scholarly journals A Comparative Review of Chemotherapy-Induced Peripheral Neuropathy in In Vivo and In Vitro Models

2019 ◽  
Vol 48 (1) ◽  
pp. 190-201 ◽  
Author(s):  
Sandy Eldridge ◽  
Liang Guo ◽  
John Hamre
Keyword(s):  
Peripheral Neuropathy ◽  
Anticancer Agents ◽  
Clinical Presentation ◽  
In Vitro Models ◽  
Comparative Review ◽  
Prevention And Treatment ◽  
Underlying Mechanisms

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect caused by several classes of widely used anticancer therapeutics. Chemotherapy-induced peripheral neuropathy frequently leads to dose reduction or discontinuation of chemotherapy regimens, and CIPN symptoms can persist long after completion of chemotherapy and severely diminish the quality of life of patients. Differences in the clinical presentation of CIPN by widely diverse classifications of anticancer agents have spawned multiple mechanistic hypotheses that seek to explain the pathogenesis of CIPN. Despite its clinical relevance, common occurrence, and extensive investigation, the pathophysiology of CIPN remains unclear. Furthermore, there is no unequivocal gold standard for the prevention and treatment of CIPN. Herein, we review in vivo and in vitro models of CIPN with a focus on histopathological changes and morphological features aimed at understanding the pathophysiology of CIPN and identify gaps requiring deeper exploration. An elucidation of the underlying mechanisms of CIPN is imperative to identify potential targets and approaches for prevention and treatment.

scholarly journals How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Salvatore Giovanni Vitale ◽  
Paola Rossetti ◽  
Francesco Corrado ◽  
Agnese Maria Chiara Rapisarda ◽  
Sandro La Vignera ◽  
...  
Keyword(s):  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Fertilization Rate ◽  
In Vitro Models ◽  
The One ◽  
High Level

Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.

scholarly journals Antioxidant and Anti-Inflammatory Effects of Citrus Flavonoid Hesperetin: Special Focus on Neurological Disorders

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 609 ◽  
Author(s):  
Amjad Khan ◽  
Muhammad Ikram ◽  
Jong Ryeal Hahm ◽  
Myeong Ok Kim
Keyword(s):  
Neurodegenerative Disorders ◽  
In Vitro Models ◽  
Experimental Models ◽  
Special Focus ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Wide Range ◽  
Underlying Mechanisms

Neurodegenerative disorders have emerged as a serious health issue in the current era. The most common neurodegenerative disorders are Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). These diseases involve progressive impairment of neurodegeneration and memory impairment. A wide range of compounds have been identified as potential neuroprotective agents against different models of neurodegeneration both in vivo and in vitro. Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits such as oranges, grapes, and lemons. It has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. In this systematic review, we have compiled all the studies conducted on hesperetin in both in vivo and in vitro models of neurodegeneration. Here, we have used an approach to lessen the bias in each study, providing a least biased, broad understanding of findings and impartial conclusions of the strength of evidence and the reliability of findings. In this review, we collected different papers from a wide range of journals describing the beneficial effects of hesperetin on animal models of neurodegeneration. Our results demonstrated consistent neuroprotective effects of hesperetin against different models of neurodegeneration. In addition, we have summarized its underlying mechanisms. This study provides the foundations for future studies and recommendations of further mechanistic approaches to conduct preclinical studies on hesperetin in different models.

scholarly journals P62 accumulates through neuroanatomical circuits in response to tauopathy propagation

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
François-Xavier Blaudin de Thé ◽  
Benjamin Lassus ◽  
Ari W. Schaler ◽  
Stephanie L. Fowler ◽  
Chris N. Goulbourne ◽  
...  
Keyword(s):  
Disease Progression ◽  
Brain Regions ◽  
In Vitro Models ◽  
Tau Pathology ◽  
Neuron Models ◽  
Protein Clearance ◽  
Underlying Mechanisms ◽  
Tau Aggregation

