Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*

OBJECTIVE: Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI. METHODS: A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function. RESULTS: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. CONCLUSION This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.
Abietanes ; Acute Lung Injury/drug therapy* ; Animals ; Cytokine Release Syndrome ; Cytokines ; Inflammation/drug therapy* ; Lipopolysaccharides/toxicity* ; Macrophage Activation ; Macrophages ; Mice ; Triacetoneamine-N-Oxyl/pharmacology*

OBJECTIVE: To explore the predictors of hematologic responses of non-transfusion-dependent β-thalassemia (NTDT) to thalidomide. METHODS: 33 patients with NTDT who treated with thalidomide in the 923rd Hospital of the Joint Logistics Support Force of the People's Liberation Army from May 2016 to June 2019 were included in the study. The basic data, hematological indexes, degree of treatment response and genetic background of the patients were analyzed. RESULTS: The baseline fetal hemoglobin (HbF) level of main responders (MaR) was significantly higher than that of minor responders (MiR) and no responders (NR) (P=0.001). And the baseline HbF level was positively correlated with hemoglobin increment after treatment (r=0.601). Genetic background analysis showed that the frequencies of the genotype CT of HBG2 rs7482144 (P=0.031), the genotypes CT/CC (P=0.030) and the minor allele C (P=0.015) of HBS1L-MYB rs9399137, the genotypes AT/TT (P=0.030) and the minor allele T (P=0.028) of HBS1L-MYB rs4895440, the genotypes AG/GG (P=0.030) and the minor allele G (P=0.028) of HBS1L-MYB rs4895441 (P=0.030) in MaR group were significantly higher than those in MiR and NR groups. Comparing the area under the ROC curve (AUC) of the above indicators to predict the main response, the results demonstrated that the predictive value of baseline HbF level was significantly better than rs7482144 (0.91 vs 0.72, P=0.003), rs9399137 (0.91 vs 0.74, P=0.022), rs4895440 (0.91 vs 0.74, P=0.023) and rs4895441 (0.91 vs 0.74, P=0.023), but there was no significant difference in the predictive value between combined single nucleotide polymorphisms (SNPs) (0.91 vs 0.88, P=0.658）and baseline HbF combined SNPs (0.91 vs 0.97, P=0.132). The AUC value of baseline HbF predicting the efficacy of thalidomide as the main response was 0.91, the cut-off value was 27.4%, the sensitivity was 100%, and the specificity was 58.3% (P=0.001). CONCLUSION The hematologic response of NTDT to thalidomide is variable and complex. Compared to genetic background, baseline HbF may be a simpler and more efficient tool to predict efficacy response.
Fetal Hemoglobin/genetics* ; Humans ; MicroRNAs ; Polymorphism, Single Nucleotide ; Repressor Proteins/genetics* ; Thalidomide/therapeutic use* ; beta-Thalassemia/genetics*

To investigate the effect of transient receptor potential melastatin 2 （TRPM2） inhibitor A10 on oxygen glucose deprivation/reperfusion （OGD/R） injury in SH-SY5Y cells．:Human neuroblastoma SH-SY5Y cells were subject to OGD/R injury，and then were divided into blank control group，model control group and A10 group randomly. The cell survival rate was detected by cell counting kit 8 （CCK-8）; the level of cellular reactive oxygen species （ROS） was detected by reactive oxygen detection kit; the mitochondrial membrane potential was detected by tetramethylrhodamine （TMRM） method; the number of apoptotic cells was detected by TUNEL apoptosis assay kit; the protein expression level of cleaved caspase 3 was detected by Western blot．:Compared with 3，20，30，50， has lower cytotoxicity and better inhibition effect on channel activity. Compared with the model control group，ROS level was reduced，the mitochondrial membrane potential was improved，the number of apoptosis cells was reduced ，and the expression of cleaved caspase 3 was significantly reduced in the A10 group（all <0.05）. : A10 can alleviate cell damage after OGD/R by inhibiting TRPM2 channel function，reducing extracellular calcium influx，reducing cell ROS levels，stabilizing mitochondrial membrane potential levels，and reducing apoptosis.
Apoptosis ; Benzeneacetamides ; Cell Survival ; Glucose ; Humans ; Oxygen/metabolism* ; Piperidones ; Reactive Oxygen Species/metabolism* ; Reperfusion ; TRPM Cation Channels

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 CONCLUSION The ITI regimen can raise the ratio of CD4
CD8-Positive T-Lymphocytes ; Humans ; Interferon-alpha ; Interleukin-2 ; Leukemia, Myeloid, Acute/drug therapy* ; Perforin ; Thalidomide

China ; Humans ; Lenalidomide/therapeutic use* ; Multiple Myeloma/drug therapy* ; Thalidomide ; Therapeutic Equivalency

Thalidomide and its derivatives have been used in the treatment of myelodysplastic syndrome (MDS) because of their anti-angiogenic and immunomodulatory effects. In recent years, some studies have found that thalidomide and its derivatives not only showed significant efficacy in lower-risk MDS patients with del (5q), but also showed advantages in non-del (5q) MDS patients. In addition, the discovery of its molecular targets and new substrates makes it possible to develop a new generation of immunomodulatory drugs (IMiDs) and to design IMiDs-based proteolysis-targeting chimeras. In this review, the new progress in mechanism and clinical application of thalidomide and its derivatives were summarized briefly, so as to provide a more scientific, reasonable and effective scheme to the treatment of MDS.
Humans ; Immunomodulating Agents ; Myelodysplastic Syndromes/drug therapy* ; Thalidomide/therapeutic use*

