Human epidermal growth factor receptor 2 (HER2) is a critical therapeutic target for HER2-positive or HER2-dependent cancers. While several HER2 kinase inhibitors have been identified, achieving high selectivity for HER2 over EGFR remains a significant challenge. In this study, we aimed to develop HER2-selective inhibitors with enhanced cellular activity.
View Article and Find Full Text PDFAims: Glycine decarboxylase (GLDC) is a mitochondrial enzyme that mediates the degradation of glycine as part of the glycine cleavage system. Although GLDC expression in the kidney is second highest next to the liver, very little is known as to the role of GLDC in the kidney. Thus, this study aimed to elucidate the role of GLDC in the kidney.
View Article and Find Full Text PDFTherapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis.
View Article and Find Full Text PDFRenal cell carcinoma (RCC) is considered as a "metabolic disease" due to various perturbations in metabolic pathways that could drive cancer development. Glycine decarboxylase (GLDC) is a mitochondrial enzyme that takes part in the oxidation of glycine to support nucleotide biosynthesis via transfer of one-carbon units. Herein, we aimed to investigate the potential role of GLDC in RCC development.
View Article and Find Full Text PDFIn this work, we report 14 novel quinazoline derivatives as immune checkpoint inhibitors, IDO1 and PD-L1. The antitumor screening of synthesized compounds on ovarian cancer cells indicated that compound V-d and V-l showed the most activity with IC values of about 5 μM. Intriguingly, compound V-d emerges as a stand out, triggering cell death through caspase-dependent and caspase-independent manners.
View Article and Find Full Text PDFSterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression.
View Article and Find Full Text PDF'Drug abuse' has been recognized as one of the most pressing epidemics in contemporary society. Traditional research has primarily focused on understanding how drugs induce neurotoxicity or degeneration within the central nervous system (CNS) and influence systems related to reward, motivation, and cravings. However, recent investigations have increasingly shifted their attention toward the detrimental consequences of drug abuse on the blood-brain barrier (BBB).
View Article and Find Full Text PDFHuman sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration.
View Article and Find Full Text PDFMethamphetamine (MA) is a extremely addictive psychostimulant drug with a significant abuse potential. Long-term MA exposure can induce neurotoxic effects through oxidative stress, mitochondrial functional impairment, endoplasmic reticulum stress, the activation of astrocytes and microglial cells, axonal transport barriers, autophagy, and apoptosis. However, the molecular and cellular mechanisms underlying MA-induced neurotoxicity remain unclear.
View Article and Find Full Text PDFCancer stem cells (CSCs) are the subpopulation of cells present within a tumor with the properties of self-renewing, differentiating, and proliferating. Owing to the presence of ATP-binding cassette drug pumps and increased expression of anti-apoptotic proteins, the conventional chemotherapeutic agents have failed to eliminate CSCs resulting in relapse and resistance of cancer. Therefore, to obtain long-lasting clinical responses and avoid the recurrence of cancer, it is crucial to develop an efficient strategy targeting CSCs by either employing a differentiation therapy or specifically delivering drugs to CSCs.
View Article and Find Full Text PDFAntioxidants (Basel)
February 2022
Studies report beneficial effects of 3-hydroxybutyrate (3-OHB) on the treatment of type 2 diabetes and obesity, but the effects of 3-OHB on diabetic nephropathy have not been elucidated. This study was designed to investigate the efficacy and mechanism of 3-OHB against progression of diabetic nephropathy (DN). Mice (db/db) were fed normal chow, high-fat, or ketogenic diets (KD) containing precursors of 3-OHB.
View Article and Find Full Text PDFThe pandemic outbreak of COVID-19 in the year of 2020 that drastically changed everyone's life has raised the urgent and intense need for the development of more efficacious antiviral material. This study was designed to develop copper nanoparticles (Cu NPs) as an antiviral agent and to validate the antiviral activities of developed copper NP. The Cu NPs were synthesized using a high energy electron beam, and the characteristic morphologies and antiviral activities of Cu NPs were evaluated.
View Article and Find Full Text PDFCathepsin K is highly expressed in various types of cancers. However, the effect of cathepsin K inhibition in cancer cells is not well characterized. Here, cathepsin K inhibitor (odanacatib; ODN) and knockdown of cathepsin K (siRNA) enhanced oxaliplatin-induced apoptosis in multiple cancer cells through Bax upregulation.
