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1.
Mol Divers ; 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37658910

RESUMO

Listeria monocytogenes is an important human and animal pathogen able to cause an infection named listeriosis and is mainly transmitted through contaminated food. Among its virulence traits, the ability to form biofilms and to survive in harsh environments stand out and lead to the persistence of L. monocytogenes for long periods in food processing environments. Virulence and biofilm formation are phenotypes regulated by quorum sensing (QS) and, therefore, the control of L. monocytogenes through an anti-QS strategy is promising. This study aimed to identify, by in silico approaches, proteins secreted by lactic acid bacteria (LAB) potentially able to interfere with the agr QS system of L. monocytogenes. The genome mining of Lacticaseibacillus rhamnosus GG and Lactobacillus acidophilus NCFM revealed 151 predicted secreted proteins. Concomitantly, the three-dimensional (3D) structures of AgrB and AgrC proteins of L. monocytogenes were modeled and validated, and their active sites were predicted. Through protein-protein docking and molecular dynamic, Serine-type D-Ala-D-Ala carboxypeptidase and L,D-transpeptidase, potentially secreted by L. rhamnosus GG and L. acidophilus NCFM, respectively, were identified with high affinity to AgrB and AgrC proteins, respectively. By inhibiting the translocation of the cyclic autoinducer peptide (cyclic AIP) via AgrB, and its recognition in the active site of AgrC, these LAB proteins could disrupt L. monocytogenes communication by impairing the agr QS system. The application of the QS inhibitors predicted in this study can emerge as a promising strategy in controlling L. monocytogenes in food processing environment and as an adjunct to antibiotic therapy for the treatment of listeriosis.

2.
Indian J Med Res ; 157(4): 293-303, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37102510

RESUMO

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.


Assuntos
COVID-19 , Ingredientes de Alimentos , Humanos , Nutrigenômica , Dióxido de Carbono , Lipopolissacarídeos , Pandemias , Síndrome da Liberação de Citocina , Ácido Palmítico , SARS-CoV-2 , Dieta/métodos , Comportamento Alimentar , Zinco , Chá , Ferro , Triglicerídeos
3.
An Acad Bras Cienc ; 95(suppl 2): e20230617, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38055447

RESUMO

Sexually Transmitted Infections (STIs) are a public health burden rising in developed and developing nations. The World Health Organization estimates nearly 374 million new cases of curable STIs yearly. Global efforts to control their spread have been insufficient in fulfilling their objective. As there is no vaccine for many of these infections, these efforts are focused on education and condom distribution. The development of vaccines for STIs is vital for successfully halting their spread. The field of immunoinformatics is a powerful new tool for vaccine development, allowing for the identification of vaccine candidates within a bacterium's genome and allowing for the design of new genome-based vaccine peptides. The goal of this review was to evaluate the usage of immunoinformatics in research focused on non-viral STIs, identifying fields where research efforts are concentrated. Here we describe gaps in applying these techniques, as in the case of Treponema pallidum and Trichomonas vaginalis.


Assuntos
Infecções Sexualmente Transmissíveis , Trichomonas vaginalis , Vacinas , Humanos , Vacinologia , Infecções Sexualmente Transmissíveis/prevenção & controle
4.
Environ Microbiol ; 24(10): 4714-4724, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35859337

RESUMO

We investigated whether a set of phylogeographical tracked emergent events of Orthocoronavirinae were related to developed, urban and polluted environments worldwide. We explored coronavirus records in response to climate (rainfall parameters), population density, CO2 emission, Human Developmental Index (HDI) and deforestation. We contrasted environmental characteristics from regions with spillovers or encounters of wild Orthocoronavirinae against adjacent areas having best-preserved conditions. We used all complete sequenced CoVs genomes deposited in NCBI and GISAID databases until January 2021. Except for Deltacoronavirus, concentrated in Hong Kong and in birds, the other three genera were scattered all over the planet, beyond the original distribution of the subfamily, and found in humans, mammals, fishes and birds, wild or domestic. Spillovers and presence in wild animals were only reported in developed/densely populated places. We found significantly more occurrences reported in places with higher HDI, CO2 emission, or population density, along with more rainfall and more accentuated seasonality. Orthocoronavirinae occurred in areas with significantly higher human populations, CO2 emissions and deforestation rates than in adjacent locations. Intermediately disturbed ecosystems seemed more vulnerable for Orthocoronavirinae emergence than forested regions in frontiers of deforestation. Sadly, people experiencing poverty in an intensely consumerist society are the most vulnerable.


