Systematic Review Centre For Laboratory Animal Experimentation Research Articles

Regulations of Immune Response by Astragalus in Animal Asthma Models: A Meta-analysis

Background Asthma is a chronic respiratory condition by airway inflammation. Traditional Chinese medicine, is commonly used to treat it. Astragalus is known for its immunoregulation, anti-inflammatory, and antioxidant effects. Purpose To systematically evaluate the efficacy of Astragalus in asthma animal models using meta-analysis methods. Methodology A systematic search was performed in various databases, such as China National Knowledge Infrastructure (CNKI), WanFang Data, PubMed, Web of Science, and Cochrane Library databases for animal studies on Astragalus intervention in asthma models, with the search period extending up to September 2023. Two researchers performed independent literature screening and data extraction. The quality of the included studies was assessed by the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) animal experiment bias risk assessment tool. Meta-analysis was performed with RevMan (version 3.6.1). Results A total of 25 experiments were included. Meta-analysis indicated that Astragalus can significantly reduce total leukocytes, neutrophils, lymphocytes, and eosinophils in animal models of asthma. It also downregulated the expression levels of interleukin-4 and interleukin-5, while upregulation of interferon-γ and interleukin-10 expression was observed; however, the impact on macrophages was found to be not statistically significant ( p > 0.05). Conclusion Our systemic review suggested the potential efficiency of Astragalus in asthma treatment in China, although its mechanism is still unclear. The functions of Astragalus may be associated with attenuating airway inflammation through the regulation of immune response.

Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis.

Animal models are critical tools in the study of psychiatric disorders; however, none of the current models fully reflect human stress-related disorders, even though most of the knowledge about the mechanisms of depression comes from animal studies. Animal studies are useful in pharmacological research, whereby we can obtain results that translate into patient treatment by controlling environmental factors, especially in behavioural research. The authors systematically reviewed this issue since medical databases provide access to many primary studies. A systematic review and meta-analysis were conducted based on 25 primary studies. The studies were identified in databases such as PubMed, Embase, and Web of Science (December 2022) according to the inclusion and exclusion criteria established at the beginning of the research and published in the form of a protocol, following the PRISMA and Cochrane Collaboration methodology for secondary studies and CAMARADES (CAMARADES Berlin, QUEST-BIH Charité) for secondary studies on animals. Forest plot analyses were performed (data presented as Mean Difference, Random Model, Inverse Variance), Risk of Bias assessment (Systematic Review Center for Laboratory animal Experimentation (SYRCLE) evaluation), quality assessment of included studies (Animal research: Reporting of In Vivo Experiments (ARRIVE)), and a range of data from source publications were compiled in tabular form. The study analysed the popularity of both animal depression models (ADM) and rat strains used in pharmacological research to test the efficacy of antidepressant drugs based on the immobility time (IT) factor (Forced Swimming Test). The study examined selective serotonin reuptake inhibitors, namely fluoxetine, sertraline, paroxetine, citalopram, and escitalopram. Additionally, the study addressed issues concerning the "data availability statement" because precise IT data analysis was impossible in the case of 212 papers. Our data confirm that the Chronic Unpredictable Mild Stress (CUMS) model is the most popular and versatile model used in preclinical depression research, while the two most popular rat strains were Wistar and Sprague-Dawley. The quality of included papers based on the ARRIVE assessment showed a ratio value equal to 0.63, meaning that studies were of intermediate overall quality. The Risk of Bias assessment based on the SYRCLE tool revealed a high risk related to the blinding and the random outcome assessment. In the meta-analysis, the results indicate that all analysed drugs demonstrated efficacy in reducing IT, and the most analysed drug was fluoxetine (confirmed based on 17 studies (19 models)). The analysis of the efficacy of ADMs showed that the most effective models were CUMS, Flinders Sensitive Line (genetic model), Social Isolation, Restraint Stress, and Low-dose Lipopolysaccharide (pharmacological model). Only 2.35% (5 out of 212) of corresponding authors responded to our data request. The study highlights the dominance of the CUMS model and the Wistar and Sprague-Dawley rat strains in preclinical depression research, affirming the efficacy of SSRIs, particularly fluoxetine, in reducing IT. The findings underscore the need for better data availability and methodological improvements despite intermediate overall study quality and notable bias risks. Enhanced transparency and rigorous assessment standards are essential for advancing the reliability of animal models in depression research.

