Mutants of the FLT3 receptor tyrosine kinase (RTK) with duplications in the juxtamembrane domain (FLT3-ITD) act as drivers of acute myeloid leukemia (AML). Potent tyrosine kinase inhibitors (TKi) of FLT3-ITD entered clinical trials and showed a promising, but transient success due to the occurrence of secondary drug-resistant AML clones. A further caveat of drugs targeting FLT3-ITD is the co-targeting of other RTKs which are required for normal hematopoiesis. This is observed quite frequently. Therefore, novel drugs are necessary to treat AML effectively and safely. Recently bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. In order to optimize these agents we synthesized novel derivatives of these methanones with various substituents. Methanone 16 and its carbamate derivative 17b inhibit FLT3-ITD at least as potently as the TKi AC220 (quizartinib). Models indicate corresponding interactions of 16 and quizartinib with FLT3. The activity of 16 is accompanied by a high selectivity for FLT3-ITD. Glucose Regulated Protein 78 kDa (GRP78) is an attractive antiangiogenic and anticancer target for its selective accumulation on the surface of cancer cells and cancer endothelial cells rather than normal cells. In this study, we identified a novel series of small molecules that binds to GRP78, exhibiting potent antiangiogenic and anticancer activities without affecting normal cells. Among these, FL5,2-(4-((4-acetamidophenoxy)methyl)phenyl)-N-isobutylbenzofuran-3-carboxamide, was superior to others due to its strong binding affinity to GRP78 (an increase in the Tm > 2 °C stabilising the GRP78 protein) and potent antiangiogenic and anticancer activities against human umbilical vein endothelial cells (HUVEC) (EC50 = 1.514 μM) and human renal cancer cells (786-O) (50% cell death at 10 μM). Furthermore, FL5 displayed no cytotoxic activity towards mouse fibroblast cells (Swiss-3T3), which do not harbour cell surface GRP78 under normal condition. FL5 was less detrimental to ATPase activity, which is essential for normal cells, as seen in the virtual docking studies. This study reports the discovery of novel small molecules targeting GRP78 with potent antiangiogenic and anticancer activities and less toxicity to normal cells, which provides prototype candidates for novel paths for cancer therapy. Monoclonal gammopathy of renal significance (MGRS) is characterized by the nephrotoxic monoclonal immunoglobulin (MIg) secreted by an otherwise asymptomatic or indolent B-cell or plasma cell clone, without hematologic criteria for treatment.  https://www.selleckchem.com/JAK.html  The spectrum of MGRS-associated disorders is wide, including non-organized deposits or inclusions such as C3 glomerulopathy with monoclonal glomerulopathy (MIg-C3G), monoclonal immunoglobulin deposition disease, proliferative glomerulonephritis with monoclonal immunoglobulin deposits and organized deposits like immunoglobulin related amyloidosis, type I and type II cryoglobulinaemic glomerulonephritis, light chain proximal tubulopathy, and so on. Kidney biopsy should be conducted to identify the exact disease associated with MGRS. These MGRS-associated diseases can involve one or more renal compartments, including glomeruli, tubules and vessels. Hydrophobic residues replacement, N-glycosylated, increase in isoelectric point in MIg causes it to transform from soluble form to tissue deposition, causing glomerular damage. Complement deposition is found in MIg-C3G, which is caused by an abnormality of the alternative pathway and may involve multiple factors including complement component 3 nephritic factor, anti-complement factor auto-antibodies or MIg which directly cleaves C3. The effect of transforming growth factor beta and platelet-derived growth factor-β on mesangial extracellular matrix is associated with glomerular and tubular basement membrane thickening, nodular glomerulosclerosis, and interstitial fibrosis. Furthermore, inflammatory factors, growth factors and virus infection may play an important role in the development of the diseases. In this review, for the first time, we discussed current highlights in the mechanism of MGRS-related lesions. INTRODUCTION Brain metastasis (BM) is a complex process that implies immune cells and microglia. Stereotactic radiation therapy (SRT) and immunotherapy (IT) are established to increase the immune response; but their association has never been prospectively studied. MATERIALS AND METHODS Two reviewers performed a systematic review in original papers published up to September 2019. We analysed OS, local (mLRF) and regional (mBRF) median disease-free survival in patients with BMs after SRT with and without IT. RESULTS Upon 14 studies, eleven concerned melanoma, three concerned lung cancers. SRT-IT showed better OS, mLRF and mBRF than SRT. mBRF was better if SRT was performed with short delay from IT. No higher rates of radionecrosis and haemorrhage were found among groups. CONCLUSION This review suggests SRT combined to IT in melanoma is safe and could provide better BRF, suggesting a lymphocytic immune reaction in brain. No improvement trend was found in lung cancer BM. Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could regulate osteoblast differentiation in ovariectomized rats with osteoporosis. miR-122 was upregulated and Purkinje cell protein 4 (PCP4) was downregulated in ovariectomized rats. PCP4 was identified as a target of miR-122 by dual-luciferase reporter gene assay. We transfected isolated osteoblasts from ovariectomized rats with miR-122 mimic or inhibitor or PCP4 overexpression vectors. Proliferation and differentiation of osteoblasts were repressed by the overexpression of miR-122 but enhanced by overexpression of PCP4. miR-122 could induce the activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, while PCP4 blocked this pathway. Rescue experiments further demonstrated that the inhibiting effects of miR-122 on osteoblast differentiation could be compensated by activation of the PCP4 or inhibition of JNK signaling pathway.