Genome Editing and Protein Energy Malnutrition.

Protein-energy malnutrition is a state of disordered catabolism resulting from metabolic derangements or starvation. It is associated with chronic disease, hypoglycemia, hypothermia, serious infections, and even an increased prevalence of morbidity and mortality in countries with poor socioeconomic or environmental factors. Adequate food administration is essential to satisfy the main caloric and nutritional demands of humans. The most significant factors seen in the development of protein-energy malnutrition in areas of high incidence, such as underdeveloped countries, are inadequate food and nutrient supplies. It has been well established that one of the strategies to alleviate undernourishment is the biofortification of staple crops. This is because vegetables and plants are significant sources of crucial nutrients for human growth and development. To enhance plant nutrition, recent tactics aim to formulated balanced and diverse diets with acceptable levels of vitamins and minerals that benefit human health. New advances in plant biotechnology and animal productivity could control key enzymes in several metabolic pathways, enriching important nutrients such as iron and vitamins and decreasing the content of disadvantageous compounds such as acrylamide-forming amino acids and phytic acids. Numerous biofortified crops such as rice, maize, and wheat have been created to resolve the problem of nutrition deficiencies. Some examples of these methodologies are genome editing engineered nucleases, transcriptional activator-like effector nucleases, zinc finger nucleases, and clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease which have been created and widely studied for their application, efficiency, and specificity.

Motifs in Natural Products as Useful Scaffolds to Obtain Novel Benzo[d]imidazole-Based Cannabinoid Type 2 (CB2) Receptor Agonists.

The endocannabinoid system (ECS) constitutes a broad-spectrum modulator of homeostasis in mammals, providing therapeutic opportunities for several pathologies. Its two main receptors, cannabinoid type 1 (CB1) and type 2 (CB2) receptors, mediate anti-inflammatory responses; however, their differing patterns of expression make the development of CB2-selective ligands therapeutically more attractive. The benzo[d]imidazole ring is considered to be a privileged scaffold in drug discovery and has demonstrated its versatility in the development of molecules with varied pharmacologic properties. On the other hand, the main psychoactive component of Cannabis sativa, delta-9-tetrahydrocannabinol (THC), can be structurally described as an aliphatic terpenoid motif fused to an aromatic polyphenolic (resorcinol) structure. Inspired by the structure of this phytocannabinoid, we combined different natural product motifs with a benzo[d]imidazole scaffold to obtain a new library of compounds targeting the CB2 receptor. Here, we synthesized 26 new compounds, out of which 15 presented CB2 binding and 3 showed potent agonist activity. SAR analysis indicated that the presence of bulky aliphatic or aromatic natural product motifs at position 2 of the benzo[d]imidazoles ring linked by an electronegative atom is essential for receptor recognition, while substituents with moderate bulkiness at position 1 of the heterocyclic core also participate in receptor recognition. Compounds 5, 6, and 16 were further characterized through in vitro cAMP functional assay, showing potent EC50 values between 20 and 3 nM, and compound 6 presented a significant difference between the EC50 of pharmacologic activity (3.36 nM) and IC50 of toxicity (30-38 µM).

Chemical Fingerprinting and Biological Evaluation of the Endemic Chilean Fruit Greigia sphacelata (Ruiz and Pav.) Regel (Bromeliaceae) by UHPLC-PDA-Orbitrap-Mass Spectrometry.

