Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes

HER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with androgen receptors (AR), a member of the steroid hormone’s family, is unwell known in BC. The present study aims to evaluate the prognostic impact of AR expression in HER2+ BC subtypes. A total of 695 BCs were selected and reviewed, AR, ER, PR and HER2 expression in tumor cells were examined by immunohistochemical method, and the SISH method was used in case of HER2 with equivocal immunohistochemical score (2+). A high prevalence of AR expression (91.5%) in BC HER+ was observed, with minimal differences between luminal and non-luminal tumor. According to steroid receptor expression, tumors were classified in four subgroups, including BC luminal and non-luminal HER2+ expressing or not AR. The luminal BC HER2 + AR+ was associated with lower histological grade, lower tumor size, higher PR expression and lower HER2 intensity of expression (2+). Also, the non-luminal tumors AR+ showed lower tumor size and lower prognostic stage but frequently higher grade and higher HER2 intensity of expression (3+). These findings should suggest a different progression of luminal and non-luminal tumors, both expressing AR, and allow us to speculate that the molecular mechanisms of AR, involved in the biology of BC HER2 + AR+, differ in relation to ER and PR expression. Moreover, AR expression may be a useful predictor of prognosis for overall survival (OS) in HER2+ BC subtypes. Our findings suggest that AR expression evaluation in clinical practice could be utilized in clinical oncology to establish different aggressiveness in BC HER2+ subtypes.

Gene Expression Evaluation of Multigenic Cotton (Gossypium hirsutum) against Cotton Leaf Curl Virus

One of the most crucial threats limiting the sustainable production of cotton is cotton leaf curl disease (CLCuD). There is dire need to produce a resistant variety that can combat CLCuD. For this purpose, virus resistant transgenic cotton plants (MNH-786) with C4 gene construct at T3 generation were selected and sown. Young fresh leaves of multigenic variety of MNH-786 were collected to confirm the transformed construct. Infected whiteflies were used for spreading on transgenic cotton MNH-786 variety with C4 construct to check percentage of infection. Whiteflies were collected from infected cotton plants showing CLCuD and reared in lab to increase the population of whiteflies. After 15 days of feeding, infected leaves of transgenic plants were collected and total DNA of infected leaves of transgenic cotton plant with virus load was extracted. At maturity, data of morphological characteristic was taken from the transgenic cotton plants of MNH-786 and control plants. Resistant transgenic cotton plants showed < 0.5% disease index and recorded more plant height in field condition. Total number of bolls per plant was 20% more in tolerant plants and 40% more in resistant plants as compared to susceptible plants. Molecular analysis of transgenic plants showed clear evidence that expression of construct 4 virus resistant gene against begomoviruses in resistant and tolerant group of transgenic plants was more as compared to susceptible group and control. © 2021 Friends Science Publishers