Comparative efficacy of the five most common traditional Chinese medicine monomers in reducing intimal hyperproliferation in arterial balloon injury models: A network meta-analysis

ObjectiveThis study utilized network meta-analysis (NMA) to compare the efficacy of five commonly used traditional Chinese medicine monomers in reducing intimal hyperproliferation in arterial balloon injury models. MethodsRelevant literature up to January 2024 was systematically retrieved from seven major databases. The intima-to-media (I/M) ratio was chosen as the primary outcome measure. The risk of bias in animal studies was assessed using the SYstematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Statistical analysis was conducted using Stata 17 software. ResultsA total of 43 studies were included in this meta-analysis. NMA results showed that in the rat model, compared to the control group, GS (SMD: 0.99, 95%CI: 1.25 to −0.73), ASIV (SMD: 1.16, 95%CI: 1.65 to −0.67), TMP (SMD: 0.68, 95%CI: 1.31 to −0.05), and TPNS (SMD: 1.36, 95%CI: 1.91 to −0.80) exhibited inhibitory effects on postoperative intimal hyperproliferation, reducing the I/M ratio. In the rabbit model, compared to the control group, TPNS (SMD: 1.23, 95%CI: 1.97 to −0.49) inhibited postoperative intimal hyperproliferation and reduced the I/M ratio. Superiority ranking analysis suggested that total Panax notoginseng saponin (TPNS) might be the most effective traditional Chinese medicine monomer in reducing intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio. ConclusionNMA indicates that traditional Chinese medicine monomers can effectively reduce postoperative intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio, with TPNS showing optimal efficacy. However, the research on TIIA is insufficient, and the limited sample size may affect the robustness of the results. Furthermore, the majority of research on traditional Chinese medicine monomers is currently limited to the experimental stage, lacking further clinical validation. Conducting standardized animal experiments and reporting their findings can enhance the quality of evidence from animal studies, laying the foundation for future clinical trials.

The Efficacy of Curcumin Application to Melanoma in Mice: A Systematic Review and Meta-analysis.

Melanoma is a skin tumor that poses a serious threat to human health. Our study explores the effectiveness and safety of curcumin in the treatment of melanoma based on animal models, and providing evidence-based medical evidence for curcumin in the treatment of malignant melanoma. The study collected all randomized controlled trial data from the establishment of the database to October 2023 of curcumin for the treatment of melanoma in mice by searching PubMed, Embase, and the Cochrane Library. According to inclusion and exclusion criteria, data were extracted and quality assessment of included studies was performed by using the SYRCLE (Systematic Review Center for Laboratory animal Experimentation) animal experiment bias risk assessment tool. RevMan 5.4 and Stata 15.1 software were used for meta-analysis. Eighteen randomized controlled trials were included in this study with a total of 185 mouse models, including 93 mice in the experimental group and 92 in the control group. The results of meta-analysis showed that the IC50 (inhibitory concentrations of 50%) in the experimental group is lower than that of the control group [standardized mean difference (SMD) = -4.68, 95% confidence interval (CI) (-7.30, -2.06), P < 0.01]; the tumor volume is significantly smaller than the control group [SMD = -3.10, 95% CI (-4.45, -1.75), P < 0.01]; the tumor weight is smaller than the control group [SMD = -3.01, 95% CI (-4.81, -1.21), P < 0.01]. However, there was no significant statistical difference in the apoptosis rate between the experimental group and the control group [SMD = 2.27, 95% CI (-1.39, 5.92), P < 0.01]. Based on animal models for meta-analysis, curcumin can inhibit the growth and proliferation of melanoma in mice. Melanoma may be an effective method for treating melanoma. However, this result still requires further in-depth research.

A Systematic Review of the Impact of Benzimidazole-based Anthelmintics on Lung Cancer in Animal Models.

