Effects of enzymatic hydrolysis technology on the physicochemical properties and biological activities of American ginseng beverages.

American ginseng (Panax quinquefolius L.) contains various biological macromolecules, such as polysaccharides, saponins, and proteins, which have various pharmacological activities, including antioxidant, anti-inflammatory, and hypoglycemic effects. Consequently, the utilization of novel processing technologies developed an American ginseng beverage to meet people's health needs and the preferences of young people. This study was the first to use American ginseng as a primary raw material, utilizing a three-step enzymatic hydrolysis approach with cellulase, pectinase, amylase, maltase, and flavor protease enzymes to prepare an American ginseng beverage. The basic nutritional and active ingredient contents of the product were determined. The antioxidant activity of enzymatic beverages was evaluated by calculating the free radical clearance rates of DPPH and ABTS, and the effect of enzymatic beverages on α-glucosidase activity was also tested. The anti-inflammatory activity of RAW264.7 cells induced by LPS was evaluated by measuring the production of NO, TNF-α, and IL-6 during the enzymatic hydrolysis process. The results indicated that the nutritional components of American ginseng beverage products met the beverage industry standards. Moreover, the application of enzymatic hydrolysis technology had improved the antioxidant and anti-inflammatory activities of American ginseng beverages. In addition, the enzymatic beverage of American ginseng exhibited certain hypoglycemic activity. Consequently, the established enzymatic hydrolysis technology provided a reference for the production of other beverage products.

Effect of high moisture extrusion on the structure and physicochemical properties of Tartary buckwheat protein and its in vitro digestion.

Tartary buckwheat is rich in nutrients and its protein supports numerous biological functions. However, the digestibility of Tartary buckwheat protein (TBP) poses a significant limitation owing to its inherent structure. This study aimed to assess the impact of high moisture extrusion (HME, 60 % moisture content) on the structural and physicochemical attributes, as well as the in vitro digestibility of TBP. Our results indicated that TBP exhibited unfolded and amorphous microstructures after HME. The protein molecular weight of TBP decreased after HME, and a greater degradation was observed at 70 °C than 100 °C. In particular, HME at 70 °C caused an almost complete disappearance of bands near 35 kDa compared with HME at 100 °C. In addition, compared with native TBP (NTBP, 44.53 µmol/g protein), TBP subjected to HME at 70 °C showed a lower disulfide bond (SS) content (42.67 µmol/g protein), whereas TBP subjected to HME at 100 °C demonstrated a higher SS content (45.70 µmol/g protein). These changes endowed TBP with good solubility (from 55.96 % to 83.31 % at pH 7), foaming ability (20.00 %-28.57 %), and surface hydrophobicity (8.34-23.07). Furthermore, the emulsifying activity (EA) and in vitro digestibility are closely related to SS content. Notably, extruded TBP (ETBP) obtained at 70 °C exhibited higher EA and digestibility than NTBP, whereas ETBP obtained at 100 °C showed the opposite trend. Consequently, HME (especially at 70 °C) demonstrated significant potential as a processing technique for improving the functional and digestive properties of TBP.

Identifying the changes in the cortical activity of various brain regions for different balance tasks: A review.

BACKGROUND: Balance support is critical to a person's overall function and health. Previous neuroimaging studies have shown that cortical structures play an essential role in postural control. OBJECTIVE: This review aims to identify differences in the pattern of neural activity induced by balance tasks with different balance control requirements. METHODS: Seventy-four articles were selected from the field of balance training and were examined based on four brain function detection technologies. RESULTS: In general, most studies focused on the activity changes of various cortical areas during training at different difficulty levels, but more and more attention has also begun to focus on the functional changes of other cortical and deep subcortical structures. Our analysis also revealed the neglect of certain task types. CONCLUSION: Based on these results, we identify and discuss future research directions that may contribute to a clear understanding of neural functional plasticity under different tasks.

circPTPN14 promotes renal fibrosis through its interaction with FUBP1 to enhance MYC transcription.

CircRNAs are a class of single-stranded molecules with tissue/development-specific expression patterns. Increasing evidence demonstrates that circRNAs play important roles in physiological or pathological conditions. Here, we provide a brief discussion of circRNA in renal fibrosis.

circNEIL3 inhibits tumor metastasis through recruiting the E3 ubiquitin ligase Nedd4L to degrade YBX1.

