Pathophysiology of Mummification Fulcheri, Ezio
Journal of Biological Research,
09/2021, Letnik:
80, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Italian mummies are a biological, historical, and cultural heritage of significant value.
However, only in the past few years has this heritage been properly appreciated, quite recently if compared ...to the history of Paleopathology. Its importance in quantitative terms and the abundance of biological, anthropological, and medical information offered to researchers are more and more appreciated. ...
Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by ...microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.
Natural killer (NK) cells are the main lymphoid population in the maternal decidua during the first trimester of pregnancy. Decidual NK (dNK) cells display a unique functional profile and play a key ...role in promoting tissue remodeling, neoangiogenesis, and immune modulation. However, little information exists on their origin and development. Here we discovered CD34⁺ hematopoietic precursors in human decidua (dCD34⁺). We show that dCD34⁺ cells differ from cord blood- or peripheral blood-derived CD34⁺ precursors. The expression of IL-15/IL-2 receptor common β-chain (CD122), IL-7 receptor α-chain (CD127), and mRNA for E4BP4 and ID2 transcription factors suggested that dCD34⁺ cells are committed to the NK cell lineage. Moreover, they could undergo in vitro differentiation into functional (i.e., IL-8- and IL-22-producing) CD56brightCD16⁻KIR⁺/⁻ NK cells in the presence of growth factors or even upon coculture with decidual stromal cells. Their NK cell commitment was further supported by the failure to undergo myeloid differentiation in the presence of GM-CSF. Our findings strongly suggest that decidual NK cells may directly derive from CD34⁺ cell precursors present in the decidua upon specific cellular interactions with components of the decidual microenvironment.
Group 3 innate lymphoid cells (ILC3) have been detected in both murine and human decidual tissues where they are thought to play a relevant role in the induction and maintenance of pregnancy. ...However, limited information exists on the molecular mechanisms that regulate these cells, including immune checkpoints. Here, we show that ILC3 express the inhibitory checkpoints programmed cell death (PD-1) and T cell immunoglobulin and mucin domain containing protein 3 (TIM-3) during the first trimester of pregnancy and that these receptors could regulate production of cytokines, including IL-22, IL-8, and TNF-α, induced by IL-23. We also show that the intermediate extravillous trophoblast (iEVT) expresses high levels of the PD-1-ligand PD-L1, suggesting that PD-1/PD-L1 interaction may regulate ILC3 function at the feto-maternal interface. Our present data provide the first evidence that human decidual ILC3 express a functional PD-1. It is possible that an altered expression or function of PD-1 may break the immune-tolerance resulting in pregnancy failure.
We evaluated the energy metabolism of human mesenchymal stem cells (MSC) isolated from umbilical cord (UC) of preterm (< 37 weeks of gestational age) and term (≥ 37 weeks of gestational age) ...newborns, using MSC from adult bone marrow as control. A metabolic switch has been observed around the 34th week of gestational age from a prevalently anaerobic glycolysis to the oxidative phosphorylation. This metabolic change is associated with the organization of mitochondria reticulum: preterm MSCs presented a scarcely organized mitochondrial reticulum and low expression of proteins involved in the mitochondrial fission/fusion, compared to term MSCs. These changes seem governed by the expression of CLUH, a cytosolic messenger RNA-binding protein involved in the mitochondria biogenesis and distribution inside the cell; in fact, CLUH silencing in term MSC determined a metabolic fingerprint similar to that of preterm MSC. Our study discloses novel information on the production of energy and mitochondrial organization and function, during the passage from fetal to adult life, providing useful information for the management of preterm birth.
During the first trimester of pregnancy NK cells represent >50% of the lymphoid cells present in the human decidua where they reside in close contact with trophoblast cells. Because in decidual ...tissues NK cell activation and function may be induced by this interaction, we analyzed the cellular ligands recognized by activating NK receptors expressed on trophoblast cells. We show that these cells primarily express the NKp44 and DNAM-1 ligands and that interaction between these ligands and their corresponding receptors results in NK cell triggering. While activated peripheral blood NK (pNK) cells lysed the trophoblast cell lines JAR and JEG3, decidual NK (dNK) cells did not. On the other hand, they released VEGF, SDF-1, IP10 and large amounts of IL-8. Interaction with K562 target cells was exploited to induce optimal NK cell triggering, allowing a parallel, quantitative assessment of both cytolytic activity and cytokine production elicited by dNK cells. While dNK cells were unable to kill K562 even at high effector:target (E:T) ratios, they released large amounts of IL-8 also at low E:T ratios, a scenario compatible with dNK trophoblast cells interaction occurring within decidual tissues.
