RESUMO
Clathrin-mediated endocytosis (CME) is vital for the regulation of plant growth and development through controlling plasma membrane protein composition and cargo uptake. CME relies on the precise recruitment of regulators for vesicle maturation and release. Homologues of components of mammalian vesicle scission are strong candidates to be part of the scission machinery in plants, but the precise roles of these proteins in this process are not fully understood. Here, we characterised the roles of the plant dynamin-related protein 2 (DRP2) family (hereafter DRP2s) and SH3-domain containing protein 2 (SH3P2), the plant homologue to recruiters of dynamins, such as endophilin and amphiphysin, in CME by combining high-resolution imaging of endocytic events in vivo and characterisation of the purified proteins in vitro. Although DRP2s and SH3P2 arrive similarly late during CME and physically interact, genetic analysis of the sh3p123 triple mutant and complementation assays with non-SH3P2-interacting DRP2 variants suggest that SH3P2 does not directly recruit DRP2s to the site of endocytosis. These observations imply that, despite the presence of many well-conserved endocytic components, plants have acquired a distinct mechanism for CME.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Dinaminas , Endocitose , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Clatrina/metabolismo , Clatrina/genética , Dinaminas/metabolismo , Dinaminas/genética , Endocitose/genética , Proteínas de Ligação ao GTP , Mutação/genéticaRESUMO
Plant cell growth responds rapidly to various stimuli, adapting architecture to environmental changes. Two major endogenous signals regulating growth are the phytohormone auxin and the secreted peptides rapid alkalinization factors (RALFs). Both trigger very rapid cellular responses and also exert long-term effects [Du et al., Annu. Rev. Plant Biol. 71, 379-402 (2020); Blackburn et al., Plant Physiol. 182, 1657-1666 (2020)]. However, the way, in which these distinct signaling pathways converge to regulate growth, remains unknown. Here, using vertical confocal microscopy combined with a microfluidic chip, we addressed the mechanism of RALF action on growth. We observed correlation between RALF1-induced rapid Arabidopsis thaliana root growth inhibition and apoplast alkalinization during the initial phase of the response, and revealed that RALF1 reversibly inhibits primary root growth through apoplast alkalinization faster than within 1 min. This rapid apoplast alkalinization was the result of RALF1-induced net H+ influx and was mediated by the receptor FERONIA (FER). Furthermore, we investigated the cross-talk between RALF1 and the auxin signaling pathways during root growth regulation. The results showed that RALF-FER signaling triggered auxin signaling with a delay of approximately 1 h by up-regulating auxin biosynthesis, thus contributing to sustained RALF1-induced growth inhibition. This biphasic RALF1 action on growth allows plants to respond rapidly to environmental stimuli and also reprogram growth and development in the long term.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ácidos Indolacéticos , Hormônios Peptídicos , Raízes de Plantas , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Hormônios Peptídicos/metabolismo , Fosfotransferases , Raízes de Plantas/crescimento & desenvolvimentoRESUMO
The hunt for novel antibiotics has become a global public health imperative due to the rise in multidrug-resistant microorganisms, untreatable infection cases, overuse, and inefficacy of modern antibiotics. Polyphenols are getting much attention in research due to their multiple biological effects; their use as antimicrobial agents is attributed to their activity and that microbes have a hard time developing resistance to these natural compounds. Polyphenols are secondary metabolites produced in higher plants. They are known to possess various functional properties in the human body. Polyphenols also exhibit antibacterial activities against foodborne pathogens. Their antibacterial mechanism is based on inhibiting bacterial biofilm formation or inactivating enzymes. This review focused on polyphenol-protein interactions and the creation of this complex as a possible antibacterial agent. Also, different phenolic interactions on bacterial proteins, efflux pump, cell membrane, bacterial adhesion, toxins, and other bacterial proteins will be explored; these interactions can work in a synergic combination with antibiotics or act alone to assure bacterial inhibition. Additionally, our review will focus on polyphenol-protein interaction as a possible strategy to eradicate bacteria because polyphenols have shown a robust enzyme-inhibitory characteristic and a high tendency to complex with proteins, a response that neutralizes any bactericidal potential.
