Exercise intolerance de novo is one of the most common reported symptoms in patients recovering from the Coronavirus Disease 2019 (COVID-19). The present study determines etiological and ...pathophysiological factors influencing the mechanism of impaired exercise tolerance in patients during Long-COVID. Consequently, the factors affecting the percentage predicted oxygen uptake at peak exercise (%VO2pred) in patients after COVID-19 with a normal left ventricular ejection fraction (LVEF) were assessment. A total of 120 patients recovering from COVID-19 at three to six months after confirmed diagnosis were included. The clinical examinations, laboratory test results, echocardiography, non-invasive body mass analysis, and spiroergometry were evaluated. The subjects were divided into the following groups: study patients’ group with worsen oxygen uptake (%VO2pred < 80%; n = 47) and control group presenting%VO2pred ≥ 80% (n = 73). ClinicalTrials.gov Identifier: NCT04828629. The male gender and the percent of total body water content (TBW%) were significantly higher in the study group compared to the control group (53 vs. 29%, p = 0.007 and 52.67 (±6.41) vs. 49.89 (±4.59), p = 0.02; respectively). Patients with %VO2pred < 80% presented significantly lower global peak systolic strain (GLPS), tricuspid annular plane systolic excursion (TAPSE), and late diastolic filling (A) velocity (19.34 (±1.72)% vs. 20.10 (±1.35)%, p = 0.03; 21.86 (±4.53) vs. 24.08 (±3.20) mm, p = 0.002 and median 59.5 (IQR: 50.0−71.0) vs. 70.5 (IQR: 62.0−80.0) cm/s, p = 0.004; respectively) compared to the controls. The results of the multiple logistic regression model show that (A) velocity (OR 0.40, 95%CI: 0.17−0.95; p = 0.03) and male gender (OR 2.52, 95%CI: 1.07−5.91; p = 0.03) were independently associated with %VO2pred. Conclusions: Men have over twice the risk of persistent limited exercise tolerance in Long-COVID than women. The decreased (A) velocity, TAPSE, GLPS, and hydration status are connected with limited exercise tolerance after COVID-19 in patients with normal LVEF.
Toll-like receptors (TLRs) have a key role in innate immunity. These receptors recognize both pathogen-associated molecular patterns and molecules that are released from damaged tissue. TLRs mediate ...signal transduction pathways through the activation of transcription factors that regulate the expression of proinflammatory cytokines and chemokines and are required for the development of adaptive immune responses. TLRs might have an important role in the pathogenesis of renal diseases: their exaggerated activation is associated with ischemic kidney damage, acute kidney injury, end-stage renal failure, acute tubulointerstitial nephritis, acute renal transplant rejection and delayed allograft function. As the results of previous studies concerning the role of TLRs in renal diseases are conflicting, further work is needed to determine the exact role of these receptors and to evaluate strategies to prevent TLR-mediated local inflammation. This Review discusses the evidence supporting a role for TLRs in contrasting bacterial infections and in causing or aggravating renal conditions when TLR activation leads to a harmful inflammatory response.
Although preeclampsia has long been recognized as a condition affecting late pregnancy, little is known of its pathogenesis or treatment. The placenta releases a number of hormones and molecules that ...influence the course of pregnancy, one of which is chromogranin A, a soluble protein secreted mainly from the chromaffin cells of the adrenal medulla. Its role in pregnancy and pregnancy-related disorders remains unclear. Therefore, the main aim of the proposed study is to determine whether chromogranin A is related with the occurrence of preeclampsia.
Placental samples were collected from 102 preeclamptic patients and 103 healthy controls, and Chromogranin A gene (CHGA) expression was measured using real-time RT-PCR, The RT-PCR results were verified on the protein level using ELISA. The normal distribution of the data was tested using the Shapiro-Wilk test. The clinical and personal characteristics of the groups were compared using the Student's t-test for normally-distributed data, and the χ
test for categorical variables. The Mann-Whitney U test was used for non-normally distributed data. As the log- transformation was not suitable for the given outcomes, the Box- Cox Transformation was used to normalize data from ELISA tests and CHGA expression. Values of P < .05 were considered statistically significant.
Chromogranin A gene expression was found to be significantly higher in the study group than in controls. Protein analyses showed that although the CgA concentration in placental samples did not differ significantly, the catestatin (CST) level was significantly lower in samples obtained from women with preeclampsia, according to the controls.
