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The article focuses on the potential use of quercetin, a flavonoid, as a senolytic molecule to counteract cellular senescence, particularly in human mesenchymal stromal/stem cells (MSCs), by activating autophagy and apoptosis in senescent cells.

The article focuses on the pro-differentiating effects of red photobiomodulation on skeletal myoblasts, with evidence suggesting its potential to enhance myoblast differentiation while maintaining myotube viability and size.

The article presents a study on equine synovial fluid mesenchymal stromal cells. Topics include information on implication of cellular senescence in osteoarthritis (OA); information on most common degenerative orthopedic disease in humans; and how cell therapy based on the application of mesenchymal stem/stromal cells (MSCs) and/or their secretome represents tool for OA treatment.

The article offers information on potential markers of skin wound vitality in forensic practice. Topics include information on NFkB and SIRT1 evaluation to discriminate antemortem lesions from postmortem damages in wounds; causal relationship between the cause of death and wounds; and how quantitative analysis of stained areas is done.

The discovery of opioid receptors expression in skin and their role in orchestrating the tissue repairing process, gave rise to questions regarding the potential effects of clinical morphine treatment in wound healing. Although short term treatment was reported to improve wounds regeneration, in vivo chronic administration was associated to immune cell recruitment delay and abnormal extracellular matrix deposition, impairing the physiological tissue healing progression and causing systemic fibrosis. Human mesenchymal stem cells (hMSCs) are a versatile class of multipotent adult stem cells. Their self-renew and multidirectional differentiation ability, combined with the release of immunoregulatory molecules, make them fundamental in restoring the damaged tissues. In this regard, opioid receptors expression was recently observed even in hMSCs[1], for which acute morphine exposition induced a significant functional characteristics decline[2]. However still little is known about its long-term effects. To determine how a prolonged treatment could impair their regenerative potential, we exposed hMSCs to increasing morphine concentrations respectively for nine and eighteen days, evaluating in particular the fibrogenic potential. Our results showed a time dependent cell viability decline and conditions compatible with a cellular senescent state. Ultrastructural analysis combined with beclin-1 (BECN1) and microtubuleassociated proteins 1A/1B light chain 3B (LC3) expression, after eighteen days of exposition, were indicative of increased autophagy, suggesting a correlation to an augmented detoxification activity. In addition, the enhanced transcription of type I collagen (COL1A1) together with the related genes involved in its regulation, namely: metalloproteinase-1 and -2 (MMP1, MMP2), transforming growth factor-beta1 (TGFB1) and tumour necrosis factor-alpha (TNFA), suggested the possibility that a prolonged morphine treatment might exert its fibrotic potential risk even involving the hMSCs. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is an age-related disease characterized by chronic inflammation, increased local activation of matrix-degrading proteinases, and weakening of the vascular wall. The main complication is the rupture of the abdominal aortic wall which leads to death. Nowadays, no pharmacological therapies are available and the understanding of the molecular mechanisms that lead to AAA onset and its development are poorly defined. Reparative abilities of vascular mesenchymal stromal cells (MSCs) have a key role in vascular remodeling. However, unbalanced activity of vascular MSCs support AAA pathogenesis. Cellular senescence is considered one of the main hallmarks of aging. It is classified as an irreversible growth arrest of the cell cycle which has beneficial roles in physiological conditions. However, the accumulation of senescent cells during aging has adverse consequences and it is believed to have a key role in the onset and development of several age-related diseases. The aim of this study was to demonstrate the presence of cellular senescence in vascular MSCs isolated from AAA segments (AAA - MSCs), responsible of an impaired vascular remodeling process. AAA-MSCs were assayed for their proliferative ability, cellular senescence markers, autophagy and in vitro vascular differentiation. The results were compared to MSCs isolated from healthy segment of the abdominal aorta of the same patients (h - MSCs). The results from AAA-MSCs clearly demonstrated a reduced proliferation ability, an increase of ROS levels, the positive expression of the senescent markers p21CIP1 and p16INK4a, a dysregulated autophagy and a strongly impaired ability in differentiating toward an endothelial phenotype. All these results indicate the presence of senescent vascular MSCs in the wall of AAA and strongly support the hypothesis that an accumulation of senescent vascular MSCs could have a pivotal role in the onset and development of AAA. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a common degenerative vascular disorder associated with sudden death due to aortic rupture. The current clinical approaches are to monitor aortic dimensions and to perform an open or endovascular surgical repair when the aortic diameter has attained sufficient expansion, condition that predispose to a high likelihood of aortic rupture. Although several studies have identified many potential mechanisms involved in AAA pathogenesis, a clear depth understanding is still lacking and further studies are needed to facilitate development of effective therapies. Recent discoveries have demonstrated the presence of mesenchymal stromal cells (MSCs) in human aortic layers. These cells possess high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic and mesenchymal cell progeny. Nevertheless, any defect of the proliferation and/or the differentiation process of vascular stem cells may determine the development of human vascular diseases. The aim of this study was to demonstrate the presence of senescent MSCs residing in human abdominal aortic wall, which could have a role in the AAA pathogenesis. MSCs isolated from healthy (HAA - MSCs) or aneurysmal abdominal aortas (AAA - MSCs) were characterized for their proliferation rate, ultrastructural morphology, senescence-associated β-galactosidase activity and differentiation properties. Results showed low growth potential, high senescence-associated β-galactosidase activity, an increased cell surface area, a reduced amount of autophagic and lysosome vesicles in AAA - MSCs compared to HAA - MSCs, thus indicated a senescent phenotype in AAA MSCs. Vascular wall-resident MSCs are deeply involved in the process of vascular remodelling, that is a dynamic and strictly regulated process of structural changes occurs as a result of a pathological vascular trigger. The presence of a senescent population of AAA MSCs in vascular wall could have implications in the genesis and progression of vascular diseases, such as AAA. [ABSTRACT FROM AUTHOR]

