RESUMO
Antibiotic resistance poses a significant threat to the global health, food security, and environment. In poultry and livestock, antibiotics are beneficial since they improve poultry performance and are economically effective. Therefore, it is crucial to search for alternatives that can be environmentally safe and successful in treating these infections. In this study, we employed molecular docking to evaluate lemon peel phytochemical's protein binding capability against various poultry pathogens. The nanoparticles (LP AgNPs) obtained from the lemon peel were characterized and tested for their antibacterial activity against more poultry pathogens. LP AgNPs were characterized by using UV-Visible absorption spectra, which revealed an absorption peak at a wavelength of 420-440 nm. The FT-IR analysis demonstrated that flavonoids and phenolic acids acted as capping, reducing, and stabilizing agents during the biosynthesis of AgNPs. EDAX showed a strong peak was observed at 3 keV which revealed the absorption of metallic silver nanoparticles. The mean diameter was from 2 to 20 nm through HRTEM. Zeta potential of the LP AgNps at - 17.2 mV showed the high stability of the green synthesized AgNps. Maximum inhibitory concentrations of LP AgNps against the isolated poultry pathogens were 50 µg/ml concentration. The toxicity tests were performed in the Vigna radiata seedlings and Artemia nauplii, which showed less toxic effects and eco-friendly nature of the LP AgNps. LP AgNps have the potential to treat antibiotic resistant poultry pathogens, thereby paving the way for the development of value-added novel products incorporated with nanoparticles for treating various infection caused by antibiotic-resistant poultry pathogens.
Assuntos
Citrus , Nanopartículas Metálicas , Animais , Nanopartículas Metálicas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Simulação de Acoplamento Molecular , Aves Domésticas , Difração de Raios X , Prata/farmacologia , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Heat stress (HS) is a major abiotic stress that negatively impacts crop yields across the globe. Plants respond to elevated temperatures by changing gene expression, mediated by transcription factors (TFs) functioning to enhance HS tolerance. The involvement of Group I bZIP TFs in the heat stress response (HSR) is not known. In this study, bZIP18 and bZIP52 were investigated for their possible role in the HSR. Localization experiments revealed their nuclear accumulation following heat stress, which was found to be triggered by dephosphorylation. Both TFs were found to possess two motifs containing serine residues that are candidates for phosphorylation. These motifs are recognized by 14-3-3 proteins, and bZIP18 and bZIP52 were found to bind 14-3-3 ε, the interaction of which sequesters them to the cytoplasm. Mutation of both residues abolished 14-3-3 ε interaction and led to a strict nuclear localization for both TFs. RNA-seq analysis revealed coordinated downregulation of several metabolic pathways including energy metabolism and translation, and upregulation of numerous lncRNAs in particular. These results support the idea that bZIP18 and bZIP52 are sequestered to the cytoplasm under control conditions, and that heat stress leads to their re-localization to nuclei, where they jointly regulate gene expression.
Assuntos
Proteínas 14-3-3/genética , Arabidopsis/genética , Resposta ao Choque Térmico/genética , RNA Longo não Codificante/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Núcleo Celular/genética , Regulação da Expressão Gênica de Plantas/genética , Fatores de Transcrição/genéticaRESUMO
Melanoma is a life threading disease when it grows outside the corium layer of the skin. Mortality rates of the Melanoma cases are maximum among the skin cancer patients. The cost required for the treatment of advanced melanoma cases is very high and the survival rate is low. Numerous computerized dermoscopy systems are developed based on the combination of shape, texture and color features to facilitate early diagnosis of melanoma. The availability and cost of the dermoscopic imaging system is still an issue. To mitigate this issue, this paper presented an integrated segmentation and Third Dimensional (3D) feature extraction approach for the accurate diagnosis of melanoma. A multi-atlas method is applied for the image segmentation. The patch-based label fusion model is expressed in a Bayesian framework to improve the segmentation accuracy. A depth map is obtained from the Two-dimensional (2D) dermoscopic image for reconstructing the 3D skin lesion represented as structure tensors. The 3D shape features including the relative depth features are obtained. Streaks are the significant morphological terms of the melanoma in the radial growth phase. The proposed method yields maximum segmentation accuracy, sensibility, specificity and minimum cost function than the existing segmentation technique and classifier.
