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Understanding the genetic, molecular, and cellular basis of ageing as the biggest risk factor of Alzheimer's disease
Get PDFAlzheimer’s disease (AD) is one of the leading causes of dementia. The disease is characterized by atrophy of brain tissue, with major physiological, molecular, and anatomical changes being observed in the hippocampus and entorhinal region of the temporal lobe. The risk of developing this disease increases with advancing age. Ageing is a chronological phenomenon wherein a considerable decline is observed in physiological functions due to the complex interplay of various exogenous and endogenous factors such as genetic construction, elevated levels of ROS, decrease in the telomerase activity, and epigenetic factors such as methylation of DNA, histone modification etc. The physiological and molecular changes in an ageing person especially in neurons overlap considerably with those observed during the progression of AD. This article highlights various factors responsible for ageing as well as AD with the latest review of literature. Understanding the factors that bring about the fated changes and how they are associated with the progression of disease can open new doors to bring about better treatment options and help cure an otherwise incurable disease.
DOI: http://dx.doi.org/10.5281/zenodo.632379
Phenolic profile and biological activities of Aloe barbadensis (Miller) from western Algeria
Get PDFAloe vera is widely used in conventional medicine in Algeria to treat various diseases. This study aims to evaluate the chemical composition and biological activities of Aloe vera collected from western Algeria. Two extracts of ethanolic (EEA) and aqueous (AEA) were used to determine the total phenolic and flavonoid content. HPLC was applied to determine the amount of 15 compounds they contain, while the antioxidant activity was determined by the DPPH method. The antimicrobial activity experiment was conducted against five selected bacterial strains. Finally, an in vivo study on Swiss albino mice was conducted to discover the toxicity using Lorke’s method and anti-inflammatory activity using the Carrageenan method. The EEA extract shows the highest total phenol content of 37.00±0.37mg GAE/g and total flavonoid content of 9.14±0.19 mg CE/g. The AEA contains hydroxybenzoic and benzoic acid with other ingredients (0.84 and 0.82 mg/g, respectively). The EEA contains 0.93 mg/g of benzoic acid. Aloe vera has antioxidant activity with IC50 values equal to 0.821 mg/ml for EEA and 1.993 mg/ml for AEA. The AEA inhibits E. coli and S. aureus with a bacteriostatic effect; EEA is the best inhibitor of S. aureus and S. mutans with the bactericidal effect. Aloe vera is practically nontoxic (LD50 is 3800 mg/kg of the AEA and superior to 5000 mg/kg of EEA). The AEA gives the best inhibition of edema, 85.96% at (100 mg/kg). Aloe vera leaves are an important resource of polyphenols, which have interesting antioxidant power, and antimicrobial and anti-inflammatory activities.
DOI: http://dx.doi.org/10.5281/zenodo.727499
Cytological and chromosomal damages induced by tartrazine and two classes (III and IV) of caramel food dyes
Get PDFFood colors such as tartrazine (E102), ammonia caramel (E150c), sulphite ammonia caramel (E150d) are widely used in the food sector. These additives are thought to be a long-term toxicity source. The goal of our research is to emphasize the cytotoxic and genotoxic effects of the three food colors at various concentrations (0.5 %, 1 %, and 2 %) using Allium cepa test. The species is thought to be one of the best for assessing genotoxicity because of its low chromosomal number and lengthy chromosomes. The findings revealed that the three dyes have a cytotoxic impact, as seen by root growth inhibition after 120 h of incubation. The three food dyes had a genotoxic effect, as measured by a decrease in mitotic index and an increase in the frequency of chromosomal aberrations such as chromosomal bridge, stickiness, and vagrant chromosomes, at both concentrations 0.5% and 1%. At 2 %, the mitotic index was reported as 0 and several cytological abnormalities (binucleate and micronucleated cells and fragmented nuclei) were noted. However, further in vitro and in vivo cytogenetic experiments treating cytotoxicity and genotoxicity of the three food dyes using alternative test models (animals, cell lines) will be needed to better understand their mechanisms of action.
