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The optimal transplantation conditions were also determined first by injecting a gradient number of labeled hMSCs percutaneously into the cranial defect of the nude mouse model. Next, we applied this method to ovariectomy-induced OP mice. Results showed long-term optical imaging with high fluorescence intensity and computed tomography (CT) scanning with significantly increased bone formation between the osteoporotic and sham-operated bones. During the tracking process, two mice from each group were sacrificed at two representative time points to examine the bony defect bridging via micro-CT morphometric analyses. Our data showed remarkable promise for efficient hMSC tracking and encouraging treatment in bioimaging-guided OP stem cell therapy.The management of respiratory diseases relies on the daily administration of multiple active pharmaceutical ingredients (APIs), leading to a lack of patient compliance and impaired quality of life. The frequency and dosage of the APIs result in increased side effects that further worsens the overall patient condition. Here, the manufacture of polymer-polymer core-shell microparticles for the sequential delivery of multiple APIs by inhalation delivery is reported. The microparticles, composed of biodegradable polymers silk fibroin (shell) and poly(L-lactic acid) (core), incorporating ciprofloxacin in the silk layer and ibuprofen (PLLA core) as the antibiotic and anti-inflammatory model APIs, respectively. The polymer-polymer core-shell structure and the spatial distribution of the APIs have been characterized using cutting-edge synchrotron macro ATR-FTIR technique, which was correlated with the respective API sequential release profiles. The APIs microparticles had a suitable size and aerosol properties for inhalation therapies (≤4.94 ± 0.21μm), with low cytotoxicity and immunogenicity in healthy lung epithelial cells. The APIs compartmentalization obtained by the microparticles not only could inhibit potential actives interactions but can provide modulation of the APIs release profiles via an inhalable single administration.Genomic deoxyribonucleic acid (DNA) stores and carries the information required to maintain and replicate cellular life. While much efforts have been devoted in decoding the sequence of DNA basis to detect the genetic mutations related to cancer disease, it is becoming clear that physical properties, like structural conformation, stiffness and shape, can play an important role to recognize DNA modifications. Here, silver-coated silicon nanowires (Ag/SiNWs) are exploited as Raman spectroscopic platform to easily discriminate healthy and cancer genomic DNA, extracted from human normal skin and malignant melanoma cells, respectively. In particular, aqueous DNA droplets are directly deposited onto a forest of Ag/SiNWs and Raman maps are acquired after sample dehydration. By applying principal component analysis (PCA) to the Raman spectra collected within the droplets, healthy and cancer cell DNA can be distinguished without false negative identifications and with few false positive results ( less then 2%). The discrimination occurs regardless the analysis of specific DNA sequencing, but through Raman bands strictly related to the interfacing of the DNA and the NWs. The observed phenomenon can be ascribed to conformational differences and/or diverse charge properties between healthy and cancer cell DNA determining a different arrangement of the molecules adsorbed onto the NWs upon water evaporation. The unique interaction with DNA and facile fabrication technology make Ag/SiNWs an effective platform for a robust, rapid and label-free cancer diagnosis, as well as a potential tool to investigate physical properties of DNA.The aim of this work was to develop a mucoadhesive iontophoretic patch for anesthetic delivery in the buccal epithelium. The patch was comprised of three different layers, namely i) drug release (0.64 cm2); ii) mucoadhesive (1.13 cm2); and iii) backing (1.13 cm2). Prilocaine and lidocaine hydrochlorides were used as model drugs (11 ratio, 12.5 mg per unit). An anode electrode (0.5 cm2 spiral silver wire) was placed in between the drug release and mucoadhesive/backing layers to enable iontophoresis. Surface microscopy; mechanical and in vitro mucoadhesive properties; drug release kinetics and mechanism; and drug permeation through the porcine esophageal epithelium were assessed. Topographic analysis evidenced differences in the physical structures for the several layers. All layers presented suitable handling properties i.e., flexibility, elasticity and resistance. Both the release and mucoadhesive layers presented features of a soft and tough material, while the backing layer matched the characteristics of a hard and brittle material. A synergy between the drug release and mucoadhesive layers on the mucoadhesive force and work of adhesion of the tri-layered patch was observed. Passive drug release of both drugs fitted to First-order, Hixson-Crowell and Weibull kinetic models; and the release mechanism was attributed to anomalous transport. Iontophoresis remarkably enhanced the permeation of both drugs, but mainly prilocaine through the mucosa as evidenced by the permeability coefficient parameter (3.0-fold). The amount of these amino amide salts retained in the mucosa were also equally enhanced (4.7-fold), while the application of a tiny constant electric current (1 mA·cm-2·h-1) significantly decreased the lag time for lidocaine permeation by about 45%. In view of possible in vitro / in vivo correlations, the buccal iontophoretic patch displays a promising strategy for needle-free