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Pharmacological Research Nov 2022As the worldwide population progresses in age, there is an increasing need for effective treatments for age-associated musculoskeletal conditions such as osteoporosis... (Review)
Review
As the worldwide population progresses in age, there is an increasing need for effective treatments for age-associated musculoskeletal conditions such as osteoporosis and osteoarthritis (OA). Fisetin, a natural flavonoid, has garnered attention as a promising pharmaceutical option for treating or delaying the progression of osteoporosis and OA. However, there is no systematic review of the effects of fisetin on bone and cartilage. The aim of this review is to report the latest evidence on the effects of fisetin on bone and cartilage, with a focus on clinical significance. The PubMed, Embase, and Cochrane Library databases were searched up to December 9th 2021 to evaluate the effects of fisetin on bone and cartilage in in vitro studies and in vivo preclinical animal studies. The risk of bias, quality, study design, sample characteristics, dose and duration of fisetin treatment, and outcomes of the 13 eligible studies were analyzed in this systematic review. Qualitative evaluation was conducted for each study due to differences in animal species, cell type, created disease model, dose and duration of fisetin treatment, and time between intervention and assessment among the eligible studies. The beneficial effects of fisetin on osteoporosis have been demonstrated in in vitro and in vivo preclinical studies across animal species. Similarly, the beneficial effects of fisetin on OA have been demonstrated in in vivo preclinical animal studies, but the reports on OA are still limited. Fisetin, a natural supplement can be use in orthobiologics treatment, as adjuvant to orthopaedic surgery, to improve clinical outcome.
Topics: Animals; Flavonols; Osteoarthritis; Osteoporosis; Cartilage
PubMed: 36243333
DOI: 10.1016/j.phrs.2022.106504 -
Stem Cell Reviews and Reports Mar 2022Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of tumor growth. Studies remain preclinical with effects ranging... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of tumor growth. Studies remain preclinical with effects ranging from inhibition of tumor growth to cancer progression. A systematic review and meta-analysis is needed to clarify the effect of MSC-EVs on tumor growth to facilitate potential translation to clinical trials.
METHODS
A systematic search of the literature (MEDLINE, Embase, and BIOSIS databases to June 1, 2019) identified all pre-clinical controlled studies investigating the effect of MSC-EVs on tumor growth. Study selection and data extraction were performed in duplicate. Potential risk of bias was assessed using the SYRCLE tool. A random effects meta-analysis of reduction in tumor weight/volume (primary outcome) was performed.
RESULTS
We identified 29 articles and 22 reported data on tumor responses that were included for meta-analysis. Studies were associated with unclear risk of bias in a large proportion of domains in accordance with the SYRCLE tool for determining risk of bias in preclinical studies. A high risk of bias was not identified in any study. MSC-EVs had a mixed response on tumor progression with some studies reporting inhibition of tumor growth and others reporting tumor progression. Overall, MSC-EVs exerted a non-significant reduction in tumor growth compared to controls (standardized mean difference (SMD) -0.80, 95 % CI -1.64 to 0.03, p = 0.06, I = 87 %). Some studies reported increased tumor growth which aligned with their stated hypothesis and some interrogated mechanisms in cancer biology. EVs isolated from MSCs that overexpressed anti-tumor RNAs were associated with significant tumor reduction in meta-analysis (SMD - 2.40, 95 % CI -3.36 to -1.44, p < 0.001). Heterogeneity between studies was observed and included aspects of study design such as enrichment of MSC-EVs with specific anti-tumor molecules, tissue source of MSCs, method of EV isolation, characterization of MSCs and EVs, dosage and administration schedules, and tissue type and source of tumor cells studied.
CONCLUSIONS
MSC-EVs are associated with mixed effects on tumor growth in animal models of cancer. In studies where anti-tumor RNAs are packaged in EVs, a significant reduction in tumor growth was observed. Reducing heterogeneity in study design may accelerate our understanding of the potential effects of MSC-EVs on cancer. [274 words] Forest plot of MSC-EV effect on tumor growth accordinggenetic modification of EVs in animal studies identified from a systematicreview of the literature. All cohorts from studies with multiple interventiongroups are presented separately with control groups divided equally among thegroups. M, modified; H, hypoxia.
