Oncolytic activity of a coxsackievirus B3 strain in patient-derived cervical squamous cell carcinoma organoids and synergistic effect with paclitaxel.

BACKGROUND: Cervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids. METHODS: The oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro. RESULTS: CVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication. CONCLUSIONS: CVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens.

The impact of plant-based diets on female bone mineral density: Evidence based on seventeen studies.

BACKGROUND: An increase in awareness of plant-based diets has brought forth numerous studies on bone mineral density (BMD). The present systematic review and meta-analysis was designed to compare the effect between plant-based diets and omnivores on female BMD. METHODS: We searched the Cochrane Library, PubMed, EMBASE, and Web of Science and up to July 1, 2020. Mean difference (MD) with its 95% confidence interval (CI) was estimated to compare the outcomes of the groups. We compared BMD at the lumbar spine, femoral neck and whole body respectively between plant-based diets and omnivores. In addition, we performed subgroup analyses according to different clinical characteristics for further exploration. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 17 cross-sectional studies including 13,888 patients were identified for the present meta-analysis. Our pooled result indicated that population with plant-based diets had lower BMD than omnivores at the lumbar spine (MD -0.03; 95% CI -0.04 to -0.02; P < .0001), femoral neck (MD -0.04; 95% CI -0.05 to -0.03; P < .00001) and whole body (MD -0.04; 95% CI -0.06 to -0.01; P = .01), respectively. Further exploration indicated that especially females with plant-based diets experienced significantly lower BMD at lumbar spine (MD -0.03; 95% CI -0.04 to -0.02; 3173 pts), femoral neck (MD -0.04; 95% CI -0.05 to -0.03; 10,656 pts) and whole body (MD -0.05; 95% CI -0.10 to -0.00; P = .04). In addition, we performed subgroup analyses and found lower BMD at lumbar spine and femoral neck in both vegetarians and vegans. CONCLUSIONS: The present meta-analysis indicated that plant-based diets may be correlated with lower BMD of women when compared with omnivore population. However, this does not diminish the fact that a plant-based diet can be a harmful option to the overall bone health of population and more prospective researches are needed to clear the impact of plant-based diets on bone health.