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Chrysin ameliorates methotrexate-induced hippocampal neurogenesis impairment by suppressing of oxidative stress and upregulating antioxidant enzyme activity in rodents

by Tanaporn Anosri, Soraya Kaewngam, Ram Prajit, Kornrawee Suwannakot, Nataya Sritawan, Anusara Aranarochana, Wanassanan Pannangrong, Jariya Umka Welbat, Peter Wigmore, Apiwat Sirichoat

Methotrexate (MTX) is used in treating several malignancies. However, MTX neurotoxicity remains a significant clinical side effect, leading to cell division malformation, and neurogenesis impairment. Chrysin, a flavonoid compound found in natural products, demonstrates various biological characteristics, including neuroprotective and antioxidant properties. The purpose of this study was to investigate the ameliorative effect of chrysin on oxidative damage and neurogenesis impairment caused by MTX. Male Sprague-Dawley rats were randomly divided into four groups, including the vehicle, MTX (75 mg/kg), chrysin (10 mg/kg), and chrysin+MTX groups. Chrysin was orally administered for 15 days. MTX was administered intravenously on days 8 and 15. The hippocampal neural stem cells were evaluated using sex determining region Y-box 2 (sox2) and nestin immunofluorescence staining. Antioxidant enzyme expression and the levels of oxidative stress marker were assessed. Additionally, the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), brain-derived neurotrophic factor (BDNF), cAMP-response element binding (CREB), and phosphorylated CREB (pCREB) were evaluated using Western blotting. Results showed that MTX significantly decreased the activity of antioxidant enzymes and produced oxidative stress. MTX also impaired neurogenesis, evidenced by decreased sox2 and nestin-positive cells and decreased expression of Nrf2, BDNF, CREB, and pCREB in the hippocampus and prefrontal cortex. However, chrysin significantly reversed the effects of MTX on these parameters. In conclusion, chrysin exhibits neuroprotective effects against MTX-induced neurogenesis impairment by upregulating antioxidant enzyme activity, reducing oxidative stress, and improving protein expression related to neurogenesis.

Protocol for a mixed-methods modified Delphi study for the development of a core domain set to assess the health-related quality of life of patients with mycosis fungoides and Sezary syndrome in clinical trials

Por: Asare · C. · Raymundo · C. · Chen · J. · Perez-Chada · L. · Tawa · M. · Thornton · S. · Ottevanger · R. · Scarisbrick · J. · Olsen · E. · Khan · N. · Kim · E. J. · Shinohara · M. M. · Larocca · C. · International Dermatology Outcomes Measures Cutaneous Lymphoma Working Group Addi
Introduction

Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin lymphomas that primarily affects the skin and can mimic inflammatory dermatoses. Unlike many skin diseases, CTCL can lead to disabling symptoms, and advanced CTCL can even be fatal. Early studies investigating health-related quality of life (HRQOL) in patients with mycosis fungoides (MF) and Sézary syndrome (SS), common subtypes of CTCL, demonstrated significant impairment across numerous domains. The aim of this current study is to develop a core domain set (CDS) to identify the essential aspects of MF/SS that influence HRQOL that should be measured in therapeutic clinical trials. In the future, this set of core concepts will be used to identify the best patient- reported outcome measure(s) (PROM) for HRQOL for MF/SS clinical research.

Methods and analysis

Multiple strategies will be used to generate candidate concepts: systematic review of the literature, qualitative study and a survey study of healthcare providers. A Delphi consensus process including a comprehensive group of stakeholders (patients, caregivers/care partners, a multidisciplinary group of healthcare professionals, patient advocacy groups, pharmaceutical industry representatives, methodologists and government agencies) will be used to achieve consensus. Statistical corrections for multiple significance testing and false positive findings will be undertaken.

Ethics and dissemination

The study was submitted for and received institutional review board approval at the University of Washington (IRB# STUDY00018890 and STUDY00019407). Informed consent will be obtained from all participants where necessary. We will disseminate our findings through peer-reviewed, open access publications and presentations at national/international conferences. We will provide a plain language summary in lay terms for patients and families to patient advocacy groups for distribution to their network.

Registration details

The protocol is registered in the Core Outcome Measures in Effectiveness Trials (COMET) database.

Understanding the effects of reductions in local government expenditure on food safety services in England, 2009-10 to 2019-20: a longitudinal ecological study

Por: Murrell · L. · Clough · H. E. · Zhang · X. · Gibb · R. · Chattaway · M. A. · Green · M. A. · Buchan · I. E. · Barr · B. · Hungerford · D.
Objective

To understand how reductions in resource allocation affect food safety services in England.

Design

This longitudinal ecological study analysed secondary observational data.

Setting

England, data at the local authority level.

Participants

Ecological study, without human participants.

Primary and secondary outcome measures

The primary outcome measures were the number of staff, represented by the number of full-time equivalents per capita, number of interventions per establishment, and proportion of hygiene-compliant establishments.

Results

A £1 decrease in food safety expenditure per capita was associated with a 2% (–3.3 to –0.7) decrease in staffing levels and a 1.6% (–3.2 to –0.1) decrease in the number of interventions achieved per establishment. A one-unit reduction in staff was associated with a 42.2% (–80.5 to –11.9) decrease in the number of interventions achieved. No evidence of an association was found between expenditure or staff levels and the proportion of compliant establishments.

Conclusions

Spending reductions negatively affected the capacity of food safety teams to provide key services. Reductions in food safety expenditure significantly affected food hygiene staff levels and service provision. This finding raises concerns about the capacity of food safety teams to operate and the potential for increased public risk of gastrointestinal infections.

Associations between heart failure-related quality of life and clinical parameters in patients with hypertrophic cardiomyopathy: a cross-sectional analysis of data from a multicentre Japanese registry

Por: Saotome · M. · Akita · K. · Kageyama · S. · Suzuki · S. · Ohno · K. · Kamakura · M. · Nawada · R. · Takanaka · C. · Wakabayashi · Y. · Kanda · T. · Tawarahara · K. · Muto · M. · Matsunaga · M. · Suwa · S. · Takeuchi · Y. · Sakamoto · H. · Saito · H. · Hayashi · K. · Wakahara · N. · Unno · K.
Objective

To investigate the relationship between a quality of life (QOL) score and clinical parameters in patients with hypertrophic cardiomyopathy (HCM).

Design

A multicentre cross-sectional study.

Setting

We analysed data from the Searching for Atrial Fibrillation and Early Recruitment of Heart Failure in HCM registry, collected between 2018 and 2023.

Participants

Patients with HCM (n=499) aged ≥18 years from 12 institutions (Shizuoka Prefecture, Japan) were consecutively enrolled.

Outcome measures

Clinical parameters, along with data from a short form of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), were collected. The association between each clinical parameter and the KCCQ-12 score was analysed. Clinical parameters with a significant univariable association (p

Results

In the univariable analysis, KCCQ-12 scores exhibited significant associations with 21 clinical parameters, including sex, left ventricular morphology and the Pittsburgh Sleep Quality Index (PSQI). The multiple regression model with 12 parameters that had a significant univariable association exhibited an adjusted R2 of 0.48. In this model, the PSQI (standardised coefficient –0.39; p

Conclusions

In patients with HCM, we investigated the association between the KCCQ-12 score and various clinical parameters. PSQI, as well as known heart failure-related clinical parameters, was significantly associated with the KCCQ-12 score. Visualising the associations of various clinical parameters with the KCCQ-12 score will help physicians to consider factors linked to the decline in QOL in patients with HCM.

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