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Analysis of the antiparasitic and anticancer activity of the coconut palm (Cocos nucifera L. ARECACEAE) from the natural reserve of Punta Patiño, Darie´n
Full text linkCocos nucifera (C. nucifera) (the coconut palm tree) has been traditionally used to fight a number of human diseases, but only a few studies have tested its components against parasites such as those that cause malaria. In this study, C. nucifera samples were collected from a private natural reserve in Punta Patiño, Darien, Panama. The husk, leaves, pulp, and milk of C. nucifera were extracted and evaluated against the parasites that cause Chagas’ disease or American trypanosomiasis (Trypanosoma cruzi), leishmaniasis (Leishmania donovani) and malaria (Plasmodium falciparum), as well as against a line of breast cancer cells. While there was no activity in the rest of the tests, five and fifteen-minute aqueous decoctions of leaves showed antiplasmodial activity at 10% v/v concentration. Removal of some HPLC fractions resulted in loss of activity, pointing to the presence of synergy between the components of the decoction. Chemical molecules were separated and identified using an ultra-performance liquid chromatography (UPLC) approach coupled to tandem mass spectrometry (LC–MS/MS) using atmospheric pressure chemical ionization quadrupole–time of flight mass spectrometry (APCI–Q–TOF–MS) and molecular networking analysis, revealing the presence of compounds including polyphenol, flavone, sterol, fatty acid and chlorophyll families, among othersCocos nucifera (C. nucifera) (the coconut palm tree) has been traditionally used to fight a number of human diseases, but only a few studies have tested its components against parasites such as those that cause malaria. In this study, C. nucifera samples were collected from a private natural reserve in Punta Patiño, Darien, Panama. The husk, leaves, pulp, and milk of C. nucifera were extracted and evaluated against the parasites that cause Chagas’ disease or American trypanosomiasis (Trypanosoma cruzi), leishmaniasis (Leishmania donovani) and malaria (Plasmodium falciparum), as well as against a line of breast cancer cells. While there was no activity in the rest of the tests, five and fifteen-minute aqueous decoctions of leaves showed antiplasmodial activity at 10% v/v concentration. Removal of some HPLC fractions resulted in loss of activity, pointing to the presence of synergy between the components of the decoction. Chemical molecules were separated and identified using an ultra-performance liquid chromatography (UPLC) approach coupled to tandem mass spectrometry (LC–MS/MS) using atmospheric pressure chemical ionization quadrupole–time of flight mass spectrometry (APCI–Q–TOF–MS) and molecular networking analysis, revealing the presence of compounds including polyphenol, flavone, sterol, fatty acid and chlorophyll families, among other
Development of anthracycline-induced dilated cardiomyopathy due to mutation on LMNA gene in a breast cancer patient: a case report
Full text linkBackground
Anthracyclines are highly effective anticancer medication prescribed for the treatment of breast cancer. Nevertheless, the use of anthracyclines as chemotherapeutic agents involves a risk for development of cardiac toxicity which may cause restrictive and dilated cardiomyopathy. Currently, genetic predisposition is not considered as a risk factor for cardiotoxicity associated to the use of anthracyclines.
Case presentation
We report the case of a 37-years old Panamanian female patient diagnosed with breast cancer who developed clinical signs of severe heart failure after treatment with doxorubicin. A diagnosis of anthracycline induced cardiomyopathy was made and treatment was initiated accordingly. A whole exome sequencing study performed to the patient showed the presence of a missense mutation in LMNA gene, which codifies for lamin A/C. Our results points to a correlation between the LMNA variant and the anthracycline cardiotoxicity developed by the woman. Improvement of the clinical symptoms and the left ventricle ejection fraction was observed after proper treatment.
Conclusions
This case report suggests for the first time a potential genetic predisposition for anthracyclines induced cardiomyopathy in patients with mutations in LMNA gene. Perhaps chemotherapies accelerate or deliver the “second-hit” in the development of DCM in patients with genetic mutations. More data is needed to understand the contribution of LMNA variants that predispose to DCM in patients receiving cardiotoxic therapies.Background
Anthracyclines are highly effective anticancer medication prescribed for the treatment of breast cancer. Nevertheless, the use of anthracyclines as chemotherapeutic agents involves a risk for development of cardiac toxicity which may cause restrictive and dilated cardiomyopathy. Currently, genetic predisposition is not considered as a risk factor for cardiotoxicity associated to the use of anthracyclines.
