Corrigendum to "BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia" [Heliyon 8(10) (October 2022) e11190].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e11190.].

The role of gastric microecological dysbiosis in gastric carcinogenesis.

Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and reducing its mortality has become an urgent public health issue. Gastric microecological dysbiosis (including bacteria, fungi, viruses, acid suppressants, antibiotics, and surgery) can lead to gastric immune dysfunction or result in a decrease in dominant bacteria and an increase in the number and virulence of pathogenic microorganisms, which in turn promotes development of GC. This review analyzes the relationship between gastric microecological dysbiosis and GC, elucidates dynamic alterations of the microbiota in Correa's cascade, and identifies certain specific microorganisms as potential biomarkers of GC to aid in early screening and diagnosis. In addition, this paper presents the potential of gastric microbiota transplantation as a therapeutic target for gastric cancer, providing a new direction for future research in this field.

BNIP3 enhances pancreatic cancer cell migration and proliferation via modulating autophagy under hypoxia.

Chemotherapy and immunotherapy for pancreatic ductal adenocarcinoma (PDAC) have limited success for the intricated surrounding cancer microenvironment. Hypoxic microenvironment in PDAC causes the activation of multiple different molecules and signaling pathways compared with normoxia. We studied the roles of BNIP3 for the migration and proliferation of PDAC and Panc1 cells in vitro. In the present study, we found that BNIP3 expression was elevated and enhanced the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. The upregulation of BNIP3 was important for the autophagic activation, while inhibition of autophagy with siRNA targeting Atg5 and Atg7 impaired the hypoxia-induced cell migration and proliferation. Additionally, blocking ERK1/2 mitogen-activated protein kinase (MAPK) signaling with PD98058 significantly down-regulated BNIP3 expression, autophagic activation, as well as the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. Collectively, our results here uncover a hitherto unknown hypoxia-BNIP3-autophagy axis in modulating the migration and proliferation and provide a potential intriguing drug target for the therapy of PDAC.

Decreased TCF1 and BCL11B expression predicts poor prognosis for patients with chronic lymphocytic leukemia.

T cell immune dysfunction is a prominent characteristic of chronic lymphocytic leukemia (CLL) and the main cause of failure for immunotherapy and multi-drug resistance. There remains a lack of specific biomarkers for evaluating T cell immune status with outcome for CLL patients. T cell factor 1 (TCF1, encoded by the TCF7 gene) can be used as a critical determinant of successful anti-tumor immunotherapy and a prognostic indicator in some solid tumors; however, the effects of TCF1 in CLL remain unclear. Here, we first analyzed the biological processes and functions of TCF1 and co-expressing genes using the GEO and STRING databases with the online tools Venny, Circos, and Database for Annotation, Visualization, and Integrated Discovery (DAVID). Then the expression and prognostic values of TCF1 and its partner gene B cell leukemia/lymphoma 11B (BCL11B) were explored for 505 CLL patients from 6 datasets and validated with 50 CLL patients from Henan cancer hospital (HNCH). TCF1 was downregulated in CLL patients, particularly in CD8+ T cells, which was significantly correlated with poor time-to-first treatment (TTFT) and overall survival (OS) as well as short restricted mean survival time (RMST). Function and pathway enrichment analysis revealed that TCF1 was positively correlated with BCL11B, which is involved in regulating the activation and differentiation of T cells in CLL patients. Intriguingly, BCL11B was highly consistent with TCF1 in its decreased expression and prediction of poor prognosis. More importantly, the combination of TCF1 and BCL11B could more accurately assess prognosis than either alone. Additionally, decreased TCF1 and BCL11B expression serves as an independent risk factor for rapid disease progression, coinciding with high-risk indicators, including unmutated IGHV, TP53 alteration, and advanced disease. Altogether, this study demonstrates that decreased TCF1 and BCL11B expression is significantly correlated with poor prognosis, which may be due to decreased TCF1+CD8+ T cells, impairing the effector CD8+ T cell differentiation regulated by TCF1/BCL11B.

All-trans retinoic acid enhanced the antileukemic efficacy of ABT-199 in acute myeloid leukemia by downregulating the expression of S100A8.

