Microbiome in sickle cell disease: Pathophysiology and therapeutic insights.

Sickle cell disease (SCD) is a complex genetic blood disorder characterized by abnormal haemoglobin, resulting in sickle-shaped red blood cells. While extensive research has concentrated on the genetic and physiological aspects of SCD, recent studies suggest a potential role of the human microbiome in SCD pathophysiology, adding new dimensions to its understanding. This review synthesizes current knowledge on the microbiome's involvement in SCD, focusing on alterations in the gut microbiome composition and diversity compared to healthy individuals, and their implications for disease pathogenesis.

Corrigendum: Comparative genomics of spp. biocontrol strains in correlation to phenotypes and plant pathogen antagonistic capacity.

[This corrects the article DOI: 10.3389/fmicb.2023.

Comparative genomics of spp. biocontrol strains in correlation to phenotypes and plant pathogen antagonistic capacity.

(Bcsl) strains are widely explored due to their capacity to antagonize a broad range of plant pathogens. These include sp. UW85, whose antagonistic capacity is attributed to the secondary metabolite Zwittermicin A (ZwA).

Spatial and temporal dynamics of microbiomes and resistomes in broiler litter stockpiles.

Farmers apply broiler chicken litter to soils to enrich organic matter and provide crops with nutrients, following varying periods of stockpiling. However, litter frequently harbors fecal-derived microbial pathogens and associated antibiotic resistance genes (ARGs), and may be a source of microbial contamination of produce. We coupled a cutting-edge Loop Genomics long-read 16S rRNA amplicon-sequencing platform with high-throughput qPCR that targeted a suite of ARGs, to assess temporal (five time points over a 60-day period) and spatial (top, middle and bottom layers) microbiome and resistome dynamics in a broiler litter stockpile.

Longitudinal study on the effects of growth-promoting and therapeutic antibiotics on the dynamics of chicken cloacal and litter microbiomes and resistomes.

Background: Therapeutic and growth-promoting antibiotics are frequently used in broiler production. Indirect evidence indicates that these practices are linked to the proliferation of antimicrobial resistance (AMR), the spread of antibiotic-resistant bacteria from food animals to humans, and the environment, but there is a lack of comprehensive experimental data supporting this. We investigated the effects of growth promotor (bacitracin) and therapeutic (enrofloxacin) antibiotic administration on AMR in broilers for the duration of a production cycle, using a holistic approach that integrated both culture-dependent and culture-independent methods.

Hidden Resistome: Enrichment Reveals the Presence of Clinically Relevant Antibiotic Resistance Determinants in Treated Wastewater-Irrigated Soils.

Treated-wastewater (TW) irrigation transfers antibiotic-resistant bacteria (ARB) to soil, but persistence of these bacteria is generally low due to resilience of the soil microbiome. Nonetheless, wastewater-derived bacteria and associated antibiotic resistance genes (ARGs) may persist below detection levels and potentially proliferate under copiotrophic conditions. To test this hypothesis, we exposed soils from microcosm, lysimeter, and field experiments to short-term enrichment in copiotroph-stimulating media.

Leishmanial CpG DNA nanovesicles: A propitious prophylactic approach against visceral leishmaniasis.

Unmethylated CpG motifs with phosphothioate backbone trigger TLR9 to elicit innate immune response characterized by the production of Th1 cytokines. The use of CpG DNA as an adjuvant has established its role in potentiating the humoral and cell mediated vaccine specific immune response. However, none of the synthetic oligodeoxynucleotides (ODNs) know and used till date are associated with the parasite itself.

Assessment of Diazotrophic in Sugarcane Rhizosphere When Intercropped With Legumes (Peanut and Soybean) in the Field.

Several factors influenced the sugarcane production, and among them, higher use of nitrogen and depletion of soil nutrient constitutes a significant concern in China. Sugarcane-legume intercropping may help to regulate the microbial structure and functions. In the present study, sugarcane rhizosphere soils of three cropping systems: Sugarcane only (S-only), sugarcane with peanut (S + P), and sugarcane + soybean (S + S) were sampled in tillering, elongation, and maturation stages from two different experimental fields.

