Partnership for International Development: Finland-Nigeria Conference on Climate, Food, Health and Entrepreneurship.

A joint collaboration between the Arctic Centre of the University of Lapland, Finland and the Federal Institute of Industrial Research, Oshodi, Lagos, Nigeria was organised as a hybrid conference on several topics that are related to climate, food, health and entrepreneurship. The utilisation of natural resources in both regions is an important theme in meeting the sustainable development goals agenda. The topics discussed were multidisciplinary, they include Nigerian indigenous foods, bioeconomy, circular economy, nutrition, health, innovation and entrepreneurship under four themes (Climate, Food, Health and Entrepreneurship). There were dignitaries from Finland and Nigeria. The presenters are researchers from Nigerian universities (University of Ibadan, University of Abuja and Eko university, Lagos), Nigerian Federal Institute of Industrial research centre and from the Finnish side we have the university of Lapland, Rovaniemi, University of Oulu, Oulu and the Centria University of Applied Sciences, Kokkola. The topics discussed will serve as training materials for students and learners, the discussion focussed on research opportunities for institutions in both countries. The experts from both countries will continue to dialogue on the possibility of promoting common topics as research agenda in these important areas with the possibilities of creating more jobs.

Phytomedicine in Disease Management: In-Silico Analysis of the Binding Affinity of Artesunate and Azadirachtin for Malaria Treatment.

In the rural communities of sub-Saharan African (sSA) countries, malaria is being managed using phytocompounds. Artesunate is reported to inhibit Gephyrin E, a central, multi-domain scaffolding protein of inhibitory post-synapses. Neem plant and its metabolites like azadirachtin are being indicated for management of malaria by traditional healers. The present study was aimed to cheminformatically analyse the binding potential of artesunate and azadirachtin with various reactive moieties of Gephyrin E, to reduce malaria scourge. With molecular dynamics (MD), binding free energy estimation and binding affinity of artesunate and azadirachtin to Gephyrin E was done. GRIP docking was done to study the interactions of these test ligands with Gephyrin E (6FGC). MD simulation gave insights to structural changes upon binding of artesunate and azadirachtin in the ligand-binding pocket of Gephyrin E. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) were calculated. From the estimation, azadirachtin had a total binding energy of -36.97 kcal/mol; artesunate had a binding energy of -35.73 kcal/mol. The GRIP docking results provided a clearer evidence that artesunate has comparatively better binding affinity to Gephyrin E than azadirachtin, and the critical binding sites (in activity order) were cavity 3, 2, 8, and 6 for artesunate while for azadirachtin, it was cavity 6, 3, 8, and 2. The GRIP docking provided detailed interactions at the atomic levels, providing evidence; both compounds have chances to overcome the drug resistance problem, albeit higher for artesunate. Our findings added another piece of evidence that azadirachtin may be effective as an anti-malarial agent. The results herein may provide impetus for more studies into bioactive components of plant origin towards the effective management of malaria disease phenotype.

Evaluation of the Anti-Plasmodial potential of Calotropis procera Latex in mice infected with Plasmodium berghei.

Current artemisinin-based combination therapy (ACT) regimen for the treatment of malaria is effective, but cases of malaria parasite's resistance to existing antimalarial drugs is worrisome. This necessitates the development of new, safe, effective and affordable chemotherapy. We describe protocols for each step involved in the Anti-Plasmodial evaluation of Calotropis procera latex in mice infected with Plasmodium berghei. The protocols include: (1) determination of the chemical/ phytochemical constituents of Calotropis procera latex, (2) determination of the acute toxicity/ median lethal dose (LD50) and therapeutic dose of the plant latex, in vivo, and (3) in vivo determination of the Anti-Plasmodial potential of Calotropis procera latex in mice infected with Plasmodium berghei. We likewise describe our methodology for direct quantitation of percentage yield of the extract of Calotropis procera latex, and the statistical methodology for assessment of toxicity and efficacy in evaluating the Anti-Plasmodial activity of the plant.•Multi-step pipeline for the extraction of the bioactive constituents of the plant latex using 0.2M phosphate buffer (pH 7.0) and cold acetone.•Detailed protocols for the determination of acute toxicity/ median lethal dose (LD50) and calculation of therapeutic dose for intraperitoneal injection to achieve effective dose levels.•Determination of the phytochemical constituents using standard procedures, and in vivo efficacy against Plasmodium berghei using methodology to directly quantify the parasite level after treatment.

