Rab11-FIP4 interacts with ARF5 to promote cancer stemness in hepatocellular carcinoma

Recent studies suggest that Rab11-family interacting proteins (Rab11-FIPs) play an important role in tumorigenesis and progression. Among the Rab11-FIPs, Rab11-FIP4 has been reported to be significantly upregulated in various cancers, including hepatocellular carcinoma (HCC). However, the possible effect on HCC stemness and the underlying mechanism has never been characterized. Here, we found that Rab11-FIP4 was dramatically increased in HCC cell lines and tissues, and had a positive correlation with cancer stemness. Functional studies revealed that elevated expression of Rab11-FIP4 in HCC cells significantly promoted sphere formation, and enhanced the mRNA and protein levels of stemness-associated markers, ALDH1A1, CD133, NANOG, and OCT4. Conversely, the knockdown of Rab11-FIP4 suppressed the cancer stem cell (CSC)-like characteristics of HCC cells. Moreover, silencing of Rab11-FIP4 obviously increased the sensitivity of HCC cells to sorafenib. Mechanistically, Rab11-FIP4 was shown to interact with ADP-ribosylation factor 5 (ARF5) to influence cell cycle-related proteins, CDK1/cyclin B, thereby promoting HCC stemness. Taken together, our results uncovered an essential role for Rab11-FIP4 in regulating CSC-like features of HCC cells and identified Rab11-FIP4 as a potential target for HCC therapy. (AU)

High molar ratios of tumor necrosis factor α (TNF α) soluble receptors I and II to the TNF ligand in human plasma from male veterans with comorbid posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI)

Background and Objectives Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are associated with chronic inflammation, as inferred from increased, but variable, peripheral levels of cytokines. We sought proof of concept for the notion that peripheral cytokine binding proteins and/or soluble receptors can confound measures of cytokines in those with a history of physical and psychological traumatic exposures. Efforts were focused on one of the major cytokines involved in inflammation, tumor necrosis factor-α (TNF- α). Methods We examined blood plasma concentrations of TNF-α, its soluble receptors (TNF-soluble receptors (sR) I and TNFsRII), and C-reactive protein (CRP-1) in a cohort of US Veterans. In a previous study, CRP-1 was shown to be reduced by probiotic anti-inflammatory treatment in this patient cohort. All participants (n = 22) were diagnosed with PTSD and had a history of mild TBI with persistent post-concussive symptoms. Exclusion criteria included medications directly targeting inflammation. Results Molar concentrations of soluble TNFsRI and II exceeded concentrations of the TNF-α ligand. TNFsRI, but not TNFsRII, was significantly associated with CRP-1 (Spearman Rho correlations = 0.518; p=.016 and 0.365; p = .104, respectively). Conclusions TNF soluble receptors may bind to and sequester free TNF-α, suggesting that only measuring ligand concentrations may not provide a fully comprehensive view of inflammation, and potentially lead to inaccurate conclusions. TNFsRI concentration may provide a better estimate of inflammation than TNF-α for those with PTSD and post-acute mTBI with post-concussive symptoms, a hypothesis that invites further testing in larger studies. (AU)

Dopaminergic and adrenergic receptors synergistically stimulate browning in 3T3-L1 white adipocytes

The browning of white adipose tissue (WAT) has attracted considerable attention in the scientific community as a popular strategy for enhancing energy expenditure to combat obesity. As a part of this strategy, β3-adrenergic receptor (β3-AR) is the most widely studied receptor that mediates thermogenesis. Parenthetically, further studies in search for additional receptors expressed in adipocytes that can mediate thermogenesis has been appearing, and this paper reports that dopaminergic receptor 1 (DRD1) and β3-AR synergistically stimulate browning in 3T3-L1 white adipocytes. qRT-PCR and immunoblot analysis methods were applied to evaluate the effects of DRD1 on the target proteins downstream of β3-AR and other markers involved in lipid metabolism, mitochondrial biogenesis, and browning events. These results show that DRD1 is expressed in epididymal WAT (eWAT), brown adipose tissue (BAT), and inguinal WAT (iWAT) of normal and high-fat-fed mice, and a deficiency of DRD1 downregulates the expression of brown adipocyte-specific proteins. Silencing of DRD1 affected lipid metabolic activity in 3T3-L1 adipocytes by reducing mitochondrial biogenesis as well as levels of lipolytic and fat oxidative marker proteins in a similar pattern to β3-AR. Moreover, mechanistic studies showed that the depletion of DRD1 downregulates β3-AR and its downstream molecules, suggesting both receptors might synergistically stimulate browning. Parallel to the UCP1-dependent thermogenesis, the depletion of DRD1 also downregulates the expression of core proteins responsible for UCP1-independent thermogenesis. Overall, DRD1 mediates β3-AR-dependent 3T3-L1 browning and UCP1-independent thermogenesis. (AU)

