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1.
Infect Genet Evol ; 84: 104399, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32512206

RESUMO

Mycobacterium lepromatosis was identified as a causative agent for leprosy in the year 2008 in the United States and later more cases were identified in Canada, Singapore, Brazil, and Myanmar. It is known to cause diffuse lepromatosis leprosy among humans. Since it is invasive, the mortality rates are higher in comparison to the M. leprae. At genomic level, there exists 90.9% similarity between M. lepromatosis and M. leprae. Codon usage analysis based on analyses of 228 coding sequences (CDSs) of M. lepromatosis, revealed that the genome is GC rich. Among the total 16 dinucleotides, CpG dinucleotide possesses the highest dinucleotide frequency in M. lepromatosis, that is strikingly an unobvious observation since higher CpG is associated with higher proinflammatory cytokine production and NF-κB activation that eventually leads to high pathogenicity. To evade immune response, CpG content is generally less in pathogens. The unusually high CpG content can be explained by the fact that the nucleotide composition of M. lepromatosis is CG rich. Various forces interplay to shape codon usage pattern of any organism including selection; mutation, nucleotide composition as well as GC biased gene conversion. To understand the interplay between various forces; neutrality, parity, Nc-GC3 (Effective number of codons-GC content at 3rd position of the codon), aromaticity (AROMO) and the general average hydropathicity score (GRAVY) analyses have been carried out. The analyses revealed that selection force is the major contributory force. Along with the selection; mutation, nucleotide composition as well as GC biased gene conversion also play role in shaping codon usage bias in M. lepromatosis. This is the first report on the codon usage in M. lepromatosis.

2.
Adv Protein Chem Struct Biol ; 120: 85-122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32085889

RESUMO

The term atherosclerosis refers to the condition of deposition of lipids and other substances in and on the artery walls, called as plaque that restricts the normal blood flow. The plaque may be stable or unstable in nature. Unstable plaque can burst and trigger clot formation adding further adversities. The process of plaque formation involves various stages including fatty streak, intermediate or fibro-fatty lesion and advanced lesion. The cells participating in the formation of atherosclerotic plaque include endothelial cells, vascular smooth muscle cells (VSMC), monocytes, monocytes derived macrophages, macrophages and dendritic cells and regulatory T cells (TREG). The role of a variety of cytokines and chemokines have been studied which either help in progression of atherosclerotic plaque or vice versa. The cytokines involved in atherosclerotic plaque formation include IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, IL-18, IL-20, IL-25, IL-27, IL-33, IL-37, TNF-α, TGF-ß and IFN-γ; whereas amongst the chemokines (family of small cytokines) are CCL2, CCL3, CXCL4, CCL5, CXCL1, CX3CL1, CCL17, CXCL8, CXCL10, CCL20, CCL19 and CCL21 and macrophage migration-inhibitory factor. These are involved in the atherosclerosis advancements, whereas the chemokine CXCL12 is play atheroprotective roles. Apart this, contradictory functions have been documented for few other chemokines such as CXCL16. Since the cytokines and chemokines are amongst the key molecules involved in orchestrating the atherosclerosis advancements, targeting them might be an effective strategy to encumber the atherosclerotic progression. Blockage of cytokines and chemokines via the means of broad-spectrum inhibitors, neutralizing antibodies, usage of decoy receptors or RNA interference have been proved to be useful intervention against atherosclerosis.

3.
Adv Protein Chem Struct Biol ; 119: 199-245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31997769

RESUMO

During the 19th century, for the first time, the linkage between inflammation and cancer was established. Inflammatory microenvironment is an essential component of the tumor microenvironment. Chronic inflammation due to persistent infection due to the microbes, viruses, helminths or constant exposure to non-infectious factors like smoke, silica or asbestos eventually might result in carcinogenesis. In tumor microenvironment, various inflammatory cells such as T lymphocytes (occasionally B cells), dendritic cells, macrophages, monocytes, neutrophils and natural killer (NK) cells are present. As a mediator of immune surveillance and host defense TRAIL cytokines are produced which upon binding with death receptors (DRs) initiate a cascade of apoptotic pathways. Anti-inflammatory drugs such as aspirin, celecoxib, diclofenac, diflunisal and ibuprofen etc. are being used against cancer, indicating the interplay between both the mechanisms. A deeper understanding of common pathways implicated between both the inflammation and cancer may pave the way to fight against both of these deleterious ailments.

