaluated by taking 100 mL (10 mg/L) of Rhodamine B (RhB) aqueous solution as the target pollutant. The muscovite (Mus) loading releases the agglomeration of TiO2 particles and the specific surface area increases from 17.6 m2/g (pure TiO2) to 39.5 m2/g (TiO2/Mus). The first-order reaction rate constant increases from 0.0009 min-1 (pure TiO2) to 0.0074 min-1 (150%TiO2/Mus). Ag element exists in elemental silver. The specific surface area of 1-ATM further increases to 66.5 m2/g. Ag modification promotes the separation of photogenerated electrons and holes and increases the visible light absorption. 1%Ag-TiO2/Mus (1-ATM) exhibits the highest photocatalytic activity. After 100 min, the rhodamine B (RhB) degradation degrees of PT, 150%TiO2/Mus and 1-ATM are 10.4%, 48.6% and 90.6%, respectively. The first-order reaction rate constant of 1-ATM reaches 0.0225 min-1, which is 25 times higher than that of pure TiO2.

11.
Front Cell Neurosci ; 16: 988732, 2022.
Article in English | MEDLINE | ID: mdl-36212693

ABSTRACT

In the vertebrate brain, GABAergic cell development and neurotransmission are important for the establishment of neural circuits. Various intrinsic and extrinsic factors have been identified to affect GABAergic neurogenesis. However, little is known about the epigenetic control of GABAergic differentiation in the developing brain. Here, we report that the number of GABAergic neurons dynamically changes during the early tectal development in the Xenopus brain. The percentage of GABAergic neurons is relatively unchanged during the early stages from stage 40 to 46 but significantly decreased from stage 46 to 48 tadpoles. Interestingly, the histone acetylation of H3K9 is developmentally decreased from stage 42 to 48 (about 3.5 days). Chronic application of valproate acid (VPA), a broad-spectrum histone deacetylase (HDAC) inhibitor, at stage 46 for 48 h increases the acetylation of H3K9 and the number of GABAergic cells in the optic tectum. VPA treatment also reduces apoptotic cells. Electrophysiological recordings show that a VPA induces an increase in the frequency of mIPSCs and no changes in the amplitude. Behavioral studies reveal that VPA decreases swimming activity and visually guided avoidance behavior. These findings extend our understanding of histone modification in the GABAergic differentiation and neurotransmission during early brain development.

12.
Nat Prod Res ; : 1-9, 2022 Aug 19.
Article in English | MEDLINE | ID: mdl-35983797

ABSTRACT

Phytochemical investigations on the fruits of Cascabela thevetia (L.) Lippold led to obtain three new cardenolides (1-3) and five known analogues (4-7). Their structures were elucidated by means of UV, IR, HR-ESI-MS, 1D and 2D NMR spectroscopic data analysis. Compounds 1 and 2 represent the first examples of naturally occurring cardenolides with 19-nor-5(10)-ene group and α-l-3-demethyl-thevetose, respectively. Compound 3 is a rare C-nor-D-homocardenolide in nature. All isolated cardenolides (1-7) were evaluated for their cytotoxic activities against four human cancer cell lines (MCF-7, HCT-116, HeLa and HepG2), and the results indicated the compounds with sugar units (1, 2, 4, and 5) exhibited stronger cytotoxic activities with IC50 values ranging between 0.022 and 0.308 µM.

13.
Int J Mol Sci ; 23(15)2022 Jul 29.
Article in English | MEDLINE | ID: mdl-35955557

ABSTRACT

Photocatalytic degradation of harmful organic matter is a feasible and environmentally friendly method. Bi2WO6 has become a hotspot of photocatalysts because of its unique layered structure and visible light response. In the present study, Sn doping was adopted to modified Bi2WO6 by hydrothermal method. The Sn-doped Bi2WO6 photocatalysts were characterized by XRD, SEM, TEM, BET, XPS, PL, and DRS, respectively. The results show that Sn-doped Bi2WO6 shows three-dimensional (3D) flower-like morphology, which is composed of two-dimensional (2D) nanosheets. Sn4+ ions enter into the Bi2WO6 lattice, producing a degree of Bi2WO6 lattice distortion, which is in favor of reducing the recombination of photogenerated electrons and holes. Moreover, the specific surface area of Bi2WO6 is significantly increased after doping, which is beneficial to providing more active sites. The photocatalytic results show that 2%Sn-Bi2WO6 exhibits the highest photocatalytic activity. After 60 min of irradiation, the photocatalytic degradation degree of methylene blue (MB) increases from 80.6% for pure Bi2WO6 to 92.0% for 2%Sn-Bi2WO6. The first-order reaction rate constant of 2%Sn-Bi2WO6 is 0.030 min-1, which is 1.7 times than that of pure Bi2WO6.