AbstractIn Alzheimer’s disease and related tauopathies, trans-synaptic transfer and accumulation of pathological tau from donor to recipient neurons is thought to contribute to disease progression, but the underlying mechanisms are poorly understood. Using complementary in vivo and in vitro models, we examined the relationship between these two processes and neuronal clearance. Accumulation of p62 (a marker of defective protein clearance) correlated with pathological tau accumulation in two mouse models of tauopathy spread; Entorhinal Cortex-tau (EC-Tau) mice where tau pathology progresses in time from EC to other brain regions, and PS19 mice injected with tau seeds. In both models and in several brain regions, p62 colocalized with human tau in a pathological conformation (MC1 antibody). In EC-Tau mice, p62 accumulated before overt tau pathology had developed and was associated with the presence of aggregation-competent tau seeds identified using a FRET-based assay. Furthermore, p62 accumulated in the cytoplasm of neurons in the dentate gyrus of EC-Tau mice prior to the appearance of MC1 positive tauopathy. However, MC1 positive tau was shown to be present at the synapse and to colocalize with p62 as shown by immuno electron microscopy. In vitro, p62 colocalized with tau inclusions in two primary cortical neuron models of tau pathology. In a three-chamber microfluidic device containing neurons overexpressing fluorescent tau, seeding of tau in the donor chamber led to tau pathology spread and p62 accumulation in both the donor and the recipient chamber. Overall, these data are in accordance with the hypothesis that the accumulation and trans-synaptic spread of pathological tau disrupts clearance mechanisms, preceding the appearance of obvious tau aggregation. A vicious cycle of tau accumulation and clearance deficit would be expected to feed-forward and exacerbate disease progression across neuronal circuits in human tauopathies.

scholarly journals Maternal mRNA deadenylation is defective in in vitro matured mouse and human oocytes

2021 ◽  
Author(s):  
Yusheng Liu ◽  
Wenrong Tao ◽  
Yiwei Zhang ◽  
Hu Nie ◽  
Zhenzhen Hou ◽  
...  
Keyword(s):  
In Vitro Maturation ◽  
Molecular Defect ◽  
Cytoplasmic Polyadenylation ◽  
Human Oocytes ◽  
Maternal Mrna ◽  
Underlying Mechanisms ◽  
New Criterion

Oocyte in vitro maturation is a technique of assisted reproductive technology that was first introduced in patients with polycystic ovarian syndrome and is now used in most fertility clinics. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (in vitro MII) oocytes compared with in vivo maturated metaphase II (in vivo MII) oocytes in bovines, mice, and humans. However, the underlying mechanisms of this abnormal expression are still poorly understood. In this study, we use PAIso-seq1 to reveal a transcriptome-wide expression profile of full-length transcripts containing entire poly(A) tails in in vivo and in vitro matured mouse and human oocytes. Our results indicate that more genes are up-regulated than down-regulated in in vitro MII oocytes in both mice and humans. Furthermore, we demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes in both mice and humans. We also found that the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes in mice and humans respectively, likely contributing to reduced translation and impaired global maternal mRNA deadenylation. Our findings highlight that impaired maternal mRNA deadenylation is a definite molecular defect in in vitro MII oocytes in both mice and humans. The findings here offer a new criterion for evaluating the quality of in vitro MII oocytes and a potential direction for improving in vitro maturation by fixing the dysregulated maternal mRNA deadenylation.

scholarly journals Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 284 ◽  
Author(s):  
Andleeb Khan ◽  
Sadaf Jahan ◽  
Zuha Imtiyaz ◽  
Saeed Alshahrani ◽  
Hafiz Antar Makeen ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Clinical Studies ◽  
Muscular Atrophy ◽  
Vascular Cognitive Impairment ◽  
In Vitro Models ◽  
Cochrane Library ◽  
Preclinical Studies ◽  
Underlying Mechanisms

