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The beneficial effects of dietary β-carotene and vitamin A on Parkinson disease (PD) have been confirmed, but some studies have yielded questionable results. Therefore, this meta-analysis investigated the effect of dietary β-carotene and vitamin A on the risk of PD.The following databases were searched for relevant paper: PubMed, Embase, Medline, Scopus, Cochrane Library, CNKI, Wanfang Med online, and Weipu databases for the relevant paper from 1990 to March 28, 2022. The studies included were as follows: β-carotene and vitamin A intake was measured using scientifically recognized approaches, such as food frequency questionnaire (FFQ); evaluation of odds ratios using OR, RR, or HR; β-carotene and vitamin A intake for three or more quantitative categories; and PD diagnosed by a neurologist or hospital records.This study included 11 studies (four cohort studies, six case-control studies, and one cross-sectional study). The high β-carotene intake was associated with a significantly lower chance of developing PD than low β-carotene intake (pooled OR = 0.83, 95%CI = 0.74-0.94). Whereas the risk of advancement of PD was not significantly distinctive among the highest and lowest vitamin A intake (pooled OR = 1.08, 95%CI = 0.91-1.29).Dietary β-carotene intake may have a protective effect against PD, whereas dietary vitamin A does not appear to have the same effect. More relevant studies are needed to include into meta-analysis in the further, as the recall bias and selection bias in retrospective and cross-sectional studies cause misclassifications in the assessment of nutrient intake.

To explore the resource utilization of phosphorus (P) in wastewater and industrial waste fly ash, we used an efficient composite material (CaO

Diabetic nephropathy (DN) is an increasing threat to human health. The impact of hyperglycemia or its metabolites, advanced glycation end-products (AGEs), on glomerular endothelial cells (GECs) and their pathophysiologic mechanisms are not well explored. Our results reveal that AGEs increased the expression and secretion of the KIT ligand (KITLG) in GECs. Both AGEs and KITLG promoted endothelial-to-mesenchymal transition (EndoMT) in GECs and further increased the permeability of GECs through the AKT/extracellular-signal-regulated kinase pathway. Inhibition of KITLG’s effects by imatinib prevented AGE-medicated EndoMT in GECs, supporting the belief that KITLG is a critical factor for GEC injury. We found higher KITLG levels in the GECs and urine of db/db mice compared with db/m mice, and urinary KITLG levels were positively correlated with the urinary albumin-to-creatinine ratio (ACR). Furthermore, type 2 diabetic patients had higher urinary KITLG levels than normal individuals, as well as urinary KITLG levels that were positively correlated with urinary ACR and negatively correlated with the estimated glomerular filtration rate. KITLG plays a pathogenic role in GEC injury in DN and might act as a biomarker of DN progression.

While 8-oxo-7,8-dihydro-2′-deoxyguanosine (dOG) on DNA G-quadruplex (G4) has been studied, the influence of 8-oxo-7,8-dihydro-guanosine (rOG) lesions on telomeric repeat-containing RNA (TERRA) G4 d...

Diabetic nephropathy (DN) is an increasing threat to human health and is regarded as an important public issue. The pathophysiologic mechanisms of DN are complicated. The initiating molecular events triggering the loss function in mesangial cells (MCs) in DN are not well known. In this cross-disciplinary study, transcriptome analysis of high glucose (HG)-treated mouse MCs (MMCs) using next-generation sequencing and systematic bioinformatics analyses indicated that miR-15b-5p and its downstream target B cell lymphoma 2 (BCL-2) contribute to HG-induced apoptosis in MMCs. HG elevated miR-15b-5p expression, which in turn decreased the translation of BCL-2, leading to MMC apoptosis under HG. Apoptosis of MCs was enhanced in the presence of extracellular vesicles isolated from the urine of type 2 diabetic patients with high levels of miR-15b-5p. Furthermore, increased levels of urinary miR-15b-5p were found in db/db mice and type 2 diabetic patients, and such levels correlated with low baseline kidney function and rapid decline in kidney function during a mean of follow-up period of 2.4 ± 0.1 years. Therefore, miR-15b-5p induced mesangial cells apoptosis by targeting BCL-2 under HG. miR-15b-5p has the potential to predict kidney injury in DN. Blocking the miR-15b-5p epigenetic regulatory network could be a potential therapeutic strategy to prevent mesangial apoptosis in DN.

