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Blueberries (Vaccinium corymbosum L.) are cultivated worldwide and are among the best dietary sources of bioactive compounds with beneficial health effects. This study aimed to investigate the components of Peruvian blueberry using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS/MS), identifying 11 compounds. Furthermore, we assessed in vitro the antioxidant activity and in vivo the antidepressant effect using a rat model and protective effect on lipid peroxidation (in the serum, brain, liver, and stomach). We also conducted molecular docking simulations with proteins involved in oxidative stress and depression for the identified compounds. Antioxidant activity was assessed by measuring total phenolic and flavonoid contents, as well as using 1,1-diphenyl-2-picrylhydrazin (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS•+), and ferric-reducing antioxidant power (FRAP) assays. Peruvian blueberries demonstrated higher antioxidant activity than Vaccinium corymbosum fruits from Chile, Brazil, the United States, Turkey, Portugal, and China. The results showed that oral administration of Peruvian blueberries (10 and 20 mg/kg) for 28 days significantly (p < 0.001) increased swimming and reduced immobility in the forced swimming test (FST). Additionally, at doses of 40 and 80 mg/kg, oxidative stress was reduced in vivo (p < 0.001) by decreasing lipid peroxidation in brain, liver, stomach, and serum. Molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed. In the molecular docking studies, quercitrin and 3,5-di-O-caffeoylquinic acid showed the best docking scores for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, and xanthine oxidase; while 3,5-dicaffeoylquinic acid methyl ester and caffeoyl coumaroylquinic acid had the best docking scores for monoamine oxidase and serotonin receptor 5-HT2. In summary, our results suggest that the antidepressant and protective effects against lipid peroxidation might be related to the antioxidant activity of Peruvian Vaccinium corymbosum L.

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We report here the virtual screening design, synthesis and activity of eight new inhibitors of SphK1. For this study we used a pre-trained Graph Convolutional Network (GCN) combined with docking calculations. This exploratory analysis proposed nine compounds from which eight displayed significant inhibitory effect against sphingosine kinase 1 (SphK1) demonstrating a high level of efficacy for this approach. Four of these compounds also displayed anticancer activity against different tumor cell lines, and three of them (5), (6) and (7) have shown a wide inhibitory action against many of the cancer cell line tested, with GI50 below 5 µM, being (5) the most promising with TGI below 10 µM for the half of cell lines. Our results suggest that the three most promising compounds reported here are the pyrimidine-quinolone hybrids (1) and (6) linked by p-aminophenylsulfanyl and o-aminophenol fragments respectively, and (8) without such aryl linker. We also performed an exhaustive study about the molecular interactions that stabilize the different ligands at the binding site of SphK1. This molecular modeling analysis was carried out by using combined techniques: docking calculations, MD simulations and QTAIM analysis. In this study we also included PF543, as reference compound, in order to better understand the molecular behavior of these ligands at the binding site of SphK1.These results provide useful information for the design of new inhibitors of SphK1 possessing these structural scaffolds.

