Effects of matcha tea extract on cell viability and estrogen receptor-ß expression on MCF-7 breast cancer cells.

PURPOSE: In the following work, we investigated the effect of matcha green tea extract (MTE) on MCF-7 breast cancer cell viability and estrogen receptor-beta expression (ERß). METHODS: MCF-7 cells were stimulated with MTE at concentrations of 5 and 10 µg/ml. Cell viability was assessed using a water-soluble tetrazolium assay (WST-1 assay) after an incubation time of 72 h. ERß was quantified at gene level by real-time polymerase chain reaction (PCR). A western blot (WB) was carried out for the qualitative assessment of the expression behavior of on a protein level. RESULTS: The WST-1 test showed a significant inhibition of viability in MFC-7 cells after 72 h at 10 µg/ml. The WB demonstrated a significant quantitative decrease of ERß at protein level with MTE concentrations of 10 µg/ml. In contrast, the PCR did not result in significant downregulation of ERß. CONCLUSION: MTE decreases the cell viability of MCF-7 cells and furthermore leads to a decrease of ERß at protein level.

Health-related quality of life and patient-centred outcomes with COVID-19 vaccination in patients with breast cancer and gynaecological malignancies.

Introduction: Safety and tolerability of COVID-19 vaccines were demonstrated by several clinical trials which led to the first FDA/EMA approvals in 2021. Because of mass immunizations, most social restrictions were waived with effects on quality of life. Therefore, our a-priori hypothesis was that COVID-19 vaccination impacted the health-related quality of life (HR-QoL) in patients with breast and gynecological cancer. Methods: From March 15th until August 11th, 2022, fully vaccinated patients with breast and gynecological cancer treated in the oncological outpatient clinics of the Department of Obstetrics and Gynecology, LMU University Hospital, Munich, Germany filled out a vaccine related QoL survey. Patients were asked about demographics (age, comorbidities), clinical parameters related to previous COVID-19 infections, and HR-QoL related parameters (living situation, responsibilities in everyday life). Subsequently, a questionnaire with 12 items was designed using a 5-point Likert scale (0 - strongly disagree/4 - strongly agree), covering the aspects health and therapy, social environment, participation in everyday life and overall assessment. Results: By August 11th, 2022, 108 out of 114 (94.7%) patients had received at least three doses of COVID-19 vaccine and six patients at least two doses. More than half of the surveyed patients were >55y (52.6%; mean: 55.1y, range 29-86y). Patients with breast cancer (n= 83) had early (59.0%) or metastatic cancer (41.0%); gynecological cancers (n=31) also included metastatic (54.8%) and non-metastatic cancer (45.2%). 83.3% of the patients stated that COVID-19 vaccination had a positive impact on their HR-QoL. Furthermore, 29 patients (25.4%) had undergone a COVID-19 infection. These patients reported self-limiting symptoms for a median duration of 5.9 days and no hospital admissions were registered. Conclusions: Our study demonstrates that vaccination against COVID-19 was positively associated with HR-QoL in patients with breast and gynecological cancer. Furthermore, vaccinated patients who underwent COVID-19 disease experienced only self-limiting symptoms.

The psychological burden of COVID-19 on the desire for parenthood in minoritized sexual identities: a study on depressive symptoms and family planning in Germany.

