Oncogenic FLT3 internal tandem duplication activates E2F1 to regulate purine metabolism in acute myeloid leukaemia.

Oncogene FLT3 internal tandem duplication (FLT3-ITD) mutation accounts for 30 % of acute myeloid leukaemia (AML) cases and induces transformation. Previously, we found that E2F transcription factor 1 (E2F1) was involved in AML cell differentiation. Here, we reported that E2F1 expression was aberrantly upregulated in AML patients, especially in AML patients carrying FLT3-ITD.

Modulators of ASIC1a and its potential as a therapeutic target for age-related diseases.

Age-related diseases have become more common with the advancing age of the worldwide population. Such diseases involve multiple organs, with tissue degeneration and cellular apoptosis. To date, there is a general lack of effective drugs for treatment of most age-related diseases and there is therefore an urgent need to identify novel drug targets for improved treatment.

Long non-coding RNAs: Potential therapeutic targets for epilepsy.

Epilepsy is a common and disastrous neurological disorder characterized by abnormal firing of neurons in the brain, affecting about 70 million people worldwide. Long non-coding RNAs (LncRNAs) are a class of RNAs longer than 200 nucleotides without the capacity of protein coding, but they participate in a wide variety of pathophysiological processes. Alternated abundance and diversity of LncRNAs have been found in epilepsy patients and animal or cell models, suggesting a potential role of LncRNAs in epileptogenesis.

LncSIK1 enhanced the sensitivity of AML cells to retinoic acid by the E2F1/autophagy pathway.

Objectives: This study aimed to investigate the biological impacts and possible mechanisms of a novel lncRNA, LncSIK1, in AML progression and retinoic acid-regulated AML cell development.

Materials And Methods: The expression pattern of LncSIK1 was evaluated by qPCR and fluorescence in situ hybridization. CCK-8 assay, immunofluorescence, Wright-Giemsa staining, flow cytometry and Western blotting were performed to assess cell proliferation and differentiation.

Estrogen protects against acidosis-mediated articular chondrocyte injury by promoting ASIC1a protein degradation.

Epidemiological data suggest that the incidence of rheumatoid arthritis (RA) increases in postmenopausal women, which may be related to estrogen deficiency. Tissue acidosis is a common symptom of RA. Acid-sensitive ion channel 1a (ASIC1a), a member of the extracellular H-activated cation channel family, could be activated by changes in extracellular pH and plays a crucial role in the pathogenesis of RA.

Design, synthesis and SARs of novel telomerase inhibitors based on BIBR1532.

Telomerase has become one of the new popular targets for the development of anti-tumor drugs. Based on the structural characteristics of the BIBR1532 which has entered the stage of clinical research, six series total of 64 new compounds with diverse structural characteristics were designed and synthesized. The inhibitory activity against SGC-7901, MGC-803, SMMC-7721, A375 and GES cell lines and their telomerase inhibitory activity were tested.

Acid-sensing ion channel 1a mediates acid-induced pyroptosis through calpain-2/calcineurin pathway in rat articular chondrocytes.

The pyroptosis is a causative agent of rheumatoid arthritis, a systemic autoimmune disease merged with degenerative articular cartilage. Nevertheless, the precise mechanism of extracellular acidosis on chondrocyte pyroptosis is largely unclear. Acid-sensing ion channels (ASICs) belong to an extracellular H -activated cation channel family.

Targeting ferroptosis contributes to ATPR-induced AML differentiation via ROS-autophagy-lysosomal pathway.

Ferroptosis, a newly discovered form of non-apoptotic cell death, is induced by an excessive degree of iron-dependent lipid peroxide. ATPR, a novel all-trans retinoic acid (ATRA) derivative, has been extensively developed to show superior anticancer effect than ATRA in acute myeloid leukemia (AML). However, whether ferroptosis exists during ATPR treatment of AML remains unclear.

ATPR triggers acute myeloid leukaemia cells differentiation and cycle arrest via the RARα/LDHB/ERK-glycolysis signalling axis.

Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown.

17β-estradiol attenuates rat articular chondrocyte injury by targeting ASIC1a-mediated apoptosis.

Epidemiological evidence suggests that the etiology and pathogenesis of rheumatoid arthritis (RA) are closely associated with estrogen metabolism and deficiency. Estrogen protects against articular damage. Estradiol replacement therapy ameliorates local inflammation and knee joint swelling in ovariectomized models of RA.

4-Amino-2-trifluoromethyl-phenyl retinate induced differentiation of human myelodysplastic syndromes SKM-1 cell lines by up-regulating DDX23.

Myelodysplastic syndrome (MDS) is a heterogeneously cloned hematopoietic stem cell malignancy with a high risk of developing acute myeloid leukemia (AML). 4-amino-2-trifluoromethyl-phenyl resinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed in our group, was proved to be a tumor inhibitor in diverse types of cancer cells in vitro. However, little has been known about the effects of ATPR on MDS.

ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathway.

Background: Acute myeloid leukemia (AML) is an aggressive and mostly incurable hematological malignancy with frequent relapses after an initial response to standard chemotherapy. Therefore, novel therapies are urgently required to improve AML clinical outcomes. 4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show biological anti-tumor characteristics in our previous studies.

Inhibition of acid‑sensing ion channel 1a attenuates acid‑induced activation of autophagy via a calcium signaling pathway in articular chondrocytes.

Acid‑sensing ion channel 1a (ASIC1a), member of the degenerin/epithelial sodium channel protein superfamily, serves a critical role in various physiological and pathological processes. The aim of the present study was to examine the role of ASIC1a in the autophagy of rat articular chondrocytes. Autophagy was induced by acidic stimulation in rat articular chondrocytes and the extent of autophagy was evaluated via the expression levels of microtubule‑associated protein 1 light chain 3II, Beclin1 and uncoordinated‑51 like kinase1.

The role of Ca in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat adjuvant arthritis.

Rheumatoid arthritis is an autoimmune disease with a poor prognosis. Pyroptosis is a type of proinflammatory programmed cell death that is characterised by the activation of caspase-1 and secretion of the proinflammatory cytokines interleukin (IL)-1β/18. Previous reports have shown that pyroptosis is closely related to the development of some autoimmune diseases, such as rheumatoid arthritis.

A novel all-trans retinoic acid derivative inhibits proliferation and induces apoptosis of myelodysplastic syndromes cell line SKM-1 cells via up-regulating p53.

Myelodysplastic syndromes (MDS) are a varied set of hematologic neoplasms and a high risk of progression to acute myeloid leukemia (AML). 4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative, play an important role in various types of cancer cells as a tumor inhibitor. However, little is known concerning its antitumor effect on MDS.

Necrostatin-1 ameliorates adjuvant arthritis rat articular chondrocyte injury via inhibiting ASIC1a-mediated necroptosis.

Necroptosis, a necrotic cell death pathway regulated by receptor interacting protein (RIP) 1 and 3, plays a key role in pathophysiological processes, including rheumatoid arthritis (RA). However, whether necroptosis is involved in RA articular cartilage damage processes remain unclear. The aim of present study was to investigate the dynamic changes in arthritic chondrocyte necroptosis and the effect of RIP1 inhibitor necrostatin-1 (Nec-1) and acid-sensing ion channels (ASICs) inhibitor amiloride on arthritic cartilage injury and acid-induced chondrocyte necroptosis.

Comparative analysis of stimulation and binding characteristics of adenosine analogs to AMP-activated protein kinase.

To compare the stimulation and binding characteristics of adenosine analogs including AMP, IMM-H007, and M1, to AMPK, and to explore the potential mechanism underlying the regulation effect of adenosine analogs on AMPK activity, [γ-P]ATP assay, circular dichroism experiments and molecular docking test were performed. We found that the interactions with Thr86, Thr88, and His150 in site 1 are probably the reason why the affinities of IMM-H007, M1, and adenosine are comparable but their allosteric activation on AMPK varies greatly, partly interpreting the mechanism of AMPK activity regulated by adenosine analogs.

[Morphological, microscopic, multiple-component assay and fingerprinting based systematic research on quality evaluation of Moutan Cortex(Paeonia suffruticosa)].

The purpose of this study was to combine morphological, microscopic, UHPLC multiple-component assay and fingerprinting studies in order to evaluate the quality of Moutan Cortex (MC) systematically. The root system of Paeonia suffruticosa was measured to compare the morphological variation and the chemical composition of different grades of MC was discussed according to previous studies. The difference between the main microscopic features of MC powder and the xylem powder is dramatic, the MC powder contains great amount of starch granules and clusters of calcium oxalate, while the xylem powder displays considerable vessels.

4-Amino-2-Trifluoromethyl-Phenyl Retinate induced leukemia cell differentiation by decreasing eIF6.

4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), an all-trans retinoic acid (ATRA) derivative, possesses the ability to relief several carcinoma. Here, we explored the potential molecular mechanism of eukaryotic translation initiation factor 6 (eIF6) in ATPR-induced leukemia cell differentiation. Our research showed that ATPR could inhibit cell proliferation and promote cell differentiation in several leukemia cell lines.

Osteoclast-Derived Extracellular Vesicles: Novel Regulators of Osteoclastogenesis and Osteoclast-Osteoblasts Communication in Bone Remodeling.

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, play an important role in cellular communication during skeletal growth and homeostasis. Bioactive molecules carried by EVs are transported to neighboring and distant cells to trigger a series of signaling cascades influencing bone homeostasis. The bioactive activities of osteoclast-derived EVs include regulation of osteoclastogenesis and osteoclast-osteoblast communication.