Meta-analysis Of Animal Studies Research Articles

The dilemma of neuroprotection trials in times of successful endovascular recanalization

BackgroundThe “translational roadblock” between successful animal stroke studies and neutral clinical trials is usually attributed to conceptual weaknesses. However, we hypothesized that rodent studies cannot inform the human disease due to intrinsic pathophysiological differences between rodents and humans., i.e., differences in infarct evolution.MethodsTo verify our hypothesis, we employed a mixed study design and compared findings from meta-analyses of animal studies and a retrospective clinical cohort study. For animal data, we systematically searched pubmed to identify all rodent studies, in which stroke was induced by MCAO and at least two sequential MRI scans were performed for infarct volume assessment within the first two days. For clinical data, we included 107 consecutive stroke patients with large artery occlusion, who received MRI scans upon admission and one or two days later.ResultsOur preclinical meta-analyses included 50 studies with 676 animals. Untreated animals had a median post-reperfusion infarct volume growth of 74%. Neuroprotective treatments reduced this infarct volume growth to 23%. A retrospective clinical cohort study showed that stroke patients had a median infarct volume growth of only 2% after successful recanalization. Stroke patients with unsuccessful recanalization, by contrast, experienced a meaningful median infarct growth of 148%.ConclusionOur study shows that rodents have a significant post-reperfusion infarct growth, and that this post-reperfusion infarct growth is the target of neuroprotective treatments. Stroke patients with successful recanalization do not have such infarct growth and thus have no target for neuroprotection.

Biological response to endodontic treatment in one versus two-visit: a systematic review and meta-analysis of animal studies.

To perform a systematic review of animal studies that compared the histopathological characteristics between teeth with apical periodontitis after endodontic treatment in one or two visits. This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) - CRD42022340849. Studies were collected from PubMed/MEDLINE, LILACS, EMBASE, Livivo, SciELO, Web of Science, Scopus, and Cochrane Library and manual and gray literature searches. Animal studies that evaluated histological characteristics after endodontic treatment of teeth with apical periodontitis in one or two visits were included. Risk of bias analysis of the included studies was performed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Data synthesis of the included studies with quantitative data was performed, and meta-analysis was conducted with the Comprehensive Meta-Analysis software, using the random effects model and odds ratio (OR). Eighteen studies met the inclusion criteria (Kappa = 0.891). Meta-analyses indicated values in inflammatory infiltrate intensity with effect size of 5.5% (95% CI: 0.020-0.148; p < 0.001), periodontal ligament thickness: 25.6% (95% CI: 0.134-0.487; p < 0.001), dentin resorption: 13% (95% CI: 0.015-1.141; p = 0.066), cementum resorption: 7.1% (95% CI: 0.015-0.325; p = 0.001), bone resorption: 1.4% (95% CI: 0.002-0.130; p < 0.001), mineralized tissue resorption: 42.8% (95% CI: 0.110-1.671; p = 0.222), biological apical sealing: 13.1% (95% CI: 0.055-0.314; p < 0.001), and presence of microorganisms: 10.3% (95% CI: 0.014-0.747; p = 0.025). When considering animal studies, the two-visit endodontic treatment, using calcium hydroxide-based intracanal medication, resulted in better biological repair characteristics. A two-visit endodontic treatment with calcium hydroxide-based intracanal medication yields superior histopathological outcomes.

Myocardial infarct size is reduced by nitrite and nitrate administration: a systematic review and meta-analysis of animal studies.

