Structural insight into SSE15206 in complex with tubulin provides a rational design for pyrazolinethioamides as tubulin polymerization inhibitors.

Tubulin protein is a promising target for antitumor drugs. Some tubulin inhibitors targeting the colchicine binding site are not substrates of the multidrug-resistance efflux pump, which can overcome the mechanism of drug resistance mediated by P-glycoprotein. SSE15206 is a colchicine binding site inhibitor with antiproliferative activity against different drug-resistant cell lines.

Basophils as a potential marker of lupus nephritis by flow cytometry.

Objective: To establish a convenient and simple flow cytometry immunophenotyping panel to explore immune cellular alterations and potential cellular biomarkers in systemic lupus erythematosus.

Materials And Methods: This is a cross-sectional, case-control study including 60 patients with systemic lupus erythematosus and 20 sex- and age-matched healthy controls. A 14-color immunophenotyping panel was applied to detect proportions of circulating immune mononuclear cells, and comparisons between patients and healthy controls, and subgroups of patients, were performed.

Prolyl Isomerase Pin1 in Human Cancer: Function, Mechanism, and Significance.

Peptidyl-prolyl isomerase NIMA-interacting 1 (Pin1) is an evolutionally conserved and unique enzyme that specifically catalyzes the isomerization of phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif and, subsequently, induces the conformational change of its substrates. Mounting evidence has demonstrated that Pin1 is widely overexpressed and/or overactivated in cancer, exerting a critical influence on tumor initiation and progression via regulation of the biological activity, protein degradation, or nucleus-cytoplasmic distribution of its substrates. Moreover, Pin1 participates in the cancer hallmarks through activating some oncogenes and growth enhancers, or inactivating some tumor suppressors and growth inhibitors, suggesting that Pin1 could be an attractive target for cancer therapy.

Therapeutic delivery of microRNA-143 by cationic lipoplexes for non-small cell lung cancer treatment in vivo.

Purpose: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide and new improvements are urgently needed. Several miRNA-targeted therapeutics have reached clinical development. MicroRNA-143 (miR-143) was found to significantly suppress the migration and invasion of NSCLC.

Erratum: Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system: Erratum.

[This corrects the article DOI: 10.7150/thno.24157.

Glioblastoma and Anaplastic Astrocytoma: Differentiation Using MRI Texture Analysis.

Glioblastoma and anaplastic astrocytoma (ANA) are two of the most common primary brain tumors in adults. The differential diagnosis is important for treatment recommendations and prognosis assessment. This study aimed to assess the discriminative ability of texture analysis using machine learning to distinguish glioblastoma from ANA.

Hollow Microcapsules with Ulcerative Colitis Therapeutic Effects Made of Multifunctional Turkish Galls Extraction.

Ulcerative colitis (UC) has been listed as one of the refractory diseases of modern society by the World Health Organization. Our previous studies found that Turkish galls Gallotannins (TGTs) have a significant effect on anti-UC. Here, TGTs were extracted using a simple method and TGTs-Fe microcapsules were prepared by a self-assembly technique.

Discovery of human TyrRS inhibitors by structure-based virtual screening, structural optimization, and bioassays.

The human tyrosyl transfer-RNA (tRNA) synthetase (TyrRS), which is well known for its essential aminoacylation function in protein synthesis, has been shown to translocate to the nucleus and protect against DNA damage caused by external stimuli. Small molecules that can fit into the active site pocket of TyrRS are thought to affect the nuclear role. The exploitation of TyrRS inhibitors has attracted attention recently.

Pre-blocked molecular shuttle as an in-situ real-time theranostics.

Real-time monitor of drug-release from drug formulations in a noninvasive way can provide spatio-temporal information for drug activation and guide further clinical rational administration. In this work, a molecular shuttle, as a typical nanosized artificial molecular machine, was managed to act as a conceptually-new nanotheranostics for oxaliplatin. A post-recognition strategy was utilized, where a default supramolecular-dye couple was pre-blocked.

Little Antimicrobial Peptides with Big Therapeutic Roles.

Antimicrobial Peptides (AMPs) are short amphipathic biological molecules generally with less than 100 amino acids. AMPs not only present high bioactivities against bacteria, fungi or protists-induced infections, but also play important roles in anticancer activity, immune response and inflammation regulation. AMPs are classified as ribosomally synthesized, non-ribosomally synthesized and post-translationally modified, non-ribosomally synthesized ones and several synthetic or semisynthetic peptides according to their synthesis with or without the involvement of ribosomes.

Identification of 5-(2,3-Dihydro-1 H-indol-5-yl)-7 H-pyrrolo[2,3- d]pyrimidin-4-amine Derivatives as a New Class of Receptor-Interacting Protein Kinase 1 (RIPK1) Inhibitors, Which Showed Potent Activity in a Tumor Metastasis Model.

We herein report the structural optimization and structure-activity relationship studies of 5-(2,3-dihydro-1 H-indol-5-yl)-7 H-pyrrolo[2,3- d]pyrimidin-4-amine derivatives as a new class of receptor-interacting protein kinase 1 (RIPK1) inhibitors. Among all obtained RIPK1 inhibitors, 1-(5-{4-amino-7-ethyl-7 H-pyrrolo[2,3- d]pyrimidin-5-yl}-2,3-dihydro-1 H-indol-1-yl)-2-[3-(trifluoromethoxy)phenyl]ethan-1-one (22b) is the most active one. This compound potently inhibited RIPK1 with a binding affinity ( K) of 0.

