Effect of quercetin's anti-breast cancer depending on presence of estrogen receptor via down-regulating long non-coding RNA MALAT-1 and its mechanism / 中国药理学通报

Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.

Network pharmacology and molecular docking reveal the mechanism of resveratrol in oral squamous cell carcinoma treatment / 口腔疾病防治

Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

Role of sex hormones in keratoconus and potential therapeutic targets / 国际眼科杂志(Guoji Yanke Zazhi)

Keratoconus is a blinding corneal disease characterized by central or paracentral corneal thinning and conical ectasia, and usually happens in adolescence. Currently, the etiology of keratoconus is unclear. Multiple studies have identified an association between genetics, eye rubbing, allergic diseases, ultraviolet exposure and keratoconus. Recently, several studies identified that sex hormones also played important roles in the pathogenesis of keratoconus. The disturbance of sex hormones may increase the risk of occurrence and progress of keratoconus. This review aims to summarize the pathophysiological effects of sex hormones on the cornea, clarify the effects of sex hormones on keratoconus and its related inflammatory or immune mechanisms, and explore the role of sex hormones in the early diagnosis and treatment of keratoconus, providing reference and help for clinical work.

Effect of Dioscorea villosa extract and the phytoestrogen diosgenin on ovariectomized mice with zymosan-induced arthritis

Abstract Humans are exposed to natural compounds such as phytoestrogens primarily through diet and supplements. These compounds promote health by alleviating the symptoms and illnesses associated with menopause and arthritis. Diosgenin (DSG) occurs naturally in plants such as Dioscorea villosa (DV) and binds to estrogen receptors, so it may have similar effects to this hormone, including against arthritis. Thus, we investigated the effect of chronic treatment with dry extract of DV and its phytoestrogen DSG on ovariectomized mice with arthritis. We found that dry extract of Dioscorea villosa (DV) contains the phytoestrogen diosgenin (DSG) in its composition. Furthermore, arthritic mice treated with DV and DSG showed reduced neutrophil accumulation in the articular cartilage. Also, the dry extract of DV administered orally (v.o) did not alter the leukocyte count in the joints or promote changes in the reproductive tract. However, DSG altered these parameters, with possible beneficial effects by reducing symptoms related to reproductive aging. Thus, oral treatment with dry extract of DV and subcutaneous (s.c) treatment with DSG showed promise by acting against inflammation caused by arthritis and reducing symptoms in the reproductive tract due to menopause.

Effect of ovarian dysfunction induced ovariectomy and Porphyromonas gingivalis induction to risk of metabolic syndrome: in vivo study / Efeito da disfunção ovariana por meio de ovariectomia e indução de Porphyromonas gingivalis no risco de desenvolvimento de síndrome metabólica: estudo in vivo

Doenças periodontais e síndrome metabólica estão relacionadas a condições multifatoriais complicadas. No entanto, a relação ainda não é evidente. A insuficiência de estrogênio pode estar correlacionada a essa condição, possivelmente causada pela remoção dos ovários e infecção por Porphyromonas gingivalis (P. gingivalis). Este estudo teve como objetivo avaliar o efeito da disfunção ovariana causada pela ovariectomia e infecção por P. gingivalis no desenvolvimento da síndrome metabólica. Este foi um estudo experimental de laboratório utilizando ratos fêmeas da linhagem Sprague Dawley. Os modelos animais foram divididos em quatro grupos: controle, ovariectomia (OVX), ovariectomia-periodontite (OPG) e periodontite (PG). O objetivo de cada tratamento em cada grupo foi obter disfunção ovariana. O grupo OVX foi submetido à cirurgia de remoção dos ovários; no grupo PG foi realizada a indução de P. gingivalis; e no grupo OPG foi feita uma combinação de ovariectomia e indução de P. gingivalis. O sangue foi coletado e observado nos dias 0, 3, 7, 14, 21 e 28. A amostra de sangue foi examinada para ácido úrico, colesterol, glicose e estrogênio. Os dados coletados foram todos examinados estatisticamente. Todos os grupos de tratamento apresentaram peso corporal e observações bioquímicas sanguíneas significativamente maiores do que o grupo controle, exceto o colesterol total (p<0,05). Além disso, a maioria das variáveis apresentou uma correlação entre os grupos com o peso corporal e indicadores bioquímicos sanguíneos, exceto o nível de ácido úrico no sangue (R>0,5). A síndrome metabólica foi desencadeada pela disfunção ovariana causada pela infecção por P. gingivalis após a ovariectomia. Ambos apresentaram o mesmo risco. Mesmo a indução por P. gingivalis piorou a síndrome metabólica no grupo de modelos animais que foram submetidos à ovariectomia.(AU)

