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1.
Vet Q ; 41(1): 107-136, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33509059

RESUMO

Mastitis (intramammary inflammation) caused by infectious pathogens is still considered a devastating condition of dairy animals affecting animal welfare as well as economically incurring huge losses to the dairy industry by means of decreased production performance and increased culling rates. Bovine mastitis is the inflammation of the mammary glands/udder of bovines, caused by bacterial pathogens, in most cases. Routine diagnosis is based on clinical and subclinical forms of the disease. This underlines the significance of early and rapid identification/detection of etiological agents at the farm level, for which several diagnostic techniques have been developed. Therapeutic regimens such as antibiotics, immunotherapy, bacteriocins, bacteriophages, antimicrobial peptides, probiotics, stem cell therapy, native secretory factors, nutritional, dry cow and lactation therapy, genetic selection, herbs, and nanoparticle technology-based therapy have been evaluated for their efficacy in the treatment of mastitis. Even though several strategies have been developed over the years for the purpose of managing both clinical and subclinical forms of mastitis, all of them lacked the efficacy to eliminate the associated etiological agent when used as a monotherapy. Further, research has to be directed towards the development of new therapeutic agents/techniques that can both replace conventional techniques and also solve the problem of emerging antibiotic resistance. The objective of the present review is to describe the etiological agents, pathogenesis, and diagnosis in brief along with an extensive discussion on the advances in the treatment and management of mastitis, which would help safeguard the health of dairy animals.

2.
Vet Q ; 41(1): 61-88, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33353489

RESUMO

Brucellosis is a zoonotic disease of great animal welfare and economic implications worldwide known since ancient times. The emergence of brucellosis in new areas as well as transmission of brucellosis from wild and domestic animals is of great significance in terms of new epidemiological dimensions. Brucellosis poses a major public health threat by the consumption of non-pasteurized milk and milk products produced by unhygienic dairy farms in endemic areas. Regular and meticulous surveillance is essentially required to determine the true picture of brucellosis especially in areas with continuous high prevalence. Additionally, international migration of humans, animals and trade of animal products has created a challenge for disease spread and diagnosis in non-endemic areas. Isolation and identification remain the gold standard test, which requires expertise. The advancement in diagnostic strategies coupled with screening of newly introduced animals is warranted to control the disease. Of note, the diagnostic value of miRNAs for appropriate detection of B. abortus infection has been shown. The most widely used vaccine strains to protect against Brucella infection and related abortions in cattle are strain 19 and RB51. Moreover, it is very important to note that no vaccine, which is highly protective, safe and effective is available either for bovines or human beings. Research results encourage the use of bacteriophage lysates in treatment of bovine brucellosis. One Health approach can aid in control of this disease, both in animals and man.

3.
Front Microbiol ; 11: 562768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101238

RESUMO

Hand, foot, and mouth disease (HFMD) is a highly contagious disease that usually affects infants and young children (<5 years). HFMD outbreaks occur frequently in the Asia-Pacific region, and these outbreaks are associated with enormous healthcare and socioeconomic burden. There is currently no specific antiviral agent to treat HFMD and/or the severe complications that are frequently associated with the enterovirus of serotype EV71. Therefore, the development of a broadly effective and safe anti-enterovirus agent is an existential necessity. In this study, human single-chain antibodies (HuscFvs) specific to the EV71-internal capsid protein (VP4) were generated using phage display technology. VP4 specific-HuscFvs were linked to cell penetrating peptides to make them cell penetrable HuscFvs (transbodies), and readily accessible to the intracellular target. The transbodies, as well as the original HuscFvs that were tested, entered the enterovirus-infected cells, bound to intracellular VP4, and inhibited replication of EV71 across subgenotypes A, B, and C, and coxsackieviruses CVA16 and CVA6. The antibodies also enhanced the antiviral response of the virus-infected cells. Computerized simulation, indirect and competitive ELISAs, and experiments on cells infected with EV71 particles to which the VP4 and VP1-N-terminus were surface-exposed (i.e., A-particles that don't require receptor binding for infection) indicated that the VP4 specific-antibodies inhibit virus replication by interfering with the VP4-N-terminus, which is important for membrane pore formation and virus genome release leading to less production of virus proteins, less infectious virions, and restoration of host innate immunity. The antibodies may inhibit polyprotein/intermediate protein processing and cause sterically strained configurations of the capsid pentamers, which impairs virus morphogenesis. These antibodies should be further investigated for application as a safe and broadly effective HFMD therapy.

