Evaluation of seaweed sulfated polysaccharides as natural antagonists targeting Salmonella typhi OmpF: molecular docking and pharmacokinetic profiling

Background Salmonella belongs to the Enterobacteriaceae family, a gram-negative, non-spore-forming, rod-shaped, motile, and pathogenic bacteria that transmit through unhygienic conditions. It is estimated that 21 million new infections arise every year, resulting in approximately 200,000 deaths. It is more prevalent among children, the old aged, and immunocompromised individuals. The frequent usage of classical antimicrobials has begun the increasing emergence of various drug-resistant pathogenic bacterial strains. Hence, this study was intended to evaluate the bioactive seaweed sulfated polysaccharides (SSPs) against the ompF (outer membrane porin F) protein target of Salmonella typhi. SSP is the sulfated compound with a wide range of biological activities, such as anti-microbial, anti-allergy, anti-cancer, anti-coagulant, anti-inflammation, anti-oxidant, and anti-viral. Results In this study, eleven compounds were targeted against S. typhi OmpF by the molecular docking approach and were compared with two commercially available typhoid medications. The SSP showed good binding affinity compared to commercial drugs, particularly carrageenan/MIV-150, carrageenan lambda, fucoidan, and 3-phenyllactate, ranked as top antagonists against OmpF. Further, pharmacokinetics and toxicology (ADMET) studies corroborated that SSP possessed drug-likeness and highly progressed in all parameters. Conclusions AutoDockTools and Schrodinger's QikProp module results suggest that SSP could be a promising drug for extensively drug-resistant (XDR) S. typhi. To the best of our knowledge, this is the first report on in silico analysis of SSP against S. typhi OmpF, thus implying the capabilities of SSPs especially compounds like carrageenans, as a potential anti-microbial agent against Salmonella typhi infections. Eventually, advanced studies could corroborate SSPs to the next level of application in the crisis of XDR microbial diseases. Graphical Abstract

Mesenchymal Stem Cell-Derived Exosome Therapy of Microbial Diseases: From Bench to Bed

Microbial diseases are a global health threat, leading to tremendous casualties and economic losses. The strategy to treat microbial diseases falls into two broad categories: pathogen-directed therapy (PDT) and host-directed therapy (HDT). As the typical PDT, antibiotics or antiviral drugs directly attack bacteria or viruses through discerning specific molecules. However, drug abuse could result in antimicrobial resistance and increase infectious disease morbidity. Recently, the exosome therapy, as a HDT, has attracted extensive attentions for its potential in limiting infectious complications and targeted drug delivery. Mesenchymal stem cell-derived exosomes (MSC-Exos) are the most broadly investigated. In this review, we mainly focus on the development and recent advances of the application of MSC-Exos on microbial diseases. The review starts with the difficulties and current strategies in antimicrobial treatments, followed by a comprehensive overview of exosomes in aspect of isolation, identification, contents, and applications. Then, the underlying mechanisms of the MSC-Exo therapy in microbial diseases are discussed in depth, mainly including immunomodulation, repression of excessive inflammation, and promotion of tissue regeneration. In addition, we highlight the latest progress in the clinical translation of the MSC-Exo therapy, by summarizing related clinical trials, routes of administration, and exosome modifications. This review will provide fundamental insights and future perspectives on MSC-Exo therapy in microbial diseases from bench to bedside.

Application of Stem Cell-Derived Extracellular Vesicles as an Innovative Theranostics in Microbial Diseases

