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Current Neuropharmacology 2023Compelling evidence from preclinical and clinical studies supports the therapeutic role of cannabidiol (CBD) in several medical disorders. We reviewed the scientific...
BACKGROUND
Compelling evidence from preclinical and clinical studies supports the therapeutic role of cannabidiol (CBD) in several medical disorders. We reviewed the scientific evidence on CBD-related toxicity and adverse events (AEs) in 2019, at the beginning of the spike in clinical studies involving CBD. However, CBD safety remained uncertain.
OBJECTIVE
With the benefit of hindsight, we aimed to provide an update on CBD-related toxicity and AEs in humans.
METHODS
A systematic literature search was conducted following PRISMA guidelines. PubMed, Cochrane, and Embase were accessed in October 2022 to identify clinical studies mentioning CBDrelated toxicity/AEs from February 2019 to September 2022. Study design, population characteristics, CBD doses, treatment duration, co-medications, and AEs were compiled.
RESULTS
A total of 51 reports were included. Most studies investigated CBD efficacy and safety in neurological conditions, such as treatment-resistant epilepsies, although a growing number of studies are focusing on specific psychopathological conditions, such as substance use disorders, chronic psychosis, and anxiety. Most studies report mild or moderate severity of AEs. The most common AEs are diarrhea, somnolence, sedation, and upper respiratory disturbances. Few serious AEs have been reported, especially when CBD is co-administered with other classes of drugs, such as clobazam and valproate.
CONCLUSION
Clinical data suggest that CBD is well tolerated and associated with few serious AEs at therapeutic doses both in children and adults. However, interactions with other medications should be monitored carefully. Additional data are needed to investigate CBD's long-term efficacy and safety, and CBD use in medical conditions other than epilepsy syndromes.
Topics: Child; Adult; Humans; Cannabidiol; Epilepsy; Anxiety; Anticonvulsants
PubMed: 36946485
DOI: 10.2174/1570159X21666230322143401 -
Journal of Nanobiotechnology Oct 2023This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area.
METHODS
We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1β, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software.
RESULTS
A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1β: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6-9).
CONCLUSIONS
This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS.
PROSPERO REGISTRATION NUMBER
CRD42022368744.
Topics: Animals; Ischemic Stroke; Interleukin-6; Tumor Necrosis Factor-alpha; Extracellular Vesicles; Infarction
PubMed: 37904204
DOI: 10.1186/s12951-023-02114-8 -
Brain Circulation 2022Ischemic stroke is a disease with worldwide economic and social negative effects. It is a serious disease with high disability and mortality. Ionic imbalance,... (Review)
Review
Ischemic stroke is a disease with worldwide economic and social negative effects. It is a serious disease with high disability and mortality. Ionic imbalance, excitotoxicity, oxidative stress, and inflammation are induced during and after ischemic stroke. Cellular dysfunction, apoptosis, and necrosis are activated directly or indirectly mechanisms. The studies about neuroprotection in neurodegenerative diseases have increased in recent years. Data about the mechanisms of progressive molecular improvement in the brain tissue are increasing in acute ischemic stroke. Based on these data, preclinical and clinical studies on new neuroprotective treatments are being designed. An effective neuroprotective strategy can prolong the indication period of recanalization treatments in the acute stage of ischemic stroke. In addition, it can reduce neuronal necrosis and protect the brain against ischemia-related reperfusion injury. The current review has evaluated the recent clinical and experimental studies. The molecular mechanism of each of the neuroprotective strategies is also summarized. This review may help develop future strategies for combination treatment to protect the cerebral tissue from ischemia-reperfusion injury.
PubMed: 37181847
DOI: 10.4103/bc.bc_52_22 -
Journal of Functional Biomaterials May 2023Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes... (Review)
Review
Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon-bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a "snowball" search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon-bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon-bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon-bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials.
PubMed: 37367263
DOI: 10.3390/jfb14060299 -
Dental and Medical Problems 2023Dental education is taking its share of the digitalization of the world. Therefore, it is of value to assess the use of the digital dental education system, especially... (Review)
Review
BACKGROUND
Dental education is taking its share of the digitalization of the world. Therefore, it is of value to assess the use of the digital dental education system, especially in the undergraduate period.
OBJECTIVES
This systematic review concisely evaluated the use of augmented and virtual reality in preclinical dental education.
MATERIAL AND METHODS
The PICOS (Population, Intervention, Comparison, Outcome, and Study design) search strategy was used with the keywords 'e-learning', 'virtual reality' and 'preclinic simulation' to search the PubMed, PubMed Central, Web of Science, and Scopus databases.
RESULTS
A total of 1,774 articles were found, and 45 articles were reviewed. The level of bias in the studies was also calculated. The studies were divided into 3 main groups: computer-assisted learning (C-AL); augmented reality-assisted learning (AR-AL); and virtual reality-assisted learning (VR-AL). Augmented and virtual reality are steadily evolving, and are increasingly being used in education and healthcare.
CONCLUSIONS
The evaluated technological applications enable the visualization of medical information and provide clear feedback during the learning process with increased security and reliability; thus, digital simulation systems can be used to enhance students' abilities in dentistry.