Ischemic heart disease (IHD) is the leading cause of mortality worldwide and can be complicated by myocardial infarction (MI), leading to cardiac failure. Inorganic nitrite and nitrate, which release nitric oxide (NO), can protect the heart against myocardial injury. This animal systematic review and meta-analysis aims to assess whether the administration of nitrite/nitrate decreases myocardial infarct size. We systematically searched PubMed, Scopus, and Web of Science databases until October 2023; 15 eligible animal studies (35 study arms for in-vivo and 10 for in-vitro studies) published between 1989 and 2023 were included. In-vivo studies were conducted on rats, mice, cats, and dogs, and in-vitro studies on rats and mice with an overall exposure of 0.03 to 12713 mg/kg to nitrate/nitrite administrated before, after, or during ischemia mainly by intravenous single bolus or by oral over 270 days. All in-vitro studies used nitrite/nitrate before ischemia, with the concentration ranging between 0.34 to 201 μM. MI was induced by occlusion of the left anterior diagonal or left circumflex arteries in in-vitro studies and by isoproterenol in in-vivo studies. Infarct size was measured by direct staining of the sliced heart sections. In in-vivo studies, nitrite (overall effect size (ES)=-17.0 %, 95 % confidence interval (CI)=-21.3, -12.8, P<0.001) and nitrate (overall ES= -9.6 %, 95 % CI=-15.7, -3.4, P=0.002) reduced myocardial infarct size. In in-vitro studies, nitrite (overall ES=-15.8 %, 95 % CI=-25.5, -6.2, P=0.001) reduced the infarct size. Sensitivity analysis showed that the overall effect of nitrite on myocardial infarct size was unaffected by doses or health conditions in in-vivo and in-vitro studies. In conclusion, our meta-analysis showed that nitrite/nitrate administration can effectively reduce myocardial infarct size. However, these results should be approached with caution because of the limitations of animal studies and the existing high heterogeneity.

Kinetics of Inflammatory Mediators in the Immune Response to Burn Injury: Systematic Review and Meta-Analysis of Animal Studies

Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related complications. Because detailed information on the various inflammatory mediators is scattered over individual studies, we systematically reviewed animal experimental data for all reported inflammatory mediators. Meta-analyses of 352 studies revealed a strong increase in cytokines, chemokines, and growth factors, particularly 19 mediators in blood and 12 in burn tissue. Temporal kinetics showed long-lasting surges of proinflammatory cytokines in blood and burn tissue. Significant time-dependent effects were seen for IL-1β, IL-6, TGF-β1, and CCL2. The response of anti-inflammatory mediators was limited. Burn technique had a profound impact on systemic response levels. Large burn size and scalds further increased systemic, but not local inflammation. Animal characteristics greatly affected inflammation, for example, IL-1β, IL-6, and TNF-α levels were highest in young, male rats. Time-dependent effects and dissimilarities in response demonstrate the importance of appropriate study design. Collectively, this review presents a general overview of the burn-induced immune response exposing inflammatory pathways that could be targeted through immunotherapy for burn patients and provides guidance for experimental set-ups to advance burn research.

Polyphyllins in cancer therapy: A systematic review and meta-analysis of animal studies

BackgroundPolyphyllins are secondary metabolites that inhibit the growth of various tumours; however, clinical trials on their use are lacking. Hypothesis/purposeIn this study, we aimed to evaluate the antitumour efficacy of polyphyllins in animal models. Study designSystematic review and meta-analysis. MethodsElectronic bibliographic databases including PubMed, Web of Science, China Science and Technology Journal Database, Wanfang Data, and China National Knowledge Infrastructure were searched for relevant articles. The Systematic Review Centre for Laboratory Animal Experimentation's Risk of Bias tool was used to assess methodological quality. RevMan V.5.4 (Cochrane) and Stata MP 17 software were used to perform a meta-analysis. ResultsThirty articles were analysed including 33 independent experiments and 452 animals in this paper. Overall, tumour volume (standardised mean difference [SMD]: −3.35; 95 % confidence interval [CI]: −4.27 to −2.43; p < 0.00001) and tumour weight (SMD: −3.79; 95% CI: −4.75 to −2.82; p < 0.00001) were reduced by polyphyllins, which showed a good cancer therapeutic effect; mouse weight (SMD: −0.22; 95% CI: −0.61 to −0.18; p = 0.28) was insignificantly different, which indicated that polyphyllins did not affect the growth of the mice within the test range. Moreover, the molecular mechanisms of the antitumour activity of polyphyllins were explained, including the P53, NF-kB, AMPK, and ERK signalling pathways. ConclusionPolyphyllins inhibit the growth of cancers within the experimental dose. However, due to heterogeneity of the results of the included studies, more studies are needed to support this conclusion.

Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.

Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue. An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293). The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected. In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.

