Change in Striatal Functional Connectivity Networks Across Two Years Due to Stimulant Exposure in Childhood ADHD: Results from the ABCD Sample.

Widely prescribed as the first choice of treatment for Attention-Deficit/Hyperactivity Disorder (ADHD), stimulants (methylphenidate and amphetamines) have been studied for their long-term effects on the brain in prospective designs that carefully control dosage and adherence. It is unknown whether those findings generalize to real-world conditions such as community-based treatment, which is marked by intermittent exposure and polypharmacy. To fill this gap, we capitalized on the observational design of the Adolescent Brain Cognitive Development (ABCD) study to examine effects of stimulant exposure on modulation of large-scale bilateral cortical networks' resting-state functional connectivity (rs-FC) with 6 striatal regions (left and right caudate, putamen, and nucleus accumbens) across two years in children with ADHD. Out of 11,878 children, 179 met criteria for an ADHD diagnosis at baseline and high-quality imaging data at baseline and the two-year timepoint. Bayesian hierarchical logistic regressions revealed that change in rs-FC over the two-year period of multiple striatal-cortical networks associated with executive functions and a visuo-motor network predicted stimulant exposure. These networks did not overlap with those that predicted non-stimulant exposure. Of these networks, change selective to stimulant exposure was limited to rs-FC with the putamen, specifically frontoparietal and visual networks, implicating motor control. 23% of stimulant-exposed children did not meet criterion for ADHD at the two-year timepoint, and they were distinguished by change in rs-FC between left putamen and frontoparietal network. Thus, while stimulant exposure for a two-year period under real-world conditions modulated striatal-cortical functional networks broadly, therapeutic effects of that exposure were limited in scale, to network connections relevant to motor control in a small subset of children.

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.

Electronic signatures of successive itinerant, antiferromagnetic transitions in hexagonal La2Ni7.

We use high-resolution angle-resolved photoemission spectroscopy (ARPES) and density functional theory (DFT) calculations to study the electronic and magnetic properties of La2Ni7, an itinerant magnetic system with a series of three magnetic transition temperatures upon cooling, which end in a weak antiferromagnetic ground state. Our APRES data reveal several electron and hole pockets that have hexagonal symmetry near the Γ point. We observe significant reconstruction of the band structure upon successive magnetic transitions atT1∼ 61 K,T2∼ 57 K andT3∼ 42 K. Several features observed in ARPES data were reasonably well reproduced by DFT calculations, while others were not. In particular, the flat band nearEFpredicted by DFT in antiferromagnet (AFM) state, was seemingly absent in ARPES data. Our results detail the effects of magnetic ordering on the electronic structure in a Ni-based weak AFM and highlight challenges of current computational methods.

Cingulate-Prefrontal Connectivity During Dynamic Cognitive Control Mediates Association Between p Factor and Adaptive Functioning in a Transdiagnostic Pediatric Sample.

BACKGROUND: Covariation among psychiatric symptoms is being actively pursued for transdiagnostic dimensions of psychopathology with predictive utility. A superordinate dimension, the p factor, reflects overall psychopathology burden and has support from genetic and neuroimaging correlates. However, the neurocognitive correlates that link an elevated p factor to maladaptive outcomes are unknown. We tested the mediating potential of dynamic adjustments in cognitive control rooted in functional connections anchored by the dorsal anterior cingulate cortex (dACC) in a transdiagnostic pediatric sample. METHODS: A multiple mediation model tested the association between the p factor (derived by principal component analysis of Child Behavior Checklist syndrome scales) and outcome measured with the Vineland Adaptive Behavior Scale-II in 89 children ages 8 to 13 years (23 female) with a variety of primary neurodevelopmental diagnoses who underwent functional magnetic resonance imaging during a socioaffective Stroop-like task with eye gaze as distractor. Mediators included functional connectivity of frontoparietal- and salience network-affiliated dACC seeds during conflict adaptation. RESULTS: Higher p factor scores were related to worse adaptive functioning. This effect was partially mediated by conflict adaptation-dependent functional connectivity between the frontoparietal network-affiliated dACC seed and the right dorsolateral prefrontal cortex. Post hoc follow-up indicated that the p factor was related to all Vineland Adaptive Behaviors Scale-II domains; the association was strongest for socialization followed by daily living skills and then communication. Mediation results remained significant for socialization only. CONCLUSIONS: Higher psychopathology burden was associated with worse adaptive functioning in early adolescence. This association was mediated by weaker dACC-dorsolateral prefrontal cortex functional connectivity underlying modulation of cognitive control in response to contextual contingencies. Our results contribute to the identification of transdiagnostic and developmentally relevant neurocognitive endophenotypes of psychopathology.

