Search

Immune effector cells in patients with multiple myeloma (MM) are at the forefront of many immunotherapy treatments, and several methods have been developed to fully utilise the antitumour potential of immune cells. T and NK cell-derived immune lymphocytes both expressed activating NK receptor group 2 member D(NKG2D). This receptor can identify eight distinct NKG2D ligands (NKG2DL), including major histocompatibility complex class I (MHC) chain-related protein A and B (MICA and MICB). Their binding to NKG2D triggers effector roles in T and NK cells. NKG2DL is polymorphic in MM cells. The decreased expression of NKG2DL on the cell surface is explained by multiple mechanisms of tumour immune escape. In this review, we discuss the mechanisms by which the NKG2D/NKG2DL axis regulates immune effector cells and strategies for promoting NKG2DL expression and inhibiting its release in multiple myeloma and propose therapeutic strategies that increase the expression of NKG2DL in MM cells while enhancing the activation and killing function of NK cells. [Display omitted] • NKG2D/NKG2DL is pivotal in MM immunotherapy, aiding immune cell-MM cell interaction. • NKG2D may promote the development of CD8+ memory T cells. • Soluble NKG2DL (sNKG2DL) shedding hampers NK cell activation, contributing to MM immune escape. • Therapeutic strategy: Increase NKG2DL expression in MM cells, enhance NK cell activation, and killing function. [ABSTRACT FROM AUTHOR]

[Display omitted] • The drug delivery system (Fe 3 O 4 @LDH/PDA) has high drug loading for curcumin. • Fe 3 O 4 @Cur-LDH/PDA has excellent magnetic property and pH-responsiveness performance. • Fe 3 O 4 @Cur-LDH/PDA can inhibit tumor cell growth by releasing Cur after endocytosis. In recent years, using magnetic nanocomposites for controlled release of drugs and target-specific drug delivery has great potential in exploring a new method for cancer chemotherapy. Nevertheless, the low loading rate of insoluble drugs greatly restricts their efficacy and clinical application. Here, an efficient magnetic nanostructure combining Fe 3 O 4 nanoparticles and layered double hydroxide (LDH) was developed and used for tumor cell inhibition. LDH was first deposited on Fe 3 O 4 nanoparticles (Fe 3 O 4 @LDH), curcumin (Cur) was then loaded and polydopamine (PDA) eventually formed a PDA-coating on Fe 3 O 4 @Cur-LDH via self-polymerization. The Fe 3 O 4 @Cur-LDH/PDA nanostructure showed a suitable nano-meter size, excellent magnetic property, and high drug loading rate (up to 38 %). In vitro release results implied that Fe 3 O 4 @Cur-LDH/PDA nanostructure had good pH-responsive performance and excellent controlled-release behaviors due to the introduction of PDA. The cellular experiments demonstrated that Fe 3 O 4 @Cur-LDH/PDA nanostructure had good biocompatibility. In addition, Fe 3 O 4 @Cur-LDH/PDA entered into the cells mainly through endocytosis and had excellent inhibition on HepG2 cell viability in a concentration-dependent manner. Therefore, Fe 3 O 4 @Cur-LDH/PDA nanostructure has a prospective application in cancer therapy as a controlled drug delivery system. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a group of malignant brain tumors with a poor prognosis, and new therapeutic approaches for this tumor urgently need to be investigated. Formulated from a long-standing anti-inflammatory drugs, ACT001 has demonstrated in clinical research to be able to pass through the blood-brain barrier (BBB) and affect the central nervous system. The effects of ACT001 on PCNSL cell apoptosis, proliferation and immune-related indexes were detected by flow cytometry, and the efficacy of ACT001 was verified in vivo by constructing a mouse PCNSL tumor model. ACT001 significantly inhibited PCNSL cell proliferation and induced apoptosis in vitro. In addition, ACT001 can significantly inhibit the PD-1/PD-L1 expression and restore the function of T cells, so that the immune system cannot allow tumor cells to escape. In vivo experiments show that co-infusion of ACT001 and T cells effectively inhibits PCNSL tumor growth in NSG mice. Our work describes the inhibitory effect of ACT001 on the PCNSL cell line and demonstrated the inhibitory effect of ACT001 on immune checkpoints. [ABSTRACT FROM AUTHOR]