Assuntos
Antibacterianos , Polifenóis , Humanos , Polifenóis/farmacologia , Antibacterianos/farmacologia , Fenóis , Proteínas de Bactérias , Aderência BacterianaRESUMO
PURPOSE OF REVIEW: Preeclampsia (PE) is a serious and distinct type of pregnancy-induced hypertension, with an incidence of 2-8% worldwide. PE is defined as pregnancy-related hypertension with proteinuria and peripheral edema after 20 weeks of gestation. Hypoxic placenta triggers the release of inflammatory and humoral substances into maternal circulation, leading to induction of oxidative stress, lipid peroxidation, endothelial dysfunction, and peripheral vasoconstriction. The objective of the present narrative review was to find the association between PE and hypoxia-inducible factor 1 (HIF-1) in pregnant women from a new perspective. RECENT FINDINGS: HIF-1 is the key transcription factor that regulates cellular responses to hypoxia and low oxygen tension. HIF-1α is involved in the differentiation and growth of the placenta mainly in the first and second trimesters. During normal gestation, HIF-1α responds to the alterations in oxygen tension, cytokine, and angiogenic factors release. HIF-1α is considered a key biomarker of placental function and vascularization during pregnancy. HIF-1α plays a crucial role in the pathogenesis of PE through activation of anti-angiogenic and inhibition of proangiogenic factors. As well, HIF-1α increases the expression of the p38MAPK and NLRP3 inflammasomes, which promote placental inflammation and dysfunction. HIF-1α acts as a potential link between inflammatory signaling pathways and the development of PE.
Assuntos
Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Feminino , Gravidez , Humanos , Pré-Eclâmpsia/metabolismo , Placenta/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia , Oxigênio/metabolismoRESUMO
Chemotherapy is an aggressive form of chemical drug therapy aiming to destroy cancer cells. Adjuvant therapy may reduce hazards of chemotherapy and help in destroying these cells when obtained from natural products, such as medical plants. In this study, the potential therapeutic effect of Rosa damascena callus crude extract produced in vitamin-enhanced media is investigated on colorectal cancer cell line Caco-2. Two elicitors, i.e., L-ascorbic acid and citric acid at a concentration of 0.5 g/L were added to the callus induction medium. Callus extraction and the GC-MS analysis of methanolic crude extracts were also determined. Cytotoxicity, clonogenicity, proliferation and migration of Caco-2 colorectal cancer cells were investigated using MTT cytotoxicity, colony-forming, Ki-67 flow cytometry proliferation and Migration Scratch assays, respectively. Our results indicated that L-ascorbic acid treatment enhanced callus growth parameters and improved secondary metabolite contents. It showed the least IC50 value of 137 ug/mL compared to 237 ug/mL and 180 ug/mL in the citric acid-treated and control group. We can conclude that R. damascena callus elicited by L-ascorbic acid improved growth and secondary metabolite contents as well as having an efficient antiproliferative, anti-clonogenic and anti-migratory effect on Caco-2 cancer cells, thus, can be used as an adjuvant anti-cancer therapy.
Assuntos
Adenocarcinoma , Neoplasias Colorretais , Rosa , Adenocarcinoma/tratamento farmacológico , Ácido Ascórbico/farmacologia , Células CACO-2 , Ácido Cítrico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Antígeno Ki-67 , Extratos Vegetais/química , Rosa/química , VitaminasRESUMO
In the current study, the anti-inflammatory and analgesic potential of Alnus nitida (leaves and fruits) was evaluated in the Sprague-Dawley rat. Traditionally, A. nitida was used for the treatment of inflammatory ailments. However, A. nitida leaves and fruits have not been yet reported regarding any potential medicinal effects. Leaves/fruits of A. nitida were extracted with methanol and fractionated to attain n-hexane, chloroform, ethyl acetate and aqueous fractions. These extracts were then evaluated for in vivo analgesic and anti-inflammatory potential. For in vivo anti-inflammatory activity, carrageenan-induced paw edema assay, Freunds' complete adjuvant-induced edema, xylene-induced ear edema and histamine-induced paw edema models were used in rats, which showed significant (p < 0.01) reduction (70−80%) in edema in comparison of inflammatory controls. On other hand, for the analgesic assessment, hot plate assay and acetic acid-induced writhing tests were used, which showed a significant (p < 0.01) rise in latency time (40−60%) as compared with pain-induced controls. These results were comparable with standard drugs in a concentration-dependent manner and no mortality or toxicity was observed during all experiments. Then, for the identification of chemical constituents gas chromatography−mass spectrometry (GC-MS) analysis was performed, which indicated the presence of neophytadiene, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, phytol and vitamin E, justifying the use of A. nitida to treat inflammatory disorders.
