Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 75
Filter
1.
J Org Chem ; 86(11): 7864-7871, 2021 06 04.
Article in English | MEDLINE | ID: mdl-34033489

ABSTRACT

A facile and metal-free method for the direct C(sp3)-H bond alkoxylation of 3-methylfuranocoumarins with alcohols has been disclosed. Selectfluor enabled the (hetero)benzylic C-H etherification by tuning the reaction temperature and solvent. Various alcohols were compatible in this transformation with suitable yields. The mechanistic studies revealed that the reaction might undergo the double addition process of alcohols, as well as the departure of a fluoride anion and the formation of an oxonium ion.


Subject(s)
Alcohols , Diazonium Compounds , Catalysis , Molecular Structure
2.
Analyst ; 146(12): 3971-3976, 2021 Jun 14.
Article in English | MEDLINE | ID: mdl-33997880

ABSTRACT

Depression is closely related to overactivation of N-methyl-d-aspartic acid (NMDA) receptors, and Zn2+ is a vital NMDA receptor modulator involved in the pathophysiological and physiological processes of depression. Therefore, quantitative and real-time detection of Zn2+ is very important for understanding the pathogenesis of depression. In this work, a near-infrared (NIR) fluorescent probe ISO-DPA was designed and synthesized for Zn2+ detection with a large Stokes shift (185 nm), high quantum yield (up to 44%), high sensitivity (LOD = 0.106 µM) and good pH stability. The probe showed rapid response within 10 s, accompanied by a distinct fluorescence change from faint to bright pink with the fluorescence intensity increasing 4.5-fold. Moreover, the sensing mechanism of ISO-DPA towards Zn2+ was supported by MALDI-TOF-MS and Job's plot. The probe ISO-DPA could detect instantaneous variation of exogenous and endogenous Zn2+ in PC12 cells. The bioimaging results reveal the increase of the endogenous Zn2+ concentration in PC12 cells under the oxidative stress induced by glutamate and confirm that overactivation of NMDA receptors results in an increase of the Zn2+ level. All the results proved that ISO-DPA is an excellent probe for detecting Zn2+ in solution and living cells and could help us better understand Zn2+ associated pathogenesis of depression.


Subject(s)
Depression , Fluorescent Dyes , Animals , Diagnostic Imaging , PC12 Cells , Rats , Zinc/toxicity
3.
Global Health ; 17(1): 32, 2021 03 29.
Article in English | MEDLINE | ID: mdl-33781286

ABSTRACT

BACKGROUND: The recent outbreak of COVID-19 has impacted adversely upon the mental health of millions of people worldwide. Impacts on the mental health conditions and the associated predictors relating to adults in Pakistan, the fifth most populous country in the world, during the COVID-19 remain understudied. Our aim was to investigate distress, anxiety, and overall mental health and their associated predictors among Pakistani adults in this pandemic. We specifically examine mental health issues based on the distance from the epicenter, (a predictor that has revealed opposing evidence in other countries) based on the theories of typhoon eye effect and ripple effect. The sample consisted of 601 adults who were surveyed online about 2.5 months into the outbreak across Pakistan with varying distances from the epicenter of COVID-19 of Karachi. RESULTS: The results showed that 9.2 and 19.0% of the participants surpassed the cut-off criteria for distress and anxiety disorders, respectively. Overall, the distance from the epicenter positively predicted the mental health of adults in Pakistan, and family size negatively moderated this effect. The distance from the epicenter negatively predicted distress and anxiety disorders for adults in large families, which are quite common in Pakistan. CONCLUSION: The evidence of the study interestingly finds that the prediction of the mental health of people by their distance from the epicenter depends on family size. The evidence of this study can help to provide initial indicators for mental health care providers to screen vulnerable groups in Pakistan, a populous country that continues struggling to cope with the COVID-19 pandemic.


