Current Concepts of Psoriasis Immunopathogenesis Vičić, Marijana; Kaštelan, Marija; Brajac, Ines ...
International journal of molecular sciences,
10/2021, Letnik:
22, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis is the most ...common inflammatory skin disease, affecting an average of 2-4% of the world's population. The disease carries a significant burden due to its numerous comorbidities and the major impact on patients' social and emotional aspects of life. According to current knowledge, psoriasis is a multifactorial disease that occurs in genetically predisposed individuals under various environmental factors, which trigger an immune response disorder with a series of complex inflammatory cascades. The disease is initiated and maintained by mutual interaction of the innate and adaptive immune cells, primarily dendritic cells, T lymphocytes, and keratinocytes, whose leading role alternates at different stages of the disease, consisting mainly in the IL-23/Th17 pathway. Inflammatory events result in consequent epidermal and dermal changes and evolution of the characteristic psoriatic phenotype, respectively. This paper aims to present a comprehensive overview of current knowledge on psoriasis genetic and environmental etiological factors, immunopathogenesis, and the leading cellular and cytokine participants in the inflammatory pathways of this disease.
Lichen planus is a chronic disease affecting the skin, appendages, and mucous membranes. A cutaneous lichen planus is a rare disease occurring in less than 1% of the general population, while oral ...illness is up to five times more prevalent; still, both forms equally impair the patient's quality of life. The etiology of lichen planus is not entirely understood. Yet, immune-mediated mechanisms have been recognized since environmental factors such as hepatitis virus infection, mechanical trauma, psychological stress, or microbiome changes can trigger the disease in genetically susceptible individuals. According to current understanding, lichen planus immunopathogenesis is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by Th1 and IL-23/Th-17 axis. However, other immunocytes and inflammatory pathways complement these mechanisms. This paper presents a comprehensive insight into the actual knowledge about lichen planus, with the causal genetic and environmental factors being discussed, the immunopathogenesis described, and the principal effectors of its inflammatory circuits identified.
Extracellular vesicles (EVs) are membranous nanostructures that can indicate undergoing processes in organs and thus help in diagnostics and prognostics. They are secreted by all cells, contained in ...body fluids, and able to transfer proteins, lipids and nucleic acids to distant cells. Intracranial EVs were shown to change their composition after severe traumatic brain injury (TBI) and therefore to have biomarker potential to evaluate brain events. Properties of intracranial EVs early after TBI, however, have not been characterized. Here, we assessed cerebrospinal fluid (CSF) up to seven days after isolated severe TBI for physical properties of EVs and their proteins associated with neuroregeneration. These findings were compared with healthy controls and correlated to patient outcome. The study included 17 patients with TBI and 18 healthy controls. EVs in TBI-CSF were visualized by electron microscopy and confirmed by immunoblotting for membrane associated Flotillin-1 and Flotillin-2. Using nanoparticle tracking analysis, we detected the highest range in EV concentration at day 1 after injury and significantly increased EV size at days 4-7. CSF concentrations of neuroregeneration associated proteins Flotillin-1, ADP-ribosylation Factor 6 (Arf6), and Ras-related protein Rab7a (Rab7a) were monitored by enzyme-linked immunosorbent assays. Flotillin-1 was detected solely in TBI-CSF in about one third of tested patients. Unfavorable outcomes included decreasing Arf6 concentrations and a delayed Rab7a concentration increase in CSF. CSF concentrations of Arf6 and Rab7a were negatively correlated. Our data suggest that the brain response within several days after severe TBI includes shedding of EVs associated with neuroplasticity. Extended studies with a larger number of participants and CSF collected at shorter intervals are necessary to further evaluate neuroregeneration biomarker potential of Rab7a, Arf6, and Flotillin-1.
Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves’ disease (GD). The pathogenesis of AITD is caused ...by an inappropriate immune response related to genetic, non-genetic, and environmental factors. Pregnancy is one of the factors that have a great influence on the function of the thyroid gland because of the increased metabolic demand and the effects of hormones related to pregnancy. During pregnancy, an adaptation of the maternal immune system occurs, especially of the innate immune system engaged in maintaining adaptive immunity in the tolerant state, preventing the rejection of the fetus. Pregnancy-related hormonal changes (estrogen, progesterone, hCG) may modulate the activity of innate immune cells, potentially worsening the course of AITD during pregnancy. This especially applies to NK cells, which are associated with exacerbation of HD and GD. On the other hand, previous thyroid disorders can affect fertility and cause adverse outcomes of pregnancy, such as placental abruption, spontaneous abortion, and premature delivery. Additionally, it can cause fetal growth retardation and may contribute to impaired neuropsychological development of the fetus. Therefore, maintaining the thyroid equilibrium in women of reproductive age and in pregnant women is of the highest importance.
Bilateral COVID-19 pneumonia is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and usually leads to life-threatening acute respiratory distress syndrome (ARDS). ...Treatment of patients with ARDS is difficult and usually involves protective mechanical ventilation and various types of recruitment maneuvers. A segmental lung recruitment maneuver by independent lung ventilation has been described as a successful recruitment maneuver in patients with lobar pneumonia, and may, therefore, be useful for the treatment of patients with bilateral COVID-19 pneumonia complicated by ARDS in the critical phase of the disease when all other therapeutic options have been exhausted. The aim of this case series was to present a case report of four mechanically ventilated patients with severe bilateral COVID-19 pneumonia complicated by ARDS using the segmental lung recruitment maneuver. The effect of the segmental lung recruitment maneuver was assessed by the increase in PaO
/FiO
ratio and the lung ultrasound (LUS) scoring system (0 points-presence of sliding lungs with A-lines or one or two isolated B-lines; 1 point-moderate loss of lung ventilation with three to five B lines; 2 points-severe loss of lung ventilation with more than five B lines (B pattern); and 3 points-lung consolidation) determined 12, 24, and 48 h after segmental lung recruitment. In three of four patients with bilateral COVID-19 pneumonia complicated by ARDS, an increase in the PaO
/FiO
ratio and an improvement in the LUS scoring system were observed 48 h after segmental lung recruitment. In conclusion, the segmental lung recruitment maneuver in patients with bilateral COVID-19 complicated by ARDS is an effective method of lung recruitment and may be a useful treatment method.
