A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods

The mesenchymal stem cell (MSC) is being broadly studied in clinical trials. Contrary to the early paradigm of cell replacement and differentiation as a therapeutic mechanism of action, evidence is mounting that the secretions of the cells are responsible for their therapeutic effects. These secretions include molecules and extracellular vesicles that have both local and distant effects. This review summarizes the up- and down-regulation of MSC anti-inflammatory, immune modulating, anti-tumor, and regenerative secretions resulting from different stimuli including: a) hypoxia, which increases the production of growth factors and anti-inflammatory molecules; b) pro-inflammatory stimuli that induce the secretion of immune modulating and anti-inflammatory factors; and c) 3 dimensional growth which up regulates the production of anti-cancer factors and anti-inflammatory molecules compared to monolayer culture. Finally we review in detail the most important factors present in conditioned medium of MSC that can be considered protagonists of MSC physiological effects including HGF, TGF-b, VEGF, TSG-6, PGE2 and galectins 1, and 9. We conclude that there is potential for the development of acellular therapeutic interventions for autoimmune, inflammatory, and malignant diseases and tissue regeneration from cellular secretions derived from MSCs cultured under the appropriate conditions.The mesenchymal stem cell (MSC) is being broadly studied in clinical trials. Contrary to the early paradigm of cell replacement and differentiation as a therapeutic mechanism of action, evidence is mounting that the secretions of the cells are responsible for their therapeutic effects. These secretions include molecules and extracellular vesicles that have both local and distant effects. This review summarizes the up- and down-regulation of MSC anti-inflammatory, immune modulating, anti-tumor, and regenerative secretions resulting from different stimuli including: a) hypoxia, which increases the production of growth factors and anti-inflammatory molecules; b) pro-inflammatory stimuli that induce the secretion of immune modulating and anti-inflammatory factors; and c) 3 dimensional growth which up regulates the production of anti-cancer factors and anti-inflammatory molecules compared to monolayer culture. Finally we review in detail the most important factors present in conditioned medium of MSC that can be considered protagonists of MSC physiological effects including HGF, TGF-b, VEGF, TSG-6, PGE2 and galectins 1, and 9. We conclude that there is potential for the development of acellular therapeutic interventions for autoimmune, inflammatory, and malignant diseases and tissue regeneration from cellular secretions derived from MSCs cultured under the appropriate conditions

The lipid content and fatty acid composition of four eastern central Pacific native fish species

Fish is an important source of nutritious n-3 fatty acids, which are necessary for the prevention of cardiovascular and neurological diseases. The lipid content and fatty acid composition of economically important fishes from the eastern central Pacific, namely, Caranx caballus, Cynoscion phoxocephalus, Lutjanus guttatus and Scomberomorus sierra, were determined. Seasonal variations in their n-3 fatty acid composition were investigated as well. The lipid content of all these fish species was less than 4% by weight. In general, the studied species have moderate proportions of n-3 fatty acids. C. caballus was the fish species with the highest concentration of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (898 mg/100 g) followed by S. sierra (596 mg/100 g), C. phoxocephalus (421 mg/100 g) and L. guttatus (342 mg/100 g). The n-3/n-6 ratio of all the species studied ranged from 4.86 to 8.12. Results of this study indicate that all these fish species are highly recommended as a source of low calorie food that can meet the n-3 fatty acid dietary requirements of the Panamanian population.Fish is an important source of nutritious n-3 fatty acids, which are necessary for the prevention of cardiovascular and neurological diseases. The lipid content and fatty acid composition of economically important fishes from the eastern central Pacific, namely, Caranx caballus, Cynoscion phoxocephalus, Lutjanus guttatus and Scomberomorus sierra, were determined. Seasonal variations in their n-3 fatty acid composition were investigated as well. The lipid content of all these fish species was less than 4% by weight. In general, the studied species have moderate proportions of n-3 fatty acids. C. caballus was the fish species with the highest concentration of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (898 mg/100 g) followed by S. sierra (596 mg/100 g), C. phoxocephalus (421 mg/100 g) and L. guttatus (342 mg/100 g). The n-3/n-6 ratio of all the species studied ranged from 4.86 to 8.12. Results of this study indicate that all these fish species are highly recommended as a source of low calorie food that can meet the n-3 fatty acid dietary requirements of the Panamanian population