Periodontal diseases and metabolic syndrome are related to complicated multifactorial conditions. However, the relationship is not yet evident. Estrogen insufficiency might correlate to this condition, possibly caused by ovarian removal and Porphyromonas gingivalis (P. gingivalis) infection. This study aimed to evaluate the effect of ovarian dysfunction caused by ovariectomy and P. gingivalis infection to metabolic syndrome development. This study was an experimental laboratory study using female rats Sprague Dawley Strain. Animal models were divided into four groups: control, ovariectomy (OVX), ovariectomy-periodontitis (OPG), and periodontitis (PG). The purpose of every treatment in each group was to induce ovarian dysfunction. The OVX group was undertaken ovaries removal surgery. PG was performed P. gingivalis induction. Therefore OPG was a combination of ovariectomy and P. gingivalis induction. Blood was drawn and observed on days 0, 3, 7, 14, 21, and 28. The blood sample was examined for uric acid, cholesterol, glucose and estrogen. The collected data were all statistically examined. All treatment groups presented body weight and blood biochemical observation significantly higher than the control group, except total cholesterol (p<0.05). Moreover, most variables presented a correlation between groups to body weight and biochemical blood indicators, except blood uric acid level (R>0.5). The metabolic syndrome was triggered by ovarian dysfunction brought on by P. gingivalis infection after ovariectomy. They both took the same risk. Even P. gingivalis induction made metabolic syndrome in the group of animal models which underwent ovariectomy worse (AU)

Expression and clinical significance of miR-141-5p as a biomarker in the serum of patients with early spontaneous abortion

Abstract Aim miR-141-5p expression in patients with Early Spontaneous Abortion (ESA) and its correlation with hormone levels during pregnancy were investigated. Methods A total of 70 pregnant women with ESA were selected as the research group, and 70 normal pregnant women who chose abortion for non-medical reasons were selected as the Con group. Serum β-HCG, Progesterone (P), and Estrogen (E2) were detected by enzyme-linked immunosorbent assay. Differentially expressed miRNAs were screened by miRNA microarray analysis. miR-141-5p expression was detected by RT-qPCR, and its correlation with serum β-HCG, P, and E2 levels was analyzed. The diagnostic value of miR-141-5p for ESA was evaluated by the ROC curve. Results Serum β-HCG, P, and E2 were decreased and serum miR-141-5p was increased in patients with ESA. Pearson correlation analysis showed that serum β-HCG, P, and E2 levels were negatively correlated with miR-141-5p expression levels. ROC curve showed that miR-141-5p had a diagnostic value for ESA. Conclusions miR-141-5p is related to hormone levels during pregnancy and is expected to become a new candidate diagnostic marker for ESA.

Estrogen deficiency influences SEC23A gene expression in the odontogenic region of incisors ­ a murine model study / A deficiência de estrógeno influencia a expressão gênica de SEC23A na região odontogênica de incisivos ­ um estudo em modelo murino

Recent scientific evidence suggests a close relationship between estrogen deficiency and vitamin D- related genes. Estrogen and vitamin D were involved with alterations in odontogenesis and tooth eruption process. Objective: The aim of the present study was to evaluate the influence of estrogen deficiency on the expression of genes related to the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model. Material and Methods: This is an experimental clinical study that used female Wistar Hannover rats. The animals were randomly divided into two groups according to the intervention received: Hypoestrogenism Group ­ animals submitted to estrogen deficiency by ovariectomy surgery and Control Group ­ animals submitted to sham surgery. Surgical intervention was performed in the prepubertal period; the animals were followed throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the mRNA expression of the vitamin D-related genes AMDHD1, CYP24A1, NADSYN1 and SEC23A in the odontogenic region of incisors through real time PCR. Student's t test was used to compare means. Kruskal-Wallis test and Dunn's posttest were also used. The level of significance was 5%. Results: SEC23A was overexpressed in the estrogen deficiency condition in the odontogenic region (p=0.021). Conclusion: Estrogen deficiency may influence the expression of the SEC23A gene involved in the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model(AU)

