Analysis of Medication Rules of Traditional Chinese Medicine for Malaria Treatment Based on Data Mining.

Objective To analyze the medication rules of traditional Chinese medicine (TCM) for malaria treatment.Methods Statistical analysis was conducted on the basic attributes of TCM drugs with regard to property, therapeutic methods, flavor, and meridian tropism. A complex network of TCM drug associations was constructed. Cluster analysis was applied to obtain the core drugs for malaria treatment. The Apriori algorithm was applied to analyze the association rules of these core drugs.Results A total of 357 herbs were used 3,194 times in 461 prescriptions for malaria treatment. Radix Glycyrrhizae (), Rhizoma Pinelliae (), Radix Bupleuri (), and Radix Dichroae () were the frequently used herbs through supplementing, exterior-releasing, heat-clearing, qi-rectifying, and damp-resolving therapeutic methods. Such herbs had warm, natural, and cold herbal properties; pungent, bitter, and sweet flavors; and spleen, lung, and stomach meridian tropisms. Cluster analysis showed 61 core drugs, including Radix Glycyrrhizae, Rhizoma Pinelliae, Radix Bupleuri, and Radix Scutellariae (). Apriori association rule analysis yielded 12 binomial rules (herb pairs) and 6 trinomial rules (herb combinations). Radix Bupleuri plus Radix Scutellariae was the core herbal pair for treating malaria. This pair could be combined with Rhizoma Atractylodis Macrocephalae () for treating warm or cold malaria, combined with Pericarpium Citri Reticulatae () or Radix Dichroae () for treating miasmic malaria, or combined with turtle shells () for treating malaria with splenomegaly.Conclusions TCM can be used to classify and treat malaria in accordance with the different stages of development. As the core herbal pair, Radix Bupleuri and Radix Scutellariae can be combined with other drugs to treat malaria with different syndrome types.

Establishment of infection prevention and control strategy in nursing managements during surgical operations in COVID-19 patients based on Delphi method.

AIM: The aim of this study was to establish an infection prevention and control strategy for nursing managements during surgical operations in coronavirus disease 2019 (COVID-19) patients. DESIGN: A Delphi method. METHODS: Between November 2021 and March 2022, we first formulated a preliminary infection prevention and control strategy based on the literature review and institutional experience. Then, we applied Delphi method and performed expert surveys to reach a final strategy for nursing managements during surgical operations in COVID-19 patients. RESULTS: The strategy included seven dimensions with 34 items. The positive coefficients of Delphi experts in both surveys were 100%, indicating a high coordination among experts. The degree of authority and expert coordination coefficient were 0.91 and 0.097-0.213. After the second expert survey, value assignments for importance of each dimension and item were 4.21-5.00 and 4.21-4.76 points, respectively. The coefficients of variation for dimension and item were 0.09-0.19 and 0.05-0.19, respectively. PATIENT OR PUBLIC CONTRIBUTION: Except the medical experts and research personnel, there was no other patient or public contribution involved in the study.

The willingness of Chinese healthcare workers to receive monkeypox vaccine and its independent predictors: A cross-sectional survey.

The global monkeypox outbreak in 2022 has severely affected the life and health of people. Currently, partial smallpox vaccines have been approved for monkeypox prevention. Considering the potential occupational health risks of monkeypox infection among healthcare workers (HCWs), this study explored the willingness of Chinese HCWs to receive the monkeypox vaccine and analyzed the factors influencing their decision. We conducted an online cross-sectional survey among HCWs of 10 Chinese hospitals from May 30th, 2022 to August 1st, 2022. Specifically, a self-report questionnaire was administered to evaluate the attitude and acceptance of HCWs toward the monkeypox vaccine, followed by a multivariate logistic regression analysis to determine the independent predictors of vaccination. The survey included 1032 participants, of whom 90.12% expressed their willingness for vaccination (vaccine hesitancy rate = 9.88%). Univariate analysis showed that 11 variables differed significantly between the vaccine acceptance and vaccine hesitancy groups. Multivariate logistic regression analysis demonstrated that the age of 30-40 years (odds ratio [OR] = 0.504, 95% confidence interval [CI]: 0.284-0.893, p = 0.019 vs. age of <30 years old), working in a secondary hospital (OR = 0.449, 95% CI: 0.249-0.808, p = 0.019 vs. working in a tertiary hospital), considering vaccination necessary for controlling monkeypox infection (OR = 4.135, 95% CI: 2.109-8.106, p < 0.001 vs. not considering it necessary), willingness to pay for the monkeypox vaccine (OR = 2.125, 95% CI: 1.206-3.745, p = 0.009 vs. no willingness to pay), considering implementation of mandatory vaccination necessary (OR = 1.990, 95% CI: 1.023-3.869, p = 0.043 vs. not considering it necessary), and recommending family members and friends to take the vaccine (OR = 13.847, 95% CI: 7.487-25.609, p < 0.001 vs. not recommending) were crucial independent predictors of the willingness to receive monkeypox-related vaccination. This study evaluated the acceptance and hesitancy rates of Chinese HCWs toward the monkeypox vaccine and found that the willingness to receive vaccination was mainly correlated to age, hospital level, and attitude toward vaccination. Therefore, to promote vaccine absorption, we recommend expanding publicity, formulating reasonable policies, and improving the recognition of vaccines.

