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Background: Atopic dermatitis (AD) is a highly prevalent inflammatory skin disorder characterized by episodic exacerbations and remissions. Why the clinically healthy skin of AD patients becomes rapidly inflamed and very pruritic is poorly understood. Objective: To investigate cowhage‐ and histamine‐induced itch and skin expression levels of their target receptors in lesional and non‐lesional skin of AD, compared to the skin of patients with psoriasis, chronic spontaneous urticaria (CSU) and healthy subjects. Methods: Patients with AD, psoriasis and chronic spontaneous urticaria (CSU) as well as healthy control subjects (HC) (n = 20 each) were assessed for differences in itch parameters, neurogenic flare reaction and local blood flow responses to skin provocations with cowhage and histamine. Skin biopsies from 10 AD, 10 psoriasis,11 CSU and 12 HC were obtained to assess expression of protease‐activated receptors 2 and 4 (PAR‐2, PAR‐4), histamine H1 and H4 receptors (H1R, H4R), and mast cells. Results: Provocation of non‐lesional skin of AD patients with cowhage resulted in prolonged itch (p = 0.020), which was not observed in psoriasis and CSU. Significantly prolonged and more intense cowhage‐ and histamine‐induced itch (for duration, peak and overall intensity) was also observed in lesional AD skin. Diminished neurogenic flare reaction and blood flow after histamine provocation were shown in AD and psoriasis patients. Non‐lesional AD skin along with lesional AD and psoriasis skin showed an increased expression of PAR‐2 and PAR‐4, H1R and H4R. Mast cell number was higher in lesional AD and psoriasis skin (p = 0.006 and p = 0.006, respectively). Conclusion: The non‐lesional skin of AD patients markedly differs from healthy skin in cowhage‐induced itch responses and the expression of receptors for proteases and histamine. Proactive therapeutic interventions that downregulate these receptors may prevent episodic exacerbation in AD. [ABSTRACT FROM AUTHOR]

The role of the process of apoptosis is investigated in the pathogenesis of many autoimmune diseases; however at present, there is not much information about its role in dermatitis herpetiformis. Skin biopsies were taken from 18 DH patients and from 10 healthy subjects. The localization and expression of Bax, Fas, FasL, TRAIL, TRAIL-R in skin lesions, and perilesional skin were studied by immunohistochemistry. Expression of Bax, Fas, and Fas ligand was detected in the keratinocytes in skin biopsies from DH patients. Expression of TRAIL and TRAIL receptor was confirmed in epidermis, infiltration cells, and some fibroblasts. The expression of examined molecules in biopsies from healthy people was observed only in single cells. There were statistically significant differences between lesional, perilesional, and healthy skin of control group in Bax expression analysis and between lesional skin and control group in Fas, FasL, and TRAIL expression. There were statistically significant differences between control group and perilesional skin in Bax and FasL expression. Our results show that selected proapoptotic molecules may take part in pathogenesis of dermatitis herpetiformis, but the role of apoptosis in this process is not clear.

