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1.
Curr Issues Mol Biol ; 46(5): 3839-3865, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38785507

RESUMEN

Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use of biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis and identification of potential therapeutic targets. Several studies have shown a correlation between the tissue expression levels of various molecules, measured through immunohistochemistry (IHC), and survival rates in PDAC. Following the hallmarks of cancer, epigenetic and metabolic reprogramming, together with immune evasion and tumor-promoted inflammation, plays a critical role in cancer initiation and development. In this study, we aim to explore via IHC and Kaplan-Meier analyses the prognostic value of various epigenetic-related markers (histones 3 and 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function 1 protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding Protein 7 (RBBP7), importin 4 (IPO4) and IPO5), metabolic regulators (Phosphoglycerate mutase (PGAM)) and inflammatory mediators (allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A and IL-18) in patients with PDAC. Also, through a correlation analysis, we have explored the possible interconnections in the expression levels of these molecules. Our results show that higher expression levels of these molecules are directly associated with poorer survival rates in PDAC patients, except in the case of IL-10, which shows an inverse association with mortality. HAT1 was the molecule more clearly associated with mortality, with a hazard risk of 21.74. The correlogram demonstrates an important correlation between almost all molecules studied (except in the case of IL-18), highlighting potential interactions between these molecules. Overall, our study demonstrates the relevance of including different markers from IHC techniques in order to identify unexplored molecules to develop more accurate prognosis methods and possible targeted therapies. Additionally, our correlation analysis reveals potential interactions among these markers, offering insights into PDAC's pathogenesis and paving the way for targeted therapies tailored to individual patient profiles. Future studies should be conducted to confirm the prognostic value of these components in PDAC in a broader sample size, as well as to evaluate the possible biological networks connecting them.

2.
Int J Mol Sci ; 24(12)2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37373400

RESUMEN

Psychosis refers to a mental health condition characterized by a loss of touch with reality, comprising delusions, hallucinations, disorganized thought, disorganized behavior, catatonia, and negative symptoms. A first-episode psychosis (FEP) is a rare condition that can trigger adverse outcomes both for the mother and newborn. Previously, we demonstrated the existence of histopathological changes in the placenta of pregnant women who suffer an FEP in pregnancy. Altered levels of oxytocin (OXT) and vasopressin (AVP) have been detected in patients who manifested an FEP, whereas abnormal placental expression of these hormones and their receptors (OXTR and AVPR1A) has been proven in different obstetric complications. However, the precise role and expression of these components in the placenta of women after an FEP have not been studied yet. Thus, the purpose of the present study was to analyze the gene and protein expression, using RT-qPCR and immunohistochemistry (IHC), of OXT, OXTR, AVP, and AVPR1a in the placental tissue of pregnant women after an FEP in comparison to pregnant women without any health complication (HC-PW). Our results showed increased gene and protein expression of OXT, AVP, OXTR, and AVPR1A in the placental tissue of pregnant women who suffer an FEP. Therefore, our study suggests that an FEP during pregnancy may be associated with an abnormal paracrine/endocrine activity of the placenta, which can negatively affect the maternofetal wellbeing. Nevertheless, additional research is required to validate our findings and ascertain any potential implications of the observed alterations.


Asunto(s)
Oxitocina , Trastornos Psicóticos , Recién Nacido , Femenino , Humanos , Embarazo , Oxitocina/genética , Oxitocina/metabolismo , Placenta/metabolismo , Receptores de Oxitocina/genética , Receptores de Oxitocina/metabolismo , Vasopresinas/genética , Vasopresinas/metabolismo , Trastornos Psicóticos/genética
3.
J Reconstr Microsurg ; 39(2): 102-110, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36162421

