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Journal of Cerebral Blood Flow and... Jun 2022This systematic review aimed to establish the range and quality of clinical and preclinical evidence supporting the association of individual microRNAs, and the use of...
This systematic review aimed to establish the range and quality of clinical and preclinical evidence supporting the association of individual microRNAs, and the use of microRNA expression in the diagnosis and prognosis of ischaemic or haemorrhagic stroke. Electronic databases were searched from 1993 to October 2021, using key words relevant to concepts of stroke and microRNA. Studies that met specific inclusion and exclusion criteria were selected for data extraction. To minimise erroneous associations, findings were restricted to microRNAs reported to change in more than two independent studies. Of the papers assessed, 155 papers reported a change in microRNA expression observed in more than two independent studies. In ischaemic studies, two microRNAs were consistently differentially expressed in clinical samples (miR-29b & miR-146a) and four were altered in preclinical samples (miR-137, miR-146a, miR-181b & miR-223-3p). Across clinical and preclinical haemorrhagic studies, four microRNAs were downregulated consistently (miR-26a, miR-126, miR-146a & miR-155). Across included studies, miR-126 and miR-146a were the only two microRNAs to be differentially expressed in clinical and preclinical cohorts following ischaemic or haemorrhagic stroke. Further studies, employing larger populations with consistent methodologies, are required to validate the true clinical value of circulating microRNAs as biomarkers of ischaemic and haemorrhagic stroke.
Topics: Biomarkers; Circulating MicroRNA; Hemorrhagic Stroke; Humans; MicroRNAs; Stroke
PubMed: 35240874
DOI: 10.1177/0271678X221085090 -
Phytotherapy Research : PTR Nov 2023Resveratrol (RES) has extensively been utilized to treat osteoporosis (OP) in animal models. However, the anti-OP effects of RES have not been tested during clinical... (Meta-Analysis)
Meta-Analysis
Resveratrol (RES) has extensively been utilized to treat osteoporosis (OP) in animal models. However, the anti-OP effects of RES have not been tested during clinical application due to the lack of evidence and poor knowledge of the underlying mechanisms. Moreover, there is little preclinical evidence to support the use of RES in the management of OP. In the present paper, we conducted a preclinical systematic review and meta-analysis to assess the efficacy of RES in animal OP models. The potential mechanisms underlying the efficacy of RES against OP were summarized. The online databases PubMed, CNKI, EMBASE, Wanfang, Web of Science, Chinese Biomedical Literature, Cochrane Library, and Chinese VIP were retrieved from inception to December 2021. The CAMARADES 10-item quality checklist was utilized to assess the risk of bias of the included studies. STATA 12.0 software was employed to analyze the data. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Thirteen studies containing 248 animals were included yielding a mean risk of bias score of 5.54 (range 4-7). The pooled estimates showed that the administration of RES could significantly elevate the bone mineral density (BMD) both at femur (SMD = 2.536; 95% CI = 1.950-3.122; p < 0.001) and lumbar spine (SMD = 1.363; 95% CI = 0894-1.832; p < 0.001), bone volume over total volume (BV/TV) (SMD = 2.543; 95% CI = 2.023-3.062; p < 0.001), trabecular linear density (Tb.N) (SMD = 2.724; 95% CI = 2.186-3.262; p < 0.001) and trabecular thickness (Tb.Th) (SMD = 1.745; 95% CI = 1.294-2.196; p < 0.001), while serum phosphorus (S-P) (SMD = -2.168; 95% CI = -2.753 to -1.583; p < 0.001) and trabecular separation (Tb.Sp) (SMD = -2.856; 95% CI = -4.218 to -1.494; p < 0.001) were significantly reduced in animal OP models. No significant change in serum calcium (S-Ca) (SMD = -2.448; 95% CI = -5.255-0.360; p = 0.087) was observed after RES treatment. Furthermore, RES could significantly improve the bone biomechanical indexes: bone maximum load (BML) (SMD = 2.563; 95% CI = 1.827-3.299; p < 0.001) and connectivity density (Conn.D) (SMD = 1.512; 95% CI = 0.909-2.116; p < 0.001) and decrease the structural model index (SMI) (SMD = -2.522; 95% CI = -3.243 to -1.801; p < 0.001). Overall, the present study revealed that RES has huge prospects as a medicine or dietary supplement for the clinical treatment of OP. High-quality studies with stringent designs and larger sample sizes are warranted to substantiate our conclusion.
