Current Opinion in Endocrine and Metabolic Research最新文献

Thyroid cancers are often initiated by the acquisition of a BRAF^V600E mutation. BRAF^V600E-driven thyroid tumors display a wide range of behaviors, from the slow-growing papillary carcinomas to the highly aggressive anaplastic. Mutations in the promoter of TERT (telomerase reverse transcriptase) gene were discovered a decade ago and identified as prevalent events in thyroid cancers. Multiple studies showed that TERT promoter mutations, particularly when co-occurring with BRAF^V600E, are markers of poor prognosis across thyroid cancer subtypes, and can be implemented for routine clinical stratification. Mechanistically, TERT promoter mutations reactivate telomerase expression via the differential recruitment of transcriptional complexes. Re-expression of TERT impacts tumor biology, plausibly via both the well-known function of telomerase maintaining telomeres and by affecting other cancer-relevant processes.

Hot flashes and night sweats, also known as vasomotor symptoms (VMS), are common and bothersome symptoms of the menopause transition. In addition to negatively impacting quality of life, VMS have been associated with multiple indicators of cardiovascular disease (CVD) risk, including an unfavorable CVD risk factor profile, increased subclinical CVD, and elevated risk of CVD events. Several facets of VMS have been associated with CVD risk, including the frequency, timing, duration, and severity of VMS. VMS may signify poor or degrading cardiovascular health among midlife women and indicate women who warrant focused CVD prevention efforts.

Anaplastic thyroid cancer (ATC) is one of the most aggressive and lethal types of cancer and treatment options remain very limited. The majority of patients present initially with metastatic disease and require systemic therapy. The shift from conventional cytotoxic therapies to more specific, molecularly targeted therapies is a rapidly developing phenomenon. Despite the recent success of BRAF-directed therapies, druggable mutations in ATC remain scarce and disappointing. Translational research in this area is key to unlocking therapeutic options in ATC, especially as molecular testing becomes increasingly routine. Increasing number of studies in the last decade have described the genomic alterations of ATC, vastly improving our understanding of its development and evolution. In this review, we provide a snapshot of the key DNA sequencing studies of ATC and their potential applications in emerging targeted therapies. We also highlight the future directions of research to tackle this devastating diagnosis.

Osteoblasts are the chief bone-making cells that specialize in producing and mineralizing large amounts of type I collagen and other matrix proteins. The bioenergetics in support of the energy-intensive osteoblast activity is not well understood but has gained renewed interest in recent years. Research in the past ten years has not only confirmed glucose as the main energy substrate for osteoblasts, but also identified contributions of amino acids and fatty acids to either bioenergetic or biosynthetic processes in the cell. Moreover, osteogenic signals have been functionally linked to substrate utilization in osteoblasts. The brief review aims to summarize the recent findings, and to identify remaining questions in the emerging field.

Recent advancements in the bone biology field have identified a novel bone-metabolism axis. In this review, we highlight several novel studies that further our knowledge of new endocrine functions of bone; explore remaining unanswered questions; and discuss translational challenges in this complex era of bone biology research.

The hypoxia-inducible factor 2alpha (HIF-2), which is a member of the HIF family of transcription factors and a critical component of the hypoxia-driven pathway, regulates adult erythropoiesis through the renal production and secretion of erythropoietin (EPO). Notably, circulating EPO also affects bone mass through either direct or indirect actions on osteoblastic and osteoclastic cells. Adding complexity to the picture, we have recently reported that osteoblastic cells produce and secrete EPO upon activation of HIF-2. Although physiological role of osteoblastic EPO in controlling hematopoiesis remains to be determined, our findings could have translational implications for the treatment of anemia.

FGF23 is essential for the regulation of serum phosphate level and the aberrant actions of FGF23 cause hypophosphatemic or hyperphosphatemic diseases. The objective of this review is to provide a current and relevant summary of the recent basic and clinical findings concerning FGF23. Recent findings: Many factors have been shown to affect FGF23 production while the precise roles of these factors in phosphate metabolism are largely unknown. Anti-FGF23 antibody has become clinically available, and the efficacy of this antibody has been reported in several hypophosphatemic diseases caused by excessive actions of FGF23.Summary: The identification of FGF23 came to the development of a new therapy for hypophosphatemic diseases. Still, there are many unanswered questions concerning FGF23.