Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity

Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity to regenerate renal tubule epithelia and repair renal function without fusing with resident tubular cells. The goal of the present project was to investigate the role of MSCs secreted cytokines on tubule cell viability and regeneration after a toxic insult, using a conditionally immortalized human proximal tubule epithelial cell (ciPTEC) line. Gentamicin was used to induce nephrotoxicity, and cell viability and migration were studied in absence and presence of human MSC-conditioned medium (hMSC-CM) i.e. medium containing soluble factors produced and secreted by MSCs. Exposure of ciPTEC to 0–3000 μg/ml gentamicin for 24 h caused a significant dose-dependent increase in cell death. We further demonstrated that the nephrotoxic effect of 2000 μg/ml gentamicin was recovered partially by exposing cells to hMSC-CM. Moreover, exposure of ciPTEC to gentamicin (1500–3000 μg/ml) for 7 days completely attenuated the migratory capacity of the cells. In addition, following scrape-wounding, cell migration of both untreated and gentamicin-exposed cells was increased in the presence of hMSC-CM, as compared to exposures to normal medium, indicating improved cell recovery. Our data suggest that cytokines secreted by MSCs stimulate renal tubule cell regeneration after nephrotoxicity.     

The effect of overbite and overjet on clinical parameters of periodontal disease: A case control study

AimTo investigate the association of overjet and overbite with clinical parameters of periodontal disease.Material and methodsThe study was performed in Riyadh, Saudi Arabia, from March 2017 to March 2018. 600 Saudi males aged 20–30 years old were included. Participants were divided into three groups (n: 200) depending on the presence of overjet (OJ) or overbite (OB) and its relationship with periodontal disease. Periodontal parameters were assessed clinically and radiographically. One-way analysis of variance was used to test for any significant differences between groups. Tukey’s post hoc comparison test was used to evaluate correlations among parameters.ResultsOJ exceeding 8 mm was correlated with debris, calculus, and periodontal scores on mandibular anterior teeth, especially on the lingual surfaces.Both OJ and OB groups showed significantly increased PD, compared to that of the control group in measurement at the lingual (P = 0.004, 0.003) and proximal (P = 0.002, 0.002) surfaces of the lower anterior teeth. Finally, the CEJ-AB was statistically significantly higher in the OB group compared to the OJ and control groups (P = 0.091, 0.008).ConclusionThe present study found a correlation between OJ and OB and periodontal disease, as measured using specific parameters. This indicates that periodontal treatment may be insufficient unless the overjet or overbite is corrected.     

Proximal Hamstring Tendinopathy: A Systematic Review of Interventions

BackgroundProximal hamstring tendinopathy affects athletic and non-athletic populations and is associated with longstanding buttock pain. The condition is common in track and field, long distance running and field-based sports. Management options need to be evaluated to direct appropriate clinical management.Purpose/HypothesisTo evaluate surgical and non-surgical interventions used in managing proximal hamstring tendinopathy.Study designSystematic reviewMethodsElectronic databases were searched to January 2019. Studies (all designs) investigating interventions for people with proximal hamstring tendinopathy were eligible. Outcomes included symptoms, physical function, quality of life and adverse events. Studies were screened for risk of bias. Reporting quality was assessed using the Cochrane Risk of Bias Tool (Randomized Controlled Trials [RCT]) and the Joanna Briggs Institute Checklist (Case Series). Effect sizes (Standard mean difference or Standard paired difference) of 0.2, 0.5 and 0.8 were considered as small, medium and large respectively. Overall quality of evidence was rated according to GRADE guidelines.ResultsTwelve studies (2 RCTs and 10 case series) were included (n=424; males 229). RCTs examined the following interventions: platelet-rich plasma injection (n=1), autologous whole-blood injection (n=1), shockwave therapy (n=1) and multi-modal intervention (n=1). Case series included evaluation of the following interventions: platelet-rich plasma injection (n=3), surgery (n=4), corticosteroid injection (n=2), multi-modal intervention + platelet-rich plasma injection (n=1). Very low-level evidence found shockwave therapy was more effective than a multi-modal intervention, by a large effect on improving symptoms (-3.22 SMD; 95% CI -4.28, -2.16) and physical function (-2.42 SMD; 95% CI-3.33, -1.50) in the long-term. There was very low-level evidence of no difference between autologous whole-blood injection and platelet-rich plasma injection on physical function (0.17 SMD; 95% CI -0.86, 1.21) to (0.24 SMD; 95% CI -0.76, 1.24) and quality of life (-0.04 SMD; 95%CI -1.05, 0.97) in the medium-term. There was very low-quality evidence that surgery resulted in a large reduction in symptoms (-1.89 SPD; 95% CI -2.36, -1.41) to (-6.02 SPD; 95% CI -8.10, -3.94) and physical function (-4.08 SPD; 95%CI -5.53, -2.63) in the long-term.ConclusionsThere is insufficient evidence to recommend any one intervention over another. A pragmatic approach would be to initially trial approaches proven successful in other tendinopathies.Level of evidenceLevel 2a     

