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1.
Med Phys ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861045

RESUMO

PURPOSE: To non-invasively evaluate the Ki-67 level in digital breast tomosynthesis (DBT) images of breast cancer (BC) patients based on subregional radiomics. METHODS: A total of 266 patients who underwent DBT scans were consecutively enrolled at two centers, between September 2017 and September 2021. The whole tumor region was partitioned into various intratumoral subregions, based on individual- and population-level clustering. Handcrafted radiomics features and deep learning-based features were extracted from the subregions and from the whole tumor region, and were selected by least absolute shrinkage and selection operator (LASSO) regression, yielding radiomics signatures (RSs). The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to assess the developed RSs. RESULTS: Each breast tumor region was partitioned into an inner subregion (S1) and a marginal subregion (S2). The RSs derived from S1 always generated higher AUCs compared with those from S2 or from the whole tumor region (W), for the external validation cohort (AUCs, S1 vs. W, handcrafted RSs: 0.583 [95% CI, 0.429-0.727] vs. 0.559 [95% CI, 0.405-0.705], P value: 0.920; deep RSs: 0.670 [95% CI, 0.516-0.802] vs. 0.551 [95% CI, 0.397-0.698], P value: 0.776). The fusion RSs, combining handcrafted and deep learning-based features derived from S1, yielded the highest AUCs of 0.820 (95% CI, 0.714-0.900) and 0.792 (95% CI, 0.647-0.897) for the internal and external validation cohorts, respectively. CONCLUSIONS: The subregional radiomics approach can accurately predict the Ki-67 level based on DBT data; thus, it may be used as a potential non-invasive tool for preoperative treatment planning in BC. This article is protected by copyright. All rights reserved.

2.
ACS Chem Neurosci ; 12(23): 4449-4464, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34762393

RESUMO

Cefepime exhibits a broad spectrum of antimicrobial activity and thus is a widely used treatment for severe bacterial infections. Adverse effects on the central nervous system (CNS) have been reported in patients treated with cefepime. Current explanation for the adverse neurobehavioral effect of cefepime is mainly attributed to its ability to cross the blood-brain barrier and competitively bind to the GABAergic receptor; however, the underlying mechanism is largely unknown. In this study, mice were intraperitoneally administered 80 mg/kg cefepime for different periods, followed by neurobehavioral tests and a brain lipidomic analysis. LC/MS-MS-based metabolomics was used to investigate the effect of cefepime on the brain lipidomic profile and metabolic pathways. Repeated cefepime treatment time-dependently caused anxiety-like behaviors, which were accompanied by reduced locomotor activity in the open field test. Cefepime profoundly altered the lipid profile, acyl chain length, and unsaturation of fatty acids in the corpus striatum, and glycerophospholipids accounted for a large proportion of those significantly modified lipids. In addition, cefepime treatment caused obvious alteration in the lipid-enriched membrane structure, neurites, mitochondria, and synaptic vesicles of primary cultured striatal neurons; moreover, the spontaneous electrical activity of striatal neurons was significantly reduced. Collectively, cefepime reprograms glycerophospholipid metabolism in the corpus striatum, which may interfere with neuronal structure and activity, eventually leading to aberrant neurobehaviors in mice.

3.
Anticancer Drugs ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845164

RESUMO

Breast cancer is a frequent tumor threatening the health of women. Circular RNAs (circRNAs) play vital roles in cancer progression and chemoresistance. Herein, we mainly investigate the role and potential mechanism of circRNA ataxin 7 (circATXN7; circ_0066436) in breast cancer. RNA expression levels were detected via quantitative real-time PCR (qPCR), western blot and immunohistochemistry. Cell viability and half inhibitory concentration (IC50) of doxorubicin were assessed by cell counting kit-8 (CCK-8) method. Cell proliferation, migration and invasion were determined by CCK-8, 5-ethynyl-2'-deoxyuridine, colony formation and transwell assays. The binding relationship between microRNA-149-5p (miR-149-5p) and circATXN7 or homeobox A11 (HOXA11) was validated via dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft assay was conducted to analyze the effect of circATXN7 on doxorubicin resistance of breast cancer. CircATXN7 and HOXA11 levels were enhanced, whereas miR-149-5p level was declined in breast cancer tissues and cells. CircATXN7 silencing suppressed breast cancer development and doxorubicin resistance. Additionally, circATXN7 upregulated HOXA11 via absorbing miR-149-5p, thereby inducing breast cancer cell progression and reducing doxorubicin sensitivity. Besides, depletion of circATXN7 enhanced doxorubicin sensitivity in vivo. Interference of circATXN7 inhibited breast cancer progression and doxorubicin resistance via mediating miR-149-5p/HOXA11 axis, which might provide a possible biomarker for breast cancer therapy.

