Osteoporosis is a multifactorial systemic skeletal disease that is characterized by a low bone mineral density (BMD) and the microarchitectural deterioration of bone tissue, leading to bone ...fragility. The search for new genes that may play an important role in the regulation of bone mass and the development of osteoporosis is ongoing. Recently, it was found that altering the activity of the endothelin-1-converting enzyme encoded by the ECE1 gene may affect bone mineral density (BMD). Another gene involved in the process of osteoblast differentiation and maturation is believed to be PPARG (peroxisome proliferator-activated receptor gamma). This participates in regulating the transformation of stem cells and affects the process of bone formation and resorption. Therefore, we analyzed the association of the ECE1 and PPARG variants with osteopenia and osteoporosis risk in the Polish population. This study included a group (n = 608) of unrelated Polish women (245 individuals with osteoporosis (aged: 57 ± 9), 109 individuals with osteopenia (aged: 53 ± 8) and 254 healthy controls (aged: 54 ± 8)). The real-time PCR technique was used to determine the genetic variants for rs213045 (-338G>T) and rs213046 (-839A>C) of the ECE1 gene and rs1801282 (Pro12Ala, C>G) of the PPARG gene. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, in the densitometric results, lower median Z-score values were observed for the T allele compared to the G allele for the rs213045 variant of the ECE1 gene (−1.11 ± 1.07 vs. −0.78 ± 1.21, p = 0.021). Moreover, the TT genotype for the rs213045 variant was more common in women with osteopenia (13.8%, OR = 2.82, p < 0.05) and osteoporosis (7.8%, OR = 1.38, p > 0.05) compared to the control group (5.5%). Additionally, our results suggested that the T allele of rs213045 was more common in women with osteopenia compared to the controls. We further observed that the haplotype containing two major GA alleles of ECE1 (rs213045, rs213046) could reduce the risk of osteopenia in our population. Finally, we found that women with osteoporosis had statistically significantly lower body mass and BMI values compared to the control group. Our results suggest that the ECE1 rs213045 variant may increase the risk of osteopenia. However, the data obtained require confirmation in further studies.
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-1β, IL-6) and vascular diseases (TGF-β, 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-β, HIF-1α, VEGF, and PlGF than TNF-α, Il-1β, 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.
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.
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.
The study included 675 unrelated women (109 women with osteopenia, 333 women with osteoporosis, and 233 healthy women). Genomic DNA was extracted from the blood samples and the CYP19A1 polymorphisms ...were determined using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Bone mineral density at the lumbar spine (L1-L4) was measured with dual energy X-ray absorptiometry (DEXA).
The analysis of the CYP19A1 rs749292 polymorphism showed that there were no statistically significant differences in the distribution of genotypes between the study groups with osteoporosis and osteopenia and the control group. However, it was noted that the GG genotype occurred more often in the group with osteopenia (35.8%; OR = 1.44) than in the control group (27.9%). Also, a difference was noted in the distribution of genotypes in women with osteoporosis. In addition, it can be assumed that the G allele may lead to an increased susceptibility to osteopenia and osteoporosis. The analysis of the CYP19A1 rs700518 polymorphism showed that heterozygotes were more common in the group with osteoporosis (58.3%) than in the control group (52.8%).
Our results suggest that the rs749292 polymorphism of the CYP19A1 gene may contribute to an elevated risk for fractures in postmenopausal Polish 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.
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-1β, IL-6) and vascular diseases (TGF-β, 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-β, HIF-1α, VEGF, and PlGF than TNF-α, Il-1β, 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.
