Doymus-Yilmaz, Meryem; Aksit, Huseyin; Taskin, Mesut

This study focused on biological activities and chemical characterization of secondary metabolites from the fungus Talaromyces annesophieae MD2 (GenBank: PQ252671). The dichloromethane extract (DCM-E) of its culture supernatant was fractionated using chromatographic techniques. Initially, three main fractions were first prepared from DCM-E. Subsequently, the selected active fraction 2 was subfractionated into six subfractions. The subfraction 3 demonstrated high water solubility and strong antibacterial activity against both gram-positive and gram-negative bacteria (MIC values of 105.41, 82.76, 71.92, and 70.38 µg/mL against B. cereus, S. aureus, E. coli, and K. pneumoniae, respectively). It exhibited selective anticancer activity through regulation of autophagy- and apoptosis-related pathways without affecting healthy cells (IC50 values of 7.65, 3.76, 10.76 µg/mL against HT-29, DU-145 and SH-SY5Y, respectively). Furthermore, it exhibited DPPH and ABTS radical-scavenging activities (48.3% and 44.1% at the concentration of 100 μg/mL, respectively) and protected dermal fibroblasts against H2O2–induced toxicity. Structural analyses elucidated that the subfraction 3 contained four nitrogenous polar compounds. Three compounds (C5H3O4N8, C15H25O4N4, and C23H21N4) were suggested to be alkaloid-like or nitrogen-rich heterocyclic secondary metabolites, while the remaining compound (C9H9O4N) was probably an aminobenzoic acid-type or heteroaromatic carboxylic acid derivative. This is the first report on bioactive metabolites of T. annesophieae. Due to multifunctional biological activities, its metabolites can find application in dermocosmetics and pharmacology.

Ucar, Mahmut; Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Guler, Mustafa Can; Tanyeli, Ayhan; Kılıclıoglu, Metin; Yılmaz, Ahmet; Yıldırım, Serkan

Vaginal microbiota is essential for mucosal immunity, pathogen defense, and homeostasis. Disruption of this balance can promote opportunistic infections, notably by Candida albicans. This study investigates the therapeutic potential of Morus alba (MA) extract and Lactobacillus rhamnosus (LR) in a rat model exposed to Candida albicans exosomes (CAE). CAE induced a 1.3–5.1-fold upregulation in SAP1–10 gene expression, with SAP4 showing the highest increase (p ≤ 0.05). MA and LR monotherapies selectively suppressed SAP6 (41%) and SAP4 (23%), respectively. Notably, combination therapy (CAE+MA+LR) synergistically inhibited all SAP genes (0.8–1.1-fold, p ≤ 0.05). 16S rRNA analysis showed that LR-containing groups maintained Lactobacillales abundance (37.77%–38.7%), while MA reduced Mycobacteriales by 68.5% (p = 0.004). Microbial diversity was lower in the MA group (H = 3.242) but higher in LR groups (H = 5.493–5.598). Histopathology revealed severe ovarian inflammation in the CAE group (87.4%, p = 0.0022) with a 4.2-fold increase in IL-6, while combination therapy reduced inflammation and IL-6 levels by 60%–72% (p ≤ 0.05). Immunofluorescence confirmed downregulation of TLR4 and Caspase-3 with treatment. FIB-SEM and NTA analyses showed that CAE exosomes had a heterogeneous morphology (99.3 ± 31.1 nm) and high polydispersity (PDI = 0.31). These results suggest that MA and LR synergistically reduce fungal virulence, restore microbial balance, and offer a promising adjuvant strategy against vaginal candidiasis.