Osteoprotegerin Gene as a Biomarker in the Development of Osteoporosis in Postmenopausal Women.

Osteoporosis is a multifactorial and polygenic disease caused by an imbalance between osteoclastogenesis and osteoblastogenesis, leading to a decrease in bone mineral density and the occurrence of disorders in the microarchitecture and metabolism of bone tissue. In postmenopausal women, there is a significant decrease in the production of estrogens, which play a key role in maintaining proper bone mineral density. Estrogens have an inhibitory effect on the development and activity of osteoclasts by reducing the synthesis of pro-resorption cytokines and stimulating the expression of osteoprotegerin (OPG). Osteoprotegerin is a cytokine that prevents bone loss by inhibiting the process of osteoclastogenesis, reducing bone resorption. The aim of our study was to determine the influence of the rs3102735 (-163A>G), rs3134070 (-245T>G), rs207361 (-950T>C), rs7844539 (6890A>C), and rs2073618 (1181G>C) polymorphisms of the OPG gene on the risk of osteoporosis and osteopenia in postmenopausal Polish women. The study included 802 unrelated women (osteoporosis: n = 317, osteopenia: n = 110, controls: n = 375) at postmenopausal age (54.7 ± 8.6 years). Genetic analysis was performed using real-time PCR. BMD values as well as clinical and bone parameters with the tested polymorphisms were analyzed among the study population. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, for the OPG rs207361 polymorphism, we observed a statistically significant association with the risk of osteoporosis, suggesting that the OPG rs207361 variant may be one of the genetic markers associated with the pathogenesis of osteoporosis.

Analysis of the Polymorphisms and Expression Levels of the BCL2, BAX and c-MYC Genes in Patients with Ovarian Cancer.

Ovarian cancer (OC) is one of the biggest problems in gynecological oncology and is one of the most lethal cancers in women worldwide. Most patients with OC are diagnosed at an advanced stage; therefore, there is an urgent need to find new biomarkers for this disease. Gene expression profiling is proving to be a very effective tool for exploring new molecular markers for OC patients, although the relationship between such markers and patient survival and clinical outcomes is still elusive. Moreover, polymorphisms in genes encoding both apoptosis-associated proteins and oncoproteins may serve as key markers of cancer susceptibility. The aim of our study was to analyze the polymorphisms and expressions of the BCL2, BAX and c-MYC genes in a group of 198 women, including 98 with OC. The polymorphisms and mRNA expressions of the BCL2, BAX and c-MYC genes were analyzed using real-time PCR. The analysis of the BAX (rs4645878; G>A) and c-MYC (rs4645943; C>T) polymorphisms showed no association with ovarian cancer risk. The BCL2 polymorphism (rs2279115; C>A) showed a significant difference in the frequency of genotypes between the studied groups (CC: 23.47% vs. 16.00%, AA: 25.51% vs. 37.00%; p = 0.046; OR = 1.61). Furthermore, the expression levels of the BCL2 and c-MYC genes showed a decrease at the transcript level for OC patients compared to the control group (BCL2: 17.46% ± 3.26 vs. 100% ± 8.32; p < 0.05; c-MYC: 37.56% ± 8.16 vs. 100% ± 9.12; p < 0.05). No significant changes in the mRNA level were observed for the BAX gene (104.36% ± 9.26 vs. 100% ± 9.44; p > 0.05). A similar relationship was demonstrated in the case of the protein expressions of the studied genes. These findings suggest that the CC genotype and C allele of the BCL2 polymorphism could be genetic risk factors for OC development. A gene expression analysis indicated that BCL2 and c-MYC are associated with OC risk.

The influence of ESR1 polymorphisms on selected hormonal, metabolic and mineral balance markers in women with hyperandrogenism.

Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance in normal estrogen and androgen levels in the blood. Androgens influence bone mineral density, body mass composition, muscle mass, mental state, and the regulation of sexual function.. The aim of the study was to assess the effect of estrogen receptor α gene (ESR1) polymorphisms on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group included 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, sRANKL (soluble receptor activator of nuclear factor-kB ligand), osteoprotegerin and 25-OH vitamin D total levels. An analysis of ESR1 gene polymorphisms was performed using the real-time PCR method. A relationship was demonstrated between the concentration of free estradiol (FEI) and the concentration of 17-OH-progesterone, and the ESR1 gene polymorphisms: rs3020314 (p = 0.031, p = 0.026 respectively) and rs1884051 (p = 0.033, p = 0.026 respectively). In conclusion, the ESR gene polymorphisms may be associated with hormonal disturbances in the concentration of estrogens and androgens, in hyperandrogenism in young women which may indirectly affect bone mineral density. However, no statistically significant relationships between the studied polymorphisms and the selected parameters of mineral metabolism have been demonstrated..

Combined Effects of Methyldopa and Baicalein or Scutellaria baicalensis Roots Extract on Blood Pressure, Heart Rate, and Expression of Inflammatory and Vascular Disease-Related Factors in Spontaneously Hypertensive Pregnant Rats.

The aim of the study was to investigate the effect of baicalein or Scutellaria baicalensis root extract interaction with methyldopa in pregnant spontaneously hypertensive rats (SHR) at the pharmacodynamic, molecular, and biochemical levels. The rats, after confirming pregnancy, received baicalein (200 mg/kg/day, p.o.) and extract (1000 mg/kg/day, p.o.), in combination with methyldopa (400 mg/kg/day; p.o.), for 14 consecutive days, 1 h before blood pressure and heart rate measurements. In the heart and placenta from mothers after giving birth to their offspring, mRNA expression of factors related to inflammatory processes (TNF-α, Il-1ß, IL-6) and vascular diseases (TGF-ß, HIF-1α, VEGF, PlGF) was measured. Levels of markers of oxidative stress (superoxide dismutase and malondialdehyde) in the placenta and indicators of myocardial damage (troponin cTnC and cTnI, creatine kinase, myoglobin, and lactate dehydrogenase) in the heart were also assessed. Baicalein co-administered with methyldopa was associated with reduced blood pressure, especially during the first three days. The interactions were more pronounced for such factors as TGF-ß, HIF-1α, VEGF, and PlGF than TNF-α, Il-1ß, and IL-6. Combined application of baicalein and extract with methyldopa may be of value in the development of a new antihypertensive medication intended for patients suffering from preeclampsia or pregnancy-induced hypertension.

Association of ACE2 Gene Variants with the Severity of COVID-19 Disease-A Prospective Observational Study.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), has triggered an enormous scientific response. Many studies have focused on understanding the entry of the SARS-CoV-2 virus into the host cell. The angiotensin-converting enzyme-2 (ACE2) is recognized as the host receptor used by SARS-CoV-2 to enter its target cells. Recent studies suggest that ACE2 gene polymorphisms might be candidates for genetic susceptibility to SARS-CoV-2 infection. The aim of this study is to evaluate the influence of ACE2 polymorphisms on COVID-19 disease risk and severity. In our study, we confirmed that there is a statistically significant increased risk of a more severe disease course of SARS-CoV-2 infection associated with the need for hospitalization in intensive care for patients with specific polymorphisms of the ACE2 gene. The most significant correlation was found for variant ACE2 rs2285666 (AA allele, OR = 2.12, p = 0.0189) and ACE2 rs2074192 (TT allele, OR = 2.05, p = 0.0016), and for ACE2 rs4646174 (GG allele, OR = 1.93, p = 0.0016), ACE2 rs4646156 (TT allele OR = 1.71, p = 0.008) and ACE2 rs2158083 (TT allele OR = 1.84, p = 0.0025). In conclusion, our findings identify that certain ACE2 polymorphisms impact the severity of COVID-19 disease independently of other well-known risk factors.

Status of Microbiota in Odontogenic Inflammatory Lesions and Dental Surgery Procedures Performed on an Outpatient Basis.

Inflammations of the facial part of the skull are most commonly caused by a bacterial infection. They are a frequently occurring pathological process, which results from a rich bacterial flora of the oral cavity, as well as diseased teeth and periodontal tissues. These inflammations have a primarily mixed character with the prevalence of anaerobic bacteria. Gangrene of the dental pulp is the most common odontogenic cause. In the case of inflammations of oral tissues an early and corrective treatment results in quick recovery. The purpose of this work was to assess the efficiency of empirical antibiotic therapy applied in patients with inflammations of oral tissues on the basis of a drug susceptibility profile of bacteria isolated from material extracted from inflammatory lesions. The research material consisted of smears collected from patients with existing acute inflammations in the oral cavity. The smear was collected from the bottom of the lesion after its prior surgical treatment and pus evacuation, and again, 7 days after surgery. In patients with acute odontogenic inflammations the recommended first-line therapy are extended-spectrum penicillins, characterized by a low risk of side effects and strong antimicrobial activity. In the study group, both clindamycin and amoxicillin exhibited high efficiency in treating acute odontogenic inflammatory lesions in the oral cavity.