Gut Microbiome and Plasma Metabolomic Analysis in Patients with Myelodysplastic Syndrome.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders. Studies have shown the involvement of an abnormal immune system in MDS pathogenesis. The gut microbiota are known to influence host immunity and metabolism, thereby contributing to the development of hematopoietic diseases. In this study, we performed gut microbiome and plasma metabolomic analyses in patients with MDS and healthy controls. We found that patients with MDS had a different gut microbial composition compared to controls. The gut microbiota in MDS patients showed a continuous evolutionary relationship from the phylum to the species level. At the species level, the abundance of Haemophilus parainfluenzae, Streptococcus luteciae, Clostridium citroniae, and Gemmiger formicilis increased, while that of Prevotella copri decreased in MDS patients compared to controls. Moreover, abundance of bacterial genera correlated with the percentage of lymphocyte subsets in patients with MDS. Metabolomic analysis showed that the concentrations of hypoxanthine and pyroglutamic acid were increased, while that of 3a,7a-dihydroxy-5b-cholestan was decreased in MDS patients compared to controls. In conclusion, gut microbiome and plasma metabolomics are altered in patients with MDS, which may be involved in the immunopathogenesis of the disease.

Impact of iron overload by transfusion on survival and leukemia transformation of myelodysplastic syndromes in a single center of China.

INTRODUCTION: Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases which are prone to progress into acute myeloid leukemia (AML). Iron overload (IOL) caused by transfusion occurred in most MDS patients. But how IOL influences MDS progression has not been clarified yet. METHODS: Herein, we collected clinical data from 143 MDS patients to investigate the impacts of IOL on patients survival and AML transformation. RESULTS: We found that median survival time, 3-year survival rate, leukemia-free survival (LFS) time were significantly shorter in patients with IOL than those with non-iron overload (NIOL) (P = 0.040; P = 0.044; P = 0.037). Besides, IOL was more likely to be found in higher-risk subgroups (assessed by IPSS and WPSS) of MDS patients which also promoted 2-year AML transformation. Furthermore, the serum ferritin (SF) was significantly correlated with the overall survival (OS) of MDS patients (r = -0.311, P < 0.05). The concentrations of both intracellular iron and reactive oxygen species (ROS) in CD34+ cells of bone marrow were higher in the IOL group than the NIOL group, respectively (P = 0.0426; P = 0.0185). Moreover, ROS level was closely correlated with the percentage of bone marrow blasts (r = 0.7200, P = 0.0370). Collectively, IOL threatened the survival of MDS patients and promoted AML transformation. CONCLUSION: Elevated intracellular iron and ROS in CD34+ cells of bone marrow could accelerate the abnormal proliferation of blasts.

Survival of cancer patients in Fujian, Southeast China: a population-based cancer registry study.

