Unraveling Immunological Dynamics: HPV Infection in Women-Insights from Pregnancy.

During pregnancy, hormonal and immune adaptations are vital for supporting the genetically distinct fetus during elevated infection risks. The global prevalence of HPV necessitates its consideration during pregnancy. Despite a seemingly mild immune response, historical gestational viral infections underscore its significance. Acknowledging the established HPV infection risks during pregnancy, our review explores the unfolding immunological changes in pregnant women with HPV. Our analysis aims to uncover strategies for safely modulating the immune system, mitigating adverse pregnancy consequences, and enhancing maternal and child health. This comprehensive narrative review delves into the existing knowledge and studies on this topic.

Mast Cell Activation Syndrome Update-A Dermatological Perspective.

Mast cells (MCs) are infamous for their role in potentially fatal anaphylaxis reactions. In the last two decades, a more complex picture has emerged, as it has become obvious that MCs are much more than just IgE effectors of anaphylaxis. MCs are defenders against a host of infectious and toxic aggressions (their interactions with other components of the immune system are not yet fully understood) and after the insult has ended, MCs continue to play a role in inflammation regulation and tissue repair. Unfortunately, MC involvement in pathology is also significant. Apart from their role in allergies, MCs can proliferate clonally to produce systemic mastocytosis. They have also been implicated in excessive fibrosis, keloid scaring, graft rejection and chronic inflammation, especially at the level of the skin and gut. In recent years, the term MC activation syndrome (MCAS) was proposed to account for symptoms caused by MC activation, and clear diagnostic criteria have been defined. However, not all authors agree with these criteria, as some find them too restrictive, potentially leaving much of the MC-related pathology unaccounted for. Here, we review the current knowledge on the physiological and pathological roles of MCs, with a dermatological emphasis, and discuss the MCAS classification.

Particular aspects of treating rectal cancer: The watch and wait approach.

Background: Rectal cancer is one of the most common malignant pathologies worldwide. Currently, the standard treatment of this pathology consists of radio-chemotherapy followed by low anterior resection with total mesorectal excision or abdominoperineal proctectomy for medium/low rectal cancer. Objectives: In recent years, another treatment strategy has been proposed, stemming from the finding that up to 40% of patients receiving neoadjuvant treatment had a complete pathological response. This method, also referred to as the watch and wait approach, implies delaying surgery and following a rigorous protocol for patients who have developed a complete response to neoadjuvant treatment with a good oncologic outcome. The objective of this study was to highlight the merits of this approach in selected patients. Case Reports: In this study, we present two patients with low-rectal tumors who developed complete response post neoadjuvant therapy and for whom the watch and wait protocol has been applied over the past 4 years. Conclusion: Although the watch and wait protocol appears to be a feasible option in the management of patients with a complete clinical and pathological response post neoadjuvant therapy, more prospective studies and randomized trials comparing this approach with standard surgical treatment are required before establishing it as the standard of care for distal rectal cancer. Therefore, establishing universal criteria for the selection and assessment of the patients with a complete clinical response following neoadjuvant treatment is required.

Maternal HPV Infection: Effects on Pregnancy Outcome.

The human papilloma virus (HPV) infection, caused by a ubiquitous virus typically transmitted through the direct contact of infected organs, either through the skin or mucosa, is the most common sexually transmitted infection, placing young women at a high risk of contracting it. Although the vast majority of cases spontaneously clear within 1-2 years, persistent HPV infection remains a serious concern, as it has repeatedly been linked to the development of multiple malignancies, including cervical, anogenital, and oropharyngeal cancers. Additionally, more recent data suggest a harmful effect of HPV infection on pregnancy. As the maternal hormonal environment and immune system undergo significant changes during pregnancy, the persistence of HPV is arguably favored. Various studies have reported an increased risk of adverse pregnancy outcomes among HPV-positive women, with the clinical impact encompassing a range of conditions, including preterm birth, miscarriage, pregnancy-induced hypertensive disorders (PIHD), intrauterine growth restriction (IUGR), low birth weight, the premature rupture of membranes (PROM), and fetal death. Therefore, understanding the mechanisms employed by HPV that negatively impact pregnancy and assessing potential approaches to counteract them would be of interest in the quest to optimize pregnancy outcomes and improve child survival and health.

Vulvar and Vaginal Melanomas-The Darker Shades of Gynecological Cancers.

