Arterial hypertension occurs in 8–29% of pregnant women and is a common form of endothelial dysfunction during gestation. In recent decades, the prevalence of arterial hypertension has increased several times largely due to the increasing maternal age of primiparous women and the increased incidence of obesity, diabetes mellitus, and carbohydrate metabolism disorders. The aim of this study was to formulate the management tactics for pregnant patients with high blood pressure, based on the current understanding of the causes and mechanisms of the disease and the ability to influence the molecular links of pathogenesis, and to identify possible markers for predicting the progression of endothelial dysfunction in pregnant women with arterial hypertension. This review, based on the literature, raises the problem of modern diagnosis of arterial hypertension in pregnancy. We discuss the consequences of late initiation of the therapy and evaluate possible complications. The severity of arterial hypertension is assessed differently in pregnant and non-pregnant women, according to current clinical guidelines. Thus, chronic arterial hypertension in pregnant women corresponds to grade II arterial hypertension in non-pregnant women, according to the American Heart Association and American College of Cardiology classification. Both untimely diagnosis and delayed or inadequate treatment result in adverse obstetric outcomes. Recent studies indicate the ability of earlier antihypertensive therapy (already at stage I according to the American Heart Association and American College of Cardiology classification) to reduce maternal and fetal adverse effects and prolong pregnancy. The CHAP 2022 study showed that using a blood pressure treatment threshold of 140/90 mmHg for pregnant women with chronic arterial hypertension provides better outcomes compared to treatment at higher numbers. Despite early initiation of therapy, some patients with elevated blood pressure subsequently develop thrombotic and gestational complications associated with endothelial dysfunction. There is an obvious need to introduce early preclinical diagnostic methods that would narrow the risk group and prevent late complications. The authors’ consensus on personalization of acetylsalicylic acid intake has emerged. The review analyzes the potential mechanisms of aspirin resistance, as well as the influence of genetic (the PTGS1, PTGS2, ITGB3, ITGA2, GP6, GP1BA, P2RY1, P2RY12 genes, other genes, and associated microRNA) and biochemical markers (11-dehydrotromboxane B2), which presumably may have prognostic value and applicability in clinical practice. Our current understanding of the problem of diagnosis and early treatment of arterial hypertension in pregnancy can reduce the number of complications. The problem of predicting the development of endothelial dysfunction remains unresolved to the end. Active implementation of the studied markers into practice requires a further more detailed study of this area and the optimization of research design.

Background: Previous EWASs (Epigenome-Wide Association Studies) have reported hundreds of blood pressure (BP) associated 5′-cytosine-phosphate-guanine-3′ (CpG) sites. However, their results were inconsistent. Longitudinal observations on the temporal relationship between DNA methylation and BP are lacking. Methods: A candidate CpG site association study for BP was conducted on 1072 twins in the Chinese National Twin Registry. PubMed and EMBASE were searched for candidate CpG sites. Cross-lagged models were used to assess the temporal relationship between BP and DNA methylation in 308 twins who completed 2 surveys in 2013 and 2018. Then, the significant cross-lagged associations were validated by adopting the Inference About Causation From Examination of Familial Confounding approach. Finally, to evaluate the cumulative effects of DNA methylation on the progression of hypertension, we established methylation risk scores based on BP-associated CpG sites and performed Markov multistate models. Results: 16 and 20 CpG sites were validated to be associated with systolic BP and diastolic BP, respectively. In the cross-lagged analysis, we detected that methylation of 2 CpG sites could predict subsequent systolic BP, and systolic BP predicted methylation at another 3 CpG sites. For diastolic BP, methylation at 3 CpG sites had significant cross-lagged effects for predicting diastolic BP levels, while the prediction from the opposite direction was observed at one site. Among these, 3 associations were validated in the Inference About Causation From Examination of Familial Confounding analysis. Using the Markov multistate model, we observed that methylation risk scores were associated with the development of hypertension. Conclusions: Our findings suggest the significance of DNA methylation in the development of hypertension.

