Chitosan-Raloxifene nanoparticle containing doxorubicin as a new double-effect targeting vehicle for breast cancer therapy

Backgroundtreatment of breast cancer as one of the most common cancers in the world remains an important area of drug development based on nanoparticulate systems. Effective targeted therapy of affected cells based on ligand conjugate biocompatible polymeric nanoparticles is an attractive perspective in this context.ObjectiveIn this study, a novel double effect nanoparticle based on Chitosan-Raloxifene conjugate was prepared for adjuvant therapy (hormone and chemo therapy) and drug targeting to breast cancer cells via estrogen receptor (ER).MethodsChitosan-raloxifene conjugate was synthesized. Related nanoparticles containing doxorubicin (DOX) were prepared and characterized. Experimental design study was performed to determine the optimum levels of variables in the preparation of nanoparticle. Drug loading, release, nanoparticle stability, and the effect of nanoparticles on cell viability were evaluated. Further, inhibition tests were performed to demonstrate that the function of these novel nanoparticles is mediated via ER.ResultsChitosan-raloxifene conjugate was successfully synthesized. The prepared nanoparticles showed sizes within 25–35 nm, more than 95% drug loading, about 60% of drug release and desired stability after 24 h. XTT assay on MCF-7 cell line illustrated that these nanoparticles could inhibit the cellular growth up to 60%. The results from inhibition tests revealed that prepared nanoparticles can inhibit cell growth via ER blocking.ConclusionThis study introduced chitosan-raloxifene nanoparticles containing doxorubicin as a novel targeting agent for adjuvant therapy of breast cancer. Open in a separate windowGraphical abstractElectronic supplementary materialThe online version of this article (10.1007/s40199-020-00338-9) contains supplementary material, which is available to authorized users.     

Hepatitis C virus infection in patients with essential mixed cryoglobulinemia, multiple myeloma and chronic lymphocytic leukemia

Increased prevalence of HCV infection in some lymphoproliferative diseases has been recently reported. In the present study, the frequency of anti-HCV antibody (Ab) together with hepatitis B surface (HBs) antigen (Ag) and anti-HBs Ab were determined in 42, 45 and 23 patients with essential mixed cryoglobulinemia (EMC), multiple myeloma (MM) and B-cell chronic lymphocytic leukemia (B-CLL), respectively. Thirty hospitalized patients with chronic rheumatoid arthritis (RA) were also included as a control. Specific antibodies to HCV antigens were detected by enzyme linked immunosorbent assay (ELISA) and positive results were confirmed by a recombinant immunoblot assay (RIBA). Our results demonstrated anti-HCV positivity in 69%, 11% and 4.3% of the EMC, MM and B-CLL samples tested, respectively. None of the RA patients were found to be anti-HCV positive. No significant differences were observed between the patients groups regarding the frequency of HBs Ag and anti-HBs Ab. Considering the low incidence of HCV infection in the control group and the normal population, these results confirm and extend previous reports on the possible role of HCV infection in the etiology of EMC and further suggest involvement of this virus in a subset of MM.     

Pretreatment with combined low-level laser therapy and methylene blue improves learning and memory in sleep-deprived mice

Lasers in Medical Science - Low-level laser therapy (LLLT) and methylene blue (MB) were proved to have neuroprotective effects. In this study, we evaluated the preventive effects of LLLT and MB...     

Venlafaxine inhibits naloxone-precipitated morphine withdrawal symptoms: Role of inflammatory cytokines and nitric oxide

Metabolic Brain Disease - Opioid-induced neuroinflammation plays a role in the development of opioid physical dependence. Moreover, nitric oxide (NO) has been implicated in several oxidative and...     

Controlled Ion Release from Novel Polyester/Ceramic Composites Enhances Osteoinductivity

Due to the growing number of patients suffering from musculoskeletal defects and the limited supply of and sub-optimal outcomes associated with biological graft materials, novel biomaterials must be created that can function as graft substitutes. For bone regeneration, composite materials that mimic the organic and inorganic phases of natural bone can provide cues which expedite and enhance endogenous repair. Specifically, recent research has shown that calcium and phosphate ions are inherently osteoinductive, so controllably delivering their release holds significant promise for this field. In this study, unique aliphatic polyesters were synthesized and complexed with a rapidly decomposing ceramic (monobasic calcium phosphate, MCP) yielding novel polymer/ceramic composite biomaterials. It was discovered that the fast dissolution and rapid burst release of ions from MCP could be modulated depending on polymer length and chemistry. Also, controlled ion release was found to moderate solution pH associated with polyester degradation. When composite biomaterials were incubated with mesenchymal stems cells (MSCs) they were found to better facilitate osteogenic differentiation than the individual components as evidenced by increased alkaline phosphate expression and more rapid mineralization. These results indicate that controlling calcium and phosphate ion release via a polyester matrix is a promising approach for bone regenerative engineering.     