Melanomas of the skin are poorly circumscribed lesions, very frequently asymptomatic but unfortunately with a continuous growing incidence. In this landscape, one can distinguish melanomas originating in the mucous membranes and located in areas not exposed to the sun, namely the vulvo-vaginal melanomas. By contrast with cutaneous melanomas, the incidence of these types of melanomas is constant, being diagnosed in females in their late sixties. While hairy skin and glabrous skin melanomas of the vulva account for 5% of all cancers located in the vulva, melanomas of the vagina and urethra are particularly rare conditions. The location in areas less accessible to periodic inspection determines their diagnosis in advanced stages, often metastatic. Moreover, despite the large number of drugs newly approved in recent decades for the treatment of cutaneous melanoma, especially in the category of biological drugs, the mortality of vulvo-vaginal melanomas has remained almost constant. This, together with the absence of specific treatment guidelines due to the lack of a sufficient number of cases to conduct randomized clinical trials, makes melanomas with this localization a discouraging diagnosis, associated with a very poor prognosis. Our aim is therefore to draw attention to this oftentimes overlooked entity in order to encourage the community to employ various strategies meant to increase research in this area. By highlighting the main risk factors of vulvar and vaginal melanomas, as well as the clinical manifestations and molecular changes underlying these neoplasms, ideally novel therapeutic schemes will, in time, be brought into effect.

Pregnancy-Related Extracellular Vesicles Revisited.

Extracellular vesicles (EVs) are small vesicles ranging from 20-200 nm to 10 µm in diameter that are discharged and taken in by many different types of cells. Depending on the nature and quantity of their content-which generally includes proteins, lipids as well as microRNAs (miRNAs), messenger-RNA (mRNA), and DNA-these particles can bring about functional modifications in the receiving cells. During pregnancy, placenta and/or fetal-derived EVs have recently been isolated, eliciting interest in discovering their clinical significance. To date, various studies have associated variations in the circulating levels of maternal and fetal EVs and their contents, with complications including gestational diabetes and preeclampsia, ultimately leading to adverse pregnancy outcomes. Furthermore, EVs have also been identified as messengers and important players in viral infections during pregnancy, as well as in various congenital malformations. Their presence can be detected in the maternal blood from the first trimester and their level increases towards term, thus acting as liquid biopsies that give invaluable insight into the status of the feto-placental unit. However, their exact roles in the metabolic and vascular adaptations associated with physiological and pathological pregnancy is still under investigation. Analyzing peer-reviewed journal articles available in online databases, the purpose of this review is to synthesize current knowledge regarding the utility of quantification of pregnancy related EVs in general and placental EVs in particular as non-invasive evidence of placental dysfunction and adverse pregnancy outcomes, and to develop the current understanding of these particles and their applicability in clinical practice.

Impact of Increased Oxidative Stress on Cardiovascular Diseases in Women With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a complex disorder that affects around 5% to 10% of women of childbearing age worldwide, making it the most common source of anovulatory infertility. PCOS is defined by increased levels of androgens, abnormal ovulation, irregular menstrual cycles, and polycystic ovarian morphology in one or both ovaries. Women suffering from this condition have also been shown to frequently associate certain cardiovascular comorbidities, including obesity, hypertension, atherosclerosis, and vascular disease. These factors gradually lead to endothelial dysfunction and coronary artery calcification, thus posing an increased risk for adverse cardiac events. Traditional markers such as C-reactive protein (CRP) and homocysteine, along with more novel ones, specifically microRNAs (miRNAs), can accurately signal the risk of cardiovascular disease (CVD) in PCOS women. Furthermore, studies have also reported that increased oxidative stress (OS) coupled with poor antioxidant status significantly add to the increased cardiovascular risk among these patients. OS additionally contributes to the modified ovarian steroidogenesis, consequently leading to hyperandrogenism and infertility. The present review is therefore aimed not only at bringing together the most significant information regarding the role of oxidative stress in promoting CVD among PCOS patients, but also at highlighting the need for determining the efficiency of antioxidant therapy in these patients.

MiRNAs: A Powerful Tool in Deciphering Gynecological Malignancies.

Accumulated evidence on the clinical roles of microRNAs (miRNAs) in cancer prevention and control has revealed the emergence of new genetic techniques that have improved the understanding of the mechanisms essential for pathology induction and progression. Comprehension of the modifications and individual differences of miRNAs and their interactions in the pathogenesis of gynecological malignancies, together with an understanding of the phenotypic variations have considerably improved the management of the diagnosis and personalized treatment for different forms of cancer. In recent years, miRNAs have emerged as signaling molecules in biological pathways involved in different categories of cancer and it has been demonstrated that these molecules could regulate cancer-relevant processes, our focus being on malignancies of the gynecologic tract. The aim of this paper is to summarize novel research findings in the literature regarding the parts that miRNAs play in cancer-relevant processes, specifically regarding gynecological malignancy, while emphasizing their pivotal role in the disruption of cancer-related signaling pathways.

