Photoperiodism, testosterone and adult neurogenesis in canaries (Serinus canaria).

被引量：- 发表：1970

The curious case of the hypothalamic-pituitary-gonadal axis dysfunction in subordinate female naked mole-rats (Heterocephalus glaber): No apparent role of opioids and glucocorticoids.

被引量：- 发表：1970

Real-world effectiveness of adjuvant octreotide therapy in patients with pancreatic neuroendocrine tumors at high recurrence risk: A multicenter retrospective cohort study.

Adjuvant therapy for pancreatic neuroendocrine tumors (PanNETs) after radical resection lacks evidence-based data and remains controversial. This study aimed to validate whether long-acting octreotide is a potential candidate for adjuvant therapy in patients with G2 PanNETs at high recurrence risk by clustering real-world data. A retrospective review of patients with nonmetastatic grade 2 PanNETs who underwent radical resection at six research centers between 2008 and 2020 was conducted. Propensity score matching and inverse probability of treatment weight analysis were used to control confounding factors. Overall, 357 patients (octreotide group, n = 82; control group, n = 275) were analyzed. Kaplan-Meier survival analyses showed that the octreotide group had longer disease-free survival (DFS) compared with the control group (36 months: 93.3% vs. 79.0%, p = .0124; 60 months: 71% vs. 67.6%, p = .0596, respectively), as well as overall survival (OS) (60 months: 98% vs. 83.8%, p = .0117, respectively). Multivariate analyses indicated that octreotide long-acting repeatable (LAR) adjuvant therapy was associated with higher OS (p = .0270) at 60 months. Propensity score matching analysis showed that octreotide adjuvant therapy was associated with higher DFS (p = .0455) and OS (p = .0190) at 60 months. Similar results were obtained via inverse probability of treatment weight analysis. Subgroup analysis indicated that octreotide LAR was associated with a high DFS in patients with lymph node metastasis or Ki-67 <10% PanNETs. Adjuvant therapy with long-acting octreotide following radical resection of nonmetastatic G2 PanNETs may be associated with improved DFS and OS in a real-world setting.

被引量：- 发表：1970

PTPRJ is a negative regulator of insulin signaling in neuronal cells, impacting protein biosynthesis, and neurite outgrowth.

Central insulin resistance has been linked to the development of neurodegenerative diseases and mood disorders. Various proteins belonging to the enzyme family of protein tyrosine phosphatases (PTPs) act as inhibitors of insulin signaling. Protein tyrosine phosphatase receptor type J (PTPRJ) has been identified as a negative regulator in insulin signaling in the periphery. However, the impact of PTPRJ on insulin signaling and its functional role in neuronal cells is largely unknown. Therefore, we generated a Ptprj knockout (KO) cell model in the murine neuroblast cell line Neuro2a by CRISPR-Cas9 gene editing. Ptprj KO cells displayed enhanced insulin signaling, as shown by increased phosphorylation of the insulin receptor (INSR), IRS-1, AKT, and ERK1/2. Further, proximity ligation assays (PLA) revealed both direct interaction of PTPRJ with the INSR and recruitment of this phosphatase to the receptor upon insulin stimulation. By RNA sequencing gene expression analysis, we identified multiple gene clusters responsible for glucose uptake and metabolism, and genes involved in the synthesis of various lipids being mainly upregulated under PTPRJ deficiency. Furthermore, multiple Ca2+ transporters were differentially expressed along with decreased protein biosynthesis. This was accompanied by an increase in endoplasmic reticulum (ER) stress markers. On a functional level, PTPRJ deficiency compromised cell differentiation and neurite outgrowth, suggesting a role in nervous system development. Taken together, PTPRJ emerges as a negative regulator of central insulin signaling, impacting neuronal metabolism and neurite outgrowth.

被引量：- 发表：1970

Understanding negative feedback: Changes in high-molecular-weight adrenocorticotropic hormone in adrenocorticotropic hormone-independent Cushing's syndrome.

Cushing's syndrome is characterized by chronic glucocorticoid oversecretion and diverse clinical manifestations. Distinguishing between adrenocorticotropic hormone (ACTH)-independent and ACTH-dependent forms is crucial for determining treatment options. Plasma ACTH levels aid in the differential diagnosis, with undetectable or low levels suggesting ACTH-independent hypercortisolemia. ACTH is derived from pro-opiomelanocortin, and its processing involves prohormone convertase 1/3. High-molecular-weight ACTH is generally found in ACTH-producing pituitary tumors and ectopic ACTH syndrome. The mechanism of negative feedback and the process of high-molecular-weight ACTH alternation during ACTH-independent Cushing's syndrome remain unclear. A 40-year-old woman with hypertension and multiple fractures developed symptoms suggestive of Cushing's syndrome. Computed tomography revealed a left adrenocortical tumor along with atrophy of the right adrenal gland. ACTH levels were undetectable at the previous clinic, indicating ACTH-independent Cushing's syndrome. However, subsequent measurements at our hospital revealed non-suppressed ACTH (18.1 pg/mL), prompting further investigation. Gel exclusion chromatography confirmed the presence of high-molecular-weight ACTH. Metyrapone treatment decreased the cortisol levels. In this situation, in which ACTH levels should be elevated, a decrease in high-molecular-weight ACTH levels was observed. Histological findings revealed cortisol-producing adenoma without ACTH expression. This case highlights the importance of assay differences in evaluating ACTH concentrations and introduces a novel finding of circulating high-molecular-weight ACTH. The observed decline in high-molecular-weight ACTH levels suggests a potential time lag in the negative feedback within the hypothalamic-pituitary-adrenal axis exhibited by glucocorticoids. This temporal aspect of the regulation of ACTH-related molecules warrants further exploration to enhance our understanding of the hypothalamic-pituitary-adrenal axis feedback mechanism.

被引量：- 发表：1970