Assuntos
Alnus , Alnus/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Carragenina/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Cromatografia Gasosa-Espectrometria de Massas , Dor/induzido quimicamente , Dor/tratamento farmacológico , Extratos Vegetais/química , Ratos , Ratos Sprague-DawleyRESUMO
The global coronavirus pandemic has burdened the human population with mass fatalities and disastrous socio-economic consequences. The frequent occurrence of these new variants has fueled the already prevailing challenge. There is still a necessity for highly effective small molecular agents to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we targeted the human transmembrane surface protease TMPRSS2, which is essential for proteolytic activation of SARS-CoV-2. Camostat is a well-known inhibitor of serine proteases and an effective TMPRSS2 inhibitor. A virtual library of camostat-like compounds was computationally screened against the catalytic site of TMPRSS2. Following a sequential in-depth molecular docking and dynamics simulation, we report the compounds that exhibited promising efficacy against TMPRSS2. The molecular docking and MM/PBSA free energy calculation study indicates these compounds carry excellent binding affinity against TMPRSS2 and found them more effective than camostat. The study will open doors for the effective treatment of coronavirus disease 2019.
RESUMO
Tropisms, growth responses to environmental stimuli such as light or gravity, are spectacular examples of adaptive plant development. The plant hormone auxin serves as a major coordinative signal. The PIN auxin exporters, through their dynamic polar subcellular localizations, redirect auxin fluxes in response to environmental stimuli and the resulting auxin gradients across organs underlie differential cell elongation and bending. In this review, we discuss recent advances concerning regulations of PIN polarity during tropisms, focusing on PIN phosphorylation and trafficking. We also cover how environmental cues regulate PIN actions during tropisms, as well as the crucial role of auxin feedback on PIN polarity during bending termination. Finally, the interactions between different tropisms are reviewed to understand plant adaptive growth in the natural environment.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Transporte Biológico , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Reguladores de Crescimento de Plantas , Raízes de Plantas/metabolismoRESUMO
Pathogen-related (PR) proteins are an integral part of plants' defense mechanisms against various types of biotic and abiotic stresses. A little is known about the importance of these PR proteins in potato defense mechanisms. In the current study, a total of 22 pathogenesis-related 1 genes were identified in the potato genome. All identified proteins possessed the CAP superfamily domain with some other motifs. The cis-acting elements analysis identified several stress-responsive elements, including MYB, ABRE, and MeJRE. The gene duplication events demonstrated purifying and positive selection pressure. Expression profiling showed high transcripts level in root compared to other tissues; however, some genes have tissue-specific expression. Furthermore, the PR-1-5 gene is transcriptionally induced under Phytophthora infestans stress and hormonal (ABA and IAA) treatments. The Real-Time qPCR analysis also validated the RNA-seq data results of genes with maximum expression in roots compared to leaves and stems. The current study results provided basic data for functional characterization and can also use as a reference study for other important crops.
Assuntos
Phytophthora infestans , Solanum tuberosum , Doenças das Plantas , Proteínas de Plantas/genética , Estresse FisiológicoRESUMO
In this present investigation, an aqueous Basella alba leaves extract was used to synthesize AgNPs. The green synthesis approach is carried out in our work due to non-toxic, less cost, and ecofriendly methods. FTIR spectra are used to confirm the biomolecules present in B.alba leaves extract along with AgNPs and these compounds are responsible for Ag particle from micro to nanostructure. The FCC structure and crystalline nature of the AgNPs are analyzed with the help of XRD and TEM techniques respectively. DLS and Zeta potential techniques are carried out to find the size and stability of AgNPs respectively and UV is used to verify the presence of AgNPs in synthesized samples employing SPR peaks around 435 nm. The antioxidant studies expose eminent scavenging activity which ranges from 13.71% to maximum 67.88%. Green synthesized AgNPs possess well organized biological activities concerning antioxidant and antibacterial, which can be used in some biologically applications.