Emerging studies have reported the potential anticancer activity of FDA-approved benzimidazole-based anthelmintics against lung cancer. Therefore, the current systematic review aimed to explore the anticancer activity of benzimidazole-based anthelmintics in lung cancer animal models. The databases including Pubmed, ScienceDirect, and Google Scholar were searched till April 2024 for the animal studies evaluating the anticancer activity of benzimidazole-based anthelmintics against lung cancer. The relevant data was extracted in the prepared format in Microsoft Excel. Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias (RoB) was used to assess the quality of included studies. The protocol for this study has been registered in PROSPERO (Registration number: CRD42022352141). Initially, we obtained 4150 articles, and finally eight articles were included in the current study. The information in the included studies was a bit diversified including different benzimidazole-based anthelmintics, dosage, route of administration, and duration of experiments. However, all studies reported that exposure to benzimidazole-based anthelmintics decreased tumor size and tumor volume in animal models of lung cancer. In conclusion, benzimidazole-based anthelmintics have the potential to treat lung cancer. However, more controlled and thorough preclinical studies are required to evaluate its efficacy, safety, and mechanism of anticancer activities.

Diabetes mellitus, hearing loss, and therapeutic interventions: A systematic review of insights from preclinical animal models.

The aim of this systematic review article is to evaluate the relationship between diabetes mellitus (DM) and sensorineural hearing loss (SNHL) utilizing preclinical animal models. The review focused on studies assessing SNHL in diabetic animal models, elucidating the mechanisms of DM-associated SNHL, and exploring the response of diabetic animal models to noise overexposure. We also discussed studies investigating the efficacy of potential therapeutic strategies for amelioration of DM-associated SNHL in the animal models. A protocol of this systematic review was designed a priori and was registered in the PROSPERO database (registration number: CRD42023439961). We conducted a comprehensive search on PubMed, Science Direct, Web of Science, Scopus, and EMBASE databases. A minimum of three reviewers independently screened, selected, and extracted data. The risk of bias assessment of eligible studies was conducted using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool. Following the screening of 238 studies, twelve original articles were included in this systematic review. The studies revealed that hyperglycemia significantly affects auditory function, with various pathological mechanisms contributing to DM-induced hearing impairment, including cochlear synaptopathy, microangiopathy, neuropathy, oxidative stress, mitochondrial abnormalities, and apoptosis-mediated cell death. Emerging interventions, such as Asiaticoside, Trigonelline, Chlorogenic acid, and Huotanquyu granules, demonstrated efficacy in providing otoprotection for preserving cochlear hair cells and hearing function. Our systematic review delves into the intricate relationship between DM and hearing impairment in animal models. Future research should focus on targeted therapies to enhance cochlear mitochondrial function, alleviate oxidative stress, and regulate apoptosis. The association between SNHL and social isolation as well as cognitive decline underscores the necessity for innovative therapeutic modalities addressing yet undiscovered mechanisms. Translating findings from animal models to human studies will validate these findings, offering a synergistic approach to effectively manage DM-associated co-morbidities such as hearing impairment.

Outcomes following cochlear implantation with eluting electrodes: A systematic review

AbstractObjectivesTo establish audiological and other outcomes following cochlear implantation in humans and animals with eluting electrodes.MethodsSystematic review and narrative synthesis. Databases searched (April 2023): MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and Web of Science. Studies reporting outcomes in either humans or animals following cochlear implantation with a drug‐eluting electrode were included. No limits were placed on language or year of publication. Risk of bias assessment was performed on all included studies using either the Brazzelli or Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) assessment tools. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement.ResultsSearches identified 146 abstracts and 108 full texts. Of these, 18 studies met the inclusion criteria, reporting outcomes in 523 animals (17 studies) and 24 humans (1 study). Eluting electrodes included dexamethasone (16 studies), aracytine (1 study), nicotinamide adenine dinucleotide (1 study), the growth factors insulin‐like growth factor 1 (IGF1) and hepatocyte growth factor (HGF) (1 study), and neurotrophin‐3 (1 study). All included studies compare outcomes following implantation with an eluting electrode with a control non‐eluting electrode. In the majority of studies, audiological outcomes (e.g., auditory brainstem response threshold) were superior following implantation with an eluting electrode compared with a standard electrode. Most studies which investigated post‐implantation impedance reported lower impedance following implantation with an eluting electrode. The influence of eluting electrodes on other reported outcomes (including post‐implantation cochlear fibrosis and the survival of hair cells and spiral ganglion neurons) was more varied across the included studies.ConclusionsEluting electrodes have shown promise in animal studies in preserving residual hearing following cochlear implantation and in reducing impedance, though data from human studies remain lacking. Further in‐human studies will be required to determine the clinical usefulness of drug‐eluting cochlear implants as a future treatment for sensorineural hearing loss.

