Humans ; Janus Kinase Inhibitors/therapeutic use* ; Vitiligo/drug therapy* ; Psoriasis ; Protein Kinase Inhibitors

Humans ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors

Abstract　　Spleen tyrosine kinase (SYK) is not only a key kinase in the B-cell receptor (BCR) signaling pathway, but also a critical component of other signal transduction pathways such as Fc receptor, complement receptor and integrin. Abnormal activation of SYK closely related to the occurrence and development of hematological malignancies, thus targeting SYK has become a research hotspot. Several SYK inhibitors including Fostamatinib, Entospletinib and Cerdulatinib were being evaluated in clincal trials. As a second generation SYK inhibitor, Entospletinib has achieved good efficacy in lymphoid and myeloid hematologic tumors. Furthermore, Entospletinib can significantly relieve hematopoietic stem cell transplantation(HCT) related graft versus host disease (GVHD). In this review the role of SYK inhibitors in treatment of hematological malignancies is summarized brifely.
Graft vs Host Disease ; Hematologic Neoplasms ; Humans ; Protein Kinase Inhibitors ; Spleen ; Syk Kinase

Currently, about 300 million people worldwide are affected by asthma. Most of these sufferers inhale immunosuppressants (ie corticosteroids) and beta-adrenergic receptor agonists for their asthma treatment. However, about 5%-10% of patients of asthma have poor response to such treatment. Investigation of kinase signaling pathway and nuclear transcription factor as a target molecule in the treatment of allergic asthma has been the concern of scholars home and abroad. This paper reviewed inhibitors of kinase signaling pathway and nuclear transcription factors for the treatment of asthma.
Animals ; Asthma ; drug therapy ; enzymology ; Humans ; Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; Phosphatidylinositol 3-Kinase ; antagonists & inhibitors ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; metabolism ; Signal Transduction ; Transcription Factors ; antagonists & inhibitors

Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Protein Kinase Inhibitors ; Protein-Tyrosine Kinases

The interaction between genistein and beta-glucosidase was studied using fluorescence quenching method and synchronous fluorimetry. The binding reaction was simultaneously studied by the AutoDock 4.2 molecular docking model. Data from fluorescence spectroscopy indicated that these interactions resulted in the endogenous fluorescence quenching of beta-glucosidase, which belongs to a static quenching mechanism. The calculated binding constants were 3.69 x 10(4), 3.06 x 10(4) and 2.36 x 10(4) L x mol(-1) at 17, 27 and 37 degrees C, respectively. The evidences from synchronous fluorescence showed the effect of genistein on the microenvironment around beta-glucosidase in aqueous solution. The inhibition test showed that the activity of beta-glucosidase could be inhibited by genistein. The determined bimolecular rate constant (k(i)) was 1.2 x 10(3) (mol x L(-1)(-1) x min(-1). Molecular docking was performed to reveal the possible binding mode or mechanism and suggested that genistein could bind strongly to beta-glucosidase. The results revealed that genistein tended to bind with beta-glucosidase mainly by hydrogen bond and hydrophobic interaction as well as electrostatic forces.
Genistein ; metabolism ; Molecular Docking Simulation ; Protein Binding ; Protein Kinase Inhibitors ; metabolism ; Spectrometry, Fluorescence ; beta-Glucosidase ; metabolism

Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors

Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Immune Checkpoint Inhibitors ; Lung Neoplasms/drug therapy* ; Mitogen-Activated Protein Kinase Kinases/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Humans ; Child ; Tyrosine Protein Kinase Inhibitors ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Protein Kinase Inhibitors/therapeutic use* ; Chronic Disease

OBJECTIVE: To investigate the protective effect of protein kinase C (PKC) inhibitor rottlerin on rat renal vascular endothelial injury induced by lipopolysaccharide (LPS). METHODS: Rat renal microvascular endothelial cells cultured for 3-6 generations were divided into three groups according to random number table: blank control group in which cells were not challenged, LPS group in which cells were only stimulated by LPS 10 mg/L for 24 hours, and PKC inhibitor group in which cells were treated with PKC inhibitor rottlerin 2 μmol/L 30 minutes before LPS stimulation. The levels of tumor necrosis factor-α (TNF-α) and interleukins (IL-1β, IL-8) were determined by enzyme-linked immunosorbent assay (ELISA). Monolayer permeability was determined by Transwell assay. The expressions of PKC, RhoA and vascular endothelial-cadherin (VE-cadherin) were detected by Western Blot. The morphological characteristic and distribution of F-actin was measured by laser confocal fluorescence microscope. RESULTS: Compared with blank control group, the levels of inflammatory cytokines at 24 hours after 10 mg/L LPS stimulation were significantly increased in LPS group [TNF-α (ng/L): 397.3±25.4 vs. 46.8±8.9, IL-1β (ng/L): 76.7±11.2 vs. 12.6±3.2, IL-8 (ng/L): 574.5±31.4 vs. 73.2±9.6, all P < 0.05], the permeability of endothelial cells was significantly increased (A value: 1.32±0.03 vs. 0.36±0.02, P < 0.05), while the expressions of PKC and RhoA were significantly up-regulated (PKC/β-actin: 0.88±0.02 vs. 0.61±0.03, RhoA/β-actin: 0.96±0.01 vs. 0.49±0.03, both P < 0.05), VE-cadherin expression was significantly down-regulated (VE-cadherin/β-actin: 0.51±0.01 vs. 0.72±0.04, P < 0.05), and the F-actin distribution disorder had obvious stress fiber formation. Compared with LPS group, the levels of inflammatory cytokines were significantly lowered in PKC inhibitor group [TNF-α (ng/L): 127.4±14.6 vs. 397.3±25.4, IL-1β(ng/L): 43.2±7.8 vs. 76.7±11.2, IL-8 (ng/L): 212.7±18.2 vs. 574.5±31.4, all P < 0.05], the permeability of endothelial cells was significantly decreased (A value: 0.81±0.02 vs. 1.32±0.03, P < 0.05), the expressions of PKC and RhoA were significantly down-regulated (PKC/β-actin: 0.44±0.03 vs. 0.88±0.02, RhoA/β-actin: 0.63±0.05 vs. 0.96±0.01, both P < 0.05), the VE-cadherin expression was significantly up-regulated (VE-cadherin/β-actin: 0.69±0.03 vs. 0.51±0.01, P < 0.05), and the F-actin remodeling and stress fiber formation were significantly reduced. CONCLUSIONS PKC inhibitor could significantly attenuate the damage of vascular endothelial barrier induced by LPS, and plays an important role in endothelial cell barrier.
Acute Kidney Injury/prevention & control* ; Animals ; Endothelium, Vascular/drug effects* ; Interleukin-1beta ; Lipopolysaccharides/toxicity* ; Protein Kinase C/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Random Allocation ; Rats