α-Synuclein misfolding versus aggregation relevance to Parkinson’s disease: Critical assessment and modeling

α-Synuclein, an abundant and conserved presynaptic brain protein, is implicated as a critical factor in Parkinson’s disease (PD). The aggregation of α-synuclein isbelieved to be a critical event in the isease process. α-Synuclein is characterized by a remarkable conformational plasticity, adopting different onformations depending on the environment. Therefore, it is classified as an “intrinsically disordered protein.” Recently, a debate has challenged theview on the intrinsically disordered behavior of α-synuclein in the cell. It has been proposed that α-synuclein is a stable tetramer with a low propensity for aggregation; however, its destabilization leads to protein misfolding and its aggregation kinetics. In our critical analysis, we discussed about major issues: (i) why α-synuclein conformational behavior does not fit into the normal secondary structural characteristics of proteins, (ii) potential amino acids involved in the complexity of misfolding in α-synuclein that leads to aggregation, and (iii) the role of metals in misfolding and aggregation. To evaluate the above critical issues, we developed ioinformatics models related to secondary and tertiary conformations, Ramachandran plot, free energy change, intrinsic disordered prediction, solvent accessibility, and FoldIndex pattern. To the best of our knowledge, this is a novel critical assessment to understand the misfolding biology of synuclein and its relevance to Parkinson’s disease.α-Synuclein, an abundant and conserved presynaptic brain protein, is implicated as a critical factor in Parkinson’s disease (PD). The aggregation of α-synuclein isbelieved to be a critical event in the isease process. α-Synuclein is characterized by a remarkable conformational plasticity, adopting different onformations depending on the environment. Therefore, it is classified as an “intrinsically disordered protein.” Recently, a debate has challenged theview on the intrinsically disordered behavior of α-synuclein in the cell. It has been proposed that α-synuclein is a stable tetramer with a low propensity for aggregation; however, its destabilization leads to protein misfolding and its aggregation kinetics. In our critical analysis, we discussed about major issues: (i) why α-synuclein conformational behavior does not fit into the normal secondary structural characteristics of proteins, (ii) potential amino acids involved in the complexity of misfolding in α-synuclein that leads to aggregation, and (iii) the role of metals in misfolding and aggregation. To evaluate the above critical issues, we developed ioinformatics models related to secondary and tertiary conformations, Ramachandran plot, free energy change, intrinsic disordered prediction, solvent accessibility, and FoldIndex pattern. To the best of our knowledge, this is a novel critical assessment to understand the misfolding biology of synuclein and its relevance to Parkinson’s disease

Effect of Post Weld Heat Treatments on the Elevated Temperature Mechanical Properties of Ti6Al4V Friction Welds

The {\alpha}+\b {eta} titanium alloy (Ti6Al4V) has been successfully joined using rotary friction welding. To investigate the influence of post weld heat treatments on the microstructure and mechanical properties of the welds, the weld joints were heat treated in {\alpha}+\b {eta} and\b {eta} regions, followed by air cooling and furnace cooling. Subsequent to heat treatment, the specimens were subjected to stress relieving treatment. The heat treatment temperatures were selected keeping in view the beta transus temperature of the alloy. Mechanical properties of the welds are evaluated in the as-welded and post weld heat treated conditions at the working temperature of this alloy. The results reported are an average of the values obtained from three tests carried out at a given set of condition. Joints produced exhibited better mechanical properties when compared to the parent metal. Coarse transgranular microstructure and coarse grains in general exhibit better creep and stress rupture properties, while finer microstructures exhibit better tensile strengthsThe {\alpha}+\b {eta} titanium alloy (Ti6Al4V) has been successfully joined using rotary friction welding. To investigate the influence of post weld heat treatments on the microstructure and mechanical properties of the welds, the weld joints were heat treated in {\alpha}+\b {eta} and\b {eta} regions, followed by air cooling and furnace cooling. Subsequent to heat treatment, the specimens were subjected to stress relieving treatment. The heat treatment temperatures were selected keeping in view the beta transus temperature of the alloy. Mechanical properties of the welds are evaluated in the as-welded and post weld heat treated conditions at the working temperature of this alloy. The results reported are an average of the values obtained from three tests carried out at a given set of condition. Joints produced exhibited better mechanical properties when compared to the parent metal. Coarse transgranular microstructure and coarse grains in general exhibit better creep and stress rupture properties, while finer microstructures exhibit better tensile strength

The effects of impaired cerebral circulation on Alzheimer's disease pathology: evidence from animal studies.

