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Abstract Background Benzodiazepines are frequently prescribed drugs; however, their prolonged use can lead to tolerance, dependence, and other adverse effects. Despite these risks, long-term use remains common, presenting a public health concern. This study aims to explore the beliefs and opinions held by the public regarding benzodiazepines, as understanding these perspectives may provide insights into their usage patterns. Methods We collected public tweets published in English between January 1, 2019, and October 31, 2020, that mentioned benzodiazepines. The content of each tweet and the characteristics of the users were analyzed using a mixed-method approach, including manual analysis and semi-supervised machine learning. Results Over half of the Twitter users highlighted the efficacy of benzodiazepines, with minimal discussion of their side effects. The most active participants in these conversations were patients and their families, with health professionals and institutions being notably absent. Additionally, the drugs most frequently mentioned corresponded with those most commonly prescribed by healthcare professionals. Conclusions Social media platforms offer valuable insights into users’ experiences and opinions regarding medications. Notably, the sentiment towards benzodiazepines is predominantly positive, with users viewing them as effective while rarely mentioning side effects. This analysis underscores the need to educate physicians, patients, and their families about the potential risks associated with benzodiazepine use and to promote clinical guidelines that support the proper management of these medications. Clinical trial number Not applicable.

IntroductionDementia comprise a broad spectrum of cognitive declines affecting 47 million people worldwide, with numbers projected to reach 131 million by 2050. Predominantly associated with older adults, dementia can also impact younger individuals, having a significant impact on daily functioning of the affected patients, relatives, caregivers and the socioeconomic system. Recent research underscores the utility of social media, particularly X (previously designed as Twitter), in understanding public perceptions and sentiments related to neurological disorders. Despite some initial studies have explored social perceptions of dementia in X, broader and deeper analysis of this condition is still warranted.Materials and methodsIn this retrospective study, we collected and examined all tweets posted in English or Spanish from 2007 to 2023 that mentioned dementia and compare the information with other highly representative neurological disorders like migraines, epilepsy, multiple sclerosis, spinal cord injury, or Parkinson's disease. We developed a codebook to analyze tweets, classifying them by themes such as trivialization, treatment perceptions, and etiopathogenesis. Manually categorized tweets trained machine learning models, BERTWEET for English and BETO for Spanish, which then classified larger datasets with high accuracy. Statistical analysis, including ANOVA, Kruskal-Wallis, and chi-square tests, was conducted to explore linguistic and cultural differences in perceptions of neurological disorders, with results visualized.ResultsOur study reveals that dementia is by far the most frequently discussed neurological disorder on X. Likewise, this condition appears to be the most trivialized neurological disorder in Spanish tweets and the second most trivialized in English tweets, with notable differences in geolocation data. Additionally, we found significant differences in perceptions of dementia treatment and associated sentiments between Spanish and English tweets. Furthermore, our study identified varying perceptions of medical content (etiology) and non-medical content (positive/negative experiences and aid requests) related to dementia and other neurological disorders, unveiling a complex landscape of these topics on X.ConclusionsThis study explores the importance of X as a social platform for addressing various critical issues related to dementia, comparing it with other neurological disorders in English and Spanish tweets. Future research could further investigate the valuable role of social media in understanding public perceptions and needs regarding dementia and neurological disorders among X users.

Major depressive disorder (MDD) is a complex, multifactorial disorder of rising prevalence and incidence worldwide. Nearly, 280 million of people suffer from this leading cause of disability in the world. Moreover, patients with this condition are frequently co-affected by essential nutrient deficiency. The typical scene with stress and hustle in developed countries tends to be accompanied by eating disorders implying overnutrition from high-carbohydrates and high-fat diets with low micronutrients intake. In fact, currently, coronavirus disease 2019 (COVID-19) pandemic has drawn more attention to this underdiagnosed condition, besides the importance of the nutritional status in shaping immunomodulation, in which minerals, vitamins, or omega 3 polyunsaturated fatty acids (ω-3 PUFA) play an important role. The awareness of nutritional assessment is greater and greater in the patients with depression since antidepressant treatments have such a significant probability of failing. As diet is considered a crucial environmental factor, underlying epigenetic mechanisms that experience an adaptation or consequence on their signaling and expression mechanisms are reviewed. In this study, we included metabolic changes derived from an impairment in cellular processes due to lacking some essential nutrients in diet and therefore in the organism. Finally, aspects related to nutritional interventions and recommendations are also addressed.

Major Depressive Disorder (MDD) is a growing disabling condition affecting around 280 million people worldwide. This complex entity is the result of the interplay between biological, psychological, and sociocultural factors, and compelling evidence suggests that MDD can be considered a disease that occurs as a consequence of an evolutionary mismatch and unhealthy lifestyle habits. In this context, diet is one of the core pillars of health, influencing multiple biological processes in the brain and the entire body. It seems that there is a bidirectional relationship between MDD and malnutrition, and depressed individuals often lack certain critical nutrients along with an aberrant dietary pattern. Thus, dietary interventions are one of the most promising tools to explore in the field of MDD, as there are a specific group of nutrients (i.e., omega 3, vitamins, polyphenols, and caffeine), foods (fish, nuts, seeds fruits, vegetables, coffee/tea, and fermented products) or dietary supplements (such as S-adenosylmethionine, acetyl carnitine, creatine, amino acids, etc.), which are being currently studied. Likewise, the entire nutritional context and the dietary pattern seem to be another potential area of study, and some strategies such as the Mediterranean diet have demonstrated some relevant benefits in patients with MDD; although, further efforts are still needed. In the present work, we will explore the state-of-the-art diet in the prevention and clinical support of MDD, focusing on the biological properties of its main nutrients, foods, and dietary patterns and their possible implications for these patients.

