LILRB4 ITIMs mediate the T cell suppression and infiltration of acute myeloid leukemia cells

We recently demonstrated that leukocyte Ig-like receptor 4(LILRB4)expressed by monocytic acute myeloid leukemia(AML)cells mediates T-cell inhibition and leukemia cell infiltration via its intracellular domain.The cytoplasmic domain of LILRB4 contains three immunoreceptor tyrosine-based inhibitory motifs(ITIMs);the tyrosines at positions 360,412,and 442 are phosphorylation sites.Here,we analyzed how the ITIMs of LILRB4 in AML cells mediate its function.Our in vitro and in vivo data show that Y412 and Y442,but not Y360,of LILRB4 are required for T-cell inhibition,and all three ITIMs are needed for leukemia cell infiltration.We constructed chimeric proteins containing the extracellular domain of LILRB4 and the intracellular domain of LILRB1 and vice versa.The intracellular domain of LILRB4,but not that of LILRB1,mediates T-cell suppression and AML cell migration.Our studies thus defined the unique signaling roles of LILRB4 ITIMs in AML cells.

Construction and screening of suppression subtractive hybridization library of renal cell carcinoma

Objective To construct and screen the suppression subtractive hybridization (SSH) library of human renal cell carcinoma (RCC). Methods Poly A+ RNA was isolated from RCC lines 786-O(tester) and renal cell(RC) lines HK-2 ( driver), respectiely. SSH procedure was performed according to the protocol of the PCR-Select cDNA Subtraction Kit ( Clontech), and PCR products were cloned into pT-Adv vector and transformed E. coli TOP10F’. All positive clones picked out were digested and some of which were sequenced. Results The SSH library contained 362 clones with SSH cDNA fragments distributed mainly from 0.3 to 0.9 kb. Among 50 clones sequenced randomly,2 represented unknown genes and the other 48 derived from 36 known genes. Conclusion The quality of the SSH library of human RCC is reliable and is construction is the basis for further screening differentially expressed genes of RCC. 6 refs,4 figs, 1 tab.

Suppressing Charge Recombination in ZnO-Nanorod-Based Perovskite Solar Cells with Atomic-Layer-Deposition TiO2

ZnO nanorods are passivated with a TiO2 interracial layer and applied in the CH3NH3PbI3 perovskite solar cell, which prepared by the atomic layer deposition method show a positive effect on the tiff factor and power conversion efficiency. With TiO2 interracial passivation, the charge recombination in the ZnO/CH3NH3PbI3 interface is effectively suppressed and the maximum power conversion efficiency is enhanced from 11.9% to 13.4%.

Converting“cold”to“hot”:epigenetics strategies to improve immune therapy effect by regulating tumor-associated immune suppressive cells

Significant developments in cancer treatment have been made since the advent of immune therapies.However,there are still some patientswithmalignant tumors who do not benefit from immunotherapy.Tumors without immunogenicity are called“cold”tumors which are unresponsive to immunotherapy,and the opposite are“hot”tumors.Immune suppressive cells(ISCs)refer to cells which can inhibit the immune response such as tumor-associated macrophages(TAMs),myeloid-derived suppressor cells(MDSCs),regulatory T(Treg)cells and so on.The more ISCs infiltrated,the weaker the immunogenicity of the tumor,showing the characteristics of“cold”tumor.The dysfunction of ISCs in the tumor microenvironment(TME)may play essential roles in insensitive therapeutic reaction.Previous studies have found that epigeneticmechanisms play an important role in the regulation of ISCs.Regulating ISCs may be a new approach to transforming“cold”tumors into“hot”tumors.Here,we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating ISCs.In addition,we summarized the mechanisms by which the epigenetic drugs convert immunotherapy-insensitive tumors into immunotherapy-sensitive tumors which would be an innovative tendency for future immunotherapy in“cold”tumor.