Greigia sphacelata (Ruiz and Pav.) Regel (Bromeliaceae) is a Chilean endemic plant popularly known as "quiscal" and produces an edible fruit consumed by the local Mapuche communities named as "chupón". In this study, several metabolites including phenolic acids, organic acids, sugar derivatives, catechins, proanthocyanidins, fatty acids, iridoids, coumarins, benzophenone, flavonoids, and terpenes were identified in G. sphacelata fruits using ultrahigh performance liquid chromatography-photodiode array detection coupled with a Orbitrap mass spectrometry (UHPLC-PDA-Orbitrap-MS) analysis for the first time. The fruits showed moderate antioxidant capacities (i.e., 487.11 ± 26.22 µmol TE/g dry weight) in the stable radical DPPH assay, 169.08 ± 9.81 TE/g dry weight in the ferric reducing power assay, 190.32 ± 6.23 TE/g dry weight in the ABTS assay, and 76.46 ± 3.18% inhibition in the superoxide anion scavenging assay. The cholinesterase inhibitory potential was evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). From the findings, promising results were observed for pulp and seeds. Our findings suggest that G. sphacelata fruits are a rich source of diverse secondary metabolites with antioxidant capacities. In addition, the inhibitory effects against AChE and BChE suggest that natural products or food supplements derived from G. sphacelata fruits are of interest for their neuroprotective potential.

Three-Dimensional Quantitative Structure-Activity Relationships (3D-QSAR) on a Series of Piperazine-Carboxamides Fatty Acid Amide Hydrolase (FAAH) Inhibitors as a Useful Tool for the Design of New Cannabinoid Ligands.

Fatty Acid Amide Hydrolase (FAAH) is one of the main enzymes responsible for endocannabinoid metabolism. Inhibition of FAAH increases endogenous levels of fatty acid ethanolamides such as anandamide (AEA) and thus consitutes an indirect strategy that can be used to modulate endocannabinoid tone. In the present work, we present a three-dimensional quantitative structure-activity relationships/comparative molecular similarity indices analysis (3D-QSAR/CoMSIA) study on a series of 90 reported irreversible inhibitors of FAAH sharing a piperazine-carboxamide scaffold. The model obtained was extensively validated (q2 = 0.734; r2 = 0.966; r2m = 0.723). Finally, based on the information derived from the contour maps we designed a series of 10 new compounds with high predicted FAAH inhibition (predicted pIC50 of the best-proposed compounds = 12.196; 12.416).

Design, synthesis, biological evaluation and binding mode modeling of benzimidazole derivatives targeting the cannabinoid receptor type 1.

A series of N-acyl-2,5-dimethoxyphenyl-1H-benzimidazoles were designed based on a CoMFA model for cannabinoid receptor type 1 (CB1) ligands. Compounds were synthesized and radioligand binding affinity assays were performed. Eight novel benzimidazoles exhibited affinity for the CB1 receptor in the nanomolar range, and the most promising derivative compound 5 displayed a K(i) value of 1.2 nM when compared to CP55,940. These results confirm our previously reported QSAR model on benzimidazole derivatives, providing new information for the development of small molecules with high CB1 affinity.

Enantioselective synthesis of α-aryl α-hydrazino phosphonates.

Catalysts generated in situ by the combination of pyridine-hydrazone N,N-ligands and Pd(TFA)2 have been applied to the addition of arylboronic acids to formylphosphonate-derived hydrazones, yielding α-aryl α-hydrazino phosphonates in excellent enantioselectivities (96 → 99% ee). Subsequent removal of the benzyloxycarbonyl (Cbz) N-protecting group afforded key building blocks en route to appealing artificial peptides, herbicides and antitumoral derivatives. Experimental and computational data support a stereochemical model based on aryl-palladium intermediates in which the phosphono hydrazone coordinates in its Z-configuration, maximizing the interactions between the substrate and the pyridine-hydrazone ligand.

Design, synthesis, binding and docking-based 3D-QSAR studies of 2-pyridylbenzimidazoles--a new family of high affinity CB1 cannabinoid ligands.

A series of novel 2-pyridylbenzimidazole derivatives was rationally designed and synthesized based on our previous studies on benzimidazole 14, a CB1 agonist used as a template for optimization. In the present series, 21 compounds displayed high affinities with Ki values in the nanomolar range. JM-39 (compound 39) was the most active of the series (KiCB1 = 0.53 nM), while compounds 31 and 44 exhibited similar affinities to WIN 55212-2. CoMFA analysis was performed based on the biological data obtained and resulted in a statistically significant CoMFA model with high predictive value (q2 = 0.710, r2 = 0.998, r2pred = 0.823).