Distant metastasis is a major contributor to cancer-related mortality. However, the role of circRNAs in this process remains unclear. Herein, we profiled the circRNA expression in a cohort of 68 colorectal carcinoma (CRC) primary tumors and their paired liver metastatic lesions. By overlapping with the TGFß-responsive circRNAs, circNEIL3 (hsa_circ_0001460) was identified as a TGFß-repressive and metastasis-related circRNA. Functionally, circNEIL3 effectively inhibited tumor metastasis in both and in vivo and in vivo models of various cancer types. Mechanistically, circNEIL3 exerts its metastasis-repressive function through its direct interaction with oncogenic protein, Y-box-binding protein 1 (YBX1), which consequently promotes the Nedd4L-mediated proteasomal degradation of YBX1. Importantly, circNEIL3 expression was negatively correlated to YBX1 protein level and metastatic tendency in CRC patient samples. Collectively, our findings indicate the YBX1-dependent antimetastatic function of circNEIL3 and highlight the potential of circNEIL3 as a biomarker and therapeutic option in cancer treatment.

Regulation of XPO5 phosphorylation by PP2A in hepatocellular carcinoma.

Exportin 5 (XPO5) is a shuttle protein that mediates precursor miRNA (pre-miRNA) export from the nucleus to the cytoplasm, an important step in miRNA maturation. We previously demonstrated that XPO5 was phosphorylated by ERK kinase and subsequently underwent conformation change by the peptidyl-prolyl isomerase Pin1, leading to the reduced miRNA expression in hepatocellular carcinoma (HCC). Protein phosphorylation modification serves as a reversible regulatory mechanism precisely governed by protein kinases and phosphatases. Here we identified that the phosphatase PP2A catalyzed XPO5 dephosphorylation. PP2A holoenzyme is a ternary complex composed of a catalytic subunit, a scaffold subunit, and a regulatory subunit that determines substrate specificity. In this study, we characterized the involvement of B55ß subunit in XPO5 dephosphorylation that favored the distribution of XPO5 into the cytoplasm and promoted miRNA expression, leading to HCC inhibition in vitro and in vivo. Our study demonstrates the regulatory role of B55ß-containing PP2A in miRNA expression and may shed light on HCC pathogenesis.

Characterization of distinct circular RNA signatures in solid tumors.

BACKGROUND: Circular RNAs (circRNAs) are differentially expressed between normal and cancerous tissues, contributing to tumor initiation and progression. However, comprehensive landscape of dysregulated circRNAs across cancer types remains unclear. METHODS: In this study, we conducted Ribo-Zero transcriptome sequencing on tumor tissues and their adjacent normal samples including glioblastoma, esophageal squamous cell carcinoma, lung adenocarcinoma, thyroid cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. CIRCexplorer2 was employed to identify circRNAs and dysregulated circRNAs and genes were determined by DESeq2 package. The expression of hsa_circ_0072309 (circLIFR) was measured by reverse transcription and quantitative real-time PCR, and its effect on cell migration was examined by Transwell and wound healing assays. The role of circLIFR in tumor metastasis was evaluated via mouse models of tail-vein injection and spleen injection for lung and liver metastasis, respectively. RESULTS: Distinct circRNA expression signatures were identified among seven types of solid tumors, and the dysregulated circRNAs exhibited cancer-specific expression or shared common expression signatures across cancers. Bioinformatics analyses indicated that aberrant expression of host genes and/or RNA-binding proteins contributed to circRNA dysregulation in cancer. Finally, circLIFR was experimentally validated to be downregulated in six solid tumors and to significantly inhibit cell migration in vitro and tumor metastasis in vivo. CONCLUSIONS: Our results provide a comprehensive landscape of differentially expressed circRNAs in solid tumors and highlight that circRNAs are extensively involved in cancer pathogenesis.

PDLIM1: Structure, function and implication in cancer.

PDLIM1, a member of the PDZ-LIM family, is a cytoskeletal protein and functions as a platform to form distinct protein complexes, thus participating in multiple physiological processes such as cytoskeleton regulation and synapse formation. Emerging evidence demonstrates that PDLIM1 is dysregualted in a variety of tumors and plays essential roles in tumor initiation and progression. In this review, we summarize the structure and function of PDLIM1, as well as its important roles in human cancers.