MO100WNT/Β-CATENIN SIGNALING PATHWAY IS ASSOCIATED WITH HYPERTENSIVE CARDIAC AND RENAL FIBROSIS

Background and Aims Arterial hypertension (AH) causes a cardiac remodeling and renal fibrosis which considered to be mediated by reactivation of fetal and pro-fibrotic signaling pathways. Signal transduction of canonical Wnt (β-catenin expression) evaluation in the settings of heart and kidney hypertensive alterations was the subject of the study. Method Systolic blood pressure (BP), serum and urinary creatinine (Cr), proteinuria (uTP), inorganic phosphate (sPi), intact parathyroid hormone (PTH), intact fibroblast growth factor 23 (FGF23), Klotho protein, were estimated in spontaneously hypertensive rats after 1 (SHR1, n=6), 2 (SHR2, n=6), 4 (SHR4, n=6) и 6 (SHR6, n=6) months of exposure. Perivascular and interstitial fibrosis (Masson's trichrome), and β-catenin expression (IHC) were analyzed by light microscopy of myocardium and kidney tissues and calculated quantitatively. Statistical comparisons among groups were performed using Mann–Whitney U-test and Kruskal-Wallis H-test. The association between biochemical and morphological variables was estimated by Spearman’s correlation. Results In all groups BP increased compared to baseline values (p = 0.011). The decline of renal function was obvious in SHR6 (vs SHR2, p=0.001). Klotho level decreased in SHR2 vs SHR1 (p = 0.026) and in SHR4-6 vs SHR2 (p &lt; 0.013). There were no differences in sPi (p = 0.50), PTH (p = 0.63), FGF23 (p = 0.62) between experimental groups. Perivascular myocardial fibrosis was already increased in SHR2 (vs SHR1, p=0.026, Figure 1a), renal interstitial fibrosis - since 6mo exposure (p = 0.012, Figure 2a). Both cardiac and renal fibrosis were associated with redistribution of β-catenin in cardiomyocytes and tubular epithelial cells (Figure 1a, 2a: decrease in membrane and increase in cytoplasm) without significant changes in tissue β-catenin expression. In heart β-catenin expression correlated with to perivascular fibrosis (Figure 1 b). Renal β-catenin expression correlated with interstitial fibrosis (Figure 2b), but not with sCr (r=-0.03, p&gt;0.05) и uTP (r=0.04, p&gt;0.05). Conclusion Reactivation of Wnt/ β-catenin signal transduction is possibly a basic molecular mechanism of cardiac and renal fibrosis in arterial hypertension. The data suggests involvement of Klotho decline mediated activation of canonical Wnt. Targeting these signaling molecules is promising therapeutic strategy for protecting both organs in cardiorenal pathology and requires further research.

Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation

Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. Equus caballus papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription factors. Moreover, Ki67 index was assessed with immunohistochemistry. EcPV2-E6 DNA was checked, and viral presence was confirmed in 21 positive out to 23 cases (91%). Oncogene expression was confirmed in 14 cases (60.8%) for E6 and in 8 (34.7%) for E2. RANKL, nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB)-p50, NFKBp65, interleukin (IL)-6, IL17, IL23p19, IL8, IL12p35, IL12p40, β-catenin (BCATN1), FOS like 1 (FOSL1), and lymphoid enhancer binding factor 1 (LEF1) showed a significant upregulation in tumor samples compared to healthy tissues. Our results describe an inflammatory environment characterized by the activation of RANKL/RANK and IL17 with the relative downstream pathways, and a positive modulation of inflammatory cytokines genes such as IL6 and IL8. Moreover, the increase of BCATN1, FOSL1, and LEF1 gene expression suggests an activation of both canonical and non-canonical Wnt signaling pathway that could be critical for carcinogenesis and tumor progression.

Robusta Extract Cream Ameliorated Ultraviolet B-induced Wrinkle Skin of Mice by the Regulation of Epidermal Thickness and Inhibition of MMP-1

BACKGROUND: Recently, coffee is widely used for preventing photoaging because of its antioxidant capacity. Among two kinds of coffee, robusta coffee has higher content of antioxidant such as chlorogenic acid (CGA) and caffeine. Researchs about robusta coffee bean effect on photoaging due to UVB radiation is still limited. Therefore, the aim of this study was to examine the effect of robusta extract cream (RE cream) on preventing wrinkle in mice induced by ultraviolet-B (UVB) radiation.METHODS: RE cream was made by mixing RE coffee with moisturizing cream in different concentration (10%, 20%, and 40%). Twenty-five male of Mus musculus Balb/c strain mice aged 4 weeks were divided into five groups; control group, UVB group, UVB + 10% RE group, UVB + 20% RE group, and UVB + 40% RE group. The UVB groups were given UVB radiation three times a week with an exposure duration of 100 seconds per time for ten weeks. At the end of the treatment, skin samples were excised and statined histologically, also were analyzed for their protein expression. Evaluation of wrinkles was carried out using the Bissete method before and after treatment. To evaluate the thickness of the epidermis, HE staining was performed, while masson Trichome staining was performed to determine the collagen content.RESULTS: RE cream-treated groups showed lower wrinkle score compared to the control group. Furthermore, in UVB + 10% RE group, the RE cream application reduce wrinkle formation. In UVB + 10% RE group and UVB + 20% RE group, the RE cream application increased epidermal thickness and collagen content (p=0.00). While collagenase, matrix metalloproteinase-1 (MMP-1) expression was lower in UVB + 20% RE group compared to the UVB group (p<0.05), however the MMP1 expression in UVB + 40% RE group was higher than other treatment group.CONCLUSION: RE cream prevents wrinkle by maintaining epidermal thickness and collagen contain. RE cream also decreases MMP-1 expression in mice.KEYWORDS: coffee, collagen, MMP-1, robusta, wrinkle