Topics: Animals; Resveratrol; Osteoporosis; Bone Density; Bone and Bones; Models, Animal
PubMed: 37482965
DOI: 10.1002/ptr.7954 -
Life Sciences Jun 2023Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, has received extensive attention as a natural activator of the Nrf2/Keap1... (Meta-Analysis)
Meta-Analysis Review
AIMS
Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, has received extensive attention as a natural activator of the Nrf2/Keap1 cytoprotective pathway. In this review, a meta-analysis and systematic review of the renoprotective effects of SFN were performed in various preclinical models of kidney diseases.
MAIN METHODS
The primary outcome was the impact of SFN on renal function biomarkers (uremia, creatininemia, proteinuria or creatinine clearance) and secondary outcomes were kidney lesion histological indices/kidney injury molecular biomarkers. The effects of SFN were evaluated according to the standardized mean differences (SMDs). A random-effects model was applied to estimate the overall summary effect.
KEY FINDINGS
Twenty-five articles (out of 209 studies) were selected from the literature. SFN administration significantly increased creatinine clearance (SMD +1.88 95 % CI: [1.09; 2.68], P < 0.0001, I = 0 %) and decreased the plasma creatinine (SMD -1.24, [-1.59; -0.88], P < 0.0001, I = 36.0 %) and urea (SMD -3.22 [-4.42, -2.01], P < 0.0001, I = 72.4 %) levels. SFN administration (median dose: 2.5 mg/kg, median duration: 3 weeks) significantly decreased urinary protein excretion (SMD -2.20 [-2.68; -1.73], P < 0.0001, I = 34.1 %). It further improved two kidney lesion histological indices namely kidney fibrosis (SMD -3.08 [-4.53; -1.63], P < 0.0001, I = 73.7 %) and glomerulosclerosis (SMD -2.24 [-2.96; -1.53], P < 0.0001, I = 9.7 %) and decreased kidney injury molecular biomarkers (SMD -1.51 [-2.00; -1.02], P < 0.0001, I = 0 %).
SIGNIFICANCE
These findings provide new insights concerning preclinical strategies for treating kidney disease or kidney failure with SFN supplements and should stimulate interest in clinical evaluations of SFN in patients with kidney disease.
Topics: Humans; Kelch-Like ECH-Associated Protein 1; Creatinine; NF-E2-Related Factor 2; Kidney Diseases; Isothiocyanates; Biomarkers
PubMed: 37023957
DOI: 10.1016/j.lfs.2023.121664 -
The Journal of Nutrition, Health & Aging Mar 2024Adiponectin is an adipokine playing a central role in the regulation of energy homeostasis, carbohydrate and lipid metabolism, as well as immunomodulation. The... (Review)
Review
Adiponectin is an adipokine playing a central role in the regulation of energy homeostasis, carbohydrate and lipid metabolism, as well as immunomodulation. The relationship between Alzheimer's disease (AD) and body composition has highlighted the bidirectional crosstalk between AD's pathophysiology and metabolic disorders. This review aimed to report the current state of knowledge about cellular and molecular mechanisms linking adiponectin and AD, in preclinical studies. Then, we reviewed human studies to assess the relationship between adiponectin levels and AD diagnosis. We also examined the risk of incident AD regarding the participants' baseline adiponectin level, as well as the relationship of adiponectin and cognitive decline in patients with AD. We conducted a systematic review, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline, of studies published over the last decade on MEDLINE and Cochrane databases. Overall, we reviewed 34 original works about adiponectin in AD, including 11 preclinical studies, two both preclinical and human studies and 21 human studies. Preclinical studies brought convincing evidence for the neuroprotective role of adiponectin on several key mechanisms of AD. Human studies showed conflicting results regarding the relationship between AD and adiponectin levels, as well as regarding the cross-sectional association between cognitive function and adiponectin levels. Adiponectin did not appear as a predictor of incident AD, nor as a predictor of cognitive decline in patients with AD. Despite solid preclinical evidence suggesting the protective role of adiponectin in AD, inconsistent results in humans supports the need for further research.