Effects of jujube (Ziziphus jujuba mill.) fruit extracts on oxidative stress: A systematic review and meta-analysis of rodent studies.

This study aimed to evaluate the effects of jujube (Ziziphus jujuba Mill.) fruit extracts on oxidative stress levels in rodent models. Animal studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Periodical Service Platform. The Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool was used to evaluate the risk of bias in the included studies. A meta-analysis was performed based on the guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions (CHSRI) by using Stata 17.0 software. Nineteen studies were included in the meta-analysis. Jujube fruit extracts significantly decreased the level of malonaldehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Meanwhile, there was no significant improvement in the catalase (CAT) levels. In addition, there was considerable heterogeneity in the results of the meta-analysis. The results of the subgroup analysis indicated that the animal model, type of extracts, and source of target parameters may have contributed to the heterogeneity. Jujube fruit extracts are healthy and effective antioxidant dietary supplements that may be an effective adjunctive therapy for diseases in which oxidative stress is a major pathological factor. However, the overall methodological quality of the included studies was low, and additional research is warranted.

Cellularized Biomaterials Used as Gingival Connective Tissue Substitutes In Vivo: A Systematic Review.

Developing an in vitro model of gingival connective tissue that mimics the original structure and composition of gingiva for clinical grafting is relevant for personalized treatment of missing gingiva. Using tissue engineering techniques allows bypassing limitations encountered with existing solutions to increase oral soft tissue volume. This review aims to systematically analyze the different currently existing cellularized materials and technologies used to engineer gingival substitutes for invivo applications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. An electronic search on PubMed, Scopus, Web of Science, and Cochrane Library databases was conducted to identify suitable studies. In vivo studies about gingival substitutes and grafts containing oral cells compared with a control to investigate the graft remodeling were included. Risk of bias in the included studies was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) 10-item checklist. Out of 631 screened studies, 19 were included. Animal models were mostly rodents, and the most used implantation was subcutaneous. According to the SYRCLE tool, low-to-unclear risk of bias was prevalent. Studies checked vascularization and extracellular remodeling up to 60 days after implantation of the cellularized biomaterial. Cells used were mostly fibroblasts and stem cells from oral origin. Grafts presenting vascularization potential after implantation were produced by tissue engineering technologies including cell seeding or embedding for 14, cell sheets for 2, microsphere for 1, and extrusion 3D bioprinting for 2. Components used to build the scaffold containing the cells are all naturally derived and are mainly fibrin, gelatin, collagen, agarose, alginate, fibroin, guar gum, hyaluronic acid, and decellularized extracellular matrix. The most recurring crosslinking method was using chemicals. All studies except one reported vascularization of the graft after implantation, and some detailed extracellular matrix remodeling. Current solutions are not efficient enough. By assessing the relevant studies on the subject, this systematic review showed that a diversity of cellularized biomaterials substituting gingival connective tissue enables vascularization and extracellular remodeling. Taking the results of this review into account could help improve current bio-inks used in 3D bioprinting for invivo applications compensating for gingival loss.

Mesenchymal stem cell based therapies for uveitis: a systematic review of preclinical studies.