Hypoxia is regarded as one of the pathophysiologic mechanisms of kidney injury and further progression to kidney failure. Epithelial-to-mesenchymal transition (EMT) in kidney tubules is a critical process of kidney fibrosis. This study utilized transcriptome analysis to investigate hypoxia-induced EMT through microRNA (miRNA)-modulated EMT in proximal tubular epithelial cells (PTECs). RNA sequencing revealed eight miRNAs were upregulated and three miRNAs were downregulated in PTECs cultured under hypoxia compared with normoxia. Among the 11 miRNAs, miR-545-3p has the highest expression in PTECs exposed to hypoxia, and miR-545-3p suppressed tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10) expression. Hypoxia induced EMT in PTECs through miR-545-3p–TNFSF10 modulation, and TNFSF10-attenuated EMT resulted from hypoxia or miR-545-3p mimic transfection. These findings provided new perceptions of the unique regulation of the miR-545-3p–TNFSF10 interaction and their potential therapeutic effect in kidney injury induced by hypoxia.

Synovitis in osteoarthritis (OA) the consequence of low grade inflammatory process caused by cartilage breakdown products that stimulated the production of pro-inflammatory mediators by fibroblast-like synoviocytes (FLS). FLS participate in joint homeostasis and low grade inflammation in the joint microenvironment triggers FLS transformation. In the current study, we aimed to identify differentially expressed genes and potential miRNA regulations in human OA FLS through deep sequencing and bioinformatics approaches. The 245 differentially expressed genes in OA FLS were identified, and pathway analysis using various bioinformatics databases indicated their enrichment in functions related to altered extracellular matrix organization, cell adhesion and cellular movement. Moreover, among the 14 dysregulated genes with potential miRNA regulations identified, src kinase associated phosphoprotein 2 (SKAP2), adaptor related protein complex 1 sigma 2 subunit (AP1S2), PHD finger protein 21A (PHF21A), lipoma preferred partner (LPP), and transcription factor AP-2 alpha (TFAP2A) showed similar expression patterns in OA FLS and OA synovial tissue datasets in Gene Expression Omnibus database. Ingenuity Pathway Analysis identified the dysregulated LPP participated in cell migration and cell spreading of OA FLS, which was potentially regulated by miR-141-3p. The current findings suggested new perspectives into understanding the novel molecular signatures of FLS involved in the pathogenesis of OA, which may be potential therapeutic targets.

Cartilage destruction in rheumatoid arthritis (RA) occurs primarily in the pannus-cartilage interface. The close contact of the synovium-cartilage interface implicates crosstalk between synovial fibroblasts and chondrocytes. The aim of this study is to explore the differentially expressed genes and novel microRNA regulations potentially implicated in the dysregulated cartilage homeostasis in joint destruction of RA. Total RNAs were extracted from human primary cultured normal and RA chondrocytes for RNA and small RNA expression profiling using next-generation sequencing. Using systematic bioinformatics analyses, we identified 463 differentially expressed genes in RA chondrocytes were enriched in biological functions related to altered cell cycle process, inflammatory response and hypoxic stimulation. Moreover, fibroblast growth factor 9 (FGF9), kynureninase (KYNU), and regulator of cell cycle (RGCC) were among the top dysregulated genes identified to be potentially affected in the RA joint microenvironment, having similar expression patterns observed in arrays of clinical RA synovial tissues from the Gene Expression Omnibus database. Additionally, among the 31 differentially expressed microRNAs and 10 candidate genes with potential microRNA-mRNA interactions in RA chondrocytes, the novel miR-140-3p-FGF9 interaction was validated in different microRNA prediction databases, and proposed to participate in the pathogenesis of joint destruction through dysregulated cell growth in RA. The findings provide new perspectives for target genes in the management of cartilage destruction in RA.

