A novel selenium nanocomposite modified by AANL inhibits tumor growth by upregulating CLK2 in lung cancer.

Lung cancer is a malignant tumor with high mortality and drug resistance. Therefore, it is urgent to explore natural and nontoxic drugs to treat lung cancer. In this study, the natural active ingredient AANL extracted from Agrocybe aegirita was used to modify nanoselenium by an oxidation-reduction method. Transmission electron microscope detection and infrared spectroscopy showed that a novel selenium nanocomposite named AANL-SeNPs was successfully prepared. The results of nanoscale characterization showed that AANL-SeNPs had good stability and uniform dispersion in aqueous solution by zeta potential and spectrum analysis. At the cellular level, we found that AANL-SeNPs significantly inhibited the cell viability of lung cancer cells, and the cell inhibition rate of 60 nM AANL-SeNPs was 39 % in H157 cells, 67 % in H147 cells, and 62 % in A549 cells. The IC50 value of AANL-SeNPs was 51.85 nM in A549 cells and 81.57 nM in H157 cells. Moreover, AANL-SeNPs could inhibit the cell proliferation and migration, and enhance the sensitivity of lung cancer cells to osimertinib and has no toxic to normal cells. In vivo, AANL-SeNPs significantly slowed tumor growth in tumor-bearing mice by establishing a subcutaneous transplantation tumor model for lung cancer, and the tumor size was smaller and was reduced about 79 % in 2 mg/kg AANL-SeNPs group compared with PBS group. Mechanistically, a total of 38 differentially expressed proteins were identified by data-independent acquisition mass spectrometry. A significantly upregulated protein, CDC-like kinase 2 (CLK2), was screened and validated for further analysis, which showed that the expression levels of CLK2 were increased in H157 and H1437 cells after AANL-SeNPs treatment. The results obtained in this study suggest that a novel selenium nanocomposite AANL-SeNPs, which inhibits lung cancer by upregulating the expression of CLK2.

A diagnostic biomarker of acid glycoprotein 1 for distinguishing malignant from benign pulmonary lesions.

BACKGROUND: The acid glycoprotein 1 (AGP1) is downregulated in lung cancer. However, the performance of AGP1 in distinguishing benign from malignant lung lesions is still unknown. METHODS: The expression of AGP1 in benign diseases and lung cancer samples was detected by Western blot. The receiver operating characteristic curves, bivariate correlation, and multivariate analysis was analyzed by SPSS software. RESULTS: AGP1 expression levels were significantly downregulated in lung cancer and correlated with carcinoembryonic antigen (CEA), CA199, and CA724 tumor biomarkers. The diagnostic performance of AGP1 for distinguishing malignant from benign pulmonary lesions was better than the other four clinical biomarkers including CEA, squamous cell carcinoma-associated antigen, neuron-specific enolase, and cytokeratin 19 fragment 21-1, with an area under the curve value of 0.713 at 88.8% sensitivity. Furthermore, the multivariate analysis indicated that the variates of thrombin time and potassium significantly affected the AGP1 levels in lung cancer. CONCLUSIONS: Our study indicates that AGP1 expression is decreased in lung cancer compared to benign samples, which helps distinguish benign and malignant pulmonary lesions.

Overexpression of SERPINA3 suppresses tumor progression by modulating SPOP/NF­κB in lung cancer.

