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1.
Microvasc Res ; 139: 104253, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520773

RESUMO

Chalcones and sulfonamides are well-known chemical groups associated with several biological activities such as antibiotic, anti-inflammatory, and antitumor activities. Over the past few decades, a series of sulfonamide-chalcone hybrids have been synthesized and assessed to develop compounds with interesting biological properties for application in disease therapy. In the present study, a new sulfonamide-chalcone hybrid µ - (2,5-dichloro-N-{4-[(3E)-4-(3-nitrophenyl) buta-1,3-dien-2-yl] phenyl} benzene sulfonamide), or simply CL185, was synthesized, and its angiogenic activity was assessed using the chick embryo chorioallantoic membrane (CAM) assay at different concentrations (12.5, 25, and 50 µg/µL). To further investigate the role of CL185 in the angiogenic process, we evaluated the levels of vascular endothelial growth factor (VEGF) in all treated CAMs. The results showed that all concentrations of CL185 significantly increased tissue vascularization (p < 0.05) as well as the parameters associated with angiogenesis, in which inflammation was the most marked phenomenon observed. In all CAMs treated with CL185, VEGF levels were significantly higher than those in the negative control (p < 0.05), and at the highest concentration, VEGF levels were even higher than in the positive control (p < 0.05). The pronounced angiogenic activity displayed by CL185 may be related to the increase in VEGF levels that were stimulated by inflammatory processes observed in our study. Therefore, CL185 presents a favorable profile for the development of drugs that can be used in pro-angiogenic and tissue repair therapies.

2.
Science ; 373(6561): 1344-1348, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34529472

RESUMO

[Figure: see text].

3.
J Inorg Biochem ; 225: 111599, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34507123

RESUMO

With increasing world population, life-span of humans and spread of viruses, myriad of diseases in human beings are becoming more and more common. Because of the interesting chemical and framework versatility and porosity of metal organic frameworks (MOFs) they find application in varied areas viz. catalysis, sensing, metal ion/gas storage, chemical separation, drug delivery, bio-imaging. This subclass of coordination polymers having interesting three-dimensional framework exhibits inordinate potential and hence may find application in treatment and cure of cancer, diabetes Alzheimer's and other diseases. The presented review focuses on the diverse mechanism of action, unique biological activity and advantages of copper-based metal organic framework (MOF) nanomaterials in medicine. Also, different methods used in the treatment of cancer and other diseases have been presented and the applications as well as efficacy of copper MOFs have been reviewed and discussed. Eventually, the current-status and potential of copper based MOFs in the field of anti-inflammatory, anti-bacterial and anti-cancer therapy as well as further investigations going on for this class of MOF-based multifunctional nanostructures in for developing new nano-medicines have been presented.

4.
J Int Med Res ; 49(9): 3000605211042975, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34510961

RESUMO

OBJECTIVE: The aim of this study was to identify and validate ferroptosis-related markers in ulcerative colitis (UC) to explore new directions for UC diagnosis and treatment. METHODS: We screened UC chips and ferroptosis-related genes from the Gene Expression Omnibus (GEO), FerrDb, and GeneCards databases. The differentially expressed genes (DEGs) and ferroptosis-related DEGs between the UC group and normal controls were analyzed using bioinformatics methods. Enrichment analysis, protein-protein interaction analysis, and hub genes were screened. Peripheral blood chip and animal experiments were used to validate the ferroptosis-related hub genes. Finally, hub gene-transcription factor, hub gene-microRNA (miRNA), and hub gene-drug interaction networks were constructed. RESULTS: Overall, 26 ferroptosis-related DEGs were identified that were significantly enriched in energy pathways and metabolism. We identified ten ferroptosis-related hub genes from the protein-protein interaction network: IL6, PTGS2, HIF1A, CD44, MUC1, CAV1, NOS2, CXCL2, SCD, and ACSL4. In the peripheral blood chip GSE94648, CD44 and MUC1 were upregulated, which was consistent with the expression trend in GSE75214. Animal experiments showed that CD44 expression was significantly increased in the colon. CONCLUSIONS: Our findings indicate that CD44 and MUC1 may be ferroptosis-related markers in UC.


