Calcium Deregulation in Neurodegeneration and Neuroinflammation in Parkinson's Disease: Role of Calcium-Storing Organelles and Sodium-Calcium Exchanger.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that lacks effective treatment strategies to halt or delay its progression. The homeostasis of Ca ions is crucial for ensuring optimal cellular functions and survival, especially for neuronal cells. In the context of PD, the systems regulating cellular Ca are compromised, leading to Ca-dependent synaptic dysfunction, impaired neuronal plasticity, and ultimately, neuronal loss.

ER-mitochondria association negatively affects wound healing by regulating NLRP3 activation.

Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative agent of acute bacterial skin and skin-structure infections (ABSSSI), one of the major challenges to the health system worldwide. Although the use of antibiotics as the first line of intervention for MRSA-infected wounds is recommended, important side effects could occur, including cytotoxicity or immune dysregulation, thus affecting the repair process. Here, we show that the oxazolidinone antibiotic linezolid (LZD) impairs wound healing by aberrantly increasing interleukin 1 β (IL-1β) production in keratinocytes.

Microplastics and Nanoplastics in Atheromas and Cardiovascular Events.

Background: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking.

Methods: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease.

Potential of acetaminophen on the sublingual microcirculation and peripheral tissue perfusion of febrile septic patients: prospective observational study.

Background: Acetaminophen (ACT) has been studied in septic patients with detectable plasmatic levels of cell-free hemoglobin (Hb), where it demonstrated to inhibit the hemoprotein-mediated lipid peroxidation and oxidative injury, with a potential of beneficial effect on the endothelium. On the basis of this background, the aim of this study was to evaluate the sublingual microcirculation and the peripheral tissue perfusion before-and-after administration of ACT on clinical judgment in a cohort of febrile septic and septic shock patients.

Methods: Prospective observational study.

Senescent Endothelial Cells Sustain Their Senescence-Associated Secretory Phenotype (SASP) through Enhanced Fatty Acid Oxidation.

Cellular senescence is closely linked to endothelial dysfunction, a key factor in age-related vascular diseases. Senescent endothelial cells exhibit a proinflammatory phenotype known as SASP, leading to chronic inflammation (inflammaging) and vascular impairments. Albeit in a state of permanent growth arrest, senescent cells paradoxically display a high metabolic activity.

MiR-422a promotes adipogenesis via MeCP2 downregulation in human bone marrow mesenchymal stem cells.

Methyl-CpG binding protein 2 (MeCP2) is a ubiquitous transcriptional regulator. The study of this protein has been mainly focused on the central nervous system because alterations of its expression are associated with neurological disorders such as Rett syndrome. However, young patients with Rett syndrome also suffer from osteoporosis, suggesting a role of MeCP2 in the differentiation of human bone marrow mesenchymal stromal cells (hBMSCs), the precursors of osteoblasts and adipocytes.

The application of cancer stem cell model in malignant mesothelioma.

The high mortality rate of malignant pleural mesothelioma led to study the mechanisms for chemoresistance. The cancer stem cell (CSC) model has been proposed to explain chemoresistance. CSCs are characterized by self-renewal capacity, that is detected through tumor-initiating cell assays.

Force-feeding malignant mesothelioma stem-cell like with exosome-delivered miR-126 induces tumour cell killing.

Malignant pleural mesothelioma (MPM) is an aggressive tumour resistant to treatments. It has been postulated that cancer stem cells (CSCs) persist in tumours causing relapse after multimodality treatment. In the present study, a novel miRNA-based therapy approach is proposed.

Visceral fat inflammation and fat embolism are associated with lung's lipidic hyaline membranes in subjects with COVID-19.

Background: Preliminary data suggested that fat embolism could explain the importance of visceral obesity as a critical determinant of coronavirus disease-2019 (COVID-19).

Methods: We performed a comprehensive histomorphologic analysis of autoptic visceral adipose tissue (VAT), lungs and livers of 19 subjects with COVID-19 (COVID-19+), and 23 people without COVID-19 (controls). Human adipocytes (hMADS) infected with SARS-CoV-2 were also studied.

Identification of multinucleated cells in human kidney cortex: A way for tissue repairing?

The presence of multinucleated cells has never been demonstrated in renal tissue, although, polyploid cells were recently observed in the tubules of normal and pathological human kidney. Therefore, the aim of the present study is to identify and quantify, by electron microscopy, multinucleated cells in the cortical tissue of normal human kidney i.e.

Potential prognostic value of circulating inflamma-miR-146a-5p and miR-125a-5p in relapsing-remitting multiple sclerosis.

Background: Inflamma-miRs are a group of microRNAs involved in the regulation of innate and adaptive immune responses. Increasing evidence support the contribution of dysregulated inflamma-miRs in the pathogenesis of multiple sclerosis. The aim of this study was to evaluate the expression of selected inflamma-miRs, i.

Normal human macula densa morphology and cell turnover: A histological, ultrastructural, and immunohistochemical investigation.

The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of four samples of normal human renal tissue, two were embedded in resin to measure the longitudinal extension and examine the ultrastructure of the MD, the other two were embedded in paraffin to study apoptosis and cell proliferation. The MD is composed of a monolayer tissue about 40 μm long, which includes 35-40 cells arranged in overlapping rows.