Assuntos
Nanopartículas Metálicas , Prata , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais , Folhas de Planta , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
In this study, we estimated the protective role of Moringa oleifera leaf ethanolic extract (MOLE) against obesity-associated testicular dysfunction. Fifty male albino rats were randomly assigned to five groups (n = 10): Group I (basal diet), group II (basal diet plus MOLE orally), group III (high-fat diet-HFD), group IV (HFD plus oral MOLE) and group V (HFD for 8 weeks followed by a basal diet plus oral MOLE for 6 weeks). The study duration extended for 14 weeks. Serum collected to investigate testosterone, FSH and LH levels. Testicular tissues were used to determine levels of SOD, glutathione, catalase and malondialdehyde. Semen was collected to estimate its quality (morphology, motility and concentration). Morphological changes in the testis were investigated by histopathological and immunohistochemical techniques. Compared with both control treatment and MOLE treatment, serum testosterone, FSH, LH, testicular enzymatic catalase, SOD, GSH, survivin immunoreactivity, sperm quality and testicular weight were all significantly decreased in rats treated with HFD, while there were significant increases in testicular malondialdehyde and caspase-3 immunoreactivity. MOLE improved all harmful effects of HFD. Improvements were more pronounced in the protected (G 4) than the treated (G 5) group. MOLE could be a potential solution for obesity-associated fertility problem.
Assuntos
Moringa oleifera , Animais , Masculino , Malondialdeído , Obesidade/tratamento farmacológico , Obesidade/etiologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , TestículoRESUMO
Accumulation of heavy metals (HMs) by ornamental plants (OPs) from contaminated agriculture soils is a unique technique that can efficiently reduce the metal load in the food chain. Amaranthus tricolor L. has attractive characteristics acquiring a higher growth rate and large biomass when grown at heavy metal contaminated soils. Site-specific detailed information is not available on the use of A. tricolor plant in metal phytoremediation from the polluted sites. The study aimed to enhance the uptake of HMs (Pb, Zn, and Cu) via amending poultry litter extract (PLE), vinasse sugarcane (VSC), and humic acid (HA) as natural mobilized organic materials compared to ethylene diamine tetraacetic acid (EDTA), as a common mobilized chemical agent by A. tricolor plant. The studied soils collected from Helwan, El-Gabal El-Asfar (Cairo Governorate), Arab El-Madabeg (Assiut Governorate), Egypt, and study have been conducted under pot condition. Our results revealed all organic materials in all studied soils, except EDTA in EL-Gabal El-Asfar soil, significantly increased the dry weight of the A. tricolor plant compared to the control treatment. The uptake of Pb and Zn significantly (p > 0.05) increased due to applying all organic materials to the studied soils. HA application caused the highest uptake as shown in Pb concentration by more than 5 times in Helwan soil and EDTA by 65% in El-Gabal El-Asfar soil while VSC increased it by 110% in El-Madabeg soil. Also, an increase in Zn concentration due to EDTA application was 58, 42, and 56% for Helwan, El-Gabal El-Asfar, and El-Madabeg soil, respectively. In all studied soils, the application of organic materials increased the remediation factor (RF) than the control. El-Madabeg soil treated with vinasse sugarcane gave the highest RF values; 6.40, 3.26, and 4.02% for Pb, Zn, and Cu, respectively, than the control. Thus, we identified A. tricolor as a successful ornamental candidate that, along with organic mobilization amendments, most efficiently develop soil health, reduce metal toxicity, and recommend remediation of heavy metal-contaminated soils. Additionally, long-term application of organic mobilization amendments and continued growth of A. tricolor under field conditions could be recommended for future directions to confirm the results.