Peculiarities of using lexical means in the work of V. V. Rozanov's «The Fallen Leaves»

The subject of the study is the lexical means used in the «Fallen Leaves» (1913, 1915) – the work by V. Rozanov, a publicist and a writer of the XIX – first third of the XX centuries – which represents a new author's genre – a leaf. Particular attention is paid to identifying the methods of using the vocabulary in this work in terms of expressing the author's thought in an aphoristic form, when the word plays a crucial role not only in generating the author's individual meaning, but also in expressing emotions and opinions.The author of the article identifies and demonstrates the most significant methods of using lexical means: subjective emotional and rational definition of concepts; interpretation of the meaning of words through contextual «increment» that creates the author's inferences; filling a word with contextual meaning by using associative images; the use of various lexical means, as well as tropes, stylistic figures to create connotative meaning and expression of the text; the method of creating a semantic opposition based on the antithesis; the use of metaphors, antitheses, gradations as textforming factors. The most significant methods of using lexical means are identified and demonstrated: subjective emotional and rational definition of concepts; interpretation of the meaning of words through contextual «increment» that creates the author's inferences; filling a word with contextual meaning using associative images; the use of various lexical means, as well as tropes, stylistic devices to create connotative meaning and expression of the text; the method of creating a semantic opposition based on the antithesis; the use of metaphors, antitheses, gradations as text-forming factors. It is stated and confirmed that the text-forming role is played by special means of creating imagery: metaphor (expanded metaphor), personification, antithesis and pun. Repetition and comparison are relevant in the «leaf» genre as the means of creating connotative meanings and enhancing expression. The author of the article considers special writer’s techniques which include semantic opposition and inferences formed both deductively and inductively and often serve as the main factors of text formation. These features, reflecting the characteristics of vocabulary, are both the methods of generating meaning, expression, evaluation and the signs of the «leaf» genre. The author concludes that the technique of using different lexical means is one of the main features of the writer's idiostyle.

BIỂU HIỆN GEN SINH CƠ Ở GÀ RI LAI VÀ LƯƠNG PHƯỢNG KHI ĐƯỢC NUÔI BẰNG CÁC KHẨU PHẦN CÓ MỨC METHIONINE KHÁC NHAU

The aim of this study was to investigate the effects of methionine concentrations in diet on the expression of myogenic genes in Ri hybrid and Luong Phuong chickens at 12 weeks of age. A total of 240 Ri hybrid and 240 Luong Phuong one-day-old chickens of uniform body weight was divided into a 2 × 3 factorial arrangement of treatments with four replicate cages of 20 chicks per treatment. Six treatments were set up including 2 chicken types and three diets with low, adequate, high methionine concentrations compared to methionine level recommended by Evonik (2010) for colored chickens. At 12 weeks of age, 36 chickens from 2 groups were randomly chosen for the absolute and relative breast muscle weight calculation, and myogenic gene expression evaluation (myostatin, myf5, MEF2B) in breast muscle using RT-realtime PCR technique. The results showed that using the 0.08% higher of methionine level in diets than Evonik recommendation (2010) improved the absolute weight of breast muscle of the two colored chicken groups. The addition of methionine with 0.08% higher than Evonik recommendation (2010) decreased myostatin and increased MEF2B gene expression in Ri hybrid. On the other hand, using the 0.08% lower of methionine level in diets had no effect on gene expression of the three myogenic genes (myostatin, myf5 and MEF2B) comparing to using the adequate methionine diets. In the case of Luong Phuong chickens, the increasing methionine level in diets reduced myostatin gene expression, but increased myf5 and MEF2B gene expression.