Maternal Exercise Impacts Offspring Metabolic Health in Adulthood: A Systematic Review and Meta-Analysis of Animal Studies.

Maternal exercise benefits offspring's metabolic health with long-term repercussions. Here, we systematically reviewed the effects of maternal exercise on offspring obesity outcomes in adulthood. The primary outcome is body weight. The secondary outcomes are glucose and lipid profiles. Two independent authors performed a search in the databases PubMed, EMBASE, and Web of Science. A total of nine studies with 17 different cohorts consisting of 369 animals (two species) were included. Study quality was assessed using the SYRCLE risk of bias. The PRISMA statement was used to report this systematic review. The results showed that maternal exercise contributes to improved glucose tolerance, reduced insulin concentration, and lower total cholesterol and low density lipoprotein levels in adult offspring in mice, which are independent of maternal body weight and offspring dietary condition. Additionally, in rats, maternal exercise leads to a higher body weight in adult offspring, which might be attributed to the high-fat diet of offspring after weaning. These findings further support the metabolic beneficial role of maternal exercise on offspring in adulthood, although the issue of translating the results to the human population is still yet to be addressed.

Comparison of the effect of saffron, crocin, and safranal on serum levels of oxidants and antioxidants in diabetic rats: Asystematic review and meta-analysis of animal studies.

This study aimed to evaluate the effect of saffron, crocin, and safranal on serum levels of oxidants and antioxidants in diabetic rats. The authors searched the databases with standard keywords until June 8, 2021. The random-effects model was used to pool standardized mean differences (SMD) with 95% confidence intervals to assess the effects of saffron and its active component. To investigate heterogeneity, subgroup analysis and meta-regression were utilized. Begg and Egger's tests were used to measure publication bias. Our results showed that saffron, crocin, and safranal were able to significantly reduce the serum levels of oxidants with strong efficacy so that saffron had the highest effectiveness on serum malondialdehyde (SMD, -2.84 (μmol/L) [95% confidence interval (CI), -4.32 to -1.36]; p < .001, I 2= 83.5%). In addition, saffron and its effective compounds were highly effective by increasing the serum level of antioxidants. In addition, saffron and its effective compounds were able to significantly increase the serum level of antioxidants with strong efficacy, while saffron had the highest effect on the serum level of total antioxidant capacity (SMD, 3.90 (μmol/L) [95% CI, 0.78-7.03]; p=.014, I 2= 86.9%). The findings of this study show that treatment with saffron, crocin, and safranal by strengthening the antioxidant defense system and modulating oxidative stress shows antidiabetic effects in the diabetic model of rats, also these findings support the potential effect of saffron and its effective compounds for the management of diabetes and its complications. However, more human studies are needed.

Effects of Berries, Phytochemicals, and Probiotics on Atherosclerosis through Gut Microbiota Modification: A Meta-Analysis of Animal Studies

Atherosclerosis is a major cause of death and disability. The beneficial effects of phytochemicals and probiotics on atherosclerosis have gained significant interest since these functional foods can improve inflammation, oxidative stress, and microbiome dysbiosis. The direct effect of the microbiome in atherosclerosis, however, needs further elucidation. The objective of this work was to investigate the effects of polyphenols, alkaloids, and probiotics on atherosclerosis using a meta-analysis of studies with mouse models of atherosclerosis. Identification of eligible studies was conducted through searches on PubMed, Embase, Web of Science, and Science Direct until November 2022. The results showed that phytochemicals reduced atherosclerosis, which was significant in male mice, but not in females. Probiotics, on the other hand, showed significant reductions in plaque in both sexes. Berries and phytochemicals modulated gut microbial composition by reducing the Firmicutes/Bacteroidetes (F/B) ratio and by upregulating health-promoting bacteria, including Akkermansia muciniphila. This analysis suggests that phytochemicals and probiotics can reduce atherosclerosis in animal models, with a potentially greater effect on male animals. Thus, consumption of functional foods rich in phytochemicals as well as probiotics are viable interventions to improve gut health and reduce plaque burden in patients suffering from cardiovascular disease (CVD).