Assuntos
Dermoscopia/métodos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Melanoma/diagnóstico , Teorema de Bayes , Cor , Humanos , Melanoma/diagnóstico por imagem , Reconhecimento Automatizado de Padrão/métodos , Sensibilidade e EspecificidadeRESUMO
In this current study, the extracts of endophytic fungi (Aspergillus niger) were utilized to synthesize the silver nanoparticles (AnNps). In silico screening was carried out by docking secondary metabolites of Aspergillus niger with drug-resistant proteins such as penicillin-binding protein (pbp2a) and clumping factor A of Staphylococcus aureus, penicillin-binding protein (PBP3), and outer membrane protein of Acinetobacter baumannii. The molecular docking analysis revealed the interaction between secondary metabolites of Aspergillus niger with virulence factors of the pathogenic bacteria. AnNps are characterized by various physicochemical methods to determine the size, shape, and stability. Antibacterial efficacy of synthesized nanoparticles (AnNps) was screened in clinical pathogens. AnNp treatment significantly reduced the growth of MDR pathogens. The results suggested that AnNps can be incorporated to produce antimicrobial agents to control drug resistant pathogenic bacteria.
Assuntos
Acinetobacter baumannii , Antibacterianos , Nanopartículas Metálicas , Staphylococcus aureus , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Bactérias , Farmacorresistência Bacteriana , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Proteínas de Ligação às Penicilinas , Prata/farmacologia , Prata/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
The presence of Vibrio parahaemolyticus, Vibrio alginolyticus, and Vibrio harveyi in aquatic organisms causes vibriosis, leading to their significant mortality. The efficacy of antibiotic treatment is reduced due to increasing antibiotic resistance. As a result, novel therapeutic agents are increasingly needed to treat outbreak of such diseases in aquatic organisms and humans. This study focuses on utilizing the bioactive compounds of Cymbopogon citratus as they are rich in a variety of secondary metabolites which promotes growth, natural immune response and disease resistance against pathogenic bacteria in various ecosystems. In silico studies were performed to evaluate the binding potential of the bioactive compounds against targeted protein beta - lactamase in Vibrio parahaemolyticus and metallo - beta - lactamase in V. alginolyticus via molecular docking. Cymbopogon citratus nanoparticles (CcNps) were synthesized, characterized and toxicity studies were performed by using Vigna radiata, and Artemia nauplii at different concentrations of Cymbopogon citratus nanoparticles. The results revealed that the synthesized nanoparticles were non-ecotoxic and act as potential growth promoters in plants. The antibacterial activity of synthesized Cymbopogon citratus was evaluated using agar well diffusion method. MIC, MBC, and biofilm assays performed by using different concentrations of synthesized nanoparticles. Thus, it was proved that Cymbopogon citratus nanoparticles showed better antibacterial activity against Vibrio species.
Assuntos
Cymbopogon , Nanopartículas , Vibrio , Poluentes Químicos da Água , Humanos , Cymbopogon/química , Organismos Aquáticos , Ecossistema , Simulação de Acoplamento Molecular , Poluentes Químicos da Água/toxicidade , Antibacterianos/toxicidadeRESUMO
Most of the thyroid surgeries are accompanied by drain placement. The possibility of hematoma or seroma formation postoperatively is of concern to surgeons, as, thyroid is a highly vascular structure and a minor hemorrhage might also turn out to be life threatening, despite actual incidence of it being only 0.3-1%. Thus, drains are placed with an intention to obliterate dead space and clear the collecting blood or serum. Conversely, several studies have indicated chances of clots blocking the drainage tube and resulting in missing out of early detection of a massive bleed. Drains have also been known to add more discomfort to the patient, increase chances of infection, increase post operative pain, scar formation and longer duration of hospital stay. Thus, some surgeons believe in not placing a drain. To compare the outcomes of thyroid surgeries done with drain versus those thyroid surgeries done without drain. 40 patients, of either sex, between 18 and 70 years of age, who underwent thyroid surgeries for various thyroid disorders over a period of 6 months, were randomly allocated to either 'with drain' (group A) or 'without drain' (group B). The surgeon was made aware of drain status only intraoperatively. Patients were assessed for post-operative pain based on Visual Analogue Scale (VAS) at 6 and 24 h post-operatively. Post-operative complications including hematoma, seroma, and wound infection, if any, along with duration of hospitalization, were also documented. Patient was followed up one week post-operatively for wound check and suture removal. Both groups were homogenous according to age, sex, TIRADS, Bethesda, diagnosis and surgery performed. Postoperative pain at 6 and 24 h was significantly higher in group A than in group B [6.15 ± 1.31 vs 3.50 ± 0.88 (p = 0.001) (6 h), 4.45 ± 0.99 vs 1.20 ± 1.10 (p = 0.001) (24 h)]. Mean duration of hospitalization following thyroid surgery was significantly higher among group A than group B [3.80 ± 1.15 vs 2.15 ± 0.36 days (p = 0.001)]. Though not statistically significant, wound pain at 1 week and overall complications were higher in Group A than in Group B (p = 0.182, p = 0.127 respectively). Thyroid surgeries done without drain placement are likely to cause significantly lesser post-operative pain and shorter duration of hospitalization.