Sodium alginate/collagen/stromal cell-derived factor-1 neural scaffold loaded with BMSCs promotes neurological function recovery after traumatic brain injury.

Stem cell therapy is promising for neural repair in devastating traumatic brain injury (TBI). However, the low survival and differentiation rates of transplanted stem cells are main obstacles to efficient stem cell therapy in TBI. Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are key factors that regulate the survival, recruitment, and differentiation of stem cells. Herein, we synthesized a sodium alginate (SA)/collagen type I (Col)/SDF-1 hydrogel and investigated whether the SA/Col/SDF-1 hydrogel loaded with bone marrow-derived mesenchymal stem cells (BMSCs) had therapeutic effects on a TBI model. Our results showed that the SA/Col/SDF-1 scaffold could stably release SDF-1 and provide biocompatible and biodegradable microenvironment for the survival, migration, and neuronal differentiation of BMSCs in vitro. In a rat model of TBI, the SA/Col/SDF-1 hydrogel loaded with BMSCs significantly ameliorated motor and cognition dysfunction and relieved anxiety and depressive-like behaviors. In addition, the BMSCs/SA/Col/SDF-1 scaffold reduced brain lesions and neuronal cell death and mitigated neuroinflammation. Further studies demonstrated that the BMSCs/SA/Col/SDF-1 hydrogel promoted the migration of BMSCs in the lesions and partly enhanced neurogenesis by activating the SDF-1/CXCR4-mediated FAK/PI3K/AKT pathway. Taken together, our results indicate that the SA/Col/SDF-1 scaffold loaded with BMSCs exerts neuroreparative effects in a TBI rat model, and thus, it may serve as an alternative neural regeneration scaffold for brain injury repair. STATEMENT OF SIGNIFICANCE: Hydrogel facilitates the biological behaviors of transplanted stem cells for tissue regeneration. In this study, we synthesized sodium alginate (SA)/collagen type I (Col)/ scaffold to simultaneously deliver stromal cell derived factor-1 (SDF-1) and bone marrow mesenchymal stem cells (BMSCs) in a rat model of traumatic brain injury (TBI). We found that the SA/Col/SDF-1 hydrogel could continuously release SDF-1 and was conducive to the survival, migration and neuronal differentiation of BMSCs in vitro. In addition, the SA/Col/SDF-1 hydrogel loaded with BMSCs significantly ameliorated neurological deficits, mitigated neuroinflammation, promoted the recruitment of BMSCs and enhanced neurogenesis in TBI partly by activating the SDF-1/CXCR4-mediated FAK/PI3K/AKT pathway. Our results may serve as an alternative neural regeneration strategy for brain injury.

ROS1-fusion protein induces PD-L1 expression via MEK-ERK activation in non-small cell lung cancer.

Introduction: Despite some of the oncogenic driver mutations that have been associated with increased expression of programmed death-ligand 1 (PD-L1), the correlation between PD-L1 expression and ROS1 fusion in NSCLC cells, especially for those with Crizotinib resistance has not been fully addressed. Materials and Methods: The expression of PD-L1 in 30 primary NSCLC tumors with/without ROS1-fusion protein was evaluated by immunohistochemical (IHC) analysis. To assess the correlation between ROS1 fusion and PD-L1 expression, we down-regulated ROS1 with RNA interference or specific inhibitor (Crizotinib) in ROS1-fusion positive NSCLC cell line HCC78; or up-regulate ROS1-fusion gene in an immortalized human bronchial epithelial cell line (HBE). Mouse xenograft models were also used to determine the effect of ROS1 expression on PD-L1 expression in vivo. Crizotinib-resistant cell line was generated for measuring the association between Crizotinib resistance and PD-L1 expression. Results: ROS1-rearrangement in primary NSCLC tumor was significantly associated with up-regulated PD-L1 expression. PD-L1 expression was significantly up-regulated in bronchial epithelial cells after forced expression of ROS1 fusion and was eliminated when HCC78 xenograft mouse models were treated with Crizotinib. We found PD-L1 expression was modulated by MEK-ERK pathway signaling in both parental and Crizotinib-resistant NSCLC cells with ROS1 fusion. Conclusions: The correlation between ROS1-fusion and PD-L1 overexpression suggested that PD-L1/PD-1 blockade could be the second-line treatment option for the Crizotinib-resistant NSCLC with ROS1 rearrangement.

