High-sensitivity piezoresistive sensors based on cellulose handsheets using origami-inspired corrugated structures.

Cellulose-based composites have attracted significant attention in the fabrication and advancement of wearable devices due to their sustainable, degradable, and cost-effective properties. However, achieving a cellulosic sensor with reliable sensory feedback remains challenging owing to the deficiency in reversible microstructures during response processes. In this study, we developed a piezoresistive sensor consisting of nearly pure cellulose handsheets using origami-inspired corrugated structures to achieve durable and sensitive piezoresistive responses. Multi-walled carbon nanotubes (MWCNTs) were used as conducting agents. With the addition of 7 wt% MWCNTs, 36.27 % of the cellulose fiber surface was covered and the conductivity of cellulose handsheets was increased to 8.7 S/m. The obtained conductive cellulose handsheets were transformed into corrugated structures and integrated orthogonally to construct the piezoresistive sensors with reversible electrical paths for electrons. The restorable corrugated structure endowed the sensors with a wide workable pressure range (0-10 kPa), high sensitivity (6.09 kPa-1 in a range of 0-0.92 kPa), fast response time (<280 ms), and good durability (>1000 cycles). Furthermore, the practical applications of the proposed sensors as wearable devices were demonstrated through phonation, real-time sports monitoring, and step pressure tests.

Lgr5-expressing secretory cells form a Wnt inhibitory niche in cartilage critical for chondrocyte identity.

Osteoarthritis is a degenerative joint disease that causes pain, degradation, and dysfunction. Excessive canonical Wnt signaling in osteoarthritis contributes to chondrocyte phenotypic instability and loss of cartilage homeostasis; however, the regulatory niche is unknown. Using the temporomandibular joint as a model in multiple species, we identify Lgr5-expressing secretory cells as forming a Wnt inhibitory niche that instruct Wnt-inactive chondroprogenitors to form the nascent synovial joint and regulate chondrocyte lineage and identity. Lgr5 ablation or suppression during joint development, aging, or osteoarthritis results in depletion of Wnt-inactive chondroprogenitors and a surge of Wnt-activated, phenotypically unstable chondrocytes with osteoblast-like properties. We recapitulate the cartilage niche and create StemJEL, an injectable hydrogel therapy combining hyaluronic acid and sclerostin. Local delivery of StemJEL to post-traumatic osteoarthritic jaw and knee joints in rabbit, rat, and mini-pig models restores cartilage homeostasis, chondrocyte identity, and joint function. We provide proof of principal that StemJEL preserves the chondrocyte niche and alleviates osteoarthritis.

Decreased platelet miR-199a-5p level might lead to high on-clopidogrel platelet reactivity in patients with coronary artery disease.

Clopidogrel combined with aspirin is widely used in coronary artery disease (CAD) patients, while some patients exhibit high platelet activity when receiving the combined treatment. Current environmental and genetic factors could only explain part of the variability in clopidogrel efficacy. Human platelets harbor abundant miRNAs which might affect clopidogrel efficacy by regulating the expression of key proteins in the clopidogrel antiplatelet signaling pathway. This study aimed to investigate the association between platelet miRNA levels and clopidogrel efficacy. Here we recruited 508 CAD patients who underwent clopidogrel antiplatelet therapy and determined the platelet reactivity index (PRI) to evaluate antiplatelet reactivity responses to clopidogrel. Subsequently, 22 patients with extreme clopidogrel response were selected for platelet small RNA sequencing. Another 41 CAD patients taking clopidogrel were collected to verify the differentially expressed candidate miRNAs. We found the metabolic types of the CYP2C19 enzyme (based on CYP2C19 * 2 and * 3 polymorphisms) could significantly affect the PRI of CAD patients with or without percutaneous coronary intervention (PCI) in Chinese. A total of 43 miRNAs were differentially expressed in the platelets from the 22 extreme clopidogrel response samples, and 109 miRNAs were differentially expressed in the 13 CYP2C19 extensive metabolizers with extreme clopidogrel response. Platelet miR-199a-5p levels were correlated negatively with PRI after clopidogrel therapy. Studies in cultured cells revealed that miR-199a-5p inhibited the expression of VASP, a key effector protein downstream of the P2Y12 receptor. In conclusion, we found the expression of VASP could be inhibited by miR-199a-5p, and decreased platelet miR-199a-5p was associated with high on-clopidogrel platelet reactivity in CAD patients.

