MiRNAs as New Tools in Lesion Vitality Evaluation: A Systematic Review and Their Forensic Applications

Wound vitality demonstration is one of the most challenging fields in forensic pathology. In recent years, researchers focused on the application of histological and immunohistochemical staining in this sphere of study. It is based on the detection of inflammation, red cell infiltration, and tissue alterations at the histological examination, all of which are supposedly present in antemortem rather than post-mortem wounds. Nevertheless, some doubts about the reliability of those markers have arisen. Furthermore, the lack of a standardized protocol and the operator dependency of this approach make the proper interpretation of its results difficult. Moreover, a differential miRNAs expression has been demonstrated in antemortem and post-mortem wounds. Herein, a systematic review concerning the current knowledge about the use of miRNAs in lesion vitality evaluation is carried out, to encourage researchers to deepen this peculiar study area. A compendium about the potential miRNAs that may be further investigated as vitality markers is also provided. The aim is to collect all available data about this topic to direct further studies on this field and highlight the future applications of miRNAs in forensic pathology. We found 20 articles and a total of 51 miRNAs that are involved in inflammation and wound healing. Further studies are certainly needed to deepen the role of miRNAs in inflammatory processes in lesioned skin and to evaluate their reliability in distinguishing between antemortem and post-mortem lesions.

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Forensic Impact of the Omics Science Involved in the Wound: A Systematic Review

Frontiers in Medicine ◽

10.3389/fmed.2021.786798 ◽

2022 ◽

Vol 8 ◽

Author(s):

Aurelia Collados Ros ◽

Stefano Bacci ◽

Aurelio Luna ◽

Isabel Legaz

Keyword(s):

Systematic Review ◽

Molecular Characterization ◽

Forensic Pathology ◽

Molecular Mechanisms ◽

Healing Process ◽

Wound Healing Process ◽

Post Mortem ◽

The Moment

Background: In forensic autopsies, examining the wounds is one of the most critical aspects to clarify the causal relationship between the cause of death and the wounds observed on the corpse. However, on many occasions, it is difficult to differentiate antemortem injuries from post-mortem injuries, mainly when they occur very close to the moment of death. At present, various studies try to find biomarkers and clarify the molecular mechanisms involved in a wound due to the high variability of conditions in which they occur, thus being one of the most challenging problems in forensic pathology. This review aimed to study the omics data to determine the main lines of investigation emerging in the diagnosis of vital injuries, time of appearance, estimation of the age and vitality of the wound, and its possible contributions to the forensic field.Methods: A systematic review of the human wound concerning forensic science was carried out by following PRISMA guidelines.Results: This study sheds light on the role of omics research during the process of wounding, identifying different cytokines and other inflammatory mediators, as well as cells involved in the specific stage of the wound healing process, show great use in estimating the age of a wound. On the other hand, the expression levels of skin enzymes, proteins, metal ions, and other biomarkers play an essential role in differentiating vital and post-mortem wounds. More recent studies have begun to analyze and quantify mRNA from different genes that encode proteins that participate in the inflammation phase of a wound and miRNAs related to various cellular processes.Conclusions: This study sheds light on the role of research in the molecular characterization of vital wounds, heralding a promising future for molecular characterization of wounds in the field of forensic pathology, opening up an important new area of research.Systematic Review Registration: URL: https://www.crd.york.ac.uk/prospero/#myprospero, Identifier: CRD42021286623.

