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1.
Autophagy ; : 1-15, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34720021

RESUMO

Mitophagy is a selective autophagy mechanism for eliminating damaged mitochondria and plays a crucial role in the immune evasion of some viruses and bacteria. Here, we report that Mycobacterium bovis (M. bovis) utilizes host mitophagy to suppress host xenophagy to enhance its intracellular survival. M. bovis is the causative agent of animal tuberculosis and human tuberculosis. In the current study, we show that M. bovis induces mitophagy in macrophages, and the induction of mitophagy is impaired by PINK1 knockdown, indicating the PINK1-PRKN/Parkin pathway is involved in the mitophagy induced by M. bovis. Moreover, the survival of M. bovis in macrophages and the lung bacterial burden of mice are restricted by the inhibition of mitophagy and are enhanced by the induction of mitophagy. Confocal microscopy analysis reveals that induction of mitophagy suppresses host xenophagy by competitive utilization of p-TBK1. Overall, our results suggest that induction of mitophagy enhances M. bovis growth while inhibition of mitophagy improves growth restriction. The findings provide a new insight for understanding the intracellular survival mechanism of M. bovis in the host.

2.
Front Chem ; 9: 737033, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646812

RESUMO

The comparative utilization of solar thermal or photovoltaic systems has significantly increased to fulfill the requirement of electricity and heat since few decades. These hybrid systems produce both thermal and electrical energy simultaneously. In recent times, increasing interest is being redirected by researchers in exploiting variety of nanoparticles mixed with miscellaneous base fluids (hybrid nanofluid) for these hybrid systems. This new class of colloidal suspensions has many fascinating advantages as compared to conventional types of nanofluids because of their modified and superior rheological and thermophysical properties which makes them appealing for solar energy devices. Here, we have attempted to deliver an extensive overview of the synthetic methodologies of hybrid nanofluids and their potential in PV/T and solar thermal energy systems. A detailed comparison between conventional types of nanofluids and hybrid nanofluids has been carried out to present in-depth understanding of the advantages of the hybrid nanofluids. The documented reports reveal that enhanced thermal properties of hybrid nanofluids promise the increased performance of solar thermal PV/T systems. Additionally, the unique properties such as nanoparticles concentration and type of base fluid, etc. greatly influence the behavior of hybrid nanofluidic systems. Finally, the outlook, suggestions, and challenges for future research directions are discussed.

3.
Cells ; 10(9)2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34572109

RESUMO

Infertility is a globally recognized issue caused by different reproductive disorders. To date, various therapeutic approaches to restore fertility have been attempted including etiology-specific medication, hormonal therapies, surgical excisions, and assisted reproductive technologies. Although these approaches produce results, however, fertility restoration is not achieved in all cases. Advances in using stem cell (SC) therapy hold a great promise for treating infertile patients due to their abilities to self-renew, differentiate, and produce different paracrine factors to regenerate the damaged or injured cells and replenish the affected germ cells. Furthermore, SCs secrete extracellular vesicles (EVs) containing biologically active molecules including nucleic acids, lipids, and proteins. EVs are involved in various physiological and pathological processes and show promising non-cellular therapeutic uses to combat infertility. Several studies have indicated that SCs and/or their derived EVs transplantation plays a crucial role in the regeneration of different segments of the reproductive system, oocyte production, and initiation of sperm production. However, available evidence triggers the need to testify the efficacy of SC transplantation or EVs injection in resolving the infertility issues of the human population. In this review, we highlight the recent literature covering the issues of infertility in females and males, with a special focus on the possible treatments by stem cells or their derived EVs.


Assuntos
Vesículas Extracelulares/fisiologia , Infertilidade Feminina/terapia , Infertilidade Masculina/terapia , Regeneração , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Animais , Feminino , Humanos , Masculino
4.
FASEB J ; 35(9): e21777, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34403519

