Rationale And Objectives: Melanoma, an aggressive skin cancer, often harbors BRAFV600E mutations driving tumor progression via the mitogen-activated protein kinase (MAPK) pathway. While targeted therapies like BRAF (dabrafenib) and MEK (trametinib) inhibitors have improved outcomes, resistance linked to metabolic reprogramming remains a challenge. This study investigates metabolic changes induced by dual BRAF/MEK inhibition in a BRAFV600E-mutant murine melanoma model using magnetic resonance spectroscopy (MRS), optical redox imaging (ORI), and biochemical assays.
View Article and Find Full Text PDF: Cancer cells rely on metabolic reprogramming that is supported by altered mitochondrial redox status and an increased demand for NAD. Over expression of Nampt, the rate-limiting enzyme of the NAD biosynthesis salvage pathway, is common in breast cancer cells, and more so in triple negative breast cancer (TNBC) cells. Targeting the salvage pathway has been pursued for cancer therapy.
View Article and Find Full Text PDFBackground: The redox status of nicotinamide adenine dinucleotide (NAD; including oxidized form NAD and reduced form NADH) plays key roles in both health and disease and has been actively studied to develop cancer biomarkers and therapeutic strategies. With the optical redox imaging (ORI) technique, we have been investigating the relationship of NADH redox status, reactive oxygen species (ROS), and invasiveness in breast cancer cell cultures, and have associated higher invasiveness with more oxidized NADH redox state. However, the cell cultures may have phenotypic drift and metabolic change with increased passage numbers.
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View Article and Find Full Text PDFAdenine nucleotide translocator (ANT) is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner membrane. It plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the cytoplasm. The isoform ANT1 predominately expresses in cardiac and skeletal muscles.
View Article and Find Full Text PDFEthnopharmacological Relevance: Sophora flavescens is often used in traditional Chinese medicine for skin issues, diarrhea, and vaginal itching (Plant names have been checked with http://www.the/plant/list.org on Feb 22nd, 2024).
View Article and Find Full Text PDFTo develop imaging biomarkers for tumors aggressiveness, our previous optical redox imaging (ORI) studies of the reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp, containing flavin adenine dinucleotide, i.e., FAD) in tumor xenografts of human melanoma associated the high optical redox ratio (ORR = Fp/(Fp + NADH)) and its heterogeneity to the high invasive/metastatic potential, without having reported quantitative results for NADH and Fp.
View Article and Find Full Text PDFMaintaining sufficient cerebral oxygen metabolism is crucial for human survival, especially in challenging conditions such as high-altitudes. Human cognitive neural activity is sensitive to fluctuations in oxygen levels. However, there is a lack of publicly available datasets on human behavioural responses and cerebral dynamics assessments during the execution of conflicting tasks in natural hypoxic environments.
View Article and Find Full Text PDFAim: Diabetes osteoporosis (DOP) is a chronic bone metabolic disease induced by diabetes, whose morbidity continues to increase. Epimedium brevicornum Maxim (EB), a popular Chinese traditional medicine, has been used to treat bone diseases in China for thousands of years. But its material basis and specific mechanism of action are not clear.
View Article and Find Full Text PDFEthnopharmacological Relevance: Bone defects are difficult to treat and have a high incidence of nonunion. The Epimedii folium-Rhizoma drynariae herbal pair (EDP) is a traditional Chinese medicine (TCM) used for treating bone diseases. However, the mechanisms by which EDP promotes osteogenesis or bone formation remain largely unclear.
View Article and Find Full Text PDFBackground: Diabetes has become a problem that plagues public healthcare systems. Recent studies have shown that intestinal flora exerts positive therapeutic effects on metabolic diseases, and plant-derived secondary metabolites are safe, effective and easy to prepare and also have an impact on intestinal flora and diabetes; these drugs have rarely been reviewed before as a class of drugs for diabetes, especially focusing on the intestinal flora. Therefore, studying the relationship between plant-derived secondary metabolites and diabetes mellitus is crucial.
View Article and Find Full Text PDFAs a phosphorus-containing molecule, nicotinamide adenine dinucleotide is visible by phosphorus magnetic resonance spectroscopy (P-MRS). However, the relatively low cellular levels of its oxidised (NAD) and reduced (NADH) forms and a significant peak overlap hinder their evaluation in live tissues. This problem is critical when using P-MR spectroscopic imaging, where signals are localised from limited tissue volumes.
View Article and Find Full Text PDFCo-enzyme nicotinamide adenine dinucleotide NAD(H) regulates hundreds of biochemical reactions within the cell. We previously reported that NAD(H) redox status may have prognostic value for predicting breast cancer metastasis. However, the mechanisms of NAD(H) involvement in metastasis remain elusive.
