Migratory Properties Research Articles

Construction of oxidized icariin functionalized collagen composite with promoting osteogenesis, vascularization and anti-inflammatory properties potential for bone repair application

Bone defects are mainly treated by transplanting bone scaffold, and lack of osteogenesis, vascularization and anti-inflammatory properties will reduce the ability of new bone tissue to grow into them, thus increasing the risk of bone repair failure. In this study, inspired by the composition of natural bone, COL-BG-MOF composite was first prepared (collagen (COL) as the organic component, aminated mesoporous bioactive glass (BG-NH2) as the inorganic non-metallic component, and mesoporous silica shell-coated Mg-MOF-74 (Mg-MOF-74@MSiO2) as the metallic trace element component). Subsequently, in order to further enhance the effectiveness of its bone repair application potential, COL-BG-MOF was functionalized by oxidized Icariin (OICA) as a “growth factor” component to endow it with simultaneous osteogenesis promoting, vascularization promoting, and anti-inflammatory properties. Notably, the –CHO of OICA can react with the –NH2 in COL-BG-MOF by Schiff base reaction, which can cross-link the COL, thus improving the interfacial binding of BG-NH2 to the COL and slowing down the release rate of OICA. The results showed that the obtained functionalized composite scaffold exhibited better compressive strength, anti-degradation and osteoconductivity, as well as sustained OICA release behavior. More importantly, the synergistic effect of OICA and Mg-MOF-74@MSiO2 greatly promoted its osteogenic differentiation, HUVEC migration and anti-inflammatory properties. Therefore, this study provided a strategy to prepare functionalized composites by using modified Chinese medicine, which has great application potential in the field of bone regeneration.

Cell migration, DNA fragmentation and antibacterial properties of novel silver doped calcium polyphosphate nanoparticles

To combat infections, silver was used extensively in biomedical field but there was a need for a capping agent to eliminate its cytotoxic effects. In this study, polymeric calcium polyphosphate was doped by silver with three concentrations 1, 3 or 5 mol.% and were characterized by TEM, XRD, FTIR, TGA. Moreover, cytotoxicity, antibacterial, cell migration and DNA fragmentation assays were done to assure its safety. The results showed that the increase in silver percentage caused an increase in particle size. XRD showed the silver peaks, which indicated that it is present in its metallic form. The TGA showed that thermal stability was increased by increasing silver content. The antibacterial tests showed that the prepared nanoparticles have an antibacterial activity against tested pathogens. In addition, the cytotoxicity results showed that the samples exhibited non-cytotoxic behavior even with the highest doping concentration (5% Ag-CaPp). The cell migration assay showed that the increase in the silver concentration enhances cell migration up to 3% Ag-CaPp. The DNA fragmentation test revealed that all the prepared nanoparticles caused no fragmentation. From the results we can deduce that 3% Ag-CaPp was the optimum silver doped calcium polyphosphate concentration that could be used safely for medical applications.

Dynamic roles of neutrophil extracellular traps in cancer cell adhesion and activation of Notch 1-mediated epithelial-to-mesenchymal transition in EGFR-driven lung cancer cells.

Neutrophil extracellular traps (NETs) are complex structures released by activated neutrophils that may modulate different steps of the metastatic cascade. The aim of our study was to investigate how NETs can modulate the adhesion properties of cancer cells and whether cell exposure to NETs can activate the epithelial-to-mesenchymal transition (EMT) program thus enhancing the migratory and invasive properties of tumor cells. Different cancer cell lines were subjected to a solid-phase adhesion assay using NET-coated plates with or without the addition of antibodies against α5β1 or CCDC25 receptor. After 1-4 h of incubation, adherent cells were expressed as the percentage of total cell number. To test EMT occurrence, cells were treated with NETs for up to 48 h and then the levels of E-cadherin, vimentin, Snail, Slug, Zeb 1 and Twist 1 along with levels of Notch 1 and cleaved Notch 1 were determined by western blotting. Untreated and NET-treated cells were subjected to migration assays using 24-multiwell plates with transwell and FBS as chemoattractant. Cancer cell adhesion to NET-coated plates varied between 30% and 92.7% and was significantly higher than that obtained in uncoated plates. The addition of antibodies against α5β1 or CCDC25 caused a strong reduction of cell adhesion to NETs. The prolonged exposure of EGFR-driven cancer cell lines to NETs caused the activation of the EMT program through the upregulation and cleavage of Notch 1 and was confirmed by the enhanced expression of EMT markers. The consequent loss of the epithelial phenotype induced a strong reduction of the expression of the oncogene driver. Cell migration was significantly enhanced in NET-treated cells as compared to untreated cells. Our findings reveal the dynamic role of NETs that may provide a DNA and fibronectin rich environment for binding of many cancer cells at distant sites where the prolonged exposure to NETs triggers the EMT through the activation of Notch 1 signaling pathway with the subsequent enhancement of migratory and invasive properties of cancer cells. Furthermore, our findings provide an example of how an immune/inflammatory microenvironment may directly modulate the sensitivity of cancer cells to oncogene targeted agents.