Benefiting from the simple DNAzyme and a duplex-specific nuclease, a series of microRNA-stimulated DNAzyme logic gates were rationally assembled for the highly accurate detection of multiple low-abundant microRNA biomarkers that correspond to the specific aberrant microRNA expression patterns of cancer tissues, thus showing a great potential in early diagnosis.

Using next-generation sequencing to decipher the molecular mechanisms underlying aberrant rheumatoid arthritis synovial fibroblasts (RASF) activation, we performed transcriptome-wide RNA-seq and small RNA-seq on synovial fibroblasts from rheumatoid arthritis (RA) subject and normal donor. Differential expression of mRNA and miRNA was integrated with interaction analysis, functional annotation, regulatory network mapping and experimentally verified miRNA&ndash, target interaction data, further validated with microarray expression profiles. In this study, 3049 upregulated mRNA and 3552 downregulated mRNA, together with 50 upregulated miRNA and 35 downregulated miRNA in RASF were identified. Interaction analysis highlighted contribution of miRNA to altered transcriptome. Functional annotation revealed metabolic deregulation and oncogenic signatures of RASF. Regulatory network mapping identified downregulated FOXO1 as master transcription factor resulting in altered transcriptome of RASF. Differential expression in three miRNA and corresponding targets (hsa-miR-31-5p:WASF3, hsa-miR-132-3p:RB1, hsa-miR-29c-3p:COL1A1) were also validated. The interactions of these three miRNA&ndash, target genes were experimentally validated with past literature. Our transcriptomic and miRNA interactomic investigation identified gene signatures associated with RASF and revealed the involvement of transcription factors and miRNA in an altered transcriptome. These findings help facilitate our understanding of RA with the hope of serving as a springboard for further discoveries relating to the disease.

Keratinocytes constitute the major cell type of epidermis, which participates in re-epithelialization during wound repair and the immune defense response to pathogens. The aim of the current study was to explore the differentially expressed genes and novel microRNA (miRNA) regulations that are potentially involved in diabetic keratinocytes through next-generation sequencing (NGS) and bioinformatics approaches. A total of 420 differentially expressed genes between normal and diabetic keratinocytes were identified, and systematic bioinformatics analyses indicated that these differentially expressed genes were functionally enriched in interferon-alpha signaling, viral defense response, and immune response. Additionally, the potential miR-340-3p-DTX3L interaction that has been systematically validated in miRNA prediction databases was proposed to participate in the disrupted skin homeostasis, altering the defense and immune response of diabetic skin. The findings may provide new insights into understanding the pathogenesis of epidermal pathologies in diabetic patients and targeting novel molecules to advance diabetic skin care in clinical practice.

The phenotypic change of chondrocytes and the interplay between cartilage and subchondral bone in osteoarthritis (OA) has received much attention. Structural changes with nerve ingrowth and vascular penetration within OA cartilage may contribute to arthritic joint pain. The aim of this study was to identify differentially expressed genes and potential miRNA regulations in OA knee chondrocytes through next-generation sequencing and bioinformatics analysis. Results suggested the involvement of SMAD family member 3 (SMAD3) and Wnt family member 5A (WNT5A) in the growth of blood vessels and cell aggregation, representing features of cartilage damage in OA. Additionally, 26 dysregulated genes with potential miRNA⁻mRNA interactions were identified in OA knee chondrocytes. Myristoylated alanine rich protein kinase C substrate (MARCKS), epiregulin (EREG), leucine rich repeat containing 15 (LRRC15), and phosphodiesterase 3A (PDE3A) expression patterns were similar among related OA cartilage, subchondral bone and synovial tissue arrays in Gene Expression Omnibus database. The Ingenuity Pathway Analysis identified MARCKS to be associated with the outgrowth of neurite, and novel miRNA regulations were proposed to play critical roles in the pathogenesis of the altered OA knee joint microenvironment. The current findings suggest new perspectives in studying novel genes potentially contributing to arthritic joint pain in knee OA, which may assist in finding new targets for OA treatment.

