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

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

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

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

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

In silico prediction of new antimicrobial peptides and proteins as druggable targets towards alternative anti-schistosomal therapy

Schistosomiasis is a debilitating disease caused by a parasitic flatworm found in fresh- water. With the exponential increase in prevalence, Praziquantel (PZQ) remains the only effective treatment drug, however, resistance to PZQ has been reported recently. There- fore, it is imperative to develop effective alternative anti-schistosomal compounds using bioinformatics-based tools utilizing the broad-spectrum therapeutic capabilities of antimi- crobial peptides (AMPs). AMPs are essential components of the innate immune system and are responsible for complete destruction and immunomodulatory effects in the host defence against pathogens. Here, Hidden Markov model was used to identify six anti- microbial peptides (TAK1–TAK6) with potential anti-schistosomal capabilities. Also, glyco- syltransferase and axonemal dynein intermediate chain protein were identified as impor- tant druggable Schistosome proteins. The 3-D structures of the AMPs and proteins were modelled using I-TASSER and it was shown that the six putative anti-schistosomal AMPs and the two proteins had low C-score, possibly due to lack of available templates for their modelling. Finally, PatchDock was employed to ascertain the interaction between the schis- tosome proteins and the putative AMPs

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 thestability 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. Salsbur

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

Biosynthesis of Silver Nanoparticles Using Bersama engleriana Fruits Extracts and Their Potential Inhibitory Effect on Resistant Bacteria

The absence of novel, safe, and effective bactericide is an urgent concern worldwide and remains a challenge in scientific communities. The unique proprieties of silver nanoparticles (SNPs) synthesized from plant extracts make them a suitable candidate to overcome these limitations. Herein, we synthesized SNPs from Bersama engleriana fruit (BEfr) extracts and determined their potential antibacterial activity and mode of action. SNPs were synthesized from BEfr methanolic fruit extracts at 25 and 70 ◦C, and the antibacterial effectiveness of SNPs against bacterial strains was investigated. The surface plasmon resonance peaked at 430.18 and 434.08 nm, respectively, for SNPs synthesized at 25 and 70 ◦C, confirming SNPs synthesis. BEfr-SNPs had minimum inhibitory concentrations (MIC) range of 0.234 to >50 µg/mL, which was 30-fold greater than extract alone (MIC of 500 µg/mL). BEfrSNPs-25 ◦C was potent against six bacterial strains (S. aureus, S. enterica, MRS. aureus, K. pneumonia, and S. pyogenes), with MIC range of 0.339 to 6.25 µg/mL. The mode of action of BEfr-SNPs-25 ◦C was achieved by an MRSA bacteria strain outer membrane and DNA nucleotide linkage. These results suggest that our synthesized SNPs, especially BEfr-SNPs-25 ◦C, demonstrated an enhanced antibacterial effect and could be potential candidates for bacterial infection treatment

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