Research progress on the role of Ndfip1 (Nedd4 family interacting protein 1) in immune cells

Nedd4 family interacting protein 1 (Ndfip1) was first mentioned in an article in 2000. Since its discovery, related studies have shown that this protein is associated with apoptosis, neuroprotection, substance transport, ubiquitination, and immune regulation. It is noteworthy that the lack of Ndfip1 can lead to death in fetal mice. Researchers generally believe that the function of Ndfip1 is closely related to individual immune capacity and have published a large number of articles. However, a comprehensive classification of the immune regulatory function of Ndfip1 is still lacking. In this review, we will overview and discuss this new perspective, focusing on the role of Ndfip1 in the proliferation, differentiation, and cell activity of CD4+ T cells, CD8+ T cells, mast cells, and eosinophils. This review provides an updated summary of Ndfip1, which will unveil novel therapeutic targets. Finally, the conclusion is that Ndfip1 mainly plays a negative regulatory role in immune cells by maintaining the stability of the immune response and limiting its overexpression (AU)

The role of the inflammasome and its related pathways in ovarian cancer

Ovarian cancer (OC) is the most lethal tumor of the female reproductive tract and one of the most prevalent causes of death among female cancer patients. The absence of suitable procedures for early diagnosis, chemoresistance, and limited surgical debulking are all contributing to poor survival in patients. Despite aggressive treatments, the majority of patients have a recurrence within 16–22 months. Inflammasomes are multimeric protein complexes that play a major role in the innate immune system and inflammation. The overexpression of inflammasome-related pathways, including NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), Absent in melanoma 2 (AIM2), caspase-1, and Interleukin (IL)-1 have been reported in OC patients and in vitro cell lines. Therefore, inflammasome-related genes and protein might have a role in OC pathogenesis. Considering the potential relationship between inflammasome and OC, this study aimed to provide a literature-based review to explain the role of inflammasome and inflammation in cancer progression in OC. (AU)

DAZAP1 overexpression promotes growth of HCC cell lines: a primary study using CEUS

PurposeHepatocellular carcinoma (HCC) is one of the most common types of hepatic carcinoma. The overall prognosis is poor. DAZAP1, a regulator of alternative splicing (AS) events, may participate in tumor growth.MethodsWe collected 105 HCC patients and tissue samples from the Department of Hepatological Surgery in the Second Affiliated Hospital of Qiqihar Medical University. TCGA datasets were downloaded and operated using the R project. DAZAP1 expressions were examined by quantitative RT-PCR and western blotting. CCK8 assay was used to investigate the cell proliferation, and transwell assay was employed to examine the ability of migration and invasion in vitro. Contrast-enhanced ultrasound (CEUS) was used to evaluate images and parameters of the tumor.ResultsDAZAP1 is highly expressed in the tissue samples of HCC. The peak intensity (PI) and area under the curve (AUC) of the tumor is higher than that of liver parenchyma, and correlated with high DAZAP1 expression. Parameters of CEUS in the tumor are correlated with TNM stage, tumor size, and vascularity. High DAZAP1 expression correlates with a shorter survival time and advanced histologic grade (G3–G4). Bioinformatical analysis revealed that downregulation of DAZAP1 identified differentiated expressed genes (DEGs) involved in the tumor growth process.ConclusionsDAZAP1 is highly expressed in hepatic carcinoma and related to the blood flow, and high DAZAP1 expression predicts poor prognosis. DAZAP1 may promote liver carcinoma cell proliferation, migration, and invasion of HEPG2 cells. CEUS parameters are related to the high DAZAP1 expression, and will help to differentiate the HCC tumor.

