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Ultrasound (US)-mediated piezocatalytic tumor therapy has attracted much attention due to its notable tissue-penetration capabilities, noninvasiveness, and low oxygen dependency. Nevertheless, the efficiency of piezocatalytic therapy is limited due to an inadequate piezoelectric response, low separation of electron-hole (e--h+) pairs, and complex tumor microenvironment (TME). Herein, an ultrathin two-dimensional (2D) sulfur-vacancy-engineered (Sv-engineered) Cu@SnS2-x nanosheet (NS) with an enhanced piezoelectric effect was constructed via the heterovalent substitution strategy of Sn4+ by Cu2+. The introduction of Cu2+ ion not only causes changes in the crystal structure to increase polarization but also generates rich Sv to decrease band gap from 2.16 to 1.62 eV and inhibit e--h+ pairs recombination, collectively leading to the highly efficient generation of reactive oxygen species under US irradiation. Moreover, Cu@SnS2-x shows US-enhanced TME-responsive Fenton-like catalytic activity and glutathione depletion ability, further aggravating the oxidative stress. Both in vitro and in vivo results prove that the Sv-engineered Cu@SnS2-x NSs can significantly kill tumor cells and achieve high-efficiency piezocatalytic tumor therapy in a biocompatible manner. Overall, this study provides a new avenue for sonocatalytic therapy and broadens the application of 2D piezoelectric materials.
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Cobre , Nanoestruturas , Enxofre , Cobre/química , Enxofre/química , Humanos , Camundongos , Animais , Nanoestruturas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sulfetos/química , Microambiente Tumoral/efeitos dos fármacos , Compostos de Estanho/química , Catálise , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/tratamento farmacológico , Terapia por Ultrassom , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Pitch-derived carbon (PC) anode features the merits of low-cost, rich edge-defect sites, and tunable crystallization degree for potassium ion batteries (PIBs). However, gaining the PC anode with both rich edge-defect sites and robust structure remains challenging. Herein, micro-sized and robust PC/expanded-graphite (EG) composites (EGC) with rich edge-defect sites are massively synthesized via melting impregnation and confined pyrolysis. The PC is in situ encapsulated in micro-sized EG skeleton with robust chemical bonds between PC and EG after thermal treatment, endowing the structural stability as micro-sized carbon-carbon composites. The confinement effect originating from EG skeleton could suppress the crystallization degree of the PC and contribute rich edge-defect sites in EGC composites. Additionally, the EG skeleton inside EGC could form continuous electronic conduction nets and establish low-tortuosity carbonaceous electrodes, facilitating rapid electron/ion migration. While applied in PIBs, the EGC anode delivers a reversible capacity that up to 338.5 mAh g-1 at 0.1 A g-1 , superior rate performance of 127.5 mAh g-1 at 5.0 A g-1 , and long-term stability with 204.8 mAh g-1 retain after 700 cycles at 1.0 A g-1 . This novel strategy highlights an interesting category of heterogeneous carbon-carbon composite materials to keep pace with the demand for the future PIBs industry.