Background: Hypertension is a common cardiovascular disease that is related to genetic and environmental factors, but its mechanisms remain unclear. DNA methylation, a classic epigenetic modification, not only regulates gene expression but is also susceptible to environmental factors, linking environmental factors to genetic modification. Therefore, globally screening differential genomic DNA methylation in patients with hypertension is important for investigating hypertension mechanisms. Methods: Differential genomic DNA methylation in patients with hypertension, individuals with prehypertension, and healthy control individuals was screened using Illumina 450K BeadChip and verified by pyrosequencing. Plasma OVGP1 (oviduct glycoprotein 1) levels were determined using an enzyme-linked immunosorbent assay. Ovgp1 transgenic and knockout mice were generated to analyze the function of OVGP1. The blood pressure levels of the mouse models were measured using the tail-cuff system and radiotelemetry methods. The role of OVGP1 in vascular remodeling was determined by vascular relaxation studies. Protein–protein interactions were investigated using a pull-down/mass spectrometry assay and verified with coimmunoprecipitation and pull-down assays. Results: We found a hypomethylated site at cg20823859 in the promoter region of OVGP1 and plasma OVGP1 levels were significantly increased in patients with hypertension. This finding indicates that OVGP1 is associated with hypertension. In Ovgp1 transgenic mice, OVGP1 overexpression caused an increase in blood pressure, dysfunctional vasoconstriction and vasodilation, remodeling of arterial walls, and increased vascular superoxide stress and inflammation, and these phenomena were exacerbated by angiotensin II infusion. In contrast, OVGP1 deficiency attenuated angiotensin II–induced vascular oxidase stress, inflammation, and collagen deposition. These findings indicate that OVGP1 is a prohypertensive factor that directly promotes vascular remodeling. Pull-down and coimmunoprecipitation assays showed that MYH9 (nonmuscle myosin heavy chain IIA) interacted with OVGP1, whereas inhibition of MYH9 attenuated OVGP1-induced hypertension and vascular remodeling. Conclusions: Hypomethylation at cg20823859 in the promoter region of OVGP1 is associated with hypertension and induces upregulation of OVGP1. The interaction between OVGP1 and MYH9 contributes to vascular remodeling and dysfunction. Therefore, OVGP1 is a prohypertensive factor that promotes vascular remodeling by binding with MYH9.

The objective was to determine the potential associations of the angiotensin II receptor type 1 (AGTR1) gene polymorphism, methylation, and lipid metabolism in Chinese farmers with hypertension. A case-control study was conducted in Wuzhi county of Henan province in China in 2013 to 2014. A total of 1034 local residents (35–74 years, 386 hypertensive cases, and 648 normotensive subjects) were enrolled in this study. Triglyceride (TG), total cholesterol (TC), high-density lipoprotein, and low-density lipoprotein were measured using automatic chemistry analyzer. The AGTR1 gene promoter methylation level was measured using quantitative methylation-specific polymerase chain reaction method. The single nucleotide polymorphism rs275653 was genotyped with TaqMan probe assay at an applied biosystems platform. The gender, body mass index (BMI), TG, TC, and family history of hypertension in the hypertension group were significantly higher than those in control group (P < .05). No significant difference was observed in the distribution of AGTR1 rs275653 polymorphism in the hypertension and controls (P > .05). The AGTR1 gene methylation in subjects carrying different genotypes was not significantly observed (P > .05). The logistic regression analysis found the AGTR1 gene methylation level was negative correlation with hypertension in the present study (odds ratio, 0.946, 95% confidence interval, 0.896–0.999) through adjusting for age, gender, BMI, education, smoking, alcohol drinking, fruit and vegetable intake, pickles intake, and family history of hypertension. The association of AGTR1 gene hypomethylation and essential hypertension was observed in Chinese farmers; no significant difference was observed in the distribution of AGTR1 rs275653 polymorphism.