Expression of ABCA1 Transporter and LXRA/LXRB Receptors in Placenta of Women with Late Onset Preeclampsia.

BACKGROUND: Appropriate levels of cholesterol are necessary for the mother and developing fetus, but theirexcess may cause preeclampsia. The ABCA1 transporter mediates the secretion of cholesterol and is highly regulated at the transcriptional level via the nuclear liver X receptors (LXRs). METHODS: Sixteen preeclamptic and 39 normotensives healthy women with uncomplicated pregnancies were involved in the case-control study. The placental levels of ABCA1, LXRA and LXRB mRNA were quantified by real-time quantitative PCR. The concentrations of ABCA1, LXRA and LXRB proteins from the placenta were determined using an enzyme-linked immunosorbent assay Results: We found in the logistic regression model significantly lower placental expression of LXRB mRNA (crude OR = 0.26, 95% CI: 0.07-0.94, p = 0.040) and LXRA protein level (crude OR = 0.19, 95% CI: 0.05-0.69, p = 0.012) in late-onset preeclamptic women compared to healthy pregnant women. The values remained statistically significant after adjustment for possible confounders. CONCLUSIONS: Our results suggest that high placenta LXRA mRNA and LXRA protein expression levels decrease the risk of late-onset preeclampsia. These nuclear receptors could play a role in the development of preeclampsia through disturbances of lipid metabolism.

Identification of New Molecular Biomarkers in Ovarian Cancer Using the Gene Expression Profile.

Ovarian cancer is a common cause of death among women worldwide. The current diagnostic and prognostic procedures available for the treatment of ovarian cancer are either not specific or are very expensive. Gene expression profiling has proved to be a very effective tool in the exploration of new molecular markers in patients with ovarian cancer, although the link between such markers and patient survival and clinical outcomes is still elusive. We are looking for genes that may function in the development and progression of ovarian cancer. The aim of our study was to evaluate the expression of selected suppressor genes (ATM, BRCA1, BRCA2), proto-oncogenes (KRAS, c-JUN, c-FOS), pro-apoptotic genes (NOXA, PUMA), genes related to chromatin remodeling (MEN1), and genes related to carcinogenesis (NOD2, CHEK2, EGFR). Tissue samples from 30 normal ovaries and 60 ovarian carcinoma tumors were provided for analysis of the gene and protein expression. Gene expression analysis was performed using the real-time PCR method. The protein concentrations from tissue homogenates were determined using the ELISA technique according to the manufacturers' protocols. An increase in the expression level of mRNA and protein in women with ovarian cancer was observed for KRAS, c-FOS, PUMA, and EGFR. No significant changes in the transcriptional levels we observed for BRCA1, BRCA2, NOD2, or CHEK2. In conclusion, we suggest that KRAS, NOXA, PUMA, c-FOS, and c-JUN may be associated with poor prognosis in ovarian cancer.

Association of the CYP19A1 rs700518 Polymorphism with Selected Markers of Bone Metabolism in Women with Hyperandrogenism.

Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance of normal estrogen and androgen levels in the blood. Androgens play an important role in the female body because they influence bone mineral density (BMD), body mass composition, muscle mass, mental state, and the regulation of sexual function. The reduced activity of aromatase, due to mutations in the CYP19A1 gene, reduces the estrogen pool in favor of androgens. Clinically, aromatase deficiency causes hyperandrogenism in women. Therefore, the aim of the study was to assess the effect of the CYP19A1 gene polymorphism on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group was comprised of 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, total sRANKL (free and bound RANKL), osteoprotegerin, and total 25-OH Vitamin D. An analysis of the CYP19A1 gene polymorphisms was performed using the real-time PCR method. The GG genotype of the CYP19A1 rs700518 polymorphism turned out to be associated with: FEI (Free Estradiol Index), SHGB concentration, estradiol concentration, and insulin concentration determined in the glucose tolerance test 60' compared to AG and AA genotypes. Patients with the AG genotype had a higher ratio of android to gynoid fat and a greater content of visceral adipose tissue. Higher visceral tissue content may reduce BMD. In conclusion, the study showed that the CYP19A1 rs700518 polymorphism may be associated with the distribution of adipose tissue in young women with hyperandrogenism. These results suggest that patients with the AG genotype may develop osteoporosis.