The pathogenesis mechanism of lung cancer is very complex, with high incidence and mortality. Serpin family A member 3 (SERPINA3) expression levels were reduced in the sera of patients with lung cancer and may be a candidate diagnostic and prognostic survival biomarker in lung cancer, as previously reported. However, the detailed biological functions of SERPINA3 in the pathogenesis of lung cancer remain unknown. In the present study, it was aimed to explore the effects of SERPINA3 on the occurrence of lung cancer. SERPINA3 expression was assessed using bioinformatics database analysis and experimental detection. Then, the biological effects of SERPINA3 were investigated in a cell culture system and a xenograft model of human lung cancer. The potential regulatory mechanism of SERPINA3 in lung cancer was explored by data­independent acquisition mass spectrometry (DIA­MS) detection and further validated by western blotting (WB). The results indicated that SERPINA3 expression levels were significantly downregulated in lung cancer tissues and cell lines. At the cellular level, it was revealed that overexpressed SERPINA3 inhibited cell growth, proliferation, migration and invasion and promoted the apoptosis of lung cancer cells. Moreover, overexpressed SERPINA3 enhanced the sensitivity of lung cancer cells to osimertinib. In vivo, a xenograft model of human lung cancer was established with BALB/c nude mice. After the injection of A549 cells, the tumor growth of the tumor­bearing mice in the SERPINA3­overexpressing group increased more slowly, and the tumor volume was smaller than that in the empty­vector group. Mechanistically, a total of 65 differentially expressed proteins were identified. It was found that the speckle­type POZ protein (SPOP) was significantly upregulated in SERPINA3­overexpressing H157 cells using DIA­MS detection and analysis. WB validation showed that SPOP expression increased, and NF­kappaB (NF­κB) p65 was inhibited in cell lines and tumor tissues of mice when SERPINA3 was overexpressed. The present findings suggest that SERPINA3 is involved in the development of lung cancer and has an antineoplastic role in lung cancer.

Preparation and usage of nanomaterials in biomedicine.

Nanotechnology is one of the most promising and decisive technologies in the world. Nanomaterials, as the primary research aspect of nanotechnology, are quite different from macroscopic materials because of their unique optical, electrical, magnetic, thermal properties, and more robust mechanical properties, which make them play an essential role in the field of materials science, biomedical field, aerospace field, and environmental energy. Different preparation methods for nanomaterials have various physical and chemical properties and are widely used in different areas. In this review, we focused on the preparation methods, including chemical, physical, and biological methods due to the properties of nanomaterials. We mainly clarified the characteristics, advantages, and disadvantages of different preparation methods. Then, we focused on the applications of nanomaterials in biomedicine, including biological detection, tumor diagnosis, and disease treatment, which provide a development trend and promising prospects for nanomaterials.

Alpha-1-antichymotrypsin as a novel biomarker for diagnosis, prognosis, and therapy prediction in human diseases.

The glycoprotein alpha-1-antichymotrypsin (AACT), a serine protease inhibitor, is mainly synthesized in the liver and then secreted into the blood and is involved in the acute phase response, inflammation, and proteolysis. The dysregulation of AACT and its glycosylation levels are associated with tumor progression and recurrence, and could be used as a biomarker for tumor monitoring. In this review, we summarized the expression level, glycosylation modification, and biological characteristics of AACT during inflammation, neurodegenerative or other elderly diseases, and tumorigenesis, as well as, focused on the biological roles of AACT in cancer. The aberrant expression of AACT in cancer might be due to genetic alterations and/or immune by bioinformatics analysis. Moreover, AACT may serve as a diagnostic or prognostic biomarker or therapeutic target in tumors. Furthermore, we found that the expression of AACT was associated with the overall survival of patients with human cancers. Decreased AACT expression was associated with poor survival in patients with liver cancer, increased AACT expression was associated with shorter survival in patients with pancreatic cancer, and decreased AACT expression was associated with shorter survival in patients with early lung cancer. The review confirmed the key roles of AACT in tumorigenesis, suggesting that the glycoprotein AACT may serve as a biomarker for tumor diagnosis and prognosis, and could be a potential therapeutic target for human diseases.

Evaluation of prognostic staging systems of multiple myeloma in the era of novel agents.

This study aimed to evaluate the existing staging systems for multiple myeloma (MM) in the real world. From January 2010 to June 2019, we retrospectively analyzed 859 newly diagnosed MM patients from two institutions. Clinical data including laboratory findings, imaging examinations and staging system were obtained by reviewing medical records. Survival distributions were estimated using the Kaplan-Meier curve analysis, and Cox proportional hazards model were used to identified risk factors. The overall survival (OS) of eligible patients was 61.0 months. The Revised International Staging System (R-ISS) had a larger receiver operating characteristic curve area (0.603) than both the International Staging System (0.573) and the Durie Salmon staging system (0.567). In the group receiving immunomodulatory agents-based regimens, the median OS was 92.0 months in R-ISS I, 63.0 months in R-ISS II and 18.0 months in R-ISS III (p < 0.0001). In the group receiving proteasome inhibitors-based regimens, the median OS was 102.0 months in R-ISS I, 63.0 months in R-ISS II and 22.0 months in R-ISS III (p < 0.0001). In different subgroups grouped according to age, hemoglobin (HGB), creatinine, and Ca, R-ISS also had a good stratification effect. Patients in R-ISS II, which accounted for 69.9% of all patients, were further analyzed. Univariate and multivariate Cox analyses revealed that age >65 years (p = 0.001), HGB < 100 g/L (p < 0.001), elevated LDH (p = 0.001), and Ca (p = 0.010) were independent predictors of worse prognosis within R-ISS II. To conclusion, R-ISS remains a valuable staging system in the real world of the novel drug era. However, patients classified as R-ISS II still have great heterogeneity.

