Effects of miR-29c on proliferation and adipogenic differentiation of porcine bone marrow mesenchymal stromal cells.

microRNAs (miRNAs), a subclass of noncoding short RNAs, direct cells fate decisions that are important for cell proliferation and cell lineage decisions. Adipogenic differentiation contributes greatly to the development of white adipose tissue, involving of highly organized regulation by miRNAs. In the present study, we screened and identified 78 differently expressed miRNAs of porcine BMSCs during adipogenic differentiation. Of which, the role of miR-29c in regulating the proliferation and adipogenic differentiation was proved and detailed. Specifically, over-expression miR-29c inhibits the proliferation and adipogenic differentiation of BMSCs, which were reversed upon miR-29c inhibitor. Interference of IGF1 inhibits the proliferation and adipogenic differentiation of BMSCs. Mechanistically, miR-29c regulates the proliferation and adipogenic differentiation of BMSCs by targeting IGF1 and further regulating the MAPK pathway and the PI3K-AKT-mTOR pathway, respectively. In conclusion, we highlight the important role of miR-29c in regulating proliferation and adipogenic differentiation of BMSCs.

Umbilical cord cysts: Classification, diagnosis, prognosis, and pregnancy recommendations.

Umbilical cord cysts (UCCs)-cysts located in the umbilical cord that are derived from an abnormal embryonic development process-are typically an incidental discovery during prenatal ultrasound. It can be described as either a pseudocyst or a true UCC, which results from focal edema or degeneration of Wharton jelly or the remnants of embryonic development, respectively. Due to the relative rarity of the UCC, the clinical guidance of UCCs is not yet available. Herein, the aim of this paper is to discuss the classification, diagnosis, prognosis, and clinical management of UCCs through a literature review, in order to improve the understanding of UCCs among clinical obstetricians and pediatricians.

The Potential Value of Ki-67 in Prognostic Classification in Early Low-Risk Endometrial Cancer.

PURPOSE: This study aims to determine the optimal cut-off value of Ki-67 to better predict the recurrence of early low-risk endometrial cancer (EC). METHODS: Seven hundred and forty-eight patients diagnosed with low-risk EC from West China Second Hospital of Sichuan University and the First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The receiver operating characteristic curve (ROC) and Youden index were used to calculate the optimal cut-off value of Ki-67 expression. The clinicopathological indexes between two groups divided by cut-off value of Ki-67 were compared. The univariate and multivariate regression analyses were performed to investigate risk factors connected to the recurrence of early low-risk EC. The survival analysis was shown in Kaplan-Meier curve. RESULT: Thirty-three patients were detected with tumor recurrence after primary surgery (4.4%); 33% was the optimal cut-off value of the Ki-67 index. A high Ki-67 was significantly associated with age (P = .002), myometrial invasion (P < .001), and the expression of P53 (P = .007). The multivariate regression analysis verified that Ki67 ≥ 33% was an independent prognostic factor for predicting recurrence. The recurrence-free survival (RFS) and the overall survival (OS) in high Ki-67 group was significantly lower than that in low Ki-67 group (P < .001 and P = .029, respectively). The prognostic values of ER, PR, and P53 in combination with Ki-67 were superior to each single predictor. CONCLUSIONS: The optimal cut-off value of Ki-67 for predicting recurrence is 33%, which quantitatively defines the specific value of Ki-67 that causes high-risk recurrence in early low-risk EC.

A Nomogram Model Based on Neuroendocrine Markers for Predicting the Prognosis of Neuroendocrine Carcinoma of Cervix.