Subject(s)
Bismuth , Tin , Bismuth/chemistry , Catalysis , Light , Tungsten Compounds
14.
Chem Biodivers ; 19(10): e202200648, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36043381

ABSTRACT

A series of novel D-ring fused or substituted steroidal N-heterocycles were synthesized, and their chemical structures were characterized by spectroscopic analysis. The anticancer activity of these compounds against four human cancer cell lines (MCF-7, H1299, HeLa and HepG2) were evaluated and the structure-activity relationship (SAR) was also investigated. Compound 3c displayed significant inhibitory activity on the four cancer cells with IC50 values ranging from 3.88 to 10.05 µM. Overall, these studies indicated that construction of N-heterocyclic system with D-ring substituted containing a double bond at C-16 and C-17 or D-ring fused with [17,16-d]azolo[1,5-a]pyrimidine could be a promising strategy to improve antitumor activity for steroids deserved further investigation.


Subject(s)
Antineoplastic Agents , Humans , Antineoplastic Agents/chemistry , Pyrimidines/chemistry , Steroids/pharmacology , Steroids/chemistry , Structure-Activity Relationship , HeLa Cells , Drug Screening Assays, Antitumor , Molecular Structure , Cell Proliferation , Cell Line, Tumor
15.
Front Immunol ; 13: 970879, 2022.
Article in English | MEDLINE | ID: mdl-36003386

ABSTRACT

Symptomatic colon metastasis from primary lung cancer is rare in clinical practice. We report the case of a 58-year-old patient with advanced lung adenocarcinoma who developed abdominal symptoms, including abdominal distention and difficulty defecating, after immunotherapy and chemotherapy. The patient was diagnosed with lung adenocarcinoma, and systemic positron emission tomography-computed tomography confirmed multiple lymph node, pleural, and adrenal metastases. Molecular detection indicated BRAF V600E mutation and high programmed death-ligand 1 (PD-L1) expression. After first-line anti-programmed cell death protein 1 immunotherapy combined with chemotherapy, the nodes in the chest remarkably diminished. However, it was followed by colon obstruction, incomplete ileus, and bone metastasis. Endoscopic histological examination confirmed adenocarcinoma but could not identify primary or secondary tumors due to insufficient tissue. We performed colon resection to remove the obstruction, and postoperative tissue pathological microscopy confirmed metastasis from the lung adenocarcinoma. We corroborated the BRAF V600E mutation and high PD-L1 expression and supported the molecular features of lung adenocarcinoma. During hospitalization, the patient presented with unbearable pain in the bone metastases, and palliative radiotherapy was administered. Then, the patient received dabrafenib plus trametinib as the second-line therapy. This report discusses the clinical characteristics, pathology, imaging, molecular profile assessments, and treatment of primary lung adenocarcinoma with colon metastasis.


Subject(s)
Adenocarcinoma of Lung , Colonic Neoplasms , Lung Neoplasms , Rectal Neoplasms , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B7-H1 Antigen/genetics , Colonic Neoplasms/drug therapy , Colonic Neoplasms/therapy , Humans , Imidazoles/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/therapy , Middle Aged , Mutation , Oximes/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Pyridones/therapeutic use , Pyrimidinones/therapeutic use , Rectal Neoplasms/drug therapy
16.
Article in English | MEDLINE | ID: mdl-35805568