[Off-label use of gabapentinoid drugs: is it necessary a deprescription strategy?] / Gabapentinoides en indicaciones no autorizadas en la ficha técnica: ¿es necesaria una estrategia de desprescripción?

OBJECTIVE: To evaluate gabapentin and pregabalin treatment adequacy to label indications, to analyze off-label use and to identify patients at high risk of respiratory depression. METHOD: An observational, retrospective study was performed. It included patients treated with pregabalin and gabapentin during 2020 in Navarre. RESULTS: A total of 9778 patients were treated with gabapentin or pregabalin during the first two months of 2020. In 56% of the cases, gabapentinoids were prescribed for off-label uses. Sixty percent of patients were taking at least one central nervous system (CNS) depressant drug concomitantly, 33% of them opioids, 20% of them combined opioids with CNS depressants and 4% of them at least one systemic antihistamine. In addition, 11% of the patients had a diagnosis of asthma or COPD. Prevalences remained constant along the year. CONCLUSIONS: It is necessary to implement a gabapentinoid deprescription strategy to improve its use and reduce safety problems.

[Nirmatrelvir/ritonavir drug-drug interactions in primary care outpatients]. / Análisis de las interacciones de nirmatrelvir/ritonavir en pacientes ambulatorios en Atención primaria

BACKGROUND: The oral antiviral nirmatrelvir/ritonavir interacts with a range of drugs. Candidate patients to receive this antiviral agent are usually vulnerable, multipathological and polymedicated. The objective is to evaluate the pharmaceutical validation prior to the administration of the antiviral. MATERIAL AND METHODS: Drug-drug interactions between nirmatrelvir/ritonavir and patients' usual treatment medications were checked in product information and in the UpToDate® and the University of Liverpool® interaction tools. We included validated prescriptions between April/2022 and April/2023 by a Primary Care pharmacist. RESULTS: Of the 159 study patients, 168 interactions were found in 83 individuals, which may have led to changes of their usual treatment. Statins (25.6%), anticoagulants (10.7%), and antihypertensives (10.7%) were the most frequently implicated therapeutic groups. Discontinuation (53.0%) and dose reduction (22.6%) were the most common treatment changes. CONCLUSIONS: Our search of potential drug interactions and subsequent dose adjustments and modifications of the patient's usual treatment has helped avoid potential toxicities ensuring a safe use of nirmatrelvir/ritonavir.

Chemical Fingerprinting, Aorta Endothelium Relaxation Effect, and Enzymatic Inhibition of Canelo (Drimys winteri J. R. Forst. & G. Forst, (D.C) A. Gray, Family Winteraceae) Fruits.

Drimys winteri J.R. Forst. & G. Forst (D.C) G. Gray, var. chilensis (canelo) is an endemic tree from Chile. Since pre-Columbian times, it has produced a fruit known as the canelo pepper, (pimienta de canelo) or Foye pepper, which can be used as a spice. The chemical and biological analysis of canelo fruits is reported for the first time in this study, that is, its phenolic fingerprinting by UHPLC-PDA- Q-orbitrap MS, the antioxidant activity, the enzymatic inhibitory activity, and its relaxation effects on rat aorta. The proximal composition and the mineral content (Ca: 1.45 ± 0.03 mg/100 g; Mg: 7.72 ± 0.03 mg/100 g; Fe: 4.54 ± 0.21 mg/100 g; Zn: 2.99 ± 0.02 mg/100 g; Mn: 1.08 ± 0.03 mg/100 g; Cu: 0.82 ± 0.02 mg/100 g; K: 53.03 ± 0.20 mg/100 g; Na: 0.087 ± 0.00 mg/100 g) are also reported. The canelo fruits showed a total phenolic content of 57.33 ± 0.82 mg GAE/g dry weight. In addition, the total flavonoid content was 38.42 ± 1.32 mg equivalent of QE/g dry weight. The antioxidant activity was evaluated by employing DPPH and ABTS methods (IC50 of 6.65 ± 0.5 and 9.5 ± 0.05 µg/mL, respectively), ORAC (25.33 ± 1.2 µmol Trolox/g dry plant) and FRAP (45.56 ± 1.32 µmol Trolox/g dry plant). The enzymatic inhibition of acetylcholinesterase, butyrylcholinesterase, and tyrosinase (IC50: 1.94 ± 0.07, 2.73 ± 0.05, and 9.92 ± 0.05 µg extract/mL, respectively) is also reported. Canelo extract led to an 89% relaxation of rat aorta. Our results confirm that D. winteri fruits are a rich source of secondary metabolites and can inhibit enzymes associated with neurodegenerative diseases; the results also suggest that canelo may induce a potentially hypotensive effect in rat aorta. The study demonstrates the medicinal properties of canelo fruit and spice.