BACKGROUND: The COVID-19 pandemic continues to spread across the globe and is associated with significant clinical and humanitarian burden. The desire for parenthood has been described to be positively correlated with psychological well-being: An unfulfilled wish for parenthood is associated with impaired mental health, and the wish for parenthood is a predictor for the development of depressive symptoms. While higher rates of anxiety and depression have been reported in individuals with minoritized sexual identities (compared to heterosexual individuals) during the COVID-19 pandemic, the specific impact of the pandemic and its social restriction measures on this population is poorly understood. METHODS: From April to July 2020, we conducted an anonymous cross-sectional survey online among N = 2463 adults living in Germany. We screened for depressive symptoms (Patient Health Questionnaire-4; PHQ-4) and assessed individuals' desire for parenthood during the pandemic, and motives for or against the desire for parenthood (Leipzig questionnaire on motives for having a child, Version 20; LKM-20), with the aim of identifying differences between individuals with minoritized sexual identities and heterosexual individuals. RESULTS: Compared to heterosexual individuals (n = 1304), individuals with minoritized sexual identities (n = 831) indicated higher levels of depressive symptoms. In our study sample the majority of all participants (81.9%) reported no change in the desire for parenthood since the COVID-19 pandemic. CONCLUSION: The findings underline the unmet need for social, psychological and medical support in regard to family-planning and the desire for parenthood during a pandemic. Furthermore, future research should explore COVID-19-related psychological consequences on individuals' desire for parenthood and building a family.

The Impact of the COVID-19 Pandemic on Sexual Health in Cis Women Living in Germany.

BACKGROUND: Preliminary research shows a substantial impact of the COVID-19 pandemic on women's sexual health, whereby empirical work on sexual well-being of minoritized sexual identities is still rare. AIM: The objective of this study was to explore sexual health in heterosexual, lesbian and bisexual cis women during the first wave of COVID-19 pandemic in Germany. METHODS: An anonymous nationwide online survey was conducted among cis women during the first nationwide lockdown in Germany from April 20th to July 20th, 2020. The questionnaire was distributed via e-mail, online chats and social-media platforms. OUTCOMES: Demographic variables and self-report measures from the Sexual Behavior Questionnaire (SBQ-G) "before the pandemic" and "since the pandemic" were collected. RESULTS: A total of 1,368 cis women participants were included: heterosexual women (n = 844), lesbian women (n = 293), bisexual women (n = 231). Results indicate overall decrease in frequency of sexual contacts and masturbation during the COVID-19 pandemic. Regarding differences before and during the pandemic lesbian women showed significant changes in sexual arousal whereas heterosexual women showed significant changes in all dimensions except capability to enjoy sexual intercourse. The data of bisexual women showed significant changes in almost all dimensions except for frequency of sexual intercourse and sexual arousal. Results of the multiple regression analysis revealed that being younger than 36 years-old, and being in a relationship as well as being heterosexual (compared with being lesbian) is positively associated with general satisfaction with sexual life during the pandemic. CLINICAL IMPLICATIONS: The findings suggest that during a pandemic sexual and mental health care for (cis) women should be provided and address the specific needs of sexual minority groups. STRENGTHS & LIMITATIONS: This is the first study to describe sexual behavior in heterosexual, lesbian and bisexual women during the COVID-19 pandemic in Germany. Limitations, however, include the fact that the data described were obtained at only one time point so there is a possibility of recall bias, and that the results cannot be generalized because of the underrepresentation of women over age 46. CONCLUSION: This study examined the impact of the COVID-19 pandemic and resulting social constraints on the sexual health of particular groups of lesbian and bisexual women, which may improve preparedness for future public health and policy crises. Batz F, Lermer E, Hatzler L, et al. The Impact of the COVID-19 Pandemic on Sexual Health in Cis Women Living in Germany. J Sex Med 2022;19:907-922.

Effects of matcha tea extract on cell viability and peroxisome proliferator-activated receptor γ expression on T47D breast cancer cells.

PURPOSE: In the following work, we investigated the nuclear peroxisome proliferator-activated receptor gamma (PPARγ)-dependent proliferation behavior of breast cancer cells after stimulation with matcha green tea extract (MTE). METHODS: T47D cells were stimulated with MTE at concentrations of 5, 10 and 50 µg/ml. Cell viability was assessed using a WST-1 assay after an incubation time of 72 h. PPARγ expression was quantified at the gene level by real-time polymerase chain reaction (PCR). A western blot (WB) was carried out for the qualitative assessment of the expression behavior of on a protein level. RESULTS: The WST-1 test showed a significant inhibition of viability in T47D cells after 72 h at 5, 10 and 50 µg/ml. The PCR showed an overexpression of PPARγ in T47D cells in all concentrations. At the concentration of 50 µg/ml the expression was significantly increased (p < 0.05). The WB demonstrated a significant quantitative increase of PPARγ at protein level with MTE concentrations of 10 and 50 µg/ml. In addition, there was a negative correlation between the overexpression of PPAR γ and the inhibition of proliferation. CONCLUSION: MTE decreases the cell viability of T47D cells and furthermore leads to an overexpression of PPARγ on protein and mRNA level.

