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Despite substantial advances in the use of proteomic technologies, their widespread application in fruit tissues of non-model and recalcitrant species remains limited. This hampers the understanding of critical molecular events during the postharvest period of fleshy tropical fruits. Therefore, we evaluated label-free quantitation (LFQ) and TMT-SPS-MS3 (TMT) approaches to analyse changes in the protein profile of mango peels during postharvest period. We compared two extraction methods (phenol and chloroform/methanol) and two peptide fractionation schemes (SCX and HPRP). We accurately identified 3065 proteins, of which, 1492 were differentially accumulated over at 6 days after harvesting (DAH). Both LFQ and TMT approaches share 210 differential proteins including cell wall proteins associated with fruit softening, as well as aroma and flavour-related proteins, which were increased during postharvest period. The phenolic protein extraction and the high-pH reverse-phase peptide fractionation was the most effective pipeline for relative quantification. Nevertheless, the information provided by the other tested strategies was significantly complementary. Besides, LFQ spectra allowed us to track down intact N-glycopeptides corroborating N-glycosylations on the surface of a desiccation-related protein. This work represents the largest proteomic comparison of mango peels during postharvest period made so far, shedding light on the molecular foundation of edible fruit during ripening.
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Mangifera , Mangifera/química , Mangifera/metabolismo , Proteómica , Frutas/metabolismo , Fenoles/análisis , Fenoles/metabolismo , Péptidos/análisisRESUMEN
BACKGROUND: Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. METHODS: We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient's clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200). No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83; 95% confidence interval [CI], 0.52 to 1.35; P = 0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of -0.46 percentage points (95% CI, -7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535.).
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Anticuerpos Neutralizantes/sangre , COVID-19/terapia , Inmunoglobulina G/sangre , Neumonía Viral/terapia , SARS-CoV-2/inmunología , Anciano , Anciano de 80 o más Años , Transfusión de Componentes Sanguíneos , COVID-19/complicaciones , COVID-19/mortalidad , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Hospitalización , Humanos , Inmunización Pasiva , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neumonía Viral/etiología , Neumonía Viral/mortalidad , Índice de Severidad de la Enfermedad , Sueroterapia para COVID-19RESUMEN
Forensic entomology requires knowledge of the developmental rates of the species that colonize a body after death to estimate the postmortem interval (PMI). These developmental rates may vary depending not only on the species but also on the geographic location due to population differences. Therefore, the objectives of this work were to determine the developmental duration of the forensically important fly Chrysomya megacephala under constant controlled and field condition temperatures and to compare these results, through a meta-analysis, with data reported by other authors on populations from different localities. For this, C. megacephala colonies were established in the laboratory, and the duration of the life cycle was studied at two controlled temperatures (25 °C and 27 °C) and field conditions (27.5 ± 3.2 °C). Analysis of variance was performed to determine differences in developmental time and larval length between constant laboratory temperatures and field conditions. A generalized linear model was performed with predictor variables extracted from the literature (diet, relative humidity, latitude, longitude) to evaluate the effect of population variation on developmental times. The results showed significant differences in developmental times between 25 and 27 °C. As expected, the complete life cycle of C. megacephala was shorter at 27 °C. Finally, the meta-analysis suggested differences between the developmental times of different populations, based on temperature and geographic location. The results of this study provide fundamental developmental data to use C. megacephala in PMI estimations. Finally, we suggest that, when making expert reports, information from local populations should be used to determine a more accurate and reliable PMI.
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Escarabajos , Dípteros , Entomología Forense , Animales , Calliphoridae , Temperatura , Larva , Estadios del Ciclo de VidaRESUMEN
Recent research has shown that Doublecortin-like kinase 1 (DCLK1) is overexpressed in different types of cancer. It has recently been described as a cancer stem cells (CSCs) marker, is associated with carcinogenesis, and positively correlates with infiltration of multiple immune cell types in some cancers. However, studies focused on assessing DCLK1 expression in HCC are limited, and the role of DCLK1 in HCC tumor immunity remains to be determined. In this study, we used a modified model of the resistant hepatocyte (MRHM) to evaluate DCLK1 expression in HCC. Furthermore, DCLK1 expression in HCC was analyzed using TIMER 2.0, UALCAN, GEPIA, GEO, and HPA web-based tools. Correlations between DCLK1 expression and clinicopathological factors in patients were analyzed using the UALCAN web-based tool. Finally, correlations between DCLK1 and immune infiltrates were investigated using the TIMER 2.0 and TISIDB web-based tools. The results showed that DCLK1 is significantly overexpressed during progression of the HCC carcinogenic process in the MRHM. DCLK1 is overexpressed in HCC according to multiple publics web-based tools, and its overexpression is associated with cancer stage. Furthermore, DCLK1 expression was correlated with infiltration levels of multiple immune cells, immunomodulatory factors, immunoinhibitors, MHC molecules, chemokines, receptors, and immune cell-specific markers. These results suggest that DCLK1 is a potential prognostic biomarker that determines cancer progression and correlates with immune cell infiltration in HCC.