PubMed: 37747703
DOI: 10.17219/dmp/156804 -
Stem Cell Research & Therapy Apr 2023The increasing incidence of osteoporosis in recent years has aroused widespread public concern; however, existing effective treatments are limited. Therefore, new... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The increasing incidence of osteoporosis in recent years has aroused widespread public concern; however, existing effective treatments are limited. Therefore, new osteoporosis treatment methods, including stem cell transplantation and exosome therapy, have been proposed and are gaining momentum. Exosomes are considered to have greater potential for clinical application owing to their immunocompatibility. This study summarises the latest evidence demonstrating the efficacy of exosomes in improving bone loss in the treatment of osteoporosis.
MAIN TEXT
This systematic review and meta-analyses searched PubMed, Embase, and Cochrane Library databases from inception to 26 March 2022 for osteoporosis treatment studies using stem cell-derived exosomes. Six endpoints were selected to determine efficacy: bone mineral density, trabecular bone volume/tissue volume fraction, trabecular number, trabecular separation, trabecular thickness, and cortical thickness. The search generated 366 citations. Eventually, 11 articles that included 15 controlled preclinical trials and 242 experimental animals (rats and mice) were included in the meta-analysis.
CONCLUSION
The results were relatively robust and reliable despite some publication biases, suggesting that exosome treatment increased bone mass, improved bone microarchitecture, and enhanced bone strength compared with placebo treatments. Moreover, stem cell-derived exosomes may favour anabolism over catabolism, shifting the dynamic balance towards bone regeneration.
Topics: Rats; Mice; Animals; Exosomes; Osteoporosis; Bone Density; Bone and Bones; Treatment Outcome
PubMed: 37038180
DOI: 10.1186/s13287-023-03317-4 -
The Lancet. Microbe Dec 2022Antimicrobial resistance of bacterial pathogens is an increasing clinical problem and alternative approaches to antibiotic chemotherapy are needed. One of these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antimicrobial resistance of bacterial pathogens is an increasing clinical problem and alternative approaches to antibiotic chemotherapy are needed. One of these approaches is the use of lytic bacterial viruses known as phage therapy. We aimed to assess the efficacy of phage therapy in preclinical animal models of bacterial infection.
METHODS
In this systematic review and meta-analysis, MEDLINE/Ovid, Embase/Ovid, CINAHL/EbscoHOST, Web of Science/Wiley, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar were searched from inception to Sept 30, 2021. Studies assessing phage efficacy in animal models were included. Only studies that assessed the efficacy of phage therapy in treating established bacterial infections in terms of survival and bacterial abundance or density were included. Studies reporting only in-vitro or ex-vivo results and those with incomplete information were excluded. Risk-of-bias assessment was performed using the Systematic Review Centre for Laboratory Animal Experimentation tool. The main endpoints were animal survival and tissue bacterial burden, which were reported using pooled odds ratios (ORs) and mean differences with random-effects models. The I measure and its 95% CI were also calculated. This study is registered with PROSPERO, CRD42022311309.
FINDINGS
Of the 5084 references screened, 124 studies fulfilled the selection criteria. Risk of bias was high for 70 (56%) of the 124 included studies; therefore, only studies classified as having a low-to-moderate risk of bias were considered for quantitative data synthesis (n=32). Phage therapy was associated with significantly improved survival at 24 h in systemic infection models (OR 0·08 [95% CI 0·03 to 0·20]; I=55% [95% CI 8 to 77]), skin infection (OR 0·08 [0·04 to 0·19]; I = 0% [0 to 79]), and pneumonia models (OR 0·13 [0·06 to 0·31]; I=0% [0 to 68]) when compared with placebo. Animals with skin infections (mean difference -2·66 [95% CI -3·17 to -2·16]; I = 95% [90 to 96]) and those with pneumonia (mean difference -3·35 [-6·00 to -0·69]; I = 99% [98 to 99]) treated with phage therapy had significantly lower tissue bacterial loads at 5 ± 2 days of follow-up compared with placebo.
INTERPRETATION
Phage therapy significantly improved animal survival and reduced organ bacterial loads compared with placebo in preclinical animal models. However, high heterogeneity was observed in some comparisons. More evidence is needed to identify the factors influencing phage therapy performance to improve future clinical application.
FUNDING
Swiss National Foundation and Swiss Heart Foundation.
Topics: Humans; Phage Therapy; Bacterial Infections; Anti-Bacterial Agents
PubMed: 36370748
DOI: 10.1016/S2666-5247(22)00288-9 -
Frontiers in Pharmacology 2022Psoriasis is a chronic and immune-mediated inflammatory skin disease. Many studies have shown that curcumin (CUR) has strong anti-inflammatory effects and can improve...
