Fibronectin-1: A Predictive Immunotherapy Response Biomarker for Muscle Invasive Bladder Cancer

Background: Muscle-invasive bladder cancer (MIBC) is characterized as bladder tumors that infiltrate into the muscle layer, along with multiple metastasis and poor prognosis. Numerous research studies have been performed to identify the underlying clinical and pathological alterations that occur. However, few studies have revealed the molecular mechanism of its progression based upon the immunotherapy response. Our present study was designed to identify biomarkers which may predict the immunotherapy response by investigating the tumor microenvironment (TME) in MIBC. Methods: The transcriptome and clinical data of MIBC patients were obtained and analyzed with R version 4.0.3 (POSIT Software, Boston, MA, USA) ESTIMATE package. Differentially expressed immune-related genes (DEIRGs) were identified and further analyzed via the protein-protein interaction network (PPI). Meanwhile, univariate Cox analysis was utilized to screen out the prognostic DEIRGs (PDEIRGs). Then, the PPI core gene was matched with PDEIRGs to obtain the target gene-fibronectin-1 (FN1). Human MIBC and control tissues were collected and FN1 was measured with Quantitative Reverse Transcription PCR (qRT-PCR) and Western-Blot. Finally, the relationship between FN1 expression level and MIBC was validated through survival, univariate Cox, multivariate Cox, Gene Set Enrichment Analysis (GSEA) and correlation analysis of tumor infiltrating immune cells. Results: TME DEIRGs were identified and the target gene FN1 was obtained. The higher expression of FN1 was confirmed in MIBC tissues via bioinformatics analysis, qRT-PCR and Western-Blot. Moreover, higher FN1 expression correlated with reduced survival time and FN1 expression was further favorably correlated with clinic-pathological features (grade, TNM stage, invasion, lymphatic and distant metastasis) (AU)

Effects of exercise on irisin in subjects with overweight or obesity. A systematic review of clinical studies / Efectos del ejercicio sobre la irisina en personas con sobrepeso u obesidad. Una revisión sistemática de estudios clínicos

Irisin is an adipomyokine involved in white adipose tissue browning, therefore, could be a key protein in metabolic health. However, exercise effects on irisin in subjects with overweight and/or obesity are conflicting. Therefore, this systematic review aims to search and analyse the literature available on this topic. From three databases: PubMed, ScienceDirect, and Medline, clinical studies published between 2010 and 2021 were considered. From 134 found, 14 studies were included. Only six reported plasma increases after exercise (~1.2 to 3-fold from pre-exercise levels). In addition, only 1 reported significant increases in skeletal muscle irisin mRNA levels (~2-fold). Also, irisin was measured from subcutaneous adipose tissue and saliva, where a ~2-fold increase in its protein levels was found in the latter. Exercise seems to increase the circulatory concentrations of irisin in subjects with overweight or obesity. However, this response is highly variable, therefore, a more integrative approach is urgently needed. (AU)

La irisina es una adipomioquina relacionada a la transformación del tejido adiposo blanco a marrón, por tanto, podría ser una proteína clave para la salud metabólica. Sin embargo, los efectos del ejercicio sobre la irisina en personas con sobrepeso u obesidad son poco claros. Por lo anterior, esta revisión sistemática apunta a buscar y analizar la literatura disponible en este tema. Desde tres bases de datos: PubMed, ScienceDirect y Medline se buscaron estudios clínicos publicados entre el 2010 y 2021. De 134 estudios encontrados, 14 fueron incluidos. Solo 6 reportaron incrementos plasmáticos de irisina después del ejercicio (~1.2 a 3-veces respecto a niveles preejercicio). Además, solo 1 estudio describió incrementos significativos en el ARNm de irisina en el músculo esquelético (~2 veces sobre niveles preejercicio). La irisina también se medió desde tejido adiposo subcutáneo y saliva, encontrándose una elevación de (~2 veces sobre niveles preejercicio) en esta última. El ejercicio físico incrementaría las concentraciones circulatorias de irisina en personas con sobrepeso u obesidad. Sin embargo, esta respuesta es muy variable, por lo que se requiere una mirada más integrativa a la hora de estudiar este fenómeno. (AU)

Irisin improves adiposity and exercise tolerance in a rat model of postmenopausal obesity through enhancing adipo-myocyte thermogenesis