Objective The present article presents a literature review concerning the microbiota of breast milk and the influence of epigenetics in the susceptibility to COVID-19. Methods A literature review. Results Breastfeeding transfers microbiota, nutrients, diverse white blood cells, prebiotics, hormones, and antibodies to the baby, which provide short- and long-term immunological protection against several infectious, gastrointestinal, and respiratory illnesses. The little evidence available shows that breast milk very rarely carries the SARS-CoV-2 virus, and even in those cases, it has been discarded as the source of contagion. Conclusion The reviewed studies show evidence of a beneficial effect of breastfeeding and highlights its importance on the current pandemic due to the immune reinforcement that it provides. Breastfed individuals showed better clinical response due to the influence on the microbiota and to the nutritional and immune contribution provided by breast milk, compared with those who were not breastfed.

According to the latest clinical data, cardiovascular diseases have ranked first in prone diseases, causing 40% of the premature deaths of China’s population. This study aimed to investigate the influence of Toll-like receptor 2- (TLR2-) mediated inflammation on the occurrence and development of familial hypertension combined with hyperlipemia and its related mechanism. Blood specimens from 66 patients undergoing coronary atherosclerosis were collected and grouped, including 22 patients into the control group, 25 into the familial hypertension group, and 19 into familial hypertension combined with hyperlipemia group. In this study, ELISA was conducted for determining the levels of four inflammatory factors of TLR2 and IL-1β, IL-6, TNF-ɑ, and CCL2 in serum and the levels of relevant indicators in mice. C57Bl/6j and genetically engineered C.129(B6)-Tlr2tm1Kir/J mice were given subcutaneous injection of normal saline (wild-saline group), 8-week 40% high-fat diet (wild-high-fat group), and subcutaneous Alzet-implanted angiotensin II micropump supplemented with the research diet (wild-high fat-Ang II group, Tlr2-/--high fat-Ang II group). Blood pressure in mice was recorded consecutively with a noninvasive hemopiezometer for eight weeks. TLR2 and IL-1β, IL-6, TNF-ɑ, and CCL2 in serum of patients with familial hypertension combined with hyperlipemia and the hypertension combined with hyperlipemia mouse model were higher than those in the normal group. Under combined intervention of Ang II and the research diet, mRNA expression related to blood pressure, blood lipid, and fat metabolism in Tlr2-/- genetically engineering mice was significantly lower than that in the wild-high fat-Ang II group. The phosphorylation levels of AKT, IKK, and p65 in mice with hypertension combined with hyperlipidemia were significantly higher than those in normal group. The levels of blood pressure and blood lipid in mice after blocking the AKT or NF-κB pathway were significantly downregulated compared with those in the wild-high fat-Ang II group, with statistically significant differences (both $P<0.05$ ). In conclusion, TLR2 regulates inflammation through Akt-NF-κB pathway, thus inducing the occurrence and development of familial hypertension combined with hyperlipemia.

DNA methylation is an epigenetic phenomenon that can alter and control gene expression. Because methylation plays a key role in cell differentiation, methylation markers have been identified that are unique to a given cell type; these markers are stable and can be measured in tissue or whole blood. The article by Katzke and colleagues, published in this issue, uses methylation markers to estimate proportions of immune cell subtypes in peripheral blood samples that were collected prior to diagnosis, thus allowing them to directly examine associations with pancreatic cancer risk. Given that immune-cell counts cannot be measured from archived blood, and that retrospective case–control studies rely on blood that is collected after cancer diagnosis, few studies have been able to examine the role of the systemic immune response in cancer risk. Measurement of DNA methylation in peripheral blood, primarily through development of whole-genome approaches, has also opened new doors to examining cancer etiology. See related article by Katzke et al., p. 2179