Diabetic nephropathy (DN) is the major cause of end stage renal disease. Proximal tubular epithelial cell (PTEC) injury occurs early in diabetic kidney, and it is correlated with consequent renal failure. Cellular senescence participates in the pathophysiology of DN, but its role remains unclear. We conducted a cross-disciplinary study, including human, in vivo, and in vitro studies, to explore the novel molecular mechanisms of PTEC senescence in DN. We found that HG induced cell senescence in PTECs, supported by enhanced β-galactosidase staining, p53 and p27 expression, and reduced cyclin E levels. Transcriptome analysis of PTECs from a type 2 diabetic patient and a normal individual using next generation sequencing (NGS) and systematic bioinformatics analyses indicated that miR-378i and its downstream target S-phase kinase protein 2 (Skp2) contribute to HG-induced senescence in PTECs. High glucose (HG) elevated miR-378i expression in PTECs, and miR-378i transfection reduced Skp2 expression. Urinary miR-378i levels were elevated in both db/db mice and type 2 diabetic patients, whereas decreased Skp2 levels were shown in proximal tubule of db/db mice and human DN. Moreover, urinary miR-378i levels were positively correlated with urinary senescence-associated secretory phenotype cytokines and renal function in in vivo and human study. This study demonstrates that the interaction between miR-378i and Skp2 regulates PTEC senescence of DN. miR-378i has the potential to predict renal injury in DN. These findings suggest future applications in both therapy and in predicting renal dysfunction of DN.

Spilanthol a phytochemical derived from the Spilanthes acmella plant has antimicrobial, antioxidant, and anti-inflammatory properties. This study evaluated its effects on the expression of intercellular adhesion molecule 1 (ICAM-1) and inflammation-related mediators in IL-1β-stimulated human lung epithelial A549 cells. Human lung epithelial A549 cells were pretreated with various concentrations of spilanthol (3–100 μM) followed by treatment with IL-1β to induce inflammation. The protein levels of pro-inflammatory cytokines, chemokines, and prostaglandin E2 (PGE2) were measured using ELISA. Cyclooxygenase-2 (COX-2), heme oxygenase (HO-1), nuclear transcription factor kappa-B (NF-κB), and mitogen-activated protein kinase (MAPK) were measured by immunoblotting. The mRNA expression levels of ICAM-1 and MUC5AC were determined by real-time polymerase chain reaction. Spilanthol decreased the expression of PGE2, COX-2, TNF-α, and MCP-1. It also decreased ICAM-1 expression and suppressed monocyte adhesion to IL-1β-stimulated A549 cells. Spilanthol also significantly inhibited the phosphorylation of MAPK and I-κB. These results suggest that spilanthol exerts anti-inflammatory effects by inhibiting the expression of the pro-inflammatory cytokines, COX-2, and ICAM-1 by inhibiting the NF-κB and MAPK signaling pathways.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. In the present study, bioinformatics tools were systematically used to investigate the potential upstream effector involved in the progression of ccRCC. Using the Gene Expression Omnibus database and Library of Integrated Network-based Cellular Signatures L1000 platform, it was identified that GA-binding protein subunit β1 (GABPB1) was a potential effector gene. GABPB1 is a transcription factor subunit and its function in ccRCC is unclear. Elevated expression of GABPB1 mRNA in ccRCC was also observed in other clinical datasets from the Oncomine database. Following reverse transcription-quantitative polymerase chain reaction and western blot analysis, the ccRCC 786-O and A498 cell lines showed higher expression levels of GABPB1 than HK-2, a normal kidney cell line. Knockdown of GABPB1 in the 786-O and A498 cells significantly decreased the ability to form colonies by inducing the expression of p21Waf/Cip1. SurvExpress database analysis indicated that a higher expression of GABPB1 was associated with poor survival outcome in patients with renal cancer. These findings imply that GABPB1 serves an important role in the progression of ccRCC.