Cell therapy has shown promising results for treating uveitis in preclinical studies. As the field continues to grow towards clinical translation, it is important to review and critically appraise existing studies. Herein, we analysed and critically appraised all preclinical studies using cell therapy or cell derived extracellular vesicles (EVs) for uveitis, and provided insight into mechanisms regulating ocular inflammation. We used PubMed, Medline, and Embase to search for preclinical studies examining stem cell therapy (e.g., mesenchymal stem cells [MSC]) and secreted EVs. All included studies were assessed for quality using the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) checklist. Sixteen preclinical studies from 2011 to 2022 were analysed and included in this review of which 75% (n = 12) focused only on cell therapy, 18.7% (n = 3) studies focused on EVs, and 6.3% (n = 1) study focused on both cells and EVs. MSCs were the most common type of cells used in preclinical studies (n = 15) and EVs were commonly isolated from MSCs (n = 3). Overall, both MSCs and EVs showed improvements in ocular inflammation (seen on fundoscopy/slit lamp and histology) and electroretinogram outcomes. Overall, MSC and MSC-derived EVs shown great potential as therapeutic agents for treating uveitis. Unfortunately, small sample size, risk of selection/performance bias, and lack of standardized cell harvesting or delivery protocols are some factors which limits clinical translation. Large scaled, randomized preclinical studies are required to understand the full potential of MSCs for treating uveitis.

Cognitive and Motor Function Effects of Antipsychotics in Traumatic Brain Injury: A Systematic Review of Pre-Clinical Studies.

Traumatic brain injury (TBI) survivors often suffer from agitated behaviors and will most likely receive pharmacological treatments. Choosing an optimal and safe treatment that will not interfere with neurological recovery remains controversial. By interfering with dopaminergic circuits, antipsychotics may impede processes important to cognitive recovery. Despite their frequent use, there have been no large randomized controlled studies of antipsychotics for the management of agitated behaviors during the acute TBI recovery period. We conducted a systematic review and meta-analysis of pre-clinical studies evaluating the effects of antipsychotics post-TBI on both cognitive and motor recovery. MEDLINE and Embase databases were searched up to August 2, 2023. Pre-clinical studies evaluating the effects of antipsychotics on cognitive and motor functions post-TBI were considered. Risk of bias was evaluated with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. We identified 15 studies including a total of 1188 rodents, mostly conducted in male Sprague-Dawley rats using cortical impact injury. The analysis revealed no consistent effect of haloperidol on motor functions, but risperidone was associated with a significant impairment in motor function on day 5 post-injury (7.05 sec; 95% confidence interval [CI]: 1.47, 12.62; I2 = 92%). Other atypical antipsychotics did not result in impaired motor function. When evaluating cognitive function, haloperidol- (23.00 sec; 95% CI: 17.42-28.59; I2 = 7%) and risperidone-treated rats (24.27 sec; 95% CI: 16.18-32.36; I2 = 0%) were consistently impaired when compared to controls. In studies evaluating atypical antipsychotics, no impairments were observed. Clinicians should avoid the regular use of haloperidol and risperidone, and future human studies should be conducted with atypical antipsychotics.

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.

Dental Stem Cell-Based Therapy for Glycemic Control and the Scope of Clinical Translation: A Systematic Review and Meta-Analysis

Background: The tooth is a repository of stem cells, garnering interest in recent years for its therapeutic potential. The aim of this systematic review and meta-analysis was to test the hypothesis that dental stem cell administration can reduce blood glucose and ameliorate polyneuropathy in diabetes mellitus. The scope of clinical translation was also assessed. Methods: PubMed, Cochrane, Ovid, Web of Science, and Scopus databases were searched for animal studies that were published in or before July 2023. A search was conducted in OpenGrey for unpublished manuscripts. Subgroup analyses were performed to identify potential sources of heterogeneity among studies. The risk for publication bias was assessed by funnel plot, regression, and rank correlation tests. Internal validity, external validity, and translation potential were determined using the SYRCLE (Systematic Review Center for Laboratory Animal Experimentation) risk of bias tool and comparative analysis. Results: Out of 5031 initial records identified, 17 animal studies were included in the review. There was a significant decrease in blood glucose in diabetes-induced animals following DSC administration compared to that observed with saline or vehicle (SMD: −3.905; 95% CI: −5.633 to −2.177; p = 0.0004). The improvement in sensory nerve conduction velocity (SMD: 4.4952; 95% CI: 0.5959 to 8.3945; p = 0.035) and capillary-muscle ratio (SMD: 2.4027; 95% CI: 0.8923 to 3.9132; p = 0.0095) was significant. However, motor nerve conduction velocity (SMD: 3.1001; 95% CI: −1.4558 to 7.6559; p = 0.119) and intra-epidermal nerve fiber ratio (SMD: 1.8802; 95% CI: −0.4809 to 4.2413; p = 0.0915) did not increase significantly. Regression (p &lt; 0.0001) and rank correlation (p = 0.0018) tests indicated the presence of funnel plot asymmetry. Due to disparate number of studies in subgroups, the analyses could not reliably explain the sources of heterogeneity. Interpretation: The direction of the data indicates that DSCs can provide good glycemic control in diabetic animals. However, methodological and reporting quality of preclinical studies, heterogeneity, risk of publication bias, and species differences may hamper translation to humans. Appropriate dose, mode of administration, and preparation must be ascertained for safe and effective use in humans. Longer-duration studies that reflect disease complexity and help predict treatment outcomes in clinical settings are warranted. This review is registered in PROSPERO (number CRD42023423423).