Assuntos
Infecções por Coronavirus , Coronavirus , Animais , Dióxido de Carbono , Conservação dos Recursos Naturais , Ecossistema , Humanos , Mamíferos
5.
Genomics ; 113(4): 2730-2743, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34118385

RESUMO

Mycoplasma genitalium is an obligate intracellular bacterium that is responsible for several sexually transmitted infections, including non-gonococcal urethritis in men and several inflammatory reproductive tract syndromes in women. Here, we applied subtractive genomics and reverse vaccinology approaches for in silico prediction of potential vaccine and drug targets against five strains of M. genitalium. We identified 403 genes shared by all five strains, from which 104 non-host homologous proteins were selected, comprising of 44 exposed/secreted/membrane proteins and 60 cytoplasmic proteins. Based on the essentiality, functionality, and structure-based binding affinity, we finally predicted 19 (14 novel) putative vaccine and 7 (2 novel) candidate drug targets. The docking analysis showed six molecules from the ZINC database as promising drug candidates against the identified targets. Altogether, both vaccine candidates and drug targets identified here may contribute to the future development of therapeutic strategies to control the spread of M. genitalium worldwide.


Assuntos
Mycoplasma genitalium , Vacinas , Feminino , Genômica , Humanos , Masculino , Mycoplasma genitalium/genética , Vacinologia
6.
Environ Microbiol ; 23(7): 3727-3742, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33476085

RESUMO

Kombucha is a multispecies microbial ecosystem mainly composed of acetic acid bacteria and osmophilic acid-tolerant yeasts, which is used to produce a probiotic drink. Furthermore, Kombucha Mutualistic Community (KMC) has been recently proposed to be used during long space missions as both a living functional fermented product to improve astronauts' health and an efficient source of bacterial nanocellulose. In this study, we compared KMC structure and functions before and after samples were exposed to the space/Mars-like environment outside the International Space Station in order to investigate the changes related to their re-adaptation to Earth-like conditions by shotgun metagenomics, using both diversity and functional analyses of Community Ecology and Complex Networks approach. Our study revealed that the long-term exposure to space/Mars-like conditions on low Earth orbit may disorganize the KMC to such extent that it will not restore the initial community structure; however, KMC core microorganisms of the community were maintained. Nonetheless, there were no significant differences in the community functions, meaning that the KMC communities are ecologically resilient. Therefore, despite the extremely harsh conditions, key KMC species revived and provided the community with the genetic background needed to survive long periods of time under extraterrestrial conditions.


Assuntos
Meio Ambiente Extraterreno , Voo Espacial , Planeta Terra , Ecossistema , Metagenoma , Metagenômica
7.
BMC Genomics ; 21(1): 33, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924165

RESUMO

BACKGROUND: Spirochetal organisms of the Treponema genus are responsible for causing Treponematoses. Pathogenic treponemes is a Gram-negative, motile, spirochete pathogen that causes syphilis in human. Treponema pallidum subsp. endemicum (TEN) causes endemic syphilis (bejel); T. pallidum subsp. pallidum (TPA) causes venereal syphilis; T. pallidum subsp. pertenue (TPE) causes yaws; and T. pallidum subsp. Ccarateum causes pinta. Out of these four high morbidity diseases, venereal syphilis is mediated by sexual contact; the other three diseases are transmitted by close personal contact. The global distribution of syphilis is alarming and there is an increasing need of proper treatment and preventive measures. Unfortunately, effective measures are limited. RESULTS: Here, the genome sequences of 53 T. pallidum strains isolated from different parts of the world and a diverse range of hosts were comparatively analysed using pan-genomic strategy. Phylogenomic, pan-genomic, core genomic and singleton analysis disclosed the close connection among all strains of the pathogen T. pallidum, its clonal behaviour and showed increases in the sizes of the pan-genome. Based on the genome plasticity analysis of the subsets containing the subspecies T pallidum subsp. pallidum, T. pallidum subsp. endemicum and T. pallidum subsp. pertenue, we found differences in the presence/absence of pathogenicity islands (PAIs) and genomic islands (GIs) on subsp.-based study. CONCLUSIONS: In summary, we identified four pathogenicity islands (PAIs), eight genomic islands (GIs) in subsp. pallidum, whereas subsp. endemicum has three PAIs and seven GIs and subsp. pertenue harbours three PAIs and eight GIs. Concerning the presence of genes in PAIs and GIs, we found some genes related to lipid and amino acid biosynthesis that were only present in the subsp. of T. pallidum, compared to T. pallidum subsp. endemicum and T. pallidum subsp. pertenue.


