Expression profiling of genes modulated by rosmarinic acid (RA) in MCF-7 breast cancer cells

Objectives: Cancer is the second most common cause of death, with breast cancer (BC) as the most frequently diagnosed neoplasm among females. The origin of BC is multifactorial and depends on environmental and genetic factors. The disease presents a significant challenge due to its drug resistance and frequent metastasis. Thus, new effective therapies and metastasis prevention are much needed. Rosmarinic acid (RA) is a natural polyphenol which possesses the ability to inhibit BC cell proliferation and demonstrates cytotoxic properties against those cells. In our study, we examined the effect of RA on the expression of ZEB1, MDM2, ABCB1, PTEN and TWIST1 genes in MCF-7 breast cancer cells.Material and methods: MCF-7 cell cultures were treated with 0.2 μM doxorubicin (DOX) and 1.5, 15 or 50 μM of RA. Real-time PCR reaction was performed to analyze gene expression levels.Results: PCR analysis showed a significant increase of the ZEB1 gene expression, which was about 3-fold for DOX 0.2 μM, 9-fold for 0.2 μM DOX + 1.5 μM RA and 0.2 μM DOX + 15 μM RA (p < 0.05), and about 6.5-fold for 0.2 μM DOX + 50 μM RA (p < 0.05). Furthermore, a decrease of the MDM2 gene expression was observed in all of the examined variants and was about 40–75% (p < 0.05). No influence of DOX and RA combined with DOX on the ABCB1, TWIST1 and PTEN genes was found.Conclusions: The results of our study suggest that RA might be used as an adjuvant therapeutic factor in BC treatment

The importance of 8993C>T (Thr399Ile) TLR4 polymorphism in etiology of osteoporosis in postmenopausal women

Introduction: Toll-like receptors (TLR) may play a key role in initiating cellular signaling pathways by increasing the levels of inflammatory cytokines which, cooperating with osteoclasts, influence bone turnover. Numerous research articles focused on the genetic background of this condition, among others on polymorphic variants in TLR genes. The aim of the study was to examine the role of 20877G>A (Arg753Gln) in TLR2 gene and 8993C>T (Thr399Ile) in TLR4 gene in the etiopathogenesis of postmenopausal osteoporosis in Polish women. Material and methods: This study included 180 postmenopausal women (t-score ≤ -2.5), 153 postmenopausal women with osteopenia (t-score between -2.5 and -1), and 91 postmenopausal healthy women with correct t-score (t-score >-1). The 20877G>A TLR2 and 8993C>T TLR4 polymorphisms were determined by PCR/RFLP analysis. Results: The analysis did not reveal statistically significant differences in the distribution of genetic variants of 20877G>A TLR2 polymorphism between the investigated groups of women. The most interesting results were connected with 8993C>T TLR4 polymorphism. Comparison of the group with osteoporosis and controls revealed overrepresentation of heterozygous 8993CT genotype (13.3 vs. 5.5%, OR=2.65, p=0.03). Also, mutated 8993T allele was overrepresented in the group with osteoporosis (6.7 vs. 2.7%, OR=2.52, p=0.04). Higher frequency of heterozygous 8993CT genotype (13.3 vs. 4.6%, OR=3.21, p=0.004) and mutated 8993T allele (6.7 vs. 2.3%, OR=3.05, p=0.005) was noted in osteoporotic women as compared to the group with osteopenia. Higher frequency of heterozygous 8993CT genotype (13.3% vs. 5.3%, OR=2.73, p=0.003) and mutated 8993T allele (6.7 vs. 2.7%, OR=2.61, p=0.004) was observed in the group with osteoporosis as compared to women with osteopenia and with correct t-score. Conclusions: Results of our study suggest an important role of mutated 8993T allele of 8993C>T TLR4 polymorphisms in the etiology of postmenopausal osteoporosis. Nevertheless, this observation requires further investigation with larger sample size comprised of Polish women

Ballota nigra L. – an overview of pharmacological effects and traditional uses

Ballota nigra, also known as black horehound is a common medical herb used in folk medicine around the world. First reported mentions of its medical properties and use goes as far as the 13th century. The use of black horehound depends on regions and countries. It is used mostly to treat e.g. mild sleep disorders, nervousness, upset stomach, wound healing. It can be used as an anti-inflammatory, antibacterial, antiprotozoal, antifungal drug. Moreover, it has been reported as a potential cancer drug. This extensive usage is particularly interesting for us. The aim of this review is to present available data on B. nigra pharmacological effects and known traditional uses gathered from a wide range of scientific articles published in 1997–2020

Ballota nigra

Ballota nigra, also known as black horehound is a common medical herb used in folk medicine around the world. First reported mentions of its medical properties and use goes as far as the 13th century. The use of black horehound depends on regions and countries. It is used mostly to treat e.g. mild sleep disorders, nervousness, upset stomach, wound healing. It can be used as an anti-inflammatory, antibacterial, antiprotozoal, antifungal drug. Moreover, it has been reported as a potential cancer drug. This extensive usage is particularly interesting for us. The aim of this review is to present available data on B. nigra pharmacological effects and known traditional uses gathered from a wide range of scientific articles published in 1997–2020