PTPRO activates TLR4/NF-kB signaling to intensify lipopolysaccharide-induced pneumonia cell injury

Background Protein tyrosine phosphatase receptor type O (PTPRO) belongs to the PTP (protein tyrosine phosphatase) family and is widely expressed in parenchymal cells, such as breast and lung epithelial cells. PTPRO has been shown to enhance inflammatory responses and has been implicated in the pathogenesis of inflammation-associated diseases. The role of PTPRO in pneumonia was investigated.Methods Human embryonic lung fibroblasts (HFL1) were treated with increasing concentrations of lipopolysaccharide at 5, 10, or 20 μg/mL to induce inflammatory and apoptotic injuries. Expression of PTPRO was detected by western blot. Inflammation and apoptosis were assessed by ELISA and flow cytometry assays, respectively.Results Lipopolysaccharide induced decreased cell viability, and increased inflammation and apoptosis in HFL1. PTPRO was upregulated in HFL1 post lipopolysaccharide treatment, and silencing of PTPRO enhanced lipopolysaccharide-induced cell viability of HFL1, and suppressed the inflammation and apoptosis. However, overexpression of PTPRO aggravated lipopolysaccharide-induced cytotoxicity in HFL1. Overexpression of PTPRO upregulated protein expression of TLR4 and p-p65 in lipopolysaccharide-induced HFL1, while knockdown of PTPRO reduced the level of p-IκBα to downregulate levels of TLR4 and p-p65.Conclusion PTPRO contributed to pro-inflammatory and pro-apoptotic effects on lipopolysaccharide-induced HFL1 through activation of TLR4/NF-κB signaling (AU)

Papel de la Nogina en obesidad: potencial biomarcador? / Noggin's role in obesity: Biomarker potential?

La obesidad es una enfermedad multifactorial resultado de la interacción entre factores genéticos, conductuales y ambientales que pueden influir en la respuesta individual a los hábitos alimenticios y de ejercicio físico. Su prevalencia ha aumentado dramáticamente durante la última década convirtiéndose en un problema de salud pública porque se asocia a patologías como diabetes tipo II, daño cardiovascular, hiperlipidemias y cáncer, que afectan a ambos sexos, todas las edades y todos los grupos étnicos. Actualmente, es la enfermedad metabólica más prevalente en los países desarrollados. Hay muchos loci y varios genes que se han asociado con la predisposición a la obesidad, a la delgadez, y al desarrollo de la obesidad y se clasifican según su expresión en diferentes etapas de esta condición, como inicio temprano, predisposición a la obesidad, inicio tardío, obesidad severa (mórbida). En este artículo se revisa el papel potencial del gen Nogina en la adipogénesis y los posibles mecanismos o vías de señalización en los que este gen interviene para conducir a la obesidad

Obesity is a multifactorial disease resulting from the interaction between genetic, behavioral and environmental factors that can influence the individual response to eating and exercise habits. Its prevalence has increased drastically in the last decade, becoming a public health problem because is associated with diseases such as type II diabetes, cardiovascular damage, hyperlipidemias and cancer, which affect both sexes, all ages and all ethnic groups. Currently, it is the most prevalent metabolic disease in developed countries. There are many loci and several genes that have been associated with the predisposition for obesity and thinness, obesity development and classified according to their expression in different stages of this condition, such as in early onset, predisposition to obesity, late onset, severe obesity (morbid). In this article I review the potential role of the Noggin gene in adipogenesis and the possible mechanisms or signaling pathways in which this gene intervenes to lead to obesity