Macromastia is an excessive, rapid, or slow growth of breast tissue in 1 or both breasts. While macromastia represents a benign lesion, it may cause breast, shoulder, back, and neck pain, poor posture, infections, and loss of nipple sensation. The pathogenesis of macromastia or hypertrophy of mammary tissue remains poorly understood. The purpose of this study is to investigate the immunohistochemical expression of several hormone receptors that may potentially influence the growth of breast tissue in women with macromastia. Immunohistochemical studies performed on representative sections of breast tissue from 63 patients diagnosed with macromastia included estrogen receptor, progesterone receptor, androgen receptor (AR), prolactin receptor, growth hormone receptor, and vascular endothelial growth factor. The expression of each stain was evaluated separately in the glandular epithelium and adipose tissue and calculated as an H-score. We observed that AR expression in breast glandular and adipose tissue in women with macromastia was significantly lower than benign, nonhypertrophic breast tissue of a control group. Although the analyses were controlled for the age, the fact the mean age and hormonal status differed between the patients and the controls could have affected the results. Additional large studies will be required to further verify this finding and increase the knowledge about the etiology of this condition and then guide pharmacological treatment of juvenile and/or idiopathic gigantomastia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The JAK/STAT signal pathway is a system of intracellular proteins used by many cytokines and growth factors to express genes responsible for the process of cell activation, proliferation and differentiation. There has been numerous inflammatory and autoimmune diseases identified where the JAK/STAT signaling is disrupted; however, there are only a few papers concerning autoimmune bullous diseases published. The aim of this study was to evaluate the expression of proteins: JAK3, STAT2, STAT4 and STAT6 in epithelium lesions in patients with pemphigus vulgaris (PV), bullous pemphigoid (BP), oral lichen planus (LP) and chronic ulcerative stomatitis (CUS), as well as in the control group. Immunohistochemistry and immunoblotting were used to evaluate expression of selected proteins. We found significantly higher expression of selected JAK/STAT proteins in oral mucosa lesions in study groups in comparison to the control group, which indicates participation of JAK/STAT pathway in pathogenesis of these diseases. In BP and PV there were no increased STAT2 expression, whereas in CUS and LP no increased STAT4 expression occurred. The differences in expression of JAK/STAT proteins in selected disorders have been observed. These results create new potential therapeutic targets for the treatment.

Supraglottic stenosis is a rare symptom, particularly in fibroinflammatory multifocal diseases, such as IgG4-related disease (IgG4-RD). There is still an inconsistency in the diagnosis of less-common locations of IgG4-RD, which causes a delay in the diagnosis and treatment. Our paper aims to analyze different aspects of IgG4-RD presenting as supraglottic stenosis, including the possible overlap with ANCA-associated vasculitis. We compare the usefulness of the recently revised ACR/EULAR and Comprehensive criteria and discuss treatment options. The review was performed according to PRISMA guidelines using the MEDLINE Pubmed and Scopus databases. The analysis includes nine papers describing supraglottic laryngeal stenosis in 13 patients. Furthermore, we present a case of a woman with ongoing supraglottic stenosis presenting with cough, temporary dyspnea and stridor as the symptoms of localized IgG4-RD. At the time of writing, the patient remains in remission while receiving treatment with cyclophosphamide and methylprednisolone. The symptoms of supraglottic localization of IgG4-RD may be severe; however, at that point, clinicians should suspect autoimmune etiology and attempt to modulate the autoimmune response instead of performing dilatation surgery-the effects of which may not result in extended intervals between interventions. The ACR/EULAR criteria show great specificity; however, when IgG4-RD is presumed, the specific treatment should be implemented.