What is the context?● Clopidogrel combined with aspirin is widely used in coronary artery disease (CAD) patients, while some patients exhibit high platelet activity when receiving the combined treatment.● Current environmental and genetic factors could only explain part of the variability in clopidogrel efficacy.● Human platelets harbor abundant miRNAs which might affect clopidogrel efficacy by regulating the expression of key proteins in the clopidogrel antiplatelet signaling pathway.What is new?● We found that decreased platelet miR-199a-5p level was associated with high on-clopidogrel platelet reactivity.● Overexpression of miR-199a-5p significantly down-regulated the expression of VASP protein in cultured cells.What is the impact?● The current study provided new insights into the exploration of interindividual variability in clopidogrel response from the perspective of miR-199a-5p and VASP interaction.

Chitosan-based nerve guidance conduit with microchannels and nanofibers promotes schwann cells migration and neurite growth.

Peripheral nerve injury (PNI) is the leading cause of permanent dysfunction in movement and sensation. Despite the rapid development of tissue engineering in peripheral nerve regeneration, autograft remains the gold standard for treating PNI. Synthesized nerve guidance conduits (NGCs) were reported as a potential alternative treatment that could replace autograft. However, most current NGCs are hollow tubular structured, or NGCs with macro or microstructures, but not both. These simple structures could not meet the need for neurite and Schwann cell guidance and accelerate peripheral nerve regeneration. In the current study, we combine unidirectional freezing with electrospinning to produce a unique NGC with longitudinal microchannels and parallel nanofibers. The in vitro study showed the importance of having both features in promoting Schwann cell growth, migration, and PC-12 cells neurite elongation. The novel NGCs could provide desirable physical support and guidance for peripheral nerve regeneration. From the current study, we found both the micro feature and the nano feature are helpful in terms of helping cell migrating through the NGCs, and the combination of both features will have a syngeneic effect.

Pharmacokinetics of Esomeprazole Magnesium After Single Oral Doses in Healthy Subjects: Bioequivalence Study and Food Effects.

This study was designed to evaluate the bioequivalence of the newly developed delayed-release oral suspension (test) 40 mg esomeprazole magnesium compared to its marketed counterpart (40 mg; reference) in healthy adult Chinese subjects. We conducted randomized, open-label, two-period, single-dose, two-way crossover trials over a 7-day washout period, comprising a fasting trial and a fed trial. The subjects were administered the test or reference products in a 1:1 ratio at random throughout each period. Then, in the next session, they received the alternate products. Liquid chromatography-tandem mass spectrometry and WinNonlin software were used to assess the bioequivalence of esomeprazole peak plasma concentration (Cmax ) and area under the concentration-time curve (AUC). Overall, 33 subjects participated in the fasting trial and 42 subjects participated in the fed trial. Under both situations, the 90% confidence interval for the ratio of geometric means of Cmax , AUC0-t , and AUC0-∞ were within equivalence ranges (80%-125%). In these trials, no severe adverse events or protocol violations were observed. Moreover, when esomeprazole was administered while fed, the tmax was delayed, and both Cmax and AUC were reduced. The results of this research suggest that the test and reference formulations were bioequivalent under fasting and fed states.

Targeting PI3K/AKT/mTOR pathway to enhance the anti-leukemia efficacy of venetoclax.

BACKGROUND: The treatment of acute myeloid leukemia (AML) is developing towards "targeted therapy", which faces challenges such as low sensitivity and drug resistance. Therefore, targeted drugs need to be used in combination with other drugs to overcome clinical problems. OBJECTIVE: AML cells and animal models were used to determine the synergistic anti-leukemic effect of Dactolisib (BEZ235) and Venetoclax (ABT199) and explore its mechanism. METHODS: In vitro experiments, we used cell counting kit-8 (CCK8), flow cytometry, real-time quantitative PCR (qPCR), and Western blot to detect the anti-leukemic effects of ABT199 and BEZ235. In vivo experiments, female nude mice were injected subcutaneously with THP-1 cells to form tumors, evaluate the combined effect of ABT199 and BEZ235 by indicators such as tumor size, tumor weight, Ki67 and cleaved-Caspase3 staining. The mice's body weight and HE staining were used to evaluate the liver injury and adverse drug reactions. RESULTS: The combination of BEZ235 and ABT199 has a synergistic effect through promoting apoptosis and inhibiting proliferation. The BEZ235 increased the drug sensitivity of ABT199 by reducing the MCL-1 protein synthesis and promoted the degradation of MCL-1 protein, which is considered as the mechanism of reversing ABT199 resistance. Furthermore, the BEZ235 and ABT199 can synergistically enhance the inhibition of PI3K/AKT/mTOR pathway. CONCLUSION: The combination of BEZ235 and ABT199 exhibits a synergistic anti-tumor effect in AML by down-regulating MCL-1 protein.

