Knockdown of Anoikis-Associated Gene OCIAD2 Reduces Proliferation and Migration of Glioblastoma Cell Lines.

BACKGROUND: Glioblastoma (GBM) severely disrupts the quality of life of patients. Anoikis represents a significant mechanism in cancer invasion and metastasis. Our study focused on the prognostic relationship between the anoikis-associated gene and GBM and its effect on GBM cell progression. METHODS: We downloaded 656 and 979 GBM sample data from TCGA and CGGA cohort datasets, respectively. Fifteen anoikis-associated genes were obtained from the GeneCards database and were subsequently clustered to identify differential genes associated with them. After LAASO screening, the expression values of the 5 differential genes were the sum of LASSO regression coefficients. Survival analysis and ROC curve analysis of anoikis scores were performed using the TCGA training and CGGA validation sets. The prognostic factors were analyzed using Cox regression analysis in GBM. Moreover, CCK-8, colony formation, wound healing, and transwell assay were used to evaluate GBM cell proliferation and migration. RESULTS: Significant differences were observed in the 5-year survival of GBM patients between the two subgroups. Then, our analysis demonstrated that high OCIAD2, FTLP3, IGFBP2, and H19 levels were associated with lower 5-year GBM survival rates, whereas high SFRP2 levels were associated with higher survival rates. Univariate Cox analysis indicated that GBM risk was linked to both anoikis score and grade, while multivariate Cox analysis indicated that GBM risk was associated with both anoikis score and age. Additionally, OCIAD2 was highly expressed in U251MG and T98G cells. Moreover, OCIAD2 silencing inhibited GBM cell proliferation and migration. CONCLUSION: This study demonstrated the potential of the anoikis-associated gene OCIAD2 as a prognostic biomarker for GBM. Furthermore, we validated in vitro that OCIAD2 promoted GBM cell progression.

Explorative Study on Volatile Organic Compounds of Cinnamon Based on GC-IMS.

Cinnamon is one of the most popular spices worldwide, and volatile organic compounds (VOCs) are its main metabolic products. The misuse or mixing of cinnamon on the market is quite serious. This study used gas chromatography-ion migration spectroscopy (GC-IMS) technology to analyze the VOCs of cinnamon samples. The measurement results showed that 66 VOCs were detected in cinnamon, with terpenes being the main component accounting for 45.45%, followed by aldehydes accounting for 21.21%. The content of esters and aldehydes was higher in RG-01, RG-02, and RG-04; the content of alcohols was higher in RG-01; and the content of ketones was higher in RG-02. Principal component analysis, cluster analysis, and partial least squares regression analysis can be performed on the obtained data to clearly distinguish cinnamon. According to the VIP results of PLS-DA, 1-Hexanol, 2-heptanone, ethanol, and other substances are the main volatile substances that distinguish cinnamon. This study combined GC-IMS technology with chemometrics to accurately identify cinnamon samples, providing scientific guidance for the efficient utilization of cinnamon. At the same time, this study is of great significance for improving the relevant quality standards of spices and guiding the safe use of spices.

A Non-targeted Metabolomics Reveals Therapeutical Effect and Mechanism of Sanmiao Pill on Adjuvant-induced Arthritis Rats.

BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is an increasingly serious disease worldwide that can damage the joints and bones of sufferers. Sanmiao Pill (SMP), a classical traditional Chinese medicine (TCM) prescription, has been used for effective treatments for RA in the clinic. To comprehensively illuminate the therapeutic mechanism of SMP in the treatment of RA, the effects of SMP on biomarkers and metabolic pathways in rats with adjuvant-induced arthritis (AIA) were examined. > Methods: Sprague Dawley rats were randomly divided into two control (CC, Control) groups, two model (MM, Model) groups, a methotrexate group (MTX, 7.6 mg/kg body weight per week), and two SMP groups (San-L, 28.7 mg/kg body weight per day and San-H, 57.4 mg/kg body weight per day). Rats' body weight, paw swelling, arthritis scores, biochemical parameters, histopathology, and so on were used to evaluate the success of the model and the therapeutic effects of SMP. The metabolic techniques were used to characterize the metabolic profile and biomarkers of the serum and urine samples of rats to reveal the metabolic changes that occurred after SMP treatment. > Results: After 21 days of treatment, SMP improved weight gain, reduced the severity of paw swelling, lowered the levels of biochemical indicators (CCP-Ab, IL-6, TNF-α, RF), decreased destruction of articular cartilage and bone erosion, and protected the affected joints.Additionally, 17 and 19 potential biomarkers associated with RA were identified in the serum and urine, respectively. SMP significantly reversed 14 potential biomarkers, such as arachidonic acid, lysoPC(20:4(5Z,8Z,11Z,14Z)), L-tryptophan, 9-cis-Retinoic acid, hippuric acid, pyridoxine, and pantothenic acid. These metabolites are associated with arachidonic acid metabolism, glycerophospholipid catabolism, tryptophan metabolism, phenylalanine metabolism, vitamin B6 metabolism, etc. > Conclusion: These results indicated that RA-related biomarkers reflected the metabolic profile of AIA rats. Meanwhile, SMP could effectively treat RA mainly by reducing inflammation and regulating abnormal lipid metabolic pathways and amino acid metabolisms. It showed that metabolomics could be used to analyze the metabolic profiles involved in RA and reveal the mechanism of SMP treatment of RA.>.

High throughput metabolomics explores the mechanism of Jigucao capsules in treating Yanghuang syndrome rats using ultra-performance liquid chromatography quadrupole time of flight coupled with mass spectrometry.

To explore the potential mechanism of the Chinese patent medicine Jigucao capsule in treating the serum metabolic profile of rats with Yanghuang syndrome, zingiber officinale Rosc. and ethanol simulates the syndrome background of traditional Chinese medicine and uses α-naphthyl isothiocyanate to induce liver damage in rats to prepare a Yanghuang syndrome model. The histopathological observation and the determination of biochemical indexes evaluate the therapeutic effect of the Jigucao capsule, and the metabolomic method analyzes the mechanism of the Jigucao capsule against Yanghuang syndrome. Jigucao capsule reduces the number of inflammatory cells, inhibits the proliferation of bile duct epithelial cells and hepatocyte necrosis. Compared with Yanghuang syndrome rats, the levels of alanine aminotransferase, alkaline phosphatase, and total bile acid were significantly reduced (P < 0.05). Furthermore, Jigucao capsule significantly reversed the abnormal levels of glucose 1-phosphate, phenylalanyl-cysteine, taurodeoxycholic acid, lysoPC (22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z), lysoPC (15:0), lysoPC (P-18:0), 7alpha-hydroxy-3-oxo-4-cholestenoate and 15(S)-hydroxyeicosatrieic acid and regulated part of the lipid metabolism and carbohydrate metabolism, Jigucao capsule has a therapeutic effect on Yanghuang syndrome rats. In short, this study sets for the first time elaborated on the underlying mechanism of Jigucao capsule resistance to Yanghuang syndrome rats from a metabolomics perspective, providing the basic data for the pharmacodynamic studies of the Jigucao capsule.

Metabolomics Analysis Coupled With UPLC/MS on Therapeutic Effect of Jigucao Capsule Against Dampness-Heat Jaundice Syndrome.

Dampness-heat Jaundice Syndrome (DHJS) is a complex Chinese medicine syndrome, while Jigucao capsule (JGCC) is an effective compound preparation of Chinese medicine for the treatment of DHJS about liver and gallbladder, but its mechanism is not clear yet. The purpose of this study is to clarify the pathogenesis of DHJS and the treatment mechanism of JGCC. We used ultra-high performance liquid chromatography/mass spectrometry (UPLC/MS) combined with pattern recognition, accompanied the advanced software and online database for the urine metabolomics of rats. The potential biomarkers disturbing metabolism were identified and the metabolic pathway was analyzed. We investigated the callback of biomarkers after treatment with JGCC. Finally, A total of 25 potential urine biomarkers were identified, including Arachidonic acid, Phenylpyruvic acid, L-Urobilin and so on, and 14 related metabolic pathways were disturbed. After treatment with JGCC, the clinical biochemical indexes and histopathological were significantly improved, and the disturbed biomarkers were also obviously adjusted. It is proved that JGCC has remarkable effect on the treatment of DHJS.

