Molecular Interactions Associated with Coagulation of Organic Pollutants by 2S Albumin of Plant Proteins: A Computational Approach

The removal of organic pollutants is a major challenge in wastewater treatment technologies. Coagulation by plant proteins is a promising technique for this purpose. The use of these proteins has been experimentally investigated and reported in the literature. However, the determination of the molecular interactions of these species is experimentally challenging and the computational approach offers a suitable alternative in gathering useful information for this system. The present study used a molecular dynamic simulation approach to predict the potentials of using Moringa oleifera (MO), Arachis hypogaea, Bertholletia excelsa, Brassica napus, and Helianthus annuus plant proteins for the coagulation of organic pollutants and the possible mechanisms of coagulation of these proteins. The results showed that the physicochemical and structural properties of the proteins are linked to their performance. Maximum coagulation of organic molecules to the proteins is between 50–100%. Among five proteins studied for coagulation, Brassica napus and Helianthus annuus performed better than the well-known MO protein. The amino acid residues interacting with the organic molecules play a significant role in the coagulation and this is peculiar with each plant protein. Hydrogen bond and π—interactions dominate throughout the protein–pollutants molecular interactions. The reusability of the proteins after coagulation derived from their structural quality analysis along with the complexes looks promising and most of them are better than that of the MO. The results showed that the seed proteins studied have good prediction potentials to be used for the coagulation of organic pollutants from the environment, as well as the insights into their molecular activities for bioremediation

Screening of apical membrane antigen-1 (AMA1), dense granule protein-7 (GRA7) and rhoptry protein-16 (ROP16) antigens for a potential vaccine candidate against Toxoplasma gondii for chickens

Toxoplasmosis is a zoonotic disease caused by the protozoan parasite, Toxoplasma gondii known to infect almost all animals, including birds and humans globally. This disease has impacted the livestock industry and public health, where infection of domestic animals increases the zoonotic risk of transmission of infection to humans, threatening public health. Hence the need to discover novel and safe vaccines to fight against toxoplasmosis. In the current study, a novel multiepitope vaccine was designed using immunoinformatics techniques targeting T. gondii AMA1, GRA7 and ROP16 antigens, consisting of antigenic, immunogenic, non-allergenic and cytokine inducing T-cell (9 CD8+ and 15 CD4+) epitopes and four (4) B-cell epitopes fused together using AAY, KK and GPGPG linkers. The tertiary model of the proposed vaccine was predicted and validated to confirm the structural quality of the vaccine. The designed vaccine was highly antigenic (antigenicity = 0.6645), immunogenic (score = 2.89998), with molecular weight of 73.35 kDa, instability and aliphatic index of 28.70 and 64.10, respectively; and GRAVY of −0.363. The binding interaction, stability and flexibility were assessed with molecular docking and dynamics simulation, which revealed the proposed vaccine to have good structural interaction (binding affinity = −106.882 kcal/mol) and stability when docked with Toll like receptor-4 (TLR4). The results revealed that the Profilin-adjuvanted vaccine is promising, as it predicted induction of enhanced immune responses through the production of cytokines and antibodies critical in blocking host invasion

Design of a Multiepitope Vaccine against Chicken Anemia Virus Disease

Chicken anemia virus (CAV) causes severe clinical and sub-clinical infection in poultry globally and thus leads to economic losses. The drawbacks of the commercially available vaccines against CAV disease signal the need for a novel, safe, and effective vaccine design. In this study, a multiepitope vaccine (MEV) consisting of T-cell and B-cell epitopes from CAV viral proteins (VP1 and VP2) was computationally constructed with the help of linkers and adjuvant. The 3D model of the MEV construct was refined and validated by different online bioinformatics tools. Molecular docking showed stable interaction of the MEV construct with TLR3, and this was confirmed by Molecular Dynamics Simulation. Codon optimization and in silico cloning of the vaccine in pET-28a (+) vector also showed its potential expression in the E. coli K12 system. The immune simulation also indicated the ability of this vaccine to induce an effective immune response against this virus. Although the vaccine in this study was computationally constructed and still requires further in vivo study to confirm its effectiveness, this study marks a very important step towards designing a potential vaccine against CAV disease

Screening of apical membrane antigen-1 (AMA1), dense granule protein-7 (GRA7) and rhoptry protein-16 (ROP16) antigens for a potential vaccine candidate against Toxoplasma gondii for chickens

