Mateusz de Mezer

Background/Objectives: Psoriasis is an incurable chronic immune-mediated inflammatory skin disorder for which effective topical treatment remains essential. Given the reported anti-inflammatory and dermatological potential of 20-hydroxyecdysone (20HE), this study evaluated its biological activity in normal and psoriatic keratinocytes and developed stable 20HE-loaded niosomes intended for potential future dermal delivery. Methods: The biological activity of 20HE was assessed in human epidermal keratinocytes (HEKs) and psoriasis-patient-derived keratinocytes (PHEKs) after 48 h of treatment by quantifying selected cytokines. Niosomes were prepared by thin-film hydration, rehydrated with water or citrate buffer, and sonicated. The formulations were characterized for particle size, polydispersity index, zeta potential, pH, encapsulation efficiency (EE), and 21-day storage stability. Potential in vivo toxicity was assessed in Danio rerio embryos by monitoring mortality, sublethal developmental changes, and locomotor behavior after exposure to nanoformulations for up to 96 h post-fertilization. Results: 20HE showed selective anti-inflammatory activity in PHEK cells, reducing IL-4, IL-17A, and IL-22 levels by 20–34% under elevated inflammatory conditions, without affecting healthy HEK cells. The formulations had particle sizes below 300 nm and acceptable polydispersity and zeta potential values, and they remained stable during storage. In the Danio rerio embryo model, the 1A/water caused sublethal developmental abnormalities at 96 hpf, whereas 1C/water (with 20HE) was associated only with mild pericardial edema after prolonged exposure. No significant behavioral alterations were observed across the tested concentration range, and the Lowest Observed Effect Concentration for 20HE was 20 μM. Conclusions: Free 20HE reduced the levels of IL-4, IL-17A, and IL-22 in PHEK cells, indicating its modulatory effect on cytokine production under the investigated inflammatory conditions. The developed 20HE-loaded niosomes showed favorable physicochemical properties and short-term stability, supporting their potential as candidate nanocarrier systems for future dermal application studies. The findings of the present study provide a basis for further investigation, particularly studies on drug release from the niosomal formulation and skin permeation from the final pharmaceutical dosage form.

Gynecological malignancies and breast cancer impose substantial health and economic burdens. This review examines how local and systemic microbiota may affect epithelial integrity, inflammation, estrogen metabolism, and immunity. The vaginal ecosystem is the most extensively studied female microbial niche. Cervical cancer serves as the most illustrative clinical example: loss of stable Lactobacillus crispatus dominance and increased prevalence of anaerobic bacteria (anaerobic dysbiosis) are associated with persistent HPV infection, which directly elevates the risk of cervical precancerous lesions. The estrobolome is particularly relevant in endometrial cancer, where intestinal bacterial beta-glucuronidase activity may increase estrogen reabsorption, particularly in obesity and metabolic disease. In ovarian cancer, microbiota is being studied as a possible risk modifier in BRCA1 carriers, but the evidence remains exploratory. In breast cancer, intratumoral bacteria may shape the immune microenvironment, particularly in triple-negative disease. The primary limitation of current research is methodological heterogeneity. Low-biomass samples, such as those from the ovary or endometrium, are highly susceptible to technical contamination. Most studies are cross-sectional and cannot establish causality. Current evidence supports microbiota as a modifier, not a standalone marker or a substitute for standard diagnosis and treatment. Its most plausible near-term role is in multiparameter risk or response models, pending standardized prospective validation.