RESUMEN

BACKGROUND: The aim of this study was to analyze the different applications of ultrasound (US) in upper extremity lymphedema (UEL) after breast cancer. METHODS: A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to December 2021. Articles describing the application of US in patients with UEL after breast cancer were included. The quality of the study, the level of reproducibility, and the different applications and type of US technique were analyzed. RESULTS: In total, 30 articles with 1,193 patients were included in the final review. Five different applications were found: (1) diagnosis of UEL (14 studies found a direct correlation between lymphedema and morphological and/or functional parameters); (2) staging/severity of UEL (9 studies found a direct correlation between the clinical stage and the soft-tissue stiffness/texture/thickness); (3) therapeutic assessment (3 studies found an improvement in the circulatory status or in the muscle/subcutaneous thickness after conservative treatments); (4) prognosis assessment of UEL (1 study found a correlation between the venous flow and the risk of UEL); and (5) surgical planning (3 studies determined the location of the lymphatic vessel for lymphovenous anastomosis [LVA] surgery). CONCLUSION: Morphological and functional parameters have been correlated with the diagnosis, stage, therapeutic effect, prognosis of UEL, and surgical planning of LVA.


Asunto(s)
Neoplasias de la Mama , Vasos Linfáticos , Linfedema , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Reproducibilidad de los Resultados , Extremidad Superior/diagnóstico por imagen , Extremidad Superior/cirugía , Linfedema/diagnóstico por imagen , Linfedema/etiología , Linfedema/cirugía , Ultrasonografía , Anastomosis Quirúrgica , Vasos Linfáticos/cirugía
4.
Medicina (Kaunas) ; 59(12)2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38138185

RESUMEN

Background and Objectives: Redistribution hypothermia occurs during anesthesia despite active intraoperative warming. Prewarming increases the heat absorption by peripheral tissue, reducing the central to peripheral heat gradient. Therefore, the addition of prewarming may offer a greater preservation of intraoperative normothermia as compared to intraoperative warming only. Materials and Methods: A single-center clinical trial of adults scheduled for non-cardiac surgery. Patients were randomized to receive or not a prewarming period (at least 10 min) with convective air devices. Intraoperative temperature management was identical in both groups and performed according to a local protocol. The primary endpoint was the incidence, the magnitude and the duration of hypothermia (according to surgical time) between anesthetic induction and arrival at the recovery room. Secondary outcomes were core temperature on arrival in operating room, surgical site infections, blood losses, transfusions, patient discomfort (i.e., shivering), reintervention and hospital stay. Results: In total, 197 patients were analyzed: 104 in the control group and 93 in the prewarming group. Core temperature during the intra-operative period was similar between groups (p = 0.45). Median prewarming lasted 27 (17-38) min. Regarding hypothermia, we found no differences in incidence (controls: 33.7%, prewarming: 39.8%; p = 0.37), duration (controls: 41.6% (17.8-78.1), prewarming: 45.2% (20.6-71.1); p = 0.83) and magnitude (controls: 0.19 °C · h-1 (0.09-0.54), prewarming: 0.20 °C · h-1 (0.05-0.70); p = 0.91). Preoperative thermal discomfort was more frequent in the prewarming group (15.1% vs. 0%; p < 0.01). The interruption of intraoperative warming was more common in the prewarming group (16.1% vs. 6.7%; p = 0.03), but no differences were seen in other secondary endpoints. Conclusions: A preoperative prewarming period does not reduce the incidence, duration and magnitude of intraoperative hypothermia. These results should be interpreted considering a strict protocol for perioperative temperature management and the low incidence of hypothermia in controls.


Asunto(s)
Hipotermia , Adulto , Humanos , Hipotermia/epidemiología , Temperatura Corporal , Cuidados Preoperatorios , Atención Perioperativa/efectos adversos , Atención Perioperativa/métodos , Anestesia General/efectos adversos
5.
Int J Med Sci ; 19(1): 186-194, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34975312

RESUMEN

Chronic Venous Disease (CVD) refers to a wide variety of venous disorders being the varicose veins its most common manifestation. It is well-established the link between pregnancy and the risk of suffering CVD, due to hormonal or haematological factors, especially during the third trimester. In the same manner, previous studies have demonstrated the detrimental effect of this condition in the placental tissue of pregnant women, including in the normal physiology and the metabolomic profile of this organ. In this context, the aim of this study was to evaluate the glucose homeostasis in the placental tissue of women presenting CVD. Through immunohistochemistry, we studied the protein expression of the glucose transporter 1 (GLUT-1), Phosphoglycerate kinase 1 (PGK1), aldolase (ALD), Glyceraldehyde-3-phosphate dehydrogenase (GA3PDH) and lactate dehydrogenase (LDH). Our results have reported a significative increase in the expression of GLUT-1, PGK1, ALD, GA3PDH and the isoenzyme LDHA in placentas of women with CVD. This work has proven for the first-time an altered glucose metabolism in the placental tissue of women affected by CVD, what may aid to understand the pathophysiological mechanisms of this condition in more distant organs such as placenta. Furthermore, our research also supports the basis for further studies in the metabolic phenotyping of the human placenta due to CVD, which may be considered during the late pregnancy in these women.