This study for the first time reveals that chromogranin A gene expression level is associated with preeclampsia. Moreover, the depletion in catestatin level, which plays a protective role in hypertension development, might be a marker of developing preeclampsia. Further studies may unravel role of Chromogranin A in the discussed disease.
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Preeclampsia is a pregnancy disorder associated with shallow placentation, forcing placental cells to live in hypoxic conditions. This activates the transcription factor kappa B (NFκB) in maternal ...and placental cells. Although the role of NFκB in preeclampsia is well documented, its mechanism of activation in trophoblastic cells has been never studied. This study investigates the mechanism of NFκB activation in a first trimester trophoblastic cell line (HTR8/SVneo) stimulated by a medium containing serum from preeclamptic (PE) or normotensive (C) women in hypoxic (2% O2) or normoxic (8% O2) conditions. The results indicate that in HTR8/SVneo cells, the most widely studied NFκB pathways, i.e., canonical, non-canonical and atypical, are downregulated in environment PE 2% O2 in comparison to C 8% O2. Therefore, other pathways may be responsible for NFκB activation. One such pathway depends on the activation of NFκB by the p53/RSK1 complex through its phosphorylation at Serine 536 (pNFκB Ser536). The data generated by our study show that inhibition of the p53/RSK1 pathway by p53-targeted siRNA results in a depletion of pNFκB Ser536 in the nucleus, but only in cells incubated with PE serum at 2% O2. Thus, the p53/RSK1 complex might play a critical role in the activation of NFκB in trophoblastic cells and preeclamptic placentas.
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The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic has brought forth various clinical manifestations and long-term complications, including a condition known as long COVID. Long COVID ...refers to a persistent set of symptoms that continue beyond the acute phase of the disease. This study investigated the risk factors and the utility of spiroergometry parameters for diagnosing patients with long COVID symptoms. The 146 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with normal left ventricular ejection fraction and without respiratory diseases were included and divided into two groups: the group demonstrating long COVID symptoms n = 44 and the group without long COVID symptoms n = 102. The clinical examinations, laboratory test results, echocardiography, non-invasive body mass analysis, and spiroergometry were evaluated. ClinicalTrials.gov Identifier: NCT04828629. Patients with long COVID symptoms had significantly higher age 58 (vs.) 44 years;
< 0.0001, metabolic age 53 vs. 45 years;
= 0.02), left atrial diameter (LA) 37 vs. 35 mm;
= 0.04, left ventricular mass index (LVMI) 83 vs. 74 g/m
,
= 0.04, left diastolic filling velocity (A) 69 vs. 64 cm/s,
= 0.01, the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion (E/E') 7.35 vs. 6.05;
= 0.01, and a lower ratio of early to late diastolic transmitral flow velocity (E/A) 1.05 vs. 1.31;
= 0.01 compared to the control group. In cardiopulmonary exercise testing (CPET), long COVID patients presented lower forced vital capacity (FVC) 3.6 vs. 4.3 L;
< 0.0001, maximal oxygen consumption measured during incremental exercise indexed per kilogram (VO
) 21 vs. 23 mL/min/kg;
= 0.04, respiratory exchange ratio (RER) 1.0 vs. 1.1;
= 0.04, forced expiratory volume in one second (FEV1) 2.90 vs. 3.25 L;
= 0.04, and a higher ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC%) 106 vs. 100%;
= 0.0002. The laboratory results pointed out that patients with long COVID symptoms also had a lower rate of red blood cells (RBC) 4.4 vs. 4.6 × 10
/uL;
= 0.01; a higher level of glucose 92 vs. 90 mg/dL;
= 0.03; a lower glomerular filtration rate (GFR) estimate by Modification of Diet in Renal Disease (MDRD) 88 vs. 95;
= 0.03; and a higher level of hypersensitive cardiac Troponin T (hs-cTnT) 6.1 vs. 3.9 pg/mL;
= 0.04. On the multivariate model, only FEV1/FVC% (OR 6.27, 95% CI: 2.64-14.86;
< 0.001) independently predicted the long COVID symptoms. Using the ROC analysis, the FEV1/FVC% ≥ 103 was the most powerful predictor of spiroergometry parameters (0.67 sensitive, 0.71 specific, AUC of 0.73;
< 0.001) in predicting the symptoms of long COVID. Spiroergometry parameters are useful in diagnosing long COVID and differentiating it from cardiovascular disease.