Persistent systemic hypoxia, a direct consequence of alterations in vascular function, can compromise the brain by increasing the risk of developing dementias such as Alzheimer’s disease (AD). Vascular contributions to cognitive impairment and AD in aged individuals are common, and several vascular risk factors for AD are linked to hypoxia. Clinical evidence confirms that structural and functional changes characteristic of AD pathology also occur following hypoxic-ischemic events such as stroke and traumatic brain injury. Studies with transgenic and non-transgenic mouse models reliably show that hypoxia increases the levels of amyloid- peptides that form the characteristic plaques in AD brains. Moreover, some studies suggest that vascular lesions also promote tau phosphorylation, modulate apolipoprotein E expression, and have more profound in effects in aged animals, but additional evidence is needed to establish these findings. Although the mechanisms underlying hypoxia-related effects remain unclear, controlled animal studies continue to reveal mechanistic aspects of the relationship between hypoxia and AD pathology that are necessary for therapeutic developments. The present review summarizes evidence from rodent studies regarding the effects of hypoxia on AD-related pathology and evaluates its impact on understanding human disease.Persistent systemic hypoxia, a direct consequence of alterations in vascular function, can compromise the brain by increasing the risk of developing dementias such as Alzheimer’s disease (AD). Vascular contributions to cognitive impairment and AD in aged individuals are common, and several vascular risk factors for AD are linked to hypoxia. Clinical evidence confirms that structural and functional changes characteristic of AD pathology also occur following hypoxic-ischemic events such as stroke and traumatic brain injury. Studies with transgenic and non-transgenic mouse models reliably show that hypoxia increases the levels of amyloid- peptides that form the characteristic plaques in AD brains. Moreover, some studies suggest that vascular lesions also promote tau phosphorylation, modulate apolipoprotein E expression, and have more profound in effects in aged animals, but additional evidence is needed to establish these findings. Although the mechanisms underlying hypoxia-related effects remain unclear, controlled animal studies continue to reveal mechanistic aspects of the relationship between hypoxia and AD pathology that are necessary for therapeutic developments. The present review summarizes evidence from rodent studies regarding the effects of hypoxia on AD-related pathology and evaluates its impact on understanding human disease

Development of Aluminium Based Surface Nano Composites Using Friction Stir Processing

Friction Stir Processing is a relatively new technique which has been developed for microstructural modification of metallic materials through intense, localized plastic deformation. The current research work deals with the development of defect free Aluminium based surface nano composites, with different volume fractions of second phase particles. The work is comprised of development and deformation behavior of aluminium based surface nano composites. Nano-structured second phases of Tungsten and Aluminium oxide were introduced into the Aluminium matrix using a novel unique technique, friction stir processing. Microstructural characterization was done using Scanning Electron Microscopy and Xray Diffraction. Mechanical behavior was evaluated using Vicker's micro hardness. Ultimately structure property correlations were established.Friction Stir Processing is a relatively new technique which has been developed for microstructural modification of metallic materials through intense, localized plastic deformation. The current research work deals with the development of defect free Aluminium based surface nano composites, with different volume fractions of second phase particles. The work is comprised of development and deformation behavior of aluminium based surface nano composites. Nano-structured second phases of Tungsten and Aluminium oxide were introduced into the Aluminium matrix using a novel unique technique, friction stir processing. Microstructural characterization was done using Scanning Electron Microscopy and Xray Diffraction. Mechanical behavior was evaluated using Vicker's micro hardness. Ultimately structure property correlations were established

An Inducible Alpha-Synuclein Expressing Neuronal Cell Line Model for Parkinson’s Disease

