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Topic Review
Overexpression of CERKL Protects Retinal Pigment Epithelium Mitochondria
The precise function of CERKL, a Retinitis Pigmentosa (RP) causative gene, is not yet fully understood. There is evidence that CERKL is involved in the regulation of autophagy, stress granule generation and mitochondrial dynamics, and it is considered a resilience gene that protects retinal cells from oxidative stress. Mutations in most RP genes affect photoreceptors, but retinal pigment epithelium (RPE) cells may be also affected. Upon oxidative stress conditions, CERKL knockdown causes RPE mitochondrial fragmentation and respiratory metabolism alterations, whereas CERKL overexpression protects mitochondria of RPE cells. Particular retinal phenotypic traits observed in patients carrying CERKL mutations may reflect a combination of photoreceptor and RPE alterations.
  • 401
  • 31 Dec 2021
Topic Review
Osteoporosis Treatments
A healthy and active lifestyle is vital for the proper maintenance of all body tissues, including bone. Several studies have highlighted the importance of physical exercise to improve the quality of life of patients with osteoporosis. Diet also plays a fundamental role in bone health. Calcium supplementation is able to decrease the rate of bone mineral density loss in women, presenting even better results in combination with vitamin D. Lately, isoflavones has gain interest as a treatment in osteoporosis but their effectiveness still remains unclear. Therefore, pharmacological therapies have been developed to counteract bone fragility based on molecular targets. Therapies for osteoporosis are focus on restoring the normal balance between bone resorption and bone formation. Bone anti-resorptive therapies focus on the inhibition or reduction of bone resorption process, these are; estrogens, selective estrogen receptor modulators (SERMs), bisphosphonates and monoclonal antibodies. On the other hand, bone formation agents target anabolic pathways to stimulate the osteoblastic activity. This include Teriparatide, a recombinant human parathyroid hormone (PTH), and Romosozumab; an anti-sclerostin monoclonal antibody with dual effect.  It increases bone formation and, to a lesser extent, it reduces bone resorption (or bone loss) which translates into a decrease in the risk of fracture. In summary, currently used osteoporosis therapies are not fully effective in all patients and present considerable side effects that seriously compromise their long-term use. Thus, the development of new therapeutic strategies for osteoporosis is necessary in an increasingly aging world population. In this context, cell-based therapeutic strategies based on mesenchymal stem cells are positioning as encouraging possibilities to address osteoporosis.
  • 778
  • 27 Oct 2020
Topic Review
ORP5 and ORP8
Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.
  • 490
  • 15 Jul 2021
Topic Review
Organoids in Radiobiology
The majority of cancer patients will be treated with radiotherapy, either alone or together with chemotherapy and/or surgery. Optimising the balance between tumour control and the probability of normal tissue side effects is the primary goal of radiation treatment. Therefore, it is imperative to understand how irradiation affects both normal and cancer tissue. Here, we discuss how organoids, three-dimensional tissue-resembling structures derived from tissue-resident, embryonic or induced pluripotent stem cells, have a growing importance in the field of radiation biology research.
  • 658
  • 07 Jan 2021
Topic Review
Organoids for Precision Medicine in Malignant Pleural Mesothelioma
MPM is an aggressive tumor originating from pleural mesothelial cells. A characteristic feature of the disease is the dominant prevalence of therapeutically intractable inactivating alterations in TSGs, making MPM one of the most difficult cancers to treat and the epitome of a cancer characterized by a significant lack of therapy options and an extremely poor prognosis (5-year survival rate of only 5% to 10%). Extensive interpatient heterogeneity poses another major challenge for targeted therapy of MPM, warranting stratified therapy for specific subgroups of MPM patients. Accurate preclinical models are critical for the discovery of new therapies and the development of personalized medicine. Organoids, an in vitro ‘organ-like’ 3D structure derived from patient tumor tissue that faithfully mimics the biology and complex architecture of cancer and largely overcomes the limitations of other existing models, are the next-generation tumor model.
  • 313
  • 29 Aug 2022
Topic Review
Organoids and iPSC-Based Models
Organoids are self-organized, three-dimensional structures derived from stem cells that can mimic the structure and physiology of human organs. Patient-specific induced pluripotent stem cells (iPSCs) and 3D organoid model systems allow cells to be analyzed in a controlled environment to simulate the characteristics of a given disease by modeling the underlying pathophysiology. 
  • 172
  • 26 Jan 2024
Topic Review
Organoids and Aging
The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans, and cell cultures. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. An organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging, and to design personalized approaches for the prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging, paving the way to personalized interventions targeting the biology of aging.
  • 1.1K
  • 19 Oct 2021
Topic Review
Organic Small Molecules in Pain-Management
There are different types of anti-inflammatory agents, including small molecules, peptides, and antibodies. In this entry, there will be a focus on small molecules for anti-inflammatory treatments as they have been the center of traditional medicine. Small molecule drugs are compounds with low molecular weight that can easily enter the body and modulate biochemical processes to treat medical conditions.
  • 464
  • 13 Jul 2021
Topic Review
Oral Submucous Fibrosis
Betel quid (BQ) chewing increased the risk of oral cancer and oral submucous fibrosis (OSMF), an oral premalignant disorder (OPMD) with malignant transformation potential. BQ components such as areca nut (AN), trauma by coarse AN fiber, catechin, copper, alkaloids, stimulated reactive oxygen species (ROS), inflammation and cytotoxicity are suggested to be the contributing factors. In this review, the expression of extracellular matrix (ECM) turnover related genes and proteins in OSMF and the relation to betel quid chewing habit is discussed. Genetic susceptibility of ECM-related genes to OSMF is also mentioned. These results can facilitate our understanding the pathogenesis of OSMF and its possible prevention/treatment in the future.
  • 903
  • 08 Dec 2020
Topic Review
Oral Pathogenic Bacteria-Inducing Neurodegenerative Microgliosis
Porphyromonas gingivalis is a gram-negative bacterium found in the human oral cavity and is responsible for the development of chronic periodontitis as well as neurological diseases, including Alzheimer’s disease (AD). Given the significance of the roles of P. gingivalis in AD pathogenesis, it is critical to understand the underlying mechanisms of P. gingivalis-driven neuroinflammation and their contribution to neurodegeneration. Herein, we hypothesize that P. gingivalis produces secondary metabolites that may cause neurodegeneration through direct or indirect pathways mediated by microglia. To test our hypothesis, we treated human neural cells with bacterial conditioned media on our brain platforms and assessed microgliosis, astrogliosis and neurodegeneration. We found that bacteria-mediated microgliosis induced the production of nitric oxide, which causes neurodegeneration assessed with high pTau level. Our study demonstrated the elevation of detrimental protein mediators, CD86 and iNOS and the production of several pro-inflammatory markers from stimulated microglia. Through inhibition of LPS and succinate dehydrogenase in a bacterial conditioned medium, we showed a decrease in neurodegenerative microgliosis. In addition, we demonstrated the bidirectional effect of microgliosis and astrogliosis on each other exacerbating neurodegeneration. Overall, our study suggests that the mouth-brain axis may contribute to the pathogenesis of AD.
  • 338
  • 19 Jul 2021
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