Background Monocyte activation, macrophage infiltration, vascular oxidative stress and matrix proteolysis are inflammatory key steps contributing to abdominal aortic aneurysm (AAA) development. A ...phenotypical and functional heterogeneity is recognizable in monocytes by the differential expression of surface molecules: CD62L− subset corresponds to activated monocytes, while CD143/ACE surface expression increases during their differentiation into macrophages. In this work, Resveratrol, which is an antioxidant polyphenol with vasoprotective properties, has been evaluated for its potential to limit aneurysm development and monocyte-dependent inflammatory response in a model of elastase-induced AAA. Methods Male Sprague-Dawley rats received Resveratrol (10 mg/kg/die) (Rsv group, n = 15) or vehicle (ethanol) alone (Et-OH group, n = 15) continuously from 7 d before until 14 d after the AAA induction with elastase; five littermates were used as untreated control group (Ctr group, n = 5). At the end of treatment, CD143 and CD62L monocyte expression was analyzed by flow cytometry, serum antioxidant capacity was evaluated using the TRAP method and circulating TNFα, and MMP-9 were measured with ELISA and gel zymography, respectively. Aortas were subjected to histology and immunohistochemistry for morphological analysis, macrophage infiltration, and MMP-9, TNFα, and VEGF expression. Results Resveratrol counteracted the CD62L-monocyte subset expansion, CD143 monocyte expression, and circulating levels of MMP-9 activity and TNFα associated to AAA induction. Similarly, treatment with Resveratrol significantly attenuated AAA expansion, vessel wall macrophage infiltration and MMP-9, VEGF, and TNFα expression, compared with AAA from Et-OH group. Conclusions Resveratrol limited the monocyte-dependent inflammatory response, macrophage differentiation and aortic lumen enlargement in elastase-induced AAA. These data suggest that Resveratrol might be tested in selected patients with small AAA to modulate the early systemic and local inflammatory response associated to AAA progression.
Mutations in the WWOX gene cause a broad range of ultra-rare neurodevelopmental and brain degenerative disorders, associated with a high likelihood of premature death in animal models as well as in ...humans. The encoded Wwox protein is a WW domain-containing oxidoreductase that participates in crucial biological processes including tumour suppression, cell growth/differentiation and regulation of steroid metabolism, while its role in neural development is less understood. We analyzed the exomes of a family affected with multiple pre- and postnatal anomalies, including cerebellar vermis hypoplasia, severe neurodevelopmental impairment and refractory epilepsy, and identified a segregating homozygous WWOX mutation leading to a premature stop codon. Abnormal cerebral cortex development due to a defective architecture of granular and molecular cell layers was found in the developing brain of a WWOX-deficient human foetus from this family. A similar disorganization of cortical layers was identified in lde/lde rats (carrying a homozygous truncating mutation which disrupts the active C-terminal domain) investigated at perinatal stages. Transcriptomic analyses of Wwox-depleted human neural progenitor cells showed an impaired expression of a number of neuronal migration-related genes encoding for tubulins, kinesins and associated proteins. These findings indicate that loss of Wwox may affect different cytoskeleton components and alter prenatal cortical development, highlighting a regulatory role of the WWOX gene in neural progenitor cells and migrating neurons across different species.
This prospective study aims to evaluate the efficacy of multislice computed tomography combined with colon distension by water enteroclysis (MSCTe) in determining the presence and depth of bowel ...endometriotic lesions. Ninety-eight women with symptoms suggestive of colorectal endometriosis underwent MSCTe; locations, number of nodule/s, size of the nodule/s and depth of bowel wall infiltration were determined. Independently from the findings of MSCTe, all women underwent laparoscopy. MSCTe findings were compared with surgical and histological results. Abnormal findings suggestive of bowel endometriotic nodules were detected by MSCTe in 75 of the 76 patients with bowel endometriosis. MSCTe identified 110 (94.8%) of the 116 bowel endometriotic nodules removed at surgery; 6 nodules missed at MSCTe were located on the rectum. MSCTe correctly determined the degree of infiltration of the bowel wall in all of the 34 serosal bowel nodules identified at MSCTe. In six nodules reaching the submucosa, the depth of infiltration was underestimated by MSCTe. MSCTe had a sensitivity of 98.7%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 95.7% in identifying women with bowel endometriosis. MSCTe is effective in determining the presence and depth of bowel endometriotic lesions.
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