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BACKGROUND AND AIMS: Sarcopenia is associated with poor prognosis, but its role in older patients with intrahepatic cholangiocarcinoma (ICC) is unclear. We aimed to evaluate the impact of sarcopenia on the prognosis of older patients with ICC undergoing hepatectomy. METHODS: A total of 363 patients with ICC following hepatectomy from 2015 to 2021 were retrospectively reviewed at five institutions. Sarcopenia was evaluated using skeletal muscle index by computed tomography images. Patients were divided into four subgroups according to sarcopenia and age. Postoperative outcomes including complication, overall survival (OS) and recurrence-free survival (RFS) were evaluated. Risk factors were identified through univariate and multivariate Cox regression analyses. RESULTS: 302 patients were included in the analysis. The median age was 63 years and there were 128 patients (42.4%) aged over 65 years. 192 patients (63.6%) were diagnosed with sarcopenia, while 180 patients (59.6%) experienced myosteatosis. Older patients experienced a higher incidence of sarcopenia and myosteatosis, and worse postoperative outcomes than younger patients. In the subgroup of patients with sarcopenia, older patients experienced a significant shorter OS than younger patients, which was not observed in patients without sarcopenia. According to the multivariate Cox regression analysis, lymphatic metastasis (p < .001), blood transfusion (p = .004), low serum albumin (p = .051), sarcopenia (p = .024), and myosteatosis (p = .004) were identified as independent risk factors of OS in older patients, meanwhile tumour size (p = .013) and lymphatic metastasis (p < .001) were independent risk factors of RFS. CONCLUSIONS: Sarcopenia and myosteatosis have a significant adverse impact on postoperative outcomes in older patients with ICC undergoing hepatectomy.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Sarcopenia , Humanos , Idoso , Pessoa de Meia-Idade , Hepatectomia/efeitos adversos , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Estudos Retrospectivos , Metástase Linfática/patologia , Colangiocarcinoma/patologia , Prognóstico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologiaRESUMO
BACKGROUND: The shortage of water resources and the increase of greenhouse gas emissions from soil seriously restrict the sustainable development of agriculture. Under the premise of ensuring a stable yield of winter wheat through a reasonable irrigation scenario, identifying a suitable straw returning method will have a positive effect on agricultural carbon sequestration and emission reduction in North China Plain. RESULTS: Straw burying (SR) and straw mulching (SM) were adopted based on traditional tillage under in the winter wheat growing season of 2020-2021 and 2021-2022. Three irrigation scenarios were used for each straw returning method: no irrigation (I0), irrigation 60 mm at jointing stage (I1), and irrigation of 60 mm each at the jointing and heading stages (I2). Soil moisture, soil respiration rate, cumulative soil CO2 emissions, yield, water use efficiency (WUE) and soil CO2 emission efficiency (CEE) were mainly studied. The results showed that, compared to SM, SR improved the utilization of soil water and enhanced soil carbon sequestration. SR reduced soil respiration rate and cumulative soil CO2 emissions in two winter wheat growing seasons, and increased yield by increasing spike numbers. In addition, with an increase in the amount of irrigation, soil CO2 emissions and yield increased. Under SR-I1 treatment, WUE and CEE were the highest. SR-I1 increases crop yields at the same time as reducing soil CO2 emissions. CONCLUSION: The combination of SR and irrigation 60 mm at jointing stage is a suitable straw returning irrigation scenario, which can improve water use and reduce soil CO2 emission in NCP. © 2023 Society of Chemical Industry.
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Solo , Triticum , Estações do Ano , Dióxido de Carbono/análise , Água , Carbono , Agricultura/métodos , ChinaRESUMO
Nowadays, Fenton chemistry-based chemodynamic therapy (CDT) is an emerging approach to killing tumor cells by converting endogenous H2 O2 into cytotoxic hydroxyl radicals (·OH). However, the elimination of ·OH by intracellular overexpressed glutathione (GSH) results in unsatisfactory antitumor efficiency. In addition, the single mode of consuming GSH and undesirable drug loading efficiency cannot guarantee the efficient cancer cells killing effect. Herein, a simple one-step strategy for the construction of Fe3+ -naphthazarin metal-phenolic networks (FNP MPNs) with ultrahigh loading capacity, followed by the modification of NH2 -PEG-NH2 , is developed. The carrier-free FNP MPNs can be triggered by acid and GSH, and rapidly release naphthazarin and Fe3+ , which is further reduced to Fe2+ that exerts Fenton catalytic activity to produce abundant ·OH. Meanwhile, the Michael addition between naphthazarin and GSH can lead to GSH depletion and thus achieve tumor microenvironment (TME)-triggered enhanced CDT, followed by activating ferroptosis and apoptosis. In addition, the reduced Fe2+ as a T1 -weighted contrast agent endows the FNP MPNs with magnetic resonance imaging (MRI) functionality. Overall, this work is the debut of naphthazarin as ligands to fabricate functional MPNs for effectively depleting GSH, disrupting intracellular redox homeostasis, and enhancing CDT effects, which opens new perspectives on multifunctional MPNs for tumor synergistic therapy.