View Article and Find Full Text PDFHistone deacetylase 6 (HDAC6) is a promising target for cancer treatment because it regulates cell mobility, protein trafficking, cell growth, apoptosis, and metastasis. However, the mechanism of HDAC6-induced anticancer drug resistance is unclear. In this study, we evaluated the anticancer effect of ACY-241, an HDAC6-selective inhibitor, on erlotinib-resistant pancreatic cancer cells that overexpress HDAC6.
View Article and Find Full Text PDFThe dysregulation of fibroblast growth factor (FGF) signaling has been implicated in tumorigenesis, tumor progression, angiogenesis, and chemoresistance. The small-molecule AZD4547 is a potent inhibitor of FGF receptors. This study was performed to investigate the antitumor effects and determine the mechanistic details of AZD4547 in ovarian cancer cells.
View Article and Find Full Text PDFWe previously reported that the duodenal-jejunal bypass (DJB) surgery altered transsulfuration and purine metabolism via flux changes in 1-carbon metabolism in the liver. In this study, we extended our study to gain further insight into mechanistic details of how the DJB-induced flux changes in 1-carbon metabolism contributes to the improvement of diet-induced nonalcoholic fatty liver disease. Rodents were subjected to surgical (sham operation and DJB) or dietary (reduced food supply to follow the weight changes in the DJB group) interventions.
View Article and Find Full Text PDFA-kinase anchor protein 12 (AKAP12) is a scaffolding protein that associates with intracellular molecules to regulate multiple signal transductions. Although the roles of AKAP12 in the central nervous system are still relatively understudied, it was previously shown that AKAP12 regulates blood-retinal barrier formation. In this study, we asked whether AKAP12 also supports the function and integrity of the blood-brain barrier (BBB).
View Article and Find Full Text PDFMethamphetamine (METH) is a powerful psychostimulant that is causing serious health problems worldwide owing to imprudent abuses. Recent studies have suggested that METH has deleterious effects on the blood-brain barrier (BBB). A few studies have also been conducted on the mechanisms whereby METH-induced oxidative stress causes BBB dysfunction.
View Article and Find Full Text PDFN-α-acetyltransferase 10 (NAA10) is an acetyltransferase that acetylates both N-terminal amino acid and internal lysine residues of proteins. NAA10 is a crucial player to regulate cell proliferation, migration, differentiation, apoptosis, and autophagy. Recently, mounting evidence presented the overexpression of NAA10 in various types of cancer, including liver, bone, lung, breast, colon, and prostate cancers, and demonstrated a correlation of overexpressed NAA10 with vascular invasion and metastasis, thereby affecting overall survival rates of cancer patients and recurrence of diseases.
View Article and Find Full Text PDFThe present study was designed to determine the effects of pineal gland‑derived melatonin on obesity by employing a rat pinealectomy (Pnx) model. After 10 weeks of a high‑fat diet, rats received sham or Pnx surgery followed by a normal chow diet for 10 weeks. Reverse transcription‑quantitative PCR, western blotting analysis, immunohistochemistry and ELISA were used to determine the effects of Pnx.
View Article and Find Full Text PDFIn this study, a new recirculation column reactor system for arsenate removal using a polyethylenimine coated bacterial biosorbent was developed. Solution pH was the most important factor in process design and operation. In order to control and optimize solution pH favorable for arsenate removal, a pH control and recirculation system was added to a column reactor.
View Article and Find Full Text PDFProtein kinase C-δ (PKCδ) is a diacylglycerol-dependent, calcium-independent novel PKC isoform that is engaged in various cell signaling pathways, such as cell proliferation, apoptosis, inflammation, and oxidative stress. In this study, we searched for proteins that bind PKCδ using a yeast two-hybrid assay and identified murine arrest-defective 1 (mARD1) as a binding partner. The interaction between PKCδ and mARD1 was confirmed by glutathione S-transferase pull-down and co-immunoprecipitation assays.
View Article and Find Full Text PDFAims: Methamphetamine (METH) is an abused psychostimulant causing public health concern worldwide. While most studies have focused on the neurotoxic effects of METH, METH-induced cerebrovascular dysfunction has recently drawn attention as an important facet of METH-related pathophysiology. In this study, we investigated the protective role of GKT136901, a NOX1/4 inhibitor, against METH-induced blood-brain barrier (BBB) dysfunction.
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