Schiff base linkage of citral to zinc-casein hydrolysate chelates for preparing starch-based active films against L. monocytogenes on ready-to-eat foods.

Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen often found in ready-to-eat (RTE) foods, posing significant threats to human health. In this study, an active film based on cross-linking via Schiff base and electrostatic interaction to inactivate L. monocytogenes on RTE foods was constructed. Zinc-casein hydrolysate chelates (Zn-HCas) was prepared and blended with cationic starch (CSt) to form the substrates of the film. Then, Citral (CI) with excellent antibacterial properties was added to enhance the biological and packaging properties of the film through covalent cross-linking (Schiff base). Based on the zinc ion-activated metalloproteinases produced by L. monocytogenes, the cross-linked film could be disrupted and the release of CI was accelerated. The variation in color, FTIR, and amino group content proved that Schiff base reaction had taken place. Enhanced mechanical properties, barrier properties, thermal stability and antimicrobial activity against L. monocytogenes (exceed 99.99 %) were obtained from the CI/Zn-HCas/CSt film. The application on RTE cheese results demonstrated that the cross-linked film could be employed in active packaging field with the ability in maintaining the original chroma and texture properties of RTE cheese. In summary, the prepared cross-linked film could be used as an active packaging against L. monocytogenes contamination with great potential.

Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7.

BACKGROUND: The dietary agent sulforaphane (SFN) has been reported to reduce diabetes-induced renal fibrosis, as well as inhibit histone deacetylase (HDAC) activity. Bone morphologic protein 7 (BMP-7) has been shown to reduce renal fibrosis induced by transforming growth factor-beta1. The aim of this study was to investigate the epigenetic effect of SFN on BMP-7 expression in diabetes-induced renal fibrosis. METHODS: Streptozotocin (STZ)-induced diabetic mice and age-matched controls were subcutaneously injected with SFN or vehicle for 4 months to measure the in vivo effects of SFN on the kidneys. The human renal proximal tubular (HK11) cell line was used to mimic diabetic conditions in vitro. HK11 cells were transfected to over-express HDAC2 and treated with high glucose/palmitate (HG/Pal) to explore the epigenetic modulation of BMP-7 in SFN-mediated protection against HG/Pal-induced renal fibrosis. RESULTS: SFN significantly attenuated diabetes-induced renal fibrosis in vivo. Among all of the HDACs we detected, HDAC2 activity was markedly elevated in the STZ-induced diabetic kidneys and HG/Pal-treated HK11 cells. SFN inhibited the diabetes-induced increase in HDAC2 activity which was associated with histone acetylation and transcriptional activation of the BMP-7 promoter. HDAC2 over-expression reduced BMP-7 expression and abolished the SFN-mediated protection against HG/Pal-induced fibrosis in vitro. CONCLUSION: Our study demonstrates that the HDAC inhibitor SFN protects against diabetes-induced renal fibrosis through epigenetic up-regulation of BMP-7.

Comprehensive analysis of long non­coding RNA using an associated competitive endogenous RNA network in Wilms tumor.

Wilms tumor (WT) is the most common malignant renal neoplasm in children; however, the underlying molecular mechanisms are not well understood. According to the competing endogenous RNA (ceRNA) theory, long non­coding RNAs (lncRNAs) can regulate the expression of target genes by adsorbing microRNAs (miRNAs/miRs). However, the role of lncRNAs in WT has not been fully elucidated. The aim of the present study was to construct a ceRNA network to identify the potential lncRNAs involved in WT. The expression profiles of lncRNAs, miRNAs and mRNAs in 120 WT and six normal tissues were obtained from the Therapeutically Applicable Research to Generate Effective Treatments database. A total of 442 lncRNAs, 214 miRNAs and 4,912 mRNAs were identified as differentially expressed in WT and were enriched in 472 Gene Ontology terms (355 biological processes, 89 cellular components and 29 molecular functions) and 18 Kyoto Encyclopedia of Genes and Genomes pathways. A lncRNA­miRNA­mRNA ceRNA network of WT consisting of with 32 lncRNAs, 14 miRNAs and 158 mRNAs was constructed, based on the bioinformatics analysis of the miR target prediction database and the miRNAcode, miRTarBase and TargetScan databases. Subsequently, three lncRNAs, three miRNAs and 17 mRNAs, which had a significant effect on the overall survival rate of patients with WT, were identified based on the survival analysis. The three lncRNAs were also differentially expressed in the late and early stages of WT and were validated using the GSE66405 dataset obtained from the Gene Expression Omnibus database. In conclusion, the present study generated a specific lncRNA­related ceRNA network of WT, which may provide a novel perspective on the molecular mechanisms underlying the progression and prognosis of the disease.