RESUMO

Mycobacterium bovis is the causative agent of bovine tuberculosis and also responsible for serious threat to public health. Koumiss is a fermented mare's milk product, used as traditional drink. Here, we explored the effect of koumiss on gut microbiota and the host immune response against M bovis infection. Therefore, mice were treated with koumiss and fresh mare milk for 14 days before M bovis infection and continue for 5 weeks after infection. The results showed a clear change in the intestinal flora of mice treated with koumiss, and the lungs of mice treated with koumiss showed severe edema, inflammatory infiltration, and pulmonary nodules in M bovis-infected mice. Notably, we found that the content of short-chain fatty acids was significantly lower in the koumiss-treated group compared with the control group. However, the expression of endoplasmic reticulum stress and apoptosis-related proteins in the lungs of koumiss-treated mice were significantly decreased. Collectively, these findings suggest that koumiss treatment disturb the intestinal flora of, which is associated with disease severity and the possible mechanism that induces lungs pathology. Our current findings can be exploited further to establish the "gut-lung" axis which might be a novel strategy for the control of tuberculosis.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Kumis/efeitos adversos , Mycobacterium bovis/efeitos dos fármacos , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Ácidos Graxos/análise , Fezes/química , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/imunologia , Cavalos , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium bovis/imunologia , Tuberculose Pulmonar/dietoterapia , Tuberculose Pulmonar/metabolismo
5.
Vet Microbiol ; 258: 109126, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34020176

RESUMO

Mycobacterium bovis (M. bovis) infection triggers cytokine production via pattern recognition receptors. These cytokines include type I interferons (IFNs) and interleukin-1ß (IL-1ß). Excessive type I IFN levels impair host resistance to M. bovis infection. Therefore, strict control of type I IFN production is helpful to reduce pathological damage and bacterial burden. Here, we found that a deficiency in caspase-1, which is the critical component of the inflammasome responsible for IL-1ß production, resulted in increased IFN-ß production upon M. bovis infection. Subsequent experiments demonstrated that caspase-1 activation reduced cyclic GMP-AMP synthase (cGAS) expression, thereby inhibiting downstream TANK-binding kinase 1 (TBK1)- interferon regulatory factor 3 (IRF3) signaling and ultimately reducing IFN production. A deficiency in caspase-1 activation enhanced the bacterial burden during M. bovis infection in vitro and in vivo and aggravated pathological lesion formation. Thus, caspase-1 activation reduced IFN-ß production upon M. bovis infection by dampening cGAS-TBK1-IRF3 signaling, suggesting that the inflammasome protects hosts by negatively regulating harmful cytokines.


Assuntos
Caspase 1/metabolismo , Animais , Inibidores de Caspase/farmacologia , Sobrevivência Celular , Dipeptídeos/farmacologia , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Inflamassomos , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon beta , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium bovis , Nucleotidiltransferases , /metabolismo , Distribuição Aleatória , para-Aminobenzoatos/farmacologia
6.
J Hazard Mater ; 415: 125574, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-33756203

RESUMO

The massive application of rare earth elements (REEs) in electronic industries cause their inevitable release into the environment; however, its effects on soil biota remain largely unaddressed. We investigated the E. fetida detoxification potential of nano and bulk La2O3 and Yb2O3 and their potential impact on biochemical and genetic markers at 50, 100, 200, 500 and 1000 mg kg-1 concentration. We found that earthworms bioremediate 3-15% La2O3 and Yb2O3 contaminated soil at low and medium levels, while this potential was limited at higher levels. Nano and bulk La2O3 and Yb2O3 treatment induced neurotoxicity in earthworm by inhibiting acetylcholinesterase by 49-65% and 22-36% at 500 and 1000 mg kg-1, respectively. Nano La2O3 proved to be highly detrimental, mainly through oxidative stress and subsequent failure of antioxidant system. Nano La2O3 and Yb2O3 at 100 mg kg-1 significantly down-regulated the expression of annetocin mRNA in the parental and progeny earthworms by 50% and 20%, which is crucial for earthworm reproduction. Similarly, expression level of heat shock protein 70 (HSP70) and metallothionein was significantly upregulated in both generations at medium exposure level. Histological observations showed that nano REEs at 200 mg kg-1 induced drastic changes in the intestinal epithelium and typhlosole of E. fetida. To date, our results enhance the understanding of interaction between REEs and earthworms.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Lantânio/toxicidade , Oligoquetos/genética , Óxidos/toxicidade , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Itérbio
7.
Animals (Basel) ; 11(3)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668845

