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The Middle Eastern prevalence of sickle cell anemia, a genetic disorder that affects red blood cells, necessitates additional research. On a molecular level, we sought to identify and sort the oral microbiota of healthy individuals and those with sickle cell anemia. Furthermore, it is crucial to comprehend how changes in the genetic makeup of the oral microbiota impact the state of sickle cell anemia. Using next-generation sequencing, the 16S rRNA amplicon was examined using saliva samples from 36 individuals with sickle cell anemia and healthy individuals. These samples were obtained from sickle cell anemia patients (18 samples) and healthy control participants (controls, 18 samples). Various analyses are conducted using bioinformatic techniques to identify distinct species and their relative abundance. Streptococcus, followed by Fusobacterium nucleatum, Prevotella, and Veillonella were the most prevalent genera of bacteria in the saliva of the SCA and non-SCA individuals according to our findings. Rothia mucilaginosa, Prevotella scoposa, and Veillonella dispar species were the dominant species in both sickle cell anemia and non-sickle cell anemia subjects. Streptococcus salivarius, Actinomyces graevenitzii, Actinomyces odontolyticus, and Actinomyces georgiae spp. were the most prevalent bacterial spp. in the studied SCA cases. The sequencing of the 16S rRNA gene yielded relative abundance values that were visualized through a heatmap analysis. Alterations in the oral microflora's constitution can significantly affect the susceptibility of sickle cell anemia patients to develop more severe health complications. Salivary diagnosis is a potential tool for predicting and preventing oral microbiome-related diseases in the future. [ABSTRACT FROM AUTHOR]

The leaves, flowers, seeds, and bark of the Nyctanthes arbor-tristis Linn plant have been pharmacologically evaluated to signify the medicinal importance traditionally described for various ailments. We evaluated the anti-inflammatory potentials of 26 natural compounds using AutoDock 4.2 and Molecular Dynamics (MDS) performed with the GROMACS tool. SwissADME evaluated ADME (adsorption, distribution, metabolism, and excretion) parameters. Arb_E and Beta-sito, natural compounds of the plant, showed significant levels of binding affinity against COX-1, COX-2, PDE4, PDE7, IL-17A, IL-17D, TNF-α, IL-1β, prostaglandin E2, and prostaglandin F synthase. The control drug celecoxib exhibited a binding energy of −9.29 kcal/mol, and among the tested compounds, Arb_E was the most significant (docking energy: −10.26 kcal/mol). Beta_sito was also observed with high and considerable docking energy of −8.86 kcal/mol with the COX-2 receptor. COX-2 simulation in the presence of Arb_E and control drug celecoxib, RMSD ranged from 0.15 to 0.25 nm, showing stability until the end of the simulation. Also, MM-PBSA analysis showed that Arb_E bound to COX-2 exhibited the lowest binding energy of −277.602 kJ/mol. Arb_E and Beta_sito showed interesting ADME physico-chemical and drug-like characteristics with significant drug-like effects. Therefore, the studied natural compounds could be potential anti-inflammatory molecules and need further in vitro/in vivo experimentation to develop novel anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