Evidências científicas recentes sugerem uma estreita relação entre a deficiência de estrógeno e os genes relacionados à vitamina D. O estrógeno e a vitamina D estão envolvidos com alterações na odontogênese e no processo de erupção dentária. Objetivo: O objetivo do presente estudo foi avaliar a influência da deficiência de estrógeno na expressão de genes relacionados à ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino. Material e Métodos: Trata-se de um estudo clínico experimental que utilizou ratas Wistar Hannover fêmeas. Os animais foram divididos aleatoriamente em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo ­ animais submetidos à deficiência de estrógeno pela cirurgia de ovariectomia e Grupo Controle ­ animais submetidos à cirurgia simulada. A intervenção cirúrgica foi realizada no período pré-púbere; os animais foram acompanhados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão de mRNA dos genes AMDHD1, CYP24A1, NADSYN1 e SEC23A, relacionados à vitamina D, na região odontogênica de incisivos por meio de PCR em tempo real. O teste t de Student foi utilizado para comparar as médias. Também foram utilizados o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: SEC23A foi superexpresso na condição de deficiência de estrógeno na região odontogênica (p=0,021). Conclusão: A deficiência de estrógeno pode influenciar a expressão do gene SEC23A envolvido na ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino (AU)

Incidence and Outcomes Associated with Menopausal Status in COVID-19 Patients: A Systematic Review and Meta-analysis / Incidência e resultados associados ao estado da menopausa em pacientes com COVID-19: Uma revisão sistemática e metanálise

Abstract Objective Menopause causes several changes in the body that may affect the response to COVID-19. We aimed to investigate the possible association between menopausal status and incidence and outcomes in COVID-19 patients. Methods Combinations of keywordsCOVID-19, menopause, and estrogen were used to search the PubMed, Embase, Web-of-Science, and Scopus databases for articles reporting the incidence and outcomes of COVID-19 (discharge, length-of-admission, intensive care, or mortality) in premenopausal women, available through December 29, 2022. Data from studies comparing the incidence of COVID-19 infection with the age-matched male population were pooled and meta-analyzed using a random-effects model. Results Overall, 1,564 studies were retrieved, of which 12 were finally included in the systematic review to compare disease outcomes, and 6 were meta-analyzed for the incidence of COVID-19 in premenopausal and postmenopausal women. All studies reported better COVID-19-associated outcomes in premenopausal women compared with postmenopausal women. After adjusting for confounding factors, three studies found better outcomes in postmenopausal women, and two found no association between menopausal status and COVID-19 outcomes. Our meta-analysis found a higher incidence of COVID-19 infection among premenopausal women than postmenopausal women, when compared with age-matched men (odds ratio = 1.270; 95% confidence interval: 1.086-1.486; p= 0.003). Conclusion The incidence of COVID-19 was significantly higher in premenopausal women than in postmenopausal women when compared with age-matched men. Although premenopausal women may have more favorable COVID-19-associated outcomes, the presumed preventive effect of estrogens on the incidence and related outcomes of COVID-19 in premenopausal women cannot be proven at present. Further longitudinal studies comparing pre- and post-menopausal women are required to provide further insight into this matter.