Atherosclerotic cardiovascular disease and acute myocardial infarction are the leading causes of mortality worldwide, and apoptosis is the major pathway of cardiomyocyte death under hypoxic conditions. Although studies have reported changes in the expression of certain pro-apoptotic and anti-apoptotic genes in hypoxic cardiomyocytes, genetic regulations are complex in human cardiomyocytes and there is much that remains to be fully elucidated. The present study aimed to identify differentially expressed genes in hypoxic human AC16 cardiomyocytes using next-generation sequencing and bioinformatics. A total of 24 genes (15 upregulated and 9 downregulated) with potential micro (mi)RNA-mRNA interactions were identified in the miRmap database. Utilising the Gene Expression Omnibus database of cardiac microvascular endothelial cells, tensin 1, B-cell lymphoma 2-interacting protein 3 like, and stanniocalcin 1 were found to be upregulated, and transferrin receptor and methyltransferase like 7A were found to be downregulated in response to hypoxia. Considering the results from miRmap, TargetScan and miRDB together, two potential miRNA-mRNA interactions were identified: hsa-miRNA (miR)-129-5p/CDC42EP3 and hsa-miR-330-3p/HELZ. These findings contribute important insights into possible novel diagnostic or therapeutic strategies for targeting cardiomyocytes under acute hypoxic stress in conditions, including acute myocardial infarction. The results of the present study also introduce an important novel approach in investigating acute hypoxic pathophysiology.

As a left‐handed helical structure, Z‐DNA is biologically active and it may be correlated with transcription and genome stability. Until recently, it remained a significant challenge to control the B/Z‐DNA transition under physiological conditions. The current study represents the first to reversibly control B/Z‐DNA transition using cucurbit[7]uril‐based supramolecular approach. It is demonstrated that cucurbit[7]uril can encapsulate the central butanediamine moiety [HN(CH2)4NH] and reverses Z‐DNA caused by spermine back to B‐DNA. The subsequent treatment with 1‐adamantanamine disassembles the cucurbit[7]uril/spermine complex and readily induces reconversion of B‐ into Z‐DNA. The DNA conformational change is unequivocally demonstrated using different independent methods. Direct evidence for supramolecular interactions involved in DNA conformational changes is further provided. These findings can therefore open a new route to control DNA helical structure in a reversible way.

Malignant immature ovarian teratomas (IOTs) most often occur in women of reproductive age. It is unclear, however, what roles estrogenic signaling plays in the development of IOT. In this study, we examined whether estrogen receptors (ERα and β) promote the cellular malignancy of IOT. Estradiol (E2), PPT (propylpyrazole), and DPN (diarylpropionitrile) (ERα- and β-specific agonists, respectively), as well as ERα- or ERβ-specific short hairpin (sh)RNA were applied to PA-1 cells, a well-characterized IOT cell line. Cellular tumorigenic characteristics, for example, cell migration/invasion, expression of the cancer stem/progenitor cell marker CD133, and evidence for epithelial-mesenchymal transition (EMT) were examined. In PA-1 cells that expressed ERα and ERβ, we found that ERα promoted cell migration and invasion. We also found that E2/ERα signaling altered cell behavior through non-classical transactivation function. Our data show non-genomic E2/ERα activations of focal adhesion kinase-Ras homolog gene family member A (FAK-RhoA) and ERK governed cell mobility capacity. Moreover, E2/ERα signaling induces EMT and overexpression of CD133 through upregulation micro-RNA 21 (miR21; IOT stem/progenitor promoter), and ERK phosphorylations. Furthermore, E2/ERα signaling triggers a positive feedback regulatory loop within miR21 and ERK. At last, expression levels of ERα, CD133, and EMT markers in IOT tissue samples were examined by immunohistochemistry. We found that cytosolic ERα was co-expressed with CD133 and mesenchymal cell markers but not epithelial cell markers. In conclusion, estrogenic signals exert malignant transformation capacity of cancer cells, exclusively through non-genomic regulation in female germ cell tumors.

The aryl hydrocarbon receptor (AhR) agonists may upregulate matrix metalloproteinases (MMPs) and contribute to many airway diseases, such as asthma and chronic obstructive pulmonary disease. Elucidation of the detailed molecular mechanisms regulating MMPs may provide the scientific basis for diagnostic and therapeutic opportunities to improve the care of various pulmonary diseases, especially those related to xenobiotic agents. In this study, we investigated the detailed mechanisms of how AhR agonists modulated the expressions and activities of MMPs in bronchial epithelial cells. Treating the cells (Beas-2B or HBE135-E6E7) with 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester or 2,3,7,8-tetrachlorodibenzo-p-dioxin, we found these AhR agonists increased the expression and activity of MMP-1 via a noncanonical AhR pathway and increased the activity of MMP-2 and MMP-9 in an MMP-1-dependent manner. AhR agonists increased the expression of MMP-1 via the activation of mitogen-activated protein kinase (MAPK) pathways by increased cytosolic calcium level and activated calcium/calmodulin-dependent protein kinase II (CaMKII). The activated MAPK pathways phosphorylated c-Jun, c-Fos, and ATF-2, resulting in their nuclear translocation and binding to the activator protein-1 (AP-1) elements of the MMP-1 promoter region. These findings correlated clinically to the significantly higher plasma/serum MMP-1 level in asthmatic patients. In conclusion, the present study demonstrated a novel signaling pathway by which AhR agonists elevated intracellular calcium levels, which activated CaMKII, leading to increased MMP-1 expression through MAPK pathways in bronchial epithelial cell lines. This novel regulatory pathway may serve as a potential target for the treatment of airway remodeling of many pulmonary diseases, such as asthma.AhR agonists increase MMP-1 expression in bronchial epithelial cells. The underlying AhR pathway involves CaMKII, MAPKs, and AP-1 elements. The upregulated MMP-1 further activated MMP-2 and MMP-9. Asthmatic patients have higher serum MMP-1 level. This novel regulatory pathway is a potential target for treating asthma.

Sulfur dioxide is a common air pollutant and extremely harmful to human health. After inhalation, SO2 is easily hydrated to two derivatives, sulfite and bisulfite. So it is valuable to develop an effective probe for these anions. In this work, a green-emissive fluorescent probe 1 is designed and synthesized, which employ 4-hydrazinyl-1, 8-naphthalimide as intramolecular charge transfer (ICT) fluorophore. Probe 1 is able to sense sulfite and bisulfite through fluorescence “turn-on” manner, and the detection limit for sufite is 0.56 μM. The green emission induced by sulfite and bisulfate can be observed by naked eyes under UV irradiation. Compared with other anions used, probe 1 shows great selectivity toward sulfite or bisulfite. We illustrate the possible recognition mechanism of probe 1 and sulfite by NMR analysis and molecular modeling experiments. The real-time monitoring of SO2 release and cell imaging of sulfite is also investigated.

A conserved guanine-rich sequence could be a new target for anti–hepatitis C virus drug development., G-quadruplex (G4) is one of the most important secondary structures in nucleic acids. Until recently, G4 RNAs have not been reported in any ribovirus, such as the hepatitis C virus. Our bioinformatics analysis reveals highly conserved guanine-rich consensus sequences within the core gene of hepatitis C despite the high genetic variability of this ribovirus; we further show using various methods that such consensus sequences can fold into unimolecular G4 RNA structures, both in vitro and under physiological conditions. Furthermore, we provide direct evidences that small molecules specifically targeting G4 can stabilize this structure to reduce RNA replication and inhibit protein translation of intracellular hepatitis C. Ultimately, the stabilization of G4 RNA in the genome of hepatitis C represents a promising new strategy for anti–hepatitis C drug development.

According to the option features that manufacturing grid resource has, this paper builds resource pricing model based on the option contract transaction. First the profits of the resource demand-sides gained by purchasing resources through option contract or directly from spot market are compared, then the condition of option contract parameters that should satisfy is obtained and the analytical solution to the optimal contract purchasing quantity for the demand-sides is deduced. Afterwards the optimal parameters of the option contract are solved in programming model of the resource supply-side built by using the game theory. Finally an example is given to illustrate the use of the model and to verify its superiority.

Bone is a frequent target of lung cancer metastasis and is associated with significant morbidity and a dismal prognosis. Interaction between cancer cells and the bone microenvironment causes a vicious cycle of tumor progression and bone destruction. This study analyzed the soluble factors secreted by lung tumor-associated osteoblast (TAOB), which are responsible for increasing cancer progression. The addition of bone morphogenetic protein-2 (BMP-2), present in large amounts in TAOB conditioned medium (TAOB-CM) and lung cancer patient sera, mimicked the inductive effect of TAOB-CM on lung cancer migration, invasion, and epithelial-to-mesenchymal transition. In contrast, inhibition of BMP by noggin decreases the inductive properties of TAOB-CM and lung cancer patient sera on cancer progression. Induction of lung cancer migration by BMP-2 is associated with increased ERK and p38 activation and the up-regulation of Runx2 and Snail. Blocking ERK and p38 by a specific inhibitor significantly decreases cancer cell migration by inhibiting Runx2 up-regulation and subsequently attenuating the expression of Snail. Enhancement of Runx2 facilitates Rux2 to recruit p300, which in turn enhances histone acetylation, increases Snail expression, and decreases E-cadherin. Furthermore, inhibiting Runx2 by siRNA also suppresses BMP-2-induced Snail up-regulation and cell migration. Our findings provide novel evidence that inhibition of BMP-2 or BMP-2-mediated MAPK/Runx2/Snail signaling is an attractive therapeutic target for osteolytic bone metastases in lung cancer patients.

This study reports the antimigration, anti-invasive effect of glabridin, a flavonoid obtained from licorice, in human non–small cell lung cancer A549 cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of A549 cells. In addition, glabridin also decreased A549-mediated angiogenesis. Further investigation revealed that glabridin’s inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of A549 cells migration was associated with an increase of ανβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 527), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of lung cancer in 3 different ways: inhibition of migration, invasion, and angiogenesis.

The aim of this study was to investigate bag3 gene expression in chronic lymphocytic leukemia (CLL)patients and its association with clinical prognosis. A total of 46 blood samples from untreated CLL patients were collected, SYBR Green-based real-time PCR was used to detect the bag3 mRNA expression, and its association with prognostic index was analyzed by statistical software. The results showed that the median values of bag3 level detected by real-time PCR in 46 CLL patients and normal controls were 0.021 (0.0007 - 1.124) and 0.0025 (0.0005 - 0.014) respectively, the former was significantly higher than the latter. The bag3 level in drug-resistant group was obviously higher as compared with the drug-responsive group. No association was found between bag3 expression and patient clinical baseline information (gender and age) as well as established prognostic factors (lymphocyte count, disease stage, IgVH mutation status, cytogenetics analysis and CD38, ZAP 70 expression). It is concluded that the bag3 expression in CLL patients is markedly higher than that in normal controls, while the high bag3 level in CML patients is probably related with drug resistance, but is not related with clinically established prognostic factors.

Scope: In this study we first report the antimigration, antiinvasive effect of glabridin, a flavonoid obtained from licorice, in MDA-MB-231 human breast adenocarcinoma cells. Methods and results: Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of MDA-MB-231 cells. In addition, glabridin also blocked human umbilical vein endothelial cells (HUVEC) migration and decreased MDA-MB-231-mediated angiogenesis. Further investigation revealed that the inhibition of cancer angiogenesis by glabridin was also evident in a nude mice model. Blockade of MDA-MB-231 cells and HUVEC migration was associated with an increase of αγβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 416), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked AKT and ERK1/2 activation, resulting in reduced activation of RhoA as well as myosin light chain phosphorylation. Conclusion: This study demonstrates that glabridin may be a novel anticancer agent for the treatment of breast cancer in three different ways: inhibition of migration, invasion and angiogenesis.

The aim of this study was to explore the immunophenotypic characteristics of Philadelphia chromosome positive (Ph(+)) acute lymphoblastic leukaemia (ALL) in adults and to evaluate their significance in predicting prognosis and guiding clinical treatment of diseases. The cell immunophenotypes of leukemic marrow or blood samples from 35 cases of Ph(+) ALL and 59 cases of Philadelphia chromosome negative (Ph(-)) ALL were detected by multiparameter flow cytometry, and their abnormal expressions were analysed. The results showed that the expression of all the Ph(+)ALL cases was found in B-cell lineage. As compared with Ph(-)B-ALL cases, the Ph(+)B-ALL cases displayed the higher expression of CD34 and CD13 (p0.05), but lower expression of CD38 (p0.05). The coexpressed rates of CD13, CD33 and CD15 in cases of Ph(+)B-ALL and Ph(-)B-ALL were 85.7% and 61.0% respectively. The former was higher than the later (p0.05). It is concluded that the Ph(+)ALL cases have the unique immunophenotype. The immunophenotypic analysis of CD34, CD13 and CD38 in adult B-ALL cases contributes to judging the existence of Ph chromosome. Thereby for adult ALL patients having above-mentioned unique immunophenotypes, the detection of bcr/abl fusion gene must be performed. Such phenotypic profile is helpful for predicting the poor outcome of the disease, and for defining patients who require different treatment strategies.

OBJECTIVES: The purpose of this study was to assess the association between subfertility and spontaneous abortion. METHODS: A total of 1572 women in New York and Vermont reported 3269 pregnancies between 1980 and 1990 and were able to provide an estimate of the waiting time to conception for 2967. Subfertility was defined as a delay of 1 year or more before a recognized conception was achieved. Rates of spontaneous abortion were determined among women with and without subfertility, and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated via multiple logistic regression. RESULTS: Spontaneous abortion rates were 23.0% in pregnancies preceded by subfertility and 14.0% in pregnancies without impaired fertility (adjusted OR = 1.71, 95% CI = 1.26, 2.94). The attributable risk of spontaneous abortion associated with subfertility was 6.2%. CONCLUSIONS: Subfertile women evidence an increased number of spontaneous abortions.

This study is the first to investigate the anticancer effect of dehydrocostuslactone [DHE (3 aS ,6 aR ,9 aR ,9 bS )-decahydro-3,6,9-tris(methylene) azuleno[4,5- b ]furan-2(3 H )-one)], a medicinal plant-derived sesquiterpene lactone, on hepatocellular carcinoma. Our results showed that DHE inhibits the proliferation of HepG2 and PLC/PRF/5 cells by inducing apoptosis. DHE induces up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, and nuclear relocation of the mitochondrial factors apoptosis-inducing factor (AIF) and endonuclease G (Endo G). DHE triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol-calcium levels, double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase phosphorylation, inositol-requiring protein 1 (IRE1) and CHOP/GADD153 up-regulation, X-box transcription factor-1 mRNA splicing, and caspase-4 activation. Enhancement of ER stress by DHE is through p38 and extracellular signal-regulated kinase 1/2-dependent manners and subsequently causes c-Jun NH 2 -terminal kinase activation, resulting in AIF and Endo G nuclear relocation. Both of IRE1 small interfering RNA transfection and 1,2-bis(2-aminophenoxy)ethane- N , N , N ′, N ′-tetraacetic acid-acetoxymethyl ester pretreatment inhibit DHE-mediated apoptosis, supporting the hypothesis that DHE induces cell death through ER stress. It is noteworthy that animal studies have revealed a dramatic 50% reduction in tumor volume after 45 days of treatment. This study demonstrates that DHE may be a novel anticancer agent for the treatment of liver cancer.

Based on graphene oxide and Hoechst 33258, bioassays towards target DNA and several enzymes including Exo III and Dam MTase were established. This strategy eliminates the need for modification of oligonucleotides, and can give similarly satisfactory results compared to traditional methods using labelled DNA. Moreover, “AND” and “INHIBIT” dual-output DNA logic gates were developed.