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Introduction: There are several hypotheses of schizophrenia pathogenesis, including the neurodegenerative theory, which is supported by evidence for the decrease of neuroprotective factors’ serum levels. The proteins, that exert a protective effect on neurons and are researched concerning schizophrenia pathogenesis, include the brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT3), and glial cell line-derived neurotrophic factor (GDNF). This review aims to discuss the role of neuroprotective factors in the development of schizophrenia and their relevance in clinical trials. Material and methods: This review was performed by search of the PubMed, Google Scholar, and Science Direct databases from December 25th, 2022, through January 31st, 2023, using keywords: ‘schizophrenia’, ‘schizophrenia pathogenesis’, ‘neuroprotection’, ‘neurodegeneration’, ‘BDNF’, ‘NGF’, ‘NT3’, and ‘GDNF’. We considered original research papers and systematic reviews published in English or Polish. Additionally, clinical trials, which included the assessment of neuroprotective factors’ levels in schizophrenia as outcome measures, were searched for on clinicaltrials.gov. Results: Lower levels of serum BDNF have been linked to cognitive impairment in schizophrenia. In clinical trials, the assessment of serum BDNF is used as a clinical outcome measure for novel schizophrenia therapies. Schizophrenia has also been associated with reduced peripheral NGF levels. During remission, lower NGF levels correlate with higher severity of negative symptoms. Decreased NT3 and GDNF levels can also be seen, but literature reports are inconsistent. Conclusions: Neuroprotective factors are most likely related to the pathogenesis of schizophrenia. Assessing the serum level of these proteins may prove to be an invaluable element of schizophrenia management. Keywords: schizophrenia, brain-derived neurotrophic factor, nerve growth factor,neurotrophin 3, glial cell line-derived neurotrophic factor

Magdalena Maciejewska,1 Albert Stec,2 Micha&lstrok; Zaremba,2 Cezary Maciejewski,3 Lidia Rudnicka,2 Mariusz Sikora4 1Department of Dermatology, Doctoral School of Medical University of Warsaw, Warsaw, Poland; 2Department of Dermatology, Medical University of Warsaw, Warsaw, Poland; 3 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland; 4National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandCorrespondence: Mariusz Sikora, National Institute of Geriatrics, Rheumatology and Rehabilitation, Sparta&nacute;ska 1, Warsaw, 02-637, Poland, Email drmariuszsikora@gmail.comBackground: Systemic sclerosis is a connective tissue disease characterized by vasculopathy and progressive fibrosis, leading to multiorgan dysfunction. Given the complex and not fully elucidated pathogenesis, biomarkers of rapid disease progression and therapeutic response are lacking. Copeptin, which reflects vasopressin activity in serum, is used in diagnosing or prognosing different cardiometabolic conditions.Objective: The aim of study was to investigate the concentration of copeptin in patients with systemic sclerosis and correlate it with specific clinical symptoms.Patients and Methods: Serum copeptin was measured in patients with systemic sclerosis (34 women and 3 men; mean age 57.6 years) and in healthy individuals (n=30) using commercially available ELISA kits. According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). The median duration of the disease was 10 [4– 14] years.Results: We found significantly higher copeptin concentration in patients with systemic sclerosis (4.21 pmol/L [3.04– 5.42]) in comparison to control group (3.40 pmol/L [2.38– 3.76], p< 0.01). Copeptin significantly correlated with Raynaud’s condition score (r=0.801, p< 0.05). Patients with “late” capillaroscopic patterns had higher copeptin concentrations (5.37 pmol/L [4.29– 8.06]) than patients with “early” (2.43 pmol/L [2.25– 3.20], p< 0.05) and “active” patterns (3.93 pmol/L [2.92– 5.16], p< 0.05]). Copeptin was found to be significantly higher in SSc patients with DUs (5.71 pmol/L [IQR 4.85– 8.06]) when compared to SSc patients without DUs (3.31 pmol/L, [2.28– 4.30], p< 0.05). Additionally, copeptin concentration had good diagnostic accuracy in discriminating between patients with and without digital ulcers (AUC=0.863). Alprostadil decreased copeptin concentration from 4.96 [4.02– 6.01] to 3.86 pmol/L [3.17– 4.63] (p< 0.01) after 4– 6 cycles of administration.Conclusion: Our findings suggest that copeptin may be a promising biomarker of microcirculation alterations in systemic sclerosis.Keywords: serum biomarkers, vasculopathy, endothelial dysfunction, digital ulcers, systemic sclerosis

