-
Behavioural Brain Research Oct 2023SARS-CoV-2 infection produces a wide range of symptoms. Some of the structural changes caused by the virus in the nervous system are found in the medial temporal lobe,... (Review)
Review
SARS-CoV-2 infection produces a wide range of symptoms. Some of the structural changes caused by the virus in the nervous system are found in the medial temporal lobe, and several neuropsychological sequelae of COVID-19 are related to the function of the hippocampus. The main objective of the systematic review is to update and further analyze the existing evidence of hippocampal and related cortices' structural and functional alterations due to SARS-CoV-2 infection. Both clinical and preclinical studies that used different methodologies to explore the effects of this disease at different stages and grades of severity were considered, besides exploring related cognitive and emotional symptomatology. A total of 24 studies were identified by searching in SCOPUS, Web Of Science (WOS), PubMed, and PsycInfo databases up to October 3rd, 2022. Thirteen studies were performed in clinical human samples, 9 included preclinical animal models, 3 were performed post-mortem, and 1 included both post-mortem and preclinical samples. Alterations in the hippocampus were detected in the acute stage and after several months of infection. Clinical studies revealed alterations in hippocampal connectivity and metabolism. Memory alterations correlated with altered metabolic profiles or changes in grey matter volumes. Hippocampal human postmortem and animal studies observed alterations in neurogenesis, dendrites, and immune response, besides high apoptosis and neuroinflammation. Preclinical studies reported the viral load in the hippocampus. Olfactory dysfunction was associated with alterations in brain functionality. Several clinical studies revealed cognitive complaints, neuropsychological alterations, and depressive and anxious symptomatology.
Topics: Animals; Humans; COVID-19; SARS-CoV-2; Hippocampus; Temporal Lobe
PubMed: 37703951
DOI: 10.1016/j.bbr.2023.114662 -
Stem Cell Reviews and Reports Aug 2023Autologous fat transplantation -i.e., lipofilling- has become a promising and popular technique in aesthetic and reconstructive surgery with several application such as... (Review)
Review
Autologous fat transplantation -i.e., lipofilling- has become a promising and popular technique in aesthetic and reconstructive surgery with several application such as breast reconstruction, facial and hand rejuvenation. However, the use of this technology is still limited due to an unpredictable and low graft survival rate (which ranges from 25%-80%). A systematic literature review was performed by thoroughly searching 12 terms using the PubMed database. The objective of this study is to present the current evidence for the efficacy of adjuvant regenerative strategies and cellular factors, which have been tested to improve fat graft retention. We present the main results (fat retention rate, histological analysis for pre-clinical studies and satisfaction/ complication for clinical studies) obtained from the studies of the three main fat grafting enrichment techniques: platelet-rich plasma (PRP), the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) and discuss the promising role of recent angiogenic cell enrichment that could induce early vascularization of fat graft. All in all, adding stem or progenitor cells to autologous fat transplantation might become a new concept in lipofilling. New preclinical models should be used to find mechanisms able to increase fat retention, assure safety and transfer these technologies to a good manufacturing practice (GMP) compliant facility, to manufacture an advanced therapy medicinal product (ATMP).
Topics: Adipose Tissue; Adipocytes; Plastic Surgery Procedures; Transplantation, Autologous; Stem Cells
PubMed: 37261667
DOI: 10.1007/s12015-023-10568-4 -
Current Oncology (Toronto, Ont.) Feb 2023Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most... (Review)
Review
Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review's primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies-one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)-were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.
Topics: Humans; Temozolomide; Retrospective Studies; Prospective Studies; Brain Neoplasms; Glioma; Chronotherapy; Randomized Controlled Trials as Topic
PubMed: 36826108
DOI: 10.3390/curroncol30020147 -
Efficacy and Safety of Oral GnRh Antagonists in Patients With Uterine Fibroids: A Systematic Review.Journal of Obstetrics and Gynaecology... Dec 2022This review aimed to assess the efficacy and safety of GnRH antagonists in patients with symptomatic uterine fibroids. (Review)
Review
OBJECTIVE
This review aimed to assess the efficacy and safety of GnRH antagonists in patients with symptomatic uterine fibroids.
DATA SOURCES
A literature search was performed on PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov using the MeSH and Emtree terms "leiomyoma" and "gonadotropin-releasing hormone."
STUDY SELECTION
All clinical trials that provided efficacy and safety data in clinical terms (i.e., reduction in menstrual bleeding and discomfort, changes in the size of leiomyoma and uterine volume, etc.) were included. We excluded all preclinical studies, case reports, meta-analyses, review articles, and clinical studies irrelevant to the study question.
DATA EXTRACTION AND SYNTHESIS
Two authors extracted data from 9 clinical studies. The extracted data included the study's characteristics, participants' baseline characteristics, treatment drugs, efficacy measures, and toxicity.