In-vivo anti-plasmodial activity of phosphate buffer extract of Calotropis procera latex in mice infected with Plasmodium berghei.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a global health problem with the greatest burden in sub-Saharan Africa (sSA). The resistance to available antimalarial agents necessitate for the development of new and safe drugs for which medicinal plants provides credible alternative sources for discovering new and cheap therapeutic agents. Calotropis procera is used in several folk or traditional medicines for the treatment of various diseases across different regions of the world. In Nigeria traditional medicine, C. procera latex is used either alone or in combination with other herbs to cure common diseases including malaria. In Malaka district (Indonesia), Calotropis gigantea (a member of Apocyanceae), is one of the most used herbs to treat malaria patient via the massage method. AIM OF THE STUDY: This study aimed to evaluate the anti-plasmodial activity of phosphate buffer extract of Calotropis procera latex in mice infected with Plasmodium berghei. MATERIALS AND METHODS: The plant's anti-plasmodial agent was extracted using 0.2 M-phosphate buffer (pH 7.0), followed by precipitation using acetone. 90 (ninety) mice were divided into three main groups of 30 (thirty) mice each, used for the curative, suppressive and prophylactic tests, respectively. The 30 (thirty) mice in each of the main groups were sub-divided into five groups of 6 (six) mice. The mice in the group 1, 2 and 3 (test groups) were made to receive graded doses of 25 mg/kg, 50 mg/kg and 75 mg/kg of the extract of C. procera latex intraperitoneally; group 4 (negative control group) received 0.2 ml of normal saline; while group 5 (positive control group) were administered with 5 mg/kg chloroquine. The phytochemical constituents of the plant and its intraperitoneal median lethal dose (LD50) were also undertaken. RESULTS: The freeze-dried acetone extract exhibited acute toxicity with median lethal dose (LD50) of 745 mg/kg body weight in mice. The highest percentage parasite suppression (61.85%), percentage parasite cure (50.26%), and percentage parasite prophylaxis (65.47%), were obtained for the groups treated with 75 mg/kg bodyweight/day of the extract. The least percentage parasite suppression (44.74%), percentage parasite cure (35.21%), and percentage parasite prophylaxis (45.21%), were obtained for the groups treated with 25 mg/kg body weight of the extract. Also, a dose-dependent percentage parasite suppression (53.03%), percentage parasite cure (39.70%), and percentage parasite prophylaxis (49.82%) were obtained for the groups treated with 50 mg/kg body weight. This is comparable to the groups treated with standard chloroquine. The extract also produced a significant elevation in body weight of the animals for suppressive and curative tests. However, there were observable significant decreases in body weight of the animals in the case of prophylactic test. CONCLUSION: This study showed that the phosphate buffer extract of C. procera latex possess anti-plasmodial activity. The results of this study can be used as a basis for further phytochemical investigations in the search for new and locally affordable antimalarial agents.

Hyperhomocysteinemia and its relations to conventional risk factors for cardiovascular diseases in adult Nigerians: the REMAH study.

BACKGROUND: Evidence linking homocysteine (Hcy) with cardiovascular diseases (CVD) or its risk factors are limited in a sub-Saharan black population. OBJECTIVE: We set out to evaluate the association between Hcy and hypertension and other CVD risk factors in a population of adult Nigerians. METHODS: Data of 156 adults aged 18-70 years was accessed from the North Central study site of the REmoving the MAsk on Hypertension (REMAH) study. Homocysteine, blood glucose and lipid profile in whole blood/serum were measured using standard laboratory methods. Hypertension was diagnosed if average of 5 consecutive blood pressure (BP) measurements obtained using a mercury sphygmomanometer was equal to or higher than 140 systolic and/or 90 mmHg diastolic or the individual is on antihypertensive medication. Hyperhomocysteinemia (HHcy) was defined as Hcy > 10 µmol/L. RESULTS: Of the 156 participants, 72 (43.5%) were hypertensive, of whom 18 had HHcy. Subjects with HHcy were significantly (p < 0.05) older (41.5 vs. 40.6yrs), had lower HDL-cholesterol (0.6 vs. 0.8 mmol/L) and higher systolic (145.5 vs. 126.0 mmHg) and diastolic BP (92.9 vs. 79.6 mmHg), compared to those without HHcy. Intake of alcohol and a 1 yr increase in age were respectively and significantly (p < 0.05) associated with a 1.54 and 0.10 µmol/L increase in Hcy. In a multivariable model adjusted for age, sex and body mass index, a 1 µmol/L increase in Hcy, was associated with a 1.69 mmHg and 1.34 mmHg increase in systolic and diastolic pressure (p < 0.0001) respectively; and a 0.01 mmol/L decrease in HDL-cholesterol (p < 0.05). CONCLUSION: HHcy occurs among hypertensive Nigerians and it is independently associated with age, HDL-cholesterol, systolic and diastolic BP.

Herbal Drug use in Sickle Cell Disease Management; Trends and Perspectives in Sub-Saharan Africa - A Systematic Review.