Case presentation
We report the case of a 37-years old Panamanian female patient diagnosed with breast cancer who developed clinical signs of severe heart failure after treatment with doxorubicin. A diagnosis of anthracycline induced cardiomyopathy was made and treatment was initiated accordingly. A whole exome sequencing study performed to the patient showed the presence of a missense mutation in LMNA gene, which codifies for lamin A/C. Our results points to a correlation between the LMNA variant and the anthracycline cardiotoxicity developed by the woman. Improvement of the clinical symptoms and the left ventricle ejection fraction was observed after proper treatment.
Conclusions
This case report suggests for the first time a potential genetic predisposition for anthracyclines induced cardiomyopathy in patients with mutations in LMNA gene. Perhaps chemotherapies accelerate or deliver the “second-hit” in the development of DCM in patients with genetic mutations. More data is needed to understand the contribution of LMNA variants that predispose to DCM in patients receiving cardiotoxic therapies
Carotenoids as Novel Therapeutic Molecules Against Neurodegenerative Disorders: Chemistry and Molecular Docking Analysis
Full text linkAlzheimer’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
Development of anthracycline-induced dilated cardiomyopathy due to mutation on LMNA gene in a breast cancer patient: a case report
Full text linkBackground Anthracyclines are highly effective anticancer medication prescribed for the treatment of breast cancer. Nevertheless, the use of anthracyclines as chemotherapeutic agents involves a risk for development of cardiac toxicity which may cause restrictive and dilated cardiomyopathy. Currently, genetic predisposition is not considered as a risk factor for cardiotoxicity associated to the use of anthracyclines. Case presentation We report the case of a 37-years old Panamanian female patient diagnosed with breast cancer who developed clinical signs of severe heart failure after treatment with doxorubicin. A diagnosis of anthracycline induced cardiomyopathy was made and treatment was initiated accordingly. A whole exome sequencing study performed to the patient showed the presence of a missense mutation in LMNA gene, which codifies for lamin A/C. Our results points to a correlation between the LMNA variant and the anthracycline cardiotoxicity developed by the woman. Improvement of the clinical symptoms and the left ventricle ejection fraction was observed after proper treatment. Conclusions This case report suggests for the first time a potential genetic predisposition for anthracyclines induced cardiomyopathy in patients with mutations in LMNA gene. Perhaps chemotherapies accelerate or deliver the “second-hit” in the development of DCM in patients with genetic mutations. More data is needed to understand the contribution of LMNA variants that predispose to DCM in patients receiving cardiotoxic therapies.Background Anthracyclines are highly effective anticancer medication prescribed for the treatment of breast cancer. Nevertheless, the use of anthracyclines as chemotherapeutic agents involves a risk for development of cardiac toxicity which may cause restrictive and dilated cardiomyopathy. Currently, genetic predisposition is not considered as a risk factor for cardiotoxicity associated to the use of anthracyclines. Case presentation We report the case of a 37-years old Panamanian female patient diagnosed with breast cancer who developed clinical signs of severe heart failure after treatment with doxorubicin. A diagnosis of anthracycline induced cardiomyopathy was made and treatment was initiated accordingly. A whole exome sequencing study performed to the patient showed the presence of a missense mutation in LMNA gene, which codifies for lamin A/C. Our results points to a correlation between the LMNA variant and the anthracycline cardiotoxicity developed by the woman. Improvement of the clinical symptoms and the left ventricle ejection fraction was observed after proper treatment. Conclusions This case report suggests for the first time a potential genetic predisposition for anthracyclines induced cardiomyopathy in patients with mutations in LMNA gene. Perhaps chemotherapies accelerate or deliver the “second-hit” in the development of DCM in patients with genetic mutations. More data is needed to understand the contribution of LMNA variants that predispose to DCM in patients receiving cardiotoxic therapies
Revisión de Modelos Hiperelásticos utilizados en Tejidos
Full text linkThis work is related to the hyperelastic models most used in soft tissue. The importance of obtaining accurate mechanical properties of tissues are of great interest for various medical applications, for example: in treatment of diseases and surgical simulations in real time. The aim of this literature review is to evaluate the modelsusedforproposingamathematicalformulationandmodellingthemechanical behaviour of a sequence of layers of soft tissues and your reply to undergo external actions of mechanical nature, in order to improve the techniques of characterization of soft tissues.This work is related to the hyperelastic models most used in soft tissue. The importance of obtaining accurate mechanical properties of tissues are of great interest for various medical applications, for example: in treatment of diseases and surgical simulations in real time. The aim of this literature review is to evaluate the modelsusedforproposingamathematicalformulationandmodellingthemechanical behaviour of a sequence of layers of soft tissues and your reply to undergo external actions of mechanical nature, in order to improve the techniques of characterization of soft tissues
Pumilacidins from the Octocoral-Associated Bacillus sp. DT001 Display Anti-Proliferative Effects in Plasmodium falciparum