Assuntos
Sífilis/microbiologia , Treponema pallidum/genética , Genoma Bacteriano/genética , Ilhas Genômicas/genética , Humanos , Filogenia , Treponema pallidum/classificação
8.
J Surg Res ; 252: 156-168, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32278970

RESUMO

BACKGROUND: India is in the process of strengthening the trauma care system, and assessment of the current situation using standard guidelines has immense use. This study reports the status of trauma care facilities in India, with a broad framework of guidelines for essential trauma care by the World Health Organization. MATERIALS AND METHODS: This study is part of a multicentric intervention study to standardize structured trauma care services in five Indian cities. Thirty trauma care facilities (five level I, 10 level II, and 15 level III facilities) were included. Data on the availability of equipment and manpower were collected. Availability of knowledge + skills and equipment + supplies was assessed based on the guidelines for essential trauma care by World Health Organization. RESULTS: There is almost 100% availability of services and equipment in level I hospitals, but availability varied between 50% and 100% at level II facilities. Very fewer number of services are available at level III facilities. Inadequacy of equipment is reported in level II and III facilities. Only level I facilities have required human resources. Availability of resources in terms of knowledge and equipment of different skills indicated that overall optimal level is observed in level I hospitals. Level II facilities are more deficient in nursing and paramedic staff, and level III facilities reported deficiencies in all categories. CONCLUSIONS: A significant imbalance between recommended resources and the resources that are available in the trauma care facilities was noted. Hence, the study warrants urgent strengthening of trauma care facilities, particularly of level II and III facilities.


Assuntos
Equipamentos e Provisões Hospitalares/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/organização & administração , Mão de Obra em Saúde/estatística & dados numéricos , Centros de Traumatologia/estatística & dados numéricos , Ferimentos e Lesões/terapia , Países em Desenvolvimento/estatística & dados numéricos , Equipamentos e Provisões Hospitalares/normas , Acessibilidade aos Serviços de Saúde/normas , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Mão de Obra em Saúde/organização & administração , Mão de Obra em Saúde/normas , Humanos , Índia , Guias de Prática Clínica como Assunto , Centros de Traumatologia/organização & administração , Centros de Traumatologia/normas , Organização Mundial da Saúde
9.
Int J Mol Sci ; 18(2)2017 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-28216574

RESUMO

Sexually transmitted infections (STIs) are caused by a wide variety of bacteria, viruses, and parasites that are transmitted from one person to another primarily by vaginal, anal, or oral sexual contact. Syphilis is a serious disease caused by a sexually transmitted infection. Syphilis is caused by the bacterium Treponema pallidum subspecies pallidum. Treponema pallidum (T. pallidum) is a motile, gram-negative spirochete, which can be transmitted both sexually and from mother to child, and can invade virtually any organ or structure in the human body. The current worldwide prevalence of syphilis emphasizes the need for continued preventive measures and strategies. Unfortunately, effective measures are limited. In this study, we focus on the identification of vaccine targets and putative drugs against syphilis disease using reverse vaccinology and subtractive genomics. We compared 13 strains of T. pallidum using T. pallidum Nichols as the reference genome. Using an in silicoapproach, four pathogenic islands were detected in the genome of T. pallidum Nichols. We identified 15 putative antigenic proteins and sixdrug targets through reverse vaccinology and subtractive genomics, respectively, which can be used as candidate therapeutic targets in the future.


