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Centromere protein A (CENP‐A), a centromere‐specific histone H3 variant, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure‐activity relationship (SAR) study of the cell‐cycle‐arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)‐6‐Br‐JP18 and (+)‐6‐Cl‐JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X‐ray crystallography analysis reveals that both molecules bind to the colchicine‐binding site of β‐tubulin. Treatment of human cells with microtubule‐targeting agents (MTAs), including these two compounds, results in CENP‐A accumulation by destabilizing Cdh1, a co‐activator of the anaphase‐promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP‐A accumulation using small‐molecule tools and highlights the role of Cdh1 in CENP‐A proteolysis. [ABSTRACT FROM AUTHOR]

Objective: To construct a recombinant adenovirus with artificial microRNA targeting the epidermal growth factor receptor (EGFR) to inhibit the proliferation and induce the apoptosis of tumor cells., Methods: An artificial microRNA (amiR) targeting EGFR was designed and cloned into an adenovirus shuttle plasmid to obtain pDC312-SLPI (secretory leukoprotease inhibitor)-EGFR amiR-pA. Then it was co-transfected into 293 cells with the adenovirus backbone plasmid pBHGloxΔE1, 3Cre to pack the recombinant adenovirus Ad-SLPI-EGFR amiR. After the recombinant adenovirus infected Hep-2 cells by Ad-SLPI-EGFR amiR, a morphological change was observed, and an MTT assay was performed to assess the proliferation of the tumor cells. The expression of EGFR was determined by western blotting analyses to assess the effect of Ad-SLPI-EGFR amiR., Results: The sequence of artificial microRNA targeting EGFR was confirmed by DNA sequencing. Ad-SLPI-EGFR amiR significantly downregulated EGFR expression at the protein level and exerted an inhibitory effect on proliferation in Hep-2 cells. The transfected cells became round, shrunken, partly grape-like and floating under a lighted microscope., Conclusion: The recombinant adenovirus of Ad-SLPI-EGFR amiR was successfully constructed, and it was able to sufficiently decrease the expression of EGFR and inhibit the proliferation of Hep-2 cells., Competing Interests: None., (IJCEP Copyright © 2019.)

Four new sesquiterpene lactones, (1 S,5 R,6 S,7 S,8 R,9 R,10 S,11 S)-6-acetoxy-9-hydroxy-4-oxo-pseudoguai-2(3)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-ethoxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-hydroxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, and 14-acetoxy-1 β,5 α,7 αH-4 β-hydroxy-guai-9(10),11(13)-dien-12,8 α-olide, along with 26 known sesquiterpene lactones, were isolated from the whole plants of Inula hookeri C. B. Clarke. Their structures were established based on spectroscopic methods including HRESIMS, 1D and 2D NMR, and CD techniques. All compounds were evaluated for their cytotoxic activities against HepG2, HeLa, PC-3, and MGC-803 cell lines by CCK-8 assay. Some of the isolates, especiallly pseudoguaianolides and guaianolides, exhibited significant cytotoxicities against these four examined cell lines., (© Georg Thieme Verlag KG Stuttgart · New York.)

A novel trinorsesquiterpene (1), three new (2-4), and 10 known sesquiterpenes were isolated from the roots of Inula racemosa Hook. f. The structures and absolute configurations of the new sesquiterpenes were elucidated by extensive spectroscopic and computational methods. All compounds were evaluated for their inhibition of LPS-induced nitric oxide production in RAW264.7 macrophages, and the results indicated that compounds 9, 12, and 13 moderately inhibited nitric oxide production with IC₅₀ values of 7.39 ± 0.36, 6.35 ± 0.26, and 5.39 ± 0.18 µM, respectively., (© Georg Thieme Verlag KG Stuttgart · New York.)

Four new compounds: an abietane (1), two isopimarane (2 and 3) diterpenes, and a dihydrobenzofuran neolignan (5), together with a sesquiterpene glycoside (6) firstly isolated from a natural source, and a known phenol glycoside (4) were isolated from leaves of Platycladus orientalis. The structures and relative configurations of these compounds were assigned on the basis of MS, IR, 1D and 2D NMR data. The absolute configuration of compound 1 was determined via density functional theory calculations of its electronic circular dichroism. In addition, the results of bioassays indicated that compounds 4 and 6 showed a potent inhibitory effect on NO production with IC₅₀ values of 24.4 and 11.9 µM, respectively. Meanwhile, compounds 1, 2, and 3 moderately inhibited TNF- α release., (© Georg Thieme Verlag KG Stuttgart · New York.)

With the development of stem cells and regenerative medicine (treatment of various diseases using stem cells) research, the induction of differentiation of human stem cell technology has also made significant progress. The development of chemical biology offers a variety of small biological molecules for stem cell biology. This review focuses on how small molecule compounds (natural and synthetic) induce differentiation of stem cells.