MiR-4497 mediates oxidative stress and inflammatory injury in keratinocytes induced by ultraviolet B radiation through regulating NF-κB expression.

BACKGROUND: To investigate the role and underlying mechanism of miR-4497 in oxidative stress and inflammatory injury in keratinocytes induced by ultraviolet B (UVB) radiation. METHODS: An injury model of keratinocytes induced by UVB radiation was constructed. RT-qPCR, MTT assay and flow cytometry were adopted to detect miR-4497 expression in HaCaT cells, cell proliferation, and cell apoptosis, respectively. The levels of cytokines TNF-α, IL-18, IL-6 and IL-1ß in cell culture supernatant were tested by ELISA. ROS levels in the cells were labeled by DCFH-DA fluorescent probe, and then quantitative fluorescence analysis was performed by flow cytometry. SOD activity in the cells was measured by xanthine oxidase assay kit. Western blot was used to determine NF-κB expression in cytoplasm and nucleus, and p-IκBα expression in the cells. RESULTS: UVB radiation significantly increased miR-4497 expression in HaCaT cells, inhibited cell proliferation, and promoted cell apoptosis. Meanwhile, UVB radiation caused the promotion of secretion of cytokines TNF-α, IL-18, IL-6 and IL-1ß. The production of reactive oxygen species (ROS) was promoted by UVB radiation, while SOD activity was inhibited. Nuclear transfer of NF-κB signal was also induced by UVB radiation. In addition, downregulation of miR-4497 expression significantly inhibited the effects of UVB radiation on cell proliferation, apoptosis, cytokine secretion, redox level and NF-κB signal in HaCaT cells, while overexpression of miR-4497 further enhanced these effects of UVB radiation on HaCaT cells. CONCLUSIONS: UVB may promote the expression of inflammatory and oxidative stress signals in keratinocytes by upregulating miR-4497 expression, thus mediating cell injury.

Identification of novel combined biomarkers in the diagnosis of multiple myeloma.

PURPOSE: Multiple myeloma (MM) is a haematological malignant disease with a clonal proliferation of plasma cells, and timely surveillance is helpful to improve the survival rate of patients with MM. However, there is a lack of simple and effective biomarkers for the diagnosis, prognosis, and residual disease evaluation of MM. MATERIAL & METHODS: In the detection cohort, we used the samples from six newly diagnosed MM patients and six control subjects. Plasma proteins were labelled with dimethyl reagents and enriched by lectin AANL6, then the deglycosylated peptides were identified by LC-MS/MS. Differentially expressed proteins were used for further exploration. In the validation cohort, we used 90 newly diagnosed patients with MM and 70 cases of unrelated diseases as controls. The diagnosis performance was analysed by ROC analysis using SPSS. RESULTS: In this study, we show, using lectin blots with AANL6, that glycosylation levels were higher in MM patients than in controls. After AANL6 enrichment, we detected 58 differentially expressed proteins using quantitative proteomics. We further validated one candidate Fibulin-1 (FBLN1). Using an Elisa assay, we showed that FBLN1 expression was increased in plasma of 90 cases of MM, and which was significantly correlated with DKK1 expression. ROC analysis showed that these two markers had a 95.7% specificity for determining the diagnosis of MM. CONCLUSION: These data suggest that the MM cases display increased glycosylation after AANL6 enrichment and that the combined expression of FBLN1 and DKK1 can be used as an effective diagnostic biomarker.

Leukapheresis and Hyperleukocytosis, Past and Future.