Asunto(s)
Glucólisis , Placenta/metabolismo , Complicaciones del Embarazo/metabolismo , Enfermedades Vasculares/metabolismo , Enfermedad Crónica , Femenino , Fructosa-Bifosfato Aldolasa/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Humanos , Inmunohistoquímica , L-Lactato Deshidrogenasa/metabolismo , Fosfoglicerato Quinasa/metabolismo , Placenta/irrigación sanguínea , Embarazo , Várices/metabolismo
6.
Int J Mol Sci ; 23(18)2022 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-36142255

RESUMEN

SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system-IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII-for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFß, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease.


Asunto(s)
COVID-19 , Interleucina-27 , Quimiocina CCL5 , Quimiocina CX3CL1 , Quimiocina CXCL10 , Citocinas , Factor de Crecimiento Epidérmico , Factor 2 de Crecimiento de Fibroblastos , Factor Estimulante de Colonias de Granulocitos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Humanos , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-10 , Subunidad p40 de la Interleucina-12 , Interleucina-15 , Interleucina-17 , Interleucina-18 , Interleucina-6 , Interleucina-8 , Factor Estimulante de Colonias de Macrófagos , SARS-CoV-2 , Factor de Crecimiento Transformador alfa , Factor de Necrosis Tumoral alfa
7.
Medicina (Kaunas) ; 58(2)2022 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-35208577

RESUMEN

Background and Objectives: Coronavirus disease 19 (COVID-19) has emerged as the most devastating syndemic of the 21st century, with worrisome and sustained consequences for the entire society. Despite the relative success of vaccination programs, the global threat of the novel coronavirus SARS-CoV-2 is still present and further efforts are needed for its containment and control. Essential for its control and containment is getting closer to understanding the actual extent of SARS-CoV-2 infections. Material and Methods: We present a model based on the mortality data of Kazakhstan for the estimation of the underlying epidemic dynamic-with both the lag time from infection to death and the infection fatality rate. For the estimation of the actual number of infected individuals in Kazakhstan, we used both back-casting and capture-recapture methods. Results: Our results suggest that despite the increased testing capabilities in Kazakhstan, official case reporting undercounts the number of infections by at least 60%. Even though our count of deaths may be either over or underestimated, our methodology could be a more accurate approach for the following: the estimation of the actual magnitude of the pandemic; aiding the identification of different epidemiological values; and reducing data bias. Conclusions: For optimal epidemiological surveillance and control efforts, our study may lead to an increased awareness of the effect of COVID-19 in this region and globally, and aid in the implementation of more effective screening and diagnostic measures.


Asunto(s)
COVID-19 , Humanos , Kazajstán/epidemiología , Pandemias/prevención & control , SARS-CoV-2
8.
J Cell Mol Med ; 25(16): 7878-7889, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34148301

RESUMEN

Chronic venous insufficiency (CVI), in which blood return to the heart is impaired, is a prevalent condition worldwide. Valve incompetence is a complication of CVI that results in blood reflux, thereby aggravating venous hypertension. While CVI has a complex course and is known to produce alterations in the vein wall, the underlying pathological mechanisms remain unclear. This study examined the presence of DNA damage, pro-inflammatory cytokines and extracellular matrix remodelling in CVI-related valve incompetence. One hundred and ten patients with CVI were reviewed and divided into four groups according to age (<50 and ≥50 years) and a clinical diagnosis of venous reflux indicating venous system valve incompetence (R) (n = 81) or no reflux (NR) (n = 29). In vein specimens (greater saphenous vein) from each group, PARP, IL-17, COL-I, COL-III, MMP-2 and TIMP-2 expression levels were determined by RT-qPCR and immunohistochemistry. The younger patients with valve incompetence showed significantly higher PARP, IL-17, COL-I, COL-III, MMP-2 and reduced TIMP-2 expression levels and a higher COL-I/III ratio. Young CVI patients with venous reflux suffer chronic DNA damage, with consequences at both the local tissue and systemic levels, possibly associated with ageing.


