-
Signal Transduction and Targeted Therapy May 2022Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult stem cells (AdSCs) derived... (Review)
Review
Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult stem cells (AdSCs) derived from healthy individuals or patients that recapitulate the cellular heterogeneity, structure, and functions of human organs. The advent of human 3D organoid systems is now possible to allow remarkably detailed observation of stem cell morphogens, maintenance and differentiation resemble primary tissues, enhancing the potential to study both human physiology and developmental stage. As they are similar to their original organs and carry human genetic information, organoids derived from patient hold great promise for biomedical research and preclinical drug testing and is currently used for personalized, regenerative medicine, gene repair and transplantation therapy. In recent decades, researchers have succeeded in generating various types of organoids mimicking in vivo organs. Herein, we provide an update on current in vitro differentiation technologies of brain, retinal, kidney, liver, lung, gastrointestinal, cardiac, vascularized and multi-lineage organoids, discuss the differences between PSC- and AdSC-derived organoids, summarize the potential applications of stem cell-derived organoids systems in the laboratory and clinic, and outline the current challenges for the application of organoids, which would deepen the understanding of mechanisms of human development and enhance further utility of organoids in basic research and clinical studies.
Topics: Adult; Adult Stem Cells; Cell Differentiation; Humans; Organoids; Pluripotent Stem Cells; Regenerative Medicine
PubMed: 35610212
DOI: 10.1038/s41392-022-01024-9 -
International Journal of Molecular... Aug 2021Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation.... (Review)
Review
Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far from being achieved. The goal of regenerative endodontics is to promote normal pulp function recovery in inflamed or necrotic teeth that would result in true regeneration of the pulpodentinal complex. Recently, rapid progress has been made related to tissue engineering-mediated pulp regeneration, which combines stem cells, biomaterials, and growth factors. Since the successful isolation and characterisation of dental pulp stem cells (DPSCs) and other applicable dental mesenchymal stem cells, basic research and preclinical exploration of stem cell-mediated functional pulp regeneration via cell transplantation and cell homing have received considerably more attention. Some of this effort has translated into clinical therapeutic applications, bringing a ground-breaking revolution and a new perspective to the endodontic field. In this article, we retrospectively examined the current treatment status and clinical goals of pulpal and periapical diseases and scrutinized biological studies of functional pulp regeneration with a focus on DPSCs, biomaterials, and growth factors. Then, we reviewed preclinical experiments based on various animal models and research strategies. Finally, we summarised the current challenges encountered in preclinical or clinical regenerative applications and suggested promising solutions to address these challenges to guide tissue engineering-mediated clinical translation in the future.
Topics: Animals; Dental Pulp; Guided Tissue Regeneration, Periodontal; Humans; Mesenchymal Stem Cells; Regeneration; Retrospective Studies; Root Canal Therapy; Stem Cells; Tissue Engineering
PubMed: 34445703
DOI: 10.3390/ijms22168991 -
Cellular & Molecular Immunology Jan 2022The clinical success of immune checkpoint therapy (ICT) has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of... (Review)
Review
The clinical success of immune checkpoint therapy (ICT) has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of immune regulation. Much of the current translational efforts are aimed at enhancing ICT by identifying therapeutic targets that synergize with CTLA4 or PD1/PD-L1 blockade and are solidly developed on the basis of currently accepted principles. Expanding these principles through continuous basic research may help broaden translational efforts. With this mindset, we focused this review on three threads of basic research directly relating to mechanisms underlying ICT. Specifically, this review covers three aspects of dendritic cell (DC) biology connected with antitumor immune responses but are not specifically oriented toward therapeutic use. First, we review recent advances in the development of the cDC1 subset of DCs, identifying important features distinguishing these cells from other types of DCs. Second, we review the antigen-processing pathway called cross-presentation, which was discovered in the mid-1970s and remains an enigma. This pathway serves an essential in vivo function unique to cDC1s and may be both a physiologic bottleneck and therapeutic target. Finally, we review the longstanding field of helper cells and the related area of DC licensing, in which CD4 T cells influence the strength or quality of CD8 T cell responses. Each topic is connected with ICT in some manner but is also a fundamental aspect of cell-mediated immunity directed toward intracellular pathogens.
Topics: CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cross-Priming; Dendritic Cells; Humans; Neoplasms
PubMed: 34480145
DOI: 10.1038/s41423-021-00741-5 -
Dialogues in Clinical Neuroscience Sep 2019Cognition has attracted a growing interest in psychiatry. Since the 1990s, cognition as a whole has become an important determinant in the outcome of psychosis. Despite...
Cognition has attracted a growing interest in psychiatry. Since the 1990s, cognition as a whole has become an important determinant in the outcome of psychosis. Despite recent progress in the genetics of cognition, the development of new pharmacological compounds in order to improve cognition has not progressed as quickly. This issue will review and discuss the main areas of clinical and basic research in this domain. .
Topics: Cognition; Cognitive Dysfunction; Humans; Psychiatry; Psychotic Disorders
PubMed: 31749646
DOI: 10.31887/DCNS.2019.21.3/fthibaut -
Current Opinion in Lipidology Aug 2019Hypertriglyceridemia occurs mainly because of metabolic disorders secondary to diabetes, alcohol intake, and/or overweight. Genetic factors have also been clearly... (Review)
Review
PURPOSE OF REVIEW
Hypertriglyceridemia occurs mainly because of metabolic disorders secondary to diabetes, alcohol intake, and/or overweight. Genetic factors have also been clearly identified in most severe cases. Triglycerides are generally considered as 'bystanders' for cardiovascular diseases. However, biological and basic research provides strong data suggesting that triglyceride-rich lipoproteins could be involved in the pathophysiology of cardiovascular diseases.