Subject(s)
Anxiety/etiology , COVID-19/psychology , Family Characteristics , Mental Disorders/etiology , Mental Health , Pandemics , Stress, Psychological/etiology , Adaptation, Psychological , Adult , Aged , Anxiety Disorders/etiology , Cyclonic Storms , Female , Humans , Male , Middle Aged , Pakistan , Risk Factors , SARS-CoV-2 , Spatial Analysis , Surveys and Questionnaires , Young Adult
4.
Brain Behav Immun ; 87: 144-146, 2020 07.
Article in English | MEDLINE | ID: mdl-32387345

ABSTRACT

This study reports the physical health, mental health, anxiety, depression, distress, and job satisfaction of healthcare staff in Iran when the country faced its highest number of total active COVID-19 cases. In a sample of 304 healthcare staff (doctors, nurses, radiologists, technicians, etc.), we found a sizable portion reached the cutoff levels of disorders in anxiety (28.0%), depression (30.6%), and distress (20.1%). Age, gender, education, access to PPE (personal protective equipment), healthcare institutions (public vs. private), and individual status of COVID-19 infection each predicted some but not all the outcome variables of SF-12, PHQ-4, K6, and job satisfaction. The healthcare workers varied greatly in their access to PPE and in their status of COVID-19 infection: negative (69.7%), unsure (28.0%), and positive (2.3%). The predictors were also different from those identified in previous studies of healthcare staff during the COVID-19 crisis in China. This study helps to identify the healthcare staff in need to enable more targeted help as healthcare staff in many countries are facing peaks in their COVID-19 cases.


Subject(s)
Coronavirus Infections/psychology , Health Personnel/psychology , Pneumonia, Viral/psychology , Adult , Anxiety/psychology , Betacoronavirus/pathogenicity , COVID-19 , Female , Humans , Iran , Job Satisfaction , Male , Mental Health/trends , Middle Aged , Pandemics , Personal Protective Equipment/trends , Risk Factors , SARS-CoV-2
5.
Epidemiol Infect ; 148: e261, 2020 10 23.
Article in English | MEDLINE | ID: mdl-33092675

ABSTRACT

Although handwashing is an effective way to prevent infections, there is scarce evidence on predictors of handwashing during a pandemic. This paper aims to identify behavioural and demographic predictors of handwashing. The study surveyed 674 adults in Malaysia in May 2020 regarding whether the time spent on social media predicted handwashing contingent on gender and number of children. More time spent on social media was positively associated with handwashing for males with three or more children. However, for males without children, social media use was negatively associated with handwashing. The association was not significant for males with one or two children. For females, more time spent on social media was significantly linked to more handwashing only for females with one child. Gender, a traditional predictor of handwashing, was a useful predictor only for those who spent more than three hours per day on social media and had at most one child. Number of children was a novel negative predictor for males who did not use social media and who averaged one hour per day on social media, a positive predictor for males who spent lots of time on social media, but not a predictor for females. In sum, social media use predicts handwashing, and is thus a helpful variable for use in targeted health communication during a pandemic - particularly through social media. Further, more conventional predictors like gender and number of children exhibit contingency effects with social media use.


Subject(s)
Coronavirus Infections/epidemiology , Hand Disinfection , Pneumonia, Viral/epidemiology , Social Media , Adult , Betacoronavirus , COVID-19 , Family Characteristics , Female , Humans , Malaysia , Male , Middle Aged , Pandemics , SARS-CoV-2 , Young Adult
6.
Anal Chem ; 91(18): 11946-11951, 2019 09 17.
Article in English | MEDLINE | ID: mdl-31423770

ABSTRACT

Sulfur dioxide (SO2) plays significant roles in regulating cell apotosis and inflammation. However, there are complex interactions between small biomolecules in cells, and the identification of these coexisting biomarkers remains a challenge. Herein, we report an AND logic gate based fluorescent probe (NY-Lyso), operating by responding to pH differences between organelles in cell and selectively reacting with bisulfite (HSO3-). This approach allows the fluorescence of the probe to remain silent under neutral or alkaline conditions, notably, is activated by costimulation of lower pH and bisulfite. Furthermore, it was confirmed to be biocompatible and could be employed to monitor HSO3- in lysosomes of living cells. The proposed method demonstrated more practical and outstanding capabilities in targeted and real-time monitoring, providing an effective optical tool for biomarker sensing.


