Gene expression profiling of peripheral blood mononuclear cells from women with cervical lesions reveals new markers of cancer.

Cervical cancer (CC) is a multifactorial disease of which human papillomavirus (HPV) is the main etiological agent. Despite cervical Pap smear screening and anti­HPV vaccination, CC remains a major public health issue. Identification of specific gene expression signatures in the blood could allow better insight into the immune response of CC and could provide valuable information for the development of novel biomarkers. The present study performed a transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from Senegalese patients with CC (n=31), low­grade cervical intraepithelial neoplasia (CIN1; n=27) and from healthy control (CTR) subjects (n=29). Individuals in the CIN1 and CTR groups exhibited similar patterns in gene expression. A total of 182 genes were revealed to be differentially expressed in patients with CC compared with individuals in the CIN1 and CTR groups. The IL1R2, IL18R1, MMP9 and FKBP5 genes were the most upregulated, whereas the T­cell receptor α gene TRA was the most downregulated in the CC group compared with in the CIN1 and CTR groups. The pathway enrichment analysis of the differentially expressed genes revealed pathways directly and indirectly linked to inflammation. To the best of our knowledge, the present study is the first large transcriptomic study on CC performed using PBMCs from African women; the results revealed the involvement of genes and pathways related to inflammation, most notably the IL­1 pathway, and the involvement of downregulation of the T­cell receptor α, a key component of the immune response. Several of the stated genes have already been reported in other cancer studies as putative blood biomarkers, thus reinforcing the requirement for deeper investigation. These findings may aid in the development of innovative clinical biomarkers for CC prevention and should be further replicated in other populations.

Pyridazino-1,3a,6a-Triazapentalenes as Versatile Fluorescent Probes: Impact of Their Post-Functionalization and Application for Cellular Imaging.

Pyridazino-1,3a,6a-triazapentalenes (PyTAP) are compact fused 6/5/5 tricyclic scaffolds which exhibit promising fluorescent properties. Chemically stable, they can be post-functionalized using standard Pd-catalyzed cross-coupling chemistry. Several original PyTAP bearing additional unsaturated substituents in positions 2 and 8 were synthetized and their spectroscopic properties analyzed. They have been successfully tested as fluorescent probes for cellular imaging.

Systematic screening for cervical cancer in Dakar region: prevalence and correlation with biological and socio-demographic parameters.

BACKGROUND: Cervical cancer is a major public health problem. In 2018, globally 569,847 cervical cancer were diagnosed and 311,000 deaths were projected due to this preventable disease. Worldwide, therefore, the cervical cancer disease ranks as the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women in 2018.The high rate of dysplasia in Senegal and the absence of well-organized screening programs informed this study, which aims to determine the prevalence of cervical dysplasia and its relationship to biological and socio-demographic characteristics. METHODS: This study is based on 1000 conventional smears collected during routine cervical cancer screening at the Gaspard Camara Health Center and the Histology - Embryology and Cytogenetics Laboratory of the Cheikh Anta DIOP University in Dakar. The smears were read according to the Bethesda and Richart systems. However, all data were returned to the Bethesda system using the correspondence table between the different classifications of squamous cell lesions of the cervix. Some of the patients with abnormal smears had colposcopy and if necessary a biopsy. Other patients with low-grade lesions were recommended to have their smears resumed in 6 months or 1 year later. RESULTS: Cytological analysis was performed for 1000 patients aged 16 to 82 years (mean age = 41 ± 11.16). Among these, 176 patients had abnormal smears, 23 had Atypical Squamous Cells of Undetermined Significance (ASCUS), 143 had a low-grade lesion, 9 had a high-grade lesion and 1 had carcinoma. Among the remaining 822 patients, cytological analysis revealed no suspected malignant lesions, but 623 among them had dystrophy and 2 were unsatisfactory. Among patients with abnormal smears, 104 patients (23 ASCUS + 71 low grade + 9 high grade + 1 carcinoma) had performed colposcopy, 40 of whom had normal colposcopy and 64 had abnormalities. Sixty-four (64) biopsies were performed. Four (4) were not satisfactory. However, for 26/60 biopsies, the histology was normal, 21/60 had a low grade, 11 displayed a high grade and only 2 had carcinoma. Among the 176 patients with abnormal smears, 72 low-grade patients had undergone cytological examination 6 months to 1 year later to determine the persistence, regression or progression of low-grade dysplasia. During follow-up, persistence was observed in 25% (n = 18) of cases, progression to High-grade squamous intraepithelial lesion (HSIL) was detected in 2.78% (n = 2), while 72.22% (n = 52) of the patients experienced regression. CONCLUSION: In this study, the prevalence of abnormal smear was 17.60% for cytology. Meanwhile, the Colposcopy and histology confirmed just 3.40%. These results underline the interest and need for a review of the discrepancies observed between pathologists.

Immunogenicity and safety of MF59-adjuvanted and full-dose unadjuvanted trivalent inactivated influenza vaccines among vaccine-naïve children in a randomized clinical trial in rural Senegal.

INTRODUCTION: Effective, programmatically suitable influenza vaccines are needed for low-resource countries. MATERIALS AND METHODS: This phase II, placebo-controlled, randomized safety and immunogenicity trial (NCT01819155) was conducted in Senegal using the 2012-2013 Northern Hemisphere trivalent influenza vaccine (TIV) formulation. Participants were allocated in a 2:2:1 ratio to receive TIV (full-dose for all age groups), adjuvanted TIV (aTIV), or placebo. Participants were stratified into age groups: 6-11, 12-35, and 36-71 months. All participants were vaccine-naïve and received two doses of study vaccine 4 weeks apart. The two independent primary objectives were to estimate the immunogenicity of TIV and of aTIV as the proportion of children with a hemagglutination inhibition (HI) antibody titer of ≥1:40 to each vaccine strain at 28 days post-dose two. Safety was evaluated by solicited local and systemic reactions, unsolicited adverse events, and serious adverse events. RESULTS: 296 children received TIV, aTIV, or placebo, and 235 were included in the final analysis. After two doses, children aged 6-11, 12-35, and 36-71 months receiving TIV had HI titers ≥1:40 against A/H1N1 (73.1%, 94.1%, and 97.0%), A/H3N2 (96.2%, 100.0%, and 100.0%), and B (80.8%, 97.1%, and 97.0%), respectively. After two doses, 100% children aged 6-11, 12-35, and 36-71 months receiving aTIV had ≥1:40 titers against A/H1N1, A/H3N2, and B. After a single dose, the aTIV response was comparable to or greater than the TIV response for all vaccine strains. TIV and aTIV reactogenicity were similar, except for mild elevation in temperature (37.5-38.4 °C) which occurred more frequently in aTIV than TIV after each vaccine dose. TIV and aTIV had similarly increased pain/tenderness at the injection site compared to placebo. CONCLUSIONS: Both aTIV and full-dose TIV were well-tolerated and immunogenic in children aged 6-71 months. These vaccines may play a role in programmatically suitable strategies to prevent influenza in low-resource settings.

Stereoselective synthesis of γ-hydroxy-α-amino acids through aldolase-transaminase recycling cascades.

Efficient bi-enzymatic cascades combining aldolases and α-transaminases were designed for the synthesis of γ-hydroxy-α-amino acids. These recycling cascades provide high stereoselectivity, atom economy, and an equilibrium shift of the transamination. l-syn or anti-4-hydroxyglutamic acid and d-anti-4,5-dihydroxynorvaline were thus prepared in 83-95% yield in one step from simple substrates.