Metformin exerts a synergistic effect with venetoclax by downregulating Mcl-1 protein in acute myeloid leukemia.

Background: Recently, one of the specific BH3-mimetics, Venetoclax has been approved by FDA providing new options for newly diagnosed AML patient especially who are unfitted to receive conventional chemotherapy. Though the clinical success of venetoclax has been achieved in clinical outcomes such as complete remission (CR) and overall survival. Acquired resistance to ABT-199 which is induced by the regulation of apoptosis pathway is still an important clinical problem. To this end, the attempt to combine drugs which can reverse the compensatory regulation is urgent. Methods: In three AML cell lines (KG-1, Kasumi-1 and THP-1), the anti-AML effects of the combination of ABT-199 (Venetoclax) and metformin or the two drugs used alone were compared. CCK8 was used to evaluate the cell viability, and flow cytometry was used to estimate the rate of apoptosis, Western blot method was performed to detect apoptosis-related protein levels. In mice experiments, female BALB/c-nu nude mice were subcutaneously injected with THP-1 cells for subcutaneous tumor formation, and the combined effect of ABT-199 and metformin was tested. The evaluation indicators were tumor size, tumor weight, and Ki67 staining. Mouse body weight and HE staining were detected to evaluate liver damage and adverse drug reactions. Results: Both in vitro and in vivo experiments showed that compared with metformin or ABT-199 alone, the combined use of the two drugs exerts a synergistic effect on promoting apoptosis, thereby producing a strong anti-leukemia effect. Furthermore, after a short incubation time, ABT-199 swiftly increased the expression level of the anti-apoptotic protein Mcl-1, while the combined use of metformin and ABT-199 significantly reduced the level of Mcl-1. Notably, Metformin significantly downregulates the level of Mcl-1 protein by inhibiting its protein production. To less extent, metformin can also downregulate the expression of another anti-apoptotic protein, BCL-xl. Conclusion: Metformin downregulates the expression of anti-apoptotic proteins Mcl-1 and Bcl-xl by inhibiting protein production, and shows a synergistic anti-tumor effect with ABT-199 in acute myeloid leukemia.

Inhibition of Nrf2-mediated glucose metabolism by brusatol synergistically sensitizes acute myeloid leukemia to Ara-C.

Chemotherapy resistance remains to be the primary barrier to acute myeloid leukemia (AML) treatment failure. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been well established as a truly pleiotropic transcription factor. Inhibition of Nrf2 function increases the sensitivity of various chemotherapeutics and overcomes chemoresistance effectively. Brusatol (Bru) has been reported to decrease Nrf2 protein expression specifically by ubiquitin degradation of Nrf2. However, it remains elusive whether combination of Brusatol and Cytarabine (Ara-C) elicits a synergistic antitumor effect in AML. Our results demonstrated that combination of Ara-C and Brusatol synergistically exerted remarkable pro-apoptosis effect in HL-60 and THP-1 cells. Mechanistically, synergistic anti-tumor effect of Ara-C/Brusatol in AML cells is mediated by attenuating Nrf2 expression. To our surprise, Nrf2 inhibition by Brusatol causes downregulation of the expression of glycolysis-related proteins and decreased glucose consumption and lactate production, whereas the level of ROS production was unaffected. The activation of Nrf2 by Sulforaphane (SFP) could reverse the chemotherapeutic effect and changes of glycolysis of concomitant of Ara-C with Brusatol in AML cell lines. Additionally, Ara-C/Brusatol co-treatment decreased Glucose-6-phosphate dehydrogenase (G6PD) protein expression and increased the sensitivity of Ara-C. Moreover, the mouse xenograft in vivo experiment confirmed that combining Ara-C with Brusatol exerted stronger antileukemia than Ara-C alone. The efficacy, together with the mechanistic observations, reveals the potential of simultaneously giving these two drugs and provides a rational basis for targeting glucose catabolism in future clinical therapeutic approach.