UHPLC-MS Metabolomic Fingerprinting, Antioxidant, and Enzyme Inhibition Activities of Himantormia lugubris from Antarctica.

Himantormia lugubris is a Chilean native small lichen shrub growing in the Antarctica region. In this study, the metabolite fingerprinting and the antioxidant and enzyme inhibitory potential from this species and its four major isolated compounds were investigated for the first time. Using ultra-high performance liquid chromatography coupled to quadrupole-Orbitrap mass spectrometry analysis (UHPLC-Q-Orbitrap-MS), several metabolites were identified including specific compounds as chemotaxonomical markers, while major metabolites were quantified in this species. A good inhibition activity against cholinesterase (acetylcholinesterase (AChE) IC50: 12.38 ± 0.09 µg/mL, butyrylcholinesterase (BChE) IC50: 31.54 ± 0.20 µg/mL) and tyrosinase (22.32 ± 0.21 µg/mL) enzymes of the alcoholic extract and the main compounds (IC50: 28.82 ± 0.10 µg/mL, 36.43 ± 0.08 µg/mL, and 7.25 ± 0.18 µg/mL, respectively, for the most active phenolic atranol) was found. The extract showed a total phenolic content of 47.4 + 0.0 mg of gallic acid equivalents/g. In addition, antioxidant activity was assessed using bleaching of DPPH and ORAC (IC50: 75.3 ± 0.02 µg/mL and 32.7 ± 0.7 µmol Trolox/g lichen, respectively) and FRAP (27.8 ± 0.0 µmol Trolox equivalent/g) experiments. The findings suggest that H. lugubris is a rich source of bioactive compounds with potentiality in the prevention of neurodegenerative or noncommunicable chronic diseases.

Alkaloid Profiling, Anti-Enzymatic and Antiproliferative Activity of the Endemic Chilean Amaryllidaceae Phycella cyrtanthoides.

This research aims to identify the alkaloid profile and to evaluate the enzyme inhibitory potential and antiproliferative effects of the Amaryllidaceae plant Phycella cyrtanthoides. The alkaloid extracts from bulbs and leaves were analyzed using ultrahigh performance liquid chromatography orbitrap mass spectrometry (UHPLC-Orbitrap-MS) analysis. A total of 70 alkaloids were detected in the P. cyrtanthoides' extracts. The enzyme inhibition potential against cholinesterases (AChE: acetylcholinesterase, and BChE butyrylcholinesterase) and tyrosinase were studied. Bulbs displayed the best IC50 values against AChE (4.29 ± 0.03 µg/mL) and BChE (18.32 ± 0.03 µg/mL). These results were consistent with docking experiments with selected major compounds in the active sites of enzymes, while no activity was observed against tyrosinase enzyme. Antiproliferative effects were investigated against human cervical (HeLa), lung (A549, SW1573), colon (WiDr), and breast (HBL-100, T-47D) tumor cell lines. Bulbs and leaves were active in all cell lines (GI50 < 2.5 µg/mL). These findings suggest that the endemic Chilean plant P. cyrtanthoides contains diverse types of bioactive alkaloids with antiproliferative activities and inhibitory effects with potential therapeutic applications for neurodegenerative diseases.