Advancements and challenges in stem/progenitor cell transplantation for dentin-pulp regeneration: a systematic review of animal studies (part I).

Dentin-pulp regeneration through stem/progenitor cell transplantation represents a promising frontier in regenerative endodontics. This systematic review meticulously evaluates animal studies to investigate the efficacy of stem cell therapy in repairing/regenerating the dentine-pulp complex in mature/immature animal teeth. Employing a comprehensive electronic search of PubMed and Scopus databases up to October 2023, relevant English studies were identified/assessed. Evaluation parameters encompassed radiographic and histological assessments of dentin-pulp complex formation. Outcome measures included pulp-like and dentin-like tissues regeneration, apical healing, dentin thickening, apical closure, and dentinal bridge formation. The risk-of-bias assessment adhered to the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) guidelines. Out of 3250 identified articles, 23 animal experiments were included, categorized into regenerative procedures in mature teeth (n=11), regenerative procedures in immature teeth (n=4), and vital pulp therapy (n=8). Despite the promising potential, the bias in the included studies was high. Notably, Various scaffolds, and growth factors were employed, highlighting the heterogeneity across the studies. Dental pulp stem cells (DPSCs) and bone marrow stem cells, especially specific subfractions, demonstrated notable regenerative potential: hypoxic conditions and extracellular vesicles from preconditioned DPSCs enhanced regeneration, with considerations of cell fate. Donor age impacted regeneration, and challenges persisted in pulpotomy and direct pulp capping. Scaffold and growth factor choices influenced outcomes, underscoring the need for standardized strategies. Despite the promise, clinical viability faces hurdles, necessitating further investigation into adverse effects, optimized scaffolds, and regulatory considerations. This systematic review illuminates the potential of stem cell transplantation for dentin-pulp complex regeneration. The overall evidence quality, influenced by study heterogeneity and biases, underscores the need for cautious interpretation of findings. Future studies should refine methodologies and establish reliable histological parameters for meaningful advancements in dentin-pulp regeneration.

Evidence and possible mechanism of Scutellaria baicalensis and its bioactive compounds for hepatocellular carcinoma treatment

Background Traditional Chinese medicines have been reported to have outstanding effects in the treating of hepatocellular carcinoma. Scutellaria baicalensis (S. baicalensis) has demonstrated anti-tumor, anti-angiogenic, and anti-inflammatory properties. Baicalein, wogonin, and baicalin are the main pharmacologically bioactive compounds of S. baicalensis. Methods Eight electronic databases were searched to select articles published from their inception to 30 May 2022. For selected articles, clinical and preclinical data was obtained on the use of S. baicalensis and its bioactive compounds in hepatocellular carcinoma therapy. Statistical analyses were performed using RevMan version 5.3 and Stata software. Quality assessment of the studies was performed using Cochrane and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)’s risk of bias tools. Results Seven clinical and 17 preclinical in vivo studies along with 31 in vitro studies were included in this research. Meta-analysis showed that a Chinese herbal medicine preparation, with S. baicalensis as the sovereign herb, combined with Transcatheter arterial chemoembolization (TACE) or primary treatment, could lead to a significantly improved tumor objective response rate (Risk ratio (RR) = 1.57, 95% confidence interval (CI): [1.30, 1.90], p < 0.00001). Scutellaria baicalensis-based extracts (standard mean difference (SMD) = –0.86, 95%CI: [–1.20, −0.53], p < 0.00001), baicalein (SMD = –4.80, 95%CI: [–6.66, − 2.95], p < 0.00001), baicalin (SMD = –2.28, 95%CI [–3.26, −1.30], p < 0.00001) and wogonin (SMD = –1.41, 95%CI [–2.26, −0.57], p < 0.00001) slowed tumor growth in vivo. These outcomes might be linked to the mechanism by which S. baicalensis promotes apoptosis, induces autophagy, and blocks the expression of vascular endothelial growth factor (p < 0.05). Conclusion Based on experimental and clinical evidence, we believe that S. baicalensis and its bioactive compounds have therapeutic potential and plausible mechanisms of action against hepatocellular carcinoma, in terms of efficacy and safety.