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.

Genetic variants of progesterone receptor in etiology of preterm delivery.

OBJECTIVES: Preterm delivery (PTD) accounts for around 11% of pregnancies worldwide. Unfortunately, no diagnostic indicator, specific mechanism or genetic predisposition has yet been identified. One of the hypotheses suggest local or functional progesterone decrease as a potential reason for preterm uterine contractions leading to preterm delivery. It is believed that any change in progesterone receptor DNA may be crucial for higher risk of preterm delivery due to abnormal response to prostaglandins, normally inhibited by properly built progesterone. The aim of this study was to determine whether there is an association between progesterone gene polymorphisms (PROGINS and +331G/A) and preterm birth. MATERIAL AND METHODS: A total of 230 women were enrolled, including 115 cases of preterm deliveries (between 22 and 36 weeks of gestation) and 115 healthy mothers of full-term infants. Genomic DNA was isolated from the blood sample. Polymerase chain reaction (PCR) amplification was carried out in a final volume of 25 µL. Genotyping was assayed by PCR. Statistical analysis of the results was conducted with p < 0.05 accepted as statistically significant. RESULTS: For both PROGINS (Alu ins/del) and +331G/A (rs10895068) polymorphisms were equally frequent in case and control group. The prevalence of PGR alleles in both groups was also comparable. CONCLUSIONS: The results of our study showed no association between progesterone gene polymorphisms (PROGINS and +331G/A) and risk of preterm delivery. Identifying mechanisms to prolong the length of gestation, particularly in women at risk for preterm delivery, will improve both maternal and fetal outcomes.

Emergence of Fermi arcs due to magnetic splitting in an antiferromagnet.

The Fermi surface plays an important role in controlling the electronic, transport and thermodynamic properties of materials. As the Fermi surface consists of closed contours in the momentum space for well-defined energy bands, disconnected sections known as Fermi arcs can be signatures of unusual electronic states, such as a pseudogap1. Another way to obtain Fermi arcs is to break either the time-reversal symmetry2 or the inversion symmetry3 of a three-dimensional Dirac semimetal, which results in formation of pairs of Weyl nodes that have opposite chirality4, and their projections are connected by Fermi arcs at the bulk boundary3,5-12. Here, we present experimental evidence that pairs of hole- and electron-like Fermi arcs emerge below the Neel temperature (TN) in the antiferromagnetic state of cubic NdBi due to a new magnetic splitting effect. The observed magnetic splitting is unusual, as it creates bands of opposing curvature, which change with temperature and follow the antiferromagnetic order parameter. This is different from previous theoretically considered13,14 and experimentally reported cases15,16 of magnetic splitting, such as traditional Zeeman and Rashba, in which the curvature of the bands is preserved. Therefore, our findings demonstrate a type of magnetic band splitting in the presence of a long-range antiferromagnetic order that is not readily explained by existing theoretical ideas.

Visualizing band selective enhancement of quasiparticle lifetime in a metallic ferromagnet.

Electrons navigate more easily in a background of ordered magnetic moments than around randomly oriented ones. This fundamental quantum mechanical principle is due to their Bloch wave nature and also underlies ballistic electronic motion in a perfect crystal. As a result, a paramagnetic metal that develops ferromagnetic order often experiences a sharp drop in the resistivity. Despite the universality of this phenomenon, a direct observation of the impact of ferromagnetic order on the electronic quasiparticles in a magnetic metal is still lacking. Here we demonstrate that quasiparticles experience a significant enhancement of their lifetime in the ferromagnetic state of the low-density magnetic semimetal EuCd2As2, but this occurs only in selected bands and specific energy ranges. This is a direct consequence of the magnetically induced band splitting and the multi-orbital nature of the material. Our detailed study allows to disentangle different electronic scattering mechanisms due to non-magnetic disorder and magnon exchange. Such high momentum and energy dependence quasiparticle lifetime enhancement can lead to spin selective transport and potential spintronic applications.

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.

Discovery of a weak topological insulating state and van Hove singularity in triclinic RhBi2.