Assuntos
Colite Ulcerativa , Ferroptose , Animais , Colite Ulcerativa/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Mapas de Interação de Proteínas
5.
Redox Biol ; 46: 102130, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34517184

RESUMO

Peroxiredoxin 6 (PRDX6), as a bifunctional enzyme with glutathione peroxidase activity (GPx) and Ca2+-independent phospholipase A2 (iPLA2) activity, has a higher expression in various cancer cells, which leads to the increase of antioxidant properties and promotes tumorigenesis. However, only a few inhibitors of PRDX6 have been discovered to date, especially the covalent inhibitors of PRDX6. Here, we firstly identified Withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PRDX6. SILAC-ABPP identified that WA could directly bind to PRDX6 and inactivate the enzyme activity of PRDX6 by the α, ß-unsaturated ketone moiety. Moreover, WA also facilitated the generation of ROS, and inhibited the GPx and iPLA2 activities. However, WA-1, with a reduced α, ß-unsaturated ketone moiety, had no significant inhibition of the GPx and iPLA2 activities. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selectively covalent binding of WA to the cysteine 47 residue (Cys47) of PRDX6, while mutation of Cys47 blocked the binding of WA to PRDX6. Notably, WA-mediated cytotoxicity and inhibition of the GPx and iPLA2 activities were almost abolished by the deficiency of PRDX6. Therefore, this study indicates that WA is a novel PRDX6 covalent inhibitor, which could covalently bind to the Cys47 of PRDX6 and holds great potential in developing anti-tumor agents for targeting PRDX6.

6.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34502195

RESUMO

Signal transducers and activators of transcription 3 (STAT3) acts as a transcriptional signal transducer, converting cytokine stimulation into specific gene expression. In tumor cells, aberrant activation of the tyrosine kinase pathway leads to excessive and continuous activation of STAT3, which provides further signals for tumor cell growth and surrounding angiogenesis. In this process, the tumor-associated protein Annexin A2 interacts with STAT3 and promotes Tyr705 phosphorylation and STAT3 transcriptional activation. In this study, we found that (20S) ginsenoside Rh2 (G-Rh2), a natural compound inhibitor of Annexin A2, inhibited STAT3 activity in HepG2 cells. (20S) G-Rh2 interfered with the interaction between Annexin A2 and STAT3, and inhibited Tyr705 phosphorylation and subsequent transcriptional activity. The inhibitory activity of STAT3 leaded to the negative regulation of the four VEGFs, which significantly reduced the enhanced growth and migration ability of HUVECs in co-culture system. In addition, (20S)G-Rh2 failed to inhibit STAT3 activity in cells overexpressing (20S)G-Rh2 binding-deficient Annexin A2-K301A mutant, further proving Annexin A2-mediated inhibition of STAT3 by (20S)G-Rh2. These results indicate that (20S)G-Rh2 is a potent inhibitor of STAT3, predicting the potential activity of (20S)G-Rh2 in targeted therapy applications.

7.
Taiwan J Obstet Gynecol ; 60(5): 905-906, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34507671

RESUMO

OBJECTIVE: We present prenatal diagnosis of a familial 9p12 amplification inherited from a father carrier. CASE REPORT: A 38-year-old, gravida 3, para 2, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a heteromorphic variant of chromosome 9 with a 9p12 amplification on G-band preparations, but it was negative on C-band preparations. Cytogenetic analysis of the parents revealed that the phenotypically normal father carried the same euchromatic 9p + polymorphism. Array comparative genomic hybridization analysis on the DNA extracted from the father's blood revealed no genomic imbalance. At 37 weeks of gestation, a healthy 2760-g female baby was delivered with no phenotypic abnormality. She was doing well at age one year during follow-up. CONCLUSION: Prenatal diagnosis of a 9p + variant can be a euchromatic chromosome variant of a familial 9p12 amplification without phenotypic consequences.