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.

Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks’ gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and β-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.

The connection between physical activity and cognitive function has become a focus of attention in educational research in recent years. Regular exercise has been shown to have significant positive effects on physical health, but it also appears to have a significant impact on cognitive function and academic performance. Of all the exercise modalities, resistance training has drawn interest for its ability to improve cerebral abilities in addition to physical well-being. However, there is limited available knowledge exploring the relationship between resistance training regimens and academic performance. This narrative review aims to investigate the underlying mechanisms linking resistance training to academic performance. Firstly, we will examine the biological mechanisms and psychosocial links that potentially connect resistance training to academic performance to find and describe the different mechanisms by which resistance training improves academic performance. In the next part of the work, we delve into the existing observational and intervention studies that have explored the relationship between resistance training and academic performance. Lastly, we provide practical recommendations for including resistance training in institutional education settings, emphasizing the need of dispelling myths and addressing barriers to increase participation as well as the relevance of considering key training variables and adaptation of protocols to developmental stages, always guided by a properly trained professional. Overall, the available evidence supports that resistance training provides potential benefits to the academic performance of youth students with many biological and psychosocial factors that explain this relationship. However, most of the studies are observational, and broader interventional studies are needed to understand and maximize the benefits of this type of physical exercise.

IntroductionCocaine abuse represents a major public health concern. The social perception of cocaine has been changing over the decades, a phenomenon closely tied to its patterns of use and abuse. Twitter is a valuable tool to understand the status of drug use and abuse globally. However, no specific studies discussing cocaine have been conducted on this platform.Methods111,508 English and Spanish tweets containing “cocaine” from 2018 to 2022 were analyzed. 550 were manually studied, and the largest subset underwent automated classification. Then, tweets related to cocaine were analyzed to examine their content, types of Twitter users, usage patterns, health effects, and personal experiences. Geolocation data was also considered to understand regional differences.ResultsA total of 71,844 classifiable tweets were obtained. Among these, 15.95% of users discussed the harm of cocaine consumption to health. Media outlets had the highest number of tweets (35.11%) and the most frequent theme was social/political denunciation (67.88%). Regarding the experience related to consumption, there are more tweets with a negative sentiment. The 9.03% of tweets explicitly mention frequent use of the drug. The continent with the highest number of tweets was America (55.44% of the total).DiscussionThe findings underscore the significance of cocaine as a current social and political issue, with a predominant focus on political and social denunciation in the majority of tweets. Notably, the study reveals a concentration of tweets from the United States and South American countries, reflecting the high prevalence of cocaine-related disorders and overdose cases in these regions. Alarmingly, the study highlights the trivialization of cocaine consumption on Twitter, accompanied by a misleading promotion of its health benefits, emphasizing the urgent need for targeted interventions and antidrug content on social media platforms. Finally, the unexpected advocacy for cocaine by healthcare professionals raises concerns about potential drug abuse within this demographic, warranting further investigation.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal tumor with increasing incidence, presenting numerous clinical challenges. The histopathological examination of novel, unexplored biomarkers offers a promising avenue for research, with significant translational potential for improving patient outcomes. In this study, we evaluated the prognostic significance of ferroptosis markers (TFRC, ALOX-5, ACSL-4, and GPX-4), circadian clock regulators (CLOCK, BMAL1, PER1, PER2), and KLOTHO in a retrospective cohort of 41 patients deceased by PDAC. Immunohistochemical techniques (IHC) and multiple statistical analyses (Kaplan–Meier curves, correlograms, and multinomial linear regression models) were performed. Our findings reveal that ferroptosis markers are directly associated with PDAC mortality, while circadian regulators and KLOTHO are inversely associated. Notably, TFRC emerged as the strongest risk marker associated with mortality (HR = 35.905), whereas CLOCK was identified as the most significant protective marker (HR = 0.01832). Correlation analyses indicate that ferroptosis markers are positively correlated with each other, as are circadian regulators, which also positively correlate with KLOTHO expression. In contrast, KLOTHO and circadian regulators exhibit inverse correlations with ferroptosis markers. Among the clinical variables examined, only the presence of chronic pathologies showed an association with the expression patterns of several proteins studied. These findings underscore the complexity of PDAC pathogenesis and highlight the need for further research into the specific molecular mechanisms driving disease progression.