With the increase in the expectancy of the life span of humans, neurodegenerative diseases (NDs) have imposed a considerable burden on the family, society, and nation. In defiance of the breakthroughs in the knowledge of the pathogenesis and underlying mechanisms of various NDs, very little success has been achieved in developing effective therapies. This review draws a bead on the availability of the nutraceuticals to date for various NDs (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, vascular cognitive impairment, Prion disease, Spinocerebellar ataxia, Spinal muscular atrophy, Frontotemporal dementia, and Pick’s disease) focusing on their various mechanisms of action in various in vivo and in vitro models of NDs. This review is distinctive in its compilation to critically review preclinical and clinical studies of the maximum phytochemicals in amelioration and prevention of almost all kinds of neurodegenerative diseases and address their possible mechanism of action. PubMed, Embase, and Cochrane Library searches were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical updates. The results from preclinical studies demonstrate the efficacious effects of the phytochemicals in various NDs while clinical reports showing mixed results with promise for phytochemical use as an adjunct to the conventional treatment in various NDs. These studies together suggest that phytochemicals can significantly act upon different mechanisms of disease such as oxidative stress, inflammation, apoptotic pathways, and gene regulation. However, further clinical studies are needed that should include the appropriate biomarkers of NDs and the effect of phytochemicals on them as well as targeting the appropriate population.

scholarly journals Fracture Healing Research—Shift towards In Vitro Modeling?

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 748
Author(s):  
Moritz Pfeiffenberger ◽  
Alexandra Damerau ◽  
Annemarie Lang ◽  
Frank Buttgereit ◽  
Paula Hoff ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Ex Vivo ◽  
3D Models ◽  
In Vitro Models ◽  
Human Patient ◽  
In Vivo Models ◽  
Underlying Mechanisms ◽  
Biological Situation

Fractures are one of the most frequently occurring traumatic events worldwide. Approximately 10% of fractures lead to bone healing disorders, resulting in strain for affected patients and enormous costs for society. In order to shed light into underlying mechanisms of bone regeneration (habitual or disturbed), and to develop new therapeutic strategies, various in vivo, ex vivo and in vitro models can be applied. Undeniably, in vivo models include the systemic and biological situation. However, transferability towards the human patient along with ethical concerns regarding in vivo models have to be considered. Fostered by enormous technical improvements, such as bioreactors, on-a-chip-technologies and bone tissue engineering, sophisticated in vitro models are of rising interest. These models offer the possibility to use human cells from individual donors, complex cell systems and 3D models, therefore bridging the transferability gap, providing a platform for the introduction of personalized precision medicine and finally sparing animals. Facing diverse processes during fracture healing and thus various scientific opportunities, the reliability of results oftentimes depends on the choice of an appropriate model. Hence, we here focus on categorizing available models with respect to the requirements of the scientific approach.

scholarly journals Peripheral Nerve Injury Treatments and Advances: One Health Perspective

2021 ◽  
Author(s):  
Bruna Lopes ◽  
Patrícia Sousa ◽  
Rui Alvites ◽  
Mariana Branquinho ◽  
Ana Sousa ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
One Health ◽  
In Vitro Models ◽  
Health Concern ◽  
In Vivo Models ◽  
Surgical Methods ◽  
Function Impairment

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions that can lead to the loss of structure and/or function impairment. These changes can cause a partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, what in turn can affect the quality of life. For those reasons, PNI is a major public health concern. This review aims to revisit the concepts associated with the PNI. First, the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to explain the urge for new approaches and to understand the methods to evaluate nerve regeneration in a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

scholarly journals In Vitro Assessment of Fluoropyrimidine-Metabolizing Enzymes: Dihydropyrimidine Dehydrogenase, Dihydropyrimidinase, and β-Ureidopropionase