4.
Travel Med Infect Dis ; 37: 101830, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32755673

RESUMO

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome - Coronavirus-2) of the family Coronaviridae, appeared in China in December 2019. This disease was declared as posing Public Health International Emergency by World Health Organization on January 30, 2020, attained the status of a very high-risk category on February 29, and now having a pandemic status (March 11). COVID-19 has presently spread to more than 215 countries/territories while killing nearly 0.75 million humans out of cumulative confirmed infected asymptomatic or symptomatic cases accounting to almost 20.5 million as of August 12, 2020, within a short period of just a few months. Researchers worldwide are pacing with high efforts to counter the spread of this virus and to design effective vaccines and therapeutics/drugs. Few of the studies have shown the potential of the animal-human interface and zoonotic links in the origin of SARS-CoV-2. Exploring the possible zoonosis and revealing the factors responsible for its initial transmission from animals to humans will pave ways to design and implement effective preventive and control strategies to counter the COVID-19. The present review presents a comprehensive overview of COVID-19 and SARS-CoV-2, with emphasis on the role of animals and their jumping the cross-species barriers, experiences learned from SARS- and MERS-CoVs, zoonotic links, and spillover events, transmission to humans and rapid spread, and highlights the new advances in diagnosis, vaccine and therapies, preventive and control measures, one health concept along with recent research developments to counter this pandemic disease.


Assuntos
Betacoronavirus , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Zoonoses , Animais , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/terapia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Pneumonia Viral/terapia
5.
Antiviral Res ; 182: 104921, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32835694

RESUMO

The four circulating serotypes of dengue virus (DENV) occasionally cause potentially fetal symptoms of severe dengue, which there is currently no specific treatment available. Extensive efforts have been made to inhibit viral replication processes by impeding the activity of an exclusive RNA-dependent RNA polymerase (RdRp) in the viral non-structural protein 5 (NS5). In our earlier work, we identified the characteristic, specific interaction between the C-terminal thumb subdomain of RdRp and an apical loop in the 3' stem-loop (SL) element in the DENV RNA genome, which is fundamental for viral replication. Here, we demonstrated a new approach for interfering viral replication via blocking of 3' SL RNA binding to RdRp by the single-chain variable fragments (scFvs). We isolated and cloned 3 different human scFvs that bound to RdRp from DENV serotype 2 and interfered with 3' SL-binding, utilizing a combination of phage-display panning and Alpha methods. When tagged with a cell penetrating peptide, a selected scFv clone, 2E3, entered cells and partially colocalized with NS5 in the cytoplasm of infected HuH-7 cells. 2E3 significantly inhibited DENV RNA replication with sub-nanomolar EC50 values and significantly reduced the production of infectious particles. The molecular docking models suggested that 2E3 recognized both palm and thumb subdomains of RdRp, and interacted with Lys841, a key residue involved in RNA binding. Our results provide a new potential therapeutic molecule specific for flaviviral infection.