Subject(s)
Fluorescent Dyes/chemistry , Naphthalimides/chemistry , Sulfites/analysis , Cell Survival , Fluorescent Dyes/chemical synthesis , HeLa Cells , Humans , Hydrogen-Ion Concentration , Lysosomes/chemistry , Molecular Structure , Naphthalimides/chemical synthesis
7.
Bioorg Med Chem ; 27(13): 2871-2882, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31126820

ABSTRACT

Betulinic acid (BA), a pentacyclic triterpenoid, exhibits broad spectrum antiproliferative activity, but generally with only modest potency. To improve BA's pharmacological properties, fluorine was introduced as a single atom at C-2, creating two diastereomers, or in a trifluoromethyl group at C-3. We evaluated the impact of these groups on antiproliferative activity against five human tumor cell lines. A racemic 2-F-BA (compound 6) showed significantly improved antiproliferative activity, while each diastereomer exhibited similar effects. We also demonstrated that 2-F-BA is a topoisomerase (Topo) I and IIα dual inhibitor in cell-based and cell-free assays. A hypothetical mode of binding to the Topo I-DNA suggested a difference between the hydrogen bonding of BA and 2-F-BA to DNA, which may account for the difference in bioactivity against Topo I.


Subject(s)
Triterpenes/chemistry , Triterpenes/chemical synthesis , Cell Proliferation , Humans , Molecular Structure , Pentacyclic Triterpenes , Betulinic Acid
8.
J Phys Chem A ; 123(7): 1285-1294, 2019 Feb 21.
Article in English | MEDLINE | ID: mdl-30688461

ABSTRACT

Graphene oxide (GO) has obvious desensitizing effect on the thermal decomposition of energetic materials such as HMX, CL-20, etc. 4,4'-Azo-1,2,4-triazole (ATRZ) is known as a new type of energetic material with high N content; the underlying thermal decomposition mechanism of graphene oxide-ATRZ (GO-ATRZ) complex with low sensitivity has not been studied. The present work studies the thermal decomposition mechanisms of GO, ATRZ,and the GO-ATRZ complex (the number of carboxyl groups on GO:ATRZ = 2:1) by the ReaxFF molecular reactive dynamic simulations and kinetics calculations. As a result, it has been found that the main decomposition pathway of GO is the exfoliation of hydroxyl and carboxyl groups on the graphene sheet, whereas ATRZ breaks its five-membered ring as the main decomposition path, and the ring further decomposes into small molecules, such as CHN, N2, HN2, H2N2, etc. The major effect of GO on ATRZ is probably derived from the stable graphene sheet, which has a space effect on ATRZ, and the strong oxidizing hydroxyl groups produced during GO decomposition, which results in the formation of CON and CHON. By calculating the activation energy of N2 generation in the reactions, it can be concluded that the addition of GO can increase the decomposition activation energy of ATRZ (41.1 kJ·mol-1) in comparison with that of its pure substance (25.0 kJ·mol-1). Therefore, GO can be combined with ATRZ as a desensitizer where GO can improve the molecular stability of ATRZ.

9.
Org Biomol Chem ; 16(11): 1912-1920, 2018 03 14.
Article in English | MEDLINE | ID: mdl-29487929

ABSTRACT

A novel and efficient regioselective C-H fluorination of 8-aminoquinoline amides and sulfonamides at the C5 position was achieved. Using Selectfluor as a "F" reagent and HOAc as an additive, the reaction proceeds smoothly via a radical pathway. This method features metal-free conditions, a broad substrate scope and operational simplicity.

