SC Cells Research Articles

Cytotoxicity and genotoxicity of bioceramic root canal sealers compared to conventional resin-based sealer

The aim of this study was to evaluate cytotoxicity and genotoxicity of calcium-silicate based sealers and comparing them with a gold standard—an epoxy-based sealant. Two experimental cell lines were used, gingival fibroblasts (hGF) and monocyte/macrophage peripheral blood cell line (SC). The cytotoxicity (XTT assay) and genotoxicity (comet assay) were evaluated both after 24-h and 48-h incubation. Additionally, after 48-h incubation, the cell apoptosis and cell cycle progression was detected. BioRoot Flow induced a significant decrease in hGF cells viability compared to the negative control groups both after 24-h (p < 0.001) and 48-h incubation (p < 0.01). In group with SC cells, after 24-h incubation significant increase in cells viability was detected for AH Plus Bioceramic Sealer in comparison to negative control (p < 0.05). BioRoot Flow and BioRoot RCS can be considered potentially genotoxic for the hGF cells after 48-h incubation (> 20% DNA damage). BioRoot Flow and BioRoot RCS, may have potential genotoxic effects and induce apoptosis in hGF cells which may irritate periapical tissues, resulting in a delayed healing. The findings of the study would be useful in selection of an appropriate sealant for root canal filling without causing cytotoxicity and genotoxicity.

An 80-GHz DCO utilizing improved SC ladder and promoted DCTL-based hybrid tuning banks

An 80-GHz DCO based on modified hybrid tuning banks is introduced in this paper. To achieve sub-MHz frequency resolution with reduced circuit complexity, the improved circuit topology replaces the conventional circuit topology with two binary-weighted SC cells, enabling eight SC-cell-based improved SC ladders to achieve the same fine-tuning steps as twelve SC-cell-based conventional SC ladders. To achieve lower phase noise and smaller chip size, the promoted binary-weighted digitally controlled transmission lines (DCTLs) are used to implement the coarse and medium tuning banks of the DCO. Compared to the conventional thermometer-coded DCTLs, control bits of the proposed DCTLs are reduced from 30 to 8, and the total length is reduced by 34.3% (from 122.76 to 80.66 μm). Fabricated in 40-nm CMOS, the DCO demonstrated in this work features a small fine-tuning step (483 kHz), a high oscillation frequency (79–85 GHz), and a smaller chip size (0.017 mm2). Compared to previous work, the modified DCO exhibits an excellent figure of merit with an area (FoMA) of –198 dBc/Hz.

Combined Treatment with Bojungikgi-tang (Buzhong Yiqi Decoction) and Riluzole Attenuates Cell Death in TDP-43-Expressing Cells.

To examine the effect of combined treatment with Bojungikgi-tang (BJIGT, Buzhong Yiqi Decoction) and riluzole (RZ) in transactive response DNA-binding protein 43 (TDP-43) stress granule (SG) cells, a amyotrophic lateral sclerosis (ALS) cell line using transcriptomic and molecular techniques. TDP-43 SG cells were pretreated with BJIGT (100 µg/mL), RZ (50 µmol/L), and combined BJIGT (100 µg/mL)/RZ (50 µmol/L) for 6 h before treatment with lipopolysaccharide (LPS, 200 µmol/L). Cell viability assay was performed to elucidate cell toxicity in TDP-43 SC cells using a cell-counting kit-8 (CCK8) assay kit. The expression levels of cell death-related proteins, including Bax, caspase 1, cleaved caspase 3 and DJ1 in TDP-43 SG cells were examined by Western blot analysis. The autophagy-related proteins, including pmTOR/mTOR, LC3b, P62, ATG7 and Bcl-2-associated athanogene 3 (Bag3) were investigated using immunofluorescence and immunoblotting assays. Cell viability assay and Western blot analysis showed that combined treatment with BJIGT and RZ suppressed LPS-induced cell death and expression of cell death-related proteins, including Bax, caspase 1, and DJ1 (P<0.05 or P<0.01). Immunofluorescence and immunoblotting assays showed that combined treatment with BJIGT and RZ reduced LPS-induced formation of TDP-43 aggregates and regulated autophagy-related protein levels, including p62, light chain 3b, Bag3, and ATG7, in TDP-43-expressing cells (P<0.05 or P<0.01). The combined treatment of BJIGT and RZ might reduce inflammation and regulate autophagy dysfunction in TDP-43-induced ALS.