[Study protocol: A strategy for deprescribing statins and ezetimibe in primary prevention of cardiovascular disease in patients older than 75 years: health outcomes analysis.] / Protocolo del estudio Estrategia de deprescripción de estatinas y ezetimiba en prevención primaria en mayores de 75 años: análisis de los resultados en salud.

OBJECTIVE: The benefit-risk balance of statins and ezetimibe as primary prevention of cardiovascular disease is controversial in elderly patients due to the doubts about their effectiveness and certainty about adverse effects. The aim of this paper was to analyze health outcomes of a statin and ezetimibe deprescription strategy in patients aged 75 or older treated with these drugs for primary prevention of cardiovascular disease. METHODS: An observational ambispective cohort study was made to evaluate health outcomes after the implementation of a strategy for deprescribing statins and ezetimibe in patients aged 75 or older who take these drugs for primary prevention of cardiovascular disease. To avoid the risk of bias due to non-random assignment of patients to different groups, a propensity score will be calculated for each patient using logistic regression. The outcome of interest will be the deprescription or not of statins or ezetimibe. Time to hospital admission or death from any cause and other variables related to health outcomes will be analysed. Groups with and without statin or ezetimibe deprescription will be compared by survival analysis using Cox regression to estimate the hazard ratio. CONCLUSIONS: It is expected to obtain health outcomes of the strategy of deprescribing statins and ezetimibe in primary prevention in patients aged 75 or older. They will provide information on the advisability of continuing the strategy.

OBJETIVO: El balance beneficio-riesgo de estatinas y ezetimiba como prevención primaria de la enfermedad cardiovascular (ECV) resulta controvertido en pacientes de edad avanzada, debido a las dudas sobre su efectividad y las certezas sobre efectos adversos. El objetivo de este estudio fue analizar los resultados en salud de una estrategia de deprescripción de estatinas y ezetimiba en prevención primaria de ECV en pacientes mayores de 75 años. METODOS: Se realizó un estudio ambispectivo de cohortes para evaluar los resultados en salud obtenidos tras la implementación de una estrategia poblacional de deprescripción de estatinas y ezetimiba en pacientes con edad igual o mayor a 75 años que tomaban estos fármacos como prevención primaria de ECV. Para evitar posibles sesgos debidos a la asignación no aleatoria de los pacientes a los distintos grupos, se calculará un índice de propensión para cada paciente utilizando una regresión logística, en la que la variable de resultado será la deprescripción o no de estatinas o ezetimiba. Se analizará el tiempo hasta el ingreso hospitalario o la muerte por cualquier causa y otras variables relacionadas con resultados en salud. Se compararán los grupos con y sin deprescripción de estatina o ezetimiba mediante un análisis de supervivencia utilizando un modelo de riesgos proporcionales de Cox para estimar el hazard ratio. CONCLUSIONES: Se espera obtener información sobre los resultados en salud de la estrategia de deprescripción de estatinas y ezetimiba en prevención primaria en mayores de 75 años que informarán sobre la conveniencia de continuarla.

Phenolic Fingerprinting and Bioactivity Profiling of Extracts and Isolated Compounds from Gypothamnium pinifolium Phil.

