RESUMO
Factor inhibiting HIF (FIH, also known as HIF1AN) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains (ARDs) have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ARD. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.
Assuntos
Hipóxia Celular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Oxigenases de Função Mista/metabolismo , Proteínas Repressoras/metabolismo , Canais de Cátion TRPV/metabolismo , Sequência de Aminoácidos , Repetição de Anquirina/genética , Células HEK293 , Humanos , Hidroxilação/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Oxigenases de Função Mista/antagonistas & inibidores , Oxigenases de Função Mista/genética , Mutação , Oxigênio/metabolismo , Ligação Proteica , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Canais de Cátion TRPV/genéticaRESUMO
This systematic review and meta-analysis assessed the efficacy of cognitive-behavioural therapy for insomnia (CBT-I) among cancer survivors and explored its effect on comorbid symptoms. Studies were included if they assessed the efficacy of CBT-I in adults diagnosed with cancer published prior to August 2020. The primary outcome was insomnia severity. The protocol was pre-registered on PROSPERO (CRD42020169986). Twenty-two studies met eligibility criteria. CBT-I significantly improved insomnia severity (g = 0.78) with durable benefits at 3- and 6-month follow-up. CBT-I produced significant small to large effects for diary-measured sleep efficiency, wake after sleep onset, total sleep time, sleep onset latency, sleep quality, anxiety, depression, fatigue, and overall quality of life. Subgroup analyses revealed no significant difference between in-person and self-help CBT-I. Overall, CBT-I is a robustly efficacious and durable treatment for insomnia among cancer survivors and can produce concomitant benefits on other symptoms. Implementation efforts are needed to ensure that people with cancer have access to CBT-I as the recommended first-line treatment for insomnia.
Assuntos
Sobreviventes de Câncer , Terapia Cognitivo-Comportamental , Neoplasias , Distúrbios do Início e da Manutenção do Sono , Actigrafia , Adulto , Terapia Cognitivo-Comportamental/métodos , Humanos , Neoplasias/complicações , Qualidade de Vida , Sono , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do TratamentoRESUMO
The psychosocial needs and experiences of transgender and gender diverse (TGD) people is an understudied area of oncology research. In response to calls to action from past researchers, we conducted a scoping review, which included published and gray literature. From the included articles, the following key themes were identified: (1) lack of coordination between gender-affirming care and cancer care; (2) impact of cancer care on gender affirmation; (3) navigating gendered assumptions; (4) variation in providers' understanding of the needs of TGD patients; and (5) lack of TGD-specific cancer resources. Following this review, we consulted 18 key stakeholders with TGD-relevant personal and/or professional experience to gain further insight into issues that were not encompassed by the original themes. Based on these themes and stakeholder feedback, we offer recommendations for future research and clinical practice to increase awareness of the psychosocial needs of TGD people who have been diagnosed with cancer and to improve patient care.