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Ferroptose , Naftoquinonas , Neoplasias , Compostos Férricos , Apoptose , Glutationa , Metais , Fenóis , Neoplasias/tratamento farmacológicoRESUMO
Metallic-phase iron sulfide (e.g., Fe7 S8 ) is a promising candidate for high power density sodium storage anode due to the inherent metal electronic conductivity and unhindered sodium-ion diffusion kinetics. Nevertheless, long-cycle stability can not be achieved simultaneously while designing a fast-charging Fe7 S8 -based anode. Herein, Fe7 S8 encapsulated in carbon-sulfur bonds doped hollow carbon fibers (NHCFs-S-Fe7 S8 ) is designed and synthesized for sodium-ion storage. The NHCFs-S-Fe7 S8 including metallic-phase Fe7 S8 embrace higher electron specific conductivity, electrochemical reversibility, and fast sodium-ion diffusion. Moreover, the carbonaceous fibers with polar CSFe bonds of NHCFs-S-Fe7 S8 exhibit a fixed confinement effect for electrochemical conversion intermediates contributing to long cycle life. In conclusion, combined with theoretical study and experimental analysis, the multinomial optimized NHCFs-S-Fe7 S8 is demonstrated to integrate a suitable structure for higher capacity, fast charging, and longer cycle life. The full cell shows a power density of 1639.6 W kg-1 and an energy density of 204.5 Wh kg-1 , respectively, over 120 long cycles of stability at 1.1 A g-1 . The underlying mechanism of metal sulfide structure engineering is revealed by in-depth analysis, which provides constructive guidance for designing the next generation of durable high-power density sodium storage anodes.
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Retinoblastoma-binding protein 8 (RBBP8) affects the prognosis of patients with malignancies through various mechanisms. However, its function in gliomas is unknown. Our study explored the effects of RBBP8 on the prognosis of glioma patients, as well as its regulatory role in the glioma immune microenvironment. We used various bioinformatics methods to analyze the transcriptional profiles and methylation data of RBBP8 in gliomas from multiple databases. Our results showed that the mRNA and protein expression of RBBP8 in gliomas was higher than that in normal tissues and positively correlated with malignant clinical features such as age and WHO grade. A Kaplan-Meier analysis showed that patients with high RBBP8 expression had a poor prognosis. Cox regression demonstrated that RBBP8 was an independent risk indicator and had good diagnostic value for the poor prognosis of glioma. Importantly, RBBP8 was positively correlated with many well-known immune checkpoints (e.g., CTLA4 and PDL-1). Finally, a gene set enrichment analysis revealed that RBBP8 was remarkably enriched in cancer-related pathways such as cell cycle, DNA replication and so on. In conclusion, this study is the first to elaborate on the value of RBBP8 in the pathological process of glioma for anti-tumor immunotherapy. In addition, the expression of RBBP8 and its methylation site, cg05513509, may provide potential targets for glioma therapy.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Metilação , Prognóstico , Glioma/diagnóstico , Glioma/genética , Glioma/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Microambiente Tumoral , Endodesoxirribonucleases/metabolismoRESUMO
Alkaline earth metal cations are ubiquitously present in natural zeolites but less exploited in synthetic zeolites due to their low solubility in water, and hence it remains elusive how they contribute to zeolite formation. Herein, harmotome, a PHI-type zeolite with Ba2+, is readily synthesized from a Ba-containing aluminosilicate glass. This glass-to-zeolite transformation process, in particular the structure-regulating role of Ba2+, is investigated by anomalous X-ray scattering and high-energy X-ray total scattering techniques. The results demonstrate that the steady Ba2+-aluminosilicate interactions not only help prevent the precipitation of barium species under alkaline synthetic conditions, but also dictate the local structures with distinct interatomic distances between the Ba2+ and the surrounding aluminosilicate species throughout the transformation process, which lead to the successful formation of harmotome without detectable impurities. This study highlights the usefulness of the comprehensive X-ray scattering techniques in revealing the formation scheme of the zeolites containing specific metal species. In addition, a promising alternative approach to design and synthesize zeolites with unique compositions and topologies by using well-crafted glasses with suitable metal cation dopants is demonstrated.