LTP allergy/sensitization in a pediatric population

Plant lipid transfer proteins (LTPs) are widespread plant food allergens, highly resistant to food processing and to the gastrointestinal environment, which have been described as the most common food allergens in the Mediterranean area. LTP allergy is widely described in adults, but it represents an emerging allergen also in the pediatric population. Little is known about the real prevalence and the clinical features of this allergy in children and it still often remains underdiagnosed in these patients. An early identification and a deeper knowledge of this allergy in childhood can avoid severe systemic reactions and improve the child's quality of life. Pediatricians should always consider the possibility of LTP involvement in cases of plant-derived food allergy

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Estudio de la expresión de factores óseos en el hueso murino ante la falta de pleiotrofina y sus cambios en la situación inflamatoria / Study of bone factor expression in murine model in the absence of pleiotrophin and its changes in the inflammatory situation

La pleitrofina (PTN) en un péptido implicado en el desarrollo y el mantenimiento del tejido óseo, y con importantes funciones en los procesos inflamatorios. Sin embargo, la deleción de la PTN en modelos murinos no produce un deterioro óseo significativo, sin que hasta la fecha se hayan estudiado los mecanismos que compensan su perdida. Con este estudio quisimos comprobar cómo afecta la deleción de PTN y la inflamación aguda a la expresión de factores óseos. Para ello empleamos ratones hembra de tres meses deficientes para la PTN (PTNKo) a las que indujimos una inflamación aguda por administración de lipopolisacárido (LPS). Se aislaron las vértebras y las tibias para poder medir la expresión de genes y realizar un recuento de osteocitos. En cultivos celulares comprobamos si la PTN podía proteger a células MC3T3 (osteoblásticas) y MLOY4 (osteocitos) de la inducción de muerte celular producida por etopósido. Nuestros resultados muestran que la expresión de osteocalcina está incrementada en las vértebras de los ratones PTNKo, y que la inflamación produjo el incremento de expresión de podaplanina (E11), conexina 43 (Cox43) y el péptido relacionado con la parathormona (PTHrP) en los ratones PTNKo tratados con LPS. La administración de PTN redujo de manera significativa la muerte inducida por etopósido en cultivos de células MC3T3 y MLOY4. En conclusión, la deficiencia de PTN indujo un aumento de la expresión de OCN, y la inflamación aguda produjo la sobrexpresión de E11, PTHrP, y Cox43 en ratones PTNKo. La PTN aumentó la viabilidad de células osteblásticas y osteocitos frente al tratamiento con etopósido

Pleiotrophin (PTN) is a peptide involved in the development and maintenance of bone tissue with important functions in inflammatory processes. However, the deletion of PTN in murine models does not produce a significant bone deterioration, but the mechanisms that compensate for its loss have not been studied to date. Our study was aimed at verifying how the deletion of PTN and acute inflammation affect the expression of bone factors. To this end, we used three-month-old female mice deficient for PTN (PTNKo) to which we induced acute inflammation by administration of lipopolysaccharide (LPS). Vertebrae and tibiae were isolated to measure gene expression and carry out an osteocyte count. In cell cultures, we checked whether PTN could protect MC3T3 (osteoblast) and MLOY4 (osteocyte) cells from the induction of cell death caused by etoposide. Our results show that the expression of osteocalcin is increased in the vertebrae of PTNKo mice, and that inflammation increased the expression of podhalanin (E11), connexin 43 (Cox43) and the parathormone-related peptide (PTHrP) in the PTNKo mice treated with LPS. Administering PTN significantly reduced etoposide-induced death in MC3T3 and MLOY4 cell cultures. Thus, PTN deficiency induced increased expression of OCN, and acute inflammation produced overexpression of E11, PTHrP, and Cox43 in PTNKo mice. PTN increased the viability of osteoblastic cells and osteocytes compared to etoposide treatment

Anatomía patológica de la patología de tiroides y paratiroides. Sistema Bethesda del diagnóstico citológico de la patología de tiroides / Thyroid and parathyroid gland pathology. The Bethesda System for reporting thyroid cytopathology

