THINC-Integrated Tool (THINC-it): A Brief Measurement of Changes in Cognitive Functioning and Its Correlation with the Life Quality of Patients with Schizophrenia and Related Disorders—A Pilot Study

Background: This pilot study aimed to assess patients’ cognitive functioning with the Polish version of the THINC-it tool and to analyze its association with self-reported quality of life (QOL). Methods: Twenty-one patients (mean age: 37.8 ± 10.4) were assessed at baseline and after six weeks of a standard therapeutic outpatient program. Participants completed the World Health Organization QOL Questionnaire (WHOQOL-BREF) and the THINC-it tool at both visits. The tool consists of tasks evaluating working memory (SYMBOL CHECK), attention (SPOTTER), executive functions (TRIALS), and cognitive skills (CODEBREAKER). Results: During the second visit, patients showed significant improvements in mean latency of correct responses of SPOTTER: p = 0.021, Cohen’s d = 0.38 and in the Physical health domain: p = 0.007, Cohen’s d = 0.37. The number of correct responses for CODEBREAKER was positively associated with the Physical health domain at visit 1 (r = 0.53, p = 0.014) and visit 2 (r = 0.42, p = 0.058). The number of correct responses at SYMBOL CHECK was positively related to QOL in the Environment domain only at visit 2 (r = 0.45, p = 0.042). Conclusions: These results suggest the THINC-it tool has utility as a cognitive measure in adults with schizophrenia in both clinical and research settings

The regulation of steroid receptors by epigallocatechin-3-gallate in breast cancer cells

Kelly Hallman,* Katie Aleck,* Meghan Quigley, Brigitte Dwyer, Victoria Lloyd, Monica Szmyd, Sumi Dinda Biomedical Diagnostic and Therapeutic Sciences, School of Health Sciences, Center for Biomedical Research, Oakland University, Rochester, MI, USA *These authors contributed equally to this work Abstract: It has been reported that phytoestrogen epigallocatechin gallate (EGCG) suppresses cancer cell proliferation and may have antitumor properties. In this study, we analyzed the effects of EGCG on estrogen receptor α (ERα) and progesterone receptor in hormone-dependent T-47D breast cancer cells. Western blot analysis revealed EGCG induced a concentration-dependent decrease in ERα protein levels, with a 56% reduction occurring with 60 µM EGCG when compared to controls. Downregulation of ERα protein levels was observed after 24-hour co-treatment of T-47D cells with 60 µM EGCG and 10 nM 17β-estradiol (E2). The proliferative effect of E2 on cell viability was reversed when treated in combination with EGCG. In contrast, the combination of EGCG with the pure ER antagonist, ICI 182, 780, showed no further reduction in cell number as only 5% of the cells were viable after 6 days of treatment. These studies may provide further understanding of the interactions among flavonoids and steroid receptors in breast cancer cells. Keywords: phytoestrogen, ER, PR, T-47D, antiestrogen

The antiestrogenic effects of black cohosh on BRCA1 and steroid receptors in breast cancer cells

Michael Crone,1,2 Kelly Hallman,1,2 Victoria Lloyd,1,2 Monica Szmyd,1,2 Briana Badamo,1,2 Mia Morse,1,2 Sumi Dinda1,2 1Department of Biomedical Diagnostic and Therapeutic Sciences, School of Health Sciences, Oakland University, Rochester, MI 48309-4476, USA; 2Institute for Stem Cell and Regenerative Medicine and Center of Biomedical Sciences, Oakland University, Rochester, MI 48309-4476, USA Background: Black cohosh (BC) is an herbal remedy often used by women to treat symptoms associated with menopause. Research has shown that the molecular activity of BC is associated with estrogen receptor alpha (ER-α) regulation. Progesterone receptor (PR) expression is found to be consistent with ER expression and mutations in the BRCA1 gene, a tumor-suppressor gene, are known to be responsible for about 40%–45% of hereditary breast cancers. Purpose: The objective of this study was to determine the effects of BC alone, as well as in combination with hormones and antihormones, on cell viability and expression of ER-α, PR, and BRCA1 in both T-47D and MCF-7 cell lines. Methods: Cells were cultured in charcoal-stripped serum prior to their treatment and subsequent protein extraction. Western blot analyses were performed following a Bio-Rad Bradford protein assay and SDS-PAGE gel electrophoresis, with ECL luminescence and Image Studio Lite software. Cellular viability assays were performed using propidium iodine (PI) staining, and the distribution of fluorescent structures was evaluated through confocal microscopy. RT-qPCR analysis was performed on extracted cellular RNA. All statistical analyses were performed using SPSS software, and data was subjected to Kruskal-Wallis testing, followed by post-hoc analysis using the Mann-Whitney U-test to determine the statistical significance of all findings. Results: Western blot analysis displayed significant alterations of ER-α, PR, and BRCA1 protein levels after 24-hour treatment with 80–500 μM BC. BC displayed a concentration-dependent decrease on ER-α and BRCA1 expression, with an 87% reduction of ER-α expression and a 43% of BRCA1 expression in T-47D cells compared to control. After six days of treatment with 400 μM BC, a 50% decrease in cell proliferation was observed. Following 24 hours of co-treatment with 400 μM BC and 10 nM E2, ER-α was downregulated by 90% and BRCA1 expression was reduced by 70% compared to control. The expression of PR, following the same treatment, exhibited similar effects. The proliferative effect of E2 was reduced in the presence of BC. Conclusion: Black Cohosh demonstrates substantial anti-cancer properties, and this study may significantly aid in the understanding of the molecular effects of BC on ER-α, PR, and BRCA1 in breast cancer cells. Keywords: tumor suppressor, MCF-7, T-47D, antitumor agent, natural anticancer, cancer treatmen

