BACKGROUND: Modulation of macrophage polarization is required for effective tissue repair and reg... more BACKGROUND: Modulation of macrophage polarization is required for effective tissue repair and regenerative therapies. Therapeutic modulation of macrophages from an inflammatory M1 to a fibrotic M2 phenotype could help in diseases, such as chronic wounds, which are stalled in a prolonged and heightened inflammatory stage within the wound healing process. OBJECTIVE: This study evaluates the efficiency of a pullulan/gelatin nanofiber scaffold loaded with retinoic acid (RA) and adipose-derived mesenchymal stem cells (ASCs) to modulate M1 to M2 anti-inflammatory transition. METHODS: Scaffolds were fabricated by electrospinning, and crosslinked using ethylene glycol diglycidyl ether (EGDE). Exposure of RA and/or ASCs to cultured macrophages have been shown to promote M1 to M2 transition. Pullulan was chosen as a scaffold material due to its ability to quench reactive oxygen species, key signaling molecules that play an important role in the progression of inflammation, as well as for its ...
ABSTRACTMetal oxide nanostructures have shown significant promise for biosensors, gas sensors, ph... more ABSTRACTMetal oxide nanostructures have shown significant promise for biosensors, gas sensors, photocatalyst and other biomedical applications. Among these, zinc oxide (ZnO) nanostructures, exhibiting interesting properties such as high catalytic activity, biocompatibility, high isoelectric point, large surface to volume ratio, make them a good candidate for biosensing applications. Here we report the synthesis of ZnO nanorods (ZnONR) on ITO films in aqueous phase and its application in Urea biosensor fabrication. ZnONR have been synthesized by a two-step method, first seed growth of ZnO by sputtering on ITO films followed by decomposition of zinc nitrate hexahydrate / hexamethylenetetramine (HMT) in aqueous phase. Exploiting the high isoelectric point of ZnO, a Urease/ZnONR/ITO bioelectrode has been fabricated by physical binding of Urease (Urs) onto ZnONRs. X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), and cyclic voltammetry (CV) have been used to ...
An important challenge in the fabrication of tissue engineered constructs for regenerative medica... more An important challenge in the fabrication of tissue engineered constructs for regenerative medical applications is the development of processes capable of delivering cells and biomaterials to specific locations in a consistent manner. Electrospraying live cells has been introduced in recent years as a cell seeding method, but its effect on phenotype nor genotype has not been explored. A promising candidate for the cellular component of these constructs are human adipose-derived stem cells (hASCs), which are multipotent stem cells that can be differentiated into fat, bone, and cartilage cells. They can be easily and safely obtained from adipose tissue, regardless of the age and sex of the donor. Moreover, these cells can be maintained and expanded in culture for long periods of time without losing their differentiation capacity. In this study, hASCs directly incorporated into a polymer solution were electrosprayed, inducing differentiation into chondrocytes, without the addition of a...
BACKGROUND The main objective of tissue engineering is to fabricate a tissue construct that mimic... more BACKGROUND The main objective of tissue engineering is to fabricate a tissue construct that mimics native tissue both biologically and mechanically. A recurring problem for tissue-engineered blood vessels (TEBV) is deficient elastogenesis from seeded smooth muscle cells. Elastin is an integral mechanical component in blood vessels, allowing elastic deformation and retraction in response to the shear and pulsatile forces of the cardiac system. OBJECTIVE The goal of this research is to assess the effect of the vitamin A derivative all-trans retinoic acid (RA) and polyphenol pentagalloyl glucose (PGG) on the expression of elastin in human aortic smooth muscle cells (hASMC). METHODS A polycaprolactone (PCL) and the gelatin polymer composite was electrospun and doped with RA and PGG. The scaffolds were subsequently seeded with hASMCs and incubated for five weeks. The resulting tissue-engineered constructs were evaluated using qPCR and Fastin assay for their elastin expression and deposit...
Much of the current understanding on molecular and cellular events of adipose developmental biolo... more Much of the current understanding on molecular and cellular events of adipose developmental biology comes from monolayer cell culture models using preadipocyte cell lines, although in vivo adipose tissue consists of a much more complex three-dimensional microenvironment of diverse cell types, extracellular network, and tissue-specific morphological and functional features. Added to this fact, the preadipocytes, on which the adipogenesis mechanisms are mostly explored, possess some serious limitations (e.g., time of initial subculture and adipogenic differentiation time), which, perhaps, can efficiently be replaced with progenitor cells such as adipose tissue-derived stem cells (ASCs). With the objective of developing a better in vitro model for adipose developmental biology, this project involves gene expression profiling of human ASCs (hASCs) during their differentiation to adipocytes in a 2D versus 3D culture model. This transcriptional-level analysis revealed that gene expression...