6.
Front Microbiol ; 11: 1172, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670218

RESUMO

The quorum sensing (QS) signaling molecule, N-(3-oxododecanoyl)-L-homoserine lactone (3O-C12-HSL), contributes to the pathogenesis of Pseudomonas aeruginosa by regulating expression of the bacterial virulence factors that cause intense inflammation and toxicity in the infected host. As such, the QS molecule is an attractive therapeutic target for direct-acting inhibitors. Several substances, both synthetic and naturally derived products, have shown effectiveness against detrimental 3O-C12-HSL activity. Unfortunately, these compounds are relatively toxic to mammalian cells, which limits their clinical application. In this study, fully human single-chain variable fragments (HuscFvs) that bind to P. aeruginosa haptenic 3O-C12-HSL were generated based on the principle of antibody polyspecificity and molecular mimicry of antigenic molecules. The HuscFvs neutralized 3O-C12-HSL activity and prevented mammalian cells from the HSL-mediated apoptosis, as observed by Annexin V/PI staining assay, sub-G1 arrest population investigation, transmission electron microscopy for ultrastructural morphology of mitochondria, and confocal microscopy for nuclear condensation and DNA fragmentation. Computerized homology modeling and intermolecular docking predicted that the effective HuscFvs interacted with several regions of the bacterially derived ligand that possibly conferred neutralizing activity. The effective HuscFvs should be tested further in vitro on P. aeruginosa phenotypes as well as in vivo as a sole or adjunctive therapeutic agent against P. aeruginosa infections, especially in antibiotic-resistant cases.

7.
Clin Microbiol Rev ; 33(4)2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32580969

RESUMO

SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Animais , Betacoronavirus/fisiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia
8.
Hum Vaccin Immunother ; 16(6): 1232-1238, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32186952

RESUMO

The novel coronavirus infection (COVID-19 or Coronavirus disease 2019) that emerged from Wuhan, Hubei province of China has spread to many countries worldwide. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS in the past decades. However, to date, no licensed antiviral treatment or vaccine exists for MERS and SARS. Most of the efforts for developing CoV vaccines and drugs target the spike glycoprotein or S protein, the major inducer of neutralizing antibodies. Although a few candidates have shown efficacy in in vitro studies, not many have progressed to randomized animal or human trials, hence may have limited use to counter COVID-19 infection. This article highlights ongoing advances in designing vaccines and therapeutics to counter COVID-19 while also focusing on such experiences and advances as made with earlier SARS- and MERS-CoVs, which together could enable efforts to halt this emerging virus infection.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Vacinas Virais , Animais , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Saúde Global , Humanos , Imunoterapia , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Vacinas Virais/normas
9.
Am J Cancer Res ; 10(2): 674-687, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32195035

RESUMO

Since the prognosis for children with high-risk osteosarcoma (OS) remains suboptimal despite intensive multi-modality therapies, there is a clear and urgent need for the development of targeted therapeutics against these refractory malignancies. Chimeric antigen receptor (CAR) modified T cells can meet this need by utilizing the immune system's potent cytotoxic mechanisms against tumor specific antigen targets with exquisite specificity. Since OS highly expresses the GD2 antigen, a viable immunotherapeutic target, we sought to assess if CAR modified T cells targeting GD2 could induce cytotoxicity against OS tumor cells. We demonstrated that the GD2 CAR modified T cells were highly efficacious for inducing OS tumor cell death. Interestingly, the OS cells were induced to up-regulate expression of PD-L1 upon interaction with GD2 CAR modified T cells, and the specific interaction induced CAR T cells to overexpress the exhaustion marker PD-1 along with increased CAR T cell apoptosis. To further potentiate CAR T cell killing activity against OS, we demonstrated that suboptimal chemotherapeutic treatment with doxorubicin can synergize with CAR T cells to effectively kill OS tumor cells.

10.
Vet Q ; 40(1): 68-76, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32036774

RESUMO

Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade's first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as 'Public Health Emergency of International Concern' on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.


Assuntos
Betacoronavirus , Quirópteros/virologia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/epidemiologia , Reservatórios de Doenças/veterinária , Animais , Betacoronavirus/classificação , Betacoronavirus/genética , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/veterinária , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Humanos , Pandemias , Filogenia , Pneumonia Viral , Zoonoses/epidemiologia , Zoonoses/prevenção & controle , Zoonoses/virologia
11.
Curr Protein Pept Sci ; 21(2): 124-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31364514

RESUMO

Allergic diseases are assuming increasing trend of prevalence worldwide. The diseases confer increasing demand on medical and healthcare facilities. Patients with allergies have poor quality of life and impaired cognition. Adult patients have subpar working efficiency while afflicted children are less effective at school, often have school absenteeism and need more attention of their caregivers. All of them lead to negative socio-economic impact. This narrative review focuses on cockroach allergy including currently recognized cockroach allergens, pathogenic mechanisms of allergy, componentresolved diagnosis and allergen-specific immunotherapy, particularly the component-resolved immunotherapy and the molecular mechanisms that bring about resolution of the chronic airway inflammation.