Resumo Objetivo A menopausa causa diversas alterações no corpo que podem afetar a resposta ao COVID-19. Nosso objetivo foi investigar a possível associação entre o status da menopausa e a incidência e os resultados em pacientes com COVID-19. Métodos Combinações de palavras-chave COVID-19, menopausa e estrogênio foram usadas para pesquisar os bancos de dados PubMed, Embase, Web-of-Science e Scopus para artigos relatando a incidência e os resultados do COVID-19 (alta, tempo de internação, tratamento intensivo cuidados ou mortalidade) em mulheres na pré-menopausa, disponível até 29 de dezembro de 2022. Dados de estudos comparando a incidência de infecção por COVID-19 com a população masculina da mesma idade foram agrupados e meta-analisados usando um modelo de efeitos aleatórios. Resultados No geral, 1.564 estudos foram recuperados, dos quais 12 foram finalmente incluídos na revisão sistemática para comparar os resultados da doença e 6 foram meta-analisados para a incidência de COVID-19 em mulheres na pré e pós-menopausa. Todos os estudos relataram melhores resultados associados ao COVID-19 em mulheres na pré-menopausa em comparação com mulheres na pós-menopausa. Após o ajuste para fatores de confusão, três estudos encontraram melhores resultados em mulheres na pós-menopausa e dois não encontraram associação entre o status da menopausa e os resultados do COVID-19. Nossa meta-análise encontrou uma maior incidência de infecção por COVID-19 entre mulheres na pré-menopausa do que mulheres na pós-menopausa, quando comparadas com homens da mesma idade (odds ratio = 1,270; intervalo de confiança de 95%: 1,086-1,486; p = 0,003). Conclusão A incidência de COVID-19 foi significativamente maior em mulheres na pré-menopausa do que em mulheres na pós-menopausa quando comparadas com homens da mesma idade. Embora as mulheres na pré-menopausa possam ter resultados mais favoráveis associados ao COVID-19, o efeito preventivo presumido dos estrogênios na incidência e nos resultados relacionados ao COVID-19 em mulheres na pré-menopausa não pode ser comprovado no momento. Mas estudos longitudinais comparando mulheres pré e pós-menopausa são necessários para fornecer mais informações sobre este assunto.

Differential Effect of ITE on the Aryl Hydrocarbon Receptor Signaling in Breast Cancer Tissue: A Histopathological Study / Efecto Diferencial de ITE en la Señalización del Receptor de Hidrocarburo de Arilo en Tejido de Cáncer de Mama: Un Estudio Histopatológico

SUMMARY: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in various types of cancers including breast cancer. However, the role of AhR with its endogenous ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the progression of breast cancer remains poorly understood. We aimed to investigate cell proliferation and migration states in breast cancer after activating AhR with the endogenous ligand ITE. Breast cancer tissue was evaluated by cell lines, immunohistochemistry, reverse transcription-polymerase chain reaction, cell proliferation, flow cytometry, migration assays and western blot techniques. We found that AhR was widely expressed in breast cancer tissues and metastasis lymph node tissues, but not in normal tissues. The expression AhR was independent between the age, grades and TNM classifications for breast cancer tissues. ITE treatment significantly induced the activation of AhR in a time-dependent manner in both MCF-7 and T47D breast cancer cell lines. Meanwhile, ITE did not affect the cell migration but significantly suppressed the cell proliferation in estrogen receptor positive (ER+) MCF-7 andT47D cells, which probably attribute to the induction of cell cycle arrest in G1 phase and shortened S phase. Further mechanism study showed that ERK1/2 and AKT signaling were required for the activation of AhR in MCF-7 cells. These data suggest that AhR is a potential new target for treating patients with breast cancer. ITE may be more potentially used for therapeutic intervention for breast cancer with the kind of ER(+).

El receptor de hidrocarburo de arilo (AhR) es un factor de transcripción activado por ligando que se expresa en gran medida en varios tipos de cáncer, incluido el cáncer de mama. Sin embargo, el papel de AhR con su ligando endógeno 2- (1'H-indol-3'-carbonil)-tiazol-4-ácido carboxílico metil éster (ITE) en la progresión del cáncer de mama sigue siendo poco conocido. Nuestro objetivo fue investigar la proliferación celular y los estados de migración en el cáncer de mama después de activar AhR con el ligando endógeno ITE. El tejido de cáncer de mama se evaluó mediante líneas celulares, inmunohistoquímica, reacción en cadena de la polimerasa con transcriptasa inversa, proliferación celular, citometría de flujo, ensayos de migración y técnicas de transferencia Western. Descubrimos que AhR se expresó ampliamente en tejidos de cáncer de mama y en linfonodos con metástasis, pero no en tejidos normales. La expresión AhR fue independiente entre la edad, grados y clasificaciones TNM para tejidos de cáncer de mama. El tratamiento con ITE indujo significativamente la activación de AhR de manera dependiente del tiempo en las líneas celulares de cancer de mama MCF-7 y T47D. Mientras tanto, ITE no afectó la migración celular, pero suprimió significativamente la proliferación celular en células MCF-7 y T47D con receptor de estrógeno positivo (ER+), lo que probablemente se atribuye a la inducción de la detención del ciclo celular en la fase G1 y la fase S acortada. Un estudio adicional del mecanismo mostró que las señales de ERK1/2 y AKT eran necesarias para la activación de AhR en las células MCF-7. Estos datos sugieren que AhR es un nuevo objetivo potencial para el tratamiento de pacientes con cáncer de mama. ITE puede ser utilizado más potencialmente en la intervención terapéutica para el cáncer de mama con el tipo de ER (+).

