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Computational insights into the aggregation mechanism of human calcitonin.

Int J Biol Macromol

January 2025

School of Physical Science and Technology, Ningbo University, Ningbo 315211, China; Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, United States. Electronic address:

Human calcitonin (hCT) is a peptide hormone that regulates calcium homeostasis, but its abnormal aggregation can disrupt physiological functions and increase the risk of medullary thyroid carcinoma. To elucidate the mechanisms underlying hCT aggregation, we investigated the self-assembly dynamics of hCT segments (hCT, hCT, and hCT) and the folding and dimerization of full-length hCT through microsecond atomistic discrete molecular dynamics (DMD) simulations. Our results revealed that hCT and hCT predominantly existed as isolated monomers with transient small-sized oligomers, indicating weak aggregation tendencies.

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Background/objective: Medullary thyroid cancer often results in elevated calcitonin levels, which can cause localized formation of calcitonin amyloid, though rarely complications of systemic calcitonin amyloidosis have been reported. The objective of this report is to encourage awareness of calcitonin amyloid causing nephrotic syndrome in patients with metastatic medullary thyroid cancer.

Case Report: A 65-year-old woman with weakness, fatigue, anasarca, anemia, thrombocytopenia, venous and arterial thrombi, and a cavitary right lung lesion was transferred for care.

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Protein aggregation in brainstem nuclei is thought to occur in the early stages of Alzheimer's disease (AD), but its specific role in driving prodromal symptoms and disease progression is largely unknown. The dorsal raphe nucleus (DRN) contains a large population of serotonin (5-hydroxytryptamine; 5-HT) neurons that regulate mood, reward-related behavior, and sleep, which are all disrupted in AD. We report here that tau pathology is present in the DRN of individuals 25-80 years old without a known history of dementia, and its prevalence was comparable to the locus coeruleus (LC).

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Misfolding and aggregation of amyloid peptides into β-structure-rich fibrils represent pivotal pathological features in various neurodegenerative diseases, including Alzheimer's disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). The development of effective amyloid detectors and inhibitors for probing and preventing amyloid aggregation is crucial for diagnosing and treating debilitating diseases, yet it poses significant challenges. Here, an aggregation-induced emission (AIE) molecule of ROF2 with multifaceted functionalities as an amyloid probe and a screening tool for amyloid inhibitors using different biophysical, cellular, and worm assays, are reported.

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Survival Outcomes of Medullary Thyroid Cancer With and Without Amyloid Deposition.

Endocr Pract

April 2024

Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, Louisiana.

Objective: Amyloid deposition within tumor stroma is a distinctive histologic feature of medullary thyroid cancer (MTC). However, its prognostic significance remains uncertain. We aimed to elucidate the impact of amyloid status on survival outcomes in a large cohort.

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