Abstract Spinal cord injury (SCI) is a devastating and disabling medical condition generally caused by a traumatic event (primary injury). This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage (secondary injury). The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI, explaining the progression and detrimental consequences related to this condition. Psychoneuroimmunoendocrinology (PNIE) is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism, considering the mind and the body as a whole. The initial traumatic event and the consequent neurological disruption trigger immune, endocrine, and multisystem dysfunction, which in turn affect the patient’s psyche and well-being. In the present review, we will explore the most important local and systemic consequences of SCI from a PNIE perspective, defining the changes occurring in each system and how all these mechanisms are interconnected. Finally, potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

Vascular diseases pose major health challenges, and understanding their underlying molecular mechanisms is essential to advance therapeutic interventions. Cellular senescence, a hallmark of aging, is a cellular state characterized by cell-cycle arrest, a senescence-associated secretory phenotype macromolecular damage, and metabolic dysregulation. Vascular senescence has been demonstrated to play a key role in different vascular diseases, such as atherosclerosis, peripheral arterial disease, hypertension, stroke, diabetes, chronic venous disease, and venous ulcers. Even though cellular senescence was first described in 1961, significant gaps persist in comprehending the epigenetic mechanisms driving vascular senescence and its subsequent inflammatory response. Through a comprehensive analysis, we aim to elucidate these knowledge gaps by exploring the network of epigenetic alterations that contribute to vascular senescence. In addition, we describe the consequent inflammatory cascades triggered by these epigenetic modifications. Finally, we explore translational applications involving biomarkers of vascular senescence and the emerging field of senotherapy targeting this biological process.

Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC—apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain—caspase 1, caspase 5, caspase 8, and interleukin 1β) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations.

Preeclampsia, a serious and potentially life-threatening medical complication occurring during pregnancy, is characterized by hypertension and often accompanied by proteinuria and multiorgan dysfunction. It is classified into two subtypes based on the timing of diagnosis: early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less severe and exhibiting distinct pathophysiological characteristics, LO-PE is more prevalent than EO-PE, although both conditions have a significant impact on placental health. Previous research indicates that different pathophysiological events within the placenta may contribute to the development of preeclampsia across multiple pathways. In our experimental study, we investigated markers of oxidative stress, ferroptosis, and lipid peroxidation pathways in placental tissue samples obtained from women with LO-PE (n = 68) compared to healthy control pregnant women (HC, n = 43). Through a comprehensive analysis, we observed an upregulation of specific molecules associated with these pathways, including NADPH oxidase 1 (NOX-1), NADPH oxidase 2 (NOX-2), transferrin receptor protein 1 (TFRC), arachidonate 5-lipoxygenase (ALOX-5), acyl-CoA synthetase long-chain family member 4 (ACSL-4), glutathione peroxidase 4 (GPX4) and malondialdehyde (MDA) in women with LO-PE. Furthermore, increased ferric tissue deposition (Fe3+) was observed in placenta samples stained with Perls’ Prussian blue. The assessment involved gene and protein expression analyses conducted through RT-qPCR experiments and immunohistochemistry assays. Our findings underscore the heightened activation of inflammatory pathways in LO-PE compared to HC, highlighting the pathological mechanisms underlying this pregnancy disorder.

Neurological disorders represent the primary cause of disability and the secondary cause of mortality globally. The incidence and prevalence of the most notable neurological disorders are growing rapidly. Considering their social and public perception by using different platforms like Twitter can have a huge impact on the patients, relatives, caregivers and professionals involved in the multidisciplinary management of neurological disorders. In this study, we collected and analyzed all tweets posted in English or Spanish, between 2007 and 2023, referring to headache disorders, dementia, epilepsy, multiple sclerosis, spinal cord injury or Parkinson’s disease using a search engine that has access to 100% of the publicly available tweets. The aim of our work was to deepen our understanding of the public perception of neurological disorders by addressing three major objectives: (1) analyzing the number and temporal evolution of both English and Spanish tweets discussing the most notable neurological disorders (dementias, Parkinson’s disease, multiple sclerosis, spinal cord injury, epilepsy and headache disorders); (2) determining the main thematic content of the Twitter posts and the interest they generated temporally by using topic modeling; and (3) analyzing the sentiments associated with the different topics that were previously collected. Our results show that dementias were, by far, the most common neurological disorders whose treatment was discussed on Twitter, and that the most discussed topics in the tweets included the impact of neurological diseases on patients and relatives, claims to increase public awareness, social support and research, activities to ameliorate disease development and existent/potential treatments or approaches to neurological disorders, with a significant number of the tweets showing negative emotions like fear, anger and sadness, and some also demonstrating positive emotions like joy. Thus, our study shows that not only is Twitter an important and active platform implicated in the dissemination and normalization of neurological disorders, but also that the number of tweets discussing these different entities is quite inequitable, and that a greater intervention and more accurate dissemination of information by different figures and professionals on social media could help to convey a better understanding of the current state, and to project the future state, of neurological diseases for the general public.

BackgroundParacetamol, codeine, and tramadol are commonly used to manage mild pain, and their availability without prescription or medical consultation raises concerns about potential opioid addiction. ObjectiveThis study aims to explore the perceptions and experiences of Twitter users concerning these drugs. MethodsWe analyzed the tweets in English or Spanish mentioning paracetamol, tramadol, or codeine posted between January 2019 and December 2020. Out of 152,056 tweets collected, 49,462 were excluded. The content was categorized using a codebook, distinguishing user types (patients, health care professionals, and institutions), and classifying medical content based on efficacy and adverse effects. Scientific accuracy and nonmedical content themes (commercial, economic, solidarity, and trivialization) were also assessed. A total of 1000 tweets for each drug were manually classified to train, test, and validate machine learning classifiers. ResultsOf classifiable tweets, 42,840 mentioned paracetamol and 42,131 mentioned weak opioids (tramadol or codeine). Patients accounted for 73.10% (60,771/83,129) of the tweets, while health care professionals and institutions received the highest like-tweet and tweet-retweet ratios. Medical content distribution significantly differed for each drug (P

