Plant Protease Inhibitors as Emerging Antimicrobial Peptide Agents: A Comprehensive Review.

Antimicrobial peptides (AMPs) are important mediator molecules of the innate defense mechanisms in a wide range of living organisms, including bacteria, mammals, and plants. Among them, peptide protease inhibitors (PPIs) from plants play a central role in their defense mechanisms by directly attacking pathogens or by modulating the plant's defense response. The growing prevalence of microbial resistance to currently available antibiotics has intensified the interest concerning these molecules as novel antimicrobial agents. In this scenario, PPIs isolated from a variety of plants have shown potential in inhibiting the growth of pathogenic bacteria, protozoans, and fungal strains, either by interfering with essential biochemical or physiological processes or by altering the permeability of biological membranes of invading organisms. Moreover, these molecules are active inhibitors of a range of proteases, including aspartic, serine, and cysteine types, with some showing particular efficacy as trypsin and chymotrypsin inhibitors. In this review, we provide a comprehensive analysis of the potential of plant-derived PPIs as novel antimicrobial molecules, highlighting their broad-spectrum antimicrobial efficacy, specificity, and minimal toxicity. These natural compounds exhibit diverse mechanisms of action and often multifunctionality, positioning them as promising molecular scaffolds for developing new therapeutic antibacterial agents.

Reemplazo esofágico mínimamente invasivo con tubo de Akiyama en un paciente pediátrico con quemadura esofágica / Minimally invasive esophageal replacement with Akiyama tube in a pediatric patient with esophageal burn

Introducción. La ingesta de cáusticos continúa siendo un problema de salud pública en los países en vía de desarrollo, por lo que a veces es necesario realizar un reemplazo esofágico en estos pacientes. Aún no existe una técnica estandarizada para este procedimiento. Caso clínico. Masculino de 10 años con estenosis esofágica por ingesta de cáusticos, quien no mejoró con las dilataciones endoscópicas. Se realizó un ascenso gástrico transhiatal por vía ortotópica mediante cirugía mínimamente invasiva como manejo quirúrgico definitivo .Discusión. Actualmente existen varios tipos de injertos usados en el reemplazo esofágico. La interposición colónica y gástrica son las que cuentan con mayores estudios, mostrando resultados similares. Conclusiones. La elección del tipo y posición del injerto debe ser individualizada, tomando en cuenta las características de las lesiones y la anatomía de cada paciente para aumentar la tasa de éxito.

Introduction. The ingestion of caustics continues to be a public health problem in developing countries, which is why sometimes is necessary to perform an esophageal replacement in these patients. There is still no standardized technique for this procedure. Clinical case. A 10-year-old male with esophageal stricture due to caustic ingestion, who did not improve with endoscopic dilations. A laparoscopic transhiatal gastric lift was performed orthotopically as definitive surgical management using minimally invasive surgery. Discussion. Currently there are several types of grafts used in esophageal replacement. Colonic and gastric interposition are the ones that have the most studies, showing similar results. Conclusions. Choice of type and position of the graft must be individualized, taking into account the characteristics of the lesions and anatomy of each patient, in order to increase the success rate.

Setd2 inactivation sensitizes lung adenocarcinoma to inhibitors of oxidative respiration and mTORC1 signaling.

SETD2 is a tumor suppressor that is frequently inactivated in several cancer types. The mechanisms through which SETD2 inactivation promotes cancer are unclear, and whether targetable vulnerabilities exist in these tumors is unknown. Here we identify heightened mTORC1-associated gene expression programs and functionally higher levels of oxidative metabolism and protein synthesis as prominent consequences of Setd2 inactivation in KRAS-driven mouse models of lung adenocarcinoma. Blocking oxidative respiration and mTORC1 signaling abrogates the high rates of tumor cell proliferation and tumor growth specifically in SETD2-deficient tumors. Our data nominate SETD2 deficiency as a functional marker of sensitivity to clinically actionable therapeutics targeting oxidative respiration and mTORC1 signaling.