The prevalence of obesity and its associated metabolic disorders, along with their healthcare costs, is rising exponentially. Irisin, an adipomyokine, may serve as a critical cross-organ messenger, linking skeletal muscle with adipose tissue and the liver to integrate the energy homeostasis under diet-induced obesity. We aimed to explore the putative role of irisin in the protection against obesity in a postmenopausal rat model by modulating energy expenditure (EE). Bilateral ovariectomy (OVX) was performed. After 3 weeks of recovery, the OVX rats were classified according to their dietary protocol into rats maintained on normal diets (ND) (OVX) or high-fat diet (HFD) groups. The HFD-fed animals were equally divided into OVX/HFD, or irisin-treated OVX/HFD groups. Sham rats, maintained on ND, were selected as the control group. We evaluated anthropometric, EE, and molecular biomarkers of browning and thermogenesis in inguinal white adipose tissue and skeletal muscle, and the activity of the proteins related to mitochondrial long chain fatty acid transport, oxidation, and glycolysis. HFD of OVX further deteriorated the disturbed glucose homeostasis, lipid profile, and the reduced irisin, thermogenic parameters in adipose tissue and skeletal muscle, and EE. Irisin treatment improved the lipid profile and insulin resistance. That was associated with reduced hepatic gluconeogenic enzyme activities and restored hepatic glycogen content. Irisin reduced ectopic lipid infiltration. Irisin augmented EE by activating non-shivering thermogenesis in muscle and adipose tissues and decreasing metabolic efficiency. Our experimental evidence suggests irisin’s use as a potential thermogenic agent, therapeutically targeting obesity in postmenopausal patients. (AU)

Swimming exercise versus L-carnosine supplementation for Alzheimer’s dementia in rats: implication of circulating and hippocampal FNDC5/irisin

Recent studies have suggested that irisin may act as a potential neurokine. Exercise and L-carnosine supplementation showed neuroprotective effects in Alzheimer’s disease (AD)–like conditions. However, the regulation of irisin in the hippocampus of streptozotocin (STZ)–induced memory impairment and its relation to insulin signalling remain to be investigated. This study was designed to compare the effect of swimming exercise and L-carnosine intake on serum, CSF and hippocampal irisin in rats received intracerebroventricular (ICV) injection of STZ. Rats were recruited in swimming paradigm, received oral carnosine (100 mg/kg/day) or vehicle treated. After 5 weeks, rats were sacrificed after neurobehavioural testing. CSF and serum irisin were determined. Hippocampal tissues were used to assess expression of FNDC5/irisin, BDNF and proteins related to insulin signalling, in addition to β-amyloid peptide and phosphorylated tau protein levels. We observed decreased hippocampal, but not CSF or serum, irisin in ICV-STZ-injected rats. Exercise and carnosine intake almost normalized hippocampal FNDC5/irisin expression which was associated with reduced soluble β-amyloid peptide and phosphorylated tau protein, improved BDNF and insulin signalling proteins, with corresponding mitigated cognitive impairments. However, hippocampal FNDC5/irisin was not correlated with serum or CSF irisin levels. Histologically, both interventions ameliorated the hippocampal damage in STZ-injected rats. The current study reveals that carnosine is equivalent to exercise in reversing cognitive decline and Alzheimer’s biomarkers. In both interventions, enhancement of hippocampal FNDC5/irisin and insulin signalling may be involved in mediating these neuroprotective effects. (AU)

Fibronectin glomerulopathy: A case report and literature review / Glomerulopatía por fibronectina: informe de un caso y revisión de la literatura

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Short time guided bone regeneration using beta-tricalcium phosphate with and without fibronectin - An experimental study in rats

BACKGROUND: The aim of this histomorphometric study was to assess the bone regeneration potential of beta-tricalcium phosphate with fibronectin (Beta-TCP-Fn) in critical-sized defects (CSDs) in rats calvarial, to know whether Fn improves the new bone formation in a short time scope. MATERIAL AND METHODS: CSDs were created in 30 Sprague Dawley rats, and divided into four groups (2 or 6 weeks of healing) and type of filling (Beta-TCP-Fn, Beta-TCP, empty control). Variables studied were augmented area (AA), gained tissue (GT), mineralized/non mineralized bone matrix (MBM/NMT) and bone substitute (BS). RESULTS: 60 samples at 2 and six weeks were evaluated. AA was higher for treatment groups comparing to controls (p < 0.001) and significant decrease in BS area in the Beta-TCP-Fn group from 2 to 6 weeks (p = 0.031). GT was higher in the Beta-TCP-Fn group than in the controls expressed in % (p = 0.028) and in mm2 (p = 0.011), specially at two weeks (p=0.056). CONCLUSIONS: Both Beta-TCP biomaterials are effective as compared with bone defects left empty in maintaining the volume. GT in defects regeneration filed with Beta-TCP-Fn are significantly better in short healing time when comparing with controls but not for Beta-TCP used alone in rats calvarial CSDs