SARS-CoV-2 identification in lungs, heart and kidney specimens by transmission and scanning electron microscopy.

From two COVID-19-related deaths, samples of lung, heart and kidney were collected and processed for Transmission and Scanning Electron Microscopy (TEM and SEM) with the aim of identifying the virus. Virions of SARS-CoV-2 were found in all tissues by TEM and SEM, corroborating the hypothesis that the virus enters the cells of different organs. This is the first report identifying SARS-CoV-2 in different human tissues by TEM and SEM.

Small extracellular vesicles deliver miR-21 and miR-217 as pro-senescence effectors to endothelial cells.

The role of epigenetics in endothelial cell senescence is a cutting-edge topic in ageing research. However, little is known of the relative contribution to pro-senescence signal propagation provided by microRNAs shuttled by extracellular vesicles (EVs) released from senescent cells. Analysis of microRNA and DNA methylation profiles in non-senescent (control) and senescent (SEN) human umbilical vein endothelial cells (HUVECs), and microRNA profiling of their cognate small EVs (sEVs) and large EVs demonstrated that SEN cells released a significantly greater sEV number than control cells.

Characterization of human costal cartilage: is it an adapt tissue as graft for articular cartilage repair?

Several techniques and different biological or artificial tissues have been proposed as graft to restore articular defects. However, among the numerous and heterogeneous procedures proposed over time, the current literature findings are not conclusive. The aim of the current study is to evaluate if human costal cartilage can be suitable as graft for restoring articular cartilage defects.

Postnatal development of the distribution of nitric oxide-producing neurons in the rat corpus callosum.

The postnatal development of nitric oxide (NO)-producing intracallosal neurons was studied in rats by nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry from postnatal day 0 (P0) to P30. NADPH-d-positive neurons (NADPH-d+) were detected already at P0, mainly in the rostral region of the corpus callosum (cc). Their location and the intensity of staining allowed them to be classified as type I NO-producing neurons.

Mesenchymal Stem Cells from Nucleus Pulposus and Neural Differentiation Potential: a Continuous Challenge.

Mesenchymal stem cells (MSCs) are well-characterized adult stem cells, recently isolated from human nucleus pulposus of degenerate and non-degenerate intervertebral disc. The attention to this source is linked to its embryologic history and cells may conserve a stronger aptitude to neuronal differentiation than other MSCs. Here, MSCs from nucleus pulposus (NP-MSCs) were successfully isolated and characterized for morphology, proliferation, and expression of selected genes.

The mitomiR/Bcl-2 axis affects mitochondrial function and autophagic vacuole formation in senescent endothelial cells.

During senescence, cells undergo distinctive biochemical and morphological changes and become dysfunctional. MiRNAs are involved in the senescence process and specific miRNAs can localize to mitochondria (mitomiRs). We hypothesized that part of the typical alterations of senescence may depends on mitomiRs deregulation.

Identification of miR-31-5p, miR-141-3p, miR-200c-3p, and GLT1 as human liver aging markers sensitive to donor-recipient age-mismatch in transplants.

To understand why livers from aged donors are successfully used for transplants, we looked for markers of liver aging in 71 biopsies from donors aged 12-92 years before transplants and in 11 biopsies after transplants with high donor-recipient age-mismatch. We also assessed liver function in 36 age-mismatched recipients. The major findings were the following: (i) miR-31-5p, miR-141-3p, and miR-200c-3p increased with age, as assessed by microRNAs (miRs) and mRNA transcript profiling in 12 biopsies and results were validated by RT-qPCR in a total of 58 biopsies; (ii) telomere length measured by qPCR in 45 samples showed a significant age-dependent shortage; (iii) a bioinformatic approach combining transcriptome and miRs data identified putative miRs targets, the most informative being GLT1, a glutamate transporter expressed in hepatocytes.

Stemness of T cells and the hematopoietic stem cells: fate, memory, niche, cytokines.

Stem cells are able to generate both cells that differentiate and cells that remain undifferentiated but potentially have the same developmental program. The prolonged duration of the protective immune memory for infectious diseases such as polio, small pox, and measles, suggested that memory T cells may have stem cell properties. Understanding the molecular basis for the life-long persistence of memory T cells may be useful to project targeted therapies for immune deficiencies and infectious diseases and to formulate vaccines.

Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation.

Clinical evidence demonstrates that ubiquinol-10, the reduced active form of coenzyme Q10 (CoQ10H₂), improves endothelial function through its antioxidant and probably its anti-inflammatory properties. We previously reported that a biomarker combination including miR-146a, its target protein IL-1 receptor-associated kinase (IRAK-1), and released interleukin (IL)-6, here collectively designated as MIRAKIL, indicates senescence-associated secretory phenotype (SASP) acquisition by primary human umbilical vein endothelial cells (HUVECs). We explore the ability of short- and long-term CoQ10H₂ supplementation to affect MIRAKIL in HUVECs, used as a model of vascular aging, during replicative senescence in the absence/presence of lipopolysaccharide (LPS), a proinflammatory stimulus.