Migratory Properties Research Articles

Clogging caused by coupled grain migration and compaction effect during groundwater recharge for unconsolidated sandstone reservoir in groundwater-source heat pump

In unconsolidated sandstone reservoirs, presence of numerous movable grains and a complex grain size composition necessitates a clear understanding of the physical clogging process for effective groundwater recharge in groundwater-source heat pump systems. To investigate this, a series of seepage experiments was conducted under in situ stress conditions using unconsolidated sandstone samples with varying grain compositions. The clogging phenomenon arises from the combined effects of grain migration and compaction, wherein the migration of both original and secondary crushed fine-grain particles blocks the seepage channels. Notably, grain composition influences the migration and transport properties of the grains. For samples composed of smaller grains, the apparent permeability demonstrates a transition from stability to decrease. In contrast, samples with larger grains experience a skip at the stability stage and directly enter the decrease stage, with a minor exception of a slight increase observed. Furthermore, a unique failure mode characterized by diameter shrinkage in the upper part of the sample is observed due to the combined effects of grain migration and in situ stress-induced compaction. These testing results contribute to a better understanding of the clogging mechanism caused by the coupled effects of grain migration and compaction during groundwater recharge in unconsolidated sandstone reservoirs used in groundwater-source heat pump systems.

Macromolecular insight into the adsorption and migration properties of CH4/CO2/N2 in bituminous coal matrix under uniaxial strain loading

Gas adsorption–migration in coal is of crucial importance for coalbed methane (CBM) recovery; however, the effect of coal deformation on it is not yet very clear, especially at the molecular level. In this study, the effects of uniaxial tension–compression strains on the CH4/CO2/N2 adsorption–migration characteristics in bituminous coal matrix were investigated by integrating the grand canonical Monte Carlo and molecular dynamics methods. The results show that the dual-mode equation fits the isothermal adsorption results, and the adsorption concentration and Langmuir volume are positively correlated with strain. Tension strain has a small effect on a thermodynamic factor but a large effect on Henry constant. In addition, the swelling resistance of coal matrix is positively correlated with tension strain which has a greater impact on the shear resistance of coal matrix containing CO2. The average mass density of the gas is linearly positively correlated with strain that has a large impact on N2 stability. More significantly, the self-diffusion coefficient (Ds) of CH4 is larger than that of CO2/N2, and the relationship between Fick diffusion coefficient and strain is roughly similar to that between Ds and strain. Also, the mass transfer of CO2 permeation is more significant compared to N2, especially for tension strain. These research results provide a basis for the optimization design of CBM recovery in deformed coal reservoirs.

The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish.

Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in the zebrafish. We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of the trunk lymphatic vessel network. Interestingly, we show that Sorbs1 interacts with the BMP pathway and could function outside of Vegfc signaling. Mechanistically, Sorbs1 controls FAK/Src signaling and subsequently impacts on the cytoskeleton processes regulated by Rac1 and RhoA GTPases. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contacts rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties. Overall, using in vitro and in vivo assays, we identify Sorbs1 as an important regulator of venous and lymphatic angiogenesis independently of the Vegfc signaling axis. These results provide a better understanding of the complexity found within context-specific vascular and lymphatic development.

CD276 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma through the TGF-β/SMAD signaling.

Aberrant expression of CD276 has been reported in malignant tumors. However, the exact role and mechanisms of CD276 influence the progression of esophageal squamous cell carcinoma (ESCC) still need to be understood. Bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus databases, along with immunohistochemistry staining, was used to explore the expression patterns of CD276 in ESCC. Cell counting kit-8 and Transwell assays were employed to evaluate the effects of CD276 expression on tumor cell proliferation and motility. Western blotting and Transwell assays were used to explore the potential pathways through which CD276 mediates the progression of ESCC. Moreover, the in vivo role of CD276 in tumor progression was investigated by establishing a lung metastasis mouse model. A significant upregulation of CD276 was observed in ESCC tissues compared to adjacent tissues. The inhibition of CD276 had no evident impact on ESCC cell proliferation but notably hindered their migratory and invasive properties and the expression of epithelial-mesenchymal transition (EMT) markers. Inversely, overexpressing CD276 led to an upregulation of EMT markers, underscoring the capacity of CD276 to amplify the motility of ESCC cells. Furthermore, CD276 was found to enhance the migratory and invasive abilities of ESCC cells by activating the TGF-β/SMAD signaling but not the PI3K/AKT pathway. In vivo studies demonstrated that CD276 facilitates pulmonary metastasis. CD276 is significant upregulation in ESCC tissues and facilitates the EMT process in ESCC cells via the TGF-β/SMAD signaling, thus promoting the progression of ESCC.