Survival rates are usually used to evaluate the effect of cancer treatment and prevention. No study has focused on the characteristic of population-based cancer survival in Fujian, which is regarded as one of the high-risk areas of cancer in China. This study aims to analyze the 5-year relative survival of patients in Fujian Province using population-based cancer registry data. A total of 8 population-based registries in Fujian Province reported cancer cases diagnosed in 2012-2014. Relative survival was calculated as the ratio between observed survival and expected survival. The 5-year relative survival for all cancers combined was 36.19% and the age-standardized 5-year relative survival for all patients was 31.80%. Females had higher relative survival than males (38.90% and 27.00%). The patients in urban areas had higher relative survival than those in rural areas (32.34% and 31.29%). Lung, gastric, liver, colorectal, and esophageal cancers were the five most common cancers, with 5-year relative survival below 50%. This is the first study that evaluated the population-based cancer relative survival in Fujian, China. Our study suggests that the overall survival of cancer patients in Fujian Province is poor. Furthermore, the results of this study can be used as a baseline for further research in Fujian, and provide important evidence for cancer etiology research.

Transcriptional programming drives Ibrutinib-resistance evolution in mantle cell lymphoma.

Ibrutinib, a bruton's tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease. Here, using genomic, chemical proteomic, and drug screen profiling, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the aggressive phenotypes of IR. Accordingly, IR MCL cells are vulnerable to inhibitors of the transcriptional machinery and especially so to inhibitors of cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Further, CDK9 inhibition disables reprogrammed signaling circuits and prevents the emergence of IR in MCL. Finally, and importantly, we find that a robust and facile ex vivo image-based functional drug screening platform can predict clinical therapeutic responses of IR MCL and identify vulnerabilities that can be targeted to disable the evolution of IR.

Oral-maxillofacial adverse events related to antimalarials.

Malaria is a worldwide parasitic disease, which affects millions of lives every year. Various medications are recommended by WHO for prevention and treatment of malaria. However, adverse events caused by antimalarials were frequently reported, some of which were severe and fatal. Disorders of many organs related to antimalarials have been well recognized, whereas few studies concentrated on the relationship between antimalarials and oral-maxillofacial system health. Current review generalized the relevance of antimalarials to the health of oral-maxillofacial part and raised an urgent need to form a standard management for antimalarial-related oral-maxillofacial adverse events.

Increased myeloid-derived suppressor cells in patients with myelodysplastic syndromes suppress CD8+ T lymphocyte function through the STAT3-ARG1 pathway.

MDSCs, which are defined as a kind of negatively regulatory cells, could suppress T cell immune response in many tumor-bearing animal models and cancer patients. We supposed that MDSCs also contributed to the impaired antitumor immunity in MDS. Here we demonstrated that STAT3-ARG1 pathway could be a critical signal transduction pathway that regulated MDSCs-mediated immunosuppression. Increased MDSCs was revealed in MDS patients when compared to healthy controls. Especially, MDSCs performed higher activated STAT3 and CCR2 expression in high-risk MDS patients. The CCL2 and IL-6 levels in MDS patients were also higher than in healthy controls, which could drive recruitment and activation of MDSCs. Meanwhile, lower expression levels of CD3ζ chain, perforin and granzyme B were demonstrated in MDS patients, which were associated with downregulated activation of CD8+ T lymphocytes. The results were supported by the decreased perforin, granzyme B and IFN-γ levels in the mixed-culture system of MDSCs and CD8+ T lymphocytes in vitro. Notably, targeting STAT3 pathway by selective inhibitor could decrease ARG1 expression in MDSCs and partially reverse the lower expression levels of effector molecules on CD8+ T lymphocytes. Therefore, this study revealed the potential STAT3-ARG1 mechanism behind MDSCs and provided a promising STAT3 targeting strategy in MDS.

Efficient removal of ginkgotoxin from Ginkgo biloba seed powder by combining endogenous enzymatic hydrolysis with resin adsorption.