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Role of active patient involvement in undergraduate medical education: a systematic review

BMJ Open ◽

10.1136/bmjopen-2020-037217 ◽

2020 ◽

Vol 10 (7) ◽

pp. e037217

Author(s):

Stijntje Willemijn Dijk ◽

Edwin Johan Duijzer ◽

Matthias Wienold

Keyword(s):

Systematic Review ◽

Medical Education ◽

Undergraduate Medical Education ◽

Patient Involvement ◽

Current Knowledge ◽

Daily Practice ◽

Pubmed Database ◽

Wide Range ◽

Active Patient

ObjectivesTo identify the scope of active patient involvement in medical education, addressing the current knowledge gaps relating to rationale and motivation for involvement, recruitment and preparation, roles, learning outcomes and key procedural contributors.MethodsThe authors performed a systematic search of the PubMed database of publications between 2003 and 2018. Original studies in which patients take on active roles in the development, delivery or evaluation of undergraduate medical education and written in English were eligible for inclusion. Included studies’ references were searched for additional articles. Quality of papers was assessed using the Mixed Methods Appraisal Tool.Results49 articles were included in the review. Drivers for patient involvement included policy requirements and patients’ own motivations to contribute to society and learning. Patients were engaged in a variety of educational settings in and outside of the hospital. The vast majority of studies describe patients taking on the role of a patient teacher and formative assessor. More recent studies suggest that patients are increasingly involved in course and curriculum development, student selection and summative assessment. The new body of empirical evidence shows the wide range of learning objectives was pursued through patient participation, including competencies as professional, communicator, collaborator, leader and health advocate, but not scholar. Measures to support sustainable patient involvement included longitudinal institutional incorporation, patient recruitment and/or training, resource support and clear commitment by faculty. The importance and advantages of patient involvement were highlighted by students, faculty and patients themselves; however, organisations must continue to consider, monitor and take steps to mitigate any potential harms to patients and students.DiscussionThis systematic review provides new knowledge and practical insights to physicians and faculty on how to incorporate active patient involvement in their institutions and daily practice, and provides suggested action points to patient organisations wishing to engage in medical education.

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More than Pneumonia: Distinctive Features of SARS-Cov-2 Infection. From Autopsy Findings to Clinical Implications: A Systematic Review

Microorganisms ◽

10.3390/microorganisms8111642 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1642

Author(s):

Stefano D’Errico ◽

Martina Zanon ◽

Martina Montanaro ◽

Davide Radaelli ◽

Francesco Sessa ◽

...

Keyword(s):

Systematic Review ◽

Case Reports ◽

Case Series ◽

Endothelial Damage ◽

Multiple Organ ◽

Post Mortem ◽

Letters To The Editor ◽

Distinctive Features ◽

First Results ◽

Inflammatory Processes

Despite safety recommendations for the management of corpses with COVID-19 infection and the high number of deaths worldwide, the post-mortem investigation rate is extremely low as well as the scientific contributions describing the pathological features. The first results of post-mortem investigations provided interesting findings and contributed to promoting unexplored therapeutic approaches and new frontiers of research. A systematic review is provided with the aim of summarizing all autopsy studies up to February 2020 in which a complete post-mortem investigation in patients with COVID-19 disease was performed, focusing on histopathological features. We included case reports, case series, retrospective and prospective studies, letters to the editor, and reviews. A total of 28 studies fulfilled the inclusion criteria, producing a pooled dataset of 407 full autopsies. Analyzing the medical history data, only 12 subjects had died without any comorbidities (for 15 cases the data were not available). The post-mortem investigation highlighted that acute respiratory distress syndrome (ARDS) and multiple organ failure represent the main clinical features of COVID-19 disease, often leading to pulmonary thromboembolism and superimposed bronchopneumonia. The discussed data showed a strict relationship among the inflammatory processes, diffuse alveolar, and endothelial damage. In light of these results, the full autopsy can be considered as the gold standard to investigate unknown infections or pathogens resulting in death.

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The Role of Poly(ADP-ribose) Polymerase-1 in Rheumatoid Arthritis

Mediators of Inflammation ◽

10.1155/2015/837250 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 16

Author(s):

Samuel García ◽

Carmen Conde

Keyword(s):

Rheumatoid Arthritis ◽

Septic Shock ◽

Dna Repair ◽

Beneficial Effect ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Genomic Stability ◽

Inflammatory Processes ◽

Parp 1

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme with a crucial role in the maintenance of genomic stability. In addition to the role of PARP-1 in DNA repair, multiple studies have also demonstrated its involvement in several inflammatory diseases, such as septic shock, asthma, atherosclerosis, and stroke, as well as in cancer. In these diseases, the pharmacological inhibition of PARP-1 has shown a beneficial effect, suggesting that PARP-1 regulates their inflammatory processes. In recent years, we have studied the role of PARP-1 in rheumatoid arthritis, as have other researchers, and the results have shown that PARP-1 has an important function in the development of this disease. This review summarizes current knowledge on the effects of PARP-1 in rheumatoid arthritis.