There is high risk of suicidality in bipolar disorder (BD), particularly in early onset cases. The literature regarding correlates and putative predictors of suicide attempts (SA), non-suicidal self-injury (NSSI) and suicidal ideation (SI) among youth with BD remains sparse. Participants included 197 adolescents with BD, divided into 4 groups: SA (with or without NSSI), NSSI (with or without SI), SI only, and comparison group (CG; no SA/NSSI/SI). Diagnoses, treatment, and suicidality measures were determined via semi-structured interviews, conducted between 2009 and 2017. Univariate analyses were followed by multinomial regression. Overall, 73.6% of participants had history of SA, NSSI, and/or SI. In comparison to CG, SA and NSSI were each associated with BD-II/-NOS (odds ratio [OR] = 15.99, p = 0.002; OR = 16.76, p = 0.003), female sex (OR = 6.89, p = 0.006; OR = 3.76, p = 0.02), and emotion dysregulation (OR = 1.10, p < 0.001; OR = 1.07, p = 0.004). NSSI and SI were each associated with most severe lifetime depression (OR = 1.10, p = 0.01; OR = 1.10, p = 0.01). SA and SI were associated with psychiatric hospitalization (OR = 19.45, p = 0.001; OR = 6.09, p = 0.03). SA was associated with poorer global functioning at most severe episode (OR = 0.88, p = 0.008). NSSI was associated with not living with both natural parents (OR = 0.22, p = 0.009). Study limitations include cross-sectional and retrospective design, stringent cut-offs for SA and NSSI, and recruitment from a tertiary clinical setting. Three quarters of adolescents with BD have had suicidality and/or self-injury. SA and NSSI were most similar to one another, and most different from CG, supporting the broader construct of self-harm. Future research should address the gap in knowledge regarding how sex differences and neurobiology are associated with the observed clinical differences.

In <20 years, we have witnessed three different epidemics with coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2 in human populations, causing widespread mortality. SARS-CoV-2, through its rapid global spread, has led to the pandemic that we call COVID-19. As of February 1, 2021, the global infections linked to SARS-CoV-2 stand at 103,503,340, with 2,236,960 deaths, and 75,108,099 recoveries. This review attempts to highlight host-pathogen interaction with particular emphasis on the role of epigenetic machinery in regulating the disease. Although researchers, since the start of the pandemic, have been intensely engaged in diverse areas to understand the mechanisms involved in SARS-CoV-2 infection to find answers that can bring about innovative ways to swiftly treat and prevent disease progression, this review provides an overview on how the host epigenetics is modulated and subverted by SARS-CoV-2 to enter the host cells and drive immunopathogenesis. Epigenetics is the study that combines genetic and non-genetic factors controlling phenotypic variation, which are primarily a consequence of external and environmental stimuli. These stimuli alter the activity of a gene without impinging on the DNA code. In viral-host interactions, DNA/RNA methylation, non-coding RNAs, chromatin remodeling, and histone modifications are known to regulate and modulate host gene expression patterns. Viruses such as Coronaviruses (an RNA virus) show intrinsic association with these processes. They have evolved the ability to tamper with host epigenetic machinery to interfere with immune sensing pathways to evade host immune response, thereby enhancing its replication and pathogenesis post-entry. These epigenetic alterations allow the virus to weaken the host's immune response to successfully spread infection. How this occurs, and what epigenetic mechanisms are altered is poorly understood both for coronaviruses and other respiratory RNA viruses. The review highlights several cutting-edge aspects of epigenetic work primarily pertinent to SARS-CoV-2, which has been published between 2019 and 2020 to showcase the current knowledge both in terms of success and failures and take lessons that will assist us in understanding the disease to develop better treatments suited to kill SARS-CoV-2.

Helicobacter pylori (H. pylori) is a bacterial pathogen implicated in gastritis, gastric ulceration, and gastric carcinoma. This study aimed to synthesize literature in providing evidence on the causative role of H. pylori in gastric carcinoma development. This study is based on assessing public literature using an applied meta-analysis, namely, quantitative evidence synthesis (QES). The analytic procedure uses DerSimonian-Laird, including assessing heterogeneity. The QES also utilizes meta-regression and the environmental effect associated with H. pylori in gastric cancer development. Eighteen studies are included in the QES. There is increased prevalence of H. pylori exposure among the cases. The heterogeneity between the CES and individual effect sizes is also significant. Despite controlling for the confoundings, there is increased exposure to H. pylori among the gastric cancer cases, regardless of the differences in the geographic location. H. pylori in this synthesized literature illustrates the contributory role of this microbe in gastric carcinoma. Additionally, regardless of geographic locale, namely, South Korea or Spain, H. pylori is implicated in gastric cancer development.