Gypothamnium pinifolium Phil. (Asteraceae) is a small shrub that grows in the Paposo Valley of the II Antofagasta Region of Chile. This initial study is of the high-resolution phenolic fingerprinting, antioxidant activity, the relaxation effects in rat aorta, the inhibitory enzyme potential, plus the antiproliferative activity of the ethyl acetate and n-hexane extract from G. pinifolium and its two major isolated secondary metabolites (one coumarin: 2-nor-1,2-secolycoserone, and one diterpene: ent-labda-8,13-E-diene-15-ol). The study involves using ultra-high-performance liquid chromatography todiode array detection coupled with Q-Orbitrap mass spectrometry analysis (UHPLC-PDA-Orbi-trap-MS), in which various compounds were identified, including specific coumarins. The n-hexane extract showed total phenolic and flavonoid contents of 517.4 ± 12.5 mg GAE/100 g extract and 72.3 ± 3.7 mg QE/100 g extract, respectively. In addition, the antioxidant activity of the n-hexane extract was assessed using in-vitro assays such as bleaching of DPPH and ABTS (IC50: 14.3 ± 0.52 and 2.51 ± 0.43 µg extract/mL, respectively), FRAP (347.12 ± 1.15 µmol Trolox equivalent/g extract), and ORAC (287.3 ± 1.54 µmol Trolox equivalents/g extract). Furthermore, the inhibition against cholinesterases (acetylcholinesterase (AChE) 4.58 ± 0.04 µg/mL, butyrylcholinesterase (BChE) IC50: 23.44 ± 0.03 µg/mL) and tyrosinase (IC50: 9.25 ± 0.15 µg/mL) enzymes of the n-hexane extract, and main compounds (IC50: 1.21 ± 0.03 µg/mL, 11.23 ± 0.02 µg/mL, 3.23 ± 0.12 µg/mL, and 103.43 ± 16.86 µg/mL, correspondingly for the most active coumarin 1) were measured. The antiproliferative potential of the extracts and the two principal compounds against several solid human cancer cells was investigated. All of them showed good activity against cancer cells. Label-free live-cell imaging studies on HeLa cells exposed to the isolated coumarin and the diterpene enabled the observation of cell death and several apoptotic hallmarks. Our results indicate that G. pinifolium Phil. is a valuable source of secondary metabolites with potential activity against noncommunicable diseases.

Phenolic Profile, Antioxidant and Enzyme Inhibition Properties of the Chilean Endemic Plant Ovidia pillopillo (Gay) Meissner (Thymelaeaceae).

Ovidia pillopillo (Lloime) is an endemic species of the Valdivian Forest of Chile. Little is known on the chemistry and biological activity of this plant. In this study, the phenolic profile, antioxidant capacities and enzyme inhibition capacities (against tyrosinase and cholinesterase) of the plant were investigated for the first time. The phenolic profile of the plant was obtained by UHPLC-MS fingerprinting with high resolution, which showed the presence of several flavonoids and coumarins. The antioxidant potential was measured by FRAP and ORAC (45.56 ± 1.32; 25.33 ± 1.2 µmol Trolox equivalents/g dry plant, respectively) plus ABTS and DPPH methods (IC50 = 9.95 ± 0.05 and 6.65 ± 0.5 µg/mL, respectively). Moreover, the flavonoid and phenolic contents were determined (57.33 ± 0.82 and 38.42 ± 1.32, µg of Trolox and quercetin equivalents/100 g dry weight, respectively). The ethanolic extract showed cholinesterase (IC50 = 1.94 ± 0.07 and 2.73 ± 0.05 µg/mL, for AChE and BuChE, respectively) and tyrosinase (4.92 ± 0.05 µg/mL) enzyme inhibition activities. Based on these in vitro studies, in silico simulations were performed, which determined that the major compounds as ligands likely docked in the receptors of the enzymes. These results suggest that Ovidia pillopillo produce interesting special coumarins and flavonoids, which are potential candidates for the exploration and preparation of new medicines.

Exploring alternative hapten tethering sites for high-affinity anti-picoxystrobin antibody generation.

The relevance of the linker tethering site in haptens was investigated for antibody generation and immunoassay development. Three derivatives of the strobilurin fungicide picoxystrobin were synthesized with the same functionalized spacer arm located at three different positions. Protein conjugates of those haptens were employed as immunogens, and novel polyclonal antibodies were produced and characterized. All haptens afforded highly specific antibodies, but different affinities to the free analyte were observed among the obtained antisera. Next, competitive enzyme-linked immunosorbent assays were studied in several formats, and site heterology was confirmed as an effective strategy for detectability improvement. An indirect heterologous immunoassay was eventually selected and optimized, showing a limit of detection for picoxystrobin of 0.02 µg/L and a working range between 0.03 and 1.30 µg/L. Finally, the developed extraction and analytical procedures revealed a practical limit of quantification of 5 µg/kg for this fungicide in soybean sprouts, well below the maximum residue limits in the European Union.

