Anthocyanins degradation mediated by ß-glycosidase contributes to the color loss during alcoholic fermentation in a structure-dependent manner.

Anthocyanins deteriorate during fermentation to varying degrees depending on the structure of the anthocyanin, thus affecting the sensory quality of the wine, and the degradation of anthocyanins is closely associated with the ß-glycosidase. In this study, the alcoholic fermentation systems containing cyanidin-3-O-glucoside (C3G), peonidin-3-O-glucoside (Pn3G), delphinidin-3-O-glucoside (D3G), petunidin-3-O-glucoside (Pt3G), and malvidin-3-O-glucoside (M3G) incubated for eight days. Our results indicated that the color of the systems containing different anthocyanins saw significant and dissimilar changes during fermentation, in relation to anthocyanin degradation. The five anthocyanins showed varying degradation degrees, which are relevant to theß-glycosidase produced by yeast. Enzyme kinetics and molecular docking analysis showed the affinity between anthocyanins and ß-glucosidase: C3G < M3G < Pn3G < Pt3G < D3G. This study demonstrated that ß-glycosidase had distinct effects on anthocyanins with diverse structures, resulting in different color changes in fermentation systems. It provided a potential strategy for sensory quality improvement during the fermentation of fruit wines rich in anthocyanins.

MiR-29a-3p Inhibits Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells via Targeting FOXO3 and Repressing Wnt/ß-Catenin Signaling in Steroid-Associated Osteonecrosis.

Background and Objectives: This study was to investigate the role of microRNA-29a-3p (miR-29a-3p) in human bone marrow mesenchymal stem cells (hBMSCs), and its relationship with steroid-associated osteonecrosis. Methods and Results: The online tool GEO2R was used to screen out the differentially expressed genes (DEGs) in GSE123568 dataset. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-29a-3p, forkhead box O3 (FOXO3), alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (OCN) and RUNX family transcription factor 2 (Runx2) in the hBMSCs isolated from the patients with steroid- associated osteonecrosis. CCK-8 assay was executed to measure cell viability; western blot assay was utilized to detect FOXO3, ALP, Runx2, OCN and ß-catenin expression. Cell apoptosis and cell cycle were detected by flow cytometry. Immunofluorescence assay was used to detect the sub-cellular localization of ß-catenin. Bioinformatics analysis and luciferase reporter gene assay were performed to confirm whether miR-29a-3p can combine with FOXO3 3'UTR. MiR-29a-3p was markedly up-regulated in the hBMSCs of patients with steroid-associated osteonecrosis, while FOXO3 mRNA was significantly down-regulated. Transfection of miR-29a-3p mimics significantly inhibited the hBMSCs' proliferation, osteogenic differentiation markers' expressions, including ALP, Runx2, OCN, and repressed the ALP activity, as well as promoted cell apoptosis and cell-cycle arrest. FOXO3 was identified as a target gene of miR-29a-3p, and miR-29a-3p can inhibit the expression of FOXO3 and ß-catenin, and inhibition of miR-29a-3p promoted translocation of ß-catenin to the nucleus. Conclusions: MiR-29a-3p can modulate FOXO3 expression and Wnt/ß-catenin signaling to inhibit viability and osteogenic differentiation of hBMSCs, thereby promoting the development of steroid-associated osteonecrosis.

Quantitative Evaluation of the Trauma of CT Navigation PELD and OD in the Treatment of HLDH: A Randomized, Controlled Study.

BACKGROUND: More evidence is required to support that computerized tomography navigation percutaneous spinal endoscopy in the treatment of highly migrated lumbar disc herniation is a more minimally invasive surgery than open discectomy . OBJECTIVE: To quantitatively evaluate the efficacy and minimal invasiveness of computerized tomography navigation percutaneous spinal endoscopy and open discectomy in highly migrated lumbar disc herniation. STUDY DESIGN: A prospective randomized study. SETTING: First Affiliated Hospital of Gannan Medical College. METHODS: From August 2016 to February 2020, 68 patients with highly migrated lumbar disc herniation had undergone discectomy. Thirty-five of them randomly received computerized tomography (CT) navigation percutaneous spinal endoscopy at the pain department (CT navigation percutaneous spinal endoscopy group), and 33 patients received open discectomy at the orthopedics department (open discectomy group). The Visual Analog Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and modified MacNab criteria were applied to evaluate the clinical situations pre- and post-operation. The serum concentrations of IL-6, TNF-alpha, creatine phosphokina (CPK), and C-reactive protein (CRP) in the 2 groups were quantitatively measured. RESULTS: The postoperative VAS scores of the back and lower extremity were lower than those pre-operation in both groups, while the VAS score of back pain in the open discectomy group was significantly higher than that in the CT navigation percutaneous spinal endoscopy group at one week post-operation (P < 0.01). The postoperative JOA scores were significantly higher than those pre-operation in both groups. The serum concentrations of IL-6, TNF-alpha, CPK, and CRP in the open discectomy group were higher than those in the computerized tomography navigation percutaneous spinal endoscopy group postoperatively (P < 0.01). LIMITATIONS: This is a single-center randomized study and with the limitation of the sample size. CONCLUSION: CT navigation percutaneous spinal endoscopy is a more minimally invasive surgery than open discectomy.Certificate number for the medical institution conducting the clinical trials for humans in China: 934.

