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Epigallocatechin gallate (EGCG) is a polyphenol present in green tea (Camellia sinensis), which has revealed anti-cancer effects toward a variety of cancer cells in vitro and protective potential against neurodegenerative diseases such as Alzheimer's and Parkinson's. Unfortunately, EGCG presents disappointing bioavailability after oral administration, primarily due to its chemical instability and poor absorption. Due to these limitations, EGCG is currently not used in medication, but only as a dietary supplement in the form of green tea extract. Therefore, it needs further modifications before being considered suitable for extensive medical applications. In this article, we review the scientific literature about EGCG derivatives focusing on their biological properties and potential medical applications. The most common chemical modifications of epigallocatechin gallate rely on introducing fatty acid chains or sugar molecules to its chemical structure to modify solubility. Another frequently employed procedure is based on blocking EGCG's hydroxyl groups with various substituents. Novel derivatives reveal interesting properties, of which, antioxidant, anti-inflammatory, antitumor and antimicrobial, are especially important. It is worth noting that the most promising EGCG derivatives present higher stability and activity than base EGCG., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Intestinal failure-associated liver disease (IFALD) is a severe liver injury occurring due to factors related to intestinal failure and parenteral nutrition administration. Different approaches are studied to reduce the risk or ameliorate the course of IFALD, including providing omega-3 fatty acids instead of soybean oil-based lipid emulsion or administering active compounds that exert a hepatoprotective effect. This study aimed to develop, optimize, and characterize magnolol-loaded intravenous lipid emulsion for parenteral nutrition. The preformulation studies allowed for chosen oils mixture of the highest capacity of magnolol solubilization. Then, magnolol-loaded SMOFlipid was developed using the passive incorporation method. The Box-Behnken design and response surface methodology were used to optimize the entrapment efficiency. The optimal formulation was subjected to short-term stress tests, and its effect on normal human liver cells and erythrocytes was determined using the MTT and hemolysis tests, respectively. The optimized magnolol-loaded SMOFlipid was characterized by the mean droplet diameter of 327.6 ± 2.9 nm with a polydispersity index of 0.12 ± 0.02 and zeta potential of -32.8 ± 1.2 mV. The entrapment efficiency of magnolol was above 98%, and pH and osmolality were sufficient for intravenous administration. The magnolol-loaded SMOFlipid samples showed a significantly lower toxic effect than bare SMOFlipid in the same concentration on THLE-2 cells, and revealed an acceptable hemolytic effect of 8.3%. The developed formulation was characterized by satisfactory stability. The in vitro studies showed the reduced cytotoxic effect of MAG-SMOF applied in high concentrations compared to bare SMOFlipid and the non-hemolytic effect on human blood cells. The magnolol-loaded SMOFlipid is promising for further development of hepatoprotective lipid emulsion for parenteral nutrition.

Background: Glioblastoma (GBM) is the most frequently occurring primary malignant central nervous system tumor, with a poor prognosis and median survival below two years. Administration of a combination of non-steroidal anti-inflammatory drugs and natural compounds that exhibit a curative or prophylactic effect in cancer is a new approach to GBM treatment. This study aimed to investigate the synergistic antitumor activity of etoricoxib (ETO) and cannabidiol (CBD) in a GBM cell line model, and to develop poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for these two substances., Methods: The activity of ETO+CBD was determined using the MTT test, cell-cycle distribution assay, and apoptosis analysis using two GBM cell lines, namely, T98G and U-138 MG. The PLGA-based NPs were developed using the emulsification and solvent evaporation method. Their physicochemical properties, such as shape, size, entrapment efficiency (EE%), in vitro drug release, and quality attributes, were determined using scanning electron microscopy, diffraction light scattering, high-performance liquid chromatography, infrared spectroscopy, and differential scanning calorimetry., Results: The combination of ETO and CBD reduced the viability of cells in a dose-dependent manner and induced apoptosis in both tested GBM cell lines. The developed method allowed for the preparation of ETO+CBD-NPs with a spherical shape, mean particle size (MPS) below 400 nm, zeta potential (ZP) values from -11 to -17.4 mV, polydispersity index (PDI) values in the range from 0.029 to 0.256, and sufficient EE% of both drugs (78.43% for CBD, 10.94% for ETO)., Conclusions: The combination of ETO and CBD is a promising adjuvant therapeutic in the treatment of GBM, and the prepared ETO+CBD-NPs exhibit a high potential for further pharmaceutical formulation development.

