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According to the GLOBOCAN 2020, prostate cancer (PCa) is the most often diagnosed male cancer in 112 countries and the leading cancer-related death in 48 countries. Moreover, PCa incidence permanently increases in adolescents and young adults. Also, the rates of metastasising PCa continuously grow up in young populations. Corresponding socio-economic burden is enormous: PCa treatment costs increase more rapidly than for any other cancer. In order to reverse current trends in exploding PCa cases and treatment costs, pragmatic decisions should be made, in favour of advanced populational screening programmes and effective anti-PCa protection at the level of the health-to-disease transition (sub-optimal health conditions) demonstrating the highest cost-efficacy of treatments. For doing this, the paradigm change from reactive treatments of the clinically manifested PCa to the predictive approach and personalised prevention is essential.Phytochemicals are associated with potent anti-cancer activity targeting each stage of carcinogenesis including cell apoptosis and proliferation, cancer invasiveness and metastatic disease. For example, their positive effects are demonstrated for stabilising and restoring mitochondrial health quality, which if compromised is strongly associated with sub-optimal health conditions and strong predisposition to aggressive PCa sub-types. Further, phytochemicals significantly enhance response of cancer cells to anti-cancer therapies including radio- and chemotherapy. Evident plant-based mitigation of negative side-effects frequently observed for conventional anti-cancer therapies has been reported. Finally, dual anti-cancer and anti-viral effects of phytochemicals such as these of silibinin have been demonstrated as being highly relevant for improved PCa management at the level of secondary and tertiary care, for example, under pandemic conditions, since PCa-affected individuals per evidence are highly vulnerable towards COVID-19 infection.Here, we present a comprehensive data analysis towards clinically relevant anti-cancer effects of phytochemicals to be considered for personalised anti-PCa protection in primary care as well as for an advanced disease management at the level of secondary and tertiary care in the framework of predictive, preventive and personalised medicine.

Mitochondria are the “gatekeeper” in a wide range of cellular functions, signaling events, cell homeostasis, proliferation, and apoptosis. Consequently, mitochondrial injury is linked to systemic effects compromising multi-organ functionality. Although mitochondrial stress is common for many pathomechanisms, individual outcomes differ significantly comprising a spectrum of associated pathologies and their severity grade. Consequently, a highly ambitious task in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM/3PM) is to distinguish between individual disease predisposition and progression under circumstances, resulting in compromised mitochondrial health followed by mitigating measures tailored to the individualized patient profile. For the successful implementation of PPPM concepts, robust parameters are essential to quantify mitochondrial health sustainability. The current article analyses added value of Mitochondrial Health Index (MHI) and Bioenergetic Health Index (BHI) as potential systems to quantify mitochondrial health relevant for the disease development and its severity grade. Based on the pathomechanisms related to the compromised mitochondrial health and in the context of primary, secondary, and tertiary care, a broad spectrum of conditions can significantly benefit from robust quantification systems using MHI/BHI as a prototype to be further improved. Following health conditions can benefit from that: planned pregnancies (improved outcomes for mother and offspring health), suboptimal health conditions with reversible health damage, suboptimal life-style patterns and metabolic syndrome(s) predisposition, multi-factorial stress conditions, genotoxic environment, ischemic stroke of unclear aetiology, phenotypic predisposition to aggressive cancer subtypes, pathologies associated with premature aging and neuro/degeneration, acute infectious diseases such as COVID-19 pandemics, among others.

Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.

Inflammation is an essential pillar of the immune defense. On the other hand, chronic inflammation is considered a hallmark of cancer initiation and progression. Chronic inflammation demonstrates a potential to induce complex changes at molecular, cellular, and organ levels including but not restricted to the stagnation and impairment of healing processes, uncontrolled production of aggressive ROS/RNS, triggered DNA mutations and damage, compromised efficacy of the DNA repair machinery, significantly upregulated cytokine/chemokine release and associated patho-physiologic protein synthesis, activated signaling pathways involved in carcinogenesis and tumor progression, abnormal tissue remodeling, and created pre-metastatic niches, among others. The anti-inflammatory activities of flavonoids demonstrate clinically relevant potential as preventive and therapeutic agents to improve individual outcomes in diseases linked to the low-grade systemic and chronic inflammation, including cancers. To this end, flavonoids are potent modulators of pro-inflammatory gene expression being, therefore, of great interest as agents selectively suppressing molecular targets within pro-inflammatory pathways. This paper provides in-depth analysis of anti-inflammatory properties of flavonoids, highlights corresponding mechanisms and targeted molecular pathways, and proposes potential treatment models for multi-level cancer prevention in the framework of predictive, preventive, and personalized medicine (PPPM / 3PM). To this end, individualized profiling and patient stratification are essential for implementing targeted anti-inflammatory approaches. Most prominent examples are presented for the proposed application of flavonoid-conducted anti-inflammatory treatments in overall cancer management. Supplementary Information The online version contains supplementary material available at 10.1007/s13167-021-00257-y.

