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Abstract Background Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. Methods A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy. Results A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury. Conclusions Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients. Graphical abstract

Acupuncture is widely used to improve ovarian function. Previously, we demonstrated that acupuncture can improve oxidative stress in rats with tripterygium glycoside tablet suspension (TG)-induced diminished ovarian reserve (DOR). Herein, we aimed to explore the antioxidation mechanism of acupuncture for ameliorating the ovarian reserve in DOR rats. We performed microRNA sequencing and bioinformatics analysis to screen differentially expressed miRNAs (DE miRNAs) in ovarian tissues. In total, 1,172 miRNAs were identified by miRNA sequencing, of which 28 DE miRNAs were detected (including 14 upregulated and 14 downregulated) in ovarian tissues from the acupuncture group when compared with the DOR model rats. Based on functional enrichment analysis, the target genes of DE miRNAs were significantly enriched in GO-biological process (BP) terms associated with biological processes, positive regulation of transcription by RNA polymerase II, signal transduction, regulation of transcription, DNA-templated processes, and oxidation–reduction processes. In the Kyoto Encyclopedia of Genes and Genomes analysis, the main pathways were the MAPK signaling pathway, hepatitis B, proteoglycans in cancer, human cytomegalovirus infection, and the Ras signaling pathway. Finally, reverse transcription-quantitative PCR results confirmed that rno-miR-92b-3p, mdo-miR-26b-5p_R+1_1ss10TC, and bta-miR-7857-3p_R-1 were downregulated in the acupuncture group. The results revealed the impact of acupuncture on miRNA profiling of ovarian tissues from DOR rats, suggesting that rno-miR-92b-3p, mdo-miR-26b-5p_R+1_1ss10TC, and bta-miR-7857-3p_R-1 might provide relevant cues to relieve DOR-mediated oxidative stress.

BACKGROUND: Oral care may decrease the development of ventilator-associated pneumonia (VAP) and improve oral hygiene. However, little evidence is available to guide the development of oral care protocols. The practical effect of toothbrushing on VAP development and oral health and hygiene improvement is inconclusive. PURPOSE: This study evaluated the effects in postneurosurgical, intensive care unit patients of brushing teeth twice daily with purified water on VAP rates and oral health or hygiene. METHODS: This study conducted a randomized controlled pilot trial. Patients consecutively admitted to the surgical intensive care unit at a suburban hospital in 2007 were invited to participate if they met two inclusion criteria: (a) under ventilator support for at least 48 to 72 hours and (b) no current pneumonia. Upon obtaining informed consent, subjects were randomized into experimental and control groups. Both groups received usual hospital care, that is, daily oral care using cotton swabs. The experimental group additionally received a twice-daily oral care protocol of toothbrushing with purified water, elevating the head of the bed, and before-and-after hypopharyngeal suctioning. The control group also received twice-daily mock oral care (elevating the head of the bed, moisturizing the lips, and before-and-after hypopharyngeal suctioning). VAP was defined by a clinical pulmonary infection score of > 6. Oral hygiene and health was assessed after conclusion of the intervention. RESULTS: Patients (N = 53) were predominantly male (64.2%), mean age was 60.6 years old, and most had received emergency surgery (75.5%). After 7 days of toothbrushing with purified water, cumulative VAP rates were significantly lower in the experimental (17%) than in the control (71%; p <.05) group. The experimental group also had significantly better scores for oral health (p <.05) and plaque index (p <.01). CONCLUSION/IMPLICATION FOR PRACTICE: Findings suggest that, as an inexpensive alternative to existing protocols, toothbrushing twice daily with purified water reduces VAP and improves oral health and hygiene. [ABSTRACT FROM AUTHOR]