ABSTRACT
Mansonone G (MG), a 1,2-naphthoquinones with antiestrogenic, antimicrobial, and anti-adipogenic activities, is derived from the heartwood of Mansonia gagei Drumm. Ethoxy mansonone G (EMG), an essential derivative of MG, has anticancer and antioxidant agent. EMG also has antiestrogen activity and is demonstrated to lower estrogen receptor expression in endocrine-resistant cells. EMG significantly inhibits cell division, invasion, and anchorage-dependent growth in all cancer types. Through the stimulation of the tumor protein (p53) and extracellular signal-regulated kinase (ERK) signaling cascades, it also causes apoptosis. Moreover, it manifests its anti-cancerous effects in toll-like receptor pathways, c-Jun N-terminal kinase (c-JNK), and nuclear factor kappa B (NF-κB). EMG inhibits the phosphorylation of glycogen synthase kinase (GSK3), Erk, protein kinase B (Akt), and mammalian target of rapamycin (mTOR). By interfering with molecular cascades, EMG significantly reduces the metabolism of cancer cells. This paper focuses on the potential use of EMG in cancer treatment. Moreover, it states the methodology by which specific assays establish the anti-cancerous role of EMG. Breast cancer, non-small cell lung cancer, and colorectal cancer are only a few of the cancers for which EMG was shown to be effective. Through further research, EMG may be developed as a therapeutic solution to complications caused by cancer. This study presents EMG as a novel candidate for cancer therapy, offering a unique combination of pharmacological advantages and mechanistic insights that warrant further exploration and development toward addressing the complexities of cancer treatment.
Subject(s)
Breast Neoplasms , Carcinoma, Non-Small-Cell Lung , Colorectal Neoplasms , Lung Neoplasms , Naphthoquinones , Humans , Naphthoquinones/pharmacology , Naphthoquinones/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Signal Transduction/drug effectsABSTRACT
Eucalyptus camaldulensis is a multifunctional tree and is globally used for the reclamation of problematic lands. Eucalyptus camaldulensis is prone to attack by a number of pathogens, but the most important threat is the Fusarium wilt (Fusarium oxysporum). Keeping in view the importance of E. camaldulensis and to manage this disease, five plant activators, i.e., salicylic acid (C7H6O3), benzoic acid (C7H6O2), citric acid (C6H8O7), dipotassium phosphate (K2HPO4), monopotassium phosphate (KH2PO4) and nutritional mixture namely Compound (NPK) and nutriotop (Fe, Zn, Cu, B, Mn) were evaluated in the Fusarium infested field under RCBD in the Research Area, Department of Forestry and Range Management, University of Agriculture, Faisalabad (UAF). Among plant activators, salicylic acid and a combination of compound + nutriotop exhibited the lowest disease incidence and enhanced fresh and dry weight of leaves compared to other treatments and control. Results of the environmental study indicated maximum disease incidence between 35-40 °C (max. T), 6-25 °C (mini. T), 70-80% relative humidity and 1.5-2.5 km/h wind speed while pan evaporation expressed weak correlation with disease development. It was concluded that Fusarium wilt of Eucalyptus camaldulensis could be managed through activation of the basal defense system of the host plant with provision of salicylic acid and balanced nutrition by considering environmental factors. Recent exploration is expected to be helpful for future research efforts on epidemiology and ecologically sound intervention of Fusarium wilt of Eucalyptus camaldulensis.