4.
Int J Gen Med ; 14: 8249-8262, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815698

RESUMO

Purpose: Endometrial cancer (EC) is a common gynaecologic malignancy with an increasing incidence rate and mortality in recent years. N6-methylandenosine (m6A)-related long noncoding RNA (lncRNA) plays a vital role in EC, emerging as one of the most abundant RNA modifications. Materials and Methods: The Cancer Genome Atlas (TCGA) database and UCSC Xena were used to download data related to EC. Survival and univariate and multifactorial prognostic analyses were performed for m6A-related lncRNAs. The expression levels of the three lncRNAs were verified using q-PCR. A nomogram was used to create a clinical tool to assess overall survival. To investigate the relationship between m6A-related lncRNA and EC, we downloaded differential genes related to EC from the TCGA database and mined three m6A-related lncRNAs, namely SCARNA9, TRAF3IP2-AS1, and AL133243.2. The data were categorized into high- and low-risk groups based on m6A-associated lncRNA. Results: Survival analysis revealed that the high-risk group had a lower survival rate. Survival analysis of three m6A-associated lncRNAs revealed that cases with high expression of SCARNA9 tended to have a poorer prognosis, whereas the opposite was true for TRAF3IP2-AS1, AL133243.2. Univariate and multifactorial prognostic analyses suggested statistical differences in patients' age, FIGO stage, pathological grade, risk score, and prognosis of EC, which was confirmed by results of the separate prognostic factor analysis for the three lncRNAs. Risk status was validated as an independent prognostic indicator, and the prognostic nomogram combined patient age, pathological stage, and FIGO classification to assess 3-5-year survival. Cases from high- and low-risk groups were analysed for the tumour microenvironment and immune cell scores, and stromal cell scores were found to be lower in the high-risk group. Correlations were analysed using different databases for immune cell classification. Conclusion: m6A-related lncRNAs may play a key role in the diagnosis and treatment of EC as targets of prognosis and the immune microenvironment.

5.
Adv Sci (Weinh) ; : e2102189, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34825783

RESUMO

Sustainable solutions on fabricating and using a face mask to block the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread during this coronavirus pandemic of 2019 (COVID-19) are required as society is directed by the World Health Organization (WHO) toward wearing it, resulting in an increasingly huge demand with over 4 000 000 000 masks used per day globally. Herein, various new mask technologies and advanced materials are reviewed to deal with critical shortages, cross-infection, and secondary transmission risk of masks. A number of countries have used cloth masks and 3D-printed masks as substitutes, whose filtration efficiencies can be improved by using nanofibers or mixing other polymers into them. Since 2020, researchers continue to improve the performance of masks by adding various functionalities, for example using metal nanoparticles and herbal extracts to inactivate pathogens, using graphene to make masks photothermal and superhydrophobic, and using triboelectric nanogenerator (TENG) to prolong mask lifetime. The recent advances in material technology have led to the development of antimicrobial coatings, which are introduced in this review. When incorporated into masks, these advanced materials and technologies can aid in the prevention of secondary transmission of the virus.