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MECHANISMS IN ENDOCRINOLOGY: Epigenetic modifications and gestational diabetes: a systematic review of published literature

Acta Endocrinologica ◽

10.1530/eje-16-1017 ◽

2017 ◽

Vol 176 (5) ◽

pp. R247-R267 ◽

Cited By ~ 18

Author(s):

Gunn-Helen Moen ◽

Christine Sommer ◽

Rashmi B Prasad ◽

Line Sletner ◽

Leif Groop ◽

...

Keyword(s):

Systematic Review ◽

Gestational Diabetes ◽

Current Knowledge ◽

Epigenetic Modifications ◽

Research Literature ◽

Small Sample ◽

Epigenetic Alterations ◽

Search Terms ◽

Small Sample Sizes

ObjectiveTo summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research.DesignSystematic review.MethodsWe performed extensive searches in PubMed, EMBASE and Google scholar, using a combination of the search terms: GDM, gestational diabetes, epigenetic(s), methylation, histone modification, histone methylation, histone acetylation, microRNA and miRNA. Studies that compared women diagnosed with GDM and healthy controls were included. Two authors independently scanned the abstracts, and all included papers were read by at least two authors. The searches were completed on October 31st, 2016.ResultsWe identified 236 articles, of which 43 were considered relevant for this systematic review. Studies published showed that epigenetic alterations could be found in both mothers with GDM and their offspring. However, differences in methodology, diagnostic criteria for GDM and populations studied, together with a limited number of published studies and small sample sizes, preclude clear conclusions about the role of epigenetic modifications in transmitting risk from GDM mothers to their offspring.ConclusionThe current research literature suggests that GDM may have impact on epigenetic modifications in the mother and offspring. However, larger studies that include multiple cohorts of GDM patients and their offspring are needed.

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The Role of Gut Microbiota on Cholesterol Metabolism in Atherosclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms22158074 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8074

Author(s):

Margaret Vourakis ◽

Gaétan Mayer ◽

Guy Rousseau

Keyword(s):

Cardiovascular Health ◽

Cholesterol Metabolism ◽

Current Knowledge ◽

Short Chain Fatty Acids ◽

Developed Countries ◽

Current Data ◽

Cholesterol Homeostasis ◽

Intestinal Microbes ◽

Inflammatory Processes

Hypercholesterolemia plays a causal role in the development of atherosclerosis and is one of the main risk factors for cardiovascular disease (CVD), the leading cause of death worldwide especially in developed countries. Current data show that the role of microbiota extends beyond digestion by being implicated in several metabolic and inflammatory processes linked to several diseases including CVD. Studies have reported associations between bacterial metabolites and hypercholesterolemia. However, such associations remain poorly investigated and characterized. In this review, the mechanisms of microbial derived metabolites such as primary and secondary bile acids (BAs), trimethylamine N-oxide (TMAO), and short-chain fatty acids (SCFAs) will be explored in the context of cholesterol metabolism. These metabolites play critical roles in maintaining cardiovascular health and if dysregulated can potentially contribute to CVD. They can be modulated via nutritional and pharmacological interventions such as statins, prebiotics, and probiotics. However, the mechanisms behind these interactions also remain unclear, and mechanistic insights into their impact will be provided. Therefore, the objectives of this paper are to present current knowledge on potential mechanisms whereby microbial metabolites regulate cholesterol homeostasis and to discuss the feasibility of modulating intestinal microbes and metabolites as a novel therapeutic for hypercholesterolemia.