Abstract Triple-negative breast cancer (TNBC) is characterized by the absence of expression of th... more Abstract Triple-negative breast cancer (TNBC) is characterized by the absence of expression of the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2). Therefore, TNBC is unresponsive to targeted hormonal therapies, which limits treatment options to nonselective chemotherapeutic agents. Basal-like breast cancers (BLBCs) represent a subset of about 70% of TNBCs, more frequently affecting younger patients, being more prevalent in African-American women and significantly more aggressive than tumors of other molecular subtypes, with high rates of proliferation and extremely poor clinical outcomes. Proper classification of BLBCs using current pathological tools has been a major challenge. Although TNBCs have many BLBC characteristics, the relationship between clinically defined TNBC and the gene expression profile of BLBC is not fully examined. The purpose of this study is to process publicly-available TNBC gene expression datasets generated by Affymetrix gene chips and define a set of genes, or gene signature, that can classify TNBC samples between BLBC and Non-BLBC subtypes. We used over 3500 breast cancer gene expression profiles from several individual publicly available datasets and extracted Affymetrix gene expression data for 580 TNBC cases. Several popular data mining methods along with dimensionality reduction and feature selection techniques were applied to the resultant dataset to build predictive models to understand molecular characteristics and mechanisms associated with BLBCs and to classify them more accurately according to important features extracted through microarray data analysis of BLBC and Non-BLBC cases. Our result can lead to proper identification and diagnosis of BLBCs, which can potentially direct clinical implications by dictating the most effective therapy.
American Journal of Physiology-Heart and Circulatory Physiology
We measured endothelial hydraulic conductivity (Lp,e) and endothelial electrical resistance (Re) ... more We measured endothelial hydraulic conductivity (Lp,e) and endothelial electrical resistance (Re) of pig vena cava in pig serum albumin (PSA) and bovine serum albumin (BSA) to determine whether specificity for the autologous albumin found in dog vena cava is a general property of mammalian endothelium. Pigs were anesthetized with pentobarbital sodium for surgical removal of the thoracic inferior vena cava. A vessel segment was placed as a membrane separating two compartments in a chamber. Vessels kept in 30 mg/ml BSA had Lp,e values of 1.30 +/- 0.81 x 10(-7) cm.s-1.cmH2O-1 (n = 9) and Re values of 13.8 +/- 2.6 omega.cm2 (n = 3). Vessels kept in PSA had Lp,e values of 0.257 +/- 0.125 x 10(-7) cm.s-1.cmH2O-1 (n = 5) and Re values of 21 +/- 6.3 omega.cm2 (n = 4). The differences between Lp,e and Re in BSA and PSA were statistically significant (P < 0.05). In vessels kept in PSA, switching to BSA caused a doubling of Lp,e. Lower Lp,e and higher Re in PSA as compared with those in BSA ...
Chloroquine (Chl) has shown its potential in cancer therapy and graphene oxide (GO) exhibited exc... more Chloroquine (Chl) has shown its potential in cancer therapy and graphene oxide (GO) exhibited excellent tumor-targeting ability, biocompatibility and low toxicity. We have endeavored to conjugate Chl to GO sheets and investigated the nonproliferation action on A549 cell lines along with cell signaling pathways. Cellular toxicity, autophagic flux modulation and cell death mechanism induced by GO-Chl have been investigated on A549 cell lines. GO-Chl induces accumulation of autophagosomes (monodansylcadaverine staining, green fluorescence protein-tagged LC3 plasmid and transmission electron microscopy observations) in A549 cells through the blockade of autophagic flux that serves as scaffold for necrosome assembling and activates necroptotic cell death. GO-Chl nanoconjugate could be used as an effective cancer therapeutic agent, by targeting the autophagy necroptosis axis.