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Introducción: La cirugía laparoscópica ginecológica permite intervenir a la paciente sin tener que abrir el abdomen, pues consiste en realizar pequeñas incisiones. Actualmente se emplea en enfermedades como el cáncer o en la extracción de quistes y miomas, por lo que se puede aplicar en casi cualquier intervención de cirugía ginecológica. Objetivo: Caracterizar los procedimientos laparoscópicos del Servicio de Ginecología en el Hospital Materno-Infantil Ángel Arturo Aballí en el período comprendido entre enero del 2018 y diciembre del 2021. Métodos: Se realizó un estudio observacional, descriptivo, retrospectivo de corte longitudinal con el fin de describir la actividad asistencial laparoscópica. La muestra fue de 180 pacientes, según el criterio de selección no probabilístico de los investigadores. Resultados: La edad promedio fue 41,6 años. Según los antecedentes, predominó el tamaño del útero con 91,1 por ciento (n = 164). Dentro de las indicaciones quirúrgicas, se encontró la paridad satisfecha en un 34,4 por ciento, seguido del tumor de ovario (18,9 por ciento), las neoplasias intraepiteliales cervicales (13,4 por ciento) y el fibroma uterino sintomático. En cuanto a la cirugía mayor, se encontró la histerectomía abdominal laparoscópica en un 49,0 por ciento (n = 78), seguido de la salpingectomía con un 38,9 por ciento, resultados con significación desde el punto de vista estadístico (p = 0,004). En cuanto a la cirugía menor, el 11,6 por ciento de la muestra recibió la ablación de los focos endometriales. Las complicaciones fueron escasas. Conclusiones: Los procederes laparoscópicos del Servicio de Ginecología del Hospital Materno-Infantil Ángel Arturo Aballí se consideraron adecuados de acuerdo a los indicadores quirúrgicos(AU)

Introduction: Laparoscopic gynecological surgery allows for the patient to undergo surgery without having to open their abdomen, since it consists in making small incisions. It is currently used in diseases such as cancer or in the removal of cysts and myomas; therefore, it can be applied in almost any gynecological surgery. Objective: To characterize the laparoscopic procedures of the gynecology service at Hospital Materno-Infantil Ángel Arturo Aballí, in the period from January 2018 to December 2021. Methods: An observational, descriptive, retrospective and longitudinal study was carried out in order to describe the laparoscopic assistance activity. The sample consisted of 180 patients, according to the researchers' nonprobabilistic selection criteria. Results: The mean age was 41.6 years. Concerning antecedents, uterine size predominated, with 91.1 percent (n = 164). Among surgical indications, satisfied parity was found in 34.4 percent , followed by ovarian tumor (18.9 percent ), cervical intraepithelial neoplasms (13.4 percent ) and symptomatic uterine fibroid. With respect to major surgery, laparoscopic abdominal hysterectomy was found in 49.0 percent (n = 78), followed by salpingectomy, with 38.9 percent ; such results are statistically significant (p = 0.004). Regarding minor surgery, 11.6 percent of the sample received ablation of endometrial focuses. Complications were rare. Conclusions: The laparoscopic procedures of the gynecology service at Hospital Materno-Infantil Ángel Arturo Aballí are considered adequate according to the surgical indicators(AU)

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Astrocytes play a critical role in the maintenance of a healthy central nervous system and astrocyte dysfunction has been implicated in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). There is compelling evidence that mouse and human ALS and ALS/FTD astrocytes can reduce the number of healthy wild-type motoneurons (MNs) in co-cultures or after treatment with astrocyte conditioned media (ACM), independently of their genotype. A growing number of studies have shown that soluble toxic factor(s) in the ACM cause non-cell autonomous MN death, including our recent identification of inorganic polyphosphate (polyP) that is excessively released from mouse primary astrocytes (SOD1, TARDBP, and C9ORF72) and human induced pluripotent stem cells (iPSC)-derived astrocytes (TARDBP) to kill MNs. However, others have reported that astrocytes carrying mutant TDP43 do not produce detectable MN toxicity. This controversy is likely to arise from the findings that human iPSC-derived astrocytes exhibit a rather immature and/or reactive phenotype in a number of studies. Here, we have succeeded in generating a highly homogenous population of functional quiescent mature astrocytes from control subject iPSCs. Using identical conditions, we also generated mature astrocytes from an ALS/FTD patient carrying the TDP43A90V mutation. These mutant TDP43 patient-derived astrocytes exhibit key pathological hallmarks, including enhanced cytoplasmic TDP-43 and polyP levels. Additionally, mutant TDP43 astrocytes displayed a mild reactive signature and an aberrant function as they were unable to promote synaptogenesis of hippocampal neurons. The polyP-dependent neurotoxic nature of the TDP43A90V mutation was further confirmed as neutralization of polyP in ACM derived from mutant TDP43 astrocytes prevented MN death. Our results establish that human astrocytes carrying the TDP43A90V mutation exhibit a cell-autonomous pathological signature, hence providing an experimental model to decipher the molecular mechanisms underlying the generation of the neurotoxic phenotype.

