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1.
J Pathol ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32356901

RESUMO

In a recent study published in The Journal of Pathology, Barrow-McGee et al described a feasibility study of real-time ex-vivo perfusion model of the axillary lymph nodes (ALNs) from breast cancer patients for immune-oncological investigations. The study showed that perfused ALNs remain viable for up to 24 h, and perfusion of therapeutic antibodies confirmed the ability to reach ALN-resident cells. This work is a highly encouraging demonstration of feasibility for further research into lymphatic system function, with applications to immune function, vaccinations and cancer. This article is protected by copyright. All rights reserved.

2.
Curr Opin Neurobiol ; 62: 133-140, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32380360

RESUMO

Our understanding of the gut system has been revolutionized over the past decade, in particular regarding its role in immune control and psychological regulation. The vagus nerve is a crucial link between gut and brain, transmitting diverse gut-derived signals, and has been implicated in many gastrointestinal, neurological, and immunological disorders. Using state-of-the-art technologies including single-cell genomic analysis, real-time neural activity recording, trans-synaptic tracing, and electron microscopy, novel physiological functions of vagal gut afferents have been uncovered, and new gut-to-brain pathways have been revealed. Here, we review the most recent findings on vagal sensory neurons and the gut-brain signaling, focusing on the anatomical basis and the underlying molecular and cellular mechanisms. Such new discoveries explain some of the old puzzling problems and also raise new questions in this exciting and rapidly growing field.

3.
Curr Med Chem ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32368969

RESUMO

Coronary heart disease (CHD) is closely related to hypercholesterolemia, and lowering serum cholesterol is currently the most important strategy in reducing CHD. In humans, the serum cholesterol level is determined mainly by three metabolic pathways, namely, dietary cholesterol intake, cholesterol synthesis, and cholesterol degradation in vivo. An intervention that targets the key molecules in the three pathways is an important strategy in lowering serum lipids. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) to reduce lowdensity lipoprotein (LDL) by about 20% to 45%. However, up to 15% of patients cannot tolerate the potential side effects of high statin dosages, and several patients also still do not reach their optimal LDL goals after being treated with statins. Ezetimibe inhibits cholesterol absorption by targeting the Niemann-Pick C1-like 1 protein (NPC1L1), which is related to cholesterol absorption in the intestines. Ezetimibe lowers LDL by about 18% when used alone and by an additional 25% when combined with statin therapy. The proprotein convertase subtilisin/kexin type 9 (PCSK9) increases hepatic LDLR degradation, thereby reducing the liver's ability to remove LDL, which can lead to hypercholesterolemia. Evolocumab, which is a PCSK9 monoclonal antibody, can reduce LDL from baseline by 53% to 56%. The three drugs exert lipidlowering effects by regulating the three key pathways in lipid metabolism. Combining any with the two other drugs on the basis of statin treatment has improved lipid-lowering effect. Whether the combination of the three musketeers will reduce the side effects of monotherapy and achieve lipid-lowering effect should be studied further in the future.

4.
Neurobiol Aging ; 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32371107

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease with a relatively unclear etiology. Previous studies have shown that N6-methyladenosine (m6A) is a vital RNA modification enriched in brain tissue, and that the genes involved in m6A modification are implicated in various neurologic diseases. Here, we conducted a comprehensive genetic analysis using targeted sequencing with molecular inversion probes (MIPs) to identify m6A-modification genes (including METTL3, METTL14, WTAP, FTO, ALKBH5, YTHDF1, YTHDF2, YTHDF3, HNRNPC, and ELAVL1) in a total of 1647 sporadic PD patients and 1372 controls of Han Chinese origin. PD patients were divided into early-onset PD (EOPD) and late-onset PD (LOPD) based on whether the onset of motor symptoms occurred before or after 50 years of age. Rare variants were subjected to gene-based burden tests and common variants were subjected to single-variant association analyses. As a result, we identified 214 rare variants in all 10 m6A-modification genes and 16 common variants in 7 genes. Gene-wise association analyses of rare variants in each m6A-modification gene did not achieved a p value of less than 0.05 in either total cohorts or 2 age groups. In fact, p values greater than 0.05 were found when conducting single-variant association analyses on common variants of these genes between PD and control patients. Our comprehensive analyses of m6A-modification genes suggest that there is no significant association between these 10 m6A-modification genes and the risk of sporadic PD.

