Electro-microenvironment modulated inhibition of endogenous biofilms by piezo implants for ultrasound-localized intestinal perforation disinfection.

Endogenous bacterial infections from damaged gastrointestinal (GI) organs have high potential to cause systemic inflammatory responses and life-threatening sepsis. Current treatments, including systemic antibiotic administration and surgical suturing, are difficult in preventing bacterial translocation and further infection. Here, we report a wireless localized stimulator composed of a piezo implant with high piezoelectric output serving as an anti-infective therapy patch, which aims at modulating the electro-microenvironment of biofilm around GI wounds for effective inhibition of bacterial infection if combined with ultrasound (US) treatment from outside the body. The pulsed charges generated by the piezo implant in response to US stimulation transfer into bacterial biofilms, effectively destroying their macromolecular components (e.g., membrane proteins), disrupting the electron transport chain of biofilms, and inhibiting bacterial proliferation, as proven by experimental studies and theoretical calculations. The piezo implant, in combination with US stimulation, also exhibits successful in vivo anti-infection efficacy in a rat cecal ligation and puncture (CLP) model. The proposed strategy, combining piezo implants with controllable US activation, creates a promising pathway for inhibiting endogenous bacterial infection caused by GI perforation.

A Wave-Driven Piezoelectrical Film for Interfacial Steam Generation: Beyond the Limitation of Hydrogel.

Solar interfacial vapor generation based on low evaporation energy requirements is an effective technology to speed up water purification under natural sunlight, offering great potential to alleviate the current global water crisis. The external electric field and hydrogel are two independent methods enabling low-energy water evaporation. However, the complicated external equipment for generating an electric field and the restricted activation area of hydrogels significantly limit their practical application in steam generation. Thus, a piezoelectric fiber membrane is embedded into a highly hydratable light-absorbing poly(vinyl alcohol) (PVA) hydrogel for synergistic water activation. The integrated evaporator is capable of continuously converting the wave energy reserved in the ocean into electrical energy, activating the water in the hydrogel. It is found that the activation effect leads to an improvement of over 23% compared to a non-piezoelectric hydrogel evaporator. This work provides an evaporation prototype based on the synergistic water activation of wave-triggered electricity and highly hydratable hydrogel.

Redox-Mediated Artificial Non-Enzymatic Antioxidant MXene Nanoplatforms for Acute Kidney Injury Alleviation.

Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti3 C2 -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti3 C2 and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.

[Sensitivity Analysis of Boundary Load Reduction in a Large Shallow Lake Water Quality Model].

To explore the spatial and temporal response of water quality to external load reduction in Lake Taihu, Jiangsu Province, China, and clarify the exogenous load reduction under different water inflow and pollution conditions, a water quality model was constructed and the inflow boundaries were divided into seven groups based on the EFDC model. Taking COD and ammonia nitrogen as output targets, the sensitivities of Taihu Lake water quality boundaries were analyzed using a local sensitivity analysis. The results showed that COD and ammonia nitrogen concentrations of each lake area were more sensitive to the boundary load of the lake area than the rest of the lake area, and the sensitivity index was the highest in the Northwest Lake area. Furthermore, the improvement rates of mean COD concentrations in the whole lake decreased by 28.40%-34.71% in the dry season relative to the wet season, and the ranked sensitivity order of the boundaries was as follows:Northwest Lake boundary > Zhushan Lake boundary > Gonghu Lake boundary > Meiliang Bay boundary > Southwest Lake area boundary > Eastern Lake area boundary > East Lake Taihu boundary. The average improvement rates of ammonia nitrogen concentrations in the whole lake were 41.59%-42.34% higher in the dry season relative to the wet season, and the ranked boundary sensitivity order was as follows:Northwest Lake boundary > Meiliang Bay boundary > Zhushan Lake boundary > Gonghu Lake boundary > Southwest Lake boundary > East Lake Taihu boundary > Eastern Lake area boundary. This difference was affected by algal growth and metabolism, and artificial water diversion and drainage. Therefore, it is necessary to consider the reduction period and inflow location according to different water-quality indicators when planning external prevention and control measures in large lakes.

Smart Ti3C2Tx MXene Fabric with Fast Humidity Response and Joule Heating for Healthcare and Medical Therapy Applications.