BACKGROUND: Combining traditional clinical parameters with neuroendocrine markers to construct a nomogram model to predict the postoperative recurrence of neuroendocrine carcinoma of cervix (NECC). METHODS: A total of 257 patients were included in this study. Univariate and multivariate Cox regression analyses were used to establish a nomogram model in the training cohorts, which was further validated in the validation cohorts. The calibration curve was used to conduct the internal and external verification of the model. RESULTS: Overall, 41 relapse cases were observed in the training (23 cases) and validation (18 cases) cohorts. The univariate analysis preliminarily showed that FIGO stage, stromal invasion, nerve invasion, lymph vascular space invasion, lymph node involvement, cervical-uterine junction invasion and CgA were correlated with NECC recurrence. The multivariate analysis further confirmed that FIGO stage (p = 0.023), stromal invasion (p = 0.002), lymph vascular space invasion (p = 0.039) and lymph node involvement (p = 0.00) were independent risk factors for NECC recurrence, which were ultimately included in the nomogram model. In addition, superior consistency indices were demonstrated in the training (0.863, 95% CI 0.784-0.942) and validation (0.884, 95% CI 0.758-1.010) cohorts. CONCLUSIONS: The established nomogram model combining traditional clinical parameters with neuroendocrine markers can reliably and accurately predict the recurrence risks in NECC patients.

Nomograms predict survival benefits of radical prostatectomy and chemotherapy for prostate cancer with bone metastases: A SEER-based study.

Purpose: This study aimed to identify independent prognosis-associated factors of bone-metastatic prostate cancer. The nomograms were further developed to obtain indicators for the prognostic evaluation. Methods: A total of 7315 bone-metastatic prostate cancer (PCa) patients from 2010 to 2016 were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training cohort (n=5,120) and test cohort (n=2,195) in a ratio of 7:3. Univariate and multivariate Cox regression models were applied to evaluate potential risk factors. A 1:1 propensity score matching (PSM) was further performed to decrease the confounding effect and re-evaluate the influence of radical prostatectomy and chemotherapy on prognosis. Combining these potential prognosis factors, the nomograms of cancer-specific survival (CSS) and overall survival (OS) at different times were established. C-indexes, calibration curves, and decision curves were developed to evaluate the discrimination, calibration, and clinical benefit of the nomograms. Results: Eleven independent prognosis factors for CSS and twelve for OS were utilized to conduct the nomograms respectively. The C-indexes of nomograms for CSS and OS were 0.712 and 0.702, respectively. A favorable consistency between the predicted and actual survival probabilities was demonstrated by adopting calibration curves. Decision curves also exhibited a positive clinical benefit of the nomograms. Conclusions: Nomograms were formulated successfully to predict 3-year and 5-year CSS and OS for bone-metastatic PCa patients. Radical prostatectomy and chemotherapy were strongly associated with the bone-metastatic PCa prognosis.

Chromosome-level assembly of the Neolamarckia cadamba genome provides insights into the evolution of cadambine biosynthesis.

Neolamarckia cadamba (Roxb.), a close relative of Coffea canephora and Ophiorrhiza pumila, is an important traditional medicine in Southeast Asia. Three major glycosidic monoterpenoid indole alkaloids (MIAs), cadambine and its derivatives 3ß-isodihydrocadambine and 3ß-dihydrocadambine, accumulate in the bark and leaves, and exhibit antimalarial, antiproliferative, antioxidant, anticancer and anti-inflammatory activities. Here, we report a chromosome-scale N. cadamba genome, with 744.5 Mb assembled into 22 pseudochromosomes with contig N50 and scaffold N50 of 824.14 Kb and 29.20 Mb, respectively. Comparative genomic analysis of N. cadamba with Co. canephora revealed that N. cadamba underwent a relatively recent whole-genome duplication (WGD) event after diverging from Co. canephora, which contributed to the evolution of the MIA biosynthetic pathway. We determined the key intermediates of the cadambine biosynthetic pathway and further showed that NcSTR1 catalyzed the synthesis of strictosidine in N. cadamba. A new component, epoxystrictosidine (C27H34N2O10, m/z 547.2285), was identified in the cadambine biosynthetic pathway. Combining genome-wide association study (GWAS), population analysis, multi-omics analysis and metabolic gene cluster prediction, this study will shed light on the evolution of MIA biosynthetic pathway genes. This N. cadamba reference sequence will accelerate the understanding of the evolutionary history of specific metabolic pathways and facilitate the development of tools for enhancing bioactive productivity by metabolic engineering in microbes or by molecular breeding in plants.

Application of X-ray diffraction and energy dispersive spectroscopy in the isolation of sulfated polysaccharide from Porphyra haitanensis and its antioxidant capacity under in vitro digestion.

