The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and ...HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2−. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.
: Oral disorders, frequently observed in patients with primary Sjögren's syndrome, can profoundly affect patients' daily lives and well-being, as oral health represents a fundamental part of general ...health. Saliva plays an essential part in maintaining and protecting oral health, so the decrease in its quantity and quality leads to chronic oral discomfort alongside a broad spectrum of problems. The objective of the present study was to evaluate the oral health of patients with primary Sjögren's syndrome and establish its effect on the different domains of their oral health-related quality of life (OHRQoL).
: The research was designed as an observational case-control study with prospective data collection. Eighty patients, divided into two groups based on their oral status, participated in the study. All subjects underwent a complete oral examination. The OHRQoL was assessed using the Oral Health Impact Profile-14 (OHIP-14).
: The most prevalent oral manifestation was exfoliative cheilitis, while 30% of subjects complained of chewing and swallowing difficulties. The OHIP-14 summary score was significantly higher in the patients with oral lesions (26.0 (5.0) vs. 17.0 (4.0), respectively;
< 0.001). Oral manifestations, systemic involvement, medication, and periodontal indexes were significantly associated with OHIP-14 scores.
: Patients with oral alterations had a substantially decreased OHRQoL. These findings emphasize the importance of oral diseases for patients' well-being. Therefore, it is essential for dentists to be included in the multidisciplinary teams managing primary Sjögren's syndrome, as improving patients' oral status would lead to better oral health and enhanced OHRQoL.
Indoleamine 2,3-dioxygenase (IDO) has the most important role in modulation of tryptophan-dependent effects in the gastrointestinal tract, including modulation of intestinal immune response. An ...increased IDO activity maintains immune tolerance and attenuates ongoing inflammation but allows immune escape and uncontrolled growth of gastrointestinal tumors. Accordingly, IDO represents a novel therapeutic target for the treatment of inflammatory and malignant diseases of the gastrointestinal tract. In this review article, we summarize current knowledge about molecular and cellular mechanisms that are involved in IDO-dependent effects. We provide a brief outline of experimental and clinical studies that increased our understanding of how enhanced IDO activity: controls host–microbiota interactions in the gut; regulates detrimental immune response in inflammatory disorders of the gastrointestinal system; and allows immune escape and uncontrolled growth of gastrointestinal tumors. Additionally, we present future perspectives regarding modulation of IDO activity in the gut as possible new therapeutic approaches for the treatment of inflammatory and malignant diseases of the gastrointestinal system.
Cisplatin therapy is often accompanied by neurotoxicity manifestation, and since the prefrontal cortex is strongly involved in emotion regulation, the aim of this study was to analyze the alterations ...in the oxidative and apoptotic status of this brain region, with its behavioral impact in rats, following cisplatin administration, with or without N-acetylcysteine supplementation. Thirty-two male Wistar albino rats were randomly divided into four equal experimental groups: control, cisplatin group (single dose of 7.5 mg/kg, intraperitoneally (i.p.), on the fifth day), N-acetylcysteine group (500 mg/kg i.p., on the first and the fifth day), cisplatin + N-acetylcysteine group. Behavioral testing was performed in the tail suspension test. Oxidative stress and apoptotic markers were determined in the prefrontal cortex tissue samples. Cisplatin administration increased lipid peroxidation and decreased the activity of antioxidant enzymes in the prefrontal cortex. Also, cisplatin induced increase in Bax and decrease in Bcl-2 relative gene expression. Simultaneous application of N-acetylcysteine diminished cisplatin-induced alterations in oxidative stress and apoptotic markers. The results obtained in the tail suspension test that nominally resembles antidepressant action of cisplatin (attenuated by N-acetylcysteine), should be attributed to strong motor expression of anxiogenic response to cisplatin (also reversed by N-acetylcysteine). The antioxidant supplementation with NAC diminished cisplatin-induced oxidative damage and pro-apoptotic action in the prefrontal cortex, and significantly influenced specific behavioral alterations.
Ethical and Safety Issues of Stem Cell-Based Therapy Volarevic, Vladislav; Markovic, Bojana Simovic; Gazdic, Marina ...
International journal of medical sciences,
2018, Letnik:
15, Številka:
1
Journal Article
Odprti dostop
Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. ...However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.
The aim of our study was to evaluate the effects of chronic administration of nandrolone-decanoate (ND) or testosterone-enanthate (TE) in supraphysiological doses and a prolonged swimming protocol, ...alone and in combination with ND or TE, on anxiety-like behavior in rats. We investigated the immunohistochemical alterations of the hippocampal neuropeptide Y (NPY) and melanocortin 4 receptor (MC4R) neurons, as a possible underlying mechanism in a modulation of anxiety-like behavior in rats. Both applied anabolic androgenic steroids (AASs) induced anxiogenic effect accompanied with decreased serum and hippocampal NPY. The exercise-induced anxiolytic effect was associated with increased hippocampal NPY expression. ND and TE increased the number of MC4R, while the swimming protocol was followed by the reduction of MC4R in the CA1 region of the hippocampus. However, NPY/MC4R ratio in hippocampus was lowered by AASs and elevated by exercise in all hippocampal regions. An augmentation of this ratio strongly and positively correlated to increased time in open arms of elevated plus maze, in the context that indicates anxiolytic effect. Our findings support the conclusion that alterations in both hippocampal NPY and MC4R expression are involved in anxiety level changes in rats, while their quantitative relationship (NPY/MC4R ratio) is even more valuable in the estimation of anxiety regulation than individual alterations for both NPY and MC4R expression in the hippocampus.
