Wenjing Wang

BACKGROUND: Tumor-associated macrophages (TAMs) are classified into two major phenotypes, M1 and M2. M1 TAMs suppress cancer progression, while M2 TAMs promote it. However, little is known regarding the role of TAMs in the development of ovarian cancer. Here, we investigated the relationship between TAM distribution patterns (density, microlocalization, and differentiation) and ovarian cancer histotypes, and we explored whether altered TAM distribution patterns influence long-term outcomes in ovarian cancer patients. METHODS: A total of 112 ovarian cancer patients were enrolled in this study, and the subjects were divided into two groups according to their survival (< 5 years vs. ≥ 5 years). Immunohistochemistry and immunofluorescence were used to determine the density, microlocalization, and differentiation status of TAMs in ovarian cancer tissues for each histotype. Kaplan-Meier survival and multivariate Cox regression analyses were used to evaluate the prognostic significance of TAM-related parameters in ovarian cancer. RESULTS: TAMs most frequently infiltrated into the cancer tissue of the serous histotype, followed by mucinous, undifferentiated, endometrioid, and clear cell histotypes (p = 0.049). The islet/stroma ratio of total TAMs varied among the cancer histotypes, with mucinous and undifferentiated cancers displaying the lowest and highest ratios, respectively (p = 0.005). The intratumoral TAM density significantly increased with increasing cancer stage and grade (p = 0.023 and 0.006, respectively). However, the overall M1/M2 TAM ratio decreased as the cancer stage increased (p = 0.012). In addition, the intra-islet M1/M2 ratio inversely correlated with the residual site size (p = 0.004). Among the TAM-related parameters, only the increased overall and intra-islet M1/M2 TAM ratios displayed prognostic significance in both the Kaplan-Meier survival and multivariate Cox regression analyses; however, the values of these two parameters did not differ significantly among the cancer histotypes. CONCLUSIONS: The patients with increased overall or intra-islet M1/M2 TAM ratios presented with an improved 5-year prognosis. Nevertheless, the TAM distribution patterns did not influence the overall outcomes of different ovarian cancer histotypes.

FOXO1A and FOXO3A are two members of the FoxO family. FOXO3A has recently been linked to human longevity in Japanese, German and Italian populations. Here we tested the genetic contribution of FOXO1A and FOXO3A to the longevity phenotype in Han Chinese population. Six tagging SNPs from FOXO1A and FOXO3A were selected and genotyped in 1817 centenarians and younger individuals. Two SNPs of FOXO1A were found to be associated with longevity in women (P = 0.01-0.005), whereas all three SNPs of FOXO3A were associated with longevity in both genders (P = 0.005-0.001). One SNP from FOXO1A was found not to be associated with longevity. In haplotype association tests, the OR (95% CI) for haplotypes TTG and CCG of FOXO1A in association with female longevity were 0.72 (0.58-0.90) and 1.38 (1.08-1.76), P = 0.0033 and 0.0063, respectively. The haplotypes of FOXO3A were associated with longevity in men [GTC: OR (95% CI) = 0.67 (0.51-0.86), P = 0.0014; CGT: OR (95% CI) = 1.48 (1.12-1.94), P = 0.0035] and in women [GTC: OR (95% CI) = 0.75 (0.60-0.94), P = 0.0094; CGT: OR (95% CI) = 1.47 (1.16-1.86), P = 0.0009]. The haplotype association tests were validated by permutation analysis. The association of FOXO1A with female longevity was replicated in 700 centenarians and younger individuals that were sampled geographically different from the original population. Thus, we demonstrate that, unlike FOXO3A, FOXO1A is more closely associated with human female longevity, suggesting that the genetic contribution to longevity trait may be affected by genders.

Abstract DNAzymes are a promising platform for metal ion detection, and a few DNAzyme‐based sensors have been reported to detect metal ions inside cells. However, these methods required an influx of metal ions to increase their concentrations for detection. To address this major issue, the design of a catalytic hairpin assembly (CHA) reaction to amplify the signal from photocaged Na + ‐specific DNAzyme to detect endogenous Na + inside cells is reported. Upon light activation and in the presence of Na + , the NaA43 DNAzyme cleaves its substrate strand and releases a product strand, which becomes an initiator that trigger the subsequent CHA amplification reaction. This strategy allows detection of endogenous Na + inside cells, which has been demonstrated by both fluorescent imaging of individual cells and flow cytometry of the whole cell population. This method can be generally applied to detect other endogenous metal ions and thus contribute to deeper understanding of the role of metal ions in biological systems.

BACKGROUND: In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. METHODS: The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. RESULTS: HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs. CONCLUSIONS: This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.