An increasing utilization of flexible healthcare electronics and biomedicine-related therapeutic materials urges the development of multifunctional wearable/flexible smart fabrics for personal therapy and health management. However, it is currently a challenge to fabricate multifunctional and on-body healthcare electronic devices with reliable mechanical flexibility, excellent breathability, and self-controllable joule heating effects. Here, we fabricate a multifunctional MXene-based smart fabric by depositing 2D Ti3C2Tx nanosheets onto cellulose fiber nonwoven fabric via special MXene-cellulose fiber interactions. Such multifunctional fabrics exhibit sensitive and reversible humidity response upon H2O-induced swelling/contraction of channels between the MXene interlayers, enabling wearable respiration monitoring application. Besides, it can also serve as a low-voltage thermotherapy platform due to its fast and stable electro-thermal response. Interestingly, water molecular extraction induces electrical response upon heating, i.e., functioning as a temperature alarm, which allows for real-time temperature monitoring for thermotherapy platform without low-temperature burn risk. Furthermore, metal-like conductivity of MXene renders the fabric an excellent Joule heating effect, which can moderately kill bacteria surrounding the wound in bacteria-infected wound healing therapy. This work introduces a multifunctional smart flexible fabric suitable for next-generation wearable electronic devices for mobile healthcare and personal medical therapy.

Vasoactive intestinal peptide inhibits the activation of murine fibroblasts and expression of interleukin 17 receptor C.

Acute respiratory distress syndrome (ARDS) is an acute, severe, and refractory pulmonary inflammation with high morbidity and mortality. Excessive activation of fibroblast during the fibroproliferative phase plays a pivotal role in the prognosis of ARDS. Our previous study demonstrated that the vasoactive intestinal peptide (VIP) is mediated by lentivirus attenuates lipopolysaccharide (LPS)-induced ARDS in a murine model, and VIP inhibits the release of interleukin-17A (IL-17A) from activation macrophages. However, the effects of VIP on the activation of murine fibroblast and expression of IL-17 receptor (IL-17R) in ARDS remain unclear. Here, a mouse model of ARDS was established by an intratracheal injection of LPS. We found that the gene expression of col3a1 and hydroxyproline contents in the lungs were significantly increased 24 h after LPS injection. IL-17RC rather than IL-17RA was increased in the lungs of mice with ARDS. In vitro, LPS activated NIH3T3 cells, which was suppressed by VIP in a dose-dependent manner. In detail, VIP reduced the hydroxyproline content and col3a1 messenger RNA induced by LPS in NIH3T3 cells, as well as the expression of α-smooth muscle actin. Furthermore, we found that VIP inhibited the expression of IL-17R in the lungs of mice with ARDS and NIH3T3 cells stimulated with LPS, which was partly inhibited by antagonists of protein kinase A and protein kinase C. Taken together, our results demonstrated that VIP inhibited the activation of fibroblast via downregulation of IL-17RC, which may contribute to the protective effects of VIP against ARDS in mice.

Toxicity and Sublethal Effects of Flupyradifurone, a Novel Butenolide Insecticide, on the Development and Fecundity of Aphis gossypii (Hemiptera: Aphididae).

The cosmopolitan pest Aphis gossypii (Glover) causes considerable economic losses on various crops by its feeding damage and transmitting diseases around the world. Flupyradifurone is a novel butenolide pesticide; its toxicity on A. gossypii parent generation (F0) was estimated following treatment with LC25 concentration for 48 h. The adult longevity and fecundity of the F0 individuals treated by flupyradifurone showed no significant decrease in comparison with the control. Life table method was used to evaluate the sublethal effects on progeny population (F1). Results showed that the development time of the fourth instar and the preadult as well as the total pre-reproductive period were significantly prolonged, while their fecundity was significantly decreased compared with the control. Additionally, the intrinsic rate of increase (r), the finite rate of increase (λ), and the net reproductive rate (R0) of F1 were all significantly lower in the group treated by LC25 than in the control group. These results reveal that the sublethal concentration of flupyradifurone could suppress the population growth of A. gossypii and indicate that this novel insecticide may be as a useful tool in pest management.

SOX7 methylation is an independent prognostic factor in myelodysplastic syndromes.