A 646C > G (rs41423247) polymorphism of the glucocorticoid receptor as a risk factor for hyperglycaemia diagnosed in pregnancy-data from an observational study.

AIM: Hyperglycaemia diagnosed in pregnancy (HiP) is a serious and frequent complication of pregnancy, increasing the risk for adverse maternal and neonatal outcomes. Investigate whether allelic variations of the glucocorticoid receptor are related to an increased risk of HiP. METHOD: The following polymorphisms of the glucocorticoid receptor (GR) were investigated in the cohort study of N = 197 pregnant women with HiP and N = 133 normoglycemic pregnant controls: 646C > G (rs41423247), N363S (rs6195), ER23/22EK (rs6190, rs6189). RESULTS: A GG variant of the rs41423247 polymorphism was associated with a significantly higher risk for HiP: OR 1.94 (1.18; 3.18), p = 0.009. The relationship remained significant after controlling for maternal age and prepregnancy BMI: OR 3.09 (1.25; 7.64), p = 0.014. CONCLUSIONS: The allelic GG variant of the 646C > G (rs41423247) polymorphism is associated with an increased risk for hyperglycaemia in pregnancy.

Influence of TGFB1 and CTLA4 polymorphisms on calcineurin inhibitors dose and risk of acute rejection in renal transplantation.

Organ transplant is often the treatment of choice as it extends and improves patient life. Immunosuppressive treatment, which prevents acute rejection of the organ, is used in transplant patients to prevent the loss of transplant. The aim of the study was to determine the impact of the CTLA4 (+49A>G, rs231775) and the TGF-ß1 (-800G>A, rs1800468) polymorphisms on the therapeutic effect of immunosuppressive drugs (cyclosporine-CsA, tacrolimus-TAC) and the risk of acute rejection in renal transplant patients. The analysis of the CTLA4 +49A>G and the TGF-ß1 -800G>A polymorphisms was carried out in 392 patients after kidney transplant using real-time PCR. The CTLA4 +49A>G polymorphism did not affect CsA or TAC dose, ratio of drug concentration to dose (C/D), and blood concentrations. As for the TGF-ß1 -800G>A polymorphism, patients with the GA genotype required lower TAC doses compared to the GG genotype (TAC 12 h: 3.63 mg vs 5.3 mg, TAC 24 h: 2.38 mg vs 3.29 mg). Comparing the C/D ratio in both groups (TAC 12 h and TAC 24 h), higher C/D ratio was observed in patients with the GA genotype. These results indicate that patients with the A allele require slightly lower doses of TAC. The results suggest that the TGF-ß1 -800 G>A polymorphism may influence the TAC dose, while the +49A>G polymorphism of the CTLA4 gene does not correlate with the dose of CsA or TAC. The analysis of the biochemical parameters of the renal profile showed no impact of the CTLA4 and the TGF-ß1 polymorphisms on the risk of organ rejection.

The Analysis of NADPH Quinone Reductase 1 (NQO1) Polymorphism in Polish Patients with Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignancies in Poland. Based on the findings of clinical trials, it is safe to conclude that genetic predisposition and environmental factors are the main factors responsible for the formation of colorectal cancer.The NQO1 gene plays an important role in reducing endogenous and exogenous quinones as well as quinone compounds to hydroquinones. It is an enzyme which is a part of the body's antioxidant defense system. The aim of the study was to evaluate the correlation between the 609C > T polymorphism of the NQO1 gene and colorectal cancer risk in the Polish population. A total of 512 people were recruited for the study, including 279 patients with colorectal cancer, diagnosed at the University Hospital, Pomeranian Medical University in Szczecin. Genomic DNA was isolated from peripheral blood and the analyzed polymorphism was determined by PCR-RFLP. In the present study, we analyzed the clinical valuesand frequency of NQO1 609C > T polymorphism in patients diagnosed with colorectal cancer and controls. In case of the carriers of the TT genotype of the NQO1 polymorphism, an elevated risk for colorectal cancer was observed (OR = 2.96; 95% CI: 1.02-10.40). The analysis of the clinical parameters concerning the location and characteristics of the tumor stage revealed a statistically significant increase in the risk for colorectal cancer in the carriers of the TT genotype of the NQO1 polymorphism.