A green approach for decolorising azo dyes by using AlCrFeMn-based high-entropy alloys doped with nonmetallic elements (S, P and C)

The effects of nonmetallic elements Sulfur (S), Phosphorus (P) and Carbon (C) on the decolorisation of azo dye direct blue 6 (DB6) by using ball-milled (BM) Co-free AlCrFeMn (S0) high-entropy alloy (HEA) are presented for the first time in this work. We report the approach of adding S, P and C into S0 HEA in a single step by ball milling, and it is environment friendly method. Moreover, HEAs added with S, P and C do not cause secondary pollution of water during decolorisation recation. DB6 dye solution (200 mg/L) can be fully decolorised in 0.3, 1.9 and 3.3 min with 0.5 g/L of BM AlCrFeMnS (SS), AlCrFeMnP (SP), and AlCrFeMnC (SC), which are about 42, 6.6 and 3.8 times faster than that of S0, respectively. The efficiency of SS for DB6 is 126,000 times that of commercially available pure iron powders. The activation energy of SS is 36.3 kJ/mol, which is lower than that of S0 (54.6 kJ/mol). The extremely high decolorisation efficiency is closely related with the formation of a large number of galvanic cells in SS, SP and SC between the metal and nonmetal elements, which greatly increases the amount and efficiency of electron transfer. The decolorisation efficiency of DB6 solution is assessed by ultraviolet–visible absorption spectrophotometry. The decolorisation rate follows pseudo-first-order reaction kinetics with respect to dye concentration. The results of this study provide some enlightenment for researchers in the application of HEAs in wastewater treatment.

Abstract 2584: Overcoming cetuximab resistance in colorectal cancer through inhibition of HGF processing

Abstract Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR) and can prolong survival in metastatic colorectal cancer (CRC) patients. However, therapeutic resistance can limit its efficiency and use. Our lab has previously identified that the activation of receptor tyrosine kinases (RTKs) MET and RON contributed to cetuximab resistance. In the absence of activating mutations of MET and RON, the activity of these RTKs depends on the availability of their ligands, hepatocyte growth factor (HGF) and hepatocyte growth factor-like (HGFL), respectively. To become biologically active, the inactive precursors of HGF and HGFL must be processed by serine proteases (HGFA, matriptase, and hepsin). A survey of TCGA datasets indicated that MET and HGF were overexpressed in several CRC CMS subtypes. However, we did not observe any significant overexpression of the serine proteases. Hepatocyte growth factor activator inhibitor type 1 and 2 (HAI-1/2) are two Kunitz-type serine protease inhibitors that displayed reduced expression in TCGA datasets. The addition of recombinant human HGF conferred cetuximab resistance to cetuximab-sensitive cells and cetuximab-sensitive cells engineered to overexpress HGF also exhibited cetuximab-resistant phenotype. Cetuximab resistance induced by HGF addition or overexpression could be overcome by downstream inhibition with crizotinib, a multi-targeted RTK inhibitor. ZFH7116 is a small molecule inhibitor of the serine proteases that mimics HAI-1 activity. ZFH7116 suppressed HGF cleavage and maturation in our cetuximab-resistant SC cells. We observed cooperative effect of ZFH7116 with cetuximab to reduce SC cell growth in 3D collagen cultures. We are currently testing if upstream inhibition with recombinant human HAI-1 addition can suppress HGF cleavage and overcome cetuximab resistance induced by HGF overexpression. Collectively, our findings suggest that inhibiting HGF cleavage and processing may be a unique strategy for overcoming EGFR-targeted therapy resistance in colorectal cancer. Citation Format: Vivian Truong Jones, Ramona Graves-Deal, Galina Bogatcheva, Zheng Cao, James Higginbotham, Sarah Harmych, Gregory Ayers, Marisol Ramirez, Qi Liu, James Janetka, Bhuminder Singh. Overcoming cetuximab resistance in colorectal cancer through inhibition of HGF processing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2584.