Opportunities and Challenges of the Human Microbiome in Ovarian Cancer.

Ovarian cancer is the most lethal malignancy among gynecological cancers worldwide. Most ovarian cancer patients are diagnosed at an advanced stage because of non-specific clinical symptoms. The human microbiome plays a crucial role in maintaining the normal physiological and pathological state of the body. With the development of technologies such as DNA and 16S rRNA sequencing, an increasing number of findings on the role of microbiome in cancers are being reported. Microbiome abnormalities are increasingly associated with diseases, including cancer development, and response to therapies. Some studies have shown the relationship between microbiome changes and ovarian cancer. However, the mechanisms underlying this relationship are not yet fully understood. Here, we summarize the key findings in this regard by focusing on estrogen metabolism and host recognition receptors in microorganisms and changes in the gut or pelvic microbiome in patients with ovarian cancer. We further discuss the potential of using the microbiome as a novel biomarker for cancers. We also highlight the possibility to use microorganisms as a treatment modality to enhance the immune system, activate anti-tumor response, mediate chemotherapy resistance, and ameliorate the adverse effects of the treatment.

miR-214-5p suppresses the proliferation, migration and invasion of trophoblast cells in pre-eclampsia by targeting jagged 1 to inhibit notch signaling pathway.

MicroRNA-214-5p has been reported to be expressed in placental tissue and suppressed the proliferation and invasion of various tumor cells. However, the role of miR-214-5p in pre-eclampsia has not been reported. We aimed to explore the effects of miR-214-5p in proliferation, migration, and invasion of placental trophoblast cells. RT-qPCR was used to quantify the miR-214-5p expression level in placental samples and four types of trophoblast cell lines. Cell proliferation was monitored by CCK-8 and Edu staining assays. Flow cytometry was used to determine the cell cycle. Wound healing and transwell assays were performed to measure the migratory and invasive capacities in JEG-3 and BEWO cells. In addition, we investigated whether miR-214-5p targeted Jagged 1 to regulate the Notch signaling pathway to affect trophoblast cells by luciferase assay and western blot. The expression of miR-214-5p was significantly increased in the placenta of patients with PE. Moreover, the proliferation, migration, and invasion of JEG-3 cells transfected with miR-214-5p mimic were inhibited. The results were reversed when BEWO cells were transfected with miR-214-5p inhibitor. The dual-luciferase assay demonstrated that miR-214-5p directly regulated Jagged 1. The expression of the proteins associated with the Notch signaling pathway, Jagged 1, Notch 1, HEY 1 and HES 1 were all decreased when Jagged 1 was negatively regulated by miR-214-5p. miR-214-5p directly down-regulated Jagged 1 expression, then suppressed proliferation, migration, and invasion of human placental trophoblast cells by inhibiting the Notch signaling pathway.

A five-gene signature derived from m6A regulators to improve prognosis prediction of neuroblastoma.

BACKGROUND AND OBJECTIVE: N6-methyladenosine (m6a) is the most abundant form of methylated modification in eukaryotic mRNA. However, the role of m6A-related genes in neuroblastoma (NB), one of the most common paediatric malignant tumours, is not well known. This study aimed to determine the prognostic role of m6A-related genes in neuroblastoma. METHODS: We analysed the expression of 20 published m6A methylation regulators in 498 patients with NB from the Gene Expression Omnibus database. To determine the independent prognostic factors, we used univariate Cox analysis, the least absolute shrinkage and selection operator (LASSO) regression. The multivariate Cox analysis was used to construct a prognostic risk prediction model. 120 NB tissues from "Therapeutically Applicable Research To Generate Effective Treatments" (TARGET ) database was used to test the prognostic value. Gene set enrichment analysis was performed to discover the potential biological function of the m6A signature. RESULTS: The risk prediction model consisted of five genes (METT14, WTAP, HNRNPC, YTHDF1 and IGF2BP2). The receiving operating characteristic curve showed the high exactitude of the risk model. Cox regression analysis revealed that the risk model was an independent prognostic factor of overall survival. These results were reproduced using another published independent dataset. Further functional enrichment analysis suggested the involvement of the 5-gene signature in several malignancies. CONCLUSION: The five m6A regulatory genes identified in this study enable clinical prognosis of NB and may serve as novel therapeutic targets for NB.