INTRODUCTION: Nigeria has the largest burden of Sickle Cell Disease (SCD) with estimated 100,000 new born affected annually. SCD is a Hemoglobin (Hb) disorder with the major form resulting from the substitution of a polar glutamate (Glu) by non-polar Valine (Val) in an invariant region of Hbß chain-subunit. Species of Hb found in the sickle cell trait are HbA and HbS in a 60:40 proportion, in SCD only HbS, in the HbC disease only HbC, and in the SC disease it's HbS and HbC in a 50:50 equal proportion. OBJECTIVE: This paper reviews herbal medicines usage in sub-Saharan Africa (sSA) to ameliorate the crisis associated with SCD. The model Hb tetramer suggests a higher membrane affinity of HbS and HbC, promoting dehydration of RBCs, with concomitant in vivo crystallization. Some drawbacks using these herbal drugs include; poor bioavailability and the lack of proper pharmacovigilance monitoring procedures arising from weak governance structure combined with under reporting of herbal usage to physicians were discussed. Probable epigenetic loci that could be targeted using phytomedicines for effective SCD management were also discussed. METHODS: Using search engines, several databases including Google scholar, PubMed, Academic Resource Index were utilized as a source for relevant publications/ literature. The protein coordinates for the Hb tetramer were obtained from the Protein Data Bank (PDB). CONCLUSION: Manipulation of epigenetics to achieve better SCD management involves careful thinking. Herein, we discuss some epigenetic interactions that could be putatively tweaked with a view of enhancing soluble bioactive small molecular components with the potential to reactivate γ -globin genes, thereby boosting immune response in patient with SCD.

A biosensor for inorganic phosphate using a rhodamine-labeled phosphate binding protein.

A novel biosensor for inorganic phosphate (Pi) has been developed based on the phosphate binding protein of Escherichia coli. Two cysteine mutations were introduced and labeled with 6-iodoacetamidotetramethylrhodamine. When physically close to each other and correctly oriented, two rhodamine dyes interact to form a noncovalent dimer. In this state, they have little or no fluorescence, unlike the high fluorescence intensity of monomeric rhodamine. The labeling sites were so placed that the distance and orientation between the rhodamines change as a consequence of the conformational change associated with Pi binding. This movement alters the extent of interaction between the dyes. The best mutant of those tested (A17C, A197C) gives rise on average to approximately 18-fold increase in fluorescence intensity as Pi binds. The kinetics of interaction with Pi were measured at 10 degrees C. Under these conditions, the fluorescence increase associated with Pi binding has a maximum rate of 267 s-1. The Pi dissociation rate is 6.6 s-1, and the dissociation constant is 70 nM. An application of the sensor is demonstrated for measuring ATP hydrolysis in real time as a helicase moves along DNA. Advantages of the new sensor are discussed, both in terms of the use of a rhodamine fluorophore and the potential of this double labeling strategy.

Novel insertions of Bruton tyrosine kinase in patients with X-linked agammaglobulinemia.

Mutations in the gene encoding Bruton tyrosine kinase (BTK) result in X-linked agammaglobulinemia (XLA), an immunodeficiency of antibody defect. By using base excision sequence scanning method (BESS) followed by direct sequencing we found in seven unrelated families with a classical XLA phenotype various mutations including six novel mutations (g.64512_64513insC, c.108_109insG, c.1700_1701insACTACAG, g.51375_51376GC>TG, g.63991_63992insGGTAGAAAAAA, c.1956_1957insCA) and a previously known silent polymorphism (c.2031C>T). Except for two mutations, the alterations affect the kinase domain. There was exceptionally high proportion of insertions in the cohort. Frameshift insertion was found altogether in five patients, three of which are on introns, one in upstream region, and one in exon 18 leading to frameshift mutation and truncation of the protein. In the intron 4 there is a substitution of two bases. Carrier detection was performed in four families. In one case the mutation was found to be de novo.

Interaction between Btk TH and SH3 domain.

Several mechanisms are involved in the regulation of cellular signaling. Bruton tyrosine kinase (Btk) of the Tec family contains in the Tec homology (TH) domain a proline-rich region (PRR) capable of interacting with several SH3 domains. The Btk has the SH3 domain adjacent to the TH domain. CD and fluorescence spectroscopy were used to study the binding of two peptides corresponding to segments in the PRR to the Btk SH3 domain. The peptide for the N-terminal half of the PRR binds specifically, whereas the other peptide had hardly any affinity. The TH domain has about four times lower affinity to the SH3 domain than the peptide, 17.0 vs 3.9 microM. The interaction was further tested with an SH3 domain construct that contained the PRR. The two peptides cannot compete for the binding to the extended protein and the TH domain has two times lower affinity to the extended SH3 domain. The intra- or intermolecular interaction between the TH and SH3 domain might have regulatory function also in the other Tec family members.