Changes in the plasma lipidome of healthy subjects after coffee consumption reveal potential cardiovascular benefits: A randomized controlled trial.

Lipid metabolism dysregulation is associated with cardiovascular disease (CVD) risk. Specific oxidized lipids are recognized CVD biomarkers involved in all stages of atherosclerosis, including foam cell formation. Moderate coffee intake is positively associated with cardiovascular health. A randomized, controlled (n = 25) clinical trial was conducted in healthy subjects to assess the changes in lipid species relevant to CVD (main inclusion criteria: coffee drinkers, nonsmokers, with no history and/or diagnosis of chronic disease and not consuming any medications). Volunteers consumed a coffee beverage (400 mL/day) containing either 787 mg (coffee A; n = 24) or 407 mg (coffee B; n = 25) of chlorogenic acids for eight weeks. We measured the total plasma levels of 46 lipids, including fatty acids, sterols, and oxysterols, at baseline and after eight weeks and assessed the effects of chlorogenic and phenolic acids, the major coffee antioxidants, in an in vitro foam cell model via targeted lipidomics. At baseline (n = 74), all participants presented oxysterols and free fatty acids (FFAs) (CVD risk markers), which are closely correlated to among them, but not with the classical clinical variables (lipid profile, waist circumference, and BMI). After eight weeks, the control group lipidome showed an increase in oxysterols (+7 ± 10%) and was strongly correlated with FFAs (e.g., arachidonic acid) and cholesteryl ester reduction (-13 ± 7%). Notably, the coffee group subjects (n = 49) had increased cholesteryl esters (+9 ± 11%), while oxysterols (-71 ± 30%) and FFAs (-29 ± 26%) decreased. No differences were found between the consumption of coffees A and B. Additionally, coffee antioxidants decreased oxysterols and regulated arachidonic acid in foam cells. Our results suggest that coffee consumption modulates the generation of oxidized and inflammatory lipids in healthy subjects, which are fundamental during CVD development. The clinical trial was registered on the International Clinical Trials Registry Platform, WHO primary registry (RPCEC00000168).

Gestational long-term hypoxia induces metabolomic reprogramming and phenotypic transformations in fetal sheep pulmonary arteries.

Gestational long-term hypoxia increases the risk of myriad diseases in infants including persistent pulmonary hypertension. Similar to humans, fetal lamb lung development is susceptible to long-term intrauterine hypoxia, with structural and functional changes associated with the development of pulmonary hypertension including pulmonary arterial medial wall thickening and dysregulation of arterial reactivity, which culminates in decreased right ventricular output. To further explore the mechanisms associated with hypoxia-induced aberrations in the fetal sheep lung, we examined the premise that metabolomic changes and functional phenotypic transformations occur due to intrauterine, long-term hypoxia. To address this, we performed electron microscopy, Western immunoblotting, calcium imaging, and metabolomic analyses on pulmonary arteries isolated from near-term fetal lambs that had been exposed to low- or high-altitude (3,801 m) hypoxia for the latter 110+ days of gestation. Our results demonstrate that the sarcoplasmic reticulum was swollen with high luminal width and distances to the plasma membrane in the hypoxic group. Hypoxic animals were presented with higher endoplasmic reticulum stress and suppressed calcium storage. Metabolically, hypoxia was associated with lower levels of multiple omega-3 polyunsaturated fatty acids and derived lipid mediators (e.g., eicosapentaenoic acid, docosahexaenoic acid, α-linolenic acid, 5-hydroxyeicosapentaenoic acid (5-HEPE), 12-HEPE, 15-HEPE, prostaglandin E3, and 19(20)-epoxy docosapentaenoic acid) and higher levels of some omega-6 metabolites (P < 0.02) including 15-keto prostaglandin E2 and linoleoylglycerol. Collectively, the results reveal broad evidence for long-term hypoxia-induced metabolic reprogramming and phenotypic transformations in the pulmonary arteries of fetal sheep, conditions that likely contribute to the development of persistent pulmonary hypertension.

Oxylipin regulation by phenolic compounds from coffee beverage: Positive outcomes from a randomized controlled trial in healthy adults and macrophage derived foam cells.