Assessment of Knowledge Regarding Osteoporosis among Pre-Menopausal Women residing in Selected Rural Communities

Background: As a woman approaches menopause there are gradual changes in the physiology of her body. One of the prominent changes is an increase in the fragility of bone due to calcium variation causing Osteoporosis. A low level of estrogen, which occurs around the time of menopause leads to increased bone loss. A woman can undergo either primary or secondary osteoporosis. In most cases, the first 'symptom' of osteoporosis is broken bone. As osteoporosis is an emerging health problem, that creates an economic burden, it needs a special focus to promote healthy ageing. Knowledge is the best contributor to reducing the risk of premenopausal women getting osteoporosis. Methods: Total 70 pre-menopausal women living in chosen rural communities in Bagalkot were chosen with a convenient sampling technique. A structured questionnaire developed by the researcher was used to gather information concerning knowledge about osteoporosis. Chi-square analysis was used to uncover the relationship between knowledge about osteoporosis with socio-demographic factors. Results: Total 24.28% of women were having good knowledge, 54.28% were having average knowledge, and 21.42% of women were having poor knowledge about osteoporosis. A significant relationship was attained between knowledge regarding osteoporosis and occupation (?2=14.20, p<0.007) and formal education (?2=16.22, p<0.039) at the position of the significance of 0.05. Conclusion: After evaluation of knowledge on the subject of osteoporosis among pre-menopausal women, it was found that most women had average knowledge regarding osteoporosis.

Efectos de la microvibración y estrógeno en la remodelación ósea: revisión sistemática / Effects of micro-vibration and estrogen on bone: a systematic review

Introducción: la pérdida de hueso es un suceso que afecta a la totalidad del esqueleto. Así, las alteraciones musculoesqueléticas afectan a millones de personas en todo el mundo y están entre las causas más comunes de dolor crónico. Objetivo: conocer los efectos de la microvibración y estrógeno en el remodelado óseo. Material y métodos: se realizó una revisión sistemática, se buscó en siete bases de datos, se incluyeron estudios clínicos controlados realizados con ratas o ratones en el periodo de publicación del 2004 al 2022. La calidad de la evidencia sintetizada se evaluó con la escala de Jadad. Resultados: se identificaron quince artículos como estudios primarios. La microvibración reportó cambios in vivo/in vitro totalmente dependientes del estímulo que conlleva incremento de la cortical externa. A su vez, con la administración de estrógeno se reportaron efectos, específicamente, en el hueso trabecular y en el periostio, así como colágeno inmaduro que indican un recambio óseo. Conclusión: tanto la microvibración como la administración de estrógeno coadyuvan a la remodelación del tejido óseo y son aprovechables como tratamiento en el momento que exista un problema de pérdida ósea (AU)

Introduction: Bone loss is an event that affects the entire skeleton. Thus, musculoskeletal disorders affect millions of people worldwide and are among the most common causes of chronic pain. Objective: to know the effects of micro-vibration and estrogen on bone remodelling. Material and methods: a systematic review was carried out; seven databases were searched; Controlled clinical studies conducted with rats or mice in the publication period from 2004 to 2022 were included. The quality of the synthesized evidence was assessed using the Jadad scale. Results: fifteen articles were identified as primary studies. Micro vibration reported in vivo/in vitro changes dependent on the stimulus that entails an increase in the outer cortex. In turn, with the administration of estrogen, effects were reported, specifically in the trabecular bone and in the periosteum, as well as immature collagen that indicates bone turnover. Conclusion: both micro-vibration and the administration of estrogen contribute to the remodelling of bone tissue and are usable as a treatment for bone loss (AU)

A logarithmic model for hormone receptor-positive and breast cancer patients treated with neoadjuvant chemotherapy

SUMMARY OBJECTIVE: The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population. METHODS: Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics. RESULTS: A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48-6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07-5.69, p=0.034). CONCLUSION: In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.

Expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu in gallbladder carcinoma in North Indian population

Background: Gallbladder carcinoma (GBC) although rare is most frequent malignant neoplasm of biliary tract system and sixth most common malignancy of digestive tract. GBC is more common in females and there are studies which show expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 neu (HER2/neu) in GBC suggesting possible molecules for targeted therapy, but results are inconsistent. Aims and Objectives: The aim of this study was to find out expression of ER, PR, and HER2/neu in GBC in North Indian population and their possible association with clinicopathological features. Materials and Methods: A total 59 resected cases of GBC diagnosed by histopathological examination were included in the study. Expression of ER, PR, and HER2/neu was accessed by immunohistochemistry method and correlated with various clinicopathological features. Results: ER expression was absent in all GBC cases. PR expression was present in only one case. Positive expression of HER2/neu was present in 13 (22%) cases, in which 12 cases were of conventional adenocarcinoma and one case was of papillary adenocarcinoma. Well and moderately differentiated tumor had significantly higher HER2/neu expression as compared to poorly differentiated tumors (P = 0.001). Pre-obese patients had significantly higher HER2/neu expression as compared to non-obese patients (P = 0.008). Conclusion: In our study, there was no expression of estrogen and PR in GBC in North Indian population. Although small in number, there is a subset of patients who overexpress HER2/neu receptor that may benefit from targeted therapy.

Mechanism research status of daidzein in the prevention and treatment of osteoporosis through estrogen-like effect / 中国药房

Osteoporosis， as a systemic bone disease with high incidence rate and high disability rate， has become a research hotspot in recent years. The daidzein in soybean isoflavones can bind with estrogen receptors， simulating the prevention and treatment of osteoporosis with estrogen-like effect. Its mechanism of action includes promoting osteoblast formation and differentiation by activating the Wnt signaling pathway， increasing bone density， and improving bone tissue health； inhibiting osteoclast differentiation and slowing down bone resorption by reducing receptor activator of nuclear factors κB ligand/ osteoprotegerin ratio， downregulating the expression of macrophage colony-stimulating factor （M-CSF）； collaborating antioxidant and immune regulation to achieve the goal of preventing and treating osteoporosis. In addition， different doses of daidzein have different effects on bone density and osteoporosis， which may be related to factors such as study design， sample selection， and individual differences.

Prognostic influencing factors analysis of patients with estrogen receptor-positive de novo stage Ⅳbreast cancer / 肿瘤研究与临床

Objective:To investigate the factors influencing the prognosis of patients with estrogen receptor (ER)-positive de novo stage Ⅳ breast cancer.Methods:The clinical data of 339 patients with ER-positive de novo stage Ⅳ breast cancer treated in Tianjin Medical University Cancer Hospital and Cangzhou Hospital of Integrated TCM-WM from February 2010 to December 2017 were retrospectively analyzed. Related factors such as age, time of chief complaint, the clinical T/N stage, site of metastasis, expressions of molecular markers and treatment mode were included. Univariate log-rank test and multivariate Cox regression model were used to analyze the effects of prognostic factors on patients' overall survival (OS).Results:Univariate analysis showed that there were statistically significant differences in the OS of patients stratified by clinical N stage at first diagnosis, metastasis sites at first diagnosis, ER expression, progesterone receptor (PR) expression, Ki-67 positive index and p53 expression, endocrine therapy, chemotherapy at first diagnosis, surgery and radiotherapy of the primary lesions (all P < 0.01). Multivariate Cox regression analysis results showed that metastasis sites at first diagnosis, Ki-67 positive index, surgery and radiotherapy of the primary lesions were all independent influencing factors of OS for breast cancer patients (all P < 0.01). Conclusions:Patients with ER-positive de novo stage Ⅳ breast cancer have a good prognosis when they have oligometastasis, Ki-67 positive index ≤ 20%, and they receive surgery and radiotherapy of the primary lesions.