Discovery of oxazine-linked pyrimidine as an inhibitor of breast cancer growth and metastasis by abrogating NF-κB activation.

Nuclear factor kappa (NF-κB) plays a key role in cancer cell proliferation; thus, small molecule inhibitors of NF-κB activity can effectively inhibit breast cancer (BC) progression. We have previously reported oxazine and piperazine-linked pyrimidines as novel anti-cancer agents that can suppress NF-κB activation in BC cells. Moreover, the TRX-01 compound, an oxazine-linked pyrimidine, inhibited MCF-7 cells at a concentration of 9.17 µM in the Alamar Blue assay. This work involved the analysis of frontier molecular orbitals, HOMO-LUMO interactions, and molecular electrostatic potential for the TRX-01 structure. Additionally, the TRX-01 compound was studied for cytotoxicity, and migration as well as invasion assays were performed on BC cells. Finally, TRX-01 blocked the translocation of NF-κB from the cytoplasm to the nucleus in MCF-7 cells and reduced NF-κB and IκBα levels in a dose-dependent manner. It also suppressed migratory and invasive properties of BC cells. Overall, the data indicates that TRX-01 can function as a novel blocker of BC growth and metastasis by targeting NF-κB activation.

Novel chromium (III)-based compound for inhibition of oxaliplatin-resistant colorectal cancer progression.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related mortality worldwide. The current standard of care includes systemic chemotherapy with cytotoxic agents, offering palliative relief for severe CRC cases and serving as the primary therapy for metastatic recurrence. However, the development of chemoresistance poses a substantial obstacle in the realm of chemotherapy. This study delved into the potential of a novel chromium (III)-based compound, hexaacetotetraaquadihydroxochromium (III) diiron (III) nitrate, for CRC treatment. The therapeutic promise of this innovative chromium (III)-based compound was explored by utilizing LoVo colon cancer cells and an in-vivo mouse model of CRC. Various dosages of the compound were administered to LoVo parental cells and LoVo oxaliplatin-resistant cells. Findings unveiled that a concentration of 2000 μg/mL of the chromium (III) compound significantly inhibited mesenchymal transition and the migratory and invasive properties of LoVo oxaliplatin-resistant cells. This novel chromium (III)-based compound also demonstrated similar efficacy in other different CRC cell lines. The tumor growth was in the in-vivo mouse model was reduced by this compound. Moreover, the chromium (III)-based compound induced apoptosis by triggering the endoplasmic reticulum (ER) stress pathway in LoVo oxaliplatin-resistant cells. This study illuminates the capacity of the novel chromium (III)-based compound to impede the progression and growth of chemotherapy-resistant CRC. This discovery instills confidence in the potential of this compound as a therapeutic agent for CRC, even in the face of drug resistance. It holds the promise of serving as a valuable asset in the future treatment of chemotherapy-resistant CRC.

STAC3 as a poor prognostic biomarker in renal clear cell carcinoma: relationship with immune infiltration.

