Curcumin loaded gold nanoparticles-chitosan/sodium alginate nanocomposite for nanotheranostic applications.

A solvent casting technique was used for the preparation of biomimetic nanocomposites scaffolds at three various concentrations of Curcumin loaded gold nanoparticles (Cur-AuNPs-1, 1.5, and 2 ml) as filler materials with chitosan-sodium alginate composite. The physico-chemical properties of prepared Cu-Au NPs and biomimetic nanocomposites were analyzed using various characterization techniques. In vitro biocompatibility of biomimetic nanocomposites are determined using simulated body fluid for biomineralization property, HAp formation and phosphate buffer saline (PBS) for swelling property, protein adsorption. Antibacterial activity of Cur-Au NPs and their nanocomposites carried out against Escherichia coli (E. coli) and Staphylococcus aureus. In vitro cytotoxicity of Cur-AuNPs is identified against UC-6 and MDA-MB 231 cell lines. The use of above studies and activity of Cur-AuNPs with contain biomimetic nanocomposites can adoptable for nanotheranostics.

Stress urinary incontinence and regenerative medicine: is injecting functional cells into the urethra feasible based on current knowledge and future prospects?

PURPOSE OF REVIEW: Stress urinary incontinence (SUI) is one of the most prevalent disorders of the lower urinary tract. Actual standard conservative and surgical therapeutic modalities are offering a symptomatic relief without treating the underlying disorder. Therefore, advances in cell-based regenerative medicine have implemented the use of autologous cells with the aim to treat urinary incontinence. RECENT FINDINGS: Different types of cells have been investigated to regain the function of the rhabdosphincter muscle in the urethral closure complex: myogenic progenitor cells, adipose tissue-derived stromal cells and mesenchymal stromal cells were mostly applied. Many of the preclinical studies published success of cell therapies. However, most clinical studies included only a few patients and rather short periods of follow-up. Furthermore, different cell types as well as injection techniques were used. SUMMARY: The use of stem cells seems to be a feasible and safe technique with promising results in patients with SUI. However, as a result of heterogeneity of preclinical and clinical trials, the best approach to cell-based therapy in SUI is still under investigation. The definition of the optimal cell type applied for the regeneration of the sphincter, the development of surgical injection advices and adequate tools for the investigation of the muscle regeneration during the follow-up have to be investigated to improve the use of autologous cells in the therapy of SUI.

Remodeling of articular cartilage and subchondral bone after bone grafting and matrix-associated autologous chondrocyte implantation for osteochondritis dissecans of the knee.

BACKGROUND: Osteochondritis dissecans (OCD) of the knee is a challenging problem. Previously, the authors implemented a novel 1-step surgical procedure for OCD treatment consisting of matrix-associated autologous chondrocyte implantation (ACI) and simultaneous bone reconstruction including the subchondral lamina. PURPOSE: This study presents the 2-to 5-year results after this technique, assessing correlations of clinical function and cartilage and bone remodeling processes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-six patients with symptomatic condylar knee OCD (International Cartilage Repair Society OCD III/IV) were treated with matrix-associated ACI and monocortical cancellous cylinders for defect filling and subchondral bone plate reconstruction using cortical graft layers as novel subchondral lamina. Evaluations were performed with clinical rating scales and 1.5-T magnetic resonance imaging using the magnetic resonance observation of cartilage repair tissue (MOCART) score and a newly implemented subchondral lamina remodeling grade. RESULTS: The defect size was 5.3 ± 2.3 cm(2). The defect depth was 8.7 ± 2.4 mm. After a follow-up of 39.8 ± 12.0 months, all scores improved significantly. Nineteen patients (73%) reached good/excellent results in the Lysholm-Gillquist score (preoperatively: 53.2 ± 18.0 points; latest follow-up: 88.5 ± 9.5 points) and the Cincinnati knee rating score (preoperatively: 51.7 ± 13.0 points; latest follow-up: 84.6 ± 11.7 points) and significant improvements in the subjective International Knee Documentation Committee (IKDC) score by 27.9% (preoperatively: 50.5% ± 16.1%; latest follow-up: 78.4% ± 13.4%). The MOCART score reached 62.4 ± 18.9 points. The clinical improvement and tissue remodeling occurred simultaneously and timed; thus, the cartilage defect filling and the lamina remodeling grades correlated significantly with each other, the follow-up time, and almost all clinical scores. CONCLUSION: The simultaneous reconstruction of deep osteochondral defects of the knee OCD with monocortical cancellous cylinders and matrix-associated ACI is a biological, 1-step alternative to osteochondral cylinder transfer or conventional ACI that leads to good clinical and magnetic resonance imaging results after an intermediate follow-up period. The present study demonstrated simultaneous remodeling processes of articular cartilage repair tissue and subchondral lamina; this synchronization is not yet understood and deserves further investigation.