Multiple genetic variants have been studied for years to try to find an association with polycystic ovary syndrome (PCOS). This meta-analysis will investigate if there are associations between increased risk of PCOS and rs6165 polymorphism in follicle stimulating hormone receptor (FSHR) gene and rs2479106 polymorphism in differentially expressed in Differentially Expressed in Normal and Neoplastic Development Isoform 1A (DENND1A) gene.Studies were identified from PubMed library, and case-control studies with correct polymorphisms and available genotype frequencies were included. The statistical analysis is done in Review Manager 5.3, and odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated to see if any association with PCOS exists.In the study of FSHR gene, eight articles with 1539 cases and 1877 controls were included. No relations were found between PCOS and rs6165 polymorphism in neither the allelic (OR=1.07, 95% CI=0.97-1.19, p=0.18), recessive (OR=1.21, 95% CI=0.98-1.50, p=0.07) nor the dominant (OR=1.05, 95% CI=0.91-1.20, p=0.53) model. The rs2479106 polymorphism in DENND1A gene included 10 studies with 3627 cases and 20325 controls. Only the Asian subgroup in the recessive model (OR=1.84, 95% CI=1.19-2.85, p=0.006) showed a positive relation with PCOS, while associations were not found within the overall results in the allelic (OR=1.09, 95% CI=0.98-1.21, p=0.10), recessive (OR=1.26, 95% CI=0.73-2.19, p=0.41) or the dominant (OR=1.31, 95% CI=1.00-1.71, p=0.05) model.This meta-analysis suggests that rs2479106 polymorphism in DENND1A gene is associated with increased risk of PCOS in the Asian population. No relations were found with increased risk of PCOS and rs6165 polymorphism in FSHR gene.

Aims. Coronavirus disease 2019 is responsible for a worldwide increase in morbidity and mortality. The relationship of this infection to mother-to-child vertical transmission has not been elucidated yet. However, recent reports indicate a foetal death rate of up to 3%. Methods. We report a case of sudden pre-term foetal demise in a woman positive for SARS-CoV-2 but asymptomatic, with physiological course of pregnancy. Results. One of the possible explanations of sudden foetal death may be acute placental insufficiency caused by a SARS-CoV-2 placental infection or the development of foetal inflammatory response syndrome (FIRS). Conclusion. Considering the potential risk of foetal demise, questions remain regarding foetal monitoring and the timing of labour and delivery in the second and third trimesters, particularly in asymptomatic or mild maternal SARS-CoV-2 infection. A relevant multidisciplinary team must also be aware of these risks associated with possibly fatal consequences.

The risks related to the COVID-19 are multi-faceted including but by far not restricted to the following: direct health risks by poorly understood effects of COVID-19 infection, overloaded capacities of healthcare units, restricted and slowed down care of patients with non-communicable disorders such as cancer, neurologic and cardiovascular pathologies, among others; social risks—restricted and broken social contacts, isolation, professional disruption, explosion of aggression in the society, violence in the familial environment; mental risks—loneliness, helplessness, defenceless, depressions; and economic risks—slowed down industrial productivity, broken delivery chains, unemployment, bankrupted SMEs, inflation, decreased capacity of the state to perform socially important programs and to support socio-economically weak subgroups in the population. Directly or indirectly, the above listed risks will get reflected in a healthcare occupation and workload which is a tremendous long-term challenge for the healthcare capacity and robustness. The article does not pretend to provide solutions for all kind of health risks. However, it aims to present the scientific evidence of great clinical utility for primary, secondary, and tertiary care to protect affected individuals in a cost-effective manner. To this end, due to pronounced antimicrobial, antioxidant, anti-inflammatory, and antiviral properties, naturally occurring plant substances are capable to protect affected individuals against COVID-19-associated life-threatening complications such as lung damage. Furthermore, they can be highly effective, if being applied to secondary and tertiary care of noncommunicable diseases under pandemic condition. Thus, the stratification of patients evaluating specific health conditions such as sleep quality, periodontitis, smoking, chronic inflammation and diseases, metabolic disorders and obesity, vascular dysfunction, and cancers would enable effective managemenet of COVID-19-associated complications in primary, secondary, and tertiary care in the context of predictive, preventive, and personalized medicine (3PM).