Objectives: The Hedgehog signaling pathway (Hh) probably plays a role in development and progression of pancreatic ductal adenocarcinoma (PDAC)., Methods: In our study, 114 patients (83 with PDAC and 31 with chronic pancreatitis [CP]) after pancreatic surgery were enrolled. The immunoexpression of Sonic hedgehog (Shh), Smoothened (Smo), and Glioblastoma transcription factor 1 (Gli1) and Ki-67 were detected in tissue specimens., Results: Mean (standard deviation) immunoexpression of all Hh pathway molecules was significantly higher in PDAC than in CP patients: Shh, 2.24 (0.57) versus 1.17 (0.25) (P < 0.01); Smo, 2.62 (0.34) versus 1.21 (0.23) (P < 0.01); and Gli1, 1.74 (0.74) versus 1.15 (0.72) (P < 0.01). Patients with a lower expression level (z score <0) of Shh and Ki-67 have longer overall survival when compared with z score >0 (15.97 vs 8.53 months [P = 0.0087] and 15.20 vs 5.53 months [P = 0.0004], respectively). In addition, Shh sensitivity in PDAC detection was 84.3%; specificity, 93.5%; positive predictive value, 97.2%; and negative predictive value, 69%., Conclusions: Our results suggest the prognostic role of the Hh pathway in PDAC and a role in the differential diagnosis with CP., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Fibrosis is observed both in pancreatic cancer (PDAC) and chronic pancreatitis (CP). The main cells involved in fibrosis are pancreatic stellate cells (PSCs), which activate alpha smooth muscle actin (αSMA), which is considered to be the best-known fibrosis marker. The aim of the study was to evaluate the expression of the αSMA in patients with PDAC and CP as the possible differentiation marker., Methods: We enrolled 114 patients undergoing pancreatic resection: 83 with PDAC and 31 with CP. Normal fragments of resected specimen from 21 patients represented the control tissue. The immunoexpressions of αSMA were detected in tissue specimens with immunohistochemistry (Abcam antibodies, GB)., Results: Mean cytoplasmatic expression of αSMA protein in PDAC stromal cells was significantly higher compared to CP: 2.42 ± 0.37 vs 1.95 ± 0.45 ( p < 0.01) and control group 0.61 ± 0.45 ( p < 0.01). Strong immunoexpression of the αSMA protein was found in the vast majority (80.7%) of patients with PDAC, in about half (58%) of patients with CP, and not at all in healthy tissue. The expression of αSMA of different intensity was found in all patients with PDAC and CP, while in healthy tissue was minimal or absent. In PDAC patients, αSMA expression was significantly higher in tumors of diameter higher than 3 cm compared to smaller ones ( p = 0.017)., Conclusions: Presented findings confirm the significant role of fibrosis in both PDAC and CP; however, they do not confirm the role of αSMA as a marker of differentiation.

BACKGROUND COVID-19 can be complicated by kidney disease, including focal segmental glomerulosclerosis (FSGS), interstitial nephritis, and acute kidney injury (AKI). Almost all known cases of COVID-19-associated glomerulonephritis have been in patients of African descent, with G1 or G2 apolipoprotein L1 (APOL1) risk alleles, and they presented collapsing type of FSGS. CASE REPORT We report a case of biopsy-confirmed non-collapsing FSGS with secondary acute interstitial nephritis and AKI in a young White man with APOL1 low-risk genotype, who had COVID-19 pneumonia. His past history included arterial hypertension, anabolic steroids, and high-protein diet. He fully recovered from type 1 respiratory failure and AKI after transfusion of COVID-19 convalescent plasma and intravenous treatment with dexamethasone administered for 16 days in a dose reduced from 16 to 2 mg/day. Due to progressing severe nephrotic proteinuria (22.6 g/24 h), intravenous methylprednisolone was administered (1500 mg divided in 3 pulses over 3 days) immediately followed by oral prednisone (0.6 mg/kg body weight), with dose reduced 19 weeks later and switched to cyclosporine A (4 mg/kg body weight). Kidney re-biopsy, at that time, showed a decrease in proportion of glomeruli affected with podocytopathy, but progression of interstitial lesions. After 23 weeks of therapy, partial remission of FSGS was attained and proteinuria dropped to 3.6 g/24 h. After 43 weeks, proteinuria decreased to 0.4 g/24 h and the serum creatinine concentration remained steady. CONCLUSIONS High-dose glucocorticoid therapy was effective in the initial treatment of COVID-19-related non-collapsing FSGS, but had no effect on interstitial changes. Introduction of cyclosporine A to the therapy contributed to remission of disease.