10.
Hum Mol Genet ; 24(20): 5855-66, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26231219

ABSTRACT

Epigenetic modifications such as cytosine methylation and histone modification are linked to the pathology of ischemic brain injury. Recent research has implicated 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (Tet) enzymes, in DNA methylation-related plasticity. Here we show that 5hmC abundance was increased after ischemic injury, and Tet2 was responsible for this increase; furthermore, inhibiting Tet2 expression abolished the increase of 5hmC caused by ischemic injury. The decrease in 5hmC modifications from inhibiting Tet2 activity was accompanied by increased infarct volume after ischemic injury. Genome-wide profiling of 5hmC revealed differentially hydroxymethylated regions (DhMRs) associated with ischemic injury, and DhMRs were enriched among the genes involved in cell junction, neuronal morphogenesis and neurodevelopment. In particular, we found that 5hmC modifications at the promoter region of brain-derived neurotrophic factor (BDNF) increased, which was accompanied by increased BDNF mRNA, whereas the inhibition of Tet2 reduced BDNF mRNA and protein expression. Finally, we show that the abundance of 5hmC in blood samples from patients with acute ischemic stroke was also significantly increased. Together, these data suggest that 5hmC modification could serve as both a potential biomarker and a therapeutic target for the treatment of ischemic stroke.


Subject(s)
Brain Ischemia/metabolism , Cytosine/analogs & derivatives , DNA Methylation , DNA-Binding Proteins/metabolism , Proto-Oncogene Proteins/metabolism , Reperfusion Injury/metabolism , 5-Methylcytosine/metabolism , Animals , Brain Ischemia/genetics , Brain Ischemia/physiopathology , Brain-Derived Neurotrophic Factor/genetics , Cytosine/metabolism , Dioxygenases , Epigenesis, Genetic , Male , Mice , Promoter Regions, Genetic , Reperfusion Injury/genetics
11.
Int J Neurosci ; 127(5): 448-453, 2017 May.
Article in English | MEDLINE | ID: mdl-27211852

ABSTRACT

PURPOSE: Fabry disease is an X-linked genetic disorder caused by the mutations of α-galactosidase A (GLA, MIM 300644) gene presenting with various clinical symptoms including small-fiber peripheral neuropathy and limb burning pain. Here, we reported a Chinese pedigree with the initial diagnosis of primary erythromelalgia in an autosomal dominant (AD)-inherited pattern. METHODS: Mutation analysis of SCN9A and GLA genes by direct sequencing and functional analysis of a novel mutation of GLA in cells were performed. RESULTS: Our data did not show any pathological mutations in SCN9A gene; however, a novel missense mutation c.139T>C (p.W47R) of GLA was identified in a male proband as well as two female carriers in this family. Enzyme assay of α-galactosidase A activity showed deficient enzyme activity in male patients and female carriers, further confirming the diagnosis of Fabry disease. Finally, a functional analysis indicated that the replacement of the 47th amino acid tryptophan (W47) with arginine (W47R) or glycine (W47G) led to reduced activity of α-galactosidase A in 293T cells. Therefore, these findings demonstrated that the novel mutation p.W47R of GLA is the cause of Fabry disease. CONCLUSIONS: Because Fabry disease and primary erythromelalgia share similar symptoms, it is a good strategy for clinical physicians to perform genetic mutation screenings on both SCN9A and GLA genes in those patients with limb burning pain but without a clear inheritant pattern.