The importance of the UGT1A1 variants in the development of osteopenia and osteoporosis in postmenopausal women.

The UDP-glucuronosyltransferase 1A1 (UGT1A1) is involved in the process of estrogen conjugation and elimination. The aim of the study was to analyze whether the UGT1A1 genetic variants are associated with the development of osteopenia and osteoporosis in postmenopausal women. The analysis of the rs4148323 (UGT1A1*6) and rs3064744 (UGT1A1*28) variants in the UGT1A1 gene was conducted using real-time PCR. A significant correlation was observed between the genotypes of the rs3064744 (UGT1A1*28) sequence variant and body mass in women with osteoporosis. The analysis of the Z-score values revealed that women with osteoporosis and carrying the 6/6 variant had the lowest Z-score values as compared to women with the 6/7 and the 7/7 variants (- 1.966 ± 0.242 vs. - 1.577 ± 0.125 and - 1.839 ± 0.233). In addition, the odds ratio for the investigated genotypes (6/6, 6/7, 7/7) indicated an increased risk for osteopenia and osteoporosis in women with the 7/7 homozygous genotype. The analysis of the frequencies of the GG, GA and AA genotypes of the rs4148323 UGT1A1 gene showed no statistically significant differences between the groups. Our analysis revealed that the UGT1A1 rs3064744 variant may affect the risk of developing osteoporosis in postmenopausal Polish women. The UGT1A1 rs4148323 variant is not directly associated with the development of osteopenia and osteoporosis.

The importance of NFκB1 rs4648068 and RUNX2 rs7771980 polymorphisms in bone metabolism of postmenopausal Polish women.

OBJECTIVES: Osteoporosis is a multifactorial disease that causes a loss of bone density. However, genetic factors play an increasingly important role in its development. To thoroughly understand the molecular mechanisms, polymorphic variants of genes candidate for osteoporosis are still being sought. The aim of our study was to investigate the influence of NFκB1 gene rs4648068 (A>G) and RUNX2 gene rs7771980 (-1025T>C) polymorphisms on the risk of osteoporosis. MATERIAL AND METHODS: A group of 675 postmenopausal Caucasian women (109 women with osteopenia, 333 with osteoporosis and 233 with normal T-score) were examined. The bone mineral density (BMD) at the lumbar spine (L1-L4) was measured by dual energy x-ray absorptiometry (DXA). The analysis of NFκB1 and RUNX2 polymorphisms was performed using real-time PCR method. RESULTS: Analysis of NFκB1 gene rs4648068 polymorphism showed that the GG genotype was slightly more frequent in the study groups compared to the control group. In the osteoporosis group, patients with the G allele in the genotype have lower bone mineral density values. For the RUNX2 rs7771980 polymorphism, in women with osteopenia we observed an increased incidence of TC heterozygotes compared to the control group (29.40% vs 24.90%, p > 0.05), and in women with osteoporosis, the TT genotype was more common (78.70% vs 73.80%, p > 0.05). No correlation was observed between the genotypes and the clinical parameters. CONCLUSIONS: The analysis showed no significant relationship between the genotypic distribution and the individual clinical parameters. However, it is suggested an association between the rs4648068 polymorphism of the NFκB1 gene and an increased risk of developing osteoporosis.

Combined Effects of Methyldopa and Flavonoids on the Expression of Selected Factors Related to Inflammatory Processes and Vascular Diseases in Human Placenta Cells-An In Vitro Study.