The effects of black cohosh on the regulation of estrogen receptor (ERα) and progesterone receptor (PR) in breast cancer cells

Monica Szmyd,1–3 Victoria Lloyd,1–3 Kelly Hallman,1–3 Katie Aleck,1–3 Viktoria Mladenovik,1–3 Christina McKee,1–3 Mia Morse,1–3 Tyler Bedgood,1–3 Sumi Dinda1–3 1Biomedical and Therapeutic Sciences, School of Health Sciences, 2Prevention Research Center, 3Center of Biomedical Sciences, Oakland University, Rochester, MI, USA Abstract: The North American plant Cimicifuga racemosa, also known as black cohosh (BC), is a herb that recently has gained attention for its hormonal effects. As the usage of hormone replacement therapy is declining due to its adverse effects in women with cancer, many are turning to herbal remedies like BC to treat menopausal symptoms. It is crucial to determine whether the effects of BC involve estrogen receptor-alpha (ERα). Previous studies from our laboratory have shown ERα to be a possible molecular target for BC. In this study, we examined the effects of BC (8% triterpene glycosides) alone and in combination with hormones and antihormones on the cellular viability, expression of ERα and progesterone receptor (PR)-A/B, and cytolocalization of ERα in ER (+) and PR-A/B (+) T-47D breast cancer cells. Cells were cultured and proteins were extracted and quantified. Western blot analysis revealed alterations in the expression of ERα and PR after treatment with BC (5–100 µM). BC induced a concentration-dependent decrease in ERα and PR protein levels when compared to the control. Image cytometric analysis with propidium iodide staining was used to enumerate changes in T-47D cell number and viability. A decrease in T-47D cell viability was observed upon treatment with 5–100 µM BC. The ideal concentration of BC (100 μM) was used in combination with hormones and antihormones in an effort to further understand the possible similarities between this compound and other known effectors of ERα and PR. After a 24-hour concomitant treatment with and/or in combination of BC, estradiol, ICI 182, 780, and Tamoxifen, downregulation of ERα and PR protein levels was observed. Delineating the role of BC in the regulation of ERα, PR, as well as its mechanisms of action, may be important in understanding the influence of BC on hormone receptors in breast cancer. Keywords: black cohosh, breast cancer, ERα, progesterone receptor, hormone replacement therap

Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters

Background: Staphylococcus aureus has important implications for the pathogenesis of atopic dermatitis (AD). In some patients S. aureus can be eradicated from the skin during anti-inflammatory treatment, while in others bacterial colonization is persistent. Potential mechanisms and features of these two distinct groups of patients are not known. Objective: Accordingly, we studied relationships between the ability to eliminate S. aureus during an anti-inflammatory treatment and selected clinical and immunological features. Methods: Quantitative assessment of S. aureus on the skin, in nasal vestibule and throat, serum IgE levels, CD4/CD8 T-cell ratio, lymphocyte proliferation and phagocyte oxidative burst were determined during the exacerbation and after 4 and 12 weeks of the treatment using topical steroid and oral antihistamine in 34 patients with AD. Results: S. aureus was found on the skin of all 34 patients during exacerbation. Disease severity scoring of atopic dermatitis (SCORAD) correlated with the density of bacteria. Treatment with oral antihistamine and topical steroid resulted in a significant alleviation of symptoms, which correlated with the elimination of S. aureus from the skin in 70% of patients. In the remaining 30% of patients, dense (more than 1010/cm2) S. aureus skin colonization, persisted despite the treatment. Patients with persistent S. aureus presented with higher serum IgE levels, lower lymphocyte proliferation in response to staphylococcal enterotoxin B, phytohaemagluttinin and anti-CD3. Persistence of S. aureus was more common in men. Conclusions: Patients with AD differ in the ability to clear S. aureus from the skin during anti-inflammatory treatment, which appears to be related to the abnormalities in immunological parameters. Local antibiotic therapy should be considered only in patients with persistent S. aureus colonization