BackgroundOpioids are used for the treatment of refractory pain, but their inappropriate use has detrimental consequences for health. Understanding the current experiences and perceptions of patients in a spontaneous and colloquial environment regarding the key drugs involved in the opioid crisis is of utmost significance. ObjectiveThe study aims to analyze Twitter content related to opioids, with objectives including characterizing users participating in these conversations, identifying prevalent topics and gauging public perception, assessing opinions on drug efficacy and tolerability, and detecting discussions related to drug dispensing, prescription, or acquisition. MethodsIn this cross-sectional study, we gathered public tweets concerning major opioids posted in English or Spanish between January 1, 2019, and December 31, 2020. A total of 256,218 tweets were collected. Approximately 27% (69,222/256,218) were excluded. Subsequently, 7000 tweets were subjected to manual analysis based on a codebook developed by the researchers. The remaining databases underwent analysis using machine learning classifiers. In the codebook, the type of user was the initial classification domain. We differentiated between patients, family members and friends, health care professionals, and institutions. Next, a distinction was made between medical and nonmedical content. If it was medical in nature, we classified it according to whether it referred to the drug’s efficacy or adverse effects. In nonmedical content tweets, we analyzed whether the content referred to management issues (eg, pharmacy dispensation, medical appointment prescriptions, commercial advertisements, or legal aspects) or the trivialization of the drug. ResultsAmong the entire array of scrutinized pharmaceuticals, fentanyl emerged as the predominant subject, featuring in 27% (39,997/148,335 posts) of the tweets. Concerning user categorization, roughly 70% (101,259/148,335) were classified as patients. Nevertheless, tweets posted by health care professionals obtained the highest number of retweets (37/16,956, 0.2% of their posts received over 100 retweets). We found statistically significant differences in the distribution concerning efficacy and side effects among distinct drug categories (P

Inflammasomes are multiprotein signaling platforms in the cytosol that senses exogenous and endogenous danger signals and respond with the maturation and secretion of IL-1β and IL-18 and pyroptosis to induce inflammation and protect the host. The inflammasome best studied is the Nucleotide-binding oligomerization domain, leucine-rich repeat-containing family pyrin domain containing 3 (NLRP3) inflammasome. It is activated in a two-step process: the priming and the activation, leading to sensor NLRP3 oligomerization and recruitment of both adaptor ASC and executioner pro-caspase 1, which is activated by cleavage. Moreover, NLRP3 inflammasome activation is regulated by posttranslational modifications, including ubiquitination/deubiquitination, phosphorylation/dephosphorylation, acetylation/deacetylation, SUMOylation and nitrosylation, and interaction with NLPR3 protein binding partners. Moreover, the connection between it and metabolism is receiving increasing attention in this field. In this review, we present the structure, functions, activation, and regulation of NLRP3, with special emphasis on regulation by mitochondrial dysfunction-mtROS production and metabolic signals, i.e., metabolites as well as enzymes. By understanding the regulation of NLRP3 inflammasome activation, specific inhibitors can be rationally designed for the treatment and prevention of various immune- or metabolic-based diseases. Lastly, we review current NLRP3 inflammasome inhibitors and their mechanism of action.

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43− and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.

Preeclampsia (PE) is a serious hypertensive disorder affecting 4–5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, being less severe than the early-onset PE (EO-PE) variant, although both entities have a notable impact on the placenta. Despite the fact that most studies have focused on EO-PE, LO-PE does not deserve less attention since its prevalence is much higher and little is known about the role of the placenta in this pathology. Via RT-qPCR and immunohistochemistry methods, we measured the gene and protein expressions of several macroautophagy markers in the chorionic villi of placentas from women who underwent LO-PE (n = 68) and compared them to normal pregnancies (n = 43). We observed a markedly distinct expression pattern, noticing a significant drop in NUP62 expression and a considerable rise in the gene and protein expressions of ULK1, ATG9A, LC3, ATG5, STX-17, and LAMP-1 in the placentas of women with LO-PE. A major induction of autophagic processes was found in the placental tissue of patients with LO-PE. Abnormal signaling expression of these molecular patterns in this condition aids in the understanding of the complexity of pathophysiology and proposes biomarkers for the clinical management of these patients.

Breast cancer is a prevalent malignancy in the present day, particularly affecting women as one of the most common forms of cancer. A significant portion of patients initially present with localized disease, for which curative treatments are pursued. Conversely, another substantial segment is diagnosed with metastatic disease, which has a worse prognosis. Recent years have witnessed a profound transformation in the prognosis for this latter group, primarily due to the discovery of various biomarkers and the emergence of targeted therapies. These biomarkers, encompassing serological, histological, and genetic indicators, have demonstrated their value across multiple aspects of breast cancer management. They play crucial roles in initial diagnosis, aiding in the detection of relapses during follow-up, guiding the application of targeted treatments, and offering valuable insights for prognostic stratification, especially for highly aggressive tumor types. Molecular markers have now become the keystone of metastatic breast cancer diagnosis, given the diverse array of chemotherapy options and treatment modalities available. These markers signify a transformative shift in the arsenal of therapeutic options against breast cancer. Their diagnostic precision enables the categorization of tumors with elevated risks of recurrence, increased aggressiveness, and heightened mortality. Furthermore, the existence of therapies tailored to target specific molecular anomalies triggers a cascade of changes in tumor behavior. Therefore, the primary objective of this article is to offer a comprehensive review of the clinical, diagnostic, prognostic, and therapeutic utility of the principal biomarkers currently in use, as well as of their clinical impact on metastatic breast cancer. In doing so, our goal is to contribute to a more profound comprehension of this complex disease and, ultimately, to enhance patient outcomes through more precise and effective treatment strategies.