The endothelial glycocalyx (EGC) is a layer of proteoglycans (associated with glycosaminoglycans) and glycoproteins, which adsorbs plasma proteins on the luminal surface of endothelial cells. Its ...main function is to participate in separating the circulating blood from the inner layers of the vessels and the surrounding tissues. Physiologically, the EGC stimulates mechanotransduction, the endothelial charge, thrombocyte adhesion, leukocyte tissue recruitment, and molecule extravasation. Hence, severe impairment of the EGC has been implicated in various pathological conditions, including sepsis, diabetes, chronic kidney disease, inflammatory disorders, hypernatremia, hypervolemia, atherosclerosis, and ischemia/reperfusion injury. Moreover, alterations in EGC have been associated with altered responses to therapeutic interventions in conditions such as cardiovascular diseases. Investigation into the function of the glycocalyx has expanded knowledge about vascular disorders and indicated the need to consider new approaches in the treatment of severe endothelial dysfunction. This review aims to present the current understanding of the molecular mechanisms underlying cardiovascular diseases and to elucidate the impact of heart surgery on EGC dysfunction.
Psoriasis is considered to be a cytokine-driven immune-mediated disease, although the cell cytotoxicity mechanisms involved remain unrecognized. Herein, we analyzed granulysin expression in different ...lymphocyte subsets of peripheral blood of 40 psoriatic patients (20 with severe and 20 with mild psoriasis) and seven sample of psoriatic skin. The simultaneous detection of intracellular granulysin and cell surface antigens was performed using flow cytometry in peripheral blood and immunohistochemistry in skin lesions. The frequency of granulysin+ cells, mean fluorescence intensity for granulysin, and the frequency of CD8+ T lymphocytes, NK cells, and NKT cells expressing granulysin molecules in peripheral blood were significantly higher in patients with severe psoriasis compared to mild disease and healthy individuals. These were also correlated with disease severity. Furthermore, granulysin+ cells, CD8+granulysin+ T lymphocytes, and CD56+granulysin+ NK cells were present in a higher frequency in the epidermal basal cell layer and in the dermal infiltrate of lesional skin as compared to non-lesional and healthy skin. In conclusion, granulysin+ cytotoxic cells are upregulated in blood and lesions of patients with psoriasis suggesting the involvement of granulysin mediated cytotoxicity in psoriasis pathogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
General anesthesia induces reversible unconsciousness, eliminating sensation and enabling painless medical procedures. Vital for dental care, it addresses patients with medical conditions, those ...needing extensive procedures, and those unable to cooperate due to fear. Dental care for patients with disabilities is a significant unmet need, with studies showing increased oral disease prevalence. This research aims to analyze postoperative morbidity both in healthy and disabled children undergoing dental procedures under general anesthesia.
This study involved 96 children aged 3 to 15 with dental caries. Two groups were formed: the control group (CTL) (52.94%) included healthy patients requiring general anesthesia due to unsatisfactory cooperation, and the other group included children with physical or intellectual disabilities (CD) (47.96%). Postoperative complications were monitored 1 h after the procedure and 1, 3, 7, and 14 days after the procedure by contacting parents/caregivers by phone. The intensity of postoperative pain was assessed using the Wong-Baker faces pain rating scale. General anesthesia was conducted following a standardized protocol for dental procedures.
CTL patients complained more often about postoperative pain 1 h after the procedure (
= 0.03). One day after the procedure, oral bleeding (
= 0.04), fever (
= 0.009), and diarrhea (
= 0.037) occurred more often in CD. In the same period, sore throat appeared more often in CTL (
= 0.036). Three days after the dental treatment, there were statistically significant increases in the occurrence of agitation (
= 0.043) and constipation (
= 0.043) in CD. Seven days later, CD demonstrated a higher occurrence of agitation (
= 0.037). According to the Wong-Baker faces pain rating scale, CTL experienced more frequent and intense pain.
CD more frequently reported complications like oral bleeding, fever, and diarrhea. In contrast, the CTL group more often reported pain-related symptoms. The conclusion underscores the need for a pain control protocol for CD and emphasizes the importance of frequent monitoring to prevent unwanted consequences during tooth restoration under general anesthesia.
Cardiac surgery is one of the highest-risk procedures, usually involving cardiopulmonary bypass and commonly inducing endothelial injury that contributes to the development of perioperative and ...postoperative organ dysfunction. Substantial scientific efforts are being made to unravel the complex interaction of biomolecules involved in endothelial dysfunction to find new therapeutic targets and biomarkers and to develop therapeutic strategies to protect and restore the endothelium. This review highlights the current state-of-the-art knowledge on the structure and function of the endothelial glycocalyx and mechanisms of endothelial glycocalyx shedding in cardiac surgery. Particular emphasis is placed on potential strategies to protect and restore the endothelial glycocalyx in cardiac surgery. In addition, we have summarized and elaborated the latest evidence on conventional and potential biomarkers of endothelial dysfunction to provide a comprehensive synthesis of crucial mechanisms of endothelial dysfunction in patients undergoing cardiac surgery, and to highlight their clinical implications.
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