Assuntos
Antígenos de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Simulação por Computador , Mapeamento de Epitopos , Sífilis/prevenção & controle , Treponema pallidum/imunologia , Antígenos de Bactérias/química , Antígenos de Bactérias/genética , Vacinas Bacterianas/genética , Biologia Computacional/métodos , Mapeamento de Epitopos/métodos , Genoma Bacteriano , Ilhas Genômicas , Genômica/métodos , Modelos Moleculares , Relação Estrutura-Atividade , Treponema pallidum/genética
10.
BMC Microbiol ; 16: 100, 2016 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-27251711

RESUMO

BACKGROUND: Corynebacterium pseudotuberculosis can be classified into two biovars or biovars based on their nitrate-reducing ability. Strains isolated from sheep and goats show negative nitrate reduction and are termed biovar Ovis, while strains from horse and cattle exhibit positive nitrate reduction and are called biovar Equi. However, molecular evidence has not been established so far to understand this difference, specifically if these C. pseudotuberculosis strains are under an evolutionary process. RESULTS: The ERIC 1 + 2 Minimum-spanning tree from 367 strains of C. pseudotuberculosis showed that the great majority of biovar Ovis strains clustered together, but separately from biovar Equi strains that also clustered amongst themselves. Using evolutionarily conserved genes (rpoB, gapA, fusA, and rsmE) and their corresponding amino acid sequences, we analyzed the phylogenetic relationship among eighteen strains of C. pseudotuberculosis belonging to both biovars Ovis and Equi. Additionally, conserved point mutation based on structural variation analysis was also carried out to elucidate the genotype-phenotype correlations and speciation. We observed that the biovars are different at the molecular phylogenetic level and a probable anagenesis is occurring slowly within the species C. pseudotuberculosis. CONCLUSIONS: Taken together the results suggest that biovar Equi is forming the biovar Ovis. However, additional analyses using other genes and other bacterial strains are required to further support our anagenesis hypothesis in C. pseudotuberculosis.


Assuntos
Proteínas de Bactérias/genética , Corynebacterium pseudotuberculosis/classificação , Corynebacterium pseudotuberculosis/genética , Análise de Sequência de DNA/métodos , Animais , Bovinos , Sequência Conservada , DNA Bacteriano/genética , Evolução Molecular , Cabras , Cavalos , Nitratos/metabolismo , Filogenia , Mutação Puntual , Ovinos
11.
BMC Genomics ; 16: 452, 2015 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-26062809

RESUMO

BACKGROUND: Organisms utilize a multitude of mechanisms for responding to changing environmental conditions, maintaining their functional homeostasis and to overcome stress situations. One of the most important mechanisms is transcriptional gene regulation. In-depth study of the transcriptional gene regulatory network can lead to various practical applications, creating a greater understanding of how organisms control their cellular behavior. DESCRIPTION: In this work, we present a new database, CMRegNet for the gene regulatory networks of Corynebacterium glutamicum ATCC 13032 and Mycobacterium tuberculosis H37Rv. We furthermore transferred the known networks of these model organisms to 18 other non-model but phylogenetically close species (target organisms) of the CMNR group. In comparison to other network transfers, for the first time we utilized two model organisms resulting into a more diverse and complete network of the target organisms. CONCLUSION: CMRegNet provides easy access to a total of 3,103 known regulations in C. glutamicum ATCC 13032 and M. tuberculosis H37Rv and to 38,940 evolutionary conserved interactions for 18 non-model species of the CMNR group. This makes CMRegNet to date the most comprehensive database of regulatory interactions of CMNR bacteria. The content of CMRegNet is publicly available online via a web interface found at http://lgcm.icb.ufmg.br/cmregnet .


