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Cells Aug 2023This study investigates the feasibility of establishing urine-derived tumor organoids from bladder cancer (BC) patients as an alternative to tissue-derived organoids. BC...
This study investigates the feasibility of establishing urine-derived tumor organoids from bladder cancer (BC) patients as an alternative to tissue-derived organoids. BC is one of the most common cancers worldwide and current diagnostic methods involve invasive procedures. Here, we investigated the potential of using urine samples, which contain exfoliated tumor cells, to generate urine-derived BC organoids (uBCOs). Urine samples from 29 BC patients were collected and cells were isolated and cultured in a three-dimensional matrix. The establishment and primary expansion of uBCOs were successful in 83% of the specimens investigated. The culturing efficiency of uBCOs was comparable to cancer tissue-derived organoids. Immunohistochemistry and immunofluorescence to characterize the uBCOs exhibited similar expressions of BC markers compared to the parental tumor. These findings suggest that urine-derived BC organoids hold promise as a non-invasive tool for studying BC and evaluating therapeutic responses. This approach could potentially minimize the need for invasive procedures and provide a platform for personalized drug screening. Further research in this area may lead to improved diagnostic and treatment strategies for BC patients.
Topics: Humans; Body Fluids; Urinary Bladder Neoplasms; Organoids; Drug Evaluation, Preclinical
PubMed: 37681920
DOI: 10.3390/cells12172188 -
Annals of Clinical and Translational... Nov 2023Numerous potential amyotrophic lateral sclerosis (ALS)-relevant pathways have been hypothesized and studied preclinically, with subsequent translation to clinical trial.... (Review)
Review
Numerous potential amyotrophic lateral sclerosis (ALS)-relevant pathways have been hypothesized and studied preclinically, with subsequent translation to clinical trial. However, few successes have been observed with only modest effects. Along with an improved but incomplete understanding of ALS as a neurodegenerative disease is the evolution of more sophisticated and diverse in vitro and in vivo preclinical modeling platforms, as well as clinical trial designs. We highlight proposed pathological pathways that have been major therapeutic targets for investigational compounds. It is likely that the failures of so many of these therapeutic compounds may not have occurred because of lack of efficacy but rather because of a lack of preclinical modeling that would help define an appropriate disease pathway, as well as a failure to establish target engagement. These challenges are compounded by shortcomings in clinical trial design, including lack of biomarkers that could predict clinical success and studies that are underpowered. Although research investments have provided abundant insights into new ALS-relevant pathways, most have not yet been developed more fully to result in clinical study. In this review, we detail some of the important, well-established pathways, the therapeutics targeting them, and the subsequent clinical design. With an understanding of some of the shortcomings in translational efforts over the last three decades of ALS investigation, we propose that scientists and clinicians may choose to revisit some of these therapeutic pathways reviewed here with an eye toward improving preclinical modeling, biomarker development, and the investment in more sophisticated clinical trial designs.
Topics: Humans; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Biomarkers
PubMed: 37641443
DOI: 10.1002/acn3.51887 -
Neuronal Signaling Jul 2023Stress exposure is associated with psychiatric conditions, such as depression, anxiety, and post-traumatic stress disorder (PTSD). It is also a vulnerability factor to... (Review)
Review
Stress exposure is associated with psychiatric conditions, such as depression, anxiety, and post-traumatic stress disorder (PTSD). It is also a vulnerability factor to developing or reinstating substance use disorder. Stress causes several changes in the neuro-immune-endocrine axis, potentially resulting in prolonged dysfunction and diseases. Changes in several transmitters, including serotonin, dopamine, glutamate, gamma-aminobutyric acid (GABA), glucocorticoids, and cytokines, are associated with psychiatric disorders or behavioral alterations in preclinical studies. Complex and interacting mechanisms make it very difficult to understand the physiopathology of psychiatry conditions; therefore, studying regulatory mechanisms that impact these alterations is a good approach. In the last decades, the impact of stress on biology through epigenetic markers, which directly impact gene expression, is under intense investigation; these mechanisms are associated with behavioral alterations in animal models after stress or drug exposure, for example. The endocannabinoid (eCB) system modulates stress response, reward circuits, and other physiological functions, including hypothalamus-pituitary-adrenal axis activation and immune response. eCBs, for example, act retrogradely at presynaptic neurons, limiting the release of neurotransmitters, a mechanism implicated in the antidepressant and anxiolytic effects after stress. Epigenetic mechanisms can impact the expression of eCB system molecules, which in turn can regulate epigenetic mechanisms. This review will present evidence of how the eCB system and epigenetic mechanisms interact and the consequences of this interaction in modulating behavioral changes after stress exposure in preclinical studies or psychiatric conditions. Moreover, evidence that correlates the involvement of the eCB system and epigenetic mechanisms in drug abuse contexts will be discussed.