Study of heat transfer in models of FCC, BCC, SC and DEM porous structures with different porosities

In the present work, we investigated the effect of the geometry of the open cell foam material on the value of the pressure drop and heat flux. We create models of porous media with an ordered (FCC, BCC, SC) and disordered (DEM) structure with different values of material porosity: 0.7; 0.75; 0.8. Numerical modeling was carried out in the ANSYS Fluent software (v. 19.0) for various air flow velocities. At material porosities of 0.7 and 0.75 there is a noticeable increase in pressure drop in BCC and FCC packings, respectively. This is due to the features of creating the geometry of these packings. At material porosity of 0.8, the largest pressure drop corresponds to the packing of FCC cells. The structures show approximately the same heat flux value at air flow velocities of 0.01 and 0.05 m/s. At material porosity of 0.7 at velocities of 0.25-1.25 m/s, the largest values show the BCC packing. At material porosities 0.75 and 0.8, the values above correspond to the packing of FCC cells. The lowest heat flux values in SC cell packaging are observed at all investigated porosities. Also, the SC packing has the lowest pressure drop values and, therefore, the highest energy efficiency values.

Production of endoglin-specific heavy chain antibody fragments (VHHs) microarrays for whole-cell SPR imaging

Cell-based Surface Plasmon Resonance imaging (SPRi) with anti-endoglin VHH antibodies microarray on a gold-covered biochip was used to characterize the binding to endoglin expressed on the surface membrane of SC cells. SPRi showed the specific capture of SC cells by the immobilized anti-endoglin VHHs, but not of THP-1 cells that do not express endoglin on their plasmatic membrane. The SPRi reflectivity shifts with SC cells bound by anti-endoglin VHHs ranged from 3.59 to 5.54% (average 4.66 ± 1.18%) and with THP-1 cells from 2.23 to 3.05% (average 2.62 ± 1.32% (p < 0.001)) and the SC cell densities with anti-endoglin VHHs ranged from 417 to 747.7, (average 548 cells/2.28 × 105 μm2 ± 132). Anti-endoglin VHHs bind epitopes located in the extracellular domains of endoglin with different avidity as suggested by the differences in SC cell densities. The cell-based SPRi of anti-endoglin VHH microarrays can be used both in studies aimed at a better understanding of endoglin function in living cells and in VHH applications as nanoprobes.

The Cytotoxicity and Genotoxicity of Bioactive Dental Materials.

The promotion of biologically based treatment strategies in restorative dentistry is of paramount importance, as invasive treatments should be avoided to maintain the tooth’s vitality. This study aimed to assess the biocompatibility of commercially available bioactive materials that can be used for dental pulp capping. The study was performed with a monocyte/macrophage peripheral blood SC cell line (ATCC CRL-9855) on the following six specific bioactive materials: ProRoot MTA (Dentsply Sirona), MTA Angelus (Angelus), Biodentine (Septodont), TheraCal LC (Bisco), ACTIVA BioACTIVE (Pulpdent) and Predicta Bioactive Bulk (Parkell). The cytotoxicity of the investigated agents was measured using a resazurin-based cell viability assay, while the genotoxicity was evaluated using an alkaline comet assay. Additionally, flow cytometry (FC) apoptosis detection was conducted with a FITC (fluorescein isothiocyanate) Annexin V Apoptosis Detection Kit I. FC cell-cycle arrest assessment was carried out with propidium iodide staining. The results of this study showed no significant cytotoxicity and genotoxicity (p > 0.05) in ProRoot MTA, MTA Angelus, Biodentine, ACTIVA BioACTIVE and Predicta Bioactive. Conversely, TheraCal LC presented a significant decrease (p < 0.001). In conclusion, due to excellent biocompatibility and low cytotoxicity, MTA, Biodentine, ACTIVA BioACTIVE and Predicta Bioactive may be suitable for pulp capping treatments. On the other hand, due to the high cytotoxicity of TheraCal LC, its use should be avoided in vital pulp therapies.

