Efficacy and safety of glucagon-like peptide-2 (GLP-2) in patients with short bowel syndrome; A Systematic Review and Network Meta-analysis.

BACKGROUND: Glucagon-like peptide-2 is a highly conserved enteroendocrine hormone that appears to be a regulator promoting intestinal adaptation. We aim to summarize the evidence on the efficacy and safety of exogenous GLP-2 in patients with SBS. METHODS: We searched PubMed, Web of Science (WoS) core collection, SCOPUS, Ovid, and Cochrane Central Register of Controlled Trials through November 2022. We included clinical trials on the effect of GLP-2 on patients with SBS. Otherwise, the article was excluded. We used the Cochrane Risk of Bias II and ROBINS-I tools for quality assessment of randomized and non-randomized trials. Extracted data were analyzed qualitatively and quantitatively using a network meta-analysis model. RESULTS: We included twenty-three clinical trials with 843 patients. Patients' ages ranged from 4 to 62.4 years. Treatment doses were (0.1, 0.05, and 0.25mg/kg/day) for Teduglutide, (5, 10mg/week) for Apraglutide, and (0.1, 1, 10mg/day) for Glepaglutide. Treatment duration ranged from one to thirty-two weeks. Regarding citrulline level, the result showed that Teduglutide 0.1mg/kg/day had the highest mean difference (MD=14.77, 95% CI [10.20;19.33]), followed by Teduglutide 0.05mg/kg/day and Teduglutide 0.025mg/kg (MD=13.04, 95% CI [9.79;16.29], and (MD=7.84, 95% CI [2.42;13.26]), respectively. Additionally, the effect estimate showed significant differences among all Teduglutide dose groups and control. Different doses of Glepaglutide were analyzed to assess the effect on alkaline phosphatase levels where Glepaglutide 0.1mg/day showed a significantly higher mean difference (MD=20.71, 95% CI [2.62;38.80]) compared to Glepaglutide 1-mg (the reference), and Glepaglutide 10-mg (MD=8.45, 95% CI [-10.72; 27.62]. However, the indirect estimate for Glepaglutide 0.1-mg vs 10-mg has an MD of (-14.57, 95% CI [-437.24; 148.11]. While Glepagutide 10-mg has an MD of (8.45, 95% CI [-10.72; 27.62]) for the network estimate. Regarding safety outcomes, there was no significant difference among all Teduglutide and Apraglutdie dose groups compared to the control. Catheter-related bloodstream infection (CRBSI) was the most common adverse event reported with Apraglutide, Teduglutide, and Glepaglutide. CONCLUSION: Despite the small number of patients in the included studies and variable follow-up duration, GLP-2 seems safe and effective in patients with SBS. GLP-2 showed a positive effect on increasing plasma citrulline level and decreasing alkaline phosphatase level. OTHER: We registered for the study on PROSPERO (CRD42023393589). There was no funding for this review.

ATR-IR and EPR spectroscopy for following the membrane restoration of isolated cortical synaptosomes in aluminium-induced Alzheimer's disease - Like rat model.

Synaptosomal membrane peroxidation and alteration in its biophysical properties are associated with Aluminium (Al) toxicity that may lead to cognitive dysfunction and Alzheimer's disease (AD) like pathogenesis. Here we investigated the therapeutic potential of Lepedium sativum (LS) as a natural anti-inflammatory, antioxidant and as acetyl cholinesterase inhibitor in treating Al induced AD-like in rat model. We utilized ATR-IR spectroscopy to follow the restoration in the damaged membrane structure of isolated rat cortical synaptosomes and its biophysical properties, electron paramagnetic resonance (EPR) spin trapping to follow NADPH oxidase activity (NOX), and EPR spin labelling in response to LS treatment after Al intoxication. We measured the concentration of Ca2+ ions in rat cortical tissue by inductively coupled plasma (ICP), the brain atrophy/curing and hydrocephalus by magnetic resonance imaging (MRI) besides light microscope histopathology. Our results revealed significant increase in synaptosomal membrane rgidification, order, lipid packing, reactive oxygen species (ROS) production and Ca2+ ion concentration as a result of Al intoxication. The dramatic increase in Ca2+ ion concentration detected in AD group associated with the increase in synaptic membrane polarity and EPR-detected order S-parameter suggest that release of synaptic vesicles into synaptic cleft might be hindered. LS treatment reversed these changes in synaptic membranes, and rescued an observed deficit in the exploratory behaviour of AD group. Our results also strongly suggest that the synaptosomal membrane phospholipids that underwent free radical attacks mediated by AlCl3, due to greater NOX activity, was prevented in the LS group. The results of ATR-IR and EPR spectroscopic techniques recommend LS as a promising therapeutic agent against synaptic membrane alterations opening a new window for AD drug developers.

