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1.
Cardiovasc Ultrasound ; 19(1): 25, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193164

RESUMO

BACKGROUND: Due to metabolic changes in the second trimester and the increasing number of pregnant women with obesity and advanced maternal age, the incidence of gestational diabetes mellitus (GDM) remains high. This study aimed to evaluate the effects of GDM on fetal cardiac morphology and function, and to determine whether these changes increase with increasing estimated fetal weight (EFW). METHODS: Fifty-eight women with GDM (GDM group) and 58 women with a healthy pregnancy (control group) were included in this prospective observational cohort study. Each group included subgroups of 31 pregnant women with a gestational age between 24+0 weeks and 27+6 weeks as well as 27 pregnant women with a gestational age between 28+0 weeks and 40+0 weeks. For all fetuses, a cine of 2-3 s in the four-chamber view was obtained, and online speckle-tracking analysis was performed using the GE Automatic Fetal Heart Assessment Tool (fetal HQ; General Electric Healthcare Ultrasound, Zipf, Austria) to measure the global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC), 24-segment sphericity index (SI), and 24-segment end-diastolic diameter of the left ventricle (LV) and right ventricle (RV). Data were analyzed using the independent t-test and Wilcoxon rank-sum test, as applicable. RESULTS: The GDM group (mean HbA1c value was 5.3 ± 0.57 mmol/L) showed a lower GSI value than the control group (1.21 vs. 1.27, P = 0.000), which indicated a rounder shape of the heart. In addition, fetuses in the GDM group demonstrated significant impairment in cardiac function compared to those in the control group (LV-GLS: -18.26% vs. -22.70%, RV-GLS: -18.52% vs. -22.74%, LV-FAC: 35.30% vs. 42.36%, RV-FAC: 30.89% vs. 36.80%; P = 0.000 for all). Subgroup analyses according to gestational age (24+0-27+6 weeks and 28+0-40+0 weeks) showed that the statistical differences were retained between the GDM and control groups in each subgroup. CONCLUSIONS: Fetuses of women with GDM present with signs of biventricular systolic dysfunction according to deformation analysis using fetal HQ. Additionally, the heart had a rounder shape in the GDM group than in the control group. This study showed that fetal HQ can be used to assess fetal cardiac morphology and function easily and quickly, and the effects of GDM on fetal cardiac morphology and function appeared from the second trimester. Thus, whether earlier and stricter clinical intervention was necessary remained to be further studied. Furthermore, future studies will need to supplement the effects of blood glucose levels on GLS, FAC, GSI, and 24-segment SI. Additionally, the long-term follow-up after birth should also be improved to observe the influence of changes in the indicators on the prognosis.

2.
Inorg Chem ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236841

RESUMO

Two-dimensional organic-inorganic hybrid perovskites (OIHPs) have gained attention as a result of their flexibility and adjustability of the structure. However, the large band gap of two-dimensional perovskites limits their application in the photoelectric field. In the present work, we report a two-dimensional organic-inorganic hybrid compound of (C7H18N2)PbI4 (1) with a narrow band gap, which consists of [PbI4]2-n layers and N-(2-aminoethyl)piperidinium cations. 1 exhibits semiconducting properties with a narrow optical band gap of ∼2.02 eV and a photoelectric response with a ratio of photocurrent to dark current of ∼100. In addition, it exhibits a reversible solid-state phase transition at 228 K. This finding should inspire research into more 2D layered OIHPs with the combination of phase transition and semiconductor properties.