Assuntos
Amaranthus/crescimento & desenvolvimento , Metais Pesados/análise , Poluentes do Solo/análise , Amaranthus/metabolismo , Biodegradação Ambiental , Biomassa , Ácido Edético/química , Egito , Substâncias Húmicas/análiseRESUMO
Obesity is a worldwide life-threatening metabolic disorder, associated with various chronic diseases, including male infertility. Obesity was induced by high fat diet (HFD), and testis RNA was used for the transcriptome analysis using RNAseq via Illumina NovaSeq 6000 System and NovaSeq 6000 Kit. Gene expression level was estimated as FPKM (Fragments Per Kilobase of transcript per Million mapped reads). Differential expressed genes (DEGs) were annotated against gene ontology (GO) and KEGG databases. More than 63.66 million reads per sample were performed with 100 bp cutoff and 6 Gb sequencing depth. Results of this study revealed that 267 GO terms (245 biological processes (BP), 14 cellular components (CC), eight molecular functions (MF)), and 89 KEGG pathways were significantly enriched. Moreover, total numbers of 136 genes were differentially expressed (107 upregulated, 29 downregulated) with |FC| ≥ 2 and bh adjusted <0.05. Interesting DEGs were detected, including obesity and lipid metabolism-related genes, immune response-related genes, cytochrome P450 genes, including aromatase were upregulated, whereas genes related to male fertility and fertilization, cell adhesion, and olfactory receptors were downregulated. The combined expression pattern of the DEGs in obese animals indicated an increase in cholesterol metabolism. Furthermore, high aromatase activity enhances the testosterone turnover into estradiol and lowers the testosterone/estradiol (T/E) ratio, which ultimately reduces fertility. In addition, downregulation of cadherens junction components genes leads to the pre-mature release of sperm from Sertoli cells resulting in the reduction of fertility. Moreover, the downregulation of olfactory receptor genes reduces the chemotaxis capacity of sperms in tracking the oocyte for fertilization, which reduces male fertility. Furthermore, various obesity molecular markers were detected in our transcriptome. The results of this study will enhance our understanding of the molecular network of obesity development, development of obesity novel molecular diagnosis markers, molecular bases of obesity-induced infertility, and the development of anti-obesity drugs.
Assuntos
Infertilidade Masculina/genética , Obesidade/genética , Testículo/metabolismo , Animais , Biomarcadores/sangue , Dieta Hiperlipídica/efeitos adversos , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Ontologia Genética , Predisposição Genética para Doença/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Masculino , Obesidade/complicações , RNA/genética , Ratos , Ratos Wistar , Células de Sertoli/metabolismo , Espermatozoides/metabolismo , Testículo/fisiologia , Testosterona/metabolismo , Transcriptoma/genéticaRESUMO
The aim of this research is to investigate the quantum geometric properties and chemical reactivity of atropine, a pharmaceutically active tropane alkaloid. Using density functional theory (DFT) computations with the B3LYP/SVP functional theory basis set, the most stable geometry of atropine was determined. Additionally, a variety of energetic molecular parameters were calculated, such as the optimized energy, atomic charges, dipole moment, frontier molecular orbital energies, HOMO-LUMO energy gap, molecular electrostatic potential, chemical reactivity descriptors, and molecular polarizability. To determine atropine's inhibitory potential, molecular docking was used to analyze ligand interactions within the active pockets of aldo-keto reductase (AKR1B1 and AKR1B10). The results of these studies showed that atropine has greater inhibitory action against AKR1B1 than AKR1B10, which was further validated through molecular dynamic simulations by analyzing root mean square deviation (RMSD) and root mean square fluctuations (RMSF). The results of the molecular docking simulation were supplemented with simulation data, and the ADMET characteristics were also determined to predict the drug likeness of a potential compound. In conclusion, the research suggests that atropine has potential as an inhibitor of AKR1B1 and could be used as a parent compound for the synthesis of more potent leads for the treatment of colon cancer associated with the sudden expression of AKR1B1.
Assuntos
Atropina , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Atropina/farmacologia , Aldo-Ceto RedutasesRESUMO
The objective of the present study was to develop a novel nanogel containing Beta vulgaris L. hydroalcoholic extract and assess its efficacy for treating testosterone-induced alopecia. Beta vulgaris L. leaf hydroalcoholic extract nanogel (BVEN) was prepared by ionic gelation method, incorporated in carbopol 934 gel. Optimization of particle size and entrapment efficiency as the responses was carried out by central composite design response surface methodology. Prepared nanoparticles were evaluated for entrapment efficiency, particle size, zeta potential, polydispersity index, Fourier transform infrared spectroscopy, transmission electron microscopy, and differential scanning calorimetry. Nanogel was evaluated for pH, colour, appearance and homogeneity, viscosity, spreadability, in vitro release study, and stability studies. Further, 2.5% and 5% BVEN were also evaluated for antialopecic activity in Swiss albino mice by using parameters as hair growth initiation, testosterone content, total protein, prostate weight measurement, hair follicular density, anagen/telogen ratio, and histopathological studies. The resulting nanoparticles had better entrapment efficiency with particle size of 274 nm, polydispersity index of 0.259, and zeta potential of +28.8. BVEN pH 6.5, drug content, i.e., quercetin 99.84 ± 1.30% and stigmasterol 99.89 ± 1.52%, spreadability 20.3 ± 0.5925 g cm/sec, and viscosity 110 × 105 cps were observed. Stability studies showed that nanogel was stable at 4°C ± 2°C/60% ± 5% RH. It was found that 5% BVEN showed better antialopecic activity as compared to 2.5% BVEN.