12.
Front Mol Biosci ; 6: 91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31750312

RESUMO

Various internal and external factors negatively affect the homeostatic equilibrium of organisms at the molecular to the whole-body level, inducing the so-called state of stress. Stress affects an organism's welfare status and induces energy-consuming mechanisms to combat the subsequent ill effects; thus, the individual may be immunocompromised, making them vulnerable to pathogens. The information presented here has been extensively reviewed, compiled, and analyzed from authenticated published resources available on Medline, PubMed, PubMed Central, Science Direct, and other scientific databases. Stress levels can be monitored by the quantitative and qualitative measurement of biomarkers. Potential markers of stress include thermal stress markers, such as heat shock proteins (HSPs), innate immune markers, such as Acute Phase Proteins (APPs), oxidative stress markers, and chemical secretions in the saliva and urine. In addition, stress biomarkers also play critical roles in the prognosis of stress-related diseases and disorders, and therapy guidance. Moreover, different components have been identified as potent mediators of cardiovascular, central nervous system, hepatic, and nephrological disorders, which can also be employed to evaluate these conditions precisely, but with stringent validation and specificity. Considerable scientific advances have been made in the detection, quantitation, and application of these biomarkers. The present review describes the current progress of identifying biomarkers, their prognostic, and therapeutic values.

13.
Sci Rep ; 9(1): 14928, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624289

RESUMO

Targeting bacterial virulence factors directly provides a new paradigm for the intervention and treatment of bacterial diseases. Pseudomonas aeruginosa produces a myriad of virulence factors to cause fatal diseases in humans. In this study, human single-chain antibodies (HuscFvs) that bound to P. aeruginosa exotoxin A (ETA) were generated by phage display technology using recombinant ETA, ETA-subdomains and the synthetic peptide of the ETA-catalytic site as baits for selecting ETA-bound-phages from the human-scFv phage display library. ETA-bound HuscFvs derived from three phage-transfected E. coli clones neutralized the ETA-induced mammalian cell apoptosis. Computerized simulation demonstrated that these HuscFvs used several residues in their complementarity-determining regions (CDRs) to form contact interfaces with the critical residues in ETA-catalytic domain essential for ADP-ribosylation of eukaryotic elongation factor 2, which should consequently rescue ETA-exposed-cells from apoptosis. The HuscFv-treated ETA-exposed cells also showed decremented apoptosis-related genes, i.e., cas3 and p53. The effective HuscFvs have high potential for future evaluation in animal models and clinical trials as a safe, novel remedy for the amelioration of exotoxin A-mediated pathogenesis. HuscFvs may be used either singly or in combination with the HuscFv cognates that target other P. aeruginosa virulence factors as an alternative therapeutic regime for difficult-to-treat infections.


Assuntos
ADP Ribose Transferases/antagonistas & inibidores , Antibacterianos/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Exotoxinas/antagonistas & inibidores , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Anticorpos de Cadeia Única/farmacologia , Fatores de Virulência/antagonistas & inibidores , ADP Ribose Transferases/genética , ADP Ribose Transferases/imunologia , ADP Ribose Transferases/metabolismo , Antibacterianos/imunologia , Antibacterianos/uso terapêutico , Apoptose/efeitos dos fármacos , Toxinas Bacterianas/genética , Toxinas Bacterianas/imunologia , Toxinas Bacterianas/metabolismo , Domínio Catalítico/genética , Regiões Determinantes de Complementaridade/imunologia , Regiões Determinantes de Complementaridade/farmacologia , Exotoxinas/genética , Exotoxinas/imunologia , Exotoxinas/metabolismo , Células HeLa , Humanos , Simulação de Acoplamento Molecular , Biblioteca de Peptídeos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/patogenicidade , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/uso terapêutico , Fatores de Virulência/genética , Fatores de Virulência/imunologia , Fatores de Virulência/metabolismo
14.
Vaccines (Basel) ; 7(3)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527552

