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Developmental Neurobiology Nov 2020The N-methyl-D-aspartate receptor (NMDAR) is an important mediator of central sensitization and nociception in the rat spinal dorsal horn. The NMDAR subunits and splice...
The N-methyl-D-aspartate receptor (NMDAR) is an important mediator of central sensitization and nociception in the rat spinal dorsal horn. The NMDAR subunits and splice variants determine the properties of the receptor. Understanding the expression of NMDAR subunits in spinal cord during the neonatal development is important as it may have consequences for the process of central sensitization and nociception in later life. In this review, a systematic literature search was conducted using three databases: Medline, Embase, and PubMed. A quality assessment was performed on predetermined entities of bias. Thirteen articles were identified to be relevant. The results show that NMDAR subunits and splice variants are dynamically expressed during postnatal development in the spinal dorsal horn. During the first 2 weeks, the expression of less excitable GluN2A subunit and more sensitive GluN2B subunit increases while the expression of high excitable GluN2C subunit decreases. During the 2nd week of postnatal development GluN1 subunits with exon 21 spliced in but exon 22 spliced out are predominantly expressed, increasing phosphorylation, and transport to the membrane. The data suggest that in rats, the nociceptive system is most susceptible to central sensitization processes during the first two postnatal weeks. This may have important consequences for nociception and pain responses in later life. From this, we conclude that targeted therapy directed toward specific NMDAR subunits is a promising candidate for mechanism-based treatment of pain in neonates.
Topics: Animals; Central Nervous System Sensitization; Neurogenesis; Pain; Rats; Receptors, N-Methyl-D-Aspartate; Spinal Cord
PubMed: 33131183
DOI: 10.1002/dneu.22789 -
International Journal of Molecular... Sep 2020Stroke is the leading cause of disability, and stroke survivors suffer from long-term sequelae even after receiving recombinant tissue plasminogen activator therapy and...
Stroke is the leading cause of disability, and stroke survivors suffer from long-term sequelae even after receiving recombinant tissue plasminogen activator therapy and endovascular intracranial thrombectomy. Increasing evidence suggests that exosomes, nano-sized extracellular membrane vesicles, enhance neurogenesis, angiogenesis, and axonal outgrowth, all the while suppressing inflammatory reactions, thereby enhancing functional recovery after stroke. A systematic literature review to study the association of stroke recovery with exosome therapy was carried out, analyzing species, stroke model, source of exosomes, behavioral analyses, and outcome data, as well as molecular mechanisms. Thirteen studies were included in the present systematic review. In the majority of studies, exosomes derived from mesenchymal stromal cells or stem cells were administered intravenously within 24 h after transient middle cerebral artery occlusion, showing a significant improvement of neurological severity and motor functions. Specific microRNAs and molecules were identified by mechanistic investigations, and their amplification was shown to further enhance therapeutic effects, including neurogenesis, angiogenesis, axonal outgrowth, and synaptogenesis. Overall, this review addresses the current advances in exosome therapy for stroke recovery in preclinical studies, which can hopefully be preparatory steps for the future development of clinical trials involving stroke survivors to improve functional outcomes.
Topics: Animals; Axons; Disease Models, Animal; Exosomes; Humans; Mesenchymal Stem Cells; MicroRNAs; Neovascularization, Physiologic; Neurogenesis; Stroke; Synapses
PubMed: 32962207
DOI: 10.3390/ijms21186894 -
Cartilage Dec 2021Chondroprogenitors have recently gained prominence due to promising results seen in and animal studies as a potential contender in cell-based therapy for cartilage...
OBJECTIVE
Chondroprogenitors have recently gained prominence due to promising results seen in and animal studies as a potential contender in cell-based therapy for cartilage repair. Lack of consensus regarding nomenclature, isolation techniques, and expansion protocols create substantial limitations for translational research, especially given the absence of distinct markers of identification. The objective of this systematic review was to identify and collate information pertaining to hyaline cartilage-derived chondroprogenitors, with regard to their isolation, culture, and outcome measures.
DESIGN
As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a web-based search of Scopus and PubMed databases was performed from January 2000 to May 2020, which yielded 509 studies. A total of 65 studies were identified that met the standardized inclusion criteria which comprised of, but was not limited to, progenitors derived from fibronectin adhesion, migrated subpopulation from explant cultures, and single-cell sorting.