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Primitive neuroectodermal tumors (PNET) are rare malignant tumors, but the mortality rate of the patients is extremely high. The aim of this study was to identify the hub genes and pathways involved in the pathogenesis of PNET and to screen the potential small molecule drugs for PNET. We extracted gene expression profiles from the Gene Expression Omnibus database and identified differentially expressed genes (DEGs) through Limma package in R. Two expression profiles (GSE14295 and GSE74195) were downloaded, including 33 and 5 cases separately. Four hundred sixty-eight DEGs (161 upregulated; 307 downregulated) were identified. Functional annotation and KEGG pathway enrichment of the DEGs were performed using DAVID and Kobas. Gene Ontology analysis showed the significantly enriched Gene Ontology terms included but not limited to mitosis, nuclear division, cytoskeleton, synaptic vesicle, syntaxin binding, and GABA A receptor activity. Cancer-related signaling pathways, such as DNA replication, cell cycle, and synaptic vesicle cycle, were found to be associated with these genes. Subsequently, the STRING database and Cytoscape were utilized to construct a protein-protein interaction and screen the hub genes, and we identified 5 hub genes (including CCNB1, CDC20, KIF11, KIF2C, and MAD2L1) as the key biomarkers for PNET. Finally, we identified potential small molecule drugs through CMap. Seven small molecule compounds, including trichostatin A, luteolin, repaglinide, clomipramine, lorglumide, vorinostat, and resveratrol may become potential candidates for PNET drugs.
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Biomarcadores Tumorais , Perfilação da Expressão Gênica , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Transcriptoma , Proteínas de Ciclo Celular/genética , Biologia ComputacionalRESUMO
BACKGROUND: It is unclear whether excessive salt intake accelerates the progression of cerebral small vessel disease (CSVD). The major objective of this study was to investigate the harmful effect of excessive salt intake on the progression of CSVD in older individuals. METHODS: Between May 2007 and November 2010, 423 community-dwelling individuals aged 60 years and older were recruited from the Shandong area, China. Salt intake was estimated using 24-hour urine collection for 7 consecutive days at baseline. Participants were classified into low, mild, moderate and high groups according to the salt intake estimation. CSVD including white matter hyperintensities (WMHs), lacunes, microbleeds and an enlarged perivascular space (EPVS) were determined using brain magnetic resonance imaging. RESULTS: During an average of five years of follow-up, the WMH volume and WMH-to-intracranial ratio were increased in the four groups. However, the increasing trends in the WMH volume and WMH-to-intracranial ratio were significantly faster in the higher salt intake groups compared with the lower salt intake groups (Padjusted < 0.001). The cumulative hazard ratios of new-incident WMHs (defined as those with Fazekas scale scores ≥ 2), new-incident lacunes, microbleeds or an EPVS, as well as composites of CSVD, were respectively 2.47, 2.50, 3.33, 2.70 and 2.89 for the mild group; 3.72, 3.74, 4.66, 4.01 and 4.49 for the moderate group; and 7.39, 5.82, 7.00, 6.40 and 6.61 for the high group, compared with the low group after adjustment for confounders (Padjusted < 0.001). The risk of new-incident WMHs, lacunes, microbleeds or an EPVS, and composites of CSVD was significantly increased with each 1-standard-deviation increment in salt intake (Padjusted < 0.001). CONCLUSION: Our data indicates that excessive salt intake is an important and independent contributor to the progression of CVSD in older adults.