Assuntos
Beta vulgaris , Nanopartículas , Masculino , Animais , Camundongos , Nanogéis , Testosterona , Nanopartículas/química , Alopecia/induzido quimicamente , Alopecia/tratamento farmacológico , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
INTRODUCTION: Mutations in GDAP1 (Ganglioside-induced differentiation-associated protein 1) gene are linked to Charcot-Marie-Tooth disease (CMT), a Heterogenous group of disorders with multiple phenotypes, characterized by peripheral nerve dysfunction that can lead to vocal cord paralysis and diaphragmatic dysfunction. MAIN BODY: All three affected children of this chosen family have manifested the same clinical symptoms with progressive weakness, mild sensory impairment, and absent tendon reflexes in their early years. Electrodiagnostic analysis displayed an axonal type of neuropathy in affected patients. Sequencing of the GDAP1 gene was requested for all members of the family. Diagnostic assessments included pulmonary and vocal cord function tests, as well as phrenic and peripheral nerve conduction studies. Pathogenicity of GDAP1 variant p.Pro419Leu with axonal CMT2 and autosomal recessive inheritance was confirmed via in silico analysis. Patients with GDAP1 mutations showed dysphonia, speech difficulties, and the characteristic symptoms of CMT. The severity of symptoms correlated with the presence of a type of GDAP1 mutation. Patients with normal vocal cords and pulmonary function exhibited milder symptoms compared to those with GDAP1 mutations. Our study provides clinical insights into the phenotypic effects of GDAP1 mutations in CMT patients. The findings highlight the adverse clinical course and severe disability associated with GDAP1 mutations, including weak limb and laryngeal muscles. CONCLUSION: Patients with GDAP1 mutations and autosomal recessive neuropathy present with dysphonia and require interventions such as surgery, braces, physical therapy, and exercise. Early diagnosis and comprehensive clinical evaluations are crucial for managing CMT patients with GDAP1 mutations.
RESUMO
The inhibition of capping enzymes such as guanine-N7-methyltransferase (GMT) is an attractive target for regulating viral replication, transcription, virulence, and pathogenesis. Thus, compounds that target the Severe Acute Respiratory Syndrome Corona Virus 2 GMT (S2GMT) will enhance drug development against COVID-19. In this study, an in-house library of 249 phytochemicals from African medicinal plants was screened using computational approaches including homology modeling, molecular docking, molecular dynamic simulations, binding free energy calculations based on molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) and Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) analysis for inhibitors of S2GMT. The top-ten ranked phytochemicals (TTRP) obtained from the docking analysis to S2GMT were further docked to SARS-COV N7-MTase. Among the TTRP, the top-four ranked phytocompounds (TFRP) viz: 3 alkaloids (Isocryptolepine, 10'-Hydroxyusambarensine and Isostrychnopentamine) and a flavonoid (Mulberrofuran F) interacted strongly with critical catalytic residues whose interference either reduce or completely abolish N7-MTase activity, indicating their potential as capping machinery disruptors. The interactions of TFRP with the catalytic residues of S2GMT were preserved in a 100 ns simulated dynamic environment, thereby, demonstrating high degree of structural stability. The MMPBSA binding free energy calculations corroborated the docking scores with biscryptolepine having the highest binding free energy to S2GMT. The TFRP showed favourable drug-likeness and ADMET properties over a wide range of molecular descriptors. Therefore, the TFRP can be further explored as potential S2GMT inhibitors in in vitro and in vivo experiments.Communicated by Ramaswamy H. Sarma.