Spinal cord injury (SCI) is a serious medical condition associated with severe morbidities and disability. Chronic SCI patients present an enhanced susceptibility to infections and comorbidities with inflammatory pathogenesis. Chronic SCI appears to be associated with a systemic dysfunction of the immune system. We investigated the alteration of the pivotal CD4+ and CD8+ T lymphocytes in patients with chronic SCI at different years of evolution. A clinically homogenous population of 105 patients with chronic SCI (31 with time of evolution less than 5 years (SCI SP); 32 early chronic (SCI ECP) with time of evolution between 5 and 15 years; and 42 late chronic (SCI LCP) with time of evolution more than 15 years) and 38 healthy controls were enrolled. SCI ECP and SCI LCP patients showed significant CD4+ and CD8+ T lymphopenia, ascribed to a reduction in naïve and CM subsets. Furthermore, SCI ECP and SCI LCP patients showed a significant reduction in the expression of CD28 on CD8+ T lymphocytes. The expression of CCR6 by CD4+ T lymphocytes was decreased during the evolution of chronic SCI, but on CD8+ T lymphocytes, it was observed during the first 15 years of evolution. In conclusion, the chronic SCI course with severe damage to T lymphocytes mainly worsens over the years of disease evolution.

Pancreatic cancer will be positioned by the year 2030 as the second cause of oncological death after lung cancer. The pathophysiology of the most common variety, which involves the adenocarcinoma of the pancreas, represents one of the main challenges for current oncology to explain its tumorigenesis and create a targeted treatment. The tumor microenvironment, metastatic capacity, and lack of early diagnosis lead patients to present advanced stages at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcomes and with respect to the improved survival of these patients. For this reason, in recent years, numerous diagnostic tests, treatments, and possible approaches in the fields of radiotherapy, chemotherapy, immunotherapy, and surgery have been developed to find a combination of methods that improves life expectancy in patients diagnosed with this disease. On the other hand, the scientific community has made numerous advances in the molecular bases of pancreatic cancer since several oncogenetic pathways have been described and the markers expressed by the tumor have proven to be useful in the prognosis of pancreatic adenocarcinoma. These molecular alterations allow the study of possible therapeutic targets that improve the prognosis of these patients, but even numerous tumor cell-individual interactions must be explained to understand the underlying pathophysiology causing the high mortality. Therefore, the purpose of our study is to examine the expression of markers such as EGFR, Cyclin D1, andCDK4 in order to find a relationship with the possible long-term prognostic factors of patients affected by pancreatic ductal adenocarcinoma. Our results show that there is a prognostic role for ErbB2, EGFR, beta catenin, cyclin D1, and CDK4. Of these, we highlight the clinical importance of ErbB2 in the survival rates of patients who overexpress this component.

Pre-eclampsia is a harmful and potentially lethal medical condition during pregnancy clinically diagnosed by hypertension and commonly accompanied by proteinuria and multiorgan affections. According to the time of diagnosis, it is differentiated between early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less dangerous and presenting distinct pathophysiological signatures, LO-PE has a greater prevalence than EO-PE, both having significant consequences on the placenta. Previous works have evidenced that exacerbated inflammation in this organ might play a potential pathogenic role in the development of pre-eclampsia, and there is some preliminary evidence that the hyperactivation of inflammasomes can be related to the altered immunoinflammatory responses observed in the placentas of these patients. However, the precise role of inflammasomes in the placentas of women with LO-PE remains to be fully understood. In this work, we have studied the gene and protein expression of the main components related to the canonical and non-canonical pathways of the inflammasome NLRP3 (NLRP3, ASC, caspase 1, caspase 5, caspase 8, interleukin 1β, and interleukin 18) in the placental tissue of women with LO-PE. Our results show a marked increase in all these components in the placentas of women who have undergone LO-PE, suggesting that NLRP3 inflammasome plays a potentially pathophysiological role in the development of this entity. Future works should aim to evaluate possible translational approaches to this dysregulation in these patients.

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.

Oxidative stress is a major cellular event that occurs in the placenta, fulfilling critical physiological roles in non-pathological pregnancies. However, exacerbated oxidative stress is a pivotal feature of different obstetric complications, like pre-eclampsia, fetal growth restriction, and other diseases. Compelling evidence supports the relevant role of diet during pregnancy, with pleiotropic consequences for maternal well-being. The present review aims to examine the complex background between oxidative stress and placental development and function in physiological conditions, also intending to understand the relationship between different dietary patterns and the human placenta, particularly how this could influence oxidative stress processes. The effects of Westernized diets (WDs) and high-fat diets (HFDs) rich in ultra-processed foods and different additives are compared with healthy patterns such as a Mediterranean diet (MedDiet) abundant in omega 3 polyunsaturated fatty acids, monounsaturated fatty acids, polyphenols, dietary fiber, and vitamins. Although multiple studies have focused on the role of specific nutrients, mostly in animal models and in vitro, further observational and intervention studies focusing on the placental structure and function in women with different dietary patterns should be conducted to understand the precise influence of diet on this organ.