Protective effects of melatonin against the toxic effects of environmental pollutants and heavy metals on testicular tissue: A systematic review and meta-analysis of animal studies.

Environmental pollution and infertility are two modern global challenges that agonize personal and public health. The causal relationship between these two deserves scientific efforts to intervene. It is believed that melatonin maintains antioxidant properties and may be utilized to protect the testicular tissue from oxidant effects caused by toxic materials. A systematic literature search was conducted in PubMed, Scopus, and Web of Science to identify the animal trial studies that evaluated melatonin therapy's effects on rodents' testicular tissue against oxidative stress caused by heavy metal and non-heavy metal environmental pollutants. Data were pooled, and standardized mean difference and 95% confidence intervals were estimated using the random-effect model. Also, the risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. (PROSPERO: CRD42022369872). Out of 10039 records, 38 studies were eligible for the review, of which 31 were included in the meta-analysis. Most of them showed beneficial effects of melatonin therapy on testicular tissue histopathology. [20 toxic materials were evaluated in this review, including arsenic, lead, hexavalent chromium, cadmium, potassium dichromate, sodium fluoride, cigarette smoke, formaldehyde, carbon tetrachloride (CCl4), 2-Bromopropane, bisphenol A, thioacetamide, bisphenol S, ochratoxin A, nicotine, diazinon, Bis(2-ethylhexyl) phthalate (DEHP), Chlorpyrifos (CPF), nonylphenol, and acetamiprid.] The pooled results showed that melatonin therapy increased sperm count, motility, viability and body and testicular weights, germinal epithelial height, Johnsen's biopsy score, epididymis weight, seminiferous tubular diameter, serum testosterone, and luteinizing hormone levels, testicular tissue Malondialdehyde, glutathione peroxidase, superoxide dismutase, and glutathione levels. On the other hand, abnormal sperm morphology, apoptotic index, and testicular tissue nitric oxide were lower in the melatonin therapy arms. The included studies presented a high risk of bias in most SYRCLE domains. In conclusion, our study demonstrated amelioration of testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress. Melatonin deserves scientific attention as a potential therapeutic agent for male infertility. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022369872.

Pharmacological modulation of conditioned fear in the fear-potentiated startle test: a systematic review and meta-analysis of animal studies.

Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over the years, a broad range of drugs have been tested in this test. Synthesis of the available data may further our understanding of the neurotransmitter systems that are involved in the expression of conditioned fear. Following a comprehensive search in Medline and Embase, we included 68 research articles that reported on 103 drugs, covering 56 different drug classes. The systematic review was limited to studies using acute, systemic drug administration in naive animals. Qualitative data synthesis showed that most clinically active anxiolytics, but not serotonin-reuptake inhibitors, reduced cued fear. Anxiogenic drugs increased fear potentiation in 35% of the experiments, reduced fear potentiation in 29% of the experiments, and were without effect in 29% of the experiments. Meta-analyses could be performed for five drug classes and showed that benzodiazepines, buspirone, 5-HT1A agonists, 5-HT1A antagonists, and mGluR2,3 agonists reduced cued conditioned fear. The non-cued baseline startle response, which may reflect contextual anxiety, was only significantly reduced by benzodiazepines and 5-HT1A antagonists. No associations were found between drug effects and methodological characteristics, except for strain. The fear-potentiated startle test appears to have moderate to high predictive validity and may serve as a valuable tool for the development of novel anxiolytics. Given the limited available data, the generally low study quality and high heterogeneity additional studies are warranted to corroborate the findings of this review.

Offspring physiology following the use of IVM, IVF and ICSI: a systematic review and meta-analysis of animal studies.