Boost DC-DC Converter with Switched-Capacitor and Four-State Switching Cell

The integration of switched-capacitor voltage multiplier cells in basic converter topologies has been studied to provide voltage gain and voltage stress reduction. However, SC cells do not provide current sharing and additionally they induce high current spikes in the devices, which are limitations of these structures to operate in high power levels. The main contribution of this paper is to overcome this drawback proposing the use of a multistate switching-cell for current sharing in SC-based boost converters, which reduces the current stress in the power devices and increases the power levels of this family of converters. The proposed concept can be generalized for m number of SC cells and n number of switching cells to increase the voltage gain and current levels. Furthermore, it can be applied to other basic structures. The theoretical analysis of the proposed structure was evaluated experimentally in a 3 kW boost-type dc-dc converter, achieving 200 V to 1200 V voltage gain, and reaching 98.4% of maximum efficiency.

Surface-Modified Polypyrrole-Coated PLCL and PLGA Nerve Guide Conduits Fabricated by 3D Printing and Electrospinning.

The efficiency of nerve guide conduits (NGCs) in repairing peripheral nerve injury is not high enough yet to be a substitute for autografts and is still insufficient for clinical use. To improve this efficiency, 3D electrospun scaffolds (3D/E) of poly(l-lactide-co-ε-caprolactone) (PLCL) and poly(l-lactide-co-glycolide) (PLGA) were designed and fabricated by the combination of 3D printing and electrospinning techniques, resulting in an ideal porous architecture for NGCs. Polypyrrole (PPy) was deposited on PLCL and PLGA scaffolds to enhance biocompatibility for nerve recovery. The designed pore architecture of these "PLCL-3D/E" and "PLGA-3D/E" scaffolds exhibited a combination of nano- and microscale structures. The mean pore size of PLCL-3D/E and PLGA-3D/E scaffolds were 289 ± 79 and 287 ± 95 nm, respectively, which meets the required pore size for NGCs. Furthermore, the addition of PPy on the surfaces of both PLCL-3D/E (PLCL-3D/E/PPy) and PLGA-3D/E (PLGA-3D/E/PPy) led to an increase in their hydrophilicity, conductivity, and noncytotoxicity compared to noncoated PPy scaffolds. Both PLCL-3D/E/PPy and PLGA-3D/E/PPy showed conductivity maintained at 12.40 ± 0.12 and 10.50 ± 0.08 Scm-1 for up to 15 and 9 weeks, respectively, which are adequate for the electroconduction of neuron cells. Notably, the PLGA-3D/E/PPy scaffold showed superior cytocompatibility when compared with PLCL-3D/E/PPy, as evident via the viability assay, proliferation, and attachment of L929 and SC cells. Furthermore, analysis of cell health through membrane leakage and apoptotic indices showed that the 3D/E/PPy scaffolds displayed significant decreases in membrane leakage and reductions in necrotic tissue. Our finding suggests that these 3D/E/PPy scaffolds have a favorable design architecture and biocompatibility with potential for use in peripheral nerve regeneration applications.