The RANK–RANKL–OPG system is a complex signaling pathway that plays a critical role in bone metabolism, mammary epithelial cell development, immune function, and cancer. RANKL is a ligand that binds to RANK, a receptor expressed on osteoclasts, dendritic cells, T cells, and other cells. RANKL signaling promotes osteoclast differentiation and activation, which leads to bone resorption. OPG is a decoy receptor that binds to RANKL and inhibits its signaling. In cancer cells, RANKL expression is often increased, which can lead to increased bone resorption and the development of bone metastases. RANKL-neutralizing antibodies, such as denosumab, have been shown to be effective in the treatment of skeletal-related events, including osteoporosis or bone metastases, and cancer. This review will provide a comprehensive overview of the functions of the RANK–RANKL–OPG system in bone metabolism, mammary epithelial cells, immune function, and cancer, together with the potential therapeutic implications of the RANK–RANKL pathway for cancer management.

The human placenta is a critical structure with multiple roles in pregnancy, including fetal nutrition and support, immunological, mechanical and chemical barrier as well as an endocrine activity. Besides, a growing body of evidence highlight the relevance of this organ on the maternofetal wellbeing not only during gestation, but also from birth onwards. Extracellular vesicles (EVs) are complex macromolecular structures of different size and content, acting as carriers of a diverse set of molecules and information from donor to recipient cells. Since its early development, the production and function of placental-derived EVs are essential to ensure an adequate progress of pregnancy. In turn, the fetus receives and produce their own EVs, highlighting the importance of these components in the maternofetal communication. Moreover, several studies have shown the clinical relevance of EVs in different obstetric pathologies such as preeclampsia, infectious diseases or gestational diabetes, among others, suggesting that they could be used as pathophysiological biomarkers of these diseases. Overall, the aim of this article is to present an updated review of the published basic and translational knowledge focusing on the role of placental-derived EVs in normal and pathological pregnancies. We suggest as well future lines of research to take in this novel and promising field.

In recent years, the incidence of different types of cancer and patient survival have been rising, as well as their prevalence. The increase in survival in recent years exposes the patients to a set of stressful factors such as more rigorous follow-up and more aggressive therapeutic regimens that, added to the diagnosis of the disease itself, cause an increase in the incidence of depressive disorders. These alterations have important consequences for the patients, reducing their average survival and quality of life, and for these reasons, special emphasis has been placed on developing numerous screening tests and early recognition of depressive symptoms. Despite that cancer and major depressive disorder are complex and heterogeneous entities, they also share many critical pathophysiological mechanisms, aiding to explain this complex relationship from a biological perspective. Moreover, a growing body of evidence is supporting the relevant role of lifestyle habits in the prevention and management of both depression and cancer. Therefore, the present study aims to perform a thorough review of the intricate relationship between depression and cancer, with a special focus on its biological links, clinical management, challenges, and the central role of lifestyle medicine as adjunctive and preventive approaches to improve the quality of life of these patients.

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.

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.

Macrophages are a type of immune cell distributed throughout all tissues of an organism. Allograft inflammatory factor 1 (AIF1) is a calcium-binding protein linked to the activation of macrophages. AIF1 is a key intracellular signaling molecule that participates in phagocytosis, membrane ruffling and F-actin polymerization. Moreover, it has several cell type-specific functions. AIF1 plays important roles in the development of several diseases: kidney disease, rheumatoid arthritis, cancer, cardiovascular diseases, metabolic diseases and neurological disorders, and in transplants. In this review, we present a comprehensive review of the known structure, functions and role of AIF1 in inflammatory diseases.

Breast cancer is one of the most common malignancies worldwide and the most common form of cancer in women. A large proportion of patients begin with localized disease and undergo treatment with curative intent, while another large proportion of patients debuts with disseminated metastatic disease. In the last subgroup of patients, the prognosis in recent years has changed radically, given the existence of different targeted therapies thanks to the discovery of different biomarkers. Serological, histological, and genetic biomarkers have demonstrated their usefulness in the initial diagnosis, in the follow-up to detect relapses, to guide targeted treatment, and to stratify the prognosis of the most aggressive tumors in those with breast cancer. Molecular markers are currently the basis for the diagnosis of metastatic disease, given the wide variety of chemotherapy regions and existing therapies. These markers have been a real revolution in the therapeutic arsenal for breast cancer, and their diagnostic validity allows the classification of tumors with higher rates of relapse, aggressiveness, and mortality. In this sense, the existence of therapies targeting different molecular alterations causes a series of changes in tumor biology that can be assessed throughout the course of the disease to provide information on the underlying pathophysiology of metastatic disease, which allows us to broaden our knowledge of the different mechanisms of tissue invasion. Therefore, the aim of the present article is to review the clinical, diagnostic, predictive, prognostic utility and limitations of the main biomarkers available and under development in metastatic breast cancer.