Topics: Animals; Disease Models, Animal; Extracellular Vesicles; Mesenchymal Stem Cells; Neoplasms
PubMed: 33860455
DOI: 10.1007/s12015-021-10163-5 -
Frontiers in Physiology 2018Astragaloside IV (AS-IV), the major pharmacological extract from , possesses a variety of biological activities in the cardiovascular systems. Here, we aimed to evaluate...
Astragaloside IV (AS-IV), the major pharmacological extract from , possesses a variety of biological activities in the cardiovascular systems. Here, we aimed to evaluate preclinical evidence and possible mechanism of AS-IV for animal models of myocardial ischemia/reperfusion (I/R) injury. Studies of AS-IV in animal models with myocardial I/R injury were identified from 6 databases from inception to May, 2018. The methodological quality was assessed by using CAMARADES 10-item checklist. All the data were analyzed using Rev-Man 5.3 software. As a result, 22 studies with 484 animals were identified. The quality score of studies ranged from 3 to 6 points. Meta-analyses showed AS-IV can significantly decrease the myocardial infarct size and left ventricular ejection fraction, and increase shortening fraction compared with control group ( < 0.01). Significant decreasing of cardiac enzymes and cardiac troponin and increasing of decline degree in ST-segment were reported in one study each ( < 0.05). Additionally, the possible mechanisms of AS-IV for myocardial I/R injury are promoting angiogenesis, improving the circulation, antioxidant, anti-inflammatory and anti-apoptosis. Thus, AS-IV is a potential cardioprotective candidate for further clinical trials of myocardial infarction.
PubMed: 30018562
DOI: 10.3389/fphys.2018.00795 -
BMJ Open Science 2020Currently there is a paucity of clinically available regenerative therapies for stroke. Extracellular vesicles (EV) have been investigated for their potential as...
OBJECTIVES
Currently there is a paucity of clinically available regenerative therapies for stroke. Extracellular vesicles (EV) have been investigated for their potential as modulators of regeneration in the poststroke brain. This systematic review and meta-analysis aims to provide a summary of the efficacy of therapeutic EVs in preclinical stroke models, to inform future research in this emerging field.
METHODS
Studies were identified by a comprehensive literature search of two online sources and subsequent screening. Studies using lesion volume or neurological score as outcome measures were included. Standardised mean difference (SMD) and 95% CIs were calculated using a restricted maximum likelihood random effects model. Publication bias was assessed with Egger's regression and presented as funnel plots with trim and fill analysis. Subgroup analysis was performed to assess the effects of different study variables. Study quality and risk of bias were assessed using the CAMARADES checklist.
RESULTS
A total of 20 publications were included in the systematic review, of which 19 were assessed in the meta-analysis (43 comparisons). Overall, EV interventions improved lesion volume (SMD: -1.95, 95% CI -2.72 to 1.18) and neurological scores (SMD: -1.26, 95% CI -1.64 to 0.87) compared with control groups. Funnel plots were asymmetrical suggesting publication bias, and trim and fill analysis predicted seven missing studies for lesion volume. Subgroup analysis suggested administration at 0-23 hours after stroke was the most effective timepoint for EV treatment. The median score on the CAMARADES checklist was 7 (IQR: 5-8).
CONCLUSIONS
EVs may offer a promising new avenue for stroke therapies, as EV-based interventions had positive impacts on lesion volume and neurological score in preclinical stroke models.
PROSPERO REGISTRATION NUMBER
CRD42019134925.
PubMed: 35047689
DOI: 10.1136/bmjos-2019-100047 -
PloS One 2017Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating neurologic condition with high mortality rates and long-term complications for surviving infants.... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating neurologic condition with high mortality rates and long-term complications for surviving infants. Mesenchymal stem/stromal cells (MSCs) have emerged as novel therapeutic agents with promising results in experimental studies of HIE. The purpose of this study is to (a) methodically review the current preclinical literature describing MSC therapy in animal models of HIE, (b) quantify the effect size in regards to functional neurologic outcome, and (c) identify research gaps/limitations that should be addressed prior to future preclinical and clinical studies.