Human dentin is formed during the process of dentinogenesis synthesized by odontoblasts that, in addition to type I collagen, also secrete a number of non-collagenous proteins (NCPs) into extracellular matrix (ECM) during the process of dentinogenesis. The Small Integrin-Binding LIgand, N-linked Glycoprotein (SIBLING) family is one category of NCPs characteristic for dentin and bone including dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP), and osteopontin (OPN) [1]. Tertiary dentin is produced in reaction to external noxious stimulus/injury, such as trauma ordental caries and based on the type and extent of external stimuli or injuries, is further classified into reactionary dentin (RD) and reparative dentin (RepD). Aim this study was to compare pattern distribution and quantification of SIBILINGs in reparative and reactionary dentin matrix, in response to stimulus, vs human sound dentin. Ten carious human molars and ten sound human molars were selected for the study, demineralized, fixed, and processed for immunohistochemical approach to detect SIBILINGs. In particular specimens were submitted to an immunolabeling technique by using primary antibodies anti dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP), osteoponti (OPN), observed at light microscopy and then submitted to quantitative analysis. Results indicate that the region exposed to carious lesion, SIBILINGs formed a layer of reparative dentin bridge sealing cavity formed by carious lesion and pulp chamber. In response to the injury, the newly differentiated odontoblast-like cells makes adjustments to meet the challenges by altering the production of these dentinogenesis-related molecules, attempting to produce a hard barrier formation in a very rapid process. [ABSTRACT FROM AUTHOR]

Articular cartilage is an avascular tissue without innervations, characterized by low cell density and abundant extracellular matrix (ECM). These characteristics leave articular cartilage with very limited capacity of repair and regeneration. Multipotent stem/stromal cells (MSC) are considered promising for cartilage tissue engineering. Stem cells are resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Previous studies have reported that hypoxic conditions could enhance the chondrogenic differentiation of mesenchymal stem cells in the presence of an inductive medium. Cobalt chloride (CoCl2) imitates hypoxia in vitro by preventing hypoxiainducible factor-alpha (HIF-a) from being destroyed by oxygen. However, the longterm hypoxic culture of stem cells is difficult and requires special attention to avoid cell death due to cobalt treatment. In this study we investigated if CoCl2 affected MSCs isolated from dental pulp, umbilical cord and adipose tissue in their potential to differentiate toward the chondrogenic phenotype. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 uM. Cell proliferation, mRNA expression of stem-cell marker and chondrogenic associated genes were analyzed by RT-PCR and Real-time PCR. The results showed that the CoCl2 supplementation had no effect on the proliferation of all the three type of cells analyzed, while the up-regulation of chondrogenic markers such as aggrecan, sox9, and type II collagen, was dependent on the cellular source. This study shows that hypoxia induced by CoCl2 treatment can differently influence the behavior of MSCs of different sources in their chondrogenic potential. These findings should be taken into consideration in the treatment of cartilage repair and regeneration based on stem cell therapies. [ABSTRACT FROM AUTHOR]

The estimation of the post-mortem interval (PMI) is a critical step in forensic medicine and remains one of the most challenging variables to determine. In general, the numerous methods currently used in estimating post-mortem interval yield to large post-mortem windows, are influenced by several factors and sometime contradict each other. With the aim to obtain a much more accurate determination of the post-mortem interval we combined morphological ultrastructural and immunoistochemical analyses to reach a more detailed knowledge on tissue organization and degradation after death. Samples of gingival tissues obtained from 20 cadavers at different post-mortem intervals were processed for transmission electron microscopy to evaluate ultrastructural modifications in the epithelium and connective tissue. Gingival cells and the extracellular matrix of gingival tissues have been observed by a transmission electron microscopy (TEM) in combination with the evaluation of potential post-mortem biochemical markers, with the final goal to find a tight correlation between the ultrastructural modifications, the biomarker expression and the time of death. All the samples were also immunostained with anti-hypoxia-induced factor 1-α (HIF1-α) antibody, a transcription factor expressed in response to hypoxia, in order to evaluate the expression of HIF1-α, and to establish a correlation between the protein presence and the time of death. Results showed nuclear chromatin changes and cytoplasmic vacuolization in both epithelial and connective tissues and a different pattern of expression of HIF1alpha protein that correlate to the time of death. In conclusion, our preliminary findings suggest that ultrastructural investigations in combination with immunohistochemistry techniques in gingival specimens may represent a new tool to accurately and systematically estimate post-mortem interval. [ABSTRACT FROM AUTHOR]