5.
Ann Transl Med ; 8(7): 519, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32395563

RESUMO

[This corrects the article DOI: 10.21037/atm.2019.11.106.].

6.
Analyst ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396150

RESUMO

Correction for 'A mini mass spectrometer with a low noise Faraday detector' by Yang Tang et al., Analyst, 2020, DOI: 10.1039/d0an00420k.

7.
Obes Surg ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32399849

RESUMO

PURPOSE: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and sleeve gastrectomy (SG) is considered to be an effective strategy to improve pre-existing DN. However, the mechanism remains unknown. MATERIALS AND METHODS: Animal model of DN was induced by high-fat diet (HFD) and streptozotocin (STZ). SG or sham surgery was performed and rats were sacrificed at 4, 8, and 12 weeks after surgery. The basic parameters (blood glucose, body weight, kidney weight), indicators of renal function including serum creatinine (Scr), blood urea nitrogen (BUN), urine microalbumin, urine creatinine (Ucr), microalbumin creatinine ratio (UACR), ultrastructural changes of glomerulus, and the expression of nephrin gene and protein in glomerular podocytes were compared among groups. RESULTS: Blood glucose and body weight of SG rats were significantly lower than those of the sham-operated rats, and renal function of SG groups were also significantly improved within the postoperative period of 12 weeks. The results of periodic acid-Schiff staining (PAS) and transmission electron microscopy (TEM) showed that glomerular hypertrophy and accumulation of extracellular matrix proteins were significantly alleviated after SG, and the thickness of basement membrane and the fusion or effacement of foot processes were also significantly improved. The mRNA and protein expression of nephrin in SG groups was significantly higher than that in the sham group. CONCLUSION: These results suggest that SG attenuates DN by upregulating the expression of nephrin and improving the ultrastructure of glomerular filtration membrane. This study indicates that SG can be used as an available therapeutic intervention for DN.

8.
Biochemistry ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32420731

RESUMO

Phytochromes regulate central responses of plants and microorganisms such as shade avoidance and photosystem synthesis. Canonical phytochromes comprise a photosensory module of three domains. The C-terminal domain interacts via a tongue element with the bilin chromophore in the central GAF (cGMP phosphodiesterase/Adenylate cyclase/FhlA) domain. The bilin isomerizes upon illumination with red light, transforming the receptor from the Pr to the Pfr state. The 'knotless' phytochrome All2699 from the cyanobacterium Nostoc sp. PCC7120 comprises three GAF domains as sensory module and a histidine kinase as effector. GAF1 and GAF3 both bind a bilin and GAF2 contains a tongue-like element. We studied the response of All2699, GAF1-GAF2, and GAF1 to red light by Fourier transform infrared difference spectroscopy including a 13C-labeled protein moiety for assignment. In GAF1-GAF2, a refolding of the tongue from ß-sheet to α-helix and an upshift of the D-ring carbonyl stretch from 1700 to 1712 cm-1 was observed. Therefore, GAF1-GAF2 is regarded the smallest model system available to study the tongue response and interaction with the chromophore. Replacement of an arginine in the tongue by proline (R387P) did not affect ß-sheet unfolding to Pfr but strongly impaired α-helix formation. In contrast, the Y55H mutation close to the bilin D-ring did not interfere with conversion to Pfr. Strikingly, the presence of GAF3 in the full-length All2699 diminished the response of the tongue and generated the signal pattern found for GAF1 alone. These results point to a regulatory or integrative role of GAF3 in All2699 which is absent in canonical phytochromes.

