Background: Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors.
View Article and Find Full Text PDFOn September 23-24 (2024) the 6th Workshop IRE on Translational Oncology, titled "Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies," took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally.
View Article and Find Full Text PDFThe human intestinal tract is colonized with microorganisms, which present a diverse array of immunological challenges. A number of antimicrobial mechanisms have evolved to cope with these challenges. A key defense mechanism is the expression of inducible antimicrobial peptides (AMPs), such as beta-defensins, which rapidly inactivate microorganisms.
View Article and Find Full Text PDFPatient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging.
View Article and Find Full Text PDFA glut of dinitrogen-derived ammonia (NH) over the past century has resulted in a heavily imbalanced nitrogen cycle and consequently, the large-scale accumulation of reactive nitrogen such as nitrates in our ecosystems has led to detrimental environmental issues. Electrocatalytic upcycling of waste nitrogen back into NH holds promise in mitigating these environmental impacts and reducing reliance on the energy-intensive Haber-Bosch process. Herein, we report a high-performance electrolyzer using an ultrahigh alkalinity electrolyte, NaOH-KOH-HO, for low-cost NH electrosynthesis.
View Article and Find Full Text PDFThe reaction mechanism of CO electroreduction on oxide-derived copper has not yet been unraveled even though high C Faradaic efficiencies are commonly observed on these surfaces. In this study, we aim to explore the effects of copper anodization on the adsorption of various CORR intermediates using surface-enhanced infrared absorption spectroscopy (SEIRAS) on metallic and mildly anodized copper thin films. The SEIRAS results show that the preoxidation process can significantly improve the overall CO reduction activity by (1) enhancing CO activation, (2) increasing CO uptake, and (3) promoting C-C coupling.
View Article and Find Full Text PDFBackground: CEACAM5 and CEACAM6 are glycosylphosphatidylinositol (GPI)- linked members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family, which are frequently upregulated in epithelial cancers where they contribute to invasion, metastasis, immune evasion, and resistance to anoikis. CT109 is a novel antibody with dual specificity to both CEACAM5 and 6.
Objectives: In this study, we aimed to perform the preclinical characterization of CT109 and antibody- drug conjugate (ADCs) derivatives of CT109, focusing on CT109-SN-38.
Biological sciences, drug discovery and medicine rely heavily on cell phenotype perturbation and microscope observation. However, most cellular phenotypic changes are subtle and thus hidden from us by natural cell variability: two cells in the same condition already look different. In this study, we show that conditional generative models can be used to transform an image of cells from any one condition to another, thus canceling cell variability.
View Article and Find Full Text PDFTopological textures of ferroelectric polarizations have promise as alternative devices for future information technology. A polarization rotation inevitably deviates from the stable orientation in axial ferroelectrics, but local energy losses compromise the global symmetry, resulting in a distorted shape of the topological vortex or inhibiting the vortex. Easy planar isotropy helps to promote rotating structures and, accordingly, to facilitate access to nontrivial textures.
View Article and Find Full Text PDFCombining multiple Parkinson's disease (PD) relevant cellular phenotypes might increase the accuracy of midbrain dopaminergic neuron (mDAN) in vitro models. We differentiated patient-derived induced pluripotent stem cells (iPSCs) with a LRRK2 G2019S mutation, isogenic control, and genetically unrelated iPSCs into mDANs. Using automated fluorescence microscopy in 384-well-plate format, we identified elevated levels of α-synuclein (αSyn) and serine 129 phosphorylation, reduced dendritic complexity, and mitochondrial dysfunction.
View Article and Find Full Text PDFContext.—: The use of saliva samples for diagnosis of SARS-CoV-2 infection offers several advantages, including ease of sample collection, feasibility of self-collection, and minimization of medical staff exposure to infection. The emergence of new SARS-CoV-2 variants has had an impact on the viral load of specimens and the results of real-time reverse transcription-polymerase chain reaction (rRT-PCR).
View Article and Find Full Text PDFAn obstacle to effective uniform treatment of glioblastoma, especially at recurrence, is genetic and cellular intertumoral heterogeneity. Hence, personalized strategies are necessary, as are means to stratify potential targeted therapies in a clinically relevant timeframe. Functional profiling of drug candidates against patient-derived glioblastoma organoids (PD-GBO) holds promise as an empirical method to preclinically discover potentially effective treatments of individual tumors.
