Improving the Drug Bioavailability Property of Myricetin through a Structural Monosubstitution Modification Approach: an In-Silico Pharmacokinetics Study

Myricetin belongs to the members of polyphenolic compounds that make up the flavonoid class, which possess antioxidant properties. Myricetin is mostly obtained from vegetables, fruits, nuts, berries, tea, and is also found in red wine. It is also similar structurally to quercetin, fisetin and luteolin and is known to possess similar functions as the other members in the flavonol class of flavonoids. The health benefits of myricetin cuts across being an anticarcinogen compound to its antiviral, antithrombotic, antidiabetic, antiatherosclerotic, neuroprotective and anti-inflammatory properties among others. It also plays a role as a cyclooxygenase 1 inhibitor, an antineoplastic agent, an antioxidant, a plant metabolite, a food component and a hypoglycemic agent. It is a hexahydroxyflavone and a 7-hydroxyflavonol. The 2D structure of myricetin was obtained from the PubChem database while the MarvinSketch software was used to effect the various structural modifications on the compound. The structural modifications entails the substitution of the OH group attached to the C1 of myricetin with different functional groups such as the C=O, C2H5, CH3, CHO, CONH2, H and OCH3 which were saved as mrv files. The saved mrv files for each 2D structures were converted into canonical SMILES with the aid of the Open Babel software while the pharmacokinetic parameters for each compound was predicted using the SwissADME server. Results from this study showed that the C2H5, CH3 and H analogues of myricetin showed a higher gastrointestinal absorption rate compared to their C=O, CHO, CONH2 and OCH3 counterparts. This result shows that the C2H5, CH3 and H analogues of myricetin might be more orally bioavailable compared to myricetin and the other modified analogues. Preclinical studies on these compounds are therefore recommende

Nucleic acid-based fluorescent probes and their analytical potential

It is well known that nucleic acids play an essential role in living organisms because they store and transmit genetic information and use that information to direct the synthesis of proteins. However, less is known about the ability of nucleic acids to bind specific ligands and the application of oligonucleotides as molecular probes or biosensors. Oligonucleotide probes are single-stranded nucleic acid fragments that can be tailored to have high specificity and affinity for different targets including nucleic acids, proteins, small molecules, and ions. One can divide oligonucleotide-based probes into two main categories: hybridization probes that are based on the formation of complementary base-pairs, and aptamer probes that exploit selective recognition of nonnucleic acid analytes and may be compared with immunosensors. Design and construction of hybridization and aptamer probes are similar. Typically, oligonucleotide (DNA, RNA) with predefined base sequence and length is modified by covalent attachment of reporter groups (one or more fluorophores in fluorescence-based probes). The fluorescent labels act as transducers that transform biorecognition (hybridization, ligand binding) into a fluorescence signal. Fluorescent labels have several advantages, for example high sensitivity and multiple transduction approaches (fluorescence quenching or enhancement, fluorescence anisotropy, fluorescence lifetime, fluorescence resonance energy transfer (FRET), and excimer-monomer light switching). These multiple signaling options combined with the design flexibility of the recognition element (DNA, RNA, PNA, LNA) and various labeling strategies contribute to development of numerous selective and sensitive bioassays. This review covers fundamentals of the design and engineering of oligonucleotide probes, describes typical construction approaches, and discusses examples of probes used both in hybridization studies and in aptamer-based assays

Single base pair mutation analysis by PNA directed PCR clamping.

A novel method that allows direct analysis of single base mutation by the polymerase chain reaction (PCR) is described. The method utilizes the finding that PNAs (peptide nucleic acids) recognize and bind to their complementary nucleic acid sequences with higher thermal stability and specificity than the corresponding deoxyribooligonucleotides and that they cannot function as primers for DNA polymerases. We show that a PNA/DNA complex can effectively block the formation of a PCR product when the PNA is targeted against one of the PCR primer sites. Furthermore, we demonstrate that this blockage allows selective amplification/suppression of target sequences that differ by only one base pair. Finally we show that PNAs can be designed in such a way that blockage can be accomplished when the PNA target sequence is located between the PCR primers

Factors influencing canine rabies vaccination among dog-owning households in Nigeria

Rabies perpetuates in Nigeria despite initiatives like the Regional Disease Surveillance System Enhancement Project, with evidence indicating suboptimal canine vaccination rates as a contributing factor. To inform effective planning of mass dog vaccination campaigns, it is crucial to understand the factors associated with variation in canine vaccination rates. We conducted a cross-sectional study in 2022 to understand factors associated with canine vaccination. We used stratified random sampling of the streets and dog-owning households to survey 4162 households from three states and the Federal Capital Territory (FCT). We then built a joint probabilistic model to understand factors associated with dog vaccination and non-vaccination. First, we modelled rabies knowledge as a latent variable indirectly measured with several targeted survey questions. This method allowed a respondent's unobserved understanding of rabies to be estimated using their responses to a collection of survey questions that targeted different aspects of rabies epidemiology and took various possible response distributions (i.e., ordinal, categorical, binary). Second, we modelled factors influencing pet owners' decisions to vaccinate their dogs against rabies and barriers to dog vaccination among dog owners whose dogs were not vaccinated against rabies. Posterior distributions revealed that the probability of dog vaccination was positively associated with the owner's latent knowledge of rabies, civil servant service employment, residence in the FCT, ownership of a single dog, providing care to dogs, and a preference for contemporary treatment following a dog bite. Conversely, non-vaccination was positively associated with private employment, residing in Anambra and Enugu states, owning multiple dogs, allowing dogs to search for leftovers, and a preference for traditional treatment after a dog bite. Cost was the primary barrier against vaccination for dog owners in Anambra and Enugu, while mistrust posed a major challenge for those in the FCT. Owners in areas with veterinary establishments cited cost as a barrier, while those without a veterinary establishment cited access as the primary barrier. Our study underscores the need to enhance rabies knowledge, tailor vaccination campaigns to specific demographics, address financial and access barriers, and combat hesitancy to improve rabies vaccination rates in Nigeria