RESUMO
Meiosis is a specialized cell division that halves the number of chromosomes in two consecutive rounds of chromosome segregation. In angiosperm plants is meiosis followed by mitotic divisions to form rudimentary haploid gametophytes. In Arabidopsis, termination of meiosis and transition to gametophytic development are governed by TDM1 and SMG7 that mediate inhibition of translation. Mutants deficient in this mechanism do not form tetrads but instead undergo multiple cycles of aberrant nuclear divisions that are likely caused by the failure to downregulate cyclin dependent kinases during meiotic exit. A suppressor screen to identify genes that contribute to meiotic exit uncovered a mutation in cyclin-dependent kinase D;3 (CDKD;3) that alleviates meiotic defects in smg7 deficient plants. The CDKD;3 deficiency prevents aberrant meiotic divisions observed in smg7 mutants or delays their onset after initiation of cytokinesis, which permits formation of functional microspores. Although CDKD;3 acts as an activator of cyclin-dependent kinase A;1 (CDKA;1), the main cyclin dependent kinase that regulates meiosis, cdkd;3 mutation appears to promote meiotic exit independently of CDKA;1. Furthermore, analysis of CDKD;3 interactome revealed enrichment for proteins implicated in cytokinesis, suggesting a more complex function of CDKD;3 in cell cycle regulation.
RESUMO
Mastitis is a widespread disease in dairy cattle occurring throughout the world. The increased use of antibiotics brings about the development of antibiotic-resistant microbes. The application of antibiotics in dairy farming led to increased antibiotic resistance and represents a major obstacle for the treatment of mastitis. Recent advancements in nanotechnology led to the development of nanocolloids to overcome disadvantages posed by conventional antimicrobial agents. Hence, a novel, environmentally friendly, cost-effective, biocompatible, and long-term antibacterial represents a promising solution for medicine and farming. Hence, polyherbal nanocolloids (PHNc) was formulated by using the extracts of Syzygium aromaticum, Cinnamomum verum, Emblica officinalis, Terminalia belerica, Terminalia chebula, and Cymbopogon citratus and physicochemically characterized. From mastitis milk samples, microorganisms were isolated including Acinetobacter junii, Klebsiella pneumoniae, Pseudomonas stutzeri, and Acinetobacter baumannii and screened for antibiotic susceptibility. All the isolated strains were tested with PHNc and compared with antibiotics. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and biofilm assays were performed at different concentrations, and antibacterial effects were quantified. In our results, PHNc showed potent bacteriostatic, bactericidal, and antibiofilm activity against all the strains. Our results indicated that PHNc can reduce the virulence factors responsible for infection by different bacterial strains. This study confirmed that PHNc had the potential to inhibit the growth of pathogenic Gram-negative and Gram-positive strains and could be utilized as an alternative to antibiotics to inhibit multidrug-resistant microbial pathogens in cattle.