Background: Glioblastoma (GBM) is an extremely invasive and heterogenous malignant brain tumor. Despite advances in current anticancer therapy, treatment options for glioblastoma remain limited, and tumor recurrence is inevitable. Therefore, alternative therapies or new active compounds that can be used as adjuvant therapy are needed. This study aimed to develop, optimize, and characterize honokiol-loaded nanoemulsions intended for intravenous administration in glioblastoma therapy., Methods: Honokiol-loaded nanoemulsion was developed by incorporating honokiol into Lipofundin MCT/LCT 20% using a horizontal shaker. The Box-Behnken design, coupled with response surface methodology, was used to optimize the incorporation process. The effect of the developed formulation on glioblastoma cell viability was determined using the MTT test. Long-term and short-term stress tests were performed to evaluate the effect of honokiol on the stability of the oil-in-water system and the effect of different stress factors on the stability of honokiol, respectively. Its physicochemical properties, such as MDD, PDI, ZP, OSM, pH, and loading efficiency (LE%), were determined., Results: The optimized honokiol-loaded nanoemulsion was characterized by an MDD of 201.4 (0.7) nm with a PDI of 0.07 (0.02) and a ZP of -28.5 (0.9) mV. The LE% of honokiol was above 95%, and pH and OSM were sufficient for intravenous administration. The developed formulation was characterized by good stability and a satisfactory toxicity effect of the glioblastoma cell lines., Conclusions: The honokiol-loaded nanoemulsion is a promising pharmaceutical formulation for further development in the adjuvant therapy of glioblastoma.

Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing beta-cells in the pancreas, caused by the interplay of genetic and environmental factors. Despite the introduction of advanced technologies for diabetes management, most patients fail to achieve target glycemic control, and T1D still has a high burden of long-term end-organ complications. Over several decades, multiple clinical trials have attempted to find prevention for T1D in at-risk individuals or to stabilize, ultimately reverse, the disease in those with T1D. To date, T1D remains yet incurable condition; however, recently improved understanding of the natural history of the disease may lead to new strategies to preserve or improve beta-cell function in those at increased risk and T1D patients. This publication aims to provide an overview of past experiences and recent findings in the prevention of T1D., Competing Interests: The authors declare no conflict of interest.

Introduction: Acute central nervous system (CNS) damage in a patient who has received organ transplant is an extremely difficult and complex clinical issue that spans a wide spectrum of differential diagnoses with ischemia, post-transplant lymphoproliferative disorders (PTLDs), infections, lymphomas, and progressive multifocal leukoencephalopathy (PML). PTLDs are a clinically and histopathologically heterogeneous group of diseases that most often occur in heavily immunocompromised populations after solid organ transplantation (SOT), probably related to the infection or reactivation of Epstein-Barr virus (EBV) infection, whereas PML is an infectious disease caused by the John Cunningham virus (JCV)., Case Description: A 56-year-old female, 20 years after renal transplantation from a deceased donor, was admitted to the hospital as an emergency due to sensory aphasia and memory disorders. Computed tomography (CT) examination revealed a diffuse expansive process in the temporo-parieto-occipital and left frontal area. Magnetic resonance imaging (MRI) results suggested changes associated with PML; however, JCV was not found in the cerebrospinal fluid. The disorders progressed quickly, both clinically and radiologically-the patient developed central facial palsy, paresis of limbs, and positive Babinski sign on the left. A second radiological examination (CT) also suggested PML. Due to the rapid deterioration of the patient's general condition, further diagnostic examinations (magnetic resonance with contrast and brain stereotactic biopsy) could not be performed. After almost 2 months of the commencement of the diagnostic process, the patient died. Autopsy revealed that the cause of death was acute CNS damage in the course of monomorphic PTLD (CNS-PTLD)., Conclusion: Rapid deterioration of mental status can be the first symptom of CNS-PTLD, a dangerous and life-threatening condition in immunocompromised patients after solid organ transplantation., (Copyright © 2018 Elsevier Inc. All rights reserved.)