Identification of bioactive metabolites from Ficus carica and their neuroprotective effects of Alzheimer's disease

Neurodegenerative disease including Alzheimer’s disease is a major cause of long-term disability. Oxidative stress is frequently implicated as one of the key contributing factors to neurodegenerative diseases. Protection against neuronal damage remains a great challenge for researchers. Ficus carica (commonly known as fig) is a species of great antioxidant nutritional value comprising a protective mechanism against innumerable health disorders related to oxidative stress as well as Alzheimer’s disease. The purpose of this work was to characterize the non-polar active metabolites in Ficus carica endocarp, mesocarp, and exocarp. Crude extracts were prepared using several extraction solvents, which included 1:1 water: ethylacetate, acetone and methanol. The dried extracts were then solvent partitioned between equivalent amounts of water and ethylacetate. Purification and fractionation were accomplished by high-throughput chromatography. The isolated metabolites were tested on their effect on human neuroblastoma cell line by cell viability test and cell cytotoxicity assay with acrolein. Molecular weights of the active metabolites were determined via LC–HRESIMS and GC-EIMS. Metabolomic profiling was performed to identify the active metabolites by using differential expression analysis software (Mzmine) and SIMCA for multivariate analysis. Structural elucidation and identification of the interested active metabolites were studied by 1-D and 2-D NMR. Significant differences in bioactivity against a concentration-dependent assay on acrolein radicals were observed between the three fruit parts. However, metabolites obtained from mesocarp and the endocarp demonstrated bioactivity to scavenge ROS radical. NMR profiling demonstrated that aliphatic compounds such as γ-sitosterol tend to induce neuronal bioactivity and exhibited bioactivity on the cell viability assay. γ-Sitosterol was found in higher concentrations in the mesocarp and was considered as one of the major phytosterol in Ficus carica

Segmental aging underlies the development of a Parkinson phenotype in the AS/AGU rat

There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4a expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson's disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging

Anti-mGluR1 encephalitis: Case illustration and systematic review

BackgroundThe literature for immune-mediated neurological disorders is evolving like no other field of neurological illnesses. Many new antibodies or disorders have been described in the last decade. The cerebellum is a brain structure susceptible to these immune-mediated pathologies, and anti-metabotropic glutamate receptor 1 (mGluR1) antibody has a predilection to the cerebellar tissue. Anti-mGluR1 encephalitis is a rare autoimmune disease affecting the central and peripheral nervous systems, triggering an acute or subacute cerebellar syndrome with varying degrees of severity. Anti-mGluR1 encephalitis is a rare autoimmune disease affecting the central nervous system. We aimed to systematically review reported cases of anti-mGluR1 encephalitis and summarize their clinical presentation, management, outcomes, and case reports.MethodsA search of the PubMed and Google Scholar databases was conducted and included all cases of anti-mGluR1 encephalitis published in English before October 1, 2022. A comprehensive systematic review was conducted using “metabotropic glutamate receptor type 1,” “mGluR1,” autoantibodies,” “autoantibodies,” “autoimmunity,” and “antibody” as keywords. The risk of bias assessment of the evidence was performed using appropriate tools. The qualitative variables were presented as frequency and percentage.ResultsIncluding our case, 36 cases of anti-mGluR1 encephalitis (19 males, median age 52.5 years, 11.1% pediatric cases) have been reported. The most common clinical manifestations are ataxia, dysarthria, and nystagmus. Initial imaging was normal in 44.4% of patients; however, 75% of patients showed abnormality later in the disease course. The first-line therapy options include glucocorticoids, intravenous immunoglobulin, and plasma exchange. Rituximab is the most commonly used second-line treatment. Complete remission was achieved in only 22.2% of patients, and 61.8% were disabled by the end of their course.ConclusionAnti-mGluR1 encephalitis manifests as symptoms of cerebellar pathology. Although the natural history has not been completely elucidated, early diagnosis with prompt initiation of immunotherapy could be imperative. Any patient suspected to have autoimmune cerebellitis should be tested for the presence of anti-mGluR1 antibody in the serum and cerebrospinal fluid. Escalation to an aggressive therapy approach should be applied in cases that do not respond to first-line therapies, and extended follow-up durations are required in all cases

Development of a GC-MS method and analysis of phenolic acids in fruit and spice matrices and evaluation of their antioxidant capacity

The aim of the present study was to develop a specific and quantitative assay to determine the individual concentrations of naturally occurring phenolic acids and their metabolites in food; then evaluate the antioxidant capacity of the quantified phenolic acids using different assays. A GC/MS method was developed for the quantification of ten commonly present phenolic acids in plant foods. Target analytes were the benzoic acid based phenolic acids - anisic, gallic, p-hydroxy benzoic, o-salicylic, protocatechuic, and vanillic acids, together with the cinnamic acid based phenolic acids - caffeic, p-coumaric, ferulic and sinapinic acids. Deuterated Anisic D7 acid was used as an internal standard to achieve accurate and reliable quantification. Purification was accomplished using C18 solid phase extraction cartridges (ENVI Chrome P, Supelco); sample extracts were derivatized prior to GC-MS analysis using BSTFA and pyridine (4:1 V/V). Resolution and quantification of all compounds were excellent with linear calibration curves over a wide range (0-500 ng/ml) and correlation coefficient (R2) of 0.999. Relative standard deviation (RSD) and response factors (RF) were satisfactory (≥1.1 and >3 respectively) and within the acceptable limits of bioanalytical method validation. The adapted method was applied to different varieties of fresh and sundried Saudi Arabian dates as well as Achacha fruit and eleven selected spices. The results revealed that phenolic acids are present in plant foods mostly in bound form as esters or glycosides. The lipophilic and hydrophilic antioxidant activities of all selected samples were examined using the ORAC assay. In addition, the antioxidant capacity of the identified free and bound phenolic acids was measured by different assays including ORAC, ABTS, DPPH and FCR. The results indicate that hydrophilic antioxidants are higher than lipophilic antioxidants in plant foods and the high phenolic acids content was not correlated with high antioxidant activity. Moreover different antioxidant capacity assays showed different results on the same phenolic acid extracts from different samples (P-value> 0.05). In conclusion the method presented is robust, safe, sensitive and generally applicable to the analysis of free and bound phenolic acids in food samples. The data obtained is sufficiently reliable to be included in food composition databases