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Fibronectin glomerulopathy in a 88 year-old male with acute kidney injury on chronic kidney disease: A case report and a review of the literature / Glomerulopatía fibronectina en un anciano de 88 años de edad con lesión renal aguda en enfermedad renal crónica: reporte de un caso y revisión sistemática de la literatura

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Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism

Exercise offers several benefits for health, including increased lean body mass and heightened energy expenditure, which may be partially attributable to secretory factors known as myokines. Irisin, a recently identified myokine, was shown to increase metabolic rate and mitochondrial content in both myocytes and adipocytes; however, the mechanism(s) of action still remain largely unexplained. This work investigated if irisin functions by acting as an inflammatory myokine leading to cellular stress and energy expenditure. C2C12 myotubes were treated with various concentrations of irisin, TNFAlpha, or IL6 for various durations. Glycolytic and oxidative metabolism, as well as mitochondrial uncoupling, were quantified by measurement of acidification and oxygen consumption, respectively. Metabolic gene and protein expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting, respectively. Mitochondrial content was assessed by fluorescent imaging. NFkappaB activity was assessed using an NFkappaB GFP-linked reporter system. Consistent with previous findings, irisin significantly increased expression of several genes including peroxisome proliferator-activated receptor Alpha coactivator-1Alpha (PGC-1Alpha) leading to increased mitochondrial content and oxygen consumption. Despite some similarities between TNFAlpha and irisin treatment, irisin failed to activate the NFkappaB pathway like TNFAlpha, suggesting that irisin may not act as an inflammatory signal. Irisin has several effects on myotube metabolism which appear to be dependent on substrate availability; however, the precise mechanism(s) by which irisin functions in skeletal muscle remain unclear. Our observations support the hypothesis that irisin does not function through inflammatory NFkappaB activation like other myokines (such as TNFAlpha)

Irisin is more strongly predicted by muscle oxidative potential than adiposity in non-diabetic men

Numerous controversies surround the peptide hormone irisin. Although implicated as a myokine promoting the browning of adipose tissue in rodents, its roles in humans remain unclear. Contradictory results have also been found with respect to the relationships between adiposity or metabolic health and plasma irisin levels in humans. We investigated the relationship between irisin levels and body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), fitness level (ergocycle VO2max) and skeletal muscle metabolic profile in 53 men (aged 34–53 years) from four groups: sedentary non-obese controls (body mass index [BMI] <25 kg/m2), sedentary obese (BMI >30 kg/m2), sedentary obese glucose-intolerant, and non-obese highly trained endurance active. Baseline plasma irisin levels were significantly different between groups, being lowest in trained men (140.6 ± 38.2 ng/mL) and highest in metabolically deteriorated glucose-intolerant subjects (204.0 ± 50.5 ng/mL; ANOVA p = 0.01). Including all subjects, irisin levels were positively associated with adiposity (e.g. fat mass, r = 0.430, p < 0.01) and negatively associated with fitness (r = −0.369, p < 0.01), insulin sensitivity (M/I, r = −0.355, p < 0.01) and muscle citrate synthase (CS) activity (r = −0.482, p < 0.01). Most correlations lost statistical significance when excluding active individuals, except for insulin resistance (r = −0.413, p < 0.01) and CS (r = −0.462,p < 0.01). Multiple regression analyses reveal CS as the strongest independent predictor of irisin levels (r 2 range 0.214 to 0.237). We conclude that muscle oxidative potential is an important factor linked to circulating irisin levels

Advances in surfaces and osseointegration in implantology. Biomimetic surfaces

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Cambios histopatológicos en la necrosis miocárdica mediante la expresión de fibronectina / Histopathological changes in myocardial necrosis through fibronectin expression