Enhanced uptake and improved anti-tumor efficacy of doxorubicin loaded fibrin gel with liposomal apatinib in colorectal cancer.

Colorectal cancer (CRC) exhibited high incidence rate worldwide and the advanced CRC had a poor prognosis. Thereupon, seeking efficient treatment for CRC is critical. Apatinib is a novel vascular epithelial growth factor receptor (VEGFR) inhibitor with inspiring therapeutic effect in some malignant cancers.

Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer around the world. Over the past several years, immunotherapy has demonstrated considerable clinical benefit in CRC therapy, and the number of immunologic therapies for cancer treatment continues to climb each year. Interleukin-15 (IL15), a potent pro-inflammatory cytokine, has emerged as a candidate immunomodulator for the treatment of CRC.

Structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of inhibitors of RET and its drug resistance mutants.

The RET tyrosine kinase is an important therapeutic target for medullary thyroid cancer (MTC), and drug resistance mutations of RET, particularly V804M and V804L, are a main challenge for the current targeted therapy of MTC based on RET inhibitors. In this investigation, we report the structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of RET inhibitors. Among all the obtained kinase inhibitors, 1-(5-(tert-butyl)isoxazol-3-yl)-3-(4-((6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-yl)amino)phenyl)urea (17d) is a multi-kinase inhibitor and potently inhibits RET and its drug resistance mutants.

Ska3 Phosphorylated by Cdk1 Binds Ndc80 and Recruits Ska to Kinetochores to Promote Mitotic Progression.

The spindle and kinetochore-associated (Ska) protein complex is required for accurate chromosome segregation during mitosis [1-6] and consists of two copies each of Ska1, Ska2, and Ska3 proteins [4, 7]. The Ska complex contains multiple microtubule-binding elements and promotes kinetochore-microtubule attachment [8-11]. The Ska1 C-terminal domain (CTD) recruits protein phosphatase 1 (PP1) to kinetochores to promote timely anaphase onset [12].

Self-Assembled Bifunctional Peptide as Effective Drug Delivery Vector with Powerful Antitumor Activity.

E-cadherin/catenin complex is crucial for cancer cell migration and invasion. The histidine-alanine-valine (HAV) sequence has been shown to inhibit a variety of cadherin-based functions. In this study, by fusing HAV and the classical tumor-targeting Arg-Gly-Asp (RGD) motif and Asn-Gly-Arg (NGR) motif to the apoptosis-inducing peptide sequence-AVPIAQK, a bifunctional peptide has been constructed with enhanced tumor targeting and apoptosis effects.

The role of ROS and subsequent DNA-damage response in PUMA-induced apoptosis of ovarian cancer cells.

PUMA is a member of the "BH3-only" branch of the BCL-2 family. Our previous study suggests a therapeutic potential of PUMA in treating ovarian cancer, however, the action mechanism of PUMA remains elusive. In this work, we found that in PUMA adenovirus-infected A2780s ovarian cancer cells, exogenous PUMA was partially accumulated in the cytosol and mainly located to the mitochondria.

Discovery of New SIRT2 Inhibitors by Utilizing a Consensus Docking/Scoring Strategy and Structure-Activity Relationship Analysis.

SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide) dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought to be potential interfering agents for relevant diseases. Discovery of SIRT2 inhibitors has attracted much attention recently.

A novel benzothiazinethione analogue SKLB-TB1001 displays potent antimycobacterial activities in a series of murine models.

New chemotherapeutic compounds and regimens are needed to combat multidrug-resistant Mycobacterium tuberculosis. Here, we used a series of murine models to assess an antitubercular lead compound SKLB-TB1001. In the Mycobacterium bovis bacillus Calmette-Guérin and the acute M.

Preclinical pharmacodynamic evaluation of drug candidate SKLB-178 in the treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a serious life-threatening malignancy. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as Gefitinib and Erlotinib, are effective clinical medicines for advanced NSCLC patients harboring EGFR-activating mutations. However, this therapy just benefits a small percentage of sufferers.

Antibacterial mechanism of daptomycin antibiotic against Staphylococcus aureus based on a quantitative bacterial proteome analysis.

Unlabelled: Daptomycin (DAP) is a novel lipopeptide antibiotic which exhibits excellent antibacterial activity against most clinically relevant Gram-positive bacteria, but the DAP-targeting protein molecules against host bacterial infection are far from clear. In order to discover bacterial protein response to DAP treatment, an iTRAQ-based quantitative proteomic analysis was applied to identify differential bacterial proteome profiling of Staphylococcus aureus (S. aureus) ATCC 25923 to 0.

Elevated Cellular PD1/PD-L1 Expression Confers Acquired Resistance to Cisplatin in Small Cell Lung Cancer Cells.

Although small cell lung cancer (SCLC) is highly responsive to chemotherapies (e.g., cisplatin-etoposide doublet), virtually almost all responsive SCLC patients experience disease recurrence characterized by drug resistance.