Asunto(s)
Envejecimiento , Daño del ADN , Inflamación/patología , Vena Safena/patología , Insuficiencia Venosa/fisiopatología , Adulto , Anciano , Enfermedad Crónica , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Persona de Mediana Edad , Vena Safena/metabolismo , Insuficiencia Venosa/metabolismo , Adulto Joven
9.
Cells Tissues Organs ; 210(4): 250-259, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34521089

RESUMEN

Immunodeficient mouse models with human skin xenografts have been developed in the past decades to study different conditions of the skin. Features such as follow-up period and size of the graft are of different relevance depending on the purpose of an investigation. The aim of this study is to analyze the different mouse models grafted with human skin. A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to June 2020. Articles describing human skin grafted onto mice were included. Animal models other than mice, skin substitutes, bioengineered skin, postmortem or fetal skin, and duplicated studies were excluded. The mouse strain, origin of human skin, graft dimensions, follow-up of the skin graft, and goals of the study were analyzed. Ninety-one models were included in the final review. Five different applications were found: physiology of the skin (25 models, mean human skin graft size 1.43 cm2 and follow-up 72.92 days), immunology and graft rejection (17 models, mean human skin graft size 1.34 cm2 and follow-up 86 days), carcinogenesis (9 models, mean human skin graft size 1.98 cm2 and follow-up 253 days), skin diseases (25 models, mean human skin graft size 1.55 cm2 and follow-up 86.48 days), and would healing/scars (15 models, mean human skin graft size 2.54 cm2 and follow-up 129 days). The follow-up period was longer in carcinogenesis models (253 ± 233.73 days), and the skin graft size was bigger in wound healing applications (2.54 ± 3.08 cm2). Depending on the research application, different models are suggested. Careful consideration regarding graft size, follow-up, immunosuppression, and costs should be analyzed and compared before choosing any of these mouse models. To our knowledge, this is the first systematic review of mouse models with human skin transplantation.


Asunto(s)
Trasplante de Piel , Piel Artificial , Animales , Humanos , Ratones , Piel , Trasplante Heterólogo , Cicatrización de Heridas
10.
Int J Med Sci ; 18(9): 1921-1934, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33850461

RESUMEN

Chronic venous insufficiency (CVI) is one of the most common vascular pathologies worldwide. One of the risk factors for the development of CVI is aging, which is why it is related to senile changes. The main trigger of the changes that occur in the venous walls in CVI is blood flow reflux, which produces increased hydrostatic pressure, leading to valve incompetence. The cellular response is one of the fundamental processes in vascular diseases, causing the activation of cell signalling pathways such as c-Jun N-terminal kinase (JNK). Metabolic changes and calcifications occur in vascular pathology as a result of pathophysiological processes. The aim of this study was to determine the expression of JNK in venous disease and its relationship with the role played by the molecules involved in the osteogenic processes in venous tissue calcification. This was a cross-sectional study that analyzed the greater saphenous vein wall in 110 patients with (R) and without venous reflux (NR), classified according to age. Histopathological techniques were used and protein expression was analysed using immunohistochemistry techniques for JNK and markers of osteogenesis (RUNX2, osteocalcin (OCN), osteopontin (OPN)). Significantly increased JNK, RUNX2, OCN, OPN and pigment epithelium-derived factor (PEDF) protein expression and the presence of osseous metaplasia and amorphous calcification were observed in younger patients (<50 years) with venous reflux. This study shows for the first time the existence of an osteogenesis process related to the expression of JNK in the venous wall.