DATA AVAILABILITY : Data will be made available on request.Toxoplasmosis is a zoonotic disease caused by the protozoan parasite, Toxoplasma gondii known to infect almost all animals, including birds and humans globally. This disease has impacted the livestock industry and public health, where infection of domestic animals increases the zoonotic risk of transmission of infection to humans, threatening public health. Hence the need to discover novel and safe vaccines to fight against toxoplasmosis. In the current study, a novel multiepitope vaccine was designed using immunoinformatics techniques targeting T. gondii AMA1, GRA7 and ROP16 antigens, consisting of antigenic, immunogenic, non-allergenic and cytokine inducing T-cell (9 CD8+ and 15 CD4+) epitopes and four (4) B-cell epitopes fused together using AAY, KK and GPGPG linkers. The tertiary model of the proposed vaccine was predicted and validated to confirm the structural quality of the vaccine. The designed vaccine was highly antigenic (antigenicity = 0.6645), immunogenic (score = 2.89998), with molecular weight of 73.35 kDa, instability and aliphatic index of 28.70 and 64.10, respectively; and GRAVY of 0.363. The binding interaction, stability and flexibility were assessed with molecular docking and dynamics simulation, which revealed the proposed vaccine to have good structural interaction (binding affinity = 106.882 kcal/mol) and stability when docked with Toll like receptor-4 (TLR4). The results revealed that the Profilin-adjuvanted vaccine is promising, as it predicted induction of enhanced immune responses through the production of cytokines and antibodies critical in blocking host invasion.The National Research Foundation (NRF) of South Africa.https://www.elsevier.com/locate/jvacxam2023Veterinary Tropical DiseasesSDG-03:Good heatlh and well-bein

Molecular Interactions Associated with Coagulation of Organic Pollutants by 2S Albumin of Plant Proteins: A Computational Approach

The removal of organic pollutants is a major challenge in wastewater treatment technologies. Coagulation by plant proteins is a promising technique for this purpose. The use of these proteins has been experimentally investigated and reported in the literature. However, the determination of the molecular interactions of these species is experimentally challenging and the computational approach offers a suitable alternative in gathering useful information for this system. The present study used a molecular dynamic simulation approach to predict the potentials of using Moringa oleifera (MO), Arachis hypogaea, Bertholletia excelsa, Brassica napus, and Helianthus annuus plant proteins for the coagulation of organic pollutants and the possible mechanisms of coagulation of these proteins. The results showed that the physicochemical and structural properties of the proteins are linked to their performance. Maximum coagulation of organic molecules to the proteins is between 50–100%. Among five proteins studied for coagulation, Brassica napus and Helianthus annuus performed better than the well-known MO protein. The amino acid residues interacting with the organic molecules play a significant role in the coagulation and this is peculiar with each plant protein. Hydrogen bond and π—interactions dominate throughout the protein–pollutants molecular interactions. The reusability of the proteins after coagulation derived from their structural quality analysis along with the complexes looks promising and most of them are better than that of the MO. The results showed that the seed proteins studied have good prediction potentials to be used for the coagulation of organic pollutants from the environment, as well as the insights into their molecular activities for bioremediation

DataSheet_1_Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter protein.docx

Buruli ulcer is a neglected tropical disease that is characterized by non-fatal lesion development. The causative agent is Mycobacterium ulcerans (M. ulcerans). There are no known vectors or transmission methods, preventing the development of control methods. There are effective diagnostic techniques and treatment routines; however, several socioeconomic factors may limit patients’ abilities to receive these treatments. The Bacillus Calmette–Guérin vaccine developed against tuberculosis has shown limited efficacy, and no conventionally designed vaccines have passed clinical trials. This study aimed to generate a multi-epitope vaccine against M. ulcerans from the major facilitator superfamily transporter protein using an immunoinformatics approach. Twelve M. ulcerans genome assemblies were analyzed, resulting in the identification of 11 CD8+ and 7 CD4+ T-cell epitopes and 2 B-cell epitopes. These conserved epitopes were computationally predicted to be antigenic, immunogenic, non-allergenic, and non-toxic. The CD4+ T-cell epitopes were capable of inducing interferon-gamma and interleukin-4. They successfully bound to their respective human leukocyte antigens alleles in in silico docking studies. The expected global population coverage of the T-cell epitopes and their restricted human leukocyte antigens alleles was 99.90%. The population coverage of endemic regions ranged from 99.99% (Papua New Guinea) to 21.81% (Liberia). Two vaccine constructs were generated using the Toll-like receptors 2 and 4 agonists, LprG and RpfE, respectively. Both constructs were antigenic, non-allergenic, non-toxic, thermostable, basic, and hydrophilic. The DNA sequences of the vaccine constructs underwent optimization and were successfully in-silico cloned with the pET-28a(+) plasmid. The vaccine constructs were successfully docked to their respective toll-like receptors. Molecular dynamics simulations were carried out to analyze the binding interactions within the complex. The generated binding energies indicate the stability of both complexes. The constructs generated in this study display severable favorable properties, with construct one displaying a greater range of favorable properties. However, further analysis and laboratory validation are required.</p

