Search

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. [ABSTRACT FROM AUTHOR]

It is estimated that approximately one in three women develop chronic venous disease (CVD) during pregnancy, a broad spectrum of morphofunctional disorders affecting the venous system in different regions of the body, including the lower limbs. A growing body of evidence supports the diverse maternofetal consequences derived from this condition, with the placenta being an organ particularly affected. Among other consequences, having CVD during pregnancy has been associated with systemic inflammation and altered cytokines and chemokine profiles in the maternal and fetal serum related to this condition. In the present work, we aimed to analyze if these inflammatory changes also occurred in the placental tissue of women with CVD, exploring by immunohistochemistry and real-time PCR (RT-qPCR) gene and protein expression of critical inflammatory markers like allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A, and IL-18. Our results demonstrate an enhanced tissue expression of AIF-1, IL-12A, and IL-18, accompanied by a decrease in IL-10 in the placentas of women who had undergone CVD during pregnancy. Overall, our results suggest a possible pathophysiological role of inflammation in the placental tissue of women with CVD during pregnancy, although the precise consequences of this feature remain to be deeply analyzed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVD) is a common condition that affects the veins in the lower limbs, resulting in a variety of symptoms, such as swelling, pain, and varicose veins (VVs). The plenty hormonal, hemodynamic and mechanical changes occurred in pregnancy make women especially vulnerable to suffer from this condition in this period. Previous works have identified that CVD is associated with an increased inflammatory milieu and significant damage in maternofetal tissues, such as the umbilical cord. However, the inflammatory status of this structure in these patients has not been studied yet. Thus, the aim of the present study was to examine gene and protein expression of a set of inflammatory markers—Allograft inflammatory factor 1 (AIF-1), the proinflammatory cytokines interleukin 12A (IL-12A) and IL-18 and the anti-inflammatory product IL-10—in the umbilical cord of women with CVD during pregnancy (N = 62) and healthy pregnant women (HC; N = 52) by the use of real time qPCR and immunohistochemistry (IHC). Our results demonstrate that the umbilical cord tissue from CVD women exhibit an increased expression of AIF-1, IL-12A and IL-18 along with a decrease in IL-10. Therefore, our study suggests an inflammatory status of this structure related to CVD. Further studies should be conducted to evaluate the expression of other inflammatory markers, as well as to analyze the maternofetal impact of these findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is one of the most heterogeneous and aggressive tumours that exist. The median survival of diagnosed patients is limited. For all these reasons, it is necessary to develop new disease markers that allow guidelines for clinical action to improve the average survival of patients with pancreatic cancer. The incidence and prevalence of pancreatic adenocarcinoma have increased in recent years. Pancreatic cancer is the seventh leading cause of cancer death, but it is projected to become the second leading cause of cancer-related mortality by 2040. Most patients are diagnosed in an advanced stage of the disease, with very limited 5-year survival. The discovery of different tissue markers has elucidated the underlying pathophysiology of pancreatic adenocarcinoma and allowed stratification of patient risk at different stages and assessment of tumour recurrence. Due to the invasive capacity of this tumour and the absence of screening markers, new immunohistochemical and serological markers may be used as prognostic markers for recurrence and in the study of possible new therapeutic targets because the survival of these patients is low in most cases. The present article reviews the currently used main histopathological and serological markers and discusses the main characteristics of markers under development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Allograft inflammatory factor 1 (AIF1) is a calcium-binding protein that participates in intracellular processes such as phagocytosis, membrane ruffling and F-actin remodeling. Due to its multiple functions, AIF1 is linked with the activation of macrophages and several diseases such as kidney disease, rheumatoid arthritis, cancer, cardiovascular diseases, metabolic diseases, neurological disorders and transplants. In this review, we present a comprehensive review of the known structure, functions and role of AIF1 in inflammatory diseases. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pancreatic cancer has a dire prognosis and will represent the second leading cause of cancer death in the next 10 years. The multifactorial approach represents one of the main issues in controlling the extension of this neoplasm. In recent years, the characteristics of the tumor microenvironment, metastasis mechanisms and the relationship between immune system and neoplastic cells have been described, which has made it possible to understand the pathophysiology of pancreatic adenocarcinoma. Currently, there is a failure to provide an effective preventive method or early detection, so patients present with an advanced stage at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcome and in improving survival in long term. Therefore, in the recent years, diverse diagnostic tests, treatments and possible approaches have been developed in the fields of radiotherapy, chemotherapy and surgery to find a combination of them that improves life expectancy in patients diagnosed with pancreatic cancer. At the moment, numerous clinical trials are being conducted to evaluate preventive diagnostic procedures such as serological markers or perfecting available imaging tests. On the other hand, implementation of immunotherapy is being studied in a neoplasm that has lagged in the application of this procedure since present possible treatments do not substantially improve quality of life. Therefore, the purpose of our study is to summarize the main progresses that have been made in the diagnosis, treatment and screening of this disease, explaining the limitations that have been observed and analyzing future prospects in the management of this illness. [ABSTRACT FROM AUTHOR]

Psychotic episodes represent one of the most complex manifestations of various mental illnesses, and these encompass a wide variety of clinical manifestations that together lead to high morbidity in the general population. Various mental illnesses are associated with psychotic episodes; in addition, although their incidence and prevalence rates have been widely described in the general population, their correct identification and treatment is a challenge for health professionals in relation to pregnancy. In pregnant women, psychotic episodes can be the consequence of the manifestation of a previous psychiatric illness or may begin during the pregnancy itself, placing not only the mother, but also the fetus at risk during the psychotic episode. In addition, we cannot forget that both pharmacological and nonpharmacological management are complex given the different teratogenic effects of various neuroleptic drugs or mood stabilizers; moreover, the recommendation is that patients should be followed together with different specialists to maintain close contact during puerperium given the high incidence of recurrence of psychotic episodes. In addition, we cannot forget that a large portion of these patients for whom the onset times of such episodes are during pregnancy have a greater probability of an unpredictable psychiatric illness that requires a postpartum follow up, in addition to the postpartum psychotic episodes, at some point in their lives. Therefore, the purpose of this review is to summarize the epidemiology of psychotic breaks during pregnancy related to the main mental illnesses that affect this population and to summarize the main pharmacological treatments available for their clinical management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Penile carcinoma is a rare urological neoplasia in men compared to other more common tumors, such as prostate, kidney, or bladder tumors. However, this neoplasm continues to affect a large number of patients worldwide, with developing countries presenting the highest incidence and mortality rates. Important risk factors such as the human papilloma virus, a factor affecting a large number of patients, have been described; however, few studies have evaluated screening programs in populations at risk for this disease, which severely affects the quality of life of older men. The management of these patients is usually complex, requiring surgical interventions that are not without risk and that have a great impact on the functionality of the male reproductive system. In addition, in cases of disseminated disease or with significant locoregional involvement, patients are evaluated by multidisciplinary oncological committees that can adjust the application of aggressive neoadjuvant or adjuvant chemotherapy on numerous occasions without clear improvement in survival. Chemotherapy regimens are usually aggressive, and unlike in other urological neoplasms, few advances have been made in the use of immunotherapy in these patients. The study of serological and histological biomarkers may help to better understand the underlying pathophysiology of these tumors and select patients who have a higher risk of metastatic progression. Similarly, the analysis of molecular markers will improve the availability of targeted therapies for the management of patients with disseminated disease that would benefit prognosis. Therefore, the purpose of this article is to summarize the main advances that have occurred in the development of serological and histological markers and their