4.
J Anim Physiol Anim Nutr (Berl) ; 104(1): 245-256, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31595607

RESUMO

Green tea (Camellia sinensis) is a popular herbal plant with abundant health benefits, and thus, it has been used as a potent antioxidant for a long time. Based on the available literature, the diversity and the availability of multifunctional compounds in green tea offer its noteworthy potential against many diseases such as liver and heart diseases, inflammatory conditions and different metabolic syndromes. Owing to its bioactive constituents including caffeine, amino acids, l-theanine, polyphenols/flavonoids and carbohydrates among other potent molecules, green tea has many pharmacological and physiological effects. The effects of green tea include anti-oxidative, anti-inflammatory, anti-arthritic, anti-stress, hypolipidaemic, hypocholesterolaemic, skin/collagen protective, hepatoprotective, anti-diabetic, anti-microbial, anti-infective, anti-parasitic, anti-cancerous, inhibition of tumorigenesis and angiogenesis, anti-mutagenic, and memory and bone health-improving activities. Apart from its utilization in humans, green tea has also played a significant role in livestock production such as in dairy, piggery, goatry and poultry industries. Supplementation of animal feeds with green tea and its products is in line with the modern concepts of organic livestock production. Hence, incorporating green tea or green tea by-products into the diet of poultry and other livestock can enhance the value of the products obtained from these animals. Herein, an effort is made to extend the knowledge on the importance and useful applications of green tea and its important constituents in animal production including poultry. This review will be a guideline for researchers and entrepreneurs who want to explore the utilization of feeds supplemented with green tea and green tea by-products for the enhancement of livestock production.


Assuntos
Ração Animal/análise , Glutamatos/farmacologia , Gado , Chá , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária
5.
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.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31757597

RESUMO

BACKGROUND: Insecticides are widely used in agriculture to curb the loss caused by insects. These insecticides are incorporated into the food chain and accumulate in the human body, as well disturb the various metabolic pathways. Imidacloprid is an insect neurotoxin commonly used in agriculture to control the insect pests. P. niruri is a traditional medicinal shrub widely used as an anti-inflammatory, antipyretic, and anti-lethality agent. OBJECTIVE: The present study is designed to evaluate the ameliorative effects of Phyllanthus niruri (Bhumi amla) on the deleterious Insecticide imidacloprid in the vital organs of Chicken embryos. MATERIALS AND METHODS: The embryonated chicken eggs were divided into the four groups (one control and three treated groups); the chorioallantoic membranes of control received 200 µl phosphate buffer saline, whereas group I and group II received 100 µg imidacloprid and 200 µl aqueous extract of P. niruri (PNE) respectively. Group III received both 100 µg imidacloprid and 200 µl PNE. The serum was collected on the 18th day its development; which was subjected to the biochemical analysis based on colorimetric assay in semi-automated biochemical analyzer using commercial kits. RESULTS: We observed significant in ovo effects of imidacloprid on chicken embryos; the values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), were increased in imidacloprid treated group I; histopathology also revealed damage to the liver (necrotic areas and dilated blood sinusoids). Alkaline phosphatase (ALP), amylase, cholesterol, triglycerides protein and albumin levels were also altered significantly (p < 0.05). CONCLUSION: The serum biochemicals were returned back to the nearly normal levels. PNE has ameliorated and overcome the effects of imidacloprid reasonably with the subsequent treatment among group III. Hence, P. niruri may be used to minimize the effects of an accidental exposure of imidacloprid.