ST6Gal1 Contributes to Pancreatic Cancer Initiation by Promoting Pancreatitis‐Induced Acinar to Ductal Metaplasia

Aberrant glycosylation is one of the earliest known hallmarks of cancer. Amongst the predominate changes in tumor cell glycosylation is an increase in α2‐6 sialylation on N‐glycans, a modification elaborated by the ST6Gal1 sialyltransferase. ST6Gal1 activity dramatically alters cellular function via the sialylation of various surface receptors such as EGFR and TNFR1, resulting in altered signal transduction and gene expression. ST6Gal1 expression is upregulated in multiple cancers, including pancreatic ductal adenocarcinoma (PDAC). Recent studies from our group suggest that the upregulation of ST6Gal1 in pancreatic acinar cells may promote PDAC initiation by facilitating acinar to ductal metaplasia (ADM), a process in which acinar cells de‐differentiate into ductal‐like, progenitor cells. In the nonmalignant pancreas, ADM is induced primarily by pancreatitis, a known risk factor for PDAC. Pancreatitis causes acinar cell apoptosis, however some cells undergo ADM and acquire regenerative capabilities essential for tissue healing. Notably, ADM‐like cells are particularly susceptible to oncogenic transformation. In the current study we determined that ST6Gal1 was strikingly upregulated in pancreatic tissues from chronic pancreatitis patients and mice with experimental pancreatitis. Furthermore, ST6Gal1 was selectively expressed in the ADM‐like cells, as identified both morphologically and by staining for ADM‐specific markers. ST6Gal1 activity was associated with a proliferative phenotype. More than 50% of cells with upregulated ST6Gal1 co‐expressed the proliferative marker, Ki67, whereas activated caspase 8 was undetectable in ST6Gal1‐positive cells. To interrogate a functional role for ST6Gal1 in ADM, we developed genetically‐engineered mice with ST6Gal1 expression in the pancreas (“SC” mice). Importantly, acinar cells from SC mice exhibited ADM‐like characteristics, indicated by increased expression of classic stem and ductal genes. RNASeq analyses comparing SC and WT pancreata indicated that SC cells had an enrichment in: stem cell pathways; a pancreatic ductal cell program; and gene networks associated with pancreatic cancer. Additionally, organoids derived from SC pancreata displayed increased expression of stem and ductal genes relative to WT organoids, as well as greater organoid‐forming potential and growth. To evaluate inflammation‐induced ADM, SC and WT mice were injected with cerulein to induce pancreatitis, and the ADM‐like cells were quantified by examining surface ADM markers by flow cytometry. Following induction of pancreatitis, more ADM‐like cells were present in SC versus WT pancreata. Finally, we crossbred SC mice to the “KC” PDAC model, which expresses oncogenic KRas (KrasG12D) in the pancreas. Mice with dual expression of ST6Gal1 and KrasG12D had greatly accelerated PDAC initiation, progression and mortality as compared with KC mice. Together these data suggest that the upregulation of ST6Gal1 during chronic pancreatitis may prime acinar cells for neoplastic transformation by facilitating ADM.

Characterization of the Three Dimensional Genome in Human Skeletal Muscle Progenitor Cells

Duchenne Muscular Dystrophy (DMD) is a devastating disease with no cure affecting approximately 1 in 3,500‐5,000 boys. Stem cell treatments using skeletal muscle stem cells (or satellite cells, SCs) provide great potential for regenerating new muscle and we have developed directed differentiation strategies to generate skeletal muscle cells from human induced pluripotent stem cells (hiPSCs). Our work has shown that hiPSCs generate PAX7+ skeletal muscle progenitor cells (SMPCs) resembling early myogenic cells that align closer to week 7‐12 in human development and are not equivalent to adult SCs. We are interested in understanding the key molecular and functional differences that control SMPC versus SC cell states. Recently, there has been an intense interest in the three dimensional (3D) organization of the genome and its involvement in cell specific gene regulation. This has led to the discovery of chromatin loops between gene enhancers and promoters as well as self‐interacting domains termed topologically associating domains (TADs). Recently published data support a role for the 3D genome in cellular differentiation, however, the differences between the 3D genome in human SMPCs compared to adult SCs is unknown. High throughput chromosome conformation capture (Hi‐C) was used to characterize the 3D genome of SMPCs. We found genome‐wide 3D configurations were different between hPSCs and SMPCs as was the number of TADs. Interestingly, TAD size was also different between cell types, suggesting dynamic control of TADs during differentiation. When focusing on the PAX7 locus, TAD boundaries differ between cell types further highlighting the dynamic nature of TADs with respect to cell specific gene expression. Not all muscle specific loci were different between cell types, however, suggesting that some TADs may be pre‐established early in the differentiation process while others are established de‐novo. With respect to chromatin looping at the PAX7 locus, we found SMPC specific looping between the PAX7 promoter and downstream sequences that were unique in SMPCs. Considering that PAX7 enhancer sequences have yet to be determined, these sequences may serve as candidate enhancers for PAX7. These data, for the first time, characterize the 3D genome of human SMPCs using Hi‐C. Moreover, these data provide candidate enhancer sequences for that could provide unique candidates for support of PAX7 SMPCs.