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The Role of Non-Gaussian Models of Diffusion Weighted MRI in Hepatocellular Carcinoma: A Systematic Review

Journal of Clinical Medicine ◽

10.3390/jcm10122641 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2641

Author(s):

Liberatore Tramontano ◽

Carlo Cavaliere ◽

Marco Salvatore ◽

Valentina Brancato

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Current Knowledge ◽

Exponential Model ◽

Response To Treatment ◽

Diffusion Kurtosis Imaging ◽

Diffusion Weighted ◽

Non Gaussian ◽

Diffusion Kurtosis

The importance of Diffusion Weighted Imaging (DWI) in hepatocellular carcinoma (HCC) has been widely handled in the literature. Due to the mono-exponential model limitations, several studies recently investigated the role of non-Gaussian DWI models in HCC. However, their results are variable and inconsistent. Therefore, the aim of this systematic review is to summarize current knowledge on non-Gaussian DWI techniques in HCC. A systematic search of the literature, including PubMed, Google Scholar, MEDLINE, and ScienceDirect databases, was performed to identify original articles since 2010 that evaluated the role of non-Gaussian DWI models for HCC diagnosis, grading, response to treatment, and prognosis. Studies were grouped and summarized according to the non-Gaussian DWI models investigated. We focused on the most used non-Gaussian DWI models (Intravoxel Incoherent Motion (IVIM), Diffusion Kurtosis Imaging (DKI), and Stretched Exponential—SE). The quality of included studies was evaluated by using QUADAS-2 and QUIPS tools. Forty-three articles were included, with IVIM and DKI being the most investigated models. Although the role of non-Gaussian DWI models in clinical settings has not fully been established, our findings showed that their parameters may potentially play a role in HCC. Further studies are required to identify a standardized DWI acquisition protocol for HCC diagnosis, grading, response to treatment, and prognosis.

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NADPH Oxidases and Their Role in Atherosclerosis

Biomedicines ◽

10.3390/biomedicines8070206 ◽

2020 ◽

Vol 8 (7) ◽

pp. 206 ◽

Cited By ~ 2

Author(s):

Anastasia V. Poznyak ◽

Andrey V. Grechko ◽

Varvara A. Orekhova ◽

Victoria Khotina ◽

Ekaterina A. Ivanova ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Remodeling ◽

Current Knowledge ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Current View ◽

Nadph Oxidases ◽

Inflammatory Processes ◽

Atherosclerosis Development ◽

Initiating Factors

The current view on atherosclerosis positions it as a multifactorial disorder that results from the interplay between lipid metabolism disturbances and inflammatory processes. Oxidative stress is proven to be one of the initiating factors in atherosclerosis development, being implicated both in the inflammatory response and in atherogenic modifications of lipoproteins that facilitate lipid accumulation in the arterial wall. The hallmark of oxidative stress is the elevated level of reactive oxygen species (ROS). Correspondingly, the activity of major ROS-generating enzymes, including nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, xanthine oxidases, and cyclooxygenases, is an important element in atherosclerosis development. In particular, the role of NADPH oxidases in atherosclerosis development has become a subject of intensive research. Aberrant activity of NADPH oxidases was shown to be associated with cardiovascular disease in humans. With regard to atherosclerosis, several important pathological components of the disease development, including endothelial dysfunction, inflammation, and vascular remodeling, involve aberrations in NADPH oxidases functioning. In humans, NADPH oxidases are represented by four isoforms expressed in vascular tissues, where they serve as the main source of ROS during atherogenesis. Moreover, recent studies have demonstrated their impact on vascular remodeling processes. Interestingly, one of the NADPH oxidase isoforms, NOX4, was shown to have an atheroprotective effect. Despite the growing evidence of the crucial involvement of NADPH oxidases in atherosclerosis pathogenesis, the available data still remains controversial. In this narrative review, we summarize the current knowledge of the role of NADPH oxidases in atherosclerosis and outline the future directions of research.