8.
Taiwan J Obstet Gynecol ; 60(5): 962, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34507691
9.
Food Res Int ; 148: 110630, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34507774

RESUMO

The feasibility was investigated of 4D printing of lotus root gel compounded with a pigment that responds to pH change and alters colour. The pigment comprised of a combination of anthocyanins and lemon yellow; it was used in gel preparation for printing. The flowability and self-support properties of the lotus root-pigment gel were studied to evaluate its 3D printing performance. The gel viscosity decreased with the increase of printing temperature over the range 40, 50, and 60 °C. The gel with a ratio (lotus root powder/compound pigment) of 0.35 extruded smoothly and maintained high formability at temperatures below 60 °C. The pH response of compound pigment enabled the printed sample to change colour from reddish/yellowish to green after spraying with NaHCO3. The a* and b* values decreased significantly (p < 0.05) after spraying for 1 min. The gel with ratios of 0.30 and 0.35 achieved rapid colour change both superficially and internally. Through several different model designs (apple, Christmas tree, letters, and Chinese characters), high-quality 4D printing could be realized without problem. Thus, lotus root gel can be mixed with suitable pigments in correct proportion for 4D printing at appropriate temperature to ensure good flowability.

10.
Int J Biol Macromol ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509521

RESUMO

In this study, cattail was researched as a natural cellulose source to extract cellulose. Dewaxing, alkali and bleaching treatments were carried out for the cattail fibers (CFs). The FTIR, SEM and XRD results indicated that hemicellulose and lignin were successfully removed from the CFs, and the content of cattail cellulose increased from 41.66 ±â€¯1.11% to 89.72 ±â€¯1.07%. Subsequently, cellulose aerogel was prepared by the extracted cattail cellulose. The Zeolitic imidazolate framework-8 (ZIF-8) was uniformly loaded onto the surface of cellulose aerogel by the in situ growth, and ZIF-8 Cattail Cellulose Aerogel (ZCCA) was finally prepared. The SEM, FTIR, XRD and TGA results further confirmed the successful preparation of ZCCA. Additionally, the results of the adsorption experiment showed that ZCCA had excellent adsorption performance for enrofloxacin, and the maximum adsorption capacity of enrofloxacin reached 172.09 mg·g-1 while showing good reusability. The adsorption process followed the pseudo-second-order kinetic model and the Langmuir isotherm model. Thermodynamic studies showed that the adsorption of enrofloxacin was a spontaneous endothermic reaction and that the adsorption mechanism involves the interaction of hydrogen bonds, electrostatic and π-π stacking.

11.
J Neurosci Res ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510531

RESUMO

Cognitive impairments are characteristics of patients with white matter hyperintensities (WMHs), and hypoperfusion is currently a relatively recognized mechanism of WMHs. Brain activity is closely coupled to the regulation of local blood flow. This study aimed to investigate the abnormal local brain activity of patients with WMHs from the viewpoint of the static amplitude of low-frequency fluctuations (sALFF) and dynamic amplitude of low-frequency fluctuations (dALFF). Seventy-four patients with WMHs and 35 healthy controls (HCs) were included. Based on the Fazekas scale, patients with WMHs were further divided into a mild WMH group (n = 33, Fazekas score 1-2) and moderate-severe WMH group (n = 41, Fazekas score 3-6). The sALFF and dALFF values were calculated separately and neuropsychological tests including the Montreal Cognitive Assessment (MoCA), Auditory Verbal Learning Test (AVLT), Trail Making Test (TMT), and Boston Naming Test (BNT) were completed by all participants. Patients with WMHs showed increased sALFF and dALFF values in the bilateral thalamus and decreased performance in the MoCA test, AVLT-immediate, AVLT-delay, AVLT-recognition, TMT-A, and BNT. The dALFF values in the bilateral thalamus was correlated with the MoCA in HCs. The sALFF values in the bilateral thalamus correlated with TMT-B in patients with WMHs. Patients with WMHs showed abnormal brain activity and decreased functional stability of the bilateral thalamus, which may be a potential mechanism of decreased executive function.