INTRODUCCIÓN Y OBJETIVO: La PAAF es el mejor método para el manejo de pacientes con nódulos tiroideos, como método de cribado y para seleccionar a los pacientes que pueden ser sometidos a tratamiento quirúrgico. El objetivo de este artículo es hacer una breve descripción de las categorías diagnósticas del Sistema Bethesda en su segunda edición (2018). SÍNTESIS: El Sistema Bethesda establece 6 categorías diagnósticas: Insatisfactorio /No diagnóstico, Benigno, Atipia de significado Indeterminado/Lesión folicular de significado indeterminado, Neoplasia folicular/Sospechoso de neoplasia folicular, Sospechoso de Malignidad Maligno. Cada categoría lleva implícito el riesgo de malignidad y el manejo de estos pacientes, con lo cual el diagnóstico va a influir en la actitud a seguir. CONCLUSIONES: El Sistema Bethesda permite a los patólogos realizar informes sistematizados y al clínico establecer la actitud a seguir en función de cada categoría diagnóstica

INTRODUCTION AND OBJECTIVE: The FNA is the best method for the management of patients with thyroid nodules, as a screening method and for selecting patients who can undergo surgical treatment. The objective of this article is to make a brief description of the diagnostic categories of the Bethesda System in its second edition (2018). SYNTHESIS: The Bethesda System establishes 6 diagnostic categories: No diagnostic-Unsatisfactory, Benign, Atypia od Undetermined Significance/Follicular Lesion of Undetermined Significance, Follicular Neoplasm/Suspicious for a Follicular Neoplasm, Suspicious for Malignant and Malignant. CONCLUSIONS: The Bethesda System allows pathologists to make systematized reports and the clinician to establish the attitude to follow according to each diagnostic category

Infecciones invasoras por Streptococcus pyogenes (2011-2018): serotipos y presentación clínica / Invasive Streptococcus pyogenes infections (2011-2018): EMM-type and clinical presentation

INTRODUCCIÓN: Streptococcus pyogenes (S. pyogenes) es un importante patógeno humano responsable de una gran diversidad de infecciones, algunas de las cuales presentan un carácter severo con elevada morbimortalidad asociada. La proteína M es un determinante de virulencia crítico de este microorganismo. Diferentes estudios comunican un incremento de enfermedad invasora por S. pyogenes (EISP) relacionado con un aumento de serotipos M1 y M3, de reconocida virulencia. El objetivo del trabajo es confirmar el incremento observado de las enfermedades invasoras por S. pyogenes durante 2011-2018, y conocer qué serotipos pudieran estar implicados. MATERIAL Y MÉTODOS: La identificación de los aislados se realizó mediante pruebas fenotípicas convencionales: morfología de las colonias, β-hemólisis, pruebas bioquímicas y detección de antígeno A de Lancefield (DiaMondiaL Strep Kit, DiaMondiaL, Langenhagen, Alemania). La sensibilidad antibiótica se determinó mediante microdilución (Vitek®2 Compact, bioMeriéux, Inc., Durham, NC). La caracterización genotípica incluyó el gen emm y el perfil de superantígenos. RESULTADOS: Entre 2011-2018 se recuperaron 29 S. pyogenes invasores de sangre (16), líquido pleural (9), líquido sinovial (3) y líquido cefalorraquídeo (1). Entre 2011 y 2013, se cuantificó una cepa por año. Entre 2014 y 2018 se aislaron 2, 5, 4, 6 y 9 cepas, respectivamente. Las entidades clínicas más frecuentes fueron bacteriemia y neumonía (10 y 9 casos). Los serotipos mayoritarios fueron M1 (11) y M3 (3), asociados predominantemente a neumonía (6/7 casos) e infección profunda de partes blandas (3/3 casos). CONCLUSIONES: Se constata un incremento de las enfermedad invasora por S. pyogenes en el periodo estudiado resultando mayoritarios, conforme a la bibliografía, los serotipos M1 y M3, los cuales se asocian con neumonía e infección profunda de partes blandas