Malformaciones linfáticas abdominales en una población pediátrica: experiencia en un centro de referencia de Medellín, Colombia / Abdominal lymphatic malformations in a pediatric population: Experience in a referral center in Medellín, Colombia

Introducción. Los linfangiomas son anormalidades benignas del sistema linfático, que corresponden a dilataciones quísticas de estos vasos y se localizan especialmente en el cuello. Solo el 10 % de todas estas malformaciones se encuentran en el abdomen y presentan síntomas variables de acuerdo al tamaño y su ubicación especifica, siendo el dolor abdominal el principal síntoma. Métodos. Se presentan cinco pacientes pediátricos con malformaciones linfáticas abdominales. Se describen su cuadro clínico, localización, tratamiento y la experiencia en el manejo de dicha patología en un hospital de referencia. Resultados. Los métodos más apropiados para hacer una aproximación diagnóstica son la ecografía, la tomografía computarizada y la resonancia nuclear magnética. Dentro de las opciones descritas para el tratamiento están la farmacológica, la escleroterapia y la resección quirúrgica, tanto por vía abierta como por laparoscopia. Conclusión. Existe una variedad de métodos para realizar la resección de los linfangiomas abdominales, pero la cirugía sigue siendo la más efectiva, especialmente cuando se cuenta con la laparoscopia como una herramienta terapéutica.

Introduction. Lymphangiomas are benign abnormalities of the lymphatic system, which correspond to cystic dilations of these vessels and are located especially in the neck. Only 10% of all these malformations are found in the abdomen and present variable symptoms according to size and their specific location, with abdominal pain being the main symptom. Methods. Five pediatric patients with abdominal lymphatic malformations are presented. Their clinical presentation, location, treatment and experience in the management of this pathology in a referral hospital are described. Results. The most appropriate methods to make a diagnostic approach are ultrasound, computed tomography and magnetic resonance imaging. Among the options described for treatment are pharmacological, sclerotherapy and surgical resection, both open and laparoscopic. Conclusion. There are a variety of methods for resecting abdominal lymphangiomas, but surgery remains the most effective, especially when laparoscopy is used as a therapeutic tool.

RB depletion is required for the continuous growth of tumors initiated by loss of RB.

The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation in vivo. In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to Rb knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function in vivo.

Purification and Characterization of a Novel Thermostable Papain Inhibitor from Moringa oleifera with Antimicrobial and Anticoagulant Properties.

Plant cystatins (or phytocystatins) comprise a large superfamily of natural bioactive small proteins that typically act as protein inhibitors of papain-like cysteine proteases. In this report, we present the purification and characterization of the first phytocystatin isolated from Moringa oleifera (MoPI). MoPI has a molecular mass of 19 kDa and showed an extraordinary physicochemical stability against acidic pHs and high temperatures. Our findings also revealed that MoPI is one of the most potent cysteine protease inhibitors reported to date, with Ki and IC50 values of 2.1 nM and 5.7 nM, respectively. More interestingly, MoPI presents a strong antimicrobial activity against human pathogens such as Enterococcus faecalis and Staphylococcus aureus. In addition, MoPI also showed important anticoagulant activity, which is an unprecedented property for this family of protease inhibitors. These results highlight the pharmaceutical potential of this plant and its derived bioactive molecules.

NPM-ALK-Induced Reprogramming of Mature TCR-Stimulated T Cells Results in Dedifferentiation and Malignant Transformation.

Fusion genes including NPM-ALK can promote T-cell transformation, but the signals required to drive a healthy T cell to become malignant remain undefined. In this study, we introduce NPM-ALK into primary human T cells and demonstrate induction of the epithelial-to-mesenchymal transition (EMT) program, attenuation of most T-cell effector programs, reemergence of an immature epigenomic profile, and dynamic regulation of c-Myc, E2F, and PI3K/mTOR signaling pathways early during transformation. A mutant of NPM-ALK failed to bind several signaling complexes including GRB2/SOS, SHC1, SHC4, and UBASH3B and was unable to transform T cells. Finally, T-cell receptor (TCR)-generated signals were required to achieve T-cell transformation, explaining how healthy individuals can harbor T cells with NPM-ALK translocations. These findings describe the fundamental mechanisms of NPM-ALK-mediated oncogenesis and may serve as a model to better understand factors that regulate tumor formation. SIGNIFICANCE: This investigation into malignant transformation of T cells uncovers a requirement for TCR triggering, elucidates integral signaling complexes nucleated by NPM-ALK, and delineates dynamic transcriptional changes as a T cell transforms.See related commentary by Spasevska and Myklebust, p. 3160.