Hyperleukocytosis is a hematologic crisis caused by excessive proliferation of leukemic cells and has a relatively high early mortality due to a series of severe complications. Therefore, prompt and effective intervention is required. Leukapheresis performed using apheresis equipment to separate leukocytes from peripheral blood, at the same time returns autologous plasma, platelets and erythrocytes to the patient, is applied clinically for the treatment of hyperleukocytosis. Leukapheresis not only removes excessive leukocytes rapidly and corrects metabolic abnormalities but also alleviates the symptoms of leukostasis. In addition, the procedure of leukapheresis is generally well tolerated. Leukapheresis has become one of the most imperative adjuvant therapies to treat hyperleukocytosis, especially in the patient who was not inappropriate to cytoreduce with Ara-C or hydroxyurea. In this review, we present the background of leukapheresis development and highlight its clinical application in hyperleukocytic leukemia patients.

Shengxuening Extracted from Silkworm Excrement Mitigates Myelosuppression via SCF-Mediated JAK2/STAT3 Signaling.

Shengxuening (SXN) is a Chinese patent medicine with main ingredients (including chlorophyll derivatives and sodium iron chlorophyllin) extracted from silkworm excrement. SXN exhibited efficacy in clinical trials of renal anemia and iron deficiency anemia; however, the specific mechanisms remain unclear. This study found that SXN increased the number of peripheral blood cells and improved the bone marrow morphology in myelosuppressed mouse model, reversed the reduction in body weight and spleen indices, and increased the serum levels of erythropoietin and granulocyte-macrophage colony-stimulating factor. Quantitative real-time PCR array and Western blot analysis showed the enhanced expression of stem cell factor (SCF), JAK2, and STAT3 in the liver. These results suggested that SXN promoted the recovery of hemopoietic function in myelosuppressed models by increasing the secretion of hematopoietic factors and activating the JAK2/STAT3 pathway. Therefore, this medicine may be applied as therapeutic pharmaceutical drug to mitigate myelosuppression.

Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver.

OBJECTIVE: Therapy for hepatocellular carcinoma (HCC) is a major challenge, and targeted therapies provide only a modest benefit in terms of overall survival. Treatment with antibodies to programmed cell death protein 1 (PD-1)/PD-L1 can restore the functions of tumor-infiltrating T cells in HCC and has shown clinical efficacy in 20% of patients with advanced HCC. Novel approaches are urgently needed to treat HCC and to augment the efficacy of immunotherapy. METHODS: Tumor-bearing mice were treated with Agrocybe aegerita galectin (AAGL) alone or in combination with anti-PD-1, and the tumor sizes and lifespans of mice were determined. Transcriptome analysis, cytokine analysis, flow cytometry analysis of the number and proportion of immune cell subsets in the liver and spleen, and molecular and cellular analyses of tumors were used to define the underlying mechanisms. RESULTS: AAGL significantly inhibited the growth of liver tumors in a dose-dependent manner. Furthermore, AAGL increased the expression of multiple cytokines and chemokines in tumor-bearing mouse livers; this effect was associated with the activation and migration of T cells and macrophages, in agreement with the in vitro results. Importantly, the aggregation of T cells and macrophages induced by AAGL in tumor-bearing mouse livers clearly enhanced the response to PD-1 blockade immunotherapy. CONCLUSIONS: The results showed that AAGL induced the activation and migration of lymphocytes to the liver, and that the combination of AAGL and anti-PD-1 may be a promising strategy for HCC treatment.

Therapeutic Plateletpheresis in Patients With Thrombocytosis: Gender, Hemoglobin Before Apheresis Significantly Affect Collection Efficiency.