The Impact of Exosomes/Microvesicles Derived from Myeloid Dendritic Cells Cultured in the Presence of Calcitriol and Tacalcitol on Acute B-Cell Precursor Cell Lines with MLL Fusion Gene.

Vitamin D analogs (VDAs) may directly inhibit the growth of normal and malignant (derived from acute lymphoblastic leukemia (ALL)) B cells, as both types of cells express vitamin D receptor (VDR). We performed anti-proliferative, morphology tests and phenotyping to evaluate the sensitivity of monocytes and iDCs (immature myeloid-derived dendritic cells) on calcitriol and tacalcitol treatment, phenotyping, morphology, and size distribution measurement to determine the characteristics of microvesicles (MVs) and exosomes (EXs) derived from them and, finally, phenotyping and Elisa test to determine the effects of VDAs on modulation of the phenotype of B cells through extracellular vesicles (EVs) released by iDCs. Our results confirmed that both SC cells and iDCs were sensitive to the VDAs and showed altered surface expression of markers associated with monocyte differentiation, which was resulting in the phenotypic changes in EVs derived from them. We also showed that obtained EVs could change the morphology and phenotype of ALL-B-derived precursor cells in a different way, depending on their origin. The differential effect of VDAs on ALL-B cells, which was associated with increased or decreased expression of CD27, CD24, CD38, and CD23 expression, was observed. Hence, further studies to explain the modulation in the composition of EVs by VDAs are required.

The SC cell line as an in vitro model of human monocytes.

In vitro analysis of human macrophages is generally hampered by the necessity to differentiate them from peripheral blood monocytes. We have analyzed to which extent noncancerous SC monocytes could be used as an in vitro macrophage model. Macrophages differentiated from peripheral monocytes using standard CSF1 and CSF2 protocols for M2 and M1 precursors, respectively, were compared with THP-1-derived macrophages treated with PMA and with SC-derived macrophages differentiated either by CSF1, CSF2, or PMA according to different protocols. The optimal condition for generation of SC macrophages was treatment with PMA for 3 days, followed by 5-days culture without PMA and 24-h polarization with LPS/IFN-γ or IL-4/IL-13. Similar to THP-1, SC cells do not express the monocyte marker CD14 and differentiation to macrophages results neither in CD68 nor in CD14 expression, both of which were expressed by monocyte-derived macrophages. Similar to THP-1-macrophages, a proportion of SC macrophages can be polarized to the M1-like subtype that is characterized by higher expression of CD38, CD86, CD80, TNF-α, and IL-1ra, whereas treatment with IL4/IL13 did not lead to expression of the M2-associated receptors CD163, CD206, and only slightly increased the CD200R expression. Still, SC-M1 express much lower levels of the M1-associated markers compared with monocyte-derived M1 and no IL-1β. The data demonstrate that SC-derived macrophages differ from monocyte-derived macrophages in respect of their morphology, expression of important macrophage markers, phagocytosis. Yet, polarized SC-M1-like cells may with restrictions serve as a model for M1 macrophages, though this model does not provide significant advantages over already well-described THP-1-M1-like cells.

Synthesis and Hemostatic Activity of New Amide Derivatives.

Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid, 4-(aminomethyl)benzoic acid, and glycine—natural amino acids) were synthesized in a three-step process with good or very good yields. DMT/NMM/TsO− (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests were used to study the effects of the dipeptides on blood components. Blood plasma clotting tests were used to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partial thromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, and aPTT did not differentiate any of the compounds. The prothrombin times for all amides 1–8 were similar. The obtained results in the presence of amides 1–4 and 8 were slightly lower than for the other compounds and the positive control, and they were similar to the results obtained for TA. In the case of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treated with amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lower than for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was used to assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolytic efficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 were among the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptides were evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did not cause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells and did not induce significant DNA damage.

Evaluation of Curcumin Therapeutic Effects on Histological Subtypes of Canine Mammary Gland Tumours

Canine mammary gland tumors (CMGTs) are the most frequent types of cancer in bitches and proposed as a model of human breast cancer. The anticancer effect of curcumin on human breast cancer has been extensively studied. The aim of this study was to evaluate the therapeutic effect of curcumin in two different histologies (simple carcinoma [SC] and squamous cell carcinoma [SCC]) of CMGTs. Primary canine mammary cells were isolated from the tumoral tissues surgically resected from two bitches (Case 1 and Case 2). Cell viability, apoptotic percentage, cell cycle progression and the changes in the cell morphology were evaluated. Curcumin inhibited the growth of both SC (Case 1) and SCC (Case 2) cells. However, Case 1 cells (43.48% ± 3.87% at 0.5 µM) were more sensitive to curcumin than Case 2 cells (59.36% ± 2.09% at 0.5 µM). Curcumin induced total apoptotic cell death through G0/G1 arrest, and this effect was more profound in Case 1 cells. Furthermore, cytoplasmic vacuolization, apoptotic bodies and membrane blebbing were observed in both cells following curcumin treatment. Our findings provide a novel approach for the effects of curcumin as a natural compound on CMGTs. Further investigations should be performed to investigate the molecular mechanisms of the differences in curcumin efficacy for different histological subtypes.

Neurophysiology of the saccadic system: The reticular formation.

This chapter discusses the neurophysiology and function of subcortical circuits and cortical areas involved in saccade generation. While cells within the different nuclei of the brainstem reticular formation shape the temporal details of ipsiversive horizontal and vertical/cyclotorsional saccade components, the cerebellar flocculus, vermis and fastigial nucleus are thought to modulate these saccadic waveforms. Burst neurons in the deep layers of the superior colliculus encode the saccade vector in the contralateral field by a localized population in a motor-error map. The complexity of the saccadic system is evident in the different subclasses of SC cells, ranging from purely visual, to visual-motor, purely motor, and quasi-visual cells. Movement-related activity in all SC cells is dissociated from the retinotopic visual activity. The chapter further discusses neurophysiological findings obtained from the substantia nigra (pars reticulata), the medial thalamus, the frontal eye fields, the supplementary motor area and the parietal lobes, discussing the ever more complex response patterns of their neurons in relation to saccades.

Estimation of energy efficiency factor for models of porous automotive heat exchangers

The present paper examines the effect of the geometry of an open cell foam material on pressure drop, heat flux, and energy efficiency. Models of highly porous media with disordered (DEM) and ordered (SC, FCC, BCC) structures with various porosities were created: ε = 0.85; ε = 0.9; ε = 0.95. The ANSYS Fluent (v. 19.2) software package was used to calculate the heat flux, pressure drop, and energy efficiency from the computational domain at different flow velocities of the gas and for different porosities of the medium. At the porosity value ε = 0.85, the highest pressure drop corresponds to the FCC cell packing, and at porosities ε = 0.9 and ε = 0.95 corresponds to the BCC cell packing. At flow rates of 0.01 m/s and 0.05 m/s, the heat flux value is approximately the same for all types of structures. At porosity of the media ε = 0.85 at velocities of 0.25-1.25 m/s, the value of heat flux and pressure drop is higher for FCC cell packing. At the porosity values ε = 0.9 and ε = 0.95, the BCC cell packaging shows a greater heat flux than the FCC structure. The lowest heat flux value corresponds to the SC structure. At the same time, the lowest pressure drop is also observed for SC cell packing, due to which this structure shows the highest values of the energy efficiency factor.