Twist1-induced miR-199a-3p promotes liver fibrosis by suppressing caveolin-2 and activating TGF-ß pathway.

The activation of hepatic stellate cells (HSCs) participates in liver fibrosis, and emerging evidences indicate that microRNAs (miRNAs) are abnormally expressed during HSC activation. However, the potential roles of miRNAs in liver fibrosis still remain elusive. Therefore, this study aimed to investigate the role of miR-199a-3p in liver fibrosis and its underlying mechanism. We found that miR-199a-3p expression was dramatically upregulated during HSC activation in vitro, and during liver fibrogenesis in CCl4-treated rats, and its liver expression was increased in the patients with cirrhosis. By the luciferase assay and RT-qPCR, we revealed that the expression of miR-199a-3p in HSCs was driven by the transcription factor Twist1 which could be further induced by TGF-ß treatment. Functional studies showed that inhibition of miR-199a-3p in both human LX2 cells and rat HSCs significantly decreased the expression of fibrotic markers, such as fibronectin and connective tissue growth factor (CTGF), whereas the forced expression of miR-199a-3p exhibited opposite effects, demonstrating the role of miR-199a-3p in promoting HSC activation. Mechanistically, miR-199a-3p plays an important role in TGF-ß signalling pathway activation through targeting CAV2 that negatively regulates the expression of transforming growth factor-beta receptor type I (TGFßRI). Importantly, administration of antagomiR-199a-3p in the CCl4-treated mice significantly ameliorated hepatic fibrosis. In conclusion, Twist1-induced miR-199a-3p mediates the activation of HSCs by suppressing CAV2 expression and subsequently increasing TGFßRI expression to promote TGF-ß pathway. Our findings highlight the therapeutic potential of miR-199a-3p for hepatic fibrosis.

The role of long noncoding RNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. However, the molecular mechanisms underlying HCC pathogenesis have not been fully understood. Emerging evidences have recently suggested the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of HCC. Various HCC-related lncRNAs have been shown to possess aberrant expression and participate in cancerous phenotypes (e.g. persistent proliferation, evading apoptosis, accelerated vessel formation and gain of invasive capability) through their binding with DNA, RNA or proteins, or encoding small peptides. Thus, a deeper understanding of lncRNA dysregulation would provide new insights into HCC pathogenesis and novel tools for the early diagnosis and treatment of HCC. In this review, we summarize the dysregulation of lncRNAs expression in HCC and their tumor suppressive or oncogenic roles during HCC tumorigenesis. Moreover, we discuss the diagnostic and therapeutic potentials of lncRNAs in HCC.

PDLIM1 Inhibits Tumor Metastasis Through Activating Hippo Signaling in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. We report that PDZ and LIM domain protein 1 (PDLIM1) is significantly down-regulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis. APPROACH AND RESULTS: Functional studies indicate that PDLIM1 knockdown induces epithelial-to-mesenchymal transition (EMT) of HCC cells, elevates their invasive capacity, and promotes metastasis in vitro and in vivo, whereas overexpression of PDLIM1 exhibits opposite phenotypes. Mechanistically, PDLIM1 competitively binds to the cytoskeleton cross-linking protein alpha-actinin 4 (ACTN4), leading to the disassociation of ACTN4 from F-actin, thus preventing F-actin overgrowth. In contrast, loss of PDLIM1 induces excessive F-actin formation, resulting in dephosphorylation of large tumor suppressor kinase 1 and activation of Yes-associated protein, thereby promoting HCC metastasis. Moreover, Asn145 (N145) of PDLIM1 is critical for its interaction with ACTN4, and N145A mutation abolishes its regulatory function in Hippo signaling and HCC metastasis. CONCLUSIONS: Our findings indicate that PDLIM1 suppresses HCC metastasis by modulating Hippo signaling, suggesting that PDLIM1 may be a potential prognostic marker for metastatic HCC.

Manufacture of the compact conical diffraction Offner hyperspectral imaging spectrometer.

The conical diffraction Offner hyperspectral imaging spectrometer (CDO-HIS) is a hyperspectral calibrator for monitoring the radiation stability of an ocean color sensor. The spectrometer adopts the structure of the conical diffraction Offner configuration (CDO-CF), containing a convex blazed grating to produce a nearly nondistortion and high spectral fidelity image. The theory analysis of the conical diffraction Offner is discussed and introduced to the instrument design. The optimization procedure and design results of CDO-HIS and the conical diffraction grating are provided based on the design ideas, which show benefits of the employment of CDO-CF. The results of laboratory characterization are presented, including the grating diffraction efficiency and the instrument performance.