Topics: Animals; Humans; Adipokines; Adiponectin; Alzheimer Disease; Cognition; Cross-Sectional Studies
PubMed: 38280832
DOI: 10.1016/j.jnha.2024.100166 -
Nanoscale Advances Jan 2023: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and... (Review)
Review
: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and release drugs selectively at desired sites using targeting or sensing strategies. As drug carriers, they could improve therapeutic outcomes while reducing systemic toxicity. They have also shown promise in improving leukemia detection and diagnosis. The study aimed to assess the potential of nanotechnology-based diagnostics and therapeutics in preclinical human acute lymphoblastic leukemia (h-ALL). : We performed a systematic search through April 2022. Articles written in English reporting the toxicity, efficacy, and safety of nanotechnology-based drugs (in the aspect of treatment) and specificity, limit of detection (LOD), or sensitivity (in the aspect of the detection field) in preclinical h-ALL were included. The study was performed according to PRISMA instructions. The methodological quality was assessed using the QualSyst tool. : A total of 63 original articles evaluating nanotechnology-based therapeutics and 35 original studies evaluating nanotechnology-based diagnostics were included in this review. As therapeutics in ALL, nanomaterials offer controlled release, targeting or sensing ligands, targeted gene therapy, photodynamic therapy and photothermic therapy, and reversal of multidrug-resistant ALL. A narrative synthesis of studies revealed that nanoparticles improve the ratio of efficacy to the toxicity of anti-leukemic drugs. They have also been developed as a vehicle for biomolecules (such as antibodies) that can help detect and monitor leukemic biomarkers. Therefore, nanomaterials can help with early diagnostics and personalized treatment of ALL. : This review discussed nanotechnology-based preclinical strategies to achieve ALL diagnosis and therapy advancement. This involves modern drug delivery apparatuses and detection devices for prompt and targeted disease diagnostics. Nonetheless, we are yet in the experimental phase and investigational stage in the field of nanomedicine, with many features remained to be discovered as well as numerous problems to be solved.
PubMed: 36756502
DOI: 10.1039/d2na00483f -
Frontiers in Immunology 2022Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of...
BACKGROUND
Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies.
METHODS
We searched Cochrane Library, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO's Global Index Medicus, and Google Scholar from inception to June 20, 2020, for EBV prophylactic vaccine studies focused on humoral immunity.
RESULTS
The search yielded 5,614 unique studies. 36 pre-clinical and 4 clinical studies were included in the analysis after screening against the exclusion criteria. In pre-clinical studies, gp350 was the most commonly used immunogen (33 studies), vaccines were most commonly delivered as monomeric proteins (12 studies), and mice were the most used animal model to test immunogenicity (15 studies). According to an adaptation of the CAMARADES checklist, 4 pre-clinical studies were rated as very high, 5 as high, 13 as moderate quality, 11 as poor, and 3 as very poor. In clinical studies, gp350 was the sole vaccine antigen, delivered in a vaccinia platform (1 study) or as a monomeric protein (3 studies). The present study was registered in PROSPERO (CRD42020198440).
CONCLUSIONS
Four major obstacles have prevented the development of an effective prophylactic EBV vaccine: undefined correlates of immune protection, lack of knowledge regarding the ideal EBV antigen(s) for vaccination, lack of an appropriate animal model to test vaccine efficacy, and lack of knowledge regarding the ideal vaccine delivery platform. Our analysis supports a multivalent antigenic approach including two or more of the five main glycoproteins involved in viral entry (gp350, gB, gH/gL, gp42) and a multimeric approach to present these antigens. We anticipate that the application of two underused challenge models, rhesus macaques susceptible to rhesus lymphocryptovirus (an EBV homolog) and common marmosets, will permit the establishment of correlates of immune protection and attainment of more generalizable data.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifier PROSPERO I.D. CRD4202019844.