STAPHYLOCOCCUS aureus can enter the bloodstream, leading to health complications such as sepsis, arthritis, endocarditis, and pneumonia. This study screened for the impact of six replication genes of cos phage 12 (φ12) on the evolution and transfer of cos S. aureus pathogenicity islands (SaPIbov5). An overnight culture of the S. aureus strain RN4220 diluted with fresh TSB was used in the bacteriophage φ12 titering assay. Phage-point mutagenesis was achieved using the pMAD vector, which facilitates homologous recombination in a two-step process. Finally, the transduction SaPI titering assays also utilized the S. aureus strain RN4220, which was then mixed with CaCl2 and fresh TSB. The study showed that ORF11, ORF12, and VirE mutants did not lyse or produce phage particles after titering into the recipient RN4220 strains. While ORF26, ORF10, and ORF04 mutants generated detectable plaques, the mutations may have an effect on phage replication or packaging after tittering. For instance, complemented φ12 ORF26, ORF10, and ORF04 mutant strains had fully restored phage titers. The experiment found that cos phages facilitate inter and intra-generically transfer of cosSaPIs. It was also established that φ12 transduces SaPIbov5. However, φ12 mutants in VirE, ORF12, and ORF11 did not show SaPI mobilization because of their effects on infective phage particles and lack of replication. The complemented φ12 VirE, ORF12, and ORF11 mutants had partly restored phage titers when they were expressed in the recipient and donor strains. Mutations in ORF26, 0RF10, and ORFO4 decrease the φ12's ability to transfer SaPIbov5. Generally, this study found a new mechanism that facilitates the transfer of SaPI and cos genes. While the VirE, ORF12, and ORF11 affect packaging and are necessary for replication and phage biology [ABSTRACT FROM AUTHOR]

The consumer demand for fresh produce (vegetables and fruits) has considerably increased since the 1980s for more nutritious foods and healthier life practices, particularly in developed countries. Currently, several foodborne outbreaks have been linked to fresh produce. The global rise in fresh produce associated with human infections may be due to the use of wastewater or any contaminated water for the cultivation of fruits and vegetables, the firm attachment of the foodborne pathogens on the plant surface, and the internalization of these agents deep inside the tissue of the plant, poor disinfection practices and human consumption of raw fresh produce. Several investigations have been established related to the human microbial pathogens (HMPs) interaction, their internalization, and survival on/within plant tissue. Previous studies have displayed that HMPs are comprised of several cellular constituents to attach and adapt to the plant's intracellular niches. In addition, there are several plant-associated factors, such as surface morphology, nutrient content, and plant–HMP interactions, that determine the internalization and subsequent transmission to humans. Based on documented findings, the internalized HMPs are not susceptible to sanitation or decontaminants applied on the surface of the fresh produce. Therefore, the contamination of fresh produce by HMPs could pose significant food safety hazards. This review provides a comprehensive overview of the interaction between fresh produce and HMPs and reveals the ambiguity of interaction and transmission of the agents to humans. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic has rapidly extended globally and killed approximately 5.83 million people all over the world. But, to date, no effective therapeutic against the disease has been developed. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enters the host cell through the spike glycoprotein (S protein) of the virus. Subsequently, RNA-dependent RNA polymerase (RdRp) and main protease (M pro ) of the virus mediate viral transcription and replication. Mechanistically inhibition of these proteins can hinder the transcription as well as replication of the virus. Recently oxysterols and its derivative, such as 25 (S)-hydroxycholesterol (25-HC) has shown antiviral activity against SARS-CoV-2. But the exact mechanisms and their impact on RdRp and M pro have not been explored yet. Therefore, the study aimed to identify the inhibitory activity of 25-HC against the viral enzymes RdRp and M pro simultaneously. Initially, a molecular docking simulation was carried out to evaluate the binding activity of the compound against the two proteins. The pharmacokinetics (PK) and toxicity parameters were analyzed to observe the 'drug-likeness' properties of the compound. Additionally, molecular dynamics (MD) simulation was performed to confirm the binding stability of the compound to the targeted protein. Furthermore, molecular mechanics generalized Born surface area (MM-GBSA) was used to predict the binding free energies of the compound to the targeted protein. Molecular docking simulation identified low glide energy -51.0 kcal/mol and -35.0 kcal/mol score against the RdRp and M pro, respectively, where MD simulation found good binding stability of the compound to the targeted proteins. In addition, the MM/GBSA approach identified a good value of binding free energies (ΔG bind) of the compound to the targeted proteins. Therefore, the study concludes that the compound 25-HC could be developed as a treatment and/or prevention option for SARS-CoV-2 disease-related complications. Although, experimental validation is suggested for further evaluation of the work.Communicated by Ramaswamy H. Sarma.