Elevated IL-38 Serum Levels in Newly Diagnosed Multiple Sclerosis and Systemic Sclerosis Patients

ObjectiveInterleukin (IL)-38 is a newly discovered member of the IL-1 cytokine family with a proposed anti-inflammatory profile. We studied the probable role of this cytokine in the pathogenesis of two autoimmune diseases: multiple sclerosis (MS) and systemic sclerosis (SSc).Subjects and MethodsA total of 87 MS patients and 86 SSc patients (40 new and recently untreated cases and 46 treated cases) were selected for this study. Eighty-seven and 80 age- and sex-matched healthy subjects were included as controls for MS and SSc, respectively. Clinical and paraclinical features of the patients were recorded at the time of sampling. Serum IL-38 was measured by ELISA.ResultsLevels of serum IL-38 did not significantly differ between the total MS or SSc patients compared to controls. However, levels of IL-38 were significantly higher in newly diagnosed patients of MS (206.43 ± 38.97 pg/mL, p < 0.0001) than in those previously treated (158.04 ± 39.45 pg/mL). Similarly, new/recently untreated cases of SSc patients showed increased IL-38 levels (185.19 ± 36.27 pg/mL, p = 0.001) compared to treated patients (166.82 ± 33.08 pg/mL). IL-38 levels in newly diagnosed MS patients (p = 0.007) and new/recently untreated SSc patients (p = 0.032) were significantly higher than those in healthy controls.ConclusionThe higher serum levels of IL-38 in new or recently untreated cases of MS and SSc patients than in treated patients and healthy controls suggest the possible role of this cytokine in the development of these diseases or as part of a feedback loop to attenuate the inflammatory conditions in early stages of these diseases.     

Platelets inhibit the induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells

We have investigated the role of platelets in regulating the hemostatic and vasomotor properties of vascular smooth muscle. Experiments were performed to examine the effect of the releasate from activated platelets on the production of nitric oxide from interleukin-1 beta (IL- 1 beta)-treated cultured rat aortic smooth muscle cells. Treatment of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite in the culture media and in marked elevation of intracellular cyclic guanosine monophosphate (GMP) levels. The releasate from collagen-aggregated platelets blocked the IL-1 beta- mediated production of nitrite and the accumulation of cyclic GMP in smooth muscle cells in a platelet number-dependent manner. In functional assays, the perfusates from columns containing IL-1 beta- treated smooth muscle cells relaxed detector blood vessels without endothelium and the addition of IL-1 beta-treated smooth muscle cells to suspensions of platelets inhibited their thrombin-induced aggregation. The simultaneous treatment of smooth muscle cells with IL- 1 beta and the platelet releasate abolished both the vasorelaxing activities of the perfusates and the inhibition of platelet aggregation. Platelet releasates treated with a neutralizing antibody to platelet-derived growth factor (PDGF) failed to block IL-1 beta- induced nitric oxide production by the smooth muscle cells, as measured by both biochemical and functional assays. The platelet releasate from a patient with gray platelet syndrome likewise failed to block IL-1 beta-induced nitrite release by smooth muscle cells. These results demonstrate that platelets downregulate the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells through the release of PDGF. This effect may represent a novel mechanism by which platelets regulate vasomotor tone and thrombus formation at sites of vascular injury.