6.
Bioengineering (Basel) ; 8(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34821733

RESUMO

Delayed fracture healing and fracture non-unions impose an enormous burden on individuals and society. Successful healing requires tight communication between immune cells and bone cells. Macrophages can be found in all healing phases. Due to their high plasticity and long life span, they represent good target cells for modulation. In the past, extremely low frequency pulsed electromagnet fields (ELF-PEMFs) have been shown to exert cell-specific effects depending on the field conditions. Thus, the aim was to identify the specific ELF-PEMFs able to modulate macrophage activity to indirectly promote mesenchymal stem/stromal cell (SCP-1 cells) function. After a blinded screening of 22 different ELF-PEMF, two fields (termed A and B) were further characterized as they diversely affected macrophage function. These two fields have similar fundamental frequencies (51.8 Hz and 52.3 Hz) but are emitted in different groups of pulses or rather send-pause intervals. Macrophages exposed to field A showed a pro-inflammatory function, represented by increased levels of phospho-Stat1 and CD86, the accumulation of ROS, and increased secretion of pro-inflammatory cytokines. In contrast, macrophages exposed to field B showed anti-inflammatory and pro-healing functions, represented by increased levels of Arginase I, increased secretion of anti-inflammatory cytokines, and growth factors are known to induce healing processes. The conditioned medium from macrophages exposed to both ELF-PEMFs favored the migration of SCP-1 cells, but the effect was stronger for field B. Furthermore, the conditioned medium from macrophages exposed to field B, but not to field A, stimulated the expression of extracellular matrix genes in SCP-1 cells, i.e., COL1A1, FN1, and BGN. In summary, our data show that specific ELF-PEMFs may affect immune cell function. Thus, knowing the specific ELF-PEMFs conditions and the underlying mechanisms bears great potential as an adjuvant treatment to modulate immune responses during pathologies, e.g., fracture healing.

7.
J Clin Transl Hepatol ; 9(5): 672-681, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34722182

RESUMO

Background and Aims: There are no comparative studies on the efficacy of hepatic resection (HR) and CyberKnife stereotactic body radiation therapy (CK-SBRT) plus transhepatic arterial chemotherapy embolization (TACE) in the treatment of large hepatocellular carcinoma (HCC). Therefore, this study aimed to compare the efficacy of HR and CK-SBRT+TACE in large HCC. Methods: A total of one hundred and sixteen patients were selected from November 2011 to December 2016. Among them, 50 were allocated to the CK-SBRT+TACE group and 66 were allocated to the HR group. The Kaplan-Meier method was applied to calculate overall survival (OS) and progression-free survival (PFS) rates. Propensity score matching was performed to control for baseline differences between the groups. Results: Thirty-six paired patients were selected from the CK-SBRT+TACE and HR groups. After propensity score matching, the 1-, 2- and 3-year OS rates were 83.3%, 77.8% and 66.7% in the HR group and 80.6%, 72.2% and 52.8% in the CK-SBRT+TACE group, respectively. The 1-, 2- and 3-year PFS rates were 71.6%, 57.3% and 42.3% in the HR group and 66.1%, 45.8% and 39.3% in the CK-SBRT+TACE group, respectively (OS: p=0.143; PFS: p=0.445). Both a high platelet count and low alpha-fetoprotein value were revealed as influencing factors in improving OS and PFS. Conclusions: CK-SBRT+TACE brought local effects that were similar to those of HR in HCC patients with a large and single lesion. Moreover, the liver injury occurrence rate was acceptable in both groups.

8.
Eur J Med Chem ; : 113986, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34802839

RESUMO

Biased agonism refers to the ability of compounds to drive preferred signaling pathways and avoid adverse signaling pathways in a ligand-dependent manner for some G-protein-coupled receptors. It is thought that the separation of therapeutic efficacy (e.g., analgesia) from adverse effects (e.g., respiration depression) can be achieved through the design of biased MOR agonists and one example is the recently approved MOR biased agonist oliceridine (TRV130). However, oliceridine only demonstrates modest beneficial effects as compared to other opioids in terms of therapeutic/adverse effect balance. One possibility attributable to the modest success of oliceridine is its limited bias, and as such developing MOR ligands with a more biased agonism profile could in theory further improve the beneficial effects of the ligands. Here, we rationally designed and synthesized a series of derivatives as potent highly biased MOR agonists (19a-v) through the modification and structure-activity relationship study of TRV130. This novel synthetic molecule, LPM3480392 (19m), demonstrated improved in vitro biased agonism (EC50 = 0.35 nM, Emax = 91.4%) with no measured ß-arrestin recruitment (EC50 > 30000 nM, Emax = 1.6%), good brain penetration (B/P ratio = 4.61, 0.25 h post-IV dosing 2.0 mg/kg), a favorable pharmacokinetic profile (distribution volume = 10766 mL/kg, t1/2 = 1.9 h) and produced potent antinociceptive effect with reduced respiratory suppression (sO2(%) = 92.17, 0.32 mg/kg, SC) as compared to TRV130. LPM3480392 has completed preclinical studies and is currently under clinical development (CTR20210370) as an analgesic for the treatment of moderate to severe pain.