View Article and Find Full Text PDFLung carcinoids are neuroendocrine tumors representing 1 to 2% of lung cancers. This study outlines the case of a patient with a metastatic lung atypical carcinoid who presented with a pleural effusion and progression of liver metastases after developing resistance to conventional treatments. Personalized functional profiling (PFP), i.
View Article and Find Full Text PDFParkinson's disease (PD) is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. The p.A30P SNCA mutation generates the pathogenic form of the alpha-synuclein protein causing an autosomal-dominant form of PD.
View Article and Find Full Text PDFAtypical chemokine receptors (ACKRs) are important regulators of chemokine functions. Among them, the atypical chemokine receptor ACKR2 (also known as D6) has long been considered as a scavenger of inflammatory chemokines exclusively from the CC family. In this study, by using highly sensitive β-arrestin recruitment assays based on NanoBiT and NanoBRET technologies, we identified the inflammatory CXC chemokine CXCL10 as a new strong agonist ligand for ACKR2.
View Article and Find Full Text PDFPatient-derived cellular models become an increasingly powerful tool to model human diseases for precision medicine approaches. The identification of robust cellular disease phenotypes in these models paved the way towards high throughput screenings (HTS) including the implementation of laboratory advanced automation. However, maintenance and expansion of cells for HTS remains largely manual work.
View Article and Find Full Text PDFPatient-based cancer models are essential tools for studying tumor biology and for the assessment of drug responses in a translational context. We report the establishment a large cohort of unique organoids and patient-derived orthotopic xenografts (PDOX) of various glioma subtypes, including gliomas with mutations in IDH1, and paired longitudinal PDOX from primary and recurrent tumors of the same patient. We show that glioma PDOXs enable long-term propagation of patient tumors and represent clinically relevant patient avatars that retain histopathological, genetic, epigenetic, and transcriptomic features of parental tumors.
View Article and Find Full Text PDFEffects of 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) on the oxidative stability were determined in soybean oil-water system at different locations including at the interface of air-oil, in the middle of oil, and at the interface of oil-water. Also, profile changes of tocopherols were determined during UV irradiation for 18 days. Although no significant changes in tocopherol profiles were observed at three different locations irrespective of DOPC from 0 to 1250 μmol/kg oil, addition of DOPC increased total tocopherols, α-tocopherol, and δ-tocopherol whereas content of β + γ tocopherols did not increase at any locations.
View Article and Find Full Text PDFAccumulating reports demonstrate that apoptosis does not explain all the effects of cancer therapy due to the innate and acquired apoptotic resistance of malignant cancer cells. Recently, paraptosis, a type of programmed cell death accompanied by dilation of mitochondria and/or the endoplasmic reticulum (ER), has garnered interest in cancer research as an alternative way to kill apoptosis-resistant cancers. We describe here the adaptation and validation of a high-content cell-based assay to screen and identify novel paraptotic regulators employing the malignant breast cancer cells undergoing curcumin-induced paraptosis.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC), a major histological subtype of liver cancer, is the third most common cause of cancer-related death worldwide. Currently, many curative standard treatments using target-specific chemotherapeutic agents are being developed. However, drug efficacy tests based on the 2D monolayer cell culture model do not effectively screen the best drug candidates because they do not accurately reflect in vivo tumor microenvironments.
View Article and Find Full Text PDFTo provide efficient antioxidant capacities, proper carriers are needed to protect antioxidants against oxidative stress. Collagen mesh structure or chitosan gel was loaded with α-tocopherol and their effects were evaluated in bulk corn oil or oil-in-water (O/W) emulsion at 60 °C. Added collagen and chitosan enhanced oxidative stability in corn oil and O/W emulsions at 60 °C compared to corn oils without carriers or with addition of α-tocopherol ( < 0.
View Article and Find Full Text PDFBackground: Cellular mobile telephone technology shows much promise for delivering and evaluating healthcare interventions in cost-effective manners with minimal barriers to access. There is little data demonstrating that these devices can accurately measure clinically important aspects of individual functional status in naturalistic environments outside of the laboratory.
Objective: The objective of this study was to demonstrate that data derived from ubiquitous mobile phone technology, using algorithms developed and previously validated by our lab in a controlled setting, can be employed to continuously and noninvasively measure aspects of participant (subject) health status including step counts, gait speed, and activity level, in a naturalistic community setting.
Background: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models.
Methods: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations.