PAR2 promotes malignancy in lung adenocarcinoma.

Proteinase-activated receptor-2 (PAR2) is closely linked to tumor malignancy, but its biological role in cancer remains underexplored. In this study, we assessed PAR2 expression in lung adenocarcinoma (LUAD) and normal lung tissues, analyzed associations between clinicopathological features and survival rates, and confirmed that PAR2 promotes apoptosis resistance and reduces cisplatin-induced cytotoxicity in lung cancer cells. Using TCGA datasets, western blotting, qPCR, and immunohistochemistry (IHC), we observed a significant increase in PAR2 levels in LUAD samples compared to normal tissues (P<0.

A high-field cellular DNP-supported solid-state NMR approach to study proteins with sub-cellular specificity.

Studying the structural aspects of proteins within sub-cellular compartments is of growing interest. Dynamic nuclear polarization supported solid-state NMR (DNP-ssNMR) is uniquely suited to provide such information, but critically lacks the desired sensitivity and resolution. Here we utilize SNAPol-1, a novel biradical, to conduct DNP-ssNMR at high-magnetic fields (800 MHz/527 GHz) inside HeLa cells and isolated cell nuclei electroporated with [C,N] labeled ubiquitin.

Site-specific chirality-conferred structural compaction differentially mediates the cytotoxicity of Aβ42.

Growing evidence supports the confident association between distinct amyloid beta (Aβ) isoforms and Alzheimer's Disease (AD) pathogenesis. As such, critical investigations seeking to uncover the translational factors contributing to Aβ toxicity represent a venture of significant value. Herein, we comprehensively assess full-length Aβ42 stereochemistry, with a specific focus on models that consider naturally-occurring isomerization of Asp and Ser residues.

Enhanced control of bioactivity of tissue plasminogen activator (tPA) through domain-directed enzymatic oxidation of terminal galactose.

In targeted enzyme prodrug constructs, it is critical to control the bioactivity of the drug in its prodrug form. The preparation of such constructs often involves conjugation reactions directed to functional groups on amino acid side chains of the protein, which result in random conjugation and incomplete control of bioactivity of a prodrug, which may result in significant nontarget effect. Thus, more specific method of modification is desired.

Long non-coding RNA HOXA11-AS protects the barrier function of corneal endothelial cells by sponging microRNA-155 to alleviate corneal endothelial injury.

Objectives: Corneal endothelial cells (CECs) are extremely vulnerable to injury. In this study, the role and mechanism of action of the long non-coding RNA HOXA11-AS during corneal endothelial injury (CEI) were evaluated in vivo and in vitro.

Methods: Scratch wounds were made to induce CEI in the corneal endothelium of rats and mice.

Highly bioresistant, hydrophilic and rigidly linked trityl-nitroxide biradicals for cellular high-field dynamic nuclear polarization.

Cellular dynamic nuclear polarization (DNP) has been an effective means of overcoming the intrinsic sensitivity limitations of solid-state nuclear magnetic resonance (ssNMR) spectroscopy, thus enabling atomic-level biomolecular characterization in native environments. Achieving DNP signal enhancement relies on doping biological preparations with biradical polarizing agents (PAs). Unfortunately, PA performance within cells is often limited by their sensitivity to the reductive nature of the cellular lumen.

CDH13 is a prognostic biomarker and a potential therapeutic target for patients with clear cell renal cell carcinoma.

CDH13 is an atypical member of the cadherin family and is closely related to the clinicopathological factors and prognosis of many types of cancer. However, the role of CDH13 in clear cell renal cell carcinoma (ccRCC) remains unknown. Therefore, we comprehensively analyzed the expression level, diagnostic efficacy, clinical significance, prognostic value, immune infiltration, methylation status, genetic alteration, and biological functions of CDH13 in ccRCC patients.

Long-term outcomes of 316 patients with STEMI following coronary stent implantation.

