Systemic antibiotics increase microbiota pathogenicity and oral bone loss / 国际口腔科学杂志·英文版

Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.

Mismatch repair gene germline mutations in patients with prostate cancer / 浙江大学学报·医学版

OBJECTIVES@#To investigate the prevalence of pathogenic germline mutations of mismatch repair (MMR) genes in prostate cancer patients and its relationship with clinicopathological characteristics.@*METHODS@#Germline sequencing data of 855 prostate cancer patients admitted in Fudan University Shanghai Cancer Center from 2018 to 2022 were retrospectively analyzed. The pathogenicity of mutations was assessed according to the American College of Medical Genetics and Genomics (ACMG) standard guideline, Clinvar and Intervar databases. The clinicopathological characteristics and responses to castration treatment were compared among patients with MMR gene mutation (MMR+ group), patients with DNA damage repair (DDR) gene germline pathogenic mutation without MMR gene (DDR+MMR－ group) and patients without DDR gene germline pathogenic mutation (DDR－ group).@*RESULTS@#Thirteen (1.52%) MMR+ patients were identified in 855 prostate cancer patients, including 1 case with MLH1 gene mutation, 6 cases with MSH2 gene mutation, 4 cases with MSH6 gene mutation and 2 cases with PMS2 gene mutation. 105 (11.9%) patients were identified as DDR gene positive (except MMR gene), and 737 (86.2%) patients were DDR gene negative. Compared with DDR－ group, MMR+ group had lower age of onset (P<0.05) and initial prostate-specific antigen (PSA) (P<0.01), while no significant differences were found between the two groups in Gleason score and TMN staging (both P>0.05). The median time to castration resistance was 8 months (95%CI: 6 months-not achieved), 16 months (95%CI: 12-32 months) and 24 months (95%CI: 21-27 months) for MMR+ group, DDR+MMR－ group and DDR－ group, respectively. The time to castration resistance in MMR+ group was significantly shorter than that in DDR+MMR－ group and DDR－ group (both P<0.01), while there was no significant difference between DDR+MMR－ group and DDR－ group (P>0.05).@*CONCLUSIONS@#MMR gene mutation testing is recommended for prostate cancer patients with early onset, low initial PSA, metastasis or early resistance to castration therapy.

Regulation of angiogenesis by Notch signaling / 中国组织工程研究

BACKGROUND:The Notch signaling pathway is evolutionarily highly conserved and mediated by cel-cel interactions, which is widely involved in cel differentiation, proliferation and apoptosis. This critical transduction system participates in coordinating various functions of vascular endothelial cels, thus playing a vital role in the formation and remodeling of vascular network. OBJECTIVE: To elucidate the components of Notch signaling pathway and its impact on angiogenesis. METHODS: A computer-based online search of PubMed and CBM databases was performed. High-quality articles related to mechanism of angiogenesis regulated by Notch signaling were included, and repetitive studies were excluded. RESULTS AND CONCLUSION:Totaly 31 literatures were selectively included in this review. Angiogenesis is a complicated and muti-stage biological event and has been delicately regulated. Notch signaling participates in the regulation of every stage of angiogenesis directly or indirectly via the crosstalk with vascular endothelial growth factor, BMP-SMAD signaling and extracelular matrix molecules. Furthermore, consistent output of Notch signaling is essential for maintaining the stability and integrity of adult vascular system. This review wil thoroughly clarify the latest progress on angiogenesis regulated by Notch signaling and provide theoretical basis and a potential target for designing therapeutic methods against vascular disease.

The immunohistochemical analysis of AGEs, SP-A in the lung of diabetic rats / 中国医师杂志

Objective To approach the changes of advanced glycosylated end products (AGEs),surfactant proteins A (SP-A) in the lung of experimental diabetic rats and their relationship. Methods 48 male SD rats were divided into diabetes mellitus (DM) group and control group, each group with 24 rats.The DM rat model was made by injecting streptozocin (60mg/kg) into caudal vein. The rats were killed and the lung was individually taken out at the end of 4, 12 and 20 weeks after the models were established. The changes of AGEs, SP-A in rats lung were observed with immunohistochemical assay and the images were analyzed( black is minimum of gray, white is maximum of gray ). Results We observed a great quantity of AGEs positive cells in the alveolar epithelial cells, bronchial mucosal epithelium, angio-endothelial cell and smooth muscle cells of the DM rats. The average gray (AG) was inferior to that of the controls(4weeks 93.92 ± 7.92 vs 104. 75 ± 8. 20; 12 weeks 76. 25 ± 6. 76 vs 93.50 ± 7.56; 20 weeks 47.63 ± 7.96 vs 142. 38 ± 19. 76; P ＜0. 05) and decreased with the DM course. In the 4 weeks DM rats, there were a few SP-A positive cells in the type Ⅱ alveolar epithelial cells, Clara cells and alveolar macrophage cells. In the 12 and 20 weeks DM rats, there were a great many CTGF and TGF-β1 positive cells. The AG was inferior to that of the controls( 12 weeks 75.63 ± 6. 70 vs 110. 50 ± 13.20;20 weeks 47.38 ± 4. 84 vs 97. 25 ± 9. 87; P ＜ 0. 01 ). Conclusion With the progress of diabetes, DM rats' pulmonary alveolar type Ⅱ cells injury appeared, that might be related with the deposition of AGEs.