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1.
Biomed Res Int ; 2021: 7251119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34651048

RESUMO

Background: B.1.617.1, a variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing respiratory illness is responsible for the second wave of COVID-19 and associated with a high incidence of infectivity and mortality. To mitigate the B.1.617.1 variant of SARS-CoV-2, deciphering the protein structure and immunological responses by employing bioinformatics tools for data mining and analysis is pivotal. Objectives: Here, an in silico approach was employed for deciphering the structure and immune function of the subunit of spike (S) protein of SARS-CoV-2 B.1.617.1 variant. Methods: The partial amino acid sequence of SARS-CoV-2 B.1.617.1 variant S protein was analyzed, and its putative secondary and tertiary structure was predicted. Immunogenic analyses including B- and T-cell epitopes, interferon-gamma (IFN-γ) response, chemokine, and protective antigens for SARS-CoV 2 S proteins were predicted using appropriate tools. Results: B.1.617.1 variant S protein sequence was found to be highly stable and amphipathic. ABCpred and CTLpred analyses led to the identification of two potential antigenic B cell and T cell epitopes with starting amino acid positions at 60 and 82 (for B cell epitopes) and 54 and 98 (for T cell epitopes) having prediction scores > 0.8. Further, RAMPAGE tool was used for determining the allowed and disallowed regions of the three-dimensional predicted structure of SARS-CoV-2 B.1.617.1 variant S protein. Conclusion: Together, the in silico analysis revealed the predicted structure of partial S protein, immunogenic properties, and possible regions for S protein of SARS-CoV-2 and provides a valuable prelude for engineering the targeted vaccine or drug against B.1.617.1 variant of SARS-CoV-2.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Algoritmos , Sequência de Aminoácidos , COVID-19/imunologia , COVID-19/metabolismo , Biologia Computacional/métodos , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Humanos , Imunogenicidade da Vacina , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/metabolismo , Relação Estrutura-Atividade , Vacinas Virais/imunologia
2.
Biomed Res Int ; 2021: 9913625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660804

RESUMO

Entamoeba histolytica (Eh) is a pathogenic eukaryote that often resides silently in humans under asymptomatic stages. Upon indeterminate stimulus, it develops into fulminant amoebiasis that causes severe hepatic abscesses with 50% mortality. This neglected tropical pathogen relies massively on membrane modulation to flourish and cause disease; these modulations range from the phagocytic mode for food acquisition to a complex trogocytosis mechanism for tissue invasion. Rab GTPases form the largest branch of the Ras-like small GTPases, with a diverse set of roles across the eukaryotic kingdom. Rab GTPases are vital for the orchestration of membrane transport and the secretory pathway responsible for transporting the pathogenic effectors, such as cysteine proteases (EhCPs) which help in tissue invasion. Rab GTPases thus play a crucial role in executing the cytolytic effect of E. histolytica. First, they interact with Gal/Nac lectins required for adhering to the host cells, and then, they assist in the secretion of EhCPs. Additionally, amoebic Rab GTPases are vital for encystation because substantial vesicular trafficking is required to create dormant amoebic cysts. These cysts are the infective agent and help to spread the disease. The absence of a "bonafide" vesicular transport machinery in Eh and the existence of a diverse repertoire of amoebic Rab GTPases (EhRab) hint at their contribution in supporting this atypical machinery. Here, we provide insights into a pseudoRab GTPase, EhRabX10, by performing physicochemical analysis, predictive 3D structure modeling, protein-protein interaction studies, and in silico molecular docking. Our group is the first one to classify EhRabX10 as a pseudoRab GTPase with four nonconserved G-motifs. It possesses the basic fold of the P-loop containing nucleotide hydrolases. Through this in silico study, we provide an introduction to the characterization of the atypical EhRabX10 and set the stage for future explorations into the mechanisms of nucleotide recognition, binding, and hydrolysis employed by the pseudoEhRab GTPase family.