Rare monophasic mediastinal pleural synovial sarcoma diagnosed via endobronchial ultrasound-transbronchial needle aspiration.

The mediastinum is a rare site for occurrence of a primary synovial sarcoma (SS) with very few cases reported in the literature. The diagnosis so far has been achieved mainly via open surgery, with only three reported cases diagnosed via endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA), however, none of those were located at the posterior mediastinum, without showing any oesophageal or endobronchial involvement. To our knowledge, this is the first reported case of a monophasic primary pleural mediastinal SS purely involving the posterior mediastinum without oesophageal or endobronchial component, diagnosed via EBUS-TBNA.

Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis.

Type 1 conventional dendritic cells (cDC1s) are typically thought to be dysregulated secondarily to invasive cancer. Here, we report that cDC1 dysfunction instead develops in the earliest stages of preinvasive pancreatic intraepithelial neoplasia (PanIN) in the KrasLSL-G12D/+ Trp53LSL-R172H/+ Pdx1-Cre-driven (KPC) mouse model of pancreatic cancer. cDC1 dysfunction is systemic and progressive, driven by increased apoptosis, and results in suboptimal up-regulation of T cell-polarizing cytokines during cDC1 maturation. The underlying mechanism is linked to elevated IL-6 concomitant with neoplasia. Neutralization of IL-6 in vivo ameliorates cDC1 apoptosis, rescuing cDC1 abundance in tumor-bearing mice. CD8+ T cell response to vaccination is impaired as a result of cDC1 dysregulation. Yet, combination therapy with CD40 agonist and Flt3 ligand restores cDC1 abundance to normal levels, decreases cDC1 apoptosis, and repairs cDC1 maturation to drive superior control of tumor outgrowth. Our study therefore reveals the unexpectedly early and systemic onset of cDC1 dysregulation during pancreatic carcinogenesis and suggests therapeutically tractable strategies toward cDC1 repair.

Blocking EGFR palmitoylation suppresses PI3K signaling and mutant KRAS lung tumorigenesis.

Non-small cell lung cancer (NSCLC) is often characterized by mutually exclusive mutations in the epidermal growth factor receptor (EGFR) or the guanosine triphosphatase KRAS. We hypothesized that blocking EGFR palmitoylation, previously shown to inhibit EGFR activity, might alter downstream signaling in the KRAS-mutant setting. Here, we found that blocking EGFR palmitoylation, by either knocking down the palmitoyltransferase DHHC20 or expressing a palmitoylation-resistant EGFR mutant, reduced activation of the kinase PI3K, the abundance of the transcription factor MYC, and the proliferation of cells in culture, as well as reduced tumor growth in a mouse model of KRAS-mutant lung adenocarcinoma. Knocking down DHHC20 reduced the growth of existing tumors derived from human KRAS-mutant lung cancer cells and increased the sensitivity of these cells to a PI3K inhibitor. Palmitoylated EGFR interacted with the PI3K regulatory subunit PIK3R1 (p85) and increased the recruitment of the PI3K heterodimer to the plasma membrane. Alternatively, blocking palmitoylation increased the association of EGFR with the MAPK adaptor Grb2 and decreased that with p85. This binary switching between MAPK and PI3K signaling, modulated by EGFR palmitoylation, was only observed in the presence of oncogenic KRAS. These findings suggest a mechanism whereby oncogenic KRAS saturates signaling through unpalmitoylated EGFR, reducing formation of the PI3K signaling complex. Future development of DHHC20 inhibitors to reduce EGFR-PI3K signaling could be beneficial to patients with KRAS-mutant tumors.

Biotechnological, biomedical, and agronomical applications of plant protease inhibitors with high stability: A systematic review.

