RhoB/ROCK mediates oxygen-glucose deprivation-stimulated syncytiotrophoblast microparticle shedding in preeclampsia.

Increased circulating syncytiotrophoblast microparticles (STBMs) are often associated with preeclampsia (PE) but the molecular mechanisms regulating STBM shedding remain elusive. Experimental evidence has shown that actin plays a key role in STBM shedding and that Rho/ROCK is important in regulating actin rearrangement. To investigate the role of RhoB/ROCK-regulated actin arrangement in STBM shedding in PE, chorionic villous explants were prepared from placenta of patients with normotensive or PE pregnancies and BeWo cells were fused to imitate syncytiotrophoblasts. The oxygen-glucose deprivation (OGD) conditions were applied to imitate the pathophysiology of PE in vitro. The results showed that RhoB and ROCK were activated in the preeclamptic placenta, accompanied by increased actin polymerization and decreased outgrowing microvilli. In villous tissue cultures or BeWo cells, OGD activated RhoB, ROCK1 and ROCK2 and promoted STBM shedding and actin stress fibers formation. In BeWo cells, RhoB overexpression activated ROCK1 and ROCK2, leading to F-actin redistribution and STBM shedding and the OGD-induced actin polymerization and STBM shedding could be reversed by RhoB or ROCK knockdown. These results reveal that RhoB and ROCK play a key role in PE by targeting STBM shedding through actin rearrangement and that RhoB/ROCK intervention may be a potential therapeutic strategy for PE.

Diversity study of 12 X-chromosomal STR loci in Hui ethnic from China.

X-chromosomal STRs (X-STRs) have been used as complements of autosomal STR application in recent years. In this work, we present population genetic data of 12 X-STRs including DXS101, DXS10159, DXS10162, DXS10164, DXS6789, DXS7133, DXS7423, DXS7424, DXS8378, DXS981, GATA165B12, and GATA31E08 loci in a sample of 231 unrelated healthy individuals from the Hui ethnic group in Ningxia Hui Autonomous Region, China. Allelic frequencies of the 12 X-STR loci and haplotypic frequencies of the reported linkage groups (DXS7424-DXS101 and DXS10159-DXS10164-DXS10162) were investigated in the group, respectively. No STR loci showed significant deviations from the Hardy-Weinberg equilibriums and no linkage disequilibriums of pairwise loci were found after Bonferroni correction, respectively. A combined power of discrimination in female individuals was 0.999999999985 and that in male individuals was 0.99999967, respectively. The combined mean exclusion chance in deficiency cases, normal trios and duo cases were 0.999934, 0.995754, and 0.999796, respectively. Significant differences were observed from 0 to 8 loci, when making comparisons between the data of Hui ethnic group and previously reported data from other 16 populations. The results indicated the new panel of 12 X-STR loci might be useful for forensic science application.

Accommodation and Binocular Vision in Children with Myopic Anisometropia.

Purpose: To assess the differences in accommodation and binocular vision in children with myopic anisometropia and determine the correlation with anisometropia. Method: A total of 110 patients with myopia aged 8-15 years were recruited from June 2021 to February 2022 from the Affiliated Hospital of Xuzhou Medical University. Based on the interocular differences of spherical equivalent refraction, patients were divided into the isometropia (35 children), low anisometropia (LA group, 42 children), and high anisometropia (HA group, 33 children). The variables assessed were refraction, heterophoria, amplitude of accommodation (AMP), accommodative response (AR), gradient AC/A, positive and negative relative accommodation (PRA/NRA), and near stereopsis in the three groups. Pearson's correlation coefficient tests were used to investigate the possible association between each parameter and interocular differences (IODs). Results: Among 110 subjects, there were 49 males and 61 females with a mean age of 11.39 ± 2.28 years. Compared with those in the isometropia group, AMP was lower and near stereopsis was higher in the LA group, and the distance and near heterophoria, PRA, AR, and near stereopsis were higher, and PRA, AMP, and gradient AC/A were lower in the HA group (all P < 0.05). Compared with those in the LA group, the near stereopsis, AR, and the near stereopsis were higher in the HA group, and the gradient AC/A was lower (all P < 0.05). However, no significant differences existed in the negative relative accommodation (P > 0.05). The distance and near heterophoria, AR, AMP, and near stereopsis were observed to be correlated with IODs, respectively (r = -0.259, p = 0.006; r = -0.201, p = 0.036; r = 0.306, p = 0.001; r = -0.315, p = 0.001; r = 0.535, p < 0.001). Conclusion: Our results suggested that with the increase of anisometropia, distance and near heterophoria, AR, AMP, and near stereopsis had a tendency to get worse in children with myopic anisometropia.