Sulforaphane Inhibits Adhesion and Migration of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro.

Only 20% of patients with muscle-invasive bladder carcinoma respond to cisplatin-based chemotherapy. Since the natural phytochemical sulforaphane (SFN) exhibits antitumor properties, its influence on the adhesive and migratory properties of cisplatin- and gemcitabine-sensitive and cisplatin- and gemcitabine-resistant RT4, RT112, T24, and TCCSUP bladder cancer cells was evaluated. Mechanisms behind the SFN influence were explored by assessing levels of the integrin adhesion receptors β1 (total and activated) and β4 and their functional relevance. To evaluate cell differentiation processes, E- and N-cadherin, vimentin and cytokeratin (CK) 8/18 expression were examined. SFN down-regulated bladder cancer cell adhesion with cell line and resistance-specific differences. Different responses to SFN were reflected in integrin expression that depended on the cell line and presence of resistance. Chemotactic movement of RT112, T24, and TCCSUP (RT4 did not migrate) was markedly blocked by SFN in both chemo-sensitive and chemo-resistant cells. Integrin-blocking studies indicated β1 and β4 as chemotaxis regulators. N-cadherin was diminished by SFN, particularly in sensitive and resistant T24 and RT112 cells, whereas E-cadherin was increased in RT112 cells (not detectable in RT4 and TCCSup cells). Alterations in vimentin and CK8/18 were also apparent, though not the same in all cell lines. SFN exposure resulted in translocation of E-cadherin (RT112), N-cadherin (RT112, T24), and vimentin (T24). SFN down-regulated adhesion and migration in chemo-sensitive and chemo-resistant bladder cancer cells by acting on integrin β1 and β4 expression and inducing the mesenchymal-epithelial translocation of cadherins and vimentin. SFN does, therefore, possess potential to improve bladder cancer therapy.

Enhanced gas and plasticizer barrier HTPB composite liner implanted with parallel orientation Fe3O4/RGO nanosheets by an ultrasound/magnet-coassisted method

It is of great significance to prepare liners with excellent inhibition of energetic plasticizer migration and gas barrier properties. Here, we have successfully prepared magnetic iron oxide decorated reduced-graphene-oxide nanosheets (MRGO) by using ultrasound-assisted method. The obtained MRGO nanosheet-fillers were filled into hydroxyl-terminated polybutadiene (HTPB) which was exposed to a magnetic field (200 mT) to achieve ordered orientation of MRGO in the HTPB matrix (Ordered MRGO/HTPB). The laser confocal microscopy demonstrates that MRGO exhibit ordered orientation structure in HTPB matrix with good dispersion, which renders the HTPB composite liners exhibiting high gas and plasticizer barrier capability, with a reduction of 18.9 % in water vapor permeability and a decrease of 14.1 % in dibutyl phthalate (DBP) migration equilibrium concentration as compared with those of random MRGO embedded HTPB composite liners (Random MRGO/HTPB). Moreover, a theoretical model accounting for such enhanced gas/plasticizer barrier performance of HTPB due to the implantation of order aligned MRGO was established, which shows that the effective diffusion pathways of plasticizer/gas for liner penetration would be significantly enhanced when the MRGO nanosheets are oriented within the HTPB matrix. This work provides an effective and facile strategy toward the design and development of composite liners with high plasticizer/gas barrier performance for industrial applications.

Ntsr1 contributes to pulmonary hypertension by enhancing endoplasmic reticulum stress via JAK2-STAT3-Thbs1 signaling

Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. In vitro, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH.