Calcium ions (Ca2+) are crucial in tumorigenesis and progression, with their elevated levels indicating a negative prognosis in Kidney Renal Clear Cell Carcinoma (KIRC). The influence of genes regulating calcium ions on the survival outcomes of KIRC patients and their interaction with the tumor's immune microenvironment is yet to be fully understood. This study analyzed gene expression data from KIRC tumor and adjacent non-tumor tissues using the TCGA-KIRC dataset to pinpoint genes that are differentially expressed in KIRC. Intersection of these genes with those regulating calcium ions highlighted specific calcium ion-regulating genes that exhibit differential expression in KIRC. Subsequently, prognostic risk models were developed using univariate Cox and LASSO-Cox regression analyses to verify their diagnostic precision. Additionally, the study investigated the correlation between tumor immunity and KIRC patient outcomes, assessing the contribution of STAC3 genes to tumor immunity. Further exploration entailed SSGASE, single-cell analysis, pseudotime analysis and both in vivo and in vitro experiments to evaluate STAC3's role in tumor immunity and progression. Notably, STAC3 was significantly overexpressed in tumor specimens and positively correlated with the degree of malignancy of KIRC, affecting patients' prognosis. Elevated STAC3 expression correlated with enhanced immune infiltration in KIRC tumors. Furthermore, silencing STAC3 curtailed KIRC cell proliferation, migration, invasion, and stemness properties. Experimental models in mice confirmed that STAC3 knockdown led to a reduction in tumor growth. Elevated STAC3 expression is intricately linked with immune infiltration in KIRC tumors, as well as with the aggressive biological behaviors of tumor cells, including their proliferation, migration, and invasion. Targeting STAC3 presents a promising strategy to augment the efficacy of current therapeutic approaches and to better the survival outcomes of patients with KIRC.

Unveiling the wound healing potential of umbilical cord derived conditioned medium: an in vitro study

Chronic wounds pose a serious threat to an individual’s health and quality of life. As such, therapeutic intervention is often needed to mitigate the improper closure of wounds. Large amounts of research and funding have been directed towards finding a suitable treatment. However, due to the severity and morbidity of such wounds, many pre-existing treatments are inefficient or costly. While the use of skin grafts and other such biological constructs in chronic wound healing has already been characterized, the use of umbilical cord tissue has only recently garnered interest, despite the cytokine-rich composition of Wharton’s jelly (cord component). Our current study aimed to characterize the use of an umbilical cord derived conditioned medium (UC-CM) to treat chronic wounds. We hypothesized that UC-CM contains higher amounts of wound healing cytokines, supporting cell proliferation, migration, and better wound healing properties compared to fetal bovine serum (FBS). Cytokine analysis demonstrated that UC-CM consistently contained desirable levels of HGF, EGF, VEGF, and TGF-β, all of which are vital to the normal wound healing process, whereas there were negligible amounts of growth factors in FBS except for TGF-β. MTT assay confirmed that UC-CM is not cytotoxic and promotes cell proliferation, while the scratch assay demonstrated that UC-CM supports migration of MSCs into the wound site. Taken altogether, our study showed that UC-CM was equally as effective as FBS-containing medium at promoting cell proliferation and wound healing.

Machine Learning-based Framework Develops a Tumor Thrombus Coagulation Signature in Multicenter Cohorts for Renal Cancer.

Background: Renal cell carcinoma (RCC) is frequently accompanied by tumor thrombus in the venous system with an extremely dismal prognosis. The current Tumor Node Metastasis (TNM) stage and Mayo clinical classification do not appropriately identify preference-sensitive treatment. Therefore, there is an urgent need to develop a better ideal model for precision medicine. Methods: In this study, we developed a coagulation tumor thrombus signature for RCC with 10 machine-learning algorithms (101 combinations) based on a novel computational framework using multiple independent cohorts. Results: The established tumor thrombus coagulation-related risk stratification (TTCRRS) signature comprises 10 prognostic coagulation-related genes (CRGs). This signature could predict survival outcomes in public and in-house protein cohorts and showed high performance compared to 129 published signatures. Additionally, the TTCRRS signature was significantly related to some immune landscapes, immunotherapy response, and chemotherapy. Furthermore, we also screened out hub genes, transcription factors, and small compounds based on the TTCRRS signature. Meanwhile, CYP51A1 can regulate the proliferation and migration properties of RCC. Conclusions: The TTCRRS signature can complement the traditional anatomic TNM staging system and Mayo clinical stratification and provide clinicians with more therapeutic options.

