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CD47 is a ubiquitously expressed cell surface receptor, which is widely known for preventing macrophage-mediated phagocytosis by interacting with signal regulatory protein α (SIRPα) on the surface of macrophages. In addition to its role in phagocytosis, emerging studies have reported numerous noncanonical functions of CD47 that include regulation of various cellular processes such as proliferation, migration, apoptosis, differentiation, stress responses, and metabolism. Despite lacking an extensive cytoplasmic signaling domain, CD47 binds to several cytoplasmic proteins, particularly upon engaging with its secreted matricellular ligand, thrombospondin 1. Indeed, the regulatory functions of CD47 are greatly influenced by its interacting partners. These interactions are often cell- and context-specific, adding a further level of complexity. This review addresses the downstream cell-intrinsic signaling pathways regulated by CD47 in various cell types and environments. Some of the key pathways modulated by this receptor include the PI3K/AKT, MAPK/ERK, and nitric oxide signaling pathways, as well as those implicated in glucose, lipid, and mitochondrial metabolism. These pathways play vital roles in maintaining tissue homeostasis, highlighting the importance of understanding the phagocytosis-independent functions of CD47. Given that CD47 expression is dysregulated in a variety of cancers, improving our understanding of the cell-intrinsic signals regulated by this molecule will help advance the development of CD47-targeted therapies.

Polymeric micelles have been extensively studied as vectors for the delivery of hydrophobic drugs for the treatment of cancers and other diseases. Despite intensive research, few formulations provide significant benefits, and even fewer have been clinically approved. While many traditional non-responsive micelles have excellent safety profiles, they lack the ability to respond to the intracellular environment and release their cargo in a spatiotemporally defined manner to effectively deliver large doses of cytotoxic drugs into the cytosol of cells that overwhelm efflux pumps. As a novel and adaptable strategy, we hypothesized that well-established non-responsive polymeric micelles could be augmented with a pH-trigger via the co-encapsulation of cytocompatible oligoelectrolytes, which would allow rapid cargo release in the endosome, leading to increased cytotoxicity. Herein, we demonstrate how this strategy can be applied to render non-responsive micelles pH-responsive, resulting in abrupt cargo release at specific and tunable pH values compatible with endosomal delivery, which significantly increased their cytotoxicity up to 3-fold in an ovarian adenocarcinoma (SKOV-3) cell line compared to non-responsive micelles. In comparison, the oligoelectrolyte-loaded micelles were significantly less toxic to healthy 3T3 fibroblasts, indicating a selective cargo release in cancer cell lines. Oligoelectrolytes can be co-encapsulated in the micelles along with drugs at high encapsulation efficiency percentages, which are both ejected from the micelle core upon oligoelectrolyte ionization. Mechanistically, the increase in cytotoxicity appears to also result from the accelerated endosomal escape of the cargo caused by disruption of the endosomal membrane by the simultaneous release of the oligoelectrolytes from the micelles. Furthermore, we show how this approach is broadly applicable to non-responsive micelles regardless of their composition and various classes of hydrophobic chemotherapeutics. The preliminary studies presented here reveal the versatility and wide scope of oligoelectrolyte-mediated, pH-triggered drug release as a compelling and powerful strategy to enhance the cytotoxicity of non-responsive polymeric micelles.

While blood‐contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings. Herein, a novel but simple strategy is described for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma‐grafting of an ultrathin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O─C─O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface. In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3 log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG‐coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice shows no evidence of toxicity nor inflammation. A novel strategy for an antifouling, antithrombosis, and antirestenosis coating is demonstrated for a range of common medical materials, involving plasma‐grafting of an ultrathin hyperbranched polyglycerol (HPG) coating. The resulting coating prevents platelet adhesion and activation, reduces bacterial attachment and prevents biofilm formation. HPG‐coated stents exhibit patency in a disease model and there is no evidence of inflammation or toxicity.

In-vitrochemical characterization and mosquitocidal screening of essential oil derived from Mikania scandens(L.) Willd. (Asteraceae) (CVO-MS) against the malarial vector Anopheles gambiaewas investigated. GC-MS analysis evidenced a total of 12 bio-active compounds, and maximum at α-bisabolol (39.34%) followed by stigmasterol (13.45%) respectively. The larvicidal activity of CVO-MS against the malarial vector An. gambiaeevidenced that the mortality rate was prominent at the maximum dosage of 1000 ppm. The Median Lethal Concentration (LC50) of CVO-MS was established at 488 ± 2.45 ppm, respectively. Enzyme inhibition assay showed that the CVO-MS delivers a significant upsurge in the level of CYP450, GST, and a decline in the level of α-β carboxylesterase activity in both the third and fourth instar (p ≤ 0.0001). The gut-histological examination of CVO-MS showed that there is severe damage in the mid-gut tissues, especially epithelial layer (EL), gut-lumen (GL), and peritrophic membrane (pM). The non-target screening against the mosquito predators (A. bouvieri, D. indicus, and third instar larvae of Tx. splendens) suggests that CVO-MS showed less toxicity as compared to Pestanal® (1 ppm) respectively. The present study has paved a new insight in understanding the bioactivity of CVO-MS as a potential larvicidal agent of malarial vector and non-toxic against mosquito predators.

Background: Methotrexate (MTX) is a widely used medication for treating various conditions, including skin infections, inflammatory diseases, autoimmune disorders, and malignancies. However, prolonged and extreme use of MTX can lead to detrimental effects on multiple organs. Green Chiretta (GC) is a traditional medicinal plant known for its anti-inflammatory, antioxidant, and immunostimulatory properties.Objective: The objective of this study is to examine the antioxidant potential of GC through in-vitro analysis and to assess the potential protective effects of aqueous leaf extracts of GC against MTXinduced cardiac and spleen toxicity.Methods: In-vitro antioxidant activity was assessed by measuring total phenolic content, DPPH, catalase and peroxidase activity. We divided rats into five groups (n=6), and after the study, rats were euthanized and the levels of antioxidants (SOD, CAT & GSH) and lipid peroxidase (MDA), as well as histopathology modification of the heart and spleen tissues were examined.Results: Our study's findings highlight the superiority of the aqueous GC extract's antioxidant capacity relative to other solvents (ethanol and methanol). Moreover, the aqueous GC extract's administration to rats yielded significant progress in antioxidant levels (Superoxide dismutase, catalase, glutathione), a reduction in lipid peroxidation (MDA), and the restoration of cardiac and spleen histoarchitecture against MTX-induced toxicity. These results collectively emphasize the extract's potential as a valuable therapeutic option against oxidative stress and tissue damage.Conclusion: The present study revealed that the aqueous GC extract demonstrated its protective efficacy against MTX-induced cardio and spleen toxicity in Wistar albino rats.