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Niang, M.

Publications and source records attributed to Niang, M..

4 recordsLinked to original sources

Promising protocol for in vivo experiments with betulin

Background/ObjectivesBetulin is a promising agent in many areas of medicine and is being investigated, particularly in the field of cancer. However, in in vivo experiments, its water insolubility becomes a significant obstacle. This study describes a promising method for the administration of betulin in in vivo experiments and the determination of betulin levels in organ samples. MethodsBetulin is dissolved first in ethanol, and this solution is introduced into acylglycerols, followed by evaporation of the ethanol. Olive oil and food-grade lard were determined to be suitable lipids for noninvasive application per os. A method for processing the organs of experimental animals for betulin determination was developed. Determination in blood is also likely the only viable option to be used in future clinical studies and practice. ResultsThe maximum amount of betulin usable (i.e., absorbable by organisms) in olive oil (10 mg/ml), suppository mass (6 mg/ml), food lard (4 mg/ml), and cocoa butter (2 mg/ml) carriers was found microscopically. A specific distribution of betulin concentration in the organs of experimental animals (Wistar rats) after a weekly diet containing betulin was discovered. The blood was shown to be particularly advantageous, as it allows continuous monitoring of betulin levels in the body. In these pilot experiments, a statistically significant (P < 0.001) synergistic effect of betulin on solid Ehrlich adenocarcinoma tumors was observed when betulin was combined with cytostatic Namitecan (NMRI mice). The high-purity betulin used in this study is very stable even under fluctuating storage conditions. ConclusionsOur study proves that both the method of betulin administration and the proposed analytical procedure could greatly increase the reliability and reproducibility of in vivo studies and future preclinical and clinical studies on the effects of betulin and possibly other similar water-insoluble triterpenoids on living organisms.

pharmacology and toxicology↗

Differential association of SARS-CoV-2 IgG responses with anti-OC43 IgG in a Senegalese cohort

Numerous studies elucidated the kinetics of the humoral immune response post-SARS-CoV-2 infection. However, in sub-Saharan Africa, the evolution of SARS-CoV-2 IgG antibody responses and their interaction with pre-existing seasonal human coronavirus (HCoVs: OC43, 229E, NL63, HKU1) immunity remain underexplored. A prospective cohort study was conducted in Senegal during the first year of the COVID-19 pandemic (March to December 2020). A total of 204 patients with laboratory-confirmed COVID-19 were included. Patients were classified as symptomatic (n=157) or asymptomatic (n=47) based on clinical presentation. Plasma samples (n=705) were collected over 6 months from SARS-CoV-2 positive individuals. IgG levels against SARS-CoV-2 and HCoVs were measured using a multiplex bead-based assay. Among the 204 participants included (95 [46.6%] female, median age, 44 [7-95]), SARS-CoV-2 IgG were detectable 6 months post-infection, peaking at 1 month for most antigens, except for Spike (S), which peaked at 3 months. Elderly patients (>60 years) exhibited higher IgG levels against both SARS- CoV-2 and HCoVs. Symptomatic patients had higher IgG levels than asymptomatic individuals, especially for WTS, RBD, S2, and N. Anti-HCoV IgG levels remained stable post-infection, with OC43 peaking at week 3 in symptomatic patients. A positive correlation was found between anti-SARS-CoV- 2 and anti-OC43 IgG in symptomatic patients. The study highlights persistent SARS-CoV-2 IgG antibodies for up to 6 months and suggests a link between pre-existing HCoV-OC43 immunity and COVID-19 outcomes in Senegal. These findings could help shape future vaccine strategies, considering the influence of circulating HCoVs on long- term protection against SARS-CoV-2. Author summaryUnderstanding how our immune system responds to SARS-CoV-2, the virus responsible for COVID- 19, is essential for guiding public health countermeasures and informing vaccine development strategies. In our study, we monitored, in COVID-19 patients, the evolution of IgG antibody responses against SARS-CoV-2 structural proteins over a six-month period. Additionally, we examined how previous exposure to common seasonal coronaviruses might influence immune responses to SARS-CoV-2. Conducting this research in an African context is particularly important, as data on immune responses to SARS-CoV-2 in this region are scarce. Our results provide valuable insights into the complex interplay between immune responses elicited by SARS-CoV-2 and pre-existing immunity from seasonal circulating coronaviruses. These findings enhance our understanding of immune memory and cross-reactivity, two critical factors for assessing long-term protection and optimizing vaccine strategies. By shedding light on the dynamics of antibody responses over time within a sub-Saharan population, our research contributes to the global effort aimed at developing effective interventions against COVID-19 and preparing for future coronavirus outbreaks.

immunology↗

Validation and multi-site deployment of a lyophilized qRT-PCR reagent for the molecular diagnosis of avian influenza and rabies in Sub-Saharan African regions