[Effect of Chlorambucil Combined with Ibrutinib on Mantle Cell Lymphoma Cell Line Jeko-1 and Its Related Mechanism].

OBJECTIVE: To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma (MCL) cell line Jeko-1 and its related mechanism. METHODS: The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs, respectively. CCK-8 assay was used to detect the proliferation of the cells, and Western blot was used to measure the protein expression levels of BCL-2, caspase-3, PI3K, AKT and P-AKT. RESULTS: After Jeko-1 cells were treated with chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibrutinib (3.125, 6.25, 12.5, 25, 50 µmol /L) alone for 24, 48, 72h respectively, the cell proliferation was inhibited in a time- and dose-dependent manner. Moreover, the two drugs were applied in combination at low doses (single drug inhibition rate<50%), and the results showed that the combination of two drugs had a more significant inhibitory effect (all P < 0.05). Compared with the control group, the apoptosis rate of the single drug group of chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibutinib (3.125, 6.25, 12.5, 25, 50 µmol/L) was increased in a dose-dependent manner. The combination of the two drugs at low concentrations (3.125, 6.25, 12.5 µmol/L) could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups (all P < 0.05). Compared with control group, the protein expression levels of caspase-3 in Jeko-1 cells were upregulated, while the protein expression levels of BCL-2, PI3K, and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone. The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins, and the differences between the combination group and the single drug groups were statistically significant (all P < 0.05). CONCLUSION: Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1, and combined application of the two drugs shows a synergistic effect, the mechanism may be associated with the AKT-related signaling pathways.

Lentivirus-mediated RNA interference targeting the H19 gene inhibits cell proliferation and apoptosis in human choriocarcinoma cell line JAR.

BACKGROUND: H19 is a paternally imprinted gene that has been shown to be highly expressed in the trophoblast tissue. Results from previous studies have initiated a debate as to whether noncoding RNA H19 acts as a tumor suppressor or as a tumor promotor in trophoblast tissue. In the present study, we developed lentiviral vectors expressing H19-specific small interfering RNA (siRNA) to specifically block the expression of H19 in the human choriocarcinoma cell line JAR. Using this approach, we investigated the impact of the H19 gene on the proliferation, invasion and apoptosis of JAR cells. Moreover, we examined the effect of H19 knockdown on the expression of insulin-like growth factor 2 (IGF2), hairy and enhancer of split homologue-1 (HES-1) and dual-specific phosphatase 5 (DUSP5) genes. RESULTS: H19 knockdown inhibited apoptosis and proliferation of JAR cells, but had no significant impact on cell invasion. In addition, H19 knockdown resulted in significant upregulation of HES-1 and DUSP5 expression, but not IGF2 expression in JAR cells. CONCLUSIONS: The finding that H19 downregulation could simultaneously inhibit proliferation and apoptosis of JAR cells highlights a putative dual function for H19 in choriocarcinoma and may explain the debate on whether H19 acts as a tumor suppressor or a tumor promotor in trophoblast tissue. Furthermore, upregulation of HES-1 and DUSP5 may mediate H19 downregulation-induced suppression of proliferation and apoptosis of JAR cells.

Population genetics and forensic efficiency of twenty-one novel microsatellite loci of Chinese Yi ethnic group.

In this study, we investigated polymorphic distributions of allelic frequencies and forensic genetic parameters of 21 novel autosomal microsatellite loci from 110 unrelated healthy individuals of Chinese Yi ethnic group. Expected heterozygosity, power of discrimination, and polymorphic information content ranged from 0.617 to 0.812, 0.777 to 0.936 and 0.560 to 0.790. The microsatellite loci showed high forensic efficiency. The total discrimination power and cumulate probability of exclusion were 0.99999999999999999986902 and 0.999998818, respectively. Locus-by-locus allelic frequencies were compared using analysis of molecular variance (AMOVA) method, and the statistically significant differences were observed between Yi group and Russian, Tujia, Kazak, Bai, Ningxia Han, Salar, Tibetan, and Uigur groups at 5, 6, 7, 7, 7, 8, 12, and 13 loci, respectively. The results of genetic distance comparisons, genetic structure analyses, and principal component analysis all indicated that the Yi group showed relatively short genetic relationships with Russian, Salar, and Bai group. The experimental results showed that the 21 loci in the multiplex system provided highly polymorphic information and forensic efficiency for forensic individual identification and paternity testing, also basic population data for population genetics and anthropological research.