Extracellular vesicles (EVs), as nano-/micro-scale vehicles, are membranous particles containing various cargoes including peptides, proteins, different types of RNAs and other nucleic acids, and lipids. These vesicles are produced by all cell types, in which stem cells are a potent source for them. Stem cell-derived EVs could be promising platforms for treatment of infectious diseases and early diagnosis. Infectious diseases are responsible for more than 11 million deaths annually. Highly transmissible nature of some microbes, such as newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), drives researcher’s interest to set up different strategies to develop novel therapeutic strategies. Recently, EVs-based diagnostic and therapeutic approaches have been launched and gaining momentum very fast. The efficiency of stem cell-derived EVs on treatment of clinical complications of different viruses and bacteria, such as SARS-CoV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Staphylococcus aureus, Escherichia coli has been demonstrated. On the other hand, microbial pathogens are able to incorporate their components into their EVs. The microbe-derived EVs have different physiological and pathological impacts on the other organisms. In this review, we briefly discussed biogenesis and the fate of EVs. Then, EV-based therapy was described and recent developments in understanding the potential application of stem cell-derived EVs on pathogenic microorganisms were recapitulated. Furthermore, the mechanisms by which EVs were exploited to fight against infectious diseases were highlighted. Finally, the deriver challenges in translation of stem cell-derived EVs into the clinical arena were explored.

Analysis and Appraisal of Fascine in Shahe Ancient Bridge Ruins, Xi’an, Shaanxi, China

The Chinese civilization has a long history, and the Chinese ancestors invented the "aquatic engineering technology" for flood control and water management as early as two thousand years ago: Fascine Body. The Fascine Body is a structure used to protect the bank and block the breach in the ancient Chinese flood control project. The excavation of the Shahe Ancient Bridge Ruins in Xi’an City, Shaanxi Province, China discovered the existence of a fascine body structure. Through C14 dating, fiber slice observation, infrared spectroscopy, X-ray diffraction, thermogravimetric analysis and SEM energy spectrum analysis of the fascine material, at the same time, conduct the microbial identification on it and the surrounding soil, analyze its dominant bacterial community, and control its microbial diseases in a targeted manner. The research on the fascine bank ruins solved the boundary problem of the width and length of the Shahe ancient bridge, evaluated the exact age of Shahe ancient bridge, provided the important materials for the research on ancient bridges, river embankments and other ruins, and also provided the important clues for the traffic and layout around Chang'an during the Qin and Han Dynasties of Chinese history.

Regular Daily Ablution (Wudu') Consequence on Reduction Coronavirus Infection during Pandemic in Saudi Society

Prophet Muhammad (peace be upon Him) said: “Cleanliness is half of faith”, protect from infectious disease. Coronavirus infection prevention closely related to Muslims advice as regular daily ablution (Wudu'). The aim was for Moslem individuals to follow regular daily ablution (Wudu'), its impact on health protection of individual and Saudi society from infectious diseases and Coronavirus during pandemic. That was used the "Study Competency" and the "Coupled Assessment" was utilized "Reaching Study Question Consequences", the "Moderate Excel Packet" was outcome defined. The results were for first question “Perform regular daily ablution for prayer”; was 100%. The second question ”Urges an individuals to perform regular daily ablution”; was 97%. The third question “Regular daily ablution helps to clean the body organs well”; was 92%. The fourth question “Regular daily ablution is one of the ways to sterilize with running water”; was 81%. The fifth question “Regular daily ablution is improved an individual health status”; was 80%. The sixth question “Regular daily ablution helps to reduce an individual pathogenic microorganisms infection”; was 81%. The seventh question “Regular daily ablution is one of the ways to protect an individual health from microbial diseases”; was 86%. The eighth question “Regular daily ablution helps the success of “Health Precautionary Measures” to prevent Coronavirus infection” was 82%. The ninth question “Regular daily ablution health way to reduces an individual Coronavirus infection”; was 86%. The tenth question “Regular daily ablution healthy ways to reduce and protect Saudi society from Coronavirus infection”; was 84%. It was concluded that through the results to the extent of the strength of Islam for the Saudi society and the strength of implementing the provisions of Islam for the individual and Saudi society. Regular daily ablution (Wudu') consequence had proven strengthen the health of the individual and Saudi society and reduce infectious microbial diseases. The individual from Saudi society, and when observing regular daily ablution (Wudu') and updating ablution (Wudu') reduce and protect from Coronavirus infection during pandemic. That beneficial to individual health and Saudi society health. It was recommend that the commitment to implement the Islamic steps as regular daily ablution (Wudu') reduces infectious microbial diseases, reduces and protects individuals and Saudi society from Coronavirus infection during pandemic.

