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The emergence of bacterial resistance to antimicrobial agents poses a serious threat to the effectiveness of treating bacterial illnesses. A major factor contributing to antimicrobial resistance is biofilm formation, driven by quorum sensing (QS). QS suppression inhibits the QS signaling pathway, obstructing cell-to-cell communication. This study focuses on N-(pyrimidin-2-yl)alkyl/arylamide derivatives, which were designed, synthesized, and characterized for their QS inhibitory effects. Among the synthesized compounds (3a-j), compounds 3b, 3d, and 3h exhibited the highest QS inhibitory activity, with inhibition zones of 17.66 ± 6.17, 14.00 ± 6.24, and 17.33 ± 0.66 mm, respectively. Further, molecular docking studies revealed binding affinities between - 8.4 and - 6.3 kcal/mol, indicating strong interactions with the target proteins. Moreover, molecular dynamic simulations confirmed the stability of the protein-ligand complexes for compounds 3b and 3 h. Additionally, in-silico methods were employed to predict the physicochemical properties of these molecules. Overall, these findings underscore the potential of N-(pyrimidin-2-yl)alkyl/arylamide derivatives as QS inhibitors, offering a new perspective for developing alternative antimicrobial therapies.
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BACKGROUND: A variety of factors influence adherence to the lengthy duration of anti-tuberculosis treatment, making it a complicated and dynamic problem. The objective of this study was to investigate the treatment interruption patterns using pre-defined criteria among a cohort of pulmonary tuberculosis patients and to elicit the associated factors. METHODS: This prospective, observational study was conducted between October 2016 to May 2018. All smear and culture positive pulmonary tuberculosis patients (age ≥ 14 years) enrolled between October 1, 2016 to March 31, 2017 across 3 Designated Microscopy Centers (DMCs) were included and followed up till end of treatment for outcome in drug-sensitive, and till interim outcome at 6 months for drug-resistant TB patients. Patterns and reasons for interruptions were recorded as per the study protocol. RESULTS: 171 patients were enrolled in this study, of which 135 (78.94 %) were on Category-I and Category-II treatment (drug-sensitive tuberculosis), 23 (13 %) were multidrug-resistant (MDR) and 13 (8 %) were extensively drug resistant (XDR) tuberculosis patients. Among the drug-sensitive group, 65 (48 %) patients completed their treatment without any interruption while 70 (52 %) patients interrupted with at least one missed dose. Among the 36 MDR/XDR patients, 19 (53 %) patients did not interrupt treatment, but 17 (47 %) patients interrupted with at least one missing dose. The 87 patients in both sub-groups interrupted for 232 times/episodes of which 140 were short and 84 were long interruptions. The main reasons for interruption were found to be busy schedule in 63 (29 %) patients, adverse drug reactions in 40 (18.4 %) and comorbidities in 43 (19.8 %) patients. Feeling of early improvement/no improvement in 23 (10.5 %) patients, addictions in 27 (12.4 %) patients, lack of family support in 14 (6.4 %), unawareness of dosage and duration of treatment in 7 (3.20 %) patients were other common reasons. CONCLUSION: The plurality of patients studied were found to be in the younger age group i.e., 14-25 years (n = 75), constituting nearly 44 % of all the patients included and male treatment interrupters (62 %) outnumbered the females (38 %), possibly owing to work schedule or addictions. The majority of interruptions were related to patient related factors (93.5 %), followed by DOTS provided factors (6.40 %) and system related factors (3.01 %). Further studies should be conducted to classify the factors of treatment interruptions in detail and also to study the impact of these interruptions' patterns on final outcomes.