BACKGROUND: Ginkgotoxin including 4'-O-methylpyridoxine (MPN) and MPN-5'-glucoside (MPNG) is responsible for Ginkgo seed food poisoning. The purpose of the work reported was to prepare detoxified Ginkgo seed powder and at the same time to retain the nutritional and functional components of Ginkgo seed powder to the maximum extent. RESULTS: Resin adsorption technology was firstly employed to remove ginkgotoxin from water extract of Ginkgo seed powder. Under optimal conditions, the adsorption efficiency of the optimal resin for MPN could reach 100%, and that for MPNG could only reach 85.4 ± 0.93%. Resin adsorption alone could not effectively remove MPN and MPNG simultaneously. Endogenous enzymatic hydrolysis was next attempted to transform MPNG to MPN. MPNG could be completely hydrolyzed to MPN by endogenous enzyme(s) at 40 °C and pH 5.0 in 180 min. Ginkgotoxin only in the form of MPN in the enzymatic hydrolysate was then adsorbed with resin and the conditions were statistically optimized. The adsorption efficiency of MPN reached 98.89 ± 0.99% under the optimized conditions. CONCLUSIONS: Removal of ginkgotoxin by combining endogenous enzymatic hydrolysis with resin adsorption could preserve the main nutritional and functional components of Ginkgo seed powder to the most extent, and did not change its main characteristics. The ginkgotoxin removal method developed in this work is a relatively simple and efficient approach. © 2020 Society of Chemical Industry.

Abnormal Ferroptosis in Myelodysplastic Syndrome.

BACKGROUND: Ferroptosis is a form of iron-dependent non-apoptotic cell death, with characteristics of loss of the activity of the lipid repair enzyme, glutathione (GSH) peroxidase 4 (GPX4), and accumulation of lethal reactive lipid oxygen species. The mechanism of ferroptosis in myelodysplastic syndrome (MDS) is unclear. METHODS: Cell viability assay, reactive oxygen species (ROS) assay, GSH assay, and GPX activity assay were performed to study the regulation of ferroptosis in MDS cells obtained from MDS patients, the iron overload model mice, and cell lines. RESULTS: The growth-inhibitory effect of decitabine could be partially reversed by ferrostatin-1 and iron-chelating agent [desferrioxamine (DFO)] in MDS cell lines. Erastin could increase the cytotoxicity of decitabine on MDS cells. The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1. The concentration of hemoglobin in peripheral blood of iron overload mice was negatively correlated with intracellular Fe2+ level and ferritin concentration. Iron overload (IO) led to decreased viability of bone marrow mononuclear cells (BMMNCs), which was negatively correlated with intracellular Fe2+ level. Ferrostatin-1 partially reversed the decline of cell viability in IO groups. The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in BMMNCs of IO mice. DFO could increase the level of GSH. Ferrostatin-1 and DFO could increase the GPX4 activity of BMMNCs in IO mice. Ferrostatin-1 could significantly reverse the growth-inhibitory effect of decitabine in MDS patients. Decitabine could significantly increase the ROS level in MDS groups, which could be inhibited by ferrostatin-1 or promoted by erastin. Ferrostatin-1 could significantly reverse the inhibitory effect of decitabine on GSH levels in MDS patients. Erastin combined with decitabine could further reduce the GSH level. Erastin could further decrease the activity of GPX4 compared with the decitabine group. CONCLUSION: Ferroptosis may account for the main mechanisms of how decitabine induced death of MDS cells. Decitabine-induced ROS raise leads to ferroptosis in MDS cells by decreasing GSH level and GPX4 activity.

China's CO2 emissions embodied in fixed capital formation and its spatial distribution.

This study aims to measure China's CO2 emissions embodied in fixed capital formation (FCF) from 2007 to 2017 by using both a multi-regional input-output (MRIO) model and a single-region input-output model (SRIO). Then decoupling analysis was performed for uncovering the relationship between embodied CO2 emissions and added values at provincial level. Logarithmic Mean Divisia Index (LMDI) method was further conducted to identify driving factors underlying the growth of embodied CO2 emissions. Results show that CO2 emission from FCF doubled from 2436 million tons (Mt) in 2007 to 4820 Mt in 2012, and increased slightly to 5089 Mt in 2017. Electric power, gas, and water production and supply sector (EGW) and manufacturing industry (MFI) sector were two dominant emitters from supply-side perspective, while construction (CON) was the largest demanding sector driving the embodied emissions from upstream sectors. From geographical point of view, northern provinces were the major inter-regional net exporters of embodied CO2 emissions, while eastern and southern provinces were net importers of embodied CO2 emissions. Based on such results, policy recommendations are proposed considering the relation between supply and demand sector, inter-provincial CO2 emission transfer, and local economic development to mitigate CO2 emissions from China's FCF.

Abnormal platelet phenotypes in patients with myelodysplastic syndromes.