The aim of the study was to investigate combined effects of flavonoids (apigenin, baicalein, chrysin, quercetin, and scutellarin) and methyldopa on the expression of selected proinflammatory and vascular factors in vitro for prediction of their action in pregnancy-induced hypertension. The research was conducted on a trophoblast-derived human choriocarcinoma cell line and a primary human umbilical vein endothelial cell line. Cytotoxicity of compounds in selected concentrations (20, 40, and 100 µmol) was measured using the MTT test and the concentration of 40 µmol was selected for further analysis. Subsequently, their effects with methyldopa on the expression of selected markers responsible for inflammation (TNF-α; IL-1ß; IL-6) and vascular effects (hypoxia-inducible factor 1α-HIF-1α; placental growth factor-PIGF; transforming growth factor ß-TGF-ß; vascular endothelial growth factor-VEGF) at the mRNA and protein levels were assessed. It was found that every combined administration of a flavonoid and methyldopa in these cells induced a down-regulating effect on all tested factors, except PIGF, especially at the mRNA expression level. As hypertension generally raises TNF-α, IL-1ß, IL-6, HIF-1α, TGF-ß, and VEGF mRNA expression and/or protein levels, the results obtained in the studied model may provide a positive prognostic factor for such activity in vivo.

Vitamin D receptor gene polymorphisms and haplotypes in the etiology of recurrent miscarriages.

A few years ago it was shown that disturbed metabolism of the vitamin D/receptor (VD/VDR) complex may be important in the etiology of spontaneous abortion, as well as in the etiology of recurrent miscarriages (RM). The goal of this study was to investigate the association between four maternal VDR polymorphisms as well as haplotypes settings and RM occurrence in a Polish population of women in reproductive age. A total of 230 women were recruited to this study (110 with RM, 120 consecutively recruited age-matched healthy women with at least two full-term pregnancies and with no history of miscarriages). DNA samples were genotyped for VDR polymorphisms: FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236). Significant differences in genotype distributions and allele frequencies between case and control groups were observed in VDR BsmI polymorphism (GG vs. GA and AA, OR = 0.56, p = 0.036 and OR = 1.49, p = 0.035, respectively). The best evidence of an association with RM prevention was observed for the TTGT haplotype, which was more frequent among controls than cases even after permutation test (0.09 vs. 0.017, p = 0.0024). Other haplotypes were also significantly more frequent in the control group: TGT (rs7975232, rs1544410, rs2228570), TG (rs7975232, rs1544410), TTG (rs731236, rs7975232, rs1544410), TT (rs731236, rs7975232). Our research indicated the possible role of VDR BsmI genetic polymorphism in RM etiology, suggesting at the same time the active role of maternal VD metabolism and its influence on pregnancy outcome. The significant influence of several maternal haplotypes was shown to prevent RM occurrence.

The Effect of Different Water Extracts from Platycodon grandiflorum on Selected Factors Associated with Pathogenesis of Chronic Bronchitis in Rats.

The aim of this study was to assess the activity of extracts from Platycodon grandiflorum A. DC (PG) in a model of chronic bronchitis in rats. The research was carried out on three water extracts: E1 - from roots of field cultivated PG; E2 - from biotransformed roots of PG; E3 - from callus of PG. The extracts differed in saponins and inulin levels-the highest was measured in E3 and the lowest in E1. Identification of secondary metabolites was performed using two complementary LC-MS systems. Chronic bronchitis was induced by sodium metabisulfite (a source of SO2). Animals were treated with extracts for three weeks (100 mg/kg, intragastrically) and endothelial growth factor (VEGF), transforming growth factors (TGF-ß1, -ß2, -ß3), and mucin 5AC (MUC5AC) levels were determined in bronchoalveolar lavage fluid, whereas C reactive protein (CRP) level was measured in serum. Moreover, mRNA expression were assessed in bronchi and lungs. In SO2-exposed rats, an elevation of the CRP, TGF-ß1, TGF-ß2, VEGF, and mucin was found, but the extracts' administration mostly reversed this phenomenon, leading to control values. The results showed a strong anti-inflammatory effect of the extracts from PG.

The effect of genetic variations for interleukin-10 (IL-10) on the efficacy of immunosuppressive therapy in patients after kidney transplantation.