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Antituberculosos , Adesão à Medicação , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Humanos , Índia , Masculino , Antituberculosos/uso terapêutico , Antituberculosos/administração & dosagem , Feminino , Adulto , Tuberculose Pulmonar/tratamento farmacológico , Fatores de Risco , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Estudos Prospectivos , Pessoa de Meia-Idade , Adesão à Medicação/estatística & dados numéricos , Adulto Jovem , Adolescente , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológicoRESUMO
A unique approach is imperative for the development of drugs aimed at inhibiting various stages of infection, rather than solely focusing on bacterial viability. Among the array of unconventional targets explored for formulating novel antimicrobial medications, blocking the quorum-sensing (QS) system emerges as a highly effective and promising strategy against a variety of pathogenic microbes. In this investigation, we have successfully assessed nine α-aminoamides for their anti-QS activity using Agrobacterium tumefaciensNT1 as a biosensor strain. Among these compounds, three (2, 3and, 4) have been identified as potential anti-QS candidates. Molecular docking studies have further reinforced these findings, indicating that these compounds exhibit favorable pharmacokinetic profiles. Additionally, we have assessed the ligand's stability within the protein's binding pocket using molecular dynamics (MD) simulations and MMGBSA analysis. Further, combination of antiquorum sensing properties with antibiotics viaself-assembly represents a promising approach to enhance antibacterial efficacy, overcome resistance, and mitigate the virulence of bacterial pathogens. The release study also reflects a slow and gradual release of the metronidazole at both pH 6.5 and pH 7.4, avoiding the peaks and troughs associated with more immediate release formulations.
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Agrobacterium tumefaciens , Antibacterianos , Metronidazol , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Percepção de Quorum , Agrobacterium tumefaciens/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Metronidazol/farmacologia , Metronidazol/química , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Géis/química , Sinergismo Farmacológico , Liberação Controlada de FármacosRESUMO
Transbronchial lung cryobiopsy (TBLC) with flexible bronchoscope represents an encouraging modality to obtain a larger size specimen without crush artifact, and a higher diagnostic yield in patients with diffuse parenchymal lung lesions/diseases as compared to conventional transbronchial lung biopsy, and fewer complications as opposed to surgical lung biopsy. Artificial airway is preferred as it provides better airway protection in cases of severe bleeding. Although various researchers have published data on different modalities, the data is not sufficient to standardize a single technique. This study describes the procedural technique, safety, and yield of TBLC using a flexible bronchoscope with an endobronchial blocker. We performed a retrospective analysis of 100 consecutive patients who underwent TBLC using flexible bronchoscopy from May 2018 to June 2022. TBLC samples were obtained under moderate sedation without the use of artificial airway or fluoroscopy. Among the 100 patients, the majority were male (63%). The mean age of the enrolled patients was 44.43±15.92 years. The predominant diagnoses in our study were hypersensitivity pneumonitis (27%), followed by sarcoidosis (12%) and tuberculosis (10%). We obtained alveolated lung tissue in 90 out of 100 cases with a median biopsy size of 5 mm (in greatest dimension, interquartile range 5-4 mm), resulting in a specific histopathological diagnosis in 82 cases. The most frequent complications were bleeding and pneumothorax (13%). Mild bleeding occurred in 58% of the patients, and moderate bleeding occurred in 20% of the patients. There was no episode of severe/life-threatening bleeding. None of the patients required intensive care unit admission or endotracheal intubation. In conclusion, the use of TBLC through flexible bronchoscopy with an endobronchial blocker emerges as a minimally invasive, secure, time-efficient, and readily reproducible technique. Significantly, this procedure can be seamlessly executed in the bronchoscopy suite, eliminating the requirement for an artificial airway or general anesthesia.
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Antibiotics have remained the cornerstone for the treatment of bacterial infections ever since their discovery in the twentieth century. The uproar over antibiotic resistance among bacteria arising from genome plasticity and biofilm development has rendered current antibiotic therapies ineffective, urging the development of innovative therapeutic approaches. The development of antibiotic resistance among bacteria has further heightened the clinical failure of antibiotic therapy, which is often linked to its low bioavailability, side effects, and poor penetration and accumulation at the site of infection. In this review, we highlight the potential use of siderophores, antibodies, cell-penetrating peptides, antimicrobial peptides, bacteriophages, and nanoparticles to smuggle antibiotics across impermeable biological membranes to achieve therapeutically relevant concentrations of antibiotics and combat antimicrobial resistance (AMR). We will discuss the general mechanisms via which each delivery system functions and how it can be tailored to deliver antibiotics against the paradigm of mechanisms underlying antibiotic resistance.