The aim of this study was to evaluate the impact of the nasopalatine canal (NPC) shape and its morphometric characteristics on expected teeth movement by assessing the distance to maxillary central ...incisors (MCIs) according to NPC type. The retrospective study was performed on 133 CBCT images. The following parameters were obtained: the antero-posterior diameter (A-P) of the nasal foramen (NF), canal length, A-P and mediolateral diameter (M-L) of the incisive foramen (IF), and the distance between NPC and MCIs. With the exception of being hourglass-shaped, each NPC shape showed specific impacts of NPC shape on the relationship between NPC diameters at different sections and distances to MCIs. In banana-shaped NPC, a significant correlation was observed for A-P NF diameter, while in cylindrical-shaped NPC, a significant correlation was observed for NPC length. The increase in M-L IF, A-P IF, A-P NF, and NPC length in funnel-shaped NPC may be a risk factor for interventions that could result in teeth movement. According to the results, it seems that the proposed methodological approach for analysis of CBCT slices in the anterior maxilla may offer detailed information that could be an additional tool in planning the procedures that result in expected teeth movement.
Background and Objectives: Thermal skin injuries are a prevalent cause of skin damage, potentially leading to severe morbidity and significant mortality. In this study, we intended to estimate the ...effects of HBO (hyperbaric oxygen treatment) and antioxidant supplementation with Filipendula ulmaria extract, individually and simultaneously, in the treatment of thermal skin injuries. Materials and Methods: As a thermal skin injury experimental model, we used two-month-old male Wistar albino rats. Thermal injuries were made with a solid aluminium bar at a constant temperature of 75 °C for 15 s. Hyperbaric oxygen treatment was performed in a specially constructed hyperbaric chamber for rats (HYB-C 300) for seven consecutive days (100% O2 at 2.5 ATA for 60 min). Antioxidant supplementation was performed with oral administration of Filipendula ulmaria extract dissolved in tap water to reach a final concentration of 100 mg/kg b.w. for seven consecutive days. Results: Simultaneous administration of hyperbaric oxygen therapy and antioxidant supplementation with Filipendula ulmaria extract significantly ameliorated the macroscopic and histopathological characteristics of the wound area and healing. Also, this therapeutic approach decreased the local expression of genes for proinflammatory mediators and increased the expression of the μ-opioid receptor and the MT1 and MT2 receptors in the wound area and spinal cord, with a consequent increase in reaction times in behavioural testing. Conclusions: In conclusion, the presented results of our study allow evidence for the advantages of the simultaneous employment of HBO and antioxidant supplementation in the treatment of thermal skin injuries, with special reference to the attenuation of painful sensations accompanied by this type of trauma.
The aim of this study was to use cone-beam computed tomography (CBCT) to evaluate the morphometric properties of the interradicular septum (IRS) in the maxillary molar region that may be indicative ...for prosthetic-driven implant placement. Following the repetitive algorithm based on the visual identification of IRS shapes, we described the following IRS shapes: arrow, boat, drop, and palatal and buccal convergence. The incidence of IRS shapes showed significant differences for the first and second maxillary molars (the highest frequency for the arrow shape, and the lowest for the drop shape) with no significant difference between the molars. The most prominent width indicative for implant placement was observed in the palatal convergence shape, whereas the height criteria were the most satisfying in the buccal convergence-shaped IRS for both molars. Apart from the parameters in the coronal view, the image analysis in the axial view revealed that IRS surface area, required for the implant placement, was the most prominent in the palatal convergence shape for the first, and boat shape for the second molars. Our results showed the benefits of CBCT diagnostics in posterior maxilla morphometric analysis. IRS shape classification may be helpful in achieving more rapid and accurate planning for interventions in this region.
Type 1 diabetes is an autoimmune disease caused by the immune-mediated destruction of pancreatic β-cells. Prevention of type 1 diabetes requires early intervention in the autoimmune process against ...beta-cells of the pancreatic islets of Langerhans, which is believed to result from disordered immunoregulation. CD4
Foxp3
regulatory T cells (Tregs) participate as one of the most important cell types in limiting the autoimmune process. The aim of this study was to investigate the effect of exogenous IL-33 in multiple low dose streptozotocin (MLD-STZ) induced diabetes and to delineate its role in the induction of protective Tregs in an autoimmune attack. C57BL/6 mice were treated i. p. with five doses of 40 mg/kg STZ and 0.4 μg rIL-33 four times, starting from day 0, 6, or 12 every second day from the day of disease induction. 16 weeks old NOD mice were treated with 6 injections of 0.4 μg/mouse IL-33 (every second day). Glycemia and glycosuria were measured and histological parameters in pancreatic islets were evaluated at the end of experiments. Cellular make up of the pancreatic lymph nodes and islets were evaluated by flow cytometry. IL-33 given simultaneously with the application of STZ completely prevented the development of hyperglycemia, glycosuria and profoundly attenuated mononuclear cell infiltration. IL-33 treatment was accompanied by higher number of IL-13 and IL-5 producing CD4
T cells and increased presence of ST2
Foxp3
regulatory T cells in pancreatic lymph nodes and islets. Elimination of Tregs abrogated protective effect of IL-33. We provide evidence that exogenous IL-33 completely prevents the development of T cell mediated inflammation in pancreatic islets and consecutive development of diabetes in C57BL/6 mice by facilitating the induction Treg cells. To extend this finding for possible relevance in spontaneous diabetes, we showed that IL-33 attenuate insulitis in prediabetic NOD mice.
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