12.
Circ Res ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515499

RESUMO

Rationale: Timely inhibition of inflammation and initiation of resolution are important to repair injured tissues. Mammalian STE20-like protein kinase 1/2 (MST1/2) acts as a regulator of macrophage-associated immune responses to bacterial infections. However, the role of MST1/2 in regulating macrophage phenotype and function in myocardial infarction (MI) remains unclear. Objective: To determine the function and underlying mechanism of macrophage MST1/2 in cardiac repair post-MI. Methods and Results: Using LysMCre-mediated Mst1/2-deficient mice, we found that MST1 deficiency exacerbated cardiac dysfunction after MI. Single-cell RNA sequencing assay indicated that the effect was attributed to a shift of macrophage subtypes from those expressing Cxcl2 and Cd163 toward Ccl2 and Ccl4 expression. Mass spectrometry identified leukotriene B4 (LTB4) as the lipid mediator that was upregulated in the absence of MST1. We found that MST1 phosphorylated 5-lipoxygenase (5-LOX) at its T218 residue, disrupting the interaction between 5-LOX and 5-LOX-activating protein, resulting in a reduction of LTB4 production. In contrast, a 5-LOXT218A variant showed no response to MST1. Moreover, treatment of peritoneal macrophages with LTB4 or medium conditioned by Mst1-deficient macrophages resulted in high Ccl2 and Ccl4 expression and low Cxcl2 and Cd163 expression, except when the cells were co-treated with the LTB4 receptor 1 (BLT1) antagonist CP105696. Furthermore, CP105696 ameliorated cardiac dysfunction in LysMCre-mediated Mst1/2-deficient mice and enhanced cardiac repair in wild-type mice treated with XMU-MP-1 after MI. Conclusions: Taken together, our results demonstrate that inhibition of MST1/2 impaired post-MI repair through activating macrophage 5-LOX-LTB4-BLT1 axis.

13.
Food Chem ; 369: 130971, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34488130

RESUMO

A highly sensitive molecularly imprinted surface-enhanced Raman scattering (SERS) sensor was developed for selective detection of histamine. A combination of two semiconductors and Ag nanoparticles (NPs) was used as the SERS substrate. The SERS was induced by Ag NPs plasmon resonances as well as charge-transfer between the semiconductors and the Ag NPs. The Raman intensity and the logarithm of the histamine concentration were linear over the range 10-8-10-3 mol L-1. The sensor exhibited good selectivity and had a sensitivity limit of 3.088 × 10-9 mol L-1. Histamine was detected in a spiked liquor sample, and its recoveries were in the range of 89.89%-109.18%.

14.
Front Endocrinol (Lausanne) ; 12: 717544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512549

RESUMO

Liver-expressed antimicrobial peptide 2 (LEAP-2), originally described as an antimicrobial peptide, has recently been recognized as an endogenous blocker of growth hormone secretagogue receptor 1a (GHS-R1a). GHS-R1a, also known as ghrelin receptor, is a G protein-coupled receptor (GPCR) widely distributed on the hypothalamus and pituitary gland where it exerts its major functions of regulating appetite and growth hormone (GH) secretion. The activity of GHS-R1a is controlled by two counter-regulatory endogenous ligands: Ghrelin (activation) and LEAP-2 (inhibition). Ghrelin activates GHS-R1a on the neuropeptide Y/Agouti-related protein (NPY/AgRP) neurons at the arcuate nucleus (ARC) to promote appetite, and on the pituitary somatotrophs to stimulate GH release. On the flip side, LEAP-2, acts both as an endogenous competitive antagonist of ghrelin and an inverse agonist of constitutive GHS-R1a activity. Such a biological property of LEAP-2 vigorously blocks ghrelin's effects on food intake and hormonal secretion. In circulation, LEAP-2 displays an inverse pattern as to ghrelin; it increases with food intake and obesity (positive energy balance), whereas decreases upon fasting and weight loss (negative energy balance). Thus, the LEAP-2/ghrelin molar ratio fluctuates in response to energy status and modulation of this ratio conversely influences energy intake. Inhibiting ghrelin's activity has shown beneficial effects on obesity in preclinical experiments, which sheds light on LEAP-2's anti-obesity potential. In this review, we will analyze LEAP-2's effects from a metabolic point of view with a focus on metabolic hormones (e.g., ghrelin, GH, and insulin), and discuss LEAP-2's potential as a promising therapeutic target for obesity.