Background: Thrombocytosis is a common symptom in myeloproliferative neoplasms (MPN), and excessive proliferation may deteriorate into thrombosis, bleeding, myelofibrosis, and may ultimately convert to acute leukemia. This study aimed to investigate the collection efficiency of plateletpheresis (CEPP) and factors influencing its efficacy in patients with thrombocytosis. Materials and Methods: From September 2010 to December 2016, 81 patients from two institutions in China with myeloproliferative neoplasms and thrombocytosis accompanied by severe symptoms were treated with plateletpheresis by Fresenius COM. TEC machine. Results: After apheresis, the median CEPP was 20.71% (IQR: 9.99-36.69%) and median PLT reduction rate was 25.87% (IQR: 21.78-36.23%). Further analysis showed that no significant difference was observed between PLT count with 800-1,000 × 109/L and > 1,000 × 109/L. The PLT counts significantly decreased (P < 0.001) after plateletpheresis, the red blood cell (RBC), white blood cell (WBC), hemoglobin (HGB), and hematocrit (HCT) levels showed no significant differences before- or after- plateletpheresis. Multivariate analysis showed that female sex (P = 0.009) and HGB (P = 0.010) before apheresis were associated with CEPP. Female (P = 0.022), HCT (P = 0.001) and blood volume (P = 0.015) were associated with the PLT reduction rate. Furthermore, symptoms were relieved after apheresis in patients whose PLT count was 800-1,000 × 109/L accompanied with symptoms. Conclusions: It is reasonable to perform plateletpheresis when the PLT count is over 800 × 109/L and patients are complicated by clinical symptoms such as dizziness, headache, somnolence, and stupor. Plateletpheresis is effective in removing PLTs especially in females with high HGB.

Anti-leukemia activities of selenium nanoparticles embedded in nanotube consisted of triple-helix ß-d-glucan.

Acute myeloid leukemia (AML) is a difficult therapeutic hematological tumor. It is urgent to find a non-toxic natural drug to treat AML. Herein, the selenium nanoparticles (SeNPs) embedded in nanotubes consisted of triple helix ß-(1, 3)-d-glucan (BFP) from the black fungus that were wrapped to form stable inclusion complex BFP-Se, which was self-assembled and exhibited high stability in water. In vitro, the BFP-Se significantly inhibited the proliferation of AML cells and increased the cytotoxicity on AML cells. On single-cell levels, the U937 cells were gradually swelled and lysed with BFP-Se treatment on optofluidics chips. Further, the blood and bone marrow analysis indicated the anti-leukemia effects of BFP-Se in vivo. Moreover, BFP-Se increased the total antioxidant capacity of AML cells and decreased the expression of c-Jun activation domain-binding protein 1 and thioredoxin 1. Our results suggest that this biocompatible polysaccharide nanotube containing Se nanoparticles would provide a novel strategy for AML therapy.

miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2.

MicroRNAs (miRNAs) can participate in many behaviors of various tumors. Prior studies have reported that miR-15b-5p in different tumors can either promote or inhibit tumor progression. In breast cancer, the role of miR-15b-5p is unclear. The main objective of this paper is to explore miR-15b-5p effects and their mechanisms in breast cancer using both in vitro and in vivo experiments. This study showed that miR-15b-5p expression was upregulated in breast cancer compared with normal breast tissue and was positively correlated with poor overall survival in patients. Knockdown of miR-15b-5p in MCF-7 and MD-MBA-231 breast cancer cells restrained cell growth and invasiveness and induced apoptosis, whereas overexpression of miR-15b-5p achieved the opposite effects. We next revealed a negative correlation between miR-15b-5p and heparanase-2 (HPSE2) expression in breast cancer. Knockdown of miR-15b-5p significantly increased HPSE2 expression at both mRNA and protein levels in breast cancer cells in vitro. The underlying mechanisms of miR-15-5p in breast cancer were investigated using luciferase activity reporter assay and rescue experiments. In addition, miR-15b-5p knockdown significantly inhibited tumor growth in a xenograft model in mice. In summary, we showed that miR-15b-5p promotes breast cancer cell proliferation, migration, and invasion by directly targeting HPSE2. Accordingly, miR-15b-5p may serve both as a tool for prognosis and as a target for therapy of breast cancer patients.

Azelaic Acid Exerts Antileukemia Effects against Acute Myeloid Leukemia by Regulating the Prdxs/ROS Signaling Pathway.

Acute myeloid leukemia (AML) is a hematological malignancy with a poor prognosis attributed to elevated reactive oxygen species (ROS) levels. Thus, agents that inhibit ROS generation in AML should be exploited. Azelaic acid (AZA), a small molecular compound, can scavenge ROS and other free radicals, exerting antitumor effects on various tumor cells. Herein, this study evaluated the antileukemic activity of AZA against AML via regulation of the ROS signaling pathway. We found that AZA reduced intracellular ROS levels and increased total antioxidant capacity in AML cell lines and AML patient cells. AZA suppressed the proliferation of AML cell lines and AML patient cells, expending minimal cytotoxicity on healthy cells. Laser confocal microscopy showed that AZA-treated AML cells surged and ruptured gradually on microfluidic chips. Additionally, AZA promoted AML cell apoptosis and arrested the cell cycle at the G1 phase. Further analysis demonstrated that peroxiredoxin (Prdx) 2 and Prdx3 were upregulated in AZA-treated AML cells. In vivo, AZA prolonged survival and attenuated AML by decreasing CD33+ immunophenotyping in the bone marrow of a patient-derived xenograft AML model. Furthermore, mice in the AZA-treated group had an increased antioxidant capacity and Prdx2/Prdx3 upregulation. The findings indicate that AZA may be a potential agent against AML by regulating the Prdxs/ROS signaling pathway.