Biopolymer-based edible packaging: a critical review on the biomaterials, formation, and applications on food products

Food substances are highly susceptible to spoilage due to their inherent properties and environmental factors during transit from farm to fork. Hence, it is necessary to protect the food from various factors by safeguarding it in proper packaging. The packaging materials include flexible pouches and rigid containers, and they have their own merits and demerits. Most of the packaging materials used nowadays are polymer-based, which takes a long time to degrade and poses a dangerous threat to terrestrial and aquatic life. Edible packaging evolved to be an alternative to conventional packaging due to its natural biopolymers, which are hyper-degradable and consumable. They exhibit improved barrier and organoleptic properties, mass transfer selectivity, and reduced migration properties of packaging ingredients into food and environmental pollution. They are classified as coatings, films, and pouches and can be used as either food wraps or heat-sealed into pouches that are applied directly on the food surface. Thus, edible packaging is a potential approach in the food packaging industry. This review explains in detail the biomaterials used for film preparation, various processes involved in film formation, different coating methods, and recent applications in the area of eco-friendly edible packaging.

Migration behavior of space charge packet researched by using electron beam irradiation and real-time space charge distribution measurement in piezo-pressure wave propagation (PWP) method

The space charge packet is a special sort of space charge phenomenon that is characterized by the migration of aggregated space charge in the form of a packet in the sample. Currently, most of the experimental and simulation studies on the generation and migration of space charge packets focus on the space charge packets with positive polarity in polyethylene and their cross-linking products, while the characteristics of the space charge packets with negative polarity still need studying. This paper presents an integrated experimental system for studying space charge packet with negative polarity, which enables experimental studies combining electron beam irradiation technique and real-time space charge distribution measurement. The beam flux for electron beam irradiation is controlled by a metal grid with an optical fiber-electric relay, and the space charge distribution measurement is performed by the piezo- pressure wave propagation method. The system achieves a withstand voltage value of 17 kV and a measuring resolution of 25 ns for space charge distribution measurement and is suitable for experimental studies of various material samples with different thickness ranges under different electric fields. In this work, the migration behaviors of space charge packets with negative polarity in polypropylene (PP) and polymethyl methacrylate (PMMA) samples under different applied electric fields (15, 20, 25, 30 kV/mm) are studied by using the experimental system. The relationship between the migration properties of carriers with negative polarity (electrons) and the electric field can be extracted from the experimental results. The “negative differential mobility” phenomenon is found for both materials, i.e. the migration rate decreases with the increase of the electric field. The threshold electric field for the “negative differential mobility” phenomenon of electrons in PP sample is about 26.0 kV/mm while the threshold electric field for the “negative differential mobility” phenomenon of electrons in PMMA sample is 19.5 kV/mm, and the phenomenon disappears at an electric field of 27.5 kV/mm. The electric field where the "negative differential mobility" phenomenon of electrons appears and disappears in different materials can be extracted by using the experimental system proposed in this paper.

Migration properties of Li<sup>+ </sup>in Li<sub>1+<i>x</i> </sub>Al<sub><i>x</i></sub>Ti<sub>2–<i>x</i></sub>(PO<sub>4</sub>)<sub>3</sub>