Since the birth of the first baby using IVF technology in 1978, over 10 million children have been conceived via ART. Although most aspects of ARTs were developed in animal models, the introduction of these technologies into clinical practice was performed without comprehensive assessment of their long-term safety. The monitoring of these technologies over time has revealed differences in the physiology of babies produced using ARTs, yet due to the pathology of those presenting for treatment, it is challenging to separate the cause of infertility from the effect of treatments offered. The use of systematic review and meta-analysis to investigate the impacts of the predominant ART interventions used clinically in human populations on animals produced in healthy fertile populations offers an alternative approach to understanding the long-term safety of reproductive technologies. This systematic review and meta-analysis aimed to examine the evidence available from animal studies on physiological outcomes in the offspring conceived after IVF, IVM or ICSI, compared to in vivo fertilization, and to provide an overview on the landscape of research in this area. PubMed, Embase and Commonwealth Agricultural Bureaux (CAB) Abstracts were searched for relevant studies published until 27 August 2021. Search terms relating to assisted reproductive technology, postnatal outcomes and mammalian animal models were used. Studies that compared postnatal outcomes between in vitro-conceived (IVF, ICSI or IVM) and in vivo-conceived mammalian animal models were included. In vivo conception included mating, artificial insemination, or either of these followed by embryo transfer to a recipient animal with or without in vitro culture. Outcomes included birth weight, gestation length, cardiovascular, metabolic and behavioural characteristics and lifespan. A total of 61 studies in five different species (bovine, equine, murine, ovine and non-human primate) met the inclusion criteria. The bovine model was the most frequently used in IVM studies (32/40), while the murine model was mostly used in IVF (17/20) and ICSI (6/8) investigations. Despite considerable heterogeneity, these studies suggest that the use of IVF or maturation results in offspring with higher birthweights and a longer length of gestation, with most of this evidence coming from studies in cattle. These techniques may also impair glucose and lipid metabolism in male mice. The findings on cardiovascular outcomes and behaviour outcomes were inconsistent across studies. Conception via in vitro or in vivo means appears to have an influence on measurable outcomes of offspring physiology, manifesting differently across the species studied. Importantly, it can be noted that these measurable differences are noticeable in healthy, fertile animal populations. Thus, common ART interventions may have long-term consequences for those conceived through these techniques, regardless of the pathology underpinning diagnosed infertility. However, due to heterogeneous methods, results and measured outcomes, highlighted in this review, it is difficult to draw firm conclusions. Optimizing animal and human studies that investigate the safety of new reproductive technologies will provide insight into safeguarding the introduction of novel interventions into the clinical setting. Cautiously prescribing the use of ARTs clinically may also be considered to reduce the chance of promoting adverse outcomes in children conceived before long-term safety is confidently documented.

The effect of selective serotonin reuptake inhibitors on unconditioned anxiety – a systematic review and meta-analysis of animal studies

The effect of selective serotonin reuptake inhibitors on unconditioned anxiety – a systematic review and meta-analysis of animal studies

Protective effect and possible mechanisms of Salvia miltiorrhiza Bge. for the treatment of diabetic nephropathy: A systematic review and meta-analysis of animal studies

To explore the protective effect and potential mechanisms of danshen root ( Salvia miltiorrhiza Bge., S . miltiorrhiza ) and its extracts for the treatment of diabetic nephropathy (DN). Preclinical studies of S . miltiorrhiza and its extracts on DN were systematically searched in nine databases. The primary outcomes were blood glucose, kidney function, proteinuria, and renal histopathology. The secondary outcomes included the related mechanisms. The methodological quality of animal studies was assessed based on the risk of bias tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) for animal studies. Meta-analysis was performed using R software (version 4.1.2). Twenty-nine animal experimental studies that met the eligibility criteria were included in this study. Compared to the control group, S . miltiorrhiza reduced the serum creatinine, blood urea nitrogen, 24-h urine protein, 24-h urine albumin, blood glucose, and kidney index (kidney weight/body weight), and alleviated renal pathological damage. In terms of the mechanism of action, compared to the control group, S . miltiorrhiza reduced the levels of transforming growth factor β1, collagen IV, malondialdehyde, tumor necrosis factor α, interleukin-6, and monocyte/macrophage (ED-1), and increased the levels of superoxide dismutase, glutathione peroxidase, nuclear factor E2–related factor 2, and heme oxygenase-1. The existing evidence shows that S . miltiorrhiza has beneficial effects on the animal model of DN, and its mechanism is mainly related to improving kidney fibrosis, oxidative stress, and inflammatory response.