DOI: http://dx.doi.org/10.5281/zenodo.583191
Zika and SARS-CoV-2: neuroinflammation and neurodegenerative outcomes
Get PDFThrough the emergence of new viral infectious diseases, epidemics and pandemics have brought great impacts on public health in recent decades. In this review, we sought to understand the association between the neurological outcomes of two relevant infectious diseases, Zika and COVID-19. Zika can trigger neurological and ophthalmic damage in children born from infected mothers, as well as, Guillain-Barré syndrome, encephalitis, and myelitis in adults. On the other hand, the SARS-CoV-2 virus has great potential to trigger an inflammatory process in the optic nerve, with optic neuritis as the most reported pathology. Although Zika and SARS-CoV-2 infections are associated with different clinical manifestations, both may trigger similar pathogenic processes, through the induction of pro-inflammatory chemokines and cytokines release, triggering neurological and ophthalmological damage in infected patients. Elements in common have been found in both infections, such as antibodies against myelin oligodendrocyte glycoprotein, and the production of CXCL10, a chemokine responsible for the activation of several cellular types (T cells, eosinophils, monocytes and NK cells) in which are responsible to the induction of a cytokine cascade in the body. Based on these last findings, we suggest that both infections have similar activation characteristics as well as common pathogenic mechanisms associated with central nervous system involvement.
DOI: http://dx.doi.org/10.5281/zenodo.737434
Impacts of prolonged exposure to low concentration of titanium dioxide nanoparticles on cell cycle control and DNA repair
Get PDFAlthough the toxicological profile of titanium dioxide nanoparticles is not fully illuminated, large quantities of titanium dioxide nanoparticles (TiO2NPs) are now produced. In our study, we evaluated the cytotoxic and genotoxic impacts of titanium dioxide nanoparticles on different cell lines (normal, cancer and DNA repair-deficient cells). MTT assay was used to evaluate the cytotoxicity, γ-H2AX and 53BP1 assay was used to evaluate the genotoxicity and G2/M assay was used to study the impacts of titanium dioxide nanoparticles on cell cycle regulation. In this study normal and DNA repair-deficient cell lines were used to study the repair mechanism of titanium dioxide nanoparticles induced DNA damage. G2/M checkpoint maintenance was also evaluated. We demonstrate that prolonged exposure to low concentrations of titanium dioxide nanoparticles does not induce significant cytotoxicity but induces significant genotoxicity, particularly DNA double-strand breaks (DNA DSBs). Furthermore, this study demonstrated that DNA DSBs at heterochromatin region are ATM-dependent and DNA DSBs at euchromatin region are ATM-independent and DNA PKcs dependent. After exposure to titanium dioxide nanoparticles, we show that the activation of G2/M checkpoint is DNA DSBs dependent threshold as does checkpoint release. All in all, we showed that prolonged exposure to low concentrations of titanium dioxide nanoparticles does not affect cell viability but causes DNA damage and cell cycle checkpoint adaptation which may lead to genetic instability.
DOI: http://dx.doi.org/10.5281/zenodo.748742
Biological properties and polyphenols content of Algerian Cistus salviifolius L. aerial parts
Get PDFThis study evaluated the in vitro antioxidant properties, antibacterial and antifungal activities and in vivo anti-inflammatory properties, and identifying the phenolic compounds in Cistus salviifolius. The methanolic leaf extract showed the highest antioxidant activity with 6.1±1.60 µg/ml IC50 value using DPPH· and 55.5±0.20 µg/ml using Reducing Power Activity. The study revealed that the butanolic leaf extract and the aqueous leaf infusion exhibited the strongest growth-inhibiting effect against all Gram positive and Gram negative strains tested, respectively, whereas the methanolic leaf extract showed the strongest antifungal activity against the yeast tested. The MIC value for the butanolic leaf extract was 4 mg/ml against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. The pharmacotoxicological tests proved the safety of the aqueous leaf infusion, which exhibit a moderate anti-inflammatory effect, with a significant inhibition of the oedema development equal to 44.7% compared to 59.3% for the reference product diclofenac sodium. Methanolic extracts of the leaf and flower buds showed varied contents of polyphenols, flavonoids, and hydrolysable tannins; which were 228.4±11.4 mg GAE/g, 34.2±0.6 mg QE/g, and 36.9±2.6 mg TAE/g of the dry weight for leaves; and 241.1±5.4 mg GAE/g, 47.6±4.5 mg QE/g, and 22.0±1.3 mg TAE/g of the dry weight for flower buds, respectively. Analysis of the ethereal and butanolic leaf extracts using Reversed Phase High Performance Liquid Chromatographic Method coupled with a Photodiode-Array Detector identified thirteen phenolic compounds, including ascorbic acid, vanillic acid, gallic acid, quercetin, and orientin.