Background: Stent thrombosis (ST)-related ST-segment elevation myocardial infarction (STEMI) has very high mortality and poor prognosis. With the extensive construction of the chest pain center in China, the question arises as to whether these special patients will benefit.

Methods: From January 2015 to February 2018, 316 patients with STEMI admitted to the coronary care unit (CCU) of Tianjin Chest Hospital after coronary stent implantation were enrolled in this retrospective study.

Highly efficient HS scavengers thiolysis of positively-charged NBD amines.

HS is a well-known toxic gas and also a gaseous signaling molecule involved in many biological processes. Advanced chemical tools that can regulate HS levels are useful for understanding HS biology as well as its potential therapeutic effects. To this end, we have developed a series of 7-nitro-1,2,3-benzoxadiazole (NBD) amines as potential HS scavengers.

CUL4B Promotes Breast Carcinogenesis by Coordinating with Transcriptional Repressor Complexes in Response to Hypoxia Signaling Pathway.

Cullin4B (CUL4B) is a scaffold protein of the CUL4B-Ring E3 ligase (CRL4B) complex. However, the role of CUL4B in the development of breast cancer remains poorly understood. Here it is shown that CRL4B interacts with multiple histone deacetylase (HDAC)-containing corepressor complexes, including MTA1/NuRD, SIN3A, CoREST, and NcoR/SMRT complexes.

Improved Antiglioblastoma Activity and BBB Permeability by Conjugation of Paclitaxel to a Cell-Penetrative MMP-2-Cleavable Peptide.

In order to solve the problems of receptor promiscuity and poor blood-brain barrier (BBB) penetration in the treatment of glioblastomas (GBM), a novel dual-functional nanocomplex drug delivery system is developed based on the strategy of peptide-drug conjugates. In this study, SynB3-PVGLIG-PTX is designed and screened out by matrix metalloproteinase-2 (MMP-2), to which it exhibits the best affinity. The MMP-2-sensitive peptide (PVGLIG) and a cell-penetration peptide (SynB3) are combined to form a dual-functional peptide.

[Comparison of two types of T-shaped coronectomy applied in extraction of impacted mandibular third molars].

Purpose: To compare the clinical efficiency of two types of T-shaped coronectomy applied in extraction of impacted mandibular third molars. METHODS：One hundred and twenty patients meeting with the criteria were randomly divided into 2 groups. Two types of T-shaped coronectomy were applied in extraction of impacted mandibular third molars.

Directional molecular sliding movement in peptide hydrogels accelerates cell proliferation.

Adjusting the mechanical cues generated in cellular microenvironments is important for manipulating cell behaviour. Here we report on mechanically dynamic hydrogels undergoing directional domain sliding motion and investigate the effect of the well-defined mechanical motion on accelerating cell proliferation. The mechanically dynamic hydrogels were prepared self-assembly of an amphiphilic peptide consisting of two alternating polar and nonpolar domains cross-linked by disulfide bonds at a nonsymmetrical position.

Genome-Wide CRISPR-Cas9 Screening Identifies NF-κB/E2F6 Responsible for EGFRvIII-Associated Temozolomide Resistance in Glioblastoma.

Amplification of epidermal growth factor receptor (EGFR) and active mutant EGFRvIII occurs frequently in glioblastoma (GBM) and contributes to chemo/radio-resistance in various cancers, especially in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in GBM could benefit cancer patients. A genome-wide screening under a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 library is conducted to identify the genes that confer resistance to TMZ in EGFRvIII-expressing GBM cells.

The potential role of circRNA_004229 in hair/epidermal regulation after MED1 ablation in keratinocytes.

/: Mediator complex subunit 1 (MED1) is an important transcriptional co-activator involved in multiple signaling pathways. Previous studies indicated an essential role of MED1 in hair cycling and wound repair through regulating the transcription of mRNAs. Circular RNAs (circRNAs), as a novel class of non-coding RNAs, are involved in various skin biological functions.