OBJECTIVE: SOX7 downregulation caused by its promoter methylation was associated with poor survival in several types of human solid tumors. However, the pattern of SOX7 methylation and its clinical significance are less studied in hematological malignancies. Herein, we evaluated the methylation pattern of SOX7 in myelodysplastic syndrome (MDS) and determined its clinical implication in patients with MDS. METHODS: SOX7 methylation was determined by real-time quantitative methylation-specific PCR (RQ-MSP) in 99 MDS patients. Bisulfite sequencing PCR was applied to confirm the results of RQ-MSP. RESULTS: SOX7 methylation was detected in 55.6% of 99 patients but not in healthy donors. No correlation was found between SOX7 methylation and clinical parameters including patient age, gender, white blood cell count, hemoglobin, and platelet count. However, patients with SOX7 methylation harbored more U2AF1 mutation than patients without SOX7 methylation (P = 0.015). Kaplan-Meier curves indicated that the patients with SOX7 methylation presented reduced overall survival (OS) (P = 0.034). Furthermore, subgroup analysis indicated that SOX7 methylation was associated with poor OS in male patients (P = 0.034) and in patients older than 60 years (P = 0.019). According to the multivariate analysis, SOX7 methylation remained as an independent prognosis factor in MDS patients both as dichotomous (HR = 2.14, P = 0.041) and as continuous (HR = 1.55, P = 0.042) variable. Importantly, SOX7 methylation was significantly increased during progression from MDS to secondary acute myeloid leukemia (sAML). CONCLUSIONS: Our findings demonstrated that SOX7 methylation conferred adverse prognosis in MDS patients and was associated with leukemia progression.

Tannic acid functionalized graphene hydrogel for organic dye adsorption.

Water purification provides a feasible way to relieve the pressure of water shortage and water pollution which we are facing and adsorption is one of the most effective ways to turn polluted water into clean water. Here, we prepared graphene-tannic acid hydrogel using graphene oxide and tannic acid, a natural green reducer and adsorbent, through one-step hydrothermal method. The composition, structure, and morphology of the compounds were systematically examined. The adsorption of dyes was mainly influenced by the morphology and chemical properties of gel. The addition of tannic acid, a molecule rich in oxygen containing functional groups, changed the surface chemistry of graphene sheets and microstructures of gels, which was beneficial for contaminate adsorption. Compared with reduced graphene oxide hydrogel, the graphene-tannic acid hydrogel showed an outstanding adsorption capacity for organic dye methylene blue, more than 500 mg/g at pH 10 and the maximum adsorption capacity was up to 714 mg/g. After adsorption, ethanol and inorganic acid solution can be used as desorption agent and there was no significant adsorption capacity loss after 5 cycles.

Vascular-homing peptides for cancer therapy.

In the past 30 years, a variety of phage libraries have been extensively utilized to identify and develop tumor homing peptides (THPs). THPs specifically bind to tumor cells or elements of the tumor microenvironment while no or low affinity to normal cells. In this regard, the efficacy of therapeutic agents in cancer therapy can be enhanced by targeting strategies based on coupling with THPs that recognize receptors expressed by tumor cells or tumor vasculature. Especially, vascular-homing peptides, targeting tumor vasculature, have their receptors expressed on or around the blood vessel including pro-angiogenic factors, metalloproteinase, integrins, fibrin-fibronectin complexes, etc. This review briefly summarizes recent studies on identification and therapeutic applications of vascular-homing peptides targeting common angiogenic markers or with unknown vascular targets in some certain types of cancers. These newly discovered vascular-homing peptides are promising candidates which could provide novel strategies for cancer therapy.

The cortical thickness correlates of clinical manifestations in the mid-stage sporadic Parkinson's disease.

The cortical thickness has gained an extensive attention as a pathological alteration of sporadic Parkinson's disease (sPD), the alteration of pathological cortical thickness may distinctly contribute to the consistent clinical manifestations. Therefore, we investigated the cortical thickness correlates of clinical manifestations in the mid-stage sPD from the Han population of Chinese mainland (HPCM). A sample of 67 mid-stage sPD patients and 35 matched controls from HPCM were performed a corticometry of magnetic resonance imaging (MRI) and the assessment of clinical manifestations including the demographic and disease-related characteristics, and underwent the final analysis of the cortical thickness correlates with the clinical manifestations. In our result, we demonstrated that no significant differences in the demographic characteristics were found among the two groups. The tests of clinical disease-related characteristics demonstrated that the significant differences in the Hoehn and Yahr scale, the UPDRS Part I-IV, the symptom-dominant side (right/left/double), the tremor subscoree off (e), the tremor subscoref on (f), Webster, MMSE, HDS-R, DF, DB, SVFT, SDS, HAMD17, HAMD 24, CDT, CDR, LEDD and PDSI were observed between the mid-stage sPD patients and the controls. The analysis about the cortical thickness correlates with the clinical manifestations revealed that a significant correlation between UPDRS-I and Frontal-Sup-Orb-R and Rectus-R; DB and Frontal-Sup-Orb-R and Frontal-Inf-Orb-R; SDS and Frontal-Sup-Orb-R, Frontal-Mid-Orb-R, Rectus-R and Cingulum-Ant-R respectively in the mid-stage sPD patients from HPCM. Our data showed that the cortical thinning in the right frontal Orb, rectus and cingulum were the pathological base of some clinical manifestations including the cognitive impairment, hallucinations, psychosis, the depressed mood, the anxious mood, apathy, the sleep problems, the nighttime or/and daytime sleepiness, the short term memory stores and the central execution, as well as the sexual desire disorder in the mid-stage sPD patients, suggesting that the dysfunctions of brain regions of some cortical thinning are closely correlated with some clinical manifestations of the mid-stage sPD.

The cortical surface correlates of clinical manifestations in the mid-stage sporadic Parkinson's disease.

The alteration of pathological cortical surface may lead to the corresponding clinical manifestations of sporadic Parkinson's disease (sPD). Therefore, we investigated the correlates of cortical surface and clinical manifestations in the mid-stage sPD. Sixty seven mid-stage sPD patients and thirty five matched controls were performed the corticometry of magnetic resonance imaging (MRI) and the assessment of clinical manifestations including the demographic and disease-related characteristics, and underwent the final analysis of the correlates between cortical surface and clinical manifestations. The result revealed a significant correlation between CDT and Frontal-Sup-Orb-L, Frontal-Sup-Medial-L, Frontal-Mid-Orb-L and Rectus-L; SVFT and Frontal-Mid-L and Frontal-Inf-Tri-L; DF and Frontal-Sup-R, Frontal-Mid-R and Frontal-Sup-Medial-R; Webster and Occipital-Mid-R, Angular-R, Temporal-Sup-R and Temporal-Mid-R respectively in the mid-stage sPD patients. Our data suggested that the alterations of cortical surface in the left Frontal-Sup-Orb, Sup-Medial, Mid-Orb, Mid, Inf-Tri and Rectus, the right Frontal-Sup, Mid, Sup-Medial, and Occipital-Mid, Angular, Temporal-Sup and Temporal-Mid were the pathological base of some clinical manifestations including the cognitive impairment, the space structure, memory, attention, the abstract thinking, design, layout, utilization, digital, calculation, the time and spatial orientation concept, the operation sequence recognition and the partial motor dysfunctions in the mid-stage sPD, and that the dysfunctions of these brain regions contributed by the cortical surface lesion were closely correlated with some clinical manifestations of mid-stage sPD.

Vasoactive intestinal peptide suppresses macrophage-mediated inflammation by downregulating interleukin-17A expression via PKA- and PKC-dependent pathways.

Interleukin (IL)-17A is a pro-inflammatory cytokine that markedly enhances inflammatory responses in the lungs by recruiting neutrophils and interacting with other pro-inflammatory mediators. Reducing the expression of IL-17A could attenuate inflammation in the lungs. However, whether VIP exerts its anti-inflammatory effects by regulating the expression of IL-17A has remained unclear. Here, we show that there is a remarkable increase of IL-17A in bronchoalveolar lavage fluid (BALF) and lung tissue of mice with acute lung injury (ALI). Moreover, lipopolysaccharides (LPS) stimulated elevated expression of IL-17A, which was evident by the enhanced levels of mRNA and protein observed. Furthermore, we also found that VIP inhibited LPS-mediated IL-17A expression in a time- and dose-dependent manner in an in vitro model of ALI and that this process might be mediated via the phosphokinase A (PKA) and phosphokinase C (PKC) pathways. Taken together, our results demonstrated that VIP might be an effective protector during ALI by suppressing IL-17A expression.

Clinical significance of reduced SFRP1 expression in acute myeloid leukemia.

Deregulation of secreted frizzled-related protein 1 (SFRP1) has been found in many types of cancer. However, the pattern of SFRP1 expression in acute myeloid leukemia (AML) is still unclear. This study determined SFRP1 expression in patients with AML. SFRP1 expression was decreased markedly in patients with AML compared to controls (p < 0.001). White blood cell (WBC) counts increased as SFRP1 expression decreased in AML (p = 0.016). Patients with low SFRP1 expression showed a different distribution of French-American-British (FAB) subtypes M1/M2/M3 from those with high SFRP1 expression (p = 0.031). NPM1 mutation was mainly observed in patients with low SFRP1 expression (p = 0.011). There was a weak trend that patients with AML with low SFRP1 expression had shorter overall survival (OS) than those with high SFRP1 expression (p = 0.103). Our results indicate that reduced SFRP1 expression is found more frequently in the less well-differentiated subgroups of AML and is associated with NPM1 mutation in AML.

