Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor survival outcomes. We utilized comprehensive multi-omics analyses of CSF from patients with lymphoma LMD to demonstrate an immunosuppressive cellular microenvironment and identified dysregulations in proteins and lipids indicating neurodegenerative processes. Strikingly, we found a significant accumulation of toxic branched-chain keto acids (BCKA) in the CSF of patients with LMD. The BCKA accumulation was found to be a pan-cancer occurrence, evident in lymphoma, breast cancer, and melanoma LMD patients. Functionally, BCKA disrupted the viability and function of endogenous T lymphocytes, chimeric antigen receptor (CAR) T cells, neurons, and meningeal cells. Treatment of LMD mice with BCKA-reducing sodium phenylbutyrate significantly improved neurological function, survival outcomes, and efficacy of anti-CD19 CAR T cell therapy. This is the first report of BCKA accumulation in LMD and provides preclinical evidence that targeting these toxic metabolites improves outcomes.

Bilosomes are innovative vesicular carriers containing bile salt with a non-ionic surfactant. Being highly flexible, bilosomes can squeeze themselves through the skin carrying the drug to the action site and improving its skin penetration. The objective of this research was to encapsulate niflumic acid (NA), a non-steroidal anti-inflammatory drug into Brij® integrated bilosomes (BIBs) for effective treatment of osteoarthritis through transdermal delivery. BIBs were formulated using 100 mg of Span 20 with different amounts of sodium cholate (NaC), sodium taurocholate (NaTC), or sodium glycocholate (NaGC) as bile salt, with the addition of 5 mg of Brij-93 or Brij-35. BIBs were prepared utilizing ethanol injection method with the application of (31 × 22) complete factorial design using Design-Expert® software. The optimal BIBs formulation determined was (B5) which contains 5 mg of NaTC used as bile salt and 5 mg of Brij-93. B5 exhibited entrapment efficiency% = 95.21 ± 0.00%, particle size = 373.05 ± 0.07 nm, polydispersity index = 0.27 ± 0.01, and zeta potential = –32.00 ± 0.00 mV. It also had a high elasticity with a spherical shape. B5 gel displayed a sustained release profile with a significantly 2.3 folds’ higher drug permeation percent across rat skin than that permeated from NA gel. Moreover, in vivo anti-osteoarthritic and histopathological studies assured the efficacy and safety of B5 gel and its superiority over NA gel. Generally, the outcomes confirmed the great efficacy of NA loaded BIBs for the topical treatment of osteoarthritis. © 2023 Elsevier B.V.

Hedera helix L. (family Araliaceae) is classified as a conventional plant used as a medicinal product in the cure and prevention of upper respiratory tract inflammation and infection due to its secretolytic and broncholytic effects. Our research was conducted to authenticate the anti-inflammatory effect of ivy leaves extract in the prevention of acute lung injury (ALI) caused by intranasal administration of lipopolysaccharides (LPS). In-vitro antimicrobial, anti-inflammatory, and anti-oxidant were evaluated, in addition to the in-vivo acute lung inflammation model induced by LPS in mice. The animals were divided into seven groups randomly (each group containing 10 mice): control negative (saline only), control positive (LPS group), standard (Dexamethasone 2 mg/kg), ethanolic ivy leaves extract (EIE, 100 mg/kg), ethanolic ivy leaves extract (EIE, 200 mg/kg), saponin rich fraction (SRF, 100 mg/kg) and phenolic rich fraction (PRF,100 mg/kg). Right lungs were homogenized to determine the levels of SOD, MDA, catalase, IL-10, TNF-α, NO, IL-1β, IL-6, PGE2, and MPO. Left lungs were excised for histopathology and histomorphometry. Immunohistochemistry of Cox-2 and TNF-α levels were measured. Additionally, Western blotting was used to determine the levels of phosphorylated MAPK. The data showed that the oral supplementation with EIE, 200 mg/kg significantly (P<0.05) decreased the pro-inflammatory mediators, and oxidative stress biomarkers induced by LPS. Interestingly, the phenolics showed promising activity, therefore they are responsible for the action. The ethanolic extract was also standardized through HPLC analysis for its content of rutin. In conclusion, the standardized ivy leaf extract could be advised for acute lung injury for its antimicrobial, anti-oxidant, and anti-inflammatory activities.

Registries resemble a systematic way of collecting data for a specific theme or a population. As well-built registries represent a wealth of information for scientists, huge investments are paid to ensure their quality. The quality of the data gathered depends on a rigorous process of data validation and updating and, the comprehensiveness of the sources providing the data. Therefore, the data release may take years after the data collection. The advancement in information and computer technologies has helped in the progress of building better disease registries. In the process of learning from experiences in building registries, we aim in this presentation at discussing the lessons learned from building cancer (and other diseases) registries in different setups to facilitate building better ophthalmological registries. Moreover, to discuss the most common mistakes that lead to delayed collection and publishing of the data.