Evaluating the protective effects of individual or combined ginsenoside compound K and the downregulation of soluble epoxide hydrolase expression against sodium valproate-induced liver cell damage.

Sodium valproate (SVP) is one of the most commonly prescribed antiepileptic drugs. However, SVP is known to induce hepatotoxicity, which limits its clinical application for treating various neurological disorders. Previously, we found that ginsenoside compound K (G-CK) demonstrated protective effects against SVP-induced hepatotoxicity by mitigating oxidative stress and mitochondrial damage, as well as downregulating the expression of soluble epoxide hydrolase (sEH) in rats. This study aimed to assess the effect of G-CK on SVP-induced cytotoxicity in human hepatocytes (L02 cell line), as well as the effect of the downregulation of sEH expression on both the hepatotoxicity of SVP and the hepatoprotective effects of G-CK. We observed that G-CK significantly ameliorated the decrease of cell viability, elevated ALT, AST and ALP activities, significant oxidative stress, and loss of mitochondrial membrane potential induced by SVP in L02 cells. G-CK also inhibited the SVP-mediated upregulation of sEH expression. Transfection of the L02 cells with siRNA-sEH led to a partial improvement in the L02 cytotoxicity caused by SVP by mitigating cellular oxidative stress without recovering the reduced mitochondrial membrane potential. Furthermore, the combination of siRNA-sEH and G-CK had better inhibitory effects on the SVP-induced changes of all detection indices except mitochondrial membrane potential than G-CK alone. Together, our results demonstrated that the combination of siRNA-sEH and G-CK better suppressed the SVP-induced cytotoxicity in L02 cells compared to either G-CK or siRNA-sEH alone.

Tumor cell membrane-based peptide delivery system targeting the tumor microenvironment for cancer immunotherapy and diagnosis.

The development of an effective delivery system for peptides targeting the tumor microenvironment has always been a hot topic of research in the field of cancer diagnosis and therapy. In this study, superparamagnetic iron oxide nanoparticles (SPIO NPs) were encapsulated with H460 lung cancer cell membranes (SPIO NP@M), and two peptides, namely PD-L1 inhibitory peptide (TPP1) and MMP2 substrate peptide (PLGLLG), were conjugated to the H460 membrane (SPIO NP@M-P). Homologous targeting, cytotoxicity, and pharmacokinetics of SPIO NP@M-P were evaluated. The TPP1 peptide was delivered and released to the tumor microenvironment through the homotypic effect of tumor cell membrane and specific digestion by the tumor-specific enzyme MMP2. The newly developed delivery system (SPIO NP@M-P) for the PD-L1 inhibitory peptide could effectively extend the half-life of the peptides (60 times longer than that for peptides alone) and could maintain the ability to reactivate T cells and inhibit the tumor growth both in vitro and in vivo. Furthermore, SPIO NPs in the system could be used as a tumor imaging agent and thus show the effect of peptide treatment. The SPIO NP@M might serve as a promising theranostic platform for therapeutic application of peptides in cancer therapy. STATEMENT OF SIGNIFICANCE: A multifunctional delivery system (SPIO NP@M) was constructed for effectively delivering therapeutic peptides into the tumor microenvironment for cancer diagnosis and therapy. In this paper, the TPP-1 peptide inhibiting the binding of PD-L1 and PD-1 was delivered and released into the tumor microenvironment by the homotypic targeting of H460 cell membrane and specific digestion by the MMP2 enzyme. SPIO NPs in this system were aggregated effectively at the tumor sites and were used for magnetic resonance imaging of tumors. The SPIO NP@M-P delivery system could effectively extend the half-life of the TPP-1 peptide (60 times longer than that of the free peptide) and could maintain the ability to re-activate T cells and inhibit tumor growth in vitro and in vivo. In conclusion, the SPIO NP@M system coated with lung cancer cell membrane and loaded with the PD-L1-blocking TPP-1 peptide could be a promising integrated platform for tumor diagnosis and treatment.

TBC1D16 predicts chemosensitivity and prognosis in adult acute myeloid leukemia (AML) patients.