Full text linkChemical examination of the octocoral-associated Bacillus species (sp.) DT001 led to the isolation of pumilacidins A (1) and C (2). We investigated the effect of these compounds on the viability of Plasmodium falciparum and the mechanism of pumilacidin-induced death. The use of inhibitors of protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K) was able to prevent the effects of pumilacidins A and C. The results indicated also that pumilacidins inhibit parasite growth via mitochondrial dysfunction and decreased cytosolic Ca2+Chemical examination of the octocoral-associated Bacillus species (sp.) DT001 led to the isolation of pumilacidins A (1) and C (2). We investigated the effect of these compounds on the viability of Plasmodium falciparum and the mechanism of pumilacidin-induced death. The use of inhibitors of protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K) was able to prevent the effects of pumilacidins A and C. The results indicated also that pumilacidins inhibit parasite growth via mitochondrial dysfunction and decreased cytosolic Ca2
An Inducible Alpha-Synuclein Expressing Neuronal Cell Line Model for Parkinson’s Disease
Full text linkAltered 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
The global burden of tuberculosis: results from the Global Burden of Disease Study 2015
Full text linkBackground The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030.Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0–100, with 0 as the 2·5th percentile estimated between 1990 and 2030, and 100 as the 97·5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment.Background The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030.Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0–100, with 0 as the 2·5th percentile estimated between 1990 and 2030, and 100 as the 97·5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment
Antimicrobial-producing Pseudoalteromonas from the marine environment of Panama shows a high phylogenetic diversity and clonal structure
Full text linkPseudoalteromonas is a genus of marine bacteria often found in association with other organisms. Although several studies have examined Pseudoalteromonas diversity and their antimicrobial activity, its diversity in tropical environments is largely unexplored. We investigated the diversity of Pseudoalteromonasin marine environments of Panama using a multilocus phylogenetic approach. Furthermore we tested their antimicrobial capacity and evaluated the effect of recombination and mutation in shaping their phylogenetic relationships. The reconstruction of clonal relationships among 78 strains including 15 reference Pseudoalteromonas species revealed 43 clonal lineages, divided in pigmented and non-pigmented strains. In total, 39 strains displayed moderate to high activity against Gram-positive and Gram-negative bacteria and fungi. Linkage disequilibrium analyses showed that the Pseudoalteromonas strains of Panama have a highly clonal structure and that, although present, recombination is not frequent enough to break the association among alleles. This clonal structure is in contrast to the high rates of recombination generally reported for aquatic and marine bacteria.We propose that this structure is likely due to the symbiotic association with marine invertebrates of most strains analyzed. Our results also show that there are several putative new species of Pseudoalteromonas in Panama to be described.Pseudoalteromonas is a genus of marine bacteria often found in association with other organisms. Although several studies have examined Pseudoalteromonas diversity and their antimicrobial activity, its diversity in tropical environments is largely unexplored. We investigated the diversity of Pseudoalteromonasin marine environments of Panama using a multilocus phylogenetic approach. Furthermore we tested their antimicrobial capacity and evaluated the effect of recombination and mutation in shaping their phylogenetic relationships. The reconstruction of clonal relationships among 78 strains including 15 reference Pseudoalteromonas species revealed 43 clonal lineages, divided in pigmented and non-pigmented strains. In total, 39 strains displayed moderate to high activity against Gram-positive and Gram-negative bacteria and fungi. Linkage disequilibrium analyses showed that the Pseudoalteromonas strains of Panama have a highly clonal structure and that, although present, recombination is not frequent enough to break the association among alleles. This clonal structure is in contrast to the high rates of recombination generally reported for aquatic and marine bacteria.We propose that this structure is likely due to the symbiotic association with marine invertebrates of most strains analyzed. Our results also show that there are several putative new species of Pseudoalteromonas in Panama to be described
Mycobacterial Lipids Induce Calcium Mobilization and Degranulation of Mast Cells
Full text linkTuberculosis (TB) remains the leading cause of death from a single infectious agent, followed by HIV/AIDS (1). Emerging countries, such as Panama, have not been able to curb TB infection rates. The development of novel biomarkers for diagnosis, treatment monitoring, and vaccine development is urgently needed. The innate immune response during TB infection is a source of biomarkers. When a susceptible host is exposed to Mycobacterium tuberculosis, the bacteria translocate to the mucosal barrier, interacting with a variety of immune cells, including mast cells (MCs). The initial interaction between M. tuberculosis and first-line defense cells induces the accumulation and subsequent activation of these immune cells within lung tissue, and the release of proinflammatory mediators (2). Mycobacterial lipids appear to define the clinical fate of the infection by modulating the immune response during TB (3). However, the precise role of M. tuberculosis lipids in the immunopathogenic and molecular mechanisms of MC activation is still unknown.