Assuntos
Corynebacterium glutamicum/genética , Bases de Dados Genéticas , Redes Reguladoras de Genes , Mycobacterium tuberculosis/genética , Biologia Computacional , Corynebacterium glutamicum/classificação , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Internet , Mycobacterium tuberculosis/classificação , Filogenia
12.
BMC Genomics ; 16 Suppl 5: S9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26041381

RESUMO

BACKGROUND: The bacterium Corynebacterium pseudotuberculosis (Cp) causes caseous lymphadenitis (CLA), mastitis, ulcerative lymphangitis, and oedema in a number of hosts, comprising ruminants, thereby intimidating economic and dairy industries worldwide. So far there is no effective drug or vaccine available against Cp. Previously, a pan-genomic analysis was performed for both biovar equi and biovar ovis and a Pathogenicity Islands (PAIS) analysis within the strains highlighted a large set of proteins that could be relevant therapeutic targets for controlling the onset of CLA. In the present work, a structural druggability analysis pipeline was accomplished along 15 previously sequenced Cp strains from both biovar equi and biovar ovis. METHODS AND RESULTS: We computed the whole modelome of a reference strain Cp1002 (NCBI Accession: NC_017300.1) and then the homology models of proteins, of 14 different Cp strains, with high identity (≥ 85%) to the reference strain were also done. Druggability score of all proteins pockets was calculated and only those targets that have a highly druggable (HD) pocket in all strains were kept, a set of 58 proteins. Finally, this information was merged with the previous PAIS analysis giving two possible highly relevant targets to conduct drug discovery projects. Also, off-targeting information against host organisms, including Homo sapiens and a further analysis for protein essentiality provided a final set of 31 druggable, essential and non-host homologous targets, tabulated in table S4, additional file 1. Out of 31 globally druggable targets, 9 targets have already been reported in other pathogenic microorganisms, 3 of them (3-isopropylmalate dehydratase small subunit, 50S ribosomal protein L30, Chromosomal replication initiator protein DnaA) in C. pseudotuberculosis. CONCLUSION: Overall we provide valuable information of possible targets against C. pseudotuberculosis where some of these targets have already been reported in other microorganisms for drug discovery projects, also discarding targets that might be physiologically relevant but are not amenable for drug binding. We propose that the constructed in silico dataset might serve as a guidance for the scientific community to have a better understanding while selecting putative therapeutic protein candidates as druggable ones as effective measures against C. pseudotuberculosis.


Assuntos
Antibacterianos/farmacologia , Biologia Computacional/métodos , Infecções por Corynebacterium/veterinária , Corynebacterium pseudotuberculosis/efeitos dos fármacos , Corynebacterium pseudotuberculosis/genética , Algoritmos , Animais , Sequência de Bases , Sítios de Ligação , Infecções por Corynebacterium/tratamento farmacológico , Genoma Bacteriano/efeitos dos fármacos , Genoma Bacteriano/genética , Humanos , Fases de Leitura Aberta/genética , Proteômica/métodos
13.
BMC Genomics ; 15 Suppl 7: S3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25573232

RESUMO

Corynebacterium pseudotuberculosis (Cp) is a pathogenic bacterium that causes caseous lymphadenitis (CLA), ulcerative lymphangitis, mastitis, and edematous to a broad spectrum of hosts, including ruminants, thereby threatening economic and dairy industries worldwide. Currently there is no effective drug or vaccine available against Cp. To identify new targets, we adopted a novel integrative strategy, which began with the prediction of the modelome (tridimensional protein structures for the proteome of an organism, generated through comparative modeling) for 15 previously sequenced C. pseudotuberculosis strains. This pan-modelomics approach identified a set of 331 conserved proteins having 95-100% intra-species sequence similarity. Next, we combined subtractive proteomics and modelomics to reveal a set of 10 Cp proteins, which may be essential for the bacteria. Of these, 4 proteins (tcsR, mtrA, nrdI, and ispH) were essential and non-host homologs (considering man, horse, cow and sheep as hosts) and satisfied all criteria of being putative targets. Additionally, we subjected these 4 proteins to virtual screening of a drug-like compound library. In all cases, molecules predicted to form favorable interactions and which showed high complementarity to the target were found among the top ranking compounds. The remaining 6 essential proteins (adk, gapA, glyA, fumC, gnd, and aspA) have homologs in the host proteomes. Their active site cavities were compared to the respective cavities in host proteins. We propose that some of these proteins can be selectively targeted using structure-based drug design approaches (SBDD). Our results facilitate the selection of C. pseudotuberculosis putative proteins for developing broad-spectrum novel drugs and vaccines. A few of the targets identified here have been validated in other microorganisms, suggesting that our modelome strategy is effective and can also be applicable to other pathogens.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/efeitos dos fármacos , Vacinas Bacterianas , Biologia Computacional , Corynebacterium pseudotuberculosis/efeitos dos fármacos , Corynebacterium pseudotuberculosis/genética , Sistemas de Liberação de Medicamentos , Proteoma/genética , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Simulação por Computador , Sequência Conservada , Corynebacterium pseudotuberculosis/metabolismo , Desenho de Fármacos , Genes Essenciais , Humanos , Software , Relação Estrutura-Atividade
15.
J Fungi (Basel) ; 10(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38248954