2020 ◽  
Vol 9 (8) ◽  
pp. 2342
Author(s):  
Eiji Hishinuma ◽  
Evelyn Gutiérrez Rico ◽  
Masahiro Hiratsuka
Keyword(s):  
Anticancer Agents ◽  
Mammalian Cells ◽  
Dihydropyrimidine Dehydrogenase ◽  
In Vitro Tests ◽  
Severe Toxicity ◽  
Metabolizing Enzymes ◽  
Underlying Mechanisms ◽  
Enzyme Metabolism

Fluoropyrimidine drugs (FPs), including 5-fluorouracil, tegafur, capecitabine, and doxifluridine, are among the most widely used anticancer agents in the treatment of solid tumors. However, severe toxicity occurs in approximately 30% of patients following FP administration, emphasizing the importance of predicting the risk of acute toxicity before treatment. Three metabolic enzymes, dihydropyrimidine dehydrogenase (DPD), dihydropyrimidinase (DHP), and β-ureidopropionase (β-UP), degrade FPs; hence, deficiencies in these enzymes, arising from genetic polymorphisms, are involved in severe FP-related toxicity, although the effect of these polymorphisms on in vivo enzymatic activity has not been clarified. Furthermore, the clinical usefulness of current methods for predicting in vivo activity, such as pyrimidine concentrations in blood or urine, is unknown. In vitro tests have been established as advantageous for predicting the in vivo activity of enzyme variants. This is due to several studies that evaluated FP activities after enzyme metabolism using transient expression systems in Escherichia coli or mammalian cells; however, there are no comparative reports of these results. Thus, in this review, we summarized the results of in vitro analyses involving DPD, DHP, and β-UP in an attempt to encourage further comparative studies using these drug types and to aid in the elucidation of their underlying mechanisms.

scholarly journals Peripheral Nerve Injury Treatments and Advances: One Health Perspective

2022 ◽  
Vol 23 (2) ◽  
pp. 918
Author(s):  
Bruna Lopes ◽  
Patrícia Sousa ◽  
Rui Alvites ◽  
Mariana Branquinho ◽  
Ana Catarina Sousa ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
One Health ◽  
In Vitro Models ◽  
In Vivo Models ◽  
Surgical Methods ◽  
Function Impairment ◽  
Different Types

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function impairment. These changes can cause partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, which in turn can affect the quality of life. This review aims to revisit the concepts associated with the PNI and the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to enhance the importance of new therapies, especially in severe lesions, to overcome limitations and achieve better outcomes. The urge for new approaches and the understanding of the different methods to evaluate nerve regeneration is fundamental from a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

Scutellaria baicalensis and Cancer Treatment: Recent Progress and Perspectives in Biomedical and Clinical Studies

2018 ◽  
Vol 46 (01) ◽  
pp. 25-54 ◽  
Author(s):  
Chien-Shan Cheng ◽  
Jie Chen ◽  
Hor-Yue Tan ◽  
Ning Wang ◽  
Zhen Chen ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Scutellaria Baicalensis ◽  
Multiple Cancer ◽  
Traditional Use ◽  
Research Attention ◽  
Underlying Mechanisms ◽  
History Of Use

Scutellaria baicalensis (Huangqin in Chinese) is a major traditional Chinese medicine (TCM) herb, which has a long history of use in the treatment of a variety of symptoms correlated with cancer. In the past decade, the potential of S. baicalensis and single compounds derived from it as anticancer agents targeting various pathways has received extensive research attention. Specifically, the proliferation and metastases inhibiting properties of the single compounds in cancer have been studied; however, the underlying mechanisms remain unclear. This review summarizes the various mechanisms, pathways and molecular targets involved in the anticancer activity of S. baicalensis and its single compounds. However, the aim of this review is to provide a more thorough view of the last 10 years to link traditional use with modern research and to highlight recently discovered molecular mechanisms. Extracts and major flavonoids derived from S. baicalensis have been found to possess anticancer effects in multiple cancer cell lines both in vitro and in vivo. Further investigation is warranted to better understand the underlying mechanisms and to discover novel targets and cancer therapeutic drugs that may improve both the survival and quality of life of cancer patients.

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