Dramatically changed immune-related molecules as early diagnostic biomarkers of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the main type of lung cancer, with a low 5-year survival rate because of the absence of effective clinical biomarkers for early diagnosis. Based on the immunosurveillance theory, we proposed that changes in the immune system are more pronounced than tumour-associated antigens during the early stage of cancer. Therefore, a new strategy was designed to screen early diagnostic biomarkers from peripheral leukocytes in early-stage NSCLCs with transcriptome sequencing. A total of 358 immune-related differentially expressed genes were identified between early-NSCLC patients and healthy individuals. Orosomucoid-1 (ORM1, a acute phase protein), the total ORM and chitotriosidase-1 (involved in degradation of chitobiose) were selected for further verification in 210 serum samples by western blotting, ELISA and nephelometry immunoassay (based on immuno-scatter turbidmetry). Receiver operating characteristic curve analysis show that ORM1 and total ORM have excellent diagnostic efficacies, with area under the curve of 0.862 and 0.920, respectively, which significantly distinguished very early-NSCLC (IA) from healthy samples. Flow cytometry results showed that CD15+ neutrophils made up 73% of ORM1+ peripheral leukocytes. In mouse lung cancer model, serum ORM1, but not liver ORM1, changed significantly in the early stage of NSCLC. ORM1 expression in peripheral leukocytes was regulated by TGF-ß and mediated by the TGF-ß/Smad signalling pathway. Our results indicated that combined ORM and TGF-ß could be a promising clinical biomarker in the diagnosis of early NSCLC.

MRPS30-DT Knockdown Inhibits Breast Cancer Progression by Targeting Jab1/Cops5.

Longnoncoding RNAs (lncRNAs) are significantly correlated with cancer pathogenesis, development, and metastasis. Microarray analysis showed that lncRNA MRPS30-DT is overexpressed in breast carcinoma; however, the function of MRPS30-DT in breast cancer tumorigenesis remains unclear. In situ hybridization and immunohistochemical analysis were used to evaluate the expression levels of MRPS30-DT and Jab1 in clinical samples of breast carcinoma and their relation to survival outcome. qRT-PCR was used to measure MRPS30-DT and Jab1 mRNA expressions. Protein levels were detected using Western blot. Cell proliferation and invasion ability were evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and transwell assays. MRPS30-DT was knocked down in breast cancer cells to investigate its potential functional roles in cell growth and metastasis in vitro and in vivo. We found that MRPS30-DT was upregulated in breast cancer specimens and was accompanied by high Jab1 expression compared with that of paired para-carcinoma tissues. Knocking down MRPS30-DT significantly inhibited cancer cell proliferation and invasion and induced apoptosis in breast cancer cells. Similarly, knocking down MRPS30-DT in MDA-MB-231 cells significantly suppressed tumor growth. Furthermore, knocking down MRPS30-DT markedly reduced Jab1 expression in breast cancer cells and murine carcinoma. Statistical analyses suggested that high MRPS30-DT or Jab1 levels in breast cancer patients were positively correlated with poor prognoses. These data indicate the possible mechanisms of MRPS30-DT and Jab1 in breast cancer; thus, MRPS30-DT and Jab1 may be novel prognostic biomarkers and potential therapeutic targets for breast cancer treatment.

A Retrospective Analysis: A Novel Index Predicts Survival and Risk-Stratification for Bone Destruction in 419 Newly Diagnosed Multiple Myelomas.