Abstract. The frequency of occurrence of arterial hypertension genes in individuals at risk of sudden cardiac death was studied. The relationship between risk factors for sudden cardiac death and the presence of polymorphisms of arterial hypertension genes was revealed. There was a high incidence of homozygous risk variants AGTR2 AA and CYP11B2 TT-polymorphisms responsible for the development of left ventricular hypertrophy, including in young individuals. A correlation was found between deaths in close relatives under 50 years of age and the presence of polymorphisms in the CYP11B2 344 C>T gene in young people at risk of sudden cardiac death. We have obtained data indicating the feasibility of conducting a study of the polymorphism of the CYP11B2 gene in the presence of a risk of sudden cardiac death. A direct correlation was found between the presence of fatal outcomes in relatives under 50 years of age by the mechanism of sudden cardiac death and the number of homozygous variants of arterial hypertension genes. Mathematical models for predicting the presence of polymorphisms in genes responsible for the possibility of arterial hypertension are constructed. Among the constructed mathematical models, the most informative were models for detecting carriers of mutations in the genes ADD1 1378 G>T, CYP11B2 344 C>T and NOS3 894 G>T. The expediency of the analysis to search for mutations of arterial hypertension genes, especially in the CYP11B2 344 C>T gene, for the possibility of earlier and more intensive preventive measures in young people is shown. The data obtained indicate that there are relationships between the risk of sudden cardiac death, some known predictors of its occurrence, and the genes for arterial hypertension.

Coronavirus disease 2019 (COVID-2019) outbreak originating in December 2019 in Wuhan, China has emerged as a global treat to human health. The highly contagious SARS-CoV-2 infection and transmission presents diversity of human host and increased disease risk with advancing age, highlighting the importance of in depth understanding of its biological properties. Structural analyses have elucidated hot spots in viral binding domains, mutations and specific proteins in the host such as the receptor angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease serine 2 (TMPRSS2) to be implicated in cell entry and viral infectivity. Furthermore, epigenetic changes that regulate chromatin structure have shown a major impact in genome stabilization and maintenance of cellular homeostasis and they have been implicated in the pathophysiology of the virus infection. Epigenetic research has revealed that global DNA methylation along with ACE2 gene methylation and post-translational histone modifications may drive differences in host tissue-, biological age- and sex-biased patterns of viral infection. Moreover, modulation of the host cells epigenetic landscape following infection represents a molecular tool used by viruses to antagonize cellular signaling as well as sensing components that regulate induction of the host innate immune and antiviral defense programs in order to enhance viral replication and infection efficiency. In this review, we provide an update of the main research findings at the interface of epigenetics and coronavirus infection. In particular, we highlight the epigenetic factors that interfere with viral replication and infection and may contribute to COVID-19 susceptibility, offering new ways of thinking in respect to host viral response.

Background: Social and health inequities predispose vulnerable populations to adverse morbidity and mortality outcomes of epidemics and pandemics. While racial disparities in cumulative incidence (CmI) and mortality from the influenza pandemics of 1918 and 2009 implicated Blacks with survival disadvantage relative to Whites in the United States, COVID-19 currently indicates comparable disparities. We aimed to: (a) assess COVID-19 CmI by race, (b) determine the Black–White case fatality (CF) and risk differentials, and (c) apply explanatory model for mortality risk differentials. Methods: COVID-19 data on confirmed cases and deaths by selective states health departments were assessed using a cross-sectional ecologic design. Chi-square was used for CF independence, while binomial regression model for the Black–White risk differentials. Results: The COVID-19 mortality CmI indicated Blacks/AA with 34% of the total mortality in the United States, albeit their 13% population size. The COVID-19 CF was higher among Blacks/AA relative to Whites; Maryland, (2.7% vs. 2.5%), Wisconsin (7.4% vs. 4.8%), Illinois (4.8% vs. 4.2%), Chicago (5.9% vs. 3.2%), Detroit (Michigan), 7.2% and St. John the Baptist Parish (Louisiana), 7.9%. Blacks/AA compared to Whites in Michigan were 15% more likely to die, CmI risk ratio (CmIRR) = 1.15, 95% CI, 1.01–1.32. Blacks/AA relative to Whites in Illinois were 13% more likely to die, CmIRR = 1.13, 95% CI, 0.93–1.39, while Blacks/AA compared to Whites in Wisconsin were 51% more likely to die, CmIRR = 1.51, 95% CI, 1.10–2.10. In Chicago, Blacks/AA were more than twice as likely to die, CmIRR = 2.24, 95% CI, 1.36–3.88. Conclusion: Substantial racial/ethnic disparities are observed in COVID-19 CF and mortality with Blacks/AA disproportionately affected across the United States.