9.
Plant Cell ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32358074

RESUMO

Strigolactones (SLs) and karrikins (KARs) are related butenolide signaling molecules that control plant development. In Arabidopsis thaliana they are recognized separately by two closely-related receptors but employ the same F-box protein MORE AXILLARY GROWTH2 (MAX2) for signal transduction, targeting different members of the SMAX1-LIKE (SMXL) family of transcriptional repressors for degradation. Both signals inhibit hypocotyl elongation in seedlings raising the question of whether signaling is convergent or parallel. Here, we show that synthetic SL analog GR244DO enhanced the interaction between the SL receptor DWARF14 (D14) and SMXL2, while the KAR surrogate GR24ent-5DS induced association of the KAR receptor KARRIKIN INSENSITIVE2 (KAI2) with SMAX1 and SMXL2. Both signals could trigger polyubiquitination and degradation of SMXL2, with GR244DO dependent on D14 and GR24ent-5DS dependent mainly on KAI2. SMXL2 is critical for hypocotyl responses to GR244DO, and functions redundantly with SMAX1 in hypocotyl response to GR24ent-5DS. Furthermore, GR244DO induced response of D14-LIKE2 (DLK2) and KAR-UP F-BOX1 (KUF1) through SMXL2, whereas GR24ent-5DS induced expression of these genes via both SMAX1 and SMXL2. These findings demonstrate that both SLs and KARs could trigger polyubiquitination and degradation of SMXL2, thus uncovering an unexpected but important convergent pathway in SL- and KAR-regulated gene expression and hypocotyl elongation.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32348275

RESUMO

BACKGROUND: Social media has become a major resource for observing and understanding public opinions, especially during emergencies such as disease outbreaks. For public health agencies, understanding the driving forces of web-based discussions will help deliver more effective and efficient information to general users on social media and the web. OBJECTIVE: The study aimed to identify the major contributors that drove overall Zika-related tweeting dynamics during the 2016 epidemic. In total, 3 hypothetical drivers were proposed: (1) the underlying Zika epidemic quantified as a time series of case counts; (2) sporadic but critical real-world events such as the 2016 Rio Olympics and World Health Organization's Public Health Emergency of International Concern (PHEIC) announcement, and (3) a few influential users' tweeting activities. METHODS: All tweets and retweets (RTs) containing the keyword Zika posted in 2016 were collected via the Gnip application programming interface (API). We developed an analytical pipeline, EventPeriscope, to identify co-occurring trending events with Zika and quantify the strength of these events. We also retrieved Zika case data and identified the top influencers of the Zika discussion on Twitter. The influence of 3 potential drivers was examined via a multivariate time series analysis, signal processing, a content analysis, and text mining techniques. RESULTS: Zika-related tweeting dynamics were not significantly correlated with the underlying Zika epidemic in the United States in any of the four quarters in 2016 nor in the entire year. Instead, peaks of Zika-related tweeting activity were strongly associated with a few critical real-world events, both planned, such as the Rio Olympics, and unplanned, such as the PHEIC announcement. The Rio Olympics was mentioned in >15% of all Zika-related tweets and PHEIC occurred in 27% of Zika-related tweets around their respective peaks. In addition, the overall tweeting dynamics of the top 100 most actively tweeting users on the Zika topic, the top 100 users receiving most RTs, and the top 100 users mentioned were the most highly correlated to and preceded the overall tweeting dynamics, making these groups of users the potential drivers of tweeting dynamics. The top 100 users who retweeted the most were not critical in driving the overall tweeting dynamics. There were very few overlaps among these different groups of potentially influential users. CONCLUSIONS: Using our proposed analytical workflow, EventPeriscope, we identified that Zika discussion dynamics on Twitter were decoupled from the actual disease epidemic in the United States but were closely related to and highly influenced by certain sporadic real-world events as well as by a few influential users. This study provided a methodology framework and insights to better understand the driving forces of web-based public discourse during health emergencies. Therefore, health agencies could deliver more effective and efficient web-based communications in emerging crises.

11.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(2): 133-138, 2020 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-32314884

RESUMO

OBJECTIVE: This work aimed to determine the expression changes in LIM domain only protein 1 (LMO1) in gene transcription and protein levels during oral squamous cell carcinoma (OSCC) development. METHODS: The tissues in this study were taken from our team's previous animal model building, and we performed hematoxylin-eosin (HE) staining on 49 cases. The pathological classification of the experiment group was determined on the basis of the abnormal epithelial hyperplasia degree. The expression part of LMO1 was determined by immunohistochemistry staining. The mRNA and protein LMO1 expression levels in five groups were detected by real-time fluorescent quantitative of nucleotide polymer chain reaction (RT-qPCR) and Western blot, respectively. RESULTS: HE staining determined 7 cases of the control group, 6 cases of mild epithelial dysplasia, 11 cases of moderate epithelial dysplasia, 9 cases of severe epithelial dysplasia, and 16 cases of OSCC. Immunohistochemistry results: LMO1 expression was localized in the cytoplasm, and the positive expression rates of the protein LMO1 in the control and experiment groups were 14.3% for normal buccal mucosal tissue, 33.3% for mild epithelial dysplasia, 81.8% for moderate epithelial dysplasia, 88.9% for severe epithelial dysplasia, and 93.8% for OSCC. RT-qPCR results: mRNA expression was lowest in the control group and highest in the OSCC group, the difference between the mild dysplasia and control groups was not significant (P>0.05). Pairwise comparison among other groups showed statistically significant differences (P<0.05). Western blot results: with the aggravation of the pathological degree, the protein LMO1 expression level increased gradually. The OSCC group expressed the highest LMO1 expression level. CONCLUSIONS: The oral mucosa carcinogenesis models showed abnormal the mRNA and protein LMO1 expression levels, and the mRNA and protein expression levels were positively correlated with the degree of abnormal proliferation.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Quinolinas , Animais , Carcinogênese , Mucosa Bucal , Óxidos , Ratos , Ratos Sprague-Dawley
12.
Psychiatry Res ; 288: 112953, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32302814