Acute myeloid leukemia (AML) is prone to relapse. Targeted therapy with a specific inhibitor of the anti-apoptotic protein Bcl-2 ABT-199 is an effective method for relapsed and refractory patients, but drug resistance is likely, which is primarily related to high Mcl-1 and S100A8 expression. All-trans retinoic acid (ATRA) can inhibit Bcl-2 and Mcl-1 expression. The study purpose was to determine whether ATRA can enhance the antileukemia effect of ABT-199 on AML cells. Our data showed that ATRA combined with ABT-199 exerts a synergistic antileukemic effect by inducing apoptosis and cell cycle arrest in AML. In vivo, combination therapy prolonged the survival of AML xenograft mice. The possible mechanism involves promoting apoptosis through downregulation of S100A8 expression by inhibiting the PI3K/AKT signaling pathway. This study provides a potential treatment strategy and theoretical support for overcoming the clinical ABT-199 resistance problem in AML patients.

The different predictive effects of the intensity and proportion of CD20 expression on the prognosis of B-lineage acute lymphocyte leukemia.

The prognostic effects of the CD20 positivity have been studied extensively in B-lineage acute lymphocyte leukemia (B-ALL) patients, but the results remain controversial. The aim of this study is to investigate the different predictive effects of the intensity and proportion of CD20 expression on the prognosis for B-ALL patients by retrospective analysis. The mean fluorescence intensity (MFI) and percentage of CD20 on B-ALL cells from 206 patients with B-ALL were dynamically measured by flow cytometry, and their optimal cut-off values were determined using the receiver operating characteristic curve. Changes in MFI and percentage of CD20 at various time points and their relationship with prognosis were analyzed. We found that a low baseline CD20 MFI or high CD20 proportion was significantly associated with shorter 5-year overall survival and progression-free survival, and the combination of these two factors could more accurately predict worse survival for B-ALL patients. Furthermore, low CD20 MFI or a high CD20 proportion had different predictive effects for ALL patients with different clinical characteristics and could serve as an independent risk factor for adverse prognosis. There were significant decreases in both the intensity and proportion of CD20 after recurrence in the absence of rituximab treatment, particularly with CD20 intensity. Notably, the decrease of CD20 intensity after recurrence indicated a more shortened survival time. Finally, we conclude that a low intensity or high proportion of CD20 expression may be used as an indicator for inferior prognosis for B-ALL patients. CD20 intensity is more likely to be a more universal biomarker for worse prognosis.

Super Early Scan of PSMA PET/CT in Evaluating Primary and Metastatic Lesions of Prostate Cancer.

68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT has been widely used in the diagnosis of prostate cancer (PCa); however, the urine lead shielding resulting from the urinary metabolism of tracers may obstruct the detection of surrounding metastasis. In this research, the additive value of super early scanning in diagnosing primary lesions and metastasis in the pelvic cavity was evaluated. Firstly, the differentiation efficiency of 68Ga-PSMA-11 PET scanned at 3 min post-injection (min P.I.) was measured in PSMA-positive (22rv1 cells) and PSMA-negative (PC3 cells) model mice. Secondly, 106 patients were scanned at 3 min P.I. for the pelvic cavity and then scanned as a standard protocol at 45 min P.I. In the results, the differential diagnosis of PSMA expression was completely reflected as early as 3 min P.I. for mice models. For patients, when correlated with the Gleason score, the quantitative results of the super early scan displayed a comparable correlation coefficient with the routine scan. The target to bladder ratios increased from 1.44 ± 2.40 at 45 min to 10.10 ± 19.10 at 3 min (p < 0.001) for the primary lesions, and it increased from 0.99 ± 1.88 to 9.27 ± 23.03 for metastasis. Meanwhile, the target to background ratios increased from 2.21 ± 2.44 at 3 min to 19.13 ± 23.93 at 45 min (p < 0.001) for the primary lesions, and it increased from 1.68 ± 2.71 to 12.04 ± 18.73 (p < 0.001) for metastasis. In conclusion, super early scanning of 68Ga-PSMA-11 PET/CT added referable information for metastasis detection in order to avoid disturbing tracer activity in the urinary system.

Tailoring Multifunctional Small Molecular Photosensitizers to In Vivo Self-Assemble with Albumin to Boost Tumor-Preferential Accumulation, NIR Imaging, and Photodynamic/Photothermal/Immunotherapy.

