Decreased survival in patients with pancreatic cancer may be associated with an increase in histopathological expression of inflammasome marker NLRP3.

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.

Advanced Hydrogel-Based Strategies for Enhanced Bone and Cartilage Regeneration: A Comprehensive Review.

Bone and cartilage tissue play multiple roles in the organism, including kinematic support, protection of organs, and hematopoiesis. Bone and, above all, cartilaginous tissues present an inherently limited capacity for self-regeneration. The increasing prevalence of disorders affecting these crucial tissues, such as bone fractures, bone metastases, osteoporosis, or osteoarthritis, underscores the urgent imperative to investigate therapeutic strategies capable of effectively addressing the challenges associated with their degeneration and damage. In this context, the emerging field of tissue engineering and regenerative medicine (TERM) has made important contributions through the development of advanced hydrogels. These crosslinked three-dimensional networks can retain substantial amounts of water, thus mimicking the natural extracellular matrix (ECM). Hydrogels exhibit exceptional biocompatibility, customizable mechanical properties, and the ability to encapsulate bioactive molecules and cells. In addition, they can be meticulously tailored to the specific needs of each patient, providing a promising alternative to conventional surgical procedures and reducing the risk of subsequent adverse reactions. However, some issues need to be addressed, such as lack of mechanical strength, inconsistent properties, and low-cell viability. This review describes the structure and regeneration of bone and cartilage tissue. Then, we present an overview of hydrogels, including their classification, synthesis, and biomedical applications. Following this, we review the most relevant and recent advanced hydrogels in TERM for bone and cartilage tissue regeneration.

Unraveling the New Perspectives on Antimicrobial Hydrogels: State-of-the-Art and Translational Applications.

The growing impact of infections and the rapid emergence of antibiotic resistance represent a public health concern worldwide. The exponential development in the field of biomaterials and its multiple applications can offer a solution to the problems that derive from these situations. In this sense, antimicrobial hydrogels represent a promising opportunity with multiple translational expectations in the medical management of infectious diseases due to their unique physicochemical and biological properties as well as for drug delivery in specific areas. Hydrogels are three-dimensional cross-linked networks of hydrophilic polymers that can absorb and retain large amounts of water or biological fluids. Moreover, antimicrobial hydrogels (AMH) present good biocompatibility, low toxicity, availability, viscoelasticity, biodegradability, and antimicrobial properties. In the present review, we collect and discuss the most promising strategies in the development of AMH, which are divided into hydrogels with inherent antimicrobial activity and antimicrobial agent-loaded hydrogels based on their composition. Then, we present an overview of the main translational applications: wound healing, tissue engineering and regeneration, drug delivery systems, contact lenses, 3D printing, biosensing, and water purification.

The Use of Prebiotics from Pregnancy and Its Complications: Health for Mother and Offspring-A Narrative Review.

Pregnancy involves a metabolic reprogramming that includes changes in the gut microbiota composition in women. Evidence shows that maternal dysbiosis is linked to neonatal dysbiosis, and this factor can determine health status in adulthood. Although there is little literature available on this topic, high heterogeneity is a limitation when examining nutritional interventions. Information has been gathered to contrast the benefits of prebiotic usage, specifically in pregnancy, in its possible complications and in newborns' gut microbiota development. The objective pursued in this brief narrative review is to provide a clear summary of relevant content when searching with regard to the use of prebiotics in pregnancy, the effects in prenatal and postnatal periods, and to help in clinical decision-making in pregnancy management and lactation. A search has found that the nutritional status of the pregnant mother is key for the earliest microbial colonization in newborns, and thus intervention programs from pregnancy could assure better outcomes in both the mother and offspring. In this sense, prebiotics (administered to mothers who breastfeed or provided in formula milk) are feasible and cost-effective elements that can prevent allergies, colic, and other maladies in newborns.

Women with psychotic episodes during pregnancy show increased markers of placental damage with Tenney-Parker changes.

