In Silico Comparison of Bioactive Compounds Characterized from Azadirachta indica with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment.

The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug.

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

Unravelling the anti-inflammatory mechanism of Allium cepa: an integration of network pharmacology and molecular docking approaches.

Allium cepa, commonly known as onion, is a widely consumed spice that possesses numerous pharmacological properties. A. cepa bioactive components are often explored in the treatment of inflammation-related complications. However, the molecular mechanism via which they exert their anti-inflammatory effects remains unknown. Therefore, this study aimed to elucidate the anti-inflammatory mechanism of A. cepa bioactive components. Consequently, the bioactive compounds of A. cepa were obtained from a database, while the potential targets of the sixty-nine compounds with desirable pharmacokinetic properties were predicted. Subsequently, the targets of inflammation were acquired from the GeneCards database. The protein-protein interaction (PPI) between the sixty-six shared targets of the bioactive compounds and inflammation was retrieved from the String database and visualized using Cytoscape v3.9.1 software. Gene Ontology (GO) analysis of the ten core targets from the PPI network revealed that A. cepa bioactive compounds could be involved in regulating biological processes such as response to oxygen-containing compounds and response to inflammation while Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis revealed that A. cepa compounds might modulate pathways including AGE-RAGE signaling pathway, interleukin (IL)-17 signalling pathway, and tumor necrosis factor signaling pathway. Molecular docking analysis showed that 1-O-(4-Coumaroyl)-beta-D-glucose, stigmasterol, campesterol, and diosgenin have high binding affinities for core targets including EGFR, ALB, MMP9, CASP3, and CCL5. This study successfully elucidated the potential anti-inflammatory mechanism of A. cepa bioactive compounds, hence, providing new insights into the development of alternative anti-inflammatory drugs.

Immunoinformatics Studies and Design of a Potential Multi-Epitope Peptide Vaccine to Combat the Fatal Visceral Leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by parasitic intracellular protozoa of the genus Leishmania. The visceral form of this disease caused by Leishmania donovani continues to constitute a major public health crisis, especially in countries of endemicity. In some cases, it is asymptomatic and comes with acute and chronic clinical outcomes such as weight loss, pancytopenia, hepatosplenomegaly, and death if left untreated. Over the years, the treatment of VL has relied solely on chemotherapeutic agents, but unfortunately, these drugs are now faced with challenges. Despite all efforts, no successful vaccine has been approved for VL. This could be as a result of limited knowledge/understanding of the immune mechanisms necessary to regulate parasite growth. Using a computational approach, this study explored the prospect of harnessing the properties of a disulfide isomerase protein of L. donovani amastigotses to develop a multi-epitope subunit vaccine candidate against the parasite. We designed a 248-amino acid multi-epitope vaccine with a predicted antigenicity probability of 0.897372. Analyses of immunogenicity, allergenicity, and multiple physiochemical parameters indicated that the constructed vaccine candidate was stable, non-allergenic, and immunogenic, making it compatible with humans and hence, a potentially viable and safe vaccine candidate against Leishmania spp. Parasites.

COVID-19 Diagnosis: A Review of Rapid Antigen, RT-PCR and Artificial Intelligence Methods.

As of 27 December 2021, SARS-CoV-2 has infected over 278 million persons and caused 5.3 million deaths. Since the outbreak of COVID-19, different methods, from medical to artificial intelligence, have been used for its detection, diagnosis, and surveillance. Meanwhile, fast and efficient point-of-care (POC) testing and self-testing kits have become necessary in the fight against COVID-19 and to assist healthcare personnel and governments curb the spread of the virus. This paper presents a review of the various types of COVID-19 detection methods, diagnostic technologies, and surveillance approaches that have been used or proposed. The review provided in this article should be beneficial to researchers in this field and health policymakers at large.

The Practicality of the Use of Liquid Biopsy in Early Diagnosis and Treatment Monitoring of Oral Cancer in Resource-Limited Settings.

