In vitro anticancer screening of 24 locally used Nigerian medicinal plants

Background Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity. Methods The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines. Results Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma cell lines. Erythrophleum suaveolens (Guill. & Perr.) Brenan was found to demonstrate potent anti-cancer activity in this study exhibiting IC50 = 0.2-1.3 μg/ml. Conclusions Based on the significantly potent activity of some plants extracts reported here, further studies aimed at mechanism elucidation and bio-guided isolation of active anticancer compounds is currently underway

Synthesis of γ-, δ-, and ε-Lactams by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)iminoesters

Highly enantiomerically enriched γ- and δ-lactams have been prepared by a simple and very efficient procedure that involves the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters followed by desulfinylation of the nitrogen atom and spontaneous cyclization to the desired lactams during the basic workup procedure. Five- and six-membered ring lactams bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and ee’s up to >99%. A slight modification of the procedure also allowed the preparation of ε-lactams in good yields and very high enantioselectivities. Both enantiomers of the final lactams could be prepared with equal efficiency by changing the absolute configuration of the sulfinyl chiral auxiliary

Mediator Kinase Inhibition Further Activates Super-Enhancer Associated Genes in AML

Super-enhancers (SEs), which are composed of large clusters of enhancers densely loaded with the Mediator complex, transcription factors (TFs), and chromatin regulators, drive high expression of genes implicated in cell identity and disease, such as lineage-controlling TFs and oncogenes 1, 2. BRD4 and CDK7 are positive regulators of SE-mediated transcription3,4,5. In contrast, negative regulators of SE-associated genes have not been well described. Here we report that Mediator-associated kinases cyclin-dependent kinase 8 (CDK8) and CDK19 restrain increased activation of key SE-associated genes in acute myeloid leukaemia (AML) cells. We determined that the natural product cortistatin A (CA) selectively inhibited Mediator kinases, had antileukaemic activity in vitro and in vivo, and disproportionately induced upregulation of SE-associated genes in CA-sensitive AML cell lines but not in CA-insensitive cell lines. In AML cells, CA upregulated SE-associated genes with tumour suppressor and lineage-controlling functions, including the TFs CEBPA, IRF8, IRF1 and ETV6 6, 7, 8. The BRD4 inhibitor I-BET151 downregulated these SE-associated genes, yet also has antileukaemic activity. Individually increasing or decreasing expression of these TFs suppressed AML cell growth, providing evidence that leukaemia cells are sensitive to dosage of SE-associated genes. Our results demonstrate that Mediator kinases can negatively regulate SE-associated gene expression in specific cell types and can be pharmacologically targeted as a therapeutic approach to AML

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Sero-prevalence of toxoplasma gondii infection among abattoir workers in Sokoto, Nigeria

Background: Toxoplasmosis is a worldwide zoonotic disease affecting all warm blooded animals including man. It is caused by an obligate, intracellular tissues cyst-forming protozoan parasite, Toxoplasma gondii, with domestic cat and other felides as definitive hosts. The infection has aroused considerable interest from various workers because of the dangers it poses and its mode oftransmission. Materials and Methods: Sera collected from 75 volunteered abattoir workers were analysed using Toxo-Latex kit by LINEAR chemicals (Cromatest, Jeanquim Costa, Barcelona, Spain) which is a rapid slide agglutination procedure. In addition, some epidemiological factors were obtained from these volunteered through structural questionnaire administered to them. Results: The adolescent (16-20 years) had the highest prevalence (57.1%) while the elderly, aged > 60 years had prevalence of 50%. No statistical significant different was however observed (p >0.05) varying degree of infarction was observed between the old groups. Sero-prevalence among workers who eat raw meat/suya, drink unpasteurized milk, smoking/eating when evisceration were 50%, 26.7%, 13.8%, 13.8% and 20% respectively, while workers that do not eat/drink during evisceration was 13.3%. No statistical significance was noted between those who eat raw meat/suya/drink unpasteurized milk and those who eat and drink during evisceration was significantly higher than those that wash hand before eating/drinking during work (p < 0.05). Conclusion: There is need for public enlightenment to abattoir personnel on the epidemiology and significance of T. gondii infection. Further studies on toxoplasma infection in the study area are desirable

Impactos do uso de climatização artificial na percepção térmica em espaços abertos no centro do Rio de Janeiro

Estudos de percepção térmica em espaços abertos são fundamentais para um planejamento urbano climaticamente orientado. O presente artigo investiga a percepção térmica de usuários de espaços abertos no Centro da cidade do Rio de Janeiro, com o objetivo de analisar o impacto do uso prolongado de ar-condicionado nos votos de sensação e preferência térmicas. As respostas obtidas por meio de entrevistas estruturadas são comparadas a índices de conforto em espaços abertos (PET e UTCI), agrupando-se as respostas segundo a utilização ou não de climatização artificial, conforme reportado pelos entrevistados. As campanhas de monitoramento foram realizadas em períodos de verão entre 2012 e 2015. A organização semiexperimental da pesquisa envolveu a permanência dos equipamentos e pesquisadores em um único ponto por campanha, durante o período de 10 às 15 horas. Uma estação meteorológica Davis Vantage Pro2 foi utilizada para a coleta de dados concomitantemente à aplicação de questionários estruturados segundo a ISO 10551, aos quais incluíram-se questões acerca do uso de ar-condicionado no local de trabalho e no ambiente doméstico. Dos resultados obtidos, notou-se que o uso frequente de ar-condicionado impacta a percepção térmica dos usuários, e influencia na definição de limites de conforto em espaços abertos, para os índices PET e UTCI avaliados

Impact of human presence on secondary organic aerosols derived from ozone-initiated chemistry in a simulated office environment

Several studies have documented reductions in indoor ozone levels that occur as a consequence of its reactions with the exposed skin, hair and clothing of human occupants. One would anticipate that consumption of ozone via such reactions would impact co-occurring products derived from ozone's reactions with various indoor pollutants. The present study examines this possibility for secondary organic aerosols (SOA) derived from ozone-initiated chemistry with limonene, a commonly occurring indoor terpene. The experiments were conducted at realistic ozone and limonene concentrations in a 240 m3 chamber configured to simulate a typical open office environment. During an experiment the chamber was either unoccupied or occupied with 18-20 workers. Ozone and particle levels were continuously monitored using a UV photometric ozone analyzer and a fast mobility particle sizer (FMPS), respectively. Under otherwise identical conditions, when workers were present in the simulated office the ozone concentrations were approximately two-thirds and the SOA mass concentrations were approximately one-half of those measured when the office was unoccupied. This was observed whether new or used filters were present in the air handling system. These results illustrate the importance of accounting for occupancy when estimating human exposure to pollutants in various indoor settings. \ua9 2013 American Chemical Society.Peer reviewed: YesNRC publication: Ye