Psychosis is a hazardous and functionally disruptive psychiatric condition which may affect women in pregnancy, entailing negative consequences for maternofetal well-being. The precise pathophysiological basis and consequences of a psychotic episode in pregnancy remain to be further elucidated. The placenta is a pivotal tissue with many functions in the gestational period, critically influencing the fate and development of pregnancy. Although detrimental alterations have been observed in women undergoing severe psychiatric disorders in pregnancy, there are little studies evaluating the consequences of suffering from a psychotic episode in the placental tissue In this work, we have evaluated the histopathological consequences of a first episode of psychosis in pregnancy (FE-PW; N=22) and compare them with healthy pregnant women (HC-PW; N=20) by using histological, immunohistochemical and gene expression techniques. Our results define that the placental tissue of FE-PW display an increase in the number of placental villi, bridges, syncytial knots and syncytial knots/villi. Besides, we have also observed an enhanced gene and protein expression in FE-PW of the hypoxic marker HIF-1α, together with the apoptotic markers BAX and Bcl-2. To our knowledge, this is the first study demonstrating significant histopathological changes in the placenta of women suffering a new-onset psychotic episode in pregnancy. Further studies should be aimed at deepening the knowledge about the pernicious effects of psychosis in the maternofetal tissues, as well as the potential implications of these alterations.

Evidence of Increased Oxidative Stress in the Placental Tissue of Women Who Suffered an Episode of Psychosis during Pregnancy.

Psychosis is a complex clinical syndrome resulting in a loss of contact with reality and alterations in behavior and sensorial and motor functions. Although the onset of psychosis can be related to any medical condition, most cases of psychosis are not fully understood. Psychosis may manifest for the first time during pregnancy, which is detrimental to maternofetal well-being. The impact of having a first episode of psychosis during pregnancy on the placenta has not yet been explored. Oxidative stress is thought to take part in the etiopathogenesis of this complex disorder, and this condition can also affect the placenta as it is highly sensitive to changes in the maternal environment. In this sense, the aim of the present work was to study the gene and protein expression through RT-qPCR and immunohistochemistry, respectively, of oxidative stress markers (NOX-1, NOX-2, iNOS, eNOS and PARP) in the placental tissue of women who underwent a first episode of psychosis during pregnancy (FE-PW) in comparison to healthy pregnant women. Our results showed augmented gene and protein expression of NOX-1, NOX-2, iNOS and PARP in the placental tissue of FE-PW. For the first time, we demonstrated that oxidative stress may have an important pathophysiological role in this tissue, aiding in explaining the impact of psychosis on pregnancy and the need for future studies in this field to guide better clinical management of these patients.

The Placentas of Women Who Suffer an Episode of Psychosis during Pregnancy Have Increased Lipid Peroxidation with Evidence of Ferroptosis.

Psychosis is a complex entity characterized by psychological, behavioral, and motor alterations resulting in a loss of contact with reality. Although it is not common, pregnancy can be a period in which a first episode of psychosis can manifest, entailing detrimental consequences for both the fetus and the mother. The pathophysiological basis and study of maternofetal wellbeing need to be further elucidated. Lipid peroxidation and ferroptosis are two phenomena that are tightly linked to the placental dysfunction commonly observed in different complications of pregnancy. In the present study, we aim to explore the histopathological and gene expression of different markers of lipid peroxidation and ferroptosis in the placentas of women who underwent a first episode of psychosis during their pregnancy (n = 22). The aim is to then compare them with healthy pregnant women (n = 20). In order to achieve this goal, iron deposits were studied using Prussian Blue staining. In addition, the protein/gene expression of a transferrin receptor (TFRC), as well as an acyl-CoA synthetase long-chain family member 4 (ACSL-4), arachidonate lipoxygenase-5 (ALOX-5), malondialdehyde (MDA), and glutathione peroxidase 4 (GPX4) were all analyzed through gene expression (RT-qPCR) and immunohistochemical procedures. Our results demonstrate an increased presence of iron deposits that are accompanied by a further expression of TFRC, ACSL-4, ALOX-5, MDA, and GPX4-all of which are observed in the placenta tissue of women who have suffered from a first episode of psychosis. Therefore, in our study, a histopathological increase in lipid peroxidation and ferroptosis markers in the affected women is suggested. However, further studies are needed in order to validate our results and to establish possible consequences for the reported alterations.