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IL-36 Cytokines: Regulators of Inflammatory Responses and Their Emerging Role in Immunology of Reproduction

International Journal of Molecular Sciences ◽

10.3390/ijms20071649 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1649 ◽

Cited By ~ 7

Author(s):

José Murrieta-Coxca ◽

Sandra Rodríguez-Martínez ◽

Mario Cancino-Diaz ◽

Udo Markert ◽

Rodolfo Favaro ◽

...

Keyword(s):

Reproductive Tract ◽

Inflammatory Responses ◽

Current Knowledge ◽

Female Reproductive Tract ◽

Inflammatory Conditions ◽

Immune Mediators ◽

Dynamic Expression ◽

Cellular Recruitment ◽

Inflammatory Processes

The IL-36 subfamily of cytokines has been recently described as part of the IL-1 superfamily. It comprises three pro-inflammatory agonists (IL-36α, IL-36β, and IL-36γ), their receptor (IL-36R), and one antagonist (IL-36Ra). Although expressed in a variety of cells, the biological relevance of IL-36 cytokines is most evident in the communication between epithelial cells, dendritic cells, and neutrophils, which constitute the common triad responsible for the initiation, maintenance, and expansion of inflammation. The immunological role of IL-36 cytokines was initially described in studies of psoriasis, but novel evidence demonstrates their involvement in further immune and inflammatory processes in physiological and pathological situations. Preliminary studies have reported a dynamic expression of IL-36 cytokines in the female reproductive tract throughout the menstrual cycle, as well as their association with the production of immune mediators and cellular recruitment in the vaginal microenvironment contributing to host defense. In pregnancy, alteration of the placental IL-36 axis has been reported upon infection and pre-eclampsia suggesting its pivotal role in the regulation of maternal immune responses. In this review, we summarize current knowledge regarding the regulatory mechanisms and biological actions of IL-36 cytokines, their participation in different inflammatory conditions, and the emerging data on their potential role in normal and complicated pregnancies.

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MicroRNA as Epigenetic Modifiers in Endometrial Cancer: A Systematic Review

Cancers ◽

10.3390/cancers13051137 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1137

Author(s):

Amélia Favier ◽

Grégoire Rocher ◽

Annette K. Larsen ◽

Romain Delangle ◽

Catherine Uzan ◽

...

Keyword(s):

Systematic Review ◽

Dna Methylation ◽

Endometrial Cancer ◽

Epigenetic Regulation ◽

Target Genes ◽

Current Knowledge ◽

Surrounding Tissue ◽

Expression Levels ◽

Meta Analyses

The objective of this systematic review is to summarize our current knowledge on the influence of miRNAs in the epigenetic deregulation of tumor-related genes in endometrial cancer (EC). We conducted a literature search on the role of miRNAs in the epigenetic regulation of EC applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following terms were used: microRNA, miRNA, miR, endometrial cancer, endometrium, epigenetic, epimutation, hypermethylation, lynch, deacetylase, DICER, novel biomarker, histone, chromatin. The miRNAs were classified and are presented according to their function (tumor suppressor or onco-miRNA), their targets (when known), their expression levels in EC tissue vs the normal surrounding tissue, and the degree of DNA methylation in miRNA loci and CpG sites. Data were collected from 201 articles, including 190 original articles, published between November 1, 2008 and September 30, 2020 identifying 313 different miRNAs implicated in epigenetic regulation of EC. Overall, we identified a total of 148 miRNAs with decreased expression in EC, 140 miRNAs with increased expression in EC, and 22 miRNAs with discordant expression levels. The literature implicated different epigenetic phenomena including altered miRNA expression levels (miR-182, -230), changes in the methylation of miRNA loci (miR-34b, -129-2, -130a/b, -152, -200b, -625) and increased/decreased methylation of target genes (miR-30d,-191). This work provides an overview of all miRNAs reported to be involved in epigenetic regulation in EC including DNA methylation and RNA-associated silencing. These findings may contribute to novel strategies in diagnosis, risk assessment, and treatments aimed at miRNAs, their target genes or DNA methylation.

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