Protease inhibitors (PIs) are regulatory proteins found in numerous animal tissues and fluids, plants, and microorganisms that reduce and inhibit the exacerbated and uncontrolled activity of the target proteases. Specific PIs are also effective tools for inactivating proteases involved in human diseases like arthritis, pancreatitis, hepatitis, cancer, AIDS, thrombosis, emphysema, hypertension, and muscular dystrophy among others. Plant PIs-small peptides with a high content of cystine residues in disulfide bridges-possess a remarkable resistance to heat treatment and a high stability against shifts in pH, denaturing agents, ionic strength, and proteolysis. In recent years, novel biologic activities have been reported for plant PIs, including antimicrobial, anticoagulant, antioxidant action plus inhibition of tumor-cell growth; thus pointing to possible applications in medicine, agriculture, and biotechnology. In this review, we provide a comparative overview of plant-PIs classifying them in four groups according of their thermal and pH stability (high stability and hyperstable -to temperature and to pHs-, respectively), then emphasizing the relevance of the physicochemical characteristics of these proteins for potential biotechnological and industrial applications. Finally, we analyze the biologic activities of the stable protease inhibitors previously characterized that are the most relevant to potential applications in biomedicine, the food industry, and agriculture.

Bioavailability of Sulforaphane Following Ingestion of Glucoraphanin-Rich Broccoli Sprout and Seed Extracts with Active Myrosinase: A Pilot Study of the Effects of Proton Pump Inhibitor Administration.

We examined whether gastric acidity would affect the activity of myrosinase, co-delivered with glucoraphanin (GR), to convert GR to sulforaphane (SF). A broccoli seed and sprout extract (BSE) rich in GR and active myrosinase was delivered before and after participants began taking the anti-acid omeprazole, a potent proton pump inhibitor. Gastric acidity appears to attenuate GR bioavailability, as evidenced by more SF and its metabolites being excreted after participants started taking omeprazole. Enteric coating enhanced conversion of GR to SF, perhaps by sparing myrosinase from the acidity of the stomach. There were negligible effects of age, sex, ethnicity, BMI, vegetable consumption, and bowel movement frequency and quality. Greater body mass correlated with reduced conversion efficiency. Changes in the expression of 20 genes in peripheral blood mononuclear cells were evaluated as possible pharmacodynamic indicators. When grouped by their primary functions based on a priori knowledge, expression of genes associated with inflammation decreased non-significantly, and those genes associated with cytoprotection, detoxification and antioxidant functions increased significantly with bioavailability. Using principal components analysis, component loadings of the changes in gene expression confirmed these groupings in a sensitivity analysis.

RB constrains lineage fidelity and multiple stages of tumour progression and metastasis.

Mutations in the retinoblastoma (RB) tumour suppressor pathway are a hallmark of cancer and a prevalent feature of lung adenocarcinoma1-3. Although RB was the first tumour suppressor to be identified, the molecular and cellular basis that underlies selection for persistent RB loss in cancer remains unclear4-6. Methods that reactivate the RB pathway using inhibitors of cyclin-dependent kinases CDK4 and CDK6 are effective in some cancer types and are currently under evaluation for the treatment of lung adenocarcinoma7-9. Whether RB pathway reactivation will have therapeutic effects and whether targeting CDK4 and CDK6 is sufficient to reactivate RB pathway activity in lung cancer remains unknown. Here we model RB loss during lung adenocarcinoma progression and pathway reactivation in established oncogenic KRAS-driven tumours in mice. We show that RB loss enables cancer cells to bypass two distinct barriers during tumour progression. First, RB loss abrogates the requirement for amplification of the MAPK signal during malignant progression. We identify CDK2-dependent phosphorylation of RB as an effector of MAPK signalling and critical mediator of resistance to inhibition of CDK4 and CDK6. Second, RB inactivation deregulates the expression of cell-state-determining factors, facilitates lineage infidelity and accelerates the acquisition of metastatic competency. By contrast, reactivation of RB reprograms advanced tumours towards a less metastatic cell state, but is nevertheless unable to halt cancer cell proliferation and tumour growth due to adaptive rewiring of MAPK pathway signalling, which restores a CDK-dependent suppression of RB. Our study demonstrates the power of reversible gene perturbation approaches to identify molecular mechanisms of tumour progression, causal relationships between genes and the tumour suppressive programs that they control and critical determinants of successful cancer therapy.

Adding value to the chia (Salvia hispanica L.) expeller: Production of bioactive peptides with antioxidant properties by enzymatic hydrolysis with Papain.

Chia expeller is a by-product of the extrusion process of chia seeds generated during oil production. Typically, this material is non-utilized or used for non-valuable applications. In the present work, the chia expeller was hydrolysed with Papain and the antioxidant properties of the resultant peptides were evaluated. Papain treatment of the chia seed expeller demonstrated an enrichment of low molecular weight peptides (molecular weight <15 kDa) as determined by SDS-PAGE and MALDI-TOF/MS analyses. Such peptides showed a potent radical scavenging effect in vitro against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals in comparison with those non-hydrolysed samples. Taken together our results demonstrate the generation of functional peptides from the chia expeller by enzymatic hydrolysis with Papain. This value-added hydrolysate can be potentially included as a supplement in functional food and nutraceutical products.

Prostatectomía convencional versus resección endoscópica de próstata monopolar en pacientes con Hiperplasia Prostática: un estudio de corte retrospectivo / Conventional prostatectomy vs. endoscopic resection of monopolar prostate in patients with Prostatic Hyperplasia: a retrospective study

La resolución quirúrgica de la hiperplasia prostática benigna se modifca conforme el acceso a las diferentes tecnologías en salud. Las complicaciones del abordaje endoscópico versus el convencional son similares. El Objetivo de este estudio fue analizar retrospectivamente los resultados de la cirugía convencional y la resección endoscópica monopolar de la hiperplasia de próstata en un hospital terciario del Ecuador. Pacientes y Métodos: Estudio retrospectivo, analítico. Fueron incluidos en el estudio 232 pacientes con diagnóstico histopatológico de hiperplasia prostática benigna atendidos en el servicio de urología del hospital Luis Vernaza en el período enero 2015 ­ diciembre 2016. Los pacientes fueron divididos en 2 subgrupos de acuerdo con el abordaje terapéutico ­ quirúrgico: prostatectomía convencional (n = 120) y resección endoscópica (n = 112). Resultados: Mediante estadística inferencial se comprobó una relación estadísticamente signifcativa entre el tipo de abordaje terapéutico con el tiempo quirúrgico (p= <0.001) y con el índice de sangrado (p= <0.001) y entre la edad y el tiempo quirúrgico (p= <0.001). Las complicaciones más importantes fueron: hemorragia inmediata (n=9) e infecciones de la herida (n=10) para la cirugía convencional y hemorragia inmediata (n=2) y sepsis (n=3) para la cirugía endoscópica. La media de tiempo quirúrgico fue 103.03 min y 75.14 min respectivamente. Conclusión: El desarrollo tecnológico ha traído la certeza de que la cirugía endoscópica tiene menores complicaciones, disminuye los tiempos quirúrgicos. Siendo una opción por considerar frente a la cirugía tradicional para la hiperplasia de próstata

Surgical resolution of benign prostatic hyperplasia is modifed as access to different health technologies. Complications of endoscopic versus conventional approach are similar. The objective of this study was to retrospectively analyze the results of conventional surgery and monopolistic endoscopic resection of prostate hyperplasia in a tertiary hospital in Ecuador. Patients and Methods: Retrospective, analytical study. 232 patients diagnosed with benign prostatic hyperplasia were included in the study in the urology service of the Luis Vernaza hospital in the period January 2015 ­ December 2016. Patients were divided into 2 subgroups according to the therapeutic­surgical approach: conventional prostatectomy (n.120) and endoscopic resection (n. 112). Results: By inferential statistics, a statistically signifcant relationship was found between the type of therapeutic approach with the surgical time (p. 0.001) and with the bleeding index (p. 0.001) and between age and surgical time (p. 0.001). The most important complications were: immediate bleeding (n-9) and wound infections (no. 10) for conventional surgery and immediate bleeding (n-2) and sepsis (no. 3) for endoscopic surgery. The surgical mean time was 103.03 min and 75.14 min respectively. Conclusions: Technological development has brought the certainty that endoscopic surgery has fewer complications, decreases surgical times. Being an option to consider against traditional prostate hyperplasia surgery

Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing.

The decompaction and re-establishment of chromatin organization immediately after mitosis is essential for genome regulation. Mechanisms underlying chromatin structure control in daughter cells are not fully understood. Here we show that a chromatin compaction threshold in cells exiting mitosis ensures genome integrity by limiting replication licensing in G1 phase. Upon mitotic exit, chromatin relaxation is controlled by SET8-dependent methylation of histone H4 on lysine 20. In the absence of either SET8 or H4K20 residue, substantial genome-wide chromatin decompaction occurs allowing excessive loading of the origin recognition complex (ORC) in the daughter cells. ORC overloading stimulates aberrant recruitment of the MCM2-7 complex that promotes single-stranded DNA formation and DNA damage. Restoring chromatin compaction restrains excess replication licensing and loss of genome integrity. Our findings identify a cell cycle-specific mechanism whereby fine-tuned chromatin relaxation suppresses excessive detrimental replication licensing and maintains genome integrity at the cellular transition from mitosis to G1 phase.

Biochemical and MALDI-TOF Mass Spectrometric Characterization of a Novel Native and Recombinant Cystine Knot Miniprotein from Solanum tuberosum subsp. andigenum cv. Churqueña.

Cystine-knot miniproteins (CKMPs) are an intriguing group of cysteine-rich molecules that combine the characteristics of proteins and peptides. Typically, CKMPs are fewer than 50 residues in length and share a characteristic knotted scaffold characterized by the presence of three intramolecular disulfide bonds that form the singular knotted structure. The knot scaffold confers on these proteins remarkable chemical, thermal, and proteolytic stability. Recently, CKMPs have emerged as a novel class of natural molecules with interesting pharmacological properties. In the present work, a novel cystine-knot metallocarboxypeptidase inhibitor (chuPCI) was isolated from tubers of Solanum tuberosum, subsp. andigenum cv. Churqueña. Our results demonstrated that chuPCI is a member of the A/B-type family of metallocarboxypeptidases inhibitors. chuPCI was expressed and characterized by a combination of biochemical and mass spectrometric techniques. Direct comparison of the MALDI-TOF mass spectra for the native and recombinant molecules allowed us to confirm the presence of four different forms of chuPCI in the tubers. The majority of such forms have a molecular weight of 4309 Da and contain a cyclized Gln in the N-terminus. The other three forms are derived from N-terminal and/or C-terminal proteolytic cleavages. Taken together, our results contribute to increase the current repertoire of natural CKMPs.

Estudio epidemiológico, observacional, transversal sobre el efecto de la nutrición parenteral en niños con comorbilidades con menos de 1,500 gramos y más 1,500 gramos de la unidad de cuidados intensivos neonatales del hospital gineco obstétrico de nueva aurora "luz elena arismendi" y "hospital matilde hidalgo de procel" en el año 2018 / Estudio epidemiológico, observacional, transversal sobre el efecto de la nutrición parenteral en niños con comorbilidades con menos de 1,500 gramos y más 1,500 gramos en la unidad de cuidados intensivos neonatales del hospital obstétrico de la nueva aurora "luz elena arismendi" y "hospital matilde hidalgo de procel "en el año 2018

Contexto: Los neonatos son susceptibles de adquirir déficits de macronutrientes por sus bajas reservas de glucógeno y grasa combinadas con mayores requerimientos de energía y proteínas para sostener su crecimiento. Por lo tanto, se recomienda el uso macronutrientes. Los beneficios del uso de nutrición parenteral incluyen un mejor equilibrio del nitrógeno, anabolismo y crecimiento, mejor control de la hiperglucemia y tasas reducidas de retinopatía del prematuro (ROP) y enterocolitis necrotizante. La NT temprana proporcionó beneficios para resultados a corto plazo sin evidencia de aumento de la morbilidad y mortalidad. Propósito: Determinar la evolución clínica y antropométrica de los neonatos con peso < 1500 gramos y > de 1500 gramos que recibieron alimentación parenteral en el servicio de neonatología del Hospital Gineco-obstétrico Luz Elena Arismendi y Hospital Matilde hidalgo de Procel. Sujetos y métodos: Diseño observacional, epidemiológico, transversal con 2 cohortes. El tipo de muestreo será propositivo debido que tenemos criterios de selección de muestra. Se llevó a cabo con 107 pacientes, total 214 pacientes. Resultados y Conclusiones: La recuperación del peso, talla y PC de los neonatos >1500 gramos y menores de 1500 gramos que recibieron nutrición parenteral presentó un incremento en ambos grupos, llegando a estabilizarse a partir del día 14. Observándose en relación a la talla un ligero incremento en los pacientes con un peso >1500 gramos, siendo la complicación más frecuente en ambos grupos.

Context: Neonates are susceptible to macronutrient deficits due to their low glycogen and fat reserves combined with higher energy and protein requirements for their growth. Therefore, the use of macronutrients is recommended. The benefits of using NT include better nitrogen balance, anabolism and growth, better control of hyperglycemia, and reductions in retinopathy of prematurity and necrotising enterocolitis. Of morbidity and mortality. Purpose: To determine the clinical and anthropometric evolution of neonates weighing <1500 grams and> 1500 grams that provide a parenteral feeding in the neonatology service of the Gineco-obstetric hospital Luz Elena Arismendi and Hospital Matilde Hidalgo de Procel. Subjects and methods: Observational, epidemiological, cross-sectional design with 2 cohorts.The type of sampling will be proactive because we have sample selection criteria. For the purposes of this study, a total of 107 patients were included, a total of 214 patients. Results and conclusions: The recovery of weight, height and CP of neonates> 1500 grams and those less than 1500 grams that respond to parenteral care. reaching a stabilization from day 14. Observing in relation to height a slight increase in patients with a weight> 1500 grams, being the most frequent complication in both groups cholestasis.

Biochemical characterization of the YBPCI miniprotein, the first carboxypeptidase inhibitor isolated from Yellow Bell Pepper (Capsicum annuum L). A novel contribution to the knowledge of miniproteins stability.

The cystine-knot metallocarboxypeptidase inhibitors (MCPIs) are peptides that contribute to control proteolytic activity, involved in storage, growth and maintenance of plants. Lately studies reported several MCPIs with potential use in biomedical applications; as anti-cancer, anti-thrombotic, anti-malaric and anti-angiogenic agents. We report the isolation, purification, chemical stability and biochemical characterization of a novel carboxypeptidase A inhibitor (YBPCI) isolated from Capsicum annuum L. var. Yellow Bell Pepper, the first cystine-knot miniprotein (CKM) of the species. We demonstrate the stability of YBPCI (IC50 = 0.90 µg/ml) to high temperatures, high salt concentration and extreme pH values. MALDI-TOF/MS analysis detected a molecular weight of 4057 Da, and peptide mass fingerprint resulted in no matches with other protease inhibitors. In vitro gastrointestinal digestion subjecting YBPCI to pH 2 incubation and proteolytic attack resulted in complete inhibitory activity. To summarize, there are no reports to date of carboxypeptidase inhibitors in C. annuum species, giving our report much more relevance.

Systematic In Vivo Inactivation of Chromatin-Regulating Enzymes Identifies Setd2 as a Potent Tumor Suppressor in Lung Adenocarcinoma.

Chromatin-modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two KrasG12D-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome-remodeling complex members Smarca4 (Brg1) or Arid1a had complex effects on lung adenocarcinoma initiation and progression. Loss of either Brg1 or Arid1a were selected against in early-stage tumors, but Brg1 loss continued to limit disease progression over time, whereas loss of Arid1a eventually promoted development of higher grade lesions. In contrast to these stage-specific effects, loss of the histone methyltransferase Setd2 had robust tumor-promoting consequences. Despite disparate impacts of Setd2 and Arid1a loss on tumor development, each resulted in a gene expression profile with significant overlap. Setd2 inactivation and subsequent loss of H3K36me3 led to the swift expansion and accelerated progression of both early- and late-stage tumors. However, Setd2 loss per se was insufficient to overcome a p53-regulated barrier to malignant progression, nor establish the prometastatic cellular states that stochastically evolve during lung adenocarcinoma progression. Our study uncovers differential and context-dependent effects of SWI/SNF complex member loss, identifies Setd2 as a potent tumor suppressor in lung adenocarcinoma, and establishes model systems to facilitate further study of chromatin deregulation in lung cancer. Cancer Res; 77(7); 1719-29. ©2017 AACR.