The efficient electrochemical transducer matrix for biosensing devices requires specific characte... more The efficient electrochemical transducer matrix for biosensing devices requires specific characteristics of fast electron transfer, stability, high surface area, biocompatibility and presence of specific functional groups facilitating for biomolecule attachment. We demonstrate the fabrication of an electrochemical immunosensor based on highly stable gold nanoparticles-reduced graphene oxide (AuNPs-rGO) composite material as transducer matrix for label-free and non-invasive detection of salivary oral cancer biomarker interleukin-8 (IL8). The synergy between rGO and AuNPs allowed the immunosensor to exhibit fast response and high sensitivity due to the improved electron transfer behavior of the composite. The immunosensor shows very fast detection (9 min) of IL8 and high sensitivity with experimental linear dynamic range of 500 fg mL-1 to 4 ng mL-1 and detection limit of 72.73±0.18 pg mL-1. The fabricated immunosensor exhibits excellent specificity towards detection of IL8 in the huma...
Heart disease remains one of the leading causes of death in industrialized nations with myocardia... more Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart. In this review, we will describe the cellular events that take place after an MI and describe current treatments. We will also describe how biomaterials, alone or in combination with a cellular component, have been used to engineer suitable myocardium replacement constructs and how new advanced culture systems will be required to achieve clinical success.
Oral cancer (OC) is one of the important cancer types in human being and its early and quick diag... more Oral cancer (OC) is one of the important cancer types in human being and its early and quick diagnosis will help clinicians to develop suitable therapeutic strategies to improve the prognosis of cancer patients. In this direction, we report a label free impedimetric immunosensor to diagnose OC by detecting CD 59, an early stage and important OC biomarker. The immunosensor probe is fabricated by immobilizing CD 59 antibodies (anti-CD 59) on a self-assembled molecular layer of L-cysteine (Cys) on a gold electrode. The fabrication of sensor probe is characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The experimental conditions were optimized in terms of antibody concentration, temperature, pH, and incubation time in order to obtain maximum sensitivity. The CD 59 is qualitatively detected using EIS which shows a wide dynamic range between 1 fg mL(-1) and 1000 fg mL(-1) with a detection limit of 0.38 (+/- 0.03) fg mL(-1). The developed immunosensor is successfully applied for direct detection of CD 59 in clinically relevant human saliva samples. Interferences due to non-target cancer antigens, stability, and regeneration of the developed immunosensor was performed.
BACKGROUND: Modulation of macrophage polarization is required for effective tissue repair and reg... more BACKGROUND: Modulation of macrophage polarization is required for effective tissue repair and regenerative therapies. Therapeutic modulation of macrophages from an inflammatory M1 to a fibrotic M2 phenotype could help in diseases, such as chronic wounds, which are stalled in a prolonged and heightened inflammatory stage within the wound healing process. OBJECTIVE: This study evaluates the efficiency of a pullulan/gelatin nanofiber scaffold loaded with retinoic acid (RA) and adipose-derived mesenchymal stem cells (ASCs) to modulate M1 to M2 anti-inflammatory transition. METHODS: Scaffolds were fabricated by electrospinning, and crosslinked using ethylene glycol diglycidyl ether (EGDE). Exposure of RA and/or ASCs to cultured macrophages have been shown to promote M1 to M2 transition. Pullulan was chosen as a scaffold material due to its ability to quench reactive oxygen species, key signaling molecules that play an important role in the progression of inflammation, as well as for its ...
ABSTRACTMetal oxide nanostructures have shown significant promise for biosensors, gas sensors, ph... more ABSTRACTMetal oxide nanostructures have shown significant promise for biosensors, gas sensors, photocatalyst and other biomedical applications. Among these, zinc oxide (ZnO) nanostructures, exhibiting interesting properties such as high catalytic activity, biocompatibility, high isoelectric point, large surface to volume ratio, make them a good candidate for biosensing applications. Here we report the synthesis of ZnO nanorods (ZnONR) on ITO films in aqueous phase and its application in Urea biosensor fabrication. ZnONR have been synthesized by a two-step method, first seed growth of ZnO by sputtering on ITO films followed by decomposition of zinc nitrate hexahydrate / hexamethylenetetramine (HMT) in aqueous phase. Exploiting the high isoelectric point of ZnO, a Urease/ZnONR/ITO bioelectrode has been fabricated by physical binding of Urease (Urs) onto ZnONRs. X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), and cyclic voltammetry (CV) have been used to ...