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Doenças de Pequenos Vasos Cerebrais , Cloreto de Sódio na Dieta , Humanos , Pessoa de Meia-Idade , Idoso , Cloreto de Sódio na Dieta/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Encéfalo , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/etiologia , Hemorragia CerebralRESUMO
Objective: To investigate the effect of IFN-α-2b in preventing postoperative arthrofibrosis in rats, its antiproliferation effect on fibroblasts in vitro, and its molecular mechanism. Methods: The rat model of arthrofibrosis was established and treated with different concentrations of drugs. Knee specimens were collected for histological and immunohistochemical staining to observe the effect of IFN-α-2b on arthrofibrosis in rats. The biological information was further mined according to the database data, and the possible regulatory mechanism of IFN-α-2b on fibroblasts was analyzed. The inhibitory effect of IFN-α-2b on fibroblast proliferation and migration in vitro was detected by cell counting kit-8 (CCK-8), immunofluorescence analysis, cell cycle test, EdU assay, wound healing test, and Transwell method, and the analysis results were verified by Western blotting method. Results: The test results of rat knee joint specimens showed that IFN-α-2b significantly inhibited the degree of fibrosis after knee joint surgery, the number of fibroblasts in the operation area was less than that of the control group, and the expression of collagen and proliferation-related proteins decreased. In vitro experimental results show that IFN-α-2b can inhibit the proliferation and migration of fibroblasts. According to the results of database analysis, it is suggested that the STAT1/P21 pathway may be involved, and it has been verified and confirmed by Western blotting and other related methods. Conclusion: IFN-α-2b can reduce surgery-induced arthrofibrosis by inhibiting fibroblast proliferation and migration, which may be related to the regulation of STAT1/p21 signaling pathway.
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Colágeno , Transdução de Sinais , Ratos , Animais , Colágeno/metabolismo , Ciclo Celular , Proliferação de Células , Fibroblastos/metabolismo , Fator de Transcrição STAT1/metabolismoRESUMO
BACKGROUND: The impacts and mechanisms of morning hypertension (MHT) on the risk of new-onset atrial fibrillation (AF) in the elderly have not been clarified. We aimed to investigate an association between MHT and new-onset AF and explore a mediating effect of subclinical inflammation on this association. METHODS: From 2008 to 2010, 1789 older adults aged ≥60 years were recruited in Shandong area, China. Morning blood pressure (BP) was assessed using 24-hour ambulatory BP monitoring. MHT was defined as BP ≥ 135/85 mm Hg during the period from wake time to 0900 a.m. Subclinical inflammation was assessed by hypersensitive C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-α), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and galectin-3. New-onset AF was rated during the follow-up period. RESULTS: Over an average 129.0 [standard deviation (SD): 21.58] months of follow-up, the hazard ratio of new-onset AF in MHT patients was 1.39 (95% confidence interval: 1.01 to 1.91) compared with non-MHT participants (Padjusted = 0.027). The risk of new-onset AF was 1.17-fold with one-SD increment of morning systolic BP. Subclinical inflammation was significantly associated with new-onset AF. The hazard ratios of new-onset AF were 2.29, 2.04, 2.08, 2.08, 2.03, and 3.25 for one-SD increment in hsCRP, TNF-α, SII, NLR, PLR, and galectin-3, respectively (Padjusted < 0.001). The analysis showed that hsCRP, TNF-α, SII, NLR, PLR, and galectin-3 separately mediated the process of MHT inducing new-onset AF (Padjusted < 0.05). CONCLUSIONS: MHT is associated with an increased risk of new-onset AF. The subclinical inflammation might play a mediating role in this association.
