Challenges in Psoriasis Research: A Systematic Review of Preclinical Models.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. METHODS: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. RESULTS: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. CONCLUSIONS: Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.

Antibiotics against Pseudomonas aeruginosa on Human Skin Cell Lines: Determination of the Highest Non-Cytotoxic Concentrations with Antibiofilm Capacity for Wound Healing Strategies.

Pseudomonas aeruginosa is one of the most common microorganisms causing infections of severe skin wounds. Antibiotic or antiseptic treatments are crucial to prevent and curb these infections. Antiseptics have been reported to be cytotoxic to skin cells and few studies evaluate the impact of commonly used antibiotics. This study evaluates how clinical antibiotics affect skin cells' viability, proliferation, migration, and cytokine secretion and defines the highest non-cytotoxic concentrations that maintain antibacterial activity. Cell proliferation, viability, and migration were evaluated on cell monolayers. Cytokines related to the wound healing process were determined. The minimum inhibitory concentrations and the impact on bacterial biofilm were assessed. Results showed that 0.02 mg/mL ciprofloxacin and 1 mg/mL meropenem are the highest non-cytotoxic concentrations for fibroblasts and keratinocytes while 1.25 mg/mL amikacin and 0.034 mg/mL colistin do not affect fibroblasts' viability and cytokine secretion but have an impact on keratinocytes. These concentrations are above the minimum inhibitory concentration but only amikacin could eradicate the biofilm. For the other antibiotics, cytotoxic concentrations are needed to eradicate the biofilm. Combinations with colistin at non-cytotoxic concentrations effectively eliminate the biofilm. These results provide information about the concentrations required when administering topical antibiotic treatments on skin lesions, and how these antibiotics affect wound management therapies. This study set the basis for the development of novel antibacterial wound healing strategies such as antibiotic artificial skin substitutes.

Medical students' interest in research: changing trends during university training.

Introduction: Research is an important aspect of medical training and plays a vital role in the advancement of evidence-based medicine. However, little is known about medical students' attitudes towards research. So, the aim of this study was to assess the opinion of medical students on scientific research. Methods: A cross-sectional study was designed that included students from the Faculty of Medicine of the University of Granada (UGR), Granada, Spain. A survey was distributed to assess their interest about research during undergraduate studies (1) and following graduation (2), participation in research activities (3), barriers towards research (4), expectation values and self-perceived skills (5). The opinions of students who had not taken clinical subjects (2nd year students) and students who had taken clinical subjects (4th and 6th year students) were compared. Results: 91 students were included in the study (32 were 2nd year students and 59 were 4th and 6th year students). More 4th and 6th year students showed no interest in research (50.4% vs. 28.1%, p = 0.042) or in pursuing a doctoral thesis (75% vs. 50.9%, p = 0.079) than 2nd year students. In addition, more 4th and 6th year students felt that they did not have sufficient skills to engage in scientific research (52.4% vs. 18.9%, p = 0.002). Likewise a greater number of 4th and 6th year students considered that the professors did not encourage scientific research activities (74.6% vs. 40.6%, p = 0.002). Generally, students do not participate in scientific dissemination events. The main barriers to research identified were lack of funding and lack of awareness of opportunities. Conclusion: Interest in research among medical students seems to decrease as the academic years progress. More research promotion could be implemented during the years of university studies.

Cortistatin deficiency reveals a dysfunctional brain endothelium with impaired gene pathways, exacerbated immune activation, and disrupted barrier integrity.

BACKGROUND: Brain activity governing cognition and behaviour depends on the fine-tuned microenvironment provided by a tightly controlled blood-brain barrier (BBB). Brain endothelium dysfunction is a hallmark of BBB breakdown in most neurodegenerative/neuroinflammatory disorders. Therefore, the identification of new endogenous molecules involved in endothelial cell disruption is essential to better understand BBB dynamics. Cortistatin is a neuroimmune mediator with anti-inflammatory and neuroprotective properties that exerts beneficial effects on the peripheral endothelium. However, its role in the healthy and injured brain endothelium remains to be evaluated. Herein, this study aimed to investigate the potential function of endogenous and therapeutic cortistatin in regulating brain endothelium dysfunction in a neuroinflammatory/neurodegenerative environment. METHODS: Wild-type and cortistatin-deficient murine brain endothelium and human cells were used for an in vitro barrier model, where a simulated ischemia-like environment was mimicked. Endothelial permeability, junction integrity, and immune response in the presence and absence of cortistatin were evaluated using different size tracers, immunofluorescence labelling, qPCR, and ELISA. Cortistatin molecular mechanisms underlying brain endothelium dynamics were assessed by RNA-sequencing analysis. Cortistatin role in BBB leakage was evaluated in adult mice injected with LPS. RESULTS: The endogenous lack of cortistatin predisposes endothelium weakening with increased permeability, tight-junctions breakdown, and dysregulated immune activity. We demonstrated that both damaged and uninjured brain endothelial cells isolated from cortistatin-deficient mice, present a dysregulated and/or deactivated genetic programming. These pathways, related to basic physiology but also crucial for the repair after damage (e.g., extracellular matrix remodelling, angiogenesis, response to oxygen, signalling, and metabolites transport), are dysfunctional and make brain endothelial barrier lacking cortistatin non-responsive to any further injury. Treatment with cortistatin reversed in vitro hyperpermeability, tight-junctions disruption, inflammatory response, and reduced in vivo BBB leakage. CONCLUSIONS: The neuropeptide cortistatin has a key role in the physiology of the cerebral microvasculature and its presence is crucial to develop a canonical balanced response to damage. The reparative effects of cortistatin in the brain endothelium were accompanied by the modulation of the immune function and the rescue of barrier integrity. Cortistatin-based therapies could emerge as a novel pleiotropic strategy to ameliorate neuroinflammatory/neurodegenerative disorders with disrupted BBB.

