Proteolysis Targeting Chimeras (PROTACs) in Breast Cancer Therapy.

Breast cancer (BC) accounts for 30 % of cancer cases among women cancer patients globally, indicating the urgent need for the development of selective therapies targeting BCs. Recently, proteolysis-targeting chimera (PROTAC) has emerged as a promising strategy to target breast cancer. PROTAC is a chimeric molecule consisting of a target protein ligand, an E3 ligase ligand, and conjugating linkers, enabling it to facilitate the degradation of desired target proteins by recruiting E3 ligase in close proximity.

Monocyte-to-lymphocyte ratio as a determinant of survival in patients with gastric cancer undergoing gastrectomy: A cohort study.

The monocyte-to-lymphocyte ratio (MLR) is an important prognostic determinant of various malignancies. However, the prognostic role of MLR in patients with gastric cancer undergoing gastrectomy remains unclear. Patients with stage I to III gastric cancer who underwent curative-intent gastric resection were enrolled in this study.

Programming inactive RNA-binding small molecules into bioactive degraders.

Target occupancy is often insufficient to elicit biological activity, particularly for RNA, compounded by the longstanding challenges surrounding the molecular recognition of RNA structures by small molecules. Here we studied molecular recognition patterns between a natural-product-inspired small-molecule collection and three-dimensionally folded RNA structures. Mapping these interaction landscapes across the human transcriptome defined structure-activity relationships.

Effect of Fermented Red Ginseng Concentrate Intake on Stool Characteristic, Biochemical Parameters, and Gut Microbiota in Elderly Korean Women.

Fermented red ginseng (FRG) has been used as a general stimulant and herbal medicine for health promotion in Asia for thousands of years. Few studies have investigated the effects of FRG containing prebiotics on the gut microbiota. Here, 29 Korean women aged ≥ 50 years were administered FRG for three weeks to determine its effect on stool characteristics, biochemical parameters, and gut microbiome.

Citizen science projects in freshwater monitoring. From individual design to clusters?

Citizen science projects spring up in freshwater monitoring, with an increasing number of projects in river, lake, and groundwater monitoring around the globe. Citizen science scholars assume that these projects have different designs, including diverse characteristics of citizens, institutions, and forms of interactions, potentially affecting the outcomes of these projects. Given the strong focus on case studies or reviews in the field, there is, however, little comparative evidence of the different types of citizen science projects in freshwater monitoring.

Intake of MPRO3 over 4 Weeks Reduces Glucose Levels and Improves Gastrointestinal Health and Metabolism.

Human gut microbiota are involved in different metabolic processes, such as digestion and nutrient synthesis, among others. For the elderly, supplements are a major means of maintaining health and improving intestinal homeostasis. In this study, 51 elderly women were administered MPRO3 ( = 17), a placebo ( = 16), or both (MPRO3: 1 week, placebo: 3 weeks; = 18) for 4 weeks.

Individual Identification with Short Tandem Repeat Analysis and Collection of Secondary Information Using Microbiome Analysis.

Forensic investigation is important to analyze evidence and facilitate the search for key individuals, such as suspects and victims in a criminal case. The forensic use of genomic DNA has increased with the development of DNA sequencing technology, thereby enabling additional analysis during criminal investigations when additional legal evidence is required. In this study, we used next-generation sequencing to facilitate the generation of complementary data in order to analyze human evidence obtained through short tandem repeat (STR) analysis.

Cell-penetrating, amphipathic cyclic peptoids as molecular transporters for cargo delivery.

Here we describe the design, synthesis, and biological evaluation of cell-penetrating, amphipathic cyclic peptoids as a novel class of molecular transporters. We demonstrated that macrocyclization, along with the introduction of hydrophobic residues, greatly enhanced cellular uptake of polyguanidine linear peptoids. The amphipathic cyclic peptoids showed an order of magnitude more efficient intracellular delivery ability, compared to a commonly used polyarginine cell-penetrating peptide, representing one of the best molecular transporters reported to date.

Targeted Degradation of Transcription Coactivator SRC-1 through the N-Degron Pathway.