The effect and mechanism of formononetin on alleviating no-reflow after myocardial ischemia and reperfusion by up-regulating the PI3K/Akt/eNOS signal pathway activated by GPER / 药学学报

To investigate the cardioprotective effect of formononetin (FMN) on no-reflow (NR) after myocardial ischemia-reperfusion and its molecular mechanism based on integrated pharmacology and experimental verification, firstly, human breast cancer MCF-7 cells and myocardial NR rats were used to confirm the estrogenic activity and the effect of alleviating NR of FMN, respectively. Male SD rats were divided into Sham, NR, FMN (20 mg·kg-1) and sodium nitroprusside (SNP, 5.0 mg·kg-1) groups, which were administered once a day for one week, the experiment was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (TCM-LAEC2019095). The pharmacological analysis and in vivo study of NR rats were integrated to reveal the mechanism of FMN improving NR. The results showed that FMN had estrogenic effect and reduced NR by improving cardiac structure and function, reducing NR, ischemic myocardial area and pathological injury of cardiomyocytes. Integrated pharmacology predicts that the mechanism of FMN improving NR is mainly related to phosphatidyinositol-3-kinase-protein kinase B (PI3K-Akt) signal pathway. Phytoestrogens play a role in cardiovascular protection mainly by activating G protein-coupled estrogen receptor (GPER). GPER is also an important regulator in the upstream of PI3K-Akt signaling pathway. This study found that FMN can significantly activate GPER, p-PI3K, p-Akt and phospho-endothelial nitric oxide synthase (p-eNOS). It has good binding ability with GPER and eNOS protein. In this study, through the integration of pharmacology and experimental evaluation, it is revealed that FMN activates PI3K/Akt/eNOS signal pathway by activating GPER, thus significantly improving NR.

Research progress of probiotics intervening osteoporosis through intestinal tract / 中国医师杂志

Osteoporosis (OP) is a systemic bone disease characterized by decreased bone density and damage to bone microstructure, leading to brittle fractures. It is a multifactorial disease that is more common in postmenopausal women, and its high incidence and serious complications are receiving increasing attention. Currently, clinical anti-osteoporosis drugs are mainly divided into two categories: inhibiting bone resorption and promoting bone formation, including bisphosphonates, calcitonin and estrogen, etc. But the side effects and high economic cost of drugs limit the scope of their use to some extent. In recent years, the effect of intestinal flora on bone health, especially on osteoporosis, has become a potential new target for regulating bone density. Probiotics belong to intestinal flora and are defined as living microorganisms. They have initially shown good efficacy in the treatment of some bone metabolic diseases, suggesting that intestinal flora can be used as a potential target for the prevention and treatment of osteoporosis and the application of probiotics as a new therapeutic method for osteoporosis. This paper mainly reviews the relevant studies on probiotics and osteoporosis, shows the latest research progress of probiotics intervention in OP, clarifies the relevant action mechanism of probiotics intervention in OP through intestinal tract, and analyzes the research status and prospect of probiotics treatment in OP.

Research progress on the mechanism of endocrine therapy resistance for breast cancer / 国际肿瘤学杂志

Endocrine therapy resistance is a major challenge in the treatment of hormone receptor-positive breast cancer. In recent years, endocrine resistance mechanisms have focused on ESR1 mutations or fusions, epigenetic regulation, abnormal regulation of signal transduction pathway, cell cycle regulation, cancer stem cells, metabolic reprogramming, tumor microenvironment and autophagy. Exploring the latest advances in the mechanisms of endocrine therapy resistance in breast cancer may provide more research ideas and treatment options for the precision treatment of hormone receptor-positive breast cancer.

Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats / 环境与职业医学

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

Effect of estradiol regulating sortilin-related receptor A expression on hippocampal spine density and synaptic protein expression via estrogen receptor of mouse / 解剖学报

Objective To study the effect and mechanism of estradiol (E