Targeting Host Glycolysis as a Strategy for Antimalarial Development

Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a known dose-limiting side effect of these inhibitors and presents a major caveat to development of antiglycolytic therapies. We developed specific inhibitors of enolase – a critical enzyme in glycolysis – and validated their metabolic and cellular effects on human erythrocytes. Enolase inhibition increases erythrocyte susceptibility to oxidative damage and induces rapid and premature erythrocyte senescence, rather than direct hemolysis. We apply our model of red cell toxicity to address questions regarding erythrocyte glycolytic disruption in the context of Plasmodium falciparum malaria pathogenesis. Our study provides a framework for understanding red blood cell homeostasis under normal and disease states and clarifies the importance of erythrocyte reductive capacity in malaria parasite growth.

Evaluation of Seaweed Sulfated Polysaccharides As Natural Antagonists Targeting Salmonella typhi OmpF: Molecular Docking and Pharmacokinetic Profiling

Background: Salmonella belongs to the Enterobacteriaceae family, a gram-negative, non-spore-forming, rod-shaped, motile, and pathogenic bacteria that transmit through unhygienic conditions. It is estimated that 21 million new infections arise every year, resulting in approximately 200,000 deaths. It is more prevalent among children, the old aged, and immunocompromised individuals. The frequent usage of classical antimicrobials has begun the increasing emergence of various drug-resistant pathogenic bacterial strains. Hence, this study was intended to evaluate the bioactive seaweed sulfated polysaccharides (SSP) against the ompF (outer membrane porin F) protein target of Salmonella typhi. SSP are sulfated compounds with a wide range of biological activities, such as anti-microbial, anti-allergy, anti-cancer, anti-coagulant, anti-inflammation, anti-oxidant, and anti-viral. Results: In this study, eleven compounds were targeted against S. typhi OmpF by molecular docking approach and were compared with two commercially available typhoid medications. The SSP showed good binding affinity compared to commercial drugs, particularly carrageenan/MIV-150, carrageenan lambda, fucoidan, and 3-Phenyllactate, ranked as top antagonists against OmpF. Further, pharmacokinetics and toxicology (ADMET) studies corroborated that SSP possessed drug-likeness and highly progressed in all parameters.Conclusion: AutoDockTools and Schrodinger's QikProp module results suggest that SSP could be a promising drug for extensively drug-resistant (XDR) S. typhi. To our best of knowledge, this is the first report on in-silico analysis of SSP against S. typhi OmpF. Thus, implying the capabilities of SSP's especially compounds like carrageenans, as a potential anti-microbial agent against Salmonella typhi infections. Eventually, advanced studies could corroborate SSPs to the next level of application in the crisis of XDR microbial diseases.

Antimicrobial Peptides from Plants: A cDNA-Library Based Isolation, Purification, Characterization Approach and Elucidating Their Modes of Action

Even in a natural ecosystem, plants are continuously threatened by various microbial diseases. To save themselves from these diverse infections, plants build a robust, multilayered immune system through their natural chemical compounds. Among the several crucial bioactive compounds possessed by plants' immune systems, antimicrobial peptides (AMPs) rank in the first tier. These AMPs are environmentally friendly, anti-pathogenic, and do not bring harm to humans. Antimicrobial peptides can be isolated in several ways, but recombinant protein production has become increasingly popular in recent years, with the Escherichia coli expression system being the most widely used. However, the efficacy of this expression system is compromised due to the difficulty of removing endotoxin from its system. Therefore, this review suggests a high-throughput cDNA library-based plant-derived AMP isolation technique using the Bacillus subtilis expression system. This method can be performed for large-scale screening of plant sources to classify unique or homologous AMPs for the agronomic and applied field of plant studies. Furthermore, this review also focuses on the efficacy of plant AMPs, which are dependent on their numerous modes of action and exceptional structural stability to function against a wide range of invaders. To conclude, the findings from this study will be useful in investigating how novel AMPs are distributed among plants and provide detailed guidelines for an effective screening strategy of AMPs.