INTRODUCTION: Streptococcus pyogenes (S. pyogenes) is an important human pathogen that is responsible for a broad range of infections, from uncomplicated to more severe and invasive diseases with high morbidity/mortality. The M protein (emm type) is a critical virulence factor. Several studies have shown an increased incidence of invasive S. pyogenes disease. This was associated with an increase in the prevalence of M1 and M3 types, well-recognised virulent M types. The aim of the present study was to confirm the resurgence of invasive S. pyogenes disease during 2011-2018 and to identify the relationship between specific M types with disease presentation. MATERIAL AND METHODS: Isolates were confirmed using standard techniques: colony morphology, β-haemolysis, biochemical tests, and agglutination with specific antisera (DiaMondiaL Strep Kit, DiaMondiaL, Langenhagen, Germany). The antibiotic sensitivity was performed using microdilution (Vitek®2 Compact, bioMeriéux, Inc., Durham, NC). Molecular analysis included the determination of the emm gene and superantigen profile. RESULTS: A total of 29 invasive isolates were collected (2011-2018) from blood (16), pleural fluid (9), synovial fluid (3), and cerebrospinal fluid (1). One strain per year was isolated between 2011 and 2013, with 2, 5, 4, 6, and 9 strains being isolated between 2014 and 2018, respectively. The most frequent clinical presentations were bacteraemia and pneumonia (10 and 9 cases). The predominant types were M1 (11 isolates) and M3 (3 isolates). A correlation was found between M1 and M3 types, and pneumonia (6/7 cases) and deep soft tissue infections (3/3 cases). CONCLUSIONS: An increased incidence of invasive S. pyogenes disease was observed during the study period, with M1 and M3 types being those most commonly isolated and associated with pneumonia and deep soft tissue infections

Advances in understanding of the oxysterol-binding protein homologous in yeast and filamentous fungi

Oxysterol-binding protein is an important non-vesicular trafficking protein involved in the transportation of lipids in eukaryotic cells. Oxysterol-binding protein is identified as oxysterol-binding protein-related proteins (ORPs) in mammals and oxysterol-binding protein homologue (Osh) in yeast. Research has described the function and structure of oxysterol-binding protein in mammals and yeast, but little information about the protein's structure and function in filamentous fungi has been reported. This article focuses on recent advances in the research of Osh proteins in yeast and filamentous fungi, such as Aspergillus oryzae, Aspergillus nidulans, and Candida albicans. Furthermore, we point out some problems in the field, summarizing the membrane contact sites (MCS) of Osh proteins in yeast, and consider the future of Osh protein development

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Valoración del sobrecrecimiento y traslocación bacterianos en el hígado graso no alcohólico, en pacientes con obesidad mórbida / An assessment of bacterial overgrowth and translocation in the non-alcoholic fatty liver of patients with morbid obesity

Antecedentes: se ha propuesto que el sobrecrecimiento bacteriano del intestino delgado (SBID) y la traslocación bacteriana a través de la pared intestinal se relacionan con el hígado graso no alcohólico (HGNA). El objetivo del presente estudio ha sido estudiar dicha relación en obesos mórbidos. Pacientes y métodos: se incluyeron consecutivamente pacientes con obesidad mórbida previo a su intervención de cirugía bariátrica. Los criterios de exclusión fueron: biopsia hepática normal, otras causas de enfermedad hepática o atrofia de la mucosa duodenal. Se realizó una gastroscopia para cultivo del aspirado duodenal, biopsias duodenales y extracción de sangre venosa periférica para estudio de lipopolisacárido (LPS) y proteína de unión del LPS (LBP). La biopsia hepática se realizó durante la intervención quirúrgica. Resultados: se incluyeron 71 pacientes; 26 fueron excluidos por biopsia hepática normal. Cuarenta y cinco tenían HGNA. Dieciocho eran varones, con edad media de 45,8 años (22-69) e índice de masa corporal (IMC) de 47,8 kg/m2 (37-58); el 25% tuvo SBID en el cultivo del aspirado duodenal. Existió significación estadística entre niveles de LBP y SBID con el grado de esteatosis (p < 0,05 y p = 0,077, respectivamente). No existió relación estadística con el índice de esteatohepatitis no alcohólica (EHNA), aunque sí hubo una tendencia a su asociación. Los niveles de LPS no guardaron relación con el grado de esteatosis o el índice de EHNA. Conclusiones: en pacientes con obesidad mórbida e HGNA se observan mayores niveles circulantes de LBP y mayor frecuencia de SBID cuanto mayor es el grado de esteatosis hepática