3.
Clin Chim Acta ; 523: 152-162, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34537216

RESUMO

Sepsis is a clinical syndrome resulting from infection followed by inflammation and is one of the significant causes of mortality worldwide. The underlying reason is the host's uncontrolled inflammatory response due to an infection led to multiple organ dysfunction/failure. Neutrophils, an innate immune cell, are forerunners to reach the site of infection/inflammation for clearing the infection and resolute the inflammation during sepsis. A relatively new neutrophil effector function, neutrophil extracellular traps (NETs), have been demonstrated to kill the pathogens by releasing DNA decorated with histone and granular proteins. A growing number of pieces of shreds of evidence suggest that unregulated incidence of NETs have a significant influence on the pathogenesis of sepsis-induced multiple organ damage, including arterial hypotension, hypoxemia, coagulopathy, renal, neurological, and hepatic dysfunction. Thus, excessive production and improper resolution of NETs are of significant therapeutic value in combating sepsis-induced multiple organ failure. The purpose of this review is intended to highlight the role of NETs in sepsis-induced organ failure. Furthermore, the current status of therapeutic strategies to intersect the harmful effects of NETs to restore organ functions is discussed.

4.
Chem Biol Drug Des ; 98(5): 930-942, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34519164

RESUMO

Entamoeba histolytica is the conductive agent of amoebiasis. Upon the parasite's infection, macrophages and neutrophils are activated by interferon γ, IL-13 and tumour necrosis factor. These immune cells then carry out the amoebicidal activity by releasing nitric oxide synthase and reactive oxygen species (ROS). This review talks about the protective and destructive role of ROS in Eh. E. histolytica has defence strategies against oxidative stress which is a result of excess ROS production. They possess antioxidants for their defence such as L-Cysteine, flavodiiron proteins, peroxiredoxin and trichostatin A, which contribute to the parasite's virulence. The ROS are harmful to the host cells as excess ROS production stimulates cell death by mechanisms like apoptosis and necroptosis. NADPH oxidase (NOX) is a key source of ROS in mammalian cells and causes apoptosis of host cells via the protein kinase transduction pathway. This review provides insights into why NOX inhibitors that could be a potent antiparasitic drug, is not effective for in vivo purposes. This paper also gives an insight into a solution that could be a potent source in generating new treatment and vaccines for amoebiasis by targeting parasite development.

5.
Indian J Microbiol ; 61(3): 270-278, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34294992

RESUMO

The era of rapid industrialization succeeded by a shift in organizational focus on research and technology development which has fueled many industries along with the dairy industry to grow at an exponential rate. The dairy industry has achieved remarkable growth in the last decade in India. Waste produced by dairy industry consists of a high organic load thus cannot be discharged untreated. Even though treatment and management of waste are well documented, but the main problem is concerned with sludge produced after treatment. There is a gap in the application of various methods for effective treatment of the waste, hence there is a need for technology-oriented research in this area because of a paradigm shift in perspectives towards sustainable management of waste to recover value added products including energy as energy demand is also rising. Sludge which is generally land spread can also be used for energy generation. This paper discusses the environmental effects of waste generated due to dairy industrial activities; various methods used for the advanced treatment of dairy waste. This review article aims to present and discuss the state-of-art information for recovery of value-added products (single cell protein, biofertilizers, biopolymers and biosurfactants) from dairy waste with emphasis on integration of technologies for environmental sustainability. This paper also includes challenges and future perspectives in this field.

6.
Chemosphere ; 282: 130954, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34082315

RESUMO

Humanity is struggling against a major problem for a proper management of generated municipal solid waste. The collected waste causes natural issues like uncontrollable emission of greenhouse gases and others. Even though, escalation of waste results in minimizing the areas accessible for disposing the waste. Creating awareness in the society to use organic products like biofuels, biofertilizers and biogas is a need of an hour. Biochemical processes such as composting, vermicomposting, anaerobic digestion, and landfilling play important role in valorizing biomass and solid waste for production of biofuels, biosurfactants and biopolymer. This paper covers the details of biomass and solid waste characteristics and its composition. It is also focused to provide updated information about reutilization of biomass for value creation. Technologies and products obtained through bio-routes are discussed in current review paper together with the integrated system of solid waste management. It also covers challenges, innovations and perspectives in this field.