Cancer immunotherapy has great potential in tumor eradication and metastasis suppression. However, systemic administration of immune adjuvants and inadequate specificity in cancer treatment, lead to restricted therapeutic benefits and potential immune-related side effects in clinical settings. In this report, the synthesis of various lengths of heptamethine cyanine small molecules to act as multifunctional photosensitizers (PS) for tumor-specific accumulation, near-infrared (NIR) fluorescent imaging, and photodynamic/photothermal/immunotherapy is optimized. In particular, it is demonstrated that C8, which contains eight carbons on two N-alkyl side chains, efficiently self-assembles with albumin to form nanosized dye-albumin complexes. This feature facilitates C8 in vivo self-assembly to remarkably improve its water-solubility, NIR fluorescent emission, long-term blood circulation, as well as tumor-specific accumulation. More importantly, C8 not only exhibits a superior phototherapeutic effect on primary tumors, but also elicits secretion of damage associated molecular patterns, cytokine secretion, dendritic cell maturation, and cytotoxic T lymphocytes activation, ultimately triggering a sufficient antitumor immune response to suppress growths of distant and metastatic tumors. Hence, this multifunctional small molecular PS is characterized with excellent tumor-preferential accumulation, imaging-guided laser irradiation, and phototherapy-induced in situ antitumor immune response, providing a prospective future of its use in tumor-targeting immunotherapy.

Metabolic Engineering of Saccharomyces cerevisiae for de Novo Dihydroniloticin Production Using Novel CYP450 from Neem (Azadirachta indica).

Azadirachtin, a limonoid isolated from the neem tree, has attracted considerable interest due to its excellent performance in pest control. Studies have also reported pharmaceutical activities of dihydroniloticin, an intermediate in azadirachtin biosynthesis, but these pharmaceutical activities could not be validated due to the limited supply. In this study, AiCYP71CD2 was first identified as involved in azadirachtin biosynthesis in neem by expressing it in Nicotiana benthamiana and yeast (Saccharomyces cerevisiae). Homology modeling and molecular docking analysis revealed that AiCYP71CD2 may exhibit a higher ability in catalyzing tirucalla-7,24-dien-3ß-ol into dihydroniloticin compared with MaCYP71CD2 from Melia azedarach L. G310 was identified as the critical residue responsible for the higher catalytic ability of AiCYP71CD2. Condon-Optimized AiCYP71CD2 greatly improved the catalytic efficiency in yeast. De novo dihydroniloticin production using the novel AiCYP71CD2 was achieved by constructing the S. cerevisiae DI-3 strain, and the titer could reach up to 405 mg/L in a fermentor, which was an alternative source for dihydroniloticin.

Predictive factors for differentiating thrombohemorrhagic disorders in high-risk acute promyelocytic leukemia.

INTRODUCTION: Acute promyelocytic leukemia (APL) is often accompanied by potentially fatal coagulopathy, especially in high-risk APL. Bleeding, particularly severe bleeding is the leading cause of early death (ED). Meanwhile, thrombosis, the other major coagulopathic complication, is being increasingly recognized. However, predictors of thrombohemorrhagic disorders are still not well investigated. MATERIALS AND METHODS: In this study, we retrospectively studied 83 patients with high-risk APL and categorized them into severe bleeding, thrombosis and no evident events groups. RESULTS: Severe bleeding was observed in 15 patients, nearly half of whom died of hemorrhage, while thrombosis was observed in 12 patients. Risk factor analysis showed that high WBC (>58.76 × 109/L) (p = 0.001) and prolonged PT (>17.7 s) (p = 0.015) could be independent predictors for severe bleeding, while high WBC/D-dimer>5.12 (p = 0.002) and low D-dimer/FIB<5.14 (p = 0.03) could be independent predictors for thrombosis in high-risk APL patients. Moreover, there are significant differences in WBC/D-dimer and D-dimer/FIB between DIC and Non-DIC groups (p < 0.001). Notably, we found that the WBC/D-dimer was dramatically higher in the thrombotic group than in the other two groups at the time of admission or during the first week of induction therapy. CONCLUSIONS: High WBC and prolonged PT could predict severe bleeding in high-risk APL patients, while high WBC/D-dimer and low D-dimer/FIB could be independent predictors for thrombosis. For high-risk APL, WBC/D-dimer and D-dimer/FIB are also beneficial in the diagnosis of DIC. WBC/D-dimer might help early identification of thrombosis at the time of admission or during the first week of induction therapy.

Saikosaponin D Alleviates DOX-induced Cardiac Injury In Vivo and In Vitro.