A novel STAT3 inhibitor, HJC0152, exerts potent antitumor activity in glioblastoma.

Aberrant expression and activation of signal transducer and activator of transcription 3 (STAT3) is implicated in several malignancies, including glioblastoma, and is correlated with poor outcomes in patients with glioblastoma, rendering STAT3 a potential therapeutic target. However, few STAT3 inhibitors have been approved for clinical use. We recently developed an orally active small-molecule compound with anti-STAT3 activity, HJC0152.

Long noncoding RNA OIP5-AS1 accelerates the ox-LDL mediated vascular endothelial cells apoptosis through targeting GSK-3β via recruiting EZH2.

An increasing amount of research is demonstrating the role of long noncoding RNAs (lncRNAs) in human cardiovascular disease, and in particular, atherosclerosis. To date, the mechanism through which lncRNA OIP5-AS1 regulates the oxidative low-density lipoprotein (ox-LDL)-mediated endothelial cell apoptosis is still unclear. Results from this study found that lncRNA OIP5-AS1 was significantly over-expressed in the human umbilical vein endothelial cells (HUVECs) administered with ox-LDL.

BRMS1 coordinates with LSD1 and suppresses breast cancer cell metastasis.

Breast carcinoma metastasis suppressor gene 1 () encodes an inhibitor of metastasis and is reported in many types of tumor metastasis. However, the mechanism of BRMS1-mediated inhibition of breast cancer metastasis at the transcriptional level remains elusive. Here, we identified using affinity purification and mass spectrometry (MS) that BRMS1 is an integral component of the LSD1/CoREST corepressor complex.

Resveratrol alleviates sepsis-induced acute lung injury by suppressing inflammation and apoptosis of alveolar macrophage cells.

Sepsis is a major cause of death in intensive care units. The purpose of this study was to investigate the effect of resveratrol (RSV) on sepsis-induced acute lung injury (ALI). The underlying molecular mechanisms were deciphered by both and experiments.

A fluorescent calixarene-based dimeric capsule constructed a M-terpyridine interaction: cage structure, inclusion properties and drug release.

Two analogues of capsule-like fluorescent cages have been constructed by dimerization of terpyridine-containing calixarene derivatives utilizing a M-terpyridine (M = Zn and Cd) interaction. H NMR spectral studies show that the self-assembled molecular capsules ZnL1 and CdL1 have a highly symmetrical -structure. The encapsulation of the anticancer drug mercaptopurine in their cavities has been documented by NMR, ESI-TOF-MS, fluorescence switching, and molecular simulation, indicating that strong S-π and π-π interactions between drug and cage are of importance for the host-guest binding.

Heparin-Regulated Prodrug-Type Macromolecular Theranostic Systems for Cancer Therapy.

Heparin is a kind of naturally occurring polymer with excellent biocompatibility and solubility. It is characterized by dense of negative charge, higher than any endogenous components. Heparin can bind with various cationic peptides and proteins, thereby providing a useful noncovalent linkage for building a drug delivery system.

Nodal signaling activates the Smad2/3 pathway to regulate stem cell-like properties in breast cancer cells.

Nodal signaling plays several vital roles in the embryogenesis process. However, its reexpression in breast cancer is correlated with cancer progression, metastasis and poor prognosis. Recently, Nodal has also been reported to regulate self-renewal capacity in pancreatic cancer.

Inhibition of miR-630 enhances the cell resistance to radiation by directly targeting CDC14A in human glioma.

Radio-resistance becomes a large obstacle for effective cancer treatment. MicroRNAs (miRNAs) play important roles in response to radiation. However, the underlying mechanism of miR-630 on the radio-resistance of human glioma is less elucidated.

HMGA2 regulates CD44 expression to promote gastric cancer cell motility and sphere formation.

High mobility group AT-hook 2 (HMGA2) is a transcriptional modulator that mediates motility and self-renewal in cancer stem cells. Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. GC contains a population of stem-like cells that promote tumor invasion and resistance to therapy.