RESUMO

Sperm of humans, non-human primates, and other mammalian subjects is considered to be antigenic. The effect of changes in autoimmunity on reproductive cells such as spermatozoa and oocytes play a critical but indistinct role in fertility. Antisperm antibodies (ASAs) are invariably present in both females and males. However, the degree of ASA occurrence may vary according to individual and gender. Although the extent of infertility due to ASAs alone is yet to be determined, it has been found in almost 9-12% of patients who are infertile due to different causes. Postcoital presence of spermatozoa in the reproductive tract of women is not a contributory factor in ASA generation. However, ASA generation may be induced by trauma to the vaginal mucosa, or by anal or oral sex resulting in the deposition of sperm inside the digestive tract. It is strongly believed that, in humans and other species, at least some antibodies may bind to sperm antigens, causing infertility. This form of infertility is termed as immunological infertility, which may be accompanied by impairment of fertility, even in individuals with normozoospermia. Researchers target ASAs for two major reasons: (i) to elucidate the association between ASAs and infertility, the reason ASAs causes infertility, and the mechanism underlying ASA-mediated infertility; and (ii) to assess the potential of ASAs as a contraceptive in humans in case ASAs influences infertility. Therefore, this review explores the potential application of ASAs in the development of anti-spermatozoa vaccines for contraceptive purposes. The usefulness of ASAs for diagnosing obstructive azoospermia, salpingitis, and oligoasthenoteratozoospermia has been reviewed extensively. Important patents pertaining to potential candidates for spermatozoa-derived vaccines that may be utilized as contraceptives are discussed in depth. Antifertility vaccines, as well as treatments for ASA-related infertility, are also highlighted. This review will address many unresolved issues regarding mechanisms involving ASAs in the diagnosis, as well as prognoses, of male infertility. More documented scientific reports are cited to support the mechanisms underlying the potential role of ASA in infertility. The usefulness of sperm antigens or ASAs (recombinant) in human and wild or captive animal contraceptive vaccines has been revealed through research but is yet to be validated via clinical testing.

15.
Vaccines (Basel) ; 7(3)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426368

RESUMO

A mass vaccination campaign in India seeks to control and eventually eradicate foot-and-mouth disease (FMD). Biosanitary measures along with FMD monitoring are being conducted along with vaccination. The implementation of the FMD control program has drastically reduced the incidence of FMD. However, cases are still reported, even in regions where vaccination is carried out regularly. Control of FMD outbreaks is difficult when the virus remains in circulation in the vaccinated population. Various FMD risk factors have been identified that are responsible for FMD in vaccinated areas. The factors are discussed along with strategies to address these challenges. The current chemically inactivated trivalent vaccine formulation containing strains of serotype O, A, and Asia 1 has limitations including thermolability and induction of only short-term immunity. Advantages and disadvantages of several new-generation alternate vaccine formulations are discussed. It is unfeasible to study every incidence of FMD in vaccinated animals/areas in such a big country as India with its huge livestock population. However, at the same time, it is absolutely necessary to identify the precise reason for vaccination failure. Failure to vaccinate is one reason for the occurrence of FMD in vaccinated areas. FMD epidemiology, emerging and re-emerging virus strains, and serological status over the past 10 years are discussed to understand the impact of vaccination and incidences of vaccination failure in India. Other factors that are important in vaccination failure that we discuss include disrupted herd immunity, health status of animals, FMD carrier status, and FMD prevalence in other species. Recommendations to boost the search of alternate vaccine formulation, strengthen the veterinary infrastructure, bolster the real-time monitoring of FMD, as well as a detailed investigation and documentation of every case of vaccination failure are provided with the goal of refining the control program.