RESULT
Literature search revealed that progenitors demonstrated inherent chondrogenesis and minimal tendency for hypertrophy. Multiple sources also demonstrated significantly better outcomes that bone marrow-derived mesenchymal stem cells and comparable results to chondrocytes. With regard to progenitor subgroups, collated evidence points to better and consistent outcomes with the use of migratory progenitors when compared to fibronectin adhesion assay-derived progenitors, although a direct comparison between the two cell populations is warranted.
CONCLUSION
Since chondroprogenitors exhibit favorable properties for cartilage repair, efficient characterization of progenitors is imperative, to complete their phenotypic profile, so as to optimize their use in translational research for neocartilage formation.
Topics: Animals; Cartilage, Articular; Chondrocytes; Chondrogenesis; Hyaline Cartilage; Mesenchymal Stem Cells
PubMed: 32840123
DOI: 10.1177/1947603520951631 -
BioMed Research International 2020To systematically evaluate the effects of red yeast rice (RYR) and its extract on bone formation in experimental animals and to provide reference data for clinical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the effects of red yeast rice (RYR) and its extract on bone formation in experimental animals and to provide reference data for clinical research on the treatment of osteoporosis.
METHODS
Chinese and English language databases, including Web of Science, PubMed, the Cochrane Library, Elsevier, Google Scholar, SpringerLink, Embase, China National Knowledge Infrastructure (CNKI), Weipu Chinese Sci-tech periodical full-text database (VIP), and Wanfang Data Knowledge Service Platform (Wanfang), were searched from their establishment to February 2020 using the following terms: "hongqu," "red yeast rice," "-fermented rice," "bone mineral density," "osteoblast," "osteoporosis," and "animal models." After excluding nonrelevant articles, Review Manager 5.2 was used to evaluate article quality and to analyze the data. Outcome indicators included bone mineral density (BMD), osteoblast proliferation, and the expression of alkaline phosphatase (ALP).
RESULTS
A total of 11 randomized controlled trials were included in the meta-analysis, all of which were animal studies. Six studies included data on BMD, five on osteoblast proliferation, and six on the expression of ALP. The results of the meta-analysis showed that RYR can significantly improve BMD (standardized mean difference (SMD) = 3.12, 95% confidence interval (CI) 1.41 to 4.83, = 0.0003), promote osteoblast proliferation (SMD = 1.64, 95% CI 1.04 to 2.23, < 0.00001), and increase ALP expression in rats (SMD = 1.25, 95% CI 0.69 to 1.80, < 0.00001).
CONCLUSIONS
RYR can promote bone formation in experimental animals and may be useful for the treatment of osteoporosis.
Topics: Animals; Biological Products; Bone Density; Cell Proliferation; Humans; Osteoblasts; Osteogenesis; Osteoporosis
PubMed: 32832555
DOI: 10.1155/2020/7231827 -
PloS One 2020Recent results have established that masticatory function plays a role not only in the balance of the stomatognathic system and in the central motor control, but also in...
Altered mastication adversely impacts morpho-functional features of the hippocampus: A systematic review on animal studies in three different experimental conditions involving the masticatory function.
Recent results have established that masticatory function plays a role not only in the balance of the stomatognathic system and in the central motor control, but also in the trophism of the hippocampus and in the cognitive activity. These implications have been shown in clinical studies and in animal researches as well, by means of histological, biochemical and behavioural techniques. This systematic review describes the effects of three forms of experimentally altered mastication, namely soft-diet feeding, molar extraction and bite-raising, on the trophism and function of the hippocampus in animal models. Through a systematic search of PubMed, Embase, Web of Science, Scopus, OpenGray and GrayMatters, 645 articles were identified, 33 full text articles were assessed for eligibility and 28 articles were included in the review process. The comprehensiveness of reporting was evaluated with the ARRIVE guidelines and the risk of bias with the SYRCLE RoB tool. The literature reviewed agrees that a disturbed mastication is significantly associated with a reduced number of hippocampal pyramidal neurons in Cornu Ammonis (CA)1 and CA3, downregulation of Brain Derived Neurotrophic Factor (BDNF), reduced synaptic activity, reduced neurogenesis in the Dentate Gyrus (DG), glial proliferation, and reduced performances in behavioural tests, indicating memory impairment and reduced spatial orientation. Moreover, while the bite-raised condition, characterized by occlusal instability, is known to be a source of stress, soft-diet feeding and molar extractions were not consistently associated with a stress response. More research is needed to clarify this topic. The emerging role of chewing in the preservation of hippocampal trophism, neurogenesis and synaptic activity is worthy of interest and may contribute to the study of neurodegenerative diseases in new and potentially relevant ways.