ABSTRACT: As a highly efficient anticancer agent, doxorubicin (DOX) is used for treatment of various cancers, but DOX-induced oxidative damages contribute to a degenerative irreversible cardiac toxicity. Saikosaponin D (SSD), which is a triterpenoid saponin with many biological activities including anti-inflammatory effects and antioxidant properties, provides protection against pathologic cardiac remodeling and fibrosis. In the present study, we investigated the work of SSD for DOX-induced cardiotoxicity and the involved mechanisms. We observed that DOX injection induced cardiac injury and malfunction and decreased survival rate. Besides, DOX treatment increased lactate dehydrogenase leakage, cardiomyocyte apoptosis, and myocardium fibrosis and decreased the size of cardiomyocytes. Meanwhile, all the effects were notably attenuated by SSD treatment. In vitro, we found that 1 µM SSD could enhance the proliferation of H9c2 cells and inhibit DOX-induced apoptosis. It was found that the levels of malondialdehyde (MDA) and reactive oxygen species were significantly reduced by improving the activities of the endogenous antioxidative enzymes including catalase and glutathione peroxidase. Furthermore, SSD treatment could downregulate the DOX-induced p38 phosphorylation. Our results suggested that SSD efficiently protected the cardiomyocytes from DOX-induced cardiotoxicity by inhibiting the excessive oxidative stress via p38-MAPK (mitogen-activated protein kinase, MAPK) signaling pathway.

A retrospective study on effectiveness of combined recombinant human interferon-α-1b, interleukin-2, and thalidomide for the treatment of acute myeloid leukemia in various disease states.

Background: Interferon-α-1b, interleukin-2 combined with thalidomide (ITI) improved the outcome and prognosis of some acute myeloid leukemia (AML) patients, but the cases was insufficient. This study observed the efficacy and safety of this regimen in the treatment of numbers of AML patients in various disease states. Methods: Starting in January 2014, patients with AML (n=188) were treated with ITI regimen, including 60 refractory/relapses patients in group A, 40 patients in group B remained minimal residual disease-positive (MRD) or changed from negative to positive again after consolidation therapy, and 88 patients in group C with initial complete remission of AML received the ITI treatment after routine consolidation therapy. Bone marrow, fusion gene and MRD were detected to judge the curative effect and the adverse reactions were observed. The remission rate, MRD status and long-term survival of three groups were analyzed. An AML mouse model was constructed to observe the anti-leukemia effect of the three drugs in vivo. Results: Sixty patients with primary AML who were unable to receive chemotherapy, or with relapsed/refractory AML, showed a total response rate of 28.3% (17/60) after receiving the ITI regimen. Forty patients with morphologically complete remission and MRD-positive achieved a response rate of 77.5% (31/40); the MRD converted to negative in 19 patients and was mitigated in 12 patients. Among 88 patients with initial complete remission, 11 failed to maintain the negative MRD, and the relapse rate was 12.5%, which was significantly lower than that of the non-maintenance treatment group (54.3%). In the mouse model, interferon, interleukin-2, and thalidomide exerted an anti-leukemia effect, prolonged the survival time of the mice, and the anti-leukemia effect was further enhanced after administration of the combination ITI regimen. Conclusions: For suitable patients, hematopoietic stem cell transplantation is still strong recommended. The ITI regimen may be an effective option for patients with AML who cannot tolerate conventional chemotherapy, including those with relapsed/refractory disease, those with a complete remission status but are MRD-positive, or those who require maintenance treatment after consolidation therapy. However, a rigorous clinical randomized controlled trial and more in-depth mechanism exploration are still needed to verify this conclusion.

Adsorption, Gas-Sensing, and Optical Properties of Molecules on a Diazine Monolayer: A First-Principles Study.

Using first-principles calculations, the structural, electronic, and optical properties of CO2, CO, N2O, CH4, H2, N2, O2, NH3, acetone, and ethanol molecules adsorbed on a diazine monolayer were studied to develop the application potential of the diazine monolayer as a room-temperature gas sensor for detecting acetone, ethanol, and NH3. We found that these molecules are all physically adsorbed on the diazine monolayer with weak adsorption strength and charge transfer between the molecules and the monolayer, but the physisorption of only NH3, acetone, and ethanol remarkably modified the electronic properties of the diazine monolayer, especially for the obvious change in electric conductivity, showing that the diazine monolayer is highly sensitive to acetone, NH3, and ethanol. Further, the adsorption of NH3, acetone, and ethanol molecules remarkably modifies, in varying degrees, the optical properties of the diazine monolayer, such as work function, absorption coefficient, and the reflectivity, whereas adsorption of other molecules has infinitesimal influence. The different adsorption behaviors and influences of the electronic and optical properties of molecules on the monolayer show that the diazine monolayer has high selectivity to NH3, acetone, and ethanol. The recovery time of NH3, acetone, and ethanol molecules is, respectively, 1.2 µs, 7.7 µs, and 0.11 ms at 300 K. Thus, the diazine monolayer has a high application potential as a room-temperature acetone, ethanol, and NH3 sensor with high performance (high selectivity and sensitivity, and rapid recovery time).

