Recapitulating thyroid cancer histotypes through engineering embryonic stem cells.

Thyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in the lineage hierarchy that serves as cell of origin for the different TC histotypes is unknown. Human embryonic stem cells (hESCs) with appropriate in vitro stimulation undergo sequential differentiation into thyroid progenitor cells (TPCs-day 22), which maturate into thyrocytes (day 30). Here, we create follicular cell-derived TCs of all the different histotypes based on specific genomic alterations delivered by CRISPR-Cas9 in hESC-derived TPCs. Specifically, TPCs harboring BRAFV600E or NRASQ61R mutations generate papillary or follicular TC, respectively, whereas addition of TP53R248Q generate undifferentiated TCs. Of note, TCs arise by engineering TPCs, whereas mature thyrocytes have a very limited tumorigenic capacity. The same mutations result in teratocarcinomas when delivered in early differentiating hESCs. Tissue Inhibitor of Metalloproteinase 1 (TIMP1)/Matrix metallopeptidase 9 (MMP9)/Cluster of differentiation 44 (CD44) ternary complex, in cooperation with Kisspeptin receptor (KISS1R), is involved in TC initiation and progression. Increasing radioiodine uptake, KISS1R and TIMP1 targeting may represent a therapeutic adjuvant option for undifferentiated TCs.

Comment on "Shiatsu as an Adjuvant Therapy for Depression in Patients With Alzheimer's Disease: A Pilot Study".

Recently, there has been increasing interest toward nonpharmacological approaches for dementia and associated clinical manifestations, such as depression, with the common goal to improve health and quality of life of both patients and caregivers. In this scenario, the role of Shiatsu is of clinical and research interest, although to date a definitive recommendation on a systematic use in clinical practice cannot be made. To overcome the heterogeneity of the previous studies, we tested Shiatsu as an add-on treatment for late-life depression in a dedicated community of patients with mild-to-moderate Alzheimer's disease. We found a significant adjuvant effect of Shiatsu for depression in these patients and hypothesized a neuroendocrine-mediated action on the neural circuits implicated in mood and affect regulation. However, this finding must be considered preliminary and requires confirmation in larger-scale controlled studies, possibly extending the range of outcome measures and including predictors of response. Future investigations should also include an objective assessment of the hypothalamus-pituitary-adrenocortical axis functioning. Nevertheless, starting from this pilot study, we suggest that a customized protocol applied for an adequate period in a controlled sample will represent a non-invasive and feasible advance for promoting patients' mood and, possibly, slowing cognitive decline.

Shiatsu as an adjuvant therapy for depression in patients with Alzheimer's disease: A pilot study.

OBJECTIVES: Among the complementary and alternative medicine, Shiatsu might represent a feasible option for depression in Alzheimer's disease (AD). We evaluated Shiatsu on mood, cognition, and functional independence in patients undergoing physical activity. DESIGN: Single-blind randomized controlled study. SETTING: Dedicated Community Center for patients with AD. INTERVENTIONS: AD patients with depression were randomly assigned to the "active group" (Shiatsu + physical activity) or the "control group" (physical activity alone). Shiatsu was performed by the same therapist once a week for ten months. MAIN OUTCOME MEASURES: Global cognitive functioning (Mini Mental State Examination - MMSE), depressive symptoms (Geriatric Depression Scale - GDS), and functional status (Activity of Daily Living - ADL, Instrumental ADL - IADL) were assessed before and after the intervention. RESULTS: We found a within-group improvement of MMSE, ADL, and GDS in the active group. However, the analysis of differences before and after the interventions showed a statistically significant decrease of GDS score only in the active group. CONCLUSIONS: The combination of Shiatsu and physical activity improved depression in AD patients compared to physical activity alone. The pathomechanism might involve neuroendocrine-mediated effects of Shiatsu on neural circuits implicated in mood and affect regulation.