Screening of Self-Assembling of Collagen IV Fragments into Stable Structures Potentially Useful in Regenerative Medicine.

The aim of the research was to check whether it is possible to use fragments of type IV collagen to obtain, as a result of self-assembling, stable spatial structures that could be used to prepare new materials useful in regenerative medicine. Collagen IV fragments were obtained by using DMT/NMM/TosO− as a coupling reagent. The ability to self-organize and form stable spatial structures was tested by the CD method and microscopic techniques. Biological studies covered: resazurin assay (cytotoxicity assessment) on BJ, BJ-5TA and C2C12 cell lines; an alkaline version of the comet assay (genotoxicity), Biolegend Legendplex human inflammation panel 1 assay (SC cell lines, assessment of the inflammation activity) and MTT test to determine the cytotoxicity of the porous materials based on collagen IV fragments. It was found that out of the pool of 37 fragments (peptides 1–33 and 2.1–2.4) reconstructing the outer sphere of collagen IV, nine fragments (peptides: 2, 4, 5, 6, 14, 15, 25, 26 and 30), as a result of self-assembling, form structures mimicking the structure of the triple helix of native collagens. The stability of spatial structures formed as a result of self-organization at temperatures of 4 °C, 20 °C, and 40 °C was found. The application of the MST method allowed us to determine the Kd of binding of selected fragments of collagen IV to ITGα1β1. The stability of the spatial structures of selected peptides made it possible to obtain porous materials based on their equimolar mixture. The formation of the porous materials was found for cross-linked structures and the material stabilized only by weak interactions. All tested peptides are non-cytotoxic against all tested cell lines. Selected peptides also showed no genotoxicity and no induction of immune system responses. Research on the use of porous materials based on fragments of type IV collagen, able to form stable spatial structures as scaffolds useful in regenerative medicine, will be continued.

Nitrogen-enriched hierarchical porous carbons derived from biomass waste-discarded pear for ultra-high energy density supercapacitor in neutral aqueous electrolyte

Herein, nitrogen-enriched hierarchical porous carbons (HPCs) were synthesized by soaking, carbonization and pickling process using natural discarded pears (DP) as the precursor, ZnCl2 as a chemical etching agent and Mg(NO3)2·6H2O as a template. The ZnCl2 activation could produce abundant micropores, while Mg(NO3)2·6H2O can serve as mesopores template. Consequently, the as-prepared carbon material exhibits a three-dimensional interconnected porous structure with a high specific surface area (SBET) of 1642 m2 g−1 and a pore volume of 1.06 cm3 g−1 as well as high nitrogen content (1.7 at.%). On the basis of electrochemical tests, the SCs involve the final products as electrode material presented remarkable gravimetric capacitance (443.5 F g−1) and volumetric capacitance (285.2 F cm−3) at the current density of 1 A g−1 and excellent rate capability (45.1% capacitance retention from 0.5 A g−1 to 40 A g−1). Most attractively, the constructed DP-Zn-Mg-PC/DP-Zn-Mg-PC symmetric SC cell in 1 M Na2SO4 with a wide potential window of 2.2 V displays an ultra-high energy density of 95.8 Wh kg−1 at 550 W kg−1 together with superior cycling stability (98.6% retention after 10,000 cycles), which is outperform those of some similar peer reported biochars. Thus, this work provides an important guideline for preparing HPCs with high-energy density from eco-friendly and sustainable biomass precursors.