CONCLUSION
Among oral GnRH antagonists, relugolix, elagolix, and linzagolix were safe in patients with uterine fibroids. These drugs, alone and in combination with E2/NETA (estradiol/norethindrone acetate), showed significantly better efficacy than placebo in improving bleeding, discomfort, uterine/leiomyoma sizes, and quality of life in premenopausal patients with symptomatic uterine fibroids. However, more randomized, double-blind, multicentre clinical trials are needed to confirm these results and to see long-term benefits.
Topics: Female; Humans; Uterine Neoplasms; Quality of Life; Leiomyoma; Gonadotropin-Releasing Hormone; Hormone Antagonists; Randomized Controlled Trials as Topic
PubMed: 36368594
DOI: 10.1016/j.jogc.2022.10.012 -
Frontiers in Pediatrics 2021There is a steadily growing number of different reconstructive surgical procedures for hypospadias that were tested on animal models prior to their human application....
There is a steadily growing number of different reconstructive surgical procedures for hypospadias that were tested on animal models prior to their human application. However, the clinical translatability and reproducibility of the results encountered in preclinical urethral reconstruction experiments is considered poor, with significant factors contributing to the poor design and reporting of animal experiments. Our objective was to evaluate the quality of the design and reporting in published articles of urethral reconstructive preclinical studies. Both PubMed and EMBASE databases were searched for animal urethral repair experiments between January 2014 and September 2019. Internal quality (bias) was evaluated through several signaling questions arising from the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE), while the quality of reporting was assessed by the Animal Research: Reporting of Experiments (ARRIVE) guidelines by scoring of a 20-item checklist. A total of 638 articles were initially screened after the literature search. Employing the inclusion and exclusion criteria, 30 studies were chosen for full-text screening and 21 studies were considered eligible for the quality assessment. The mean score of the checklist was 66%. The elements that accomplished the highest grades included the number of animals utilized, the number in each investigational and control group, and the delineation of investigational conclusions. The items that were least commonly stated comprised information about the experimental method, housing and husbandry, rationalization of the number of animals, and reporting of adverse events. No paper stated the sample size estimation. We found that several critical experiment design principles were poorly reported, which hinders a rigorous appraisal of the scientific quality and reproducibility of the experiments. A comprehensive implementation of the ARRIVE guidelines in animal studies exploring urethral repair is necessary to facilitate the effective translation of preclinical research findings into clinical therapies.
PubMed: 34458213
DOI: 10.3389/fped.2021.718647 -
BMJ Open Science 2022Systematic review and meta-analysis are a gift to the modern researcher, delivering a crystallised understanding of the existing research data in any given space. This...
Systematic review and meta-analysis are a gift to the modern researcher, delivering a crystallised understanding of the existing research data in any given space. This can include whether candidate drugs are likely to work or not and which are better than others, whether our models of disease have predictive value and how this might be improved and also how these all interact with disease pathophysiology. Grappling with the literature needed for such analyses is becoming increasingly difficult as the number of publications grows. However, narrowing the focus of a review to reduce workload runs the risk of diminishing the generalisability of conclusions drawn from such increasingly specific analyses. Moreover, at the same time as we gain greater insight into our topic, we also discover more about the flaws that undermine much scientific research. Systematic review and meta-analysis have also shown that the quality of much preclinical research is inadequate. Systematic review has helped reveal the extent of selection bias, performance bias, detection bias, attrition bias and low statistical power, raising questions about the validity of many preclinical research studies. This is perhaps the greatest virtue of systematic review and meta-analysis, the knowledge generated ultimately helps shed light on the limitations of existing research practice, and in doing so, helps bring reform and rigour to research across the sciences. In this commentary, we explore the lessons that we have identified through the lens of preclinical systematic review and meta-analysis.
PubMed: 35360370
DOI: 10.1136/bmjos-2021-100219 -
International Journal of Molecular... Jul 2023Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and... (Review)
Review
Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and potentially serving as a therapeutic agent for chronic inflammatory diseases. The aim of this review was to systematically investigate preclinical and clinical studies on maresin to inform translational research. Two independent reviewers performed comprehensive searches with the term "Maresin (NOT) Review" on PubMed. A total of 137 studies were included and categorized into 11 human organ systems. Data pertinent to clinical translation were specifically extracted, including delivery methods, optimal dose response, and specific functional efficacy. Maresins generally exhibit efficacy in treating inflammatory diseases, attenuating inflammation, protecting organs, and promoting tissue regeneration, mostly in rodent preclinical models. The nervous system has the highest number of original studies ( = 25), followed by the cardiovascular system, digestive system, and respiratory system, each having the second highest number of studies ( = 18) in the field. Most studies considered systemic delivery with an optimal dose response for mouse animal models ranging from 4 to 25 μg/kg or 2 to 200 ng via intraperitoneal or intravenous injection respectively, whereas human in vitro studies ranged between 1 and 10 nM. Although there has been no human interventional clinical trial yet, the levels of MaR1 in human tissue fluid can potentially serve as biomarkers, including salivary samples for predicting the occurrence of cardiovascular diseases and periodontal diseases; plasma and synovial fluid levels of MaR1 can be associated with treatment response and defining pathotypes of rheumatoid arthritis. Maresins exhibit great potency in resolving disease inflammation and bridging tissue regeneration in preclinical models, and future translational development is warranted.
