CircRNA SEC24A promotes osteoarthritis through miR-107-5p/CASP3 axis.

Background: Osteoarthritis (OA) is the most frequently diagnosed chronic joint disease. CircSEC24A is significantly elevated in OA chondrocytes upon IL-1ß stimulation. However, its biological function in OA is still not fully understood. Methods: The circRNAs-miRNA-mRNA network was predicted by bioinformatics analysis. An in vitro OA chondrocytes model was established by IL-1ß stimulation. The expression of circSEC24A, miR-107-5p, CASP3, apoptosis-related molecules and extracellular matrix (ECM) components were detected by Western blot and qRT-PCR. MTT assay and Annexin V/PI staining were employed to monitor cell viability and apoptosis, respectively. The interaction between circSEC24A and miR-107-5p, as well as the binding between miR-107-5p and CASP3 3' UTR were detected by luciferase reporter and RIP assays. Cytokine secretion was monitored by ELISA assay. The role of circSEC24A was also explored in anterior cruciate ligament transection (ACLT) rat models. Results: CircSEC24A and CASP3 were increased, but miR-107-5p was decreased in rat OA cartilage tissues and OA chondrocytes. CircSEC24A acted as a sponge of miR-107-5p. Knockdown of circSEC24A promoted chondrocyte proliferation, but suppressed chondrocyte apoptosis, ECM degradation and inflammation via sponging miR-107-5p. CASP3 was identified as a miR-107-5p target gene. MiR-107-5p mimics protected against OA progression via targeting CASP3. Silencing of circSEC24A alleviated OA progression in ACLT model. Conclusion: CircSEC24A promotes OA progression through miR-107-5p/CASP3 axis.

Study on the Correlation between Blood Urea Nitrogen, Creatinine Level, Proteinuria and Parkinson's Disease.

Introduction: Parkinson's disease (PD) is related to renal insufficiency. The purpose of this study was to explore the correlation between PD and blood urea nitrogen, creatinine, and proteinuria. Methods: The case-control study method was adopted in this study. In total, 200 patients with PD who were hospitalized in the Department of Neurology of the Second Affiliated Hospital of Anhui Medical University were selected as the PD group, and 110 healthy patients during the same period were selected as the control group. The differences in clinical data and laboratory results between the two groups were compared. Logistic regression analysis, ROC curve, and Spearman correlation analysis were used to determine the correlation between PD and blood urea nitrogen, creatinine, and urine protein. Results: The levels of cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and apolipoprotein B in the PD group were lower than those in the control group. The levels of creatinine, urea nitrogen, and proteinuria in the PD group were higher than those in the control group. Multivariate logistic regression analysis showed that elevated blood urea nitrogen, creatinine, and urine protein levels were risk factors for PD, and elevated LDL-C levels were protective factors for PD. The blood urea nitrogen level of patients with PD was positively correlated with the course of PD, Hoehn-Yahr staging, and UPDRS exercise score (r = 0.309, 0.434, and 0.540, respectively; P < 0.01). Serum creatinine level was positively correlated with the course of PD, Hoehn-Yahr staging, and UPDRS exercise score (r = 0.139, 0.320, and 0.290, respectively; P < 0.01). Conclusion: Blood urea nitrogen, creatinine levels, and proteinuria can be regarded as the onset of PD and a biomarker of disease progression.

Filamin B extensively regulates transcription and alternative splicing, and is associated with apoptosis in HeLa cells.

Post­transcriptional mechanisms are an important approach in the treatment of cancer, and may also be hijacked by tumor cells to help adapt to the local microenvironment. Filamin B (FLNB), an actin­binding protein that provides crucial scaffolds for cell motility and signaling, has also been identified as an RNA­binding protein. Recent studies demonstrated that FLNB might play an important role, not only in skeletal development, but also in regulating tumorigenesis; however, the effects of dysregulated expression of FLNB at the molecular level are not clear. In the present study, RNA­sequencing was performed to analyze changes in overall transcriptional and alternative splicing between the knocked­down FLNB and the control in HeLa cells. Decreased FLNB levels resulted in significantly lower apoptosis compared with control cells. FLNB knockdown extensively regulated the expression of genes in cell apoptosis, tumorigenesis, metastases, transmembrane transport and cartilage development. Moreover, FLNB regulated alternative splicing of a large number of genes involved in 'cell death' and the 'apoptotic process'. Some genes and alternative splicing related to skeletal development were enriched and regulated by FLNB. Reverse transcription­quantitative­PCR identified FLNB­regulated transcription and alternative splicing of genes, such as NLR family apoptosis inhibitory protein, interleukin 23 subunit α, metastasis associated lung adenocarcinoma transcript 1, phosphofurin acidic cluster sorting protein 2, bone morphogenetic protein 7, matrix metallopeptidase 13, collagen type II α 1 chain, fibroblast growth factor receptor 2 and vitamin D receptor. The present study is the first study, to the best of the authors' knowledge, to provide transcriptome­wide analysis of differential gene expression and alternative splicing upon FLNB silencing. The present results suggested that FLNB may play an important regulatory role in cervical cancer cell apoptosis via regulation of transcription and alternative splicing, which provide insight for the current understanding of the mechanisms of FLNB­mediated gene regulation.