Background/Objectives: Psoriasis is a chronic, immune-mediated inflammatory skin disorder affecting millions of individuals worldwide. It remains a therapeutic challenge due to the limited skin penetration of many drugs, adverse systemic effects, and the need for long-term management. Transferosomal nanoformulations containing natural products were proposed as a potential therapeutic tool. Methods: Transferosomes containing 20-hydroxyecdysone and resveratrol were prepared using the thin-film hydration method followed by probe ultrasonication, generating several formulation variants differing in composition. The vesicles were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) to determine size, polydispersity index (PDI), and zeta potential. Furthermore, time-domain nuclear magnetic resonance (TD-NMR) relaxation measurements were employed to evaluate local molecular dynamics and membrane fluidity, providing deeper insights into the structural integrity and elasticity of the transferosomal systems. The stability of the nanoformulations was assessed for one month in water and phosphate-buffered saline (PBS). Viability was evaluated in vitro using the MTS assay on human epidermal keratinocyte (HEK) and psoriasis-patient derived human epidermal keratinocyte (PHEK) cell lines, alongside antimicrobial profiling against four representative human skin microbiome strains. Acute toxicity was further examined in vivo using the Danio rerio FET test. Results: The formulations demonstrated high physicochemical stability over the tested period, maintained desirable particle sizes within 100–200 nm, and showed no cytotoxicity toward skin-associated bacteria or in the zebrafish model. Conclusions: The developed nanoformulations present suitable properties in terms of safety and stability and can be considered for potential use in psoriasis treatment.

Background: Human papillomavirus (HPV)-related diseases remain a major global health problem, with cervical intraepithelial neoplasia (CIN) representing a key precursor to cervical cancer. Identification of high-risk HPV genotypes is essential for early diagnosis and appropriate management. This study aimed to evaluate the usefulness of in situ hybridization (ISH) for detecting HPV DNA in formalin-fixed, paraffin-embedded (FFPE) cervical tissue and to compare automated signal detection with manual histopathological assessment. Methods: This prospective, non-randomized study included 83 women undergoing diagnostic procedures for abnormal cytology or confirmed CIN between 2022 and 2023. Tissue specimens obtained during a loop electrosurgical excision procedure (LEEP) were examined using two ISH probes: ISH II for low-risk HPV types 6 and 11, and ISH III for high-risk HPV genotypes. Staining patterns and distributions were evaluated and correlated with molecular HPV testing and histopathological outcomes. Results: ISH II distribution was significantly associated with the presence of HPV type 6 or 11 (p < 0.001), although stain structure itself was not. ISH III stain structure was significantly associated with high-risk HPV genotypes (p = 0.020). A positive ISH II result predicted low-risk HPV infection with a sensitivity of 62.5% and specificity of 64.0%, while ISH III predicted high-risk HPV infection with a sensitivity of 86.36% but lower specificity (23.53%). Overall diagnostic accuracy was 63.86% for ISH II and 73.49% for ISH III. Conclusions: ISH proved to be a reproducible method for detecting HPV in archived cervical tissue, enabling assessment even years after specimen collection. Although PCR-based methods remain more widely used due to higher sensitivity and less invasive sampling, ISH provides valuable morphological context and may serve as a complementary diagnostic tool, particularly when only archival tissue is available.

Vitamin D plays a key role in pregnancy beyond calcium–phosphate regulation, modulating immune responses and glucose metabolism via the vitamin D receptor (VDR). Placental expression may be altered in gestational diabetes mellitus (GDM). This study aimed to assess placental VDR expression in GDM and evaluate its association with maternal vitamin D levels and clinical parameters. VDR expression in the placental tissue of 53 women with GDM and 26 healthy controls was assessed semi-quantitatively by immunohistochemistry. Maternal serum 25-hydroxyvitamin D (25(OH)D) levels, body mass index, weight gain, neonatal outcomes, and other variables were evaluated. Univariate and multivariate linear regression analyses were performed. VDR expression was significantly higher in the GDM group compared to controls (p = 0.0297 for mean, p = 0.0378 for median). No significant differences were observed in serum 25(OH)D concentrations between groups. Stepwise regression revealed that diabetes was the only independent predictor of VDR expression. Within the GDM subgroup, VDR expression was not associated with any clinical parameters, including maternal vitamin D status. Upregulated placental VDR in GDM may represent an adaptive response to metabolic stress. These findings suggest complex regulation of vitamin D signalling in diabetic pregnancies, warranting further investigation.