Development of a novel intraarticular injection of diclofenac for the treatment of arthritis: a preclinical study in the rabbit model.

PURPOSE: To develop a novel intraarticular injection of diclofenac for the treatment of arthritis. METHOD: Diclofenac loaded nanoparticles were prepared by a nanoprecipitation technique using Eudragit L 100 as the polymer and polyvinyl alcohol as the surfactant. The nanoparticles were evaluated for particle size, zeta potential, scanning electron microscopy, drug release, encapsulation efficiency, and loading efficiency studies. The optimized nanoparticulate formulation was developed for intra articular injection. Intraarticulate injection was evaluated for pH, appearance, viscosity, osmolarity and syringability studies. The optimized injection formulation was tested in an arthritic model consisting of 25 rabbits. RESULT: Nanoprecipitation method was found to be suitable for diclofenac nanoparticles. The shape of the prepared nanoparticles was found to be spherical and devoid of any cracks and crevices. The average particle size of a diclofenac nanoparticle was found to range from 87±0.47 to 103±0.26 nm. The zeta potential of the prepared nanoparticles was found to be in the range of 0.598±0.34 to 0.826±0.25 mV. The encapsulation efficiency was found to be between 73.45% to 99.03%, while the drug loading was observed between 10.34 to 35.32%. The percentage drug release at 12 hours was found to range from 73.45% to 99.03%. CONCLUSION: The developed intraarticular injection was found to be within the physically and chemically accepted limits. Animals treated with the intra articular injection of diclofenac showed a significant reduction in swelling as compares to the other groups.

FBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivo.

BACKGROUNDS: A number of circular RNAs (circRNAs) have been identified in various cancer including F-box and WD repeat domain containing 7 (FBXW7) circular RNA (circ-FBXW7), which can suppress glioma cell growth. However, the role of circ-FBXW7 in colorectal cancer (CRC) remains unclear. We aimed to investigate the effect and mechanisms of circ-FBXW7 on CRC progression. METHODS: The expression of circ-FBXW7 in CRC patients was detected by PCR. Stably knockdown of circ-FBXW7 (si circ-FBXW7) cell lines and overexpression of circ-FBXW7 (oe circ-FBXW7) cell lines were constructed by small interfering RNA method and plasmids transfection in CRC SW480 and SW620 cells. The functional experiments including cell proliferation, migration and invasion were carried out by cell counting kit-8 (CCK-8) assay, wound healing assay and trans well assay. The xenograft animal models were established to evaluate the effect and the underlying molecular mechanisms of circ-FBXW7 on CRC progression. RESULTS: CRC samples had a significantly lower level of circ-FBXW7 compared to normal tissue. si circ-FBXW7 notably promoted the proliferation, colony formation, cell migration and invasion of CRC cell in vitro. On contrast, circ-FBXW7 overexpressed significantly suppressed CRC cell proliferation, migration and invasion. Similarly, si circ-FBXW7 stimulated the tumor growth and circ-FBXW7 overexpression repressed the tumor progression in SW480 and SW620 tumor models, which suggested that circ-FBXW7 could serve as a target biomarker of CRC. Further study found that si circ-FBXW7 up-regulated the mRNA and protein expressions of NEK2 and mTOR, and diminished the PTEN expression. Whereas, overexpressed circ-FBXW7 induced the tumor suppression via reversing the expressions of NEK2, mTOR, and PTEN. CONCLUSION: circ-FBXW7 plays a major role in controlling the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and may be a potential therapeutic target for CRC treatment. Circ-FBXW7 controls the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and its overexpression inhibits colorectal cancer cell migration and invasion, suggesting the potential therapeutic target for CRC treatment.

Long-term Follow-up of Patients Treated with Percutaneous Radiofrequency Thermocoagulation via the Foramen Rotundum for Isolated Maxillary Nerve Idiopathic Trigeminal Neuralgia.

