RESUMO
Advancing age and environmental stressors lead to mitochondrial dysfunction in the skin, inducing premature aging, impaired regeneration, and greater risk of cancer. Cells rely on the communication between the mitochondria and the nucleus by tight regulation of long non-coding RNAs (lncRNAs) to avoid premature aging and maintain healthy skin. LncRNAs act as key regulators of cell proliferation, differentiation, survival, and maintenance of skin structure. However, research on how the lncRNAs are dysregulated during aging and due to stressors is needed to develop therapies to regenerate skin's function and structure. In this article, we discuss how age and environmental stressors may alter lncRNA homeodynamics, compromising cell survival and skin health, and how these factors may become inducers of skin aging. We describe skin cell types and how they depend on mitochondrial function and lncRNAs. We also provide a list of mitochondria localized and nuclear lncRNAs that can serve to better understand skin aging. Using bioinformatic prediction tools, we predict possible functions of lncRNAs based on their subcellular localization. We also search for experimentally determined protein interactions and the biological processes involved. Finally, we provide therapeutic strategies based on gene editing and mitochondria transfer/transplant (AMT/T) to restore lncRNA regulation and skin health. This article offers a unique perspective in understanding and defining the therapeutic potential of mitochondria localized lncRNAs (mt-lncRNAs) and AMT/T to treat skin aging and related diseases.
Assuntos
Senilidade Prematura , Neoplasias , RNA Longo não Codificante , Envelhecimento da Pele , Humanos , RNA Longo não Codificante/genética , Envelhecimento da Pele/genética , Senilidade Prematura/metabolismo , Neoplasias/genética , Mitocôndrias/genética , Mitocôndrias/metabolismoRESUMO
Around two-thirds of women who are of reproductive age use some type of contraception. Two of the most effective long-acting reversible contraceptives (LARC) are the intrauterine device (IUD) and the subdermal contraceptive implant (SCI). Despite their effectiveness, women often report abnormal uterine bleeding as the reason for discontinuation. In this review, we analyze key aspects regarding the mechanisms of action of IUDs (both copper-containing and levonorgestrel-releasing) and SCIs, as well as how they change the intrauterine environment in order to provide effective contraception at a physiological level. Additionally, we introduce the pathophysiology of different types of abnormal intrauterine bleeding provoked by the mentioned LARCs. These three contraceptive methods work in diverse ways, thus, the etiology of abnormal uterine bleeding is different and multifactorial according to each LARC. This review intends to provide information in order to better our understanding of bleeding induced by these contraceptive methods, as well as introduce current and potential new therapies. Furthermore, this review intends to provide updated and concise information that could be available firsthand not only to health care providers but scientists who are innovating and revolutionizing this field. In 2013, the American College of Obstetricians and Gynecologists published a management of abnormal uterine bleeding, however, there is limited updated data regarding the physiology and pathophysiology of abnormal uterine bleeding and its treatment based on different LARCs (hormonal and non-hormonal).
Assuntos
Anticoncepcionais Femininos , Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos Medicados , Dispositivos Intrauterinos , Anticoncepção/métodos , Anticoncepcionais , Anticoncepcionais Femininos/efeitos adversos , Feminino , Humanos , Dispositivos Intrauterinos de Cobre/efeitos adversos , Dispositivos Intrauterinos Medicados/efeitos adversos , Levanogestrel/efeitos adversos , Hemorragia Uterina/tratamento farmacológico , Hemorragia Uterina/etiologiaRESUMO
Breast cancer is one of the most frequent malignancies among women worldwide. Methods for screening and diagnosis allow health care professionals to provide personalized treatments that improve the outcome and survival. Scientists and physicians are working side-by-side to develop evidence-based guidelines and equipment to detect cancer earlier. However, the lack of comprehensive interdisciplinary information and understanding between biomedical, medical, and technology professionals makes innovation of new screening and diagnosis tools difficult. This critical review gathers, for the first time, information concerning normal breast and cancer biology, established and emerging methods for screening and diagnosis, staging and grading, molecular and genetic biomarkers. Our purpose is to address key interdisciplinary information about these methods for physicians and scientists. Only the multidisciplinary interaction and communication between scientists, health care professionals, technical experts and patients will lead to the development of better detection tools and methods for an improved screening and early diagnosis.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Comunicação , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Programas de RastreamentoRESUMO
BACKGROUND: Artificial Mitochondrial Transfer or Transplant (AMT/T) can be used to reduce the stress and loss of viability of damaged cells. In MitoCeption, a type of AMT/T, the isolated mitochondria and recipient cells are centrifuged together at 4 °C and then co-incubated at 37 °C in normal culture conditions, inducing the transfer. Ultraviolet radiation (UVR) can affect mitochondria and other cell structures, resulting in tissue stress, aging, and immunosuppression. AMT/T could be used to repair UVR cellular and mitochondrial damage. We studied if a mitochondrial mix from different donors (Primary Allogeneic Mitochondrial Mix, PAMM) can repair UVR damage and promote cell survival. RESULTS: Using a simplified adaption of the MitoCeption protocol, we used peripheral blood mononuclear cells (PBMCs) as the recipient cell model of the PAMM in order to determine if this protocol could repair UVR damage. Our results showed that when PBMCs are exposed to UVR, there is a decrease in metabolic activity, mitochondrial mass, and mtDNA sequence stability as well as an increase in p53 expression and the percentage of dead cells. When PAMM MitoCeption was used on UVR-damaged cells, it successfully transferred mitochondria from different donors to distinct PBMCs populations and repaired the observed UVR damage. CONCLUSION: Our results represent an advancement in the applications of MitoCeption and other AMT/T. We showed that PBMCs could be used as a PAMM source of mitochondria. We also showed that these mitochondria can be transferred in a mix from different donors (PAMM) to UVR-damaged, non-adherent primary cells. Additionally, we decreased the duration of the MitoCeption protocol.