7.
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
8.
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
9.
Front Microbiol ; 10: 886, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156564

RESUMO

A recent outbreak of Nipah virus (NiV) in India has caused 17 deaths in people living in districts of Kerala state. Its zoonotic nature, as well as high rate of human-to-human transmission, has led researchers worldwide to work toward understanding the different aspects of the NiV. We performed a codon usage analysis, based on publicly available nucleotide sequences of NiV and its host adaptation, along with other members of the Henipavirus genus in ten hosts. NiV genome encodes nine open reading frames; and overall, no significant bias in codon usage was observed. Aromaticity of proteins had no impact on codon usage. An analysis of preferred codons used by NiV and the tRNA pool in human cells indicated that NiV prefers codons from a suboptimal anticodon tRNA pool. We observed that codon usage by NiV is mainly constrained by compositional and selection pressures, not by mutational forces. Parameters that define NiV and host relatedness in terms of codon usage were analyzed, with a codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index calculations; which indicated that, of all hosts analyzed, NiV was best adapted to African green monkeys. A comparative analysis based on the relative codon deoptimization index (RCDI) for host adaptation of NiV, Hendra virus (HeV), Cedar virus (CedV), and Hendra like Mojiang virus (MojV) revealed that except for dogs and ferrets, all evaluated hosts were more susceptible to HeV than NiV.

10.
Vet Q ; 39(1): 26-55, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31006350

RESUMO

Nipah (Nee-pa) viral disease is a zoonotic infection caused by Nipah virus (NiV), a paramyxovirus belonging to the genus Henipavirus of the family Paramyxoviridae. It is a biosafety level-4 pathogen, which is transmitted by specific types of fruit bats, mainly Pteropus spp. which are natural reservoir host. The disease was reported for the first time from the Kampung Sungai Nipah village of Malaysia in 1998. Human-to-human transmission also occurs. Outbreaks have been reported also from other countries in South and Southeast Asia. Phylogenetic analysis affirmed the circulation of two major clades of NiV as based on currently available complete N and G gene sequences. NiV isolates from Malaysia and Cambodia clustered together in NiV-MY clade, whereas isolates from Bangladesh and India clusterered within NiV-BD clade. NiV isolates from Thailand harboured mixed population of sequences. In humans, the virus is responsible for causing rapidly progressing severe illness which might be characterized by severe respiratory illness and/or deadly encephalitis. In pigs below six months of age, respiratory illness along with nervous symptoms may develop. Different types of enzyme-linked immunosorbent assays along with molecular methods based on polymerase chain reaction have been developed for diagnostic purposes. Due to the expensive nature of the antibody drugs, identification of broad-spectrum antivirals is essential along with focusing on small interfering RNAs (siRNAs). High pathogenicity of NiV in humans, and lack of vaccines or therapeutics to counter this disease have attracted attention of researchers worldwide for developing effective NiV vaccine and treatment regimens.


Assuntos
Infecções por Henipavirus/veterinária , Vírus Nipah/imunologia , Vacinas Virais , Zoonoses , Animais , Doenças do Gato/epidemiologia , Doenças do Gato/prevenção & controle , Doenças do Gato/virologia , Gatos , Doenças do Cão/epidemiologia , Doenças do Cão/prevenção & controle , Doenças do Cão/virologia , Cães , Infecções por Henipavirus/epidemiologia , Infecções por Henipavirus/prevenção & controle , Infecções por Henipavirus/virologia , Humanos , Vírus Nipah/classificação , Vacinas Virais/administração & dosagem , Vacinas Virais/análise , Vacinas Virais/uso terapêutico , Zoonoses/epidemiologia , Zoonoses/prevenção & controle , Zoonoses/virologia
11.
Front Immunol ; 9: 2478, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30483247