3.
Pharmacology ; : 1-10, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237728

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent digestive tract tumors in the world with an increasing incidence. Currently, surgical resection and chemotherapy are the main therapeutic options; however, their effects are limited by various adverse reactions. Rauwolfia vomitoria extract (Rau) has been shown to repress the progression of multiple human cancers; however, whether Rau plays a role in CRC remains undetermined. METHODS: Influences of Rau treatment on HCT-116 and LoVo cells were estimated via MTT and colony formation experiments. Flow cytometry analysis was adopted to evaluate the apoptosis rate of HCT-116 and LoVo cells. Apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and autophagy-related proteins (LC3 and P62) were assessed by Western blotting. Effects of Rau on autophagy of HCT-116 and LoVo cell were evaluated through GFP-LC3 analysis. In vivo xenograft tumor assay was conducted to further examine the role of Rau in CRC tumor growth. RESULTS: Rau remarkably repressed HCT-116 and LoVo cell viability and promoted HCT-116 and LoVo cell apoptosis in vitro in a dose-dependent manner. Rau increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2 in HCT-116 and LoVo cells. Moreover, Rau was demonstrated to decrease the LC3||/LC3| ratio and increase the level of P62 in HCT-116 and LoVo cells. In addition, we found that Rau repressed xenograft tumor growth and also repressed autophagy in vivo. CONCLUSION: Our findings revealed that Rau repressed CRC cell viability and autophagy in vitro and in vivo, suggesting that Rau might be a potent therapeutic agent of CRC.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34239051

RESUMO

The objective of this study was to compare clinical outcomes between noninherited maternal antigen (NIMA)-mismatched and noninherited paternal antigen (NIPA)-mismatched haploidentical hematopoietic stem cell transplantation (haplo-HSCT) among patients with hematological malignancies and perform a subgroup analysis. We retrospectively analyzed 378 patients with hematological malignancies who received haplo-HSCT from NIMA-mismatched (n = 201) and NIPA-mismatched (n = 177) donors between January 2012 and December 2017. The cumulative incidence of 100-d grades II-IV acute graft-versus-host disease (aGVHD) (19.2% vs. 32.8%, P = 0.003) was significantly lower in NIMA mismatch. Multivariate analysis showed that NIMA mismatch was associated with lower incidence of grades II-IV aGVHD and better overall survival (OS) and disease-free survival (DFS). According to the subgroup analysis, the clinical outcomes of older and/or female NIMA mismatches were comparable to those of younger and/or male NIPA mismatches with respect to grades II-IV aGVHD, chronic GVHD (cGVHD), nonrelapse mortality (NRM), relapse, DFS, and OS. In conclusion, this study confirmed the NIMA effect on aGVHD and demonstrated that NIMA mismatch was associated with better survival. In the NIMA mismatch context, donor age and sex did not seem to influence haplo-HSCT, which provides a basis for the selection of sibling donors.

6.
Dalton Trans ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34240090

RESUMO

In this work, in order to meet the application of near-infrared phosphor-converted light emitting diodes (pc-LEDs), an ultra-broadband emission phosphor, LiScGeO4:Cr, was synthesized. Its FWHM reaches 335 nm, and its emission spectrum ranges from 800 nm to 1650 nm, which almost covers the entire near-infrared second window (NIR-II). The broadband emission is thought to be caused by the 4T2 → 4A2 transition of the Cr3+ ion. This transition occurs due to the olivine structure of the crystal, which causes the Cr3+ ions to inhabit a low-symmetric crystal field, and the crystal field strength is very weak. NIR pc-LEDs were fabricated by combining a 460 nm blue LED with this phosphor, which penetrates 4 cm thick beef. The results indicate that there may be a potential application for this phosphor in the field of biological tissue penetration and non-destructive testing.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34240605

RESUMO

Stimuli-responsive hydrogels possess unique advantages in drug delivery due to their variable performance and status based on the external environment. In the present study, a dual-responsive (pH and reactive oxygen species (ROS)) hydrogel was prepared to realize drug release properties under inflammatory stimulation. By grafting 3-carboxy-phenylboronic acid to the gelatin molecular backbone and cross-linking with poly(vinyl alcohol), we successfully synthesized the inflammation-responsive drug-loaded hydrogels after encapsulation with vancomycin-conjugated silver nanoclusters (VAN-AgNCs) and pH-sensitive micelles loaded with nimesulide (NIM). This novel design not only retained the dynamic functions of hydrogels, such as injectability, self-healing, and remodeling, but also realized sequential and on-demand drug delivery at diabetic-infected wound sites. In this work, we found that the hydrogel exhibited excellent biocompatibility and hemostasis properties owing to the enhanced cell-adhesive property of the gelatin component. The significant antibacterial and anti-inflammatory effect of the hydrogel was demonstrated in an in vitro experiment. Moreover, in the in vivo experiment, the hydrogel was found to play a role in promoting infected wound healing through sequential hemostasis and antibacterial and anti-inflammatory processes. Collectively, this inflammation-responsive hydrogel design containing VAN-AgNCs and NIM-loaded micelles has great potential in the application of chronically infected diabetic wound treatment, as well as in other inflammatory diseases.