Spinal cord injury (SCI) is a progressive and complex neurological disorder accompanied by multiple systemic challenges. Peripheral immune dysfunction is a major event occurring after SCI, especially in its chronic phase. Previous works have demonstrated significant changes in different circulating immune compartments, including in T cells. However, the precise characterization of these cells remains to be fully unraveled, particularly when considering important variants such as the time since the initial injury. In the present work, we aimed to study the level of circulating regulatory T cells (Tregs) in SCI patients depending on the duration of evolution. For this purpose, we studied and characterized peripheral Tregs from 105 patients with chronic SCI using flow cytometry, with patients classified into three major groups depending on the time since initial injury: short period chronic (SCI-SP,

Spinal cord injury (SCI) is a disabling neurological condition coursing with serious multisystem affections and morbidities. Changes in immune cell compartments have been consistently reported in previous works, representing a critical point of study for understanding the pathophysiology and progression of SCI from acute to chronic stages. Some relevant variations in circulating T cells have been noticed in patients with chronic SCI, although the number, distribution, and function of these populations remain to be fully elucidated. Likewise, the characterization of specific T cell subpopulations and their related cytokine production can aid in understanding the immunopathological role of T cells in SCI progression. In this sense, the objective of the present study was to analyze and quantify the total number of different cytokine-producers T cells in the serum of patients with chronic SCI (n = 105) in comparison to healthy controls (n = 38) by polychromatic flow cytometry. Having this goal, we studied CD4 and CD8 lymphocytes as well as naïve, effector, and effector/central memory subpopulations. SCI patients were classified according to the duration of the lesion in chronic SCI with a short period of evolution (SCI-SP) (comprised between 1 and 5 years since initial injury), early chronic phase (SCI-ECP) (between 5 and 15 years since initial injury) and late-chronic phase (SCI-LCP) (>15 years since initial injury). Our results show that patients with chronic SCI exhibited an altered immune profile of cytokine-producer T cells, including CD4/CD8 naïve, effector, and memory subpopulations in comparison to HC. In particular, IL-10 and IL-9 production seems to be importantly altered, especially in patients with SCI-LCP, whereas changes in IL-17, TNF-α, and IFN-γ T cell populations have also been reported in this and other chronic SCI groups. In conclusion, our study demonstrates an altered profile of cytokine-producer T cells in patients with chronic SCI, with marked changes throughout the course of the disease. In more detail, we have observed significant variations in cytokine production by circulating naive, effector, and effector/central memory CD4 and CD8 T cells. Future studies should be directed to explore the possible clinical consequences of these changes or develop additional translational approaches in these groups of patients.

In recent years, the importance of epigenetic markers in the carcinogenesis of different malignant neoplasms has been demonstrated, also demonstrating their utility for understanding metastatic spread and tumor progression in cancer patients. Among the different biomarkers, microRNAs represent a set of non-coding RNAs that regulate gene expression, having been involved in a wide variety of neoplasia acting in different oncogenic pathways. Both the overexpression and downregulation of microRNAs represent a complex interaction with various genes whose ultimate consequence is increased cell proliferation, tumor invasion and interaction with various driver markers. It should be noted that in current clinical practice, even though the combination of different microRNAs has been shown to be useful by different authors at diagnostic and prognostic levels, there are no diagnostic kits that can be used for the initial approach or to assess recurrences of oncological diseases. Previous works have cited microRNAs as having a critical role in several carcinogenic mechanisms, ranging from cell cycle alterations to angiogenesis and mechanisms of distant metastatic dissemination. Indeed, the overexpression or downregulation of specific microRNAs seem to be tightly involved in the modulation of various components related to these processes. For instance, cyclins and cyclin-dependent kinases, transcription factors, signaling molecules and angiogenic/antiangiogenic products, among others, have been recognized as specific targets of microRNAs in different types of cancer. Therefore, the purpose of this article is to describe the main implications of different microRNAs in cell cycle alterations, metastasis and angiogenesis, trying to summarize their involvement in carcinogenesis.

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.

Objective To measure plasma levels of malondialdehyde (MDA), a marker of oxidative stress (OS), in patients with major depressive disorder (MDD) compared with healthy control (HC) subjects in order to determine if it is a possible biomarker of depression. Methods This prospective cross-sectional study enrolled patients with MDD and HC subjects. The plasma levels of MDA were measured using a commercially-available colorimetric assay. Results A total of 30 patients with MDD and 20 HC subjects with similar sex, age and body mass index distribution were enrolled in the study. Patients with MDD had significantly higher plasma levels of MDA than the HC subjects. Receiver operating characteristic curve analysis for plasma MDA levels in patients with MDD demonstrated an area under the curve of 0.9767. Conclusion The findings of this current study provide further evidence of the role pathophysiological relevance of OS and MDA in MDD. This study provides the basis for the use of MDA as a biomarker for MDD.

Major depressive disorder (MDD) is a complex psychiatric disorder that, presented alone or with other comorbidities, requires different adjustments of antidepressant treatments. Some investigations have demonstrated that psychoactive drugs, such as serotonin and norepinephrine reuptake inhibitors (SNRIs), can exert more effective and faster antidepressant effects than other common medications used, such as serotonin selective reuptake inhibitors (SSRIs), although these differences are still controversial. During the last five years, the SNRI duloxetine has shown favorable results in clinical practice for the treatment of MDD, anxiety, and fibromyalgia. Through an online self-completed survey, in the present article, we collected information from 163 psychiatrists regarding the use of duloxetine and its comparison with other psychiatric drugs, concerning psychiatrists’ knowledge and experience, as well as patients’ preferences, symptoms, and well-being. We discussed and contrasted physicians’ reports and the scientific literature, finding satisfactory concordances, and finally concluded that there is agreement regarding the use of duloxetine, not only due to its tolerability and effectiveness but also due to the wide variety of situations in which it can be used (e.g., somatic symptoms in fibromyalgia, diabetes) as it relieves neuropathic pain as well.

