Bmc Med
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The benefits of first-line, cisplatin-based chemotherapy for muscle-invasive bladder cancer are limited due to intrinsic or acquired resistance to cisplatin. Increasing evidence has revealed the implication of cancer stem cells in the development of chemoresistance. However, the underlying molecular mechanisms remain to be elucidated. This study investigates the role of LASS2, a ceramide synthase, in regulating Wnt/β-catenin signaling in a subset of stem-like bladder cancer cells and explores strategies to sensitize bladder cancer to cisplatin treatment. ⋯ Targeting the LASS2 and β-catenin pathways may be an effective strategy to overcome cisplatin resistance and inhibit tumor growth in bladder cancer patients.
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Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-naïve TNBC patients according to BRCA1 status, taking sTILs into account. ⋯ Although both gBRCA1m and tumor BRCA1-PM alter BRCA1 gene transcription, they are associated with different outcomes in young, node-negative, chemotherapy-naïve TNBC patients. By combining sTILs and BRCA1 status for risk classification, we were able to identify potential subgroups in this population to intensify and optimize adjuvant treatment.
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Aggregate trends can be useful for summarizing large amounts of information, but this can obscure important distributional aspects. Some population subgroups can be worse off even as averages climb, for example. Distributional information can identify health inequalities, which is essential to understanding their drivers and possible remedies. ⋯ Maternal and child health indicators show progress, but the distributional effects show differential evolutions in inequalities. Several reasons may explain why countries had smaller wealth-related gap trends in vaccination-related indicators compared to others. In addition to service delivery differences, we hypothesize that the allocation of development assistance for health, the prioritization of vaccine-preventable diseases on the global agenda, and indirect effects of structural adjustment programs on health system-related indicators might have played a role.
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Dilation may be the first right ventricular change and accelerates the progression of threatening ventricular tachyarrhythmias and heart failure for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), but the treatment for right ventricular dilation remains limited. ⋯ This study provided a comprehensive analysis of the lineage-specific changes in the blood and myocardium from ARVC patients at a single-cell resolution. Pharmacological inhibition of NLRP3 could prevent right ventricular dilation and dysfunction of mice with ARVC.
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Observational Study
Human lifespan and sex-specific patterns of resilience to disease: a retrospective population-wide cohort study.
Slower paces of aging are related to lower risk of developing diseases and premature death. Therefore, the greatest challenge of modern societies is to ensure that the increase in lifespan is accompanied by an increase in health span. To better understand the differences in human lifespan, new insight concerning the relationship between lifespan and the age of onset of diseases, and the ability to avoid them is needed. We aimed to comprehensively study, at a population-wide level, the sex-specific disease patterns associated with human lifespan. ⋯ Health interventions focused on delaying aging and age-related diseases should be the most effective in increasing not only lifespan but also health span. The findings of this research highlight the relevance of Electronic Health Records in studying the aging process and open up new possibilities in age-related disease prevention that should assist primary care professionals in devising individualized care and treatment plans.