Double hit of NEMO gene in preeclampsia Sakowicz, Agata; Pietrucha, Tadeusz; Rybak-Krzyszkowska, Magda ...
PloS one,
06/2017, Volume:
12, Issue:
6
Journal Article
Peer reviewed
Open access
The precise etiology of preeclampsia is unknown. Family studies indicate that both genetic and environmental factors influence its development. One of these factors is NFkB, whose activation depends ...on NEMO (NFkB essential modulator. This is the first study to investigate the association between the existence of single nucleotide variant of the NEMO gene and the appearance of preeclampsia. A total of 151 women (72 preeclamptic women and 79 controls) and their children were examined. Sanger sequencing was performed to identify variants in the NEMO gene in the preeclamptic mothers. The maternal identified variants were then sought in the studied groups of children, and in the maternal and child controls, using RFLP-PCR. Real-time RT-PCR was performed to assess NEMO gene expression in maternal blood, umbilical cord blood and placentas. The sequencing process indicated the existence of two different variants in the 3'UTR region of the NEMO gene of preeclamptic women (IKBKG:c.*368C>A and IKBKG:c.*402C>T). The simultaneous occurrence of the TT genotype in the mother and the TT genotype in the daughter or a T allele in the son increased the risk of preeclampsia development 2.59 fold. Additionally, we found that the configuration of maternal/fetal genotypes (maternal TT/ daughter TT or maternal TT/son T) of IKBKG:c.*402C/T variant is associated with the level of NEMO gene expression. Our results showed that, the simultaneous occurrence of the maternal TT genotype (IKBKG:c.*402C>T variants) and TT genotype in the daughter or T allele in the son correlates with the level of NEMO gene expression and increases the risk of preeclampsia development. Our observations may offer a new insight into the genetic etiology and pathogenesis of preeclampsia.
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The prevalence of long-COVID (LC) presents a significant challenge to healthcare systems globally. There are still some discrepancies on the role of sex as an independent risk factor of LC ...complications. Thus, we aimed to determine the differences in clinical and cardiovascular complications between males and females without comorbidities after COVID-19.
Clinical data on the course of the disease with the accompanying symptoms and post-COVID-19 symptoms were compiled from both male and female subjects with a minimum 12-week interval after COVID-19 recovery. Next, the patients were followed for 12 months. ECG, echocardiography, 24 h ECG monitoring, 24 h ambulatory blood pressure monitoring (ABPM), and selected biochemical tests were performed. LC was diagnosed based on the World Health Organization (WHO) definition. To reduce the impact of confounders, i.e., body mass index (BMI) and age, on the results of the study, the nearest neighbour (NN) propensity score matching (PSM) method with a 1:1 ratio was used.
: The results were obtained following the removal of cases with comorbidities from the database consisting of 1237 males and 2192 females, and PSM of the new database included 886 cases (443 males and 443 females). At both the 3-month and 1-year post-recovery marks, females consistently reported a higher frequency of LC symptoms compared to males (
< 0.001 for both comparisons). Moreover, after 1 year of follow-up, females exhibited a higher prevalence of LC compared to males, with rates of 14% versus 8.3%, respectively (
= 0.013). The symptoms that significantly differed between females and males in the 12-month follow-up were hair loss (5.4 vs. 0.7%,
< 0.001), memory and concentration disturbances (8.4 vs. 4.3%,
= 0.013), and headaches (4.3 vs. 1.4%,
= 0.008). Females presented lower mean arterial pressure (MAP) 89 (83-95) mmHg versus (vs.) 94 (89-100);
< 0.001 and lower pulse pressure (PP) 46 (42-52) mmHg vs. 51 (48-57);
< 0.001 in 24 h ABPM and more elevated heart rates (HRs) in 24 h ECG monitoring as well as arrhythmia (
< 0.001 and
= 0.018, respectively). Males had a higher occurrence of ECG abnormalities such as QRS >= 120 ms, ST-T changes, T inversion, arrhythmia, and QRS fragmentation (27.3% vs. 19.2%;
= 0.004). No significant differences were observed between males and females concerning physical activity levels, stress, fatigue, alcohol consumption, and smoking habits.
One year post-COVID-19 recovery, regardless of age and BMI, healthy females more often suffered from LC symptoms than males. They had lower MAP and PP in 24 h ABPM, more often had higher HRs and arrhythmia in 24 h ECG monitoring, and fewer ECG abnormalities than males.