El objetivo principal del estudio ha sido la aplicación de técnicas inmunohistoquímicas para poder efectuar el diagnóstico de la isquemia miocárdica en fases precoces con un margen mayor de seguridad. Se han seleccionado casos de muerte súbita de origen cardíaco en sujetos adultos, y se ha realizado una valoración descriptiva y semicuantitativa de los hallazgos. El diagnóstico histopatológico mediante la utilización de fibronectina por procedimientos inmunohistoquímicos ha demostrado una sensibilidad muy superior a la de las tinciones habituales. Los resultados altamente satisfactorios y la simplificación al máximo de la técnica pueden contribuir a su implantación en los laboratorios forenses y a que sea aplicada en un número importante de casos judiciales (AU)

The main objective of the study was the application of immunohistochemical techniques in the diagnosis of myocardial ischemia in the early stages with a greater margin of assuredness. We have selected cases of sudden cardiac death in adults, making a descriptive and semiquantitative assessment of the findings. Histopathological diagnosis by inmunohistochemical techniques using fibronectin antibodies has shown higher sensitivity than routine techniques. The satisfactory results as well as well as the simplification of the technique contributes to its implementation in forensic laboratories and application in an important number of forensic cases (AU)

Let-7f microRNA negatively regulates hepatic differentiation of human adipose tissue-derived stem cells

MicroRNAs (miRNAs) are noncoding RNAs involved in the regulation of the diverse biological processes such as metabolism, proliferation, and cell cycle, in addition to regulation of differentiation. So far, some miRNAs have been recognized to have important role in regulating hepatic functions. Statistically, let-7f has been revealed as a negative regulator of hepatic differentiation. In the present study, we investigated the effect of let-7f on hepatic differentiation of human adipose tissue-derived stem cells (hADSCs). hADSCs were transduced with recombinant lentivirus containing human inhibitor let-7 f. The expression of hepatocyte nuclear factors alpha (HNF4a), albumin (ALB), alpha fetoprotein (AFP), cytokeratin 18 (CK18), and cytokeratin 19 (CK19) was evaluated using quantitative real-time PCR (qRT-PCR). Immunocytochemistry was used to investigate the expression levels of the hepatocyte markers including ALB, AFP, and HNF4a, and biochemical analysis was implemented for hepatic function, glycogen deposition, and urea secretion. qRT-PCR showed significant upregulation in HNF4a, ALB, AFP, CK18, and CK19 expression in cells transduced with let-7f inhibitor lentiviruses. Moreover, positive staining was detected for ALB, AFP, and HNF4a using immunocytochemistry. Urea production and glycogen deposits were also found in the treated cells, the two specific features of the hepatic cells. Therefore, let-7f silencing led to the increased expression of the hepatocyte-specific factors and the accelerated hADSCs hepatic differentiation. Summing all these finding together, our present report has provided evidences that inhibition of let-7f would facilitate induction of hADSCs into hepatocyte-like cells and possibly in regenerative therapy of the liver disease in a wider spectrum

Fibronectin as an adjuvant in the diagnosis of oral inflammatorymyofibroblastic tumor

Inflammatory myofibroblastic tumor is a distinctive lesion composed of myofibroblastic spindle shaped cells accompaniedby inflammatory infiltrate that may arise in various organs. It is believed to be a noneoplastic inflammatorycondition, although this is still controversial. The recognition of inflammatory myofibroblastic tumor asan entity is important especially to avoid unnecessary surgery. A few cases have been reported in the oral cavity.This report primarily presents a case of inflammatory myofibroblastic tumor that arose in the floor of mouth ofa 23-year-old woman. The proliferating spindle cells were immunoreactive for vimentin, smooth muscle actin,and muscle specific actin and negative for desmin, AE1/AE3, S-100, CD68, MyoD1 and caldesmon. In an attemptto assess the potential neoplastic nature of this lesion, immunohistochemical expression of ALK protein wasperformed, although no immunoreactivity was detected. Also, the presence of well differentiated myofibroblastsidentified by fibronectin is discussed, as well as the importance in establishing an immunoprofile to better consolidatethe diagnosis. We conclude that the study of fibronectin in case series may aid the diagnosis as well as theprediction of the tumor course (AU)

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Presence of fibronectin peptides in saliva of patients with Sjögren’s Syndrome: A potential indicator of salivary gland destruction

