ASO Author Reflections: Recurrence Following Post-neoadjuvant Pancreatectomy: How Can We Do Better?

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Implication of Cellular Senescence in Osteoarthritis: A Study on Equine Synovial Fluid Mesenchymal Stromal Cells

: Osteoarthritis (OA) is described as a chronic degenerative disease characterized by the loss of articular cartilage. Senescence is a natural cellular response to stressors. Beneficial in certain conditions, the accumulation of senescent cells has been implicated in the pathophysiology of many diseases associated with aging. Recently, it has been demonstrated that mesenchymal stem/stromal cells isolated from OA patients contain many senescent cells that inhibit cartilage regeneration. However, the link between cellular senescence in MSCs and OA progression is still debated. In this study, we aim to characterize and compare synovial fluid MSCs (sf-MSCs), isolated from OA joints, with healthy sf-MSCs, investigating the senescence hallmarks and how this state could affect cartilage repair. Sf-MSCs were isolated from tibiotarsal joints of healthy and diseased horses with an established diagnosis of OA with an age ranging from 8 to 14 years. Cells were cultured in vitro and characterized for cell proliferation assay, cell cycle analysis, ROS detection assay, ultrastructure analysis, and the expression of senescent markers. To evaluate the influence of senescence on chondrogenic differentiation, OA sf-MSCs were stimulated in vitro for up to 21 days with chondrogenic factors, and the expression of chondrogenic markers was compared with healthy sf-MSCs. Our findings demonstrated the presence of senescent sf-MSCs in OA joints with impaired chondrogenic differentiation abilities, which could have a potential influence on OA progression

The hypoxia-mimetic agent cobalt chloride differently affects human mesenchymal stem cells in their chondrogenic potential

Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1\ue1), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 \uecM. Cell viability, HIF-1\ue1 protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from 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

The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1α), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 μM. Cell viability, HIF-1α protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from 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

A synergic effect of alginate and hypoxia-inducing ions on chondrogenic differentiation in adipose derived mesenchymal stem cells

Cartilage is a highly organized tissue with complex biomechanical properties, but since it has a poor intrinsic capacity of self-healing, injuries at this site usually lead to several problems, often ending in disabling symptoms. Although, different approach- es have been proposed, even now cartilage repair represents a great challenge for orthopaedic surgeons (1, 2). One of the promising approach is given from tissue engineering, employing the combination of biomaterials and cell therapy to develop new therapeutic strategies. In this paper, we describe the behaviour of human adipose derived mesenchymal stem cells encapsulated into Ca/Co alginate beads as potential chondrogenic inducing biomaterial tacking advance on the synergy between alginate matrix and Co+2 ions without employing other expensive growth factors such as TGFbs or BMPs. Cells were cultured up to 3 weeks into alginate beads at different Ca/Co ratio, Calcein/Ethidium assay was performed to evaluate cell viability, light, and transmis- sion electron microscopy were carried out to check the cells behaviour. The expression of chondrogenic markers such as sox9, collagen type II, and versican was investigated by Real Time PCR. The expression of hif1mRNA was investigated to check the capability of Co+2 ions to induce a chemical hypoxia. Results showed an high cell viability at high Ca/Co ratio value of alginate beads. Real Time PCR data reveal a different cells behaviour on chondrogenic marker expression. In conclusion, the synergic effect of alginate and Co+2 ions can represent a valid strategy for chondrogenic differentiation of stem cells

A synergic effect of alginate and hypoxia-inducing ions on chondrogenic differentiation in adipose derived mesenchymal stem cells

Cartilage is a highly organized tissue with complex biomechanical properties, but since it has a poor intrinsic capacity of self-healing, injuries at this site usually lead to several problems, often ending in disabling symptoms. Although, different approach- es have been proposed, even now cartilage repair represents a great challenge for orthopaedic surgeons (1, 2). One of the promising approach is given from tissue engineering, employing the combination of biomaterials and cell therapy to develop new therapeutic strategies. In this paper, we describe the behaviour of human adipose derived mesenchymal stem cells encapsulated into Ca/Co alginate beads as potential chondrogenic inducing biomaterial tacking advance on the synergy between alginate matrix and Co+2 ions without employing other expensive growth factors such as TGFbs or BMPs. Cells were cultured up to 3 weeks into alginate beads at different Ca/Co ratio, Calcein/Ethidium assay was performed to evaluate cell viability, light, and transmis- sion electron microscopy were carried out to check the cells behaviour. The expression of chondrogenic markers such as sox9, collagen type II, and versican was investigated by Real Time PCR. The expression of hif1mRNA was investigated to check the capability of Co+2 ions to induce a chemical hypoxia. Results showed an high cell viability at high Ca/Co ratio value of alginate beads. Real Time PCR data reveal a different cells behaviour on chondrogenic marker expression. In conclusion, the synergic effect of alginate and Co+2 ions can represent a valid strategy for chondrogenic differentiation of stem cells