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Infusions of Valeriana pilosa are commonly used in Peruvian folk medicine for treating gastrointestinal disorders. This study aimed to investigate the spasmolytic and antispasmodic effects of Valeriana pilosa essential oil (VPEO) on rat ileum. The basal tone of ileal sections decreased in response to accumulative concentrations of VPEO. Moreover, ileal sections precontracted with acetylcholine (ACh), potassium chloride (KCl), or barium chloride (BaCl2) were relaxed in response to VPEO by a mechanism that depended on atropine, hyoscine butylbromide, solifenacin, and verapamil, but not glibenclamide. The results showed that VPEO produced a relaxant effect by inhibiting muscarinic receptors and blocking calcium channels, with no apparent effect on the opening of potassium channels. In addition, molecular docking was employed to evaluate VPEO constituents that could inhibit intestinal contractile activity. The study showed that α-cubebene, ß-patchoulene, ß-bourbonene, ß-caryophyllene, α-guaiene, γ-muurolene, valencene, eremophyllene, and δ-cadinene displayed the highest docking scores on muscarinic acetylcholine receptors and voltage-gated calcium channels, which may antagonize M2 and/or M3 muscarinic acetylcholine receptors and block voltage-gated calcium channels. In summary, VPEO has both spasmolytic and antispasmodic effects. It may block muscarinic receptors and calcium channels, thus providing a scientific basis for its traditional use for gastrointestinal disorders.

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BACKGROUND: The solubilization of aluminum ions (Al3+) that results from soil acidity (pH < 5.5) is a limiting factor in oil palm yield. Al can be uptaken by the plant roots affecting DNA replication and cell division and triggering root morphological alterations, nutrient and water deprivation. In different oil palm-producing countries, oil palm is planted in acidic soils, representing a challenge for achieving high productivity. Several studies have reported the morphological, physiological, and biochemical oil palm mechanisms in response to Al-stress. However, the molecular mechanisms are just partially understood. RESULTS: Differential gene expression and network analysis of four contrasting oil palm genotypes (IRHO 7001, CTR 3-0-12, CR 10-0-2, and CD 19 - 12) exposed to Al-stress helped to identify a set of genes and modules involved in oil palm early response to the metal. Networks including the ABA-independent transcription factors DREB1F and NAC and the calcium sensor Calmodulin-like (CML) that could induce the expression of internal detoxifying enzymes GRXC1, PER15, ROMT, ZSS1, BBI, and HS1 against Al-stress were identified. Also, some gene networks pinpoint the role of secondary metabolites like polyphenols, sesquiterpenoids, and antimicrobial components in reducing oxidative stress in oil palm seedlings. STOP1 expression could be the first step of the induction of common Al-response genes as an external detoxification mechanism mediated by ABA-dependent pathways. CONCLUSIONS: Twelve hub genes were validated in this study, supporting the reliability of the experimental design and network analysis. Differential expression analysis and systems biology approaches provide a better understanding of the molecular network mechanisms of the response to aluminum stress in oil palm roots. These findings settled a basis for further functional characterization of candidate genes associated with Al-stress in oil palm.