Objective: The purpose of this preliminary study was to monitor the degree of destruction of salivary glands inSjögren disease by the detection of fibronectin peptides in patients’ saliva. Study design: The sample consisted of10 subjects divided in 2 groups, one with Sjögren disease and a control group. Saliva samples were submitted to aninmunodetection analysis. In addition, non pathological salivary glands, obtained from 2 subjects who underwentminor oral surgery, were incubated with leukocyte homogenates and analysed to compare the obtained fragments.Results: The inmunodetection analysis of Sjögren saliva revealed multiple protein bands, including fibronectin,that were not present in saliva from healthy individuals. The inmunostained bands varied depending on the courseof the disease, showing more fibronectin fragments in an active phase . Furthermore, results obtained from thenon-pathological glands incubated with leukocyte homogenates were similar to those revealed in saliva from Sjögrenpatients. Conclusion: The presence of fibronectin peptides in Sjögren patients’ saliva can constitute a methodto monitor activity in Sjögren’s disease (AU)

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Amenaza de parto prematuro. Rotura prematura de membranas. Corioamnionitis / Preterm labour. Premature rupture of membranes. Chorioamnionitis

Cuanto menor es la edad gestacional al nacer, mayores el riesgo de morbimortalidad perinatal y de morbilidadmaterna (aumento del número de cesáreas, metritispostparto). Es importante diagnosticar a tiempouna amenaza de parto prematuro (APP) para comenzarcon el tratamiento tocolítico y conseguir una maduraciónpulmonar fetal eficaz. También es necesario distinguirlo que es una verdadera de una falsa APP. Hayuna alta incidencia de sobrediagnóstico y de sobretratamientoy es frecuente la hospitalización prolongada.Con las pruebas que informan sobre la modificacióncervical y la dinámica uterina se puede establecer undiagnóstico certero que conlleve una conducta adecuada.La identificación temprana y la prevención primariano están tan desarrolladas como la actitud terapeútica,pero es importante tener en cuenta mecanismos paraidentificar pacientes de alto riesgo. Entre ellos estánlos antecendentes de parto pretérmino, signos y síntomas,modificación cervical, etc. La rotura prematurade membranas y la corioamnionitis conllevan riesgo departo pretérmino si se producen en edades gestacionestempranas(AU)

The lower the gestational age at birth, the greaterthe risk of perinatal morbidity and mortality and maternalmorbidity (increase in the number of caesareans,postnatal metritis). It is important for there to be a timelydiagnosis of threatened preterm labour (TPL) inorder to begin tocolytic treatment and to obtain efficientfoetal pulmonary maturity. It is also necessary todistinguish between a true and a false TPL. There is ahigh tendency of overdiagnosis and overtreatment andprolonged hospitalisation is frequent. With cervicalalteration and uterine dynamics tests it is possible toestablish an accurate diagnosis that will result in suitablemanagement. Early identification and primaryprevention are not as developed as the therapeutic attitude,but it is important to bear in mind mechanismsfor identifying high risk patients. They include antecedentsof preterm labour, signs and symptoms, cervicalalteration, etc. Premature rupture of membranes andchorioamnionitis involve the risk of preterm labour ifthey occur in early gestational ages(AU)

Utilidad de la prueba de la fibronectina fetal y de la longitud del c¨¦rvix en la predicci¨®n del parto prematuro en gestantes sintom¨¢ticas / Utility of fetal fibronectin and cervical length in predicting preterm birth in women with preterm uterine contractions

Objetivo: Evaluar la utilidad de la prueba de la fibronectina fetal (fFN) y de la longitud cervical para la predicci¨®n del parto prematuro, en mujeres que presentan din¨¢mica uterina antes del t¨¦rmino. Material y m¨¦todos: Estudio prospectivo realizado en el Hospital Virgen Macarena de Sevilla, en el que se incluy¨® a 153 gestantes con bolsa ¨ªntegra y amenaza de parto pret¨¦rmino (PP) a las que se les realiz¨®, en el momento de la consulta de urgencia, una cervicometr¨ªa mediante ecograf¨ªa transvaginal y una prueba r¨¢pida de fibronectina. No se procedi¨® a hospitalizar ni a someter a tratamiento farmacol¨®gico a las mujeres con una longitud cervical ¡Ý a 30 mm y una fFN negativa. Resultados: La edad gestacional media al diagn¨®stico fue de 223,02 ¡À 19,98 d¨ªas, y de 267,52 ¡À 14,15 d¨ªas en el parto, siendo la tasa de p < 37 semanas del 23% y la de p < 35 semanas del 7,4%. Hay una relaci¨®n significativa entre la longitud cervical < 30 mm y el p < 37 semanas (OR = 3,68; IC del 95%: 1,53-8,84) y el parto en los siguientes 14 d¨ªas (OR = 5,35; IC del 95%: 1,30-21,95). Asociando ambas pruebas se obtiene una mejor¨ªa discreta en la especificidad para la predicci¨®n del parto prematuro. Conclusi¨®n: La cervicometr¨ªa es el par¨¢metro que presenta mejor especificidad (E) y valor predictivo negativo (VPN) para la predicci¨®n del parto pret¨¦rmino en las gestantes con ametaza de parto prematuro (APP) (AU)