ABSTRACT

The Qinghai-Tibet Plateau (QTP) is a sensor of global climate change and regional human activities, and drought monitoring will help to achieve its ecological protection and sustainable development. In order to effectively control the geospatial scale effect, we divided the study area into eight geomorphological sub-regions, and calculated the Temperature-Vegetation Drought Index (TVDI) of each geomorphological sub-region based on MODIS Normalized Difference Vegetation Index (NDVI) and Land Surface Temperature (LST) data, and synthesized the TVDI of the whole region. We employed partial and multiple correlation analyses to identify the relationship between TVDI and temperature and precipitation. The random forest model was further used to study the driving mechanism of TVDI in each geomorphological division. The results of the study were as follows: (1) From 2000 to 2019, the QTP showed a drought trend, with the most significant drought trend in the central region. The spatial pattern of TVDI changes of QTP was consistent with the gradient changes of precipitation and temperature, both showing a gradual trend from southeast to northwest. (2) There was a risk of drought in the four seasons of the QTP, and the seasonal variation of TVDI was significant, which was characterized by being relatively dry in spring and summer and relatively humid in autumn and winter. (3) Drought in the QTP was mainly driven by natural factors, supplemented by human factors. The driving effect of temperature and precipitation factors on TVDI was stable and significant, which mainly determined the spatial distribution and variation of TVDI of the QTP. Geomorphological factors led to regional intensification and local differentiation effects of drought, especially in high mountains, flat slopes, sunny slopes and other places, which had a more significant impact on TVDI. Human activities had local point-like and linear impacts, and grass-land and cultivated land that were closely related to the relatively high impacts on TVDI of human grazing and farming activities. In view of the spatial-temporal patterns of change in TVDI in the study area, it is important to strengthen the monitoring and early warning of changes in natural factors, optimize the spatial distribution of human activities, and scientifically promote ecological protection and restoration.


Subject(s)
Climate Change , Environmental Monitoring , China , Droughts , Ecosystem , Environmental Monitoring/methods , Humans , Seasons , Temperature , Tibet
17.
Cancer Med ; 11(16): 3035-3047, 2022 08.
Article in English | MEDLINE | ID: mdl-35546443

ABSTRACT

BACKGROUND: The prognostic significance of insulin-like growth factor binding protein 2 (IGFBP2) expression has been explored in plenty of studies in human cancers. Because of the controversial results, the meta-analysis was carried out to evaluate the relevance of IGFBP2 expression with the prognosis in various tumors. METHODS: The data searched from four databases (Pubmed, Embase, Cochrane library, and Web of science) was used to calculate pooled hazard ratios (HRs) in this meta-analysis. Subgroup analyses were stratified by ethnicity, cancer type, publication year, Newcastle-Ottawa Scale score, treatments, and populations. RESULTS: Twenty-one studies containing 5560 patients finally met inclusion criteria. IGFBP2 expression was associated with lower overall survival (HR = 1.57, 95% CI = 1.31-1.88) and progression-free survival (HR = 1.18, 95% CI = 1.04-1.34) in cancer patients, but not with disease-free survival (HR = 1.50, 95% CI = 0.91-2.46) or recurrence-free survival (HR = 1.50, 95% CI = 0.93-2.40). The subgroup analyses indicated IGFBP2 overexpression was significantly correlated with overall survival in Asian patients (HR = 1.42, 95% CI = 1.18-1.72), Caucasian patients (HR = 2.20, 95% CI = 1.31-3.70), glioma (HR = 1.36, 95% CI = 1.03-1.79), and colorectal cancer (HR = 2.52, 95% CI = 1.43-4.44) and surgery subgroups (HR = 1.97, 95% CI = 1.50-2.58). CONCLUSION: The meta-analysis showed that IGFBP2 expression was associated with worse prognosis in several tumors, and may serve as a potential prognostic biomarker in cancer patients.


Subject(s)
Insulin-Like Growth Factor Binding Protein 2 , Neoplasms , Disease-Free Survival , Humans , Insulin-Like Growth Factor Binding Protein 2/genetics , Neoplasms/diagnosis , Neoplasms/pathology , Prognosis , Proportional Hazards Models
18.
Article in English | MEDLINE | ID: mdl-35328915