BACKGROUND: The separation and purification of Porphyra haitanensis polysaccharide (PHP), and the determination of changes in molecular weight (Mw) and antioxidant capacity after in vitro digestion, were undertaken. RESULTS: Analysis of two polysaccharide fractions (PHP0.5-1-UF and PHP1.0-1-UF) by various techniques showed that they were very pure sulfated polysaccharides without pigment or protein. PHP0.5-1-UF was filamentous or 'tape-like' sheets, whereas PHP1.0-1-UF had some filaments and large numbers of rounded aggregates. The Mw of PHP, PHP0.5-1-UF and PHP1.0-1-UF was 2.06 × 106 (±2.02%), 6.68 × 106 (±3.17%), and 1.14 × 106 (±3.44%) (g mol-1 ), respectively. After in vitro digestion, the Mw of PHP, PHP0.5-1-UF, and PHP1.0-1-UF decreased. Their antioxidant capacities were markedly higher than before digestion, especially PHP0.5-1-UF and its digestion products, which might be related to the reductions in Mw. CONCLUSION: These findings provide a greater understanding of the separation and purification of sulfated polysaccharides and the influence of digestion on biological activity. They also contribute to the practical application of sulfated polysaccharides in functional foods. © 2021 Society of Chemical Industry.

A self-assembled fluorescent organic nanoprobe and its application for sulfite detection in food samples and living systems.

Sulfur dioxide (SO2) is a widely distributed air pollutant, and humans can easily be exposed to sulfite by inhaling SO2, thus inducing respiratory responses and diseases. Hence, to develop a rapid, sensitive and selective method for detection of sulfites is of great importance. Herein, we designed and synthesized a novel tetraphenyl imidazole compound TIBM with aggregation-induced emission enhancement (AIEE). TIBM can self-assemble into well-organized nanoparticles and is reported as an excellent probe for detection of sulfite with high selectivity and sensitivity. The nanoprobe performed very well for the detection of sulfite with an ultrafast detection time (15 s) and an ultralow detection limit (7.4 nM), which is superior to most of the reported probes. Moreover, the nanoprobe was successfully used to detect sulfite in food samples with a favorable accuracy. In addition, we developed paper-based devices for point-of-care detection of sulfite with naked eyes. Furthermore, due to its high water solubility, cell membrane permeability and good biocompatibility, the nanoproboe was further applied to detect sulfite in living systems. This study may offer some helpful insights for designing other AIE-based fluorescent nanosensors for various analytes.

The early-onset febrile reaction following vaccination and associated factors: An exploratory sub-study based on the Ebola vaccine clinical trial.

A phase-1 clinical trial aimed to assess the safety and immunogenicity of the type-5 adenovirus vector based Ebola vaccine (Ad5-EBOV) was conducted in China. To provide more evidence for the safety evaluation and dose-selection, an exploratory sub-study using a wireless automatic temperature measuring platform was done based on the phase-1 clinical trial. The main aim of the sub-study was to obtain more information about the occurrence of fever and detect the potential associated factors, second was to assess the feasibility of the temperature measuring platform in vaccine clinical trials. Temperature data of 3 treatment groups all presented a rising tendency during the first 6 hours after vaccination, the incidence of elevated temperature and possible associated factors were analyzed. For the incidence of elevated temperature, no marked dose-response relationship was found in 6 hours with wireless thermometers; the information from mercury thermometers showed that the grade-1 fever proportion peaked at 6 hours and there was no difference between groups, while grade-2 fever proportion peaked at 24 hours and was significantly higher in high-dose group than those in the other 2 groups. Significant differences were found between sex groups (males vs. female, incidence rate ratios (IRR) = 2.93 and 7.62 for any-grade, grade-2 fever respectively, P<0.001); a decline in grade-2 fever incidence was found with the increasing age groups (IRR = 0.78, P = 0.003) and body mass index (BMI, IRR = 0.67, P<0.001) .Our findings show that the dose-dependent manner between fever and the dose of Ad5-EBOV in this study might emerge after 6 hours, and which is slight and transient. Wireless thermometers secured on the skin surface are not suitable for a long time (longer than 6 hours) measurement, new methods for temperature monitoring, like ear temperature measurement, should be tested in the further research.