MOF-silsesquioxane synergistic modified hybrid porous membrane for high-performance and high-safety lithium battery

As an emerging alternative separator, electrospun PVDF-HFP (polyvinylidene fluoride-hexafluoropropylene) has been widely studied in lithium battery over the years. However, some shortcomings of PVDF-HFP have limited its further application, such as, poor thermal stability, mechanical and electrochemistry properties. In this work, the cage-like silsesquioxanes (CSQ) and metal–organic-framework (MOF) were chemically bound to PVDF-HFP, and a modified hybrid fibrous membrane with hierarchical pore was fabricated. These hybrid groups were successfully introduced into the backbone of PVDF-HFP, which was not only demonstrated by characterization of their chemical structures, and also demonstrated by morphologies and elemental mass spectrometry with the help of scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS). Due to the incorporation of these hybrid groups, the membrane exhibited high thermal stabilities and good flame-retardant performance, and could also play an important role in regulating and improving the migration property of lithium ions and interface performance between electrolyte and electrodes during battery charging/discharging process.

Growth differentiation factor-11 upregulates matrix metalloproteinase 2 expression by inducing Snail in human extravillous trophoblast cells

The human extravillous trophoblast (EVT) cell invasion is an important process during placentation. Although the placenta is normal tissue, the EVT cells exhibit some features common to cancer cells, including high migratory and invasive properties. Snail and Slug are transcription factors that mediate the epithelial-mesenchymal transition (EMT), a crucial event for cancer cell migration and invasion. It has been shown that GDF-11-induced matrix metalloproteinase 2 (MMP2) expression is required for EVT cell invasion. Whether GDF-11 can regulate Snail and Slug expression in human EVT cells remains unknown. If it does, the involvement of Snail and Slug in GDF-11-induced MMP2 expression and EVT cell invasion must also be defined. In the present study, using the immortalized human EVT cell line, HTR-8/SVneo, and primary cultures of human EVT cells as experimental models, our results show that GDF-11 upregulates Snail and Slug expression. ALK4 and ALK5 mediate the stimulatory effects of GDF-11 on Snail and Slug expression. In addition, we demonstrate that SMAD2 and SMAD3 are required for the GDF-11-upregulated Snail expression, while only SMAD3 is involved in GDF-11-induced Slug expression. Moreover, our results reveal that Snail mediates GDF-11-induced MMP2 expression and cell invasion but not Slug. This study increases our understanding of the biological function of GDF-11 in human EVT cells and provides a novel mechanism for regulating MMP2 and EVT cell invasion.

Yifei Sanjie formula alleviates lung cancer progression via regulating PRMT6-YBX1-CDC25A axis.

Lung cancer (LC) is the most prevalent cancer type, with a high mortality rate worldwide. The current treatment options for LC have not been particularly successful in improving patient outcomes. Yifei Sanjie (YFSJ), a well-applicated traditional Chinese medicine formula, is widely used to treat pulmonary diseases, especially LC, yet little is known about its molecular mechanisms. This study was conducted to explore the molecular mechanism by which YFSJ ameliorated LC progression. The A549, NCI-H1975, and Calu-3 cells were treated with the YFSJ formula and observed for colony number, apoptosis, migration, and invasion properties recorded via corresponding assays. The PRMT6-YBX1-CDC25A axis was tested and verified through luciferase reporter, RNA immunoprecipitation, and chromatin immunoprecipitation assays and rescue experiments. Our results demonstrated that YFSJ ameliorated LC cell malignant behaviors by increasing apoptosis and suppressing proliferation, migration, and invasion processes. We also noticed that the xenograft mouse model treated with YFSJ significantly reduced tumor growth compared with the control untreated group in vivo. Mechanistically, it was found that YFSJ suppressed the expression of PRMT6, YBX1, and CDC25A, while the knockdown of these proteins significantly inhibited colony growth, migration, and invasion, and boosted apoptosis in LC cells. In summary, our results suggest that YFSJ alleviates LC progression via the PRMT6-YBX1-CDC25A axis, confirming its efficacy in clinical use. The findings of our study provide a new regulatory network for LC growth and metastasis, which could shed new insights into pulmonary medical research.