Asunto(s)
Envejecimiento/fisiología , Calcinosis/fisiopatología , Proteínas Quinasas JNK Activadas por Mitógenos/análisis , Vena Safena/patología , Insuficiencia Venosa/fisiopatología , Adulto , Anciano , Circulación Sanguínea/fisiología , Calcinosis/patología , Calcinosis/cirugía , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Persona de Mediana Edad , Vena Safena/cirugía , Insuficiencia Venosa/patología , Insuficiencia Venosa/cirugía
11.
Int J Med Sci ; 18(13): 2814-2827, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34220309

RESUMEN

Lower limbs venous insufficiency refers to a wide variety of venous disorders grouped by the term of chronic venous disease (CVD). Hemodynamic and hormonal changes related to pregnancy period, may promote the development of CVD affecting approximately 1 in 3 women. It has been shown that the presence of this condition is associated with damage and placental suffering. Thus, taking IGF-1/PAPP-A/STC-2, inflammatory cytokines production, PI3K/Akt and Wnt/ ß-catenin pathways as a part of the alterations that occurs in the placenta due to CVD, the aim of this study will be to examine the main components of these pathways. Genic and protein expression of PAPP-A, STC-2, IGF-1, IRS-4 Wnt-1, ß-catenin, c-myc, Cyclin D1, IL-4/IL-6 and PI3K/Akt/mTOR pathway will be analysed through RT-qPCR and immunohistochemical techniques in women with CVD (n=62) and pregnant women without this condition (HC) (n=52). PAPP-A, IGF-1, IL-4, IL-6, IRS-4, PI3K, Akt, mTOR, Wnt-1, ß-catenin, c-myc and Cyclin D1 expression were found to be increased in women with CVD, whereas STC-2 were decreased in this group, compared to non-affected women. Our study has demonstrated that IGF-1/PAPP-A/STC-2 axis, PI3K/Akt and Wnt/ß-catenin pathways, along with c-myc, Cyclin D1 and inflammatory cytokines are altered in placenta women with CVD. These results extent the knowledge that CVD is associated to a placenta damage with abnormal tissue environment and cellular regulation.


Asunto(s)
Placenta/patología , Complicaciones Cardiovasculares del Embarazo/inmunología , Insuficiencia Venosa/inmunología , Vía de Señalización Wnt/inmunología , Adulto , Enfermedad Crónica , Femenino , Glicoproteínas/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Placenta/citología , Embarazo , Complicaciones Cardiovasculares del Embarazo/patología , Proteína Plasmática A Asociada al Embarazo/metabolismo , Estudios Prospectivos , Insuficiencia Venosa/patología , Adulto Joven , beta Catenina/metabolismo
12.
J Cell Mol Med ; 24(7): 4157-4170, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32141705

RESUMEN

The development of lower extremity venous insufficiency (VI) during pregnancy has been associated with placental damage. VI is associated with increased oxidative stress in venous wall. We have investigated potential disturbance/dysregulation of the production of reactive oxygen species (ROS) in placenta and its eventual systemic effects through the measurement of malondialdehyde (MDA) plasma levels in women with VI. A total of 62 women with VI and 52 healthy controls (HCs) were studied. Levels of nicotinamide adenine dinucleotide phosphate-oxidase 1 (NOX1), 2 (NOX2), inducible nitric oxide synthase (iNOS), endothelial (eNOS), poly(ADP-ribose) polymerase PARP (PARP) and ERK were measured in placental tissue with immunohistochemistry and RT-qPCR. Plasma and placental levels of MDA were determined by colorimetry at the two study times of 32 weeks of gestation and post-partum. Protein and gene expression levels of NOX1, NOX2, iNOS, PARP and ERK were significantly increased in placentas of VI. eNOS activity was low in both study groups, and there were no significant differences in gene or protein expression levels. Women with VI showed a significant elevation of plasma MDA levels at 32 weeks of gestation, and these levels remained elevated at 32 weeks post-partum. The MDA levels were significantly higher in placentas of women with VI. Placental damage that was found in the women with VI was characterized by overexpression of oxidative stress markers NOX1, NOX2, and iNOS, as well as PARP and ERK. Pregnant women with VI showed systemic increases in oxidative stress markers such as plasma MDA levels. The foetuses of women with VI had a significant decrease in their venous pH as compared to those from HC women. The situation of oxidative stress and cellular damage created in the placenta is in coexpression with the production of a pH acidification.