Uterine fibroids are benign tumors that occur in a large proportion of women and interfere with the proper functioning of this organ. One of the factors leading to these proliferative changes appears to be the appearance of extracellular matrix (ECM) fibrosis at the site of local inflammatory foci. Due to the potential impact of cytokines in this process, it is interesting to determine their expression levels in fibroids and surrounding tissues, which may contribute to a better understanding of the mechanisms leading to the formation of these tumors. In tissue material from 50 women with uterine fibroids who underwent hysterectomy and 45 women operated on for other reasons (most often prolapse of the reproductive organ), the concentration of inflammatory cytokines IL-1β and IL-6 and the concentration of the transcription nuclear factor NF-κβ were determined. The tissue from the fibroid, the peripheral myometrium, and the unchanged myometrium were examined in women who underwent surgery for reasons other than uterine fibroids. A significant decrease in IL-1β levels was observed in the center of the fibroid compared to both peripheral and control muscle tissue (p=0.001). The concentrations of IL-6 were found to be similar across all three locations examined. The NF-κβ levels were significantly lower in the fibroid and peripheral tissues (p<0.001) compared to the control group. The concentration of IL-1β was found to be significantly and positively correlated with the concentration of NF-κβ in uterine fibroids.

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the paranasal sinuses with a yet unknown etiology. As studies continue to elucidate the disease’s heterogeneity inflammatory profile and presentation, there is a growing interest in the influence of the nasal microbiome on disease pathogenesis and chronicity. The sinus microbiota appear dominated by the Staphylococcus and Corynebacterium genera; known upper airway pathogens, such as Haemophilus influenza, are present in the upper airways of healthy individuals, though at relatively lower abundances than in CRS patients. Viral culprits may induce an unhindered local immune response that contributes to the recurrence and chronicity of inverted papillomas—benign mucosal lesions with the propensity for local destruction and malignant transformation that can be found in patients with a history of nasal infection. The persistence of inverted papillomas warrants investigation into their pathogenesis and how they may contribute to a nasal landscape promoting the chronicity of CRS. Further investigation is needed to uncover the interplay between resident microbiota and viral, fungal, and immunological influence. Discerning between ‘healthy’ and ‘diseased’ sinonasal microbiomes and ‘keystone’ species could shed light on CRS etiology and provide the opportunity for CRS treatment tailored to an individual’s microbiome. This review aims to explore the interrelation of microbial residents in the pathogenesis and chronicity of the diseased sinonasal environment.

Background: Cervical cancer is fourth the most common cancer in women worldwide. Due to the prevalence of human papillomavirus (HPV) in the population (80–90%), scientists are likely to discover even more associations of this pathogen with other diseases in the future. In recent years, In Situ Hybridization (ISH) assays that use automated signal-detecting methods in formalin-fixed, paraffin-embedded (FFPE) cervical tissue, such as the enzyme-categorized signal-detecting system, have shown a higher sensitivity. Objectives and Methods: To evaluate automatic signal detection of ISH assay for detecting HPV DNA, we compared the ability of an ISH probe, Inform HPV II and III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with cervical intraepithelial neoplasia (CIN; CIN 1, 28 cases; CIN 2, 22 cases; and CIN 3, 20 cases) and normal cervix (2 cases). Results: Our findings showed a significant relation was confirmed between ISH III level and HPV outcome (positive/negative). Patients with positive HPV outcomes had significantly lower ISH III levels, MD = −7961.82 CI₉₅ [−17,230.00; −199.21], p = 0.005. Conclusions: Automatic signal detection of ISH assay is not particularly applicable to cervical tissue material. A more useful method of confirming the presence of HPV in the cervix is the HPV test with genotyping, as it allows for collecting a larger amount of material from the cervical disc and canal. The interpretation of a positive or negative ISH test must be guided in the context of clinical history and morphology.