Influence of lipid composition on the phase transition temperature of liposomes composed of both DPPC and HSPC.

OBJECTIVE: Phase transition of the lipid membrane is one of the most important properties of liposomes. The objective of this study was to investigate the influence of molar ratio of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and hydrogenated soy phosphatidylcholine (HSPC) on the phase transition temperature (T(m)) of the liposomes. MATERIALS AND METHODS: The T(m)s of the liposomes with different phosphatidylcholine (PC) composition were determined by calcein release test and differential scanning calorimetry (DSC). RESULTS: Only one phase transition was observed for liposomes composed of both DPPC and HSPC, indicating that DPPC and HSPC might combine into one phase with single phase transition. The T(m) of the liposomes composed of both DPPC and HSPC was directly dependent on the molar ratio of the two PCs. Moreover, DPPC percentage and T(m) relationship could be fitted with a linear equation (r(2) > 0.98). In addition, the serum stability of the liposomes at 37°C was directly increased with the increase of DPPC percentage. When 10% DSPE-PEG2000 was added, the significant increase of calcein release at T(m) and decrease at 37°C were observed. DISCUSSION: It is easy to obtain liposomes with a T(m) in between that of DPPC and HSPC by modifying the molar ratio of DPPC and HSPC. CONCLUSION: With the modification of T(m), the liposomes containing various ratios of DPPC and HSPC may have promising application potential in the field of thermosensitive liposomes (TSLs). After 10% DSPE-PEG2000 is added, a formulation of sterically stabilized liposomes with the proper thermal sensitivity can be obtained.

Genetic polymorphism analysis of killer cell immunoglobulin-like receptor genes in the Chinese Uygur population.

Human killer cell immunoglobulin-like receptors are expressed in natural killer cells and subsets of T lymphocytes. They regulate these cells upon interaction with human leukocyte antigen class I molecules and other ligands presented by target cells. KIR gene frequencies and haplotype distributions have been shown to differ significantly between populations from different geographical regions and ethnic origins, which relates to functional variations in the immune response. We have investigated KIR gene frequencies and genotype diversities of 15 KIR genes (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, ID, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and two pseudogenes (KIR3DP1 and 2DP1) in 120 unrelated healthy individuals of the Uygur population living in the Xinjiang autonomous region of China. All individuals were typed positive for the four framework loci KIR3DL3, 2DL4, 3DL2 and KIR3DP1, while activating genes (KIR2DS1, 2DS2, 2DS3, 2DS5 and KIR3DS1) indicated some variation in this population. KIR3DS1 was found in a higher frequency in the studied population than in other groups from China. Linkage disequilibrium among KIR genes displayed a wide range. χ(2) analysis, conducted among non-ubiquitous genes, based on the KIR gene frequency data from our study population and previously published population data, revealed significant differences in the KIR2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 2DS1, 2DS2, 2DS3, 2DS5, and 3DS1 genes. A neighbor-joining phylogenic tree, built using the observed carrier frequencies data of 13 KIR loci (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 3DL1, 3DL2, 3DL3, 2DS1, 2DS2, 2DS3, 2DS5, and 3DS1), showed relationships between the population studied and other previously reported populations. The present study can therefore be valuable for enriching the ethnical gene information resources of the KIR gene pool, for population origin studies and for KIR-related clinical practice.

[Comparison of in vivo confocal microscopic and histopathological findings in limbal tumors].

OBJECTIVE: To explore the depth of invasion of limbal tumors using in vivo confocal microscope and to compare the result to that in histopathological findings. METHODS: Five cases of limbal tumors with clinical diagnosis of squamous cell carcinoma were evaluated with in vivo confocal microscope. Tumor excision and lamella corneal transplantation were performed for each patient. The results of confocal microscopy were compared to that in histopathologic sections. RESULTS: One case of invasive squamous carcinoma, three cases of intraepithelial dysphasia and one case of squamous papilloma were identified by histopathological examination. The main pathological features could be recognized by confocal microscope images, including papillomatous hyperplasia, cytonuclear atypias, and activation of dendritic cells. Intersection of neoplasm and normal tissue could be displayed by oblique scanning. CONCLUSIONS: With appropriated oblique scanning, in vivo confocal microscopy can provide information of cellular structure and the depth of invasion, this is useful in the diagnosis and management of limbal neoplasm. However, the identification of tumor cell phenotypes still needs ex vivo histopathological examination.