METHODS
Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed. Eligible studies were identified and data regarding study characteristics and outcome measures was extracted. After quality assessment, meta-analysis and meta-regression were performed to generate random effect size using standardized mean difference (SMD). Funnel plots and Egger's tests were utilized to evaluate for the presence of publication bias.
RESULTS
A total of 19 studies met inclusion in the current systematic review. Meta-analysis revealed that MSCs have a significant positive effect on neurobehavioral outcome following HIE injury. Sensorimotor function was improved by 2.25 SMD (95% CI; 2.04-2.46) in cylinder rearing and 2.97 SMD (95% CI; 2.56-3.38) in rotarod. Likewise, cognitive function was improved by 2.76 SMD (95% CI; 2.53-2.98) on the water maze and 2.97 SMD (95% CI; 2.58-3.35) in object recognition. Stratification demonstrated an increased effect size depending on various study characteristics.
CONCLUSIONS
Overall, these results suggest a promising role for MSCs in preclinical studies of HIE. MSC treatment demonstrates improved functional outcomes that are encouraging for future translational studies. While risk of bias and heterogeneity limited the strength of our meta-analysis, our results are consistent with those seen in this field of research.
Topics: Animals; Cognition; Humans; Hypoxia-Ischemia, Brain; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Publication Bias; Treatment Outcome
PubMed: 29261798
DOI: 10.1371/journal.pone.0189895 -
Frontiers in Pharmacology 2023Myocardial ischemia-reperfusion (I/R) injury is a complex clinical problem that often leads to further myocardial injury. Curcumin is the main component of turmeric,...
Myocardial ischemia-reperfusion (I/R) injury is a complex clinical problem that often leads to further myocardial injury. Curcumin is the main component of turmeric, which has been proved to have many cardioprotective effects. However, the cardioprotective potential of curcumin remains unclear. The present systematic review and meta-analysis aimed to evaluate the clinical and preclinical (animal model) evidence regarding the effect of curcumin on myocardial I/R injury. Eight databases and three register systems were searched from inception to 1 November 2022. Data extraction, study quality assessment, data analyses were carried out strictly. Then a fixed or random-effects model was applied to analyze the outcomes. SYRCLE's-RoB tool and RoB-2 tool was used to assess the methodological quality of the included studies. RevMan 5.4 software and stata 15.1 software were used for statistical analysis. 24 animal studies, with a total of 503 animals, and four human studies, with a total of 435 patients, were included in this study. The meta-analysis of animal studies demonstrated that compared with the control group, curcumin significantly reduced myocardial infarction size ( < 0.00001), and improved the cardiac function indexes (LVEF, LVFS, LVEDd, and LVESd) ( < 0.01). In addition, the indexes of myocardial injury markers, myocardial oxidation, myocardial apoptosis, inflammation, and other mechanism indicators also showed the beneficial effect of curcumin ( < 0.05). In terms of clinical studies, curcumin reduced the incidence of cardiac dysfunction, myocardial infarction in the hospital and MACE in the short term, which might be related to its anti-inflammatory and anti-oxidative property. Dose-response meta-analysis predicted, 200 mg/kg/d bodyweight was the optimal dose of curcumin in the range of 10-200 mg/kg/d, which was safe and non-toxic according to the existing publications. Our study is the first meta-analysis that includes both preclinical and clinical researches. We suggested that curcumin might play a cardioprotective role in acute myocardial infarction in animal studies, mainly through anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis effects. In addition, from the clinical studies, we found that curcumin might need a longer course of treatment and a larger dose to protect the myocardium, and its efficacy is mainly reflected on reducing the incidence of myocardial infarction and MACE. Our finding provides some meaningful advice for the further research.