NASICON-type materials are specific skeleton structures in which ions move in three dimensions. Li<sub>1+<i>x</i></sub>Al<sub><i>x</i></sub>Ti<sub>2–<i>x</i></sub>(PO<sub>4</sub>)<sub>3</sub> (LATP) is a promising NASICON-type solid-state electrolyte for Li-ion batteries, due to its relatively high Li<sup>+</sup> conductivity, chemical stability to air and moisture, and mechanical strength. Motivated by this, we study the doping and electronic properties of Li<sub>1+<i>x</i></sub>Al<sub><i>x</i></sub>Ti<sub>2–<i>x</i></sub>(PO<sub>4</sub>)<sub>3</sub> (<i>x</i> = 0.00, 0.16, 0.33, 0.50) and the transport properties of Li<sup>+</sup> in them by using first-principles calculations based on density functional theory as implemented in Vienna <i>ab initio</i> Simulation Package (VASP). The results indicate that Al can substitute Ti to form a stable structure. When the Al doping concentration is <i>x</i> = 0.16, the average bond length of Li—O bond is longest and the bonding strength is weakest, this may lead to the expansion of channels for Li<sup>+</sup> migration, which facilitates the diffusion of Li<sup>+</sup>. With the increase of Al doping concentration, the strength of Ti—O bond remains almost unchanged. The electronic structure calculations exhibit that with the increase of Al doping concentration, the bandgap of LATP does not change much, and LATP shows semiconductor characteristic. The differential charge results indicate that more electrons are localized on O-atoms surrounding the Al-dopant, causing the AlO<sub>6</sub> groups to form polarization centers. The study on the migration properties of Li<sup>+</sup> indicates that Li<sup>+</sup> exhibits different migration characteristics in three different migration modes (vacancy migration, interstitial migration, and cooperative migration). With the increase of Al doping concentration, the migration barrier of Li<sup>+</sup> increases via vacancies involving only lattice site migration, and the migration barrier for LATP-0.16 is lowest (0.369 eV). While in interstitial migration involving only interstitial sites, the migration barrier of Li<sup>+</sup> decreases accordingly. When the Al doping concentration is <i>x</i> = 0.50, the migration barrier is lowest (0.342 eV). In terms of cooperative migration, this migration mode involves both vacancy and interstitial sites, so the migration barrier first decreases and then increases with the increase of Al doping concentration. Thus, our study suggests that by varying the concentration of Al doping, the interstitial Li<sup>+</sup> content, migration channel structure, and the migration performance of Li<sup>+</sup> can be changed favorably. Our results provide a theoretical basis for improving the ion conductivity of Li in LATP by varying the Al doping concentration in experiment.

Exosomes Derived from Metastatic Colon Cancer Cells Induced Oncogenic Transformation and Migratory Potential of Immortalized Human Cells

Tiny vesicles, synthesized from cell membranes through endocytosis, form multivesicular bodies (MVBs). These MVBs can either undergo lysosomal degradation or be released to the extracellular environment. The vesicle that ranges in size from 30-300 nm that were positive for markers such as CD63 or CD9 are known as exosomes. Exosomes are shown to contain various biological macromolecules such as DNA, RNA, miRNA, proteins, and lipids. Releasing exosomes from cells to the extracellular environment is an important strategy to transfer information between the cells. Exosomes from primary colon cancer cells have been shown to induce the oncogenic transformation of normal cells. In this study, we have demonstrated that treating normal cells (HEK) with exosomes derived from the metastatic colon cancer cell line (SW620) increases cell proliferation, allowing the normal cells to grow anchored independently, suggesting the oncogenic transformation of normal cells. In addition, there was an increase in migration and invasion properties of HEK cells exposed to exosomes from SW620 cells. Our results suggest that following the treatment with metastatic colon cancer cell-derived exosomes, the HEK cells underwent an oncogenic transformation and Epithelial-Mesenchymal Transition (EMT) that will allow the cancerous cells to metastasize.

Tofacitinib restores psoriatic arthritis fibroblast-like synoviocytes function via autophagy and mitochondrial quality control modulation

ObjectivesTo evaluate the in vitro effect of tofacitinib on autophagy activity of psoriatic arthritis (PsA) fibroblast-like synoviocytes (FLS), and to confirm its activity on inflammatory and invasive properties of FLS and synovial cells, deepening the impact on mitochondrial function. MethodsFLS, peripheral blood mononuclear cells (PBMCs), and synovial cells from active PsA patients were cultured with tofacitinib 1 μM or vehicle control for 24 h. Autophagy was measured by Western blot and by fluorescence microscopy. Chemokines/cytokines released into culture supernatants were quantified by ELISA, while invasive properties of FLS by migration assays. Specific mitochondrial probes were adopted to measure intracellular reactive oxygen species (ROS), mitochondrial potential, morphology, turnover and mitophagy. Oxygen consumption rate (OCR), reflecting oxidative phosphorylation, was quantified using the Seahorse technology. Differences were determined by adopting the non-parametric Wilcoxon signed rank test. Results18 patients with moderately-to-severely active PsA were enrolled. Tofacitinib significantly increased the levels of the autophagy markers LC3-II and ATG7 in PsA FLS compared to vehicle control, suggesting an increase in spontaneous autophagy activity; no effect was highlighted in PBMCs and synovial cells cultures. Tofacitinib reduced migration properties of PsA FLS, and reduced MCP-1 and IL-6 release into FLS and synovial cells cultures supernatants. Furthermore, tofacitinib decreased intracellular ROS production, increased basal OCR, ATP production and maximal respiratory capacity, and enhanced mitophagy and mitochondrial turnover. ConclusionsThe JAK inhibitor tofacitinib reduces the pro-invasive and pro-inflammatory properties of PsA FLS. Autophagy induction and mitochondrial quality control modulation by tofacitinib might contribute to FLS function restoration.