RECENT FINDINGS
The REDUCE-IT trial recently showed that icosapent ethyl reduces major cardiovascular events and related death.
SUMMARY
For many years, low-density lipoproteins (LDLs) have been considered the Holy Grail for atherosclerotic cardiovascular disease management. New data from basic research in biology, epidemiology, genetics, and preliminary clinical trials support the hypothesis that triglyceride-rich lipoproteins could be the causal factors for atherosclerotic cardiovascular disease; hence, triglyceride should be taken into consideration in the management of these patients. Omega-3-fatty acids used in the REDUCE-IT trial reduced the residual cardiovascular risk efficiently beyond statins. However, its effect has to be completely understood as it seems to be unrelated to LDLc or triglyceride reduction, but linked to pleiotropic effects involving inflammation, platelet adhesion, and plaque instability reduction, paving the way for trials that will target more specific potential pathophysiologic pathways.
Topics: Animals; Atherosclerosis; Humans; Hypertriglyceridemia; Risk Factors
PubMed: 31145120
DOI: 10.1097/MOL.0000000000000622 -
Nutrients May 2023The ketogenic diet (KD) has become widespread for the therapy of epileptic pathology in childhood and adulthood. In the last few decades, the current re-emergence of its... (Review)
Review
BACKGROUND
The ketogenic diet (KD) has become widespread for the therapy of epileptic pathology in childhood and adulthood. In the last few decades, the current re-emergence of its popularity has focused on the treatment of obesity and diabetes mellitus. KD also exerts anti-inflammatory and neuroprotective properties, which could be utilized for the therapy of neurodegenerative and psychiatric disorders.
PURPOSE
This is a thorough, scoping review that aims to summarize and scrutinize the currently available basic research performed in in vitro and in vivo settings, as well as the clinical evidence of the potential beneficial effects of KD against neurodegenerative and psychiatric diseases. This review was conducted to systematically map the research performed in this area as well as identify gaps in knowledge.
METHODS
We thoroughly explored the most accurate scientific web databases, e.g., PubMed, Scopus, Web of Science, and Google Scholar, to obtain the most recent in vitro and in vivo data from animal studies as well as clinical human surveys from the last twenty years, applying effective and characteristic keywords.
RESULTS
Basic research has revealed multiple molecular mechanisms through which KD can exert neuroprotective effects, such as neuroinflammation inhibition, decreased reactive oxygen species (ROS) production, decreased amyloid plaque deposition and microglial activation, protection in dopaminergic neurons, tau hyper-phosphorylation suppression, stimulating mitochondrial biogenesis, enhancing gut microbial diversity, restoration of histone acetylation, and neuron repair promotion. On the other hand, clinical evidence remains scarce. Most existing clinical studies are modest, frequently uncontrolled, and merely assess the short-term impacts of KD. Moreover, several clinical studies had large dropout rates and a considerable lack of compliance assessment, as well as an increased level of heterogeneity in the study design and methodology.
CONCLUSIONS
KD can exert substantial neuroprotective effects via multiple molecular mechanisms in various neurodegenerative and psychiatric pathological states. Large, long-term, randomized, double-blind, controlled clinical trials with a prospective design are strongly recommended to delineate whether KD may attenuate or even treat neurodegenerative and psychiatric disease development, progression, and symptomatology.
Topics: Humans; Animals; Diet, Ketogenic; Neuroprotective Agents; Epilepsy; Alzheimer Disease; Mental Disorders; Randomized Controlled Trials as Topic
PubMed: 37242153
DOI: 10.3390/nu15102270 -
Audiology Research Sep 2023The importance of translational research in the medical sciences is growing logarithmically, as this type of research provides the translation of basic research into a...
The importance of translational research in the medical sciences is growing logarithmically, as this type of research provides the translation of basic research into a clinical product (a drug, therapeutic agent or means of monitoring a disease), as well as the inverse translation of clinical findings into basic research models [...].
PubMed: 37887844
DOI: 10.3390/audiolres13050063 -
Frontiers in Pharmacology 2020Heart failure is a systemic syndrome caused by multiple pathological factors. Current treatments do not have satisfactory outcomes. Several basic studies have revealed... (Review)
Review
Heart failure is a systemic syndrome caused by multiple pathological factors. Current treatments do not have satisfactory outcomes. Several basic studies have revealed the protective effect of trimetazidine on the heart, not only by metabolism modulation but also by relieving myocardial apoptosis, fibrosis, autophagy, and inflammation. Clinical studies have consistently indicated that trimetazidine acts as an adjunct to conventional treatments and improves the symptoms of heart failure. This review summarizes the basic pathological changes in the myocardium, with an emphasis on the alteration of cardiac metabolism in the development of heart failure. The clinical application of trimetazidine in heart failure and the mechanism of its protective effects on the myocardium are carefully discussed, as well as its main adverse effects. The intention of this review is to highlight this treatment as an effective alternative against heart failure and provide additional perspectives for future studies.
PubMed: 33597865
DOI: 10.3389/fphar.2020.569132 -
Frontiers in Physiology 2022
PubMed: 35547582
DOI: 10.3389/fphys.2022.888676 -
Science Advances Jun 2021
PubMed: 34193421
DOI: 10.1126/sciadv.abj8363