Exploring the vertical variations in volatile organic compounds (VOCs) in the atmosphere and quantifying the sources of VOCs at different heights can help control atmospheric photochemical pollution in summer. Here, VOCs were vertically detected at three heights (47 m, 200 m and 320 m) along a 325 m tower of the Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing, in the mornings (8:00) and afternoons (15:00) from May 19 to June 18, 2021. The VOC concentrations in Beijing in summer were 16.2 ± 5.6 ppbv, 14.7 ± 2.5 ppbv and 14.9 ± 3.8 ppbv at 47 m, 200 m and 320 m, respectively, and alkanes accounted for the largest proportion at all heights (>56%). The vertical gradients of the VOC concentrations and components did not significantly change, which was consistent with the summer observations of other stations in North China in recent years, but these results significantly differed from observations from more than a decade ago. To determine the reason for this, a classification based on atmospheric stability was performed, revealing that the vertical distribution of VOCs was uniform in convective and stable conditions and decreased with increasing height in neutral condition. With the transition of atmospheric stability from neutral to convective to stable, the contributions of fuel combustion sources and solvent use sources gradually increased, while those of biogenic sources and background sources gradually decreased. With increasing height, the contributions of background sources increased, those of biogenic sources, solvent use and gasoline vehicular emissions decreased, and those of fuel combustion and industrial emissions remained basically unchanged. The above results indicated that with air pollution treatment, the potential for reducing emissions of VOCs in Beijing has decreased. Therefore, regional joint prevention and control are the main ways to control VOC pollution in Beijing. [Display omitted] • The vertical gradients of VOCs did not change obviously. • Atmospheric stability affected the vertical distribution of VOCs. • With increasing height, the contributions of background sources increased. • Regional emission reduction can effectively control VOC pollution. [ABSTRACT FROM AUTHOR]

Chidamide as a newly designed and synthesized histone deacetylase inhibitor induces an antitumor effect in various cancer, and it has been used in several clinical trials such as peripheral T cell lymphoma (PTCL). Here we demonstrate that Chidamide was able to increase the acetylation levels of histone H3 and decrease HDAC activity in MDS cell lines(SKM-1,MUTZ-1)and AML cell line(KG-1). In vitro, at low concentration (<250 nM) of Chidamide inhibited cell proliferation and delayed G0/G1 cell cycle progression by down-regulating CDK2 and regulating p -P53 and P21 protein expression. Meanwhile,it also induced cell apoptosis by down-regulating Bcl-2 and up-regulating cleaved Caspase-3 and Bax protein expression.The results of the present study demonstrates the potential utility of Chidamide for the treatment of Myelodysplastic syndromes. [ABSTRACT FROM AUTHOR]

Abstract: A simulated oxidation technique was used to examine the impacts of degradation on the surface properties of biochar and the potential implications of the changes in biochar properties were discussed. To simulate the short- and long-term environmental degradation, mild and harsh degradation were employed. Results showed that after mild degradation, the biochar samples showed significant reductions in surface area and pore volumes. After harsh degradation, the biochar samples revealed dramatic variations in their surface chemistry, surface area, pore volumes, morphology and adsorption properties. The results clearly indicate that changes of biochar surface properties were affected by biochar types and oxidative conditions. It is suggested that biochar surface properties are likely to be gradually altered during environmental exposure. This implies that these changes have potential effects for altering the physicochemical properties of biochar amended soils. [Copyright &y& Elsevier]

Stimulus-responsive nanomaterials have become a hot spot in controllable drug delivery systems researches owing to their spatiotemporal controllable properties based on the differences between tumor microenvironment and normal tissue. Herein, iron (III) carboxylate metal-organic framework nanoparticles coated with glycyrrhetinic acid-chitosan conjugate (MIL-101/GA-CS) were successfully fabricated and acted as the pH-responsive and target-selective system to deliver doxorubicin (DOX) for hepatocellular carcinoma (HCC) therapy. The prepared nanocarrier possess the advantages of uniform size, comparable drug loading efficiency (28.89%), and superior pH-dependent controlled drug release (DOX release of 2.74% and 89.18% within 72 h at pH 7.4 and 5.5, respectively). In vitro cytotoxicity assays showed that the drug-loaded nanocarriers exhibited excellent inhibitory effects on HepG2 cells due to the sustained release of DOX, while the nanocarriers showed no significant toxicity. Furthermore, cell uptake experiments demonstrated that MIL-101-DOX/GA-CS could target HepG2 cells based on receptor-dependent internalization of glycyrrhetinic acid receptors mediated. In vitro 3D hepatoma cell microspheres experiments showed that MIL-101-DOX/GA-CS had excellent penetration and tumor killing ability. Therefore, MIL-101-DOX/GA-CS nanoparticles have a prospective application in cancer therapy as a pH-responsive controlled drug delivery system. • The pH-responsive and target-selective system (MIL-101/GA-CS) was constructed. • MIL-101/GA-CS exhibits good biocompatibility and high drug loading. • MIL-101-DOX/GA-CS exhibits enhanced cellular uptake due to targeting effect of GA. [ABSTRACT FROM AUTHOR]