An important driving force for precision and individualized medicine is the provision of tailor-made care for patients on an individual basis, in accordance with best evidence practice. Liquid biopsy(LB) has emerged as a critical tool for the early diagnosis of cancer and for treatment monitoring, but its clinical utility for oral squamous cell carcinoma (OSCC) requires more research and validation. Hence, in this review, we have discussed the current applications of LB and the practicality of its routine use in Africa; the potential advantages of LB over the conventional "gold-standard" of tissue biopsy; and finally, practical considerations were discussed in three parts: pre-analytic, analytic processing, and the statistical quality and postprocessing phases. Although it is imperative to establish clinically validated and standardized working guidelines for various aspects of LB sample collection, processing, and analysis for optimal and reliable use, manpower and technological infrastructures may also be an important factor to consider for the routine clinical application of LB for OSCC. LB is poised as a non-invasive precision tool for personalized oral cancer medicine, particularly for OSCC in Africa, when fully embraced. The promising application of different LB approaches using various downstream analyses such as released circulating tumor cells (CTCs), cell free DNA (cfDNA), microRNA (miRNA), messenger RNA (mRNA), and salivary exosomes were discussed. A better understanding of the diagnostic and therapeutic biomarkers of OSCC, using LB applications, would significantly reduce the cost, provide an opportunity for prompt detection and early treatment, and a method to adequately monitor the effectiveness of the therapy for OSCC, which typically presents with ominous prognosis.

Deciphering the interaction of puerarin with cancer macromolecules: An in silico investigation.

The worldwide expanding increment in cancer pervasiveness is disturbing and this disease ranks among the main causes of mortality in both developing and developed countries. Unfortunately, available treatment options come with serious side effects and do not guarantee complete success. Although numerous models have been proposed for the development of better therapeutic agent, however the exact mechanism are still poorly understood. This then calls for continued research aimed at developing new drugs as an alternative or adjuvant anticancer agents. Here we have identified five vital proteins (CDK-2, Bcl-2, CDK-6, VEGFR, and IGF-1R) that aid tumor growth and we inhibited the activity of these proteins with Puerarin. Puerarin is an isoflavonoid C-glycosides used as a therapeutic agent against various human ailments. Our findings revealed that Puerarin fulfilled Veber's rule. Added to this, CDK-6 and Bcl-2 had better glide scores for puerarin than the control (doxorubicin) and molecular simulation showed the stability of the complexes. These findings suggest that inhibiting CDK-6 and Bcl-2 with Puerarin could prove more effective in the management of cancer than doxorubicin. Overall, this study provides a new direction that could facilitate rational drug design for cancer.Communicated by Ramaswamy H. Sarma.

Inhibitory potential of repurposed drugs against the SARS-CoV-2 main protease: a computational-aided approach.

The exponential increase in cases and mortality of coronavirus disease (COVID-19) has called for a need to develop drugs to treat this infection. Using in silico and molecular docking approaches, this study investigated the inhibitory effects of Pradimicin A, Lamivudine, Plerixafor and Lopinavir against SARS-CoV-2 Mpro. ADME/Tox of the ligands, pharmacophore hypothesis of the co-crystalized ligand and the receptor, and docking studies were carried out on different modules of Schrodinger (2019-4) Maestro v12.2. Among the ligands subjected to ADME/Tox by QikProp, Lamivudine demonstrated drug-like physico-chemical properties. A total of five pharmacophore binding sites (A3, A4, R9, R10, and R11) were predicted from the co-crystalized ligand and the binding cavity of the SARS-CoV-2 Mpro. The docking result showed that Lopinavir and Lamivudine bind with a higher affinity and lower free energy than the standard ligand having a glide score of -9.2 kcal/mol and -5.3 kcal/mol, respectively. Plerixafor and Pradimicin A have a glide score of -3.7 kcal/mol and -2.4 kcal/mol, respectively, which is lower than the co-crystallized ligand with a glide score of -5.3 kcal/mol. Molecular dynamics confirmed that the ligands maintained their interaction with the protein with lower RMSD fluctuations over the trajectory period of 100 nsecs and that GLU166 residue is pivotal for binding. On the whole, present study specifies the repurposing aptitude of these molecules as inhibitors of SARS-CoV-2 Mpro with higher binding scores and forms energetically stable complexes with Mpro.Communicated by Ramaswamy H. Sarma.