Rapid characterization of the constituents in Jigucao capsule using ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Jigucao capsule is a well-known Chinese patent medicine for the treatment of acute and chronic hepatitis and cholecystitis. The chemical components of Jigucao capsule were not clear resulting from the paucity of relevant studies, which hindered the research of the pharmacological mechanism, the comprehensive development, and utilization of Jigucao capsule in clinical studies. By establishing a high-throughput ultra-performance liquid chromatography quadrupole time of flight mass spectrometry in combination with intelligent UNIFI software data processing platform to automatically characterize and identify the chemical profile of Jigucao capsule, 144 compounds were determined rapidly, including 34 terpenoids, 25 flavonoids, 22 steroids, 21 phenylpropanoids, 10 glycosides, six alkaloids, 13 organic acids, and other 13 components. These compounds may be the active components of Jigucao capsule. In this study, a rapid and robust method for comprehensively analyzing the chemical composition of Jigucao capsule was described and established for the first time. The results will provide a reference for the quality control of Jigucao capsule and the establishment of a higher quality standard, as well as for the pharmacodynamic material basis research.

Efficacy of berberine in treatment of rheumatoid arthritis: From multiple targets to therapeutic potential.

Rheumatoid arthritis is a systemic autoimmune disorder involved in persistent synovial inflammation. Berberine is a nature-derived alkaloid compound with multiple pharmacological activities in different pathologies, including RA. Recent experimental studies have clarified several determinant cellular and molecular targets of BBR in RA, and provided novel evidence supporting the promising therapeutic potential of BBR to combat RA. In this review, we recapitulate the therapeutic potential of BBR and its mechanism of action in ameliorating RA, and discuss the modulation of gut microbiota by BBR during RA. Collectively, BBR might be a promising lead drug with multi-functional activities for the therapeutic strategy of RA.

The Efficacy of Natural Bioactive Compounds for the Treatment of Nasopharyngeal Carcinoma.

The death toll associated with cancer worldwide is constantly on the increase. Efforts to combat and treat the different forms of this disease is also evolving. Nasopharyngeal carcinoma (NPC) is a lethal form of cancer, which is prevalent in Southern China, that is normally treated by using radiotherapy. Here, we will review products obtained from natural sources that have potential cytotoxic and apoptotic properties against NPC. These include grifolin, dihydroartemisinin, luteolin, honokiol, indole-3-carbinol, caffeic acid phenethyl ester, 6-O-angeloylenolin, cucurbitacin E, genistein, helenalin, celastrol, coronarin D, quercetin, trans-cinnamaldehyde, 5'-epimer episilvestrol, silvestrol, arnicolide D, brevilin A, and baicalin hydrate. Ethyl acetate extracts of Wedelia chinensis and aqueous extracts of Ajuga bracteosa are also included although the bioactive compounds involved have yet to be identified. The known mechanism of action of these products is discussed. It is anticipated that one or more of these substances may provide the general population with alternative and cost-effective ways to combat this fatal disease.

[The effect of Yiqi Wenyang Huoxue Huatan Fang on hypoxia-hypercarbia induced pulmonary hypertension and its mechanism].