Asunto(s)
Estrés Oxidativo/genética , Placenta/metabolismo , Complicaciones Hematológicas del Embarazo/genética , Insuficiencia Venosa/genética , Adulto , Femenino , Humanos , Malondialdehído/sangre , NADPH Oxidasa 1/genética , Óxido Nítrico Sintasa de Tipo II/genética , Placenta/irrigación sanguínea , Placenta/patología , Poli(ADP-Ribosa) Polimerasa-1/genética , Poli(ADP-Ribosa) Polimerasas/genética , Embarazo , Complicaciones Hematológicas del Embarazo/sangre , Complicaciones Hematológicas del Embarazo/patología , Especies Reactivas de Oxígeno/sangre , Insuficiencia Venosa/sangre , Insuficiencia Venosa/complicaciones , Insuficiencia Venosa/patología
13.
Int J Med Sci ; 17(17): 2790-2798, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33162806

RESUMEN

Background: Chronic venous disease (CVD) is a prevalent lower limb venous pathology that especially affects women, who also show an increased risk of this disease during pregnancy. Studies have shown significant structural changes in the placentas of women with CVD and several markers of tissue damage have been also described. Patients and Methods: To try to understand the different placental pathologies, research efforts have focused on examining metabolomic profiles as indicators of the repercussions of these vascular disorders. This study examines changes produced in the metabolomic profiles of chorionic villi in the placentas of women with CVD. In a study population of 12 pregnant women, 6 with and 6 without CVD, we compared through mass spectroscopy coupled to ultra-high performance liquid chromatography (UHPLC-MS), 240 metabolites in chorionic villus samples. Results: This study is the first to detect in the placental villi of pregnant women with CVD, modifications in lysophosphatidylcholines and amino acids along with diminished levels of other lipids such as triglycerides, sphingomyelins, and non-esterified omega 9 fatty acids, suggesting a role of these abnormalities in the pathogenesis of CVD. Conclusions: Our findings are a starting point for future studies designed to examine the impacts of CVD on maternal and fetal well-being.


Asunto(s)
Vellosidades Coriónicas/patología , Lisofosfatidilcolinas/análisis , Complicaciones Cardiovasculares del Embarazo/patología , Insuficiencia Venosa/patología , Adulto , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Voluntarios Sanos , Humanos , Lipidómica , Lisofosfatidilcolinas/metabolismo , Embarazo
14.
Int J Mol Sci ; 21(7)2020 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-32260158

RESUMEN

Pregnancy is a period in a woman's life associated with an increased risk of developing lower extremity chronic venous disease (CVD). Pregnancy-associated CVD is associated with changes in placental villi. We investigated angiogenesis and lymphangiogenesis in the placental villi of women with CVD during pregnancy compared with healthy controls with no history of CVD (HC). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). Sixty-two participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expression of CD31, podoplanin (D2-40), Flt-1, and placental growth factor (PIGF) was analysed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. CD31 and D2-40 gene expression was significantly greater in the placental villi of women with CVD, as were the numbers of vessels positive for CD31 and D2-40. Significantly higher gene and protein expression of Flt-1 and PIGF was observed in the placental villi of women with CVD. Histological analysis showed more placental villi with periodic acid of Schiff (PAS)-positive material in women with CVD. Our results show a connection between pregnancy-associated CVD and leading to higher proangiogenic and lymphangiogenic activity in placental villi.


Asunto(s)
Vellosidades Coriónicas/metabolismo , Glicoproteínas de Membrana/genética , Factor de Crecimiento Placentario/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Regulación hacia Arriba , Várices/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Adulto , Biomarcadores/metabolismo , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Edad Materna , Glicoproteínas de Membrana/metabolismo , Factor de Crecimiento Placentario/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Embarazo , Complicaciones Cardiovasculares del Embarazo , Estudios Prospectivos , Várices/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven
15.
Cells Tissues Organs ; 206(4-5): 272-282, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-31203288