Altered expression of α-synuclein is linked to Parkinson’s disease (PD). A major challenge to explore how the increased α-synuclein affect neurotoxicity is the lack of a suitable human neuronal cell model that mimics this scenario. Its expression in neural precursors affects their differentiation process, in addition to the neuronal adaptability and variability in maintaining a constant level of expression across passages. Here, we describe an SH-SY5Y line harboring Tet-ON SNCA cDNA cassette that allows for induction of controlled α-synuclein expression after neuronal differentiation, which can be an important tool for PD research.Altered expression of α-synuclein is linked to Parkinson’s disease (PD). A major challenge to explore how the increased α-synuclein affect neurotoxicity is the lack of a suitable human neuronal cell model that mimics this scenario. Its expression in neural precursors affects their differentiation process, in addition to the neuronal adaptability and variability in maintaining a constant level of expression across passages. Here, we describe an SH-SY5Y line harboring Tet-ON SNCA cDNA cassette that allows for induction of controlled α-synuclein expression after neuronal differentiation, which can be an important tool for PD research

Carotenoids as Novel Therapeutic Molecules Against Neurodegenerative Disorders: Chemistry and Molecular Docking Analysis

Alzheimer’s disease (AD) is the most devastating neurodegenerative disorder that affects the aging population worldwide. Endogenous and exogenous factors are involved in triggering this complex and multifactorial disease, whose hallmark is Amyloid-β (Aβ), formed by cleavage of amyloid precursor protein by β- and γ-secretase. While there is no definitive cure for AD to date, many neuroprotective natural products, such as polyphenol and carotenoid compounds, have shown promising preventive activity, as well as helping in slowing down disease progression. In this article, we focus on the chemistry as well as structure of carotenoid compounds and their neuroprotective activity against Aβ aggregation using molecular docking analysis. In addition to examining the most prevalent anti-amyloidogenic carotenoid lutein, we studied cryptocapsin, astaxanthin, fucoxanthin, and the apocarotenoid bixin. Our computational structure-based drug design analysis and molecular docking simulation revealed important interactions between carotenoids and Aβ via hydrogen bonding and van der Waals interactions, and shows that carotenoids are powerful anti-amyloidogenic molecules with a potential role in preventing AD, especially since most of them can cross the blood-brain barrier and are considered nutraceutical compounds. Our studies thus illuminate mechanistic insights on how carotenoids inhibit Aβ aggregation. The potential role of carotenoids as novel therapeutic molecules in treating AD and other neurodegenerative disorders are discussed.Alzheimer’s disease (AD) is the most devastating neurodegenerative disorder that affects the aging population worldwide. Endogenous and exogenous factors are involved in triggering this complex and multifactorial disease, whose hallmark is Amyloid-β (Aβ), formed by cleavage of amyloid precursor protein by β- and γ-secretase. While there is no definitive cure for AD to date, many neuroprotective natural products, such as polyphenol and carotenoid compounds, have shown promising preventive activity, as well as helping in slowing down disease progression. In this article, we focus on the chemistry as well as structure of carotenoid compounds and their neuroprotective activity against Aβ aggregation using molecular docking analysis. In addition to examining the most prevalent anti-amyloidogenic carotenoid lutein, we studied cryptocapsin, astaxanthin, fucoxanthin, and the apocarotenoid bixin. Our computational structure-based drug design analysis and molecular docking simulation revealed important interactions between carotenoids and Aβ via hydrogen bonding and van der Waals interactions, and shows that carotenoids are powerful anti-amyloidogenic molecules with a potential role in preventing AD, especially since most of them can cross the blood-brain barrier and are considered nutraceutical compounds. Our studies thus illuminate mechanistic insights on how carotenoids inhibit Aβ aggregation. The potential role of carotenoids as novel therapeutic molecules in treating AD and other neurodegenerative disorders are discussed

Production of pullulan using jaggery as substrate by Aureobasidium pullulans MTCC 2195