Subject(s)
Eucalyptus , Fusarium , Salicylic Acid , Plant Leaves , PhosphatesABSTRACT
Radioresistant microorganisms possess inimitable capabilities enabling them to thrive under extreme radiation. However, the existence of radiosensitive microorganisms inhabiting such an inhospitable environment is still a mystery. The current study examines the potential of radioresistant microorganisms to protect radiosensitive microorganisms in harsh environments. Bacillus subtilis strain ASM-1 was isolated from the Thal desert in Pakistan and evaluated for antioxidative and radioprotective potential after being exposed to UV radiation. The strain exhibited 54.91% survivability under UVB radiation (5.424 × 103 J/m2 for 8 min) and 50.94% to mitomycin-C (4 µg/mL). Extracellular fractions collected from ASM-1 extracts showed significant antioxidant potential, and chemical profiling revealed a pool of bioactive compounds, including pyrrolopyrazines, amides, alcoholics, and phenolics. The E-2 fraction showed the maximum antioxidant potential via DPPH assay (75%), and H2O2 scavenging assay (68%). A combination of ASM-1 supernatant with E-2 fraction (50 µL in a ratio of 2:1) provided substantial protection to radiosensitive cell types, Bacillus altitudinis ASM-9 (MT722073) and E. coli (ATCC 10536), under UVB radiation. Docking studies reveal that the compound supported by literature against the target proteins have strong binding affinities which further inferred its medical uses in health care treatment. This is followed by molecular dynamic simulations where it was observed among trajectories that there were no significant changes in major secondary structure elements, despite the presence of naturally flexible loops. This behavior can be interpreted as a strategy to enhance intermolecular conformational stability as the simulation progresses. Thus, our study concludes that Bacillus subtilis ASM-1 protects radiosensitive strains from radiation-induced injuries via biofilm formation and secretion of antioxidative and radioprotective compounds in the environment.
ABSTRACT
The precise biological function and activity of the deoxylulose-5-phosphate reductoisomerase (DXR) gene and its promoter in Osmanthus fragrans var. semperflorens remain unclear, even though OfDXR is known as the crucial enzyme involved in plant terpenoid synthesis. This study aimed to shed light on the role and activity of the OfDXR gene and its promoter in O. fragrans var. semperflorens by employing RACE-PCR and Hi-TAIL-PCR techniques for the cloning of the gene and promoter sequence from the petal tissue. Subsequently, genetic transformation and histochemical staining methods were utilized to analyze their function and activity. The OfDXR gene exhibited a DNA sequence length of 5241 bp, encompassing 12 exons and 11 introns. The corresponding cDNA sequence of the OfDXR gene was 1629 bp, encoding 474 amino acid residues. Expression analysis revealed that the OfDXR gene was predominantly active in the petals during the early full blooming stage. Overexpression of the OfDXR gene in Arabidopsis plants at the primary or full blooming stage led to an augmentation in the total terpenoid content. Furthermore, the promoter sequence of the OfDXR gene spanned a length of 1174 bp and contained conserved regulatory/response elements, demonstrating functional activity. These findings indicate that the OfDXR gene plays a pivotal role in terpenoid synthesis, while its promoter exhibits robust activity.
Subject(s)
Arabidopsis , Phosphates , Introns , Arabidopsis/genetics , Promoter Regions, Genetic , Terpenes , Cloning, MolecularABSTRACT
Understanding the origins of variation in agricultural pathogens is of fundamental interest and practical importance, especially for diseases that threaten food security. Fusarium oxysporum is among the most important of soil-borne pathogens, with a global distribution and an extensive host range. The pathogen is considered to be asexual, with horizontal transfer of chromosomes providing an analog of assortment by meiotic recombination. Here, we challenge those assumptions based on the results of population genomic analyses, describing the pathogen's diversity and inferring its origins and functional consequences in the context of a single, long-standing agricultural system. We identify simultaneously low nucleotide distance among strains, and unexpectedly high levels of genetic and genomic variability. We determine that these features arise from a combination of genome-scale recombination, best explained by widespread sexual reproduction, and presence-absence variation consistent with chromosomal rearrangement. Pangenome analyses document an accessory genome more than twice the size of the core genome, with contrasting evolutionary dynamics. The core genome is stable, with low diversity and high genetic differentiation across geographic space, while the accessory genome is paradoxically more diverse and unstable but with lower genetic differentiation and hallmarks of contemporary gene flow at local scales. We suggest a model in which episodic sexual reproduction generates haplotypes that are selected and then maintained through clone-like dynamics, followed by contemporary genomic rearrangements that reassort the accessory genome among sympatric strains. Taken together, these processes contribute unique genome content, including reassortment of virulence determinants that may explain observed variation in pathogenic potential.