OBJECTIVE: The purpose of this study is to evaluate the effectiveness and safety of percutaneous radiofrequency thermocoagulation (PRT) via the foramen rotundum (FR) for the treatment of isolated maxillary (V2) idiopathic trigeminal neuralgia (ITN) and assess the appropriate puncture angle through the anterior coronoid process to reach the FR. METHODS: Between January 2011 and October 2016, 87 patients with V2 ITN refractory to conservative treatment were treated by computed tomography (CT)-guided PRT via the FR at our institution. The outcome of pain relief was assessed by the visual analog scale (VAS) and Barrow Neurological Institute (BNI) pain grade and grouped as complete pain relief (BNI grades I-III) or unsuccessful pain relief (BNI grades IV-V). Recurrence and complications were also monitored and recorded. The puncture angle for this novel approach was assessed based on intraoperative CT images. RESULTS: Of the 87 treated patients, 85 (97.7%) achieved complete pain relief, and two patients (2.3%) experienced unsuccessful pain relief immediately after operation. During the mean follow-up period of 44.3 months, 15 patients (17.2%) experienced recurring pain. No severe complications occurred, except for hypoesthesia restricted to the V2 distribution in all patients (100%) and facial hematoma in 10 patients (11.5%). The mean puncture angle to reach the FR was 33.6° ± 5.7° toward the sagittal plane. DISCUSSION: CT-guided PRT via the FR for refractory isolated V2 ITN is effective and safe and could be a rational therapy for patients with V2 ITN.

MiR-552 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells by inhibiting AJAP1 expression.

Our goal was to explore the function of miR-552 and its potential target AJAP1 in hepatocellular carcinoma (HCC) oncogenesis and progression. In this study, bioinformatics analysis was performed to detect abnormally expressed miRNAs. The relationship between miR-552 and AJAP1 was validated using luciferase reporter assays. RT-qPCR and Western blot assays were applied to explore the expression level of miR-552, AJAP1 and epithelial-mesenchymal transition (EMT) markers. HCC cell proliferation was examined using CCK8 assays, while migration and invasion were investigated using Transwell assays. Nude mouse tumourigenesis models were established to facilitate observation of HCC progression in vivo. Finally, prognostic analysis was performed to discover how the prognosis of HCC patients correlated with miR-552 and AJAP1 expression. MiR-552 overexpression in HCC cells promoted HCC cell migration, invasion and EMT by targeting/suppressing AJAP1. Poorer prognosis appeared in HCC patients with higher miR-552 expression or lower AJAP1 levels. Our findings suggested that miR-552 promotes HCC oncogenesis and progression by inhibiting AJAP1 expression.

Heteroplasmy and Copy Number Variations of Mitochondria in 88 Hepatocellular Carcinoma Individuals.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. In this study, we had analysed the copy number variations and heteroplasmic mutations of mitochondria (MT) in 88 HCC individuals. The average copy number of MT genome in normal samples was significantly greater than that in tumor samples. Overall, the number of heteroplasmic mutations in 88 tumor and their matched normal samples were 241 and 173, respectively. There was higher positive ratio of heteroplasmic mutations in tumor samples (86%) than normal samples (73%). Worthwhile mention, ND1 gene harbored greater mutation frequency and more nonsynonymous mutations in tumor samples. Interestingly, 202 tumor-specific heteroplasmic mutations were detected. Moreover, ND1, ND3, ND4, ND5 and ND6 genes had higher ratio of nonsynonymous versus synonymous mutations in tumor-specific heteroplasmic mutations. It might suggest that the disorder of NADH dehydrogenase (complex I) resulted by heteroplasmic mutations may have close relation with tumorigenesis of hepatocellular carcinoma. This study provided theoretical basis for further understanding mechanism of tumorigenesis from the perspective of mitochondrial heteroplasmic mutations.

Outcome of gallbladder preservation in surgical management of primary bile duct stones.

AIM: To evaluate the methods and outcome of gallbladder preservation in surgical treatment of primary bile duct stones. METHODS: Thirty-five patients with primary bile duct stones and intact gallbladders received stone extraction by two operative approaches, 23 done through the intrahepatic duct stump (RBD-IDS, the RBD-IDS group) after partial hepatectomy and 12 through the hepatic parenchyma by retrograde puncture (RBD-RP, the RBD-RP group). The gallbladders were preserved and the common bile duct (CBD) incisions were primarily closed. The patients were examined postoperatively by direct cholangiography and followed up by ultrasonography once every six months. RESULTS: In the RBD-IDS group, residual bile duct stones were found in three patients, which were cleared by a combination of fibrocholedochoscopic extraction and lithotripsy through the drainage tracts. The tubes were removed on postoperative day 22 (range: 16-42 days). In the RBD-RP group, one patient developed hemobilia and was cured by conservative therapy. The tubes were removed on postoperative day 8 (range: 7-11 days). Postoperative cholangiography showed that all the gallbladders were well opacified, contractile and smooth. During 54 (range: 6-120 months) months of follow-up, six patients had mildly thickened cholecystic walls without related symptoms and further changes, two underwent laparotomies because of adhesive intestinal obstruction and gastric cancer respectively, three died of cardiopulmonary diseases. No stones were found in all the preserved gallbladders. CONCLUSION: The intact gallbladders preserved after surgical extraction of primary bile duct stones will not develop gallstones. Retrograde biliary drainage is an optimal approach for gallbladder preservation.