Topics: Animals; Cognition; Dentate Gyrus; Hippocampus; Humans; Mastication; Memory Disorders; Models, Animal; Neurogenesis; Neurons
PubMed: 32817680
DOI: 10.1371/journal.pone.0237872 -
Foot and Ankle Surgery : Official... Apr 2021The aim of this study is to systematically review the literature on clinical outcomes of patients who have undergone autologous matrix-induced chondrogenesis (AMIC) for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study is to systematically review the literature on clinical outcomes of patients who have undergone autologous matrix-induced chondrogenesis (AMIC) for treatment of osteochondral lesions of the talus (OCL) and compare the studies' outcomes.
METHODS
Pubmed and Embase were searched in January 2020 for articles concerning OCL surgery. Studies were included if they had a minimum 1-year follow-up and the primary measures were functional outcomes. The meta-analysis compared the Visual Analogic Score (VAS), the American Orthopedic Foot and Ankle Score (AOFAS), and the Foot Function Index (FFI) between baseline and follow-up of 1-2years, and 3-5years. A random effects model was used to evaluate outcome changes.
RESULTS
The search returned 15 studies, with a total of 492 patients. The VAS improved 4.45 and 4.6 points from baseline to the 1-2year and 3-5yearfollow-up, respectively (p<0.001). AOFAS improved 31.59 and 32.47 points from baseline to the 1-2year and 3-5yearfollow-up, respectively (p<0.001). The FFI showed a significant improvement of 30.93 points from baseline to year 3-5 (p<0.001). A total of 6 patients with revision surgeries have been reported within the follow up period. It was not possible to correlate clinical features like lesion size, surgical approach, and bone marrow stimulation technique to the reported outcome.
CONCLUSION
Surgical treatment of OCL via the AMIC procedure provided significant improvement in the functional outcome and pain scores when compared to the pre-operative values. Improvements were observed up to 5years post-operatively.
Topics: Adolescent; Adult; Aged; Ankle Injuries; Ankle Joint; Cartilage, Articular; Child; Chondrogenesis; Female; Follow-Up Studies; Humans; Intra-Articular Fractures; Male; Middle Aged; Reoperation; Talus; Transplantation, Autologous; Treatment Outcome; Visual Analog Scale; Young Adult
PubMed: 32811744
DOI: 10.1016/j.fas.2020.07.011 -
Arteriosclerosis, Thrombosis, and... Oct 2020There has been little success in translating preclinical studies of mouse hind limb ischemia into benefit for patients with peripheral artery disease. Using systematic...
OBJECTIVE
There has been little success in translating preclinical studies of mouse hind limb ischemia into benefit for patients with peripheral artery disease. Using systematic strategies, we sought to define the injury and angiogenesis landscapes in mice subjected to hind limb ischemia and ascertain whether published studies to date have used an analysis strategy concordant with these data. Approach and Results: Maps of ischemic injury were generated from 22 different hind limb muscles and 33 muscle territories in 12-week-old C57BL/6 mice, based on loss or centralization of myofiber nuclei. Angiogenesis was similarly mapped based on CD (cluster of differentiation) 31-positive capillary content. Only 10 of 33 muscle territories displayed consistent muscle injury, with the distal anterior hind limb muscles most reliably injured. Angiogenesis was patchy and exclusively associated with zones of regenerated muscle (central nuclei). Angiogenesis was not observed in normal appearing muscle, necrotic muscle, or injury border zones. Systematic review of mouse hind limb angiogenesis studies identified 5147 unique publications, of which 509 met eligibility criteria for analysis. Only 7% of these analyzed manuscripts evaluated angiogenesis in distal anterior hind limb muscles and only 15% consistently examined for angiogenesis in zones of muscle regeneration.
CONCLUSIONS
In 12-week C57BL/6 mice, angiogenesis postfemoral artery excision proceeds exclusively in zones of muscle regeneration. Only a minority of studies to date have analyzed angiogenesis in regions of demonstrably regenerating muscle or in high-likelihood territories. Quality assurance standards, informed by the atlas and mapping data herein, could augment data reliability and potentially help translate mouse hind limb ischemia studies to patient care.
Topics: Animals; Data Accuracy; Disease Models, Animal; Hindlimb; Ischemia; Male; Mice, Inbred C57BL; Muscle Development; Muscle, Skeletal; Necrosis; Neovascularization, Physiologic; Regeneration; Regional Blood Flow; Research Design; Time Factors
PubMed: 32787524
DOI: 10.1161/ATVBAHA.120.315028 -
Nutrients Aug 2020Osteoporosis and associated low energy fractures are a significant clinical problem, especially in the elderly population. The occurrence of a hip fracture is associated...