RESUMEN

Chronic venous disorder (CVeD), is a disorder in which there is a modification in the conditions of blood return to the heart. The disorder may arise from incompetent valves and the resultant venous reflux (chronic venous insufficiency, CVI). The economic burden of CVeD on health systems is high, and research efforts have sought to elucidate the mechanisms involved as possible therapeutic targets. The mitogen-activated protein kinase (MAPK) enzymes mediate a wide array of physiopathological processes in human tissues. In this family of proteins, extracellular signal-regulated kinase (ERK)1/2 plays a direct role in the cell homeostasis that determines the viability of mammalian tissues. This study sought to examine whether ERK1/2 plays a role in venous reflux. This was a prospective study performed on 56 participants including 11 healthy controls. Of the CVeD patients, 23 had venous reflux with CVI (CVI-R) and 22 had no reflux (NR). Distribution by age was: controls <50 years (n = 4) and ≥50 years (n = 7); NR <50 years (n = 9) and ≥50 years (n = 13); CVI-R <50 years (n = 11) and ≥50 years (n = 12). Great saphenous vein specimens were subjected to gene (real-time polymerase chain reaction, RT-qPCR) and protein (immunohistochemistry, IHC) expression techniques to identify ERK1/2. Data was compared between groups using the Mann Whitney U test. Patients with CVI showed significant gene activation of ERK1/2 protein, and, in those with venous reflux, the expression of this gene was significantly greater. The CVI-R group <50 years showed significantly greater ERK1/2 gene expression than their age-matched controls. Expression patterns were consistent with IHC findings. Our studies suggest that ERK1/2 expression is involved in venous vascular disease.

16.
Xenotransplantation ; 22(6): 476-86, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26602493

RESUMEN

INTRODUCTION: Research into the transplantation of solid organs from animals (xenotransplantation) is generating interest and curiosity given that this could be a way of resolving the shortage in transplant organs. However, the fact is that currently xenotransplantation is far from becoming a clinical practice. OBJECTIVE: To analyse the attitude of medical students from Spanish universities towards the donation of organs from animals and to determine the factors affecting their attitudes. TYPE OF STUDY: A sociological, interdisciplinary, observational and multicentre study in Spain. STUDY POPULATION: Students enrolled on the medical degree in Spain (n = 34 000). SAMPLE SIZE: A sample of 9598 students (a confidence level of 99% and precision of ± 1%) stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ xenotransplantation (PCID-XenoTx RIOS) which was self-administered and completed anonymously. RESULTS: A completion rate of 95.7% (n = 9275) was obtained. If the results of xenotransplantation were as good as in human donation, 81% (n = 7491) would be in favour, 3% (n = 308) against and 16% (n = 1476) undecided. The following variables affected this attitude: sex (P < 0.001); academic year (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); the opinion of one's partner (P < 0.001); the respondent's attitude towards organ donation (P < 0.001); religion (P < 0.001); and participation in altruistic activities (P < 0.001). The following variables persisted in the multivariate analysis: (1) being a female (OR = 1.794; P < 0.001); (2) academic year (OR = 2.487; P < 0.001); (3) having spoken about the issue with one's family (OR = 1.200; P = 0.019); (4) the favourable opinion of one's partner (OR = 1.526; P = 0.028); (5) an attitude in favour of donation (OR = 2.087; P < 0.001); (6) being an atheist/agnostic, (OR = 2.5; P < 0.001); and (7) a belief that one's religion is in favour of transplantation (OR = 1.317; P = 0.005). CONCLUSIONS: Spanish medical students have a favourable attitude towards xenotransplantation. This willingness and interest could be a decisive platform for the development and strengthening of research, both for centres with a pre-clinical xenotransplantation programme and new healthcare centres.


Asunto(s)
Actitud , Donadores Vivos , Estudiantes de Medicina/psicología , Encuestas y Cuestionarios , Obtención de Tejidos y Órganos , Trasplante Heterólogo/estadística & datos numéricos , Humanos , Facultades de Medicina/estadística & datos numéricos , España , Obtención de Tejidos y Órganos/métodos
17.
Histol Histopathol ; 39(1): 35-40, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37057822