Analysis of Carotenoids in Haloarchaea Species from Atacama Saline Lakes by High Resolution UHPLC-Q-Orbitrap-Mass Spectrometry: Antioxidant Potential and Biological Effect on Cell Viability.

Haloarchaea are extreme halophilic microorganisms belonging to the domain Archaea, phylum Euryarchaeota, and are producers of interesting antioxidant carotenoid compounds. In this study, four new strains of Haloarcula sp., isolated from saline lakes of the Atacama Desert, are reported and studied by high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) for the first time. In addition, determination of the carotenoid pigment profile from the new strains of Haloarcula sp., plus two strains of Halorubrum tebenquichense, and their antioxidant activity by means of several methods is reported. The effect of biomass on cellular viability in skin cell lines was also evaluated by MTT assay. The cholinesterase inhibition capacity of six haloarchaea (Haloarcula sp. ALT-23; Haloarcula sp. TeSe-41; Haloarcula sp. TeSe-51; Haloarcula sp. Te Se-89 and Halorubrum tebenquichense strains TeSe-85 and Te Se-86) is also reported for the first time. AChE inhibition IC50 was 2.96 ± 0.08 µg/mL and BuChE inhibition IC50 was 2.39 ± 0.09 µg/mL for the most active strain, Halorubrum tebenquichense Te Se-85, respectively, which is more active in BuCHe than that of the standard galantamine. Docking calculation showed that carotenoids can exert their inhibitory activity fitting into the enzyme pocket by their halves, in the presence of cholinesterase dimers.

UHPLC-MS Chemical Fingerprinting and Antioxidant, Antiproliferative, and Enzyme Inhibition Potential of Gaultheria pumila Berries.

Gaultheria pumila (Ericaceae) (known as Chaura or Mutilla) is a Chilean native small shrub that produces berry fruits consumed by local Mapuche people. In this study, the chemical fingerprinting and antioxidant, enzyme inhibition, and antiproliferative activities of the berries were investigated for the first time. Thirty-six metabolites were identified in the fruits by ultra-high performance liquid chromatography-photodiode array detection, hyphenated with Orbitrap mass spectrometry analysis (UHPLC-DAD-Orbitrap-MS). Metabolites, included anthocyanins, phenolic acids, flavonoids, iridoids, diterpenes, and fatty acids. Moderate inhibitory activities against acetylcholinesterase (7.7 ± 0.3 µg/mL), butyrylcholinesterase (34.5 ± 0.5 µg/mL), and tyrosinase (3.3 ± 0.2 µg/mL) enzymes were found. Moreover, selected major compounds were subjected to docking assays in light of their experimental inhibition. Results indicated that hydrogen bonding, π-π interaction, and a salt bridge interaction contributed significantly. Gaultheria pumila berries showed a total phenolic content of 189.2 ± 0.2 mg of gallic acid equivalents/g, total flavonoid content of 51.8 ± 0.1 mg quercetin equivalents/g, and total anthocyanin content of 47.3 ± 0.2 mg of cianydin-3-glucoside equivalents/g. Antioxidant activity was assessed using DPPH (92.8 ± 0.1 µg/mL), FRAP (134.1 ± 0.1 µmol Trolox equivalents/g), and ORAC (4251.6 ± 16.9 µmol Trolox equivalents/g) assays. Conversely, Gaultheria pumila showed a scarce antiproliferative potential against several solid human cancer cells. Our findings suggest that Gaultheria pumila berries have several bioactive metabolites with inhibitory effects against acetylcholinesterase, butyrylcholinesterase, and tyrosinase, and have the potential for use in food supplements.

Overestimation of ulcerative colitis due to melanosis coli.

Melanosis coli is a benign pigment deposition in the colonic mucosa that can be seen at the time of colonoscopy especially in patients with history of laxative use. In conditions in which the endoscopic findings influence therapeutic decisions, melanosis coli can lead to overestimation of disease aggressiveness and unnecessary therapy. We describe a case in which the finding of melanosis coli affected the treatment of a patient with mild ulcerative colitis exacerbation.