Topics: Animals; Disease Models, Animal; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Infectious Mononucleosis; Macaca mulatta; Mice; Serologic Tests
PubMed: 35493498
DOI: 10.3389/fimmu.2022.867918 -
Journal of Neurotrauma Feb 2023Photobiomodulation (PBM) is a therapeutic modality that has gained increasing interest in neuroscience applications, including acute traumatic brain injury (TBI). Its... (Meta-Analysis)
Meta-Analysis Review
Photobiomodulation (PBM) is a therapeutic modality that has gained increasing interest in neuroscience applications, including acute traumatic brain injury (TBI). Its proposed mechanisms for therapeutic effect when delivered to the injured brain include antiapoptotic and anti-inflammatory effects. This systematic review summarizes the available evidence for the value of PBM in improving outcomes in acute TBI and presents a meta-analysis of the pre-clinical evidence for neurological severity score (NSS) and lesion size in animal models of TBI. A systematic review of the literature was performed, with searches and data extraction performed independently in duplicate by two authors. Eighteen published articles were identified for inclusion: seventeen pre-clinical studies of animal models and one clinical study in human patients. The available human study supports safety and feasibility of PBM in acute moderate TBI. For pre-clinical studies, meta-analysis for NSS and lesion size were found to favor intervention versus control. Subgroup analysis based on PBM parameter variables for these outcomes was performed. Favorable parameters were identified as: wavelengths in the region of 665 nm and 810 nm; time to first administration of PBM ≤4 h; total number of daily treatments ≤3. No differences were identified between pulsed and continuous wave modes or energy delivery. Mechanistic substudies within included studies are presented and were found to support hypotheses of antiapoptotic, anti-inflammatory, and pro-proliferative effects, and a modulation of cellular metabolism. This systematic review provides substantial meta-analysis evidence of the benefits of PBM on functional and histological outcomes of TBI in mammalian models. Study design and PBM parameters should be closely considered for future human clinical studies.
Topics: Animals; Humans; Low-Level Light Therapy; Brain Injuries; Brain Injuries, Traumatic; Brain; Mammals
PubMed: 35698294
DOI: 10.1089/neu.2022.0140 -
PloS One 2023Cross-neutralizing strategy has been applied to improve access to antivenoms, a key to reducing mortality and disability of snakebite envenoming. However, preclinical...
BACKGROUND
Cross-neutralizing strategy has been applied to improve access to antivenoms, a key to reducing mortality and disability of snakebite envenoming. However, preclinical studies have been conducted to identify antivenoms' cross-neutralizing ability when clinical studies may not be considered ethical. Therefore, this study aimed to identify and summarize scattered evidence regarding the preclinical efficacy of antivenoms against Asian snakes.
METHODOLOGY/PRINCIPLE FINDINGS
In this systematic review, we searched for articles published until May 30, 2022, in PubMed, Scopus, Web of Science, and Embase. Preclinical studies that reported the available antivenoms' neutralizing ability against Asian snake lethality were included. Quality assessment was performed using the Systematic Review Centre for Laboratory animal Experimentation's risk of bias tool and the adapted the Animal Research Reporting In Vivo Experiments guidelines. The availability of effective antivenoms against Asian snakes was analyzed by comparing data from included studies with snakebite-information and data platforms developed by the World Health Organization. Fifty-two studies were included. Most studies assessed the antivenom efficacy against snakes from Southeast Asia (58%), followed by South Asia (35%) and East Asia (19%). Twenty-two (49%) medically important snakes had antivenom(s) with confirmed neutralizing ability. Situation analyses of the availability of effective antivenoms in Asia demonstrated that locally produced antivenoms did not cover all medically important snakes in each country. Among countries without local antivenom production, preclinical studies were conducted only in Bangladesh, Sri Lanka, and Malaysia. Risk of bias assessment was limited in some domains because of unreported data.