View Article and Find Full Text PDFImportance of the redox status of nicotinamide adenine dinucleotide (NAD), including its oxidized (NAD) and reduced (NADH) forms, has been shown in many biological processes. However, NAD(H) redox status assessment is traditionally limited to biochemical assays in vitro or optical redox imaging (ORI) for superficial tissues in vivo and for deep tissues ex vivo. In recent years, phosphorous-31 magnetic resonance spectroscopy (P-MRS) was utilized to quantify NAD, NADH, and the redox ratio NAD/NADH in normal tissues in vivo.
View Article and Find Full Text PDFBreast cancer is the most diagnosed cancer type in women, with it being the second most deadly cancer in terms of total yearly mortality. Due to the prevalence of this disease, better methods are needed for both detection and treatment. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are autofluorescent biomarkers that lend insight into cell and tissue metabolism.
View Article and Find Full Text PDFA substantial decline in nicotinamide adenine dinucleotide (NAD) has been reported in brain tissue homogenates or neurons isolated from Alzheimer's disease (AD) models. NAD, together with flavin adenine dinucleotide (FAD), critically supports energy metabolism and maintains mitochondrial redox homeostasis. Optical redox imaging (ORI) of the intrinsic fluorescence of reduced NAD (NADH) and oxidized FAD yields cellular redox and metabolic information and provides biomarkers for a variety of pathological conditions.
View Article and Find Full Text PDFSignificance: Stratification of malignancy is valuable for cancer treatment. Both optical redox imaging (ORI) indices and nuclear-to-cytoplasmic volume/area ratio (N:C ratio) have been investigated to differentiate between cancers with varying aggressiveness, but these two methods have not been directly compared. The redox status in the cell nucleus has not been studied by ORI, and it remains unknown whether nuclear ORI indices add new biological information.
View Article and Find Full Text PDFProgrammable metasurfaces allow real-time electromagnetic (EM) manipulation in a digital manner, showing great potential to construct advanced multifunctional EM devices. However, the current programmable metasurfaces typically need human participation to achieve various EM functions. In this Letter, we propose, design, and construct a self-adaptive metasurface platform that can achieve beam control automatically based on image recognition.
View Article and Find Full Text PDFWe evaluated the utility of optical redox imaging (ORI) to identify the therapeutic response of triple-negative breast cancers (TNBC) under various drug treatments. Cultured HCC1806 and MDA-MB-231 cells treated with FK866 (nicotinamide phosphoribosyltransferase (Nampt) inhibitor), FX11 (lactate dehydrogenase A inhibitor), paclitaxel, and their combinations were subjected to ORI, followed by imaging fluorescently labeled reactive oxygen species (ROS). Cell growth inhibition was measured by a cell viability assay.
View Article and Find Full Text PDFEmploying the optical redox imaging technique, we previously identified a significant redox shift of nicotinamide adenine dinucleotide (NAD and the reduced form NADH) in freshly isolated alveolar macrophages (AM) from ozone-exposed mice. The goal here was twofold: (a) to determine the NAD(H) redox shift in cryopreserved AM isolated from ozone-exposed mice and (b) to investigate whether there is a difference in the redox status between cryopreserved and freshly isolated AM. We found: (i) AM from ozone-exposed mice were in a more oxidized redox state compared to that from filtered air (FA)-exposed mice, consistent with the results obtained from freshly isolated mouse AM; (ii) under FA exposure, there was no significant NAD(H) redox difference between fresh AM that had been placed on ice for 2.
View Article and Find Full Text PDFTriple-negative breast cancer (TNBC) is a highly diverse group of cancers with limited treatment options, responsible for about 15% of all breast cancers. TNBC cells differ from each other in many ways such as gene expression, metabolic activity, tumorigenicity, and invasiveness. Recently, many research and clinical efforts have focused on metabolically targeted therapy for TNBC.
View Article and Find Full Text PDFPredicting tumor metastatic potential remains a challenge in cancer research and in clinical diagnosis. Cancer invasion to neighboring tissues is a significant event in cancer progression to metastasis. Optical redox imaging (ORI) is based on detecting the endogenous fluorescence signals of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD).
View Article and Find Full Text PDFThe Warburg effect, representing enhanced glycolysis and lactate production in adequately oxygenated cancer cells, has been widely regarded to cause increased extracellular acidification. Converting pyruvate to lactate by lactate dehydrogenase A (LDHA) is the last step of glycolysis. Here, we report an interesting counterintuitive observation that inhibition of LDHA resulted in enhanced glycolysis in MDA-MB-231 breast cancer cells.
View Article and Find Full Text PDFCo-enzyme nicotinamide adenine dinucleotide (NAD(H)) redox plays a key role in macrophage function. Surfactant protein (SP-) A modulates the functions of alveolar macrophages (AM) and ozone (O) exposure in the presence or absence of SP-A and reduces mouse survival in a sex-dependent manner. It is unclear whether and how NAD(H) redox status plays a role in the innate immune response in a sex-dependent manner.
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