Subject(s)
Erythromelalgia/physiopathology , Fabry Disease/genetics , Family Health , Mutation/genetics , alpha-Galactosidase/genetics , China , DNA Mutational Analysis , Female , HEK293 Cells , Humans , Male , Phenotype , Transfection
13.
Biomacromolecules ; 17(6): 2120-7, 2016 06 13.
Article in English | MEDLINE | ID: mdl-27169722

ABSTRACT

Photoactivated therapy has become a complementary and attractive modality for traditional cancer treatment. Herein, we demonstrated a novel single-stimulus dual-drug sensitive nanoplatform, Cur-loaded Dex-Pt(N3) nanoparticles (Cur@DPNs) for enhanced photoactivated therapy. The developed Cur@DPNs could be photoactivated by UVA light to simultaneously generate instant reactive oxygen species from Cur for fast photodynamic therapy and release lasting Pt(II) from Pt(N3) for long-acting photochemotherapy. Compared with small free drugs and individual photoactivated therapy, Cur@DPNs exhibited enhanced photoactivated cytotoxicity and in vivo antitumor efficacy with low systemic toxicity accompanied. Therefore, the single-stimulus dual-drug sensitive nanoplatform is convinced to be a promising strategy for multidrug delivery, site-selective and combinational photoactivated therapy in the near future.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/prevention & control , Drug Carriers/chemistry , Drug Delivery Systems , Liver Neoplasms/prevention & control , Nanoparticles/administration & dosage , Photochemotherapy , Apoptosis/drug effects , Carcinoma, Hepatocellular/pathology , Cisplatin/pharmacology , Curcumin/pharmacology , Humans , Liver Neoplasms/pathology , Nanoparticles/chemistry , Photosensitizing Agents/administration & dosage , Reactive Oxygen Species/metabolism , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
14.
Bioorg Med Chem Lett ; 26(1): 68-71, 2016 Jan 01.
Article in English | MEDLINE | ID: mdl-26598461

ABSTRACT

Several fluorinated derivatives of the anti-HIV maturation agent bevirimat (1) were synthesized and evaluated for anti-HIV replication activity. The modified positions were the C-2, C-3, C-28, and C-30 positions, either directly on the betulinic acid (2) skeleton or in the attached side chains. Compound 18, which has a trifluoromethyl group added to C-30 of its isopropenyl group, exhibited similar potency to 1 against HIV-1NL4-3. In total, our current studies support our prior conclusion that C-30 allylic modification is unlikely to be a pharmacophore for anti-HIV activity, but could be a meaningful route to manipulate other properties of 2-related compounds.


Subject(s)
Anti-HIV Agents/pharmacology , HIV/drug effects , Triterpenes/pharmacology , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/chemistry , Dose-Response Relationship, Drug , Halogenation , Microbial Sensitivity Tests , Molecular Conformation , Pentacyclic Triterpenes , Structure-Activity Relationship , Triterpenes/chemical synthesis , Triterpenes/chemistry , Virus Replication/drug effects , Betulinic Acid
16.
J Neurosci Res ; 92(10): 1252-8, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24861203

ABSTRACT

White matter tracts are composed of axons and myelinating oligodendrocytes. Oligodendrocytes are the myelinating cells in the central nervous system that allow formation of myelin and saltatory nerve conduction. Cerebral white matter is highly vulnerable to ischemic injury in adults and neonates. White matter injury in newborn brains results in cerebral palsy and cognitive disability. In this study, we found that XAV939, a small-molecular inhibitor that stimulated ß-catenin degradation by stabilizing axin, protected against serum and glucose deprivation (SGD)-induced cell death in oligodentrocyte cell line OLN-93 cells in a concentration-dependent manner. We further showed that XAV939 reduced caspase-3 and caspase-8 levels and increased the expression of phosphorylated Akt in SGD-induced OLN-93 cells. Our data demonstrate that XAV939 protects against neonatal hypoxic/ischemic injury. In summary, our results demonstrate that XAV939 confers neuroprotection against SGD-induced injury in OLN-93 cells via its antiapoptotic activity and the loss of oligodendrocytes and neurons in neonatal hypoxic/ischemic injury.