Albert Stec,1 Magdalena Maciejewska,1 Karolina Paralusz-Stec,1 Milena Michalska,2 Joanna Giebu&lstrok;towicz,3 Lidia Rudnicka,1 Mariusz Sikora4 1Department of Dermatology, Medical University of Warsaw, Warsaw, Poland; 2Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland; 3Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland; 4National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandCorrespondence: Mariusz Sikora, National Institute of Geriatrics, Rheumatology and Rehabilitation, Sparta&nacute;ska 1, Warsaw, 02-637, Poland, Tel +48 22 670 91 00, Fax +48 22 844 77 97, Email drmariuszsikora@gmail.comBackground: Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease characterized by fibrosis of the skin and internal organs, whose pathogenesis is not fully understood. Recent studies have revealed dysbiosis in patients with systemic sclerosis and have indicated the possible role of the microbiota and its metabolites in the pathogenesis of the disease. Trimethylamine N-oxide (TMAO) is a compound produced by dysbiotic microbiota observed at higher concentrations in several autoimmune diseases.Objective: To determine concentrations of the bacteria-derived metabolite TMAO in patients with systemic sclerosis and to assess possible correlation between TMAO and a specific manifestation of the disease.Patients and Methods: The study included 63 patients with SSc and 47 matched control subjects. The concentration of TMAO was measured with high-performance liquid chromatography.Results: Plasma TMAO level was significantly increased in patients with SSc (283.0 [188.5– 367.5] ng/mL versus 205.5 [101.0– 318.0] ng/mL; p < 0.01). An increased concentration of TMAO was observed in patients with concomitant interstitial lung disease (ILD) (302.0 ng/mL [212.0– 385.5] ng/mL versus 204.0 [135.5– 292.0] ng/mL; p < 0.01) and esophageal dysmotility (289.75 [213.75– 387.5] ng/mL versus 209.5 ng/mL [141.5– 315.0] ng/mL; p < 0.05) compared to patients without these complications. Furthermore, TMAO concentration exhibited significant correlation with markers of heart involvement (left ventricle ejection fraction, NT-proBNP), marker of ILD severity and Scleroderma Clinical Trials Consortium Damage Index.Conclusion: The concentration of TMAO, gut microbiota-associated metabolite, is increased in systemic sclerosis, particularly in patients with advanced organ involvement. This is the first study evaluating plasma TMAO in systemic sclerosis. Bacterial metabolites may be a link between dysbiosis and organ involvement in the course of the disease. Modulation of gut bacterial-derived metabolites may represent a new therapeutic approach in the management of systemic sclerosis.Keywords: gut microbiota, systemic sclerosis, trimethylamine N-oxide, bacterial metabolites, dysbiosis, damage index

Systemic sclerosis (SSc) is an immune-mediated connective tissue disease. Recent studies reported differences in the composition of intestinal microbiota (dysbiosis) in patients with SSc compared to nonsclerodermic subjects. Dysbiosis may disrupt the intestinal barrier, which leads to immunological activation via microbial antigen and metabolite translocation. The study aimed to assess the differences in intestinal permeability between SSc patients and controls and to examine the correlation between intestinal permeability and complications of SSc. The study comprised 50 patients with SSc and 30 matched subjects. Serum intestinal permeability markers: intestinal fatty acid binding protein, claudin-3, and lipopolysaccharides (LPS) were determined using an enzyme-linked immunosorbent assay. SSc patients had a significantly increased concentration of LPS compared to control subjects (232.30 [149.00–347.70] versus 161.00 [83.92–252.20] pg/mL, p < 0.05). The patients with shorter SSc duration (≤6 years) had an increased concentration of LPS and claudin-3 compared to the subgroup with longer disease length: LPS (280.75 [167.30–403.40] versus 186.00 [98.12–275.90] pg/mL, p < 0.05), and claudin-3 (16.99 [12.41–39.59] versus 13.54 [10.29–15.47] ng/mL, p < 0.05). The patients with esophageal dysmotility had a decreased LPS level compared to those without this complication (188.05 [102.31–264.40] versus 283.95 [203.20–356.30] pg/mL, p < 0.05). Increased intestinal permeability in SSc may exacerbate the course of the disease and increase the risk of developing complications. Lower LPS levels in SSc might be a hallmark of esophageal dysmotility.