9.
Front Pharmacol ; 12: 741794, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594228

RESUMO

Toludesvenlafaxine hydrochloride dihydrate is a novel chemical entity and a potential triple monoamine reuptake inhibitor. This study characterized the in vitro triple reuptake inhibition activity, antidepressant-like activity in animals, and pharmacokinetic profiles in rats of toludesvenlafaxine. Binding affinity was determined using human serotonin transporter (SERT) protein, norepinephrine transporter (NET) protein and dopamine transporter (DAT) protein, and the reuptake inhibition was determined using Chinese hamster ovary cells expressing human SERT, NET and DAT. The antidepressant-like activity was examined in rat chronic unpredictable mild stress model and olfactory bulbectomized model. In rats, the tissue distribution and pharmacokinetic parameters were determined. Toludesvenlafaxine had high binding affinity on SERT, NET and DAT, and significantly inhibited the reuptake of serotonin (IC50 = 31.4 ± 0.4 nM), norepinephrine (IC50 = 586.7 ± 83.6 nM) and dopamine (IC50 = 733.2 ± 10.3 nM) in vitro. Toludesvenlafaxine demonstrated significant antidepressant-like effects in rat models at 8-16 mg/kg. In addition, toludesvenlafaxine significantly reduced serum corticosterone and significantly increased testosterone levels in rats. Toludesvenlafaxine was quickly absorbed and converted to O-desvenlafaxine (ODV) after oral administration, both of which were selectively distributed into the hypothalamus with high concentration. Plasma ODV exposure was proportionally related to the doses after oral dosing. These results suggest that toludesvenlafaxine is a triple reuptake inhibitor with relatively fast-acting antidepressant-like activity and good therapeutic profile including improvement of anhedonia and sexual function.

10.
Front Hum Neurosci ; 15: 713823, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658815

RESUMO

Depression has become one of the main afflictions that threaten people's mental health. However, the current traditional diagnosis methods have certain limitations, so it is necessary to find a method of objective evaluation of depression based on intelligent technology to assist in the early diagnosis and treatment of patients. Because the abnormal speech features of patients with depression are related to their mental state to some extent, it is valuable to use speech acoustic features as objective indicators for the diagnosis of depression. In order to solve the problem of the complexity of speech in depression and the limited performance of traditional feature extraction methods for speech signals, this article suggests a Three-Dimensional Convolutional filter bank with Highway Networks and Bidirectional GRU (Gated Recurrent Unit) with an Attention mechanism (in short 3D-CBHGA), which includes two key strategies. (1) The three-dimensional feature extraction of the speech signal can timely realize the expression ability of those depression signals. (2) Based on the attention mechanism in the GRU network, the frame-level vector is weighted to get the hidden emotion vector by self-learning. Experiments show that the proposed 3D-CBHGA can well establish mapping from speech signals to depression-related features and improve the accuracy of depression detection in speech signals.