Assuntos
Compostagem , Eliminação de Resíduos , Gerenciamento de Resíduos , Anaerobiose , Biocombustíveis , Biomassa , Resíduos Sólidos/análise
7.
Microbiol Res ; 249: 126784, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33989978

RESUMO

Millions of people worldwide lie at the risk of parasitic protozoic infections that kill over a million people each year. The rising inefficacy of conventional therapeutics to combat these diseases, mainly due to the development of drug resistance to a handful of available licensed options contributes substantially to the rising burden of these ailments. Cysteine proteases are omnipresent enzymes that are critically implicated in the pathogenesis of protozoic infections. Despite their significance and druggability, cysteine proteases as therapeutic targets have not yet been translated into the clinic. The review presents the significance of cysteine proteases of members of the genera Plasmodium, Entamoeba, and Leishmania, known to cause Malaria, Amoebiasis, and Leishmaniasis, respectively, the protozoic diseases with the highest morbidity and mortality. Further, projecting them as targets for molecular tools like the CRISPR-Cas technology for favorable manipulation, exploration of obscure genomes, and achieving a better insight into protozoic functioning. Overcoming the hurdles that prevent us from gaining a better insight into the functioning of these enzymes in protozoic systems is a necessity. Managing the burden of parasitic protozoic infections pivotally depends upon the betterment of molecular tools and therapeutic concepts that will pave the path to an array of diagnostic and therapeutic applications.


Assuntos
Antiprotozoários/farmacologia , Cisteína Proteases/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Entamoeba histolytica/enzimologia , Leishmania/enzimologia , Plasmodium/enzimologia , Animais , Sistemas CRISPR-Cas , Cisteína Endopeptidases/metabolismo , Entamoeba histolytica/efeitos dos fármacos , Entamoeba histolytica/genética , Entamebíase/tratamento farmacológico , Entamebíase/parasitologia , Humanos , Leishmania/efeitos dos fármacos , Leishmania/genética , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Malária/tratamento farmacológico , Malária/parasitologia , Plasmodium/efeitos dos fármacos , Plasmodium/genética
8.
J Mol Recognit ; 34(9): e2894, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33719110

RESUMO

Enterococcus faecalis (E. faecalis) is a Gram-positive coccoid, non-sporulating, facultative anaerobic, multidrug resistance bacterium responsible for almost 65% to 80% of all enterococcal nosocomial infections. It usually causes infective endocarditis, urinary tract and surgical wound infections. The increase in E. faecalis resistance to conventionally available antibiotic has rekindled intense interest in developing useful antibacterial drugs. In E. faecalis, diaminopimelate epimerase (DapF) is involved in the lysine biosynthetic pathway. The product of this pathway is precursors of peptidoglycan synthesis, which is a component of bacterial cell wall. Also, because mammals lack this enzyme, consequently E. faecalis diaminopimelate epimerase (EfDapF) represents a potential target for developing novel class of antibiotics. In this regard, we have successfully cloned, overexpressed the gene encoding DapF in BL-21(DE3) and purified with Ni-NTA Agarose resin. In addition to this, binding studies were performed using fluorescence spectroscopy in order to confirm the bindings of the identified lead compounds (acetaminophen and dexamethasone) with EfDapF. Docking studies revealed that acetaminophen found to make hydrogen bonds with Asn72 and Asn13 while dexamethasone interacted by forming hydrogen bonds with Asn205 and Glu223. Thus, biochemical studies indicated acetaminophen and dexamethasone, as potential inhibitors of EfDapF and eventually can reduce the catalytic activity of EfDapF.

9.
J Mol Recognit ; 34(6): e2886, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33393093

RESUMO

Entamoeba histolytica (Eh), a parasitic protozoan and the causative agent of invasive Amoebiasis, invade the host tissue through an effective secretory pathway. There are several lines of evidence suggesting that amoebic trophozoite pore-forming complex amoebapore and a large class of proteases enzymes including rhomboid proteases, cysteine proteases, and metalloproteases are implicated in host tissue invasion. For successful delivery of these molecules/cargos, trophozoites heavily rely on sorting machinery from the endoplasmic reticulum, Golgi to plasma membrane. Although, sole secretion machinery in E. histolytica is not characterized yet. Therefore, here our aim is to understand the properties of key molecules N-ethylmaleimide-sensitive fusion protein attached to protein receptors (SNAREs) in E. histolytica. SNAREs proteins are an important component of the membrane-trafficking machinery and have been associated in a range of processes including vesicle tethering, fusion as well as specificity of vesicular transport in all eukaryotic cells. SNARE proteins are architecturally simple, categorized by the presence of one copy of a homologous coiled-coil forming motif. However, the structural information and protein-protein interaction study of Eh-associated syntaxin proteins are still not known. Here, we characterize the syntaxin 1 like molecule and VAMP from Eh through physiochemical profiling, modeling, atomistic simulation, protein-protein interaction, and docking approaches on the proteins containing SNARE and synaptobrevin domain. The modeled structures and the critical residues recognized through protein interaction and docking study may provide better structural and functional insights into these proteins and may aid in the development of newer diagnostic assays.