HPVs representing the most common sexually transmitted disease are a group of carcinogenic viruses with different oncogenic potential. The immune system and the vaginal microbiome represent the modifiable and important risk factors in HPV-induced carcinogenesis. HPV infection significantly increases vaginal microbiome diversity, leading to gradual increases in the abundance of anaerobic bacteria and consequently the severity of cervical dysplasia. Delineation of the exact composition of the vaginal microbiome and immune environment before HPV acquisition, during persistent/progressive infections and after clearance, provides insights into the complex mechanisms of cervical carcinogenesis. It gives hints regarding the prediction of malignant potential. Relative high HPV prevalence in the general population is a challenge for modern and personalized diagnostics and therapeutic guidelines. Identifying the dominant microbial biomarkers of high-grade and low-grade dysplasia could help us to triage the patients with marked chances of lesion regression or progression. Any unnecessary surgical treatment of cervical dysplasia could negatively affect obstetrical outcomes and sexual life. Therefore, understanding the effect and role of microbiome-based therapies is a breaking point in the conservative management of HPV-associated precanceroses. The detailed evaluation of HPV capabilities to evade immune mechanisms from various biofluids (vaginal swabs, cervicovaginal lavage/secretions, or blood) could promote the identification of new immunological targets for novel individualized diagnostics and therapy. Qualitative and quantitative assessment of local immune and microbial environment and associated risk factors constitutes the critical background for preventive, predictive, and personalized medicine that is essential for improving state-of-the-art medical care in patients with cervical precanceroses and cervical cancer. The review article focuses on the influence and potential diagnostic and therapeutic applications of the local innate immune system and the microbial markers in HPV-related cancers in the context of 3P medicine.

Hypertensive disorders in pregnancy represent severe complications of pregnancy, which, if not treated, can result in serious health consequences for the mother and the child. Flavonoids are bioactive secondary metabolites commonly found in fruits, vegetables, green tea, whole grains, and medicinal plants. Flavonoids exert potent protective efficacy in experimental models of hypertensive disorders in pregnancy, especially preeclampsia, demonstrated through their capacity to modulate inflammatory responses, oxidative stress, and vascular dysfunction. In addition to their potential as therapeutics, flavonoids or flavonoid-rich food could be helpful to decrease the risk of hypertensive disorders in pregnancy when included in the diet pattern before and during pregnancy. However, the clinical evaluation of the potential capacity of flavonoids in hypertensive disorders in pregnancy is insufficient. Due to promising results from experimental studies, we highlight the need for the evaluation of flavonoids also in an appropriate clinical setting, which can be, together with proper preventive strategies, helpful in the overall management of hypertensive disorders in pregnancy.

The formation of new blood vessels from previous ones, angiogenesis, is critical in tissue repair, expansion or remodeling in physiological processes and in various pathologies including cancer. Despite that, the development of anti-angiogenic drugs has great potential as the treatment of cancer faces many problems such as development of the resistance to treatment or an improperly selected therapy approach. An evaluation of predictive markers in personalized medicine could significantly improve treatment outcomes in many patients. This comprehensive review emphasizes the anticancer potential of flavonoids mediated by their anti-angiogenic efficacy evaluated in current preclinical and clinical cancer research. Flavonoids are important groups of phytochemicals present in common diet. Flavonoids show significant anticancer effects. The anti-angiogenic effects of flavonoids are currently a widely discussed topic of preclinical cancer research. Flavonoids are able to regulate the process of tumor angiogenesis through modulation of signaling molecules such as VEGF, MMPs, ILs, HIF or others. However, the evaluation of the anti-angiogenic potential of flavonoids within the clinical studies is not frequently discussed and is still of significant scientific interest.

Systemic lupus erythematosus is a chronic inflammatory autoimmune disease with high prevalence in female in reproductive age. In recent years the prognosis of pregnant patients with SLE has improved significantly. Even though the treatment options have improved, the risk of flares, preeclampsia, pregnancy loss, and premature labours remains high compared to healthy women. The aim of this article is to offer a review of current treatment options in pregnant patients with SLE and to present a case report of 32-year-old patient with newly diagnosed acute outbreak of SLE, who experienced a life-threatening multisystem flare at 24 weeks of gestational age. This case represents one of the most extreme manifestations of lupus disease activity associated with pregnancy that has been reported in literature and emphasizes the importance of preconception evaluation and counseling and amultidisciplinary management approach in cases with a complex and evolving clinical course.