Schematic of IFN-α signaling through lipid raft in PNH patients and normal controls. [Display omitted] • PNH cells more resistant to the inhibitory colony-forming activity of IFN-α. • PNH cells demonstrated significant attenuation of STAT2 Tyr690 in response to IFN-α. • PNH cells showed obviously defected endocytosis of IFNα/βRs in lipid rafts causing suppressed IFN-α signal transduction. • IFNα/βR endocytosis was dependent by cavin1. Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal disorder of haematopoietic stem cells caused by somatic PIGA mutations, resulting in a deficiency in glycosylphosphatidylinositol-anchored proteins (GPI-AP). Some researchers uncovered that PNH cells displayed a GPI-mediated defect in lipid-raft formation. However, Lipid rafts play a crucial role in signaling, the signaling underlying lipid rafts in PNH have not yet been addressed. In this study, we reported that, IFN-α was significantly increased in PNH plasma compared with normal controls. And PNH cells more resistant to the inhibitory colony[1]-forming activity of IFN-α. Here we have already established PIGA knock out K562 cell line by CRISPR/cas9, the most recognized in vitro model of PNH. PNH cells showed obviously defected endocytosis of IFNα/βRs in lipid rafts, causing suppressed STAT2 activation and the inflammatory response. We further investigated the possible mechanisms of interferon signaling endosomes mediate by cavin1. Our findings provide crucial insight into the process of reduced IFNα signal transduction in PNH cells mediated by lipid rafts and suggest that cavin1 are a potential target for suppression of IFN-α inflammatory signaling. These results might further explain the growth advantage of PNH cells in an unfavorable microenvironment. [ABSTRACT FROM AUTHOR]

• MDS-MSC possess high level of apoptosis and disorganized morphology, especially in iron overload group. • MDS-MSCs uptake and accumulate excessive iron due to prolonged iron exposure, resulted in up-regulating ROS level. • High level of ROS increases the expression of HIF-1a through inhibiting PHD2. • Increased HIF-1a promote the expression of IL-6, IL-8, VEGF and TGF-β in MSC. • Iron chelation and antioxidant treatment can reverse above process in iron overload MDS-MSC. Iron overload is a significant feature of myelodysplastic syndromes (MDS) patients due to ineffective hematopoiesis and transfusion dependence. Excess iron results in organ dysfunction through the generation of reactive oxygen species (ROS) which can cause oxidative stress even mutation. Mesenchymal stromal cells (MSCs) are responsible for supporting and regulating hematopoiesis, whether MSCs is involved in the pathogenesis of MDS still need further elucidation. Hypoxia-inducible factors-1 (HIF-1) is an integral signal of inflammation that has been shown to up-regulating in MDS patient. We found that MDS-derived MSC had disorganized clones and increased level of apoptosis (n = 53). Iron transportation-related gene, such as DMT1 and ZIP14, and ROS level were increased in iron overload-MDS-MSC (n = 23). HIF-1a, as a crucial part of HIF-1, was also elevated in iron overload-group and PHD2 involved in the degradation of HIF-1a was reduced. Furthermore, HIF-1 downstream cytokines such IL-6, IL-8, TGF-βand VEGF that were also involved in the pathogenesis of MDS were increased in IO-MDS-MSC. When treated with DFO and NAC for iron chelation and antioxidation, the level of HIF-1a and related cytokines could decrease. We conclude that iron overload regulates the cytokine of mesenchymal stromal cells through ROS/HIF-1α pathway in Myelodysplastic syndromes, result in dysfunction of MSC and damage of microenvironment that may be involved in the pathogenesis of MDS. [ABSTRACT FROM AUTHOR]