scholarly journals Chondroprotective Actions of Selective COX-2 Inhibitors In Vivo: A Systematic Review

2020 ◽  
Vol 21 (18) ◽  
pp. 6962 ◽  
Author(s):  
Ufuk Tan Timur ◽  
Marjolein M. J. Caron ◽  
Ralph M. Jeuken ◽  
Yvonne M. Bastiaansen-Jenniskens ◽  
Tim J. M. Welting ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Studies ◽  
Slow Release ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Preclinical Studies ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Slow Release System

Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of OA-related cartilage damage. Selective COX-2 inhibitors may, next to their pain killing properties, act chondroprotective in vivo. To determine whether the route of administration is important for the efficacy of the chondroprotective properties of selective COX-2 inhibitors, a systematic review was performed according to the PRISMA guidelines. Studies investigating OA-related cartilage damage of selective COX-2 inhibitors in vivo were included. Nine of the fourteen preclinical studies demonstrated chondroprotective effects of selective COX-2 inhibitors using systemic administration. Five clinical studies were included and, although in general non-randomized, failed to demonstrate chondroprotective actions of oral selective COX-2 inhibitors. All of the four preclinical studies using bolus intra-articular injections demonstrated chondroprotective actions, while one of the three preclinical studies using a slow release system demonstrated chondroprotective actions. Despite the limited evidence in clinical studies that have used the oral administration route, there seems to be a preclinical basis for considering selective COX-2 inhibitors as disease modifying osteoarthritis drugs when used intra-articularly. Intra-articularly injected selective COX-2 inhibitors may hold the potential to provide chondroprotective effects in vivo in clinical studies.

scholarly journals Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies

2018 ◽  
Vol 29 (3) ◽  
pp. 321-332 ◽  
Author(s):  
Suleiman Alhaji Muhammad ◽  
Norshariza Nordin ◽  
Sharida Fakurazi
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Conditioned Medium ◽  
Tissue Regeneration ◽  
Therapeutic Benefit ◽  
Risk Of Bias ◽  
Preclinical Studies

AbstractInjury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium inin vivoanimal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials.

The Effect of Plantago major on Wound Healing in Preclinical Studies: A Systematic Review

2021 ◽  
Vol 67 (1) ◽  
pp. 27-34
Author(s):  
Fernanda Cardoso ◽  
Jéssica Breder ◽  
Priscila Apolinário ◽  
Henrique Oliveia ◽  
Maria Saidel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Risk Of Bias ◽  
Preclinical Studies ◽  
Plantago Major ◽  
Best Response ◽  
Meta Analyses

BACKGROUND: Plantago major is a medicinal plant that has been used for centuries to treat various health conditions including wounds. PURPOSE: To investigate the effectiveness of the topical use of P major in healing skin wounds in animal models. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted. Seven (7) electronic databases (Virtual Health Library, Public/Publisher MEDLINE, Scopus, Web of Science, Embase, Cumulative Index of Nursing and Allied Health Literature, and CAB Direct) were searched for controlled studies published in English from January 2006 to March 2020. The Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies tools guided the evaluation of the studies and determined their quality. The Systematic Review Center for Laboratory Animal Experimentation was used to assess the risk of bias. RESULTS: Of the 176 publications identified, 4 met the inclusion criteria. Studies included 20 to 100 animals and varying concentrations of P major. There were no reports of losses during research. Wound healing was assessed between 17 and 21 days following wounding. The best response in terms of wound contraction rate occurred with 10%, 20%, and 50% concentrations when compared with control groups. One (1) study did not have an animal ethics committee review. All studies had a high risk of bias and a lack of methodological rigor. CONCLUSION: The results of this review did not find evidence about the in vivo effectiveness of P major for wound healing. More rigorous preclinical studies with adequate sample sizes are required to identify the best concentrations and formulations as well as increase understanding about the mechanisms of action of P major in wound healing.

scholarly journals Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Yingchi Zhang ◽  
Gaohong Sheng ◽  
Bowei Ni ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Therapeutic Effects ◽  
Exact Role

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

2-Substituted Benzoxazoles as Potent Anti-Inflammatory Agents: Synthesis, Molecular Docking and In Vivo Anti-Ulcerogenic Studies

2021 ◽  
Vol 18 ◽  
Author(s):  
Iqra Hamid ◽  
Humaira Nadeem ◽  
Sameen Fatima Ansari ◽  
Sonia Khiljee ◽  
Inzamam Abbasi ◽  
...  
Keyword(s):  
Side Effects ◽  
Therapeutic Interventions ◽  
Binding Potential ◽  
Spectroscopic Techniques ◽  
Standard Drug ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Protein Pocket

