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Role of Natural Polyphenols in Oxidative Stress: Prevention of Diabetes
Published in Megh R. Goyal, Durgesh Nandini Chauhan, Assessment of Medicinal Plants for Human Health, 2020
Brahm Kumar Tiwari, Kanti Bhooshan Pandey
Influence of oxidative stress in pathogenesis of both T1D and T2D is very vital. ROS are formed in a disproportionate manner during diabetes as a result of different metabolic activities, such as impaired oxidation of glucose, glycation of proteins by non-enzymatic means, and subsequently their oxidative degradation.53,57 Excessive generation of ROS may cause altered cellular physiology by deterioration of cellular organelles, involved in redox homeostasis via peroxidation of lipids, malfunctioning enzymes, and promoting the insulin resistance. All these ramifications of severe oxidative stress can induce the progression of diabetic pathologies.54,80
Signal Transduction Mechanisms Regulating Cytokine-Mediated Induction of Acute Phase Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Until recently, protein phosphatases were not considered to be key players in signal transduction cascades and were thought to be important only for reversing the effect of protein kinases. However, this viewpoint has changed and protein phosphatases are considered to play central and specific roles in cellular physiology.61-63 The role of protein phosphatases has been evaluated in the signal transduction mechanisms regulating the synthesis of acute phase proteins by IL-6 in the absence or presence of cytokines, and these studies have revealed that the serine protein phosphatase 1 and/or 2A may be important in regulating the induction of some of the acute phase proteins.49
Intracellular Double Labeling of Substantia Nigra and Pedunculopontine Neurons in in vitro Slice Preparation
Published in Avital Schurr, Benjamin M. Rigor, BRAIN SLICES in BASIC and CLINICAL RESEARCH, 2020
We have suggested some procedures that allow the method of intracellular injection of biocytin or Lucifer Yellow to be readily combined with immunocytochemical methods in an in vitro slice preparation. The combination offers the possibility of solving a variety of problems in neurobiology. It allows direct correlation between cellular physiology and morphological and transmitter phenotype. The intracellularly labeled neuron is the distinctly stained element in the tissue and can be easily reconstructed with serial sections for a complete morphological analysis. When converted to the HRP reaction product it is permanent, and sections can be exposed to a variety of rigorous treatments (Nissl stain, electron microscopy) or can be stored archivally. This method can be applied to a variety of preparations, including in vivo, in vitro slice and whole-cell patch-clamp, intact organ preparation, and tissue culture.
RNAi therapeutics for diseases involving protein aggregation: fazirsiran for alpha-1 antitrypsin deficiency-associated liver disease
Published in Expert Opinion on Investigational Drugs, 2023
Pavel Strnad, Javier San Martin
To maintain protein homeostasis, cells have built-in pathways that ensure the fidelity of protein synthesis and folding and that misfolded proteins are properly cleared. In normal cellular physiology, misfolded proteins are typically cleared by the endoplasmic reticulum (ER)-associated protein degradation (ERAD), and the disposal is supported by the unfolded protein response (UPR), two key homeostatic machineries in the cell [1,3–5]. ERAD is responsible for the translocation of misfolded proteins from the ER into the cytoplasm, and their ubiquitination and proteasomal degradation. UPR, a conserved cellular mechanism induced by cellular/ER stress, is activated in response to the accumulation of misfolded proteins and reduces their load to maintain cell viability [6]. As another line of defense, aggregated proteins are targeted for degradation by autophagy, which leads to lysosome-mediated degradation of cytoplasmic contents and organelles. Liver diseases characterized by intracellular protein aggregates often arise when there is an imbalance between production of the misfolded protein and the ability of these endogenous pathways to clear it.
The discovery and development of RNA-based therapies for treatment of HIV-1 infection
Published in Expert Opinion on Drug Discovery, 2023
Michelle J Chen, Anne Gatignol, Robert J. Scarborough
Ribozymes are RNAs that catalyze biochemical reactions. The first ribozyme was identified in self-splicing introns, where the RNA catalyzes both cleavage and ligation reactions that result in the excision of the intron from the transcript [38]. Subsequently, it was shown that RNA is the catalytic moiety in RNase P complexes that cleave pre-transfer (t)RNAs [39] and in ribosomes, where ribosomal RNA is responsible for catalyzing the linkage of amino acids to form proteins [40]. The most diverse group of ribozymes are the small, naturally occurring, self-cleaving ribozymes from which most ribozyme therapies have been derived [29,41]. Although these ribozymes catalyze self-cleavage reactions, they can be easily modified to cleave in trans and designed to target an RNA through complementary base pairing. An advantage of small self-cleaving ribozyme motifs is that they do not require cellular proteins to catalyze target cleavage, limiting their ability to disturb cellular physiology. Examples of trans-cleaving ribozymes based on these motifs are shown in Figure 1.
Developing models of cholangiocarcinoma to close the translational gap in cancer research
Published in Expert Opinion on Investigational Drugs, 2021
Scott H. Waddell, Luke Boulter
Tumor heterogeneity among patients makes modeling CCA exceptionally difficult, and the same issue occurs with CCA cell lines. Cell lines are normally derived from a single site from one patient, and therefore only represent the genetic complexity of that sample or biopsy core. Initial studies of CCA in vitro utilized immortalized cell lines, such as the human line HChol-Y1 and rat line BDE1-Neu [36–38]. While being easy to manipulate, cell lines are simple tools that do not represent cellular physiology (normal nor diseased) in vivo due to a lack of bona fide extracellular interactions and being homogeneous in cell-type. To overcome these limitations, cancer studies have moved to animal models and more sophisticated cell culture systems, namely organoid cultures, to address whether new therapies show promise in reducing CCA growth.