DWPPI: A Deep Learning Approach for Predicting Protein-Protein Interactions in Plants Based on Multi-Source Information With a Large-Scale Biological Network.

The prediction of protein-protein interactions (PPIs) in plants is vital for probing the cell function. Although multiple high-throughput approaches in the biological domain have been developed to identify PPIs, with the increasing complexity of PPI network, these methods fall into laborious and time-consuming situations. Thus, it is essential to develop an effective and feasible computational method for the prediction of PPIs in plants. In this study, we present a network embedding-based method, called DWPPI, for predicting the interactions between different plant proteins based on multi-source information and combined with deep neural networks (DNN). The DWPPI model fuses the protein natural language sequence information (attribute information) and protein behavior information to represent plant proteins as feature vectors and finally sends these features to a deep learning-based classifier for prediction. To validate the prediction performance of DWPPI, we performed it on three model plant datasets: Arabidopsis thaliana (A. thaliana), mazie (Zea mays), and rice (Oryza sativa). The experimental results with the fivefold cross-validation technique demonstrated that DWPPI obtains great performance with the AUC (area under ROC curves) values of 0.9548, 0.9867, and 0.9213, respectively. To further verify the predictive capacity of DWPPI, we compared it with some different state-of-the-art machine learning classifiers. Moreover, case studies were performed with the AC149810.2_FGP003 protein. As a result, 14 of the top 20 PPI pairs identified by DWPPI with the highest scores were confirmed by the literature. These excellent results suggest that the DWPPI model can act as a promising tool for related plant molecular biology.

Genetic diversities of 21 non-CODIS autosomal STRs of a Chinese Tibetan ethnic minority group in Lhasa.

In the present study, we investigated 21 short tandem repeat (STR) loci (D6S474, D12ATA63, D22S1045, D10S1248, D1S1677, D11S4463, D1S1627, D3S4529, D2S441, D6S1017, D4S2408, D19S433, D17S1301, D1GATA113, D18S853, D20S482, D14S1434, D9S1122, D2S1776, D10S1435, D5S2500), which are not included in the Combined DNA Index System and Amelogenin locus in 104 randomly selected healthy autochthonous individuals from the Tibetan ethnic minority group residing in the Lhasa region, Tibet Autonomous Region of China. Allelic frequencies, common forensic statistical parameters, and the Hardy-Weinberg equilibrium in this population were calculated with a modified PowerState V12.xls. A total of 143 alleles were found in the Tibetan group with corresponding allelic frequencies ranging from 0.005 to 0.582. The observed heterozygosity, the expected heterozygosity, the power of discrimination, the power of exclusion, and the polymorphic information content ranged from 0.615 to 0.817, 0.559 to 0.787, 0.727 to 0.926, 0.310 to 0.632, and 0.488 to 0.760, respectively. Chi-square tests of the observed genotype frequencies and expected genotype frequencies in the samples showed no departure from the Hardy-Weinberg equilibrium at all loci except for D5S2500. Our results demonstrate that these 21 STRs are highly polymorphic and suitable for anthropological research, population genetics, and forensic paternity testing and human individual identification in this region, and can enrich Chinese ethnical genetic informational resources.

Monocyte-induced NK cell inactivation: role of reactive oxygen and nitrogen metabolites.

Here in a co-cultivation system of natural killer (NK) cells and K562 cells, monocytes (MO) and/or interleukin (IL)-2/phytohemagglutinin (PHA) were administered. After MO were administered, reactive oxygen metabolites (ROM)/reactive nitrogen metabolites (RNM) productions increased, while tumor necrosis factor (TNF)-ß/interferon (IFN)-γ levels and NK cell cytotoxicity (NCC) decreased, the changes of which after administering tiopronin (TIP) or glutamylcysteinylglycine (GSH) were opposite. In conclusions, the activated MO could inhibit the NK cell activity to kill K562 cell by secreting ROM and RNM. And TIP and GSH could scavenge both ROM and RNM to reverse the inhibitory effect of MO.

Correlation of the retinopathy degree with the change of ocular surface and corneal nerve in patients with type 2 diabetes mellitus.

AIM: To investigate the change of ocular surface and corneal nerve and their correlation in patients suffering from type 2 diabetes mellitus under different degrees of retinopathy. METHODS: Totally 129 type 2 diabetes mellitus patients (257 eyes) were included. They were divided into three groups: no diabetic retinopathy (NDR) group (33 cases, 66 eyes), non-proliferative diabetic retinopathy (NPDR) group (32 cases, 64 eyes), and proliferative diabetic retinopathy (PDR) group (34 cases, 67 eyes). Healthy normal individuals were enrolled as controls (30 cases, 60 eyes). Ocular Surface Disease Index (OSDI) questionnaire was completed by all subjects, and dry eye analyzer was applied to examine tear meniscus height (TMH), first tear break-up time (FTBUT), average tear break-up time (ATBUT), tear film lipid layer thickness classification, and meibomian gland loss (MGL) score. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) were examined by in vivo confocal microscopy (IVCM). The differences and correlation among these parameters were analyzed. RESULTS: Total OSDI score, TMH, FTBUT, ATBUT, tear film lipid layer thickness, MGL score, CNFD, CNBD, CNFL, and CNFT were statistically different among the four groups (P<0.05). In NDR group, CNFL was positively correlated with TMH (r=0.493, both P<0.01) and ATBUT (r=0.437, P<0.05). CNFL in NPDR group was positively correlated with TMH (r=0.642, P<0.01) and ATBUT (r=0.6, P<0.01). CNFL in PDR group was positively correlated with TMH (r=0.364, P<0.05) and ATBUT (r=0.589, P<0.01), with low negative correlation with MGL score (r=-0.331, P<0.05). CONCLUSION: With the progression of diabetic retinopathy, TMH, BUT, lipid layer thickness, CNFL, CNFD, and CNBD gradually decreased, while total OSDI score, MGL score, and CNFT increased. CNFL is correlated with TMH and ATBUT in diabetic patients.

Vehicle mix evaluation in Beijing's passenger-car sector: From air pollution control perspective.

The transport sector has been one of the largest source of carbon emission and urban air pollutants. The research on the coordinated development of pollutant and carbon emission reduction in transport industry is helpful to the realization of urban pollutant prevention and carbon emission reduction, especially in big cities. Thus, a multi-period bottom-up vehicle development mathematical model is proposed to analyze the technology development path, emission path and energy structure adjustment path, and the synergistic benefits of carbon dioxide (CO2) emission reduction under a expected air pollution emission standard. Four pollutants, carbon monoxide (CO), hydrocarbons (HC), nitrogen oxides (NOx), and particulate matter (PM), generated from the vehicle are considered in this model. Then, the proposed model is used to analyze the related vehicle structure and energy consumption under the expected emission standards for Beijing during 2020 and 2035. The technology development path, emission path and energy structure adjustment path are examined, and the synergistic benefits of CO2 emission reduction are also studied. Some important implication are found as follows: (1) Even with the goal of environmental pollution control only, new energy vehicles will have an explosive growth period, starting from about 2025. (2) Strict air pollution emission policies do not always lead to the rapid development of new energy vehicles before 2025. (3) The four main pollutants show different levels of synergistic effect among which CO on HC and NOx on PM are obvious, respectively. (4) Even under the control of the air pollution policy, the synergistic effect to CO2 emission reduction is also obvious. Compared to the baseline case, the reduction benefit from the MILD and STRICT environmental policies are 30 and 70 million yuan, respectively.

Expression and clinical implications of homeobox gene Six1 in cervical cancer cell lines and cervical epithelial tissues.

