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Residual and also Frequent Condition Following Endoscopic Endonasal Strategy as being a Representation regarding Anatomic Issue to the Resection associated with Midline Anterior Head Base Meningiomas.
Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease, associated with significant risk of limb loss, morbidity and mortality; however, there remains unmet therapeutic needs for arterial revascularization and ischemic tissue repair. Stem cell therapies have emerged as compelling candidates due to beneficial proangiogenic and immunosuppressive function. Nevertheless, in vivo efficacy was insufficient in proliferation, differentiation and survival/engraftment rate. Cardiac stem cells (CSCs) was firstly attempted for CLI as a novel therapeutic modality to provide superior angiogenic potency to bone marrow-derived stem cells (BMSCs). It was noted that CSCs demonstrated 3.2-fold in HGF, 2.9-fold in VEGF and 8.7-fold in PDGF-B higher gene expressions compared to BMSCs. To enhance the hypoxia-induced proangiogenic effect, CSCs were transfected with hypoxia-inducible factor-1 alpha (HIF-1α) by using electroporation method, specifically optimized for CSCs yielding 45.77% of transfection efficiency and 89.75% of viability. HIF-1α overexpression significantly increased CSC survival in hypoxia, proangiogenic factors production and endothelial differentiation. In mouse hind limb ischemia model, local intramuscular delivery of CSC overexpressing HIF-1α (HIF-CSC) significantly improved the blood flow recovery. Histological analysis revealed that muscle degeneration and fibrosis in the ischemic limb were attenuated. Local delivery of HIF-CSC might be a promising option for ischemic tissue restoration. V.Using polyethylene glycol (PEG) to functionalize liposomes improves their stealth properties and stability in blood. However, PEG is known to induce the accelerated blood clearance (ABC) phenomenon, which occurs for multiple doses owing to anti-PEG IgM being produced after the initial injection. In this study, as an alternative to PEG, polysarcosine (PSar) was selected owing to its low antigenicity and its highly dense chains with controllable lengths, similar to PEG. Furthermore, we directly evaluate the potential of PSar for avoiding the ABC phenomenon by comparing PSar with PEG on the same liposome platform, which has similar physicochemical properties such as hydrophobic region, membrane fluidity, and size. PEG- and PSar-liposomes were prepared and characterized for comparison. PSar-liposomes showed similar physicochemical properties to PEG-liposomes in terms of size control, zeta potential, membrane polarity, and fluidity; however, ELISA results showed noticeably lower levels and faster production speeds of both IgM and IgG for PSar-liposomes than for PEG-liposomes. In addition, a pharmacokinetics experiment with multiple injections showed that PSar-PE coating of liposomes may help to circumvent the ABC phenomenon. Gene therapy is one of the most promising medical fields which holds the potential to rapidly advance the treatment of difficult ailments such as cancer as well as inherited genetic diseases. However, clinical translation is limited by several drug delivery hurdles including renal clearance, phagocytosis, enzymatic degradation, protein absorption, as well as cellular internalization barriers. Additionally, successful treatments require sustained release of drug payloads to maintain the effective therapeutic level. As such, controlled and sustained release is a significant concern as the localization and kinetics of nucleic acid therapeutics can significantly influence the therapeutic efficacy. This is an unmet need which calls for the development of controlled-release nanoparticle (NP) technologies to further improve the gene therapy efficacy by prolonging the release of nucleic acid drug payload for sustained, long-term gene expression or silencing. Herein, we present a polymeric NP system with sustained genvarious nucleic acid-based therapeutics with applications in both fundamental biological studies and clinical translations. V.Melanoma is an aggressive disease with rapid progression and fast relapse, representing one of the formidable challenges in clinic. Current systemic therapies for melanoma exhibit limited anticancer potential due to the lack of specificity and limited efficacy. Herein, we design a cationic polymer (SCP-HA-PAE) by conjugating skin/cell penetrating peptide (SCP) and hyaluronic acid (HA) to the amphipathic polymer (poly β-amino esters, PAE), then fabricate the nanocarriers (SHP) composed by SCP-HA-PAE for delivering siRNA to skin melanoma by transdermal application. compound library inhibitor SHP not only manifests the excellent ability in penetrating through skin stratum corneum (SC), targeting melanoma and being sensitive to pH, but also expresses the advantages in compacting the vector/siRNAs nanocomplexes and stimulating their endosome escape inside cells, which ensure the enhanced siRNA delivery efficiency. SHP/siRNA induce the strong efficacy in retarding the progression and relapse of skin melanoma through the enhanced apoptosis effect both in vitro & in vivo. This study provides a proof-of-concept design of pH-switchable cationic micelles as transdermal gene delivery nanoplatforms with targeting effect for melanoma therapy, which may be adapted widely in the treatment of various superficial tumors and skin genetic diseases. V.Physiological barriers encountered in the clinical translation of cancer nanomedicines inspire the community to more deeply understand nano-bio interactions in not only tumor microenvironment but also entire body and develop new nanocarriers to tackle these barriers. Renal clearable nanocarriers are one kind of these newly emerged drug delivery systems (DDSs), which enable drugs to rapidly penetrate into the tumor cores with no need of long blood retention and escape macrophage uptake in the meantime they can also enhance body elimination of non-targeted anticancer drugs. As a result, they can improve therapeutic efficacies and reduce side effects of anticancer drugs. Not limited to anticancer drugs, diagnostic agents can also be achieved with these renal clearable DDSs, which might also be applied to improve the precision in the gene editing and immunotherapy in the future. V.
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