Journal of Molecular Pathology

Objectives: This study evaluated the impact of combining icariin with a bovine xenograft on the enhancement of early socket healing in Wistar rats. Methods: Male Wistar rats underwent incisive extraction and were randomized into three groups (n = 8/group): (1) control, (2) xenograft, and (3) icariin–xenograft. On days 7 and 14, the animals were decapitated and their mandibles were examined. Histological analysis was conducted to assess the collagen matrix and the expression of BMP-2 and HIF-1α. Results: The icariin–xenograft group exhibited superior outcomes compared to the xenograft-alone and control groups. Histological analysis showed an earlier arrangement of connective tissue and an improved collagen matrix outcome in the icariin-treated sockets. Immunohistochemistry revealed elevated BMP-2 and HIF-1α expression in the icariin–xenograft group, indicating enhanced osteogenic and angiogenic signaling. Conclusions: Icariin-enhanced xenografts speed up the repair of early extraction sockets by enhancing the development of the collagen matrix and increasing the activity of pathways that promote osteogenesis and angiogenesis in low-oxygen conditions. This bioactive grafting technology appears to be a cost-effective method for preserving sockets and performing regenerative therapy in dentistry.

Background: Differentiating atypical endometrial hyperplasia, also known as endometrial intraepithelial neoplasia (EAH/EIN) from endometrial hyperplasia without atypia is crucial due to the higher risk of progression to endometrioid adenocarcinoma, associated with atypical lesions. Immunohistochemical markers such as PAX2 and PTEN have emerged as potential adjuncts to improve diagnostic accuracy in morphologically challenging cases. Objective: To evaluate the diagnostic value of PAX2 and PTEN expression in distinguishing atypical from endometrial hyperplasia without atypia in the Bulgarian population. Materials and Methods: A total of 96 endometrial hyperplasia cases (48 typical, 48 atypical) were included. Histopathological evaluation was performed on hematoxylin and eosin–stained sections, with two experienced pathologists confirming diagnoses according to the WHO criteria. Immunohistochemical analysis of PTEN and PAX2 was conducted on formalin-fixed, paraffin-embedded tissue sections. Results: PTEN expression loss was observed in 6% (3/48) of hyperplasia without atypia cases, compared with 81.3% (38/48) of EAH/EIN cases. For PAX2, strong nuclear staining was retained in 60% (29/48) of endometrial hyperplasia without atypia cases, with no complete loss of expression. In contrast, 64.6% (31/48) of EAH/EIN cases showed complete loss of PAX2 expression, while only 35.4% (17/48) preserved nuclear immunoreactivity. Together, these results highlight clear and consistent differences in PTEN and PAX2 expression between hyperplasia without atypia and EAH/EIN and may aid pathologists in distinguishing these two entities in routine diagnostic practice. Conclusions: Expression loss of PAX2 and PTEN is significantly associated with EAH/EIN. Immunohistochemical evaluation of these markers provides valuable adjunctive information for the diagnosis of morphologically ambiguous cases and may enhance diagnostic reproducibility and accuracy. Incorporating PAX2 and PTEN into routine assessment may guide appropriate clinical management and risk stratification of patients with endometrial hyperplasia.

The human microbiome is often presented as “the next genetics,” with the expectation that microbial profiles will explain complex diseases and yield new therapies. Yet for most conditions, it remains unclear whether microbiome changes act as causal drivers or primarily mirror underlying host biology and pathology. In this narrative review, we argue that microbiome causality is frequently overstated relative to the roles of host genetics and the environment, and we explore the implications for molecular pathology. We outline a simple framework in which the microbiome can act as (i) a primary driver, (ii) a conditional mediator or effect modifier or (iii) an association biomarker that mainly reflects upstream processes. We then use marital and household studies as natural experiments to test whether chronic diseases track more strongly with a shared microbiome or with a shared lifestyle and host susceptibility. Across metabolic, inflammatory, neurodegenerative and ageing-related outcomes, spouses show only low to modest disease concordance, which is difficult to reconcile with a universally strong, transmissible microbiome causality. Adult microbiomes instead appear mostly host-constrained and context-dependent, acting more as destabilisers of homeostasis and amplifiers of allostatic load than as independent disease-causing factors. For molecular pathology, this suggests that microbiome features are often most informative as biomarkers integrated alongside host genomics, immune context and histopathology, rather than as standalone targets. Study designs and diagnostic workflows should therefore jointly model the host genome, environment, behaviour and microbiome within broader systems medicine frameworks.