Corrigendum: HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K/AKT Pathway.

[This corrects the article DOI: 10.3389/fncel.2018.00498.].

Circular RNA F-circSR derived from SLC34A2-ROS1 fusion gene promotes cell migration in non-small cell lung cancer.

Cancer-associated chromosomal translocations are reported to generate oncogenic circular RNA (circRNA), contributing to tumorigenesis. The fusion gene SLC34A2-ROS1 (solute carrier family 34 member 2 and ROS proto-oncogene 1) plays an important role in non-small cell lung cancer (NSCLC) progression. However, whether SLC34A2-ROS1 gene can produce circRNA remains unknown. Here, we identified two novel circRNAs (F-circSR1 and F-circSR2) generated from SLC34A2-ROS1 fusion gene, while F-circSR1 has higher expression than F-circSR2. Functional studies through gain- and loss-of-function strategies showed that both F-circSRs promote cell migration in lung cancer cells, whereas they have little effect on cell proliferation. Using the minigene GFP reporter assay, we verified that the flanking complementary sequences with canonical splicing sites are essential for F-circSR biogenesis. Therefore, our findings demonstrate the oncogenic role of F-circSR in NSCLC and highlight its therapeutic potential.

Histone deacetylases inhibitor MS-275 suppresses human esophageal squamous cell carcinoma cell growth and progression via the PI3K/Akt/mTOR pathway.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with low survival rate, so new therapies are urgently needed. Histone deacetylases (HDACs) play a critical role in tumorigenesis, and HDACs inhibition is a potential therapeutic target in ESSC. In our study, we evaluated the effect and molecular mechanism of MS-275 (an inhibitor of HDACs) on ESCC cells. We found that HDAC1 and HDAC2 were overexpressed in ESCC tissues and related with clinical pathological features of patients with ESCC. MS-275 markedly reduced HDAC1 and HDAC2 expression, whereas increased the level of AcH3 and AcH2B. MS-275 suppressed proliferation and clonogenicity of ESCC cells in a concentration-dependent manner. In addition, MS-275 induced apoptosis, arrested cell cycle, and inhibited migration, epithelial-mesenchymal transition, and sphere-forming ability of ESCC cells in vitro. Moreover, p-Akt1 and p-mTOR were downregulated by MS-275. Finally, MS-275 significantly inhibited tumor growth in vivo. Taken together, HDAC1 and HDAC2 are associated with the progression of ESCC, and MS-275 hinders the progression and stemness of ESCC cells by suppressing the PI3K/Akt/mTOR pathway. Our findings show that MS-275 inhibits ESCC cells growth in vitro and in vivo, which is a potential drug for the ESCC therapy.

Novel ROR1 inhibitor ARI-1 suppresses the development of non-small cell lung cancer.

Limited drug response and severe drug resistance confer the high mortality of non-small-cell lung cancer (NSCLC), a leading cause of cancer death worldwide. There is an urgent need for novel treatment against NSCLC. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is aberrantly overexpressed and participats in NSCLC development and EGFR-TKIs-induced drug resistance. Increasing evidences indicate that oncogenic ROR1 is a potential target for NSCLC therapy. However, nearly no ROR1 inhibitor was reported until now. Here, combining the computer-aided drug design and cell-based activity screening, we discover (R)-5,7-bis(methoxymethoxy)-2-(4-methoxyphenyl)chroman-4-one (ARI-1) as a novel ROR1 inhibitor. Biological evaluation demonstrates that ARI-1 specifically targets the extracellular frizzled domain of ROR1 and potently suppresses NSCLC cell proliferation and migration by regulating PI3K/AKT/mTOR signaling in a ROR1-dependent manner. Moreover, ARI-1 significantly inhibits tumor growth in vivo without obvious toxicity. Intriguingly, ARI-1 is effective to EGFR-TKIs-resistant NSCLC cells with high ROR1 expression. Therefore, our work suggests that the ROR1 inhibitor ARI-1 is a novel drug candidate for NSCLC treatment, especially for EGFR-TKIs-resisted NSCLC with high ROR1 expression.