Association of the <i>CYP19A1</i> 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

Expression of genes modulated by epigallocatechin-3-gallate in breast cancer cells

Introduction: Breast cancer is the most common malignant cancer among women. Both drug resistance and metastasis are major problems in the treatment of breast cancer. Therefore, adjuvant therapy may improve patients’ survival and affect their quality of life. It is suggested that epigallocatechin gallate (EGCG) which is well known for its chemopreventive activity and acts on numerous molecular targets may inhibit the growth and metastasis of some cancers. Hence, discovering the metastatic molecular mechanisms for breast cancer may be useful for therapy

Genetic diversity of CYP3A5 and ABCB1 variants in East-Central and South European populations

Background CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. Aim The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. Subjects and methods Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. Results In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively. Conclusion In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely

A Disorder of Sex Development in a Holstein–Friesian Heifer with a Rare Mosaicism (60,XX/90,XXY): A Genetic, Anatomical, and Histological Study

In this study, we describe an eighteen-month-old Holstein–Friesian heifer with a deformed vulva, located abdominally. The heifer showed typical signs of estrus. A comprehensive anatomical and histopathological examination revealed a blind-ended vagina and an additional section of urethra, which became a part of the shortened penis. Cytogenetic analysis showed the presence of two cell lines: 60,XX and 90,XXY. The frequency of the triploid cell line was low (3%) in leukocytes and elevated (35%) in fibroblasts. The molecular detection of Y-linked genes (SRY and AMELY) in the blood, skin, hair follicles, and buccal epithelial cells confirmed the presence of a cell line carrying the Y chromosome. Genotyping of 16 microsatellite markers in DNA isolated from hair follicles and fibroblast culture showed the presence of one (homozygous) or two variants (heterozygous) at all the studied loci, and allowed chimerism to be excluded. We concluded that the heifer had diploid/triploid (60,XX/90,XXY) mosaicism. To our knowledge, this is only the fifth such case to be reported worldwide in this species. Since cytogenetic studies are routinely performed on in vitro cultured leukocytes, we suspect that the prevalence of this chromosome abnormality is underestimated, as it is known from published reports that the frequency of the triploid cell line is usually very low in leukocytes

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 &gt; 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 &gt; 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 Influence of Maternal-Foetal Parameters on Concentrations of Zonulin and Calprotectin in the Blood and Stool of Healthy Newborns during the First Seven Days of Life. An Observational Prospective Cohort Study

Background: It can be hypothetically assumed that maternal and perinatal factors influence the intestinal barrier. Methods: The study was conducted with 100 healthy, full-term newborns breastfed in the first week of life, with similar analyses for their mothers. Zonulin and calprotectin levels were used as intestinal permeability markers. Results: The median (range) zonulin concentrations (ng/mL) were in mothers: serum, 21.39 (6.39&#8211;57.54); stool, 82.23 (42.52&#8211;225.74); and newborns: serum cord blood, 11.14 (5.82&#8211;52.34); meconium, 54.15 (1.36&#8211;700.65); and stool at age seven days, 114.41 (29.38&#8211;593.72). Calprotectin median (range) concentrations (&#181;g/mL) in mothers were: stool, 74.79 (3.89&#8211;211.77); and newborns: meconium, 154.76 (6.93&#8211;8884.11); and stool at age seven days 139.12 (11.89&#8211;627.35). The use of antibiotics during pregnancy resulted in higher zonulin concentrations in umbilical-cord serum and calprotectin concentrations in newborn stool at seven days, while antibiotic therapy during labour resulted in higher zonulin concentrations in the stool of newborns at seven days. Zonulin concentrations in the stool of newborns (at seven days) who were born via caesarean section were higher compared to with vaginal birth. With further analyses, caesarean section was found to have a greater effect on zonulin concentrations than prophylactic administration of antibiotics in the perinatal period. Pregnancy mass gain &gt;18 kg was associated with higher calprotectin concentrations in maternal stool. Body Mass Index (BMI) increase &gt;5.7 during pregnancy was associated with decreased zonulin concentrations in maternal stool and increased calprotectin concentrations in stool of mothers and newborns at seven days. There was also a negative correlation between higher BMI increase in pregnancy and maternal zonulin stool concentrations and a positive correlation between BMI increase in pregnancy and maternal calprotectin stool concentrations. Conclusion: Maternal-foetal factors such as caesarean section, antibiotic therapy during pregnancy, as well as change in mother&#8217;s BMI during pregnancy may increase intestinal permeability in newborns. Changes in body mass during pregnancy can also affect intestinal permeability in mothers. However, health consequences associated with increased intestinal permeability during the first days of life are unknown. Additionally, before the zonulin and calprotectin tests can be adopted as universal diagnostic applications to assess increased intestinal permeability, validation of these tests is necessary