Early and Later Perceptions and Reactions to the COVID-19 Pandemic in Germany: On Predictors of Behavioral Responses and Guideline Adherence During the Restrictions.

In March 2020, the German government enacted measures on movement restrictions and social distancing due to the COVID-19 pandemic. As this situation was previously unknown, it raised numerous questions about people's perceptions of and behavioral responses to these new policies. In this context, we were specifically interested in people's trust in official information, predictors for self-prepping behavior and health behavior to protect oneself and others, and determinants for adherence to social distancing guidelines. To explore these questions, we conducted three studies in which a total of 1,368 participants were surveyed (Study 1 N=377, March 2020; Study 2 N=461, April 2020; Study 3 N=530, April 2021) across Germany between March 2020 and April 2021. Results showed striking differences in the level of trust in official statistics (depending on the source). Furthermore, all three studies showed congruent findings regarding the influence of different factors on the respective behavioral responses. Trust in official statistics predicted behavioral responses in all three studies. However, it did not influence adherence to social distancing guidelines in 2020, but in 2021. Furthermore, adherence to social distancing guidelines was associated with higher acceptance rates of the measures and being older. Being female and less right-wing orientated were positively associated with guidelines adherence only in the studies from 2020. This year, political orientation moderated the association between acceptance of the measures and guideline adherence. This investigation is one of the first to examine perceptions and reactions during the COVID-19 pandemic in Germany across 1year and provides insights into important dimensions that need to be considered when communicating with the public.

Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer.

The aim of this retrospective study was to assess the prognostic value of cytoplasmic versus nuclear RXRα expression in breast cancer (BC) tissue samples and to correlate the results with clinicopathological parameters. In 319 BC patients, the expression of RXRα was evaluated via immunohistochemistry. Prognosis-determining aspects were calculated through uni- and multivariate analyses. Correlation analysis revealed a trend association with nuclear RXRα expression regarding an improved overall survival (OS) (p = 0.078), whereas cytoplasmic RXRα expression was significantly correlated with a poor outcomes in terms of both OS (p = 0.038) and disease-free survival (DFS) (p = 0.037). Strengthening these results, cytoplasmic RXRα was found to be an independent marker for DFS (p = 0.023), when adjusted to clinicopathological parameters, whereas nuclear RXRα expression was positively associated with lower TNM-staging, i.e., pT (p = 0.01), pN (p = 0.029) and pM (p = 0.001). Additionally, cytoplasmic RXRα expression was positively associated with a higher histopathological tumor grading (p = 0.02). Cytoplasmic RXRα was also found to be a negative prognosticator for Her-2neu-negative and triple-negative patients. Altogether, these findings support the hypothesis that the subcellular localization of RXRα plays an important role in carcinogenesis and the prognosis of BC. The expression of cytoplasmic RXRα is correlated with a more aggressive course of the disease, whereas nuclear RXRα expression appears to be a protective factor. These data may help to identify high-risk BC subgroups in order to find possible specific options in targeted tumor therapy.

How the COVID-19 Pandemic Affects Sexual Behavior of Hetero-, Homo-, and Bisexual Males in Germany.