Objective: To evaluate the usefulness of fetal fibronectin and cervical length in predicting preterm birth in women with preterm uterine contractions. Material and methods: A prospective study was conducted at the Virgen Macarena Hospital in Seville that included 153 pregnant women with suspected preterm labor and intact membranes. Cervical length was measured by transvaginal sonography and a rapid qualitative fibronectin test was performed in the emergency consultation. Women with a negative fibronectin test and cervical length ¡Ý 30 mm were not hospitalized or treated with tocolytics or corticosteroids. Results: The mean gestational age at diagnosis was 223,02 ¡À 19,98 days, and 267,52 ¡À 14,15 days at delivery. Preterm birth <37 weeks rate was 23% and 7,4% for deliveries <35 weeks. There is an association between cervical length <30 mm and birth <37 weeks (OR, 3,68; 95% CI, 1,53-8,84), and with delivery in the following 14 days (OR, 3,35; 95% CI, 1,30-21,95). With the association of both tests we gain specificity in predicting preterm birth. Conclusion: Cervical length is the test with higher specificity (E) and negative predictive value (VPN) for the prediction of preterm birth in women with symptomatic contractions (AU)

The myofibroblast in health and disease

El miofibroblasto es fundamental para la integridad delorganismo de los mamíferos dado su papel en la curación de las heridas, pero puede resultar deletéreo por su capacidad para producir tumores. Se trata de un componente celular prácticamente universal en lesiones de mamíferos, pero no es un componente típico del tejido normal no traumatizado. Debido, en parte, a su ausencia en tejidos normales, no suele formar parte de la enseñanza convencional de la histología, loque ha dificultado su estudio y definición. El presente trabajo documenta las características del miofibroblasto con el fin de proporcionar una definición para científicos interesados en los mecanismos de enfermedad y para histopatólogos involucrados en el diagnóstico de lesiones miofibroblásticas. Las característicashistológicas que permiten la identificación del miofibroblasto son: morfología fusocelular, abundante matriz y positividad inmunohistoquímica para a-actina específica de músculo liso (en ausencia de desmina y h-caldesmón) y EDAfibronectina. En microscopía electrónica los hallazgos más importantes son: evidencia de retículo endoplásmico rugoso bien desarrollado, miofilamentos subplasmalemales de tipo muscular liso, aparato de Golgi con gránulos de secreción de colágeno y uniones tipo fibronexo que se considera como una organela característica; no debe encontrarse lámina externa.En el presente trabajo se comentan los mecanismo por los que el miofibroblasto aparece en el tejido de granulación y da lugar a tumores y como la anterior definición puede aplicarse al diagnóstico de las lesiones miofibroblásticas

The myofibroblast is essential for the integrity of themammalian body by virtue of its role in wound-healing, but it can also threaten it by its ability to promote tumour development. It is an almost universal cellular component in mammalian lesions, but not a typical component of normal untraumatised tissues. Partly because of its absence from normal tissue, it has not been part of conventional histology teaching. This has contributed to difficulties in appreciating the nature of the myofibroblast and defining it. This paperdocuments the features of the myofibroblast which providea definition for the myofibroblast needed by scientists interested in the mechanism of disease and pathologists wanting to diagnose myofibroblastic lesions. Light microscopy features emphasised for defining the myofibroblast include: spindled cell morphology, an abundant matrix, immunostaining for a-smooth-muscle actin (in the absence of desmin and h-caldesmon) and the ED-A splice variant of cellular fibronectin. By electron microscopy, rough endoplasmic reticulum, peripherally located smooth-muscle type myofilaments,a Golgi apparatus producing collagen-secretiongranules and fibronexus junctions are important. The fibronexus is emphasised as a distinctive organelle for identifying the myofibroblast and lamina is emphasised as absent. The mechanism by which myofibroblasts arise in granulation tissue and promote tumour development, and the how the above definition can be used in diagnosing myofibroblastic lesions, is discussed (AU)