Assuntos
Anti-Infecciosos , Bactérias/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Mastite Bovina , Extratos Vegetais , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/classificação , Bovinos , Feminino , Mastite Bovina/tratamento farmacológico , Mastite Bovina/microbiologia , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Aquaculture production is affected by disease outbreak, which affects the production, profitability, and sustainability of the global aquaculture industry. Antibiotics have been widely used to control various infectious diseases. Indiscriminate usage of antibiotics results in development of antibiotic resistance in pathogens. This current study aims to synthesize myrobalan-mediated green silver nanocolloids (MBNc) by using the extract of three myrobalans and characterized by using various physiochemical techniques. Antibacterial potential of MBNc was screened in vibriosis causing pathogens (V. harveyi, V. alginolyticus, V. Parahaemolyticus), and foodborne pathogen S. haemolyticus, isolated from infected fish. Further, the presence of ESBL genes including CTX-M-15 and Amp C was analyzed in control and MBNc-treated strains. From our studies, it was observed that MBNc was very effective in controlling the growth. MBNc confirmed the anti-biofilm property in all tested marine pathogens and effectively abolish the genes encoding CTX-M-15 in tested pathogens. Thus, MBNc can be formulated to control the growth of marine pathogens and it can be used as an alternative to antibiotics to prevent infection in cage culturing and aquafarming.
Assuntos
VibriosesRESUMO
Fungal diseases in plants are creating numerous problems in the developed and developing nations. Silver, a notable metal because of its inertness and its role in nanoscience, has received a considerable amount of focus in the development of an ecofriendly green solution to control many microbial infections. The herbal product from various plant sources with the combination of silver was used to develop nanoparticles, against the pathogens. In this study, we developed Moringa oleifera leaf- and flower-mediated silver nanoparticles with the particle size of 77.45 nm and 63.20 nm respectively. Fungicidal activity of both Moringa oleifera leaf (MLNp) and flower (MFNp) nanoparticles was studied in vitro against plant pathogenic fungi Pestalotiopsis mangiferae isolated from infected coconut palm. Nanoparticles from Moringa oleifera leaves and flowers reduced the radial growth of fungi significantly even at lower concentrations and acted as a potent fungistatic agent.
Assuntos
Nanopartículas Metálicas , Moringa oleifera , Antifúngicos/farmacologia , Fungos , Extratos Vegetais/farmacologia , Folhas de Planta , Prata/farmacologiaRESUMO
Nanotechnology involves the synthesis of nanoparticles that have been used in the therapeutic application for treating diseases. In this present study, we have adopted the synthesis of myconanoparticles from the extracellular extract of endophytic fungi Penicillium sclerotiorum (PsNps) and validated its antibacterial potential against antibiotic-resistant uropathogenic E. coli and ATCC (25,922) strain of Escherichia coli. Endophytic fungi were isolated from the healthy leaves of Tamarindus indica. The genomic DNA from endophytic fungi was isolated and the ITS region was amplified by polymerase chain reaction (PCR) using universal fungal primers ITS1 and ITS4 and sequenced for the identification of endophytic fungal isolates. Penicillium sclerotiorum extract was used for the synthesis of silver nanoparticles (PsNps) and was characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), zeta potential, FE-SEM, and Energy dispersive X-ray analysis (EDAX). Antibacterial activity of PsNps was tested against the antibiotic-resistant uropathogenic E. coli and ATCC (25,922) strain of E. coli. Further experiments were carried out to explore the potential of PsNps in regulating the CTX-M-15 gene. The antimicrobial activity showed that the PsNps inhibited growth, biofilm formation in both the strains of E. coli. The expression of the gene encoding CTX-M-15 was downregulated in a resistant strain of uropathogenic E. coli. Our results suggest that the PsNps could be used as an alternative source for antibiotics. Thus, further studies can be conducted to prove the in vivo potential of PsNps and can be formulated for commercialization.
