Exploring the inhibitory impact of Mongolian medicinal He-Zi-3 soup on mammary gland hyperplasia in rats induced by estrogen and progestogen.

ETHNOPHARMACOLOGICAL RELEVANCE: Mammary gland hyperplasia, a prevalent benign breast condition, often serves as a precursor to various other breast diseases. He-Zi-3 soup (HZ-3), a traditional Mongolian remedy, is utilized for treating this condition. AIM OF THE STUDY: To explore the effect and underlying mechanism of HZ-3, a Mongolian medicinal preparation, on mammary gland hyperplasia. MATERIALS AND METHODS: This study aimed to assess the impact of different doses of HZ-3 in a rat model of mammary hyperplasia. The active components within HZ-3 drug serum were identified and analyzed through network pharmacology and target prediction. To elucidate the underlying mechanism of HZ-3 in addressing mammary hyperplasia, we conducted a series of investigations on estradiol-induced mammary hyperplasia in model rates. Assessments included measurements of papilla width and height, hematoxylin and eosin staining, Masson staining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry. RESULTS: Our investigation revealed the identification of 21 compounds, primarily terpenoids, through serum medicinal chemistry screening. Utilizing network pharmacological analysis, we observed predominant regulation through the estrogen pathway, closely associated with key genes including esr1,esr2, ncoa1, krt 19, ctsd, ebag 9, and bcl-2. Assessments encompassing nipple height and width, histological examination, immunohistochemical analysis, and serum hormone levels via enzyme-linked immunosorbent assay demonstrated the inhibitory effect of HZ-3 on mammary hyperplasia in rat models. RT-qPCR and Western blot analyses corroborated these findings, affirming the suppression of mammary hyperplasia by HZ-3 through the activation of estrogen pathway signaling.

Deoxynivalenol Damages Corneal Epithelial Cells and Exacerbates Inflammatory Response in Fungal Keratitis.

BACKGROUND: Fungal keratitis (FK) is a kind of infectious keratopathy with a high rate of blindness worldwide. Deoxynivalenol (DON) has been proven to have multiple toxic effects on humans and animals. OBJECTIVES: The aim of this study was to explore a possible pathogenic role of DON in FK. METHODS: We first made an animal model of FK in New Zealand white rabbits, and then attempted to detect DON in a culture medium in which Fusarium solani had been grown and also in the corneal tissue of the animal model of Fusarium solani keratitis. Next, a model of DON damage in human corneal epithelial cells (HCECs) was constructed to evaluate effects of DON on the activity, migration ability, cell cycle, and apoptosis in the HCECs. Then, putative the toxic damaging effects of DON on rabbit corneal epithelial cells and the impact of the repair cycle were studied. The expression levels of inflammatory factors in the corneas of the animal model and in the model of DON-damaged HCECs were measured. RESULTS: The Fusarium solani strain used in this study appeared to have the potential to produce DON, since DON was detected in the corneal tissue of rabbits which had been inoculated with this Fusarium solani strain. DON was found to alter the morphology of HCECs, to reduce the activity and to inhibit the proliferation and migration of HCECs. DON also induced the apoptosis and S-phase arrest of HCECs. In addition, DON was found to damage rabbit corneal epithelial cells, to prolong the corneal epithelial regeneration cycle, and to be associated with the upregulated expression of inflammatory factors in HCECs and rabbit corneas. CONCLUSIONS: DON appears to have a toxic damaging effect on HCECs in FK, and to induce the expression of inflammatory factors, leading to the exacerbation of keratitis and the formation of new blood vessels. Future studies will explore the possibility of developing a test to detect DON in ophthalmic settings to aid the rapid diagnosis of FK, and to develop DON neutralizers and adsorbents which have the potential to improve keratocyte status, inhibit apoptosis, and alleviate inflammation, therein providing new thinking for therapy of clinical FK.

Effect of human umbilical cord mesenchymal stem cell exosomes on aerobic metabolism of human retinal pigment epithelial cells.

PURPOSE: To investigate the effect of exosomes secreted by human umbilical cord mesenchymal stem cells (HUCMSC-Exo) on aerobic metabolism of cobalt chloride (CoCl2)-induced oxidative damage in the human retinal pigment epithelial cell line (ARPE-19), and to explore the protective mechanism of HUCMSC-Exo on oxidative damage in ARPE-19 cells. METHODS: HUCMSC-Exo were extracted and identified; CCK-8 assay was used to established the oxidative damage mode of ARPE-19 cells induced by CoCl2; JC-1 flow cytometry was used to detect the effects of exosomes with different concentrations (0, 25, 50, or 100 µg/mL) on the mitochondrial membrane potential (MMP) of oxidatively damaged ARPE-19 cells. The effects of exosomes with different concentrations on the activity of oxidative metabolic enzymes (oxidative respiratory chain complexes I, III, IV, and V) and ATP synthesis in oxidatively damaged ARPE-19 cells were detected by spectrophotometry. RESULTS: Under transmission electron microscope, HUCMSC-Exo were round or oval membrane vesicles with diameters of about 40-100 nm. Western blot results showed that HUCMSC-Exo expressed specific marker proteins CD63 and CD81. CCK-8 dates showed that the cell viability of ARPE-19 cells was significantly decreased with increasing CoCl2 concentration, and the concentration of 400 µmol/L CoCl2 was chosen to be the optimal concentration for oxidative damage. MMP was increased in exosomes intervention group (25, 50 or 100 µg/mL), and the dates were statistically different from 0 µg/mL exosome intervention group (P < 0.05). The activities of mitochondrial complexes I, IV, and V in exosomes intervention groups (100 µg/mL) were higher than those in 0 µg/mL exosome intervention group. In 50 µg/mL and 100 µg/mL exosome intervention group, ATP synthesis was significantly different from the 0 µg/mL exosome intervention group (P < 0.05). CONCLUSION: HUCMSC-Exo had a certain protective effect on ARPE-19 cells induced by CoCl2 in vitro. The protective mechanism of HUCMSC-Exo on oxidative damage ARPE-19 cells might be through saving its aerobic metabolic function, restoring cell ATP synthesis, and improving the ability of cells to repair damage and deal with the hypoxic environment.