An important challenge in the fabrication of tissue engineered constructs for regenerative medica... more An important challenge in the fabrication of tissue engineered constructs for regenerative medical applications is the development of processes capable of delivering cells and biomaterials to specific locations in a consistent manner. Electrospraying live cells has been introduced in recent years as a cell seeding method, but its effect on phenotype nor genotype has not been explored. A promising candidate for the cellular component of these constructs are human adipose-derived stem cells (hASCs), which are multipotent stem cells that can be differentiated into fat, bone, and cartilage cells. They can be easily and safely obtained from adipose tissue, regardless of the age and sex of the donor. Moreover, these cells can be maintained and expanded in culture for long periods of time without losing their differentiation capacity. In this study, hASCs directly incorporated into a polymer solution were electrosprayed, inducing differentiation into chondrocytes, without the addition of a...
BACKGROUND The main objective of tissue engineering is to fabricate a tissue construct that mimic... more BACKGROUND The main objective of tissue engineering is to fabricate a tissue construct that mimics native tissue both biologically and mechanically. A recurring problem for tissue-engineered blood vessels (TEBV) is deficient elastogenesis from seeded smooth muscle cells. Elastin is an integral mechanical component in blood vessels, allowing elastic deformation and retraction in response to the shear and pulsatile forces of the cardiac system. OBJECTIVE The goal of this research is to assess the effect of the vitamin A derivative all-trans retinoic acid (RA) and polyphenol pentagalloyl glucose (PGG) on the expression of elastin in human aortic smooth muscle cells (hASMC). METHODS A polycaprolactone (PCL) and the gelatin polymer composite was electrospun and doped with RA and PGG. The scaffolds were subsequently seeded with hASMCs and incubated for five weeks. The resulting tissue-engineered constructs were evaluated using qPCR and Fastin assay for their elastin expression and deposit...
Much of the current understanding on molecular and cellular events of adipose developmental biolo... more Much of the current understanding on molecular and cellular events of adipose developmental biology comes from monolayer cell culture models using preadipocyte cell lines, although in vivo adipose tissue consists of a much more complex three-dimensional microenvironment of diverse cell types, extracellular network, and tissue-specific morphological and functional features. Added to this fact, the preadipocytes, on which the adipogenesis mechanisms are mostly explored, possess some serious limitations (e.g., time of initial subculture and adipogenic differentiation time), which, perhaps, can efficiently be replaced with progenitor cells such as adipose tissue-derived stem cells (ASCs). With the objective of developing a better in vitro model for adipose developmental biology, this project involves gene expression profiling of human ASCs (hASCs) during their differentiation to adipocytes in a 2D versus 3D culture model. This transcriptional-level analysis revealed that gene expression...
Abstract Triple-negative breast cancer (TNBC) is characterized by the absence of expression of th... more Abstract Triple-negative breast cancer (TNBC) is characterized by the absence of expression of the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2). Therefore, TNBC is unresponsive to targeted hormonal therapies, which limits treatment options to nonselective chemotherapeutic agents. Basal-like breast cancers (BLBCs) represent a subset of about 70% of TNBCs, more frequently affecting younger patients, being more prevalent in African-American women and significantly more aggressive than tumors of other molecular subtypes, with high rates of proliferation and extremely poor clinical outcomes. Proper classification of BLBCs using current pathological tools has been a major challenge. Although TNBCs have many BLBC characteristics, the relationship between clinically defined TNBC and the gene expression profile of BLBC is not fully examined. The purpose of this study is to process publicly-available TNBC gene expression datasets generated by Affymetrix gene chips and define a set of genes, or gene signature, that can classify TNBC samples between BLBC and Non-BLBC subtypes. We used over 3500 breast cancer gene expression profiles from several individual publicly available datasets and extracted Affymetrix gene expression data for 580 TNBC cases. Several popular data mining methods along with dimensionality reduction and feature selection techniques were applied to the resultant dataset to build predictive models to understand molecular characteristics and mechanisms associated with BLBCs and to classify them more accurately according to important features extracted through microarray data analysis of BLBC and Non-BLBC cases. Our result can lead to proper identification and diagnosis of BLBCs, which can potentially direct clinical implications by dictating the most effective therapy.