OBJECTIVE: Multiple myeloma (MM) patients with bone destruction are difficult to restore, so it is of great clinical significance to further explore the factors affecting MM bone destruction. METHODS AND RESULTS: This study retrospectively analyzed 419 cases with MM. Multiple linear regression analysis showed that those MM patients with a higher concentration of Ca2+ in serum, higher positive rate of CD138 immuno-phenotype and advanced in stage with 13q34 deletion in cytogenetics would be more prone to bone destruction, while total bile acid (TBA) and kappa chain isotope negatively correlated with bone destruction in MM patients. The Kaplan-Meier analysis indicated that Ca2+, serum ß2-microglobulin (ß2-MG), hemoglobin (HGB), creatinine (CREA), uric acid (UA) and age correlated with the survival of bone destruction in MM patients. Cox regression analysis further showed that the independent prognostic factors of ß2-MG and CREA had a higher risk for early mortality in bone destruction patients. Moreover, an index was calculated based on ß2-MG and globulin (GLB) to white blood cell (WBC) ratio to predict the poor survival of bone destruction patients. CONCLUSION: We provide a novel marker to predict the prognosis of myeloma patients using routine examination method instead of bone marrow aspiration, and provide a reference for clinical evaluation.

Antiproliferative and Immunoregulatory Effects of Azelaic Acid Against Acute Myeloid Leukemia via the Activation of Notch Signaling Pathway.

Acute myeloid leukemia (AML) is a common type of hematological malignancy that can progress rapidly. AML has a poor prognosis and a high incidence of relapse due to therapeutic resistance. Azelaic acid (AZA), a small molecular compound is known to exhibit antitumor effect on various tumor cells. This study aimed to evaluate the antiproliferative and immunoregulatory effects of AZA against AMLviathe activation of the notch signaling pathway. We found that AZA can inhibit the proliferation of AML cells. In addition, laser confocal microscopy showed AZA-treated AML cells began to swelling and undergo cytoplasmic vacuolization. Importantly, AZA promoted the proliferation of NK and T cells and increased the secretion of TNF-αand IFN-γ. AZA also increased the expression levels of CD107a and TRAIL in NK cells, and CD25 and CD69 in T cells to influence their activation and cytotoxic ability. AZA-treated NK cells can kill AML cells more efficiently at the single-cell level as observed under the microfluidic chips. Further mechanistic analysis using protein mass spectrometry analysis and Notch signaling reporter assay demonstrated that Notch1and Notch2 were up-regulated and the Notch signaling pathway was activated. Moreover, combining AZA with the Notch inhibitor, RO4929097, decreased the expression of Notch1and Notch2, and downstream HES1 and HEY1, which rendered AML cells insensitive to AZA-induced apoptosis and alleviated AZA-mediated cytotoxicity in AML. In vivo, AZA relieved the leukemic spleen infiltration and extended the survival. The percentage of CD3-CD56+NK cells and CD4+CD8+T cells as well as the secretion of cytotoxic cytokines was increased after the treatment of AZA. The overall findings reveal that AZA is a potential Notch agonist against AML in activating the Notch signaling pathway.

Efficacy of SXN in the Treatment of Iron Deficiency Anemia: A Phase IV Clinical Trial.

Shengxuening (SXN) tablet is extracted from the excrement of the silkworm and has effects on hematopoiesis. The main components of SXN are chlorophyll derivatives and sodium iron chlorophyllin (SIC). The present study aims to investigate the efficiency and safety of SXN on iron deficiency anemia. This phase IV, multicenter, open-label, randomized clinical trial was conducted in 31 hospitals in China from June 2001 to April 2002. Adults and children were randomly divided into low-dose (L-SXN), medium-dose (M-SXN), and high-dose (H-SXN) groups, respectively. The course of treatment was 1 month. Peripheral hemogram levels and iron status were examined before and after treatment. Adults in all three dose groups demonstrated a significant increase in hemoglobin (HGB) concentration. Children who received SXN treatment in medium and high doses also demonstrated increased HGB concentration. Reticulocyte counts increased at the end of treatment in the M-SXN and H-SXN adult groups and in the M-SXN child group. For both children and adults, SXN in the three dose groups was found to significantly elevate red blood cell level, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The total effective rate in the SXN-treated group reached 84.8%. The incidence of adverse events was 4.07%. The most common side effects were nausea (2.83%), diarrhea (0.74%), and rash (0.25%). SXN was proved to be efficient and safe for adults and children with iron deficiency anemia.