RESUMO

A series of unexplained pneumonia appeared in Wuhan, Hubei Province, China, which is highly contagious. The virus is prone to nervous and anxious psychological reactions. In the objective environment of complex and densely populated hospitals, it is a high-risk area for virus-transmitted infections and children generally have lower immunity who are more likely to develop infections. The results showed that the mental health problems of parents of hospitalized children during the epidemic were more serious, and the anxiety and depression were more obvious.


Assuntos
Criança Hospitalizada , Infecções por Coronavirus , Pandemias , Pais , Pneumonia Viral , Adulto , Ansiedade/epidemiologia , Betacoronavirus , Criança , China/epidemiologia , Infecções por Coronavirus/psicologia , Depressão/epidemiologia , Feminino , Humanos , Masculino , Relações Pais-Filho , Pais/psicologia , Pneumonia Viral/psicologia
13.
Psychiatry Res ; 288: 112955, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32302815

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which appeared in early December 2019, had an atypical viral pneumonia outbreak in Wuhan, Hubei, China. And there is a high risk of global proliferation and impact. The sudden increase in confirmed cases has brought tremendous stress and anxiety to frontline surgical staff. The results showed that the anxiety and depression of surgical staff during the outbreak period were significantly higher and mental health problems appeared, so psychological interventions are essential.


Assuntos
Transtornos de Ansiedade , Infecções por Coronavirus/psicologia , Depressão , Recursos Humanos em Hospital , Pneumonia Viral/psicologia , Ansiedade , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/virologia , Betacoronavirus , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Depressão/epidemiologia , Depressão/virologia , Surtos de Doenças , Cirurgia Geral , Humanos , Serviços de Saúde Mental , Pandemias , Recursos Humanos em Hospital/psicologia , Pneumonia Viral/epidemiologia , Estresse Psicológico
14.
Am J Trop Med Hyg ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32342847

RESUMO

We aimed to identify the contribution of central nervous system (CNS) viral coinfection to illness in African children with retinopathy-negative or retinopathy-positive cerebral malaria (CM). We collected cerebrospinal fluid (CSF) from 272 children with retinopathy-negative or retinopathy-positive CM and selected CSF from 111 of these children (38 retinopathy positive, 71 retinopathy negative, 2 retinopathy unknown) for analysis by metagenomic next-generation sequencing. We found CSF viral coinfections in 7/38 (18.4%) retinopathy-positive children and in 18/71 (25.4%) retinopathy-negative children. Excluding HIV-1, human herpesviruses (HHV) represented 61% of viruses identified. Excluding HIV-1, CNS viral coinfection was equally likely in children who were retinopathy positive and retinopathy negative (P = 0.1431). Neither mortality nor neurological morbidity was associated with the presence of virus (odds ratio [OR] = 0.276, 95% CI: 0.056-1.363). Retinopathy-negative children with a higher temperature, lower white blood cell count, or being dehydrated were more likely to have viral coinfection. Level of consciousness at admission was not associated with CNS viral coinfection in retinopathy-negative children. Viral CNS coinfection is unlikely to contribute to coma in children with CM. The herpesviruses other than herpes simplex virus may represent incidental bystanders in CM, reactivating during acute malaria infection.

15.
Chin J Integr Med ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32291608

RESUMO

OBJECTIVE: To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach. METHODS: Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction. RESULTS: A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P<0.05). During the treatment course, no signifificant changes were observed in safety indicators between the two groups (P>0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B. CONCLUSIONS: CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).