Evaluation of the Antioxidant Properties of Carvacrol as a Prospective Replacement for Crude Essential Oils and Synthetic Antioxidants in Food Storage

The phenolic structural analogues of synthetic antioxidants such as butylated hydroxytoluene (BHT) in essential oils have been reported to exhibit antioxidant properties. Additionally, their lipophilicity makes them suitable for use in lipid-rich foods. This study evaluated the antioxidant capacity of carvacrol, a monoterpenoid antioxidant compound in the Monodora myristica (Gaertn.) seed essential oil, compared to the seed essential oil and BHT. In vitro studies (ferric reducing antioxidant power (FRAP), metal chelating activity (MCA), and nitric oxide scavenging activity (NOSA)) were conducted to ascertain if the antioxidant capacity of carvacrol was comparable to that of the seed essential oil. The potential binding affinity and molecular interactions between carvacrol and lipoxygenase (LOX) and its homologous model were investigated in silico. The molecular docking was performed using Autodock Vina, and the best poses were subjected to molecular dynamics simulation. The IC50 for MCA and NOSA were: carvacrol 50.29 µL/mL, seed essential oil (SEO) 71.06 µL/mL; and carvacrol 127.61 µL/mL, SEO 165.18 µL/mL, respectively. The LOX model was Ramachandran favoured (97.75%) and the overall quality factor in the ERRAT plot was 95.392. The results of the molecular docking and molecular dynamics simulations revealed that lipoxygenase has a higher affinity (−22.79 kcal/mol) for carvacrol compared to BHT. In the LOX–BHT and LOX–carvacrol complexes, the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and the radius of gyration (RoG) were not significantly different, indicating similar molecular interactions. The results obtained from this study suggest that carvacrol exhibits an antioxidant capacity that may be explored as an alternative for crude essential oils and synthetic compounds during the storage of lipid-rich foods

Adaptation of the Wound Healing Questionnaire universal-reporter outcome measure for use in global surgery trials (TALON-1 study): mixed-methods study and Rasch analysis

BackgroundThe Bluebelle Wound Healing Questionnaire (WHQ) is a universal-reporter outcome measure developed in the UK for remote detection of surgical-site infection after abdominal surgery. This study aimed to explore cross-cultural equivalence, acceptability, and content validity of the WHQ for use across low- and middle-income countries, and to make recommendations for its adaptation.MethodsThis was a mixed-methods study within a trial (SWAT) embedded in an international randomized trial, conducted according to best practice guidelines, and co-produced with community and patient partners (TALON-1). Structured interviews and focus groups were used to gather data regarding cross-cultural, cross-contextual equivalence of the individual items and scale, and conduct a translatability assessment. Translation was completed into five languages in accordance with Mapi recommendations. Next, data from a prospective cohort (SWAT) were interpreted using Rasch analysis to explore scaling and measurement properties of the WHQ. Finally, qualitative and quantitative data were triangulated using a modified, exploratory, instrumental design model.ResultsIn the qualitative phase, 10 structured interviews and six focus groups took place with a total of 47 investigators across six countries. Themes related to comprehension, response mapping, retrieval, and judgement were identified with rich cross-cultural insights. In the quantitative phase, an exploratory Rasch model was fitted to data from 537 patients (369 excluding extremes). Owing to the number of extreme (floor) values, the overall level of power was low. The single WHQ scale satisfied tests of unidimensionality, indicating validity of the ordinal total WHQ score. There was significant overall model misfit of five items (5, 9, 14, 15, 16) and local dependency in 11 item pairs. The person separation index was estimated as 0.48 suggesting weak discrimination between classes, whereas Cronbach's α was high at 0.86. Triangulation of qualitative data with the Rasch analysis supported recommendations for cross-cultural adaptation of the WHQ items 1 (redness), 3 (clear fluid), 7 (deep wound opening), 10 (pain), 11 (fever), 15 (antibiotics), 16 (debridement), 18 (drainage), and 19 (reoperation). Changes to three item response categories (1, not at all; 2, a little; 3, a lot) were adopted for symptom items 1 to 10, and two categories (0, no; 1, yes) for item 11 (fever).ConclusionThis study made recommendations for cross-cultural adaptation of the WHQ for use in global surgical research and practice, using co-produced mixed-methods data from three continents. Translations are now available for implementation into remote wound assessment pathways

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research