Assuntos
Antimaláricos , COVID-19 , Antagonistas do Ácido Fólico , Humanos , SARS-CoV-2 , Metiltransferases , Simulação de Acoplamento Molecular , Compostos FitoquímicosRESUMO
Virachola livia (Lepidoptera: Lycaenidae) and Ectomyelois ceratoniae (Lepidoptera: Pyralidae) are the key pests of pomegranates in Saudi Arabia that are managed mainly using broad-spectrum pesticides. Interactions between the entomopathogenic nematodes (EPNs) Steinernematids, and Heterorhabditids, and their entomopathogenic bacterial symbionts (EPBs) have long been considered monoxenic 2-partner associations responsible for killing insects and, therefore, are widely used in insect pest biocontrol. However, there are limited reports identifying such organisms in Taif, Saudi Arabia. The current study aimed to identify the EPNs and their associated bacteria isolated from Taif, Saudi Arabia, and evaluate their biocontrol potential on third instar larvae of V. livia and E. ceratoniae under laboratory conditions. A total of 35 EPN isolates belonging to Steinernema (20) and Heterorhabditis (15) were recovered from 320 soil samples. Twenty-six isolates of symbiotic or associated bacteria were isolated from EPNs and molecularly identified as Xenorhabdus (6 isolates), Photorhabdus (4 isolates), Pseudomonas (7), or Stenotrophomonas (9). A pathogenicity assay revealed that Steinernema spp. were more virulent than Heterorhabditis spp. against the two pomegranate insects, with LC50 values of 18.5 and 13.6 infective juveniles (IJs)/larva of V. livia for Steinernema spp. and 52 and 32.4 IJs/larva of V. livia for Heterorhabditis spp. at 48 and 72 h post-treatment, respectively. Moreover, LC50 values of 9 and 6.6 IJs/larva (Steinernema spp.) and 34.4 and 26.6 IJs/larva (Heterorhabditis spp.) were recorded for E. ceratoniae larvae at 48 and 72 h post-treatment. In addition, the EPB Stenotrophomonas maltophilia CQ1, isolated from Steinernema spp., surpassed Pseudomonas mosselii SJ10, associated with Heterorhabditis spp., in their ability to kill V. livia or E. ceratoniae larvae within 6 h post-application, resulting in 100% mortality in both insects after 24 and 48 h of exposure. We conclude that either application of EPNs' IJs or their associated EPBs could serve as potential biocontrol agents for V. livia and E. ceratoniae.
RESUMO
The potato is one of the most important and valuable crops in terms of consumption worldwide. However, abiotic stressors are the critical delimiters for the growth and productivity of potato. Invertase genes play key roles in carbon metabolism, plant development, and responses to stress stimuli. Therefore, a comprehensive genome-wide identification, characterization and expression analysis of invertase genes was performed in the potato. The current study identified 19 invertase genes, randomly distributed throughout the potato genome. To further elucidate their evolutionary, functional and structural relationship within family and with other plant species, we performed sequence and phylogenetic analysis, which segregated invertase genes into two main groups based on their sequence homology. A total of 11 genes are included in acidic invertases and 8 genes are in neutral or alkaline invertases, elucidating their functional divergence. Tissue specific expression analyses (RNA sequencing and qRT-PCR) of different plant tissues showed differential expression pattern. Invertase genes have higher expression in flower, leaf, root and shoot tissues, while under abiotic stress conditions, the expression of the invertase gene is significantly upregulated. Results of this study revealed that vacuolar and cell wall destined invertases are mainly the functional member genes of the invertase family. This study provides comprehensive data and knowledge about StINV genes in Solanum tuberosum for future genetic and epigenetic studies.
RESUMO
Jatropha curcas is a tropical species that has been recognized as a promising biodiesel plant. During 2018-2021, researchers at Forest College and Research Institute, Mettupalayam, elicited information on Jatropha's biochemical characteristics, growth performance, variability, and association studies for biometric variables using five backcross (BC4F1) hybrid clones of Jatropha with a control variety TNMC 7. In terms of seed yield, two hybrid clones, CJH 13 (1,218.60 g) and CJH 12 (1,034.40 g), outperformed the other hybrid clones. The seed oil content was higher in CJH 5 (34.19%). The seed oil content had moderate PCV (16.49%) and GCV (16.39%) values, as well as high heritability (99%) and genetic advance (33.56%) as a percentage of the mean. The number of fruits per bunch (0.845 and 0.850) and the number of bunches per branch (0.771 and 0.788) had significant positive phenotypic and genotypic correlations with seed yield, respectively. The iodine numbers, cetane numbers, and saponification values of all hybrid clones were acceptable and satisfactory and were in good compliance with Indian and international biodiesel standards.