Normal development of fetal hepatic haematopoiesis during the second trimester of gestation is upregulated by fibronectin expression in the stromal cells of the portal triads

Objetivo: en el segundo trimestre de la gestación, el principalfoco de hematopoyesis del feto es el hígado. En los órganoshematopoyéticos, las células del estroma, como fibroblastos,células epiteliales y células de tipo macrófago, desarrollan redespara mantener la hematopoyesis, es decir, la auto-renovación,la proliferación y el crecimiento de las células madre hematopoyéticas,al interactuar con las células progenitoras hematopoyéticas.Se sabe que las glucoproteínas de la MEC producidaspor las células del estroma desempeñan un papel crítico enla regulación del crecimiento y la diferenciación celulares. Sehan documentado numerosos factores solubles y de membranaque regulan directamente la hematopoyesis, pero se sabe pocode la actividad de las células del estroma hepático y de laproteína (fibronectina) de la matriz extracelular en el feto en relacióncon la hematopoyesis hepática. La unión de las célulaseritroides tardías a la fibronectina está bien tipificada y se creeque es crítica para las etapas terminales de la diferenciación eritroide.La intención de este artículo es determinar el papel dela fibronectina en la proliferación y diferenciación hematopoyéticadel hígado fetal en las distintas etapas del desarrollo.Material y método: examinamos y comparamos la expresióninmunohistoquímica de fibronectina en los campos portalesdel estroma hepático durante los trimestres primero, segundoy tercero del embarazo en relación con la aparición decélulas progenitoras hematopoyéticas CD34, progenitoras delestroma y endoteliales vasculares, respectivamente.Resultados: nuestros resultados mostraron una diferenciacuantitativa en cuanto a expresión de fibronectina en el estromadel tejido conjuntivo de los campos portales en el segundotrimestre de embarazo respecto al primero (p < 0,0001, pruebade la t) y respecto al tercero (p < 0,0001, prueba de la t). Sehallaron también cambios similares en cuanto a la expresión deCD34 respecto al primer (p < 0,0001, prueba de la t) y el tercertrimestres (p < 0,0001, prueba de la t), lo que indica la participacióndirecta de la fibronectina en el mantenimiento de laactividad hematopoyética

Objective: in midtrimester fetuses the principal site ofhematopoiesis is the liver. In hematopoietic organs, stromal cellssuch as fibroblasts, epithelial cells, and macrophage-like cells developnetworks to maintain hematopoiesis, i.e. hematopoietic stemcell self-renewal, proliferation, and growth, by interaction withhematopoietic progenitor cells. ECM glycoproteins produced by thestromal cells are known to play a critical role in the regulation of cellgrowth and differentiation. Numerous soluble and membraneboundfactors directly regulating haematopoiesis have been documented,but little is known about fetal hepatic stromal cell activityand stromal extracellular matrix protein-fibronectin, on fetal hepatichaematopoiesis. The binding of late stage erythroid cells to fibronectinhas been well characterized and is believed to be criticalfor the terminal stages of erythroid differentiation. The intention ofthis article is to determine the role of fibronectin in fetal hepatichematopoietic proliferation and differentiation in different stages ofdevelopment.Material and method: we examined and compared the immunohistochemicalexpression of fibronectin in the hepatic stromalportal fields in the 1st, 2nd, and 3rd trimester of gestation respectively,in relation to the appearance of CD34 progenitor hematopoietic,stromal progenitor and vascular endothelial positive cells.Results: our results demonstrated a quantitative difference inthe second trimester of gestation concerning the expression of fibronectinin the connective tissue stroma of the hepatic portalfields over the equivalent expression of the protein in the first (p <0.0001, t-test) and third trimester (p < 0.0001, t-test). Similarchanges in the above period were found concerning the expressionof CD34 during the second trimester of gestation, over thefirst (p < 0.0001, t-test) and third trimesters (p < 0.0001, t-test),suggesting a direct involvement of fibronectin in the sustaining ofhematopoietic activity

Fibronectina sérica como marcador de infección respiratoria en UCI / Serum fibronectin as respiratory infection marker in ICU