DOCA and TGF-beta induce early growth response gene-1 (Egr-1) expression.

Renal fibrosis is characterized by excessive accumulation of extracellular matrix proteins. Recent findings show that transforming growth factor-beta (TGF-beta) induces a rapid but transient expression of early growth response gene-1 (Egr-1) by skin fibroblasts. The present study aims to define the role of Egr-1 in mineralocorticoid-induced renal fibrosis. Therefore, we transiently transfected immortalized human renal fibroblasts (TK188) with recombinant Egr-1 and analysed the transcription of several pro-fibrotic genes (Coll1A1, Coll1A2, osteopontin, TIMP-1, and CTGF). We also examined Egr-1 expression and the regulation of pro-fibrotic genes in DOCA- (deoxycorticosterone acetate) and TGF-beta-treated renal fibroblasts. Finally, we compared Egr-1 gene expression in DOCA/high salt-induced fibrotic kidneys and untreated mice. Egr-1 transfection of TK188 fibroblasts induced the expression of TIMP-1 and osteopontin mRNA. Similar results were obtained after DOCA-activation of TK188 cells. Stimulation of TK188 with TGF-beta, but not with DOCA, resulted in elevated Coll1A1/Coll1A2 and CTGF levels. Co-stimulation with DOCA and TGF-beta was followed by enhanced Egr-1, Coll1A1, TIMP-1, and CTGF transcription. In conclusion, both DOCA and TGF-beta alone or in combination synergistically induced Egr-1 expression by human renal fibroblasts. DOCA induction of TIMP-1/osteopontin is Egr-1 dependent, whereas TGF-beta appears to induce Coll1A1 and CTGF by an Egr-1 independent pathway. In vivo analyses revealed significantly higher Egr-1 transcript levels in DOCA/high salt-induced fibrotic kidneys compared to untreated mice. Thus, we show for the first time that Egr-1 might participate in DOCA-induced renal fibrosis.

Influence of standard haemodialysis treatment on transcription of human serum- and glucocorticoid-inducible kinase SGK1 and taurine transporter TAUT in blood leukocytes.

BACKGROUND: Standard haemodialysis (HD) rapidly alters osmolality and composition of extracellular fluid and, thus, challenges cell volume constancy. Cell volume-sensitive genes upregulated by osmotic cell shrinkage include those encoding for taurine transporter TAUT as well as for serum- and glucocorticoid-inducible kinase SGK1. METHODS: Six HD patients were haemodialysed for 4 h with high-flux dialysers. Blood was drawn from the arterial section of the fistula immediately prior to start of HD and subsequently after 60, 120 and 240 min of HD treatment and, in addition, 120 min after HD treatment. Taurine plasma concentrations ([taurine]p) and erythrocytic taurine content ([taurine]e) were determined by high-performance liquid chromatography. SGK1 and TAUT transcript levels in leukocytes were quantified by real-time polymerase chain reaction. RESULTS: The [taurine]p was significantly higher in HD patients before HD treatment when compared with healthy controls and it decreased significantly during 4 h of HD. The ratio of SGK1/GAPDH and of TAUT/GAPDH transcript levels increased significantly by 50% or 27%, respectively, during HD. CONCLUSIONS: Standard HD treatment decreases plasma taurine concentration and upregulates leukocyte SGK1 and TAUT transcription. As SGK1 is a potent regulator of ion channels and transporters in nervous system, heart muscle and epithelial cells, the deranged regulation of SGK1 may contribute to acute side effects of HD treatment.