Breast cancer incidence is actually the highest one among all cancers. Overall breast cancer management is associated with challenges considering risk assessment and predictive diagnostics, targeted prevention of metastatic disease, appropriate treatment options, and cost-effectiveness of approaches applied. Accumulated research evidence indicates promising anti-cancer effects of phytochemicals protecting cells against malignant transformation, inhibiting carcinogenesis and metastatic spread, supporting immune system and increasing effectiveness of conventional anti-cancer therapies, among others. Molecular and sub-/cellular mechanisms are highly complex affecting several pathways considered potent targets for advanced diagnostics and cost-effective treatments. Demonstrated anti-cancer affects, therefore, are clinically relevant for improving individual outcomes and might be applicable to the primary (protection against initial cancer development), secondary (protection against potential metastatic disease development), and tertiary (towards cascading complications) care. However, a detailed data analysis is essential to adapt treatment algorithms to individuals’ and patients’ needs. Consequently, advanced concepts of patient stratification, predictive diagnostics, targeted prevention, and treatments tailored to the individualized patient profile are instrumental for the cost-effective application of natural anti-cancer substances to improve overall breast cancer management benefiting affected individuals and the society at large.

One pillar of the predictive, preventive, and personalized medicine framework strategies is the female health. The evaluation of women’s lifestyle and dietary habits in context with genetic and modifiable risk factors may reflect the prevention of cervical cancer before the occurrence of clinical symptoms and prediction of cervical lesion behavior. The main aim of this review is to analyze publications in the field of precision medicine that allow the use of research knowledge of cervical microbiome, epigenetic modifications, and inflammation in potential application in clinical practice. Personalized approach in evaluating patient’s risk of future development of cervical abnormality should consider the biomarkers of the local microenvironment characterized by the microbial composition, epigenetic pattern of cervical epithelium, and presence of chronic inflammation. Novel sequencing techniques enable a more detailed characterization of actual state in cervical epithelium. Better understanding of all changes in multiomics level enables a better assessment of disease prognosis and selects the eligible targeted therapy in personalized medicine. Restoring of healthy vaginal microflora and reversing the outbreak of cervical abnormality can be also achieved by dietary habits as well as uptake of prebiotics, probiotics, synbiotics, microbial transplantation, and others.

Sticky platelet syndrome (SPS) is a thrombophilia caused by the increased aggregability of platelets in response to the addition of low concentrations of epinephrine (EPI) and/or adenosine diphosphate (ADP). Some of the single nucleotide polymorphisms (SNP), alleles and haplotypes of platelet glycoprotein receptors were proved to have a role in the etiology of thrombotic episodes When comparing SPS and the control group, in VEGFA rs3025039, the p value for both CC vs. TT and CT vs. TT analyses was

Phyllodes tumors (PTs) are rare fibroepithelial neoplasms of the breast. They have a proliferating stromal component that can be graded as benign, borderline, and malignant. In addition, they are associated with an increased risk of local recurrence and distant metastasis. The authors hereby present a case report of a 34-year-old woman with recurrent malignant PT with an increasing aggressiveness. There were two recurrences of giant tumors that consumed the entire right breast, which developed over a three-year period. The final surgical treatment was a total extirpation of the tumor with subsequent plastic reconstruction using a cutaneous flap from the region of the latissimus dorsi muscle. The patient died three months after the last recurrence due to multiorgan failure.

Multi-factorial mitochondrial damage exhibits a “vicious circle” that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.

An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised “normal” body weight and individually optimal weight. To this end, the basic principle of personalised medicine “one size does not fit all” has to be applied. Contextually, “normal” but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters—all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice.

Vaginal dryness (VD) affects both pre- and postmenopausal women at any age. Since the hormonal regulation changes during the climacteric period are considered as being the main course of the VD, affected women prefer not to talk about the problem. However, the problem does exist, and unfortunately if any, relatively minor group in the population possesses the health literacy at sufficient level to understand that VD is a suboptimal health condition which carries a multi-factorial character. Thereby, some of the contributing factors are clearly preventable and, therefore, if treated properly, have a potential to milden the VD. Current chapter demonstrates specific signs and symptoms of Flammer syndrome in women suffering from vaginal dryness, although individualised patient profiles clearly discriminate between pre- and postmenopausal women regarding the subgroup-specific symptoms. Noteworthy, about 20% of the VD patients involved in the study notify a delayed or even impaired wound healing observed for themselves over a couple of years. Optimising modifiable risk factors accompanying FS phenotype at the level of primary prevention is strongly recommended. Individualised patient profiles provide important information for VD mitigating measures tailored to the person. Further, future projects should essentially deal with the complexity of vulvar-vaginal dryness as part of the Sicca syndrome in individuals with FS phenotype, in order to prevent genital female cancers which may occur at any age. In contrast to the human papilloma virus as possible trigger of the disease, the role of the vulvar-vaginal dryness as an important risk factor is strongly underestimated in currently applied diagnostic and treatment approaches.

Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease. This study evaluated pregnancy-related issues in patients with MS in one perinatological centre.A single-centre, retrospective study of the perinatal period in patients with MS admitted at the Dpt. of Gynaecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University and the University Hospital in Martin, Slovak Republic, European Union from January 1, 2015 to December 1, 2020 was performed. Selected parameters from personal, obstetric, and neurological histories were analysed.A cohort of 15 patients (32.5±5.3 years) with a relapsing-remitting form of MS gave birth to 16 children. The mean length of MS at the time of delivery was 9±3.6 years. The severity of the Expanded Disability Status Scale score was 2.0±1.5. Caesarean section (CS) was indicated in 14 deliveries (87.5%). It was elective CS in 10 patients. The most common indication for elective CS was a combination of significant chronic fatigue syndrome and neurological deficit (paresis).The basis for the management of pregnancy, childbirth, and the postpartum period in women with MS is a planned pregnancy based on close cooperation among patients, gynaecologists, and neurologists. Vaginal delivery is not primarily contraindicated. Indications for CS should be considered individually. One way to minimise the indications for CS is a more accurate diagnosis and personalised treatment of fatigue in pregnant women with MS. Presumably, both obstetricians and neurologists prefer vaginal delivery as the first choice in patients with fatigue syndrome.

Cervical cancer (CC) is one of the most common cancers of the female reproductive system. In advanced stages, it might lead to metastases via hematogenous or lymphatic spread. Patients with hematogenous metastases are less common with a higher risk of death. This article focuses on a case of CC with comedo-like spinocellular skin metastases. These structures, typical for basaloid squamous cell carcinoma, represent an uncommon and extremely rare finding even in advanced CC and are associated with a poor prognosis.

Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are:- Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects;- Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities.

MicroRNAs (miRNAs) are one of the important regulators of cellular functions fundamental for healthy pregnancy processes, including angiogenesis and differentiation of trophoblast cells, and their deregulation could be implicated in the pathogenesis of pregnancy complications, including preeclampsia (PE). The aim of this study was to assess the association of miRNA expression in plasma samples with PE, its onset, and severity. Our study enrolled 59 pregnant women, 27 in the preeclamptic study group and 32 in the control group with physiological pregnancy. Preeclamptic pregnancies were divided into subgroups based on the severity and onset of disease. Relative expression of miR-21-5p, miR-155-5p, miR-210-5p, miR-16-5p, and miR-650 isolated from plasma samples was analysed by quantitative real-time PCR and normalised to experimentally established reference genes. Our results revealed upregulation of miR-21-5p (1.16-fold change, p = 0.0015), miR-155-5p (1.62-fold change, p = 0.0005) in preeclamptic pregnancies, compared to controls. Overexpression of these two miRNAs was observed, especially in subgroups of severe and late-onset PE compared to healthy pregnancies. Although we hypothesised that the expression level of studied miRNAs could vary between PE subtypes (mild vs. severe, early onset vs. late-onset), no obvious differences were detected. In conclusion, our study could contribute to the large-scale studies for the identification of non-invasive biomarkers for PE detection to improve outcomes for women and their new-borns.

Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with a plethora of biological activities. Carotenoids exert a potent anti-cancer capacity in various cancer models in vitro and in vivo, mediated by the modulation of signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of the epithelial–mesenchymal transition and regulatory molecules, such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), urokinase plasminogen activator (uPA) and its receptor (uPAR), hypoxia-inducible factor-1α (HIF-1α), and others. Moreover, carotenoids modulate the expression of genes associated with cancer progression and inflammatory processes as key mediators of the complex process involved in metastasis. Nevertheless, due to the predominantly preclinical nature of the known anti-tumor effects of carotenoids, and unclear results from certain carotenoids in specific cancer types and/or specific parts of the population, a precise analysis of the anti-cancer effects of carotenoids is essential. The identification of carotenoids as effective compounds targeting the complex process of cancer progression could improve the outcomes of advanced cancer patients.

Preeclampsia is a multisystemic disorder that occurs in 5-8% of pregnant women and remains a leading cause of both maternal and fetal morbidity and mortality. The disease is characterized by the abnormal vascular response to placentation, but the exact pathophysiology and pathogenesis of preeclampsia remain unknown. Risk factors for preeclampsia include increased maternal age, obesity, multiple gestations, and a history of preeclampsia. Several studies have suggested that altered expression of some microRNAs (miRNAs) in placental tissue, and maternal circulation, may be associated with several types of pregnancy complications such as preeclampsia, preterm birth, and spontaneous abortion. It is assumed that these miRNAs play an important role in various cellular processes important for maintaining a healthy pregnancy, including promoting angiogenesis and the differentiation of trophoblast cells. In this review, we discuss the role of miRNAs as potential biomarkers of preeclampsia.

