lncRNAs as Hallmarks for Individualized Treatment of Gastric Cancer.

Gastric cancer is a global cancer with a high mortality rate. A growing number of studies have found the abnormal expression of lncRNA (long noncoding RNA) in many tumors, which plays a role in promoting or inhibiting cancer. Similarly, lncRNA abnormal expression plays an essential biological function in gastric cancer. This article focuses on lncRNA involvement in the development of gastric cancer in terms of cell cycle disorder, apoptosis inhibition, metabolic remodeling, promotion of tumor inflammation, immune escape, induction of angiogenesis, and Epithelial Mesenchymal Transition (EMT). The involvement of lncRNA in the development of gastric cancer is related to drug resistance, such as cisplatin and multi-drug resistance. It can also be used as a potential marker for the diagnosis and prognosis of gastric cancer and a target for the treatment. With an in-depth understanding of the mechanism of lncRNA in gastric cancer, new ideas for personalized treatment of gastric cancer are expected.

Computing the Elastic Mechanical Properties of Rodlike DNA Nanostructures.

To study the elastic properties of rodlike DNA nanostructures, we perform long simulations of these structures using the oxDNA coarse-grained model. By analyzing the fluctuations in these trajectories, we obtain estimates of the bend and twist persistence lengths and the underlying bend and twist elastic moduli and couplings between them. Only on length scales beyond those associated with the spacings between the interhelix crossovers do the bending fluctuations behave like those of a wormlike chain. The obtained bending persistence lengths are much larger than that for double-stranded DNA and increase nonlinearly with the number of helices, whereas the twist moduli increase approximately linearly. To within the numerical error in our data, the twist-bend coupling constants are of order zero. That the bending persistence lengths that we obtain are generally somewhat higher than in experiment probably reflects both that the simulated origamis have no assembly defects and that the oxDNA extensional modulus for double-stranded DNA is too large.

BCL10 in cell survival after DNA damage.

The complex defense mechanism of the DNA damage response (DDR) developed by cells during long-term evolution is an important mechanism for maintaining the stability of the genome. Defects in the DDR pathway can lead to the occurrence of various diseases, including tumor development. Most cancer treatments cause DNA damage and apoptosis. However, cancer cells have the natural ability to repair this damage and inhibit apoptosis, ultimately leading to the development of drug resistance. Therefore, investigating the mechanism of DNA damage may contribute markedly to the future treatment of cancer. The CARMA-BCL10-MALT1 (CBM) complex formed by B cell lymphoma/leukemia 10 (BCL10) regulates apoptosis by activating NF-κB signaling. BCL10 is involved in the formation of complexes that antagonize apoptosis and contribute to cell survival after DNA damage, with cytoplasmic BCL10 entering the nucleus to promote DNA damage repair, including histone ubiquitination and the recruitment of homologous recombination (HR) repair factors. This article reviews the role of BCL10 in cell survival following DNA damage.

Autophagy and its role in gastric cancer.

Autophagy, which is tightly regulated by a series of autophagy-related genes (ATGs), is a vital intracellular homeostatic process through which defective proteins and organelles are degraded and recycled under starvation, hypoxia or other specific cellular stress conditions. For both normal cells and tumour cells, autophagy not only sustains cell survival but can also promote cell death. Autophagy-related signalling pathways include mTOR-dependent pathways, such as the AMPK/mTOR and PI3K/Akt/mTOR pathways, and non-mTOR dependent pathways, such as the P53 pathway. Additionally, autophagy plays a dual role in gastric carcinoma (GC), including a tumour-suppressor role and a tumour-promoter role. Long-term Helicobacter pylori infection can impair autophagy, which may eventually promote tumourigenesis of the gastric mucosa. Moreover, Beclin1, LC3 and P62/SQSTM1 are regarded as autophagy-related markers with GC prognostic value. Autophagy inhibitors and autophagy inducers show promise for GC treatment. This review describes research progress regarding autophagy and its significant role in gastric cancer.