10.
Chem Biol Drug Des ; 96(2): 731-744, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32356312

RESUMO

Amoebiasis is a parasitic infectious disease caused by the enteric protozoan Entamoeba histolytica, a leading basis of deaths accounted to parasites, succeeding malaria and schistosomiasis. Conventional treatment methodologies used to deal with amoebiasis mainly rely on the administration of anti-amoebic compounds and vaccines but are often linked with substantial side-effects on the patient. Besides, cases of development of drug resistance in protozoans have been recorded, contributing further to the reduction in the efficiency of the treatment. Loopholes in the efficacious management of the disease call for the development of novel methodologies to manage amoebiasis. A way to achieve this is by targeting the essential metabolic processes of 'encystation' and 'excystation', and the associated biomolecules, thus interrupting the biphasic life cycle of the parasite. Technologies like the CRISPR-Cas9 system can efficiently be exploited to discover novel and essential molecules that regulate the protozoan's metabolism, while efficiently manipulating and managing the known drug targets, leading to an effective halt and forestall to the enteric infection. This review presents a perspective on these essential metabolic processes and the associated molecules that can be targeted efficaciously to prevent the transmission of amoebiasis, thus managing the disease and proving to be a fruitful endeavour.


Assuntos
Amebíase/tratamento farmacológico , Entamoeba histolytica/efeitos dos fármacos , Entamebíase/tratamento farmacológico , Peptaibols/química , Animais , Quitinases/metabolismo , Humanos , Lectinas/metabolismo , Modelos Biológicos , Conformação Molecular , Terapia de Alvo Molecular , Peptaibols/farmacologia , Transdução de Sinais
11.
Environ Sci Pollut Res Int ; 27(22): 27172-27180, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30868465

RESUMO

Petroleum industry is one of the fastest growing industries, and it significantly contributes to economic growth in developing countries like India. The wastewater from a petroleum industry consist a wide variety of pollutants like petroleum hydrocarbons, mercaptans, oil and grease, phenol, ammonia, sulfide, and other organic compounds. All these compounds are present as very complex form in discharged water of petroleum industry, which are harmful for environment directly or indirectly. Some of the techniques used to treat oily waste/wastewater are membrane technology, photocatalytic degradation, advanced oxidation process, electrochemical catalysis, etc. In this review paper, we aim to discuss past and present scenario of using various treatment technologies for treatment of petroleum industry waste/wastewater. The treatment of petroleum industry wastewater involves physical, chemical, and biological processes. This review also provides scientific literature on knowledge gaps and future research directions to evaluate the effect(s) of various treatment technologies available.


Assuntos
Petróleo/análise , Poluentes Químicos da Água , Índia , Resíduos Industriais/análise , Indústria de Petróleo e Gás , Eliminação de Resíduos Líquidos , Águas Residuárias
12.
Int J Biol Macromol ; 143: 785-796, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31778699

RESUMO

Protein-protein interactions of cellular importance are mediated by coiled coils (CCs), the ubiquitous structural motif formed by the association of two or more α-helices in a knobs into holes manner. Coronins, actin-associated multi-functional proteins that possess distinct cytoskeleton-dependent and independent functions, oligomerize through their C-terminal CC domain. The structure of the L. donovani coronin CC domain (LdCoroCC; PDB ID 5CX2) revealed, in addition to a novel topology and architecture, an inherent asymmetry, with one of the helices of the 4-helix bundle axially shifted (~2 turns). The structural analysis identified that steric hindrance by Ile 486, Leu 493 and Met 500 as the cause for this asymmetry. To experimentally validate this hypothesis and to better understand the sequence-structure relationship in CCs, these amino acids have been mutated (I486A, L493A, M500V and the double mutant I486A-L493A) and characterized. Thermal CD studies suggest that the I486A and M500V mutants have comparable Tm values to LdCoroCC, while the other mutants have lower melting temperatures. The mutant crystal structures (I486A, M500V and the double mutant) retain the 'ade' core packing as LdcoroCC. While the M500V structure is similar to LdCoroCC, the I486A and the I486A-L493A structures show an asymmetry to symmetry transition. This study reveals crucial role of residues at position 'a' in coiled-coil domain play an important role in stabilizing the asymmetry in LdCoroCC, which might be necessary pursue specific biological function(s) inside the Leishmania.