RESUMO

Human papillomavirus (HPV) is a viral infection with skin-to-skin based transmission mode. HPV annually caused over 500,000 cancer cases including cervical, anogenital and oropharyngeal cancer among others. HPV vaccination has become a public-health concern, worldwide, to prevent the cases of HPV infections including precancerous lesions, cervical cancers, and genital warts especially in adolescent female and male population by launching national programs with international alliances. Currently, available prophylactic and therapeutic vaccines are expensive to be used in developing countries for vaccination programs. The recent progress in immunotherapy, biotechnology, recombinant DNA technology and molecular biology along with alternative and complementary medicinal systems have paved novel ways and valuable opportunities to design and develop effective prophylactic and therapeutic vaccines, drugs and treatment approach to counter HPV effectively. Exploration and more researches on such advances could result in the gradual reduction in the incidences of HPV cases across the world. The present review presents a current global scenario and futuristic prospects of the advanced prophylactic and therapeutic approaches against HPV along with recent patents coverage of the progress and advances in drugs, vaccines and therapeutic regimens to effectively combat HPV infections and its cancerous conditions.


Assuntos
Antivirais/uso terapêutico , Condiloma Acuminado/imunologia , Neoplasias Orofaríngeas/imunologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Neoplasias do Colo do Útero/imunologia , Adolescente , Condiloma Acuminado/prevenção & controle , Desenho de Fármacos , Desenvolvimento de Medicamentos , Feminino , Humanos , Programas de Imunização , Masculino , Neoplasias Orofaríngeas/prevenção & controle , Infecções por Papillomavirus/tratamento farmacológico , Neoplasias do Colo do Útero/prevenção & controle , Vacinação
12.
Front Microbiol ; 9: 1941, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30237788

RESUMO

Among all the emerging and re-emerging animal diseases, influenza group is the prototype member associated with severe respiratory infections in wide host species. Wherein, Equine influenza (EI) is the main cause of respiratory illness in equines across globe and is caused by equine influenza A virus (EIV-A) which has impacted the equine industry internationally due to high morbidity and marginal morality. The virus transmits easily by direct contact and inhalation making its spread global and leaving only limited areas untouched. Hitherto reports confirm that this virus crosses the species barriers and found to affect canines and few other animal species (cat and camel). EIV is continuously evolving with changes at the amino acid level wreaking the control program a tedious task. Until now, no natural EI origin infections have been reported explicitly in humans. Recent advances in the diagnostics have led to efficient surveillance and rapid detection of EIV infections at the onset of outbreaks. Incessant surveillance programs will aid in opting a better control strategy for this virus by updating the circulating vaccine strains. Recurrent vaccination failures against this virus due to antigenic drift and shift have been disappointing, however better understanding of the virus pathogenesis would make it easier to design effective vaccines predominantly targeting the conserved epitopes (HA glycoprotein). Additionally, the cold adapted and canarypox vectored vaccines are proving effective in ceasing the severity of disease. Furthermore, better understanding of its genetics and molecular biology will help in estimating the rate of evolution and occurrence of pandemics in future. Here, we highlight the advances occurred in understanding the etiology, epidemiology and pathobiology of EIV and a special focus is on designing and developing effective diagnostics, vaccines and control strategies for mitigating the emerging menace by EIV.