[Altitudinal variation of floral organs in Saussurea przewalskii and its relationship with the number and mass of seeds]. / å¼¯é½¿é£Žæ¯›èŠèŠ±éƒ¨å™¨å®˜çš„æµ·æ‹”å˜å¼‚åŠå ¶ä¸Žç§å­è´¨é‡å’Œæ•°ç›®çš„å ³ç³».

We examined the variation of floral organs of Sausssurea przewalskii along altitude and its relationship with the number and mass of seeds from 12 populations in the northeastern edge of Qinghai-Tibetan Plateau, China. At the altitude of 3500-4500 m, the filament length, anther length, column length and style branch length were 0.52-1.01, 0.23-0.63, 0.74-1.58, and 0.11-0.22 cm, respectively. All the indices significantly increased with altitude, while the number of pollens (26.5×104-73.5×104) significantly decreased. There was a significant negative correlation between the lengths of filament, style, column branches and pollen numbers, and a significant positive correlation between column length and filament length. The number of seeds was negatively correlated with the lengths of filament, column and style branches, but positively correlated with the number of pollen. The hundred kernals weight was positively correlated with the length of the filament, column and style branches, and negatively correlated with the number of pollen. With the increases of altitude, S. przewalskii extends the length of flower organs to increase the pollen carrying capacity and input of insects in the flowering period, and produces large seeds with more competitive advantage and survival rate in fruiting stage to improve its fitness.

Cerebral glucose metabolic prediction from amnestic mild cognitive impairment to Alzheimer's dementia: a meta-analysis.

Brain 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been utilized to monitor disease conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's dementia (AD). However, the conversion patterns of FDG-PET metabolism across studies are not conclusive. We conducted a voxel-wise meta-analysis using Seed-based d Mapping that included 10 baseline voxel-wise FDG-PET comparisons between 93 aMCI converters and 129 aMCI non-converters from nine longitudinal studies. The most robust and reliable metabolic alterations that predicted conversion from aMCI to AD were localized in the left posterior cingulate cortex (PCC)/precuneus. Furthermore, meta-regression analyses indicated that baseline mean age and severity of cognitive impairment, and follow-up duration were significant moderators for metabolic alterations in aMCI converters. Our study revealed hypometabolism in the left PCC/precuneus as an early feature in the development of AD. This finding has important implications in understanding the neural substrates for AD conversion and could serve as a potential imaging biomarker for early detection of AD as well as for tracking disease progression at the predementia stage.

Aberrant pattern of regional cerebral blood flow in Alzheimer's disease: a voxel-wise meta-analysis of arterial spin labeling MR imaging studies.

Many studies have applied arterial spin labeling (ASL) to characterize cerebral perfusion patterns of Alzheimer's disease (AD). However, findings across studies are not conclusive. A quantitatively voxel-wise meta-analysis to pool the resting-state ASL studies that measure regional cerebral blood flow (rCBF) alterations in AD was conducted to identify the most consistent and replicable perfusion pattern using seed-based d mapping. The meta-analysis, including 17 ASL studies encompassing 327 AD patients and 357 healthy controls, demonstrated that decreased rCBF in AD patients relative to healthy controls were consistently identified in the bilateral posterior cingulate cortices (PCC)/precuneus, bilateral inferior parietal lobules (IPLs), and left dorsolateral prefrontal cortex. The meta-regression analysis showed that more severe cognitive impairment in the AD samples correlated with greater decreases of rCBF in the bilateral PCC and left IPL. This study characterizes an aberrant ASL-rCBF perfusion pattern of AD involving the posterior default mode network and executive network, which are implicated in its pathophysiology and hold promise for developing imaging biomarkers.

Two new triterpenes from Euphorbia alatavica.

A phytochemical investigation on Euphorbia alatavica Boiss resulted in the isolation of nine compounds, including two new ones, alatavolide and alatavoic acid (1-2). Chemical structures of these compounds were established on the basis of 1D, 2D NMR, and HR-MS techniques, and by comparison with data reported in the literature. Compounds 1, 2, 4, 6, 8, and 9 were screened for cytotoxicity using the MTT assay. Among these compounds, the new compound 2 showed moderate cytotoxicity against Hela, MCF-7 and A549 cell lines (IC50 values of 16.4 ± 3.2, 14.5 ± 2.8, 22.3 ± 3.1 µM, respectively), while the known compound 8 exhibited the most potent cytotoxicity with the IC50 values of 6.5 ± 3.1, 1.9 ± 0.9, 8.6 ± 3.5 µM, respectively.

Two new sesquiterpenoid glycosides from the leaves of Lycium barbarum.

Two new sesquiterpenoid glycosides, lyciumionosides A-B (1-2), together with four known compounds (3-6), were isolated from the leaves of Lycium barbarum. Their structures were mainly established on the basis of MS, 1D and 2D NMR spectroscopic techniques. The antiproliferative activities of compounds 1-5 were evaluated. Compound 1 showed highest inhibitory activity against A549 cells with IC50 value of 32.6 ± 2.6 µM, compound 3 showed highest inhibitory activity against PC-3 cells with IC50 value of 36.0 ± 2.9 µM, and compound 5 exhibited highest inhibitory activity against HeLa cells with IC50 value of 32.3 ± 4.2 µM.