Introduction: Full-thickness rotator cuff tear is present in almost 50% of patients over age 65 years, and its degree is known to be a good predictor of the severity of muscle-wasting (MW) sarcopaenia, also known as fatty degeneration (FD). A FD CT grade > 2° is recognized as a borderline of its reversibility. A disuse model of supraspinatus FD (grade 2) in rabbits provides clinically relevant data. Therefore, the present study evaluates the correlation between eccentric mechanotransduction, neuromuscular transmission (NT), and reversibility of muscle fatty infiltration (MFI) in rabbit supraspinatus FD > 2°., Material and Methods: The supraspinatus tendon was detached from the greater tubercle, infraspinatus, and subscapularis in 16 rabbits. The tendon was reinserted after 12 weeks, and the animals were euthanized 24 weeks after reconstruction. MFI was measured in the middle part of the supraspinatus. Single-fibre EMG (SFEMG) examination of the supraspinatus NT was performed on 4 animals., Results: The power of analysis was 99%. Significant differences in MFI volume were found between the operated (4.6 ±1.1%) and the opposite control sides (2.91 ±0.61%) ( p < 0.001). SFEMG revealed no significant differences between the disuse and the control supraspinatus muscles ( p > 0.05); however, 6.5% of the examined muscle fibres exhibited NT disorders combined with blockade of conduction in 2.5% of muscle fibres., Conclusions: Critical MFI in a disuse model of rabbit supraspinatus FD, CT grade > 2°, is substantially reversible by eccentric training despite subclinical impairment of neuromuscular transmission. In addition, 0.63% reversal of MFI is correlated with 1% hypertrophy of type I and II muscle fibre diameter., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)

During metastasis, cancer cells undergo phenotype changes in the epithelial-mesenchymal transition (EMT) process. Extracellular vesicles (EVs) released by cancer cells are the mediators of intercellular communication and play a role in metastatic process. Knowledge of factors that influence the modifications of the pre-metastatic niche for the migrating carcinoma cells is important for prevention of metastasis. We focus here on how cancer progression is affected by EVs released from either epithelial-like HT29-cells or from cells that are in early EMT stage triggered by Snail transcription factor (HT29-Snail). We found that EVs released from HT29-Snail, as compared to HT29-pcDNA cells, have a different microRNA profile. We observed the presence of interstitial pneumonias in the lungs of mice injected with HT29-Snail cells and the percent of mice with lung inflammation was higher after injection of HT29-Snail-EVs. Incorporation of EVs released from HT29-pcDNA, but not released from HT29-Snail, leads to the increased secretion of IL-8 from macrophages. We conclude that Snail modifications of CRC cells towards more invasive phenotype also alter the microRNA cargo of released EVs. The content of cell-released EVs may serve as a biomarker that denotes the stage of CRC and EVs-specific microRNAs may be a target to prevent cancer progression.

There is growing evidence which indicates that the development and the biological features of cancer such as the invasion, metastases and recurrence are related to the presence and behavior of the cancer stem cells (CSC). However, the regulatory mechanisms underlying CSCs-specific properties are poorly determined, the Hippo pathway has emerged as a fundamental regulator underlying CSCs stemness. Immunohistochemical method was used to examine the immunoexpression of SOX2, TAZ and α-SMA in oral squamous cells carcinomas: with metastases - OSCC M+ (n = 42), and without metastases - OSCC M- (n = 44), and 17 control cases. The immunoexpression of SOX2, TAZ and α-SMA was significantly increased in both group of OSCC in comparison to control groups. Moreover, significantly increased TAZ and α-SMA immunoexpression were found in OSCC M+ compared to OSCC M-. In OSCC M+ and OSCC M- groups there were statistically significant correlations between the immunoexpression of TAZ vs SOX2 (r = 0.56, p < 0.001; r = 0.33, p < 0.03 respectively), and TAZ vs α-SMA (r = 0.64, p < 0.001; r = 0.67, p < 0.001 respectively). Moreover, there was statistically significant association between TAZ high /SOX2 high coexistent immunoexpression and the presence of metastases (p < 0.007). Our results may suggest that SOX2 and TAZ could potentially cooperate and contribute to process of metastasis, especially in cases with TAZ high /SOX2 high expression.