therapeutic implications in patients diagnosed with penile carcinoma, explaining the limitations that have been observed and analyzing future perspectives in the management of this disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune-mediated inflammatory diseases (IMIDs) are growing in prevalence and relevance in our society, entailing notable consequences for the individual and healthcare systems. These medical conditions are associated with a systemic inflammatory milieu and an aberrant functioning of the immune system, establishing a bidirectional interplay with other organs and systems of the body. Psychoneuroimmunoendocrinology (PNIE) is an area of great interest relating the immune system with the individual's psyche, nervous, and endocrine system. As compelling evidence supports the pivotal role of PNIE in the understanding and clinical management of IMIDs, the aim of the present review is to deepen the current basic and clinical knowledge in this field. 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. [ABSTRACT FROM AUTHOR]

Over the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to evolve. In this sense, different organizations have identified and classified the different variants that have been emerging, distinguishing between variants of concern (VOC), variants of interest (VOI), or variants under monitoring (VUM). The following review aims to describe the latest updates focusing on VOC and already de-escalated variants, as well as to describe the impact these have had on the global situation. Understanding the intrinsic properties of SARS-CoV-2 and its interaction with the immune system and vaccination is essential to make out the underlying mechanisms that have led to the appearance of these variants, helping to determine the next steps for better public management of this pandemic. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Histone acetylation plays a vital role in organizing chromatin, regulating gene expression and controlling the cell cycle. The first histone acetyltransferase to be identified was histone acetyltransferase 1 (HAT1), but it remains one of the least understood acetyltransferases. HAT1 catalyzes the acetylation of newly synthesized H4 and, to a lesser extent, H2A in the cytoplasm. However, 20 min after assembly, histones lose acetylation marks. Moreover, new noncanonical functions have been described for HAT1, revealing its complexity and complicating the understanding of its functions. Recently discovered roles include facilitating the translocation of the H3H4 dimer into the nucleus, increasing the stability of the DNA replication fork, replication-coupled chromatin assembly, coordination of histone production, DNA damage repair, telomeric silencing, epigenetic regulation of nuclear lamina-associated heterochromatin, regulation of the NF-κB response, succinyl transferase activity and mitochondrial protein acetylation. In addition, the functions and expression levels of HAT1 have been linked to many diseases, such as many types of cancer, viral infections (hepatitis B virus, human immunodeficiency virus and viperin synthesis) and inflammatory diseases (chronic obstructive pulmonary disease, atherosclerosis and ischemic stroke). The collective data reveal that HAT1 is a promising therapeutic target, and novel therapeutic approaches, such as RNA interference and the use of aptamers, bisubstrate inhibitors and small-molecule inhibitors, are being evaluated at the preclinical level. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The PD-1/PD-L1 axis is a complex signaling pathway that has an important role in the immune system cells. Programmed cell death protein 1 (PD-1) acts as an immune checkpoint on the T lymphocytes, B lymphocytes, natural killer (NK), macrophages, dendritic cells (DCs), monocytes, and myeloid cells. Its ligand, the programmed cell death 1 ligand (PD-L1), is expressed in the surface of the antigen-presenting cells (APCs). The binding of both promotes the downregulation of the T cell response to ensure the activation to prevent the onset of chronic immune inflammation. This axis in the tumor microenvironment (TME) performs a crucial role in the tumor progression and the escape of the tumor by neutralizing the immune system, the engagement of PD-L1 with PD-1 in the T cell causes dysfunctions, neutralization, and exhaustion, providing the tumor mass production. This review will provide a comprehensive overview of the functions of the PD-1/PD-L1 system in immune function, cancer, and the potential therapeutic implications of the PD-1/PD-L1 pathway for cancer management. [ABSTRACT FROM AUTHOR]