15.
Front Immunol ; 12: 670040, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512623

RESUMO

Worldwide, non-small cell lung cancer (NSCLC) has the highest morbidity and mortality of all malignancies. The lack of responsiveness to checkpoint inhibitors is a central problem in the modern era of cancer immunotherapy, with the rapid development of immune checkpoint inhibitors (ICIs) in recent years. The human switch/sucrose nonfermentable (SWI/SNF) chromatin-remodeling complex has been reported to be recurrently mutated in patients with cancer, and those with SWI/SNF mutations have been reported to be sensitive to ICIs. Six reported cohorts, a total of 3416 patients, were used to analyze the mutation status of ARID1A, ARID1B, ARID2 and SMARCA4 in patients with NSCLC and the effect of mutations on prognosis after ICIs. Finally, a nomogram was established to guide the clinical use of ICIs. The results show that patients with NSCLC who have ARID1A, ARID1B, and ARID2 mutations of the SWI/SNF complex were more likely to benefit from ICI therapy.

16.
Ann Med ; 53(1): 1621-1631, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34498502

RESUMO

PURPOSES: There is increasing concern regarding cardiovascular risk in non-alcoholic fatty liver disease (NAFLD) patients with liver fibrosis. This study aims: (1) to assess the association between NAFLD and liver fibrosis status and the development of carotid plaque (CP), and (2) to identify CP risk factors among general population with different baseline NAFLD and liver fibrosis status. METHODS: This retrospective cohort study included 14,288 adult participants who went for regular health check-ups between 2014 and 2019, in one hospital in Zhejiang, China. NAFLD was diagnosed by abdominal ultrasound and the NAFLD fibrosis score (NFS) was calculated to reflect the extent of liver fibrosis. Cox proportional hazards analyses were applied to assess the risk of CP development across groups with different baseline NAFLD and NFS status. RESULTS: NAFLD participants with high NFS had higher risk of CP compared to non-NAFLD participants (adjusted hazard ratio 1.68, 95% confidence interval [CI] 1.43-1.96, p < .001). Progression from NAFLD free and NAFLD with low NFS to NAFLD with high NFS are associated with 1.56-fold (95% CI 1.21-2.01, p = .001) and 1.43-fold (95% CI 1.11-1.84, p = .006) increased risk of CP, respectively. Risk factors associated with CP vary based on baseline NAFLD and NFS status. Among NAFLD participants with high NFS, hypertension is the only significant risk factor after adjustment for other potential influencing factors. CONCLUSIONS: NAFLD and liver fibrosis status can be an independent predictor for CP development regardless of metabolic abnormalities. Hypertension is a major risk factor for CP development among NAFLD patients with high NFS.KEY MESSAGESNon-alcoholic fatty liver disease (NAFLD) and liver fibrosis status can be an independent predictor for development of carotid plaque.Progression from NAFLD free and NAFLD with low NAFLD fibrosis score (NFS) to NAFLD with high NFS are associated with increased risk of carotid plaque.Risk factors associated with carotid plaque vary based on baseline NAFLD and NFS status, and hypertension plays the most important role among patients with NAFLD and high NFS.

17.
J Agric Food Chem ; 69(36): 10749-10759, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34474557

RESUMO

Gestational diabetes mellitus (GDM) not only has a bad effect on the development of infants but also causes variations in breastmilk composition. This study aims to investigate the changes in the protein profile of colostrum between mothers with GDM and healthy mothers (H) by sequential windowed acquisition of all theoretical fragment ion proteomics techniques. A total of 1295 proteins were detected, with 192 proteins being significantly different between GDM and H. These significantly different proteins were enriched with the carbohydrate and lipid metabolism pathway as well as immunity. Some proteins had an AOC value of 1, such as apolipoprotein E and lipoprotein lipase. In addition, we identified 42 glycated and 93 glycosylated peptides in colostrum without any enrichment, with glycated peptides being upregulated and glycosylated peptides being downregulated in colostrum with GDM. These results help us to better understand the GDM-induced changes in proteomes and glycated and glycosylated level and provide guidance on infant formula adjustment for infants from mothers with GDM.