A Systematic Review of Butterfly Pea Flowers (Clitoria ternatea L.) in Reducing Body Weight and Improving Lipid Profile in Rodents with Obesity

Background: Butterfly pea flowers (Clitoria ternatea L.) are edible plants found in Asian countries that have several phytochemical compounds thathave potential anti-obesity and anti-dyslipidemia. From several in vivo studies, the administration of various extracts of butterfly pea flowers has different effects to reduce body weight (BW) or body mass index (BMI), and lipid profiles. Objectives: To analyze systematically the effects of butterfly pea flowers on BW or BMI and lipid profiles in rodents with or without obesity. Methods: This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and bias risk using the Systematic Review Centre for Laboratory Animal Experimentation (SyRCLEs).Original articles were from Google Scholar, PubMed, ResearchGate, and Science-Direct with criteria: randomized control trial (RCT), published from 2019 to 2023, rodents, and research outcomes (BW and lipid profiles). Results: Four original articles met the research criteria. Giving 1,000 mg/kg BW of the aqueous extract of butterfly pea flower for seven days reduced BW. Another study reported that giving 130 mg/kg BW butterfly pea flowers kombucha inhibited weight gain. Doses of 0.25 and 0.50% of the aqueous extracts of butterfly pea flowers for 15 weeks did not affect BW butthe dose of 2% prevented weight gain. Conclusions: Butterfly pea flowers have beneficial effects on reducing BW and improving lipid profiles in rodents with severaldiets although vary in animal models, diet types, extraction methods, and research design. This study becomes important evidence for further study.

The Pharmacological Effect of Hemin in Inflammatory-Related Diseases: Protocol for a Systematic Review.

Hemin is a commonly used drug in the treatment of acute attacks of porphyria, due to its capability of restoring normal levels of hemoproteins and respiratory pigments. In addition, this drug has demonstrated the capacity to induce the heme oxygenase (HO) enzyme. At the moment, there are 3 known HO isoenzymes in mammals: HO-1, HO-2, and HO-3. The first of these shows cytoprotective, antioxidant, and anti-inflammatory effects. Currently, medicines used in inflammatory disorders have increased toxicity, especially over longer time frames, which highlights the need to investigate new, safer options. Indeed, the current nonclinical evidence demonstrates the potential that hemin has a significant anti-inflammatory effect in several animal models of inflammation-related diseases, such as experimental colitis, without significant side effects. However, the underlying mechanism(s) are still not fully understood. In addition, past nonclinical studies have applied different therapeutic regimens, making it relatively difficult to understand which is optimal. According to the literature, there is a lack of review articles discussing this topic, highlighting the need for a summary and analysis of the available preclinical evidence to elucidate the abovementioned issues. Therefore, a qualitative synthesis of the current evidence is essential for the research and medical communities. This systematic review aims to summarize and analyze currently available nonclinical data to ascertain the potential anti-inflammatory effect of hemin in animal models. Throughout the development of this protocol, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The comprehensive search strategy will be carried out in MEDLINE (PubMed), Web of Science, and Scopus without any filters associated with publication date. Only in vivo, nonclinical studies that evaluated the potential anti-inflammatory effect of hemin will be included. The evaluated outcomes will be the observed clinical signs, inflammatory and other biochemical markers, and macroscopic and microscopic evaluations. To analyze the potential risk of bias, we will use the risk of bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). Currently, it is not possible to disclose any results since the project is still in initial steps. More specifically, we are currently engaged in the identification of eligible articles through the application of the inclusion and exclusion criteria. The work was initiated in April 2023, and it is expected to be finished at the end of 2023. Concerning the major gap in the literature regarding the underlying mechanism(s) and treatment-related properties, this systematic review will be essential to clearly summarize and critically analyze the nonclinical data available, promoting a clearer vision of the potential anti-inflammatory effect of hemin. PROSPERO CRD42023406160; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=406160. PRR1-10.2196/48368.

