Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer?

Camptothecin (CPT) was discovered from plant extracts more than 60 years ago. Since then, only two CPT analogues (irinotecan and topotecan) have been approved for cancer treatment, although several thousand CPT derivatives have been synthesized and many of them were actively studied in our research community over the past 6+ decades. In this review article, we briefly summarize: (1) the discovery and early development of CPTs, (2) the recognized CPT mechanism of action (MOA), (3) the synthesis of CPT and CPT analogues, and (4) the structure-activity relationship (SAR) of CPT and its analogues.

A novel multi-target inhibitor harboring selectivity of inhibiting EGFR T790M sparing wild-type EGFR.

Non-Small Cell Lung Cancer (NSCLC) is driven by a variety of deregulated kinases and the development of multi-target inhibitor for multiple signaling pathways or multiple steps is required. Here, we reported that ZWM026, an indolocarbazoles analogue, derived from mangrove in coastal marine wetland, exhibited selectivity and reversibility against T790M mutant over wild-type EGFR in naturally occurring NSCLC cells and constructed NIH-3T3 cells. It simultaneously inhibited activities of HER2, HER3, HER4 and RET but was different from current multi-target kinase inhibitors.

Analysis of Bacterial Community Composition of Corroded Steel Immersed in Sanya and Xiamen Seawaters in China via Method of Illumina MiSeq Sequencing.

Metal corrosion is of worldwide concern because it is the cause of major economic losses, and because it creates significant safety issues. The mechanism of the corrosion process, as influenced by bacteria, has been studied extensively. However, the bacterial communities that create the biofilms that form on metals are complicated, and have not been well studied.

Analysis of the Sequences, Structures, and Functions of Product-Releasing Enzyme Domains in Fungal Polyketide Synthases.

Product-releasing enzyme (PRE) domains in fungal non-reducing polyketide synthases (NR-PKSs) play a crucial role in catalysis and editing during polyketide biosynthesis, especially accelerating final biosynthetic reactions accompanied with product offloading. However, up to date, the systematic knowledge about PRE domains is deficient. In the present study, the relationships between sequences, structures, and functions of PRE domains were analyzed with 574 NR-PKSs of eight groups (I-VIII).

Continuous Timescale Long-Short Term Memory Neural Network for Human Intent Understanding.

Understanding of human intention by observing a series of human actions has been a challenging task. In order to do so, we need to analyze longer sequences of human actions related with intentions and extract the context from the dynamic features. The multiple timescales recurrent neural network (MTRNN) model, which is believed to be a kind of solution, is a useful tool for recording and regenerating a continuous signal for dynamic tasks.

Characterization of Full-Length and Truncated Recombinant κ-Carrageenase Expressed in .

κ-Carrageenase belongs to glycoside hydrolase family 16 and cleaves the β-(1→4) linkages of κ-carrageenan. In this study, genes encoding the full-length (), Por secretion tail-truncated (Δ) and carbohydrate binding domain-truncated (Δ) κ-carrageenase proteins were expressed in . The copy numbers of gene , Δ and Δ were 7, 7 and 6, respectively.

Bacterial Community Associated with Healthy and Diseased Pacific White Shrimp () Larvae and Rearing Water across Different Growth Stages.

Bacterial communities are called another "organ" for aquatic animals and their important influence on the health of host has drawn increasing attention. Thus, it is important to study the relationships between aquatic animals and bacterial communities. Here, bacterial communities associated with larvae at different healthy statuses (diseased and healthy) and growth stages (i.

Identification, Bioactivity, and Productivity of Actinomycins from the Marine-Derived .

In the process of profiling the secondary metabolites of actinobacteria isolated from the Saudi coastal habitats for production of antibiotics and anti-cancer drugs, the cultures of strain WH1 that was identified as exhibited strong antibacterial activity against . By means of MS and NMR techniques, the active compounds were characterized as actinomycins X, X, and D, respectively. The research on the productivity of this strain for actinomycins revealed that the highest production of actinomycins X, X, and D was reached in the medium MII within 5% salinity and pH 8.