Fabrication of scaffolds for nerve regeneration is one of the most challenging topics in regenerative medicine at the moment, which is also interlinked with the development of biocompatible substrates for cells growth. This work is targeted towards the development of green biomaterial composite scaffolds for nerve cell culture applications. Hybrid scaffolds of hydroxyethyl cellulose/glycine (HEC/Gly) composite doped with different concentrations of green ruthenium oxide (RuO2) were synthesized and characterized via a combination of different techniques. X-rays diffraction (XRD) and differential scanning calorimetry (DSC) analyses showed a crystalline nature for all the samples with noticeable decrease in the peak intensity of the fabricated scaffolds as compared to that for pure glycine. Fourier transform infrared spectroscopy (FTIR) tests revealed an increase in the vibrational bands of the synthesized RuO2 containing scaffolds which are related to the functional groups of the natural plant extract (Aspalathuslinearis) used for RuO2 nanoparticles (NPs) synthesis. Scanning electron microscopy (SEM) results revealed a 3D porous structure of the scaffolds with variant features attributed to the concentration of RuO2 NPs in the scaffold. The compressive test results recorded an enhancement in mechanical properties of the fabricated scaffolds (up to 8.55 MPa), proportionally correlated to increasing the RuO2 NPs concentration in HEC/Gly composite scaffold. Our biocompatibility tests revealed that the composite scaffolds doped with 1 and 2 ml of RuO2 demonstrated the highest proliferation percentages (152.2 and 135.6%) compared to control. Finally, the SEM analyses confirmed the impressive cells attachments and differentiation onto the scaffold surfaces as evidenced by the presence of many neuron-like cells with apparent cell bodies and possessing few short neurite-like processes. The presence of RuO2 and glycine was due to their extraordinary biocompatibility due to their cytoprotective and regenerative effects. Therefore, we conclude that these scaffolds are promising for accommodation and growth of neural-like cells.

With the growing warning for accrediting the traditional combustion of fossil fuels for energy production, not only for their limited supply but also for their environmental risks (air pollution, climate change, …. etc), it became necessary to realize alternative greener and abundant sources for energy. Instead, the interest to sustain biodiesel for the energy production has recently been renewed as a replacement for petroleum diesel in conventional diesel engines. This was due to its renewable nature, low toxicity, high degradability and unique physical properties (high flash points & lubrication). Castor oil, in particular, appeared promising for biodiesel production with extremely low cloud and pour points; making it suitable for tropical climates. Blending petroleum diesel with castor oil biodiesel has been proven efficient for enhancing both the environmental effect and the kinematic flow properties of the mineral fuel. Nonetheless, because of the current market price of conventional diesel, the blended product appeared cost-ineffective; steering research to tune the use of castor oil biodiesel alone. In this study, a simple method is recommended to produce biodiesel from castor oil by a transesterification process. The effect of mixing time of oil and alcohol is optimized with a thorough analysis to optimize the best condition for the biodiesel production © 2006-2022 Asian Research Publishing Network (ARPN). All rights reserved

Bioethanol is a promising biofuel produced from agricultural wastes. The problem is that the bioconversion of cellulose to bioethanol takes a long time for excellent results. Predominantly, efficient enzymes and active microorganisms (yeast) can enhance the enzymatic saccharification and fermentation bioprocesses, respectively. The addition of nutrients and electron acceptors in form of nanomaterials was found to modify the bioenvironment and to biostimulate the microorganisms to accomplish the target bioprocesses efficiently. The objective of this investigation was to increase bioethanol production from agricultural wastes using nanomaterials. In this study, the bioethanol production from potato peels (as an example of agricultural wastes) was increased using ZnO nanomaterials and ZnO/g-C3N4 nanomaterials with the concentration of 5, 10, 15, 50, 100, and 150 mg/L each as well as the control (without the addition of nanomaterials). It was hypothesized that yeast treatment with nanomaterials (nutrients) leads to biostimulate yeast cells and increases cell activity. Consequently, it is hypothesized that these procedures increase bioethanol production from potato peels over a shorter Hydraulic Retention Time (HRT), i.e., residence time. It was found that the biostimulation of the fungi (yeast) Saccharomyces cerevisiae using 150 mg/L of ZnO/g-C3N4 nanomaterials generated the highest bioethanol concentration of 33.2% compared to all other treatments. © 2022 National Information and Documentation Center (NIDOC)