LncRNA TDRG1/miR-214-5p axis affects preeclampsia by modulating trophoblast cells.

Because of limited treatment options, preeclampsia (PE) is the leading cause of perinatal morbidity and mortality worldwide. Recently, lncRNA TDRG1 is reported to be aberrantly down-regulated in PE placenta, and the abnormal expression of TDRG1 might play a key or partial role in PE development. In this study, we found that TDRG1 was significantly down-regulated in PE placenta compared with the normal placenta. The cell proliferation, migration, invasion, and cell cycle were explored by CCK-8, wound-healing, transwell, and flow cytometer assay, respectively. Experimental results showed that TDRG1 accelerated the proliferation, migration, and invasion of trophoblast cells. Dual-luciferase reporter assays confirmed that TDRG1 could bind to miR-214-5p. Besides, knockdown of TDRG1 suppressed the cell proliferation, migration, and invasion, while knockdown of miR-214-5p reversed the effect. Jagged1 and Notch1 were negatively regulated by miR-214-5p while positively modulated by TDRG1. In conclusion, TDRG1 promoted trophoblast cells viability and invasion by negatively regulating miR-214-5p expression, contributing to a better understanding of PE pathogenesis and providing new light on TDRG1-directed diagnosis and treatment. SIGNIFICANCE OF THE STUDY: In this work, we observed that TDRG1 was able to promote cell proliferation, migration, and invasion cells by suppressing the expression of miR-214-5p and regulating the Notch signalling pathway in trophoblast cells. As far as we know, the effect of TDRG1/miR-214-5p axis on cell viability, migration, and invasion of trophoblast cells was firstly introduced. Our findings provided a better understanding of the mechanism of PE. Moreover, it is reasonable to believe that TDRG1 may be employed as a strategy to treat PE in the future.

Macrophage Polarization in the Development and Progression of Ovarian Cancers: An Overview.

Ovarian cancer is the most lethal gynecological malignancy worldwide. Most patients are diagnosed at late stages because of atypical symptoms and the lack of effective early diagnostic measures. The mechanisms underlying the oncogenesis and development of ovarian cancer are not clear. Macrophages, immune cells derived from the innate immune system, have two states of polarization (M1 and M2) that develop in response to different stimuli. The polarization and differentiation of macrophages into the cancer-inhibiting M1 and cancer-promoting M2 types represent the two states of macrophages in the tumor microenvironment. The interaction of polarized macrophages with cancer cells plays a crucial role in a variety of cancers. However, the effects of macrophage M1/M2 polarization on ovarian cancer have not yet been systematically and fully discussed. In this review, we discuss not only the occurrence, development and influences of macrophage polarization but also the association between macrophage polarization and ovarian cancer. The polarization of macrophages into the M1 and M2 phenotypes plays a pivotal role in ovarian cancer initiation, progression, and metastasis, and provides targets for macrophage-centered treatment in the cancer microenvironment for ovarian cancer therapy. We also addressed the regulation of macrophage polarization in ovarian cancer via noncoding RNAs, exosomes, and epigenetics.

Perineal Groove: Report of Two Cases and Review of the Literature.

Perineal groove is a rare anoperineal congenital malformation disease that usually affects newborn females. It is unknown to many clinicians, which usually leads to misdiagnosis. The pathogenesis of perineal groove is not clear, and there are few cases reported in the current medical literature. Perineal grooves in two newborn babies were described in this report, and the literature on perineal groove was also reviewed and analyzed to improve the recognition of this disease.