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Drugs Feb 2022Gliomas represent most common primary brain tumors. Glioblastoma (GBM) is the most common subtype and carries a poor prognosis. There is growing interest in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gliomas represent most common primary brain tumors. Glioblastoma (GBM) is the most common subtype and carries a poor prognosis. There is growing interest in the anti-glioma properties of statins. The aim of this study was to conduct a systematic review of the preclinical literature and to meta-analyze existing clinical studies to determine what benefit, if any, statins may confer in the context of glioma.
METHODS
The PubMed, Embase, Cochrane, and Web of Science libraries were queried in May 2021. Preclinical studies were included if they investigated the anti-cancer effects of statins in glioma in vitro and in vivo. Clinical studies were included if they reported incidence rates of glioma by statin use, or mortality outcomes among GBM patients by statin use. Pooled point estimates were calculated using a random-effects model.
RESULTS
In total, 64 publications, 51 preclinical and 13 clinical, were included. Preclinical studies indicated that statins inhibited glioma cell proliferation, migration, and invasion. These effects were time- and concentration-dependent. Synergistic anti-glioma effects were observed when statins were combined with other anti-cancer therapies. Clinical observational studies showed an inverse, albeit non-statistically significant, association between statin use and incidence rate of glioma (HR = 0.84, 95% CI 0.62-1.13, I = 72%, p-heterogeneity = 0.003, 6 studies). Statin use was not associated with better overall survival following GBM surgery (HR = 1.05, 95% CI 0.85-1.30, I = 30%, p-heterogeneity = 0.23, 4 studies).
CONCLUSION
Statins were potent anti-cancer drugs that suppressed glioma growth through various mechanisms in vitro; these effects have translated into the clinical realm, clinically but not statistically, in terms of glioma incidence but not GBM survival.
Topics: Antineoplastic Agents; Glioma; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 35122635
DOI: 10.1007/s40265-021-01668-x -
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 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 -
Clinical Rheumatology Jan 2022Corticosteroid-sparing disease-modifying anti-rheumatic drugs are an area of active exploration in large vessel vasculitis (LVV), i.e., Takayasu arteritis (TAK) and... (Review)
Review
Corticosteroid-sparing disease-modifying anti-rheumatic drugs are an area of active exploration in large vessel vasculitis (LVV), i.e., Takayasu arteritis (TAK) and Giant Cell Arteritis (GCA). The role of Janus kinase (JAK) inhibitors has been recently identified in different inflammatory rheumatic diseases. We conducted a systematic review of the use of JAK inhibitors in LVV across MEDLINE, Scopus, Web of Science, EMBASE, PubMed Central, Cochrane database of controlled trials, clinicaltrials.gov, and major recent international conferences. We identified four cohort studies and ten case reports. The JAK inhibitors used in these studies were tofacitinib, baricitinib, and ruxolitinib. A cohort study in TAK compared 27 patients treated with tofacitinib with 26 others treated with methotrexate, with better clinical outcomes with tofacitinib but similar angiographic stabilization, relapses, corticosteroid-sparing effect, and adverse events in both groups. Most of the other studies favored clinical responses with JAK inhibitors in LVV but with a paucity of data on other outcomes. Most of the included studies were of moderate quality. Evidence from pre-clinical models of LVV as well as limited in vivo data in patients with TAK appears to suggest that JAK inhibition reduces adventitial fibrosis, intimal proliferation, and inflammatory T lymphocyte infiltration in the media as well as reduces resident memory T cells in the vascular wall (which are otherwise resistant to corticosteroids). Ongoing clinical trials of tofacitinib, baricitinib, and upadacitinib in LVV shall help to further clarify the potential promise of JAK inhibitors for LVV (PROSPERO registration number CRD42021273359). KEY POINTS : •Tofacitinib appeared to associate with better clinical outcomes than methotrexate in TAK. •JAKinibs reduce adventitial fibrosis, intimal proliferation, and inflammatory vascular infiltrate in pre-clinical models of LVV. •Tofacitinib downregulates resident memory vascular T lymphocytes in pre-clinical models of LVV.
Topics: Antirheumatic Agents; Cohort Studies; Giant Cell Arteritis; Humans; Janus Kinase Inhibitors; Memory T Cells; Takayasu Arteritis
PubMed: 34729652
DOI: 10.1007/s10067-021-05973-4 -
Viruses Nov 2022The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review... (Review)
Review
The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review research done on preclinical studies focusing on the potential monkeypox treatment and immunization. The presented juxtaposition of efficacy of potential treatments and vaccination that had been tested in preclinical trials could serve as a useful primer of monkeypox virus. The literature identified using key terms such as monkeypox virus or management or vaccine stringed using Boolean operators was systematically reviewed. Pubmed, SCOPUS, Cochrane, and preprint databases were used, and screening was performed in accordance with PRISMA guidelines. A total of 467 results from registered databases and 116 from grey literature databases were screened. Of these results, 72 studies from registered databases and three grey literature studies underwent full-text screening for eligibility. In this systematic review, a total of 27 articles were eligible according to the inclusion criteria and were used. Tecovirimat, known as TPOXX or ST-246, is an antiviral drug indicated for smallpox infection whereas brincidofovir inhibits the viral DNA polymerase after incorporation into viral DNA. The ability of tecovirimat in providing protection to poxvirus-challenged animals from death had been demonstrated in a number of animal studies. Non-inferior with regard to immunogenicity was reported for the live smallpox/monkeypox vaccine compared with a single dose of a licensed live smallpox vaccine. The trial involving the live vaccine showed a geometric mean titre of vaccinia-neutralizing antibodies post two weeks of the second dose of the live smallpox/monkeypox vaccine. Of note, up to the third generation of smallpox vaccines-particularly JYNNEOS and Lc16m8-have been developed as preventive measures for MPXV infection and these vaccines had been demonstrated to have improved safety compared to the earlier generations.