Microglial TLR9: Plausible Novel Target for Therapeutic Regime Against Glioblastoma Multiforme.

An understanding of pattern recognition receptors (PRRs) and immunomodulatory approach based on activation of these receptors has provided insights critical for the management of neurological health disorders. Toll-like receptors (TLRs) are one of the most widely explored PRRs and have been exploited in the recent past for development of novel immunomodulatory therapeutic agents. Glioblastoma multiforme is characterized by significant infiltration of resident microglia and expresses all the members of the TLR family.

Repolarization of glioblastoma macrophage cells using non-agonistic Dectin-1 ligand encapsulating TLR-9 agonist: plausible role in regenerative medicine against brain tumor.

Aim Of The Study: Glioblastoma multiforme (GBM) is the most severe forms of brain cancer, eventually becoming the leading cause of brain cancer-related death worldwide. Owing to the bleak surgical interventions and resistance to the different treatment regime, GBM is a parlous disease demanding newer therapeutical perspective for its treatment. Toll-like receptors (TLRs) are well-known members of pathogen recognition receptors (PRRs) and have been extensively explored for their therapeutic and prophylactic potential in an array of disease including cancer.

Platforms for elucidating antibiotic resistance in single genomes and complex metagenomes.

Antibiotic or antimicrobial resistance (AR) facilitated by the vertical and/or horizontal transfer of antibiotic resistance genes (ARGs), is a serious global health challenge. While traditionally associated with pathogens in clinical environments, it is becoming increasingly clear that non-clinical environments may also be reservoirs of ARGs. The recent improvements in rapid and affordable next generation sequencing technologies along with sophisticated bioinformatics platforms has the potential to revolutionize diagnostic microbiology and microbial surveillance.

Impelling TLR9: Road to perspective vaccine for visceral leishmaniasis.

Recent trends in immunotherapy have shown enthusiasm in exploring Toll-like receptors (TLRs) for designing therapeutical interventions against numerous deadly diseases. TLRs are subfamily of pathogen recognition receptor playing pivotal role in innate immunity. TLR9 is one such critical member belonging to intracellular TLRs which is associated with mounting inflammatory response in response to intruders.

Antiproliferative activity and mode of action analysis of novel amino and amido substituted phenantrene and naphtho[2,1-b]thiophene derivatives.

Herein we present and describe the design and synthesis of novel phenantrene derivatives substituted with either amino or amido side chains and their biological activity. Antiproliferative activities were assessed in vitro on a panel of human cancer cell lines. Tested compounds showed moderate activity against cancer cells in comparison with 5-fluorouracile.

Pharmacophore-based virtual screening approach for identification of potent natural modulatory compounds of human Toll-like receptor 7.

Toll-like receptor 7 (TLR7) is a transmembrane glycoprotein playing very crucial role in the signaling pathways involved in innate immunity and has been demonstrated to be useful in fighting against infectious disease by recognizing viral ssRNA & specific small molecule agonists. In order to find novel human TLR7 (hTLR7) modulators, computational ligand-based pharmacophore modeling approach was used to identify the molecular chemical features required for the modulation of hTLR7 protein. A training set of 20 TLR7 agonists with their known experimental activity was used to create pharmacophore model using 3D-QSAR pharmacophore generation (HypoGen algorithm) module in Discovery Studio.

Neuraminidase inhibitors susceptibility profiles of highly pathogenic influenza A (H5N1) viruses isolated from avian species in India (2006-2015).

We tested 65 highly pathogenic avian influenza (HPAI) A(H5N1) viruses, isolated from avian species in India between 2006 and 2015, for susceptibility to the FDA approved neuraminidase (NA) inhibitors (NAIs), oseltamivir and zanamivir using a phenotypic fluorescence-based assay. The overall incidence of resistant variants among HPAI A(H5N1) viruses was 7.69% (5/65).

Low-density lipoprotein receptor-related protein 6 is a novel coreceptor of protease-activated receptor-2 in the dynamics of cancer-associated β-catenin stabilization.