INTRODUCTION: Hemorrhage and infection are two main causes of death in patients with myelodysplastic syndromes (MDS), and it is becoming increasingly clear that platelet dysfunction can also affect the process of hemostasis and anti-infection. The aim of this study was to evaluate activation function and immune-related function of platelets in MDS. METHODS: We included 29 MDS patients and divided them into different subgroups (low-risk group and high-risk group; untreated group and treated group; pretransfusion group and post-transfusion group) according to IPSS-R score, hypomethylating agents (HMAs) therapy, and platelet transfusion history. Platelet light scatter properties, expression of CD41a, activation-associated phenotypes (CD62p and CD63), and immune-associated phenotypes (CD154 and TLR4) were detected by multiparameter flow cytometry. RESULTS: Expression of CD41a was decreased (P < .05), and no difference was found in platelet light scatter properties between MDS patients and healthy subjects (P > .05). Significantly decreased expression frequency and intensity of activation phenotype CD63 were found in patients with MDS (P < .05). Low-risk MDS showed lower expression frequency while high-risk MDS showed reduced mean fluorescence intensity (MFI) of CD63. Decreased expression of CD154 and TLR4 was found in MDS patients (P < .05) which was significantly elevated after HMAs therapy (P < .05). Particularly, MFI of CD154 and TLR4 reduced in high-risk MDS patients (P < .05). CONCLUSION: Myelodysplastic syndromes patients displayed defective expression of both activation- and immune-associated platelet phenotypes, with differential mechanisms between low-risk and high-risk groups regarding phenotype alterations. The findings confirmed impaired platelet phenotypes in MDS which may assist in the diagnosis and identification of MDS patients.

[Aesthetic effect of orthodontics treatment combined with periodontal splint in the treatment of fan-shaped displacement of anterior teeth caused by periodontitis].

PURPOSE: To explore the aesthetic effect of orthodontics treatment combined with periodontal splint in the treatment of fan-shaped displacement of anterior teeth caused by periodontitis. METHODS: Fifty patients with fan-shaped displacement of anterior teeth caused by periodontitis in PLA air force hospital from January 2013 to October 2018 were selected and randomly divided into the control group (n=25) and the experimental group (n=25). Patients in the control group were treated with conventional periodontal splint, while patients in the experimental group were treated with combined orthodontic treatment on the basis of the control group. Florida periodontal probe exploration depth (PD), gingival index (GI), attachment loss (AL), sulcus bleeding index (SBI), plaque index (PLI) and mobility were observed and compared before and 1 month after treatment between both groups. The levels of serum inflammatory factors interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and osteocalcin (OC) were measured and compared by ELISA before treatment and 1 month after treatment in both 2 groups. The data were analyzed with SPSS 21.0 software package. RESULTS: Compared with before treatment, PD and GI in both groups decreased significantly after treatment, and significantly lower in the experimental group than that in the control group (P<0.05); the levels of AL, SBI, PLI and tooth looseness in both 2 groups were significantly lower after treatment, and significantly lower in the experimental than in the control group (P<0.05); compared with before treatment, the levels of IL-4, IL-6, TNF-a and serum CRP in both 2 groups were significantly lower after treatment, and the experimental group was much lower than that in the control group (P<0.05). The level of osteocalcin in the experimental group was significantly higher than that in the control group at different time points after treatment (P<0.05). The level of osteocalcin in the experimental group reached its peak one day after treatment, and then gradually declined, the preoperative level was basically restored 7 days after treatment. CONCLUSIONS: Using orthodontics combined with periodontal splint in the treatment of fan-shaped displacement of anterior teeth caused by periodontitis has a remarkable effect. The symptoms of periodontitis can be effectively improved, the teeth can be effectively corrected and facial profiles of the patients can be improved.

Anti-tumor efficacy of phellamurin in osteosarcoma cells: Involvement of the PI3K/AKT/mTOR pathway.