9.
J Chem Phys ; 154(23): 234505, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34241277

RESUMO

Nitrogen and water are very abundant in nature; however, the way they chemically react at extreme pressure-temperature conditions is unknown. Below 6 GPa, they have been reported to form clathrate compounds. Here, we present Raman spectroscopy and x-ray diffraction studies in the H2O-N2 system at high pressures up to 140 GPa. We find that clathrates, which form locally in our diamond cell experiments above 0.3 GPa, transform into a fine grained state above 6 GPa, while there is no sign of formation of mixed compounds. We point out size effects in fine grained crystallites, which result in peculiar Raman spectra in the molecular regime, but x-ray diffraction shows no additional phase or deviation from the bulk behavior of familiar solid phases. Moreover, we find no sign of ice doping by nitrogen, even in the regimes of stability of nonmolecular nitrogen.

11.
Hemodial Int ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34235847

RESUMO

OBJECTIVE: To investigate the correlation between serum ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) level and severity of abdominal vascular calcification in end-stage renal disease (ESRD) patients receiving dialysis. METHODS: A total of 124 patients were consecutively enrolled into the study in our local institution. Based on the Kidney Disease Improving Global Outcomes (KDIGO) guidelines and recommendations, abdomen lateral X-ray was used to determine abdominal aortic calcification score (AACS) for each patient at enrollment. Patients were divided into three groups based on AACS: no or mild calcification group, moderate calcification group, and severe calcification group. The relationships between ENPP1 levels and AACS were assessed by Spearman analysis and the value of ENPP1 in predicting severity of abdominal aortic calcification was evaluated by receiver operating characteristic (ROC). RESULTS: The level of ENPP1 in dialysis patients was (7.68 ± 1.67) ng/ml. There was no significant difference in serum ENPP1 level between peritoneal dialysis patients and hemodialysis patients (p > 0.05). The AACS of dialysis patients was negatively correlated with ENPP1 value (r = -0.70). Compared to no/mild calcification patients, the levels of serum ENPP1 in patients with moderate/severe calcification were decreased significantly (p < 0.01). The severity of vascular calcification was correlated with serum ENPP1 value, the severer the vascular calcification, the lower the serum ENPP1 level, and the difference was statistically significant (all p < 0.05). The area under ROC curve of ENPP1 was 0.90, the corresponding sensitivity was 0.86, and the specificity was 0.87. CONCLUSION: Levels of serum ENPP1 in non-diabetic ESRD patients are negatively related to the severity of abdominal aortic vascular calcification.

12.
Adv Sci (Weinh) ; 8(12): 2003712, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34194927

RESUMO

Mesenchymal stromal cells (MSCs) function as a formidable regulator of inflammation and tissue homeostasis and expanded MSCs are shown to be effective in treating various inflammatory diseases. Their therapeutic effects require the existence of certain inflammatory cytokines. However, in the absence of sufficient proinflammatory stimuli or in the presence of anti-inflammatory medications, MSCs are animated to promote immune responses and unable to alleviate inflammatory disorders. In this study, it is demonstrated that steroid co-administration interferes the efficacy of MSCs in treating acute graft-versus-host disease (aGvHD). Molecular analysis reveals that vascular endothelial growth factor C (VEGF-C) is highly induced in MSCs by steroids and TNFα and VEGF-C in turn promotes CD8+ T cell response. This immune promoting effect is abolished by blockade or specific genetic ablation of VEGFR3 in CD8+ T cells. Additionally, administration of VEGF-C alone exacerbates aGvHD progression through eliciting more vigorous CD8+ T cell activation and proliferation. Further studies demonstrate that VEGF-C augments the PI3K/AKT signaling process and the expression of downstream genes, such as Cyclin D1. Thus, the data demonstrate that steroids can reverse the immunosuppressive effect of MSCs via promoting VEGF-C-augmented CD8+ T cell response and provide novel information for designing efficacious MSC-based therapies.

