Soyasaponin Ag inhibits triple-negative breast cancer progression via targeting the DUSP6/MAPK signaling

Introduction. Soyasaponins are triterpenoid glycosides discovered in soybean and have anti-cancer properties. Soyasaponin A was reported to repress estrogen-insensitive breast cancer cell proliferation. This study intends to explore the role of one isomer of soyasaponin A, i.e. soyasaponin Ag (Ssa Ag), in triple-negative breast cancer (TNBC) development. Material and methods. Bioinformatic databases were used to predict DUSP6 expression in breast cancer (BC) as well as the correlation between the expression of DUSP6 (or MAPK1, MAPK14) with the prognosis of patients with BC. The expression of DUSP6/MAPK signaling-related genes (DUSP6, MAPK1, and MAPK14) in TNBC cell lines was assessed via Western blot analysis and RT-qPCR. Levels of cell apoptosis proteins (Bax and Bcl-2) in TNBC cells were assessed via Western blot analysis. CCK-8 assay, colony formation assay, and flow cytometry analysis were conducted for the measurement of TNBC cell growth and apoptosis. In vivo xenograft assay was employed for investigating the biological influence of Ssa Ag on tumor growth. Results. The poor prognosis of BC patients was linked to the aberrant expression of DUSP6/MAPK pathwaygenes. Low expression of DUSP6 or high expression of MAPK1 (or MAPK14) was correlated to poor prognosis. DUSP6 was downregulated while MAPK1 and MAPK14 were upregulated in TNBC cells versus normal cells. Ssa Ag upregulated DUSP6 expression while downregulated MAPK1 and MAPK14 expression, inhibiting the MAPK signaling pathway. Additionally, Ssa Ag promoted in vitro TNBC cell apoptosis and restrained cell growth, and repressed in vivo tumor growth. Conclusions. Ssa Ag inhibited TNBC progression via upregulating DUSP6 and inactivating the MAPK signaling pathway

A novel voltage limiter circuit for passive RFID tag

This paper presents a novel voltage limiter circuit used in passive RFID tag to avoid possible damage to the tag. The proposed voltage limiter design takes advantage of the implemented band-gap reference to provide low temperature and process deviation of the limiting voltage and has low current consumption. The simulation result shows the limiting voltage is 2V with a voltage variation of 81.86mV. The quiescent current is only 120nA. The circuit is designed with TSMC 0.18??m CMOS process. The circuit area is 92??96??m2.EI

Immunomodulation-based strategy for improving soft tissue and metal implant integration and its implications in the development of metal soft tissue materials

The difficulties associated with metal implants and soft tissue integration have significantly affected the applications of metal implants in soft-tissue-related areas. Prompted by the close association between soft tissue integration and the immune response, an immunomodulation-based strategy is proposed to manipulate the immune microenvironment and improve metal implant–soft tissue integration. Considering their vital roles in soft tissue responses to metal implants, macrophages are used and the cytokines fingerprints of M1 and M2 macrophage immune microenvironments are evaluated for their potential modulatory effects on metal implant–soft tissue integration. The modulatory effects of different immune microenvironments on model soft tissue cells (human gingival epithelium cells) cultured on model metal implants (titanium alloy disks) are then described, with the underlying possible mechanism FAK-AKT-mTOR signaling unveiled. As further proof of concept, IL-4/PDA (polydopamine)-coated titanium alloy implants, aiming at modulating M2 macrophage polarization, are prepared and found to improve the in vivo metal implant-soft tissue integration. It is the authors' ambition that this immunomodulation-based strategy will change the negative perception and encourage the active development of metal materials with favorable soft tissue integration properties, thus improving the success rates of perforating metal implants and broadening their application in soft-tissue-related areas.</p

Tumor budding of cervical squamous cell carcinoma: epithelial-mesenchymal transition-like cancer stem cells?

Recent evidence indicates that cancer stem cells (CSCs) are the origin of cancers. Scientists have identified CSCs in various tumors and have suggested the existence of a variety of states of CSCs. The existence of epithelial–mesenchymal transition (EMT)-like CSCs has been confirmed in vitro, but they have not been identified in vivo. Tumor budding was defined as single cell or clusters of ≤ 5 cells at the invasive front of cancers. Such tumor budding is hypothesized to be closely related to EMT and linked to CSCs, especially to those migrating at the invasive front. Therefore, tumor budding has been proposed to represent EMT-like stem cells. However, this hypothesis has not yet been proven. Thus, we studied the expression of EMT markers, certain CSC markers of tumor budding, and the tumor center of cervical squamous cell carcinoma (CxSCC). We performed tissue chip analyses of 95 primary CxSCCs from patients. Expression of EMT and CSC markers (E-cadherin, β-catenin, vimentin, Ki67, CD44, SOX2 , and ALDH1A1) in a set of tumor samples on tissue chips (87 cases of tumor budding/the main tumor body) were evaluated by immunohistochemistry. We found that the cell-membranous expression of β-catenin was stronger in the main tumor body than in tumor buds. Compared with the main tumor body, tumor buds had reduced proliferative activity as measured by Ki67. Moreover, vimentin expression was high and E-cadherin expression was low in tumor buds. Expression of EMT-related markers suggested that tumor buds were correlated with EMT. We noted that CxSCC tumor buds had a CD44negative/low/SOX2high/ALDH1A1high staining pattern, indicating that tumor buds of CxSCC present CSC-like immunophenotypic features. Taken together, our data indicate that tumor buds in CxSCC may represent EMT-like CSCs in vivo

Downregulation of PPA2 expression correlates with poor prognosis of kidney renal clear cell carcinoma