Sleeve Gastrectomy as Sole and Definitive Bariatric Procedure: 5<Emphasis Type="Bold">-</Emphasis>Year Results for Weight Loss and Ghrelin

Background  

Due to excellent efficacy for weight loss in the short-term follow-up, sleeve gastrectomy (SG) has gained enormous popularity as bariatric procedure, not only as first step in high-risk or super-obese patients but mainly as a sole and definitive operation in morbidly obese. In contrast to a large number of short and intermediate-term results, no series of SG with a follow-up of 5 years or more has been published so far.     

Comparison of salivary nitric oxide and epidermal growth factor level between diabetic patients and healthy individuals

The purpose of the current study was to compare salivary Nitric oxide and epidermal growth factor level in diabetic patients and healthy individuals. In this paired-control study 20 patients with type 1 diabetes mellitus, 20 patients with type 2 diabetes mellitus and 20 age and sex matched healthy subjects participated. The level of salivary Nitric oxide was increased in type 1 and 2 diabetic patients in comparison to control individuals (P = 0.037 and P = 0.058), respectively. Epidermal growth factor concentration was higher in type 1 and 2 diabetic patients compare to healthy ones, (P = 0.037 and P = 0.005) respectively. There was no significant difference between salivary Nitric oxide and Epidermal growth factor level regarding to the type of diabetes (P > 0.05). Significant statistical correlation was found between Nitric oxide and Epidermal growth factor levels and the fasting blood glucose and HbA1c (P < 0.001). Conclusions: Salivary Nitric oxide and Epidermal growth factor levels were higher in type 1 and type 2 diabetic patients and there was correlation with severity of disease.

     

Off-the-shelf acellular fetal skin scaffold as a novel alternative to buccal mucosa graft: the development and characterization of human tissue-engineered fetal matrix in rabbit model of hypospadiasis

Aim

In this study, we aimed to develop a novel alternative to buccal mucosal graft from the acellular human fetal skin to manage hypospadias in a rabbit model. We optimized the decellularization protocol to develop and characterize the human tissue-engineered fetal dermal matrix as an “off-the-shelf” natural biomaterial.

Material and Methods

Human fetal skin was obtained at 16–19 weeks gestational age with respect to a signed informed consent from parents under the university ethical committee approval. The dissected full-thickness fetal skin tissues were placed into SDS and Triton X-100 in different dosages to achieve the optimum decellularization protocol. Histopathology of the acellular fetal matrix was assessed by Hematoxylin & Eosin (H&E) and DAPI staining to confirm the removal of all cell materials, Masson’s trichrome staining for collagen evaluation, DNA quantification for confirmation of DNA content, and scanning electron microscopy (SEM) for evaluation of scaffold microstructure. Immunohistochemistry (IHC) staining was used to detect specific dermal markers, namely vimentin, type I collagen, cytokeratin (CK)19. The prepared dermal scaffolds were then grafted on the 8 rabbit models of hypospadias. The rabbits underwent evaluations at 1, 2, 3, and 6 months postoperatively.

Results

H&E, Masson’s trichrome, DAPI staining, and SEM confirmed the significant removal of cells; meanwhile, the ECM was completely preserved. At the time of biopsy, after 2, 4, and 6 months, no evidence of inflammation, fibrosis, necrosis, or rejection was observed. The grafted dermal scaffolds appeared histologically and anatomically normal. It was observed that the scaffolds were recellularized by circulating CD 34?+?bone marrow stem cells (BMSCs) inside the body, implicating the body as a natural bioreactor.

Conclusion

The application of acellular fetal skin (AFS) is a safe and feasible method that can decrease surgical time in a complex hypospadias reconstruction. Moreover, AFS demonstrated excellent angiogenesis characteristics and migration of the stem cells to the scaffold observed during the course of treatment. Novel natural AFS scaffold without cell seeding is an excellent alternative to buccal mucosal graft; hence, it can overcome the limitations concerning the graft size and prevent the creation of wounds in oral mucosal tissue.