Type D Personality as a Marker of Poorer Quality of Life and Mood Status Disturbances in Patients with Skin Diseases: A Systematic Review.

Type D personality is characterized by social inhibition and negative affectivity. Poorer outcomes and worse quality of life have been linked to type D personality in patients with a variety of non-dermatological diseases. Despite increasing evidence of the importance of type D personality in skin diseases, there are no reviews on this subject. The aim of this review is to summarize the current evidence regarding type D personality and skin diseases. A systematic search was performed using Medline and Web of Science databases from inception to 11 October 2022. Studies addressing the presence of type D personality, its associated factors, its impact on the outcomes of the disease or the quality of life of the patients were included in the systematic review. A total of 20 studies, including 3,124 participants, met the eligibility criteria and were included in the review. Acne, hidradenitis suppurativa, psoriasis, melanoma, atopic dermatitis, chronic spontaneous urticaria and pruritic disorders were the main diseases assessed. Type D personality was more frequent among patients with skin diseases than among controls. Type D personality was found to be associated with poorer quality of life and higher rates of psychological comorbidities in patients with skin diseases. In conclusion, type D personality appears to be a marker of patients with increased risk of poorer quality of life and higher rates of psychological comorbidities. Screening for type D personality in specialized dermatology units might be beneficial to identify patients who are more psychologically vulnerable to the consequences of chronic skin diseases.

Cytotoxicity, Epidermal Barrier Function and Cytokine Evaluation after Antiseptic Treatment in Bioengineered Autologous Skin Substitute.

Bioengineered autologous skin substitutes (BASS) technology is an emerging field for skin burn therapy. However, further studies on BASS characterization, viability against standard procedures for wound healing, and protocol optimization are necessary for the improvement of BASS technology for clinical use. The aim of this study is to evaluate the effect of common antiseptics for clinical use in BASS, focusing on cell viability, inflammatory cytokine pattern, and epithelium and skin barrier integrity, in order to establish the most adequate treatment for wound care after BASS grafting. Human keratinocytes (hKT) and dermal fibroblasts (hDF) were isolated from foreskin samples and integrated into hyaluronic acid-based BASS. The following antiseptics were applied every 48 h: ethanol (70%), chlorhexidine digluconate (1%), sodium hypochlorite (0.02%), povidone iodine (100 mg/mL), and polyhexanide (0.1%), during a follow-up of 16 days. Sodium hypochlorite was the only treatment that showed a high cell viability percentage throughout the evaluation time compared to other antiseptic treatments, as well as a similar cytokine secretion pattern as control BASS. No significant differences were found regarding epidermal barrier function. These findings point towards sodium hypochlorite being the least aggressive antiseptic treatment for BASS post-transplantation wound care.

Cytotoxicity and Wound Closure Evaluation in Skin Cell Lines after Treatment with Common Antiseptics for Clinical Use.

In recent years, new therapies, such as skin cell lines injections, have emerged to promote re-epithelialization of damaged areas such as chronic ulcers or to treat patients with severe burns. Antiseptics are commonly used during wound clinical management to avoid serious infections, but they may delay the healing process due to their apparent cytotoxicity to skin cells. The cytotoxicity of ethanol, chlorhexidine digluconate, sodium hypochlorite, povidone iodine and polyhexanide was evaluated in this in vitro study on human fibroblasts and keratinocytes. Treatments were applied to each cell type culture every 48 h for 14 days. To determine the cytotoxic of antiseptics, cell viability (Live/Dead®) and cell proliferation (AlamarBlue™) assays were performed on cell monolayers. Cell migration capacity was evaluated with a wound closure assay. Results showed how chlorhexidine digluconate and ethanol significantly reduced the viability of keratinocytes and inhibited cell migration. Povidone iodine followed by chlorhexidine digluconate significantly reduced fibroblast cell viability. Povidone iodine also inhibited cell migration. Sodium hypochlorite was the least detrimental to both cell types. If epithelial integrity is affected, the wound healing process may be altered, so the information gathered in this study may be useful in selecting the least aggressive antiseptic after treatment with new emerging therapies.