Anti-Heparanase Aptamers as Potential Diagnostic and Therapeutic Agents for Oral Cancer

Peer reviewe

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

Caspase-3 activation and increased procollagen type I in irradiated hearts

The caspase-3-cleaved presence was evaluated in this study in the heart of irradiated rats, during the decline of ventricular function. Female Wistar rats were irradiated with a single dose of radiation (15 Gy) delivered directly to the heart and the molecular, histological and physiological evaluations were performed at thirteen months post-irradiation. The expressions of procollagen type I, TGF-ß1 and caspase-3-cleaved were analyzed using Western blotting. Cardiac structural and functional alterations were investigated by echocardiography and electron microscopy. In the irradiated group, the levels of procollagen type I, TGF-ß1 and caspase-3-cleaved are increased. Significant histological changes (degeneration of heart tissue and collagen deposition) and functional (reduced ejection fraction) were observed. Data suggest that the cardiac function decline after exposure to ionizing radiation is related, in part, to increased collagen and increased caspase-3-cleaved

The MTS absorbance at 490 nm is shown over 24, 48 and 72 h in the presence and absence of the 1.5 M short aptamer.

<p>The presence of the aptamer at 1 mM concentration was found to have no effect on the cell growth in comparison with the control.</p

Stern-Volmer plots for HSA titrated by short and long apatmers 37°C.

<p>Excitation wavelength 290 nm, [HSA]  =  6 µM. Excitation wavelength at 290 mM in a solution of sodium phosphate. Data is the mean of six values showing no greater standard deviation than 11%. The quenching effect is more considerable for long than short aptamer.</p

EIA and RIA assays.

<p>A: EIA (IIINTP indirect enzyme immunoassays) detecting N-terminal telopeptide from collagen type III degradation products at day 10 media change. Increasing absorbance means less collagen degradation product present. Hpa Ab (p = 0.03), 1.5 M Short (p = 0.007) and 1.5 M Long (p = 0.03) showed significant increase in absorbance compared to no inhibitor, suggesting they have inhibited the invasion of HSC-3 cells. B: The graph shows previous EIA values adjusted for negative control at day 10 media change. C: RIA (radioimmunoassay for type III collagen) detecting C-terminal telopeptide at day 10 media change. Increasing levels mean less collagen degradation product. Hpa Ab (p = 0.07), 1.5 M Short (p = 0.004) and 1.5 M Long (p = 0.02). D: RIA has confirmed the EIA assays showing significantly lower collagen degradation products than that for tissues without inhibitor added, indicating that they were successful inhibitors of invasion.</p

UV wavelength scan of HSA (left) and plot of PBS (right) titrated with 1.5 M short aptamer (A) and UV wavelength scan of HSA (left) and plot of PBS (right) titrated with 1.5 M long aptamer (B).

<p>UV wavelength scan of HSA (left) and plot of PBS (right) titrated with 1.5 M short aptamer (A) and UV wavelength scan of HSA (left) and plot of PBS (right) titrated with 1.5 M long aptamer (B).</p

The aptamer sequences used in this study.

<p>In bold the sequence of the short aptamer, which is the part of the long aptamer that is structured.</p><p>The aptamer sequences used in this study.</p