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Parthenocarpy is the development without fertilization of seedless fruits. In the oil palm industry, the development of parthenocarpic fruits is considered an attractive option to increase palm oil production. Previous studies have shown the application of synthetic auxins in Elaeis guineensis, and interspecific O×G hybrids (Elaeis oleifera (Kunth) Cortés × E. guineensis Jacq.) induces parthenocarpy. The aim of this study was to identify the molecular mechanism through transcriptomics and biology system approach to responding to how the application of NAA induces parthenocarpic fruits in oil palm O×G hybrids. The transcriptome changes were studied in three phenological stages (PS) of the inflorescences: i) PS 603, pre-anthesis III, ii) PS 607, anthesis, and iii) PS 700, fertilized female flower. Each PS was treated with NAA, Pollen, and control (any application). The expression profile was studied at three separate times: five minutes (T0), 24 hours (T1), and 48 h post-treatment (T2). The RNA sequencing (RNA seq) approach was used with 27 oil palm O×G hybrids for a total of 81 raw samples. RNA-Seq showed around 445,920 genes. Numerous differentially expressed genes (DEGs) were involved in pollination, flowering, seed development, hormone biosynthesis, and signal transduction. The expression of the most relevant transcription factors (TF) families was variable and dependent on the stage and time post-treatment. In general, NAA treatment expressed differentially more genes than Pollen. Indeed, the gene co-expression network of Pollen was built with fewer nodes than the NAA treatment. The transcriptional profiles of Auxin-responsive protein and Gibberellin-regulated genes involved in parthenocarpy phenomena agreed with those previously reported in other species. The expression of 13 DEGs was validated by RT-qPCR analysis. This detailed knowledge about the molecular mechanisms involved in parthenocarpy could be used to facilitate the future development of genome editing techniques that enable the production of parthenocarpic O×G hybrid cultivars without growth regulator application.

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Valeriana pilosa is usually employed in Peruvian folk medicine in the form of infusion to treat stomach pain, and has antispasmodic, relaxing, sleep-promoting, and sedative properties, as well as is an anti-inflammatory. In this study, Valeriana pilosa essential oil (VPEO) was obtained by hydrodistillation, analyzed by GC and GC/MS, and 47 compounds were identified. Major oil components were α-patchoulene (5.8%), α-humulene (6.1%), seychellene (7.6%), and patchoulol (20.8%). Furthermore, we assessed the in vitro antioxidant activities, molecular docking, and Ligand Efficiency studies on enzymes involved in cellular redox pathways such as CYP2C9, catalase, superoxide dismutase, and xanthine oxidase. Essential oil antioxidant activities were assessed by FRAP, ABTS•+, and DPPH• radical scavenging activity. VPEO displays high antioxidant activity as compared to essential oils of Valeriana jatamansi and Valeriana officinalis oil roots. In addition, molecular docking and ADMET prediction was employed to compare the absorption, metabolism, and toxicity properties of Valeriana pilosa compounds. In the molecular docking studies, limonene, p-cimene, carvone, α-cubebene, cyclosativene, α-guaiene, allo-aromadendrene, valencene, and eremophyllene were the compounds with the best docking score on CYP2C9 and xanthine oxidase. Thus, volatile components of Valeriana pilosa could be associated with the detected antioxidant activity, acting as putative inhibitors of CYP2C9 and xanthine oxidase.

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Non-cell-autonomous mechanisms contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), in which astrocytes release unidentified factors that are toxic to motoneurons (MNs). We report here that mouse and patient iPSC-derived astrocytes with diverse ALS/FTD-linked mutations (SOD1, TARDBP, and C9ORF72) display elevated levels of intracellular inorganic polyphosphate (polyP), a ubiquitous, negatively charged biopolymer. PolyP levels are also increased in astrocyte-conditioned media (ACM) from ALS/FTD astrocytes. ACM-mediated MN death is prevented by degrading or neutralizing polyP in ALS/FTD astrocytes or ACM. Studies further reveal that postmortem familial and sporadic ALS spinal cord sections display enriched polyP staining signals and that ALS cerebrospinal fluid (CSF) exhibits increased polyP concentrations. Our in vitro results establish excessive astrocyte-derived polyP as a critical factor in non-cell-autonomous MN degeneration and a potential therapeutic target for ALS/FTD. The CSF data indicate that polyP might serve as a new biomarker for ALS/FTD.

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