13.
Dis Markers ; 2021: 9434944, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257749

RESUMO

The clinical outcome of porcine circovirus 3 (PCV3) infection is still controversial. Herein, a novel PCV3 isolate (PCV3-China/DB-1/2017) with the molecular characterization of 24A and 27K in the Cap protein was used to inoculate three-week-old cesarean-derived, colostrum-deprived piglets. The nine PCV3 DB-1 inoculated piglets exhibited no obvious clinical symptoms or macroscopic lesions. PCV3 displayed a broad histotropism, including the heart, liver, spleen, lung, kidney, brain, lymph nodes, and tonsil, and the lungs and lymph nodes contained a higher quantity of viral genomes compared to that of the other organs. From 7 days after PCV3 DB-1 inoculation, the piglets showed obvious IgG antibody responses against PCV3 rCap-VLPs. The cumulative results demonstrated that PCV3 trend to low pathogenicity.

14.
Oxid Med Cell Longev ; 2021: 6695613, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257818

RESUMO

Aging is a complex phenomenon associated with oxidative stress and mitochondrial dysfunction. The objective of this study was to investigate the potential ameliorative effects of the phosphodiesterase inhibitor pentoxifylline (PTX) on the aging process and its underlying mechanisms. We treated D-galactose- (D-gal-) induced aging mice with PTX and measured the changes in behavior, degree of oxidative damage, and mitochondrial ultrastructure and content as well as the expression of nuclear factor erythroid 2-related factor 2- (Nrf2-) mediated antioxidant genes and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha- (PGC-1α-) dependent mitochondrial biogenesis genes. The results demonstrated that PTX improved cognitive deficits, reduced oxidative damage, ameliorated abnormal mitochondrial ultrastructure, increased mitochondrial content and Nrf2 activation, and upregulated antioxidant and mitochondrial biogenesis gene expression in the hippocampus of wild-type aging mice. However, the above antiaging effects of PTX were obviously decreased in the brains of Nrf2-deficient D-gal-induced aging mice. Moreover, in hydrogen peroxide-treated SH-SY5Y cells, we found that cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and Nrf2/PGC-1α act in a linear way by CREB siRNA transfection. Thus, PTX administration improved the aging-related decline in brain function by enhancing antioxidative capability and promoting mitochondrial biogenesis, which might depend on increasing Nrf2 and PGC-1α by activating the cAMP-CREB pathway.

15.
Arch Microbiol ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34258643

RESUMO

The soil-dwelling, opportunistic pathogenic bacterium "Bacillus nematocida" B16 exhibits strong killing activities against a variety of pathogenic nematodes via a "Trojan horse" mechanism that can kill worm species like Caenorhabditis elegans. The bacterial strain CPCC 101271 was previously isolated from the intestines of C. elegans that were recovered from natural habitats and can serve as a probiotic for C. elegans, while also assisting in resistance to infection by the pathogenic strain B16. In this study, the lifespan of C. elegans fed with strain CPCC 101271 cells was extended by approximately 40% compared with that of worms fed with Escherichia coli OP50 cells. In addition, the colonization of C. elegans by the pathogenic bacterium "B. nematocida" B16 was inhibited when pre-fed with strain CPCC 101271. Metagenomic sequence analysis of intestinal microbiota of C. elegans fed with strain CPCC 101271 and infected with B16 revealed that pre-feeding worms with CPCC 101271 improved the diversity of the intestinal bacteria. Moreover, community structure significantly varied in coordination with Stenotrophomonas spp. and Bacillus spp. abundances when competition between strains CPCC 101271 and B16 was evaluated. In conclusion, the nematode microbiota strain CPCC 101271 assisted in its host resistance to colonization by the pathogen "Bacillus nematocida" and can also promote life span-prolongation in C. elegans. These results underscore that understanding the interactions between C. elegans microbiota and pathogens can provide new insights into achieving effective biological control of agricultural pests.