13.
Front Immunol ; 9: 1803, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147687

RESUMO

Ebola virus (EBOV), a member of the family Filoviridae, is responsible for causing Ebola virus disease (EVD) (formerly named Ebola hemorrhagic fever). This is a severe, often fatal illness with mortality rates varying from 50 to 90% in humans. Although the virus and associated disease has been recognized since 1976, it was only when the recent outbreak of EBOV in 2014-2016 highlighted the danger and global impact of this virus, necessitating the need for coming up with the effective vaccines and drugs to counter its pandemic threat. Albeit no commercial vaccine is available so far against EBOV, a few vaccine candidates are under evaluation and clinical trials to assess their prophylactic efficacy. These include recombinant viral vector (recombinant vesicular stomatitis virus vector, chimpanzee adenovirus type 3-vector, and modified vaccinia Ankara virus), Ebola virus-like particles, virus-like replicon particles, DNA, and plant-based vaccines. Due to improvement in the field of genomics and proteomics, epitope-targeted vaccines have gained top priority. Correspondingly, several therapies have also been developed, including immunoglobulins against specific viral structures small cell-penetrating antibody fragments that target intracellular EBOV proteins. Small interfering RNAs and oligomer-mediated inhibition have also been verified for EVD treatment. Other treatment options include viral entry inhibitors, transfusion of convalescent blood/serum, neutralizing antibodies, and gene expression inhibitors. Repurposed drugs, which have proven safety profiles, can be adapted after high-throughput screening for efficacy and potency for EVD treatment. Herbal and other natural products are also being explored for EVD treatment. Further studies to better understand the pathogenesis and antigenic structures of the virus can help in developing an effective vaccine and identifying appropriate antiviral targets. This review presents the recent advances in designing and developing vaccines, drugs, and therapies to counter the EBOV threat.


Assuntos
Antivirais/uso terapêutico , Desenho de Fármacos , Desenvolvimento de Medicamentos , Vacinas contra Ebola/imunologia , Ebolavirus/genética , Ebolavirus/imunologia , Doença pelo Vírus Ebola/tratamento farmacológico , Doença pelo Vírus Ebola/prevenção & controle , Animais , Antivirais/farmacologia , Ebolavirus/fisiologia , Engenharia Genética , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos
15.
Biol Open ; 7(6)2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-29967127

RESUMO

In montane Drosophila species, cold-induced plastic changes in energy metabolites are likely developed to cope with cold and starvation stress. Adult Drosophila immigrans reared at 15°C were acclimated at 0°C or 7°C for durations of up to 6 days (fed or unfed conditions). Such flies were tested for plastic changes in resistance to cold or starvation stress as well as for possible accumulation and utilization of four energy metabolites (body lipids, proline, trehalose and glycogen). Adults acclimated at 7°C revealed a greater increase in cold tolerance than flies acclimated at 0°C. Different durations of cold acclimation at 7°C led to increased level of body lipids only in fed flies which were utilized under starvation stress. However, such plastic responses were not observed in the flies acclimated at 0°C, which remained unfed due to chill-coma. These observations suggest a possible role of feeding to improve starvation resistance only in the flies acclimated at 7°C with food. Cold acclimated D. immigrans flies revealed improved cold resistance through a possible reshuffling of trehalose and glycogen; and starvation-induced proline which was utilized under cold stress durations. Finally, greater reduction in mean daily fecundity due to cold or starvation was observed in 0°C acclimated flies as compared to 7°C acclimated flies. Thus, cold acclimation conditions (0°C or 7°C) greatly impact resistance to cold and starvation in D. immigrans.

16.
Front Immunol ; 9: 597, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29740424

RESUMO

Antibody-dependent enhancement (ADE) is a phenomenon in which preexisting poorly neutralizing antibodies leads to enhanced infection. It is a serious concern with mosquito-borne flaviviruses such as Dengue virus (DENV) and Zika virus (ZIKV). In vitro experimental evidences have indicated the preventive, as well as a pathogenicity-enhancing role, of preexisting DENV antibodies in ZIKV infections. ADE has been confirmed in DENV but not ZIKV infections. Principally, the Fc region of the anti-DENV antibody binds with the fragment crystallizable gamma receptor (FcγR), and subsequent C1q interactions and immune effector functions are responsible for the ADE. In contrast to normal DENV infections, with ADE in DENV infections, inhibition of STAT1 phosphorylation and a reduction in IRF-1 gene expression, NOS2 levels, and RIG-1 and MDA-5 expression levels occurs. FcγRIIA is the most permissive FcγR for DENV-ADE, and under hypoxic conditions, hypoxia-inducible factor-1 alpha transcriptionally enhances expression levels of FcγRIIA, which further enhances ADE. To produce therapeutic antibodies with broad reactivity to different DENV serotypes, as well as to ZIKV, bispecific antibodies, Fc region mutants, modified Fc regions, and anti-idiotypic antibodies may be engineered. An in-depth understanding of the immunological and molecular mechanisms of DENV-ADE of ZIKV pathogenicity will be useful for the design of common and safe therapeutics and prophylactics against both viral pathogens. The present review discusses the role of DENV antibodies in modulating DENV/ZIKV pathogenicity/infection and strategies to counter ADE to protect against Zika infection.