Background: small intestinal bacterial overgrowth (SIBO) and bacterial translocation across the intestinal wall have been allegedly associated with non-alcoholic fatty liver (NAFL). Our goal was to study such alleged association in morbidly obese patients. Patients and methods: patients with morbid obesity were consecutively included prior to bariatric surgery. Exclusion criteria included normal liver biopsy, other causes of liver disease, and duodenal mucosal atrophy. A gastroscopy was performed for duodenal aspirate culture and duodenal biopsy, and peripheral venous blood was drawn to assess lipopolysaccharide (LPS) and LPS-binding protein (LBP) levels. A liver biopsy was carried out during surgery. Results: seventy-one patients were included; 26 were excluded because of normal liver biopsy. Forty-five had NAFL. Eighteen were male, mean age was 45.8 years (22-69), and BMI was 47.8 kg/m2 (37-58). A total of 25% had SIBO in their duodenal aspirate culture. There was statistical significance for the association of LBP levels and SIBO with steatosis grade (p < 0.05 and p = 0.077, respectively). There was no statistical association with non-alcoholic steatohepatitis (NASH) index, but a trend towards association was found. LPS levels were not associated with steatosis grade or NASH index. Conclusions: the higher the grade of liver steatosis, the higher were the circulating LBP levels and SIBO rates seen in patients with morbid obesity and NAFL

A novel TTC37 mutation causing clinical symptoms of trichohepatoenteric syndrome such as pyoderma gangrenosum and immunodeficiency without severe diarrhea

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Anaphylaxis caused by lipid transfer proteins: an unpredictable clinical syndrome

INTRODUCTION: Lipid transfer proteins (LTPs) are panallergens found in many plant foods. They are a common cause of food-induced anaphylaxis (FIA) in adults living in the Mediterranean area. LTPs have also been proposed as a main cause of food-dependent exercise-induced anaphylaxis (FDEIA). OBJECTIVES: Describe clinical characteristics and allergen sensitization profiles in patients with FIA related to LTP. MATERIALS AND METHODS: Forty-three patients were included, aged 3-52 years with a clinical history of FIA and proven sensitization to LTP. Patients were tested with a multiple plant food and pollen panel and specific IgE to LTP allergens. LTP sensitization was assessed by in vivo (Pru p 3, LTP extract) and/or by in vitro tests (specific IgE, ImmunoCAP/ISAC(R)). RESULTS: Median age of first anaphylactic episode was 24 years (range 2-51), 44% had asthma, 74% were atopic and 42% had pollinosis (olive, mugwort, plane tree, wall pellitory and cypress). Co-sensitization to profilins was found in 22%. Overall in our center, LTP-induced anaphylaxis represents 17% of all causes of FIA. Foods implicated in anaphylactic reactions were: fresh fruits 51%, tree nuts 42%, vegetables (including peanut) 40% and seeds 14%. Seven patients had FDEIA. CONCLUSIONS: LTPs are important allergens of FIA in Portugal. Clinical reactivity to several taxonomically unrelated plant foods may raise suspicion toward LTP sensitization. The association of LTP-induced anaphylaxis with pollinosis is relevant in our country. The unpredictable clinical expression depends on the effect of cofactors such as exercise. The management of avoidance plans can be challenging due to LTP being a widely cross-reacting allergen in plant foods

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Fisiopatología de los transportadores de glutamato y de glicina: nuevas dianas terapéuticas / Pathophysiology of the glutamate and the glycine transporters: new therapeutic targets