Acute myeloid leukemia (AML) is a hematopoietic disease with poor survival. Chemotherapy resistance is one of the determinant factors influencing AML prognosis. To identify genes possibly affecting the drug responses in AML, the Illumina Infinium MethylationEPIC (850K) was used to screen for differential DNA methylation loci between patients achieved complete remission (CR) or not (non-CR) after induction therapy in 37 AML patients. Then, 32 differentially methylated sites (DMS) were selected for replication in another 86 AML patients by next-generation sequencing. Nine sites including cg03988660, cg16804603, cg18166936, cg11308319, cg09095403, cg18493214, cg01443536, cg16030878 and cg10143426 were replicated. Analysis of the Gene Expression Omnibus (GEO) database showed that mRNA expression of TBC1D16 and HDAC4 was associated with AML prognosis. Methylation level of the cg16030878 in TBC1D16 3'-UTR correlated positively with TBC1D16 mRNA expression in samples both in the TCGA database and clinically collected in the study. Both higher cg16030878 methylation and higher TBC1D16 mRNA expression were associated with increased risk of non-CR and worse overall survival (OS) in AML patients. In AML cells, knockdown of TBC1D16 decreased cell proliferation and ERK phosphorylation levels, as well as increased sensitivity to mitoxantrone and decitabine indicated by IC50. In patients with combined use of decitabine, those patients with CR showed significantly lower TBC1D16 mRNA expression. On the contrary, knockdown of TBC1D16 resulted in decreased sensitivity to cytarabine in U937 cells. Our findings implicated that TBC1D16 is a potential predictor for chemosensitivity and prognosis in adult AML patients.

Two new biflavanoids from Selaginella trichoclada Alsto.

Two new robustaflavones, (±)-trichocladabiflavone A (1) and uncinatabiflavone E (2), along with seven known biflavanoids (3-9) were isolated from the 70% EtOH extract of Selaginella trichoclada. Their structures and absolute configurations were established by extensive spectroscopic and circular dichroism (CD) analyses. Compound 1 was resoluted into optically pure enantiomers (+)-1 and (-)-1 by chiral-phase HPLC. Moreover, compounds 1 and 2 exhibited moderate cytotoxicity against A549 and HepG2 human cancer cell lines.

Fabrication of polylactic acid (PLA)-based porous scaffold through the combination of traditional bio-fabrication and 3D printing technology for bone regeneration.

Artificial bone grafts possess the advantages of good biodegradability, customizable dimensions, and sufficient mechanical properties, which can promote cell proliferation and differentiation in bone tissue regeneration. 3D printing is a delicate approach that endows the scaffolds with excellent controllability and repeatability when compared with conventional bio-fabrication methods. However, the limitation of printing resolution somehow makes it difficult to prepare bone defect substitution with high porosity and hierarchical construct. In this study, we utilized polylactic acid (PLA) as printing materials and developed a smart strategy to combine 3D printing technology with bio-fabrication methods. A porous planar scaffold was printed and then rolled up into a spiral structure with adjustable pore size and porosity. The topographic features and morphology of the artificial scaffolds were examined through stereomicroscope and SEM, respectively. The porous spiral scaffold presented good mechanical properties in a set of mechanical testing. Later, the human fetal osteoblasts (hFOB) were cultured on the porous spiral scaffold and its control groups for a total of 28 days. The MTS analysis, alkaline phosphatase (ALP) assay, and alizarin red S (ARS) staining were used to analyze the cell proliferation, osteogenic differentiation, and mineral deposition after a certain period of time. The results indicated that compared with the other two scaffolds, the porous spiral scaffold with larger surface area and better interconnections between internal porous networks could significantly improve the spatial cell compartment and promote cell growth and differentiation. The porous spiral scaffold may see versatile applications in large-volume bone defects regeneration.

Effect of maternal dietary supplementation with phytosterol esters on muscle development of broiler offspring.

Recently, embryo muscle development, which is crucial for postnatal skeletal muscle growth, has been investigated widely. Nutrients in ovo were suggested to be critical in embryo muscle development since the chick growth mostly relies on nutrients in eggs at the early developmental stage. Phytosterol esters (PE), which are derived from the reactions between phytosterols and fatty acids, were demonstrated to have important effects on lipid and cholesterol metabolism regulation. In order to reveal the effect of maternal lipid metabolism on the deposition of nutrients in eggs and the development of embryonic muscles, broiler hens were fed with a diet supplemented with 5% PE or control diet. Lipid deposition in eggs and growth of the hatched chicks were studied. We found that PE increased bile acid (BA) deposition in the eggs and serum of hens (p=0.02 and p<0.01, respectively), altered insulin and glucose level differentially in female and male offspring, and promoted body weight (p=0.02 for male and female on day 49), muscle fiber density (p=0.02 for female on day 49), and myogenin and myogenic determination factor (myoD) expression (p=0.03 and p=0.02 on day 49) by the activation of BA receptors in female, but not in male, offspring. Our study determined for the first time that PE promoted muscle development of chicks hatching from eggs laid by the hens, through regulating bile acid (BA) deposition and this may be attributed to the activation of BA receptors.