Assuntos
Anticorpos Antivirais/imunologia , Anticorpos Facilitadores/imunologia , Reações Cruzadas/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Animais , Anticorpos Biespecíficos/genética , Anticorpos Biespecíficos/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/genética , Linfócitos B/imunologia , Linfócitos B/metabolismo , Proteção Cruzada/imunologia , Dengue/virologia , Humanos , Fragmentos Fab das Imunoglobulinas/genética , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/imunologia , Imunomodulação , Mutação , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
17.
Front Microbiol ; 9: 87, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29472902

RESUMO

Zika virus (ZIKV) is the most recent intruder that acquired the status of global threat creating panic and frightening situation to public owing to its rapid spread, attaining higher virulence and causing complex clinical manifestations including microcephaly in newborns and Guillain Barré Syndrome. Alike other flaviviruses, the principal mode of ZIKV transmission is by mosquitoes. Advances in research have provided reliable diagnostics for detecting ZIKV infection, while several drug/therapeutic targets and vaccine candidates have been identified recently. Despite these progresses, currently there is neither any effective drug nor any vaccine available against ZIKV. Under such circumstances and to tackle the problem at large, control measures of which mosquito population control need to be strengthened following appropriate mechanical, chemical, biological and genetic control measures. Apart from this, several other known modes of ZIKV transmission which have gained importance in recent past such as intrauterine, sexual intercourse, and blood-borne spread need to be checked and kept under control by adopting appropriate precautions and utmost care during sexual intercourse, blood transfusion and organ transplantation. The virus inactivation by pasteurization, detergents, chemicals, and filtration can effectively reduce viral load in plasma-derived medicinal products. Added to this, strengthening of the surveillance and monitoring of ZIKV as well as avoiding travel to Zika infected areas would aid in keeping viral infection under check. Here, we discuss the salient advances in the prevention and control strategies to combat ZIKV with a focus on highlighting various intervention approaches against the vector mosquitoes of this viral pathogen along with presenting an overview regarding human intervention measures to counter other modes of ZIKV transmission and spread. Additionally, owing to the success of vaccines for a number of infections globally, a separate section dealing with advances in ZIKV vaccines and transmission blocking vaccines has also been included.

18.
Artigo em Inglês | MEDLINE | ID: mdl-29485014

RESUMO

BACKGROUND: Mesenchymal Stem Cells (MSCs) are self-renewing, multipotent progenitor cells with multilineage potential to differentiate into all cell types of mesodermal origin, such as adipocytes, osteocytes and chondrocytes. Mesenchymal Stem Cells (MSCs) are adult stem cells which can be isolated from human and animal sources. OBJECTIVE: Besides the differentiation potential of MSCs, these also regulate the immune response in numerous ailments. The present review expedites the immunomodulating prospective of MSCs. METHODS: Scrupulous search of the literature and patents available on MSCs and their role in the immunomodulation was carried out using Medline, PubMed, PubMed Central, Science Direct and other scientific databases. The retrieved information has been analyzed and compiled. RESULTS: MSCs have unique regulation of microenvironment in the host tissue by secreting cytokines and immune-receptors which results in immunomodulatory effects. MSCs can be used as an effective tool in the treatment of chronic diseases because of its property to secrete anti-inflammatory molecules, having multilineage potential and immunomodulation. CONCLUSION: The present review is focused on the use of MSCs due to their unique immunomodulatory characteristics. MSCs reach to the site of inflammation and interact with immune cells to bring immunosuppressive and anti-inflammatory effects. Along with these unique therapeutic properties, MSCs may be a useful therapeutic approach for various disorders.