16.
BMC Cardiovasc Disord ; 21(1): 341, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261448

RESUMO

BACKGROUND: Catheter ablation is widely used in atrial fibrillation (AF) management. In this study, we are aimed to investigate the incidence of postprocedural cognitive decline in a larger population undergoing AF ablation under local anesthesia, and to evaluate the associated risk factors. METHODS: This study included 287 patients with normal cognitive functions, with 190 ablated AF patients (study group) and 97 AF patients who are awaiting ablation (practice group). We assessed the neuropsychological function of each patient for twice (study group: 24 h prior to ablation and 48 h post ablation; practice group: on the day of inclusion and 72 h later but before ablation). The reliable change index was used to analyze the neuropsychological testing scores and to identify postoperative cognitive dysfunction (POCD) at 48 h post procedure. Patients in the study group accepting a 6-month follow up were given an extra cognitive assessment. RESULTS: Among the ablated AF patients, 13.7% (26/190) had POCD at 48 h after the ablation procedure. Multivariable analysis revealed that, a minimum intraoperative activated clotting time (ACT) < 300 s (OR 3.82, 95% CI 1.48-9.96, P = 0.006) and not taking oral anticoagulants within one month prior to ablation(OR 10.35, 95% CI 3.54-30.27, P < 0.001) were significantly related to POCD at 48 h post-ablation. In 172 patients of the study group accepting a 6-month follow up, there were 23 patients with POCD at 48 h post-ablation and 149 patients without POCD. The global cognitive scores were decreased in 48 h post-operation tests (0 ± 1 vs - 0.15 ± 1.10, P < 0.001) and improved significantly at 6 months post-operation (0 ± 1 vs 0.43 ± 0.92, P < 0.001). In the 23 patients with POCD at 48 h after the procedure, global cognitive performance at 6 months was not significantly different compared with that at baseline (- 0.05 ± 1.25 vs - 0.19 ± 1.33, P = 0.32), while 13 of them had higher scores than baseline level. CONCLUSIONS: Incident of POCD after ablation procedures is high in the short term. Inadequate periprocedural anticoagulation are possible risk factors. However, most POCD are reversible at 6 months, and a general improvement was observed in cognitive function at 6 months after ablation.

17.
Drug Des Devel Ther ; 15: 2947-2959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262260

RESUMO

Purpose: TPN171H is a novel, potent and selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of pulmonary arterial hypertension (PAH). The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of TPN171H in healthy subjects after single and multiple dosing, in addition, to investigate the food effect on pharmacokinetics and safety of TPN171H. Methods: The entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 63 healthy subjects were enrolled in the study. TPN171H tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events. Results: In Part I, AUC and Cmax were proved to be linear within the 5-30 mg dose range. T1/2 of TPN171H was 8.02-10.88 h. In Part II, we figured out that TPN171H administration under fed condition could decrease Cmax, prolong Tmax, but had no effect on AUC. In Part III, the accumulation ratio at steady-state for AUC and Cmax indicated that TPN171H has a slight accumulation upon repeated dosing. Subjects were generally tolerable after TPN171H administration. Compared with other PDE5 inhibitors, TPN171H was found to have no impact on blood pressure and color discrimination. Conclusion: TPN171H was safe and generally tolerated in healthy subjects. Based on the half-life, food effect, and safety profile of TPN171H, we recommend a once-daily, post-meal administration of TPN171H in subsequent clinical studies in healthy subjects and patients with PAH.