11.
Healthcare (Basel) ; 9(10)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34682931

RESUMO

In the process of rehabilitation, the objectivity and the accuracy of rehabilitation assessment have an obvious impact on the follow-up training. To improve this problem, using a multi-sensor source, this paper attempts to establish a comprehensive assessment method of the finger rehabilitation effect, including three indicators of finger muscle strength, muscle fatigue degree, and range of motion. Firstly, on the basis of the fingertip pressure sensor of the End-Effector Finger Rehabilitation Robot, a mathematical model of finger muscle strength estimation was established, and the estimated muscle strength was scored using the entropy weight method. Secondly, using an sEMG signal sensor, a fatigue monitoring system was designed in the training process, and the fatigue degree was determined on the basis of the change trend of the eigenvalues of MAV and RMS. Lastly, a human-machine motion coupling model was established, and the joint range of motion acquisition and scoring model were obtained on the basis of the motor encoder. According to the above three indicators, using the AHP assessment method to establish a comprehensive rehabilitation assessment method, the effectiveness of the method was verified by experiments. This paper provides a potential new idea and method for objective, accurate, and convenient assessment of finger function rehabilitation, which is of positive significance for alleviating the burden on rehabilitation doctors and improving rehabilitation efficiency.

12.
Stem Cells Int ; 2021: 1434856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650608

RESUMO

Endometrial cancer (EC) is commonly diagnosed cancer in women, and the prognosis of advanced types of EC is extremely poor. Kinesin family member 2C (KIF2C) has been reported as an oncogene in cancers. However, its pathophysiological roles and the correlation with tumor-infiltrating lymphocytes in EC remain unclear. The mRNA and protein levels of KIF2C in EC tissues were detected by qRT-PCR, Western blot (WB), and IHC. CCK8, Transwell, and colony formation assay were applied to assess the effects of KIF2C on cell proliferation, migration, and invasion. Cell apoptosis and cell cycle were analyzed by flow cytometry. The antitumor effect was further validated in the nude mouse xenograft cancer model and humanized mouse model. KIF2C expression was higher in EC. Knockdown of KIF2C prolonged the G1 phases and inhibited EC cell proliferation, migration, and invasion in vitro. Bioinformatics analysis indicated that KIF2C is negatively correlated with the infiltration level of CD8+ T cells but positively with the poor prognosis of EC patients. The apoptosis of CD8+ T cell was inhibited after the knockdown of KIF2C and was further inhibited when it is combined with anti-PD1. Conversely, compared to the knockdown of KIF2C expression alone, the combination of anti-PD1 further promoted the apoptosis of Ishikawa and RL95-2 cells. Moreover, the knockdown of KIF2C inhibited the expression of Ki-67 and the growth of tumors in the nude mouse xenograft cancer model. Our study found that the antitumor efficacy was further evaluated by the combination of anti-PD1 and KIF2C knockdown in a humanized mouse model. This study indicated that KIF2C is a novel prognostic biomarker that determines cancer progression and also a target for the therapy of EC and correlated with tumor immune cells infiltration in EC.

13.
Cell Stem Cell ; 28(12): 2062-2075.e5, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34525347

RESUMO

Select subsets of immune effector cells have the greatest propensity to mediate antitumor responses. However, procuring these subsets is challenging, and cell-based immunotherapy is hampered by limited effector-cell persistence and lack of on-demand availability. To address these limitations, we generated a triple-gene-edited induced pluripotent stem cell (iPSC). The clonal iPSC line was engineered to express a high affinity, non-cleavable version of the Fc receptor CD16a and a membrane-bound interleukin (IL)-15/IL-15R fusion protein. The third edit was a knockout of the ecto-enzyme CD38, which hydrolyzes NAD+. Natural killer (NK) cells derived from these uniformly engineered iPSCs, termed iADAPT, displayed metabolic features and gene expression profiles mirroring those of cytomegalovirus-induced adaptive NK cells. iADAPT NK cells persisted in vivo in the absence of exogenous cytokine and elicited superior antitumor activity. Our findings suggest that unique subsets of the immune system can be modeled through iPSC technology for effective treatment of patients with advanced cancer.