Introducción. Los aminoácidos glutamato y glicina, aparte de su papel en la síntesis de proteínas, son dos neurotransmisores fundamentales en el sistema nervioso central de los mamíferos. El primero es ubicuo y está implicado en vías excitatorias de la neocorteza, la retina y el cerebelo, y el segundo está asociado a vías inhibitorias de zonas caudales del cerebro. Sin embargo, ambos comparten su manera de actuar al integrarse en el funcionamiento de los receptores de glutamato del tipo NMDA, fundamentales en la regulación de sistemas motores, sensitivos y cognitivos. Objetivo. Evidenciar la necesidad de una regulación exquisita de las concentraciones de glutamato y de glicina en los espacios intra y extracelulares del sistema nervioso mediante la actuación de transportadores muy específicos para ambos neurotransmisores localizados en la membrana plasmática de las neuronas y de las células de la glía. Desarrollo. Se describe el papel de los transportadores de glutamato y glicina en la neurotransmisión glutamatérgica y glicinérgica, y en el funcionamiento del sistema nervioso. Se señalan las consecuencias patológicas de los desequilibrios en estas vías de señalización. También se describe su participación en patologías como la esquizofrenia, el dolor crónico, la isquemia cerebral, la hiperplexia hereditaria, la hiperglicinemia no cetósica o trastornos neurodegenerativos. Conclusiones. El conocimiento de la forma molecular de actuar de los transportadores de glutamato y de glicina está permitiendo la identificación y el desarrollo de nuevas estrategias terapéuticas para patologías como las descritas y el desarrollo de nuevos fármacos

Introduction. The amino acids glutamate and glycine, apart from their role in protein synthesis, are two fundamental neurotransmitters in the central nervous system of mammals. The first one is ubiquitous and is involved in excitatory pathways of the neocortex, the retina and the cerebellum, and the second is involved in inhibitory pathways of brain caudal areas. However, both share their way of acting by integrating into the functioning of glutamate receptors of the NMDA type fundamentals in the regulation of motor, sensory and cognitive systems. Aim. To highlight the need for a fine regulation of glutamate and glycine concentrations in the intracellular and extracellular spaces of the nervous system through the action of very specific transporters for both neurotransmitters located in the plasma membrane of neurons and glial cells. Development. The role of the glutamate and glycine transporters in glutamatergic and glycinergic neurotransmission and in the functioning of the nervous system is described. The pathological consequences of imbalances in these signaling pathways are pointed out. We also describe its involvement in pathologies such as schizophrenia, chronic pain, cerebral ischemia, diseases such as hereditary hyperekplexia and the non-ketotic hyperglycinemia, and neurodegenerative disorders. Conclusions. The knowledge at molecular level of the way of acting of these transporters for glutamate and glycine is allowing the identification and development of new therapeutic strategies for pathologies such as those described above and the development of new drugs

Evaluation of serum IgE in peach-allergic patients with systemic reaction by using recombinant Pru p 7 (gibberellin-regulated protein)

BACKGROUND: Lipid transfer protein (LTP) is a major fruit allergen. It has, however, recently been revealed that the systemic reaction in peach-allergic patients is related not only to LTP (Pru p 3) but also to gibberellin-regulated protein (Pru p 7). We investigated recombinant Pru p 7 (rPru p 7) for its potential use in worldwide standardization for the diagnosis of peach allergy. METHODS: Natural Pru p 7 (nPru p 7) was purified from peach crude extract using a monoclonal antibody affinity column. Complementary DNA for Pru p 7 was cloned and expressed in Escherichia coli and Pichia pastoris. Serum immunoglobulin (Ig) E in peach-allergic patients was examined by enzyme-linked immunosorbent assay (ELISA) using nPru p 7 and rPru p 7 (E. coli product: erPru p 7 and P. pastoris product: prPru p 7). RESULTS: Peach-allergic patients (n = 27) were diagnosed and categorized into oral reaction (n=10) or systemic reaction (n = 17). The nPru p 7 positivity based on serum IgE levels was 52% in the systemic-reaction group and 0% in the oral-reaction group (P<0.05). In the systemic-reaction group, there was no significant difference in reactivity between nPru p 7 and prPru p 7, but the reactivity of erPru p 7 was significantly lower than those of nPru p 7 and prPru p 7 (P < 0.05). CONCLUSIONS: We found that prPru p 7 exhibited reactivity in ELISA comparable to that of nPru p 7 for the diagnosis of peach allergy with systemic reaction

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