Curcuminoid Co-Loading Platinum Heparin-Poloxamer P403 Nanogel Increasing Effectiveness in Antitumor Activity.

Nanosized multi-drug delivery systems provide synergistic effects between drugs and bioactive compounds, resulting in increased overall efficiency and restricted side effects compared to conventional single-drug chemotherapy. In this study, we develop an amphiphilic heparin-poloxamer P403 (HP403) nanogel that could effectively co-load curcuminoid (Cur) and cisplatin hydrate (CisOH) (HP403@CisOH@Cur) via two loading mechanisms. The HP403 nanogels and HP403@CisOH@Cur nanogels were closely analyzed with 1H-NMR spectroscopy, FT-IR spectroscopy, TEM, and DLS, exhibiting high stability in spherical forms. In drug release profiles, accelerated behavior of Cur and CisOH at pH 5.5 compared with neutral pH was observed, suggesting effective delivery of the compounds in tumor sites. In vitro studies showed high antitumor activity of HP403@CisOH@Cur nanogels, while in vivo assays showed that the dual-drug platform prolonged the survival time of mice and prevented tail necrosis. In summary, HP403@CisOH@Cur offers an intriguing strategy to achieve the cisplatin and curcumin synergistic effect in a well-designed delivery platform that increases antitumor effectiveness and overcomes undesired consequences caused by cisplatin in breast cancer treatment.

A Comprehensive Measure of Lifeyears Lost due to COVID-19 in 2020: A Comparison across Countries and with Past Disasters.

Typically, disaster damages are measured separately in four dimensions: fatalities, injuries, dislocations, and the financial damage that they wreak. Noy (2016) developed a lifeyears index of disaster damage which aggregates these disparate measures. Here, we use this lifeyears index to assess the costs of the COVID-19 pandemic across countries and compare these costs to the average annual costs of all other disasters that have occurred in all countries in the past 20 years. We find that the costs of the pandemic, measured for 2020, far outweigh the annual costs associated with other disasters in the past two decades. It is the economic loss that dominates this impact. The human and social implications of this economic loss are plausibly much greater than the direct toll in mortality and morbidity in almost all countries. Finally, it is small countries like the Maldives and Guyana that have experienced the most dramatic and painful crisis, largely under the radar of the world's attention. Our conclusion from these findings is not that governments' policy reactions were unwarranted. If anything, we find that the loss of lifeyears is correlated positively across the three dimensions we examine. Countries that experienced a deeper health crisis also experienced a deeper economic one.

Decellularization of Bone Tissue.

Decellularization technology is a process that uses different methods such as physical, chemical or enzymatic methods in order to eliminate cellular remnants from original tissues or organs while minimizing any adverse effect on the structural properties, biological activity, and mechanical integrity of the remaining ECM. Regenerative medicine uses the most promising therapies to replace or regenerate tissues and organs in human, restore or establish normal functions lost due to disease or injury. By the combination between new biomaterials and cells, one of the goals of regenerative medicine is to create autologous grafts for transplantation therapies in the future.Various decellularization methods have been developed include chemical treatment, biological treatment and physical treatment. The aim of this chapter is to evaluate the decellularization method and all available materials that preserves the matrix without structural disruption.

In vitro study on chondrogenic differentiation of human adipose-derived stem cells on treated bovine pericardium.

Bovine pericardium has been proposed as an available material for tissue engineering and bioprosthetic reconstruction. In this study, bovine pericardium was fabricated into a scaffold for culturing and chondrogenic differentiation of human adipose-derived stem cells (hADSCs). Bovine pericardium was treated in 10 mM Tris-HCl and 0.15% SDS, followed by crosslinking in 0.1% glutaraldehyde. Treated bovine pericardium (tBP) was characterized as a slight yellowish thin membrane with enhanced tensile strength and strain property. The membrane maintained stability under enzymatic conditions for up to 16 days of incubation. The results confirmed tBP as a cell-friendly scaffold for hADSCs due to low cytotoxicity and its ability to support an appropriate attachment and proliferation of hADSCs. Moreover, there was an accumulation of the extracellular matrix proteoglycan in tBP seeded with hADSCs after 7 and 14 days of chondrogenic induction. COMP as a specific marker of chondrogenesis was detected after 7 days, whereas type X-a1 collagen (Col10a1) expression was stable up to day 14. However, minor expression of aggrecan was found. Taken together, these results indicate that tBP is a potential scaffold for hADSCs for cartilage tissue engineering.Key words: Bovine pericardium, scaffold, adipose-derived stem cells, chondrogenic differentiation, cartilage regeneration, augmentation rhinoplasty.