INTRODUCTION: The homeobox gene Six1 is overexpressed in multiple human tumors, playing a role in promoting tumorigenesis and metastasis. The present study was aimed to investigate the clinical implications of Six1 expression in cervical cancer. METHODS: Six1 messenger RNA (mRNA) and protein expression was detected by reverse transcription (RT) polymerase chain reaction and Western blotting, respectively, in human cervical cancer cell lines CaSki, HeLa, C33A and 20 normal cervical specimens, 21 specimens of cervical intraepithelial neoplasias (CINs), and 54 specimens of cervical cancer tissue, and the clinical implications of Six1 gene expression was analyzed. RESULTS: There was Six1 mRNA and protein overexpression in cervical cancer cell lines CaSki, HeLa, and C33A. The Six1 expression level was higher in CaSki and HeLa cells than in C33A cells (P < 0.05). Six1 mRNA and protein expression increased from normal cervical epithelial tissues, to CINs, and then to cervical cancer tissue (normal cervical epithelial tissue vs CIN, P < 0.05; normal cervical epithelial tissue vs cervical cancer, and CIN vs cervical cancer, P < 0.01). The status of Six1 overexpression was correlated to clinical staging and lymph node metastasis of cervical cancer (P < 0.01) but not to pathological grading, tumor size, and age of the patient (P > 0.05). CONCLUSION: Six1 was overexpressed in cervical cancer cell lines and in cervical cancer tissues. Alteration of Six1 expression might contribute to the occurrence and development of cervical cancer.

[Effects of reactive nitrogen metabolites on NK cell-mediated killing of K562 cells].

OBJECTIVE: To explore the effects of the exogenous and endogenous reactive nitrogen metabolites (RNM) as NK cell inhibitors on NK cell-mediated killing of K562 cells and the influence of Tiopronin (TIP), glutamylcysteinylglycine (GSH) and histamine dihydrochloride (DHT) as RNM scavengers on reversing the suppressing effect of RNM. METHODS: The exogenous ONOO(-) was administered in the NK+K562 culture system, then the RNM scavengers were added in the NK+K562+ONOO(-) culture system, respectively. The concentrations of RNM, TNF-beta and IFN-gamma, K562 cell inhibition rate (KIR) and the percentage of living NK cells were examined. IL-2+PHA were used as monocyte (MO) activators in the culture system of MO+NK+K562. Then TIP, GSH and DHT were administered and the parameters of NK cell activity were analyzed. RESULTS: After exogenous ONOO(-) was administered in NK+K562 culture system, the percentage of living NK cells was decreased from (93.17 +/- 2.57)% to (71.87 +/- 1.02)% (P < 0.01) and KIR was decreased from (67.47 +/- 2.64)% to (43.44 +/- 2.87)% (P < 0.01). When TIP, GSH and DHT were administered into the systems, the percentage of living NK cells was increased to (91.13 +/- 3.67)% (P < 0.05), (88.03 +/- 1.46)% (P < 0.05), (73.60 +/- 2.76)% (P > 0.05), respectively; KIR was increased to (61.58 +/- 1.89)% (P < 0.05), (60.68 +/- 2.07)% (P < 0.05) and (45.26 +/- 3.31)% (P > 0.05), respectively. When IL-2/PHA were administered in the NK+K562+MO culture system, RNM products was increased from (82.10 +/- 6.60) micromom/L to (193.65 +/- 5.95) micromom/L(P < 0.01);KIR was decreased from (90.64 +/- 3.06)% to (61.29 +/- 2.22)% (P < 0.01). When the TIP, GSH and DHT were administered in the systems, RNM products were decreased to (91.32 +/- 6.81) micromom/L (P < 0.05), (84.66 +/- 5.99) micromom/L (P < 0.05) and (188.92 +/- 5.00) micromom/L (P > 0.05), respectively; KIR was increased to (84.31 +/- 4.56)%(P < 0.05), (81.65 +/- 3.09)% (P < 0.05) and (72.20 +/- 4.10)% (P < 0.05), respectively. CONCLUSION: NK Cell-mediated killing of K562 cells can be suppressed by exogenous and endogenous RNM administration. Both of TIP and GSH can protect NK cells by scavenging RNM and enhance the antineoplasmic activity of NK cells.

[MiR-124-3p Enhances the Sansitivity of Chronic Myelogenous Leukemia Cell K562-R to Imatinib by Targeting ABCA2].

