scholarly journals The role of the Notch pathway in healthy and osteoarthritic articular cartilage: from experimental models to ex vivo studies

2011 ◽  
Vol 13 (2) ◽  
pp. 208 ◽  
Author(s):  
Nadia Sassi ◽  
Lilia Laadhar ◽  
Maha Driss ◽  
Meriam Kallel-Sellami ◽  
Slaheddine Sellami ◽  
...  
F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1197
Author(s):  
Morgan K. Groover ◽  
Jillian M. Richmond

Chemokines play important roles in homeostasis and inflammatory processes. While their roles in leukocyte recruitment are well-appreciated, chemokines play additional roles in the body, including mediating or regulating angiogenesis, tumor metastasis and wound healing. In this opinion article, we focus on the role of CXCR3 and its ligands in fibrotic processes. We emphasize differences of the effects of each ligand, CXCL9, CXCL10 and CXCL11, on fibroblasts in different tissues of the body. We include discussions of differences in signaling pathways that may account for protective or pro-fibrotic effects of each ligand in different experimental models and ex vivo analysis of human tissues. Our goal is to highlight potential reasons why there are disparate findings in different models, and to suggest ways in which this chemokine axis could be manipulated for the treatment of fibrosis.


Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1660
Author(s):  
Jorge Yaulema ◽  
Jose Bon ◽  
M. Carmen Gómez-Collado ◽  
Juan José Pérez ◽  
Enrique Berjano ◽  
...  

Radiofrequency (RF)-based monopolar (MM) and bipolar mode (BM) applicators are used to thermally create coagulation zones (CZs) in biological tissues with the aim of destroying surface tumors and minimizing blood losses in surgical resection. Both modes have disadvantages as regards safely and in obtaining a sufficiently deep coagulation zone (CZ). In this study, we compared both modes versus a switching monopolar mode (SMM) in which the role of the active electrode changes intermittently between the two electrodes of the applicator. In terms of clinical impact, the three modes can easily be selected by the surgeon according to the surgical maneuver. We used computational and experimental models to study the feasibility of working in MM, BM, and SMM and to compare their CZ characteristics. We focused exclusively on BM and SMM, since MM only creates small coagulation zones in the area between the electrodes. The results showed that SMM produces the deepest CZ between both electrodes (33% more than BM) and SMM did not stop the generator when an electrode lost contact with the tissue, as occurred in BM. Our findings suggest that the selective use of SMM and BM with a bipolar applicator offers greater advantages than using each type alone.


Author(s):  
Konstantinos Toutouzas ◽  
Eleftherios Tsiamis ◽  
Maria Drakopoulou ◽  
Christodoulos Stefanadis

This chapter completes the description of the Thermography within this publication. While the previous chapter of this section dealt with principles of data acquisition, this chapter provides a detailed description of the research and clinical utility of thermography. Separate sections are devoted to the ex vivo thermography studies, to the role of thermography in experimental models and finally to the contribution of thermography in clinical studies.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3727
Author(s):  
Dafne Jacome Sanz ◽  
Juuli Raivola ◽  
Hanna Karvonen ◽  
Mariliina Arjama ◽  
Harlan Barker ◽  
...  

Background: Dysregulated lipid metabolism is emerging as a hallmark in several malignancies, including ovarian cancer (OC). Specifically, metastatic OC is highly dependent on lipid-rich omentum. We aimed to investigate the therapeutic value of targeting lipid metabolism in OC. For this purpose, we studied the role of PCSK9, a cholesterol-regulating enzyme, in OC cell survival and its downstream signaling. We also investigated the cytotoxic efficacy of a small library of metabolic (n = 11) and mTOR (n = 10) inhibitors using OC cell lines (n = 8) and ex vivo patient-derived cell cultures (PDCs, n = 5) to identify clinically suitable drug vulnerabilities. Targeting PCSK9 expression with siRNA or PCSK9 specific inhibitor (PF-06446846) impaired OC cell survival. In addition, overexpression of PCSK9 induced robust AKT phosphorylation along with increased expression of ERK1/2 and MEK1/2, suggesting a pro-survival role of PCSK9 in OC cells. Moreover, our drug testing revealed marked differences in cytotoxic responses to drugs targeting metabolic pathways of high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC) PDCs. Our results show that targeting PCSK9 expression could impair OC cell survival, which warrants further investigation to address the dependency of this cancer on lipogenesis and omental metastasis. Moreover, the differences in metabolic gene expression and drug responses of OC PDCs indicate the existence of a metabolic heterogeneity within OC subtypes, which should be further explored for therapeutic improvements.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 782
Author(s):  
Sona Ciernikova ◽  
Michal Mego ◽  
Michal Chovanec

Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Due to this fact, long-term cancer survivors often suffer from late effects, including cognitive impairment and cardiovascular toxicity. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem, leading to gastrointestinal toxicity. Animal models and clinical studies have revealed the associations between intestinal dysbiosis and depression, anxiety, pain, impaired cognitive functions, and cardiovascular diseases. Recently, a possible link between chemotherapy-induced gut microbiota disruption and late effects in cancer survivors has been proposed. In this review, we summarize the current understanding of preclinical and clinical findings regarding the emerging role of the microbiome and the microbiota–gut–brain axis in chemotherapy-related late effects affecting the central nervous system (CNS) and heart functions. Importantly, we provide an overview of clinical trials evaluating the relationship between the gut microbiome and cancer survivorship. Moreover, the beneficial effects of probiotics in experimental models and non-cancer patients with neurocognitive disorders and cardiovascular diseases as well as several studies on microbiota modulations via probiotics or fecal microbiota transplantation in cancer patients are discussed.


Author(s):  
Lina Y Alkaissi ◽  
Martin E Winberg ◽  
Stéphanie DS Heil ◽  
Staffan Haapaniemi ◽  
Pär Myrelid ◽  
...  

Abstract Background The first visible signs of Crohn’s disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human α-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.


Sign in / Sign up

Export Citation Format

Share Document