The extracts of Phellodendron amurense (P. amurense) have been shown to contain many active ingredients e.g. flavone glycosides and to exert a wide range of physiological activities including anti-tumor activity. However, the effects of phellamurin (Phe), a plant flavonone glycoside from the leaves of P. amurense, on osteosarcoma (OS) have never been reported. The effects of Phe on cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. Western blot analysis was performed to detect the protein levels of phosphorylated phosphatidylinositol 3 kinase (PI3K) (p-PI3K), phosphorylated protein kinase B (AKT) (p-AKT), AKT, phosphorylated mammalian target of rapamycin (mTOR) (p-mTOR), and mTOR. We found that Phe suppressed the viability and promoted apoptosis in OS cells in a dose-dependent manner. Notably, Phe repressed the PI3K/AKT/mTOR pathway in OS cells. LY294002 effectively inhibited the PI3K/AKT/mTOR signaling pathway, repressed cell viability and induced apoptosis in OS cells. Activation of PI3K/AKT/mTOR pathway by 740Y-P abolished the effects of Phe on the viability and apoptosis of OS cells. We also found that Phe repressed OS tumor growth and inhibited the PI3K/AKT/mTOR pathway in vivo. In conclusion, Phe suppressed the viability and induced apoptosis in OS cells, at least, partially by inhibiting the PI3K/AKT/mTOR pathway. Our study suggested that Phe might be a new and potential chemotherapeutic agent for the treatment of OS.

BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models.

Drug-tolerant "persister" tumor cells underlie emergence of drug-resistant clones and contribute to relapse and disease progression. Here we report that resistance to the BCL-2 targeting drug ABT-199 in models of mantle cell lymphoma and double-hit lymphoma evolves from outgrowth of persister clones displaying loss of 18q21 amplicons that harbor BCL2. Further, persister status is generated via adaptive super-enhancer remodeling that reprograms transcription and offers opportunities for overcoming ABT-199 resistance. Notably, pharmacoproteomic and pharmacogenomic screens revealed that persisters are vulnerable to inhibition of the transcriptional machinery and especially to inhibition of cyclin-dependent kinase 7 (CDK7), which is essential for the transcriptional reprogramming that drives and sustains ABT-199 resistance. Thus, transcription-targeting agents offer new approaches to disable drug resistance in B-cell lymphomas.

SATB2-AS1 Suppresses Colorectal Carcinoma Aggressiveness by Inhibiting SATB2-Dependent Snail Transcription and Epithelial-Mesenchymal Transition.

Accumulating evidence suggests that long noncoding RNA (lncRNA) plays important regulatory roles in cancer biology. However, the involvement of lncRNA in colorectal carcinoma progression remains largely unknown, especially in colorectal carcinoma metastasis. In this study, we investigated the changes in lncRNA expression in colorectal carcinoma and identified a new lncRNA, the antisense transcript of SATB2 (SATB2-AS1), as a key regulator of colorectal carcinoma progression. SATB2-AS1 was frequently downregulated in colorectal carcinoma cells and tissues, and patients whose tumors expressed SATB2-AS1 at low levels had a shorter overall survival and poorer prognosis. Downregulation of SATB2-AS1 significantly promoted cell proliferation, migration, and invasion in vitro and in vivo, demonstrating that it acts as a tumor suppressor in colorectal carcinoma. SATB2-AS1 suppressed colorectal carcinoma progression by serving as a scaffold to recruit p300, whose acetylation of H3K27 and H3K9 at the SATB2 promoter upregulated expression of SATB2, a suppressor of colorectal carcinoma growth and metastasis. SATB2 subsequently recruited HDAC1 to the Snail promoter, repressing Snail transcription and inhibiting epithelial-to-mesenchymal transition. Taken together, these data reveal SATB2-AS1 as a novel regulator of the SATB2-Snail axis whose loss facilitates progression of colorectal carcinoma. SIGNIFICANCE: These data show that the lncRNA SATB2-AS1 mediates epigenetic regulation of SATB2 and Snail expression to suppress colorectal cancer progression.See related commentary by Li, p. 3536.

Decitabine shows synergistic effects with arsenic trioxide against myelodysplastic syndrome cells via endoplasmic reticulum stress-related apoptosis.