Cancer nanotherapeutics have shown promise in resolving some of the limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, and low therapeutic indices, Among the various nanoparticles that are available, dendrimers, highly branched macromolecules with a specific size and shape, are one of the most promising ones. In this preliminary study, we tested the anti-tumor activity of maltotriose-modified fourth-generation poly(propylene imine) glycodendrimers (PPI-G4-M3) in vivo in the subcutaneous MEC-1 xenograft model of human chronic lymphocytic leukemia (CLL) in NOD scid gamma mice. Fludarabine was used for model validation and as a positive treatment control. The anti-tumor response was calculated as tumor volume, tumor control ratio, and tumor growth inhibition. The study showed that PPI-G4-M3 inhibited subcutaneous tumor growth more efficiently than fludarabine. The anti-tumor response was dose-dependent. Cationic PPI-G4-M3 showed the highest anti-tumor activity but also higher toxicity than the neutral dendrimers and fludarabine. These first promising results warrant further studies in the optimization of dendrimers charge, dose, route and schedule of administration to combat CLL., Competing Interests: Declaration of Competing Interest All authors have no relevant conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Chronic venous disease (CVD) is a disabling condition affecting about 1% to 3% of the general population. Besides varicose veins, CVD can result also in the formation of severe skin lesions, especially venous ulcerations (VU). The exact mechanism of VU is still unknown., Aim: To evaluate immunoexpression of vascular endothelial growth factor (VEGF) and cathepsin K in healthy individuals and patients with VU., Material and Methods: The study included 12 patients with venous ulcers and 10 healthy individuals who served as controls; both groups were sex- and age-matched. Biopsy samples were obtained from lower leg areas and submitted to histochemical analysis., Results: There was a significant difference between the study group and the control group in cathepsin K expression (1.007 ±0.3 vs. 0.22 ±0.2, respectively, p < 0.001) and VEGF expression (1.17 ±0.59 vs. 0.27 ±0.19, respectively, p < 0.001). Additionally, the microvessel density (per mm 2 ) differed significantly between the study group and the control group (97.6 ±28.81 vs. 59.32 ±12.71, respectively, p < 0.001). We found no correlation between cathepsin K and microvessel density, and cathepsin K and VEGF in both groups, but there was a significant correlation between microvessel density and VEGF immunoexpression in the study group ( r = 0.82, p = 0.002)., Conclusions: Increased immunoexpression of VEGF and cathepsin K suggests that both of these proteins may play a role in VU development., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia Sp. z o. o.)

Background Juvenile breast hypertrophy is characterised by massive enlargement of the breast in the peri-pubertal period. We aimed to analyse body size measurements (body mass index [BMI], waist-to-hip circumference ratio [WHR]), digit ratio (ratio of II and IV digits' length [2D:4D]) and oestrogen receptor (ER) alpha (ERα) and progesterone receptors (PRs) in the breast gland in women with juvenile gigantomastia. Methods The study involved 30 women (mean age 25.7 years) (mean age of onset - 14.8 years). ERα and PR expressions were detected immunohistochemically in breast gland samples. For comparison, 100 controls (50 women and 50 men) were included. Results BMI and WHR in women with gigantomastia were higher than in control women and the former had a higher WHR than expected for their BMI. 2D:4D in the examined women did not differ from that in control women. However, left 2D:4D was negatively related to the age of gigantomastia onset. There were no correlations between ER and PR expressions and the analysed body and digit ratios. Conclusions The lack of a relationship between 2D:4D and juvenile breast hypertrophy may suggest that foetal exposure to sex hormones may not be crucial in its aetiology. However, the link between high left 2D:4D and early development of gigantomastia suggests that prenatal sex hormones have a role in its development timing. High WHR, and particularly high WHR relative to BMI, may indicate that these women had at some stage of development higher circulating androgens, which may have been converted to oestrogens in breasts due to local aromatase activity. Verification of this hypothesis could allow consideration of the role of aromatase inhibitors in juvenile breast hypertrophy.