Wstęp Pozbawione komórek przeszczepy ludzkiej skóry właściwej (ADM), wypreparowane w Banku Tkanek CLO, stanowią substytut skóry z powodzeniem stosowany u pacjentów rozlegle i głęboko oparzonych oraz ...cierpiących z powodu ran trudno gojących się. Ponadto zastosowanie matryc ADM obejmuje procedury chirurgii uroginekologicznej w ramach leczenia zaburzeń statyki narządów rodnych. Cel Celem pracy było przedstawienie obecnie proponowanych metod preparatyki przeszczepów ADM jako substytutów skóry w leczeniu ran oraz w innych dziedzinach medycyny regeneracyjnej, a także zaproponowanie możliwych kryteriów kontroli jakości tych preparatów. Materiał i metody Używając słów kluczowych związanych z usuwaniem komórek z allogenicznej skóry właściwej człowieka i leczeniem oparzeń, dokonano przeglądu piśmiennictwa i przeanalizowano dostępne medyczne bazy danych (NCBI MedLine, Clinical Key, Clinicaltrials.gov i MedlinePlus). Wyniki i wnioski Główne metody usuwania komórek to metody chemiczne (detergenty, kwasy, zasady, związki chelatujące, roztwory hipertoniczne i hipotoniczne), fizyczne (zamrażanie, sonikacja, mieszanie, usuwanie mechaniczne), biologiczne (enzymy) oraz metody mieszane, które synergistycznie łączą skuteczność wyżej wymienionych metod. Należy podkreślić, że zachowanie naturalnego składu i właściwości opracowywanego ADM podczas procesu usuwania komórek jest wysoce pożądane. Kolejnym istotnym aspektem, który należy zapewnić, jest czystość mikrobiologiczna i brak cytotoksyczności otrzymanych przeszczepów. Stosowanie metod fizycznych do usuwania komórek może pozostawiać elementy błony komórkowej, kwasy nukleinowe itp. Stosowanie metod biologicznych i chemicznych, pomimo ich dużej skuteczności, może powodować zaburzenia składu i struktury macierzy pozakomórkowej wraz z utratą ważnych składników matrycy. Ponadto zastosowanie metod chemicznych może znacząco przyczynić się do uzyskania cech cytotoksyczności.
Colorectal cancer (CRC) is one of the most common cancers in the world. Despite improvements in screening for early diagnosis, CRC is one of the leading causes of cancer deaths.
The aim of the study ...was to determine a potential association between the frequency of GSTM1 and GSTT1 null genotypes and the risk of CRC in the Polish population. Moreover, we analyzed the clinical parameters with the glutathione S-transferase (GST) gene polymorphisms in patients with CRC.
The study was conducted on 512 Caucasians, including 279 patients (105 women and 174 men) with CRC. DNA from peripheral blood was extracted and the multiplex polymerase chain reaction (PCR) technique was used for glutathione S-transferase theta (GSTT1) and mu (GSTM1) gene deletion genotyping.
We found no statistically significant differences in the frequency of the GST gene polymorphisms in patients with CRC and controls. The prevalence of the GSTM1*0 variant in the test subjects was higher than in controls (45.9% vs 42.9%; p > 0.05). The frequency of the GSTT1*0 variant was also higher in patients with CRC compared to the control population (21.1% vs 18.9%; p > 0.05). In addition, the effect of the GSTM1 and GSTT1 polymorphisms on the incidence of CRC was also analyzed. There was a slight, but not statistically significant, increase of the risk of colon cancer for the GSTM1*0 and GSTT1*0 variants. Moreover, we examined the GST genotype due to the cancer TNM classification and the location of the primary tumor. Statistically significant differences in the distribution of the GSTT1*0 and GSTT1*1 genotypes in both the stage and the location of the primary tumor were observed.
It is suggested that the GSTT1 polymorphism may have an impact on the severity of the tumor and its location.
The risk of aortic dissection should be assessed based not only on the aortic diameter, but also on other biomechanical parameters that have an impact on the stress in the aortic wall. This study ...evaluates very rare clinical scenarios of patients with both pre- and post-dissection computed tomography (CT) images and evaluates whether an increased wall stress correlates with the localization of an intimal entry tear in Type A aortic dissection.
CT-angiography images of 4 patients performed shortly prior to and after developing Type A aortic dissection were evaluated. The stress distribution in the pre-dissection aortas was evaluated using the finite elements method. Then, the areas of high stress in the pre-dissection aortas were compared to the localization of the intimal entry tears in the dissected vessels.
In all the patients, the pre-dissection areas of high wall stress correlated with the location of the intimal tears. The highest stress was not observed in the most dilated segments of the aorta but was predominantly found in the areas of an abrupt change in the geometry of the aorta.
Wall stress can indicate the areas susceptible to the formation of an intimal tear and subsequent aortic dissection. Stress analysis may be a valuable tool to predict the risk of aortic dissection in patients with aortic dilatation.
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