Data integration with phenotypes such as gene expression, pathways or function, and protein-protein interactions data has proven to be a highly promising technique for improving human complex diseases, particularly cancer patient outcome prediction. Hepatocellular carcinoma is one of the most prevalent cancers, and the most common cause is chronic HBV and HCV infection, which is linked to the majority of cases, and HBV and HCV play a role in multistep carcinogenesis progression. We examined the list of known hepatocellular carcinoma biomarkers with the publicly available expression profile dataset of hepatocellular carcinoma infected with HCV from day 1 to day 10 in this study. The study covers an overexpression pattern for the selected biomarkers in clinical hepatocellular carcinoma patients, a combined investigation of these biomarkers with the gathered temporal dataset, temporal expression profiling changes, and temporal pathway enrichment following HCV infection. Following a temporal analysis, it was discovered that the early stages of HCV infection tend to be more harmful in terms of expression shifting patterns, and that there is no significant change after that, followed by a set of genes that are consistently altered. PI3K, cAMP, TGF, TNF, Rap1, NF-kB, Apoptosis, Longevity regulating pathway, signaling pathways regulating pluripotency of stem cells, Cytokine-cytokine receptor interaction, p53 signaling, Wnt signaling, Toll-like receptor signaling, and Hippo signaling pathways are just a few of the most commonly enriched pathways. The majority of these pathways are well-known for their roles in the immune system, infection and inflammation, and human illnesses like cancer. We also find that ADCY8, MYC, PTK2, CTNNB1, TP53, RB1, PRKCA, TCF7L2, PAK1, ITPR2, CYP3A4, UGT1A6, GCK, and FGFR2/3 appear to be among the prominent genes based on the networks of genes and pathways based on the copy number alterations, mutations, and structural variants study.

Cyclophosphamide (CP) is commonly used as an anticancer agent but has been associated with high toxicity in several animal organs, including the testes. Inositol hexaphosphate (IP6) is a polyphosphorylated carbohydrate that is present in foods with high fibre contents and has a wide range of essential physiological and pathological activities. Thus, we estimated the defensive effects of IP6 against CP-related testicular toxicity in rats. Sperm counts, motilities, viabilities and abnormalities and levels of testosterone, luteinising hormone and follicle-stimulating hormone were evaluated. Testicle specimens were also processed for histological and biochemical analyses, including determinations of malondialdehyde, nitric oxide, total antioxidant capacity, alkaline phosphatase, acid phosphatase, gamma glutamyl transferase, ß-glucuronidase, c-reactive protein, monocyte chemoattractant protein and leukotriene-4 and in comet assays. CP treatments were associated with deleterious histopathological, biochemical and genetic changes in rat testicles, and these were ameliorated by IP6 supplements in drinking water.

The functional processes and mutual benefits of the wild plant Moringa oleifera and its rhizosphere microbiome were studied via metagenomic whole-genome shotgun sequencing (mWGS) in comparison with a bulk soil microbiome. The results indicated high gene abundance of the four KEGG categories, “Cellular Processes”, “Environmental Information Processing”, “Genetic Information Processing”, and “Metabolism”, in the rhizosphere microbiome. Most of the enriched enzymes in rhizobacteria are assigned to the pathway “Amino acids metabolism”, where soil-dwelling microbes use amino acids as a defense mechanism against phytopathogens, while promoting growth, colonizing the cohabiting commensal microbes and conferring tolerance against abiotic stresses. In the present study, it was proven that these beneficial microbes include Bacillus subtilis, Pseudomonas fluorescens, and Escherichia coli. Mineral solubilization in these rhizobacteria can make nutrients available for plant utilization. These rhizobacteria extensively synthesize and metabolize amino acids at a high rate, which makes nitrogen available in different forms for plants and microbes. Amino acids in the rhizosphere might stand mainly as an intermediate switcher for the direction of the soil nitrogen cycle. Indole acetic acid (IAA) was proven to be synthesized by these beneficial rhizobacteria via route indole-3-pyruvate (IPyA) of the pathway “Tryptophan metabolism”. This hormone might stand as a shuttle signaling molecule between M. oleifera and its rhizobacteria. Tryptophan is also metabolized to promote other processes with important industrial applications. Rhizobacteria were also proven to breakdown starch and sucrose into glucose, which is the primary metabolic fuel of living organisms. In conclusion, we assume that the metabolic processes in the rhizosphere microbiome of this wild plant can be eventually utilized in boosting the sustainability of agriculture applications and the plant’s ability to benefit from soil nutrients when they are not in the form available for plant root absorption.