Nanofibrous Nerve Conduits with Nerve Growth Factors and Bone Marrow Stromal Cells Pre-Cultured in Bioreactors for Peripheral Nerve Regeneration.

Peripheral nerve injury (PNI) was the leading cause of permanent dysfunction in movement and sensation. Synthesized nerve guide conduits (NGCs) with Schwann Cells (SCs) can help peripheral nerve regeneration. However, poor accessibility of SCs and lack of full coverage of seeded cells on NGCs can lead to failure of nerve regeneration across long gaps and full functional recovery. To overcome these limitations, bone marrow stromal cells (BMSCs) and a novel culture method were proposed in the current study. BMSCs were harvested and seeded on a never growth factor (NGF)-loaded PCL nanofibrous NGCs and cultured with a rotary cell culture system (RCCS) before implantation. The NGCs were tested in vitro with PC-12 cells to validate the bioactivity of released NGF and to access its ability to promote neurite extension. Also, the NGCs were tested in vivo with rat sciatic nerve model to exam its potential in bridging the long gap (15 mm segmental defect). The efficacy of the NGCs was investigated based on the results of the functional test, electrophysiology test, muscle atrophy, and histological analysis. The results of in vitro PC-12 cell study confirmed the bioactivity of released NGF and showed a significant increase in the neurite extension with the help of PEG-diamine and BSA. These results showed that the novel loading method could preserve the bioactivity of growth factors and achieve a sustained release in vitro. Besides, the results of the in vivo study exhibited a significant increase with the combination of all additives. These results showed that with the help of NGF and RCCS, the NGCs with the seeded BMSCs could enhance peripheral nerve regeneration across long nerve injury gaps.

The potentiation of menadione on imatinib by downregulation of ABCB1 expression.

Imatinib was the first BCR-ABL inhibitor used in clinical practice to treat chronic myeloid leukaemia (CML) and significantly improve the life expectancy of CML patients in the chronic phase. However, a portion of CML patients are resistant to imatinib. This study aimed to determine whether menadione (Vitamin K3) can improve imatinib efficacy in CML and to thoroughly explore the combination regimen mechanism between imatinib and menadione. Menadione improved imatinib efficacy in K562 cells by downregulating ABCB1 expression and increased the intracellular concentration of imatinib, which confirmed that this combination regimen is more effective than imatinib monotherapy. The results demonstrate that menadione and imatinib combination therapy may be a promising approach to refractory CML.

Down-regulating NQO1 promotes cellular proliferation in K562 cells via elevating DNA synthesis.

BACKGROUND: NQO1 protein acts as a cellular protective system, on account of its role as a quinone reductase and redox regulator. Nonetheless, new NQO1 roles are emerging-including its regulation of the cellular proliferation of many tumor cells-and this enzyme has been found to relate to the incidence of various diseases, including chronic myeloid leukemia. However, the mechanisms through which NQO1 influences leukemia progression remain unclear. MARTIAL AND METHODS: The current study looks to name NQO1 as a novel molecular target that modulates DNA synthesis and chronic myeloid leukemia growth. RESULTS AND CONCLUSION: Our results indicate that the frequency of the T allele of NQO1 polymorphism in chronic myeloid leukemia patients is higher than that among healthy East Asian individuals (0.492 vs. 0.419) and much higher than the average level of the general population (0.492 vs. 0.289) (1000 Genomes). Functionally, NQO1 knockdown increases the protein expression of the TOP2A and MCM complex, and consequently promotes DNA synthesis and K562 cell growth. NQO1 knockdown also promotes tumorigenesis in a xenograft model. NQO1 overexpression, on the other hand, was found to have the opposite effects. SIGNIFICANCE: Our results show that NQO1 downregulation promotes K562 cellular proliferation via the elevation of DNA synthesis.