Synergic Activity Against MCF-7 Breast Cancer Cell Growth of Nanocurcumin-Encapsulated and Cisplatin-Complexed Nanogels.

Nanogel-based systems loaded with single anticancer drugs display miscellaneous effectiveness in tumor remission, gradually circumventing mutation and resistance in chemotherapy. Hence, the existence of dual-drug delivered nano-sized systems has been contemporaneous with drug development and preceded the conventional-dose chemotherapy. Among outstanding synergistic drug nanoplatforms, thermosensitive copolymer heparin-Pluronic F127 (Hep-F127) co-delivering cisplatin (CDDP) and curcumins (Cur) (Hep-F127/CDDP/Cur) has emerged as a notable candidate for temperature-responsive drug delivery. The procedure was based on the entrapment of curcumin into the hydrophobic core of bio-degradable co-polymer Hep-F127 while the hydrophilic drug CDDP subsequently conjugated to the backbone heparin to form the core-shell structure. The copolymer was characterized by Fourier transform infrared (FT-IR) spectrophotometry, Transmission Electron Microscopy (TEM), and Dynamic Light Scattering (DLS), to corroborate the successful synthesis and via HPLC along with AES-ICP to evaluate the high drug loading along with a controllable release from the nano-gels. A well-defined nano-shell with size in the 129.3 ± 3.8 nm size range could enhance higher the efficacy of the conjugated-CDDP to Hep-F127 than that of single doses. Moreover, the considerable amount of dual-drug released from thermosensitive nanogels between different conditions (pH = 7.4 and pH = 5.5) in comparison to CDDP from Hep-F127 partially indicated the significantly anti-proliferative ability of Hep-F127/CDDP/Cur to the MCF-7 cell line. Remarkably, drug testing in a xenograft model elucidates the intricate synergism of co-delivery in suppressing tumor growth, which remedies some of the problems affecting in cancer chemotherapy.

Injectable Nanocurcumin-Formulated Chitosan-g-Pluronic Hydrogel Exhibiting a Great Potential for Burn Treatment.

Burn wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Curcumin is believed to be a potent antioxidant and anti-inflammatory agent; therefore, it can prevent the prolonged presence of oxygen free radicals which is a significant factor causing inhabitation of optimum healing process. This study describes an extension of study about the biofunctional nanocomposite hydrogel platform that was prepared by using curcumin and an amphiphilic chitosan-g-pluronic copolymer specialized in burn wound healing application. This formular (nCur-CP, nanocomposite hydrogel) was a free-flowing sol at ambient temperature and instantly converted into a nonflowing gel at body temperature. In addition, the storage study determined the great stability level of nCur-CP in long time using UV-Vis and DLS. Morphology and distribution of nCur in its nanocomposite hydrogels were observed by SEM and TEM, respectively. In vitro studies suggested that nCur-CP exhibited well fibroblast proliferation and ability in antimicrobacteria. Furthermore, second- and third-degree burn wound models were employed to evaluate the in vivo wound healing activity of the nCur-CP. In the second-degree wound model, the nanocomposite hydrogel group showed a higher regenerated collagen density and thicker epidermis layer formation. In third degree, the nCur-CP group also exhibited enhancement of wound closure. Besides, in both models, the nanocomposite material-treated groups showed higher collagen content, better granulation, and higher wound maturity. Histopathologic examination also implied that the nanocomposite hydrogel based on nanocurcumin and chitosan could enhance burn wound repair. In conclusion, the biocompatible and injectable nanocomposite scaffold might have great potential to apply for wound healing.

