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Blocking IgE with L-glutamic acid analogs as an alternative approach to allergy treatment
Get PDFIgE-mediated allergic diseases have increased in the last decades. The most prevalent allergens from these seeds are Ric c1 and Ric c3, isoforms of 2S albumin. These allergenic proteins cross-react with allergens from peanut, shrimp, fish, corn, gramineous, house dust, and tobacco. The usual allergy treatment employs antihistaminic, immunotherapies and, omalizumab (Xolair)-based anti-IgE therapy. However, antihistaminics relieve symptoms, and the high cost of omalizumab limits its use for continuous treatment. We propose an alternative immunotherapeutic approach, denoted “IgE-blockage” by L-glutamic acid or modified-glutamic acid. Six compounds, D-glutamic acid, L-glutamic acid, N-methyl-L-glutamic acid, N-acetyl-L-glutamic acid, N-(4-nitrobenzoyl)-L-glutamic acid, and N-carbamyl-L-glutamic, were tested as a blocker. To evaluate motor coordination and the sedative/hypnotic activity of L-glutamic acid, a rota-rod test and a thiopental sodium-induced sleeping test were used. The compounds, L-glutamic acid and L-nitrobenzoyl glutamic acid, were the most active compounds to block the interaction of castor allergens with IgE. These compounds also prevent cross-responses with allergens from food sources and inhalants that cross-react with them. In the sleeping test, the groups that received L-glutamic acid at doses of 10 and 30 mg/kg had a sleeping time similar to the vehicle control group. No changes in the animals' behavior were observed and there was no difference between the L-glutamic acid groups and the vehicle control groups in the rota-rod test. L-glutamic acid and L-nitrobenzoyl glutamic acid can used as IgE blocker to prevent allergic diseases.
DOI: http://dx.doi.org/10.5281/zenodo.768610
In vivo assessment of anti-inflammatory and antioxidant activities of Phlomis crinita polyphenols
Get PDFThe leaves of Phlomis crinita are traditionally used in Algerian medicine for the treatment of pain and inflammatory conditions. In order to find a potential application for this native species, the anti-inflammatory and antioxidant effects were investigated on various in vivo experimental models, and the total phenolic compounds and flavonoid contents were determined. The carrageenan-induced paw edema method was used to evaluate the anti-inflammatory activity of the extract in vivo, while the in vivo antioxidant effect was assessed by estimating oxidative stress parameters (MDA, CAT, and SOD). Phytochemical screening revealed the presence of substances with high therapeutic values. In vivo anti-inflammatory studies show that plant extract has a significant and dose-dependent impact on the inhibition of edema formation. The maximum percentage inhibition value was 87.79% after 4 h at a concentration of 500 mg/kg. Moreover, the administration of the extract significantly enhanced the activities of antioxidant enzymes in the livers of mice. It significantly (p ˂ 0.05) increased CAT and SOD activities and significantly (p ˂ 0.05) decreased the MDA level activity, compared to the control inflammatory group. Our findings support that Phlomis crinita can be considered as a promising source of therapeutic bioactive compounds.
DOI: http://dx.doi.org/10.5281/zenodo.786033
Accumulation of heavy metals in soil: sources, toxicity, health impacts, and remediation by earthworms
Get PDFHeavy metals pose serious threats to both individuals and the environment, and there is growing global concern over potentially harmful elements. Heavy metal contamination can have a significant impact on the soil ecosystem's functioning. This requires convenient, efficient, and beneficial remediation approaches. The “ecosystem engineer”, earthworms, can modify and enhance soil quality. The ability of earthworms to bioaccumulate metals in substantial amounts in their tissues makes them potentially beneficial as an ecological indicator of soil pollution. Vermiremediation is a new discipline of research in which earthworms are used to detoxify organically contaminated soils. Earthworms have an influential metabolic system, and their gut bacteria and chloragocyte cells play a significant role in their tendency to valorize and detoxify heavy metals. Remediation by earthworms can be considered sustainable, efficient, and ecologically beneficial. The present review provides a wide range of information on earthworms' appropriateness as prospective species for bioremediation and detoxification of toxic metal-contaminated soil to mitigate human health and environmental problems.