RESUMO

Histoplasmosis is a widespread systemic disease caused by Histoplasma capsulatum, prevalent in the Americas. Despite its significant morbidity and mortality rates, no vaccines are currently available. Previously, five vaccine targets and specific epitopes for H. capsulatum were identified. Immunoinformatics has emerged as a novel approach for determining the main immunogenic components of antigens through in silico methods. Therefore, we predicted the main helper and cytotoxic T lymphocytes and B-cell epitopes for these targets to create a potential multi-epitope vaccine known as HistoVAC-TSFM. A total of 38 epitopes were found: 23 common to CTL and B-cell responses, 11 linked to HTL and B cells, and 4 previously validated epitopes associated with the B subunit of cholera toxin, a potent adjuvant. In silico evaluations confirmed the stability, non-toxicity, non-allergenicity, and non-homology of these vaccines with the host. Notably, the vaccine exhibited the potential to trigger both innate and adaptive immune responses, likely involving the TLR4 pathway, as supported by 3D modeling and molecular docking. The designed HistoVAC-TSFM appears promising against Histoplasma, with the ability to induce important cytokines, such as IFN-γ, TNF-α, IL17, and IL6. Future studies could be carried out to test the vaccine's efficacy in in vivo models.

16.
J Biomol Struct Dyn ; : 1-15, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38239063

RESUMO

Equine strangles is a prevalent disease that affects the upper respiratory in horses and is caused by the Gram-positive bacterium Streptococcus equi. In addition to strangles, other clinical conditions are caused by the two S. equi subspecies, equi and zooepidemicus, which present relevant zoonotic potential. Treatment of infections caused by S. equi has become challenging due to the worldwide spreading of infected horses and the unavailability of effective therapeutics and vaccines. Penicillin treatment is often recommended, but multidrug resistance issues arised. We explored the whole genome sequence of 18 S. equi isolates to identify candidate proteins to be targeted by natural drug-like compounds or explored as immunogens. We considered only proteins shared among the sequenced strains of subspecies equi and zooepidemicus, absent in the equine host and predicted to be essential and involved in virulence. Of these, 4 proteins with cytoplasmic subcellular location were selected for molecular docking with a library of 5008 compounds, while 6 proteins were proposed as prominent immunogens against S. equi due to their probabilities of behaving as adhesins. The molecular docking analyses revealed the best ten ligands for each of the 4 drug target candidates, and they were ranked according to their binding affinities and the number of hydrogen bonds for complex stability. Finally, the natural 5-ring compound C25H20F3N5O3 excelled in molecular dynamics simulations for the increased stability in the interaction with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB). This research paves the way to developing new therapeutics to minimize the impacts caused by S. equi infections.Communicated by Ramaswamy H. Sarma.

17.
BMC Genomics ; 14 Suppl 6: S5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24564251

RESUMO

Lung cancer accounts for the highest number of cancer-related deaths worldwide. Early diagnosis significantly increases the disease-free survival rate and a large amount of effort has been expended in screening trials and the development of early molecular diagnostics. However, a gold standard diagnostic strategy is not yet available. Here, based on miRNA expression profile in lung cancer and using a novel in silico reverse-transcriptomics approach, followed by analysis of the interactome; we have identified potential transcription factor (TF) markers that would facilitate diagnosis of subtype specific lung cancer. A subset of seven TF markers has been used in a microarray screen and was then validated by blood-based qPCR using stage-II and IV non-small cell lung carcinomas (NSCLC). Our results suggest that overexpression of HMGA1, E2F6, IRF1, and TFDP1 and downregulation or no expression of SUV39H1, RBL1, and HNRPD in blood is suitable for diagnosis of lung adenocarcinoma and squamous cell carcinoma sub-types of NSCLC. Here, E2F6 was, for the first time, found to be upregulated in NSCLC blood samples. The miRNA-TF-miRNA interaction based molecular mechanisms of these seven markers in NSCLC revealed that HMGA1 and TFDP1 play vital roles in lung cancer tumorigenesis. The strategy developed in this work is applicable to any other cancer or disease and can assist in the identification of potential biomarkers.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Simulação por Computador , Perfilação da Expressão Gênica/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Transcrição Reversa/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Pulmonares/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Fatores de Transcrição/metabolismo
18.
J Cancer Res Ther ; 19(2): 457-460, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37313917