Subject(s)
Brain Infarction/prevention & control , Heterocyclic Compounds, 3-Ring/pharmacology , Oligodendroglia/drug effects , Animals , Animals, Newborn , Apoptosis/drug effects , Brain Infarction/etiology , Brain Infarction/pathology , Brain Ischemia/complications , Brain Ischemia/pathology , Caspases/metabolism , Cell Line, Transformed , Cells, Cultured , Chromones/pharmacology , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Heterocyclic Compounds, 3-Ring/therapeutic use , Morpholines/pharmacology , Neurons/drug effects , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Rats , Rats, Sprague-Dawley , Serum/metabolism , Time Factors , beta Catenin/metabolism
17.
Neurochem Res ; 39(2): 269-75, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24343531

ABSTRACT

Daphnetin (DAP), a coumarin derivative, has been reported to have multiple pharmacological actions including analgesia, antimalarial, anti-arthritic, and anti-pyretic properties. It is unclear whether DAP has neuroprotective effects on ischemic brain injury. In this study, we found that DAP treatment (i.c.v.) reduced the infarct volume at 24 h after ischemia/reperfusion injury and improved neurological behaviors in a middle cerebral artery occlusion mouse model. Moreover, we provided evidences that DAP had protective effects on infarct volume in neonate rats even it was administrated at 4 h after cerebral hypoxia/ischemia injury. To explore its neuroprotective mechanisms of DAP, we examined the protection of DAP on glutamate toxicity-induced cell death in hippocampal HT-22 cells. Our results demonstrated that DAP protected against glutamate toxicity in HT-22 cells in a concentration-dependent manner. Further, we found that DAP maintained the cellular levels of glutathione and superoxide dismutase activity, suggesting the anti-oxidatant activity of DAP. Since DAP has been used for the treatment of coagulation disorder and rheumatoid arthritis for long time with a safety profile, DAP will be a promising agent for the treatment of stroke.


Subject(s)
Brain Ischemia/prevention & control , Glutamic Acid/toxicity , Hippocampus/drug effects , Neuroprotective Agents/pharmacology , Umbelliferones/pharmacology , Animals , Animals, Newborn , Cell Death/drug effects , Cell Line , Disease Models, Animal , Glutathione/metabolism , Hippocampus/enzymology , Hippocampus/metabolism , Hippocampus/pathology , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/pathology , Male , Mice , Mice, Inbred ICR , Rats , Superoxide Dismutase/metabolism
18.
Front Pharmacol ; 15: 1417951, 2024.
Article in English | MEDLINE | ID: mdl-39086389

ABSTRACT

Introduction: Eplerenone is approved for the treatment of hypertension as well as symptomatic heart failure with reduced ejection fraction (HFrEF) following an acute myocardial infarction. However, the adverse events (AEs) have not been systematically analyzed. The aim of this study was to identify adverse drug reactions (ADRs) related to eplerenone using the FDA Adverse Event Reporting System (FAERS) database. By identifying previously unreported AEs, the study could potentially contribute to updating the drug's label. Methods: In order to find significant AEs, four algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Empirical Bayesian Geometric Mean (EBGM), were used to analyze the signal strength of the ADRs connected to eplerenone that were gathered from the FAERS database over the previous 20 years. Results: From 2004Q1 to 2023Q4, a total of 20, 629, 811 reported cases were gathered from the FAERS database for this study. After processing the data and filtering, 1,874 case reports were analyzed. Of these cases, 1,070 AEs were identified, 128 of which were eplerenone-related ADRs. We investigated the occurrence of ADRs induced by eplerenone in 27 organ systems. Our study showed that the AEs listed in the medication's package insert correspond with those listed in the literature, including hyperkalemia and increased creatinine. Additionally, the prescription label for eplerenone does not include all system organ class (SOC) terms, like Vascular disorders, hepatobiliary Disorders, etc. Discussion: The study used multiple algorithms to quantify the signal strength and then identified any previously unrecognized ADRs, further studies are needed to confirm the association of ADRs with eplerenone. The findings of this study may provide important insights into the safety profile of eplerenone, ensure that healthcare providers have up-to-date information about their potential risks and help guide them in the correct use of the drug.