INTRODUCTION: The COVID-19 pandemic drastically altered the way of life around the world. Due to social distancing measures, contact restrictions and fears of infection, social life has changed significantly. These measures along with the stressors associated with the current worldwide situation, will inevitably have an effect on people's interpersonal and personal behaviors. AIM: This study evaluates the effect the COVID-19 pandemic and nationwide German lockdown had on the sexual behavior of cis men. METHODS: An anonymous nationwide web-based questionnaire was conducted among cis men in Germany during the first COVID-19 home isolation (April 20, 2020-July 20, 2020). The questionnaire was distributed via e-mail, online chats and social-media platforms. MAIN OUTCOME MEASURES: Data was collected on general characteristics including demographics and socio-economic backgrounds. To evaluate sexual health, questions from the Sexual Behavior Questionnaire were included. RESULTS: 523 cis male participated. 414 met the inclusion criteria. Most were heterosexual (n = 248, 59.9%; vs homosexual n = 97, 23.4%; vs bisexual n = 69, 16.7%). 243 (59%) were employed, 153 (37.1%) were students and 16 (3.9%) were unemployed. Most of the participants reported an annual income lower than 75.000€. During the lockdown, average weekly frequency of sexual intercourse and masturbation was increased in all groups. Consistently, a significant rise of higher satisfaction with the frequency of sexual contacts during the quarantine was observed (P < .05). Furthermore, the level of sexual arousal increased significantly in all groups (P < .0005). Capability to enjoy sexual intercourse or masturbation increased significantly in heterosexual (P < .0005) and homosexual men (P < .005). Bisexual participants showed a significant increase in general satisfaction with sexual life (P < .05) and a significant decrease in satisfaction in relationship or single life (P < .05). Positive confounders in the changing of sexual behavior during the COVID-19 pandemic were: Being in a relationship or being single, parenthood and being employed. CONCLUSION: Our study firstly describes how COVID-19 pandemic related restrictions and social distancing measurements altered sexual behavior amongst cis male in Germany. Further studies, including sexual minorities specifically, are needed to clarify if the behavior in the first German nationwide quarantine has persisted or transformed as the pandemic proceeded. Mumm J-N, Vilsmaier T, Schuetz JM, et al. How the COVID-19 Pandemic Affects Sexual Behavior of Hetero-, Homo-, and Bisexual Males in Germany. Sex Med 2021;9:100380.

Identification of a Novel Tumor Microenvironment Prognostic Signature for Advanced-Stage Serous Ovarian Cancer.

(1) Background: The tumor microenvironment is involved in the growth and proliferation of malignant tumors and in the process of resistance towards systemic and targeted therapies. A correlation between the gene expression profile of the tumor microenvironment and the prognosis of ovarian cancer patients is already known. (2) Methods: Based on data from The Cancer Genome Atlas (379 RNA sequencing samples), we constructed a prognostic 11-gene signature (SNRPA1, CCL19, CXCL11, CDC5L, APCDD1, LPAR2, PI3, PLEKHF1, CCDC80, CPXM1 and CTAG2) for Fédération Internationale de Gynécologie et d'Obstétrique stage III and IV serous ovarian cancer through lasso regression. (3) Results: The established risk score was able to predict the 1-, 3- and 5-year prognoses more accurately than previously known models. (4) Conclusions: We were able to confirm the predictive power of this model when we applied it to cervical and urothelial cancer, supporting its pan-cancer usability. We found that immune checkpoint genes correlate negatively with a higher risk score. Based on this information, we used our risk score to predict the biological response of cancer samples to an anti-programmed death ligand 1 immunotherapy, which could be useful for future clinical studies on immunotherapy in ovarian cancer.

Well-being during COVID-19 pandemic: A comparison of individuals with minoritized sexual and gender identities and cis-heterosexual individuals.