Assuntos
Leishmania/metabolismo , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/metabolismo , Sequência de Aminoácidos , Animais , Bovinos , Modelos Moleculares , Proteínas Mutantes/química , Domínios Proteicos , Multimerização Proteica , Estrutura Secundária de Proteína
13.
Small GTPases ; 11(5): 320-333, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-30273093

RESUMO

Rab GTPases constitute the largest subgroup in the Ras superfamily of GTPases. It is well established that different Rab GTPases are localized in discrete subcellular localization and regulate the membrane trafficking in nearly all eukaryotic cells. Rab GTPase diversity is often regarded as an expression of vesicular trafficking complexity. The pathogenic amoeba Entamoeba histolytica harbours 91 Rab GTPases which is the highest among the currently available genome sequences from the eukaryotic kingdom. Here, we review the current status of amoebic Rab GTPases diversity, unique biochemical and structural features and summarise their predicted regulators. We discuss how amoebic Rab GTPases are involved in cellular processes such as endocytosis, phagocytosis, and invasion of host cellular components, which are essential for parasite survival and virulence.


Assuntos
Entamoeba histolytica/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Humanos
14.
J Mol Recognit ; 32(12): e2808, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31432591

RESUMO

The enteric protozoan parasite, Entamoeba histolytica (Eh), is the causative agent of amoebic dysentery and liver abscess in humans. It infects around 50 million people worldwide, which is a third general cause of death from parasitic diseases after malaria and schistosomiasis. The other prevalent form of the disease is Visceral leishmaniasis caused by Leishmania donovani which is a human blood parasite. On the other hand, the Toxoplasma gondii is an obligate intracellular protozoan parasite; it causes serious opportunistic infections in HIV-positive persons. The biological processes in all living organisms are mostly mediated by the proteins, and recognizing new target proteins and finding their function in pathogenesis will help in choosing better diagnostic markers. In eukaryotes, Rab protein plays a major role in pathogenesis. Rabs represent the largest branch in the Ras superfamily of GTPases. Among them, the Rab5 is important in the endocytosis and thus involved in pathogenesis. In this paper, we discussed the physiochemical profiling, modelling, and docking of the Rab5 protein from pathogenic species that is Entamoeba histolytica, Leishmania donovani, and Toxoplasma gondii. The modeled structures from this study and the key residues identified would give a better understanding of the three-dimensional structure and functional insights into these proteins and help in developing new drug targets.


Assuntos
Simulação por Computador , Entamoeba histolytica/metabolismo , Leishmania donovani/metabolismo , Toxoplasma/metabolismo , Proteínas rab5 de Ligação ao GTP/química , Motivos de Aminoácidos , Sequência de Aminoácidos , Ligação de Hidrogênio , Ligantes , Simulação de Acoplamento Molecular , Homologia Estrutural de Proteína , Proteínas rab5 de Ligação ao GTP/genética
15.
J Mol Recognit ; 32(11): e2802, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31353747

RESUMO

Enterococcus faecalis is a gram-positive, rod-shape bacteria responsible for around 65% to 80% of all enterococcal nosocomial infections. It is multidrug resistant (MDR) bacterium resistant to most of the first-line antibiotics. Due to the emergence of MDR strains, there is an urgent need to find novel targets to develop new antibacterial drugs against E. faecalis. In this regard, we have identified naphthoate synthase (1,4-dihydroxy-2-naphthoyl-CoA synthase, EC: 4.1.3.36; DHNS) as an anti-E. faecalis target, as it is an essential enzyme for menaquinone (vitamin K2 ) synthetic pathway in the bacterium. Thus, inhibiting naphtholate synthase may consequently inhibit the bacteria's growth. In this regard, we report here cloning, expression, purification, and preliminary structural studies of naphthoate synthase along with in silico modeling, molecular dynamic simulation of the model and docking studies of naphthoate synthase with quercetin, a plant alkaloid. Biochemical studies have indicated quercetin, a plant flavonoid as the potential lead compound to inhibit catalytic activity of EfDHNS. Quercetin binding has also been validated by spectrofluorimetric studies in order to confirm the bindings of the ligand compound with EfDHNS at ultralow concentrations. Reported studies may provide a base for structure-based drug development of antimicrobial compounds against E. faecalis.