Effects of garlic and its major bioactive components on non-alcoholic fatty liver disease: A systematic review and meta-analysis of animal studies

• Garlic had beneficial effects on the liver's histopathological features, fat content, enzymes, and weight. • Types and duration of interventions, disease and study models, and risk of bias did not affect the pooled results. • Fermented and raw garlic had similar effects on liver enzymes and weight. • The certainty of the evidence was very low to low according to GRADE. This systematic review and meta-analysis study was conducted to summarize the effects of garlic or its major components on hepatic triglyceride and cholesterol content, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, and liver weight. We searched PubMed, Embase, Scopus, and Web of Knowledge databases. Data were pooled, and standardized mean difference (SMD) and 95% confidence intervals (CI) were estimated using the random-effect model. Out of 958 reports, 28 articles were eligible, of which 22 studies were included in the meta-analysis. Most of the included studies demonstrated the beneficial effects of garlic on hepatic histopathological features. The pooled results showed that garlic significantly decreased hepatic triglyceride and cholesterol, ALT, AST, and liver weight. The certainty of the estimates was very low to low according to GRADE. In conclusion, our study demonstrated amelioration of hepatic histopathological characteristics, hepatic lipid content, serum liver enzymes, and liver weight following garlic administration.

The protective antioxidant activity of ginger extracts (Zingiber Officinale) in acute kidney injury: A systematic review and meta-analysis of animal studies

• The current study aimed to assess the protective antioxidant effects of ginger extracts in acute kidney injury. • For this purpose, 17 eligible animal articles were included in our systematic review and meta-analysis. • There was a significant effect of antioxidant activities, especially for studies that has administrated < 200 mg/kg of ginger extracts. • It was found that ethanol form of ginger extracts could have a better result. • Ginger extracts supplementation with dose frequency fewer than 20 times also showed a more significant effect . Zingiber officinale (Ginger) is considered an herbal medicinal plant with antioxidant features. This study attempted to perform a meta-analysis of the data obtained from previously conducted animal studies on the protective antioxidant effect of ginger extracts on acute kidney injury. This literature search was conducted using some databases, including PubMed, Embase, and Scopus published up to August 2021, by searching relevant keywords. Thereafter, the pooled effect size was estimated using the random effect model. The SYRCLE’s risk of bias tool was then conducted to assess the quality of the obtained studies. The source of heterogeneity among these studies was detected using meta-regression and subgroup analyses. Finally, the meta-analysis on 17 eligible articles revealed that ginger extract supplementation significantly increased SOD (SMD = 5.451 U/mg protein; 95 % CI: 2.099, 8.804; P = 0.005), CAT (SMD = 2.912 U/mg protein; 95 % CI: 0.583, 5.241; P = 0.024), GSH (SMD = 3.400 µg/mg protein; 95 % CI: 1.941,4.859; P < 0.001), and TAC (SMD = 5.923 mmol/L; 95 % CI: 0.900,10.947; P = 0.005). In addition, Ginger extracts decreased MDA (SMD = −3.069 nmol/g tissue; 95 % CI: −5.971, −0.166; P = 0.005). However, no significant effect was noticed in terms of both GPx (SMD = 1.096 U/mg protein; 95 % CI: −0.699, 2.891; P = 0.177), and GST (SMD = 0.199 U/g protein; 95 % CI: −6.558, 6.957; P = 0.911). Therefore, the results of the meta-analysis support the convincing evidence regarding the protective antioxidant activity of ginger extracts in animals with acute kidney injury.

Burn-Induced Local and Systemic Immune Response: Systematic Review and Meta-Analysis of Animal Studies

Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to preventing secondary complications. This systematic review, which includes 247 animal studies, shows the postburn response of 14 different immune cell types involved in immediate and long-term effects in both wound tissue and circulation. Peripheral blood neutrophil and monocyte numbers increased directly after burns, whereas thrombocyte numbers increased near the end of the first week. However, lymphocyte numbers were decreased for at least 2 weeks. In burn wound tissue, neutrophil and macrophage numbers accumulated during the first 3 weeks. Burns also altered cellular functions because we found an increased migratory potential of leukocytes, impaired antibacterial activity of neutrophils, and enhanced inflammatory mediator production by macrophages. Neutrophil surges were positively associated with burn size and were highest in rats. Altogether, this comprehensive overview of the temporal immune cell dynamics shows that unlike normal wound healing, burn injury induces a long-lasting inflammatory response. It provides a fundamental research basis to improve experimental set-ups, burn care, and outcomes.