Oxylipins are considered biomarkers related to cardiovascular diseases (CVDs). They are generated in vivo via the oxygenation of polyunsaturated fatty acids as a result of oxidative stress and inflammation. Oxylipins are involved in vascular functions and are produced during foam cell formation in atherogenesis. Additionally, the consumption coffee is associated with the regulation on a particular oxylipin group, the F2t-isoprostanes (F2t-IsoPs). This function has been attributed to the chlorogenic acids (CGAs) from the coffee beverage. Considering the anti-inflammatory and antioxidant properties of CGAs, we evaluated the effects of two types of coffee that provided 787 mg CGAs/day (Coffee A) and 407 mg CGAs/day (Coffee B) by reducing 35 selected oxylipins in healthy subjects. Furthermore, we assessed the effect of CGAs on the cellular proatherogenic response in foam cells by using an oxidized LDL (oxLDL)-macrophage interaction model. After eight weeks of coffee consumption, the contents of 12 urine oxylipins were reduced. However, the effect of Coffee A showed a stronger decrease in IsoPs, dihomo-IsoPs, prostaglandins (PGs) and PG metabolites, probably due to its higher content of CGAs. Neither of the two coffees reduced the levels of oxLDL. Moreover, the in vitro oxylipin induction by oxLDL on foam cells was ameliorated by phenolic acids and CGAs, including the inhibition of IsoPs and PGs by caffeoylquinic and dicaffeoylquinic acids, respectively, while the phenolic acids maintained both antioxidant and anti-inflammatory activities. These findings suggest that coffee antioxidants are strong regulators of oxylipins related to CVDs. The clinical trial was registered on the International Clinical Trials Registry Platform, WHO primary registry (RPCEC00000168).

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee.

BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.

Alkaloid metabolite profiles by GC/MS and acetylcholinesterase inhibitory activities with binding-mode predictions of five Amaryllidaceae plants.

Acetylcholinesterase (AChE) enzymatic inhibition is an important target for the management of Alzheimer disease (AD) and AChE inhibitors are the mainstay drugs for its treatment. In order to discover new sources of potent AChE inhibitors, a combined strategy is presented based on AChE-inhibitory activity and chemical profiles by GC/MS, together with in silico studies. The combined strategy was applied on alkaloid extracts of five Amaryllidaceae species that grow in Colombia. Fifty-seven alkaloids were detected using GC/MS, and 21 of them were identified by comparing their mass-spectral fragmentation patterns with standard reference spectra in commercial and private library databases. The alkaloid extracts of Zephyranthes carinata exhibited a high level of inhibitory activity (IC50 = 5.97 ± 0.24 µg/mL). Molecular modeling, which was performed using the structures of some of the alkaloids present in this extract and the three-dimensional crystal structures of AChE derived from Torpedo californica, disclosed their binding configuration in the active site of this AChE. The results suggested that the alkaloids 3-epimacronine and lycoramine might be of interest for AChE inhibition. Although the galanthamine group is known for its potential utility in treating AD, the tazettine-type alkaloids should be evaluated to find more selective compounds of potential benefit for AD.

Neuroprotective activity and acetylcholinesterase inhibition of five Amaryllidaceae species: a comparative study.

AIMS: Amaryllidaceae alkaloids exhibit a wide range of physiological effects, of which the acetylcholinesterase (AChE) inhibitory activity is the most relevant. However, scientific evidence related to their neuroprotective effectiveness against glutamate-induced toxicity has been lacking. Thus, the purpose of this study was to conduct a comparative study of the neuroprotective activity and the AChE inhibitory activity of species of Amaryllidaceae. MAIN METHODS: The neuroprotective activity against glutamate-induced toxicity was measured in rat cortical neurons and the Ellman method was employed for the quantification of acetylcholinesterase inhibitory activity of alkaloidal extracts of five species of Amaryllidaceae (Crinum jagus, Crinum bulbispermum, Hippeastrum barbatum, Hippeastrum puniceum and Zephyranthes carinata). The alkaloid Amaryllidaceae patterns based on GC/MS analyses were also investigated. KEY FINDINGS: The results showed that the alkaloidal extract from C. jagus presented a high neuroprotective activity in both pre- and post-treatments against a glutamate excitotoxic stimulus. Furthermore, the alkaloid extracts from C. jagus and Z. carinata revealed an inhibitory activity of AChE from the electric eel with IC50 values of 18.28±0.29 and 17.96±1.22µg/mL, respectively. In addition, 46 alkaloids were detected by GC/MS, and 20 of them were identified based on their mass spectra and retention index. The results suggest that the neuroprotective effects might be associated with lycorine and crinine-type alkaloids, whereas the acetylcholinesterase enzyme inhibitory activity could be related to galanthamine and lycorine-type alkaloids, although not based on synergistic processes. SIGNIFICANCE: In summary, Amaryllidaceae species are sources of alkaloids with potential use for Alzheimer's disease.

