Background/Objectives: Cervical cancer remains a significant global health issue, with high incidence and mortality rates, particularly in Eastern Europe. Despite the availability of vaccines against human papillomavirus (HPV), regular screening remains crucial for prevention. Testing for HPV, alone or combined with cytology, has become an alternative to traditional methods. However, since many HPV infections are transient, additional tests are needed to identify high-risk cases. Methods: This study aims to generate detailed statistical data specific to the Bulgarian population, reinforcing the necessity of incorporating updated European methodologies and algorithms for the prophylaxis and prevention of cervical carcinoma. Results: By evaluating epidemiological trends, risk factors, and the effectiveness of current preventive measures, this research seeks to provide a strong foundation for enhancing cervical cancer screening and early detection programs. This method improves triage by identifying women who require further evaluation, ensuring timely referrals for colposcopy or biopsy. Conclusions: While liquid-based cytology (LBC) and HPV genotyping improve detection, the introduction of p16/Ki-67 dual staining has enhanced risk stratification, offering higher sensitivity and specificity for detecting high-grade lesions. These advancements are improving cervical cancer screening and patient outcomes.

Recently, compounds of plant origin have been the focus of increased scientific interest. Micromeria frivaldszkyana is a rare species endemic to Bulgaria, whose biological activity remains unknown. This article aims to evaluate the subchronic toxicity of Micromeria frivaldszkyana methanolic extract and its effect on cognition in rats. Following 90 days of oral administration, a histopathological evaluation of brain, kidney, and liver tissues was conducted. Additionally, serum levels of total bilirubin (TB), conjugated bilirubin (CB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CR), uric acid (UA), and urea (U) were measured. Cognitive function was studied after 7 d of treatment using activity cage test, along with tests for active memory, passive memory, anxiety, spatial and working memory, and explorative activity. The experiments showed no toxic effects of the extract in subchronic application. No adverse effects on brain function were observed after 14 days of treatment. While the extract increased the motor activity of the animals, it did not significantly improve the learning and memory processes. In conclusion, the methanolic extract of Micromeria frivaldszkyana in doses 250 and 500 mg/kg bw did not induce toxicity after 90-day treatment in rats. These doses did not significantly affect central nervous system (CNS) functions, although increased motor activity was observed after 14 days of treatment with the extract.

Acetaminophen (APAP) overdose can result in potentially fatal acute liver failure, with free radical formation identified as a major mechanism of liver tissue damage. Micromeria frivaldszkyana (M. frivaldszkyana), a rare species endemic to Bulgaria, has demonstrated significant antioxidant activity. Male Wistar rats were treated orally for 7 days with saline; 250, 400, or 500 mg/kg of a water solution of dried methanolic extract of M. frivaldszkyana; 100 mg/kg rosmarinic acid (RA); or 125 mg/kg silymarin. Liver toxicity was induced by oral application of 2000 mg/kg APAP on the last day of treatment. Forty-eight hours later, blood and livers were collected for histological and biochemical analysis. The results revealed that treatment with 500 mg/kg of the dried methanolic extract significantly reduced the elevated levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and tumor necrosis factor-alpha in APAP overdose. The present results clearly demonstrate, for the first time, that pre-treatment with methanolic extract of M. frivaldszkyana results in significant hepatoprotective effects in the APAP-induced rat model of liver injury. The mechanism of this effect may involve cell membrane protection, decreased lipid peroxidation and DNA damage, and attenuation of aseptic inflammation. These effects can be attributed to the main compounds identified in the extract (linarin, chlorogenic acid, rutin, eupatorin, apigenin, RA).

Chronic inflammation (CI), a common finding in the human prostate, is associated with the most frequent socially important prostate diseases: prostatitis, benign prostatic hyperplasia, and prostate adenocarcinoma. Programmed cell death protein 1 (PD-1) and its ligand (PD-L1) expression are induced on the surface of immune and epithelial cells of healthy and tumor tissues in response to various cytokines. Here, we provide a comprehensive review of the PD-1/PD-L1 pathway in the non- and peri-tumoral inflammatory prostate, focusing on the structure and expression of PD-L1 and the diverse biological functions of PD-L1 signaling in health, high-grade CI (National Institutes of Health, category IV prostatitis or histologic prostatitis), and immune-related diseases, including autoimmunity, tumor microenvironmental immunity, and immune privilege. This review explores the possible pathophysiological interpretations of clearly visible, selective, and strong PD-L1 expression in the immuno-inflammatory-induced and related, histologically distinct sites of this expression: the ductal lymphoepithelial lesions and prostatic granulomas.

Background/Objectives: For successful wound management, dressings must be maintained in a moist environment to optimally enhance the microenvironment of the wound and efficiently deliver bioactive agents. Sodium humate has demonstrated potential wound-healing activity, although its topical delivery is still a challenge. This study aimed to develop and optimize polysaccharide-based dermal patches incorporating sodium-humate-loaded transferosomes and to assess their physicochemical and wound-healing properties. Methods: Transferosomes were obtained via thin-film hydration and prepared utilizing the Taguchi experimental design based on the impact of lipid content, lipid-to-surfactant ratio, and lipid-to-drug ratio on vesicle size, ζ-potential, and drug entrapment efficiency. The optimized transferosomes were loaded into alginate/HPMC composite dermal patches prepared through solvent evaporation. Results: The optimized transferosome formulation had an average size of 250.9 ± 2.3 nm, a ζ-potential of −3.57 ± 0.25, a high deformability of 93.01 ± 2.41%, and an effective drug-entrapment efficiency of 30.13 ± 1.04%. The use of transferosomes greatly affected patch thickness, moisture content, and surface morphology. A biphasic drug release profile of sodium humate was demonstrated via an in vitro release study, showing an initial burst followed by sustained drug release within 6 h. In vivo evaluation of transferosome-loaded patches showed that the formulations were able to effectively promote wound healing compared with the control. Conclusions: The developed transferosome-embedded alginate/HPMC dermal patches constitute a promising platform for the controlled topical administration of sodium humate and show promising enhancement of wound healing.