The discovery of water-soluble indazole derivatives as potent microtubule polymerization inhibitors.

Taking a previously discovered indazole derivative 1 as a lead, systematic structural modifications were performed with an indazole core at the 1- and 6-positions to improve its aqueous solubility. Among the designed indazole derivatives, 6-methylpyridin-3-yl indazole derivative 8l and 1H-indol-4-yl indazole derivative 8m exhibited high potency in the low nanomolar range against A549, Huh-7, and T24 cancer cells, including Taxol-resistant variant cells (A549/Tax). As a hydrochloride salt, 8l exhibited much improved aqueous solubility, and its log P value fell into a favorable range.

The Latest Research Advances of Danggui Buxue Tang as an Effective Prescription for Various Diseases: A Comprehensive Review.

Danggui Buxue Tang (DBT) is composed of Astragali Radix and Angelicae Sinensis Radix in a weight ratio of 5:1. The recipe of the decoction is simple, and DBT has been widely used in the treatment of blood deficiency syndrome for more than 800 years in China. Studies on its chemical constituents show that saponins, flavonoids, volatile oils, organic acids, and polysaccharides are the main components of DBT.

Hydroxyapatite From the Skull of Tuna () Head Combined With Chitosan to Restore Locomotive Function After Spinal Cord Injury.

Hydroxyapatite is an important fish bone calcium in tuna head, which is widely used to repair of bone defect. Chitosan is a degradable basic polysaccharide with good biocompatibility and bone guiding, which can achieve targeted delivery to the injured spinal cord after spinal cord injury (SCI). This study aimed to evaluate the beneficial effects of chitosan combined hydroxyapatite (chitosan-hydroxyapatite) nanoparticles on SCI.

Exposure to soil environments during earlier life stages is distinguishable in the gut microbiome of adult mice.

Environmental exposure during earlier life stages can govern the assembly and development of gut microbiota, yet it is insufficiently understood. In this study, ex-germ-free mice were cohoused with distinct soil-microbiota (from desert, steppe, and forest) beddings within 60 days after birth and subsequently transferred to new soil beddings from 60 to 90th day. Using metagenomic shotgun sequencing, firstly, we found soil microbes from natural environments (birthplace) greatly influenced the gut community assembly in the housing experiment.

[Variation analysis of genomic methylation induced by high temperature stress in Pinellia ternata].

Pinellia ternata belongs to the Araceae family and is a medicinal herb. The tuber is the medicinal organ with antitussive, antiemetic and anti-tumor activities. It is easy to encounter high temperature environment during the growth periods, leading to decrease of tuber production.

The discovery of novel indazole derivatives as tubulin colchicine site binding agents that displayed potent antitumor activity both in vitro and in vivo.

Tubulin inhibitors that bind to the colchicine site are widely studied anticancer agents. In continuous our researches, we designed a series of novel indazole derivatives as microtubule-targeting agents (MTAs). The structure-activity relationships (SARs) investigations indicated that a 3,4,5-trimethoxyphenyl moiety and a methyl or methoxy substitution were preferred for the better antiproliferative activity.

Discovery of novel quinazolinone derivatives as high potent and selective PI3Kδ and PI3Kδ/γ inhibitors.

PI3Kδ and PI3Kγ regulate immune cell signaling. Selective PI3Kδ or PI3Kγ inhibitors and dual PI3Kδ/γ inhibitors have the potential for the treatment of immune cell-mediated diseases and hematological malignancies. Based on the quinazolinone pharmacophore, we used a pyrazolo[3,4-d]pyrimidin-4-amine portion as the hinge region binding moiety, an aromatic or a heteroaromatic substituent at the 3-position of the pyrazolo[3,4-d]pyrimidine core as the affinity element, and designed novel 2-tolyl and 2,6-dimethylphenyl quinazolinone derivatives as potential PI3Kδ inhibitors.

Empathy skill-dependent modulation of working memory by painful scene.

As an important online information retaining and processing function, working memory plays critical roles in many other cognitive functions. Several long-term factors, such as age, addiction and diseases, have been affirmed to impair working memory, but whether or how the short-term factors, like painful stimuli or emotions, regulate the human working memory ability is not well explored. Here we investigated the influences of empathic pain on upcoming working memory and existing working memory, by presenting human subjects with the pictures depicting painful or neutral scene.

Design and Synthesis of Coumarin Derivatives as Novel PI3K Inhibitors.

Background: Coumarins possess a broad spectrum of biological activities and are important pharmacophores in drug developments. Since aberrant upregulation of PI3K/Akt signaling is related to uncontrolled tumor cell proliferation, enhanced migration, and adhesion-independent tumor growth, it is of interests to find novel coumarin derivatives as anticancer agents targeting the PI3K/Akt signaling pathway.

Objective: A variety of coumarin derivatives possessing the pyridinylurea units were designed to increase their potency and isoform selectivity against PI3Ks.

Developments of DNA-dependent Protein Kinase Inhibitors as Anticancer Agents.

Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity, cell survival, and prevention tumorigenesis. Three pathways are responsible for the repair of DNA DSBs: homologous recombination (HR), single strand annealing (SSA) and non-homologous end joining (NHEJ). DNA-dependent Protein Kinase (DNA-PK), the key component of the NHEJ pathway, becomes an important target for cancer therapy.