PubMed: 36969839
DOI: 10.3389/fphar.2023.1111459 -
Experimental Biology and Medicine... Jul 2016We systematically reviewed published preclinical studies to evaluate the effectiveness of cell-seeded tissue engineering approach for urethral reconstruction in an... (Meta-Analysis)
Meta-Analysis Review
We systematically reviewed published preclinical studies to evaluate the effectiveness of cell-seeded tissue engineering approach for urethral reconstruction in an animal model. The outcomes were summarized by success factors in the animal experiments, which evaluate the possibility and feasibility of a clinical application in the future. Preclinical studies of tissue engineering approaches for urethral reconstruction were identified through a systematic search in PubMed, Embase, and Biosis Previews (web of science SP) databases for studies published from 1 January 1980 to 23 November 2014. Primary studies were included if urethral reconstruction was performed using a tissue-engineered biomaterial in any animal species (with the experiment group being a cell-seeded scaffold and the control group being a cell-free scaffold) with histology and urethrography as the outcome measure. A total of 15 preclinical studies were included in our meta-analysis. The histology and urethrography outcome between the experimental and control groups were considered to be the most clinically relevant. Through this systematic approach, our outcomes suggested that applying the cell-seeded biomaterial in creating a neo-urethra was stable and effective. And multi-type cells including epithelial cells as well as smooth muscle cells or fibroblasts seemed to be a better strategy. Stem cells, especially after epithelial differentiation, could be a promising choice for future researches.
Topics: Animals; Dogs; Female; Male; Rabbits; Plastic Surgery Procedures; Regenerative Medicine; Tissue Engineering; Tissue Scaffolds; Urethra
PubMed: 27022134
DOI: 10.1177/1535370216640148 -
Bioengineering (Basel, Switzerland) Sep 2022Though surgical techniques profoundly influence in vivo experiments, significant heterogeneity exists in current surgeries for inducing rat femoral bone defects. Such... (Review)
Review
Though surgical techniques profoundly influence in vivo experiments, significant heterogeneity exists in current surgeries for inducing rat femoral bone defects. Such variations reduce the reproducibility and comparability of preclinical studies, and are detrimental to clinical translation. The purposes of this study were: (1) to conduct a systematic review of rat femoral defect models, summarizing and analyzing the surgical techniques; (2) to analyze surgical design and potential pitfalls via 3D anatomy and virtual surgeries for fostering future precision research; and (3) to establish a surgical classification system, for improving the reproducibility and comparability among studies, avoiding unnecessary repetitive experiments. The online database PubMed was searched to identify studies from January 2000 to June 2022 using keywords, including rat, femur, bone defect. Eligible publications were included for a review of surgical methods. Anatomical analysis and virtual surgeries were conducted based on micro-CT reconstruction of the rat femur for further investigation and establishment of a classification system. A total of 545 publications were included, revealing marked heterogeneity in surgical methods. Four major surgical designs were reported for inducing defects from the proximal to distal femur: bone tunnel, cortical window, segmental defect, and wedge-shaped defect. Anatomical analysis revealed potential pitfalls hindering efficient clinical translation. A classification system was established according to the anatomical region, surgical design, and fixation devices. This systematic review in combination with 3D analysis and virtual surgery provides a general overview of current surgical approaches to inducing femoral defects in rats, and establishes a surgical classification facilitating preclinical research of quality and translational value.
PubMed: 36135022
DOI: 10.3390/bioengineering9090476 -
Acta Neurochirurgica Jan 2017Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In... (Review)
Review
BACKGROUND
Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma.
METHODS
We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.
RESULTS
The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.
CONCLUSIONS
5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.
Topics: Aminolevulinic Acid; Animals; Brain Neoplasms; Fluorescent Dyes; Glioma; Humans; Neurosurgical Procedures; Photosensitizing Agents
PubMed: 27878374
DOI: 10.1007/s00701-016-3028-5 -
Molecules (Basel, Switzerland) Nov 2020The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an...
The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity.
Topics: Arthritis, Rheumatoid; Betacoronavirus; COVID-19; Chikungunya Fever; Chikungunya virus; Coronavirus Infections; Drug Administration Schedule; HIV; HIV Infections; Humans; Hydroxychloroquine; Lupus Erythematosus, Systemic; Pandemics; Pneumonia, Viral; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Sjogren's Syndrome; Zika Virus; Zika Virus Infection
PubMed: 33202656
DOI: 10.3390/molecules25225318