Mouse models of diabetes-related ulcers: a systematic review and network meta-analysis

Diabetic foot ulcers (DFUs) are a common complication of diabetes, associated with important morbidity. Appropriate animal models of DFUs may improve drug development, and subsequently the success rate of clinical trials. However, while many models have been proposed, they are extremely heterogeneous, and no standard has emerged. We thus propose a systematic review with a network meta-analysis (NMA) to gather direct and indirect evidence, and compare the different mouse models of diabetes-related ulcers. The systematic search was performed in Pubmed and Embase. The main outcomes were wound size measurement at days 3, 7, 11 and 15 (±1 day). The risk of bias and methodological quality of all included studies was assessed by using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool. Meta-regressions were done on prespecified variables, including mouse strain, type of ulcer, sex, age, and use of a splint. We included 295 studies. Among all models, only db/db, ob/ob, streptozotocin (STZ), and STZ+high fat diet mice showed a significantly delayed wound healing, compared with controls, at each time point. Age, sex and ulcer type had influence on wound healing, although not at all time points. In conclusion, the db/db model is associated with the largest delay in wound healing The STZ model also exhibits significantly decreased wound healing. STZ+high fat diet and ob/ob mice may also be relevant models of diabetes-related ulcers, although the results rely on a more limited number of studies. This work was funded by the Agence Nationale de la Recherche (grant ANR-18-CE17-0017).

Comparative effects of finasteride and minoxidil on the male reproductive organs: A systematic review of in vitro and in vivo evidence

Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.

Protective effects and possible mechanisms of catalpol against diabetic nephropathy in animal models: a systematic review and meta-analysis.

Aim of the Study: Rehmannia glutinosa is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000years. Catalpol is the main active compound in Rehmannia roots. Current evidence suggests that catalpol exhibits significant anti-diabetic bioactivity, and thus it has attracted increasing research attention for its potential use in treating DN. However, no studies have systematically evaluated these effects, and its mechanism of action remains unclear. This study aimed to evaluate the effects of catalpol on DN, as well as to summarize its possible mechanisms of action, in DN animal models. Materials and Methods: We included all DN-related animal studies with catalpol intervention. These studies were retrieved by searching eight databases from their dates of inception to July 2022. In addition, we evaluated the methodological quality of the included studies using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool. Furthermore, we calculated the weighted standard mean difference (SMD) with 95% confidence interval (CI) using the Review Manager 5.3 software and evaluated publication bias using the Stata (12.0) software. A total of 100 studies were retrieved, of which 12 that included 231 animals were finally included in this review. Results: As compared to the control treatment, treatment with catalpol significantly improved renal function in DN animal models by restoring serum creatinine (Scr) (p = 0.0009) and blood urea nitrogen (BUN) (p < 0.00001) levels, reducing proteinuria (p < 0.00001) and fasting blood glucose (FBG) (p < 0.0001), improving kidney indices (p < 0.0001), and alleviating renal pathological changes in the animal models. In addition, it may elicit its effects by reducing inflammation and oxidative stress, improving podocyte apoptosis, regulating lipid metabolism, delaying renal fibrosis, and enhancing autophagy. Conclusion: The preliminary findings of this preclinical systematic review suggest that catalpol elicits significant protective effects against hyperglycemia-induced kidney injury. However, more high-quality studies need to be carried out in the future to overcome the methodological shortcomings identified in this review.