Double CEBPA mutations are prognostically favorable in non-M3 acute myeloid leukemia patients with wild-type NPM1 and FLT3-ITD.

This study is aimed to investigate the pattern of CEBPA mutations and its clinical significance in Chinese non-M3 acute myeloid leukemia (AML) patients. The entire coding region of CEBPA gene was amplified by PCR and then sequenced in samples from 233 non-M3 AML patients. Fifty mutations were identified in 37 (15.8%) patients with eleven (4.7%) double mutated CEBPA (dmCEBPA) and twenty-six (11.1%) single mutated CEBPA (smCEBPA). dmCEBPA was exclusively observed in M1 and M2 subtypes of FAB classification (P = 0.008), whereas smCEBPA occurred in almost all subtypes (P = 0.401). Patients with dmCEBPA had significantly younger age and higher WBC counts than those with wtCEBPA (P = 0.016 and 0.043, respectively). Both dmCEBPA and smCEBPA were mainly present in cytogenetically normal patients. Patients with dmCEBPA achieved higher rate of complete (CR) than wtCEBPA patients (88% vs. 51%, P = 0.037), whereas smCEBPA and wtCEBPA groups are similar (47% vs. 51%, P = 0.810). Patients with dmCEBPA had a superior overall survival (OS) compared with patients with wtCEBPA (P = 0.033), whereas patients with smCEBPA had a similar OS as patients with wtCEBPA (P = 0.976). dmCEBPA but not smCEBPA was also associated with favorable outcome in patients with wild-type NPM1 and FLT3-ITD (NPM1(wt)FLT3-ITD(wt) ). Our data confirm that dmCEBPA but not smCEBPA is prognostically favorable in NPM1(wt)FLT3-ITD(wt) AML, and suggest that the entity AML with mutated CEBPA should be definitely designated as AML with dmCEBPA in WHO classification and smCEBPA should be excluded from the favorable risk of molecular abnormalities.

Decreased SFRP2 expression is associated with intermediate and poor karyotypes in de novo acute myeloid leukemia.

Dysregulation of secreted frizzled-related protein 2 (SFRP2) has been found in various cancers. However, it is little known about the pattern of SFRP2 expression in acute myeloid leukemia (AML). This study was aimed to analyze the expression status of SFRP2 gene in AML patients and explore its clinical significance using real-time quantitative PCR (RQ-PCR). The level of SFRP2 expression significantly decreased in AML compared to controls (P<0.001). Receiver operating characteristic curve (ROC) analysis revealed that an area under the ROC curve (AUC) of 0.871 (P<0.001) or 0.902 (P<0.001) in discriminating all patients or cytogenetically normal (CN) patients from controls, respectively. Low level of SFRP2 expression was found more frequently in cytogenetically intermediate and poor groups (72% and 62%, respectively) than in favorable group (42%) (P<0.05). However, there was no significant difference in the rate of complete remission (CR) and overall survival between the groups with low SFRP2 and high expression (P>0.05). SFRP2 expression significantly increased after CR compared to initial diagnosis (P<0.05). These findings suggest that decreased SFRP2 expression is associated with intermediate/poor karyotypes in AML patients and detection of SFRP2 expression may be helpful to the diagnosis and disease monitoring in CN-AML.

Low SOX17 expression: prognostic significance in de novo acute myeloid leukemia with normal cytogenetics.

BACKGROUND: Aberrant expression of SRY-box containing gene 17 (SOX17) has been observed in several solid tumors. However, little is known about SOX17 expression in acute myeloid leukemia (AML). The purpose of this study was to investigate the alteration of SOX17 expression and to explore its clinical significance in AML. METHODS: Real-time quantitative PCR (RQ-PCR) was performed to analyze the status of SO1X17 expression in 103 patients with de novo AML and 26 normal controls. The clinical relevance of SOX17 expression was analyzed in AML. RESULTS: SOX17 level in AML was significantly down-regulated compared to controls (p<0.001). Receiver operating characteristic curve (ROC) curve analysis revealed that an area under the ROC curve (AUC) of 0.834 (95% CI 0.765-0.903; p<0.0001) or 0.789 (95% CI 0.690-0.888, p<0.001) in discriminating all patients or cytogenetically normal patients from controls, respectively. The cohort of AML patients was divided into two groups according to the cut-off value of 0.017 (60% sensitivity and 100% specificity, respectively). Cytogenetically normal patients with low SOX17 expression had significantly shorter OS than those with high SOX17 expression (median 4 vs. 25 months, respectively, p=0.035). Multivariate analysis confirmed low SOX17 expression as an independent risk factor. CONCLUSIONS: Our findings indicated that low SOX17 level may define an important risk factor in AML with normal cyotgenetics.