Uterine Arteriovenous Malformation (UAVM) is a rare but life-threating cause of uterine bleeding. The clinical management of this condition is challenging, and there is a need to describe the most adequate approach for these patients. Uterine artery embolization (UAE) is the most widely-published treatment in the literature in recent years, although there is a need to update the evidence on this treatment and to compare it with other available therapies. Thus, the objective of this systematic review is to quantify the efficacy of UAE of UAVM. In addition, we evaluated the clinical context of the patients included, the treatment complications, and the pregnancy outcomes after UAE. With this goal in mind, we finally included 371 patients spread over all continents who were included in 95 studies. Our results show that, similar to other medical therapies, the global success rate after embolization treatment was 88.4%, presenting a low risk of adverse outcomes (1.8%), even in women with later pregnancy (77% had no complications). To date, this is the largest systematic review conducted in this field, although there are still some points to address in future studies. The results obtained in our study should be outlined in UAE protocols and guidelines to aid in clinical decision-making in patients with UAVM. [ABSTRACT FROM AUTHOR]

Chronic infections are one of the most serious adverse outcomes of prosthetic surgery. Prosthetic revision surgery using a bone cement loaded with antibiotics between the two stages of the surgery is commonly performed. However, this method often fails to reach the minimum inhibitory concentration and promotes antibiotic resistance, thus emphasizing the need for improving the current available therapies. Materials and methods: In this study, we performed a study of the in vivo response of a polymer-based construct of poly (lactic-co-glycolic acid) (PLGA) in the solid phase of Palacos R® in combination with vancomycin, daptomycin, and/or linezolid. To test its effectiveness, we applied an in vivo model, using both histological and immunohistochemical analyses to study the bone tissue. Results: The presence of PLGA in the combination of vancomycin with daptomycin showed the most promising results regarding the preservation of bone cytoarchitecture and S. aureus elimination. Conversely, the combination of vancomycin plus linezolid was associated with a loss of bone cytoarchitecture, probably related to an increased macrophage response and inefficient antimicrobial activity. Conclusions: The modification of Palacos R® bone cement with PLGA microspheres and its doping with the antibiotic daptomycin in combination with vancomycin improve the tissue response to bone infection. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVD) is a multifactorial vascular disorder frequently manifested in lower limbs in the form of varicose veins (VVs). Women are a vulnerable population for suffering from CVD, especially during pregnancy, when a plethora of changes occur in their cardiovascular system. Previous studies have indicated a worrisome association between CVD in pregnancy with the placental structure and function. Findings include an altered cellular behavior and extracellular matrix (ECM) composition. Integrin-linked kinase (ILK) is a critical molecule involved in multiple physiological and pathological conditions, and together with cadherins, is essential to mediate cell to ECM and cell to cell interplay, respectively. Thus, the aim of this study was to evaluate the implication of ILK and a set of cadherins (e-cadherin, cadherin-6 and cadherin-17) in placentas of women with CVD in order to unravel the possible pathophysiological role of these components. Gene expression (RT-qPCR) and protein expression (immunohistochemistry) studies were performed. Our results show a significant increase in the gene and protein expression of ILK, cadherin-6 and cadherin-17 and a decrease of e-cadherin in the placenta of women with CVD. Overall, this work shows that an abnormal expression of ILK, e-cadherin, cadherin-6 and cadherin-17 may be implicated in the pathological changes occurring in the placental tissue. Further studies should be conducted to determine the possible associations of these changes with maternal and fetal well-being. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a complex and common disorder, with many factors involved in its onset and development. The clinical management of this condition is frequently based on the use of some pharmacological antidepressant agents, together with psychotherapy and other alternatives in most severe cases. However, an important percentage of depressed patients fail to respond to the use of conventional therapies. This has created the urgency of finding novel approaches to help in the clinical management of those individuals. Nutraceuticals are natural compounds contained in food with proven benefits either in health promotion or disease prevention and therapy. A growing interest and economical sources are being placed in the development and understanding of multiple nutraceutical products. Here, we summarize some of the most relevant nutraceutical agents evaluated in preclinical and clinical models of depression. In addition, we will also explore less frequent but interest nutraceutical products which are starting to be tested, also evaluating future roads to cover in order to maximize the benefits of nutraceuticals in MDD. [ABSTRACT FROM AUTHOR]