Time reversal symmetric (TRS) invariant topological insulators (TIs) fullfil a paradigmatic role in the field of topological materials, standing at the origin of its development. Apart from TRS protected strong TIs, it was realized early on that more confounding weak topological insulators (WTI) exist. WTIs depend on translational symmetry and exhibit topological surface states only in certain directions making it significantly more difficult to match the experimental success of strong TIs. We here report on the discovery of a WTI state in RhBi2 that belongs to the optimal space group P[Formula: see text], which is the only space group where symmetry indicated eigenvalues enumerate all possible invariants due to absence of additional constraining crystalline symmetries. Our ARPES, DFT calculations, and effective model reveal topological surface states with saddle points that are located in the vicinity of a Dirac point resulting in a van Hove singularity (VHS) along the (100) direction close to the Fermi energy (EF). Due to the combination of exotic features, this material offers great potential as a material platform for novel quantum effects.

Design and performance of closed cycle sample cooling stage for angle resolved photoemission spectroscopy capable of reaching temperatures below 2 K.

We have designed, constructed, and tested a unique cold finger suitable for angle resolved photoemission spectroscopy. This design is based on in situ helium reliquification and utilizes pulse tube cryocooler. The pulse tube can be removed for baking without breaking Ultra High Vacuum (UHV). This design also allows the use of non-UHV heater that can be replaced without the need to vent the system. The cold finger has minimal vibration, operates over a temperature range of 1.7 K-400 K, and has no measurable residual magnetization. In continuous mode, it can maintain a sample temperature of 2.6 K, while in single shot mode (by pumping on liquid helium), it can reach temperatures down to 1.8 K for a period of several hours.

Correlation of rs749292 and rs700518 polymorphisms in the aromatase gene (CYP19A1) with osteoporosis in postmenopausal Polish women.

MATERIAL AND METHODS: 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). RESULTS: 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%). CONCLUSIONS: Our results suggest that the rs749292 polymorphism of the CYP19A1 gene may contribute to an elevated risk for fractures in postmenopausal Polish women.

The importance of the Wnt/ß-catenin pathway and LRP5 protein in bone metabolism of postmenopausal women.

BACKGROUND: Postmenopausal osteoporosis is the most common metabolic bone disease among women. The Wnt signaling pathway has been known to be the critical regulator of osteoblastogenesis. Alterations in this mechanism may have consequences for bone remodeling in humans. OBJECTIVES: The aim of the study was to evaluate the frequency of genotypes and alleles of single nucleotide polymorphism (SNP) rs4988321 and rs312009 of LRP5 in Polish postmenopausal women with osteopenia (n = 109) and osteoporosis (n = 333). Potential correlations between genetic polymorphisms, bone mineral density (BMD), risk for bone fractures, and other clinical parameters were analyzed. MATERIAL AND METHODS: Genomic DNA was extracted from the blood samples and the sequence polymorphisms of LRP5 gene were detected using real-time polymerase chain reaction (RT-PCR) methods with melting curve analysis. We also calculated the odds ratio (OR) for the LRP5 genotypes and the alleles. Then, we evaluated the effect of the LRP5 polymorphism on T-score, Z-score, L2L4AM, L2L4YA, L2L4BMD, body mass index (BMI), and other clinical parameters. RESULTS: No statistically significant differences in the distribution of LRP5 rs312009 genotypes between the groups were observed. Furthermore, our findings indicate that there is no correlation between LRP5 genotypes and the clinical characteristics of women with osteopenia/osteoporosis. In contrast, there was an increased value of OR in heterozygotes for rs4988321, both in patients with osteopenia (OR = 1.47) and in those with osteoporosis (OR = 1.33). In our study, we were not able to calculate the OR parameter for the AA genotype due to its low prevalence in the population. CONCLUSIONS: Our results suggest that the Val667Met LRP5 (rs312009) polymorphism may contribute to an elevated risk for fractures in postmenopausal Polish women.

Relaxation Dynamics of Zero-Field Skyrmions over a Wide Temperature Range.

The promise of magnetic skyrmions in future spintronic devices hinges on their topologically enhanced stability and the ability to be manipulated by external fields. The technological advantages of nonvolatile zero-field skyrmion lattice (SkL) are significant if their stability and reliability can be demonstrated over a broad temperature range. Here, we study the relaxation dynamics including the evolution and lifetime of zero-field skyrmions generated from field cooling (FC) in an FeGe single-crystal plate via in situ Lorentz transmission electron microscopy (L-TEM). Three types of dynamic switching between zero-field skyrmions and stripes are identified and distinguished. Moreover, the generation and annihilation of these metastable skyrmions can be tailored during and after FC by varying the magnetic fields and the temperature. This dynamic relaxation behavior under the external fields provides a new understanding of zero-field skyrmions for their stability and reliability in spintronic applications and also raises new questions for theoretical models of skyrmion systems.

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.