14.
Front Chem ; 9: 706343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557472

RESUMO

Broad solar light harvesting and fast photoinduced electron-hole migration are two critical factors for the catalytic capacity of photocatalytic system. In this study, novel visible light-driven carbon dot-TiO2 nanosheet (CD-TN) photocatalysts are successfully prepared by loading CDs on the surface of TNs through the hydrothermal method. The microstructure, chemical components, and optical properties of the prepared samples are characterized via X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, UV-visible diffuse reflectance spectroscopy, and X-ray photoelectron spectroscopy analysis. Congo red (CR), rhodamine B (RhB), and tetracycline (TC) are selected as pollutants to assess the catalytic performance of CD-TNs. As expected, the removal efficiencies of CD-TNs for CR, RhB, and TC are 94.6% (120 min), 97.2% (150 min), and 96.1% (60 min), respectively, obviously higher than that of pure TNs. The enhanced degradation efficiency of CD-TNs is predominantly ascribed to the merits of CDs (excellent up-conversion property and electron transfer property). Moreover, according to the several degradation cycles, CD-TNs possess the excellent stability, having removed 93.3% of CR after 120 min irradiation.

15.
Exp Ther Med ; 22(5): 1224, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34539820

RESUMO

Studies have indicated that collagen α-1 (IV) chain (COL4A1) has an indispensable regulatory role in the complex pathological mechanisms of numerous types of malignant tumor. However, its role in the development of glioma has remained elusive. Therefore, the present study sought to determine the association between the expression levels of COL4A1 and the clinical characteristics of gliomas by analyzing large samples. First, analysis of thousands of glioma tissue samples collected from the Gene expression profiling interactive analysis, Gene Expression Omnibus database, the Ivy glioblastoma atlas, The Human Protein Atlas, Chinese Glioma Genome Atlas and The Cancer Genome Atlas. In addition, glioma tissues and normal brain tissues from patients with glioma and epilepsy undergoing surgical resection were collected. These samples, which were subjected to a variety of different detection techniques (including sequencing data, chip data, reverse transcription-quantitative PCR, cell lines and tissue samples, in situ hybridization and immunology) revealed that COL4A1 expression was not only increased at the mRNA level but also at the protein level as compared with that in normal brain tissue. Furthermore, Kaplan-Meier analysis revealed that COL4A1 expression was associated with reduced overall survival of patients, particularly those with World Health Organization grade III glioma. Receiver operating characteristic analysis suggested that COL4A1 had a moderate diagnostic value for glioma. In addition, the Mann-Whitney U-test or Kruskal-Wallis test indicated that the expression levels of COL4A1 were positively associated with the histological type and historical grade of the tumor, patient age, 'Primary, Recurrent, Secondary' type and the chemotherapy status, and negatively associated with isocitrate dehydrogenase mutation and 1p19q co-deletion (P<0.001). Gene-set enrichment analysis indicated that overexpression of COL4A1 promoted cancer-associated pathways, such as the JAK/STAT signaling pathway and cell cycle regulation. Finally, an MTT assay, immunohistochemical analysis of the cell cycle regulator KI67 and a wound-healing assay further confirmed that knockdown of COL4A1 inhibited the proliferation and migration ability of glioma cells. In conclusion, COL4A1, as a novel oncogene, is a marker for poor prognosis in patients with glioma. The present study expanded the understanding of the pathogenesis of glioma and identified COL4A1 as a potential target for the diagnosis and treatment of gliomas.

16.
Front Genet ; 12: 666106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512713

RESUMO

Research has confirmed that extra spindle pole bodies-like 1 (ESPL1), an etiological factor, promotes the malignant progression of cancers. However, the relationship between ESPL1 and glioma has not yet been demonstrated. The purpose of this study was to reveal the potential mechanisms of ESPL1-mediated malignant glioma progression. Gene expression data and detailed clinical information of glioma cases were obtained from multiple public databases. Subsequently, a series of bioinformatics analyses were used to elucidate the effects of ESPL1 on glioma. The results demonstrated that the mRNA and protein levels of ESPL1 in glioma were higher than those in normal brain tissues. In addition, ESPL1 expression was considerably associated with the clinical and pathological features of gliomas, such as World Health Organization grade, histology, and 1p19q co-deletion status. Importantly, ESPL1 reduced the overall survival (OS) of glioma patients and had prognostic value for gliomas. Gene set enrichment analysis (GSEA) indirectly revealed that ESPL1 regulates the activation of cancer-related pathways, such as the cell cycle and base excision repair pathways. In addition, we used the Connectivity Map (CMap) database to screen three molecular drugs that inhibit ESPL1: thioguanosine, antimycin A, and zidovudine. Finally, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of ESPL1 in glioma cell lines. This study plays an important role in revealing the etiology of glioma by revealing the function of ESPL1, providing a potential molecular marker for the diagnosis and treatment of glioma, especially low-grade glioma.