Shake-flask fermentation, under batch cultivation, was investigated for the production of fungal exopolysaccharide, pullulan using jaggery (a traditional concentrated sugar cane juice) as a carbon substrate by Aureobasidium pullulans MTCC 2195. Change in the initial pH (from 3.0 to 7.0) of media containing jaggery was varied to study the effect of pH in the fermentation and maximum pullulan yield was obtained at a pH of 5.0. An increase in the initial concentrations (50, 75, 100 g/L) of jaggery in the media produced the maximum pullulan content as 21.6, 19.7 and 18.6 g per 100 g of jaggery, respectively, used. A sucrose based defined media were also used for comparison purposes. Fourier Transform InfraRed (FTIR) spectroscopic analysis was done to confirm the functional groups of synthesized pullulan and compared with that of commercial pullulan.Shake-flask fermentation, under batch cultivation, was investigated for the production of fungal exopolysaccharide, pullulan using jaggery (a traditional concentrated sugar cane juice) as a carbon substrate by Aureobasidium pullulans MTCC 2195. Change in the initial pH (from 3.0 to 7.0) of media containing jaggery was varied to study the effect of pH in the fermentation and maximum pullulan yield was obtained at a pH of 5.0. An increase in the initial concentrations (50, 75, 100 g/L) of jaggery in the media produced the maximum pullulan content as 21.6, 19.7 and 18.6 g per 100 g of jaggery, respectively, used. A sucrose based defined media were also used for comparison purposes. Fourier Transform InfraRed (FTIR) spectroscopic analysis was done to confirm the functional groups of synthesized pullulan and compared with that of commercial pullulan

Panamanian Start-ups that Propel Research and Higher Learning

The Republic of Panama can boast of a steadily rising GDP with among the highest economic growth rates in the region, an expanding international services sector, robust financial and banking systems, and relative political stability and citizen security. Unfortunately, none of these advantages has led to strong education system or an extensive research and development agenda. In both education and research, Panama ranks among the lowest in the region. Nevertheless, certain initiatives advanced over the past decade show promise for shifting this tendency, at least in certain sectors.This paper explores several of these endeavors, all of which involve strong international components with regard to partnerships, knowledge transfers and collaborative programming that serve to contribute to these programs' sustainability, performance in line with globally established standards, and role in national capacity development. These innovative initiatives are the following: 1) INDICASAT, a public-private institute for scientific research and high technology services that concentrates on biomedical study; 2) the ProEd Foundation, a local non-governmental organization that has developed and implemented the only international standard driven K-12 teacher training program recognized by the Ministry of Education; 3) the University of South Florida Health Panama program at the City of Knowledge that develops regional courses and international research in areas related to public health and education; 4) the Panamanian Association for Anthropology and History, a young academic association that is driving and promoting research in the social sciences; and 5) CIEdu, a new concept currently being developed for a national, autonomous Center for Education Research.The paper concludes with recommendations for supporting these types of research-driven start-ups and expanding their collaborative potential. It also highlights how Panama´s City of Knowledge, an international education free-zone, is uniquely positioned to propel these higher learning initiatives for the country and the region.The Republic of Panama can boast of a steadily rising GDP with among the highest economic growth rates in the region, an expanding international services sector, robust financial and banking systems, and relative political stability and citizen security. Unfortunately, none of these advantages has led to strong education system or an extensive research and development agenda. In both education and research, Panama ranks among the lowest in the region. Nevertheless, certain initiatives advanced over the past decade show promise for shifting this tendency, at least in certain sectors.This paper explores several of these endeavors, all of which involve strong international components with regard to partnerships, knowledge transfers and collaborative programming that serve to contribute to these programs' sustainability, performance in line with globally established standards, and role in national capacity development. These innovative initiatives are the following: 1) INDICASAT, a public-private institute for scientific research and high technology services that concentrates on biomedical study; 2) the ProEd Foundation, a local non-governmental organization that has developed and implemented the only international standard driven K-12 teacher training program recognized by the Ministry of Education; 3) the University of South Florida Health Panama program at the City of Knowledge that develops regional courses and international research in areas related to public health and education; 4) the Panamanian Association for Anthropology and History, a young academic association that is driving and promoting research in the social sciences; and 5) CIEdu, a new concept currently being developed for a national, autonomous Center for Education Research.The paper concludes with recommendations for supporting these types of research-driven start-ups and expanding their collaborative potential. It also highlights how Panama´s City of Knowledge, an international education free-zone, is uniquely positioned to propel these higher learning initiatives for the country and the region