Remarkable Response of Toripalimab Combined with Chemotherapy in Sarcomatoid Carcinoma of Palatine Tonsil: A Case Report.

BACKGROUND: Sarcomatoid carcinoma (SaCa) of the palatine tonsil is a rare and aggressive subset of head and neck (H&N) cancer which is characterized by insensitivity to surgery and radiotherapy and a poor prognosis. Immunotherapy has led advances in the treatment of melanoma and H&N cancer, but the combined effects of immunotherapy and chemotherapy have not been sufficiently investigated. CASE PRESENTATION: Herein, we report the case of 29-year-old Chinese women with local advanced non-resectable SaCa of the palatine tonsil who exhibited a substantial partial response to toripalimab and chemotherapy followed by radiation therapy. To the best of our knowledge, this is the first report of its successful application in this context. CONCLUSION: Toripalimab combined with chemotherapy may be an effective approach for locally advanced H&N cancer in rare categories of patients, which was the first application as far as we know.

Deuteration enhances the anti-tumor effects and relative anti-inflammatory effects via affecting proliferation and apoptosis.

Apigenin (AP) is a plant flavonoid with potential biomedical applications. To enhance the anti-tumour effect, AP was deuterated via hydrogen-deuterium exchange under hydrothermal conditions. The anti-tumor effects of deuterated AP (D-AP) were then tested on HCT116 cells and on a murine model of turpentine-induced inflammation. Cell cycle progression and cell proliferation were measured by flow cytometry, and in vivo immuno-inflammation was evaluated by quantitating glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography. According to the mass spectral results, the efficiency of AP deuteration was 62.96%. For both the two groups of AP and D-AP at 24 h and 48 h, there were an obvious increase on perception of G2 phage. Apigenin showed the ability of blocking in G2 phage to inhibit cellular proliferation. Additionally, D-AP induced early apoptosis in more cells than did AP (12.1% vs. 10.4%). Moreover, D-AP induced a more severe process of anti-inflammation during the early period, resulting in a more effective anti-inflammatory response. Therefore, given the innate ability of D-AP to block cell proliferation and induce early apoptosis, we conclude that deuteration enhances the systemic anti-cancer effect of this flavonoid.

[Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML). METHODS: Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls. RESULTS: The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of perforin and Granzyme B of NK cells in the peripheral blood of patients with hematological malignancies were lower than those of healthy controls. The level of VEGF, IL-6 and TNF-α in the peripheral plasma were higher than those of the healthy control group, and the difference was statistically significant. The level of IFN-γ was lower, and the difference was not statistically significant. The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of Granzyme B and Perforin of NK cells in peripheral blood were higher after the therapy of thalidomide combined with rhIFNα-1b for 3 months as compared with those before treatment of ITI, the level of the IFN-γ in peripheral plasma was higher while that of VEGF was lower, the difference was statistically significant; after treatment, the ratio of CD3+ CD4+ and CD3+ CD8+ lymphocytes and the level of TNF-α in peripheral blood were higher those that before treatment, IL-6 was lower, while the difference was not statistically significant. CONCLUSION: The ITI regimen can raise the ratio of CD4+/CD8+ T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.

Association between polymorphism near the MC4R gene and cancer risk: A meta-analysis.

OBJECTIVE: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near the melanocortin 4 receptor (MC4R), gene which are associated with risk of obesity. Since obesity is an established risk factor of cancer, several studies have examined the association between SNPs near the MC4R gene and cancer risk, but the findings are inconsistent. The present study aimed to perform a meta-analysis to clarify the association between SNPs near MC4R and cancer risk. METHODS: The PubMed and Embase databases were searched for potentially eligible publications. All studies that evaluated the association between MC4R rs17782313 SNP (or its proxy rs12970134) and cancer risk were included. The pooled odds ratios with 95% confidence intervals (CIs) were calculated using the random-effects model. And subgroup analysis by cancer type (colorectal cancer, endometrial cancer and breast cancer) was conducted for further investigate the association. RESULTS: A total of 6 eligible studies (6517 cases and 16,886 controls) were included in the present meta-analysis. The results indicated that MC4R rs17782313 SNP was moderately associated with cancer risk (odds ratio = 1.12, 95% CI = 1.01-1.24). However, the subgroup analysis between different cancer types shows that rs17782313 is only associated with colorectal cancer but not the endometrial cancer and breast cancer. Risk factor in colorectal cancer was both significantly associated with rs17782313 with and without adjustment for body mass index; while the risk factor of the endometrial cancer and breast cancer were both not associated with the rs17782313 with and without adjustment for body mass index. There was no publication bias for the association between MC4R rs17782313 and cancer risk. CONCLUSION: The present meta-analysis confirmed the moderate association between MC4R rs17782313 and cancer risk.