Most of the International Prognostic Scoring System (IPSS) high-risk patients with myelodysplastic syndrome partly responded to hypomethylating therapy even with transient remission, while arsenic trioxide (ATO) had partial effect in patients with MDS. Therefore, we sought to investigate the effects and possible mechanisms of the combination of ATO and decitabine (DAC) in MDS cells. In our study, the MUTZ-1 and SKM-1 cells were treated with ATO, DAC or both. Cell viability, cell apoptosis, levels of reactive oxygen species (ROS) and expressions of the endoplasmicreticulum (ER) stress-associated genes and proteins were examined. Results showed the combination of ATO and DAC synergistically inhibited the proliferation and induced apoptosis of MDS cells. Through the RNA-sequence and GSEA gene function analysis, ER stress-related pathway played an important role in apoptosis of MDS cells induced by the combination of ATO and DAC. ER stress-related genes DNA damage inducible transcript 3, GRP78, and activating transcription factor-6 were significantly highly expressed in combination group than those in single agent groups; proteins were confirmed by western blot. The levels of ROS significantly increased in the combination group. Furthermore, the apoptosis of (ATO+DAC) group MDS cells could be partially reversed by antioxidant agent N-acetylcysteine, accompanied by decreased expression of intracellular ROS and ER stress-related genes. These results suggested that the combination of ATO and DAC synergistically induced the apoptosis of MDS cells by increased ROS-related ER stress in MDS cells.

Ribophorin II potentiates P-glycoprotein- and ABCG2-mediated multidrug resistance via activating ERK pathway in gastric cancer.

Multidrug resistance (MDR) is a critical reason of cancer chemotherapy failure. Ribophorin II (RPN2) has emerged as a vital regulator of MDR in multiple cancers including gastric cancer (GC). However, the roles and molecular mechanisms of RPN2 in MDR have not been well featured till now. The present study aimed to explore the roles and molecular mechanisms of RPN2 in MDR of drug-resistant GC cells. Results showed that the expressions of RPN2, multidrug resistance 1 (MDR1), and ATP binding cassette subfamily G member 2 (ABCG2) were upregulated in SGC7901/DDP and SGC7901/VCR cells. Knockdown of RPN2 alleviated MDR through downregulating MDR1 and ABCG2 expressions in SGC7901/DDP and SGC7901/VCR cells. RPN2 depletion inhibited the activation of MEK/ERK pathway. RPN2 overexpression enhanced MDR by upregulating P-glycoprotein (P-gp) and ABCG2 protein expressions in SGC7901/DDP or SGC7901/VCR cells, while this effect of RPN2 was abrogated by ERK knockdown or treatment with ERK inhibitor PD98059. Our findings suggested that RPN2 potentiated P-gp- and ABCG2-mediated MDR via activating MEK/ERK pathway in GC, hinting the critical values of RPN2 in ameliorating MDR and providing a promising target for GC therapy.

miR-4262, low level of which predicts poor prognosis, targets proto-oncogene CD163 to suppress cell proliferation and invasion in gastric cancer.

BACKGROUND: miR-4262 was identified as a tumor promoter in several cancers, but its exact role in gastric carcinoma is still largely unknown. METHODS: The expression of miR-4262 was detected in gastric cancer tissues. Different concentrations of miR-4262 mimic and miR-4262 antagomir were respectively transfected into primary gastric carcinoma cells. After incubation for 72 h, the overexpression efficiencies were confirmed by qPCR, cell proliferation was detected with the CCK-8 assay, cell apoptosis was detected by using the PI/Annexin V Cell Apoptosis Kit, and cell invasion was detected with the Transwell invasion assay. The molecular mechanisms underlying the action of miR-4262 in gastric carcinoma cells were also explored. RESULTS: In this study, we found that miR-4262 was significantly downregulated in gastric tissue from gastric cancer patients compared with that from the control group. Moreover, the level of miR-4262 was significantly lower in advanced gastric carcinoma. Additionally, lower level of miR-4262 was correlated with poorer prognosis and lower survival rate in gastric cancer patients. Then, different concentrations of miR-4262 mimic and miR-4262 antagomir were transfected into primary gastric carcinoma cells, respectively. The results showed that miR-4262 mimic suppressed proliferation and invasion and promoted cell apoptosis in a dose-dependent manner in gastric carcinoma cells. In contrast, miR-4262 antagomir increased proliferation and invasion and decreased cell apoptosis in a dose-dependent manner in gastric carcinoma cells. Furthermore, miR-4262 could directly target and suppress the expression of the proto-oncogene CD163. CONCLUSION: Our findings indicate that lower level of miR-4262 predicts poorer prognosis in gastric patients, and miR-4262 can target proto-oncogene CD163 to suppress gastric cancer cell proliferation and invasion.