CONCLUSIONS/SIGNIFICANCE
Cross-neutralizing of antivenoms against some medically important snakes in Asia was confirmed. This strategy may improve access to geographically effective antivenoms and bypass investment in novel antivenom development, especially in countries without local antivenom production. A database should be developed to aid the development of a snakebite-information system.
Topics: Animals; Antivenins; Snake Bites; Snakes; Sri Lanka; Asia, Eastern
PubMed: 37467278
DOI: 10.1371/journal.pone.0288723 -
Journal of Lasers in Medical Sciences 2022While a wound caused by a minor cutaneous incision routinely heals in a short time, wounds from major surgical operations might need numerous days to heal and may leave... (Review)
Review
While a wound caused by a minor cutaneous incision routinely heals in a short time, wounds from major surgical operations might need numerous days to heal and may leave an obvious cicatrix. The use of blue light therapy (BLT) to destroy infectious microorganisms and disrupt biofilm formation could be an efficient method for healing ulcers. This systematic review focused on the effects of BLT in different preclinical studies and clinical models of skin wound healing. Furthermore, this study attempted to determine what main light parameters should be tested in preclinical and clinical studies. The online databases PubMed.gov, Google Scholar, Scopus, Web of Science, and Cochrane were searched using the keywords "blue light" and "wound healing" according to PRISMA guidelines. No publication time limit was enforced. A total of 858 articles were identified, and 17 articles in three distinct categories were included for review. They comprised two articles on humans, fourteen articles on healthy animals, and one article on diabetic animals. Some studies have shown that the application of BLT on preclinical and clinical models of wound healing is able to significantly accelerate the healing process. Few studies, however, have explored the bactericidal effect of BLT on skin injury repair in burn patients. Further preclinical investigations designed to provide a better understanding of the bactericidal effect of BLT using standardized protocols, different BLT wavelengths, and different stages of the wound healing process of infected wounds and ulcers in healthy and diabetic animals should be carried out before clinical trials can be considered. BLT could eventually be a good option for treating infected chronic wounds, including those in diabetic patients.
PubMed: 37041783
DOI: 10.34172/jlms.2022.69 -
Journal of Clinical Medicine Oct 2019The preclinical studies in vivo provide means of characterizing physiologic interactions when our understanding of such processes is insufficient to allow replacement... (Review)
Review
The preclinical studies in vivo provide means of characterizing physiologic interactions when our understanding of such processes is insufficient to allow replacement with in vitro systems and play a pivotal role in the development of a novel therapeutic drug cure. Chemically induced colitis models are relatively easy and rapid to develop. The 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis model is one of the main models in the experimental studies of inflammatory bowel disease (IBD) since inflammation induced by TNBS mimics several features of Crohn's disease. This review aims to summarize the existing literature and discuss different protocols for the induction of chronic model of TNBS-induced colitis. We searched MEDLINE via Pubmed platform for studies published through December 2018, using MeSH terms (Crohn Disease.kw) OR (Inflammatory Bowel Diseases.kw) OR (Colitis, Ulcerative.kw) AND (trinitrobenzenesulfonic acid.kw) AND (disease models, animal.kw) AND (mice.all). The inclusion criteria were original articles, preclinical studies in vivo using mice, chronic model of colitis, and TNBS as the inducer of colitis and articles published in English. Chronic TNBS-induced colitis is made with multiple TNBS intrarectal administrations in an average dose of 1.2 mg using a volume lower than 150 μL in 50% ethanol. The strains mostly used are Balb/c and C57BL/6 with 5-6 weeks. To characterize the preclinical model the parameters more used include body weight, stool consistency and morbidity, inflammatory biomarkers like interferon (IFN)-γ, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of the inflammation. Experimental chronic colitis is induced by multiple rectal instillations of TNBS increasing doses in ethanol using Balb/c and C57BL/6 mice.
PubMed: 31581545
DOI: 10.3390/jcm8101574