Discovery of a Novel Potent EGFR Inhibitor Against EGFR Activating Mutations and On-Target Resistance in NSCLC.

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) serve as the standard first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC). Despite the sustained clinical benefits achieved through optimal EGFR-TKI treatments, including the third-generation EGFR-TKI osimertinib, resistance inevitably develops. Currently, there are no targeted therapeutic options available postprogression on osimertinib.

Evaluation of Oxygen Absorbers Using Food Simulants and Inductively Coupled Mass Spectrometry.

In this study, we developed and validated an analytical method to evaluate the heavy metal elution from an active packaging material's oxygen absorber to a food simulant. Using water, 4% acetic acid, n-heptane, 20% ethanol, and 50% ethanol as food simulants, we quantified cobalt, copper, platinum, and iron with inductively coupled plasma-mass spectrometry. The method was thoroughly validated for linearity, accuracy, precision, LOD, and LOQ through inter-day and intra-day analysis repetitions.

Altered Mitochondrial Function and Accelerated Aging Phenotype in Neural Stem Cells Derived from Dnm1l Knockout Embryonic Stem Cells.

Mitochondria are crucial for cellular energy metabolism and are involved in signaling, aging, and cell death. They undergo dynamic changes through fusion and fission to adapt to different cellular states. In this study, we investigated the effect of knocking out the () gene, a key regulator of mitochondrial fission, in neural stem cells (NSCs) differentiated from knockout embryonic stem cells ( ESCs).

In Vitro Embryogenesis and Gastrulation Using Stem Cells in Mice and Humans.

During early mammalian embryonic development, fertilized one-cell embryos develop into pre-implantation blastocysts and subsequently establish three germ layers through gastrulation during post-implantation development. In recent years, stem cells have emerged as a powerful tool to study embryogenesis and gastrulation without the need for eggs, allowing for the generation of embryo-like structures known as synthetic embryos or embryoids. These in vitro models closely resemble early embryos in terms of morphology and gene expression and provide a faithful recapitulation of early pre- and post-implantation embryonic development.

Mettl14 mutation restrains liver regeneration by attenuating mitogens derived from non-parenchymal liver cells.

Liver regeneration is a well-known systemic homeostatic phenomenon. The N-methyladenosine (mA) modification pathway has been associated with liver regeneration and hepatocellular carcinoma. mA methyltransferases, such as methyltransferase 3 (METTL3) and methyltransferase 14 (METTL14), are involved in the hepatocyte-specific-regenerative pathway.

Preclinical Study of a Biparatopic METxMET Antibody-Drug Conjugate, REGN5093-M114, Overcomes MET-driven Acquired Resistance to EGFR TKIs in EGFR-mutant NSCLC.

Purpose: MET amplification is a frequent mechanism of resistance to EGFR tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non-small cell lung cancer (NSCLC), and combined treatment with EGFR TKIs and MET TKIs has been explored as a strategy to overcome resistance. However, durable response is invariably limited by the emergence of acquired resistance. Here, we investigated the preclinical activity of REGN5093-M114, a novel antibody-drug conjugate targeting MET in MET-driven patient-derived models.

Endotracheal intubation in rabbits using a video laryngoscope with a modified blade.

Rabbits are being increasingly used as companion animals, and in research; thus, the need for proper veterinary care for rabbits has increased. Surgical access is more challenging in rabbits under inhalation anesthesia compared to other animals, such as dogs and cats. Rabbits have a very narrow and deep oral cavity, large incisors, and a large tongue.

The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice.

Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) plays a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet/streptozotocin-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower body weight, fasting blood glucose levels, and serum insulin levels than wild-type (WT) mice.

Colorimetric detection of Co2+ ion using silver nanoparticles with spherical, plate, and rod shapes.

A highly sensitive colorimetric sensing platform for the selective trace analysis for Co(2+) ions is reported, based on glutathione (GSH)-modified silver nanoparticles (AgNP). The shape of metallic nanoparticles used in colorimetric detection, using the unique optical properties of plasmonic nanoparticles, is almost spherical. Therefore, in this work we attempted to investigate the selective detection of heavy metal ion (Co(2+)), with the shape of AgNPs (nanosphere, nanoplate, and nanorod).

Luteolin exerts anti-tumor activity through the suppression of epidermal growth factor receptor-mediated pathway in MDA-MB-231 ER-negative breast cancer cells.

This study investigated the inhibitory effect of luteolin on MDA-MB-231 estrogen receptor (ER) negative breast tumor growth both in vitro and in vivo. Study results showed that luteolin suppresses (3)H thymidine incorporation indicating cell growth inhibition, and this was accompanied by cell cycle arrest at the G2/M and S stages and apoptotic activity. Further analyses showed that luteolin exhibited cell cycle arrest and apoptotic activity by decreasing AKT, PLK1, cyclin B(1), cyclin A, CDC2, CDK2, and Bcl-xL expression and increasing p21 and Bax expression.

Modulatory effects of alpha- and gamma-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells.

The elevated level of circulating estradiol increases the risk of breast tumor development. To gain further insight into mechanisms involved in their actions, we investigated the molecular mechanisms of 4-hydroxyestradiol (4-OHE(2)) to initiate and/or promote abnormal cell growth, and of alpha- or gamma-tocopherol to inhibit this process. MCF-10A, human breast epithelial cells were incubated with 0.

Mammaglobin expression in lymph nodes is an important marker of metastatic breast carcinoma.

Context: Organ specificity is a desirable property of a tumor marker, especially in metastatic adenocarcinomas of unknown primary origin. Mammaglobin, a mammary-specific member of the uteroglobin family, is known to be overexpressed in human breast cancer.

Objective: We investigated mammaglobin A expression in metastatic carcinomas of lymph nodes from the breast and various other organs and its usefulness in identifying metastatic carcinoma of the breast.