Altered Organelle Calcium Transport in Ovarian Physiology and Cancer.

Calcium levels have a huge impact on the physiology of the female reproductive system, in particular, of the ovaries. Cytosolic calcium levels are influenced by regulatory proteins (i.e., ion channels and pumps) localized in the plasmalemma and/or in the endomembranes of membrane-bound organelles. Imbalances between plasma membrane and organelle-based mechanisms for calcium regulation in different ovarian cell subtypes are contributing to ovarian pathologies, including ovarian cancer. In this review, we focused our attention on altered calcium transport and its role as a contributor to tumor progression in ovarian cancer. The most important proteins described as contributing to ovarian cancer progression are inositol trisphosphate receptors, ryanodine receptors, transient receptor potential channels, calcium ATPases, hormone receptors, G-protein-coupled receptors, and/or mitochondrial calcium uniporters. The involvement of mitochondrial and/or endoplasmic reticulum calcium imbalance in the development of resistance to chemotherapeutic drugs in ovarian cancer is also discussed, since Ca2+ channels and/or pumps are nowadays regarded as potential therapeutic targets and are even correlated with prognosis.

Simulation and Modeling of Telocytes Behavior in Signaling and Intercellular Communication Processes.

BACKGROUND: Telocytes (TCs) are unique interstitial or stromal cells of mesodermal origin, defined by long cellular extensions called telopodes (Tps) which form a network, connecting them to surrounding cells. TCs were previously found around stem and progenitor cells, and were thought to be most likely involved in local tissue metabolic equilibrium and regeneration. The roles of telocytes are still under scientific scrutiny, with existing studies suggesting they possess various functions depending on their location. METHODS: Human myometrium biopsies were collected from pregnant and non-pregnant women, telocytes were then investigated in myometrial interstitial cell cultures based on morphological criteria and later prepared for time-lapse microscopy. Semi-analytical and numerical solutions were developed to highlight the geometric characteristics and the behavior of telocytes. RESULTS: Results were gathered in a database which would further allow efficient telocyte tracking and indexing in a content-based image retrieval (CBIR) of digital medical images. Mathematical analysis revealed pivotal information regarding the homogeneity, hardness and resistance of telocytes' structure. Cellular activity models were monitored in vitro, therefore supporting the creation of databases of telocyte images. CONCLUSIONS: The obtained images were analyzed, using segmentation techniques and mathematical models in conjunction with computer simulation, in order to depict TCs behavior in relation to surrounding cells. This paper brings an important contribution to the development of bioinformatics systems by creating software-based telocyte models that could be used both for diagnostic and educational purposes.

MicroRNA Involvement in Signaling Pathways During Viral Infection.

The study of miRNAs started in 1993, when Lee et al. observed their involvement in the downregulation of a crucial protein known as LIN-14 in the nematode Caenorhabditis elegans. Since then, great progress has been made regarding research on microRNAs, which are now known to be involved in the regulation of various physiological and pathological processes in both animals and humans. One such example is represented by their interaction with various signaling pathways during viral infections. It has been observed that these pathogens can induce the up-/downregulation of various host miRNAs in order to elude the host's immune system. In contrast, some miRNAs studied could have an antiviral effect, enabling the defense mechanisms to fight the infection or, at the very least, they could induce the pathogen to enter a latent state. At the same time, some viruses encode their own miRNAs, which could further modulate the host's signaling pathways, thus favoring the survival and replication of the virus. The goal of this extensive literature review was to present how miRNAs are involved in the regulation of various signaling pathways in some of the most important and well-studied human viral infections. Further on, knowing which miRNAs are involved in various viral infections and what role they play could aid in the development of antiviral therapeutic agents for certain diseases that do not have a definitive cure in the present. The clinical applications of miRNAs are extremely important, as miRNAs targeted inhibition may have substantial therapeutic impact. Inhibition of miRNAs can be achieved through many different methods, but chemically modified antisense oligonucleotides have shown the most prominent effects. Though scientists are far from completely understanding all the molecular mechanisms behind the complex cross-talks between miRNA pathways and viral infections, the general knowledge is increasing on the different roles played by miRNAs during viral infections.

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis.

MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.