Design, synthesis of novel purin-6-one derivatives as phosphodiesterase 2 (PDE2) inhibitors: The neuroprotective and anxiolytic-like effects.

Phosphodiesterase 2 (PDE2) has received much attention for the potential treatment of the central nervous system (CNS) disorders. Herein, based on the existing PDE2 inhibitors and their binding modes, a series of purin-6-one derivatives were designed, synthesized and evaluated for PDE2 inhibitory activities, which led to the discovery of the best compounds 6p and 6s with significant inhibitory potency (IC50: 72 and 81 nM, respectively). Docking simulation was performed to insert compound 6s into the crystal structure of PDE2 at the active site to determine the binding mode. Furthermore, compound 6s significantly protected HT-22 cells against corticosterone-induced cytotoxicity and rescued corticosterone-induced decreases in cAMP and cGMP levels. It also produced anxiolytic-like effect in the elevated plus-maze test and exhibited favorable pharmacokinetic properties in vivo. These results might bring significant instruction for further development of potent PDE2 inhibitors.

Signalling mechanism(s) of epithelial-mesenchymal transition and cancer stem cells in tumour therapeutic resistance.

Epithelial-mesenchymal transition (EMT) leads to tumour progression, including tumour metastasis, disease recurrence and therapy resistance. Cancer stem cells (CSCs) are a small group of cells that have the ability to undergo self-renewal and heterogeneous differentiation, which play a key role in the occurrence and development of cancer. EMT can promote tumour cells to develop stem cell characteristics, which makes tumours more difficult to treat. Therefore, exploring the role of EMT and CSCs in the metastasis of cancer is of great significance to guide tumour treatment and prognosis. In this review, we discuss EMT and CSCs in cancer progression and therapeutic resistance, with a special focus on the common characteristics and relationships between these processes, to explore the crucial relationships in the development of improved anti-tumour therapies. AREAS COVERED: In this brief review article, the author has searched PubMed and Wikipedia for original research and reviewed articles to gather current information on the association of CSCs and EMT with therapeutic resistance characteristics, cancer growth and metastasis, which are believed to be regulated by the TGF-ß, Wnt, Hedgehog (Hh), ß-catenin, STAT3, Notch, and Nanog signalling pathways and other factors (miRNAs, microenvironment and additional cytokines).

Exploring the binding mechanisms of PDE5 with chromeno[2,3-c]pyrrol-9(2H)-one by theoretical approaches.

Cyclic nucleotide phosphodiesterase type 5 (PDE5), exclusively specific for the cyclic guanosine monophosphate (cGMP), is an important drug target for the treatment of erectile dysfunction and pulmonary arterial hypertension (PAH). Although many PDE5 inhibitors have been approved, such as sildenafil, vardenafil, tadalafil and so on, extensive studies have reported some side effects, such as vision disturbance and hearing loss as a result of the amino acid sequence and the secondary structural similarity of other PDEs to the catalytic domain of PDE5. In this study, multiple docking strategies, molecular dynamics (MD) simulations, free energy calculations and decomposition were employed to explore the structural determinants of PDE5 with a series of chromeno[2,3-c]pyrrol-9(2H)-one derivatives. First, reliable docking results were obtained using quantum mechanics/molecular mechanics (QM/MM) docking. Then, MD simulations and MM/GBSA free energy calculations were used to explore the dynamic binding process and characterize the binding modes of the inhibitors with different activities. The predicted binding free energies are in good agreement with the experimental data, and the MM/GBSA free energy decomposition analysis sheds light on the importance of hydrogen bonds with Gln817, π-π stacks against Phe820 and hydrophobic residues for the PDE5 binding of the studied inhibitors. The structural and energetic insights obtained here are useful for understanding the molecular mechanism of ligand binding and designing novel potent and selective PDE5 inhibitors with new scaffolds.