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Fibrilação Atrial , Hipertensão , Idoso , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Proteína C-Reativa , Galectina 3 , Fator de Necrose Tumoral alfa , Inflamação/complicações , Hipertensão/complicaçõesRESUMO
Osteoarthritis (OA) is a degenerative disease characterized by cartilage wear and degradation. Ginkgolide K (GK) is a natural compound extracted from Ginkgo biloba leaves and possesses anti-inflammatory and anti-apoptotic effects. We found that the biological characteristics of GK were highly consistent with those of OA medications. This study aimed to determine and verify the therapeutic effect of GK on OA and mechanism of its therapeutic effect. For the in vivo experiment, OA rats were regularly injected in the articular cavity with GK, and the curative effects were observed after 4 and 8 weeks. For the in vitro experiment, we treated OA chondrocytes with different concentrations of GK and then detected the related indices of OA. Through the in vivo and in vitro experiments, we found that GK could promote the production of major components of the cartilage extracellular matrix. Transcriptome sequencing revealed that GK may activate hypoxia-inducible factor 1 alpha via the hypoxia signaling pathway, which, in turn, activates yes-associated protein and inhibits apoptosis of OA chondrocytes. GK has a therapeutic effect on OA and, therefore, has the potential to be developed into a new drug for OA treatment.
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Cartilagem Articular , Osteoartrite , Ratos , Animais , Cartilagem/metabolismo , Osteoartrite/tratamento farmacológico , Condrócitos , Matriz Extracelular/metabolismoRESUMO
BACKGROUND: Although nonfat milk has been used worldwide in the industrial dairy process, little is known about the effects of fat separation during the manufacturing process on skim milk's structural and digestive properties. This study investigated the effects of the manufacturing process on the structure and in vitro digestion properties of skim goat milk, particularly emphasizing fat separation. RESULTS: Changes in the surface charge and hydrophobicity of milk proteins caused by fat separation resulted in oxidation and aggregation in the subsequent homogenization, heat and spray-drying processing, which affected its digestibility. Compared with separation by dish separator (DS), skim milk after tubular centrifugal separation (CS) showed a higher initial and final digestibility. The CS samples also had a lower surface hydrophobicity level and higher free sulfhydryl content, ζ-potential, and average particle size (P < 0.05). Goat milk protein after CS was more readily oxidized and aggregated during the subsequent homogenization and heat treatment, as evidenced by the higher carbonyl content and particle size. Centrifugal separation also converted more ß-sheets to α-helices, thus promoting the aggregation of oxidized skim milk protein. CONCLUSION: The skim milk after CS and DS demonstrated different structural and digestive properties. Skim goat milk products after CS were more susceptible to oxidant-induced protein structural changes, resulting in higher protein digestibility. These findings provide insights into the mechanism involved in the control of gastric digestion of skim milk during manufacturing process. © 2023 Society of Chemical Industry.
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Cabras , Proteínas do Leite , Animais , Proteínas do Leite/análise , Leite/química , Oxirredução , DigestãoRESUMO
Despite the growing recognition of ITGB3BP as an essential feature of various cancers, the relationship between ITGB3BP and glioma remains unclear. The main aim of this study was to determine the prognostic and diagnostic value of ITGB3BP in glioma. RNA-Seq and microarray data from 2222 glioma patients were included, and we found that the expression level of ITGB3BP in glioma tissues was significantly higher than that in normal brain tissues. Moreover, ITGB3BP can be considered an independent risk factor for poor prognosis and has great predictive value for the prognosis of glioma. Gene Set Enrichment Analysis results showed that ITGB3BP contributes to the poor prognosis of glioma by activating tumour-related signalling pathways. Some small-molecule drugs were identified, such as hexestrol, which may specifically inhibit ITGB3BP and be useful in the treatment of glioma. The TIMER database analysis results revealed a correlation between the expression of ITGB3BP and the infiltration of various immune cells in glioma. Our findings provide the first evidence that the up-regulation of ITGB3BP correlates with poor prognosis in human glioma. Thus, ITGB3BP is a potential new biomarker that can be used for the clinical diagnosis and treatment of glioma.