Interfering with the high-affinity interaction between wheat amylase trypsin inhibitor CM3 and toll-like receptor 4: in silico and biosensor-based studies

Wheat amylase/trypsin bi-functional inhibitors (ATIs) are protein stimulators of innate immune response, with a recently established role in promoting both gastrointestinal and extra-gastrointestinal inflammatory syndromes. These proteins have been reported to trigger downstream intestinal inflammation upon activation of TLR4, a member of the Toll-like family of proteins that activates signalling pathways and induces the expression of immune and pro-inflammatory genes. In this study, we demonstrated the ability of ATI to directly interact with TLR4 with nanomolar affinity, and we kinetically and structurally characterized the interaction between these macromolecules by means of a concerted approach based on surface plasmon resonance binding analyses and computational studies. On the strength of these results, we designed an oligopeptide capable of preventing the formation of the complex between ATI and the receptor

From In Silico Simulation between TGF-β Receptors and Quercetin to Clinical Insight of a Medical Device Containing Allium cepa: Its Efficacy and Tolerability on Post-Surgical Scars

1) objective: keloid and hypertrophic scars are a challenge in clinical management, causing functional and psychological discomfort. these pathological scars are caused by a proliferation of dermal tissue following skin injury. the TGF-beta/smad signal pathway in the fibroblasts and myofibroblasts is involved in the scarring process of skin fibrosis. today, multiple therapeutic strategies that target the TGF-beta/smad signal pathway are evaluated to attenuate aberrant skin scars that are sometimes difficult to manage. we performed a head-to-head, randomized controlled trial evaluating the appearance of the post-surgical scars of 64 subjects after two times daily topical application to compare the effect of a class I pullulan-based medical device containing allium cepa extract 5% and hyaluronic acid 5% gel versus a class I medical device silicone gel on new post-surgical wounds. (2) methods: objective scar assessment using the vancouver scar scale (VSS), POSAS, and other scales were performed after 4, 8, and 12 weeks of treatment and statistical analyses were performed. the trial was registered in clinical trials.gov ( NCT05412745). In parallel, molecular docking simulations have been performed to investigate the role of allium cepa in TGF-beta/smad signal pathway. (3) results: we showed that VSS, POSAS scale, itching, and redness reduced significantly at week 4 and 8 in the subjects using devices containing allium cepa and HA. no statistically significant differences in evaluated scores were noted at 12 weeks of treatment. safety was also evaluated by gathering adverse events related to the application of the gel. subject compliance and safety with the assigned gel were similar between the two study groups. molecular docking simulations have shown how allium cepa could inhibit fibroblasts proliferation and contraction via TGF- beta/smad signal pathway. (4) conclusions: the topical application of a pullulan-based medical device containing allium cepa and HA showed a clear reduction in the local inflammation, which might lead to a reduced probability of developing hypertrophic scars or keloids

Rugosidad de resinas Filtek Z-250 frente a la acción de dos tipos de agentes blanqueadores, estudio in vitro, Tacna 2022

Objetivo: Demostrar el efecto de dos agentes blanqueadores sobre la rugosidad superficial de las resinas compuestas Filtek z-250, Tacna, 2022. Metodología: científico, aplicada, explicativo, experimental prospectivo longitudinal. Resultados: rugosidad.superficial final de la.resina Filtek z-250 expuesto al peróxido de carbamida al 22 % contó con una media de 0,523 μm, varianza de 0,126 μm, desviación estándar de 0,355 μm, valor mínimo de 0,222 μm y máxima de 1,390 μm. Rugosidad superficial final de la resina Filtek z-250 expuesto a peróxido de hidrógeno al 35 % contó con una media de 0,496 μm, varianza de 0,078 μm, desviación estándar de 0,279 μm, valor mínimo de 0,166 μm y máxima de 0,902 μm. Conclusión: no existen diferencias en la rugosidad.superficial de la resina compuesta Filtek z-250 al utilizar peróxido de carbamida al 22 % y peróxido de hidrógeno al 35 %, Tacna, 2022 (valor p = 0,852)

Biosynthesis and physico-chemical characterization of high performing peptide hydrogels@graphene oxide composites

: Hydrogels based on short peptide molecules are interesting biomaterials with wide present and prospective use in biotechnologies. A well-known possible drawback of these materials can be their limited mechanical performance. In order to overcome this problem, we prepared Fmoc-Phe3self-assembling peptides by a biocatalytic approach, and we reinforced the hydrogel with graphene oxide nanosheets. The formulation here proposed confers to the hydrogel additional physicochemical properties without hampering peptide self-assembly. We investigated in depth the effect of nanocarbon morphology on hydrogel properties (i.e. morphology, viscoelastic properties, stiffness, resistance to an applied stress). In view of further developments towards possible clinical applications, we have preliminarily tested the biocompatibility of the composites. Our results showed that the innovative hydrogel composite formulation based on FmocPhe3 and GO is a biomaterial with improved mechanical properties that appears suitable for the development of biotechnological applications