Simplified conditions for storing and cryopreservation of dental pulp stem cells.

OBJECTIVES: This study aimed to simplify the collection, isolation and cryopreservation procedure of human dental pulp stem cells (DPSCs) to ease the establishment of dental stem cell banking. DESIGN: Extracted third molars were collected and stored either in growth medium or in gentamicin-saline (480µg/ml) for 6, 9 or 12h. DPSCs were isolated and subjected to cryopreservation by a controlled-rate or rapid freezing method in 5 or 10% DMSO. Flow cytometry and growth pattern of DPSCs before and after cryopreservation were conducted. RESULTS: Rate of contamination by which the extracted teeth were stored in control and gentamicin-saline were 9.1% (N=33) and 2.3% (N=43), respectively. Successful cell isolation rate of teeth preserved in gentamicin-saline at 6h (92.9%) was comparable to those of growth media group (90.3%). At 9 and 12h, the rates dropped significantly to 75% and 54%, respectively. Cryopreservation by controlled-rate freezing either in 5 or 10% DMSO resulted in a significantly higher percentage of viable cells than by rapid freezing. Cells conserved by controlled-rate freezing in 5% DMSO showed a pattern of growth similar to control unfrozen cells; 10% DMSO significantly deteriorated the growth pattern of the cells. After thawing, DPSCs conserved by controlled-rate freezing still expressed stemness characteristics, although hematopoietic stem cell markers were slightly increased. CONCLUSION: Gentamicin-saline was effective in preserving human teeth for DPSC isolation. Controlled-rate freezing in 5% DMSO gave the highest rate of cell viability. This study simplifies the storage conditions and proposes a simple method for cryopreservation of DPSCs.

Human dental pulp stem cells cultured onto dentin derived scaffold can regenerate dentin-like tissue in vivo.

Regeneration of dentin tissues in the pulp space of teeth serves the ultimate goal of preserving teeth via endodontic approaches. In recent times, many studies suggested that human dentin scaffolds combined with dental stem cells was a potential strategy for the complete dentin tissue regeneration. In this study, human dental pulp stem cells (DPSCs) were isolated and cultured. Dentin specimens were prepared from human third molars and treated with ethylene diamine tetra-acetic acid and citric acid to remove the smear layer. Then, DPSCs were cultured onto human treated dentin (hTD) and implanted in mouse model for 4, 6 and 8 weeks. The resulting grafts were assessed by hematoxylin and eosin stain and immunohistochemical stains. As a result, DPSCs were supported and induced to regenerate of dentin-like tissues which expressed specific dentin markers such as dentin sialophosphoprotein and dentin matrix protein 1 by combination with hTD in vivo. Furthermore, cells existed in the newly-formed dentin-like tissues also expressed typical human mitochondria antibodies, demonstrated that new tissues originated from human. In conclusion, the obtain results extend hopefully newly-established therapy to apply in endodontics and traumatic dental hard tissues.

Various methods for isolation of multipotent human periodontal ligament cells for regenerative medicine.

Periodontal ligament (PDL) is a specialized connective tissue that connects cementum and alveolar bone to maintain and support the teeth in situ and preserve tissue homeostasis. Recent studies have revealed the existence of stem cells in human dental tissues including periodontal ligament that play an important role, not only in the maintenance of the periodontium but also in promoting periodontal regeneration. In this study, human periodontal ligament cells (hPDLCs) were isolated by outgrowth and enzymatic dissociation methods. Expression of surface markers on PDLCs as human mesenchymal stem cells (MSCs) was identified by flow cytometry. In addition, proliferation and differentiation capacity of cultured cells to osteoblasts, adipocytes were evaluated. As a result, we successfully cultured cells from the human periodontal ligament tissues. PDLCs express mesenchymal stem cell (MSC) markers such as CD44, CD73, and CD90 and do not express CD34, CD45, and HLA-DR. PDLCs also possess the multipotential to differentiate into various types of cells, such as osteoblast and adipocytes, in vitro. Therefore, these cells have high potential to serve as materials for tissue engineering, especially dental tissue engineering.