Methylation of CTNNA1 promoter: frequent but not an adverse prognostic factor in acute myeloid leukemia.

The reduced expression of CTNNA1 gene, a putative tumor suppressor gene, has been found in several cancers including acute myeloid leukemia (AML). CTNNA1 expression is regulated by methylation and histone deacetylation. However, the clinical significance of CTNNA1 methylation in AML is rarely known. The present study was aimed to investigate the methylation status of CTNNA1 promoter region using methylation-specific PCR (MSP) and its clinical relevance in Chinese AML patients. Patients with CTNNA1 hypermethylation had significantly lower level of CTNNA1 transcript than those without CTNNA1 hypermethylation (P=0.031). The relationship of CTNNA1 methylation with clinical parameters was evaluated. Aberrant hypermethylation of CTNNA1 gene was found in 23.9% (37/155) AML cases. The status of CTNNA1 methylation was not correlated with the mutations of seven genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, N/K-RAS and C/EBPA). There was no significant difference in the rates of complete remission (CR) between patients with and without CTNNA1 methylation. Although the overall survival (OS) time of the CTNNA1-methylated AML was shorter than that of CTNNA1-unmethylated group (6 months vs 9 months), the difference was not statistically significant (P=0.681). Our data suggest that CTNNA1 methylation is a recurrent event but has no influence on prognosis in AML.

DDX43 promoter is frequently hypomethylated and may predict a favorable outcome in acute myeloid leukemia.

DEAD box polypeptide 43 (DDX43), a cancer/testis antigen (CTA), has been found to be overexpressed in various solid tumors and some hematologic malignancies. In the present work hypomethylation of the DDX43 gene was detected in 15% (32/214) of primary acute myeloid leukemia (AML) using real-time quantitative methylation-specific PCR (RQ-MSP). The level of DDX43 expression was correlated with DDX43 hypomethylation (R=0.277, P=0.014). Moreover, bisulfite sequencing confirmed the significant correlation between the methylation density and the level of DDX43 hypomethylation. Additionally, restoration of DDX43 expression in the K562 cell line by 5-aza-2'-deoxycytidine treatment confirmed a direct contribution of methylation in regulating the DDX43 gene. DDX43 hypomethylation was observed more frequently in favorable group (21.4%) and intermediate group (15.8%) than in poor group (0%) (P=0.009). AML patients with DDX43 hypomethylation had a better overall survival (median not obtained) than those with DDX43 methylation (median 8 months, 95% confidence interval 5.6-10.4 months) (P=0.014). In summary, the DDX43 gene is activated by promoter hypomethylation and DDX43 hypomethylation may be a favorable prognostic factor in AML.

Dysregulation of miR-124-1 predicts favorable prognosis in acute myeloid leukemia.

OBJECTIVE: MicroRNA miR-124 has been suggested as a tumor suppressor for its role in inhibiting cell growth, inducing differentiation and promoting apoptosis. The present study was aimed to investigate the expression status of miR-124-1 and its clinical relevance in patients with acute myeloid leukemia (AML). DESIGNS AND METHODS: Real-time quantitative PCR was performed to detect the expression level of miR-124-1 in AML patients. The clinical significance of miR-124-1 expression in AML was investigated. RESULTS: miR-124-1 underexpression was identified in 30 (36%) of 83 AML patients. No significant difference could be observed in sex, age and blood parameters between the patients with and without miR-124-1 underexpression. The frequency of miR-124-1 underexpression was higher in the patients with t(15;17) than in others (62% versus 30%, P = 0.040). The status of miR-124-1 expression was not correlated with the mutations of nine genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, N/K-RAS and C/EBPA). The patients with miR-124-1 underexpression had borderline longer overall survival and relapse-free survival than those without miR-124-1 underexpression (P = 0.052 and 0.045, respectively). CONCLUSIONS: These findings suggest that miR-124-1 underexpression is a common event and might have a favorable impact on prognosis in AML.