16.
Vaccines (Basel) ; 7(3)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340571

RESUMO

Exploration of novel candidates for vaccine development against Mycoplasma capricolum subspecies capripneumoniae (Mccp), the causative agent of contagious caprine pleuropneumonia (CCPP), has recently gained immense importance due to both the increased number of outbreaks and the alarming risk of transboundary spread of disease. Treatment by antibiotics as the only therapeutic strategy is not a viable option due to pathogen persistence, economic issues, and concerns of antibiotic resistance. Therefore, prophylactics or vaccines are becoming important under the current scenario. For quite some time inactivated, killed, or attenuated vaccines proved to be beneficial and provided good immunity up to a year. However, their adverse effects and requirement for larger doses led to the need for production of large quantities of Mccp. This is challenging because the required culture medium is costly and Mycoplasma growth is fastidious and slow. Furthermore, quality control is always an issue with such vaccines. Currently, novel candidate antigens including capsular polysaccharides (CPS), proteins, enzymes, and genes are being evaluated for potential use as vaccines. These have shown potential immunogenicity with promising results in eliciting protective immune responses. Being easy to produce, specific, effective and free from side effects, these novel vaccine candidates can revolutionize vaccination against CCPP. Use of novel proteomic approaches, including sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional gel electrophoresis, immunoblotting, matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry, tandem mass spectroscopy, fast protein liquid chromatography (FPLC), bioinformatics, computerized simulation and genomic approaches, including multilocus sequence analysis, next-generation sequencing, basic local alignment search tool (BLAST), gene expression, and recombinant expression, will further enable recognition of ideal antigenic proteins and virulence genes with vaccination potential.

17.
Parasitol Res ; 118(8): 2353-2359, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31263951

RESUMO

Simulium dermatitis is an IgE-mediated skin reaction in animals and humans caused by the bites of black flies. Although Simulium nigrogilvum has been incriminated as the main human-biting black fly species in Thailand, information on its salivary allergens is lacking. Salivary gland extract of S. nigrogilvum females was subjected to sodium dodecylsulfate-polyacrylamide gel electrophoresis, and the separated components were applied onto nitrocellulose membranes for immunoblotting, which was performed by probing the protein blots with sera from 17 individuals who were allergic to the bites of S. nigrogilvum. IgE-reactive protein bands were characterized further by liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Nine protein bands (79, 42, 32, 25, 24, 22, 15, 13, and 11 kDa) were recognized in the serum of the subjects. Four of the nine protein bands (32, 24, 15, and 11 kDa) showed IgE reactivity in all (100%) of the tested sera, and they were identified as salivary secreted antigen 5-related protein, salivary serine protease, erythema protein, and hypothetical secreted protein, respectively. Three other proteins, salivary serine protease (25 kDa), salivary D7 secreted protein (22 kDa), and hypothetical protein (13 kDa), reacted with > 50% of the sera. The relevance of the identified protein bands as allergens needs to be confirmed by using pure recombinant proteins, either in the in vivo skin prick test or in vitro detection of the specific IgE in the serum samples of allergic subjects. This will be useful for the rational design of component-resolved diagnosis and allergen immunotherapy for the allergy mediated by the bites of black flies.


Assuntos
Mordeduras e Picadas/imunologia , Galectina 3/imunologia , Proteínas de Insetos/química , Glândulas Salivares/química , Simuliidae/fisiologia , Alérgenos/química , Alérgenos/imunologia , Animais , Mordeduras e Picadas/parasitologia , Cromatografia Líquida , Eletroforese em Gel de Poliacrilamida , Feminino , Galectina 3/química , Humanos , Imunoglobulina E/imunologia , Proteínas de Insetos/imunologia , Glândulas Salivares/imunologia , Simuliidae/química , Simuliidae/imunologia , Espectrometria de Massas em Tandem , Tailândia
18.
Cells ; 8(7)2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277291

RESUMO

Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn's disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.


Assuntos
Autofagia , Doença , Desenho de Fármacos , Tratamento Farmacológico/métodos , Humanos , Medicina Preventiva/métodos
19.
Vet Q ; 39(1): 76-94, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31288621

RESUMO

Mastitis, an inflammation of the udder, is a challenging problem in dairy animals accounting for high economic losses. Disease complexity, degree of economic losses and increasing importance of the dairy industries along with public health concerns envisages devising appropriate diagnostics of mastitis, which can offer rapid, accurate and confirmatory diagnosis. The various diagnostic tests of mastitis have been divided into general or phenotypic and specific or genotypic tests. General or phenotypic tests are those that identify general alterations, which are not specific to any pathogen. Genotypic tests are specific, hence confirmatory for diagnosis of mastitis and include specific culture, polymerase chain reaction (PCR) and its various versions (e.g. qRT-PCR), loop-mediated isothermal amplification, lateral flow assays, nucleotide sequencing, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, and other molecular diagnostic methods. However, for highly specific and confirmatory diagnosis, pure cultures still provide raw materials for more sophisticated diagnostic technological interventions like PCR and nucleotide sequencing. Diagnostic ability of like infra-red thermography (IRT) has been shown to be similar to California mastitis test and also differentiates clinical mastitis from subclinical mastitis cases. As such, IRT can become a convenient and portable diagnostic tool. Of note, magnetic nanoparticles-based colorimetric biosensor assay was developed by using for instance proteolytic activity of plasmin or anti-S. aureus antibody. Last but not least, microRNAs have been suggested to be potential biomarkers for diagnosing bovine mastitis. This review summarizes the various diagnostic tests available for detection of mastitis including diagnosis through general and specific technological interventions and advances.


Assuntos
Técnicas de Laboratório Clínico/veterinária , Mastite Bovina/diagnóstico , Animais , Biomarcadores , Bovinos , Técnicas de Laboratório Clínico/métodos , Indústria de Laticínios , Feminino , Genótipo , Reação em Cadeia da Polimerase/veterinária
20.
J Cell Biochem ; 120(10): 18077-18087, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31172597

RESUMO

Most patients suffering from non-small cell lung cancer (NSCLC) have epidermal growth factor receptor (EGFR) overexpression. Currently, EGFR tyrosine kinase inhibitors (TKIs) that act as the ATP-analogs and monoclonal antibodies (MAbs) to EGFR-ectodomain that block intracellular signaling are used for the treatment of advanced NSCLC. Unfortunately, adverse effects due to the TKI off-target and drug resistance occur in a significant number of the treated patients while some NSCLC genotypes do not respond to the therapeutic MAbs. Thus, a more effective remedy for the treatment of EGFR-overexpressed cancers is deemed necessary. In this study, VH/VH H displayed-phage clones that are bound to recombinant EGFR-TK were fished-out from a humanized-camel VH/VH H phage display library. VH/VH H of three phage-infected Escherichia coli clones (VH18, VH H35, and VH36) were linked molecularly to nonaarginine (R9) for making them cell penetrable. R9-VH18, R9-VH H35, and R9-VH36 were cytotoxic to human adenocarcinomic alveolar basal epithelial cells (A549) at the fifty percent inhibitory concentration (IC50 ) 0.181 ± 0.132, 0.00961 ± 0.00516, and 0.00996 ± 0.00752 µM, respectively, which were approximately 1000-fold more effective than small molecular TKIs. R9-VH18 and R9-VH36 also delayed cancer cell migration in a scratch-wound assay. Computerized homology modeling and intermolecular docking revealed that VH18 and VH H35 used CDR3 to interact with EGFR-TK residues close to the catalytic site, which might sterically hinder the ATP-binding of the TK; VH36 used CDR2 to bind at the asymmetric dimerization surface, which might disrupt EGFR dimerization leading to inhibition of intracellular signaling. The humanized-cell penetrable nanobodies have a high potential for developing further towards a clinical application.


Assuntos
Adenocarcinoma de Pulmão/patologia , Movimento Celular , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/farmacologia , Anticorpos de Domínio Único/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Mapeamento de Epitopos , Receptores ErbB/metabolismo , Humanos , Simulação de Acoplamento Molecular
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