RESUMEN

Pancreatic cancer is a malignant neoplasm that, despite its low frequency, has a 5-year survival rate of less than 10%. The study of different histopathological markers has allowed a better understanding of the onset and development of this type of tumor as well as facilitating an approach to clinical variables based on their diagnostic, prognostic, and predictive value. In this sense, the NLRP3 protein of the inflammasome has been shown to be a component of great relevance in the initiation and progression of pancreatic cancer, although the value of this biomarker in patients has not yet been clarified. In this study, we selected 41 patients with pancreatic cancer and followed them for 60 months (5 years), evaluating their NLRP3 expression using immunohistochemical techniques. Furthermore, by performing Kaplan-Meier curves, we evaluated the survival of these patients in relation to their NLRP3 expression. Our results show that a significant percentage of our cohort had high expression of this component (90.74%) and that there is an inverse relationship between the expression of NLRP3 and patient survival. High levels of NLRP3 expression are related to lower survival and worse prognosis in these patients, possibly due to an ineffective immune system response and increased tumor-promoted inflammation. Future studies should be aimed at confirming these results in larger groups and evaluating various clinical strategies based on this knowledge.


Asunto(s)
Inflamasomas , Neoplasias Pancreáticas , Humanos , Biomarcadores , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neoplasias Pancreáticas/patología , Pronóstico
18.
J Cardiovasc Dev Dis ; 10(3)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36975866

RESUMEN

The coronavirus disease 19 (COVID-19) pandemic represented a great challenge for health systems, which had to quickly readapt and dedicate most of their resources to managing this crisis. The postponement of programmed interventions such as coronary revascularization procedures represented a critical issue in the first wave of the COVID-19 pandemic, especially in the hardest-hit countries such as Spain. However, the precise consequences of the delay of coronary revascularizations are not clearly determined. In the present work, interrupted time series (ITS) analysis was used to evaluate the utilization rates and assessment of the risk profiles of patients receiving two main coronary revascularization procedures (percutaneous coronary intervention-PCI and coronary artery bypass graft-CABG) and compared them in the periods before and after March 2020 using the Spanish National Hospital Discharge Database (SNHDD). Our results show that the abrupt reorganization of hospital care that represented the first wave of COVID-19 in March 2020 in Spain led to a reduction in cases, which was accompanied by an increase in the risk profile of CABG patients, but not PCI. On the other hand, the risk profile of both coronary revascularization procedures began before the pandemic, showing a significant temporal trend toward an increase in the risk profile. Future works should be directed to study and validate our results, evaluating other databases, regions, or countries.

19.
Front Bioeng Biotechnol ; 11: 1010679, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37152658

RESUMEN

Introduction: This study aimed to develop an individualized artificial intelligence model to help radiologists assess the severity of COVID-19's effects on patients' lung health. Methods: Data was collected from medical records of 1103 patients diagnosed with COVID-19 using RT- qPCR between March and June 2020, in Hospital Madrid-Group (HM-Group, Spain). By using Convolutional Neural Networks, we determine the effects of COVID-19 in terms of lung area, opacities, and pulmonary air density. We then combine these variables with age and sex in a regression model to assess the severity of these conditions with respect to fatality risk (death or ICU). Results: Our model can predict high effect with an AUC of 0.736. Finally, we compare the performance of the model with respect to six physicians' diagnosis, and test for improvements on physicians' performance when using the prediction algorithm. Discussion: We find that the algorithm outperforms physicians (39.5% less error), and thus, physicians can significantly benefit from the information provided by the algorithm by reducing error by almost 30%.

20.
Histol Histopathol ; : 18700, 2023 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-38230588

RESUMEN

Pancreatic cancer is a highly lethal malignancy with a growing incidence reported worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, which is often diagnosed at advanced stages, making its prognosis and medical management difficult. The identification of histopathological biomarkers has allowed a more precise stratification of pancreatic cancer patients, providing additional information about their prognosis and offering possible therapeutic targets to be explored. The prognostic value of the receptor activator of nuclear factor-kappa B (RANK) and its ligand (RANKL) has been evaluated in breast and prostate tumors, however, their usefulness has not been assessed in pancreatic cancer. In the present work, we analyzed the relationship between the protein expression of RANK and RANKL with the survival of 41 patients with pancreatic cancer followed for 60 months, by performing immunohistochemistry and Kaplan-Meier curves. Our results demonstrate a direct association of high expression levels of RANK and RANKL with poorer survival of pancreatic cancer patients in comparison to those with low/medium and null expression levels of both markers. Further studies should be conducted to explore the carcinogenic role of both components in this type of tumor, as well as additional promising translational uses.

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