MCs are abundant in the lung tissue, where they act as sentinels for a wide variety of invading pathogens, as well as regulatory cells during the course of acute inflammation (4). Besides specific antigen-driven IgE crosslink stimulation, MCs can be activated by complement components, IgG, neuropeptides, pathogen-associated molecular patterns, mainly peptides, and whole M. tuberculosis interaction (5). MC activation promotes the secretion of stored proinflammatory mediators as well as de novo synthesis of leukotrienes, platelet-activating factor, and prostaglandins. Together with the transcription and release of cytokines and chemokines by MCs, the host begins to make an adaptive immune response (6).
Recently, Garcia-Rodriguez and colleagues revised our perspective of the MC strategies used in bacterial defense and reported interactions occurring between M. tuberculosis and MCs (7). Shortly after exposure, MCs recognize M. tuberculosis via the TLR2 and CD48 receptors. During this initial stage, ESAT-6 and MPT-63 induce MC degranulation, cytokine release, and the secretion of antimicrobial peptides such as β-hexosaminidase and LL-37. We hypothesized that M. tuberculosis lipid extracts are able to activate MCs. In this preliminary study, we aimed to elucidate the role of single phospholipids and whole-lipid extracts in MC activation. Some results from these studies have been previously reported in the form of an abstract (8).Tuberculosis (TB) remains the leading cause of death from a single infectious agent, followed by HIV/AIDS (1). Emerging countries, such as Panama, have not been able to curb TB infection rates. The development of novel biomarkers for diagnosis, treatment monitoring, and vaccine development is urgently needed. The innate immune response during TB infection is a source of biomarkers. When a susceptible host is exposed to Mycobacterium tuberculosis, the bacteria translocate to the mucosal barrier, interacting with a variety of immune cells, including mast cells (MCs). The initial interaction between M. tuberculosis and first-line defense cells induces the accumulation and subsequent activation of these immune cells within lung tissue, and the release of proinflammatory mediators (2). Mycobacterial lipids appear to define the clinical fate of the infection by modulating the immune response during TB (3). However, the precise role of M. tuberculosis lipids in the immunopathogenic and molecular mechanisms of MC activation is still unknown.
MCs are abundant in the lung tissue, where they act as sentinels for a wide variety of invading pathogens, as well as regulatory cells during the course of acute inflammation (4). Besides specific antigen-driven IgE crosslink stimulation, MCs can be activated by complement components, IgG, neuropeptides, pathogen-associated molecular patterns, mainly peptides, and whole M. tuberculosis interaction (5). MC activation promotes the secretion of stored proinflammatory mediators as well as de novo synthesis of leukotrienes, platelet-activating factor, and prostaglandins. Together with the transcription and release of cytokines and chemokines by MCs, the host begins to make an adaptive immune response (6).
Recently, Garcia-Rodriguez and colleagues revised our perspective of the MC strategies used in bacterial defense and reported interactions occurring between M. tuberculosis and MCs (7). Shortly after exposure, MCs recognize M. tuberculosis via the TLR2 and CD48 receptors. During this initial stage, ESAT-6 and MPT-63 induce MC degranulation, cytokine release, and the secretion of antimicrobial peptides such as β-hexosaminidase and LL-37. We hypothesized that M. tuberculosis lipid extracts are able to activate MCs. In this preliminary study, we aimed to elucidate the role of single phospholipids and whole-lipid extracts in MC activation. Some results from these studies have been previously reported in the form of an abstract (8)