BACKGROUND: Preliminary empirical data indicates a substantial impact of the COVID-19 pandemic on well-being and mental health. Individuals with minoritized sexual and gender identities are at a higher risk of experiencing such negative changes in their well-being. The objective of this study was to compare levels of well-being among cis-heterosexual individuals and individuals with minoritized sexual and gender identities during the COVID-19 pandemic. METHODS: Using data obtained in a cross-sectional online survey between April 20 to July 20, 2020 (N = 2332), we compared levels of well-being (WHO-5) across subgroups (cis-individuals with minoritized sexual identities, individuals with minoritized gender identities and cis-heterosexual individuals) applying univariate (two-sample t-test) and multivariate analysis (multivariate linear regression). RESULTS: Results indicate overall lower levels of well-being as well as lower levels of well-being in minoritized sexual or gender identities compared to cis-heterosexual individuals. Further, multivariate analyses revealed that living in urban communities as well as being in a relationship were positively associated with higher levels of well-being. Furthermore, a moderation analysis showed that being in a relationship reduces the difference between groups in terms of well-being. CONCLUSION: Access to mental healthcare for individuals with minoritized sexual and gender identities as well as access to gender-affirming resources should be strengthened during COVID-19 pandemic. Healthcare services with low barriers of access such as telehealth and online peer support groups should be made available, especially for vulnerable groups.

The Prognostic Impact of Retinoid X Receptor and Thyroid Hormone Receptor alpha in Unifocal vs. Multifocal/Multicentric Breast Cancer.

The aim of this study was to assess the prognostic value of the steroid hormone receptor expression, counting the retinoid X receptor (RXR) and thyroid hormone receptors (THRs), on the two different breast cancer (BC) entities: multifocal/multicentric versus unifocal. The overall and disease-free survival were considered as the prognosis determining aspects and analyzed by uni- and multi-variate analysis. Furthermore, histopathological grading and TNM staging (T = tumor size, N = lymph node involvement, M = distant metastasis) were examined in relation to RXR and THRs expression. A retrospective statistical analysis was carried out on survival-related events in a series of 319 sporadic BC patients treated at the Department of Gynecology and Obstetrics at the Ludwig-Maximillian's University in Munich between 2000 and 2002. The expression of RXR and THRs, including its two major isoforms THRα1 and THRα2, was analyzed by immunohistochemistry and showed to have a significant correlation for both BC entities in regard to survival analysis. Patients with multifocal/multicentric BC were exposed to a significantly worse disease-free survival (DFS) when expressing RXR. Patients with unifocal BC showed a significantly worse DFS when expressing THRα1. In contrast, a statistically significant positive association between THRα2 expression and enhanced DFS in multifocal/multicentric BC was shown. Especially the RXR expression in multifocal/multicentric BC was found to play a remarkably contradictory role for BC prognosis. The findings imply the need for a critical review of possible molecular therapies targeting steroid hormone receptors in BC treatment. Our results strengthen the need to further investigate the behavior of the nuclear receptor family, especially in relation to BC focality.

IFN Regulatory Factor 4 Controls Post-ischemic Inflammation and Prevents Chronic Kidney Disease.

Ischemia reperfusion injury (IRI) of the kidney results in interferon regulatory factor 4 (IRF4)-mediated counter-regulation of the acute inflammatory response. Beyond that, IRF4 exerts important functions in controlling the cytokine milieu, T-cell differentiation, and macrophage polarization. The latter has been implicated in tissue remodeling. It therefore remains elusive what the role of IRF4 is in terms of long-term outcome following IRI. We hypothesized that an inability to resolve chronic inflammation in Irf4-/- mice would promote chronic kidney disease (CKD) progression. To evaluate the effects of IRF4 in chronic upon acute injury in vivo, a mouse model of chronic injury following acute IRI was employed. The expression of Irf4 increased within 10 days after IRI in renal tissue. Both mRNA and protein levels remained high up to 5 weeks upon IRI, suggesting a regulatory function in the chronic phase. Mice deficient in IRF4 display increased tubular cell loss and defective clearance of infiltrating macrophages. These phenomena were associated with increased expression of pro-inflammatory macrophage markers together with reduced expression of alternatively activated macrophage markers. In addition, IRF4-deficient mice showed defective development of alternatively activated macrophages. Hints of a residual M1 macrophage signature were further observed in human biopsy specimens of patients with hypertensive nephropathy vs. living donor specimens. Thus, IRF4 restricts CKD progression and kidney fibrosis following IRI, potentially by enabling M2 macrophage polarization and restricting a Th1 cytokine response. Deteriorated alternative macrophage subpopulations in Irf4-/- mice provoke chronic intrarenal inflammation, tubular epithelial cell loss, and renal fibrosis in the long course after IRI in mice. The clinical significance of these finding for human CKD remains uncertain at present and warrants further studies.