PURPOSE: Reduction-oxidation reaction homeostasis is vital for regulating inflammatory conditions and its dysregulation may affect the pathogenesis of chronic airway inflammatory diseases such as asthma. Peroxiredoxin-6, an important intracellular anti-oxidant molecule, is reported to be highly expressed in the airways and lungs. The aim of this study was to analyze the expression pattern of peroxiredoxin-6 in the peripheral blood mononuclear cells (PBMCs) of asthmatic patients and in bronchial epithelial cells (BECs).METHODS: The expression levels and modifications of peroxiredoxin-6 were evaluated in PBMCs from 22 asthmatic patients. Phosphorylated and acetylated peroxiredoxin-6 in hydrogen peroxide-treated human BECs was detected using immunoprecipitation analysis. The expression level of peroxiredoxin-6 was also investigated in BECs treated with hydrogen peroxide. Cycloheximide and proteasome inhibitors were used to determine whether peroxiredoxin-6 is degraded by proteasomes.RESULTS: Peroxiredoxin-6 expression was significantly reduced in the PBMCs of asthmatic patients compared to control subjects. Distinct modification patterns for peroxiredoxin-6 were observed in the PBMCs of asthmatic patients using 2-dimensional-electrophoresis. The levels of phosphorylated serine and acetylated lysine in peroxiredoxin-6 were significantly increased in the BECs following hydrogen peroxide treatment. The level of peroxiredoxin-6 expression was reduced in hydrogen peroxide-stimulated BECs, presumably due to proteasomes.CONCLUSIONS: The expression of peroxiredoxin-6, which is down-regulated in the immune cells of asthmatic patients and BECs, can be modified by oxidative stress. This phenomenon may have an effect on asthmatic airway inflammation.
Asthma ; Cycloheximide ; Epithelial Cells ; Homeostasis ; Humans ; Hydrogen ; Hydrogen Peroxide ; Immunoprecipitation ; Inflammation ; Lung ; Lysine ; Oxidative Stress ; Proteasome Inhibitors ; Protein Processing, Post-Translational ; Serine

OBJECTIVE: To explore the effects of different concentration of pomalidomide on human multiple myeloma cell line MM1.S and the expression of CRBN. METHODS: CCK-8 method was used for detecting inhibition effect of promalidomide on proliferation of MM1.S cells. Apoptosis rate of MM1.S cells was detected by flow cytometry with Annexin V-FITC/PI double staining. Real-time quantitative PCR was used to determine CRBN gene expression level. Western blot was used to detect the effect of pomalidomide on the protein expression of CRBN in MM1.S cells. RESULTS: Pomalidomide has an inhibitory effect on MM1.S cells with time-and dose-dependent manners. Pomalidomide induced apoptosis in MM1.S cells. When the concentration of pomalidomide was 0, 40 and 80 μmol/L, the expression of CRBN gene after the treatment of MM1.S cells for 72 hours was 1.487±0.340, 0.211±0.054 and 0.055±0.005, by using actin as internal refereme. Pomalidomide significantly reduced CRBN protein expression in MM1.S cells. CONCLUSION Pomalidomide can inhibit the proliferation of MM1.S cells and promote its apoptosis. A certain concentration of pomalidomide can reduce the expression of CRBN gene and down-regulate its protein expression in MM1.S cells.
Adaptor Proteins, Signal Transducing ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma ; Thalidomide ; analogs & derivatives

OBJECTIVE: To evaluate the prognostic value of R-ISS staging system in patients with newly diagnosed multiple myeloma (NDMM). METHODS: The Chinical data of 412 patients with NDMM in our hospital from May 2010 to May 2016 were retrospectively analyzed. All the patients received conventional chemotherapy or thalidomide or bortezomib-based chemotherapy. All the patients with NDMM were divided into R-ISS-Ⅰ, R-ISS-Ⅱ and R-ISS-Ⅲ groups according to R-ISS staging system on the basis of ISS staging system, cytogenetics and LDH level. The progression-free survival (PFS) time and overall survival(OS) of different groups were compared. RESULTS: Among all 412 patients, 76 were rated as R-ISS-Ⅰ, 259 as R-ISS-Ⅱ and 77 as R-ISS-Ⅲ. The median PFS time in 3 groups were 44, 25 and 14 months respectively (P<0.01). The median OS time of the 3 groups were not reached 54 and 25 months respectively (P<0.01). Further analysis also found that statistically different survival associated with different R-ISS groups in the conventional chemotherapy group (P<0.05), bortezomib-based chemotherapy group (P<0.01), thalidomide-based chemotherapy group (P<0.01), transplantation group (P<0.05), different-age stratified group (≤65y P<0.01, 66-75y P<0.01,≥76y P<0.01), damaged renal function group (P<0.01) and extramedullary infiltration group (P<0.01). CONCLUSION PFS and OS in the patients with multiple myeloma were different among three distrinct R-ISS stages. The R-ISS staging system has important clinical significance for the prognosis evaluation of multiple myeloma.
Antineoplastic Combined Chemotherapy Protocols ; Bortezomib ; Humans ; Multiple Myeloma ; diagnosis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Thalidomide ; Treatment Outcome