DOI: http://dx.doi.org/10.5281/zenodo.820648
Mucosal membranes, their interactions to microbial infections and immune susceptibility in human hosts
Get PDFThis article presents mucosal immune defense in response to various pathogenic infections in different hosts including man. Internally, the mucosal layer (membrane) covers the respiratory, digestive, nasal, and urogenital systems and serves as a physical barrier against many groups of infections. The host pathogen's interaction with membrane receptors is highlighted in this article, as well as the commensal gut microbiota's protective function in directing both general and targeted immune defense. In order to combat numerous diseases of various types, this review emphasizes the importance of crosstalk between mucosal locations, mucosal adjuvant design, and antigen delivery mechanisms. Additionally, it denotes the function of inflammasomes, lipocalin 2, Muc2 hyaluronan, and probiotics in maintaining homeostasis, regulating the gut microbiota, and enhancing immunological protection against enteric infection and gastrointestinal inflammation. For novel potential vaccines that could activate innate and adaptive immunity in mucosal tissue, there is an urgent need to look for new protective antigens, delivery mechanisms, and mucosal adjuvants. In order to prevent the spread of infections that are drug-resistant, seek protection, and assure host immunological tolerance, this article emphasizes the necessity for new antigens in the construction of new vaccines.
DOI: http://dx.doi.org/10.5281/zenodo.769367
Multidrug resistance of Staphylococcus aureus strains isolated from medical centers of Batna (north-east Algeria)
Get PDFThe emergence of resistant strains of Staphylococcus aureus is a major public health problem mainly in hospitals around the world and in Algeria in particular. This work aims to assess the resistance of Staphylococcus aureus in the University Hospital Center of Batna and the Hematology Unit of the Anti-Cancer Center using conventional standardized methods during a study period of four months. A total of 70 strains of S. aureus were isolated and their antibiotic susceptibility study showed significant resistance to β-lactam especially to penicillin (95.71%) and 61.43% to tobramycin. The methicillin-resistant strains (MRSA) formed 30%. Resistant strains to macrolide-lincosamide streptogramin B (MLSB) and aminoglycosides (KTG) classes presented 17.14% and 21.43% respectively. These results require a control plan by compliance with the hygiene conditions and the organization of the prescription of antibiotics and other molecular and epidemiological studies.
DOI: http://dx.doi.org/10.5281/zenodo.799635
Prevalence of tuberculosis among symptomatic individuals and the risk areas in Ondo State, Nigeria
Get PDFTuberculosis (TB) has been one of the diseases that are of public health problem globally. Nigeria was one out of eight countries accounting for two-thirds of people who developed TB. Of the global gap in TB case detection and notification, Ondo State reportedly has a notification gap of almost 11,100 TB cases in the year 2019 out of which only 1,891 cases were detected. The research was carried out in the three geopolitical zones of Ondo State: North, South and Central. Ondo State has 18 LGAs and an area of 14,788.7 km² with a population of 3,460,877. Participants were recruited through outreaches for the selected communities in each of the zones. The only inclusion criterion for participation in the study was those have been coughing consistently for more than two weeks. The participants were screened for HIV seropositivity by standard protocols, while screening for TB was conducted by a combination Acid Fast Bacilli (AFB) microscopy and Nucleic Acid Amplification Test (Gene Xpert MTB/RIF®). Over 10,000 participants were screened, of which 3200 subjects were found having symptoms related to TB. 513 were HIV patients and 41% were TB positive. Overall TB prevalence was found to be 623(19.5%). Akure South LGA recorded the highest overall prevalence of 39.0%. In the North district, Owo LGA recorded the highest prevalence (18.0%) while the least prevalence of (3.5%) was obtained in Ose LGA. The males were more infected (26.5%) than the females (15.3%). According to age groups, age group above 55 recorded the highest prevalence of 26.8% while the least prevalence of 15.3% was obtained in the age group 16-25. Dry season recorded higher prevalence of TB than the rainy season. Patients with low microbial load recorded the highest percentage of 45% while those with low intensities recorded the lowest percentage. Ondo State, Nigeria, has a high prevalence of TB disease, therefore there is need to increase public awareness and monitoring of individuals resident in the State.
DOI: http://dx.doi.org/10.5281/zenodo.1037091
Indigenous plant Cannabis sativa: a comprehensive ethnobotanical and pharmacological review
Get PDFCannabis sativa (L.) is a plant indigenous to Central Asia and South-East Asia. It is widely used in ethnomedicines as an anti-inflammatory, antioxidant, analgesic, anticonvulsive, antidepressant, anticancer, antitumor, neuroprotective, anti-mutagenic, anti-allergic, and antibiotic. Numerous in vitro and in vivo investigations have already established these attributes of Cannabis. Numerous toxicological studies have demonstrated the dose-dependent toxicity of C. sativa against various pests. The exact identity of the phytoconstituents of C. sativa responsible for the observed biological effects and their mode of action at the molecular level is yet to be ascertained. This review provides a comprehensive update to the ethnomedicinal, phytochemistry, pharmacological activity, and toxicological profile of Cannabis sativa.