Protease-activated receptor-2 (PAR2) plays a central role in cancer; however, the molecular machinery of PAR2-instigated tumors remains to be elucidated. We show that PAR2 is a potent inducer of β-catenin stabilization, a core process in cancer biology, leading to its transcriptional activity. Novel association of low-density lipoprotein-related protein 6 (LRP6), a known coreceptor of Frizzleds (Fz), with PAR2 takes place following PAR2 activation.

Functional attributes of evolutionary conserved Arg45 of Wolbachia (Brugia malayi) translation initiation factor-1.

Aim: Wolbachia is a promising antifilarial chemotherapeutic target. Translation initiation factor-1 (Tl IF-1) is an essential factor in prokaryotes. Functional characterization of Wolbachia's novel proteins/enzymes is necessary for the development of adulticidal drugs.

In Silico Elucidation and Inhibition Studies of Selected Phytoligands Against Mitogen-Activated Protein Kinases of Protozoan Parasites.

Parasitic MAPKs exhibiting significant divergence with humans and playing an imperative role in parasitic metabolic activities have been exploited from several years as important targets for development of novel therapeutics. In addition, the emergence of the drug-resistant variants of parasitic diseases in the recent years has aroused a great need for the development of potent inhibitors against them. In the present study, we selected the metabolically active MAPKs LmxMPK4, PfMAP2 and TbMAPK5 of the three parasitic protozoans Leishmania mexicana, Plasmodium falciparum and Trypanosoma brucei, respectively.

In silico analysis of human Toll-like receptor 7 ligand binding domain.

Toll-like receptors recognizing pathogen-associated molecular patterns are preface actors for innate immunity. Among them TLR7 is a transmembrane protein playing very crucial role in the signaling pathways involved in innate immunity by recognizing viral ssRNA and specific small molecule agonists. The unavailability of experimental 3D structure of this receptor till date hampers the focused exploration of TLR7 interaction with its ligands.

Cross talk between Leishmania donovani CpG DNA and Toll-like receptor 9: an immunoinformatics approach.

The precise and potential contribution of Toll-like receptors (TLRs) signaling pathways in fighting parasitic infections of Leishmania spp., an intracellular protozoan parasite, has gained significant attention during the last decades. Although it is well established that TLR9 recognizes CpG motifs in microbial genomes, the specificity of the CpG DNA pattern of Leishmania parasite interacting with endosomal TLR9 is still unknown.

In silico elucidation and inhibition studies of selected phytoligands against Mitogen activated protein kinases of protozoan parasites.

Parasitic MAPKs exhibiting significant divergence with humans and playing an imperative role in parasitic metabolic activities have been exploited from several years as important targets for development of novel therapeutics. In addition, the emergence of the drug resistant variants of parasitic diseases in the recent years has aroused a great need for the development of potent inhibitors against them. In the present study we selected the metabolically active MAPKs LmxMPK4, PfMAP2 and TbMAPK5 of the three parasitic protozoans Leishmania mexicana, Plasmodium falciparum and Trypanosoma brucei respectively.

In silico elucidation and inhibition studies of selected phytoligands against Mitogen activated protein kinases of protozoan parasites.

Parasitic MAPKs exhibiting significant divergence with humans and playing an imperative role in parasitic metabolic activities have been exploited from several years as important targets for development of novel therapeutics. In addition, the emergence of the drug resistant variants of parasitic diseases in the recent years has aroused a great need for the development of potent inhibitors against them. In the present study we selected the metabolically active MAPKs LmxMPK4, PfMAP2 and TbMAPK5 of the three parasitic protozoans Leishmania mexicana, Plasmodium falciparum and Trypanosoma brucei respectively.

Wolbachia transcription elongation factor "Wol GreA" interacts with α2ββ'σ subunits of RNA polymerase through its dimeric C-terminal domain.

Objectives: Wolbachia, an endosymbiont of filarial nematode, is considered a promising target for therapy against lymphatic filariasis. Transcription elongation factor GreA is an essential factor that mediates transcriptional transition from abortive initiation to productive elongation by stimulating the escape of RNA polymerase (RNAP) from native prokaryotic promoters. Upon screening of 6257 essential bacterial genes, 57 were suggested as potential future drug targets, and GreA is among these.