Objetivo. La fibronectina (FBN) es una proteína moduladora de la fagocitosis y como tal podría relacionarse con los procesos infecciosos. Evaluamos la eficacia de la fibronectina sérica como marcador precoz de infección respiratoria en pacientes críticos bajo ventilación mecánica (VM). Diseño. Estudio prospectivo de casos-control. Ámbito. Unidad de Cuidados Intensivos (UCI) polivalente en Hospital de tercer nivel con 42 camas. Pacientes. Setenta y siete pacientes con VM sin signos de infección al ingreso (casos) y 55 pacientes tras cirugía programada como muestra de validación (controles). Intervenciones. FBN sérica y cultivos cualitativos de aspirado endobronquial (AE) el primer, cuarto y séptimo día (si mantenían la VM) con seguimiento hasta el día décimo. Variables. Variables demográficas, SOFA y APACHE II al ingreso y aparición de neumonía o traqueobronquitis durante el seguimiento. Resultados. Los casos presentaban niveles más bajos de FBN (0,24 ± 0,11 g/l frente 0,39 ± 0,29 g/l, p < 0,01), pero ni el diagnóstico, los índices de gravedad o el pronóstico en este grupo se relacionaron con la FBN. Los casos con aislamiento de algún microorganismo en AE no presentaron niveles de FBN diferentes al ingreso (0,23 ± 0,10 frente a 0,25 ± 0,12) (independientemente del grupo diagnóstico), así como al cuarto o séptimo día. Presentaron infección respiratoria 27 (35,1%) pacientes, neumonía 19 y traqueobronquitis en 8. La FBN no mostró diferencias significativas con el resto de casos en ninguna de las tres determinaciones realizadas. Conclusiones. La FBN sérica en pacientes ingresados en UCI no es marcador de gravedad ni se relaciona con el pronóstico, no mostrando tampoco utilidad como marcador de infección respiratoria

Objective. Fibronectin (FBN) is a phagocytosis modulating protein and, as such, could be related with the infectious condition. We evaluate the efficacy of serum fibronectin as an early marker of respiratory infection in critical patients receiving mechanical ventilation (MV). Design. Prospective study of cases-control. Scope. Polyvalent ICU in third level Hospital with 42 beds. Patients. Seventy seven patients with MV without signs of infection on admission (cases) and 55 patients after elective surgery as validation sample (controls). Interventions. Serum FBN and qualitative cultures of endobronchial aspirate (EA) on days 1, 4 and 7 (if MV was maintained) with follow-up to day 10. Variables. Demographic variables, SOFA and APACHE II on admission and appearance of pneumonia or tracheobronchitis during follow-up. Results. The cases had low levels of FBN (0.24 ± 0.11 g/l vs 0.39 ± 0.29, p < 0.01), however, neither the diagnosis, seriousness indexes or prognosis in this group were related with the FBN. Cases with isolation of some microorganism in EA did not have different FBN levels on admission (0.23 ± 0.10 vs 0.25 ± 0.12) (regardless of the diagnostic group) nor on the fourth or seventh day. A total of 27 (35.1) patients had respiratory infection, 19 pneumonia and 8 tracheobronchitis. FBN did not shown any significant differences with the remaining cases in any of the three measurements made. Conclusions. Serum FBN in patients hospitalized in the ICU is not a marker of seriousness nor is it related with prognosis. It also does not have any utility as a marker of respiratory infection

Diagnóstico de la amenaza de parto prematuro / Diagnosis of preterm labour

La prematuridad está aumentando en todoel mundo y es actualmente uno de los principalesproblemas obstétricos. En la mayoría de loscasos de parto prematuro se produce previamenteun cuadro clínico de trabajo de partopretérmino. El diagnóstico clásico de esta entidadmediante la presencia de contraccionesuterinas y modificaciones cervicales clínicamentemuestra una baja capacidad diagnósticacon una alta tasa de falsos positivos. La valoraciónecográfica transvaginal y la determinaciónde fibronectina en las secreciones cervico-vaginales presentan una buena especificidady valor predictivo negativo y su incorporacióna un algoritmo diagnóstico podría ayudara diferenciar la verdadera de la falsa amenazade parto prematuro

Preterm birth have soared all over the world and is one of the top obstetric problems nowadays. Most cases of preterm delivery present clinical signs of preterm labor. Classic diagnosis of this disease by the presence of uterine contractions and clinical cervix effacement and dilatation show a low diagnostic accuracy with a high false-positive rate. Cervical ultrasound measurement and determination of fibronectin in cervico-vaginal secretions present a high especificity and negative predictive value and its inclusion in a diagnostic algorithm may help to differenciate the true from the false preterm labor (AU)