RESUMO

The role of radiotherapy (RT) in partial radiographic response (PR)/unresectable has not been evaluated earlier in nonseminomatous germ cell tumor (NSGCT). Can the PR/unresectable be treated with consolidation RT instead of surgery? This approach will allow avoidance of surgical morbidity and be an additional tool for treatment. We report a series of five cases with poor prognosis NSGCT, who were treated with consolidation RT after PR/un-resectable disease and complete serum marker decline. The median survival of these patients was 52 months (range 21-112 months).


Assuntos
Neoplasias Embrionárias de Células Germinativas , Radioterapia (Especialidade) , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/radioterapia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/radioterapia , Doença Crônica
19.
Natl J Maxillofac Surg ; 14(2): 317-320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37661975

RESUMO

A systemic parasitic infestation caused by the larval stages of the pork tapeworm, Taenia solium is known as Cysticercosis. While encysted form of the larval stage is attributed to rare variant of Cysticercosis of soft tissues. Muscle infestation by this parasite can lead to vague clinical presentation. We are presenting a series of 4 rare cases of extracranial, cervicofacial cysticercosis their clinical attributes and imaging characteristics leading to diagnosis of cysticercosis and approach to successful outcome with pharmacotherapy alone that spared the need of surgical management.

20.
Cureus ; 15(7): e42167, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37602137

RESUMO

Introduction Trauma is the third most common cause of death in all age groups. One out of four trauma patients die due to thoracic injury or its complications. Seventy percent of thoracic traumas are due to blunt injury. This indicates the importance of chest trauma among all traumas. Quick and precise assessment bears paramount importance in deciding life-saving and definitive management. Often, the initial management in blunt injury patients is based on subjective assessment by the attending clinician. A scoring system that provides early identification of the patients at the greatest risk for respiratory failure and more likely to require mechanical ventilation and require prolonged care, as well as those with a higher mortality risk, may allow the early institution of intervention to improve outcomes. Thoracic Trauma Severity Score (TTSS) poses to be a precise tool in directing the management modality to be employed. Methodology This was an observational study including 112 patients of age >12 years, with blunt chest injury, sustaining ≤3 rib fractures, and with a stable chest wall. The patients with penetrating injury, those with blunt chest injury having flail segment, patients in the pediatric age group (<12 years), or polytrauma patients were excluded from our study. Of the 112 patients, 56 had been managed by intercostal drainage (ICD), and the rest (56) had been managed conservatively. Result Road traffic accidents (RTA) were the most common mode of injury in both groups. The percentage of the patients with one, two, and three rib fractures was 57.14%, 32.14%, and 10.71%, respectively, in the ICD group and 85.71%, 7.14%, and 7.14%, respectively, in the conservative management group (p = 0.124). The mean TTSS score was significantly more in the ICD group as compared to the conservative management group in the single rib fracture patients (p = 0.001*), as well as all patients of any number of rib fractures (p < 0.01*) (significance was defined as a value of p less than 0.05 {indicated by an asterisk}). The mean hospital stay was significantly lower in the conservative group as compared to the ICD group (p < 0.01*). The mean SF-36 (outcome) was significantly more in the conservative management group as compared to the ICD group (p = 0.020*). The mean cost of treatment was significantly more in the ICD group as compared to the conservative management group (p < 0.001*). Conclusion In our study, a TTSS (as measured by the primary care surgeon) of >7, across any number of rib fractures, was preferably predictive of management by ICD, while a <7 value was favorable for conservative management. TTSS can be used as an important tool to predict the management modality in blunt chest injury patients with ≤3 rib fractures.

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