DOI: http://dx.doi.org/10.5281/zenodo.656150
CAR-T cell: an epitome for the cure of hematologic malignancies
Get PDFThere is an increasing reliance on modern cancer therapies on immunotherapeutic approaches such as immune checkpoint inhibitors and adoptive cell therapy (ACT), which includes tumor-infiltrating lymphocytes (TILs), T cell receptor (TCR)-modified T cells, and chimeric antigen receptor (CAR). CAR-T cell therapy provides a unique approach to redirect T cells against distinct tumor antigens. It has generated widespread interest in oncology following several clinical successes in patients suffering from chemorefractory B cell malignancies. Since CAR-T cell therapy is a novel treatment, it does not have a clearly defined protocol. However, a rough protocol for CAR-T cell production is outlined in this article. The manufacturing of clinical-grade CAR-T cells under Current Good Manufacturing Practices (cGMP) is a very critical step in CAR-T cell production. However, this step has also become a bioprocessing bottleneck that needs to be surmounted for CAR-T cell therapy to reach a global patient population. CAR-T cells have a wide-ranging application in treatment of cancer. The first trials on B-ALL patients were conducted at MSKCC with conditioning chemotherapy of cyclophosphamide only. In case of CML patients, CAR-T cells that target the IL-1RAP protein have demonstrated the ability to selectively target the quiescent CML stem cells in various preclinical studies. Apart from CML, CAR-T cells can also be used to treat Acute Myeloid Leukemia (AML). For example, CD7 targeting CAR-T cells have shown effective cytotoxic effect against AML.
DOI: http://dx.doi.org/10.5281/zenodo.651228
Antimicrobial activity of endophytic fungi associated with halophytic species Salsola vermiculata
Get PDFEndophytic fungi are known for their production of bioactive compounds with antibacterial and antifungal activity. In this study, an evaluation of the antibacterial and antifungal activity of endophytic fungi isolated from Salsola vermiculata, a halophyte species collected from Chott el Hodna, M'sila (Algeria) was carried out. The eleven isolated endophytic fungi were identified as belonging to the genera Alternaria sp., Aureobasidium sp., Phoma sp., Chrysosporium sp., Fusarium sp., Aspergillus sp., Papulaspora sp., Ulocladium sp., Humicola sp. and Pencillium sp. The antimicrobial activity of endophyte isolates was tested against phytopathogenic fungi and pathogenic bacteria using the dual culture and the agar plug diffusion methods respectively. The higher percentage inhibition of 79% was obtained by the isolate Penicillium sp. 1 against Fusarium oxysporum f.sp. ciccri. All isolated endophytic fungi showed antibacterial activity against at least one pathogenic bacterium, the greatest effect was obtained by Fusarium sp. against Pseudomonas aeruginosa ATCC 27853 and Bacillus cereus ATCC 10876 with inhibition zones of 26.33 and 25.33 mm respectively. After the comparison of the means of the zones of inhibition, the isolate Chrysosporium sp. was the most active against all pathogenic bacteria with average inhibition zones of 20.55 mm.
DOI: http://dx.doi.org/10.5281/zenodo.703603
About food safety, viruses and fish
Get PDFFish is considered an essential food in the human diet due to its nutritional qualities and is widely consumed around the world. The source of fish destined for human use and consumption is through capture fisheries and aquaculture activities. Although fish is a food of nutritional quality, it is also a food susceptible to deterioration and microbiological contamination, putting the health of consumers at risk. The different viruses are considered hazards of biological origin in food that cause various outbreaks of diseases through the consumption of fish, and products derived from their contamination in distinct phases of the food chain, through contaminated water and food handlers. Therefore, this document aims to provide an overview of foodborne diseases and causative agents, especially viruses, through a bibliographic review. In the production and commercialization of foods such as fish and products, it is considered that actions to control and prevent viral diseases, sanitary regulation and microbiological analysis tests should be involved, all in favor of the promotion and safeguarding of public health through the availability and consumption of safe food and water.
DOI: http://dx.doi.org/10.5281/zenodo.586504
Synthesis of nicotine derivatives and evaluation of their anti-bacterial activity
Get PDFUsing a convergent synthetic method, a series of nicotine derivatives were synthesized from the basic materials nicotine-N-oxide in good yields. The structures of the synthesized compounds were confirmed by spectral methods of analysis (FT-IR, 1H-NMR, and 13C-NMR). Most of the target compounds were tested for antibacterial activity against five kinds of bacteria; the tested compounds exhibited varying levels of activity against both gram-negative and gram-positive bacteria. The results of bioactivities showed that some of the target compounds exhibited good antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes, and Klebsiella pneumoniae. In addition, the broad spectrum anti-microbial action of nicotine derivatives developed in the present study may find immense applications in formulating new disinfection or decontamination strategies against widely spreading pathogens of clinical significance.
DOI: http://dx.doi.org/10.5281/zenodo.699073