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PURPOSE/BACKGROUND: Since the emergence of the coronavirus disease 2019 (COVID-19), many efforts have been made to prevent and to treat the disease. In this line, the anti-inflammatory effect of selective serotonin reuptake inhibitors (SSRI) as alternatives for treating chronic inflammatory diseases has been studied. There is previous evidence of the usefulness of these drugs for reducing COVID-19 impact. METHODS/PROCEDURES: We conducted a retrospective single-center cohort study of adult patients with a positive reverse transcriptase-polymerase chain reaction for COVID-19, evaluating the association between SSRI use and in-hospital mortality. FINDINGS/RESULTS: Of 1689 included patients, 182 (10.8%) were exposed to SSRI. A total of 291 patients died during the hospitalization, representing an in-hospital mortality of 17.2% (95% confidence interval [CI], 15.4%-19.0%): 44 (24.2%) of the exposed to SSRIs versus 247 (16.4%) of those not exposed to SSRIs (crude odds ratio [OR], 1.62; 95% CI, 1.12-2.34; P = 0.009). No independent effect of SSRIs on in-hospital mortality was found when applying either the inverse probability of treatment weighting (OR, 1.15; 95% CI, 0.71-1.89; P = 0.56) or with conventional multivariable analysis 0.81 (95 % CI: 0.28-2.31, P = 0.69). IMPLICATIONS/CONCLUSIONS: In the present retrospective study of patients hospitalized for COVID-19, prior use of SSRIs did not reduce mortality.
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COVID-19 , Inhibidores Selectivos de la Recaptación de Serotonina , Adulto , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Estudios Retrospectivos , Estudios de CohortesRESUMEN
INTRODUCTION AND OBJECTIVES: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. MATERIALS AND METHODS: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. RESULTS: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. CONCLUSIONS: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032).
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Infecciones Bacterianas , Infecciones Comunitarias Adquiridas , Infección Hospitalaria , Infecciones Urinarias , Humanos , Estudios Prospectivos , Argentina/epidemiología , Uruguay/epidemiología , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Antibacterianos/uso terapéutico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Bacterias , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Infecciones Comunitarias Adquiridas/tratamiento farmacológicoRESUMEN
Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss the preclinical evidence that suggests that EP300 inhibition can attenuate fibrosis-related molecular processes, including extracellular matrix deposition, inflammation, and epithelial-to-mesenchymal transition. We also highlight the contributions of small molecule inhibitors and gene therapy approaches targeting EP300 as novel therapies against fibrosis.
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Epigénesis Genética , Histonas , Humanos , Fibrosis , Histonas/metabolismo , Matriz Extracelular/metabolismo , Histona Acetiltransferasas/metabolismo , Proteína p300 Asociada a E1A/genética , Proteína p300 Asociada a E1A/metabolismoRESUMEN
Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHT-associated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, epistaxis severity score, red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. 238 HHT patients received bevacizumab for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% CI, 2.9-3.5 g/dL) [mean hemoglobin 8.6 (8.5, 8.8) g/dL versus 11.8 (11.5, 12.1) g/dL, p<0.0001)] and decreased the epistaxis severity score (ESS) by 3.4 (3.2-3.7) points [mean ESS 6.8 (6.6-7.1) versus 3.4 (3.2-3.7), P<0.0001] during the first year of treatment. Compared with 6 months pretreatment, RBC units transfused decreased by 82% [median of 6.0 (IQR 0.0-13.0) units versus 0 (IQR, 0.0-1.0) units, P<0.0001] and iron infusions decreased by 70% [median of 6.0 (1.0-18.0) infusions versus 1.0 (0.0-4.0) infusions, P<0.0001] during the first 6 months of bevacizumab treatment. Outcomes were similar regardless of underlying pathogenic mutation. Following initial induction infusions, continuous/scheduled bevacizumab maintenance achieved higher hemoglobin and lower ESS than intermittent/as needed maintenance but with more drug exposure. Bevacizumab was well tolerated: hypertension, fatigue, and proteinuria were the most common adverse events. Venous thromboembolism occurred in 2% of patients. In conclusion, systemic bevacizumab was safe and effective to manage chronic bleeding and anemia in HHT.