Effects of Shugan Jianpi Formula(疏肝健脾方)on Myeloid-Derived Suppression Cells-Mediated Depression Breast Cancer Mice

Objective： To observe the intervention effect of Shugan Jianpi Formula （疏肝健脾方,SGJPF） on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer. Metkods： The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups： normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF＋chemotherapy groups. The last 3 groups were depression breast cancer mice and treated respectively with SGJPF, chemotherapy drug gemcitabine （GEM）, and SGJPF alongside GEM. The condition of the mice was evaluated by the expression of 5-hydroxytryptamine in hippocampus after the sucrose water test and open field test, weight change, and survival time. Tumor growth was monitored with in vivo imaging. Flow cytometry was used to analyze the level of myeloid-derived suppression cell （MDSC） in the mouse spleen, T cell subsets, and the early apoptosis of CD8~ T cells, Results： The SGJPF＋GEM group had the highest inhibition rate and the longest survival time （P〈0.01）. The MDSC level and the apoptosis rate of CD8＊ T cells was the highest in the SGJPF＋GEM group （P〈0.05）. Conclusions： Depressive disorders and tumor growth could suppress the immune function of mice to different degrees, and the microenvironment in late 4T1 inflammatory breast cancer may play an important role in the pathological process. SGJYF could regulate the immune microenvironment by reducing CD8＊ T lymphocyte apoptosis and tumor cell activity, increasing immune surveillance capability, and inhibiting MDSC proliferation, thus prolonging the survival time of tumor-bearing mice.

Targeted suppression of miRNA-21 inhibit K562 cells growth through PTEN-PI3K/AKT signaling pathway

Objective To investigate the K562 cells biological function and related molecular changes in PTEN-PI3K/AKT signaling pathway of leukemia K562 cells by inhibiting the miRNA-21 expression to explore its pathogenesis of leukemia.Methods The chemical synthetic miRNA-

Anthocyanins extracted from Chinese blueberry （Vaccinium uliginosum L.） and its anticancer effects on DLD-1 and COLO205 cells

Background Vaccinium uliginosum L. is a type of blueberry found in the Chinese Changbai Mountains. We extracted Vaccinium uliginosum Anthocyanins （Av.uli） to investigate its bioactivity on suppressing cancer cells. Methods Av.lli was extracted under different conditions of temperature （10℃-35℃）, pH 1.0-3.0, and diatomaceous earth （1.0 g-3.0 g）, followed by a HPLC analysis for the determination of the ingredients. Its anticancer bioactivities on human colon and colorectal cancer cells （DLD-1 and COLO205） were compared with those on Lonicera caerulea Anthocyanins （AL.cae） and Vaccinium myrtillus Anthocyanins （Av.myr）, using cell viability assays, DNA electrophoresis and nuclear morphology assays. Results The optimum process of Av.uli extraction involved conditions of temperature 20℃, pH 2.0, and diatomaceous earth 1.0 g/50 g of fruit weight. Av.uli contained 5 main components： delphinidin （40.70±1.72）%, cyanidin （3.40±0.68）%, petunidin （17.70±0.54）%, peonidin （2.90±0.63）% and malvidin （35.50±1.11）%. The malvidin percentage was significantly higher （P 〈0.05） than it in Av.myr. Av.uli complied with a dose-dependent repression of cancer cell proliferation with an IC50 （50% inhibitory concentration） value of 50 μg/ml, and showed greater anticancer efficiency than AL. cae and Av. myr under the same cell treatment conditions. These observations were further supported by the results of nuclear assays. Conclusions The extraction protocol and conditions we used were effective for anthocyanin extraction. Av.uli could be a feasible practical research tool and a promising therapeutic source to suppress human colon or colorectal cancers.

Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis

Immunomodulatory signaling imposes tight regulations on metabolic programs within immune cells and consequentially determines immune response outcomes.Although the glucocorticoid receptor(GR)has been recently implicated in regulating the function of myeloid-derived suppressor cells(MDSCs),whether the dysregulation of GR in MDSCs is involved in immune-mediated hepatic diseases and how GR regulates the function of MDSCs in such a context remains unknown.Here,we revealed the dysregulation of GR expression in MDSCs during innate immunological hepatic injury(IMH)and found that GR regulates the function of MDSCs through modulating HIF1α-dependent glycolysis.Pharmacological modulation of GR by its agonist(dexamethasone,Dex)protects IMH mice against inflammatory injury.Mechanistically,GR signaling suppresses HIF1αand HIF1α-dependent glycolysis in MDSCs and thus promotes the immune suppressive activity of MDSCs.Our studies reveal a role of GR-HIF1αin regulating the metabolism and function of MDSCs and further implicate MDSC GR signaling as a potential therapeutic target in hepatic diseases that are driven by innate immune cell-mediated systemic inflammation.

Electron transport layer driven to improve the open-circuit voltage of CH_3NH_3PbI_3 planar perovskite solar cells

Suitable electron transport layers are essential for high performance planar perovskite heterojunction solar cells. Here, we use ZnO electron transport layer sputtered under oxygen-rich atmosphere at room temperature to decrease the hydroxide and then suppress decomposition of perovskite films. The perovskite films with improved crystallinity and morphology are achieved. Besides, on the ZnO substrate fabricated at oxygen-rich atmosphere, open-circuit voltage of the CH_3NH_3PbI_3-based perovskite solar cells increased by 0.13 V.A high open-circuit voltage of 1.16 V provides a good prospect for the perovskite-based tandem solar cells. The ZnO sputtered at room temperature can be easily fabricated industrially on a large scale, therefore, compatible to flexible and tandem devices. Those properties make the sputtered ZnO films promising as electron transport materials for perovskite solar cells.

Myeloid-specific expression of Stat3C results in conversion of bone marrow mesenchymal stem cells into alveolar type Ⅱ epithelial cells in the lung

Bone marrow mesenchymal stem cells (BMSCs) and myeloid lineage cells originate from the bone marrow, and influence each other in vivo. To elucidate the mechanism that controls the interrelationship between these two cell types, the signaling path- way of signal transducer and activator of transcription 3 (Stat3) was activated by overexpressing Stat3C in a newly established c-fms-rtTA/(TetO)7-CMV-Stat3C bitransgenic mouse model, In this system, Stat3C-Flag fusion protein was overexpressed in myeloid lineage cells after doxycycline treatment. Stat3C overexpression induced systematic elevation of macrophages and neutrophils in multiple organs. In the lung, tissue neoplastic pneumocyte proliferation was observed. After in vitro cultured hSP-B 1.5-kb lacZ BMSCs were injected into the bitransgenic mice, BMSCs were able to repopulate in multiple organs, self-renew in the bone marrow and spleen, and convert into alveolar type II epithelial cells. The bone marrow transplantation study indicated that increases of myeloid lineage cells and BMSC-AT II cell conversion were due to malfunction of myeloid progenitor cells as a result of Stat3C overexpression. The study supports the concept that activation of the Stat3 pathway in myeloid cells plays an important role in BMSC function, including homing, repopulating and converting into residential AT II epithelial cells in the lung.

A Long Type of TBCK Is a Novel Cytoplasmic and Mitotic Apparatus-Associated Protein Likely Suppressing Cell Proliferation

Autoantibodies from patients with various connective tissue diseases have been shown to be specific probes that can detect cellular structures, including centrosome, centromere/kineto- chore, spliceosome, Golgi complex and the rough endoplasmic reticulum （Louvard et al., 1982; Rattner et al., 1998;

Estrogen-estrogen receptor signaling suppresses the transcription of ERRF in breast cancer cells

The estrogen receptor （ER）-related factor （ERRF） was previously reported as a novel modulator of breast cancer （Suet al., 2012）. Its expression was upregulated in breast cancer, and increased ERRF expression was significantly associated with ER and/or progesterone receptor （PR） positivity and human epidermal growth factor receptor 2 （HER2） negativity （Suet al., 2012）. In addition, ERRF was necessary for ER-positive breast cancer cells to form tumors in nude mice （Suet al., 2012）. Unexpectedly,