Metastasis represents a serious complication in the treatment of cancer. Flavonoids are plant secondary metabolites exerting various health beneficiary effects. The effects of flavonoids against cancer are associated not only with early stages of the cancer process, but also with cancer progression and spread into distant sites. Flavonoids showed potent anti-cancer effects against various cancer models in vitro and in vivo, mediated via regulation of key signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of epithelial-mesenchymal transition or regulatory molecules such as MMPs, uPA/uPAR, TGF-β and other contributors of the complex process of metastatic spread. Moreover, flavonoids modulated also the expression of genes associated with the progression of cancer and improved inflammatory status, a part of the complex process involved in the development of metastasis. Flavonoids also documented clear potential to improve the anti-cancer effectiveness of conventional chemotherapeutic agents. Most importantly, flavonoids represent environmentally-friendly and cost-effective substances; moreover, a wide spectrum of different flavonoids demonstrated safety and minimal side effects during long-termed administration. In addition, the bioavailability of flavonoids can be improved by their conjugation with metal ions or structural modifications by radiation. In conclusion, anti-cancer effects of flavonoids, targeting all phases of carcinogenesis including metastatic progression, should be implemented into clinical cancer research in order to strengthen their potential use in the future targeted prevention and therapy of cancer in high-risk individuals or patients with aggressive cancer disease with metastatic potential.

Chronic hypersensitivity cough syndrome affects mainly postmenopausal women; however, the pathogenesis of cough hypersensitivity in this demographic is not entirely understood. The role of sex hormones in cough has never been studied in detail; however, sex hormones seem to play an important role in the lung health of women. Our study was aimed to analyse the effect of female sex hormones (oestrogen – E2 and progesterone – Pg) on cough sensitivity measured by inhalation of capsaicin in follicular and luteal phases of menstrual cycle, characterized by significantly different concentrations of sex hormones. These data were compared with a matched group of women taking oral contraceptives. Cough sensitivity to capsaicin increased in luteal phase in subjects with normal menstrual cycle, and this functional change was not present in group with contraceptive pills. The cough sensitivity correlates with the Pg/E2 ratio, and relative lack of oestrogen in luteal phase is associated with higher cough sensitivity to capsaicin.

Preeclampsia (PE) is a pregnancy specific disease with several risk factors such as genetic polymorphisms, environmental and social factors participating in its development. The aim of this study was to investigate whether distribution of three putative regulatory SNPs rs13430086, rs5186, rs4606 in 3'UTR of genes ACVR2A, AGTR1 and RGS2, respectively, that have been associated with hypertension and regulation of trophoblast invasion differ between women with PE and control group. The associations of rs13430086, rs5186 and rs4606 with preeclampsia were tested in two groups - the group of 50 women with PE and the control group of 42 healthy pregnant women at term. DNA was isolated from blood samples and the determination of genotypes was performed using Real-Time PCR. Power analysis for the size of the cohort was performed and the results were analyzed using Fisher exact test. The AA genotype of ACVR2A rs13430086 was significantly associated with higher risk to preeclampsia compared with TT genotype (p = 0.026, OR: 5.39, 95%CI: 1.21-31.54). Results showed no association between genotypes and preeclampsia for polymorphisms rs5186, rs4606. Further studies are important in order to better understand the role of ACVR2A in the pathogenesis of PE.

Highlights • We present the first case of bilateral ovarian angiosarcoma arising from the mature teratomas. • Due to widespread disease, we performed limited surgical procedure consisting of bilateral adnexectomy and omentectomy. • This work summarizes the current knowledge in the diagnosis and treatment of angiosarcomas arising in the mature teratomas. • Promising results are expected from the trials devoted to antiangiogenic strategies in treatment of aggressive sarcomas., Introduction Ovarian teratomas undergo the malignant transformation in 0.2–2% of cases. The behavior of malignancies in mature cystic teratomas (MCT) is determined by their phenotype and not their derivation from germ cells. We can recognize pure angiosarcomas or as a part of other tumors like malignant mixed Mullerian tumors and adenosarcomas. Presentation of case We present the first case of bilateral ovarian angiosarcoma arising from the mature teratomas. Due to widespread disease, we performed limited surgical procedure consisting of bilateral adnexectomy and omentectomy. Exploratory laparotomy in 44-year old patient showed massive ascites, necrotic tissue of omentum and bilateral tumors originating from both ovaries measuring 8 and 6 cm with necrotic surface. Immunohistochemistry of the tumors showed positive staining for CD31, vimentin, desmin and focal positivity for CD34. Discussion Sarcomas of gynecologic origin are extremely rare tumors. They present with unspecified symptoms and are diagnosed in late stages of the disease. The appropriate management of angiosarcomas is difficult due to the rarity of disease and late stage of the diseases. Surgical therapy should contain the hysterectomy with bilateral salpingo-oophorectomy and omentectomy. Pelvic lymphadenectomy was not performed in published cases with no effect on patient survival. Conclusion This work summarizes the current knowledge in the diagnosis and treatment of angiosarcomas arising in the mature teratomas. Promising results are expected from the trials devoted to antiangiogenic strategies in treatment of aggressive sarcomas.