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Telangiectasia Hemorrágica Hereditaria , Administración Intravenosa , Bevacizumab/uso terapéutico , Hemorragia/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológicoRESUMEN
We studied the quality of dry pasta packaged and stored for 45 days in biodegradable bags made from triticale flour films. Results were compared with the quality of pasta packaged in commercial bags. Characterization of films and technologic and microbiological quality of pasta were performed. Biodegradable bags presented adequate properties during storage. There was no microbiological growth or differences in moisture and breaking force of dry pasta within both types of packaging during storage. Cooking quality of pasta was not affected by the type of packaging or storage time. We also studied the antioxidant capacity of pasta enriched with partially-deoiled-chia flour during storage in both types of packaging. A decrease in the antioxidant activity measured by ABTS assay was found at 45 days of storage in pasta packaged in biodegradable bags. Nevertheless, the total phenolic content and the antioxidant activity evaluated by FRAP method did not change significantly with time or type of packaging.
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Telangiectasia Hemorrágica Hereditaria , Humanos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/diagnóstico , Poliposis Intestinal/congénito , Poliposis Intestinal/diagnóstico , Poliposis Intestinal/complicaciones , Poliposis Intestinal/genética , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/complicaciones , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/diagnóstico , Adulto , Masculino , Femenino , Angiografía CerebralRESUMEN
Paracoccidioidomycosis is endemic in subtropical rainforests of Latin America. Acute/subacute presentations involve an aggressive dissemination throughout the lymphatic system, while chronic forms (more frequent) arise as differential diagnosis for other conditions involving lung, oropharynx, skin, and eventually the brain. We present the case of a man referred for evaluation and treatment of a possible lung tumor with brain metastasis. The finding of multibudded yeasts and the microbiological isolation of a dimorphic fungus identified as Paracoccidioides sp. from a brain biopsy prompted a cardinal change in prognosis and treatment. This case alerts on the importance of considering systemic fungal diseases as differential diagnosis of compatible clinical presentations in patients who had lived in, or visited, endemic areas.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Paracoccidioidomicosis/diagnóstico , Biopsia , Diagnóstico Diferencial , Humanos , Inmunocompetencia , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
5-Fluorouracil (5-FU) has long been used for the treatment of gastrointestinal tumors harboring interindividual variability in both the pharmacokinetic and the pharmacogenetic profiles, which in turn may lead to life-threatening toxicities. We carried out a prospective cohort study of adult patients initiating treatment with 5-FU between 2013 and 2015. Primary exposures of interest were the methylenetetrahydrofolate reductase single nucleotide polymorphism in exons 4 and 7 and 5'-untranslated region-thymidylate synthase VNTR genotypes, in addition to baseline clinical and demographic variables. The primary outcome was the time to the occurrence of severe toxicity. We used a Cox regression model to evaluate patients' survival and toxicity experience and its association with baseline characteristics and a priori determined genetic polymorphisms. A total of 197 patients were included, 40.1% developed severe toxicity during follow-up. Variables that were significantly associated with developing severe toxicity were the European Organization for Research and Treatment of Cancer functional score [hazard ratio (HR): 0.98; 95% confidence interval (CI): 0.97-0.99]; type of tumor [anus (HR: 2.50; 95% CI: 1.07-5.82), head and neck/esophagus/stomach (HR: 2.95; 95% CI: 1.64-5.33)] and 5-FU continuous infusion regimens over 4-5 days (HR: 9.35; 95% CI: 2.68-32.59). We found a significant association between baseline functional status, type of tumor and continuous infusion regimens and the occurrence of severe toxicity during the follow-up of patients receiving 5-FU. No association was found with the genotypic variants evaluated. Future validation and modeling of an everyday easy-to-use score to predict toxicity among these subgroup of patients remains warranted.