Marine Group II Dominates Planktonic Archaea in Water Column of the Northeastern South China Sea.

Temperature, nutrients, and salinity are among the important factors constraining the distribution and abundance of microorganisms in the ocean. Marine Group II (MGII) belonging to Euryarchaeota commonly dominates the planktonic archaeal community in shallow water and Marine Group I (MGI, now is called Thaumarchaeota) in deeper water in global oceans. Results of quantitative PCR (qPCR) and 454 sequencing in our study, however, showed the dominance of MGII in planktonic archaea throughout the water column of the northeastern South China Sea (SCS) that is characterized by strong water mixing.

Characterization of Lipopeptide Biosurfactants Produced by MB01 from Marine Sediments.

Antibiotic resistance has become one of the world's most severe problems because of the overuse of antibiotics. Antibiotic-resistant bacteria are more difficult to kill and more expensive to treat. Researchers have been studied on antibiotic alternatives such as antimicrobial peptides and lipopeptides.

DK1622 Coordinates Expressions of the Duplicate and Single Genes for Synergistic Functions of GroELs and GroES.

Chaperonin GroEL (Cpn60) requires cofactor GroES (Cpn10) for protein refolding in bacteria that possess single and genes in a bicistronic operon. Among 4,861 completely-sequenced prokaryotic genomes, 884 possess duplicate genes and 770 possess genes with no neighboring . It is unclear whether stand-alone requires in order to function and, if required, how duplicate genes and unequal genes balance their expressions.

Discovery of Antimycin-Type Depsipeptides from a Gene Mutant Strain of Deepsea-Derived SCSIO ZH66 and Their Effects on Pro-inflammatory Cytokine Production.

Deepsea microbes are a rich source of novel bioactive compounds, which have developed unique genetic systems as well as biosynthetic pathways compared with those of terrestrial microbes in order to survive in extreme living environment. However, a large variety of deepsea-microbial secondary metabolic pathways remain "cryptic" under the normal laboratory conditions. Manipulation of global regulators is one of the effective approaches for triggering the production of cryptic secondary metabolites.

Study of natural IgG antibodies against vascular endothelial growth factor receptor 1 in hepatocellular carcinoma.

Natural antibodies have been found to have anti-tumorigenic function. This study was designed to investigate whether natural IgG antibodies against vascular endothelial growth factor receptor 1 (VEGFR1) could suppress the growth of hepatocellular carcinoma (HCC) cells. Three HCC cell lines and A549 lung cancer cells were used for this study.

A High-Level Fungal Diversity in the Intertidal Sediment of Chinese Seas Presents the Spatial Variation of Community Composition.

The intertidal region is one of the most dynamic environments in the biosphere, which potentially supports vast biodiversity. Fungi have been found to play important roles in marine ecosystems, e.g.

Serum glycoprotein-derived N- and O-linked glycans as cancer biomarkers.

Early detection of cancer is the key to improving survival. Since most clinically used serum cancer biomarkers are either glycoproteins or glycan structures that can be recognized by specific monoclonal antibodies, developing glycan structure-based biomarkers from human serum/plasma glycoproteins through mass spectrometry (MS) analysis are active research field during the past decades. Numerous studies have shown that changes in serum/plasma glycan structures occur during cancer initiation, progression, and treatment.

Diversity, Abundance, and Niche Differentiation of Ammonia-Oxidizing Prokaryotes in Mud Deposits of the Eastern China Marginal Seas.

The eastern China marginal seas (ECMS) are prominent examples of river-dominated ocean margins, whose most characteristic feature is the existence of isolated mud patches on sandy sediments. Ammonia-oxidizing prokaryotes play a crucial role in the nitrogen cycles of many marine environments, including marginal seas. However, few studies have attempted to address the distribution patterns of ammonia-oxidizing prokaryotes in mud deposits of these seas.