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Bacteriophages infect and replicate within bacteria and play a key role in the environment, particularly in microbial ecosystems and bacterial population dynamics. The increasing recognition of their significance stems from their wide array of environmental and biotechnological uses, which encompass the mounting issue of antimicrobial resistance (AMR). Beyond their therapeutic potential in combating antibiotic-resistant infections, bacteriophages also find vast applications such as water quality monitoring, bioremediation, and nutrient cycling within environmental sciences. Researchers are actively involved in isolating and characterizing bacteriophages from different natural sources to explore their applications. Gaining insights into key aspects such as the life cycle of bacteriophages, their host range, immune interactions, and physical stability is vital to enhance their application potential. The establishment of diverse phage libraries has become indispensable to facilitate their wide-ranging uses. Consequently, numerous protocols, ranging from traditional to cutting-edge techniques, have been developed for the isolation, detection, purification, and characterization of bacteriophages from diverse environmental sources. This review offers an exploration of tools, delves into the methods of isolation, characterization, and the extensive environmental applications of bacteriophages, particularly in areas like water quality assessment, the food sector, therapeutic interventions, and the phage therapy in various infections and diseases.
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Bacteriófagos , Terapia por Fagos , Ecossistema , Bactérias , Biotecnologia , Terapia por Fagos/métodos , AntibacterianosRESUMO
Once thought to be a unique capability of the Langerhans islets in the pancreas of mammals, insulin (INS) signaling is now recognized as an evolutionarily ancient function going back to prokaryotes. INS is ubiquitously present not only in humans but also in unicellular eukaryotes, fungi, worms, and Drosophila. Remote homologue identification also supports the presence of INS and INS receptor in corals where the availability of glucose is largely dependent on the photosynthetic activity of the symbiotic algae. The cnidarian animal host of corals operates together with a 20,000-sized microbiome, in direct analogy to the human gut microbiome. In humans, aberrant INS signaling is the hallmark of metabolic disease, and is thought to play a major role in aging, and age-related diseases, such as Alzheimer's disease. We here would like to argue that a broader view of INS beyond its human homeostasis function may help us understand other organisms, and in turn, studying those non-model organisms may enable a novel view of the human INS signaling system. To this end, we here review INS signaling from a new angle, by drawing analogies between humans and corals at the molecular level.
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Antozoários , Ilhotas Pancreáticas , Animais , Humanos , Antozoários/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Pâncreas/metabolismo , Transdução de SinaisRESUMO
Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation1,2. Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation3, we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells. Because of its far superior reactivity towards peroxyl radicals, 7-DHC effectively shields (phospho)lipids from autoxidation and subsequent fragmentation. We provide validation in neuroblastoma and Burkitt's lymphoma xenografts where we demonstrate that the accumulation of 7-DHC is capable of inducing a shift towards a ferroptosis-resistant state in these tumours ultimately resulting in a more aggressive phenotype. Conclusively, our findings provide compelling evidence of a yet-unrecognized antiferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.
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Linfoma de Burkitt , Desidrocolesteróis , Ferroptose , Neuroblastoma , Animais , Humanos , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Sobrevivência Celular , Desidrocolesteróis/metabolismo , Peroxidação de Lipídeos , Transplante de Neoplasias , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Oxirredução , Fenótipo , Reprodutibilidade dos TestesRESUMO
Salmonella enterica serovar Typhi is a significant cause of typhoid fever and a major public health problem. The ability of S. Typhi to form biofilms on living and non-living surfaces results in antibiotic resistance and poses a major challenge in health care. In this study, we assessed the ability of zingerone alone and in combination with antibiotics against the motility phenotypes and biofilm-forming ability of S. Typhi. Results showed that zingerone effectively reduced the swimming, swarming, and twitching phenotypes and exhibited biofilm inhibition potential. Moreover, zingerone enhanced the antibiofilm activity of ciprofloxacin and kanamycin. Microscopic analysis revealed a thinner biofilm in the presence of zingerone, which may have enhanced the antibiofilm efficacy of the antibiotics. The microscopic analysis showed that the presence of zingerone resulted in a reduction in the thickness of the biofilm, potentially increasing the antibiofilm efficacy of the antibiotics. In silico molecular docking and simulation studies further indicated that zingerone may bind to the fimbriae subunits (FimA, FimC, FimH, and FimY) of S. Typhi and form stable interactions. These findings provide important insights into the potential of zingerone to target biofilm-associated Salmonella infections. Further research is considered a promising option for designing innovative approaches to prevent infections associated with biofilms. Schematic representation of the role of zingerone in biofilm, motility inhibition and molecular interactions with biofilm associated proteins.