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Antimetabolitos Antineoplásicos/efectos adversos , Fluorouracilo/efectos adversos , Neoplasias Gastrointestinales/tratamiento farmacológico , Regiones no Traducidas 5' , Antimetabolitos Antineoplásicos/administración & dosificación , Estudios de Cohortes , Exones , Femenino , Fluorouracilo/administración & dosificación , Neoplasias Gastrointestinales/enzimología , Neoplasias Gastrointestinales/genética , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Estudios Prospectivos , Timidilato Sintasa/genéticaRESUMEN
Mannheimia haemolytica is a Gram negative bacterium that is part of the bovine respiratory disease, which causes important economic losses in the livestock industry. In the present work, the interaction between M. haemolytica A1 and bovine lactoferrin (BLf) was studied. This iron-chelating glycoprotein is part of the mammalian innate-immune system and is present in milk and mucosal secretions; Lf is also contained in neutrophils secondary granules, which release this glycoprotein at infection sites. It was evidenced that M. haemolytica was not able to use iron-charged BLf (BholoLf) as a sole iron source; nevertheless, iron-lacked BLf (BapoLf) showed a bactericidal effect against M. haemolytica with MIC of 4.88 ± 1.88 and 7.31 ± 1.62 µM for M. haemolytica strain F (field isolate) and M. haemolytica strain R (reference strain), respectively. Through overlay assays and 2-D electrophoresis, two OMP of 32.9 and 34.2 kDa with estimated IP of 8.18 and 9.35, respectively, were observed to bind both BapoLf and BholoLf; these OMP were identified by Maldi-Tof as OmpA (heat-modifiable OMP) and a membrane protein (porin). These M. haemolytica BLf binding proteins could be interacting in vivo with both forms of BLf depending on the iron state of the bovine.
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Proteínas de la Membrana Bacteriana Externa/metabolismo , Lactoferrina/metabolismo , Mannheimia haemolytica/metabolismo , Animales , Apoproteínas/metabolismo , Proteínas de la Membrana Bacteriana Externa/inmunología , Bovinos , Electroforesis en Gel Bidimensional , Inmunidad Innata , Lactoferrina/inmunología , Mannheimia haemolytica/inmunología , Simulación del Acoplamiento Molecular , Pasteurelosis Neumónica/inmunología , Pasteurelosis Neumónica/metabolismoRESUMEN
Trastuzumab emtansine (T-DM1) is a targeted therapy combining trastuzumab and emtansine for human epidermal growth factor receptor 2(HER2)-positive breast cancer, with common side effects including fatigue, nausea, pain, headache, low platelet count, and elevated liver enzymes. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by vascular malformations and telangiectasias in various organs. We present a case of a female patient with advanced breast cancer who developed HHT-like symptoms while on T-DM1 treatment. A 59-year-old woman treated with radiotherapy and T-DM1 every 21 days developed recurring nosebleeds and mucocutaneous and liver telangiectasias indistinguishable from HHT three months after receiving the first dose of T-DM1. Other organ vascular malformations were ruled out through screening protocols. The patient had no previous HHT symptoms or family history. Nasal care measures like lubrication and antifibrinolytics (tranexamic acid) were provided. In addition, propranolol was also prescribed due to its antiangiogenic and antitumoral properties, leading to significantly decreased epistaxis and telangiectasias. Microtubule disruptions caused by T-DM1, along with other angiogenic mechanisms may contribute to the development of telangiectasias resembling HHT. The use of propranolol, an initial approach for HHT, proved to be effective in this case. It is crucial for oncologists and HHT specialists to be aware of this rare adverse event associated with T-DM1 and to implement appropriate management strategies.