DOI: http://dx.doi.org/10.5281/zenodo.811801
HLA-A*02 affinity to SARS-CoV-2 and susceptibility to COVID-19
Get PDFCoronavirus disease 2 (SARS-CoV-2) was declared by the World Health Organization as a global public health urgency. Considering the crucial role of HLA molecules in emerging infections, the interference of different HLA alleles on susceptibility to COVID-19 has been questioned in the scientific academy. Intending to elucidate the target ligand interactions, this present work selected the genotypes HLA-A*02, HLA-B*15, HLA-B*35 and HLA-B*44, as the most frequent in the Bahian population and the viral epitopes YLQPRTFLL, QYIKWPWYI, LTDEMIAQY, NYNYLYRLF, FIAGLIAIV, the most immunogenics of the spike glycoprotein peak. For protein selection, modeling and molecular docking was used the Allele Frequency Net Database (AFND), Immune Epitope Database and Analysis Resource (IEDB), the HADDOCK online server and the PEP-FOLD 3. Our findings suggest that HLA-A*02:01 is a risk genotype, since it showed lower energy affinity compared to HLA-B*15, HLA-B*35 and HLA-B*44.
DOI: http://dx.doi.org/10.5281/zenodo.1037197
The effect of low doses of glyphosate on reactive oxygen species production by human granulocytes
Get PDFGlyphosate is the base of numerous herbicides used widely all over the world. Strong hepato- and nephrotoxicity of high doses of this reagent was reported in laboratory animal studies. In European Union countries the acceptable daily intake for humans is set at 0.5 mg/kg body weight. We investigated the effects of glyphosate on peripheral blood polymorphonuclear cells (PMNs) at relatively low concentrations of the reagent, from 0.01 mg/L to 10 mg/L (from ~0.06 μM to 59 μM). As the biological half-life of this compound in the human body is estimated to be 3 to 10 hours, we decided to incubate blood samples with glyphosate for a period of one hour. Such incubation caused a statistically significant increase of reactive oxygen species production in granulocytes stimulated with N-formylmethionine-leucyl-phenylalanine and Escherichia coli cells. This increase was not associated with the toxic effects of glyphosate or with increased phagocytic activity of granulocytes. The reagent, when applied at specified concentrations, did not induce a respiratory burst in granulocytes or affect the amount of production of reactive oxygen species in blood samples stimulated with 12-myristate phorbol 13-acetate. On the basis of the results obtained, it may be suggested that glyphosate affects signaling pathways leading to NADPH oxidase activation, independent of protein kinase C activation. Thus, it can be concluded that although low doses of glyphosate are not harmful to humans, synergistic effects of this compound with other environmental pollutants may be an important part of pathogenic mechanisms.
DOI: http://dx.doi.org/10.5281/zenodo.842857
Analyses of Omicron genomes from India reveal BA.2 as a more transmissible variant
Get PDFIn the current study, the phylodynamics and phylogenomics of Omicron variants are being examined to provide insight into their evolution. We analyzed 564 genomes deposited to the GISAID database from various states of India. A Pangolin COVID-19 Lineage Assigner tool was used to assign lineages to all retrieved genomes. Maximum likelihood (MLE) tree construction and Reduced Median Joining (RM) network were performed. For phylodynamic analysis, the basic reproduction number (R0) was estimated. A Maximum likelihood tree (MLE) confirms the separation of genomes into two distinct clades, BA. 1. and BA. 2. A very high reproduction number (R0) of 2.445 was estimated for the lineage BA.2. Telangana has the highest R0 value in the country, indicating a high prevalence of the BA.2 lineage. The construction of the Reduced Median (RM) network reveals an evolution of some autochthonous haplogroups and haplotypes, which further supports the rapid evolution of Omicron as opposed to its previous variants. Phylogenomic analyses using maximum likelihood (ML) and RM also reveal the likelihood of the emergence of sub-sublineages and novel haplogroups respectively. Due to the recombinant nature and high transmissibility of the Omicron virus, we suggest continuous and more widespread genome sequencing in all states of India to track the evolution of SARS-CoV-2.
DOI: http://dx.doi.org/10.5281/zenodo.760799