Background Kidney renal clear cell carcinoma (KIRC) is the most common subtype of kidney cancer. Inorganic pyrophosphatase (PPA2) is an enzyme that catalyzes the hydrolysis of pyrophosphate to inorganic phosphate; few studies have reported its significance in cancers. Therefore, we aimed to explore the prognostic value of PPA2 in KIRC. Methods PPA2 expression was detected via immunohistochemistry in a tissue chip containing specimens from 150 patients with KIRC. We evaluated the correlation between PPA2 expression, clinicopathological characteristics, and survival. Data from online databases and another cohort (paraffin-embedded specimens from 10 patients with KIRC) were used for external validation. Results PPA2 expression was significantly lower in KIRC tissues than in normal renal tissues (p < 0.0001). Low expression of PPA2 was significantly associated with a high histologic grade and poor prognosis. The differential expression of PPA2 was validated at the gene and protein levels. Multivariate Cox regression analysis showed that PPA2 expression was an independent prognostic factor in patients with KIRC. Gene set enrichment analysis suggested that decreased expression of PPA2 might be related to the epithelial-mesenchymal transition in KIRC. Conclusions Our study demonstrated that PPA2 is an important energy metabolism-associated biomarker correlated with a favorable prognosis in KIRC

Identification of new M 31 star cluster candidates from PAndAS images using convolutional neural networks

Context. Identification of new star cluster candidates in M 31 is fundamental for the study of the M 31 stellar cluster system. The machine-learning method convolutional neural network (CNN) is an efficient algorithm for searching for new M 31 star cluster candidates from tens of millions of images from wide-field photometric surveys. Aims. We search for new M 31 cluster candidates from the high-quality g- and i-band images of 21 245 632 sources obtained from the Pan-Andromeda Archaeological Survey (PAndAS) through a CNN. Methods. We collected confirmed M 31 clusters and noncluster objects from the literature as our training sample. Accurate double-channel CNNs were constructed and trained using the training samples. We applied the CNN classification models to the PAndAS g- and i-band images of over 21 million sources to search new M 31 cluster candidates. The CNN predictions were finally checked by five experienced human inspectors to obtain high-confidence M 31 star cluster candidates. Results. After the inspection, we identified a catalogue of 117 new M 31 cluster candidates. Most of the new candidates are young clusters that are located in the M 31 disk. Their morphology, colours, and magnitudes are similar to those of the confirmed young disk clusters. We also identified eight globular cluster candidates that are located in the M 31 halo and exhibit features similar to those of confirmed halo globular clusters. The projected distances to the M 31 centre for three of them are larger than 100 kpc

TRIM6: An Upregulated Biomarker with Prognostic Significance and Immune Correlations in Gliomas

This study investigates the expression and prognostic value of TRIM6 in gliomas, the most prevalent primary brain and spinal cord tumors. Our results show that TRIM6 is predominantly overexpressed in glioma tissues and is associated with reduced overall survival, disease-specific survival, and progression-free interval. Furthermore, TRIM6 expression is correlated with WHO grade and primary treatment outcomes. Functional analysis indicates that interactions between cytokines and their receptors play a critical role in the prognosis of glioma patients. A protein-protein interaction network reveals 10 hub genes closely linked to cytokine-cytokine receptor interaction. In vitro experiments demonstrate that silencing TRIM6 impairs the proliferation, invasion, and migration of glioma cells, while overexpressing TRIM6 enhances these abilities. Additionally, TRIM6 expression is positively associated with the abundance of innate immune cells and negatively associated with the abundance of adaptive immune cells. In summary, TRIM6 is significantly upregulated in gliomas and linked to poor prognosis, making it a potential diagnostic and prognostic biomarker. TRIM6 plays a crucial role in promoting cell viability, clonogenic potential, migration, and invasion in glioma cells. It may regulate glioma progression by modulating cytokine-cytokine receptor interaction, leading to an inflammatory response and an imbalance in immunomodulation, thereby representing a potential therapeutic target

The osteoimmunomodulatory property of a barrier collagen membrane and its manipulation via coating nanometer-sized bioactive glass to improve guided bone regeneration

A barrier membrane is a major component of guided bone regeneration (GBR), which is traditionally viewed as a physical barrier. Due to its “foreign body” nature, the implantation of a barrier membrane would inevitably modulate immune response and subsequently affect bone dynamics, which has long been neglected. To bridge this knowledge gap, we investigated the osteoimmunomodulatory effects of barrier collagen membranes. It is found that barrier collagen membranes elicit significant effects on modulating the osteoimmune response of macrophages, by upregulating the expression of pro-inflammatory cytokines (TNFα, IL-1β, IL-6, and IL-18) and osteogenic factors (BMP2/6, WNT10b, OSM). The modulated-osteoimmune environment was beneficial for the osteogenic differentiation of BMSCs, due to the activation of BMP, canonical WNT/β-catenin, and OSM signalling pathways. The membrane-mediated osteoimmunomodulation was further modulated to show whether osteogenesis could be enhanced via manipulating the membrane-mediated osteoimmunomodulation. The membrane-mediated osteoimmune response was successfully tuned through coating the collagen membranes with nanometer-sized bioactive glass Ca2ZnSi2O7 by pulsed laser deposition, which is indicated from the change in the expression profile of inflammatory cytokines and the upregulated expression of osteogenic factors. The modulated osteoimmune environment enhanced the osteogenic differentiation of BMSCs, suggesting that collagen membranes with nanometer-sized Ca2ZnSi2O7 coating can be promising for GBR applications. These results collectively imply that barrier membranes are bioactive barriers with an osteoimmunomodulatory effect and not just physical barriers. New generation barrier membranes should be designed with a favourable osteoimmunomodulatory property