Ageing in the mammalian brain

With a globally ageing population diseases associated with this natural process are becoming major issues worldwide. Research into the process of ageing and its concomitant issues is rapidly expanding; the need for new tools and models to investigate this rapidly expanding arena of research is paramount. The discovery of a spontaneous mutation in the AS rat strain which introduces a premature stop mutation into the gene encoding protein kinase C (PKC lead to the development of a model for one such age related disorder, Parkinson‟s disease. Consequently, this model has been selected to investigate age related changes in specific areas of the brain (the cerebellum, basal ganglia, cerebral cortex and brainstem). These regions were selected because they have previously been shown to demonstrate changes with age (cerebellum, cerebral cortex and basal Ganglia), they show differences between the AS and AS/AGU strains (basal ganglia) or they show differences in PKC knockout models (cerebellum). The Brainstem was selected as it shows little change due to age and shows no differences in PKC knockouts or AS/AGU rats. This study used established qPCR methods to measure a validated biomarker of ageing, CDKN2A (the transcript for p16INK4a) in the brains of these rats to determine whether this model is in fact a genuine model for accelerated ageing. This thesis demonstrates that CDKN2A expression, in combination with senescence-associated -galactosidase staining, provides clear evidence of accelerated ageing in the brains of AS/AGU rats when compared with the parent AS strain. These investigations were furthered by an investigation of members of the Sirtuin family of proteins. The changes in expression of these Sirtuins indicates that there may be increased levels of cellular stress, disruption of metabolism and DNA damage in the AS/AGU rats, this would be congruent with the accelerated ageing phenotype present in this strain. Furthermore, the levels of these Sirtuins were in line with the predictions from the MTR trinity in regards to the accelerated ageing phenotype. Whilst some of the changes in senescence and metabolic disruption may be attributable to the PKC mutation in the AS/AGU rats, it would appear that there is some element of accelerated ageing that is independent of this mutation

Using Dooyeweerd's aspects to understand down to earth issues in use of medical records

This research is about experience of using electronic medical records (EMR). Chapter 1introduces and justifies the main research question “How can Down To Earth issues that areimportant in uses of EMR be studied by using Dooyeweerd's aspects?” Down To Earth (DTE) issues are those meaningful in daily uses of patient medical recordsrather than those meaningful for management, ICT suppliers and academics. A survey of the literature (Chapter 2) reveals that high level issues rather than DTE issues aremostly discussed. Even where the literature mentions DTE issues, there is a need for threeresearch activities1-reveal DTE issues to bring to light those which are significant and important2-uncover the hidden issues and the reasons for these hidden issues.3-classify the issues to identify which of these are the most significant After considering a range Information Systems (IS) Theories, Dooyeweerd’s aspects emergedas a suitable theoretical framework to reveal, uncover and classify DTE issues (Chapter 3).Interpretivism was the philosophical lens of choice given that it primarily seeks meaning andinsights, much in keeping with this research which looks for the meaningful issues ofMedical Record (MR) users and aims to gain insights into DTE issues of MR uses. So aninterpretive approach is used (Chapter 4). Users of MR are interviewed and Dooyeweerd’saspects are employed to analyse the transcripts and a selection of excerpts from papers(Chapter 5). Using the results of aspectual analysis of these texts, five quantitative and qualitativecomparisons are made of the following (Chapter.6) The comparison of hospitalsThe comparison of paper and electronic records.The comparison of nursesThe comparison of nationalitiesThe research has three main findings (Chapter 7). 1-The meaningful DTE issues for medical record users are different from the meaningfulissues discussed in the literature. 2-Aspectual analysis enables us to reveal, uncover and classify DTE issues that aremeaningful for medical record users. 3- Each type of user tends to have a unique aspectual profile.Chapter.8 discusses limitations of the research and how this research might contribute topractice methodology and theory. The research contributes to practice of designing andevaluating EMR systems. Furthermore the research could help to generate a theory ofmedical records. Also the research offers a method for analysing DTE issues for otherresearchers in other sectors

Barbeya oleoides Leaves Extracts: In Vitro Carbohydrate Digestive Enzymes Inhibition and Phytochemical Characterization

This study investigated the in vitro inhibitory potential of different solvent extracts of leaves of Barbeya oleoides on key enzymes related to type 2 diabetes mellitus (α-glucosidase and α-amylase) in combination with an aggregation assay (using 0.01% Triton X-100 detergent) to assess the specificity of action. The methanol extract was the most active in inhibiting α-glucosidase and α-amylase, with IC_{50} values of 6.67 ± 0.30 and 25.62 ± 4.12 µg/mL, respectively. However, these activities were significantly attenuated in the presence of 0.01% Triton X-100. The chemical analysis of the methanol extract was conducted utilizing a dereplication approach combing LC-ESI-MS/MS and database searching. The chemical analysis detected 27 major peaks in the negative ion mode, and 24 phenolic compounds, predominantly tannins and flavonol glycosides derivatives, were tentatively identified. Our data indicate that the enzyme inhibitory activity was probably due to aggregation-based inhibition, perhaps linked to polyphenols