Assuntos
Imunomodulação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Animais , Diferenciação Celular , Humanos , Hipersensibilidade/terapia , Hipertensão/terapia , Óxido Nítrico/fisiologia , Osteoartrite/terapia , Patentes como Assunto
19.
Curr Drug Metab ; 19(3): 236-263, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29380697

RESUMO

BACKGROUND: Recently, there has been a remarkable progress in the field of antiviral herbal therapy owing to increasing concerns about the development of drug resistance and limited advances in the field of antiviral drug discovery. In almost all countries, medicinal plants have been used widely throughout history for the treatment of diseases and infections as traditional healing remedies due to their broad therapeutic spectrum and minimal or no side effects. As synthetic antiviral drugs are not available against most of the viral agents, hence all possible efforts have been focused on the search for new drugs and complementary/alternative medicines from different herbal formulations. METHODS: We have retrieved the related information from the online published resources (Medline, PubMed, Pub- Med Central, Science Direct and other scientific databases); which were further analyzed and compiled. RESULTS: Medicinal plants contain extractable biochemical and bioactive compounds, which can target certain viruses or can cure or prevent several viral diseases and infections. Despite their long history of use, the research and scientific evidences regarding the use of medicinal plants and natural products as prophylactics, therapeutics, and their health multiple beneficial applications have only gained momentum in past few decades. Many scientific studies have been undertaken, which range from the separation of active substances to the comprehension of the therapeutic mechanisms of antiviral herbs, their potent applications in the neutralization of viral pathogens and clinical trials. Consequently, hundreds of herbs and plant metabolites have been screened, identified, and tested for their antiviral activities; fortunately, some have shown significant medicinal activity in the amelioration or prevention of various viral diseases in both preclinical and clinical studies. CONCLUSION: This review addresses the scientific significance of various herbal formulations of different medicinal plants and their extracts, which have shown promise or been proven effective for the treatment of diseases caused by various viral pathogens, including emerging and re-emerging viruses that infect humans, animals, poultry and fish.


Assuntos
Antivirais/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Viroses/tratamento farmacológico , Animais , Antivirais/farmacologia , Humanos , Extratos Vegetais/farmacologia , Plantas Medicinais/metabolismo
20.
Biol Open ; 6(11): 1698-1706, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29141954

RESUMO

Plastic responses to multiple environmental stressors in wet or dry seasonal populations of tropical Drosophila species have received less attention. We tested plastic effects of heat hardening, acclimation to drought or starvation, and changes in trehalose, proline and body lipids in Drosophila ananassae flies reared under wet or dry season-specific conditions. Wet season flies revealed significant increase in heat knockdown, starvation resistance and body lipids after heat hardening. However, accumulation of proline was observed only after desiccation acclimation of dry season flies while wet season flies elicited no proline but trehalose only. Therefore, drought-induced proline can be a marker metabolite for dry-season flies. Further, partial utilization of proline and trehalose under heat hardening reflects their possible thermoprotective effects. Heat hardening elicited cross-protection to starvation stress. Stressor-specific accumulation or utilization as well as rates of metabolic change for each energy metabolite were significantly higher in wet-season flies than dry-season flies. Energy metabolite changes due to inter-related stressors (heat versus desiccation or starvation) resulted in possible maintenance of energetic homeostasis in wet- or dry-season flies. Thus, low or high humidity-induced plastic changes in energy metabolites can provide cross-protection to seasonally varying climatic stressors.

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