Organic anion transporter OAT3 enhances the glucosuric effect of the SGLT2 inhibitor empagliflozin.

The sodium-glucose cotransporter SGLT2 inhibitor empagliflozin (plasma protein binding ~88%) may reach its target in the brush border of the early proximal tubule by glomerular filtration and tubular secretion. Here we determined whether empagliflozin is secreted by renal tubules in mice and whether genetic knockout of the basolateral organic anion transporter 3 ( Oat3-/-) affects its tubular secretion or glucosuric effect. Renal clearance studies in wild-type (WT) mice showed that tubular secretion accounted for 50-70% of empagliflozin urinary excretion. Immunostaining indicated that SGLT2 and OAT3 localization partially overlapped in proximal tubule S1 and S2 segments. Glucosuria in metabolic cage studies was reduced in Oat3-/- vs. WT mice for acute empagliflozin doses of 1, 3, and 10 mg/kg, whereas 30 mg/kg induced similar maximal glucosuria in both genotypes. Chronic application of empagliflozin (~25 mg·kg-1 ·day-1) in Oat3-/- mice was associated with lower urinary glucose-to-creatinine ratios despite maintaining slightly higher blood glucose levels than WT. On a whole kidney level, renal secretion of empagliflozin was largely unchanged in Oat3-/- mice. However, the absence of OAT3 attenuated the influence of empagliflozin on fractional glucose excretion; higher levels of plasma or filtered empagliflozin were needed to induce similar increases in fractional renal glucose excretion. We conclude that empagliflozin is excreted into the urine to similar extent by glomerular filtration and tubular secretion. The latter can occur largely independent of OAT3. However, OAT3 increases the glucosuric effect of empagliflozin, which may relate to the partial overlap of its localization with SGLT2 and thus OAT3-mediated tubular secretion of empagliflozin in the early proximal tubule.

PPARγ agonist-induced fluid retention depends on αENaC expression in connecting tubules.

BACKGROUND/AIMS: Thiazolidinediones (TZDs, like rosiglitazone (RGZ)) are peroxisome proliferator-activated receptor γ (PPARγ) agonists used to treat type 2 diabetes. Clinical limitations include TZD-induced fluid retention and body weight (BW) increase, which are inhibited by amiloride, an epithelial-sodium channel (ENaC) blocker. RGZ-induced fluid retention is maintained in mice with αENaC knockdown in the collecting duct (CD). Since ENaC in the connecting tubule (CNT) rather than in CD appears to be critical for normal NaCl retention, we aimed to further explore the role of ENaC in CNT in RGZ-induced fluid retention. METHODS: Mice with conditional inactivation of αENaC in both CNT and CD were used (αENaC lox/lox AQP2-Cre; 'αENaC-CNT/CD-KO') and compared with littermate controls (αENaC lox/lox mice; 'WT'). BW was monitored and total body water (TBW) and extracellular fluid volume (ECF) were determined by bioelectrical impedance spectroscopy (BIS) before and after RGZ (320 mg/kg diet for 10 days). RESULTS: On regular NaCl diet, αENaC-CNT/CD-KO had normal BW, TBW, ECF, hematocrit, and plasma Na(+), K(+), and creatinine, associated with an increase in plasma aldosterone compared with WT. Challenging αENaC-CNT/CD-KO with a low NaCl diet unmasked impaired NaCl and K homeostasis, consistent with effective knockdown of αENaC. In WT, RGZ increased BW (+6.1%), TBW (+8.4%) and ECF (+10%), consistent with fluid retention. These changes were significantly attenuated in αENaC-CNT/CD-KO (+3.4, 1.3, and 4.3%). CONCLUSION: Together with the previous studies, the current results are consistent with a role of αENaC in CNT in RGZ-induced fluid retention, which dovetails with the physiological relevance of ENaC in this segment.