Aim Colposcopic indexes including Reid index and Swede score were developed to make the colposcopy more objective. The aim of our study was to evaluate the significance of colposcopic indexes in the evaluation of ASC-H cervical lesions. Methods We carried out a cross-sectional study in the Clinic of Obstetrics and Gynecology between January 2013 and December 2018. The study included 535 women, from which 66 women had a cytological result ASC-H. Scoring of all colposcopic findings was assessed according to Reid modified index and Swede score and a composite score was determined. Frequency distributions were compared using χ2 /Fisher exact test. Spearman rank correlation coefficient was computed between RCI and Swede score. Results Sensitivity, specificity, positive and negative predictive value and positive likelihood ratio of modified Reid colposcopic index at a cutoff of ≥4 for the detection of HSIL+ lesions were: 86.11% (95% CI: 70.5-95.3), 83.33% (95% CI: 65.3-94.4), 86.11% (95% CI: 69.7-94.8), 83.33% (95% CI: 64.5-93.7) and 5.17 (95% CI: 2.3-11.6). Swede score with the cutoff value ≥5 showed comparable results to modified Reid index with the increased sensitivity: 94.44% (95% CI: 81.3-99.3). Conclusion ASC-H category represents the trickiest cytological diagnosis as it is underlined with the high risk of severe cervical dysplasia. Evaluating the cervical lesion by the use of colposcopic indices helps the gynecologist to objectively evaluate all the pathologies of uterine cervix. Swede score with the cutoff value 8 also enables a 'see and treat' option in management of atypical squamous cells, cannot exclude high-grade lesions.

Why does healthcare of breast cancer (BC) patients, especially in a young population, matter and why are innovative strategies by predictive, preventive, and personalized medicine (PPPM) strongly recommended to replace current reactive medical approach in BC management? Permanent increase in annual numbers of new BC cases with particularly quick growth of premenopausal BC patients, an absence of clearly described risk factors for those patients, as well as established screening tools and programs represent important reasons to focus on BC in young women. Moreover, "young" BC cases are frequently "asymptomatic", difficult to diagnose, and to treat effectively on time. The objective of this article is to update the knowledge on BC in young females, its unique molecular signature, newest concepts in diagnostics and therapy, and to highlight the concepts of predictive, preventive, and personalized medicine with a well-acknowledged potential to advance the overall disease management.

Vaginal dryness (VD) affects both pre- and postmenopausal women at any age. Since the hormonal changes during the climacteric period are considered as being the main course of the VD, affected women prefer not to talk about the problem. However, the problem does exist, and unfortunately if any, relatively minor group in the population possesses the health literacy at sufficient level to understand that VD is a suboptimal health condition which carries a multi-factorial character. Thereby, some of the contributing factors are clearly preventable and, therefore, if treated properly, have a potential to milden the VD. Current chapter demonstrates specific signs and symptoms of Flammer Syndrome (FS) in women suffering from vaginal dryness, although individualised patient profiles clearly discriminate between pre- and postmenopausal women regarding the subgroup-specific symptoms. Noteworthy, about 20% of the VD patients involved in the study notify a delayed or even impaired wound healing self-reported over a couple of years.

Phytochemicals are naturally occurring plant-derived compounds and some of them have the potential to serve as anticancer drugs. Based on recent evidence, aberrantly regulated expression of microRNAs (miRNAs) is closely associated with malignancy. MicroRNAs are characterized as small non-coding RNAs functioning as posttranscriptional regulators of gene expression. Accordingly, miRNAs regulate various target genes, some of which are involved in the process of carcinogenesis. This comprehensive review emphasizes the anticancer potential of phytochemicals, either isolated or in combination, mediated by miRNAs. The ability to modulate the expression of miRNAs demonstrates their importance as regulators of tumorigenesis. Phytochemicals as anticancer agents targeting miRNAs are widely studied in preclinical in vitro and in vivo research. Unfortunately, their anticancer efficacy in targeting miRNAs is less investigated in clinical research. Significant anticancer properties of phytochemicals as regulators of miRNA expression have been proven, but more studies investigating their clinical relevance are needed.