BRG1 mediates epigenetic regulation of TNFα-induced CCL2 expression in oral tongue squamous cell carcinoma cells.

Strong evidence has indicated that upregulation of chemokine (CC motif) ligand-2 (CCL2) expression and the presence of an inflammatory tumor microenvironment significantly contribute to the migratory and invasive properties of oral squamous cell carcinoma, specifically oral tongue squamous cell carcinoma (OTSCC). However, the precise epigenetic mechanism responsible for enhanced CCL2 expression in response to the inflammatory mediator tumor necrosis factor alpha (TNF-α) in OTSCC remains inadequately elucidated. We have demonstrated that the production of CCL2 can be induced by TNF-α, and this induction is mediated by the chromatin remodel protein BRG1. Through the use of a chromatin immunoprecipitation (ChIP) assay, we have found that BRG1 was involved in the recruitment of acetylated histones H3 and H4 at the CCL2 promoter, thereby activating TNF-α-induced CCL2 transcription. Furthermore, we have observed that recruitment of NF-κB p65 to the CCL2 promoter was increased following BRG1 overexpression and decreased after BRG1 knockdown in OTSCC cells. Our Re-ChIP assay has shown that BRG1 knockdown completely inhibits the recruitment of both acetylated histone H3 or H4 and NF-κB to the CCL2 promoter. In summary, the findings of our study demonstrate that BRG1 plays a significant role in mediating the production of CCL2 in OTSCC cells in response to TNF-α stimulation. This process involves the cooperative action of acetylated histone and NF-κB recruitment to the CCL2 promoter site. Our data suggest that BRG1 serves as a critical epigenetic mediator in the regulation of TNF-α-induced CCL2 transcription in OTSCC cells.

Metformin rejuvenates Nap1l2-impaired immunomodulation of bone marrow mesenchymal stem cells via metabolic reprogramming.

Ageing and cell senescence of mesenchymal stem cells (MSCs) limited their immunomodulation properties and therapeutic application. We previously reported that nucleosome assembly protein 1-like 2 (Nap1l2) contributes to MSCs senescence and osteogenic differentiation. Here, we sought to evaluate whether Nap1l2 impairs the immunomodulatory properties of MSCs and find a way to rescue the deficient properties. We demonstrated that metformin could rescue the impaired migration properties and T cell regulation properties of OE-Nap1l2 BMSCs. Moreover, metformin could improve the impaired therapeutic efficacy of OE-Nap1l2 BMSCs in the treatment of colitis and experimental autoimmune encephalomyelitis in mice. Mechanistically, metformin was capable of upregulating the activation of AMPK, synthesis of l-arginine and expression of inducible nitric oxide synthase in OE-Nap1l2 BMSCs, leading to an increasing level of nitric oxide. This study indicated that Nap1l2 negatively regulated the immunomodulatory properties of BMSCs and that the impaired functions could be rescued by metformin pretreatment via metabolic reprogramming. This strategy might serve as a practical therapeutic option to rescue impaired MSCs functions for further application.

THM model of rock tunnels in cold regions and numerical simulation

The freezing damage of rock tunnels in cold region involves ice-water phase change and complicated interaction of Thermo–Hydro–Mechanical (THM) field. Taking the fractured rock mass of cold region tunnels as research subject, the THM coupling model of cold region tunnels was established, which is based on the seepage mechanics, heat transfer theory, damage mechanics and equivalent continuum theory. This model could reflect the anisotropic properties of deformation, water migration and heat transfer caused by the initial fracture of rock mass. The construction and operation processes of a rock tunnel in cold region were simulated, and results were compared with the measured value and predecessor’s achievements. It shows that proposed model could reflect the anisotropic property of surrounding rock and the simulated deformation and stress are not symmetrical. Compared with the literature, the calculated results in this paper are closer to the measured values. The insulating layer has a significant effect on the stress of the supporting structures. The maximum tension stress of the lining is 4.5 times as that without insulating layer, and the lining will be destroyed for the overlarge tension stress.

Chitosan Hydrogel Dressing Loaded with Adipose Mesenchymal Stem Cell-Derived Exosomes Promotes Skin Full-Thickness Wound Repair.