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Neoplasias Encefálicas , Glioma , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Glioma/metabolismo , Humanos , Proteínas Nucleares/genética , Transdução de Sinais , Regulação para CimaRESUMO
Chemotherapy is a commonly utilized treatment strategy for colon cancer, a prevalent malignancy. The study intends to probe the function and mechanism of protocadherin 7 (PCDH7) in colon cancer. Gain or loss of functional assays of PCDH7 was performed. MTT and colony formation assay monitored cell proliferation. Transwell measured migration and invasion. Real-time quantitative polymerase chain reaction and western blot verified the profiles of PCDH7 and the MEK1/2/ERK/c-FOS pathway. Western blot was implemented to confirm the profiles of PP1α, MLC2, and p-MLC2 for evaluating the impact of PCDH7 on homotypic cells in cell (hocic) structures. Further, an in-vivo nude mouse model was engineered to figure out the function and mechanism of PCDH7 in tumor cell growth. As indicated by the data, PCDH7 knockdown boosted the cells' sensitivity to chemotherapy. PCDH7 overexpression facilitated their proliferation and invasion, altered autophagy, induced ferroptosis and hocic, and initiated the profile of the MEK1/2/ERK/c-FOS pathway. MEK1/2/ERK inhibition impaired the inhibitory impact of PCDH7 on colon cancer cells' chemotherapy sensitivity and dampened its pro-cancer function in the cells. In-vivo experiments displayed that PCDH7 overexpression stepped up tumor growth and pulmonary metastasis in colon cancer cells. All in all, the research has discovered that PCDH7 knockdown affects autophagy and induces ferroptosis, hence strengthening colon cancer cells' sensitivity to chemotherapy by repressing the MEK1/2/ERK/c-FOS axis.
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Autofagia , Neoplasias do Colo , Ferroptose , Animais , Camundongos , Autofagia/efeitos dos fármacos , Autofagia/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , MAP Quinase Quinase Quinases/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Protocaderinas/genéticaRESUMO
BACKGROUND: Cysteine cathepsin C encoded by the CTSC gene is an important member of the cysteine cathepsin family that plays a key role regulation of many types of tumors. However, whether CTSC is involved in the pathological process of glioma has not yet been reported. We comprehensively analyzed data from multiple databases and for the first time revealed a role and specific mechanism of action of CTSC in glioma, identifying it as a novel and efficient biomarker for the diagnosis and treatment of this brain tumor. METHODS: The expression of CTSC in glioma and its relationship with clinical characteristics and prognosis of patients with glioma were analyzed at different levels by using clinical sample information from several databases. CTSC expression levels in glioma and normal brain tissues, as well as in glioma cells and normal brain cells, was validated by real-time quantitative polymerase chain reaction (RT-qPCR). Gene set enrichment analysis (GSEA) was used to reveal the signaling pathways that CTSC may participate in. The connectivity map was used to reveal small molecules that may inhibit CTSC expression in glioma, and the putative effect of these compounds was verified by RT-qPCR. RESULTS: Our analyses showed that the expression of CTSC in glioma was higher than that in non-cancerous cells. GSEA showed that CTSC expression may regulate the malignant development of glioma through Toll-like receptor signaling pathways, pathways in cancer, and extracellular matrix receptor interaction signaling pathways. And we proved piperlongumine and scopoletin could inhibit CTSC expression in glioma cells. CONCLUSIONS: CTSC may serve as an efficient molecular target for the diagnosis and therapy of glioma, thereby improving the poor prognosis of patients with glioma.