OBJECTIVE: To investigate the effect and mechanism of miR-124-3p-targeing regulating ABCA2 on chronic myelogenous leukemia cell K562-R. METHODS: CML cells with miR-124-3p-overexpression and ABCA2-over-expression as well as subcutaneoustrans planted tumor nude mice were used as study objects. And the CML cells were divided into four groups: K562-R blank control, miR-124-3p mimic control, ABCA2-overexpression and mimic+PC ABCA2. The effects of miR-124-3p and ABCA2 on CML cells were analyzed. The levels of proliferation-, apoptosis- and autophagy- related protein were determined by Western blot. qRT-PCR was employed to detect the levels of miR-124-3p and ABCA2 in K562-R cells. The relationship between miR-124-3p and ABCA2 was validated by luciferase reporter system assays and bioinformatics. Hoechst/immunohistochemical staining and CCK-8 assay were performed to investigate the function involved. RESULTS: miR-124-3p highly expressed in K562-S cells and lowly expressed in K562-R cells, however, ABCA2 lowly expressed in K562-S cells and highly expressed in K562-R cells. Over-expression of miR-124-3p significantly decreased ABCA2 level and cell growth, but increased autophagy and apoptosis in K562-R cells (P＜0.01). When ABCA2 was over-expressed, the K562-R cell growth was promoted and autophagy and apoptosis were inhibited (P＜0.01). The miR-124-3p promoted cell autophagy and apoptosis but inhibited cell growth in nude mice transplant tumor model (P＜0.01). CONCLUSION: miR-124-3p can target ABCA2 to inhibit the growth of CML cells and promote the cell autophagy and apoptosis of CML cells.

Predicting lncRNA-miRNA Interaction via Graph Convolution Auto-Encoder.

The interaction of miRNA and lncRNA is known to be important for gene regulations. However, the number of known lncRNA-miRNA interactions is still very limited and there are limited computational tools available for predicting new ones. Considering that lncRNAs and miRNAs share internal patterns in the partnership between each other, the underlying lncRNA-miRNA interactions could be predicted by utilizing the known ones, which could be considered as a semi-supervised learning problem. It is shown that the attributes of lncRNA and miRNA have a close relationship with the interaction between each other. Effective use of side information could be helpful for improving the performance especially when the training samples are limited. In view of this, we proposed an end-to-end prediction model called GCLMI (Graph Convolution for novel lncRNA-miRNA Interactions) by combining the techniques of graph convolution and auto-encoder. Without any preprocessing process on the feature information, our method can incorporate raw data of node attributes with the topology of the interaction network. Based on a real dataset collected from a public database, the results of experiments conducted on k-fold cross validations illustrate the robustness and effectiveness of the prediction performance of the proposed prediction model. We prove the graph convolution layer as designed in the proposed model able to effectively integrate the input data by filtering the graph with node features. The proposed model is anticipated to yield highly potential lncRNA-miRNA interactions in the scenario that different types of numerical features describing lncRNA or miRNA are provided by users, serving as a useful computational tool.

Inhibition of ZIP4 reverses epithelial-to-mesenchymal transition and enhances the radiosensitivity in human nasopharyngeal carcinoma cells.

ZIP4 is a zinc transporter involved in epithelial cell morphology and migration in various cancers. In the epithelial-to-mesenchymal transition (EMT), epithelial cells transition into mesenchymal cells. The EMT plays a crucial role in invasiveness and metastasis during tumorigenesis. The aim of this study was to investigate the role of ZIP4 in the invasiveness and radiosensitivity of human nasopharyngeal carcinoma (NPC). In this study, results from 99 human patients with NPC showed that ZIP4 expression levels significantly correlated with a higher TN (tumor, lymph node) classification, as well as shorter overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). Forced overexpression of ZIP4 promoted the migration and invasion of C666-1 cells through regulation of the EMT process. In contrast, ZIP4 silencing by lentivirus-mediated shRNA inhibited the EMT and metastasis of C666-1 cells in vitro and in vivo. Importantly, protein microarray analyses showed that downregulation of ZIP4 in C666-1 cells resulted in the decreased abundance of phosphoinositide 3-kinase (PI3K) p85 (Tyr607), phosphorylated (p)-Akt (Ser473), phosphorylated (p)-Akt (Thr308), and phosphorylated glycogen synthase kinase 3ß (pGSK3ß; Ser9). These data suggest that ZIP4 induces the EMT and promotes migration and invasion via the PI3K/Akt signaling pathway in NPC. Moreover, ZIP4 silencing significantly enhanced radiation-induced apoptosis and growth inhibition of human C666-1 cells in vitro and enhanced the antitumor activity of ionizing radiation (IR), leading to tumor growth inhibition in vivo. These results demonstrate that ZIP4 is a novel prognostic factor for malignant NPC progression. More importantly, targeting ZIP4, along with radiotherapy, may be an effective new treatment for NPC.