Cutaneous trauma repair is still a challenge in the clinic due to the scar formation and slow healing rate, especially for diabetic patients. Various drug-loading wound dressings have been explored to solve this problem. Mesenchymal stem cell (MSC)-derived exosomes have been considered as a potential cell-free drug because of their anti-inflammation function and tissue repair property that are comparable to that of MSCs. Herein, a composite wound dressing (Exo/Gel) consisting of the chitosan hydrogel and adipose MSC-derived exosome (ADMSC-Exo) was designed and fabricated by a physical mixing method to promote the skin full-thickness wound repair. The exosomes were slowly released from the Exo/Gel dressing with the degradation of the chitosan hydrogel. The Exo/Gel displayed enhanced cell migration and angiogenic properties in vitro. And the results in the rat skin wound model showed that the Exo/Gel could promote the regular collagen deposition, angiogenesis, and hair follicle mosaicism regeneration. These results proved that the hydrogel dressing with ADMSCs-derived exosomes can accelerate skin wound healing, which is a strategy for developing wound dressings.

Engineering a self-healing grafted chitosan–sodium alginate based hydrogel with potential keratinocyte cell migration property and inhibitory effect against fluconazole resistance Candida albicans biofilm

Biofilms developed by microorganisms cause an extremely severe clinical problem that leads to drug failure. Bioactive polymeric hydrogels display potential for controlling the formation of microorganism-based biofilms, but their rapid biodegradability in these biofilm sites is still a major challenge. To overcome this, chitosan (CS), a natural functional biomaterial, has been used because of its effective penetrability in the cell wall of microorganisms; however, its fast biodegradability has restricted its further use. Hence, in this study, to improve the stability of CS and increase its penetration retention inside a biofilm, grafted CS was prepared and then crosslinked with sodium alginate (SA) to synthesize CS-poly(MA-co-AA)SA hydrogel via a free radical grafting method, therefore enhancing its antibiofilm efficiency against biofilms. The prepared hydrogel demonstrated excellent effectiveness against (≥90 % inhibition) biofilms of Candida albicans. Additionally, in vitro and in vivo safety assays established that the prepared hydrogel can be used in a biofilm microenvironment and might reduce drug resistance burden owing to its long-term antibiofilm effect and improved CS stability at the biofilm site. Furthermore, in vitro wound healing outcomes of hydrogel indicated its potential application for chronic wound treatment. This research opens a new advanced strategy for biofilm-associated infection treatment, including wound treatment.

Plectin plays a role in the migration and volume regulation of astrocytes: a potential biomarker of glioblastoma

BackgroundThe expression of aquaporin 4 (AQP4) and intermediate filament (IF) proteins is altered in malignant glioblastoma (GBM), yet the expression of the major IF-based cytolinker, plectin (PLEC), and its contribution to GBM migration and invasiveness, are unknown. Here, we assessed the contribution of plectin in affecting the distribution of plasmalemmal AQP4 aggregates, migratory properties, and regulation of cell volume in astrocytes.MethodsIn human GBM, the expression of glial fibrillary acidic protein (GFAP), AQP4 and PLEC transcripts was analyzed using publicly available datasets, and the colocalization of PLEC with AQP4 and with GFAP was determined by immunohistochemistry. We performed experiments on wild-type and plectin-deficient primary and immortalized mouse astrocytes, human astrocytes and permanent cell lines (U-251 MG and T98G) derived from a human malignant GBM. The expression of plectin isoforms in mouse astrocytes was assessed by quantitative real-time PCR. Transfection, immunolabeling and confocal microscopy were used to assess plectin-induced alterations in the distribution of the cytoskeleton, the influence of plectin and its isoforms on the abundance and size of plasmalemmal AQP4 aggregates, and the presence of plectin at the plasma membrane. The release of plectin from cells was measured by ELISA. The migration and dynamics of cell volume regulation of immortalized astrocytes were assessed by the wound-healing assay and calcein labeling, respectively.ResultsA positive correlation was found between plectin and AQP4 at the level of gene expression and protein localization in tumorous brain samples. Deficiency of plectin led to a decrease in the abundance and size of plasmalemmal AQP4 aggregates and altered distribution and bundling of the cytoskeleton. Astrocytes predominantly expressed P1c, P1e, and P1g plectin isoforms. The predominant plectin isoform associated with plasmalemmal AQP4 aggregates was P1c, which also affected the mobility of astrocytes most prominently. In the absence of plectin, the collective migration of astrocytes was impaired and the dynamics of cytoplasmic volume changes in peripheral cell regions decreased. Plectin’s abundance on the plasma membrane surface and its release from cells were increased in the GBM cell lines.ConclusionsPlectin affects cellular properties that contribute to the pathology of GBM. The observed increase in both cell surface and released plectin levels represents a potential biomarker and therapeutic target in the diagnostics and treatment of GBMs.