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Antibacterianos , Salmonella , Antibacterianos/farmacologia , Simulação de Acoplamento Molecular , Biofilmes , Salmonella typhiRESUMO
The development of bacterial resistance to chemical therapy poses a severe danger to efficacy of treating bacterial infections. One of the key factors for resistance to antimicrobial medications is growth of bacteria in biofilm. Quorum sensing (QS) inhibition was created as an alternative treatment by developing novel anti-biofilm medicines. Cell-cell communication is impeded by QS inhibition, which targets QS signaling pathway. The goal of this work is to develop newer drugs that are effective against Pseudomonas aeruginosa by decreasing QS and acting as anti-biofilm agents. In this investigation, N-(benzo[d]thiazol-2-yl)benzamide/N-(thiazol-2-yl)benzamide derivatives 3a-h were designed and synthesized in good yields. Further, molecular docking analyses revealed that binding affinity values were founded -11.2 to -7.6â kcal/mol that were moderate to good. The physicochemical properties of these prepared compounds were investigated through in-silico method. Molecular dynamic simulation was also used to know better understanding of stability of the protein and ligand complex. Comparing N-(benzo[d]thiazol-2-yl)benzamide 3a to salicylic acid (4.40±0.10) that was utilised as standard for quorum sensing inhibitor, the anti-QS action was found greater for N-(benzo[d]thiazol-2-yl)benzamide 3a (4.67±0.45) than salicylic acid (4.40±0.10). Overall, research results suggested that N-(benzo[d]thiazol-2-yl)benzamide/N-(thiazol-2-yl)benzamide derivatives 3a-h may hold to develop new quorum sensing inhibitors.
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Pseudomonas aeruginosa , Percepção de Quorum , Simulação de Acoplamento Molecular , Biofilmes , Ácido Salicílico/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Proteínas de Bactérias/metabolismoRESUMO
Biofilm-associated infections have emerged as a significant public health challenge due to their persistent nature and increased resistance to conventional treatment methods. The indiscriminate usage of antibiotics has made us susceptible to a range of multidrug-resistant pathogens. These pathogens show reduced susceptibility to antibiotics and increased intracellular survival. However, current methods for treating biofilms, such as smart materials and targeted drug delivery systems, have not been found effective in preventing biofilm formation. To address this challenge, nanotechnology has provided innovative solutions for preventing and treating biofilm formation by clinically relevant pathogens. Recent advances in nanotechnological strategies, including metallic nanoparticles, functionalized metallic nanoparticles, dendrimers, polymeric nanoparticles, cyclodextrin-based delivery, solid lipid nanoparticles, polymer drug conjugates, and liposomes, may provide valuable technological solutions against infectious diseases. Therefore, it is imperative to conduct a comprehensive review to summarize the recent advancements and limitations of advanced nanotechnologies. The present Review encompasses a summary of infectious agents, the mechanisms that lead to biofilm formation, and the impact of pathogens on human health. In a nutshell, this Review offers a comprehensive survey of the advanced nanotechnological solutions for managing infections. A detailed presentation has been made as to how these strategies may improve biofilm control and prevent infections. The key objective of this Review is to summarize the mechanisms, applications, and prospects of advanced nanotechnologies to provide a better understanding of their impact on biofilm formation by clinically relevant pathogens.
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Cancer is a significant challenge for effective treatment due to its complex mechanism, different progressing stages, and lack of adequate procedures for screening and identification. Pancreatic cancer is typically identified in its advanced progression phase with a low survival of ~5 years. Among cancers, pancreatic cancer is also considered a high mortality-causing casualty over other accidental or disease-based mortality, and it is ranked seventh among all mortality-associated cancers globally. Henceforth, developing diagnostic procedures for its early detection, understanding pancreatic cancer-linked mechanisms, and various therapeutic strategies are crucial. This review describes the recent development in pancreatic cancer progression, mechanisms, and therapeutic approaches, including molecular techniques and biomedicines for effectively treating cancer.