and patient-friendly local anesthesia in dentistry.Design features of phase I, II, and III clinical trials of pharmaceutical interventions in myelofibrosis (MF) are discussed. Model-assisted and model-based designs for phase I trials are useful for maximizing therapeutic benefit and include novel approaches to dose escalation. Trials in MF have shifted to accommodate new challenges following approval of JAK inhibitor therapies. Standardized response criteria exist; however, alternative measures of response when evaluating newer agents may be needed. Noninferiority and other adaptive designs can be used to incorporate design changes over time. Patient-reported outcomes, including quality-of-life and symptom assessment, should be included as outcome measures.Myeloproliferative neoplasms are characterized by chronic inflammation. The discovery of constitutively active JAK-STAT signaling associated with driver mutations has led to clinical and translational breakthroughs. Insights into the other pathways and novel factors of potential importance are being actively investigated. Various classes of agents with immunomodulating or immunosuppressive properties have been used with varying degrees of success in treating myeloproliferative neoplasms. Early clinical trials are investigating the feasibility, effectiveness, and safety of immune checkpoint inhibitors, cell-based immunotherapies, and SMAC mimetics. The dynamic landscape of immunotherapy and immunomodulation in myeloproliferative neoplasms is the topic of the present review.Myelofibrosis (MF) belongs to a group of clonal stem cell disorders known as the BCR-ABL-negative myeloproliferative neoplasms. Allogeneic hematopoietic stem cell transplantation (HCT) is currently the only curative treatment option for MF. Because HCT can be associated with significant morbidity and mortality, patients need to be carefully selected based on disease-risk, fitness, and transplant factors. Furthermore, in the era of JAK inhibitors, the timing of transplantation has become a challenging question. Here the authors review recent developments in HCT for MF, focusing on risk stratification and optimal timing.Myeloproliferative neoplasms include essential thrombocythemia, polycythemia vera, and myelofibrosis. They are characterized by abnormal myeloid proliferation. Patients suffer from debilitating constitutional symptoms and splenomegaly. learn more There have been advances in understanding the impact on quality of life in myeloproliferative neoplasms. Owing to the chronicity of these diseases, symptoms are considered in response criteria for clinical trials. This review wills cover how quality of life is measured in patients with myeloproliferative neoplasm. We review the impact of treatment options, including JAK inhibitors, allogeneic stem cell transplantation, and medications in development. We discuss nonpharmacologic methods of improving symptoms and quality of life.The US Food and Drug Administration (FDA) approval of Janus kinase 2 inhibitors, ruxolitinib and fedratinib for the treatment of intermediate-2 or high-risk primary or secondary myelofibrosis (MF) has revolutionized the management of MF. Nevertheless, these drugs do not reliably alter the natural history of disease. Burgeoning understanding of the molecular pathogenesis and the bone marrow microenvironment in MF has galvanized the development of targeted therapeutics. This review provides insight into the novel therapies under clinical evaluation.Myelodysplastic syndrome/Myeloproliferative neoplasms (MDS/MPNs) are molecularly complex, clinically heterogeneous diseases that exhibit proliferative and dysplastic features. Diagnostic criteria use clinical, pathologic, and genomic features to distinguish between disease entities, though considerable clinical and genetic overlap persists. MDS/MPNs are associated with a poor prognosis, save for MDS/MPN with ring sideroblasts and thrombocytosis, which can behave more indolently. The current treatment approach is risk-adapted and symptom-directed and largely extrapolated from experience in MDS or MPN. Gene sequencing has demonstrated frequent mutations involving signaling, epigenetic, and splicing pathways, which present numerous therapeutic opportunities for clinical investigation.Accelerated and blast phase myeloproliferative neoplasms are advanced stages of the disease with historically a poor prognosis and little improvement in outcomes thus far. The lack of responses to standard treatments likely results from the more aggressive biology reflected by the higher incidence of complex karyotype and high-risk somatic mutations, which are enriched at the time of transformation. Treatment options include induction chemotherapy (7 + 3) as that used on de novo acute myeloid leukemia or hypomethylating agent-based therapy, which has shown similar outcomes. Allogeneic stem cell transplantation remains the only potential for cure.Thrombotic, vascular, and bleeding complications are the most frequent causes of morbidity and mortality in myeloproliferative neoplasms (MPNs). The interplay and reciprocal amplification between two factors are considered to lead to thrombosis in MPNs (1) circulating blood cell-intrinsic abnormalities caused by an MPN driver mutation in their hematopoietic progenitor/stem cells, interacting with vascular endothelial cells, show prothrombotic and proadhesive phenotypes; and (2) a state of usually subclinical systemic inflammation that fuels the thrombotic tendency. Prevention and treatment require maintenance of hematocrit less than 45% and cytoreductive therapy in patients with a high risk for thrombotic and vascular complications.