16.
Future Oncol ; 16(11): 655-663, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32242461

RESUMO

Aims: We aimed to explore diagnostic efficiencies of long noncoding RNAs (lncRNAs) adjacent to PGC combining with sPGC and anti-Helicobacter pylori IgG in identifying GC (gastric cancer) and precancerous disease. Patients & methods: A total of 265 patients with different gastric diseases were collected. ELISA was to detect sPGC and anti-H. pylori IgG. LncRNAs was determined by qRT-PCR. Results: The area under receiver operating characteristic curve of lncRNAs in discriminating GC+AG (atrophic gastritis) and superficial gastritis (SG) were 79.0, 68.1 and 75.9%. The diagnostic performance of lncRNAs with sPGC had increasing trends in distinguishing GC from non-GC, SG from GC+AG comparing with lncRNAs, with no statistic difference. Diagnosis efficacies of lncRNAs with anti-H. pylori IgG improved dramatically. Conclusions: Serum lncRNAs could distinguish GC, AG and SG. Diagnosis efficiencies of lncRNAs with sPGC and anti-H. pylori-IgG could be improved.

17.
Biomacromolecules ; 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32271548

RESUMO

The conventional synthesis of methacryloyl hyaluronic acid (HA-MA) requires an extremely high amount of modification reagents, the organic solvents, and strenuous purification steps. Herein, a new green synthetic approach for the methacryloyl hyaluronic acid preparation with a tailorable substitution degree (SD) is reported, in which methacryloyl hydrazide is used as a more reactive reagent and only water is used as the solvent. The new method significantly reduces the amount of functionalization reagents (as low as only 0.3 equiv) and avoids the use of any organic solvents. The substitution degree can be tailored from 26% to 86% in a facile controllable manner. The new HA-MA (termed as HA-MA-H) can be UV-cross-linked to form a biocompatible hydrogel.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32223191

RESUMO

The balance between second harmonic generation (SHG) intensity and laser-induced damage threshold (LIDT), together with phase-matchable behavior, is the key point for exploration of novel nonlinear optical (NLO) materials. In this work, the NLO property of defect wurtzite-type hexagonal-In2Se3 (γ) is extensively explored first. It exhibits a strong SHG intensity of 2.6 × AgGaS2 (AGS) at 2.1 µm, and a high powder LIDT of 7.3 × AGS. From wurtzite to γ-In2Se3, the birefringence changes from 0.003 to 0.075, resulting in the phase-matchable phenomenon of γ-In2Se3. This is well ascribed to the contribution of the unique InSe5 unit in γ-In2Se3 from the result of birefringence calculation and analysis.

19.
Analyst ; 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32297893

RESUMO

An ion trap mass spectrometer is conventionally featured with an electron multiplier as its detector. However, an electron multiplier can typically work at pressures below 20 mTorr with a high voltage applied, which limits the further miniaturization of ion trap mass spectrometers. In this work, a low noise Faraday detector was developed and integrated in our miniature mass spectrometer instrument, and a post data processing method was applied to improve its performance. A limit of detection of 1 ng mL-1 was achieved, and quantitation performance and mass resolution were characterized. This technology could be useful in the further development of miniature mass spectrometers by increasing background pressures.

20.
Signal Transduct Target Ther ; 5(1): 21, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32296014

RESUMO

Internal tandem duplication (ITD) mutations of FMS-like tyrosine kinase-3 (FLT3) are the most frequent genetic alterations in acute myeloid leukemia (AML) and predict a poor prognosis. FLT3 tyrosine kinase inhibitors (TKIs) provide short-term clinical responses, but the long-term prognosis of FLT3/ITD+ AML patients remains poor. Notch signaling is important in numerous types of tumors. However, the role of Notch signaling in FLT3/ITD+ AML remains to be elucidated. In the current study, we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD+ cell lines and primary cells. As Notch signaling can be blocked by γ-secretase inhibitors (GSIs), we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD+ AML and explored the underlying molecular mechanisms. As a result, we observed synergistic cytotoxic effects, and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD+ AML cell lines and in primary AML cells. Furthermore, the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD+ patient-derived xenograft AML model. Mechanistically, differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy, possibly through ERK signaling. Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD+ AML.

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