Assuntos
Biofilmes/efeitos dos fármacos , Nanopartículas/química , Penicillium/química , Prata , Escherichia coli Uropatogênica/fisiologia , Biofilmes/crescimento & desenvolvimento , Prata/química , Prata/farmacologiaRESUMO
Corona virus pandemic outbreak also known as COVID-19 has created an imbalance in this world. Scientists have adopted the use of natural or alternative medicines which are consumed mostly as dietary supplements to boost the immune system as herbal remedies. India is famous for traditional medicinal formulations which includes 'Trikadu'-a combination of three acrids, namely Zingiber officinale, Piper nigrum and Piper longum which have antioxidant properties that boost our immune system hence acting as a strong preventive measure. In this study, AutoDock 4.0 was used to study interaction between the phytocompounds of Trikadu with RNA-dependent polymerase protein and enveloped protein of the SARS-CoV-2 virus. Analysis of the results showed that coumarin, coumaperine and bisdemethoxycurcumin showed strong bonding interactions with both the proteins. We can conclude that Trikadu has the potential molecules; hence, it can be incorporated in the diet to boost the immune system as a preventive measure against the virus.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19/imunologia , Fitoterapia , Preparações de Plantas/uso terapêutico , SARS-CoV-2 , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , COVID-19/virologia , Simulação por Computador , RNA-Polimerase RNA-Dependente de Coronavírus/química , RNA-Polimerase RNA-Dependente de Coronavírus/efeitos dos fármacos , Suplementos Nutricionais , Zingiber officinale/química , Humanos , Sistema Imunitário/efeitos dos fármacos , Índia , Ligantes , Medicina Tradicional , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Piper/química , Piper nigrum/química , Preparações de Plantas/isolamento & purificação , Plantas Medicinais/química , SARS-CoV-2/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/efeitos dos fármacosRESUMO
Identification of catalytic residues can help unveil interesting attributes of enzyme function for various therapeutic and industrial applications. Based on their biochemical roles, the number of catalytic residues and sequence lengths of enzymes vary. This article describes a prediction approach (PINGU) for such a scenario. It uses models trained using physicochemical properties and evolutionary information of 650 non-redundant enzymes (2136 catalytic residues) in a support vector machines architecture. Independent testing on 200 non-redundant enzymes (683 catalytic residues) in predefined prediction settings, i.e., with non-catalytic per catalytic residue ranging from 1 to 30, suggested that the prediction approach was highly sensitive and specific, i.e., 80% or above, over the incremental challenges. To learn more about the discriminatory power of PINGU in real scenarios, where the prediction challenge is variable and susceptible to high false positives, the best model from independent testing was used on 60 diverse enzymes. Results suggested that PINGU was able to identify most catalytic residues and non-catalytic residues properly with 80% or above accuracy, sensitivity and specificity. The effect of false positives on precision was addressed in this study by application of predicted ligand-binding residue information as a post-processing filter. An overall improvement of 20% in F-measure and 0.138 in Correlation Coefficient with 16% enhanced precision could be achieved. On account of its encouraging performance, PINGU is hoped to have eventual applications in boosting enzyme engineering and novel drug discovery.
Assuntos
Domínio Catalítico , Biologia Computacional/métodos , Enzimas/química , Enzimas/metabolismo , Algoritmos , Sequência de Aminoácidos , Catálise , Conjuntos de Dados como Assunto , Dados de Sequência Molecular , Reprodutibilidade dos Testes , Máquina de Vetores de SuporteRESUMO
Wnt signaling plays a central role in development, adult tissue homeostasis, and cancer. Several steps in the canonical Wnt/ß-catenin signaling cascade are regulated by ubiquitylation, a protein modification that influences the stability, subcellular localization, or interactions of target proteins. To identify regulators of the Wnt/ß-catenin pathway, we performed an RNA interference screen in Caenorhabditis elegans and identified the HECT domain-containing ubiquitin ligase EEL-1 as an inhibitor of Wnt signaling. In human embryonic kidney 293T cells, knockdown of the EEL-1 homolog Huwe1 enhanced the activity of a Wnt reporter in cells stimulated with Wnt3a or in cells that overexpressed casein kinase 1 (CK1) or a constitutively active mutant of the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6). However, knockdown of Huwe1 had no effect on reporter gene expression in cells expressing constitutively active ß-catenin, suggesting that Huwe1 inhibited Wnt signaling upstream of ß-catenin and downstream of CK1 and LRP6. Huwe1 bound to and ubiquitylated the cytoplasmic Wnt pathway component Dishevelled (Dvl) in a Wnt3a- and CK1ε-dependent manner. Mass spectrometric analysis showed that Huwe1 promoted K63-linked, but not K48-linked, polyubiquitination of Dvl. Instead of targeting Dvl for degradation, ubiquitylation of the DIX domain of Dvl by Huwe1 inhibited Dvl multimerization, which is necessary for its function. Our findings indicate that Huwe1 is part of an evolutionarily conserved negative feedback loop in the Wnt/ß-catenin pathway.