Live macrophages loaded with Fe3O4 and sulfasalazine for ferroptosis and photothermal therapy of rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the infiltration of inflammatory cells and proliferation of synovial cells. It can cause cartilage and bone damage as well as disability and is regarded as an incurable chronic disease. Available therapies cannot prevent the development of diseases due to the high toxicity of the therapeutic agents and the inefficient drug delivery. Ferroptosis, an iron-dependent manner of lipid peroxidative cell death, indicates great potential for RA therapy due to ability to damage the infiltrated inflammatory cells and proliferated fibroblast-like synoviocytes. Here, we use macrophages as vector to deliver Fe3O4 nanoparticles and sulfasalazine (SSZ) for ferroptosis and photothermal therapy of RA. The inherent property of migration towards the inflamed joints under the guidance of inflammatory factors enables macrophages to targetedly deliver the payload into the RA. Upon the irradiation of the near infrared light, the Fe3O4 nanoparticles convert the light into heat to damage the proliferated synovium. Meanwhile, the iron released from Fe3O4 nanoparticles works with SSZ to generate synergetic ferroptosis effect. The resident inflammatory cells and proliferated synovium are efficiently damaged by the ferroptosis and photothermal effect, showing pronounced therapeutic effect for RA.

Mechanism of miR-548b-5p down-regulating FZD7 to impede the migratory and invasive behavior of gastric carcinoma cells.

This study aimed to investigate the possible mechanism of Micro RNA-548b-5p (miR-548b-5p) down-regulating frizzled (FZD) 7 to suppress the migration and invasion of gastric carcinoma cells. For this purpose, HGCC (Human gastric carcinoma cell) lines were selected (Hs-746T, NCI-N87, SGC-7901, MKN-45, SNU-1), and human normal gastric mucosa cells GES-1. QRT PCR was adopted to reveal and screen the cell line with low expression of mir-548b-5p (hs-746t) for research; the Hs-746T cells were randomly assigned into control group, miR-548b-5p NC group, miR-548b-5p mimic group, miR-548b-5p mimic+pc-FZD7 group. The CCK-8 assay was utilized to measure Hs-746T cell viability, while flow cytometry, Trans well chamber, and scratch test were utilized to examine the apoptotic, invasive, and migratory properties of the cells, respectively. WB was used to detect the SATB1, as well as the expression levels of proteins involved in apoptosis, including Caspase-3, Bax, and Bcl-2, as well as Matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9) in SW620 cells. The binding of miR-548b-5p to FZD7 was evaluated through the dual-luciferase reporter assay. The results indicate that MiR-548b-5p showed low expression in HGCCs; in contrast to the control group (P>0.05), the Hs-746T cell viability, invasion, migration ability, MMP-2, MMP-9 protein significantly downregulated in miR-548b-5p mimic group (P<0.05), the apoptosis rate, Caspase-3, Bax protein expression were upregulated markedly, and Bcl-2 protein expression was downregulated significantly (P<0.05); in contrast to miR-548b-5p mimic group, the Hs-746T cell viability, invasion, migration ability, MMP-2, MMP-9 protein significantly were upregulated in miR-548b-5p mimic+pc-FZD7 group (P<0.05), the apoptosis rate, Caspase-3, Bax protein expression were significantly, and the level of Bcl-2 was down-regulated significantly (P<0.05); Double Luciferase Report shows that mir-548b-5p can target and regulate fzd7. It was concluded that MiR-548b-5p can suppress cell growth and migration of HGCC Hs-746T, which may be achieved by targeted down-regulation of FZD7.