Simple Summary Metabolic reprogramming is required for both malignant transformation and tumor development, including invasion and metastasis. Melatonin (5-methoxy-N-acetyltryptamine) is a methoxyindole that is synthesized in the pineal gland. Importantly, melatonin has anticancer effects by stimulating apoptosis, regulation of survival signaling, suppression of metastasis and angiogenesis and regulation of epigenetic modifications that contribute to malignant transformation. Furthermore, melatonin affects steps associated with the Warburg phenotype and suppresses the switch from oxidative phosphorylation to aerobic glycolysis through the regulation of critical enzymes and glucose transporters. Melatonin is involved in regulation of p53 and HIF-1, directly participate in signaling cascades that modulate aerobic glycolysis, gluconeogenesis, the tricarboxylic acid cycle and the pentose phosphate pathway. A significant impact of melatonin in the modulation of metabolic cascades represent a unique opportunity to inhibit pathways metabolic reprogramming. Abstract Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

Breast cancer, which is the most common malignancy in women, does not form a uniform nosological unit but represents a group of malignant diseases with specific clinical, histopathological, and molecular characteristics. The increasing knowledge of the complex pathophysiological web of processes connected with breast cancercarcinogenesis allows the development of predictive and prognostic gene expressionand molecular classification systems with improved risk assessment, which could be used for individualized treatment. In our review article, we present the up-to-date knowledge about the role of miRNAs and their prognostic and predictive value in luminal A breast cancer. Indeed, an altered expression profile of miRNAs can distinguish not only between cancer and healthy samples, but they can classify specific molecular subtypes of breast cancer including HER2, Luminal A, Luminal B, and TNBC. Early identification and classification of breast cancer subtypes using miRNA expression profilescharacterize a promising approach in the field of personalized medicine. A detection of sensitive and specific biomarkers to distinguish between healthy and early breast cancer patients can be achieved by an evaluation of the different expression of several miRNAs. Consequently, miRNAs represent a potential as good diagnostic, prognostic, predictive, and therapeutic biomarkers for patients with luminal A in the early stage of BC.

The aim of this case report is to describe a rare non-hypoxic cause of pathological changes in fetal heart rate pattern during labor, and to determine management, including a description of important prenatal aspects when pathologic cardiotocographic recording is performed during labor. A fetus with rare arteriovenous malformation of the vein of Galen, which represents less than 1% of all intracranial arteriovenous malformations, was monitored by intrapartum external cardiotocography in the 37 + 5 gestational week. The baby was born by cesarean section because of signs of imminent intrauterine hypoxia on cardiotocography. However, metabolic acidosis was not confirmed in umbilical cord blood sampling. Despite intensive neonatal care management, the newborn died 31 h after delivery because of progressive cardiac decompensation, hypotension and multi-organ failure. Precise diagnosis of the abovementioned pathology, a pre-labor plan for delivery and postnatal prognosis assessment can significantly contribute to the avoidance of a misdiagnosis of fetal hypoxia and unnecessary operative delivery with marked medico-legal consequences.

Introduction The aim of this study was to evaluate the genetic variability of selected single nucleotide polymorphisms (SNPs) within GAS6 and PEAR1 genes and explore the association between selected SNPs and risk for fetal loss in women with sticky platelet syndrome (SPS). Materials and Methods We examined 23 female patients with SPS and history of spontaneous abortion, and 42 healthy women who served as controls. The diagnosis of SPS was established by light transmission aggregometry according to methods and criteria developed by Mammen et al. We also assessed four SNPs within the GAS6 gene (rs7400002, rs1803628, rs8191974, rs9550270) and two SNPs within PEAR1 gene (rs12041331, rs12566888). Results We identified two SNPs within PEAR1 gene (rs12041331, rs12566888) and one SNP within GAS6 gene (rs9550270) that have higher occurrence in SPS patients with history of abortion. An increased risk for abortion was observed in carriers of the rs7400002 within GAS6 gene. Conversely, we found that the T allele of PEAR1 c. -9–4663G > T polymorphism appears to be protective for fetal loss. Conclusion Our results support the idea that genetic variability of GAS6 and PEAR1 genes may be associated with platelet hyperaggregability. The study also suggests a possible polygenic type of SPS heredity.