Towards the Search for Potential Biomarkers in Osteosarcoma: State-of-the-Art and Translational Expectations.

Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause of malignant bone neoplasm in children, adolescents and young adults under 20 years of age. It also presents another peak of incidence in people over 50 years of age and is associated with rheumatic diseases. Numerous environmental risk factors, such as bone diseases, genetics and a history of previous neoplasms, have been widely described in the literature, which allows monitoring a certain group of patients. Diagnosis requires numerous imaging tests that make it possible to stratify both the local involvement of the disease and its distant spread, which ominously determines the prognosis. Thanks to various clinical trials, the usefulness of different chemotherapy regimens, radiotherapy and surgical techniques with radical intent has now been demonstrated; these represent improvements in both prognosis and therapeutic approaches. Osteosarcoma patients should be evaluated in reference centres by multidisciplinary committees with extensive experience in proper management. Although numerous genetic and rheumatological diseases and risk factors have been described, the use of serological, genetic or other biomarkers has been limited in clinical practice compared to other neoplasms. This limits both the initial follow-up of these patients and screening in populations at risk. In addition, we cannot forget that the diagnosis is mainly based on the direct biopsy of the lesion and imaging tests, which illustrates the need to study new diagnostic alternatives. Therefore, the purpose of this study is to review the natural history of the disease and describe the main biomarkers, explaining their clinical uses, prognosis and limitations.

Irregular Expression of Cellular Stress Response Markers in the Placenta of Women with Chronic Venous Disease.

Pregnancy comprises a period in a woman's life in which the circulatory system is subjected to hemodynamical and biochemical changes. During this period, while restructuring blood vessels and exchanging maternal-fetal products there is an increased risk of developing chronic venous disease (CVD), which may have an echo in life after childbirth for both mother and child. Previously, we investigated that pregnancy-associated CVD involves changes in placental architecture at angiogenesis, lymphangiogenesis and villi morphology compared with healthy controls (HC) with no history of CVD. We aimed to more deeply investigate the oxidative stress response in placenta from women with CVD versus HC through several markers (NRF2, KEAP1, CUL3, GSK-3ß). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). A total of 62 participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expressions of NRF2, KEAP1, CUL3, GSK-3ß were analyzed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. Nrf2 gene and protein expression was significantly greater in placental villi of women with CVD, while Keap1, CUL-3 and GSK-3ß gene and protein expressions were significantly lower. Our results defined an aberrant gene and protein expression of Nrf2 and some of their main regulators Keap1, CUL-3 and GSK-3 ß in the placenta of women with CVD, which could be an indicator of an oxidative environment observed in this tissue.

Venous Wall of Patients with Chronic Venous Disease Exhibits a Glycolytic Phenotype.

Chronic venous disease (CVeD) is a rising medical condition characterized by a broad spectrum of disorders in the venous system. Varicose veins (VVs) represent a frequent clinical manifestation of CVeD, particularly in the lower limbs. Prior histopathological studies have defined a set of alterations observed in the venous wall of patients with VVs, affecting their structure and behavior. Metabolic changes in the veins appear to be a critical biological mechanism aiding our understanding of the pathogenesis of CVeD. In this sense, previous studies have identified a potential role of a glycolytic phenotype in the development of different vascular disorders; however, its precise role in CVeD remains to be fully explored. Thus, the aim of the present study was to analyze the gene and protein expression of glucose transporter 1 (GLUT-1) and the glycolytic enzymes PGK-1, ALD, GA3PDH and LDH in the VVs of patients with CVeD (n = 35) in comparison to those expressed in healthy subjects. Our results display enhanced gene and protein expression of GLUT-1, PGK-1, ALD, GA3PDH and LDH in patients with CVeD, suggesting a glycolytic switch of the venous tissue. Greater understanding of the impact of this glycolytic switch in patients with CVeD is required to define a possible pathophysiological role or therapeutic implications of these changes.