Psoriasis is a chronic and immune-mediated inflammatory skin disease. Many studies have shown that curcumin (CUR) has strong anti-inflammatory effects and can improve psoriasis; however, its efficacy and safety have not been confirmed, and the specific mechanism remains to be elucidated. To evaluate the efficacy, safety, and possible mechanisms of CUR in the treatment of psoriasis. The Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP (China Science and Technology Journal Database) were systematically searched for clinical trials and preclinical studies on the use of CUR in psoriasis treatment. All databases were searched from inception to January 2022. The meta-analysis was performed using RevMan 5.3 software. Our meta-analysis included 26 studies, comprising seven clinical randomized controlled trials and 19 preclinical studies. A meta-analysis of clinical trials showed that both CUR monotherapy and combination therapy improved Psoriasis Area and Severity Index (PASI) scores in patients compared to controls (standard mean difference []: confidence interval []: -1.53 to 0.14; p = 0.02). In preclinical studies, CUR showed better performance in improving the phenotype of psoriatic dermatitis mice compared to controls, including total PASI score (std.MD: 6.50%; 95% CI: 10.10 to 2.90; p = 0.0004); ear thickness (); and the expression of inflammatory cytokines such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-17F, and IL-22 (). In cell studies, CUR inhibited cell proliferation () and the cell cycle () and downregulated the inflammatory cytokines IL-6 and IL-8 (). CUR has excellent efficacy and broad potential to treat psoriasis in multiple ways. Its use also plays a crucial role in improving the psoriasis phenotype and reducing the inflammatory microenvironment. In conclusion, our findings suggest that CUR alone or in combination with other conventional treatments can effectively treat psoriasis.
PubMed: 36120325
DOI: 10.3389/fphar.2022.903160 -
Celecoxib for Mood Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Journal of Clinical Medicine May 2023The effects of celecoxib on a broad spectrum of mood disorders and on inflammatory parameters have not yet been comprehensively evaluated. The aim of this study was to... (Review)
Review
The effects of celecoxib on a broad spectrum of mood disorders and on inflammatory parameters have not yet been comprehensively evaluated. The aim of this study was to systematically summarize the available knowledge on this topic. Data from both preclinical and clinical studies were analyzed, considering the efficacy and safety of celecoxib in the treatment of mood disorders, as well as the correlation of inflammatory parameters with the effect of celecoxib treatment. Forty-four studies were included. We found evidence supporting the antidepressant efficacy of celecoxib in a dose of 400 mg/day used for 6 weeks as an add-on treatment in major depression (SMD = -1.12 [95%Cl: -1.71,-0.52], = 0.0002) and mania (SMD = -0.82 [95% CI:-1.62,-0.01], = 0.05). The antidepressant efficacy of celecoxib in the above dosage used as sole treatment was also confirmed in depressed patients with somatic comorbidity (SMD = -1.35 [95% CI:-1.95,-0.75], < 0.0001). We found no conclusive evidence for the effectiveness of celecoxib in bipolar depression. Celecoxib at a dose of 400 mg/d used for up to 12 weeks appeared to be a safe treatment in patients with mood disorders. Although an association between celecoxib response and inflammatory parameters has been found in preclinical studies, this has not been confirmed in clinical trials. Further studies are needed to evaluate the efficacy of celecoxib in bipolar depression, as well as long-term studies evaluating the safety and efficacy of celecoxib in recurrent mood disorders, studies involving treatment-resistant populations, and assessing the association of celecoxib treatment with inflammatory markers.
PubMed: 37240605
DOI: 10.3390/jcm12103497 -
Antibiotic-induced gut dysbiosis and autoimmune disease: A systematic review of preclinical studies.Autoimmunity Reviews Sep 2022Antibiotic-induced gut dysbiosis is believed to be associated with the onset and development of autoimmune diseases. To evaluate microbiota's variations triggered by... (Review)
Review
Antibiotic-induced gut dysbiosis is believed to be associated with the onset and development of autoimmune diseases. To evaluate microbiota's variations triggered by antibiotic therapy and its outcomes on autoimmune diseases, preclinical studies regarding these subjects were included in this review. The studies were selected on PubMed, Scopus and Web of Science from 2011 to 2021 by three researchers that extracted study data and risk of bias, which were verified by a further 3 independent researchers. The team assessed the strength of evidence across studies. Of the eligible studies, 17 showed an improvement of the studied disease after antibiotic therapy and 10 had a negative effect on the course of the condition. The ameliorating factors of the studied diseases were mostly seen when using an antibiotic cocktail. Male animals had a good outcome after therapy and, for all genders, the increase in IL-10 and Treg cells was often shown to ameliorate disease after the antibiotic intervention. Firmicutes, Proteobacteria and Bacteroidetes appeared altered after the antibiotic intervention, leading to amelioration or worsening of the condition depending on the autoimmune disease. We identified that the number of autoimmune conditions approached leads to specific conclusions regarding the interventions, making it difficult to achieve an overall conclusion. Overall, even though pre-clinical studies must be translated to the human model, the studied aspects of gender, age, lineage and disease model substantially impact the outcomes that make for many intricacies that were not-established in the study of antibiotic-induced gut dysbiosis and autoimmunity.
Topics: Animals; Anti-Bacterial Agents; Autoimmune Diseases; Bacteroidetes; Dysbiosis; Female; Gastrointestinal Microbiome; Humans; Male
PubMed: 35830954
DOI: 10.1016/j.autrev.2022.103140