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee

BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.

Necrosis cutánea profunda por la aplicación local de hojas de Piper auritum Kunth (caisimón de anís) / Deep cutaneous necrosis caused by the local application of Piper aurifum Kunth (caisimón de anis) leaves

Introducción: Piper auritum Kunth (caisimón de anís) es una de las plantas más utilizadas tradicionalmente en Cuba por sus propiedades antiinflamatorias, analgésicas y cicatrizantes. Objetivos: reportar un caso clínico que sufrió una reacción adversa por automedicación de hojas de Piper auritum. Métodos: se revisó la literatura y la historia clínica de una paciente femenina atendida en el servicio del Hospital Universitario Dr Miguel Enríquez, Servicio de Cirugía Plástica y Caumatología. Resultados: se presentó el caso de una paciente que sufrió lesiones por quemaduras hipodérmicas y sus consecuencias al aplicar hojas de P auritum de forma incorrecta sobre la piel de las mamas, que necesitaron autoinjertos de piel laminar de espesor parcial medio con resultados satisfactorios. Conclusiones: es importante la orientación por personal especializado para el uso de las plantas medicinales

Introduction: Piper aurifum Kunth (caisimón de anis) is one of the most used plants traditionally in Cuba because of its anti-inflammatory, analgesic and healing properties. Objectives: to report a clinical case suffering from an adverse reaction caused by self-medication with Piper aurifum leaves. Methods: the medical literature and the medical history of a female patient, who was seen at Dr Miguel Enríquez university hospital plastic surgery and burn treatment service, were reviewed. Results: the case of a patient who suffered lesions from hypodermic burns caused by the wrong application of P aurifum leaves on the breast skin was presented. It was necessary to use laminar skin autografts of average partial thickness to cure the lesions, with satisfactory results. Conclusions: it is important that specialists provide appropriate instructions about the use of medicinal plants

Necrosis cutánea profunda por la aplicación local de hojas de Piper auritum Kunth (caisimón de anís) / Deep cutaneous necrosis caused by the local application of Piper aurifum Kunth (caisimón de anis) leaves

Introducción: Piper auritum Kunth (caisimón de anís) es una de las plantas más utilizadas tradicionalmente en Cuba por sus propiedades antiinflamatorias, analgésicas y cicatrizantes. Objetivos: reportar un caso clínico que sufrió una reacción adversa por automedicación de hojas de Piper auritum. Métodos: se revisó la literatura y la historia clínica de una paciente femenina atendida en el servicio del Hospital Universitario Dr Miguel Enríquez, Servicio de Cirugía Plástica y Caumatología. Resultados: se presentó el caso de una paciente que sufrió lesiones por quemaduras hipodérmicas y sus consecuencias al aplicar hojas de P auritum de forma incorrecta sobre la piel de las mamas, que necesitaron autoinjertos de piel laminar de espesor parcial medio con resultados satisfactorios. Conclusiones: es importante la orientación por personal especializado para el uso de las plantas medicinales(AU)

Introduction: Piper aurifum Kunth (caisimón de anis) is one of the most used plants traditionally in Cuba because of its anti-inflammatory, analgesic and healing properties. Objectives: to report a clinical case suffering from an adverse reaction caused by self-medication with Piper aurifum leaves. Methods: the medical literature and the medical history of a female patient, who was seen at Dr Miguel Enríquez university hospital plastic surgery and burn treatment service, were reviewed. Results: the case of a patient who suffered lesions from hypodermic burns caused by the wrong application of P aurifum leaves on the breast skin was presented. It was necessary to use laminar skin autografts of average partial thickness to cure the lesions, with satisfactory results. Conclusions: it is important that specialists provide appropriate instructions about the use of medicinal plants(AU)