Chronic Venous Disease during Pregnancy Causes a Systematic Increase in Maternal and Fetal Proinflammatory Markers.

Chronic venous disease (CVD) is a common vascular disorder characterized by increased venous hypertension and insufficient venous return from the lower limbs. Pregnancy is a high-risk situation for developing CVD. Approximately a third of the women will develop this condition during pregnancy, and similarly to arterial hypertensive disorders, previous evidence has described a plethora of alterations in placental structure and function in women with pregnancy-induced CVD. It is widely known that arterial-induced placenta dysfunction is accompanied by an important immune system alteration along with increased inflammatory markers, which may provide detrimental consequences for the women and their offspring. However, to our knowledge, there are still no data collected regarding cytokine profiling in women with pregnancy-induced CVD. Thus, the aim of the present work was to examine cytokine signatures in the serum of pregnant women (PW) with CVD and their newborns (NB). This study was conducted through a multiplex technique in 62 PW with pregnancy-induced CVD in comparison to 52 PW without CVD (HC) as well as their NB. Our results show significant alterations in a broad spectrum of inflammatory cytokines (IL-6, IL-12, TNF-α, IL-10, IL-13, IL-2, IL-7, IFN-γ, IL-4, IL-5, IL-21, IL-23, GM-CSF, chemokines (fractalkine), MIP-3α, and MIP-1ß). Overall, we demonstrate that pregnancy-induced CVD is associated with a proinflammatory environment, therefore highlighting the potentially alarming consequences of this condition for maternal and fetal wellbeing.

Infecciones por hantavirus y por el virus de la coriomeningitis linfocitaria / No disponible

Los virus transmitidos al hombre a partir de roedores se incluyen en dos géneros: hantavirus y arenavirus. Los hantavirus y arenavirus pueden transmitirse al hombre a partir de los roedores infectados; los animales infectados eliminan los virus por saliva, orina y heces. El ser humano adquiere la infección por la inhalación de aerosoles de materiales contaminados, y a través heridas; el virus de la coriomeningitis linfocitaria(VCML) puede transmitirse por vía vertical y es un virus teratógeno. Los hantavirus pueden causar varios cuadros clínicos: fiebre hemorrágica con síndrome renal, con formas graves, moderadas y leves, y el síndrome pulmonar por hantavirus. Los virus del género arenavirus, con la excepción del VCML, están implicados en la etiología de las fiebres hemorrágicas. Las infecciones por el VCML son habitualmente asintomáticas, pero cuando este virus causa enfermedad puede provocar meningitis aséptica omeningoencefalitis; la infección fetal puede causar abortos o alteraciones congénitas. Carecemos de tratamiento específico para las infecciones por hantavirus y arenavirus. La única forma de prevenir estas enfermedades es reducir el contacto humano con roedores infectados y sus fluidos (AU)

Rodents virus transmitted to human are included in two genus: hantavirus and arenavirus. Hantavirus and arenavirus can be transmitted to people from infected rodents; infected animals eliminate virus by saliva, urine and feces. Human acquires infection by aerosols inhalation of contaminated materials, and by wounds; vertical transmission can occur with lymphocytic choriomeningitis virus (LCMV) and this virus is a fetalteratogen. Hantavirus can provoke several clinical pictures: hemorrhagic fever with renal syndrome with severe, moderate and slight forms, and hantavirus pulmonary syndrome. Viruses of arenavirus genus, with LCMV exception, are involved in the etiology of the hemorrhagic fevers. Habitually LCMV infections are asymptomatic, but when this virus causes disease it can provoke aseptic meningitis or meningoencephalitis; the foetal infection can cause abortions or congenital alterations. We lack specific treatment for hantavirus and arenavirus infections. To reduce the human contact with infected rodents and its fluids is the only way for the prevention of these diseases (AU)