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INTRODUCTION: Honey bees provides valuable pollination services for world food crops and wild flowering plants which are habitats of many animal species and remove carbon dioxide from the atmosphere, a powerful tool in the fight against climate change. Nevertheless, the honey bee population has been declining and the majority of colony losses occur during the winter. OBJECTIVES: The goal of this study was to understand the mechanisms underlying overwinter colony losses and develop novel therapeutic strategies for improving bee health. METHODS: First, pathogen prevalence in overwintering bees were screened between 2015 and 2018. Second, RNA sequencing (RNA-Seq) for transcriptional profiling of overwintering honey bees was conducted and qRT-PCR was performed to confirm the results of the differential expression of selected genes. Lastly, laboratory bioassays were conducted to measure the effects of cold challenges on bee survivorship and stress responses and to assess the effect of a novel medication for alleviating cold stress in honey bees. RESULTS: We identified that sirtuin signaling pathway is the most significantly enriched pathway among the down-regulated differentially expressed genes (DEGs) in overwintering diseased bees. Moreover, we showed that the expression of SIRT1 gene, a major sirtuin that regulates energy and immune metabolism, was significantly downregulated in bees merely exposed to cold challenges, linking cold stress with altered gene expression of SIRT1. Furthermore, we demonstrated that activation of SIRT1 gene expression by SRT1720, an activator of SIRT1 expression, could improve the physiology and extend the lifespan of cold-stressed bees. CONCLUSION: Our study suggests that increased energy consumption of overwintering bees for maintaining hive temperature reduces the allocation of energy toward immune functions, thus making the overwintering bees more susceptible to disease infections and leading to high winter colony losses. The novel information gained from this study provides a promising avenue for the development of therapeutic strategies for mitigating colony losses, both overwinter and annually.
Subject(s)
Signal Transduction , Sirtuin 1 , Bees , Animals , Polymerase Chain Reaction , Disease Susceptibility , PollinationABSTRACT
Background: At present, bone union delay or failure remains challenging for clinicians. It has been reported that adipose-derived mesenchymal stem cells (ADMSCs) offer a promising way to promote bone fracture healing. In recent years, nanomaterials have been applied in regenerative medicine. This study aimed to investigate whether ADMSCs combined with platinum nanoparticles (PtNPs) could further improve fracture healing on the basis of ADMSCs. Methods: ADMSCs were co-cultured with PtNPs in vitro to investigate the effect of PtNPs on the differentiation of ADMSCs. Twenty Sprague-Dawley (SD) rats were randomly divided into four groups (with five rats in each group). The left tibias of all rats were fractured. Phosphate-buffered saline (PBS), PtNPs, ADMSC, and ADMSC mixed with PtNPs were then injected into the fracture sites based on the group classifications. The fracture was monitored by X-ray immediately after the fracture and on days 14 and 28 post-fracture. The tibias of the rats were subsequently harvested after the last X-ray and evaluated by micro computed tomography (micro-CT), histological analysis, and immunohistochemical detection. Results: PtNPs significantly enhanced the osteogenic differentiation of ADMSCs in vitro. On days 14 and 28 post-fracture, the radiographic score of the ADMSC + PtNPs group was higher than that of the ADMSC group, the score of the ADMSC group was higher than that of the PtNPs and control groups, and there was no significant difference between the PtNPs and control groups. Micro-CT confirmed that combined ADMSCs with PtNPs were more effective than using ADMSCs alone in promoting fracture healing. The histological and immunohistochemical results further supported this conclusion. Conclusions: Our findings demonstrated that PtNPs could promote osteogenic differentiation of ADMSC in vitro. ADMSCs combined with PtNPs could accelerate fracture healing further in vivo and are a promising a potential method for the treatment of fracture healing.