Comprehensive Tools of Alkaloid/Volatile Compounds-Metabolomics and DNA Profiles: Bioassay-Role-Guided Differentiation Process of Six Annona sp. Grown in Egypt as Anticancer Therapy.

Trees of the Annona species that grow in the tropics and subtropics contain compounds that are highly valuable for pharmacological research and medication development and have anticancer, antioxidant, and migratory properties. Metabolomics was used to functionally characterize natural products and to distinguish differences between varieties. Natural products are therefore bioactive-marked and highly respected in the field of drug innovation. Our study aimed to evaluate the interrelationships among six Annona species. By utilizing six Start Codon Targeted (SCoT) and six Inter Simple Sequence Repeat (ISSR) primers for DNA fingerprinting, we discovered polymorphism percentages of 45.16 and 35.29%, respectively. The comparison of the profiles of 78 distinct volatile oil compounds in six Annona species was accomplished through the utilization of GC-MS-based plant metabolomics. Additionally, the differentiation process of 74 characterized alkaloid compound metabolomics was conducted through a structural analysis using HPLC-ESI-MSn and UPLC-HESI-MS/MS, and antiproliferative activities were assessed on five in vitro cell lines. High-throughput, low-sensitivity LC/MS-based metabolomics has facilitated comprehensive examinations of alterations in secondary metabolites through the utilization of bioassay-guided differentiation processes. This has been accomplished by employing twenty-four extracts derived from six distinct Annona species, which were subjected to in vitro evaluation. The primary objective of this evaluation was to investigate the IC50 profile as well as the antioxidant and migration activities. It should be noted, however, that these investigations were exclusively conducted utilizing the most potent extracts. These extracts were thoroughly examined on both the HepG2 and Caco cell lines to elucidate their potential anticancer effects. In vitro tests on cell cultures showed a significant concentration cytotoxic effect on all cell lines (HepG2, HCT, Caco, Mcf-7, and T47D) treated with six essential oil samples at the exposure time (48 h). Therefore, they showed remarkable antioxidant activity with simultaneous cytotoxic effects. In total, 50% and 80% of the A. muricata extract, the extract with the highest migratory activity, demonstrated a dose-dependent inhibition of migration. It was strong on highly metastatic Caco cells 48 h after treatment and scraping the Caco cell sheet, with the best reduction in the migration of HepG2 cells caused by the 50% A. reticulata extract. Also, the samples showing a significant IC50 value showed a significant effect in stopping metastasis and invasion of various cancer cell lines, making them an interesting topic for further research.

Energizing the Lung Vasculature in the Premature Infant to Promote Alveolar Formation