The study aimed to assess the clinical significance of selected single nucleotide polymorphisms (SNPs) in patients with diastolic heart failure (HF): inflammation -174 G/C Interleukin -6 (IL-6) ...rs1800795, tumor necrosis factor (TNF)-608 G/A rs1800629, fibrosis Arg25Pro transforming growth factor β (TGF β) rs1800471, endothelial function -786 T/C nitric oxide synthase (NOS) rs2070744, glucose and lipid metabolism Pro12Ala peroxisome proliferator activated receptor (PPAR)γ rs1801282, and vitamin D metabolism cytochrome P450 27B1 (CYP27B1) C-1260A.110 patients with HF with preserved and mid-range ejection fraction (HFpEF and HFmrEF) were recruited. GG homozygotes in 174 G/C of IL6 polymorphism are characterized by higher values of estimated glomerular filtration rate based on the study Modification of Diet in Renal Disease (eGFR MDRD) and C allele in the NOS polymorphism and AA profile in C-1260A of CYP27B1 polymorphism correlated with a lower eGFR (MDRD). In multivariate analysis the CG genotype for 174 G/C of IL-6 and allele A in C-1260A of CYP27B1 are the only SNPs independently associated with worse course of HFpEF and HFmrEF. These data confirm the importance of the selected SNPs in aggravation and complications of hypertension.
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The ADRB3 gene plays a role in energy expenditure by participating in lipolysis, which affects body composition and performance. The ADRB3 rs4994 polymorphism has been studied in groups of athletes, ...overweight individuals, and obese and diabetic patients, but it has not been studied in young and healthy adults so far. In the present study, we examined the association of ADRB3 rs4994 polymorphism with body composition, somatotype, cardiorespiratory fitness and physical activity in young, healthy adults (N = 304). All subjects had anthropometric measurements, and somatotypes were assessed using the Heath–Carter method. In addition, cardiorespiratory fitness and physical activity levels were assessed. Genotyping for the ADRB3 gene was performed using a PCR-RFLP method. In the male group, body components were associated with the Trp64Trp genotype (waist circumference (p = 0.035), hip circumference (p = 0.029), BF (%) (p = 0.008), and BF (kg) (p = 0.010), BMI (p = 0.005), WHtR (p = 0.021), and BAI (p = 0.006)). In addition, we observed that the Trp64Trp genotype was associated with somatotype components (p = 0.013). In contrast, the Arg allele was associated with the ectomorphic components (0.006). We also observed a positive impact of the Trp64Trp genotype with maximal oxygen uptake (p= 0.023) and oxygen pulse (p = 0.024). We observed a negative relationship of the Trp64Trp genotype in the female group with reported moderate-intensity exercise (p = 0.036). In conclusion, we found an association of the Trp64 allele with anthropometric traits, somatotype and parameters describing physical performance in the male group. In the female subpopulation, we only found an effect of the polymorphism Trp64Arg on the level of physical activity for moderate-intensity exercise.
The aim of this study was to identify the potential influence of obesity and body mass components on exercise tolerance assessed in cardiopulmonary exercise testing (CPET), biochemical and ...echocardiographic parameters and factors correlated with oxygen absorption at the anaerobic threshold in hypertensive women with low levels of physical activity in the perimenopausal period. The study comprised 188 hypertensive women divided, based on body mass index (BMI), into an obesity group and a non-obesity group. Women with BMI ≥ 30 kg/m2 had significantly higher parameters of left ventricular diastolic dysfunction in echocardiography, lower total body water (TBC) in percentage assessed by bioimpedance and significantly worse exercise capacity assessed by CPET. In the study group, VO2 AT (mL/kg/min) correlated positively with TBW (r = 0.4, p < 0.0001) and with the ratio of extracellular water to total body water (ECW/TBW) (r = 0.4, p < 0.00001) and negatively with fat (% and kg) (r = −0.4, p < 0.0001 for both). Obesity negatively affects parameters of diastolic left ventricular function, as well as exercise tolerance in CPET in hypertensive females during the perimenopausal period. The oxygen uptake at anaerobic threshold correlates positively with total body water and ECW/TBW and negatively with body fat; this connection is more pronounced in women without obesity. ClinicalTrials.gov Identifier: NCT04802369.
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