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are the commonly used therapeutic interventions of inflammation and pain that competitively inhibit the cyclooxygenase (COX) enzymes. Several side effects like gastrointestinal and renal toxicities are associated with the use of these drugs. The therapeutic anti-inflammatory benefits of NSAIDs are produced by the inhibition of COX-2 enzymes, while undesirable side effects arise from the inhibition of COX-1 enzymes. Objectives: In the present study, a new series of 2-substituted benzoxazole derivatives 2(a-f) and 3(a-e) were synthesized in our lab as potent anti-inflammatory agents with outstanding gastro-protective potential. The new analogs 2(a-f) and 3(a-e) were designed depending upon the literature review to serve as ligands for the development of selective COX-2 inhibitors. Methods: The synthesized analogs were characterized using different spectroscopic techniques (FTIR, 1HNMR, 13CNMR) and elemental analysis. All synthesized compounds were screened for their binding potential in the protein pocket of COX-2 and evaluated for their anti-inflammatory potential in animals using the carrageenan-induced paw edema method. Further 5 compounds were selected to assess the in vivo anti-ulcerogenic activity in an ethanol-induced anti-ulcer rat model. Results: Five compounds (2a, 2b, 3a, 3b and 3c) exhibited potent anti-inflammatory activity and significant binding potential in the COX-2 protein pocket. Similarly, these five compounds demonstrated a significant gastro-protective effect (p<0.01) in comparison to the standard drug, Omeprazole. Conclusion: Depending upon our results, we hypothesize that 2-substituted benzoxazole derivatives have excellent potential to serve as candidates for the development of selective anti-inflammatory agents (COX-2 inhibitors). However, further assessments are required to delineate their underlying mechanisms.

Preclinical studies conducted on nanozyme antioxidants: shortcomings and challenges based on US FDA regulations

Nanomedicine ◽  
2021 ◽  
Author(s):  
Milad Ghorbani ◽  
Zhila Izadi ◽  
Samira Jafari ◽  
Eudald Casals ◽  
Foroogh Rezaei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Clinical Studies ◽  
In Vivo Studies ◽  
Preclinical Studies ◽  
Future Studies ◽  
Clinical Stages ◽  
Us Fda ◽  
Considerable Body

The wide prevalence of oxidative stress-induced diseases has led to a growing demand for antioxidant therapeutics worldwide. Nanozyme antioxidants are drawing enormous attention as practical alternatives for conventional antioxidants. The considerable body of research over the last decade and the promising results achieved signify the potential of nanozyme antioxidants to secure a place in the expanding market of antioxidant therapeutics. Nonetheless, there is no report on clinical trials for their further evaluation. Through analyzing in-depth selected papers which have conducted in vivo studies on nanozyme antioxidants, this review aims to pinpoint and discuss possible reasons impeding development of research toward clinical studies and to offer some practical solutions for future studies to bridge the gap between preclinical and clinical stages.

scholarly journals Nrf2 Activators as Dietary Phytochemicals Against Oxidative Stress, Inflammation, and Mitochondrial Dysfunction in Autism Spectrum Disorders: A Systematic Review

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiaxin Yang ◽  
Xi Fu ◽  
Xiaoli Liao ◽  
Yamin Li
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Mitochondrial Dysfunction ◽  
Clinical Studies ◽  
Autism Spectrum ◽  
Research Progress ◽  
Current Evidence ◽  
Preclinical Studies ◽  
Dietary Phytochemicals ◽  
Nrf2 Activator

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with limited available treatments and diverse causes. In ASD patients, numerous researches demonstrated various alterations in inflammation/immune, oxidative stress, and mitochondrial dysfunction, and these alterations could be regulated by Nrf2. Hence, we aimed to systematically review the current evidence about the effects of Nrf2 activator supplementation on ASD objects from in vitro studies, animal studies, and clinical studies. Relevant articles were retrieved through searching for the Cochrane Library, PubMed, Web of Science, Scope, Embase, and CNKI databases (through September 23, 2020). Ultimately, we identified 22 preclinical studies, one cell culture study, and seven clinical studies, covering a total of five Nrf2 activators. For each Nrf2 activator, we focused on its definition, potential therapeutic mechanisms, latest research progress, research limitations, and future development directions. Our systematic review provided suggestive evidence that Nrf2 activators have a potentially beneficial role in improving autism-like behaviors and abnormal molecular alterations through oxidant stress, inflammation, and mitochondrial dysfunction. These dietary phytochemicals are considered to be relatively safer and effective for ASD treatment. However, there are few clinical studies to support the Nrf2 activators as dietary phytochemicals in ASD, even though several preclinical studies. Therefore, caution should be warranted in attempting to extrapolate their effects in human studies, and better design and more rigorous research are required before they can be determined as a therapeutic option.