Background/Objective: Chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD) occurs when infants born with underdeveloped immature lungs are forced to navigate the expansion of future air spaces, with irregular vascular formation proceeding development of BPD. Lung development has distinct and dynamic metabolic requirements. We recently identified by mass spectrometry that nicotinamide adenine dinucleotide (NAD+), generated from vitamin B3 ‘Nicotinamide’ (NAM), was significantly reduced in a hyperoxia murine model of BPD. As NAM/NAD+ are dynamic regulators of tissue regenerating neovascularization in otherdisease processes, we hypothesized that NAM/NAD+ metabolic deficiencies contribute to compromised angiogenesis formation and alveolar formation.
 Methods: Impact of NAM supplementation on circulating human neonatal endothelial colonyforming cells (ECFCs) were assessed for differential capillary formation properties of angiogenesis (Matrigel), migration (wound healing), proliferation (WST1 and crystal violetstaining), and mitochondrial function in normoxia and hyperoxia (85% oxygen) conditions.
 Results: Hyperoxia suppresses ECFC angiogenesis, while NAM supplementation in hyperoxia significantly rescued vascular networks, branched nodes, and branch points (p<0.001). Wound healing assays suggest that NAM promotes cell migration in normoxia and hyperoxia (p<0.0001). Although NAM increased WST1 activity in hyperoxia, crystal violet analysis determined that NAM had no impact on ECFC proliferation. Lastly, NAM significantly reduced hyperoxia induced mitochondrial oxidative stress in a dose dependent manner (p<0.05).
 Conclusion and Clinical Implications: Lung development has specific metabolic needs during different stages of development that are disrupted by premature birth. Replenishment of NAM promotes angiogenesis and migration in hyperoxia while reducing mitochondrial activity. Future studies are necessary to explore the role of NAM/NAD+ axis in the developing lung.

CCDC88B interacts with RASAL3 and ARHGEF2 and regulates dendritic cell function in neuroinflammation and colitis

CCDC88B is a risk factor for several chronic inflammatory diseases in humans and its inactivation causes a migratory defect in DCs in mice. CCDC88B belongs to a family of cytoskeleton-associated scaffold proteins that feature protein:protein interaction domains. Here, we identified the Rho/Rac Guanine Nucleotide Exchange Factor 2 (ARHGEF2) and the RAS Protein Activator Like 3 (RASAL3) as CCDC88B physical and functional interactors. Mice defective in Arhgef2 or Rasal3 show dampened neuroinflammation, and display altered cellular response and susceptibility to colitis; ARHGEF2 maps to a human Chromosome 1 locus associated with susceptibility to IBD. Arhgef2 and Rasal3 mutant DCs show altered migration and motility in vitro, causing either reduced (Arhgef2) or enhanced (Rasal3) migratory properties. The CCDC88B/RASAL3/ARHGEF2 complex appears to regulate DCs migration by modulating activation of RHOA, with ARHGEF2 and RASAL3 acting in opposite regulatory fashions, providing a molecular mechanism for the involvement of these proteins in DCs immune functions.

Influence of the electrolyte concentration and amount on the performance of textile electrodes in electrostimulation: A systematic study

BackgroundTextile-based stimulation electrodes are a fast-growing research area. With their advantages including flexibility, reusability and the possibility for integration into garments, textile electrodes open up new possibilities that are not yet feasible today, e.g. various self-administrated treatments and rehabilitation based on neuromuscular electrical stimulation (NMES) or transcutaneous electrical nerve stimulation (TENS). So far, most research has shown that textile-based stimulation electrodes perform more reliable when wetted with an electrolyte. However, there is no systematic investigation about which type and amount of electrolyte to use. MethodsIn this study, double-layered textile electrodes have been produced by machine knitting with a size of 3 × 3 cm2. The electrodes were wetted stepwise with a liquid amount from 5 µL up to 320 µL; four levels of sodium chloride (NaCl) concentrations, i.e. 0.9%, 1.5%, 5% and 35%, plus pure deionized water as a reference liquid were chosen. The study analyzed the behavior of the skin-electrode impedance when changing the moisture content and NaCl concentration. In addition, equivalent circuits were modelled for deeper insights into the mechanisms causing an impedance change. ResultsResults showed that the impedance was greatly influenced by the liquid amount with amounts of 5 µL already significantly reducing the impedance compared to dry electrodes, caused by a substantial reduction in resistance. The reactance, on the other hand, was only partly influenced by the liquid amount showing a reduction upon higher liquid amounts only within a range of 5 – 40 µL. Further, a significant influence on the impedance by the presence of ions was found where the skin-electrode systems wetted with NaCl solution were showing generally lower impedances than systems wetted with deionized water. However, within this, no remarkable influence of the NaCl concentration could be observed. As the impedance was found to be very sensitive to the moisture content in the system, it is recommended to introduce standardizations for impedance testing of wet textile electrodes with precisely controlled electrolyte volumes and liquid migration properties to make independent studies of textile electrodes more comparable.