18.
Mikrochim Acta ; 188(8): 255, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264390

RESUMO

As an extremely important post-transcriptional regulator, miRNAs are involved in a variety of crucial biological processes, and the abnormal expressions of miRNAs are closely related to a variety of diseases. In this work, for the first time, we designed a nucleic acid lock nanostructure for specific detection of miRNA-21, which changes the self-structure to "active conformation" by binding the target, in order to generate triggers to initiate the subsequent reaction. Emphatically, this flexible nucleic acid lock is capable of self-cleaving without the assistance of external component, overcoming the disadvantages of the complex design and requiring protease assistance in traditional nanostructure. Moreover, the combination of DNAzyme and RCA technology not only greatly improves the efficiency of signal amplification but also enables primer generation to simultaneous cascade RCA amplification. Additionally, the electrochemical detection technology based on silver nanoclusters overcomes the shortcomings of traditional detection methods such as low sensitivity and complex operation. The detection limit achieved was 9.3 aM with a wide dynamic response ranging from 10 aM to 100 pM (at the DPV peak of - 0.5 V), which is comparable to most of the reported studies. Therefore, our work provided an ultra-sensitive way for the detection of miRNAs using nanostructures and revealed an effective means for disease theranostics and cancer diagnosis. In this work, for the first time, we designed a nucleic acid lock nanostructure based on its self-structural transformation for the specific detection of miRNA. And the combination of DNAzyme and cascade RCA reaction greatly improved the signal amplification efficiency.

19.
Brain Res Bull ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34265390

RESUMO

OBJECTIVE: Long non-coding RNAs (lncRNAs) have diagnostic and therapeutic values in the setting of ischemic stroke (IS). Here, we evaluated the value of myocardial infarction-associated transcript (MIAT) in IS with the involvement of microRNA (miR)-874-3p/interleukin (IL) 1B. METHODS: MIAT, miR-874-3p and IL1B levels in serum of patients with IS were measured. A middle cerebral artery occlusion (MCAO) model was established in mice. MCAO mice were injected with Agomir of miR-874-3p, shRNA or overexpression vector of MIAT or siRNA of IL1B. Subsequently, behavioral activities and neurological function of mice were assessed. The number of Nissl bodies, brain damage, neuronal apoptosis and inflammatory factors in brain tissues of mice were measured. The targeting relationship between MIAT and miR-874-3p, as well as that between miR-874-3p and IL1B was explored. RESULTS: In patients with IS, MIAT and IL1B were up-regulated and miR-874-3p was down-regulated. MIAT absorbed miR-874-3p while miR-874-3p targeted IL1B. Silencing of MIAT or IL1B, or promotion of miR-874-3p improved behavioral activities and neurological function of mice, reduced the number of Nissl bodies, as well as improved brain damage, neuronal apoptosis and inflammation. Overexpression of miR-874-3p abrogated up-regulated MIAT-mediated influence on MCAO mice. CONCLUSION: Shortly, this study figures out that MIAT impairs neurological function in IS via up-regulating miR-874-3p-targeted IL1B.

20.
Transl Oncol ; 14(9): 101159, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34252711

RESUMO

The persistence of leukemia stem cells (LSCs) is one of the leading causes of chemoresistance in acute myeloid leukemia (AML). To explore the factors important in LSC-mediated resistance, we use mass spectrometry to screen the factors related to LSC chemoresistance and defined IFN-γ-inducible lysosomal thiol reductase (GILT) as a candidate. We found that the GILT expression was upregulated in chemoresistant CD34+ AML cells. Loss of function studies demonstrated that silencing of GILT in AML cells sensitized them to Ara-C treatment both in vitro and in vivo. Further mechanistic findings revealed that the ROS-mediated mitochondrial damage plays a pivotal role in inducing apoptosis of GILT-inhibited AML cells after Ara-C treatment. The inactivation of PI3K/Akt/ nuclear factor erythroid 2-related factor 2 (NRF2) pathway, causing reduced generation of antioxidants such as SOD2 and leading to a shifted ratio of GSH/GSSG to the oxidized form, contributed to the over-physiological oxidative status in the absence of GILT. The prognostic value of GILT was also validated in AML patients. Taken together, our work demonstrated that the inhibition of GILT increases AML chemo-sensitivity through elevating ROS level and induce oxidative mitochondrial damage-mediated apoptosis, and inhibition of the PI3K/Akt/NRF2 pathway enhances the intracellular oxidative state by disrupting redox homeostasis, providing a potentially effective way to overcome chemoresistance of AML.

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