17.
Acta Pharmacol Sin ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34522005

RESUMO

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

18.
Nanomicro Lett ; 13(1): 194, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519929

RESUMO

It is of great importance to explore a creative route to improve the degradation efficiency of organic pollutants in wastewater. Herein, we construct a unique hybrid system by combining self-powered triboelectric nanogenerator (TENG) with carbon dots-TiO2 sheets doped three-dimensional graphene oxide photocatalyst (3DGA@CDs-TNs), which can significantly enhance the degradation efficiency of brilliant green (BG) and direct blue 5B (DB) owing to the powerful interaction of TENG and 3DGA@CDs-TNs photocatalyst. The power output of TENG can be applied for wastewater purification directly, which exhibits a self-powered electrocatalytic technology. Furthermore, the results also verify that TENG can replace conventional electric catalyst to remove pollutants effectively from wastewater without any consumption. Subsequently, the unstable fragments and the plausible removal pathways of the two pollutants are proposed. Our work sheds light on the development of efficient and sustainable TENG/photocatalyst system, opening up new opportunities and possibilities for comprehensive utilization of random energy.

19.
Biochem Pharmacol ; 193: 114767, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34537248

RESUMO

Homologous recombination repair (HRR) is crucial for genomic stability of cancer cells and is an attractive target in cancer therapy. Holliday junction (HJ) is a four-way DNA intermediate that performs an essential role in homology-directed repair. However, few studies about regulatory mechanisms of HJs have been reported. In this study, to better understand the biological effects of HJs, VE-822 was identified as an effective DNA HJ stabilizer to promote the assembly of HJs both in vitro and in cells. This compound could inhibit the HRR level, activate DNA-PKCS to trigger DNA damage response (DDR) and induce telomeric DNA damage via stabilizing DNA HJs. Furthermore, VE-822 was demonstrated to sensitize the osteosarcoma cells to doxorubicin (Dox) by enhancing DNA damage and cellular apoptosis. This work thus reports one novel HJ stabilizer, and provide a potential anticancer strategy through the modulation of DNA HJs.

20.
J Womens Health (Larchmt) ; 30(11): 1546-1555, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34448599

RESUMO

Objective: The outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens a surging number of community groups within society, including women actively breastfeeding. Breastfeeding involves intimate behaviors, a major transmission route of SARS-CoV-2, and is integral to the close mother-baby relationship highly correlated with maternal psychological status. Materials and Methods: Twenty-three pregnant women and puerperae with either confirmed or suspected diagnoses of COVID-19 were enrolled in the study. The clinical characteristics and outcomes of the mothers and neonates were recorded. The presence of SARS-CoV-2, IgG, and IgM in breast milk, maternal blood, and infant blood, together with feeding patterns, was assessed within 1 month after delivery. Feeding patterns and maternal psychological status were also recorded in the second follow-up. Results: No positive detection of SARS-CoV-2 was found in neonates. All breast milk samples were negative for the detection of SARS-CoV-2. The presence of IgM for SARS-CoV-2 in breast milk was correlated with IgM presence in the maternal blood. The results of IgG detection for SARS-CoV-2 were negative in all breast milk samples. All infants were in a healthy condition in two follow-ups, and antibody tests for SARS-CoV-2 were negative. The rate of breast milk feeding increased during two follow-ups. All mothers receiving a second follow-up experienced negative psychological factors and status. Conclusions: Our findings support the feasibility of breastfeeding in women infected with SARS-CoV-2. The additional negative psychological status of mothers due to COVID-19 should also be considered during the puerperium period.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Aleitamento Materno , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Laboratórios , Mães , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , SARS-CoV-2
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