Topics: Animals; Humans; Mpox (monkeypox); Smallpox Vaccine; Smallpox; Pandemics; COVID-19; Monkeypox virus; Variola virus; Vaccinia virus; Vaccines, Attenuated; COVID-19 Drug Treatment
PubMed: 36423105
DOI: 10.3390/v14112496 -
Pain Apr 2020Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and... (Meta-Analysis)
Meta-Analysis
Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and meta-analysis of preclinical studies of the commercially successful drug pregabalin. Our primary objective was to describe design characteristics and outcomes of studies testing the efficacy of pregabalin in behavioral models of pain. Secondarily, we examined the relationship between design characteristics and effect sizes. We queried MEDLINE, Embase, and BIOSIS to identify all animal studies testing the efficacy of pregabalin published before January 2018 and recorded experimental design elements addressing threats to validity and all necessary data for calculating effect sizes, expressed as the percentage of maximum possible effect. We identified 204 studies (531 experiments) assessing the efficacy of pregabalin in behavioral models of pain. The analgesic effect of pregabalin was consistently robust across every etiology/measure tested, even for pain conditions that have not responded to pregabalin in patients. Experiments did not generally report using design elements aimed at reducing threats to validity, and analgesic activity was typically tested in a small number of model systems. However, we were unable to show any clear relationships between preclinical design characteristics and effect sizes. Our findings suggest opportunities for improving the design and reporting of preclinical studies in pain. They also suggest that factors other than those explored in this study may be more important for explaining the discordance between outcomes in animal models of pain and those in clinical trials.
Topics: Analgesics; Animals; Humans; Pain; Pregabalin
PubMed: 31977931
DOI: 10.1097/j.pain.0000000000001749 -
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 -
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 -
Nutrition Reviews Aug 2020Recent evidence suggests that modulation of the gut microbiota may help prevent colorectal cancer.
CONTEXT
Recent evidence suggests that modulation of the gut microbiota may help prevent colorectal cancer.
OBJECTIVE
The aim of this systematic review was to investigate the role of probiotics and synbiotics in the prevention of colorectal cancer and to clarify potential mechanisms involved.
DATA SOURCES
The PubMed, ScienceDirect, and LILACS databases were searched for studies conducted in humans or animal models and published up to August 15, 2018.
STUDY SELECTION
Clinical trials and placebo-controlled experimental studies that evaluated the effects of probiotics and synbiotics in colorectal cancer and cancer associated with inflammatory bowel disease were included. Of 247 articles identified, 31 remained after exclusion criteria were applied. A search of reference lists identified 5 additional studies, for a total of 36 included studies.
DATA EXTRACTION
Two authors independently assessed risk of bias of included studies and extracted data. Data were pooled by type of study, ie, preclinical or clinical.
RESULTS
The results showed positive effects of probiotics and synbiotics in preventing colorectal cancer. The main mechanisms identified were alterations in the composition and metabolic activity of the intestinal microbiota; reduction of inflammation; induction of apoptosis and inhibition of tumor growth; modulation of immune responses and cell proliferation; enhanced function of the intestinal barrier; production of compounds with anticarcinogenic activity; and modulation of oxidative stress.
CONCLUSIONS
Probiotics or synbiotics may help prevent colorectal cancer, but additional studies in humans are required to better inform clinical practice.
Topics: Adult; Aged; Aged, 80 and over; Animals; Carcinogenesis; Colorectal Neoplasms; Female; Gastrointestinal Microbiome; Humans; Inflammation; Inflammatory Bowel Diseases; Intestines; Male; Mice; Middle Aged; Probiotics; Rats; Synbiotics
PubMed: 31917829
DOI: 10.1093/nutrit/nuz087 -
Ageing Research Reviews Sep 2023Quercetin, a natural flavonoid, has shown promise as a senolytic agent for various degenerative diseases. Recently, its protective effect against osteoarthritis (OA), a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quercetin, a natural flavonoid, has shown promise as a senolytic agent for various degenerative diseases. Recently, its protective effect against osteoarthritis (OA), a representative age-related disease of the musculoskeletal system, has attracted much attention. The aim of this study is to summarize and analyze the current literature on the effects of quercetin on OA cartilage in in vivo preclinical studies.
METHODS
The Medline (via/using PubMed), Embase, and Web of Science databases were searched up to March 10th, 2023. Risk of bias and the qualitative assessment including mechanisms of all eligible studies and a meta-analysis of cartilage histological scores among the applicable studies was performed.
RESULTS
A total of 12 in vivo animal studies were included in this systematic review. A random-effects meta-analysis was performed on six studies using the Osteoarthritis Research Society International (OARSI) scoring system, revealing that quercetin significantly improved OA cartilage OARSI scores (SMD, -6.30 [95% CI, -9.59 to -3.01]; P = 0.0002; heterogeneity: I2 = 86%). The remaining six studies all supported quercetin's protective effects against OA during disease and aging.
CONCLUSIONS
Quercetin has shown beneficial effects on cartilage during OA across animal species. Future double-blind randomized controlled clinical trials are needed to verify the efficacy of quercetin in the treatment of OA in humans.
Topics: Animals; Humans; Quercetin; Senotherapeutics; Osteoarthritis; Aging; Osteoarthritis, Knee; Randomized Controlled Trials as Topic
PubMed: 37442369
DOI: 10.1016/j.arr.2023.101989