PubMed: 37520658
DOI: 10.1042/NS20220034 -
Pharmaceutics Nov 2021The blood-brain barrier (BBB) precisely controls brain microenvironment and neural activity by regulating substance transport into and out of the brain. However, it... (Review)
Review
The blood-brain barrier (BBB) precisely controls brain microenvironment and neural activity by regulating substance transport into and out of the brain. However, it severely hinders drug entry into the brain, and the efficiency of various systemic therapies against brain diseases. Modulation of the BBB via opening tight junctions, inhibiting active efflux and/or enhancing transcytosis, possesses the potential to increase BBB permeability and improve intracranial drug concentrations and systemic therapeutic efficiency. Various strategies of BBB modulation have been reported and investigated preclinically and/or clinically. This review describes conventional and emerging BBB modulation strategies and related mechanisms, and safety issues according to BBB structures and functions, to try to give more promising directions for designing more reasonable preclinical and clinical studies.
PubMed: 34959306
DOI: 10.3390/pharmaceutics13122024 -
Evidence-based Complementary and... 2022is a plant native to America, with applications in folk medicine for a wide range of diseases, such as bronchial infections, lung disorders, nervous system disorders... (Review)
Review
is a plant native to America, with applications in folk medicine for a wide range of diseases, such as bronchial infections, lung disorders, nervous system disorders (depression, anxiety), and inflammatory processes, among others. However, investigations about this species and its biological actions are still scarce. This literature review was carried out using articles published in the past 30 years on the PubMed, SciELO, and Web of Science platforms, with the focus on the method of extraction, chemical composition, and clinical and preclinical studies on the pharmacological properties of . We noticed that the main constituents of are guaiol, pinocamphone, -pinene, and 1,8-cineole. Additionally, preclinical studies reveal that extracts present antidepressant, anti-inflammatory, antinociceptive, antibacterial, antifungal, and virucidal effects. The results also demonstrate that there is a greater interest on the part of researchers from 2012 onwards in studying extracts with potential for possible new drugs.
PubMed: 35096101
DOI: 10.1155/2022/1119435 -
Journal of Clinical Pharmacology Sep 2022Preterm birth (PTB; defined as delivery before 37 weeks of pregnancy) is the leading cause of morbidity and mortality in infants and children aged <5 years, conferring...
Preterm birth (PTB; defined as delivery before 37 weeks of pregnancy) is the leading cause of morbidity and mortality in infants and children aged <5 years, conferring potentially devastating short- and long-term complications. Despite extensive research in the field, there is currently a paucity of medications available for PTB prevention and treatment. Over the past few decades, inflammation in gestational tissues has emerged at the forefront of PTB pathophysiology. Even in the absence of infection, inflammation alone can prematurely activate the main components of parturition resulting in uterine contractions, cervical ripening and dilatation, membrane rupture, and subsequent PTB. Mechanistic studies have identified critical elements of the complex inflammatory molecular pathways involved in PTB. Here, we discuss therapeutic options that target such key mediators with an aim to prevent, postpone, or treat PTB. We provide an overview of more traditional therapies that are currently used or being tested in humans, and we highlight recent advances in preclinical studies introducing novel approaches with therapeutic potential. We conclude that urgent collaborative action is required to address the unmet need of developing effective strategies to tackle the challenge of PTB and its complications.
Topics: Child; Female; Humans; Infant, Newborn; Inflammation; Pregnancy; Premature Birth
PubMed: 36106783
DOI: 10.1002/jcph.2107 -
Regenerative Engineering and... 2023Organoids are three-dimensional cultures of stem cells in an environment similar to the body's extracellular matrix. This is also a novel development in the realm of... (Review)
Review
PURPOSE
Organoids are three-dimensional cultures of stem cells in an environment similar to the body's extracellular matrix. This is also a novel development in the realm of regenerative medicine. Stem cells can begin to develop into 3D structures by modifying signaling pathways. To form organoids, stem cells are transplanted into the extracellular matrix. Organoids have provided the required technologies to reproduce human tissues. As a result, it might be used in place of animal models in scientific study. The key goals of these investigations are research into viral and genetic illnesses, malignancies, and extracellular vesicles, pharmaceutical discovery, and organ transplantation. Organoids can help pave the road for precision medicine through genetic editing, pharmaceutical development, and cell therapy.
METHODS
PubMed, Google Scholar, and Scopus were used to search for all relevant papers written in English (1907-2021). The study abstracts were scrutinized. Studies on the use of stem-cell-derived organoids in regenerative medicine, organoids as 3D culture models for EVs analysis, and organoids for precision medicine were included. Articles with other irrelevant aims, meetings, letters, commentaries, congress and conference abstracts, and articles with no available full texts were excluded.
RESULTS
According to the included studies, organoids have various origins, types, and applications in regenerative and precision medicine, as well as an important role in studying extracellular vesicles.
CONCLUSION
Organoids are considered a bridge that connects preclinical studies to clinical ones. However, the lack of a standardized protocol and other barriers addressed in this review, hinder the vast use of this technology.