Effects of grape juice intake on the cell migration properties in overweight women: Modulation mechanisms of cell migration in vitro by delphinidin-3-O-glucoside

Overweight and obesity are typical conditions of chronic low-intensity systemic inflammatory responses, and both have become more common in recent decades, which emphasizes the necessity for healthier diet intake. Fruits such as grapes are rich in anthocyanins, one of which is delphinidin, a promising chemopreventive agent with anti-inflammatory properties. Considering that polymorphonuclear cells (PMNs) are rapidly mobilized to tissues when the inflammatory process is initiated, this study aimed to understand the impact of grape juice intake and delphinidin on the migration properties of PMNs. Overweight women ingested 500 mL of grape juice for 28 days, and then lipid and inflammatory profiles, as well as the white blood cell count (WBC), were evaluated. Additionally, the gene expression of inflammatory markers and quantified migration molecules such as CD11/CD18, ICAM-1 and VCAM-1 were evaluated in PMNs. The influence of delphinidin-3-O-glucoside in vitro on some migration properties was also evaluated. Grape juice intake did not influence the lipid profile or affect the WBC. However, NFκB gene expression was reduced in PMNs, also reducing the circulating values of IL-8, sICAM-1, and sVCAM-1. The in vitro results demonstrated that delphinidin significantly reduced the migration potential of cells and reduced CD11-/CD18-positive cells, the gene expression of ICAM-1, and the phosphorylation and gene expression of NFκB. Additionally, delphinidin also reduced the production of IL-6, IL-8, and CCL2. Grape juice, after 28 days of intervention, influenced some properties related to cell migration, and delphinidin in vitro can modify the cell migration properties.

Progesterone improved the behavior of PC12 cells under OGD/R by reducing FABP5 expression and inhibiting TLR4/NF-κB signaling pathway

Herein, PC12 cells were applied to detect the impact of progesterone under oxygen glucose deprivation/reperfusion (OGD/R) stimulation. The cell proliferation of PC12 cells was evaluated by cell counting kit-8 assay, and the concentrations of MDA, ROS and SOD were examined by their corresponding Enzyme Linked Immunosorbent Assay kits. The invasion and migration properties of PC12 cells were evaluated by transwell and wound healing assays, respectively. The expression patterns of related genes were evaluated by western blot and qPCR. Under OGD/R stimulation, progesterone treatment could elevate the viability of PC12 cells, reduce the levels of MDA and ROS, and elevate the concentration of SOD. Moreover, progesterone treatment could strengthen the invasion and migration abilities of PC12 cells under OGD/R condition, as well as decrease the apoptosis and inflammation. FABP5 expression was significantly increased in PC12 cells under OGD/R stimulation, which was reversed after progesterone stimulation. Under OGD/R stimulation, the protective effects of progesterone on PC12 cells were strengthened after si-FABP5 treatment. The protein levels of TLR4, p-P65 NF-κB, and P65 NF-κB in OGD/R-induced PC12 cells were increased, which were inhibited after progesterone treatment. Progesterone exerted protective effects on PC12 cells by targeting FABP5 under OGD/R stimulation.

Effects of fucoidan and ferulic acid on potato starch: Pasting, rheological and retrogradation properties and their interactions

The study aimed to investigate the effects of fucoidan (FU) and ferulic acid (FA) on the pasting, thermal, rheological, microstructural and moisture migration properties of potato starch (PS) gels. Pasting results showed that the presence of FU and FA significantly enhanced the thermal stability and resistance to breakdown, and inhibited the stickiness of starch, with the ternary system (PS-FU-FA) showing the best performance. Thermodynamic results indicated that the PS-FU-FA ternary system markedly reduced the retrogradation rate, with FA counteracting the aging phenomenon induced by FU. Rheological tests revealed that all gel systems exhibited weak gel and pseudoplastic fluid behaviors. FA increased the elasticity of PS gels, while FU and FU-FA reduced the viscoelasticity and thickening coefficient of PS, and improved its resistance to shear thinning. Scanning electron microscopy, infrared spectroscopy and low-field nuclear magnetic resonance results suggested that the changes in the above results were due to the interactions among FU, FA and PS, which increased the short-range order structure, and made the microstructure more uniform, compact and continuous, unfavorable for moisture movement, with better water-holding capacity and thermal stability. This study confirmed that the addition of FU and FA had positive effects on the gel properties of PS, providing new insights for the design strategy of starch-based foods, and promoting the practical application of FU, FA and PS in food industry.