Topics: Animals; Humans; Mice; Anti-Inflammatory Agents; Chronic Disease; Docosahexaenoic Acids; Inflammation; Macrophages
PubMed: 37446190
DOI: 10.3390/ijms241311012 -
Neurosurgical Review Apr 2021Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit...
Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care.
Topics: Adrenergic beta-Antagonists; Brain Neoplasms; Cell Death; Cell Proliferation; Clinical Trials as Topic; Drug Evaluation, Preclinical; Glioblastoma; Glioma; Humans; Neovascularization, Pathologic
PubMed: 32172480
DOI: 10.1007/s10143-020-01277-4 -
Clinical Oral Implants Research Sep 2019Implantoplasty, that is, the mechanical modification of the implant, including thread removal and surface smoothening, has been proposed during surgical peri-implantitis... (Review)
Review
OBJECTIVES
Implantoplasty, that is, the mechanical modification of the implant, including thread removal and surface smoothening, has been proposed during surgical peri-implantitis treatment. Currently, there is no information about any potential mechanical and/or biological complications after this approach. The aim of the current review was to systematically assess the literature to answer the focused question "Are there any mechanical and/or biological complications due to implantoplasty?".
MATERIALS AND METHODS
A systematic literature search was performed in three databases until 23/09/2018 to assess potential mechanical and/or biological complications after implantoplasty. All laboratory, preclinical in vivo, and clinical studies involving implantoplasty were included, and any complication potentially related to implantoplasty was recorded and summarized.
RESULTS
Out of 386 titles, 26 publications were included in the present review (six laboratory, two preclinical in vivo, and 18 clinical studies). Laboratory studies have shown that implantoplasty does not result in temperature increase, provided proper cooling is used, but leads in reduced implant strength in "standard" dimension implants; further, preclinical studies have shown titanium particle deposition in the surrounding tissues. Nevertheless, no clinical study has reported any remarkable complication due to implantoplasty; among 217-291 implants subjected to implantoplasty, no implant fracture was reported during a follow-up of 3-126 months, while only a single case of mucosal discoloration, likely due to titanium particle deposition, has been reported.
CONCLUSIONS
Based on all currently available, yet limited, preclinical in vivo and clinical evidence, implantoplasty seems not associated with any remarkable mechanical or biological complications on the short- to medium-term.
Topics: Dental Implants; Humans; Peri-Implantitis; Surface Properties; Titanium
PubMed: 31254417
DOI: 10.1111/clr.13499 -
Acta Tropica Mar 2023It has been tested and proven that vaccination is still the best strategy to combat infectious diseases. However, to date, there are still no vaccines against human... (Review)
Review
It has been tested and proven that vaccination is still the best strategy to combat infectious diseases. However, to date, there are still no vaccines against human soil-transmitted helminthic diseases, despite their high prevalence globally, particularly in developing countries and rural areas with tropical climates and poor sanitation. The development of vaccines against helminths is riddled with obstacles. Helminths have a complex life cycle, multiple stages within the same host with stage-specific antigen expression, and the ability to regulate host immune reactions to evade the immune response. These elements contribute to the main challenge of helminthic vaccines: the identification of effective vaccine candidates. Therefore, this article reviews the current progress and potential future direction of soil-transmitted helminthic vaccines, particularly against Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, Necator americanus and Ancylostoma duodenale. The study design employed was a systematic review, using qualitative meta-summary synthesis. Preclinical studies and clinical trials on the development of protein subunit vaccines against the five soil-transmitted helminths were searched on PubMed and Scopus. Effectiveness was indicated by a reduction in worm burden or larval output, an increase in specific IgG levels, or an increase in cytokine production. Our findings show that only the hookworm vaccine against N. americanus is in the clinical trial phase, while the rest is still in exploratory research and pre-clinical development phase.
Topics: Animals; Humans; Soil; Hookworm Infections; Ascaris lumbricoides; Ancylostomatoidea; Necator americanus; Vaccines; Helminthiasis; Feces
PubMed: 36586174
DOI: 10.1016/j.actatropica.2022.106796