ABSTRACT

Multitemporal geohazard susceptibility analysis can not only provide reliable results but can also help identify the differences in the mechanisms of different elements under different temporal and spatial backgrounds, so as to better accurately prevent and control geohazards. Here, we studied the 12 counties (cities) that were severely affected by the Wenchuan earthquake of 12 May 2008. Our study was divided into four time periods: 2008, 2009-2012, 2013, and 2014-2017. Common geohazards in the study area, such as landslides, collapses and debris flows, were taken into account. We constructed a geohazard susceptibility index evaluation system that included topography, geology, land cover, meteorology, hydrology, and human activities. Then we used a random forest model to study the changes in geohazard susceptibility during the Wenchuan earthquake, the following ten years, and its driving mechanisms. We had four main findings. (1) The susceptibility of geohazards from 2008 to 2017 gradually increased and their spatial distribution was significantly correlated with the main faults and rivers. (2) The Yingxiu-Beichuan Fault, the western section of the Jiangyou-Dujiangyan Fault, and the Minjiang and Fujiang rivers were highly susceptible to geohazards, and changes in geohazard susceptibility mainly occurred along the Pingwu-Qingchuan Fault, the eastern section of the Jiangyou-Dujiangyan Fault, and the riparian areas of the Mianyuan River, Zagunao River, Tongkou River, Baicao River, and other secondary rivers. (3) The relative contribution of topographic factors to geohazards in the four different periods was stable, geological factors slowly decreased, and meteorological and hydrological factors increased. In addition, the impact of land cover in 2008 was more significant than during other periods, and the impact of human activities had an upward trend from 2008 to 2017. (4) Elevation and slope had significant topographical effects, coupled with the geological environmental effects of engineering rock groups and faults, and river-derived effects, which resulted in a spatial aggregation of geohazard susceptibility. We attributed the dynamic changes in the areas that were highly susceptible to geohazards around the faults and rivers to the changes in the intensity of earthquakes and precipitation in different periods.


Subject(s)
Earthquakes , Landslides , China , Geology , Humans , Hydrology , Rivers
20.
Autophagy ; 17(12): 4083-4101, 2021 12.
Article in English | MEDLINE | ID: mdl-33764843

ABSTRACT

Chemotherapy is currently the main treatment for unresectable or advanced postoperative gastric cancers. However, its efficacy is negatively affected by the occurrence of chemoresistance, which severely affects patient prognosis. Recently, dysregulation in autophagy has been suggested as a potential mechanism for chemoresistence, and long noncoding RNA (lncRNA) also shows its regulatory role in cancer drug resistance. Using RNA sequencing, we found that lncRNA EIF3J-DT was highly expressed in drug-resistant gastric cancer cells. In-vitro and in-vivo experiments showed that EIF3J-DT activated autophagy and induced drug resistance in gastric cancer cells by targeting ATG14. Bioinformatics and experimental results showed that EIF3J-DT regulated the expression of ATG14 through direct binding to enhance stabilization of ATG14 mRNA and via blocking the degradation of ATG14 mRNA through competitively binding with microRNA (miRNA) MIR188-3p. Therefore, EIF3J-DT increased the expression of ATG14, contributing to activation of autophagy and chemoresistance. Furthermore, it was confirmed that EIF3J-DT and ATG14 were highly expressed in gastric cancer patients resistant to chemotherapy, and this was closely associated with patient prognosis. In conclusion, EIF3J-DT is involved in the regulation of autophagy and chemoresistance in gastric cancer cells by targeting ATG14. It may be a suitable new target for enhancing chemosensitivity and improving prognosis.Abbreviations: 3-MA: 3-methyladenine; 5-Fu: 5-fluorouracil; ATG: autophagy related; C-CASP3: cleaved caspase 3; C-CASP7: cleaved caspase 7; C-PARP: cleaved PARP; CQ: chloroquine; CR: complete response; DIG: digoxigenin; ESR1: estrogen receptor 1; FBS: fetal bovine serum; FISH: fluorescence in situ hybridization; IHC: immunohistochemistry; ISH: in situ hybridization; lncRNA: long noncoding RNA; miRNA: microRNA; MUT: mutant; NC: negative control; OXA: oxaliplatin; PBS: phosphate-buffered saline; PD: progressive disease; PFA: paraformaldehyde; PR: partial response; qPCR: quantitative polymerase chain reaction; RAPA: rapamycin; SD: stable disease; TEM: transmission electron microscopy; WT: wild type.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Stomach Neoplasms , Autophagy/genetics , Cell Line, Tumor , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Humans , In Situ Hybridization, Fluorescence , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics
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