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INTRODUCTION: Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation. Lack of knowledge about the correct inhalation techniques leads to poor control of both diseases. This study aimed to study the effectiveness of inhalation technique training in patients with COPD and asthma. MATERIALS AND METHODS: A total of 132 patients fulfilling the inclusion criteria were trained with the correct technique of inhalation on day 0 and at the end of 1 and 6 months. Evaluation of technique training was done on these three occasions posttraining. The mean score of devices was obtained, and the mean inhalation technique score of various devices was compared. RESULTS: Out of 132 patients, 65.1% (86/132) patients were using a dry powdered inhaler (DPIs), 26.5% (35/132) patients used metered dose inhalers (MDIs), and 8.4% (11/132) patients used MDI with spacer. The mean scores of patients using MDI at baseline were 5.68 ± 0.83, and after 1 month, 6.68 ± 0.58 (p < 0.000). The inhalation technique mean score of MDI improved after 6 months, 7.02 ± 0.56 as compared to baseline (p < 0.008) mean score of the patients using DPIs improved after 1 month, 5.53 ± 0.58 as compared to baseline 4.37 ± 5.53 (p < 0.000). There was no statistical improvement in the device mean score of DPIs after 6 months, 5.62 ± 0.55 when compared with 1 month, 5.53 ± 0.58 (p < 0.117). Patients who used pressurized metered-dose inhalers (pMDI) with spacers improved their inhalation score after 1 month by 6.90 ± 0.94 as compared to the baseline score of 6.90 ± 0.94 (p < 0.001). The mean score decreased marginally after 6 months, 7.818 ± 0.60, as compared to the score at the end of 1 month of 8.27 ± 0.64 (p < 0.053). DISCUSSION: Patients showed improvement in the technique of inhalation after educational training, reinstructions, and a standard checklist.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Asma/tratamento farmacológico , Inaladores Dosimetrados , Administração por Inalação , Nebulizadores e VaporizadoresRESUMO
Environment stress is a major threat to the existence of coral reefs and has generated a lot of interest in the coral research community. Under the environmental stress, corals can experience tissue loss and/or the breakdown of symbiosis between the cnidarian host and its symbiotic algae causing the coral tissue to appear white as the skeleton can be seen by transparency. Image analysis is a common method used to assess tissue response under the environmental stress. However, the traditional approach is limited by the dynamic nature of the coral-algae symbiosis. Here, we observed coral tissue response in the scleractinian coral, Montipora capricornis, using high frequency image analysis throughout the experiment, as opposed to the typical start/end point assessment method. Color analysis reveals that the process can be divided into five stages with two critical stages according to coral tissue morphology and color ratio. We further explore changes to the morphology of individual polyps by means of the Pearson correlation coefficient and recurrence plots, where the quasi-periodic and nonstationary dynamics can be identified. The recurrence quantification analysis also allows the comparison between the different polyps. Our research provides a detailed visual and mathematical analysis of coral tissue response to environmental stress, which potentially shows universal applicability. Moreover, our approach provides a robust quantitative advancement for improving our insight into a suite of biotic responses in the perspective of coral health evaluation and fate prediction.
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Antozoários , Animais , Antozoários/fisiologia , Projetos Piloto , Recifes de Corais , Estresse Fisiológico , Simbiose/fisiologiaRESUMO
Sepsis is a life-threatening condition characterized by an uncontrolled inflammatory response to an infectious agent and its antigens. Immune cell activation against the antigens causes severe distress that mediates a strong inflammatory response in vital organs. Sepsis is responsible for a high rate of morbidity and mortality in immunosuppressed patients. Monoclonal antibody (mAb)-based therapeutic strategies are now being explored as a viable therapy option for severe sepsis and septic shock. Monoclonal antibodies may provide benefits through two major strategies: (a) monoclonal antibodies targeting the pathogen and its components, and (b) mAbs targeting inflammatory signaling may directly suppress the production of inflammatory mediators. The major focus of mAb therapies has been bacterial endotoxin (lipopolysaccharide), although other surface antigens are also being investigated for mAb therapy. Several promising candidates for mAbs are undergoing clinical trials at present. Despite several failures and the investigation of novel targets, mAb therapy provides a glimmer of hope for the treatment of severe bacterial sepsis and septic shock. In this review, mAb candidates, their efficacy against controlling infection, with special emphasis on potential roadblocks, and prospects are discussed.