Subject(s)
Fusarium , Fusarium/genetics , Host Specificity , Genomics , Agriculture , Plant Diseases/geneticsABSTRACT
The emergence and spread of drug-resistant microorganisms that have acquired new resistance mechanisms, leading to antibiotic resistance, continue to threaten the health of humans and animals worldwide. Non-human primates (NHPs), as close living relatives of human beings in the world, have a high degree of genetic and physiological similarity to humans. However, despite its importance, we lack a comprehensive characterization or understanding of the similarities and differences of the antibiotic resistance genes of the gut microbiome carried by non-human primates and humans. In the present study, the diversity and abundance of antibiotic resistance genes carried by the gut microbiota of cynomolgus monkeys (Macaca fascicularis) were investigated by metagenomic analysis. In total, 60 resistance types conferring resistance to 11 categories of antibiotics were identified in the gut microbiome of cynomolgus monkeys. Interestingly, the composition and abundance of ARGs carried by the gut microbiota of cynomolgus monkeys can be significantly affected by dietary changes. Moreover, we found that all ARG types carried by humans are also present in cynomolgus monkeys. The tetracycline resistance gene tet(37) is evolutionarily conserved and highly homologous. Taken together, our study provides a comprehensive overview of the diversity and richness of ARGs in the gut microbiota of cynomolgus monkeys and underlines the potentially crucial role of diet in the gut health of monkeys and humans.
Subject(s)
Drug Resistance, Microbial , Gastrointestinal Microbiome , Haplorhini , Animals , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/genetics , Haplorhini/microbiology , MetagenomicsABSTRACT
Multiple and consecutive application of fungicide might damage the rhizosphere bacterial community of citrus. In order to evaluated effect of mancozeb on the chemical properties of citrus-cultivated soil and the richness and diversity of rhizosphere bacterial community. The abundance response of rhizosphere bacterial groups without application or with application of 1.333 g mg-1 mancozeb for 2, 4, 6 and 8 times were investigated, and further studied the relationship between the rhizosphere bacterial community and chemical properties of citrus-cultivated soil. We found the rhizosphere bacterial composition and diversity were distinct between soil planted with citrus and without citrus, in addition, the abundance of rhizosphere-associated bacterial species in the soil planted with citrus increased significantly. Meanwhile, the chemical properties and the richness and diversity of rhizosphere bacterial community of the soil planted with citrus did not significantly change among different application frequence of mancozeb. Moreover, with the increased applying times of mancozeb, the relative abundance of Candidatus, Saccharibacteria, Parcubacteria, and Proteobacteria increased but the abundance of Nitrospirae decreased. In our one-year trial, there were less adverse effects of mancozeb on the citrus-cultivated rhizosphere by the repeated application of mancozeb. Therefore, mancozeb, as a fungicide, could be used multiple times to control citrus disease.
Subject(s)
Citrus , Rhizosphere , Bacteria , Maneb , Soil , Soil Microbiology , ZinebABSTRACT
Pectobacterium punjabense is a newly described species causing blackleg disease in potato plants. Therefore, by the combination of long (Oxford Nanopore Technologies, MinION) and short (Illumina MiSeq) reads, we sequenced the complete genome of P. punjabense SS95T, which contains a circular chromosome of 4.793 Mb with a GC content of 50.7%.
ABSTRACT
The tangerine pathotype of A. alternata, which produces a unique host-selective ACT toxin causes brown spots on citrus leaves and fruits. In this study, we report a methionine biosynthesis regulator (MetR), which belong to bZIP transcription factor, is required for methionine metabolism, oxidative stress tolerance and pathogenicity. We generated two ΔAaMetR mutants in the tangerine pathotype of Alternaria alternata and investigated the resulting mutant phenotypes. The ΔAaMetR disruption mutant grew poorly in the absence of methionine and unable to produce conidia. Furthermore, pathogenicity tests have shown that ΔAaMetR mutant on their tangerine host can neither penetrate nor cause disease. These ΔAaMetR mutants exhibit an increased sensitivity to exogenous H2O2 and many ROS generating oxidants. To elucidate the transcription network of AaMetR, we performed RNA-Seq experiments on wild-type and ΔAaMetR mutant and identified genes that were differentially expressed between the two genotypes. Transcriptome data demonstrated that AaMetR contributes in many other biological processes including ROS detoxification, sulfur transfer, and amino acid metabolism. Comparative transcriptome analysis indicated that the ΔAaMetR mutant up-regulated several genes involved in cysteine and methionine metabolism. In conclusion, our results highlight the global regulatory role of AaMetR in cysteine and methionine metabolism and provide new insights into the crucial role of ROS detoxification, sporulation and pathogenicity in the tangerine pathotype of A. alternata.