Molecular methods are widely accepted as gold standard techniques for the laboratory diagnosis of most human and animal pathogens. However, most molecular protocols rely on reagents that need to be transported and stored at a freezing temperature, a requirement that might affect their reliability in areas where the cold chain cannot be guaranteed. Over the years, several lyophilized molecular products have been marketed to circumvent this issue. We therefore evaluated the feasibility of replacing liquid reagents with freeze-dried formulations for the molecular diagnosis of avian influenza (AIV) and rabies (RABV) viruses, two priority zoonotic pathogens widely spread in Sub-Saharan Africa. Among the available kits, we selected the Qscript lyo 1-step kit (Quantabio) due to its easy-to-use features, single-reaction format, and preliminary performance assessment. Through a more in-depth evaluation, we determined its analytical and diagnostic performance and formulation stability, and obtained results comparable to those of standard liquid master mixes. Notably, for the detection of divergent lyssaviruses, the lyophilized reagents sensitivity was affected by suboptimal complementarity between the oligonucleotides and the target sequences. Finally, a multi-site evaluation in four veterinary diagnostic laboratories located in Sub-Saharan Africa demonstrated the successful deployment of AIV and RABV assays utilizing freeze-dried reagents, which can interchangeably replace liquid master mixes. Altogether our results indicate that the Qscript lyo 1-step kit (Quantabio) represents a valid alternative to wet reagents for the molecular diagnosis of avian influenza and rabies, and has the potential for broader applications to other relevant infectious diseases upon proper validation. Author summaryMolecular diagnostic protocols rely on reagents that need to be transported and stored at freezing temperatures. Meeting this requirement can be challenging in areas where the maintenance of the cold chain is not guaranteed, such as in sub-Saharan Africa. Our study aimed to assess the feasibility of using lyophilized reagents as a replacement for liquid reagents in the molecular diagnosis of two widespread zoonotic pathogens in Sub-Saharan Africa, namely avian influenza and rabies. To accomplish this, we selected a commercially available lyophilized reagent based on its format and performance characteristics. We conducted a laboratory validation to assess the use of the lyophilized reagent throughout the entire diagnostic process. We also conducted a reproducibility test involving African laboratories as potential end-users. Our findings confirm that the lyophilized reagent can replace traditional liquid reagents to diagnose rabies and avian influenza and suggest its possible use for a wider range of infectious diseases after undergoing appropriate validation.

microbiology↗

Blood donor variability is a modulatory factor for P. falciparum invasion phenotyping assays

Human erythrocytes are indispensable for Plasmodium falciparum development. Unlike other eukaryotic cells, there is no existing erythroid cell line capable of supporting long-term P. falciparum in vitro experiments. Consequently, invasion phenotyping experiments rely on erythrocytes of different backgrounds. However, the contribution of the erythrocytes variation in influencing invasion rates remains unknown, which presents a challenge for conducting large-scale comparative studies. Here, we used erythrocytes of different blood groups harboring different hemoglobin genotypes to assess the relative contribution of blood donor variability in P. falciparum invasion phenotyping assays. For each donor, we investigated the relationship between parasite invasion phenotypes and erythrocyte phenotypic characteristics, including; the expression levels of surface receptors (e.g. the human glycophorins A and C, the complement receptor 1 and decay accelerating factor), blood groups (e.g. ABO/Rh system), and hemoglobin genotypes (e.g. AA, AS and AC). Across all donors, there were significant differences in invasion efficiency following treatment with either neuraminidase, trypsin or chymotrypsin relative to the control erythrocytes. Primarily, we showed that the levels of key erythrocyte surface receptors and their sensitivity to enzyme treatment, significantly differed across donors. However, invasion efficiency correlated neither with susceptibility to enzyme treatment nor with the levels of the selected erythrocyte surface receptors. Upon further analysis, we found no relationship between P. falciparum invasion phenotype and blood group or hemoglobin genotype. ImportanceAssays to decipher P. falciparum invasion phenotypes are of great importance in the quest for an efficient malaria vaccine. Malaria associated mortality is mainly attributed to the blood stage of the parasites life cycle, a major focus of vaccine development strategies. Further, testing and validating blood stage vaccines necessitates conducting large-scale studies in endemic countries. However, comparing results from such studies is challenged by the lack of standard assays. As human erythrocytes play a pivotal role in P. falciparum invasion assays, the need to investigate the effect of blood donor variability in the outcome of such assays is apparent. The significance of our study is in reporting the absence of relationship between P. falciparum invasion efficiency and commonly shared erythrocyte features across different erythrocyte donors, therefore emphasizing the need to consider erythrocyte donor uniformity and to anticipate challenges associated to blood donor variability in early stages of large-scale study design.

microbiology↗