Kidney transplantation is the target method of treating chronic kidney disorders. It improves the comfort of patient life by eliminating the need for repeated dialysis. The aim of the study was to examine the correlation between tacrolimus (TAC) dose and genetic variation for interleukin-10 (IL-10) and its effect on the therapeutic outcome. In addition, the correlations between the IL-10 polymorphism andthe clinical and the biochemical parameters of TAC patients were also analyzed. The study included 209 subjects after kidney transplantation, who received TAC every 12 and 24 h. Drug concentrations in blood, selected morphological and biochemical parameters, and the genetic variation of IL-10 (-1082A > G) which may affect immunosuppressant dosage and risk of acute graft rejection were analyzed. Genetic analyses were performed using real-time PCR. No significant correlations between the clinical and the biochemical parameters and IL-10-1082A > G polymorphism for patients receiving TAC after kidney transplantation were found. The analysis of the correlation between TAC dose and IL-10 genetic variation for the -1082A > G polymorphism revealed that patients with the AA genotype required lower immunosuppressive drug doses (AA: 3.54 ± 2.38 mg/day vs AG: 6.18 ± 5.10 mg/day, GG: 4.44 ± 3.01 mg/day). Furthermore, frequencies of the genotypes for the IL-10 -1082A > G polymorphism were characterized by a significantly higher frequency of the AA genotype among TAC 24 as compared to TAC 12 patients. The results of the study indicated that the IL-10 -1082A > G polymorphism may in fact influence the TAC dose. The biochemical parameters of the renal profile in relation to the IL-10 genetic variations were not indicative of higher risk of acute rejection after transplantation.

COVID-19: The Influence of ACE Genotype and ACE-I and ARBs on the Course of SARS-CoV-2 Infection in Elderly Patients.

Since the beginning of 2020, the whole world has been struggling with the pandemic of Coronavirus Disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2. The SARS-CoV-2 infection depends on ACE2, TMPRSS2, and CD147, which are expressed on host cells. Several studies suggest that some single nucleotide polymorphisms (SNPs) of ACE2 might be a risk factor of COVID-19 infection. Genotypes affect ACE2 structure, its serum concentration, and levels of circulating angiotensin (1-7). Moreover, there is evidence that ACE genotype affects the outcomes of acute respiratory distress syndrome (ARDS) treatment, the most severe consequence of SARS-CoV-2 infection. COVID-19 morbidity, infection course, and mortality might depend on ACE D allele frequency. The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. There is no direct evidence yet for ACE-I or ARBs in the treatment of COVID-19. However, for those already taking these medications, both the European Society of Cardiology and the American College of Cardiology recommend continuing the treatment, because at present, there is no clear clinical or scientific evidence to justify the discontinuation of ACE-I or ARBs. Individualized treatment decisions should be based on the clinical condition and co-morbidities of each patient.

Polymorphism analysis of the Gly972Arg IRS-1 and Gly1057Asp IRS-2 genes in obese pregnant women.

Genes encoding insulin receptor substrates IRS-1 and IRS-2 perform key functions in the insulin pathway. Numerous authors have suggested that single-nucleotide polymorphism (SNP) changes in the DNA sequence may be associated with the development of obesity, insulin resistance and type 2 diabetes. The Gly972Arg polymorphism of the IRS-1 gene and the Gly1057Asp polymorphism of the IRS-2 gene are believed to be associated with the occurrence of insulin resistance and obesity according to many sources. The aim of our study was to investigate the influence of these polymorphisms on the clinical parameters and to assess their correlations in obese Polish pregnant women. A total of 154 pregnant Caucasian women from the Wielkopolska region were analyzed: 78 diagnosed with overweight or obesity (study group) and 76 with normal body mass (controls). The analysis of the polymorphisms was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. The IRS-2 Gly1057Asp polymorphism revealed no significant correlations with excessive weight gain during pregnancy. The analysis of the IRS-1 Gly972Arg polymorphism showed an association with obesity between the study and control groups (GG-80.77%, GR-17.95%, RR-1.28% vs GG-94.74%, GR-5.26%; p = 0.023). We also observed slightly increased BMI values ​​and higher values ​​of the waist and hip circumference before pregnancy in the case of the IRS-1 Gly972Arg polymorphism. The analysis of the clinical and anthropometric parameters demonstrated no significant relationships between the genotypes of the polymorphic variants of the IRS-1 and IRS-2 genes but suggested an association between the IRS-1 Gly972Arg polymorphism and the risk for obesity.