Creutzfeldt–Jakob disease in a post-COVID-19 patient: did SARS-CoV-2 accelerate the neurodegeneration?

Abstract Background Creutzfeldt–Jakob disease (CJD) is a rare, fatal neurodegenerative disorder, with few months as a usual duration from onset to death. Case presentation In this case report, a patient of Sporadic CJD (sCJD) who presented one month after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The diagnosis of this case was established after confirming findings from clinical, neurophysiology, radiological, and laboratory features of this disease. Conclusion Putting in mind all the updated data on the pathogenesis of CJD and the immune responses to SARS-CoV-2, we can suggest that COVID-19 can lead to accelerated pathogenesis and exaggerated manifestations of this fatal neurodegenerative disease

Recent advances in herbal combination nanomedicine for cancer: delivery technology and therapeutic outcomes

Introduction: The use of herbal compounds in cancer therapy has great potential to promote the efficacy of current cancer therapeutic strategies. Herbal compounds were successfully reported to enhance tumor cells sensitization to the action of chemo-, hormonal- and gene-therapeutic agents via different mechanisms. Herbal ingredients can affect different signaling pathways, reduce the toxic side effects or inhibit the efflux of anticancer drugs. Areas covered: This review will discuss the delivery of herbal compounds with other cancer treatments such as hormonal, small molecule inhibitors and inorganic hybrids to tumor cells. An overview of physicochemical properties of herbal components that require intelligent design of combo-nanomedicines for efficient co-delivery of those herbal-derived and other anticancer agents was discussed. Nanocarriers provide various benefits to overcome the shortcomings of the encapsulated herbal compounds including improved solubility, increased stability and enhanced tumor targeting. Different nanocarrier systems were the focus of this review. Expert opinion: Multifunctional nanocarrier systems encapsulating herbal and different anticancer drugs showed to be a wonderful approach in the treatment of cancer enabling the co-delivery of anticancer drugs with versatile modes of action in an accurate manner in an attempt to enhance the efficacy, benefit from the synergism between the drugs as well as to minimize the development of multi-drug resistance. The main challenge point is the early detection and management of any developed adverse effect

Engineering nanomedicines for immunogenic eradication of cancer cells: Recent trends and synergistic approaches

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment (TME) leading to failure of immune response. Numerous therapeutic strategies including chemotherapy, radiotherapy, photodynamic, photothermal, magnetic, chemodynamic, sonodynamic and oncolytic therapy, have been developed to induce immunogenic cell death (ICD) of cancer cells and thereby elicit immunogenicity and boost the antitumor immune response. However, many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic response. Here, we outline the current state of using nanomedicines for boosting ICD of cancer cells. Moreover, synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints, phagocytosis, macrophage polarization, tumor hypoxia, autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were analyzed. We further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune responses. Endoplasmic reticulum localized ICD, focused ultrasound hyperthermia, cell membrane camouflaged nanomedicines, amplified reactive oxygen species (ROS) generation, metallo-immunotherapy, ion modulators and engineered bacteria are among the most innovative approaches. Various challenges, merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy

Use of cilomilast-loaded phosphatiosomes to suppress neutrophilic inflammation for attenuating acute lung injury: the effect of nanovesicular surface charge

Abstract Background Cilomilast is a phosphodiesterase 4 (PDE4) inhibitor for treating inflammatory lung diseases. This agent has a narrow therapeutic index with significant adverse effects on the nervous system. This study was conducted to entrap cilomilast into PEGylated phosphatidylcholine-rich niosomes (phosphatiosomes) to improve pulmonary delivery via the strong affinity to pulmonary surfactant film. Neutrophils were used as a cell model to test the anti-inflammatory activity of phosphatiosomes. In an in vivo approach, mice were given lipopolysaccharide to produce acute lung injury. The surface charge in phosphatiosomes that influenced the anti-inflammatory potency is discussed in this study. Results The average diameter of the phosphatiosomes was about 100 nm. The zeta potential of anionic and cationic nanovesicles was − 35 and 32 mV, respectively. Cilomilast in both its free and nanocapsulated forms inhibited superoxide anion production but not elastase release in activated neutrophils. Cationic phosphatiosomes mitigated calcium mobilization far more effectively than the free drug. In vivo biodistribution evaluated by organ imaging demonstrated a 2-fold ameliorated lung uptake after dye encapsulation into the phosphatiosomes. The lung/brain distribution ratio increased from 3 to 11 after nanocarrier loading. The intravenous nanocarriers deactivated the neutrophils in ALI, resulting in the elimination of hemorrhage and alveolar wall damage. Only cationic phosphatiosomes could significantly suppress IL-1β and TNF-α in the inflamed lung tissue. Conclusions These results suggest that phosphatiosomes should further be investigated as a potential nanocarrier for the treatment of pulmonary inflammation