Calcium alginate beads as a slow-release system for delivering angiogenic molecules In Vivo and In Vitro

1992 ◽  
Vol 152 (2) ◽  
pp. 422-429 ◽  
Author(s):  
Elizabeth C. Downs ◽  
Nancy E. Robertson ◽  
Terry L. Riss ◽  
Marian L. Plunkett
Keyword(s):  
Calcium Alginate ◽  
Slow Release ◽  
Alginate Beads ◽  
Calcium Alginate Beads ◽  
Release System ◽  
Slow Release System

Synthesis of novel thiadiazole derivatives as selective COX-2 inhibitors

MedChemComm ◽  
2016 ◽  
Vol 7 (12) ◽  
pp. 2309-2327 ◽  
Author(s):  
Fatma A. Ragab ◽  
Helmi I. Heiba ◽  
Marwa G. El-Gazzar ◽  
Sahar M. Abou-Seri ◽  
Walaa A. El-Sabbagh ◽  
...  
Keyword(s):  
Paw Oedema ◽  
Analgesic Agents ◽  
Thiadiazole Derivatives ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Cox 2 Inhibitors ◽  
Rat Paw Oedema

A novel series of thiadiazole derivatives were designed and synthesized for evaluation as selective COX-2 inhibitors in vitro and were investigated in vivo as anti-inflammatory and analgesic agents against carrageenan-induced rat paw oedema model in irradiated rats.

scholarly journals Mapping the preclinical to clinical evidence and development trajectory of the oncolytic virus talimogene laherparepvec (T-VEC): a systematic review

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e029475 ◽  
Author(s):  
Manoj Lalu ◽  
Garvin J Leung ◽  
Yuan Yi Dong ◽  
Joshua Montroy ◽  
Claire Butler ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Studies ◽  
Clinical Evidence ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Risk Of Bias ◽  
Preclinical Studies ◽  
Talimogene Laherparepvec ◽  
Development Trajectory

ObjectiveThis study aimed to conduct a systematic review of preclinical and clinical evidence to chart the successful trajectory of talimogene laherparepvec (T-VEC) from the bench to the clinic.DesignThis study was a systematic review. The primary outcome of interest was the efficacy of treatment, determined by complete response. Abstract and full-text selection as well as data extraction were done by two independent reviewers. The Cochrane risk of bias tool was used to assess the risk of bias in studies.SettingEmbase, Embase Classic and OvidMedline were searched from inception until May 2016 to assess its development trajectory to approval in 2015.ParticipantsPreclinical and clinical controlled comparison studies, as well as observational studies.InterventionsT-VEC for the treatment of any malignancy.Results8852 records were screened and five preclinical (n=150 animals) and seven clinical studies (n=589 patients) were included. We saw large decreases in T-VEC’s efficacy as studies moved from the laboratory to patients, and as studies became more methodologically rigorous. Preclinical studies reported complete regression rates up to 100% for injected tumours and 80% for contralateral tumours, while the highest degree of efficacy seen in the clinical setting was a 24% complete response rate, with one study experiencing a complete response rate of 0%. We were unable to reliably assess safety due to the lack of reporting, as well as the heterogeneity seen in adverse event definitions. All preclinical studies had high or unclear risk of bias, and all clinical studies were at a high risk of bias in at least one domain.ConclusionsOur findings illustrate that even successful biotherapeutics may not demonstrate a clear translational road map. This emphasises the need to consider increasing rigour and transparency along the translational pathway.PROSPERO registration numberCRD42016043541.

Synthesis, 3D pharmacophore, QSAR and docking studies of novel quinazoline derivatives with nitric oxide release moiety as preferential COX-2 inhibitors

MedChemComm ◽  
2015 ◽  
Vol 6 (2) ◽  
pp. 283-299 ◽  
Author(s):  
Doaa Boshra Farag ◽  
Nahla A. Farag ◽  
Ahmed Esmat ◽  
Sally A. Abuelezz ◽  
Eman Abdel-Salam Ibrahim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Docking Studies ◽  
Nitric Oxide Release ◽  
Nitrate Esters ◽  
Hybrid Molecules ◽  
Quinazoline Derivatives ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Four novel series of quinazoline derivatives IIIa–c, VIa–c and their NO-hybrid molecules as nitrate esters Va–c and VIIIa–c have been synthesized and evaluated for their anti-inflammatory activity in vivo and in vitro.

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