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[en] Human osteoarthritic chondrocytes (hOACs) are characterized by their “dedifferentiated” and catabolic phenotype and lack the ability for restoring their inherent functions by themselves. Here we investigated whether extrinsically supplemented mechanical signal via compression loading would affect the phenotype of hOACs. Specifically, we applied cyclic compression loading on cultured hOACs-collagen constructs and measured the expression of the major chondrogenic factors, cell-matrix interaction molecules and matrix degradation enzymes. Dynamic compression loading stimulates the expression and nuclear localization of sox9 in hOACs and reduces the catabolic events via downregulated expression of collagenases. These results contribute to better understanding towards mechanoregulation of hOACs.
[en] RAB3A interacting protein (Rab3IP) has been determined to be involved in cancer progression; however, its expression pattern and function in gastric cancer remain unknown. The aim of this study was to determine the association between Rab3IP and gastric cancer, in addition to its functional role in this disease. Overexpression of Rab3IP in gastric cancer was verified at both transcriptional and translational levels. Analysis of clinical data indicated its role as an independent risk factor for survival. Cellular studies showed that Rab3IP could induce an aggressive phenotype in gastric cancer cells and that its expression was correlated with markers of the epithelial-mesenchymal transition (EMT). In addition, we verified the co-expression of and interplay between Rab3IP and SSX2 during gastric cancer progression. Thus, these findings elucidated the central role of Rab3IP in inducing an invasive phenotype in gastric cancer cells, in addition to its involvement in EMT. Our results could be exploited for the clinical prognosis and treatment of this important disease.
[en] Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.
[en] Highlights: • mmu-miR-1963 could downregulate the expression of Smoc2 by binding to its 3’UTR. • Smoc2 could promote the amelogenic differentiation of LS8. • mmu-miR-1963 inhibits the ameloblast differentiation of LS8 via Smoc2. RUNX2 is a key regulator of osteogenic differentiation and odontoblastic differentiation. RUNX2 mutations could cause Cleidocranial dysplasia (CCD; OMIM119600), which is featured by abnormal development of bone and teeth. By using microRNA array, we identified a large number of microRNAs that showed different expression between wild-type Runx2 group and mutant groups. The aim of this study is to find out the effect of mmu-miR-1963, which was downregulated in all mutant Runx2 groups, on the ameloblast differentiation of LS8 cells. qPCR and Western Blot results showed the suppressive effect of mmu-miR-1963 on ameloblast differentiation of LS8 cell line. We further confirmed Smoc2 as one direct target of mmu-miR-1963. For the first time, we showed that mmu-miR-1963 could regulate the ameloblast differentiation of LS8 by targeting Smoc2. This study suggests the suppressive role of mmu-miR-1963 on ameloblast differentiation of LS8 via directly targeting the 3’UTR of Smoc2. We also demonstrated that Smoc2 itself could promote the ameloblast differentiation of LS8 for the first time. Our results indicate a novel explanation to the enamel hypoplasia phenotype in part of CCD patients.
[en] Studies on the adaptability of some soybean mutant lines at four locations. Eight soybean mutant lines and control (Orba variety) were tested for phenotypic, genotypic, environmental and adaptability values at four different locations during the dry season of 1985. According to Chang's formula, the mutant lines no. 63/PsJ, no. 71/PsJ, no. 82/PsJ, no. 91/PsJ, and no. 134/PsJ seem to have a high phenotypic value. While the other mutant no. 62/PsJ, no. 95/PsJ, no. 147/PsJ, and the orba variety seem to be low. All mutant lines and orba variety had the highest environmental value in polmas location but the lowest in the location of Bengkulu utara. The stability of genotypes were measured by Eberhard and Russel method. It was found that the mutant lines no. 62/PsJ, no. 91/PsJ, no. 95/PsJ, no. 147/PsJ, and orba variety could adapt better in infertile soil, while the others no. 63/PsJ, no. 71/PsJ, and no. 82/PsJ in fertile soil. The mutant lines no. 91/PsJ, no. 95/PsJ, no. 134/PsJ were relatively stable compared to the other mutants. (author). 5 refs
[en] In addition to the majority of T cells which carry the αβ T cell receptor (TCR) for antigen, a distinct subset of about 1–5% of human peripheral blood T cells expressing the γδ TCR contributes to immune responses to infection, tissue damage and cancer. T cells with the Vδ2+ TCR, usually paired with Vγ9, constitute the majority of these γδ T cells. Analogous to αβ T cells, they can be sorted into naive (CD27+CD45RA+), central memory (CD27+CD45RA−), effector memory (CD27−CD45RA−), and terminally-differentiated effector memory (CD27−CD45RA+) phenotypes. Here, we found that CD27−CD45RA+ γδ T cells can be further divided into two populations based on the level of expression of CD45RA: CD27−CD45RAint and CD27−CD45RAhi. Those with the CD27−CD45RAhi phenotype lack extensive proliferative capacity, while those with the CD27−CD45RAint phenotype can be easily expanded by culture with zoledronate and IL-2. These CD27-CD45RAhi potentially exhausted γδ T cells were found predominantly in cancer patients but also in healthy subjects. We conclude that γδ T cells can be divided into at least 5 subsets enabling discrimination of γδ T cells with poor proliferative capacity. It was one of our goals to predict the feasibility of γδ T cell expansion to sufficient amounts for adoptive immunotherapy without the necessity for conducting small-scale culture tests. Fulfilling the ≥1.5% criterion for γδ T cells with phenotypes other than CD27−CD45RAhi, may help avoid small-scale culture testing and shorten the preparation period for adoptive γδ T cells by 10 days, which may be beneficial for patients with advanced cancer. - Highlights: • CD27-CD45+ γδ T cells can be divided into two populations, CD27-CD45hi and CD27-CD45int. • CD27-CD45hi γδ T cells are detected in the peripheral blood of both cancer patients and healthy subjects. • CD27-CD45hi γδ T cells are distinct from so-called terminally differentiated CD27-CD45int γδ T cells. • CD27-CD45hi γδ T cells lack vigorous proliferative potential.
[en] Highlights: • AUX1 acts upstream of PIN2 in the control of root gravitropism by regulating the asymmetric auxin distribution. AUX1 and PIN2 auxin transporter are required for the asymmetric distribution of auxin for root gravitropic response. However, the relationship between AUX1 and PIN2 in root gravitropism is unclear. Here, we report that aux1-T mutant show stronger defects in root gravitropism than pin2-T, and aux1-T pin2-T double mutants display similar agravitropic phenotype to aux1-T. The gravity-induced asymmetric distribution of auxin responses could not be established in pin2-T, aux1-T and aux1-T pin2-T mutants; whereas aux1-T pin2-T double mutants showed similar auxin responses to aux1-T mutant. These findings support AUX1 plays a role in root gravitropism upstream of PIN2.
[en] Neuroblastoma (NB) is the most common extracranial solid tumor in children. NB tumors and derived cell lines are phenotypically heterogeneous. Cell lines are classified by phenotype, each having distinct differentiation and tumorigenic properties. The neuroblastic phenotype is tumorigenic, has neuronal features and includes stem cells (I-cells) and neuronal cells (N-cells). The non-neuronal phenotype (S-cell) comprises cells that are non-tumorigenic with features of glial/smooth muscle precursor cells. This study identified miRNAs associated with each distinct cell phenotypes and investigated their role in regulating associated differentiation and tumorigenic properties. A miRNA microarray was performed on the three cell phenotypes and expression verified by qRT-PCR. miRNAs specific for certain cell phenotypes were modulated using miRNA inhibitors or stable transfection. Neuronal differentiation was induced by RA; non-neuronal differentiation by BrdU. Changes in tumorigenicity were assayed by soft agar colony forming ability. N-myc binding to miR-375 promoter was assayed by chromatin-immunoprecipitation. Unsupervised hierarchical clustering of miRNA microarray data segregated neuroblastic and non-neuronal cell lines and showed that specific miRNAs define each phenotype. qRT-PCR validation confirmed that increased levels of miR-21, miR-221 and miR-335 are associated with the non-neuronal phenotype, whereas increased levels of miR-124 and miR-375 are exclusive to neuroblastic cells. Downregulation of miR-335 in non-neuronal cells modulates expression levels of HAND1 and JAG1, known modulators of neuronal differentiation. Overexpression of miR-124 in stem cells induces terminal neuronal differentiation with reduced malignancy. Expression of miR-375 is exclusive for N-myc-expressing neuroblastic cells and is regulated by N-myc. Moreover, miR-375 downregulates expression of the neuronal-specific RNA binding protein HuD. Thus, miRNAs define distinct NB cell phenotypes. Increased levels of miR-21, miR-221 and miR-335 characterize the non-neuronal, non-malignant phenotype and miR-335 maintains the non-neuronal features possibly by blocking neuronal differentiation. miR-124 induces terminal neuronal differentiation with reduction in malignancy. Data suggest N-myc inhibits neuronal differentiation of neuroblastic cells possibly by upregulating miR-375 which, in turn, suppresses HuD. As tumor differentiation state is highly predictive of patient survival, the involvement of these miRNAs with NB differentiation and tumorigenic state could be exploited in the development of novel therapeutic strategies for this enigmatic childhood cancer
[en] Highlights: • Treatment with GL could improve the neurological function recovery and reduce the lesion volume after TBI. • Administration of GL could inhibit the release and expression of HMGB1. • Treatment with GL could inhibit M1 phenotype while promoted M2 phenotype activation of microglia/macrophages after TBI. Microglia/Macrophages have a double-edged role in secondary brain damage after traumatic brain injury (TBI) depending on polarization toward proinflammatory M1 or anti-inflammatory M2 phenotypes. Recently, high-mobility group box 1 (HMGB1) was found to influence the polarization of macrophages. In this study, glycyrrhizin (GL), an inhibitor of HMGB1, was used to investigate whether the inhibition of HMGB1 could modulate microglia/macrophage polarization after TBI. The results showed that treatment with GL improved the neurological function recovery, reduced the lesion volume, and inhibited the release and expression of HMGB1 after TBI. In addition, the administration of GL suppressed M1 phenotype activation and promoted M2 phenotype activation of microglia/macrophages. In conclusion, the results suggested that GL attenuated TBI by inhibiting M1 phenotype while inducing M2 phenotype activation of microglia/macrophages, at least partly through inhibiting HMGB1. Also, targeting HMGB1 to modulate the microglia/macrophage polarization should be one potential therapeutic approach for TBI.