IFN-γ stimulates Paneth cell secretion through necroptosis mTORC1 dependent.

Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-γ a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown. In this study, using in vivo and in vitro models we demonstrate that IFN-γ is spontaneously secreted in the small intestine. Furthermore, we observed that this cytokine stimulates mitochondrial activity, ROS production, and Paneth and Paneth-like cell secretion. Paneth and Paneth-like secretion downstream of IFN-γ, as identified here, is mTORC1 and necroptosis-dependent. Thus, our findings revealed that the pleiotropic function of IFN-γ also includes the regulation of Paneth cell function in the homeostatic gut.

The Proteome Profile of Olfactory Ecto-Mesenchymal Stem Cells-Derived from Patients with Familial Alzheimer's Disease Reveals New Insights for AD Study.

Alzheimer's disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment, and its pathological mechanisms are not yet fully understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer's Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second compared carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in the pre-symptom stages. Finally, we analyzed the differentially expressed proteins (DEPs) for biological and functional enrichment. These proteins showed impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways, in line with previous AD reports. Our study is the first to conduct a proteomic analysis of MSCs from the Jalisco FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies.

Y chromosome diversity in Aztlan descendants and its implications for the history of Central Mexico.

Native Mexican populations are crucial for understanding the genetic ancestry of Aztec descendants and coexisting ethnolinguistic groups in the Valley of Mexico and elucidating the population dynamics of the prehistoric colonization of the Americas. Mesoamerican societies were multicultural in nature and also experienced significant admixture during Spanish colonization of the region. Despite these facts, Native Mexican Y chromosome diversity has been greatly understudied. To further elucidate their genetic history, we conducted a high-resolution Y chromosome analysis with Chichimecas, Nahuas, Otomies, Popolocas, Tepehuas, and Totonacas using 19 Y-short tandem repeat and 21 single nucleotide polymorphism loci. We detected enormous paternal genetic diversity in these groups, with haplogroups Q-MEH2, Q-M3, Q-Z768, Q-L663, Q-Z780, and Q-PV3 being identified. These data affirmed the southward colonization of the Americas via Beringia and connected Native Mexicans with indigenous populations from South-Central Siberia and Canada. They also suggested that multiple population dispersals gave rise to Y chromosome diversity in these populations.

Erratum to "From ACTH-Dependent to ACTH-Independent Cushing's Syndrome from a Malignant Mixed Corticomedullary Adrenal Tumor: Potential Role of Embryonic Stem Cells".

[This corrects the article DOI: 10.1155/2020/4768281.].

From ACTH-Dependent to ACTH-Independent Cushing's Syndrome from a Malignant Mixed Corticomedullary Adrenal Tumor: Potential Role of Embryonic Stem Cells.

OBJECTIVE: To report the immunohistochemical and molecular evaluation of a patient with ectopic ACTH syndrome (EAS) from a MCAT which has single cells with features of both 96 medullary and cortical differentiation. Case Description and Methods. A 16-year-old woman presented with severe EAS and a large right MCAT composed of ACTH-secreting cells resembling pheochromocytoma and another lineage similar to adrenal carcinoma. Immunohistochemistry (IHC) showed positivity for medullary (ACTH, chromogranin A, synaptophysin, and PS-100) and epithelial components (inhibin, melan-A, and calretinin). Embryonic stem cell markers were evaluated using RT/PCR and immunofluorescence. After initial surgery, the tumor recurred shifting to rapidly progressive ACTH-independent liver metastasis. RESULTS: Histopathology and IHC revealed two distinct and intermingled cellular patterns, while some cells immunostained for both medullary and cortical markers. Demonstration of all stem cell biomarkers by RT/PCR and immunofluorescence was predominantly localized to the nucleus, whereas SOX2 immunoreactivity was evident in the cytoplasm as well. CONCLUSION: The expression of cancer stem cell biomarkers points towards the involvement of primitive embryonic cells as the origin of this neoplasm and maybe to the clinically aggressive and biochemically changing behavior.