Osteoporosis and associated low energy fractures are a significant clinical problem, especially in the elderly population. The occurrence of a hip fracture is associated with significant mortality and a high risk of disability. For this, apart from the treatment of osteoporosis, effective prevention of both the development of the disease and related fractures is extremely important. One aspect of osteoporosis prevention is proper dietary calcium intake and normal vitamin D3 levels. However, there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention, too. This review aims to summarize the current knowledge about the role of vitamin C in osteoporosis development, prevention and treatment. The PubMed/Medline search on the role of vitamin C in bone metabolism database was performed for articles between 2000 and May 2020. Reports from in vitro and animal studies seem promising. Epidemiological studies also indicate the positive effect of high vitamin C content in the daily diet on bone mineral density. Despite promising observations, there are still few observational and intervention studies and their results do not allow for unequivocal determination of the benefits of high daily intake of vitamin C or its long-term supplementation.
Topics: Animals; Ascorbic Acid; Bone Density; Bone and Bones; Cell Line; Dietary Supplements; Fractures, Spontaneous; Humans; Nutritional Physiological Phenomena; Osteogenesis; Osteoporosis
PubMed: 32785080
DOI: 10.3390/nu12082394 -
Nutrients Jul 2020Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Although dietary and, in some cases, pharmacological treatment has been successful in...
Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Although dietary and, in some cases, pharmacological treatment has been successful in preventing intellectual disability in PKU patients who are treated early, suboptimal outcomes have been reported, including bone mineral disease. In this systematic review, we summarize the available evidence on bone health in PKU patients, including data on bone mineral density (BMD) and bone turnover marker data. Data from cohort and cross-sectional studies of children and adults (up to 40 years of age) were obtained by searching the MEDLINE and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For each selected study, quality assessment was performed applying the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS I) tool. We found that mean BMD was lower in PKU patients than in reference groups, but was within the normal range in most patients when expressed as Z-score values. Furthermore, data revealed a trend towards an imbalance between bone formation and bone resorption, favoring bone removal. Data on serum levels of minerals and hormones involved in bone metabolism were very heterogeneous, and the analyses were inconclusive. Clinical trials that include the analysis of fracture rates, especially in older patients, are needed to gather more evidence on the clinical implications of lower BMD in PKU patients.
Topics: Adolescent; Adult; Bone Density; Bone Remodeling; Bone Resorption; Bone and Bones; Child; Cohort Studies; Cross-Sectional Studies; Diet, Protein-Restricted; Female; Fractures, Bone; Humans; Male; Osteogenesis; Phenylalanine; Phenylketonurias; Young Adult
PubMed: 32698408
DOI: 10.3390/nu12072154 -
Brazilian Dental Journal 2020Several studies have aimed to develop alternative therapeutic biomaterials for bone repair. The purpose of this systematic review was to evaluate how statins carried by... (Meta-Analysis)
Meta-Analysis
Several studies have aimed to develop alternative therapeutic biomaterials for bone repair. The purpose of this systematic review was to evaluate how statins carried by calcium phosphate affect the formation and regeneration of bone tissue in animal models when compared to other biomaterials or spontaneous healing. This systematic review followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, the PRISMA guidelines, and the Preclinical Systematic Review & Meta-analysis Facility (SyRF). The protocol of this systematic review was registered in PROSPERO (CRD42018091112) and in CAMARADES. In addition, ARRIVE checklists were followed in order to increase the quality and transparency of the search. An electronic search was performed using the MEDLINE/PubMed, Scopus, SciELO, and PROSPERO library databases. The authors used a specific search strategy for each database, and they also conducted a search in the grey literature and cross-references. The eligibility criteria were animal studies, which evaluated bone repair treated with calcium phosphate as a simvastatin carrier. The selection process yielded 8 studies from the 657 retrieved. All manuscripts concluded that locally applied simvastatin carried by calcium phosphate is biocompatible, enhanced bone repair and induced statistically greater bone formation than cloth or calcium phosphate alone. In conclusion, the pertinent pre-clinical studies evidenced the calcium phosphate biocompatibility and its effectiveness in delivering SIM to improve the repair of bone defects. So, clinical trials are encouraged to investigate the impact of SIM associated with calcium phosphate bone graft in repairing bone defect in humans.
Topics: Animals; Bone Regeneration; Bone Transplantation; Calcium Phosphates; Humans; Osteogenesis; Simvastatin
PubMed: 32556021
DOI: 10.1590/0103-6440202002971