Mariusz Sikora,1 Albert Stec,1 Magdalena Chrabaszcz,1 Joanna Giebultowicz,2 Emilia Samborowska,3 Radoslaw Jazwiec,3 Michal Dadlez,3,4 Malgorzata Olszewska,1 Lidia Rudnicka1 1Department of Dermatology, Medical University of Warsaw, Warsaw, Poland; 2Department of Bioanalysis and Drug Analysis, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Warsaw, Poland; 3Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland; 4Institute of Genetics and Biotechnology, Biology Department, Warsaw University, Warsaw, PolandCorrespondence: Mariusz SikoraDepartment of Dermatology, Medical University of Warsaw, Koszykowa 82A, Warsaw 02-008, PolandTel +48 22 502 13 24Fax +48 22 502 21 06Email msikora@wum.edu.plBackground: An increasing amount of evidence suggests an association between increased intestinal permeability and the pathogenesis of chronic inflammatory diseases. However, the clinical significance of gut barrier dysfunction in psoriasis remains to be established.Objective: To evaluate whether there are differences in disease activity, the severity of gastrointestinal symptoms and the blood concentration of bacterial metabolites in psoriatic patients with a normal and altered intestinal barrier.Patients and Methods: Gut barrier integrity was assessed with the serum concentrations of claudin-3, a modulator of intestinal tight junctions and an intestinal fatty acid-binding protein, a marker of enterocyte damage. Gastrointestinal symptoms were evaluated with a validated questionnaire. The concentration of trimethylamine N-oxide (TMAO), a gut microbiota-associated metabolite, was measured with high-performance liquid chromatography.Results: One hundred and fourteen patients with psoriasis were finally enrolled in the study – 68 with an altered gut barrier and 46 with a properly functioning intestinal barrier. Patients with an altered gut barrier showed a significantly higher score in the Gastrointestinal Symptom Rating Scale (3.20 vs 1.46, p< 0.001). Moreover, patients with psoriasis and a disrupted intestinal barrier demonstrated a higher disease activity (PASI: 19.7 vs 10.3, p< 0.001) and systemic inflammatory parameters (neutrophil-to-lymphocyte ratio: 2.86 vs 1.71, p< 0.001; C-reactive protein 3.76 vs 1.92; p< 0.05). The marker of bacterial translocation was significantly higher in psoriatic patients with damaged gut integrity (TMAO: 375.7± 51.9 vs 119.4± 27.5 ng/mL; p< 0.05).Conclusion: The altered gut barrier in psoriasis is associated with gastrointestinal symptoms, systemic inflammatory profile and the increased blood concentration of gut microbiota-derived metabolite – TMAO. Intestinal barrier modulation represents a new promising therapeutic approach.Keywords: gut barrier, microbiome, psoriasis, systemic sclerosis, TMAO

Introduction Trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, is involved in the pathogenesis of atherosclerosis and cardiovascular diseases. Psoriasis is associated with increased cardiovascular risk that is not captured by traditional biomarkers. The aim of the present study was to assess TMAO concentration in psoriasis and evaluate the relationship between TMAO and cardiovascular risk in psoriatic patients. Methods In 72 patients with psoriasis and 40 age- and sex-matched non-psoriatic controls, we evaluated fasting plasma TMAO, measured by high-performance liquid chromatography, and cardiovascular risk assessed by various scoring systems such as Framingham, QRISK2, AHA/ACC, and Reynolds risk scores. Results In patients with psoriasis, TMAO concentration was significantly higher than in the control group (195.68 [133.54–332.58] ng/ml versus 126.06 [84.29–156.88] ng/ml, respectively; p

Alterations of intestinal microbiota play a significant role in the pathogenesis of psoriasis. Dysbiosis may cause disruption of the intestinal barrier, which contributes to immune activation by translocation of microbial antigens and metabolites. Intestinal fatty acid binding protein (I-FABP) serves as a biomarker of enterocyte damage. The aim of this study was to investigate clinical and metabolic factors affecting plasma concentration of I-FABP in patients with psoriasis. Eighty patients with psoriasis and 40 control subjects were enrolled in the study. Serum I-FABP (243.00 (108.88&ndash, 787.10) vs. 114.38 (51.60&ndash, 241.60) pg/ml, p &lt, 0.001) and neutrophil to lymphocyte ratio (NLR, 2.59 (1.96&ndash, 3.09) vs. 1.72 (1.36&ndash, 47 2.11), p &lt, 0.01) were significantly increased in patients with psoriasis compared to controls. A significant positive correlation was found between I-FABP and body mass index (BMI) (r = 0.82, p &lt, 0.001), Psoriasis Area Severity Index (PASI) (r = 0.78, p &lt, 0.001) and neutrophil to lymphocyte ratio (NLR) (r = 0.24, p &lt, 0.001). Rising quartiles of I-FABP were associated with increasing values of BMI, PASI and NLR. The results of the logistic regression model confirmed an increased risk of higher disease severity with I-FABP concentration &ndash, odds ratio 3.34 per 100 pg/mL I-FABP increase. In conclusion, intestinal integrity in patients with psoriasis is affected by obesity, severity of the disease and systemic inflammation. The modulation of gut barrier may represent a new therapeutic approach for psoriasis.

Psoriasis has been linked to several comorbidities, including metabolic syndrome, atopy, and celiac disease. However, the association between immune thrombocytopenia and psoriasis has rarely been described. We report the case of an adolescent with severe psoriasis and concomitant immune thrombocytopenia who obtained remission during treatment with adalimumab. Increased concentration of tumor necrosis factor-α seems to be a pathogenic linkage and therapeutic target for both diseases.

(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.