In silico inhibition of SGTP4 as a therapeutic target for the treatment of schistosomiasis.

Schistosomiasis is an infectious tropical disease caused by parasitic flatworm of the genus Schistosoma. This debilitating disease chronically infects about 200 million people globally and management relies on chemotherapy. Unfortunately, the solely available schistosomicide (praziquantel) against all forms of adult schistosmes has been faced with numerous drawbacks. Thus, there is an urgent need to design and develop a new regimen for schistosomiasis. In light of this, the current study focuses on inhibiting the schistosome glucose transporter 4 (SGTP4) as a therapeutic candidate for schistosomiasis. Several studies have revealed that Schistosoma parasites require an adequate amount of energy/glucose to survive. We modelled the 3D structure and subsequently used the homology model for docking with praziquantel (PZQ), Licochalcone A, Licarin and Harmonine. The docked complexes were subjected to molecular dynamics using Desmond system of Schrodinger software. Furthermore, the pharmacokinetic parameters of the ligands were investigated using the QikProp tool in the Schrodinger-2019-4 software suite. After performing all the computational analysis, our findings reveal that all four ligands were able to inhibit SGTP4 effectively through the higher glide G score (dock score) of -5.8 (-5.8), -6.5 (-6.4), -7.3 (-7.3) and -4.9 (-4.9) in kcal/mol for praziquantel, licochalcone A, licarin and harmonine respectively against the protein. The molecular simulation further confirmed that the stability of the complexes formed between the ligands and protein is excellent. More so, all the ligands fulfilled oral drugability of both the Lipinski's rule of five and Veber's rules.The findings in this present study provide new useful insights for the design of drugs which can serve as an alternative to praziquantel in the treatment of schistosomiasis through the inhibition of SGTP4.Communicated by Freddie R. Salsbury.

Interleukin-4 Responsive Dendritic Cells Are Dispensable to Host Resistance Against Leishmania mexicana Infection.

IL-4 and IL-13 cytokines have been associated with a non-healing phenotype in murine leishmaniasis in L. mexicana -infected BALB/c mice as demonstrated in IL-4-/-, IL-13-/- and IL-4Rα-/- global knockout mouse studies. However, it is unclear from the studies which cell-type-specific IL-4/IL-13 signaling mediates protection to L. mexicana. Previous studies have ruled out a role for IL-4-mediated protection on CD4+ T cells during L. mexicana infections. A candidate for this role may be non-lymphocyte cells, particularly DCs, as was previously shown in L. major infections, where IL-4 production drives dendritic cell-IL-12 production thereby mediating a type 1 immune response. However, it is unclear if this IL-4-instruction of type 1 immunity also occurs in CL caused by L. mexicana, since the outcome of cutaneous leishmaniasis often depends on the infecting Leishmania species. Thus, BALB/c mice with cell-specific deletion of the IL-4Rα on CD11c+ DCs (CD11ccreIL-4Rα-/lox) were infected with L. mexicana promastigotes in the footpad and the clinical phenotype, humoral and cellular immune responses were investigated, compared to the littermate control. Our results show that CL disease progression in BALB/c mice is independent of IL-4Rα signaling on DCs as CD11ccreIL-4Rα-/lox mice had similar footpad lesion progression, parasite loads, humoral responses (IgE, IgG1, IgG 2a/b), and IFN-γ cytokine secretion in comparison to littermate controls. Despite this comparable phenotype, surprisingly, IL-4 production in CD11ccreIL-4Rα-/lox mice was significantly increased with an increasing trend of IL-13 when compared to littermate controls. Moreover, the absence of IL-4Rα signaling did not significantly alter the frequency of CD4 and CD8 lymphocytes nor their activation, or memory phenotype compared to littermate controls. However, these populations were significantly increased in CD11ccreIL-4Rα-/lox mice due to greater total cell infiltration into the lymph node. A similar trend was observed for B cells whereas the recruitment of myeloid populations (macrophages, DCs, neutrophils, and Mo-DCs) into LN was comparable to littermate IL-4Rα-/lox mice. Interestingly, IL-4Rα-deficient bone marrow-derived dendritic cells (BMDCs), stimulated with LPS or L. mexicana promastigotes in presence of IL-4, showed similar levels of IL-12p70 and IL-10 to littermate controls highlighting that IL-4-mediated DC instruction was not impaired in response to L. mexicana. Similarly, IL-4 stimulation did not affect the maturation or activation of IL-4Rα-deficient BMDCs during L. mexicana infection nor their effector functions in production of nitrite and arginine-derived metabolite (urea). Together, this study suggests that IL-4 Rα signaling on DCs is not key in the regulation of immune-mediated protection in mice against L. mexicana infection.