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PURPOSE: Young age is an independent negative predictor of breast cancer (BC) survival and correlates with the risk of local recurrence and contralateral BC. We aimed to design an effective and comprehensive nomogram to predict prognosis in very young patients with curatively resected BC. METHODS: Female patients with a diagnosis of BC aged ≤35 years at presentation were identified from the SEER database as a training cohort. The validation cohort consisted of 1002 consecutive women with BC aged ≤35 years that had received curative resection for BC at the Sun Yat-sen University Cancer Center. A nomogram was built based on the identified variables in multivariate Cox proportional hazards model. The performance of the nomogram was quantified using Harrell's concordance index (C-index) and calibration curves. RESULTS: Overall, 10,872 young female patients who underwent surgery for BC were enrolled in the training cohort, while 1002 very young female BC patients were identified as independent validation cohort. Eight covariables (age, race, grade; ER, PR, and HER2 status; T, and N stages) were identified and incorporated to construct a nomogram. The C-index values of the nomogram were 0.727 (95% CI: 0.714-0.740) and 0.722 (95% CI: 0.666-0.778) for OS in the training and validation cohorts, respectively. The calibration curves showed a high degree of agreement between the predicted and actual observed survival rates in both training and validation cohorts. The nomogram displayed good calibration and acceptable discrimination. Based on the TPS of the nomogram model for OS with the X-tile program, patients were divided into 3 risk groups, which were easily discriminated on survival analyses for OS. CONCLUSION: We have successfully constructed an effective nomogram to predict survival outcomes for young female patients with curatively resected BC, which may provide individual survival prediction to benefit prognosis evaluation and individualized therapy.
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PURPOSE: Inflammation is closely associated with prognosis in gastric cancer (GC). We aimed to assess the predictive value of existing inflammatory and tumor markers in GC, to establish a systemic score based on valuable predictors for early risk stratification of patients, and to create a nomogram for individual risk prediction. PATIENTS AND METHODS: We retrospectively analyzed 401 GC patients who underwent curative gastrectomy from 2007 to 2016. RESULTS: Through univariate and multivariate survival analysis, age (>60 years), depth of invasion (pT3-4), lymph node invasion (pN1-3), histologic classification (poor), adjuvant chemotherapy (no), albumin fibrinogen ratio (AFR) (<13.33), and carbohydrate antigen 19-9 (CA19-9) (>27 U/mL) independently indicated inferior disease-free survival (DFS). In addition, depth of invasion, lymph node invasion, histologic classification, adjuvant chemotherapy, AFR, and CA19-9 were incorporated in the prediction of cancer-specific survival (CSS). A combined AFR and CA19-9 prognostic score (CACPS) was established. Lower AFR (<13.33) and higher CA19-9 (>27 U/mL) were allocated 1 point each in the CACPS (range, 0-2). CACPS can be used as an independent predictor for DFS and CSS in multivariate analysis (for DFS: CACPS 1: HR=2.039, 95% CI: 1.357-3.065, P=0.001; CACPS 2: HR=2.419, 95% CI: 1.397-4.186, P=0.002; for CSS: CACPS 1: HR=2.035, 95% CI: 1.292-3.205, P=0.002; CACPS 2: HR=2.255, 95% CI: 1.252-4.059, P=0.007), with a higher CACPS indicating poor survival according to Kaplan-Meier curves (both P<0.001). Moreover, a nomogram for DFS and CSS was generated using the significant characteristics in the multivariate analysis, which exhibited high accuracy (for DFS: C-index=0.743, 95% CI: 0.698-0.788; for CSS: C-index=0.766, 95% CI: 0.718-0.814) versus tumor-node-metastasis staging (for DFS: C-index=0.692, 95% CI: 0.650-0.734; for CSS: C-index=0.720, 95% CI: 0.675-0.764). CONCLUSION: Preoperative CACPS exhibited high accuracy in predicting prognosis for GC patients who underwent curative resection.
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OBJECTIVE: To study the expression and secretion of alternative complement pathway regulator complement factor H (CFH) in spontaneously produced or induced human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). METHODS: RPE cells were acquired by spontaneous differentiation from hESC (sdRPE), a source of hESC-RPE, according to the method used in clinical trials. RPE cells were also acquired under the induction of growth factors and small molecules for 14 d (iRPE). Acquired cells were kept culturing for 3 month for maturation. All differentiated cellsï¼P3ï¼were cultivated for 4-5 weeks prior to characterization with qRT-PCR and immunofluorescence. Secretion levels of CFH were investigated by ELISA. ARPE-19 cell line was served as control. RESULTS: Both sdRPE and iRPE showed high similarity in cell morphology and the pattern of specific gene expression with human RPE. The relative CFH mRNA expression levels of both sdRPE and iRPE were significantly higher than that of ARPE-19 ( P<0.05). The CFH secretion levels of sdRPE in the 24 h-, 48 h- and 72 h-culture medium were higher than those of iRPE ( P=0.000 2); and this CFH secretion levels of both sdRPE and iRPE were higher than that of the ARPE-19 cell line ( P<0.000 1). CONCLUSION: Both sdRPE and iRPE derived by different differentiation methods expressed and secreted CFH, suggesting that hESC-RPE may have certain ability to regulate the alternative complement pathway.