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Derived from industrial processing waste, peanut skins contain polyphenols that delay oxidative food spoilage. However, these compounds are susceptible to light, heat, and oxygen exposure. Microencapsulation provides a solution by offering protection from these factors. The aim of this study was to evaluate the protective effect of peanut skin extract microcapsules on the chemical, microbiological, and sensory property and shelf life of sunflower seeds during storage. Five roasted sunflower seed samples were prepared: control (S-C); added with butylhydroxytoluene (S-BHT); coated with carboxymethyl cellulose (S-CMC); coated with CMC and the addition of peanut skin crude extract (S-CMC-CE); coated with CMC and the addition of microcapsules (S-CMC-M20). Sensory acceptability was determined using hedonic testing. Chemical (peroxide value, conjugated dienes, hexanal and nonanal content, and fatty acid profile), microbiological, and descriptive analyses were carried out on samples stored for 45 days at room temperature. Shelf life was calculated using a simple linear regression. All samples were microbiologically fit for human consumption and accepted by consumer panelists, scoring above five points on the nine-point hedonic scale. S-CMC-M20 exhibited the lowest peroxide value (6.59 meqO2/kg) and hexanal content (0.4 µg/g) at the end of the storage. Estimated shelf life showed that S-MC-M20 (76.3 days) extended its duration nearly ninefold compared to S-C (8.3 days) and doubled that of S-CMC-CE (37.5 days). This indicates a superior efficacy of microencapsulated extract compared to its unencapsulated form, presenting a promising natural strategy for improving the shelf life of analogous food items. PRACTICAL APPLICATION: Incorporating peanut skin extract microcapsules in coating sunflower seeds presents a promising strategy to extend the shelf life of lipid-rich foods, capitalizing on the antioxidant properties of polyphenols. This innovative approach not only enhances nutritional quality but also addresses sustainability concerns by repurposing agro-industrial byproducts, such as peanut skins. By meeting consumer demand for functional foods with added health benefits, this technique offers potential opportunities for the development of novel, value-added food products while contributing to circular economy principles and waste management efforts.
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Arachis , Almacenamiento de Alimentos , Helianthus , Polifenoles , Semillas , Semillas/química , Helianthus/química , Almacenamiento de Alimentos/métodos , Arachis/química , Humanos , Composición de Medicamentos/métodos , Comportamiento del Consumidor , Gusto , Extractos Vegetales/química , Extractos Vegetales/farmacología , Conservación de Alimentos/métodosRESUMEN
This case report discusses the medical history of a 64-year-old woman diagnosed with scleroderma and diffuse gastrointestinal angiodysplasia. The patient received bevacizumab (BVZ) therapy to address gastrointestinal bleeding that was unresponsive to endoscopic treatment. Subsequently, she developed severe thrombocytopenia. Although there were suspicions of an immune-mediated mechanism resulting from BVZ treatment, the laboratory results did not provide conclusive evidence. The patient underwent transfusions, received gamma globulin, and was treated with Romiplostim. Over time, her platelet levels gradually improved, and the bleeding was successfully controlled. It's worth noting that BVZ-induced thrombocytopenia is a relatively rare yet severe adverse effect. Recognizing and understanding the mechanisms behind thrombocytopenia is essential for developing safer treatment approaches. Further research is required to identify potential risk factors associated with this condition.
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Anemia , Angiodisplasia , Trombocitopenia , Humanos , Femenino , Persona de Mediana Edad , Bevacizumab/efectos adversos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Transfusión Sanguínea , Trombocitopenia/complicaciones , Trombocitopenia/tratamiento farmacológico , Angiodisplasia/complicaciones , Angiodisplasia/tratamiento farmacológicoRESUMEN
BACKGROUND: With the emergence of multidrug-resistant infections, healthcare professionals must evaluate the effectiveness of empiric antibiotic treatments. AIMS: To assess the antibiotic susceptibility patterns of microorganisms causing spontaneous infections in patients with cirrhosis and to evaluate the suitability of empiric antibiotic treatments based on major clinical guidelines. METHODS: This cross-sectional study utilized two datasets from prospective studies of patients with cirrhosis and culture-positive spontaneous bacterial infections in Argentina and Uruguay. We estimated susceptibility to commonly used antibiotics and assessed coverage following European and American recommendations. RESULTS: We analyzed 238 episodes of culture-positive spontaneous infections in 229 patients. When implementing the recommendations for empiric treatment of community-acquired spontaneous infections, ceftazidime would result in 39 % coverage, whereas ceftriaxone would reach 70 %. Cefepime, which is not included in the recommendations, would have provided coverage of 74 %. Using ertapenem for nosocomial infections would have only covered 56 % of these episodes, whereas meropenem or imipenem reached 73 % coverage. Only the combination of meropenem or imipenem plus vancomycin would achieve a coverage surpassing 85 % in healthcare-associated or nosocomial spontaneous bacterial infections. CONCLUSIONS: Our study uncovers inadequate coverage in specific clinical scenarios when adhering to recommendations, underscoring the necessity of guidelines based on local epidemiological data.