The elderly may represent a specific cluster of high-risk patients for developing COVID-19 with rapidly progressive clinical deterioration. Indeed, in older individuals, immunosenescence and comorbid disorders are more likely to promote viral-induced cytokine storm resulting in life-threatening respiratory failure and multisystemic involvement. Early diagnosis and individualized therapeutic management should be developed for elderly subjects based on personal medical history and polypharmacotherapy. Our review examines the pathogenesis and clinical implications of ageing in COVID-19 patients; finally, we discuss the evidence and controversies in the management in the long-stay residential care homes and aspects of end-of-life care for elderly patients with COVID-19.

The recent pandemic SARS-CoV-2 outbreak affects all kinds of individuals worldwide. The health, social, and economic impacts of the pandemic are dramatic, and vaccines or specific treatment options are not yet available. The only approaches that we currently have available to stop the epidemic are those of classical epidemic control, such as case isolation, contact tracing and quarantine, physical distancing, and hygiene measures. It is therefore essential to find further preventive measures and possible interventions that can slow down the number of infected individuals and decrease the severity of disease when affected by SARS-CoV-2. It seems that epigenetic mechanisms are an important part of the pathophysiology and illness severity of COVID-19. These mechanisms have been identified in SARS-CoV-2 but also in other viral infections. If and when these mechanisms are confirmed, then epigenetic interventions influencing DNA methylation could be indicated as primary and/or secondary preventive options.

Вступ. Серцево-судинна патологія є однією з найбільш частих коморбідностей у пацієнтів з рематоїдним артритом (РА). Активація ангіогенезу в синовіальній оболонці відіграє ключову роль у патогенезі РА. Ця патологія може впливати на перебіг імунозапальних і ангіогенних процесів, у яких беруть участь тол-подібні рецептори 2 (TLR2) та васкулоендотеліальний фактор росту (VЕGF). Мета дослідження – встановити вплив чинників серцево-судинного ризику на рівні тол-подібних рецепторів 2 та васкулоендотеліального фактора росту в сироватці крові хворих на ревматоїдний артрит. Методи дослідження. Обстежено 67 хворих на РА (73,1 % жінок) середнім віком (45,20±8,75) року та 25 практично здорових осіб контрольної групи. Діагноз РА встановлювали за критеріями ACR/EULAR 2010. Рівні TLR2 та VЕGF у сироватці крові визначали імуноферментним методом (Cloud-Clone Corp., США). Дослідження проводили з дотриманням біоетичних норм. Статистичну обробку результатів здійснювали в пакеті STATISTICA 6,0. Результати й обговорення. У хворих на РА рівні TLR2 та VEGF були достовірно більшими (у 2,78 і 2,69 раза, р5,1 – вищими (в 1,3–1,4 раза), ніж у пацієнтів з помірною активністю захворювання (індекс DAS28-ШОЕ 3,2–5,1). Більш значуще зростання рівня TLR2 відмічали в серопозитивних за антитілами до цитрулінованого циклічного пептиду пацієнтів. Підвищення рівнів TLR2 і VEGF у хворих на РА асоціювалось із супутньою артеріальною гіпертензією та ожирінням і не залежало від віку, статі, дисліпідемії, тютюнокуріння. Висновки. У хворих на РА відзначають збільшення рівнів TLR2 та VEGF у сироватці крові порівняно з практично здоровими особами. Зростання рівня TLR2 сильніше асоціюється з високою активністю захворювання і серопозитивністю за антитілами до цитрулінованого циклічного пептиду, тоді як збільшення рівня VEGF ‒ з коморбідною артеріальною гіпертензією та високим індексом маси тіла.