Assuntos
Enterococcus faecalis/enzimologia , Inibidores Enzimáticos/farmacologia , Hidroliases/antagonistas & inibidores , Quercetina/farmacologia , Clonagem Molecular , Simulação por Computador , Cristalização , Enterococcus faecalis/efeitos dos fármacos , Hidroliases/química , Hidroliases/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Quercetina/química
16.
Chem Biol Drug Des ; 94(4): 1721-1739, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31260188

RESUMO

Enterococcus faecalis (Ef) is one of the major pathogens involved in hospital-acquired infections. It can cause nosocomial bacteremia, surgical wound infection, and urinary tract infection. It is important to mention here that Ef is developing resistance against many commonly occurring antibiotics. The occurrence of multidrug resistance (MDR) and extensive-drug resistance (XDR) is now posing a major challenge to the medical community. In this regard, to combat the infections caused by Ef, we have to look for an alternative. Rational structure-based drug design exploits the three-dimensional structure of the target protein, which can be unraveled by various techniques such as X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. In this review, we have discussed the complete picture of Ef infections, the possible treatment available at present, and the alternative treatment options to be explored. This study will help in better understanding of novel biological targets against Ef and the compounds, which are likely to bind with these targets. Using these detailed structural informations, rational structure-based drug design is achievable and tight inhibitors against Ef can be prepared.


Assuntos
Antibacterianos , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Enterococcus faecalis/crescimento & desenvolvimento , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Ressonância Magnética Nuclear Biomolecular
17.
Clin Chim Acta ; 495: 606-610, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31181192

RESUMO

BACKGROUND: Previous study from this lab has discerned oxidative, nitrosative stress and their relationship with cytokines contributing to the severity of sepsis and organ dysfunction. Cytokines are known to induce neutrophil extracellular traps (NETs) formation via free radicals generation. Hyper-activation of neutrophil leads to the increased NETs formation or ineffective clearance of NETs would likely increase the risk of auto-antibody generation against NETs components and being partly responsible for the sepsis severity and organ dysfunction. The present study was undertaken to further assess the status of NETs formation and their correlation with severity of sepsis, with the cytokines and organ dysfunction. METHODS: The level of NETs formation, DNA release, elastase release, and inflammatory cytokines was determined in 80 sepsis patients and 45 healthy volunteers. Their linearity with organ parameters and associations with sepsis severity were also assessed. RESULTS: NETs formation experiment was carried out and it was significantly higher in sepsis (70%) compared to control (30%). NETs % were positively correlated with severity of sepsis and organ dysfunction. Pearson's correlation coefficient demonstrated a direct relation between NETs components and organ parameters with Sepsis severity scores. CONCLUSION: NETs formation is significantly higher due to which it is contributing to the sepsis severity and organ failure.


Assuntos
Armadilhas Extracelulares/metabolismo , Insuficiência de Múltiplos Órgãos/imunologia , Neutrófilos/citologia , Sepse/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Semin Cell Dev Biol ; 96: 77-90, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30951893

RESUMO

Phosphorus (P), an essential macronutrient, is pivotal for growth and development of plants. Availability of phosphate (Pi), the only assimilable P, is often suboptimal in rhizospheres. Pi deficiency triggers an array of spatiotemporal adaptive responses including the differential regulation of several transcription factors (TFs). Studies on MYB TF PHR1 in Arabidopsis thaliana (Arabidopsis) and its orthologs OsPHRs in Oryza sativa (rice) have provided empirical evidence of their significant roles in the maintenance of Pi homeostasis. Since the functional characterization of PHR1 in 2001, several other TFs have now been identified in these model plants. This raised a pertinent question whether there are any likely interactions across these TFs. Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has provided an attractive paradigm for editing genome in plants. Here, we review the applications and challenges of this technique for genome editing of the TFs for deciphering the function and plausible interactions across them. This technology could thus provide a much-needed fillip towards engineering TFs for generating Pi use efficient plants for sustainable agriculture. Furthermore, we contemplate whether this technology could be a viable alternative to the controversial genetically modified (GM) rice or it may also eventually embroil into a limbo.


Assuntos
Sistemas CRISPR-Cas/genética , Edição de Genes , Homeostase/genética , Modelos Biológicos , Fosfatos/metabolismo , Plantas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Variação Genética/genética , Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo
19.
Int J Biol Macromol ; 120(Pt B): 1906-1916, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30268755

RESUMO

Enterococcus faecalis (Ef) is a Gram positive multidrug resistant (MDR) bacterium contributing about 70% of total enterococcal infections. In Ef, a membrane anchored transpeptidase Sortase A plays a major role in biofilm formation. Therefore, it has been recognized as an ideal drug target against Ef. In this regard to identify the potential inhibitors of Ef Sortase A (EfSrtA∆59), we have cloned, expressed and purified EfSrtA∆59. We have also done the in-silico docking studies to identify lead molecules interacting with EfSrtA∆59. Furthermore, the binding studies of these identified lead molecules were performed with EfSrtA∆59 using fluorescence and CD spectroscopic studies. We also identified the interaction partner of EfSrtA∆59 using STRING. Protein-protein docking studies were also performed. Docking experiment revealed that benzylpenicillin, cefotaxime, pantoprazole and valsartan were bound to same site on the protein with similar interactions. Binding studies using fluorescence spectroscopic studies confirmed the binding of all the ligands to EfSrtA∆59, which was further validated by far and near-UV CD experiments. Thermo stability experiments validate the stability-activity trade-off hypothesis. Sequence based interaction studies identified that EfSrtA∆59 interact with the Ef_1091, Ef_1093 and Ef_2658 proteins. Homology model of Ef_1091 and Ef_1093 was docked with modeled EfSrtA∆59 and their interactions are also discussed.


Assuntos
Aminoaciltransferases/antagonistas & inibidores , Aminoaciltransferases/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Cisteína Endopeptidases/metabolismo , Enterococcus faecalis/enzimologia , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Sequência de Aminoácidos , Aminoaciltransferases/química , Proteínas de Bactérias/química , Simulação por Computador , Cisteína Endopeptidases/química , Ligação Proteica , Conformação Proteica
20.
IET Nanobiotechnol ; 12(7): 981-986, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30247141

RESUMO

Multiple drug resistance and treatment of contaminated water has become a serious issue in past years. Silver nanoparticles (AgNPs), being bactericidal, non-toxic, cheap and environment friendly behaviour, have drawn attention to overcome these problems. This study has been designed to synthesise AgNPs from Pseudomonas aeruginosa. AgNPs formation was confirmed by colour change and UV-vis spectroscopy. Furthermore, Fourier transform infrared spectroscopy peaks demonstrated the presence of capped proteins as reducing and stabilising agent. Transmission electron microscopy micrograph revealed spherical shape AgNPs with the size ranging between 10 and 20 nm. Antibacterial activity of AgNPs was evaluated against the most prevalent waterborne pathogens enterohaemorrhagic Escherichia coli and Salmonellae typhimurium. Moreover, the antibacterial activity of AgNPs was tested for the treatment of contaminated water which showed attenuation in bacterial load within 8 h as demonstrated by growth kinetics data. Furthermore, AgNPs did not exhibit haemolytic effects on human red blood cells (RBCs) even at 100 mg L-1 concentration of AgNPs. The results herein suggest that AgNPs synthesised by P. aeruginosa under optimised conditions exhibit microbicidal property against waterborne pathogens and having no toxic effect on human RBCs. These AgNPs could be employed for treatment of contaminated water after process optimisation.


Assuntos
Antibacterianos , Nanopartículas Metálicas/química , Pseudomonas aeruginosa/metabolismo , Prata , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Química Verde , Humanos , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Salmonella typhimurium/efeitos dos fármacos , Prata/química , Prata/metabolismo , Prata/farmacologia , Temperatura , Doenças Transmitidas pela Água/microbiologia
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