Preclinical evidence of the effect of quercetin on diabetic nephropathy: A meta-analysis of animal studies

Quercetin, which is present in numerous fruits and vegetables, has shown promise in improving inflammation, lipid profiles, and blood pressure in humans. However, the efficacy of quercetin in diabetic nephropathy (DN) remains preclinical and unclear. Therefore, a meta-analysis based on preclinical animal data is needed to assess the efficacy, optimal dosage, and underlying mechanism of DN treatment to accelerate new drug research and clinical translation. We conducted a literature search in PubMed, Embase, Web of Science, and Cochrane Library to retrieve randomized controlled trials evaluating the effects of quercetin in rat or mouse diabetic models. We assessed the quality of the studies individually according to SYRCLE's risk of bias tool for animal studies. Twenty animal studies, including 378 animals, were included in the meta-analysis. Meta-analysis data showed that renal function indices, such as renal index, urine protein, uric acid, urine albumin, and serum creatinine levels, significantly improved with quercetin administration. However, no significant association was observed between quercetin and creatinine clearance. Quercetin remarkably alleviated oxidative stress by reducing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) and catalase (CAT) activities. In addition, quercetin exhibits anti-inflammatory activity by reducing tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）levels. Subgroup analysis performed using quercetin doses and animal species indicated that animal species were a source of heterogeneity. This meta-analysis suggests that quercetin is a promising drug for DN treatment, facilitating clinical prediction and therapy.

The impact of weight cycling on health outcomes in animal models: A systematic review and meta-analysis.

The pattern of weight loss and regain, termed "weight cycling," is common in overweight individuals. It is unclear whether the well-established benefits of weight loss persist following weight regain or whether weight cycling is harmful. Human studies of weight cycling have conflicting results reflecting limitations of the observational designs of these studies. By controlling the macronutrient content of diets in animal studies, weight cycling can be studied in a highly controlled manner, thereby overcoming the limitations of human studies. We conducted a systematic review and meta-analysis of animal studies which assessed the health consequences of weight cycling. Studies were classified into those which compared weight cycling to lifelong obesity and those which compared weight cycling to later onset obesity. There were no differences in health outcomes between weight cycled animals and those with lifelong obesity, highlighting that weight regain reverses health benefits achieved by weight loss. In comparison with animals with later onset obesity, weight cycled animals had higher fasting glucose levels and more impaired glucose tolerance following weight regain. Our review of animal studies suggests that health benefits of diet-induced weight loss do not persist after weight regain and weight cycling results in adverse metabolic outcomes.

Effects of natural dihydrochalcones in sweet tea (Lithocarpus polystachyus) on diabetes: a systematical review and meta-analysis of animal studies.

Sweet tea (Lithocarpus polystachyus Rehd.), a natural functional food highly rich in dihydrochalcones including trilobatin, phlorizin and phloretin, is reported to possess numerous biological activities especially for treating diabetes. Here, the aim of this systematical review and meta-analysis is to assess the effect of dihydrochalcones in sweet tea (DST) on diabetes and summarize their possible mechanisms. We searched in eight databases including Embase, PubMed, Cochrane, Web of Science, WanFang database, VIP database, China National Knowledge Infrastructure and China Biology Medicine from Jan 2000 to Nov 2021 and ultimately included 21 animal studies in this review. A total of 10 outcome measurements including blood lipid indexes, blood glucose, insulin resistance indicators and oxidative stress biomarkers were extracted for meta-analysis using RevMan 5.4 software. DST significantly decreased the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), blood glucose (BG), homeostasis model assessment of insulin resistance (HOMA-IR) and malondialdehyde (MDA), and increased high-density lipoprotein cholesterol (HDL-c), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in diabetic animal models. In summary, DST could treat diabetes by regulation of blood glucose/lipid metabolism, oxidative/carbonyl stress, inflammatory response etc.