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Interzeolite conversion, which refers to the synthesis of zeolites using a pre-made zeolite as the starting material, has enabled promising outcomes that could not be easily achieved by the conventional synthesis from a mixture of amorphous aluminum and silicon sources. Understanding the mechanism of interzeolite conversion is of particular interest to exploit this synthesis route for the preparation of tailor-made zeolites as well as the discovery of new structures. It has been assumed that the structural similarity between the starting zeolite and the target one is crucial to a successful interzeolite conversion. Nevertheless, an image as to how one type of zeolite evolves into another one remains unclear. In this work, a series of dealuminated FAU zeolites were created through acid leaching and employed as the starting zeolites in the synthesis of AEI zeolite under various conditions. This experimental design allowed us to create a comprehensive diagram of the interzeolite conversion from FAU to AEI as well as to figure out the key factors that enable this kinetically favourable crystallization pathway. Our results revealed different scenarios of the interzeolite conversion from FAU to AEI and pinpointed the importance of the structure of the starting FAU in determining the synthesis outcomes. A prior dealumination was proven effective to modify the structure of the initial FAU zeolite and consequently facilitate its conversion to the AEI zeolite. In addition, this strategy allowed us to directly transfer the knowledge obtained from the interzeolite conversion to a successful synthesis of the AEI zeolite from dealuminated amorphous aluminosilicate precursors. These results offer new insights to the design and fabrication of zeolites via the interzeolite conversion as well as to the understandings of the crystallization mechanisms.
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Aim: PYGL has been reported to have carcinogenic effects in a variety of tumors. This study is the first to reveal the relationship between PYGL and the prognosis of glioma. Materials & methods: Analyzing the Chinese Glioma Genome Atlas database, the authors revealed the expression status and prognostic value of PYGL in gliomas and used quantitative real-time PCR to verify PYGL expression again. Subsequently, they used Gene Set Enrichment Analysis to explore the biological pathways that PYGL may participate in. The authors also used the tumor immune estimation resource database to explore the relationship between PYGL and tumor immune cells. Results: PYGL is involved in the malignant progression of glioma. Conclusions: PYGL can be used as a new biomarker and molecular target for evaluating the prognosis and immunotherapy of glioma.
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Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Perfilação da Expressão Gênica , Glioma/genética , Glicogênio Fosforilase Hepática/genética , Neoplasias Encefálicas/metabolismo , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Glicogênio Fosforilase Hepática/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Prognóstico , Receptores Notch/metabolismo , Transdução de Sinais , Análise de Sobrevida , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: GINS4, an indispensable component of the GINS complex, is vital for a variety of cancer. However, no known empirical research has focused on exploring relationships between GINS4 and glioma. Thus, this study aims to understand and explain the role of GINS4 in glioma. METHOD: First, we used the data in the CGGA, TCGA, GEO, GEPIA, and HPA databases to explore the expression level of GINS4 in glioma, the correlation between GINS4 expression and the clinical features of glioma, its impact on the survival of glioma patients, and verified the analysis results through RT-qPCR, IHC, and meta-analysis. Subsequently, GSEA enrichment analysis is used to find the potential molecular mechanism of GINS4 to promote the malignant process of glioma and the anti-glioma drugs that may target GINS4 screened by CMap analysis. Moreover, we further explored the influence of the GINS4 expression on the immune microenvironment of glioma patients through the TIMER database. RESULTS: Our results suggested that GINS4 was elevated in glioma, and the overexpression of GINS4 was connected with a vast number of clinical features. The next, GINS4 as an independent prognostic factor, which can result in an unfavorable prognosis of glioma. Once more, GINS4 may be participating in the oncogenesis of glioma through JAK-STAT signaling pathways, etc. 6-thioguanine, Doxazosin, and Emetine had potential value in the clinical application of drugs targeting GINS4. Finally, the expression exhibited a close relationship with some immune cells, especially Dendritic cells. CONCLUSION: GINS4 is an independent prognostic factor that led to a poor prognosis of glioma. The present study revealed the probable underlying molecular mechanisms of GINS4 in glioma and provided a potential target for improving the prognosis of glioma.