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BACKGROUND: The identification of biomarkers for the early diagnosis of nonalcoholic fatty liver disease (NAFLD) is urgently needed. Here, we aimed to identify NAFLD biomarkers in the early stages of steatosis (SS) and nonalcoholic steatohepatitis (NASH) based on differential gene expression from bioinformatics data. METHODS: A meta-analysis was performed from transcriptomic databases retrieved from public repositories containing data from biopsies of patients at various stages of NAFLD development. The status of the selected molecules was validated in the serum of patients with NAFLD by ELISA. RESULTS: We identified 121 differentially expressed genes (DEGs) associated with SS and 402 associated with NASH. Gene Ontology (GO) enrichment revealed that the altered genes were primarily associated with dysfunction of primary cellular processes, and pathway analyses were mainly related to cholesterol metabolism. We identified ACSS2, PCSK9, and CYP7A1 as candidate biomarkers for SS and ANGPTL3, CD36, CYP51A1, FASN, FAS, FDFT1, and LSS as candidate biomarkers for NASH. CONCLUSIONS: By experimental validation of bioinformatics data from patients with NAFLD, we identified promising biomarkers for detecting SS and NASH that might be useful for screening and diagnosing early NAFLD stages in humans.
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The worst-case scenario related to alcoholic liver disease (ALD) arises after a long period of exposure to the harmful effect of alcohol consumption along with other hepatotoxics. ALD encompasses a broad spectrum of liver-associated disorders, such as steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Based on the chronic administration of different hepatotoxics, including ethanol, sucrose, lipopolysaccharide, and low doses of diethylnitrosamine over a short period, here we aimed to develop a multiple hepatotoxic (MHT)-ALD model in the mouse that recapitulates the human ALD-associated disorders. We demonstrated that the MHT-ALD model induces ADH1A and NXN, an ethanol metabolizer and a redox-sensor enzyme, respectively; promotes steatosis associated with the induction of the lipid droplet forming FSP27, inflammation identified by the infiltration of hepatic neutrophils-positive to LY-6G marker, and the increase of MYD88 level, a protein involved in inflammatory response; and stimulates the early appearance of cellular senescence identified by the senescence markers SA-ß-gal activity and p-H2A.XSer139. It also induces fibrosis associated with increased desmin, a marker of hepatic stellate cells whose activation leads to the deposition of collagen fibers, accompanied by cell death and compensatory proliferation revealed by increased CASP3-mediated apoptosis, and KI67- and PCNA-proliferation markers, respectively. It also induces histopathological traits of malignancy and the level of the HCC marker, GSTP1. In conclusion, we provide a useful model for exploring the chronological ALD-associated alterations and stages, and addressing therapeutic approaches.
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Hepatocellular carcinoma (HCC) is a tumor with minimal chance of cure due to underlying liver diseases, late diagnosis, and inefficient treatments. Thus, HCC treatment warrants the development of additional strategies. Lactoferrin (Lf) is a mammalian multifunctional iron-binding glycoprotein of the innate immune response and can be found as either a native low iron form (native-Lf) or a high iron form (holo-Lf). Bovine Lf (bLf), which shares many functions with human Lf (hLf), is safe for humans and has several anticancer activities, including chemotherapy boost in cancer. We found endogenous hLf is downregulated in HCC tumors compared with normal liver, and decreased hLf levels in HCC tumors are associated with shorter survival of HCC patients. However, the chemoprotective effect of 100% iron saturated holo-bLf on experimental hepatocarcinogenesis has not yet been determined. We aimed to evaluate the chemopreventive effects of holo-bLf in different HCC models. Remarkably, a single dose (200 mg kg-1) of holo-bLf was effective in preventing early carcinogenic events in a diethylnitrosamine induced HCC in vivo model, such as necrosis, ROS production, and the surge of facultative liver stem cells, and eventually, holo-bLf reduced the number of preneoplastic lesions. For an established HCC model, holo-bLf treatment significantly reduced HepG2 tumor burden in xenotransplanted mice. Finally, holo-bLf in combination with sorafenib, the advanced HCC first-line treatment, synergistically decreased HepG2 viability by arresting cells in the G0/G1 phase of the cell cycle. Our findings provide the first evidence suggesting that holo-bLf has the potential to prevent HCC or to be used in combination with treatments for established HCC.