LAY SUMMARY
Organoids are 3D stem cell propagations in biological or synthetic scaffolds that mimic ECM to allow intercellular or matrix-cellular crosstalk. Because these structures are similar to organs in the body, they can be used as research models. Organoids are medicine's future hope for organ transplantation, tumor biobank formation, and the development of precision medicine. Organoid models can be used to study cell-to-cell interactions as well as effective factors like inflammation and aging. Bioengineering technologies are also used to define the size, shape, and composition of organoids before transforming them into precise structures. Finally, the importance of organoid applications in regenerative medicine has opened a new window for a better understanding of biological research, as discussed in this study.
PubMed: 35968268
DOI: 10.1007/s40883-022-00271-0 -
Heliyon Dec 2022In vivo imaging in preclinical and clinical settings can enhance knowledge of the host-microbiome interactions. Imaging techniques are a crucial node between findings at... (Review)
Review
In vivo imaging in preclinical and clinical settings can enhance knowledge of the host-microbiome interactions. Imaging techniques are a crucial node between findings at the molecular level and clinical implementation in diagnostics and therapeutics. The purpose of this study was to review existing knowledge on the microbiota in the field of imaging and provide guidance for future research, emphasizing the critical role that molecular imaging plays in increasing understanding of the host-microbe interaction. Preclinical microbiota animal models lay the foundation for the clinical translatability of novel microbiota-based therapeutics. Adopting animal models in which factors such as host genetic landscape, microbiota profile, and diet can be controlled enables investigating how the microbiota contributes to immunological dysregulation and inflammatory disorders. Current preclinical imaging of gut microbiota relies on models where the bacteria can be isolated, labelled, and re-administered. , optical imaging, ultrasound and magnetic resonance imaging define the bacteria's biodistribution in preclinical models, whereas nuclear imaging investigates bacterial metabolic activity. For the clinical investigation of microbe-host interactions, molecular nuclear imaging is increasingly becoming a promising approach. Future microbiota research should develop selective imaging probes to investigate microbiota profiles and individual strains of specific microbes. Preclinical knowledge can be translated into the molecular imaging field with great opportunities for studying the microbiome.
PubMed: 36593827
DOI: 10.1016/j.heliyon.2022.e12511 -
Frontiers in Cell and Developmental... 2022Tendinopathy has a high incidence in athletes and the aging population. It can cause pain and movement disorders, and is one of the most difficult problems in... (Review)
Review
Tendinopathy has a high incidence in athletes and the aging population. It can cause pain and movement disorders, and is one of the most difficult problems in orthopedics. Animal models of tendinopathy provide potentially efficient and effective means to develop understanding of human tendinopathy and its underlying pathological mechanisms and treatments. The selection of preclinical models is essential to ensure the successful translation of effective and innovative treatments into clinical practice. Large animals can be used in both micro- and macro-level research owing to their similarity to humans in size, structure, and function. This article reviews the application of large animal models in tendinopathy regarding injuries to four tendons: rotator cuff, patellar ligament, Achilles tendon, and flexor tendon. The advantages and disadvantages of studying tendinopathy with large animal models are summarized. It is hoped that, with further development of animal models of tendinopathy, new strategies for the prevention and treatment of tendinopathy in humans will be developed.
PubMed: 36393858
DOI: 10.3389/fcell.2022.1031638 -
The Journal of Neuroscience : the... Dec 2023Neurodevelopmental disorders (NDDs) are a group of complex neurologic and psychiatric disorders. Functional and molecular imaging techniques, such as resting-state... (Review)
Review
Neurodevelopmental disorders (NDDs) are a group of complex neurologic and psychiatric disorders. Functional and molecular imaging techniques, such as resting-state functional magnetic resonance imaging (rs-fMRI) and positron emission tomography (PET), can be used to measure network activity noninvasively and longitudinally during maturation in both humans and rodent models. Here, we review the current knowledge on rs-fMRI and PET biomarkers in the study of normal and abnormal neurodevelopment, including intellectual disability (ID; with/without epilepsy), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), in humans and rodent models from birth until adulthood, and evaluate the cross-species translational value of the imaging biomarkers. To date, only a few isolated studies have used rs-fMRI or PET to study (abnormal) neurodevelopment in rodents during infancy, the critical period of neurodevelopment. Further work to explore the feasibility of performing functional imaging studies in infant rodent models is essential, as rs-fMRI and PET imaging in transgenic rodent models of NDDs are powerful techniques for studying disease pathogenesis, developing noninvasive preclinical imaging biomarkers of neurodevelopmental dysfunction, and evaluating treatment-response in disease-specific models.
Topics: Infant; Humans; Adult; Autism Spectrum Disorder; Magnetic Resonance Imaging; Epilepsy; Positron-Emission Tomography; Attention Deficit Disorder with Hyperactivity; Biomarkers; Brain
PubMed: 38073598
DOI: 10.1523/JNEUROSCI.1043-23.2023