Isoflavones extracted from chickpea Cicer arietinum L. sprouts induce mitochondria-dependent apoptosis in human breast cancer cells.

Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation-7 (MCF-7). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that ICS (10-60 µg/mL) significantly inhibited the proliferation of both cell lines in a time-dependent and dose-dependent fashion. Wright-Giemsa staining as well as annexin V-fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose-dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis-promoting gene Bcl-2-associated X protein and decreased the expression of the antiapoptotic gene Bcl-2. Western blot analysis showed that treatment of SKBr3 and MCF-7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose-dependent manner. Flow cytometry assays using the fluorescent probe 3,3'-dihexyloxacarbocyanine iodide showed a dose-dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose-dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer.

Discovery of diethyl 2,5-diaminothiophene-3,4-dicarboxylate derivatives as potent anticancer and antimicrobial agents and screening of anti-diabetic activity: synthesis and in vitro biological evaluation. Part 1.

Series of diethyl 2,5-diaminothiophene-3,4-dicarboxylate (DDTD) derivatives: azomethines of DDTD (2a-l) have been synthesized and screened for their anticancer, antimicrobial and anti-diabetic activities. The novel synthesized compounds were characterized by (1)H, (13)C NMR, MS and FT-IR analyses. All compounds were evaluated for their antiproliferative activity against three types of cancer cell line such as T47D and MCF-7 (human breast cancer), Hela (human cervical cancer) and Ishikawa (human endometrial cancer) lines. The results showed that most compounds exhibited significant antiproliferative activity against breast cancer cells. The majority of azomethines DDTD influenced strongly against breast cancer cells T47D and MCF-7, among them compounds 2b (2.3 µM), 2c (12.1 µM), 2e (13.2 µM), 2i (14.9 µM), 2j (16.0 µM), 2k (7.1 µM), 2l (8.6 µM) manifest potent anticancer activity against cancer cell T47D than Doxorubicin (DOX, 15.5 µM). Compound 2j has shown potent activity on all three types of cancer cells concurrently and IC50 values were considerably low in comparison with positive control DOX. In addition, all compounds were tested for antimicrobial activity against Staphylococcus aureus ATCC 6538 (Gram positive bacteria), Escherichia coli ATCC 11229 (Gram negative bacteria) and Candida albicans ATCC 10231 (Fungi) strains and 2j which contains in the ring nitrofurfural fragment, showed the highest effect on the three species of microbial pathogens simultaneously. Some compounds induced enzymatic inhibition in a concentration-dependent manner on PTP-1B inhibitor.

Icariin and icaritin stimulate the proliferation of SKBr3 cells through the GPER1-mediated modulation of the EGFR-MAPK signaling pathway.

Icariin (ICA) and icaritin (ICT), with a similar structure to genistein, are the important bioactive components of the genus Epimedium, and regulate many cellular processes. In the present study, using the estrogen receptor (ER)-negative breast cancer cell line, SKBr3, as a model, we examined the hypothesis that ICA and ICT at low concentrations stimulate SKBr3 cell proliferation in vitro through the functional membrane, G protein­coupled estrogen receptor 1 (GPER1), mediated by the epithelial growth factor receptor (EGFR)­mitogen-activated protein kinase (MAPK) signaling pathway. MTT assay revealed that ICA and ICT at doses of 1 nM to 1 µM markedly stimulated SKBr3 cell proliferation in a dose-dependent manner. The ICA- and ICT-stimulated cell growth was completely suppressed by the GPER1 antagonist, G-15, indicating that the ICA­ and ICT-stimulated cell proliferation was mediated by GPER1 activation. Semi-quantitative RT-PCR analysis revealed that treatment with ICA and ICT enhanced the transcription of c-fos, a proliferation-related early gene. The ICA- and ICT-stimulated mRNA expression was markedly attenuated by G-15, AG-1478 (an EGFR antagonist) or PD98059 (a MAPK inhibitor). Our data also demonstrated that ICA and ICT increased the phosphorylation of ERK1/2. The ICA- and ICT-stimulated ERK1/2 phosphorylation was blocked by pre-treatment of the cells with G-15 and AG-1478 or PD 98059. Flow cytometric analysis confirmed that the ICA- and ICT-stimulated SKBr3 cell proliferation involved the GPER1-mediated modulation of the EGFR­MAPK signaling pathway. To the best of our knowledge, our current findings demonstrate for the first time that ICA and ICT promote the progression of ER-negative breast cancer through the activation of membrane GPER1.

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats.

AIM: Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. METHODS: Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg(-1)·d(-1)) for 5 weeks. Their uterine weight and serum levels of 17ß-estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. RESULTS: Treatments of OVX rats with ICS (50 or 100 mg·kg(-1)·d(-1)) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E2 (0.25 mg·kg(-1)·d(-1)) produced similar, but more prominent effects. CONCLUSION: ICS exhibits moderate estrogenic activities as compared to E2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.