Moringa oleifera (or the miracle tree) is a wild plant species widely grown for its seed pods and leaves, and is used in traditional herbal medicine. The metagenomic whole genome shotgun sequencing (mWGS) approach was used to characterize antibiotic resistance genes (ARGs) of the rhizobiomes of this wild plant and surrounding bulk soil microbiomes and to figure out the chance and consequences for highly abundant ARGs, e.g., mtrA, golS, soxR, oleC, novA, kdpE, vanRO, parY, and rbpA, to horizontally transfer to human gut pathogens via mobile genetic elements (MGEs). The results indicated that abundance of these ARGs, except for golS, was higher in rhizosphere of M. oleifera than that in bulk soil microbiome with no signs of emerging new soil ARGs in either soil type. The most highly abundant metabolic processes of the most abundant ARGs were previously detected in members of phyla Actinobacteria, Proteobacteria, Acidobacteria, Chloroflexi, and Firmicutes. These processes refer to three resistance mechanisms namely antibiotic efflux pump, antibiotic target alteration and antibiotic target protection. Antibiotic efflux mechanism included resistance-nodulation-cell division (RND), ATPbinding cassette (ABC), and major facilitator superfamily (MFS) antibiotics pumps as well as the two-component regulatory kdpDE system. Antibiotic target alteration included glycopeptide resistance gene cluster (vanRO), aminocoumarin resistance parY, and aminocoumarin self-resistance parY. While, antibiotic target protection mechanism included RbpA bacterial RNA polymerase (rpoB)-binding protein. The study supports the claim of the Frontiers in Microbiology 01 frontiersin.org Shami et al. 10.3389/fmicb.2022.990169 possible horizontal transfer of these ARGs to human gut and emergence of new multidrug resistant clinical isolates. Thus, careful agricultural practices are required especially for plants used in circles of human nutrition industry or in traditional medicine.

The present study aimed to predict differential enrichment of pathways and compounds in the rhizosphere microbiomes of the two wild plants (Abutilon fruticosum and Nitrosalsola vermiculata) and to predict functional shifts in microbiomes due to water. Amplicon sequencing of 16S rRNA region V3-V4 was done and gene-based microbial compositions were enrolled in PICRUSt to predict enriched pathways and compounds. The results indicated that "ABC transporters" and "Quorum sensing" pathways are among the highest enriched pathways in rhizosphere microbiomes of the two wild plants compared with those of the bulk soil microbiomes. The highest enriched compounds in soil microbiomes of the two wild plants included five proteins and three enzymes participating in one or more KEGG pathways. Six of these eight compounds showed higher predicted enrichment in rhizosphere soil microbiomes, while only one, namely phosphate transport system substrate-binding protein, showed higher enrichment in the surrounding bulk soil microbiomes. In terms of differentially enriched compounds due to watering, only the dual-specific aspartyl-tRNA (Asn)/glutamyl-tRNA (Gln) amidotransferase subunit A showed higher enrichment in rhizosphere soil of the two wild plants after 24 h of watering. Two of the highly enriched compounds namely branched-chain amino acid transport system ATP-binding protein and branched-chain amino acid transport system substrate-binding protein, are encoded by genes stimulated by the plant's GABA that participates in conferring biotic and abiotic stresses in plants and improves the plant's growth performance. The 3-Oxoacyl-[ACP] reductase, a member of the short-chain alcohol dehydrogenase/ reductase (SDR) superfamily, participates in fatty acids elongation cycles and contributes to plant-microbe symbiotic relationships, while enoyl-CoA hydratase has a reverse action as it participates in "Fatty acid degradation" pathway. The methyl-accepting chemotaxis protein is an environmental signal that sense "Bacterial chemotaxis" pathway to help establishing symbiosis with plant roots by recruiting/colonizing of microbial partners (symbionts) to plant rhizosphere. This information justifies the high enrichment of compounds in plant rhizosphere. The dual-specific aspartyl-tRNA (Asn)/glutamyl-tRNA (Gln) amidotransferase subunit A contributes to the plant ability to respond to watering as it participates in attaching the correct amino acid during translation to its

IntroductionThe study aims to describe phageome of soil rhizosphere of M.oleifera in terms of the genes encoding CAZymes and other KEGG enzymes.MethodsGenes of the rhizospheric virome of the wild plant species Moringa oleifera were investigated for their ability to encode useful CAZymes and other KEGG (Kyoto Encyclopedia of Genes and Genomes) enzymes and to resist antibiotic resistance genes (ARGs) in the soil.ResultsAbundance of these genes was higher in the rhizospheric microbiome than in the bulk soil. Detected viral families include the plant viral family Potyviridae as well as the tailed bacteriophages of class Caudoviricetes that are mainly associated with bacterial genera Pseudomonas, Streptomyces and Mycobacterium. Viral CAZymes in this soil mainly belong to glycoside hydrolase (GH) families GH43 and GH23. Some of these CAZymes participate in a KEGG pathway with actions included debranching and degradation of hemicellulose. Other actions include biosynthesizing biopolymer of the bacterial cell wall and the layered cell wall structure of peptidoglycan. Other CAZymes promote plant physiological activities such as cell-cell recognition, embryogenesis and programmed cell death (PCD). Enzymes of other pathways help reduce the level of soil H2O2 and participate in the biosynthesis of glycine, malate, isoprenoids, as well as isoprene that protects plant from heat stress. Other enzymes act in promoting both the permeability of bacterial peroxisome membrane and carbon fixation in plants. Some enzymes participate in a balanced supply of dNTPs, successful DNA replication and mismatch repair during bacterial cell division. They also catalyze the release of signal peptides from bacterial membrane prolipoproteins. Phages with the most highly abundant antibiotic resistance genes (ARGs) transduce species of bacterial genera Pseudomonas, Streptomyces, and Mycobacterium. Abundant mechanisms of antibiotic resistance in the rhizosphere include “antibiotic efflux pump” for ARGs soxR, OleC, and MuxB, “antibiotic target alteration” for parY mutant, and “antibiotic inactivation” for arr-1.DiscussionThese ARGs can act synergistically to inhibit several antibiotics including tetracycline, penam, cephalosporin, rifamycins, aminocoumarin, and oleandomycin. The study highlighted the issue of horizontal transfer of ARGs to clinical isolates and human gut microbiome.

The plant rhizosphere microbiomes were thought to help the plant stands adverse condition. The study aims at deciphering signatures of rhizosphere soil microbiomes of the medicinal plant Nitrosalsola vermiculata and those of the surrounding bulk soil as well as to detect influence of watering in restructuring soil microbes that can improve the plant’s ability to tolerate drought stress. Amplicon sequencing of partial 16S rRNA gene indicated that alpha diversity indices are higher in rhizosphere than in bulk soils, while no distinctive differences were observed due to the watering. Relative abundance of phylum Cyanobacteria and its descendent unidentified genus is the highest among phyla and genera of bulk soil. Relative abundance of phyla Euryarchaeota, Chloroflexi, Actinobacteria, Proteobacteria, Bacteroidetes, Firmicutes, Acidobacteria and Gemmatimonadetes as well as genera Bacillus, Ammoniphilus, Sphingomonas, Microvirga, Pontibacter, Adhaeribacter and Arthrobacter was significantly higher in rhizosphere soil. The latter taxa were reported to act as plant growth-promoting bacteria (PGPB) through symbiotic associations. We speculate that relative abundance and mutual dominance of these taxa in rhizosphere of N. vermiculata were due to the intensity and type of plant root exudates. Other factors include soil pH where microbes favoring high soil pH can show better growth in rhizosphere soil. Also, co-existence of phyla that promote sustainability of cohabiting phyla in the rhizosphere and have high synergism prevalence in biofilm formation can be one extra factor. Quorum sensing (QS) also mediates bacterial population density in a given environment and elicit specific plant responses. The low abundance of Cyanobacteria in rhizosphere soil can be due to the inhibitory effect of highly abundant members of Firmicutes, especially those of genus Bacillus. The latter conclusion was confirmed by the occurrence of high expression rate of comQ gene triggering QS in genus Bacillus. Highly abundant microbes whose abundance was not changed due to watering are phyla Firmicutes, Proteobacteria, Chloroflexi and Cyanobacteria and their descendent genera Bacillus, Ammoniphilus, Sphingomonas, Microvirga and unidentified genus of Cyanobacteria. We speculate that non-responsive taxa to watering were drought tolerant and can help plants stand adverse conditions of water scarce. In conclusion, insights on the factors involved in shaping microbiome signatures and those eliciting differential plant responses to drought stress are raised and warrant further investigations.

The metagenomic whole genome shotgun sequencing (mWGS) approach was used to detect signatures of the rhizosphere microbiomes of Dipterygium glaucum and surrounding bulk soil microbiomes, and to detect differential microbial responses due to watering. Preliminary results reflect the reliability of the experiment and the rationality of grouping microbiomes. Based on the abundance of non-redundant genes, bacterial genomes showed the highest level, followed by Archaeal and Eukaryotic genomes, then, the least abundant viruses. Overall results indicate that most members of bacteria have a higher abundance/relative abundance (AB/RA) pattern in the rhizosphere towards plant growth promotion, while members of eukaryota have a higher pattern in bulk soil, most likely acting as pathogens. The results also indicate the contribution of mycorrhiza (genus Rhizophagus) in mediating complex mutualistic associations between soil microbes (either beneficial or harmful) and plant roots. Some of these symbiotic relationships involve microbes of different domains responding differentially to plant root exudates. Among these are included the bacterial genus Burkholderia and eukaryotic genus Trichoderma, which have antagonistic activities against the eukaryotic genus Fusarium. Another example involves Ochrobactrum phage POA1180, its bacterial host and plant roots. One of the major challenges in plant nutrition involves other microbes that manipulate nitrogen levels in the soil. Among these are the microbes that perform contraversal actions of nitrogen fixation (the methanogen Euryarchaeota) and ammonia oxidation (Crenarchaeota). The net nitrogen level in the soil is originally based on the AB/RA of these microbes and partially on the environmental condition. Watering seems to influence the AB/RA of a large number of soil microbes, where drought-sensitive microbes (members of phyla Acidobacteria and Gemmatimonadetes) showed an increased AB/RA pattern after watering, while others (Burkholderia and Trichoderma) seem to be among microbes assisting plants to withstand abiotic stresses. This study sheds light on the efficient use of mWGS in the taxonomic assignment of soil microbes and in their response to watering. It also provides new avenues for improving biotic and abiotic resistance in domestic plant germplasm via the manipulation of soil microbes.