Assuntos
Diabetes Gestacional , Colostro , Feminino , Humanos , Leite Humano , Gravidez , Proteoma , Proteômica
18.
J Hazard Mater ; 416: 126227, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492981

RESUMO

The high-voltage electric field can effectively capture charged aerosols and has the effect of killing microbial aerosols simultaneously. In this article, an innovative visualization method for investigating the dynamic characteristic of submicron-scale aerosol particles in the high-voltage electric field is developed. Based on reasonable working principles and reliable experimental schemes, the movement of submicron-scale aerosol particles is observed and visualization images in different working conditions are photographed. Besides, with the aid of numerical method and solution of related equations, simulation researches on flow field distribution, electrostatic field characteristics, particle charging and motion behavior characteristics are also carried out. Visualization results prove the linear motion law of aerosol particles in an electric field of 0-3 kV/cm unit. As for 1 µm diameter particle, its migration velocity in 1 kV/cm electric field is measured as 0.016 m/s and 0.019 m/s after positive and negative charging of 1.5 kV voltage, respectively. A reliable calculation formula (η=(VjqpLj)/(3πµD2uxdp)) for predicting collection efficiency is derived and established based on actual particle migration velocity. The researches on the migration and capture law of submicron-scale aerosol in the high voltage electric field gives a key reference for the development and design of efficient removal of microbial aerosol and air purification equipment.

19.
J Org Chem ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478300

RESUMO

Copper-catalyzed conjugate addition is a classic method for forming new carbon-carbon bonds. However, copper has never showed catalytic activity for umpolung carbanions in hydrazone chemistry. Herein, we report a facile conjugate addition of hydrazone catalyzed by readily available copper complexes at room temperature. The employment of mesitylcopper(I) and electron-rich phosphine bidentate ligand is a key factor affecting reactivity. The reaction allows various aromatic hydrazones to react with diverse conjugated compounds to produce 1,4-adducts in yields of about 20 to 99%.

20.
Mol Neurobiol ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480336

RESUMO

The Notch signaling pathway plays an important role in the regulation of neurogenesis. The objective of this study was to investigate whether the Notch signaling pathway was involved in the neurogenesis impairment and long-term neurocognitive dysfunction caused by neonatal exposure to ketamine. On postnatal day 7 (PND-7), male Sprague-Dawley (SD) rats were intraperitoneally injected with 40 mg/kg ketamine four consecutive times (40 mg/kg × 4) at 1-h intervals. Notch ligand Jagged1 (0.5 mg/kg) and lentivirus overexpressing the Notch1 intracellular domain (LV-NICD1) were microinjected into the hippocampal dentate gyrus (DG) 1 h or 4 days before ketamine administration, respectively. The expression of Notch1 signaling pathway-related proteins was detected by Western blotting 24 h after ketamine administration. The proliferation and differentiation of the neural stem cells (NSCs) in the hippocampal DG were evaluated by double immunofluorescence staining 24 h after treatment. Moreover, changes in hippocampus-dependent spatial memory of 2-month-old rats were investigated with the Morris water maze test. Ketamine anesthesia in neonatal rats decreased the expression levels of Jagged1, Notch1, NICD1, and hairy enhancer of split 1 (Hes1); inhibited the proliferation and astrocytic differentiation of NSCs; and promoted the differentiation of neurons. Neonatal exposure to ketamine caused deficits in hippocampus-dependent spatial reference memory tasks in 2-month-old rats. Microinjection of Jagged1 or LV-NICD1 reversed the inhibitory effect of ketamine on the expression of Notch1-related proteins in the hippocampal DG, attenuated the ketamine-mediated decrease in NSC proliferation and differentiation, and improved the cognitive function of 2-month-old rats after neonatal exposure to ketamine. These results suggest that neonatal exposure to ketamine in rats inhibits the proliferation and differentiation of hippocampal NSCs and impairs neurocognitive function in adulthood. The Notch1 signaling pathway may be involved in the impairment of hippocampus-dependent learning and memory during adulthood caused by neonatal exposure to ketamine. These findings contribute to further understanding the neurotoxicity induced by neonatal exposure to ketamine and the underlying mechanisms.

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