19.
J Imaging Inform Med ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020152

ABSTRACT

Superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery represents the primary treatment for Moyamoya disease (MMD), with its efficacy contingent upon collateral vessel development. This study aimed to develop and validate a machine learning (ML) model for the non-invasive assessment of STA-MCA bypass surgery efficacy in MMD. This study enrolled 118 MMD patients undergoing STA-MCA bypass surgery. Clinical features were screened to construct a clinical model. MRI features were extracted from the middle cerebral artery supply area using 3D Slicer and employed to build five ML models using logistic regression algorithm. The combined model was developed by integrating the radiomics score (Rad-score) with the clinical features. Model performance validation was conducted using ROC curves. Platelet count (PLT) was identified as a significant clinical feature for constructing the clinical model. A total of 3404 features (851 × 4) were extracted, and 15 optimal features were selected from each MRI sequence as predictive factors. Multivariable logistic regression identified PLT and Rad-score as independent parameters used for constructing the combined model. In the testing set, the AUC of the T1WI ML model [0.84 (95% CI, 0.70-0.97)] was higher than that of the clinical model [0.66 (95% CI, 0.46-0.86)] and the combined model [0.80 (95% CI, 0.66-0.95)]. The T1WI ML model can be used to assess the postoperative efficacy of STA-MCA bypass surgery for MMD.

20.
J Exp Clin Cancer Res ; 43(1): 231, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39155374

ABSTRACT

BACKGROUND: Glioblastoma (GB) is recognized as one of the most aggressive brain tumors, with a median survival of 14.6 months. However, there are still some patients whose survival time was greater than 3 years, and the biological reasons behind this clinical phenomenon arouse our research interests. By conducting proteomic analysis on tumor tissues obtained from GB patients who survived over 3 years compared to those who survived less than 1 year, we identified a significant upregulation of SelK in patients with shorter survival times. Therefore, we hypothesized that SelK may be an important indicator related to the occurrence and progression of GBM. METHODS: Proteomics and immunohistochemistry from GB patients were analyzed to investigate the correlation between SelK and clinical prognosis. Cellular phenotypes were evaluated by cell cycle analysis, cell viability assays, and xenograft models. Immunoblots and co-immunoprecipitation were conducted to verify SelK-mediated ubiquitin-dependent degradation of CDK4. RESULTS: SelK was found to be significantly upregulated in GB samples from short-term survivors (≤ 1 year) compared to those from long-term survivors (≥ 3 years), and its expression levels were negatively correlated with clinical prognosis. Knocking down of SelK expression reduced GB cell viability, induced G0/G1 phase arrest, and impaired the growth of transplanted glioma cells in nude mice. Down-regulation of SelK-induced ER stress leads to a reduction in the expression of SKP2 and an up-regulation of ß-TrCP1 expression. Up-regulation of ß-TrCP1, thereby accelerating the ubiquitin-dependent degradation of CDK4 and ultimately inhibiting the malignant proliferation of the GB cells. CONCLUSION: This study discovered a significant increase in SelK expression in GB patients with poor prognosis, revealing a negative correlation between SelK expression and patient outcomes. Further mechanistic investigations revealed that SelK enhances the proliferation of GB cells by targeting the endoplasmic reticulum stress/SKP2/ß-TrCP1/CDK4 axis.


Subject(s)
Cell Proliferation , Cyclin-Dependent Kinase 4 , Glioblastoma , Animals , Female , Humans , Male , Mice , Middle Aged , beta-Transducin Repeat-Containing Proteins/metabolism , beta-Transducin Repeat-Containing Proteins/genetics , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Cell Line, Tumor , Cyclin-Dependent Kinase 4/metabolism , Glioblastoma/metabolism , Glioblastoma/pathology , Glioblastoma/genetics , Mice, Nude , Prognosis , Proteolysis , Ubiquitin/metabolism , Ubiquitination , Selenoproteins/genetics , Selenoproteins/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL