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2.
BackgroundC4ST-1 catalyzes the transfer of sulfate groups in the sulfonation of chondroitin during chondroitin sulfate synthesis. Chondroitin sulfate consists of numerous copies of negatively charged sulfonic acid groups that participate in the nucleation process of biomineralization. In the present study, we obtained two CHST11 genes (PmCHST11a and PmCHST11b) which encoded the C4ST-1 and explored the functions of these genes in the synthesis of chondroitin sulfate and in the formation of the nacreous layer of shells.ResultsBoth PmCHST11a and PmCHST11b had a sulfotransferase-2 domain, a signal peptide and a transmembrane domain. These properties indicated that these genes localize in the Golgi apparatus. Real-time PCR revealed that both PmCHST11a and PmCHST11b were highly expressed in the central zone of the mantle tissue. Inhibiting PmCHST11a and PmCHST11b via RNA interference significantly decreased the expression levels of these genes in the central zone of the mantle tissue and the concentration of chondroitin sulfate in extrapallial fluid. Moreover, shell nacre crystallized irregularly with a rough surface after RNA interference.ConclusionsThis study indicated that PmCHST11a and PmCHST11b are involved in the nacre formation of Pinctada fucata martensii through participating in the synthesis of chondroitin sulfate.  相似文献   

3.
The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase with essential cellular function via processing various extracellular and intracellular inputs. Two distinct multi-protein mTOR complexes (mTORC), mTORC1 and mTORC2, have been identified and well characterized in eukaryotic cells from yeast to human. Sin1, which stands for Sty1/Spc1-interacting protein1, also known as mitogen-activated protein kinase (MAPK) associated protein (MAPKAP)1, is an evolutionarily conserved adaptor protein. Mammalian Sin1 interacts with many cellular proteins, but it has been widely studied as an essential component of mTORC2, and it is crucial not only for the assembly of mTORC2 but also for the regulation of its substrate specificity. In this review, we summarize our current knowledge of the structure and functions of Sin1, focusing specifically on its protein interaction network and its roles in the mTOR pathway that could account for various cellular functions of mTOR in growth, metabolism, immunity and cancer.  相似文献   

4.
The human epidermal receptor-2/neu (HER-2/neu) oncogene encodes a transmembrane tyrosine kinase receptor. This molecule could have a diagnostic value since the extracellular domain of c-erbB-2 (HER-2) transmembrane is shed into the blood as a circulating antigen. The diagnostic value of serum HER-2/neu was calculated along with the conventional marker carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) at 85th percentiles. Serum levels of breast carcinoma antigens HER-2/neu, CEA and CA15-3 were determined in 175 normal individuals and 268 malignant patients. The soluble form of serum HER-2/neu, CEA and CA15-3 was assayed by enzyme linked immunosorbent assay in control and breast cancer patients prior to treatment. Serum levels of the tested tumor markers HER-2/neu and CA15-3 and CEA were significantly higher in cancer patients compared to controls. At 85th percentile the sensitivity of HER-2/neu was 51.12 %; the specificity was 86.29 % and the overall accuracy was 64.56 %. The sensitivity of CA15-3 was 73.13 %; the specificity was 85.14 % and the overall accuracy was 77.88 %. The sensitivity of the combined testing was 82.84 %; the specificity was 73.71 % and the overall accuracy was 80.01 %. The sensitivity and the overall accuracy of combined testing were higher than those of HER-2/neu and CA15-3 testing single. The combined testing of HER-2/neu and CA15-3 can increase the sensitivity and overall accuracy of breast cancer diagnosis. The results of this study suggest that the use of multiple tumor markers may be employed as combination and at 85th percentiles to assess the prognosis.  相似文献   

5.
BackgroundCancer is a life-threatening disease that affects approximately 18 million individuals worldwide. Breast cancer is the most common female neoplasm globally with more than 276,480 new cases of invasive breast cancer expected to be diagnosed in women in the U.S. alone in 2020. Genetic and epigenetic factors play role in the carcinogenesis and progression of this disease. In this study, MCF-7 adenocarcinoma cells were transfected with CRISPR/Cas9 plasmid to either knock out CDK11 or to activate CDH1. Treated cells were allografted into the mammary glands of female rats (150–190 g, 6–8 weeks) to evaluate the capability of these cells to control cancer progression and metastasis.ResultsqPCR data revealed a significant downregulation of CDK11 and upregulation of CDH1. Cell cycle analysis and apoptosis assays indicated the knockout of CDK11 and simultaneous activation of CDH1 resulted in cell cycle arrest at G2/M phase and accumulation of cells at G2. Meanwhile, the percentage of cells that underwent late apoptosis increased in both genome editing hits. Histopathological sectioning data indicated that untransfected MCF-7 cells were capable of developing tumors in the mammary gland and initiation g angiogenesis. Transfected cells significantly restricted cancer cell infiltration/invasion by minimally localizing tumors and inhibiting angiogenesis.ConclusionsAlthough further investigation is needed, the present data indicate the potentiality of using CRISPR/Cas9-based therapy as a promising approach to treat breast cancer. Impact: these data indicate targeting cancer-related genes via any genome editing tool might represent a novel approach to combat cancer.How to cite: Al-Mulhim F, Alqosaibi AI, Al-Muhnna A, et al. CRISPR/Cas9-mediated activation of CDH1 suppresses metastasis of breast cancer in rats. Electron J Biotechnol 2021;53. https://doi.org/10.1016/j.ejbt.2021.06.002  相似文献   

6.
Identification of reliable biomarkers for detection and staging of cancer and monitoring the outcome of anticancer therapy has been considered to be of high importance. We aimed to estimate the levels of serum glycoproteins, protein bound-hexose, protein bound hexosamine, protein bound fucose, protein bound sialic acid and protein bound carbohydrate in 32 ovarian cancer patients and compared them with the levels that found in 25 normal subjects. As compared to the normal subjects, all the four fractions of glycoproteins level were significantly elevated in ovarian cancer patients (p < 0.05). Chemotherapy in these patients significantly decreased the levels of serum glycoproteins (p < 0.05). Thus, high levels of serum glycoproteins in ovarian cancer patients could be due to abnormal protein glycosylation indicating malignant transformation of the cells.  相似文献   

7.
In order to quantize Dirac's classical point electron1 we supplement Einstein's classical equation (E/c)2 ? p2 = b2 with a reciprocal classical equation (CΔt)2 ? (Δr)2 = a2 where b = mc and a is Dirac's signal radius. Δt is the time saved by a light signal in various states of motion of the electron, and a/c is the rest time saved. Our former efforts2 of obtaining an integral equation for the probability amplitude have been rectified by Born.3 There is no solution of the integral equation, however, unless advanced and retarded phases are introduced simultaneously, along with Dirac's advanced and retarded potentials. We have obtained a transcendental equation for the eigen-value μ = αγ where α is the Sommerfeld fine-structure constant, and γ is the numerical factor in Dirac's signal radius a = γe2/mc2. The smallest eigen-value is μ = 0.0299.That is, ab = hγ = h/210.  相似文献   

8.
Reactive oxygen species (ROS) are known to be a key factor in the development of cancer, and many exogenous sources are supposed to be related to the formation of ROS. In this paper, a microfluidic chip was developed for studying the production of ROS in lung cancer cells under different chemical and physical stimuli. This chip has two unique features: (1) five relative concentrations of 0, 1/8, 1/2, 7/8, and 1 are achieved in the culture regions; (2) a shear stress gradient is produced inside each of the five culture areas. Lung cancer cells were seeded inside this biocompatible chip for investigating their response to different concentrations of H2O2, a chemical stimulus known to increase the production of ROS. Then the effect of shear stress, a physical stimulus, on lung cancer cells was examined, showing that the production of ROS was increased in response to a larger shear stress. Finally, two antioxidants, α-tocopherol and ferulic acid, were used to study their effects on reducing ROS. It was found that high-dose α-tocopherol was not able to effectively eliminate the ROS produced inside cells. This counter effect was not observed in cells cultured in a traditional chamber slide, where no shear stress was present. This result suggests that the current microfluidic chip provides an in vitro platform best mimicking the physiological condition where cells are under circulating conditions.  相似文献   

9.
Sun YS  Peng SW  Lin KH  Cheng JY 《Biomicrofluidics》2012,6(1):014102-014102-14
In this paper, we report a new method to incorporate 3D scaffold with electrotaxis measurement in the microfluidic device. The electrotactic response of lung cancer cells in the 3D foam scaffolds which resemble the in vivo pulmonary alveoli may give more insight on cellular behaviors in vivo. The 3D scaffold consists of ordered arrays of uniform spherical pores in gelatin. We found that cell morphology in the 3D scaffold was different from that in 2D substrate. Next, we applied a direct current electric field (EF) of 338 mV/mm through the scaffold for the study of cells’ migration within. We measured the migration directedness and speed of different lung cancer cell lines, CL1-0, CL1-5, and A549, and compared with those examined in 2D gelatin-coated and bare substrates. The migration direction is the same for all conditions but there are clear differences in cell morphology, directedness, and migration speed under EF. Our results demonstrate cell migration under EF is different in 2D and 3D environments and possibly due to different cell morphology and/or substrate stiffness.  相似文献   

10.
Epigenetic mechanisms, such as DNA methylation, DNA hydroxymethylation, post-translational modifications (PTMs) of histone proteins affecting nucleosome remodelling, and regulation by small and large non-coding RNAs (ncRNAs) work in concert with cis and trans acting elements to drive appropriate gene expression. Advances in detection methods and development of dedicated platforms and methylation arrays resulted in an explosion of information on aberrantly methylated sequences linking deviations in epigenetic landscape with the initiation and progression of complex diseases. Here, we consider how DNA methylation changes in malignancies, such as breast, pancreatic, colorectal, and gastric cancer could be exploited for the purpose of developing specific diagnostic tools. DNA methylation changes can be applicable as biomarkers for detection of malignant disease in easily accessible tissues. Methylation signatures are already proving to be an important marker for determination of drug sensitivity. Even more, promoter methylation patterns of some genes, such as MGMT, SHOX2, and SEPT9, have already been translated into commercial clinical assays aiding in patient assessment as adjunct diagnostic tools. In conclusion, the changes in DNA methylation patterns in tumour cells are slowly gaining entrance into routine diagnostic tests as promising biomarkers and as potential therapeutic targets.Key words: biomarkers, CpG islands, DNA methylation, molecular diagnostics, epigenetics  相似文献   

11.
To examine the possible involvement of human B cell leukemia/lymphoma 2 (Bcl-2), CD4+ cells, hepatocyte growth factor (HGF), and metalloproteinase-9 (MMP-9), as biomarkers in early diagnosis of hepatocellular carcinoma (HCC), activities of these biomarkers in serum were demonstrated by the method of Enzyme Linked Immunosorbant Assay. Two groups of subjects (60 for each), were examined in this study; healthy controls and patients with HCC. The present results declare that, significant decrease in Bcl-2 (p ≤ 0.0001), and CD 4+ (p ≤ 0.001), while significant increase in HGF and MMP-9 (p ≤ 0.05). These findings imply an influence of these biomarkers by the existence of hepatic carcinoma that might reflect the progression of disease and a distinction between the pathological mechanisms involved in hepatic carcinoma. Since, the serum MMP-9 activity was significantly varied between each stage of HCC. An individual profile of the present investigated parameters was detected that might serve as an easy accessing serum marker to monitor the progression of hepatic cell disorders.  相似文献   

12.
Ovarian cancer has been emerged as a most common and lethal gynecological malignancy in India. High serum insulin and low adiponectin have been associated with increased risk of ovarian cancer. But their role in development of ovarian cancer is conflicting and little evidence is available. We aimed to evaluate blood levels of insulin and adiponectin in epithelial ovarian cancer (EOC) patients and their association with the risk to develop EOC. The study included following three groups; Group 1: fifty cases of cytohistopathologically confirmed cases of EOC, Group 2: fifty age matched cases of benign ovarian conditions and Group 3: fifty ages matched healthy controls with no evidence of any benign or malignant ovarian pathology as ruled out by clinical examination and relevant investigations. Cytohistopathologically confirmed and newly diagnosed cases of EOC and benign ovarian cancer were included in this study. The median value of fasting serum insulin was significantly high (15.0 µlU/ml, P = 0.02) and adiponectin were significantly low (5.1 µg/ml, P < 0.001) in ovarian cancer patients compared to benign ovarian tumors and healthy controls group. A significant increase risk of ovarian cancer was found in high tertile (≥ 18.7 µlU/ml) of serum insulin level (OR = 2.7; 95% CI = 1.00–6.67, P = 0.04) and lower tertile (≤ 5.45 µg/ml) of adiponectin level (OR = 3.2; 95% CI = 1.10–9.71, P = 0.03). High serum insulin level and low adiponectin levels were significantly associated with increased risk for development of ovarian cancer.  相似文献   

13.
In the era of the targeted therapy identification of EGFR mutation detection in lung cancer is extremely helpful to predict the treatment efficacy of EGFR tyrosine kinase inhibitors (TKIs). Unfortunately, the inadequacy and quality of the biopsy samples are the major obstacles in molecular testing of EGFR mutation in lung cancer. To address this issue, the present study intended to use liquid biopsy as the non-invasive method for EGFR mutation detection. A total of 31 patients with an advanced stage of lung cancer were enrolled in the study from which cell-free DNA (cfDNA) and FFPE tissue DNA was extracted. Extracted DNA samples were analyzed for further EGFR exon specific mutation analysis by ARMS-PCR. Data were analyzed statistically using SPSS software. In cfDNA samples, the prevalence of wild type EGFR was 48% while the prevalence of TKI resistant and TKI sensitive mutations were 3%. Conversely, in tissue DNA samples, the prevalence of wild type, TKI sensitive and TKI resistant mutations were 48%, 19%, and 3%, respectively. The overall concordance of EGFR mutation between cfDNA and tissue DNA was 83%. McNemar’s test revealed that there was no significant difference between EGFR expression of cfDNA and tissue DNA samples. Additionally, the significant-high incidence of TKI resistant mutations was observed in tobacco habituates, indicating the role of carcinogens present in the tobacco in developing resistant mutations. In conclusion, our data suggest that evaluation of EGFR mutation from cfDNA samples is practicable as a non-invasive tool in patients with advanced-stage of lung cancer.  相似文献   

14.
After the significant discovery of the hole-doped nickelate compound Nd0.8Sr0.2NiO2, analyses of the electronic structure, orbital components, Fermi surfaces and band topology could be helpful to understand the mechanism of its superconductivity. Based on first-principle calculations, we find that Ni states contribute the largest Fermi surface. The states form an electron pocket at Γ, while 5dxy states form a relatively bigger electron pocket at A. These Fermi surfaces and symmetry characteristics can be reproduced by our two-band model, which consists of two elementary band representations: B1g@1a ⊕ A1g@1b. We find that there is a band inversion near A, giving rise to a pair of Dirac points along M-A below the Fermi level upon including spin-orbit coupling. Furthermore, we perform density functional theory based Gutzwiller (DFT+Gutzwiller) calculations to treat the strong correlation effect of Ni 3d orbitals. In particular, the bandwidth of has been renormalized largely. After the renormalization of the correlated bands, the Ni 3dxy states and the Dirac points become very close to the Fermi level. Thus, a hole pocket at A could be introduced by hole doping, which may be related to the observed sign change of the Hall coefficient. By introducing an additional Ni 3dxy orbital, the hole-pocket band and the band inversion can be captured in our modified model. Besides, the nontrivial band topology in the ferromagnetic two-layer compound La3Ni2O6 is discussed and the band inversion is associated with Ni and La 5dxy orbitals.  相似文献   

15.
The cell''s micro-environment plays an important role in various physiological and pathological phenomena. To better investigate in vivo cellular behaviors, researchers have expended great effort in building controlled in vitro biophysical and biochemical environments. Because a cell''s gaseous environment affects properties such as its division, metastasis, and differentiation, we developed a zero-flow based platform for studying mammalian cell chemotaxis behavior in different oxygen environments. This platform can construct a linear range of oxygen tensions within one chip (i.e., from 1.4% to 3.6% or 5.5% to 14.5%). To study cell chemotaxis behavior under varying oxygen environments, the chemical gradient direction is established perpendicularly to oxygen change within an observation area. Because the observation area is not subject to flow, shear force is of no concern. In addition, water flow around the cell chambers greatly reduces evaporation and makes long-term microscope imaging possible. In this study, we precisely measure the chemotaxis velocity of MCF-7 human breast cancer cells under different oxygen tension conditions towards CXCL12, which is a stromal cell-derived factor. We find that cell migration rates are not equivalent, even under two close oxygen tensions. We also observed that cells move faster towards high concentrations of chemoattractant when the oxygen tension is below 3% due to the increased expression of HIF-1 (hypoxia-inducible factor 1), which promotes a transition to the amoeboid rather than mesenchymal mode of movement. Our experiments demonstrate that this new microfluidic platform is useful for the quantitative study of mammalian cell chemotaxis under different oxygen conditions in the absence of shear force. We also shed light on the study of chemotaxis under other gaseous environments.  相似文献   

16.
BackgroundOral cancer is one of the common malignant tumors of the head and neck. However, current treatments have numerous side effects, and drugs from natural sources may have better therapeutic potential. This research investigated the induction of apoptosis by α-hederin (α-HN), a constituent of Pulsatilla chinensis (Bunge) Regel, in the oral cancer cell line SCC-25 and its underlying mechanism.ResultsSCC-25 cells were treated with 50, 100, and 200 μmol/L α-HN. Cell proliferation; extent of apoptosis; activities of caspases-3, 8, and 9; and the expression of Bcl-2, Bax, phosphorylated (p)-phosphoinositide 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) proteins were determined using the 3-(4,5)-2-thiazole-(2,5)-diphenyl tetrazolium bromide, flow cytometry, caspase activity detection kits, and western blot assays, respectively. The results showed that the proliferation of SCC-25 cells in the α-HN-treated groups decreased significantly, and the inhibitory effect was time and concentration dependent. Compared with cells in the control group, the extent of apoptosis increased significantly, caspase-3 and -9 activities were significantly enhanced, and the Bcl-2 level was lowered and the Bax level was elevated significantly in SCC-25 cells treated with α-HN for 48 h (P < 0.05). The expression of p-PI3K, p-Akt, and p-mTOR was also significantly lower in SCC-25 cells treated with α-HN than that in the control group (P < 0.05).ConclusionThese results indicate that α-HN can inhibit proliferation and induce apoptosis of SCC-25 cells and may exert these effects by inhibiting the PI3K/Akt/mTOR signaling pathway.How to cite: Wang H, Wu B, Wang H. Alpha-hederin induces the apoptosis of oral cancer SCC-25 cells by regulating PI3K/Akt/mTOR signaling pathway. Electron J Biotechnol 2019;38. https://doi.org/10.1016/j.ejbt.2018.12.005  相似文献   

17.
In human tumors, somatic mutation frequently occur in K-ras gene at codon 12, which makes the K-ras protein hyper active leading to uncontrolled signaling for cell division: one of the important hall mark of cancer. In order to correlate mutations in K-ras to cause, response to treatment, disease progression and recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) the following study was undertaken. By using PCR–RFLP method prevalence of codon 12 in K-ras gene was studied in 56 HNSCC patients. High frequency of K-ras mutation was detected in codon 12 (60.71%). The result of this study helps us in understanding the role of K-ras somatic mutations in HNSCC patients and in designing novel treatment protocols for HNSCC patients.Electronic supplementary materialThe online version of this article (10.1007/s12291-020-00882-w) contains supplementary material, which is available to authorized users.  相似文献   

18.
BackgroundThe study of plant-associated microorganisms is very important in the discovery and development of bioactive compounds. Pseudomonas is a diverse genus of Gammaproteobacteria comprising more than 60 species capable of establishing themselves in many habitats, which include leaves and stems of many plants. There are reports of metabolites with diverse biological activity obtained from bacteria of this genus, and some of the metabolites have shown cytotoxic activity against cancer cell lines.Because of the high incidence of cancer, research in recent years has focused on obtaining new sources of active compounds that exhibit interesting pharmacodynamic and pharmacokinetic properties that lead to the development of new therapeutic agents.ResultsA bacterial strain was isolated from tumors located in the stem of Pinus patula, and it was identified as Pseudomonas cedrina. Extracts from biomass and broth of P. cedrina were obtained with chloroform:methanol (1:1). Only biomass extracts exhibited antiproliferative activity against human tumor cell lines of cervix (HeLa), lung (A-549), and breast (HBL-100). In addition, a biomass extract from P. cedrina was fractioned by silica gel column chromatography and two diketopiperazines were isolated: cyclo-(l-Prolyl-l-Valine) and cyclo-(l-Leucyl-l-Proline).ConclusionsThis is the first report on the association of P. cedrina with the stems of P. patula in Mexico and the antiproliferative activity of extracts from this species of bacteria against human solid tumor cell lines.How to cite: Sánchez-Tafolla L, Padrón JM, Mendoza G, et al. Antiproliferative activity of biomass extract from Pseudomonas cedrina. Electron J Biotechnol 2019;40. https://doi.org/10.1016/j.ejbt.2019.03.010.  相似文献   

19.
Soybean accounts for more than half of the global production of oilseed and more than a quarter of the protein used globally for human food and animal feed. Soybean domestication involved parallel increases in seed size and oil content, and a concomitant decrease in protein content. However, science has not yet discovered whether these effects were due to selective pressure on a single gene or multiple genes. Here, re-sequencing data from >800 genotypes revealed a strong selection during soybean domestication on GmSWEET10a. The selection of GmSWEET10a conferred simultaneous increases in soybean-seed size and oil content as well as a reduction in the protein content. The result was validated using both near-isogenic lines carrying substitution of haplotype chromosomal segments and transgenic soybeans. Moreover, GmSWEET10b was found to be functionally redundant with its homologue GmSWEET10a and to be undergoing selection in current breeding, leading the the elite allele GmSWEET10b, a potential target for present-day soybean breeding. Both GmSWEET10a and GmSWEET10b were shown to transport sucrose and hexose, contributing to sugar allocation from seed coat to embryo, which consequently determines oil and protein contents and seed size in soybean. We conclude that past selection of optimal GmSWEET10a alleles drove the initial domestication of multiple soybean-seed traits and that targeted selection of the elite allele GmSWEET10b may further improve the yield and seed quality of modern soybean cultivars.  相似文献   

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