Synchrotron Fourier transform infrared microspectroscopy (sFTIRM) analysis of Al-induced Alzheimer's disease in rat brain cortical tissue.

Aluminium (Al) is reported to promote beta amyloid (Aß) aggregation, free radical production and disturb acetylcholine metabolism leading to cognitive dysfunction that are strongly associated with Alzheimer's disease (AD). Here we utilized synchrotron Fourier transform infrared microspectroscopy (sFTIRM) to analyse the fine structure of proteins and lipids in the rat cortical brain tissues in response to AlCl3 toxicity and Lepidium sativum (LS) treatment after 42 and 65 days. For statistical analysis, we used principal component analysis (PCA). Our results showed profusion of gauche rotomers form in membrane lipid acyl chains that increases the membrane fluidity and disorder only in AD group indicated by the detected sνCH2 band shift to higher frequency. All half bands width (HBW) values of the decomposed amide I band showed marked decrease in AD group compared to the other tested groups, together with an increase in the amounts of ß-sheets (1641 cm-1) protein and random coil structure (1654 cm-1). These were indicated by a drastic increase in the percentage areas ratios of (1638 cm-1/1654 cm-1) and (1641 cm-1/1654 cm-1) that may be attributed to a stronger the hydrogen bonds that stabilize the protein conformational structure and/or the increase of the ß-strand length due to misfolded Aß formation in response to Al toxicity through transit phase/phases dominated by random coil structure. In curative group, LS treatment reversed these changes and restored the protein and lipid integrities. To conclude, sFTIRM is a powerful tool that shed light on the biomolecular structure of AD-like cortical brain tissue and considered the therapeutic potential of LS as a promising natural AD treatment.

ATR-IR and EPR spectroscopy for detecting the alterations in cortical synaptosomes induced by aluminium stress.

Aluminium (Al) is reported to promote free radical production, decrease the antioxidant enzyme status and disturb the enzyme activity involved in acetylcholine metabolism leading to cognitive dysfunction that are strongly associated with Alzheimer's disease (AD) pathogenesis. This work aimed at investigating the effect of Al-toxicity on synaptosomal membrane biophysical properties and lipid peroxidation during 65 days. We utilized ATR-IR spectroscopy to study the changes in membrane biochemical structure and biophysical properties of isolated rat cortical synaptosomes, and EPR spin trapping and labeling to follow NADPH oxidase activity and changes of membrane order parameter, respectively. The results showed increase in membrane fluidity and disorder in early 21d of AlCl3 treatment, while after 42d the membrane rigidity, packing, and order increased. The late (65d) an increase in the amount of unsaturated fatty acids, the accumulation of lipid peroxide end products, and ROS production were detected in rat cortex synaptosomes mediated by Al toxicity and oxidative stress (OS). A dramatic increase was also detected in Ca2+ level, synaptic membrane polarity, and EPR-detected order S-parameter. These outcomes strongly suggest that the synaptosomal membrane phospholipids underwent free radical attacks mediated by AlCl3 due to greater NOX activity, and the release of synaptic vesicles into synaptic cleft might be hindered. The adopted spectroscopic techniques have shed light on the biomolecular structure and membrane biophysical changes of isolated cortical synaptosomes for the first time, allowing researchers to move closer to a complete understanding of pathological tissues.

Biocompatibility enhancement of graphene oxide-silver nanocomposite by functionalisation with polyvinylpyrrolidone.

Several materials such as silver are used to enhance graphene oxide (GO) sheets antimicrobial activity. However, these toxic materials decrease its biocompatibility and hinder its usage in many biological applications. Therefore, there is an urgent need to develop nanocomposites that can preserve both the antimicrobial activity and biocompatibility simultaneously. This work highlights the importance of functionalisation of GO sheets using Polyvinylpyrrolidone (PVP) and decorating them with silver nanoparticles (AgNPs) in order to enhance their antimicrobial activity and biocompatibility at the same time. The structural and morphological characterisations were performed by UV-Visible, Fourier transform infrared (FTIR), and Raman spectroscopic techniques, X-ray diffraction (XRD), and high-resolution transmission electron microscopy (HR-TEM). The antimicrobial activities of the prepared samples against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans were studied. The cytotoxicity of prepared materials was tested against BJ1 normal skin fibroblasts. The results indicated that the decoration with AgNPs showed a significant increase in the antimicrobial activity of GO and FGO sheets, and functionalisation of GO sheets and GO-Ag nanocomposite with PVP improved the cell viability about 40 and 35%, respectively.