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The effectiveness of treating bacterial infections is seriously threatened by the emergence of bacterial resistance to chemical treatment. Growth of microbes in biofilm is one of the main causes of resistance to antimicrobial drugs. Quorum sensing (QS) inhibition, which targets the QS signalling system by obstructing cell-cell communication, was developed as an alternative treatment by creating innovative anti-biofilm drugs. Therefore, the goal of this study is to develop novel antimicrobial drugs that are effective against Pseudomonas aeruginosa by inhibiting QS and acting as anti-biofilm agents. In this study, N-(2- and 3-pyridinyl)benzamide derivatives were selected to design and syntheses. Antibiofilm activity was revealed by all the synthesized compounds and the biofilm was visibly impaired, and the OD595nm readings of solubilized biofilm cells presented a momentous difference between the treated and untreated biofilms. The best anti-QS zone was observed for compound 5d and found to be 4.96â mm. Through inâ silico research, the physicochemical characteristics and binding manner of these produced compounds were examined. For the purpose of understanding the stability of the protein and ligand complex, molecular dynamic simulation was also carried out. The overall findings showed that N-(2- and 3-pyridinyl)benzamide derivatives could be the key to creating effective newer anti-quorum sensing drugs that are effective against different bacteria.
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Anti-Infecciosos , Pseudomonas aeruginosa , Antibacterianos/química , Percepção de Quorum , Biofilmes , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/metabolismoRESUMO
With the ease of gene sequencing and the technology available to study and manipulate non-model organisms, the extension of the methodological toolbox required to translate our understanding of model organisms to non-model organisms has become an urgent problem. For example, mining of large coral and their symbiont sequence data is a challenge, but also provides an opportunity for understanding functionality and evolution of these and other non-model organisms. Much more information than for any other eukaryotic species is available for humans, especially related to signal transduction and diseases. However, the coral cnidarian host and human have diverged over 700 million years ago and homologies between proteins in the two species are therefore often in the gray zone, or at least often undetectable with traditional BLAST searches. We introduce a two-stage approach to identifying putative coral homologues of human proteins. First, through remote homology detection using Hidden Markov Models, we identify candidate human homologues in the cnidarian genome. However, for many proteins, the human genome alone contains multiple family members with similar or even more divergence in sequence. In the second stage, therefore, we filter the remote homology results based on the functional and structural plausibility of each coral candidate, shortlisting the coral proteins likely to have conserved some of the functions of the human proteins. We demonstrate our approach with a pipeline for mapping membrane receptors in humans to membrane receptors in corals, with specific focus on the stony coral, P. damicornis. More than 1000 human membrane receptors mapped to 335 coral receptors, including 151 G protein coupled receptors (GPCRs). To validate specific sub-families, we chose opsin proteins, representative GPCRs that confer light sensitivity, and Toll-like receptors, representative non-GPCRs, which function in the immune response, and their ability to communicate with microorganisms. Through detailed structure-function analysis of their ligand-binding pockets and downstream signaling cascades, we selected those candidate remote homologues likely to carry out related functions in the corals. This pipeline may prove generally useful for other non-model organisms, such as to support the growing field of synthetic biology.
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Antozoários , Receptores Acoplados a Proteínas G , Transdução de Sinais , Animais , Humanos , Antozoários/genética , Antozoários/fisiologia , Genoma , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Modelos AnimaisRESUMO
The rhizomes of ginger have been in use in many forms of traditional and alternative medicines. Besides being employed as condiment and flavoring agent, it is used in the treatment of nausea, osteoarthritis, muscle pain, menstrual pain, chronic indigestion, Alzheimer's disease, and cancer. Ginger rhizome contains volatile oils, phenolic compounds and resins, and characterization studies showed that [6]-gingerol, [6]-shogaol, and [6]-paradol are reported to be the pharmacologically active components. Gingerol is a major chemical constituent found as volatile oil in the rhizomes of ginger. It has several medicinal benefits and used for the treatment of rheumatoid arthritis, nausea, cancer, and diabetes. Many studies have been carried out in various parts of the world to isolate and standardize gingerol for their use as a complementary medicine. The present review summarizes wide range of research studies on gingerol and its pharmacological roles in various metabolic diseases.
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Catecóis , Zingiber officinale , Catecóis/farmacologia , Catecóis/uso terapêutico , Álcoois Graxos/farmacologia , Álcoois Graxos/uso terapêutico , Álcoois Graxos/química , Extratos Vegetais/química , Zingiber officinale/química , Zingiber officinale/metabolismoRESUMO
Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications.