Oleanolic Acid Acetate Alleviates Cisplatin-Induced Nephrotoxicity via Inhibition of Apoptosis and Necroptosis In Vitro and In Vivo.

Cisplatin is a widely used anti-cancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas it increased Bcl-2 expression. Moreover, in a cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor-interacting protein kinase (RIPK) and mixed lineage kinase domain-like (MLKL) were identified. In an in vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted via co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anti-cancer adjuvant.

Gender-based Disparity Exists in the Surgical Experience of Female and Male Urology Residents.

OBJECTIVE: To determine if a discrepancy exists in the number and type of cases logged between female and male urology residents. MATERIALS AND METHODS: ACGME case log data from 13 urology residency programs was collected from 2007 to 2020. The number and type of cases for each resident were recorded and correlated with resident gender and year of graduation. The median, 25th and 75th percentiles number of cases were calculated by gender, and then compared between female and male residents using Wilcoxon rank sum test. RESULTS: A total of 473 residents were included in the study, 100 (21%) were female. Female residents completed significantly fewer cases, 2174, compared to male residents, 2273 (P = .038). Analysis by case type revealed male residents completed significantly more general urology (526 vs 571, P = .011) and oncology cases (261 vs 280, P = .026). Additionally, female residents had a 1.3-fold increased odds of logging a case in the assistant role than male residents (95% confidence interval: 1.27-1.34, P < .001). CONCLUSION: Gender-based disparity exists within the urology training of female and male residents. Male residents logged nearly 100 more cases than female residents over 4years, with significant differences in certain case subtypes and resident roles. The ACGME works to provide an equal training environment for all residents. Addressing this finding within individual training programs is critical.

Inhibitory Effect of Elaeagnus umbellata Fractions on Melanogenesis in α-MSH-Stimulated B16-F10 Melanoma Cells.

When skin is exposed to UV radiation, melanocytes produce melanin. Excessive melanin production leads to skin pigmentation, which causes various cosmetic and health problems. Therefore, the development of safe, natural therapeutics that inhibit the production of melanin is necessary. Elaeagnus umbellata (EU) has long been widely used as a folk medicinal plant because of pharmacological properties that include anti-ulcer, antioxidant, and anti-inflammatory properties. In this study, we investigated the antioxidant activity and melanogenesis inhibitory effects of EU fractions in B16-F10 melanoma cells. EU fractions showed a dose-dependent increase in antioxidant activity in radical scavenging activity. In addition, we evaluated the effect of EU fractions on tyrosinase activity and melanogenesis in α-melanocyte-stimulating hormone-induced B16-F10 melanoma cells. EU was noncytotoxic at 12.5-50 µg/mL. EU fractions effectively inhibited tyrosinase activity and melanogenesis, suppressed the phosphorylation of CREB and ERK involved in the melanogenesis pathway, and down-regulated expression of melanogenesis-related proteins. Interestingly, the anti-melanogenesis effect was most effective at a concentration of 50 µg/mL EU, and the effects of the fractions were superior to those of the extract. Therefore, our study suggests that EU has potential as a safe treatment for excessive pigmentation or as a natural ingredient in cosmetics.

Pre-screening of patient-reported symptoms using the Edmonton Symptom Assessment System in outpatient palliative cancer care.

OBJECTIVES: Although early palliative care is associated with a better quality of life and improved outcomes in end-of-life cancer care, the criteria of palliative care referral are still elusive. METHODS: We collected patient-reported symptoms using the Edmonton Symptom Assessment System (ESAS) at the baseline, first and second follow-up visits. A total of 71 patients were evaluable, with a median age of 65 years, male (62%) and Eastern Cooperative Oncology Group (ECOG) performance status distribution of 1/2/3 (28%/39%/33%) respectively. RESULTS: Twenty (28%) patients had moderate/severe symptom burden with the mean ESAS ≥ 5. Interestingly, most of the patients with moderate/severe symptom burdens (ESAS ≥ 5) had globally elevated symptom expression. While the mean ESAS score was maintained in patients with mild symptom burden (ESAS < 5; 2.7 at the baseline; 3.4 at the first follow-up; 3.0 at the second follow-up; p = .117), there was significant symptom improvement in patients with moderate/severe symptom burden (ESAS ≥ 5; 6.5 at the baseline; 4.5 at the first follow-up; 3.6 at the second follow-up; p < .001). CONCLUSIONS: In conclusion, advanced cancer patients with ESAS ≥ 5 may benefit from outpatient palliative cancer care. Pre-screening of patient-reported symptoms using ESAS can be useful for identifying unmet palliative care needs in advanced cancer patients.

Extract of Boehmeria nivea Suppresses Mast Cell-Mediated Allergic Inflammation by Inhibiting Mitogen-Activated Protein Kinase and Nuclear Factor-κB.

Mast cells are effector cells that initiate allergic inflammatory immune responses by inducing inflammatory mediators. Boehmeria nivea (Linn.) Gaudich is a natural herb in the nettle family Urticaceae that possesses numerous pharmacological properties. Despite the various pharmacological benefits of Boehmeria nivea, its effects on allergic inflammation have not yet been determined. Here, we investigated the effect of the ethanol extract of Boehmeria nivea (BNE) on degranulation rat basophilic leukemia (RBL)-2H3 mast cells stimulated with anti-dinitrophenyl (anti-DNP) and bovine serum albumin (BSA) during immunoglobulin E (IgE)-mediated allergic immune response. The results showed inhibition of the release of ß-hexosaminidase and histamine from the cells. BNE suppressed pro-inflammatory cytokines (Tumor necrosis factor (TNF)-α, Interleukin (IL)-1ß, and IL-6) and reduced T helper (Th)2 cytokine IL-4 expression and/or secretion correlated with the downregulation of p38, extracellular signal-regulated kinases (ERK) mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signaling pathways in treated RBL-2H3 mast cells. In passive cutaneous anaphylaxis, treatment with BNE during IgE-mediated local allergic reaction triggered a reduction in mouse ear pigmentation and thickness. Taken together, these results indicated that BNE suppressed mast cell-mediated inflammation, suggesting that BNE might be a candidate for the treatment of various allergic disorders.

Development of an affirming and customizable electronic survey of sexual and reproductive health experiences for transgender and gender nonbinary people.

To address pervasive measurement biases in sexual and reproductive health (SRH) research, our interdisciplinary team created an affirming, customizable electronic survey to measure experiences with contraceptive use, pregnancy, and abortion for transgender and gender nonbinary people assigned female or intersex at birth and cisgender sexual minority women. Between May 2018 and April 2019, we developed a questionnaire with 328 items across 10 domains including gender identity; language used for sexual and reproductive anatomy and events; gender affirmation process history; sexual orientation and sexual activity; contraceptive use and preferences; pregnancy history and desires; abortion history and preferences; priorities for sexual and reproductive health care; family building experiences; and sociodemographic characteristics. Recognizing that the words people use for their sexual and reproductive anatomy can vary, we programmed the survey to allow participants to input the words they use to describe their bodies, and then used those customized words to replace traditional medical terms throughout the survey. This process-oriented paper aims to describe the rationale for and collaborative development of an affirming, customizable survey of the SRH needs and experiences of sexual and gender minorities, and to present summary demographic characteristics of 3,110 people who completed the survey. We also present data on usage of customizable words, and offer the full text of the survey, as well as code for programming the survey and cleaning the data, for others to use directly or as guidelines for how to measure SRH outcomes with greater sensitivity to gender diversity and a range of sexual orientations.

The Imperative for Transgender and Gender Nonbinary Inclusion: Beyond Women's Health.

We aim to make evident that solely referencing cisgender women in the context of sexual and reproductive health-particularly pregnancy planning and care-excludes a diverse group of transgender and gender nonbinary people who have sexual and reproductive health needs and experiences that can be similar to but also unique from those of cisgender women. We call on clinicians and researchers to ensure that all points of sexual and reproductive health access, research, sources of information, and care delivery comprehensively include and are accessible to people of all genders. We describe barriers to sexual and reproductive health care and research participation unique to people of marginalized gender identities, provide examples of harm resulting from these barriers, and offer concrete suggestions for creating inclusive, accurate, and respectful care and research environments-which will lead to higher quality health care and science for people of all genders.

Soshiho-Tang, a Traditional Herbal Medicine, Alleviates Atopic Dermatitis Symptoms via Regulation of Inflammatory Mediators.

Soshiho-tang (SST) is a well-known traditional herbal medicine used for the treatment of many diseases. The aims of this study are to investigate the effects of SST on atopic dermatitis (AD) symptoms and to examine its mechanism. Human keratinocyte (HaCaT) cells were stimulated with tumor necrosis factor alpha (TNF-α)/IFN-γ to induce AD-like keratinocyte environment. 2,4-Dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in the dorsal skin of BALB/c mice. SST and dexamethasone were administered orally for 14 day. As a result, SST treatment increased the expression of heme oxygenase-1 (HO-1), an anti-oxidative factor, and the nuclear translocation of NF-E2 p45-related factor 2 (Nrf2). In addition, the treatment also decreased the expression level of inflammatory mediator nuclear factor-κB (NF-κB) and the adhesion molecule intercellular adhesion molecule-1 (ICAM-1). SST treatment (75 and 150 mg/kg) significantly relieved AD symptoms in DNCB-induced AD-like mice by restoring skin thickness, spleen weight, immunoglobulin E (IgE), interleukin 4 (IL-4), pro-inflammatory cytokine expression, and expression of several other mediators. We found that SST alleviates AD-like skin lesions and skin inflammation by modulating various atopic symptoms and inflammatory mediators. Therefore, SST can be used as an alternative drug for the treatment of AD.

Effect of Enzymatic Treatment of Chrysanthemum indicum Linné Extracts on Lipid Accumulation and Adipogenesis in High-Fat-Diet-Induced Obese Male Mice.

Enzyme treatment of the foods and herbs has been used to improve the absorption rate the efficiency of plant extracts by converting the glycosides of the plant into aglycones. In this study, we examined the obesity-inhibitory effect of Chrysanthemum indicum Linné (CI) treated with enzymes such as viscozyme and tannase, which are highly efficient in converting glycosides to aglycones and then compared with untreated CI extract. The enzyme-treated CI ethanol extract (CIVT) was administered orally at various doses for 7 weeks in the high fat diet (HFD)-fed male mice. CIVT administration reduced the body weights, the food efficiency and the serum levels of lipid metabolism-related biomarkers, such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and leptin in the dose-dependent manner but not those high-density lipoprotein cholesterol (HDL-c) and adiponectin. CIVT also reduced considerably the total lipid amount in the liver and the size of adipocytes in the epididymal white adipose tissue (eWAT). CIVT effectively downregulated the adipogenesis-related transcription factors such as peroxisome proliferation activated receptor (PPAR)-γ and CCAAT/enhancer binding protein-α (C/EBP-α) but up-regulated PPAR-α, in the liver and eWAT. In addition, when compared to the enzyme-untreated CI 50% ethanol extract (CIEE), CIVT enhanced the reduction of body weight and lipid accumulation. Moreover, the viscozyme and tannase treatment of CI increased the flavonoid contents of the aglycone form. Therefore, our results support that the enzymatic treatment induced the production of aglycones for potentially suppressing the adipogenesis and lipid accumulation in HFD-fed mice. It suggests that CIVT might be an effective candidate for attenuating the over-weight and its related diseases.

Antioxidant and skin-whitening effects of aerial part of Euphorbia supina Raf. Extract.

BACKGROUND: Euphorbia supina (ES) has been widely used in folk medicine owing to its antibacterial, hemostatic, and anti-inflammatory properties. The aim of this study was to evaluate the antioxidant and skin-whitening effects of a 70% ethanol extract of ES. METHODS: The aerial parts of ES plant were extracted with 70% ethanol. The viability of B16F10 cells was evaluated by MTT assay to determine the non-toxic doses for further experiments. The tyrosinase and cellular tyrosinase activities were then measured using an enzyme-substrate assay. In addition, the expression of whitening-related proteins was measured using western blot. RESULTS: The antioxidant activity of the ES samples increased in a dose-dependent manner, as confirmed by their radical scavenging activities in the 2,2-diphenyl-1-1-picrylhydrazyl and 2,2-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) assays. The ES extract significantly reduced tyrosinase activity and melanin content in a dose-dependent manner. Furthermore, it decreased α-melanocyte stimulating hormone (MSH)-induced protein expression of tyrosinase and microphthalmia-associated transcription factor (MITF). CONCLUSIONS: Our results indicate that the ES extract attenuated α-MSH-stimulated melanin synthesis by modulating tyrosinase and MITF expression. Therefore, the ES extract could be a promising therapeutic agent to treat hyperpigmentation and as an ingredient for skin-whitening cosmetics.