OBJECTIVE: To investigate the effect of Yiqi Wenyang Huoxue Huatan Fang (YWHHF) on alleviating hypoxia-hypercarbia pulmonary hypertension by inhibiting endothelial-mesenchymal transition (EndoMT) via BMP-7/Smads pathway. METHODS: Fifty male healthy SD rats of clean grede, weighting (180~220) g, were randomly divided into 5 groups (n=10):normoxia group (N), hypoxia-hypercarbia group (HH); YWHHF high dose group (YH), middle dose group (YM) and low dose group (YL). The rats in N group were kept in normal oxygen environment, the remaining four groups were intermittently exposed to hypoxia-hypercarbia environment (9%~11% O2, 5%~6% CO2) for 4 weeks, 6 days a week, 8 hours per day. The rats in YH, YM, YL groups were received YWHHF gavage in a dosageof 0.6, 0.3, 0.15g/kg respectively (3 ml/kg),the rats in N and HH groups were received equal volume of normal saline. After 4 weeks, the mean pulmonary arterial pressure(mPAP) was detected,the right ventricular free wall and left ventricle plus ventricular septum were isolated to determine the right ventricular hypertrophy index. Lung ultrastructural changes were surveyed under an electronic microscopy, the changes of pulmonary artery structure surveyed by immunofluorescence, the mRNA levels of alpha-smooth muscle actin (α-SMA)、platelet endothelial cell adhesion molecule-1 (CD31)、bone morphogenetic protein-7 (BMP-7)、drosophila mothers against decapentaplegic protein1/5/8 (Smad1/5/8) were detected by RT-PCR, and the protein levels of α-SMA、CD31、BMP-7、p-Smad1/5/8 and Smad1/5/8 were detected by Western blot. RESULTS: Compared with N group, mPAP and the right ventricular hypertrophy index were increased,some significant injuries also were discovered under microscopic observation,the mRNA and protein expression of α-SMA was increased, and the mRNA expressions of CD31、BMP-7、Smad1/5/8 were decreased in the other four groups, the protein expressions of CD31、BMP-7、p-Smad1/5/8 were decreased(P<0.05). Compared with HH group, the above changes in YH、YM、YL groups were all improved (P<0.05). CONCLUSIONS: YWHHF can inhibit EndoMT to alleviate pulmonary hypertension, and the mechanism may be related to the promotion of the expression of BMP-7/Smads pathway.

The nematocysts venom of Chrysaora helvola Brandt leads to apoptosis-like cell death accompanied by uncoupling of oxidative phosphorylation.

The present work investigated the effects of the nematocysts venom (NV) from the Chrysaora helvola Brandt (C. helvola) jellyfish on the human nasopharyngeal carcinoma cell line, CNE-2. The medium lethal concentration (LC50), quantified by MTT assays, was 1.7 ± 0.53 µg/mL (n = 5). An atypical apoptosis-like cell death was confirmed by LDH release assay and Annexin V-FITC/PI staining-based flow cytometry. Interestingly, activation of caspase-4 other than caspase-3, -8, -9 and -1 was observed. Moreover, the NV stimuli caused a time-dependent loss of mitochondrial membrane potential (ΔΨm) as was an intracellular ROS burst. These results indicated that there was uncoupling of oxidative phosphorylation (UOP). An examination of the intracellular pH value by a pH-sensitive fluorescent probe, BCECF, suggested that the UOP was due to the time-dependent increase in the intracellular pH. This is the first report that jellyfish venom can induce UOP.

Studies on cellulase-ultrasonic assisted extraction technology for flavonoids from Illicium verum residues.

BACKGROUND: Illicium verum is widely cultivated in southern China especially in Guangxi province. Its fruits has been traditionally used in Chinese medicine. In recent years, it has been the industrial source of shikimic acid. Usually the residues after extracting shikimic acid are treated as waste. Thus, the aim of this study was to optimize the extraction conditions of cellulase-ultrasonic assisted extraction technology for flavonoids from I. verum residues. RESULTS: The optimum extraction conditions with a maximum flavonoids yield of 14.76 % are as follows: the concentration of ethanol is 51.14 %, the liquid-solid ratio is 20.52 mL/g, the enzymatic hydrolysis pH is 5.303, the sonication time is 60 min, the enzyme solution temperature is kept at 45 °C, the amount of added enzyme is 70 mg/g, the enzymatic hydrolysis time is 2 h and the crushed mesh size is 0.355-0.85 mm. CONCLUSIONS: The data indicate that the cellulase-ultrasonic assisted extraction technology has the potential be used for the industrial production of flavonoids from I. verum.