American Journal of Physiology-Heart and Circulatory Physiology
We measured endothelial hydraulic conductivity (Lp,e) and endothelial electrical resistance (Re) ... more We measured endothelial hydraulic conductivity (Lp,e) and endothelial electrical resistance (Re) of pig vena cava in pig serum albumin (PSA) and bovine serum albumin (BSA) to determine whether specificity for the autologous albumin found in dog vena cava is a general property of mammalian endothelium. Pigs were anesthetized with pentobarbital sodium for surgical removal of the thoracic inferior vena cava. A vessel segment was placed as a membrane separating two compartments in a chamber. Vessels kept in 30 mg/ml BSA had Lp,e values of 1.30 +/- 0.81 x 10(-7) cm.s-1.cmH2O-1 (n = 9) and Re values of 13.8 +/- 2.6 omega.cm2 (n = 3). Vessels kept in PSA had Lp,e values of 0.257 +/- 0.125 x 10(-7) cm.s-1.cmH2O-1 (n = 5) and Re values of 21 +/- 6.3 omega.cm2 (n = 4). The differences between Lp,e and Re in BSA and PSA were statistically significant (P < 0.05). In vessels kept in PSA, switching to BSA caused a doubling of Lp,e. Lower Lp,e and higher Re in PSA as compared with those in BSA ...
Chloroquine (Chl) has shown its potential in cancer therapy and graphene oxide (GO) exhibited exc... more Chloroquine (Chl) has shown its potential in cancer therapy and graphene oxide (GO) exhibited excellent tumor-targeting ability, biocompatibility and low toxicity. We have endeavored to conjugate Chl to GO sheets and investigated the nonproliferation action on A549 cell lines along with cell signaling pathways. Cellular toxicity, autophagic flux modulation and cell death mechanism induced by GO-Chl have been investigated on A549 cell lines. GO-Chl induces accumulation of autophagosomes (monodansylcadaverine staining, green fluorescence protein-tagged LC3 plasmid and transmission electron microscopy observations) in A549 cells through the blockade of autophagic flux that serves as scaffold for necrosome assembling and activates necroptotic cell death. GO-Chl nanoconjugate could be used as an effective cancer therapeutic agent, by targeting the autophagy necroptosis axis.
The efficient electrochemical transducer matrix for biosensing devices requires specific characte... more The efficient electrochemical transducer matrix for biosensing devices requires specific characteristics of fast electron transfer, stability, high surface area, biocompatibility and presence of specific functional groups facilitating for biomolecule attachment. We demonstrate the fabrication of an electrochemical immunosensor based on highly stable gold nanoparticles-reduced graphene oxide (AuNPs-rGO) composite material as transducer matrix for label-free and non-invasive detection of salivary oral cancer biomarker interleukin-8 (IL8). The synergy between rGO and AuNPs allowed the immunosensor to exhibit fast response and high sensitivity due to the improved electron transfer behavior of the composite. The immunosensor shows very fast detection (9 min) of IL8 and high sensitivity with experimental linear dynamic range of 500 fg mL-1 to 4 ng mL-1 and detection limit of 72.73±0.18 pg mL-1. The fabricated immunosensor exhibits excellent specificity towards detection of IL8 in the huma...
Heart disease remains one of the leading causes of death in industrialized nations with myocardia... more Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart. In this review, we will describe the cellular events that take place after an MI and describe current treatments. We will also describe how biomaterials, alone or in combination with a cellular component, have been used to engineer suitable myocardium replacement constructs and how new advanced culture systems will be required to achieve clinical success.
Oral cancer (OC) is one of the important cancer types in human being and its early and quick diag... more Oral cancer (OC) is one of the important cancer types in human being and its early and quick diagnosis will help clinicians to develop suitable therapeutic strategies to improve the prognosis of cancer patients. In this direction, we report a label free impedimetric immunosensor to diagnose OC by detecting CD 59, an early stage and important OC biomarker. The immunosensor probe is fabricated by immobilizing CD 59 antibodies (anti-CD 59) on a self-assembled molecular layer of L-cysteine (Cys) on a gold electrode. The fabrication of sensor probe is characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The experimental conditions were optimized in terms of antibody concentration, temperature, pH, and incubation time in order to obtain maximum sensitivity. The CD 59 is qualitatively detected using EIS which shows a wide dynamic range between 1 fg mL(-1) and 1000 fg mL(-1) with a detection limit of 0.38 (+/- 0.03) fg mL(-1). The developed immunosensor is successfully applied for direct detection of CD 59 in clinically relevant human saliva samples. Interferences due to non-target cancer antigens, stability, and regeneration of the developed immunosensor was performed.
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Papers by Jaime Ramirez-Vick