Quality by Design Galvanized development of resveratrol loaded PLGA nanoparticles: In vitro and Ex vivo evaluation for the non-invasive treatment of metastatic melanoma

Melanoma is a lethal form of skin cancer, which progresses with poor prognosis. The melanoma tumors are highly metastatic in nature, which often leads to tumorigenesis in lungs and brain tissues. Invasion and migration are mainly responsible for poor 5-year survival rate of ∼32 % after diagnosis of melanoma. The limitations of conventional melanoma therapy include insufficient drug accumulation in tumor due to distal nature of the tumor, and chemoresistance. Resveratrol (RES) is a TGF-β and WNT/β-catenin inhibitor reported to suppress cancer cell proliferation, invasion, and migration. Therefore, we developed RES-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (RES-PLGA-NPs), and embedded within the carbopol hydrogel to achieve site-specific delivery of resveratrol to melanoma cells. During development stage, we employed quality by design (QbD) approach to understand the process parameters. Consequently, we observed 1.26-fold reduction in IC50 for RES-PLGA-NPs compared to unformulated RES. Scratch assay demonstrated the ability of RES and RES-PLGA-NPs to inhibit the migratory properties of melanoma (B16–F10) cells. Further, cell cycle analysis demonstrated that RES and RES-PLGA-NPs arrested cell cycle progression in G2/M phase. Based on these studies we concluded that RES-PLGA-NPs offered enhanced therapeutic effect by inhibiting cell cycle progression, proliferation and invasion of metastatic melanoma cells. Therefore, delivery of RES via nanoparticulate delivery system may have immense potential for metastatic melanoma treatment.

Restoring microRNA-34a overcomes acquired drug resistance and disease progression in human breast cancer cell lines via suppressing the ABCC1 gene

PurposeBreast cancer is one of the leading types of cancer diagnosed in women. Despite the improvements in chemotherapeutic cure strategies, drug resistance is still an obstacle leading to disease aggressiveness. The small non-coding RNA molecules, miRNAs, have been implicated recently to be involved as regulators of gene expression through the silencing of mRNA targets that contributed to several cellular processes related to cancer metastasis. Hence, the present study aimed to investigate the beneficial role and mechanism of miRNA-34a-based gene therapy as a novel approach for conquering drug resistance mediated by ATP-binding cassette (ABC) transporters in breast cancer cells, besides exploring the associated invasive behaviors.Material and MethodsBioinformatics tools were used to predict miRNA ABC transporter targets by tracking the ABC transporter pathway. After the establishment of drug-resistant breast cancer MCF-7 and MDA-MB-231 sublines, cells were transfected with the mimic or inhibitor of miRNA-34a-5p. The quantitative expression of genes involved in drug resistance was performed by QRT-PCR, and the exact ABC transporter target specification interaction was confirmed by dual-luciferase reporter assay. Furthermore, flow cytometric analysis was utilized to determine the ability of miRNA-34a-treated cells against doxorubicin uptake and accumulation in cell cycle phases. The spreading capability was examined by colony formation, migration, and wound healing assays. The apoptotic activity was estimated as well.ResultsOur findings firstly discovered the mechanism of miRNA-34a-5p restoration as an anti-drug-resistant molecule that highly significantly attenuates the expression of ABCC1 via the direct targeting of its 3′- untranslated regions in resistant breast cancer cell lines, with a significant increase of doxorubicin influx by MDA-MB-231/Dox-resistant cells. Additionally, the current data validated a significant reduction of metastatic potentials upon miRNA-34a-5p upregulation in both types of breast cancer-resistant cells.ConclusionThe ectopic expression of miRNA-34a ameliorates the acquired drug resistance and the migration properties that may eventually lead to improved clinical strategies and outcomes for breast cancer patients. Additionally, miRNA-34a could be monitored as a diagnostic/prognostic biomarker for resistant conditions.