Identification of apelin/APJ signaling dysregulation in a human iPSC-derived granulosa cell model of Turner syndrome.

The interaction between germ cells and somatic cells in the ovaries plays a crucial role in establishing the follicle reserve in mammals. Turner syndrome (TS) predominantly affects females who have a partial or complete loss of one X chromosome. Our understanding of the role that granulosa cells (GCs) play in TS disease progression and pathogenesis remains limited.

Antiviral drug development by targeting RNA binding site, oligomerization and nuclear export of influenza nucleoprotein.

The quasispecies of the influenza virus poses a significant challenge for developing effective therapies. Current antiviral drugs such as oseltamivir, zanamivir, peramivir and baloxavir marboxil along with seasonal vaccines have limitations due to viral variability caused by antigenic drift and shift as well as the development of drug resistance. Therefore, there is a clear need for novel antiviral agents targeting alternative mechanisms, either independently or in combination with existing modalities, to reduce the impact of influenza virus-related infections.

Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects.

Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches.

A two-step approach for calculating chloride diffusion coefficient in concrete with both natural and recycled concrete aggregates.

This paper presents an analytical approach to calculate the effective diffusion coefficient of chlorides in concrete with both natural and recycled concrete aggregates. In the approach the concrete is treated as a composite consisting of three phases, namely mortar, natural aggregate plus interfacial transition zone, and recycled concrete aggregate plus interfacial transition zone. The effective diffusion coefficient of chlorides in the composite is calculated through two steps.

Recent Developments in Steelmaking Industry and Potential Alkali Activated Based Steel Waste: A Comprehensive Review.

The steel industry is responsible for one-third of all global industrial CO emissions, putting pressure on the industry to shift forward towards more environmentally friendly production methods. The metallurgical industry is under enormous pressure to reduce CO emissions as a result of growing environmental concerns about global warming. The reduction in CO emissions is normally fulfilled by recycling steel waste into alkali-activated cement.

Molecular Simulation Study on Mechanical Properties of Microcapsule-Based Self-Healing Cementitious Materials.

Microcapsule-based self-healing concrete can effectively repair micro-cracks in concrete and improve the strength and durability of concrete structures. In this paper, in order to study the effect of epoxy resin on the cement matrix at a microscopic level, molecular dynamics were used to simulate the mechanical and interfacial properties of microcapsule-based self-healing concrete in which uniaxial tension was carried out along the -axis. The radial distribution function, interface binding energy, and hydrogen bonding of the composite were investigated.

Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy.

T‑cell acute lymphoblastic leukemia (T‑ALL) is a common pediatric malignancy, characterized by the abnormal presence of immature T‑cell progenitors. Conventional treatments for T‑ALL fail to prevent or cure the disease, with a high‑risk of recurrence after the first remission. Thus, medical options are in demand to develop novel therapies for patients suffering with T‑ALL.

Behavior of Alkali-Activated Fly Ash through Underwater Placement.

Underwater concrete is a cohesive self-consolidated concrete used for concreting underwater structures such as bridge piers. Conventional concrete used anti-washout admixture (AWA) to form a high-viscosity underwater concrete to minimise the dispersion of concrete material into the surrounding water. The reduction of quality for conventional concrete is mainly due to the washing out of cement and fine particles upon casting in the water.

Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells.

The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro.

Interfacial Binding Energy between Calcium-Silicate-Hydrates and Epoxy Resin: A Molecular Dynamics Study.

Microcapsules encapsulated within epoxy as a curing agent have been successfully applied in self-healing materials, in which the healing performance significantly depends on the binding behaviour of the epoxy curing agent with the cement matrix. In this paper, the binding energy was investigated by molecular dynamics simulation, which could overcome the shortcomings of traditional microscopic experimental methods. In addition to the construction of different molecular models of epoxy, curing agents, and dilutants, seven models were established to investigate the effects of chain length, curing agent, and epoxy resin chain direction on the interfacial binding energy.

Properties of a New Insulation Material Glass Bubble in Geo-Polymer Concrete.

This paper details analytical research results into a novel geopolymer concrete embedded with glass bubble as its thermal insulating material, fly ash as its precursor material, and a combination of sodium hydroxide (NaOH) and sodium silicate (NaSiO) as its alkaline activator to form a geopolymer system. The workability, density, compressive strength (per curing days), and water absorption of the sample loaded at 10% glass bubble (loading level determined to satisfy the minimum strength requirement of a load-bearing structure) were 70 mm, 2165 kg/m, 52.58 MPa (28 days), 54.

Self-Sensing Carbon Nanotube Composites Exposed to Glass Transition Temperature.

This paper reported the effect of high temperature on the electro-mechanical behavior of carbon nanotube (CNT) reinforced epoxy composites. CNT/epoxy composites were fabricated by dispersing CNTs in the epoxy matrix using a solution casting method. Electrical conductivity measurements obtained for the CNT/epoxy composites indicated a steadily increasing directly proportional relationship with CNT concentration with a percolation threshold at 0.

YY1 and HDAC9c transcriptionally regulate p38-mediated mesenchymal stem cell differentiation into osteoblasts.

Mesenchymal stem cells (MSCs) have a high self-renewal potential and can differentiate into various types of cells, including adipocytes, osteoblasts, and chondrocytes. Previously, we reported that the enhancer of zeste homolog 2 (EZH2), the catalytic component of the Polycomb-repressive complex 2, and HDAC9c mediate the osteogenesis and adipogenesis of MSCs. In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation.

Total body irradiation tremendously impair the proliferation, differentiation and chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells.

Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT.

A targeted next-generation sequencing in the molecular risk stratification of adult acute myeloid leukemia: implications for clinical practice.

Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable-risk groups; however, patients with intermediate-risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next-generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1 /FLT3- internal tandem duplication (ITD) were independent prognostic factors for the entire cohort.

GSK3β inactivation promotes the oncogenic functions of EZH2 and enhances methylation of H3K27 in human breast cancers.

During the process of tumorigenesis, inactivation of tumor suppressors is a critical step. EZH2, a histone methyltransferase, promotes cell growth and migration through catalyzing trimethylation of histone H3 at Lys 27 (H3K27me3) and plays an important role in tumorigenesis. Its expression can be controlled by phosphorylation.

Enhancer of Zeste Homolog 2 and Histone Deacetylase 9c Regulate Age-Dependent Mesenchymal Stem Cell Differentiation into Osteoblasts and Adipocytes.

Mesenchymal stem cells (MSCs) are multipotent precursors that can undergo multilineage differentiation, including osteogenesis and adipogenesis, which are two mutually exclusive events. Previously, we demonstrated that enhancer of zeste homolog 2 (EZH2), the catalytic component of the Polycomb-repressive complex 2, mediates epigenetic silencing of histone deacetylase 9c (HDAC9c) in adipocytes but not in osteoblasts and that HDAC9c accelerates osteogenesis while attenuating adipogenesis of MSCs through inactivation of peroxisome proliferator-activated receptor gamma 2 activity. Importantly, disrupting the balance between adipogenesis and osteogenesis can lead to age-associated bone loss (osteoporosis) and obesity.

Multiple gene sequencing for risk assessment in patients with early-onset or familial breast cancer.

Since BRCA mutations are only responsible for 10-20% of cases of breast cancer in patients with early-onset or a family history and since next-generation sequencing technology allows the simultaneous sequencing of a large number of target genes, testing for multiple cancer-predisposing genes is now being considered, but its significance in clinical practice remains unclear. We then developed a sequencing panel containing 68 genes that had cancer risk association for patients with early-onset or familial breast cancer. A total of 133 patients were enrolled and 30 (22.

AKT1 Inhibits Epithelial-to-Mesenchymal Transition in Breast Cancer through Phosphorylation-Dependent Twist1 Degradation.

Epithelial-to-mesenchymal transition (EMT) is an essential physiologic process that promotes cancer cell migration, invasion, and metastasis. Several lines of evidence from both cellular and genetic studies suggest that AKT1/PKBα, but not AKT2 or AKT3, serves as a negative regulator of EMT and breast cancer metastasis. However, the underlying mechanism by which AKT1 suppresses EMT remains poorly defined.

Phosphorylation of EZH2 at T416 by CDK2 contributes to the malignancy of triple negative breast cancers.

Triple-negative breast cancer (TNBC), which is closely related to basal-like breast cancer, is a highly aggressive subtype of breast cancer that initially responds to chemotherapy but eventually develops resistance. This presents a major clinical challenge as there are currently no effective targeted therapies available due to its lack of HER2 and estrogen receptor expression. Here, we show that cyclin E and the enhancer of zeste 2 (EZH2) are closely co-expressed in TNBC patients, and cyclin E/CDK2 phosphorylates EZH2 at T416 (pT416-EZH2) in vivo.

Targeted expression of BikDD combined with metronomic doxorubicin induces synergistic antitumor effect through Bax activation in hepatocellular carcinoma.

Conventional chemotherapy is commonly used to treat advanced non-resectable hepatocellular carcinoma (HCC) but this treatment modality has not demonstrated convincing survival benefit in HCC patients. Our previous studies indicated that targeted expression of therapeutic BikDD driven by a liver cancer-specific α-fetoprotein promoter/enhancer (eAFP) in the VISA backbone (eAFP-VISA-BikDD) significantly and specifically kills HCC cells in multiple orthotopic animal models. To enhance its therapeutic efficacy, we combined eAFP-VISA-BikDD with chemotherapeutic agents and found that eAFP-VISA-BikDD plus doxorubicin (Dox) or 5-fluorouracil (5-FU) demonstrated synergistic cytotoxicity in HCC cells.

Activation of Keap1/Nrf2 signaling pathway by nuclear epidermal growth factor receptor in cancer cells.

Nuclear translocation of EGFR has been shown to be important for tumor cell growth, survival, and therapeutic resistance. Previously, we detected the association of EGFR with Keap1 in the nucleus. Keap1 is a Kelch-like ECH-associated protein, which plays an important role in cellular response to chemical and oxidative stress by regulating Nrf2 protein stability and nuclear translocation.

EZH2: novel therapeutic target for human cancer.

Enhancer of Zeste homlog 2 (EZH2) is a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), which trimethylates Lys 27 of histone H3, leading to silencing of the target genes that are involved in a variety of biological processes including tumor progression and stem cell maintenance. However, in addition to its canonical PRC2-dependent transcriptional repression function, EZH2 also acts as a gene activator in a noncanonical PRC2-independent manner. Overexpression of EZH2 has been detected in diverse cancers, and is associated with tumor malignancy.

Safety and efficacy of pegylated liposomal doxorubicin-based adjuvant chemotherapy in patients with stage I-III triple-negative breast cancer.

Background/aim: Pegylated liposomal doxorubicin (PLD) has been proven to be an effective antitumor drug for metastatic breast cancer, with less toxicity than conventional anthracycline. Our objective was to evaluate the efficacy and safety of PLD-based adjuvant chemotherapy compared to conventional chemotherapy for patients with stages I-III Triple-negative breast cancer (TNBC).

Patients And Methods: A total of 162 patients, histologically proven to have TNBC at stages I-III between 2003 and 2010, were enrolled to evaluate the impact of PLD- and non-PLD-based adjuvant chemotherapy by using the end-pint of overall survival (OS) and relapse-free survival (RFS).