The CXCR4 Antagonist, AMD3100, Reverses Mesenchymal Stem Cell-Mediated Drug Resistance in Relapsed/Refractory Acute Lymphoblastic Leukemia.

PURPOSE: To investigate the role of the CXCR4/CXCL12 axis in chemotherapy resistance in refractory/relapsed (R/R) ALL patients. METHODS: CXCR4 expression on ALL cells from newly diagnosed or R/R ALL patients were detected using flow cytometry. The CXCR4/CXCL12 signaling pathway was blocked by the CXCR4 inhibitor AMD3100 in a co-culture model of primary drug-resistant ALL cells and umbilical cord mesenchymal stem cells (UCMSCs). Surface CXCR4 expression, apoptosis rate, and apoptosis-related protein expression in primary ALL cells under various treatments were detected. RESULTS: Of the 37 ALL patients examined, CXCR4 expression was higher in R/R patients than that in those with newly diagnosed disease. Similarly, in in vitro co-cultures of drug-resistant ALL cells with UCMSCs, the expression of CXCR4 was increased in the presence of vincristine (VCR), but reduced when VCR was combined with the CXCR4 antagonist AMD3100. Additionally, the supernatants of ALL-UCMSC co-cultures contained high CXCL12 concentrations, which were upregulated by VCR and significantly decreased by the combination of VCR plus AMD3100. Furthermore, the apoptosis rate of ALL cells significantly decreased, Bax expression was downregulated, and Bcl-2 was upregulated when ALL was co-cultured with UCMSCs compared with ALL cells alone. With the addition of VCR, the apoptosis rate mildly increased, Bax was upregulated, and Bcl-2 was downregulated. Nevertheless, the above results were further intensified, particularly Bax expression, when VCR was combined with AMD3100. CONCLUSION: The CXCR4 antagonist could effectively reverse MSC-mediated drug resistance by blocking the CXCR4/CXCL12 axis and sensitizing leukemic cells from R/R ALL patients to chemotherapy drugs.

Interactive effects of carbohydrate, lipid, protein composition and carbon/nitrogen ratio on biogas production of different food wastes.

The anaerobic co-digestion (AcoD) of FWs produces variable methane yields, mainly due to variable carbon/nitrogen (C/N) ratio and proportions of lipids (L), carbohydrates (C), and proteins (P) in different FW samples. In this study, a significant interaction between C/N ratio and LCP composition was found and contributed to the differing trends between special (SMP) and theoretical methane production. The highest SMP of 595 mL CH4 gVS-1 occurred at C/N of 25 and LCP of 63.25:22.62:14.13, followed by 592 mL CH4 gVS-1 at C/N of 30 and LCP of 48.94:39.74:11.32, which also reflected their interaction. Attributing to their interactive effect on obtaining optimal process parameters and microbial community, the inhibition threshold of lipid as well as the methane yield was increased. Understanding the interaction between C/N ratio and LCP composition is an effective and promising way to obtain suitable mixture ratios of organic wastes under AcoD.

LncRNA SNHG4 regulates miR-138/c-Met axis to promote the proliferation of glioblastoma cells.

LncRNA SNHG4 has been reported to be an oncogenic lncRNA in osteosarcoma. Our preliminary analysis of the cancer genome atlas dataset revealed the upregulation of SNHG4 in glioblastoma (GBM). In this study, we confirmed the upregulation of SNHG4 in GBM tissues collected from GBM patients. In addition, lower survival rate of GBM patients was observed in patients with high SNHG4 expression level. SNHG4 can directly interact with miR-138, while SNHG4 expression was no altered after miR-138 overexpression. Interestingly, SNHG4 overexpression led to the upregulation of c-Met, a target of miR-138. Cell counting kit-8 assay showed that miR-138 overexpression resulted in decreased proliferation rate of GBM cells. SNHG4 and c-Met overexpression played opposite roles and reduced the effects of miR-138. Therefore, SNHG4 regulates miR-138/c-Met axis to promote the proliferation of GBM cells.