Can We Harness Immune Responses to Improve Drug Treatment in Leishmaniasis?

Leishmaniasis is a vector-borne parasitic disease that has been neglected in priority for control and eradication of malaria, tuberculosis, and HIV/AIDS. Collectively, over one seventh of the world's population is at risk of being infected with 0.7-1.2 million new infections reported annually. Clinical manifestations range from self-healing cutaneous lesions to fatal visceral disease. The first anti-leishmanial drugs were introduced in the 1950's and, despite several shortcomings, remain the mainstay for treatment. Regardless of this and the steady increase in infections over the years, particularly among populations of low economic status, research on leishmaniasis remains under funded. This review looks at the drugs currently in clinical use and how they interact with the host immune response. Employing chemoimmunotherapeutic approaches may be one viable alternative to improve the efficacy of novel/existing drugs and extend their lifespan in clinical use.

Unravelling the unsolved paradoxes of cytokine families in host resistance and susceptibility to Leishmania infection.

Leishmaniasis is a neglected disease caused by protozoan parasites of the genus Leishmania. Successful clearance of Leishmania relies on a robust human immune response and various cytokines have been implicated in resistance and susceptibility to Leishmania infection. Accordingly, various immunotherapeutic approaches involving cytokines and cytokine receptors are being considered as novel avenues of treatment given the limited efficacy of current anti-leishmanial drugs. These approaches target canonical T helper (Th)1/Type 1 cytokines as intended mediators of host-protection to infection whilst concomitantly suppressing Th2/Type 2 cytokines and their anticipated disease-promoting roles. However, the use of cytokine and cytokine receptor gene-deficient mice over the years has challenged this simplistic view of Th1/Type 1-mediated resistance and Th2/Type 2-mediated susceptibility. Indeed, contribution to susceptibility vs resistance is only a partial consequence to cytokine action as the overall response is multi-faceted due to the pleiotropic, redundant, antagonistic and synergistic action of cytokines and interactions with immune cells in the diseased state. Notably, while the responses of certain cytokines are selectively host-protective or characteristic disease-enhancers, some ligands exert a response depending on the parasite-species initiating infection. Paradoxically, others play dual or contradictory roles in different Leishmania immunopathologies. Hence, cytokines in disease is an unsolved paradox and a comprehensive knowledge of cytokine interplay is important to guide the development of novel immunotherapeutics against leishmaniasis. In this review, we characterize various cytokine families in persistence and clearance of the Leishmania parasite and particularly elucidate unsolved cytokine puzzles in leishmaniasis based on information acquired from "gain of knowledge by loss of function" studies in cytokine and cytokine receptor gene-deficient mice.

Applications of Computational Methods in Biomedical Breast Cancer Imaging Diagnostics: A Review.

With the exponential increase in new cases coupled with an increased mortality rate, cancer has ranked as the second most prevalent cause of death in the world. Early detection is paramount for suitable diagnosis and effective treatment of different kinds of cancers, but this is limited to the accuracy and sensitivity of available diagnostic imaging methods. Breast cancer is the most widely diagnosed cancer among women across the globe with a high percentage of total cancer deaths requiring an intensive, accurate, and sensitive imaging approach. Indeed, it is treatable when detected at an early stage. Hence, the use of state of the art computational approaches has been proposed as a potential alternative approach for the design and development of novel diagnostic imaging methods for breast cancer. Thus, this review provides a concise overview of past and present conventional diagnostics approaches in breast cancer detection. Further, we gave an account of several computational models (machine learning, deep learning, and robotics), which have been developed and can serve as alternative techniques for breast cancer diagnostics imaging. This review will be helpful to academia, medical practitioners, and others for further study in this area to improve the biomedical breast cancer imaging diagnosis.

Spondias mombim L. (Anacardiaceae): Chemical fingerprints, inhibitory activities, and molecular docking on key enzymes relevant to erectile dysfunction and Alzheimer's diseases.

Due to the exceptional wide range in biochemical activities of natural plant products, Spondias mombim L. are attaining a new height because they present great prospects for drug advancement. This research was designed to analyze the pharmaceutical properties of S. mombim L. ethyl acetate fraction (SMEAF) on key enzymes relevant to erectile and cognitive dysfunction. SMEAF inhibitory activities of the specified enzymes were determined spectrophotometrically. Chemical profile of SMEAF were assessed by HPLC/MS analysis. Thereafter, molecular docking of the studied enzymes with chlorogenic acid, lutein, and zeaxanthin were carried out using PATCHDOCK. SMEAF had remarkable enzyme inhibitory effects against phosphodiesterase-5 (PDE-5), arginase, angiotensin I-converting enzyme (ACE), cholinesterase, monoamine oxidase A (MAO), ecto-5' nucleotidase (E-NTDase), tyrosinase, and stimulated sodium-potassium ATPase (Na+/K+-ATPase) activities. HPLC/MS analysis revealed that phenolics and carotenoids were major components in these fraction notably, chlorogenic acid, lutein, and zeaxanthin. Our results suggested that SMEAF could be explored as phytopharmaceuticals. PRACTICAL APPLICATIONS: Spondias mombim L. are cooked as green vegetable with enormous medicinal value probably due to its polyphenols with potent antioxidant activity. Furthermore, the leaves could also be useful for therapeutic purposes against erectile dysfunction and central nervous system disorders.

PZQ Therapy: How Close are we in the Development of Effective Alternative Anti-schistosomal Drugs?

Today schistosomiasis, caused mainly by the three major schistosome species (S. mansoni, S. haematobium and S. japonicum), has for many decades and still continues to be on a rapid and swift rise globally, claiming thousands of lives every year and leaving 800 million people at the risk of infection. Due to the high prevalence of this disease and the steady increase in the infection rates, praziquantel (PZQ) remains the only effective drug against this acute disease although it has no effect on the juvenile schistosome parasite. However, no significant approaches have been made in recent years in the discovery of new or alternative drugs and unfortunately, resistance to this drug has been reported in some parts of the world. Therefore, it is imperative to develop a new drug for this debilitating disease. In this review, a brief history of past, present, and new promising anti-schistosomal drugs is presented.

Structure-Based Docking Studies of GLUT4 Towards Exploring Selected Phytochemicals from Solanum xanthocarpum as a Therapeutic Target for the Treatment of Cancer.

BACKGROUND: In recent years, there has been an exponential increase in the global burden of cancer which has been associated with several factors including environmental influence, aging, diet, infectious agents, hormonal imbalance and chronic inflammation, among others. Cancerous cells utilize more glucose for its proliferation and survival than normal cells. Thus, the regulation of glucose consumption of cancerous cells through the inhibition of glucose transporter-4-protein (GLUT4) encoded by solute carrier family-2-member-4-gene (Slc2a4) by selected phytochemicals from Solanum xanthocarpum may serve as a new therapeutic candidate for the treatment of cancer. METHODS: The seven identified potential inhibitors of GLUT4 from Solanum xanthocarpum were retrieved from PubChem database. Examination of their drug-likeness, toxicity prediction and molecular docking studies of these compounds with GLUT4 were carried out using online tools such as Molinspiration, PreADMET V.2.0 and Patchdock server. RESULTS: The findings revealed that, five out of the seven compounds fulfil oral drugability of Lipinski's rule of five (RO5) while two slightly meet the criteria of RO5. Conversely, five of the compounds are predicted to be mutagen while the remaining two are predicted to be safe for the body. Additionally, stigmasterol glucoside has higher binding-affinity (7590) with GLUT4 when compared to doxorubicin (6600) the control. CONCLUSION: These findings suggest that stigmasterol glucoside from Solanum xanthocarpum could be a promising therapeutic agent with better therapeutic efficacy than doxorubicin in the treatment of cancer via the inhibition of GLUT4.

The Effect of Climate Change and the Snail-Schistosome Cycle in Transmission and Bio-Control of Schistosomiasis in Sub-Saharan Africa.

In the next century, global warming, due to changes in climatic factors, is expected to have an enormous influence on the interactions between pathogens and their hosts. Over the years, the rate at which vector-borne diseases and their transmission dynamics modify and develop has been shown to be highly dependent to a certain extent on changes in temperature and geographical distribution. Schistosomiasis has been recognized as a tropical and neglected vector-borne disease whose rate of infection has been predicted to be elevated worldwide, especially in sub-Saharan Africa; the region currently with the highest proportion of people at risk, due to changes in climate. This review not only suggests the need to develop an efficient and effective model that will predict Schistosoma spp. population dynamics but seeks to evaluate the effectiveness of several current control strategies. The design of a framework model to predict and accommodate the future incidence of schistosomiasis in human population dynamics in sub-Saharan Africa is proposed. The impact of climate change on schistosomiasis transmission as well as the distribution of several freshwater snails responsible for the transmission of Schistosoma parasites in the region is also reviewed. Lastly, this article advocates for modelling several control mechanisms for schistosomiasis in sub-Saharan Africa so as to tackle the re-infection of the disease, even after treating infected people with praziquantel, the first-line treatment drug for schistosomiasis.

Structural Studies of Predicted Ligand Binding Sites and Molecular Docking Analysis of Slc2a4 as a Therapeutic Target for the Treatment of Cancer.

Presently, many studies have focused on exploring in silico approaches in the identification and development of alternative therapy for the treatment and management of cancer. Solute carrier family-2-member-4-gene (Slc2a4) which encodes glucose transporter 4 protein (GLUT4), has been identified as a promising therapeutic target for cancer. Though Slc2a4 is known to play a major regulatory role in the pathophysiology of type 2 diabetes, emerging evidence suggests that successful pharmacological inhibition of this protein may lead to the development of a novel drug candidate for the treatment of cancer. In this study, Slc2a4 protein sequence was retrieved and analysed using in silico approaches, and we identified seven putative antimicrobial peptides (AMPs; RAB1-RAB7) as anti-cancer. The structures of the protein and AMPs were modelled using I-TASSER server, and the overall quality of the Slc2a4 model was validated using PROCHECK. Subsequently, the probable motifs and active site of the protein were forecasted. Also, the molecular interaction between the AMPs and Slc2a4 was ascertained using PatchDock. The result revealed that, all the AMPs are good Slc2a4 inhibitors with RAB1 having the highest binding affinity of 12,392 and binding energy of -39.13 kcal/mol. Hence, this study reveals that all the generated AMPs can serve as therapeutic drug in treating cancer by inhibiting Slc2a4 which is responsible for the production of energy for cancer cells during angiogenesis. This is the first report on AMPs as inhibitors of Slc2a4 for the treatment of cancer.

Structural Analysis and Epitope Prediction of MHC Class-1-Chain Related Protein-A for Cancer Vaccine Development.

Major histocompatibility complex class 1 chain-related gene sequence A is a polymorphic gene found at about 46.6 kb centromeric to HLA-B. It encodes a transmembrane protein, which is a non-classical human leukocyte antigen whose expression is normally induced by stress conditions like cancer and viral infections. The expression of MIC-A leads to the activation of NKG2D receptors of natural killer and T cells, leading to the generation of innate immune response that can easily eliminate/cleanse tumour cells and other cells that express the protein. Several bioinformatics and immunoinformatics tools were used to analyse the sequence and structure of the MIC-A protein. These tools were used in building and evaluating modelled structure of MIC-A, and to predict several antigenic determinant sites on the protein. The MIC-A protein structure generated an average antigenic propensity of 1.0289. Additionally, the hydrophilic regions on the surface of the MIC-A protein where antibodies can be attached were revealed. A total of fourteen antigenic epitopes were predicted, with six found in the transmembrane protein topology, and are predicted to play a role in the development of vaccines that can reactivate the functionalities of the MIC-A protein on the surface of cancer cells in order to elicit a desired immune response.