Aberrantly elevated steroid receptor coactivator-1 (SRC-1) expression and activity are strongly correlated with cancer progression and metastasis. Here we report, for the first time, the development of a proteolysis targeting chimera (PROTAC) that is composed of a selective SRC-1 binder linked to a specific ligand for UBR box, a unique class of E3 ligases recognizing N-degrons. We showed that the bifunctional molecule efficiently and selectively induced the degradation of SRC-1 in cells through the N-degron pathway.

Bridged α-helix mimetic small molecules.

Herein, we report a strategy for generating conformationally restricted α-helix mimetic small molecules by introducing covalent bridges that limit rotation about the central axis of α-helix mimetics. We demonstrate that the bridged α-helix mimetics have enhanced binding affinity and specificity to the target protein due to the restricted conformation as well as extra interaction of the bridge with the protein surface.

A solid-phase method for synthesis of dimeric and trimeric ligands: Identification of potent bivalent ligands of 14-3-3σ.

Multivalent protein-protein interactions including bivalent and trivalent interactions play a critical role in mediating a wide range of biological processes. Hence, there is a significant interest in developing molecules that can modulate those signaling pathways mediated by multivalent interactions. For example, multimeric molecules capable of binding to a receptor protein through a multivalent interaction could serve as modulators of such interactions.

A Forkhead Box Protein C2 Inhibitor: Targeting Epithelial-Mesenchymal Transition and Cancer Metastasis.

The epithelial-mesenchymal transition (EMT) has been suggested as a new target for therapeutic intervention of metastatic cancer. Forkhead box protein C2 (FOXC2) is known to be necessary for initiating and maintaining EMT, and therefore bestows on cancer cells metastatic and cancer stem cell (CSC)-like phenotypes, allowing cells to acquire higher motility, invasiveness, self-renewal, and therapy resistance. Here, we describe the first inhibitor of FOXC2, MC-1-F2.

Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction.

The complex formation between transcription factors (TFs) and coactivator proteins is required for transcriptional activity, and thus disruption of aberrantly activated TF/coactivator interactions could be an attractive therapeutic strategy. However, modulation of such protein-protein interactions (PPIs) has proven challenging. Here we report a cell-permeable, proteolytically stable, stapled helical peptide directly targeting nuclear receptor coactivator 1 (NCOA1), a coactivator required for the transcriptional activity of signal transducer and activator of transcription 6 (STAT6).

Skp2 Inhibitors: Novel Anticancer Strategies.

Skp2 is frequently overexpressed in many human cancers and plays a key role in tumorigenesis. As a component of the SCFSkp2ubiquitin E3 ligase complex, Skp2 is responsible for recruiting substrate proteins for their ubiquitination and subsequent degradation by the 26S proteasome. Thus, Skp2 promotes the cell cycle by down-regulating cell cycle proteins such as the tumor suppressor p27.

Analysis of expert consultation referrals for anesthesia-related issues (December 2008-July 2010): KSA legislation committee report.

Background: Since 2009, database construction of anesthesia-related adverse events has been initiated through the legislation committee of the Korean Society of Anesthesiologists (KSA), based on expert consultation referrals provided by police departments, civil courts, and criminal courts.

Methods: This study was a retrospective descriptive analysis of expert consultation referrals on surgical anesthesia-related cases between December 2008 and July 2010.

Results: During the given period, 46 surgical anesthesia-related cases were referred to the KSA legislation committee for expert consultation.

The effect of mechanical ventilation tidal volume during pneumoperitoneum on shoulder pain after a laparoscopic appendectomy.

Background: Postlaparoscopic shoulder pain (PLSP) frequently occurs after various laparoscopic surgical procedures. Its mechanism is commonly assumed to be overstretching of the diaphragmatic muscle fibers due to the pressure of a pneumoperitoneum, which causes phrenic nerve-mediated referred pain to the shoulder. Based on this hypothesis, we speculated that during inspiration, the lung could squeeze out the phrenic nerve with carbon dioxide gas against the constantly pressurized abdominal cavity with increasing tidal volume (V(T)).