Deregulation of New Cell Death Mechanisms in Leukemia.

Hematological malignancies are among the top five most frequent forms of cancer in developed countries worldwide. Although the new therapeutic approaches have improved the quality and the life expectancy of patients, the high rate of recurrence and drug resistance are the main issues for counteracting blood disorders. Chemotherapy-resistant leukemic clones activate molecular processes for biological survival, preventing the activation of regulated cell death pathways, leading to cancer progression. In the past decade, leukemia research has predominantly centered around modulating the well-established processes of apoptosis (type I cell death) and autophagy (type II cell death). However, the development of therapy resistance and the adaptive nature of leukemic clones have rendered targeting these cell death pathways ineffective. The identification of novel cell death mechanisms, as categorized by the Nomenclature Committee on Cell Death (NCCD), has provided researchers with new tools to overcome survival mechanisms and activate alternative molecular pathways. This review aims to synthesize information on these recently discovered RCD mechanisms in the major types of leukemia, providing researchers with a comprehensive overview of cell death and its modulation.

Involvement of regulated cell deaths in aging and age-related pathologies.

Aging is a pathophysiological process that causes a gradual and permanent reduction in all biological system functions. The phenomenon is caused by the accumulation of endogenous and exogenous damage as a result of several stressors, resulting in significantly increased risks of various age-related diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. In addition, aging appears to be connected with mis-regulation of programmed cell death (PCD), which is required for regular cell turnover in many tissues sustained by cell division. According to the recent nomenclature, PCDs are physiological forms of regulated cell death (RCD) useful for normal tissue development and turnover. To some extent, some cell types are connected with a decrease in RCD throughout aging, whereas others are related with an increase in RCD. Perhaps the widespread decline in RCD markers with age is due to a slowdown of the normal rate of homeostatic cell turnover in various adult tissues. As a result, proper RCD regulation requires a careful balance of many pro-RCD and anti-RCD components, which may render cell death signaling pathways more sensitive to maladaptive signals during aging. Current research, on the other hand, tries to further dive into the pathophysiology of aging in order to develop therapies that improve health and longevity. In this scenario, RCD handling might be a helpful strategy for human health since it could reduce the occurrence and development of age-related disorders, promoting healthy aging and lifespan. In this review we propose a general overview of the most recent RCD mechanisms and their connection with the pathophysiology of aging in order to promote targeted therapeutic strategies.

Development and mechanical properties of a locking T-plate / Desenvolvimento e as propriedades mecânicas de uma placa bloqueada em formato de T

This study aimed to develop a locking T-plate and to evaluate its mechanical properties in synthetic models. A titanium 2.7mm T-plate was designed with a shaft containing three locked screw holes and one dynamic compression hole, and a head with two locked screw holes. Forty T-shaped polyurethane blocks, and 20 T-plates were used for mechanical testing. Six bone-plate constructs were tested to failure, three in axial compression and three in cantilever bending. Fourteen bone-plate constructs were tested for failure in fatigue, seven in axial compression and seven in cantilever bending. In static testing higher values of axial compression test than cantilever bending test were observed for all variables. In axial compression fatigue testing all bone-plate constructs withstood 1,000,000 cycles. Four bone-plate constructs failure occurred before 1,000,000 cycles in cantilever bending fatigue testing. In conclusion, the locking T-plate tested has mechanical properties that offer greatest resistance to fracture under axial loading than bending forces.(AU)

O objetivo deste estudo foi desenvolver uma placa bloqueada em formato de T e avaliar as propriedades mecânicas em um modelo sintético. Uma placa-T em liga de titânio 2,7mm foi desenhada com uma haste contendo três orifícios para parafusos bloqueados e um orifício para realização de compressão dinâmica. 40 blocos de poliuretano em formato de T e 20 placas-T foram utilizados para os ensaios mecânicos. Seis montagens osso-placa foram testados até a falha, sendo três em força de compressão axial e três em flexão engastada. 14 montagens osso-placa foram testadas até a falha em fatiga, sendo 7 em força de compressão axial e 7 em flexão engastada. No teste estático, os valores mais altos foram observados em todas as variáveis no teste de compressão axial quando comparado à flexão engastada. Já nos testes de fadiga na força de compressão axial, todas as montagens osso-placa resistiram à 1000000 de ciclos. No teste de fadiga em flexão engastada, quatro montagens osso-placa falharam antes de alcançarem 1000000 de ciclos. Em conclusão, a placa-T estudada apresenta propriedades mecânicas que oferecem uma melhor resistência em estabilizar as fraturas na atuação das forças de compressão axial que nas forças de flexão.(AU)