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.

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.

Objectives Chronic venous disease (CVeD) is a multifactorial and debilitating condition that has a high prevalence in Western countries and an important associated socioeconomic burden. Varicose veins (VVs) are the most common manifestations of CVeD. Pathologically, many morphological and functional changes have been described in VVs, which most notably affect venous wall integrity. Previous studies have found several molecular alterations that negatively affect normal cell signaling pathways. Insulin receptor substrate (IRS)-4 is a central adaptor protein that is closely related to insulin/insulin-like growth factor-1 signaling upstream, phosphatidylinositol 3-kinase/Akt or mitogen-activated protein kinases downstream, and other proteins. These molecular pathways have been implicated in CVeD pathogenesis. Thus, the aim of our study was to identify the role of IRS-4 in VV tissue. Methods We conducted a histopathological study to analyze IRS-4 protein expression in CVeD patients compared with healthy controls. Results Our results demonstrate a significant increase in IRS-4 expression in VV tissue. Conclusions IRS-4 may be implicated in CVeD development and progression. Therefore, IRS-4 could be a potential diagnostic or therapeutic target for patients with this condition.

The umbilical cord is a critical anatomical structure connecting the placenta with the foetus, fulfilling multiple functions during pregnancy and hence influencing foetal development, programming and survival. Histologically, the umbilical cord is composed of three blood vessels: two arteries and one vein, integrated in a mucous connective tissue (Wharton’s jelly) upholstered by a layer of amniotic coating. Vascular alterations in the umbilical cord or damage in this tissue because of other vascular disorders during pregnancy are worryingly related with detrimental maternofoetal consequences. In the present work, we will describe the main vascular alterations presented in the umbilical cord, both in the arteries (Single umbilical artery, hypoplastic umbilical artery or aneurysms in umbilical arteries) and the vein (Vascular thrombosis, aneurysms or varicose veins in the umbilical vein), together with other possible complications (Velamentous insertion, vasa praevia, hypercoiled or hypocoiled cord, angiomyxoma and haematomas). Likewise, the effect of the main obstetric vascular disorders like hypertensive disorders of pregnancy (specially pre-eclampsia) and chronic venous disease on the umbilical cord will also be summarized herein.

Osteosarcoma represents a rare cause of cancer in the general population, accounting for

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-3β). 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-3β 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-3β 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 β in the placenta of women with CVD, which could be an indicator of an oxidative environment observed in this tissue.

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-1β). 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.

Immune-mediated inflammatory diseases (IMIDs) represent a large group of diseases (Crohn’s, ulcerative colitis, psoriasis, lupus, and rheumatoid arthritis) evidenced by systemic inflammation and multiorgan involvement. IMIDs result in a reduced quality of life and an economic burden for individuals, health care systems, and countries. In this brief descriptive review, we will focus on some of the common biological pathways of these diseases from the point of view of psychoneuroimmunoendocrinology (PNIE). PNIE consists of four medical disciplines (psychology, nervous system, immune system, and endocrine system), which are key drivers behind the health–disease concept that a human being functions as a unit. We examine these drivers and emphasize the need for integrative treatments that addresses the disease from a psychosomatic point of view.

Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.

Cellular trafficking is the set of processes of distributing different macromolecules by the cell. This process is highly regulated in cells, involving a system of organelles (endomembranous system), among which are a great variety of vesicles that can be secreted from the cell, giving rise to different types of extracellular vesicles (EVs) that can be captured by other cells to modulate their function. The cells of the immune system are especially sensitive to this cellular traffic, producing and releasing different classes of EVs, especially in disease states. There is growing interest in this field due to the therapeutic and translational possibilities it offers. Different ways of taking advantage of the understanding of cell trafficking and EVs are being investigated, and their use as biomarkers or therapeutic targets is being investigated. The objective of this review is to collect the latest results and knowledge in this area with a specific focus on immune-mediated diseases. Although some promising results have been obtained, further knowledge is still needed, at both the basic and translational levels, to understand and modulate cellular traffic and EVs for better clinical management of these patients.

Pancreatic cancer is a malignancy of rising prevalence, especially in developed countries where dietary patterns and sedentariness favor its onset. This malady ranks seventh in cancer-related deaths in the world, although it is expected to rank second in the coming years, behind lung cancer. The low survival rate is due to the asymptomatic course of the early stages, which in many cases leads to metastases when becoming evident in advanced stages. In this context, molecular pathology is on the way towards finding new approaches with biomarkers that allow a better prognosis and monitoring of patients. So the present study aims to evaluate a series of molecular biomarkers, PARP1, NOX1, NOX2, eNOS and iNOS, as promising candidates for prognosis and survival by using immunohistochemistry. The analysis performed in 41 patients with pancreatic cancer showed a correlation between a high expression of all these components with a low survival rate, with high statistical power for all. In addition, a 60-month longitudinal surveillance program was managed, accompanied by several clinical parameters. The derivative Kaplan–Meier curves indicated a low cumulative survival rate as well. Ultimately, our research emphasized the value of these molecules as survival-associated biomarkers in pancreatic cancer, offering new gates for clinical management.