RESUMO

BACKGROUND: The use of wheat and flaxseed to produce omega-3 (ω-3) enriched poultry meat and eggs is very popular in the world. However, wheat and flaxseed contain some anti-nutritional factors (ANFs), and enzymes are usually used to alleviate the deleterious influence of ANFs. METHOD: A 2 × 3 two factors design was used in the experiment. A total of 540 twenty-week-old Nongda-3 laying hens were randomly allocated to six dietary treatments, two diets (corn/flaxseed and wheat/flaxseed), and three enzymes (enzyme-a contains neutral protease 10,000, xylanase 35,000, ß-mannanase 1500, ß-glucanase 2000, cellulose 500, amylase 100, and pectinase 10,000 (U g-1); enzyme-b contains alkaline protease 40,000 and neutral protease 10,000 (U g-1); enzyme-c contains alkaline protease 40,000, neutral protease 10,000, and cellulase 4000 (U g-1). RESULTS: There was an interaction between dietary treatment and supplemental enzymes for liver weight and liver inflammatory cytokines of broilers. A significant increase was observed in the fat weight of birds fed a corn diet as compared with a wheat diet. A corn diet and wheat diet with the addition of enzyme-a (p < 0.001) showed the highest level of liver fat followed by enzyme-c (p < 0.01) and enzyme-b. Moreover, a high level of secretory IL-1ß, IL-6, and IL-10 and comparatively higher inflammatory changes in the liver tissue were found in birds fed a corn diet as compared with a wheat diet, and enzyme-b showed more beneficial effects as compared with enzyme-a and -c. The gut microbial composition of hens fed a corn diet was significantly different than that of birds fed a wheat diet. Bacteroides were significantly (p < 0.05) abundant in the corn-fed birds as compared with wheat-fed birds. However, Firmicutes were less abundant in the wheat-fed birds than the corn-fed birds (16.99 vs. 31.80%, respectively). The microbial community at the genus level differed significantly in the dietary groups and we observed that Bacteroides are the predominant cecal microbiota. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of co-factors, carbohydrates, vitamins, protein, and energy were expressed at slightly higher levels in the microbiota of the wheat-fed birds, whereas, metabolic pathways for nucleotides, lipids, and glycine were expressed at higher levels in the wheat-fed birds. Furthermore, expression of the growth and cellular processes pathway and endocrine system pathway levels were predicted to be higher for the wheat-fed group as compared with the corn-fed group. CONCLUSIONS: In conclusion, our findings suggest that inflammatory changes in laying birds were mediated by a corn diet with flaxseed and enzymes instead of a wheat diet. Additionally, in the wheat-fed group, enzyme-b and -c showed more encouraging results as compared to enzyme-a.

8.
Biomed Pharmacother ; 137: 111341, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33561646

RESUMO

Mycobacterium bovis (M. bovis) is a member of mycobacterium tuberculosis complex (MTBC), and a causative agent of chronic respiratory disease in a wide range of hosts. Bacillus Calmette-Guerin (BCG) vaccine is mostly used for the prevention of childhood tuberculosis. Further substantial implications are required for the development and evaluation of new tuberculosis (TB) vaccines as well as improving the role of BCG in TB control strategies. In this study, we prepared PLGA nanoparticles encapsulated with argF antigen (argF-NPs). We hypothesized, that argF nanoparticles mediate immune responses of BCG vaccine in mice models of M. bovis infection. We observed that mice vaccinated with argF-NPs exhibited a significant increase in secretory IFN-γ, CD4+ T cells response and mucosal secretory IgA against M. bovis infection. In addition, a marked increase was observed in the level of secretory IL-1ß, TNF-α and IL-10 both in vitro and in vivo upon argF-NPs vaccination. Furthermore, argF-NPs vaccination resulted in a significant reduction in the inflammatory lesions in the lung's tissues, minimized the losses in total body weight and reduced M. bovis burden in infected mice. Our results indicate that BCG prime-boost strategy might be a promising measure for the prevention against M. bovis infection by induction of CD4+ T cells responses and mucosal antibodies.


Assuntos
Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Mycobacterium bovis , Nanopartículas/administração & dosagem , Ornitina Carbamoiltransferase/imunologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/imunologia , Tuberculose Bovina/prevenção & controle , Administração Intranasal , Animais , Formação de Anticorpos/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Bovinos , Linhagem Celular , Modelos Animais de Doenças , Feminino , Imunoglobulina A Secretora/metabolismo , Imunoglobulina G/sangue , Interferon gama/metabolismo , Interleucina-10/sangue , Interleucina-1beta/sangue , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos BALB C , Mycobacterium bovis/crescimento & desenvolvimento , Mycobacterium bovis/patogenicidade , Nanopartículas/química , Ornitina Carbamoiltransferase/administração & dosagem , Ornitina Carbamoiltransferase/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Baço/microbiologia , Baço/patologia , Fator de Necrose Tumoral alfa/sangue
9.
Front Public Health ; 8: 602434, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363092

RESUMO

The World Health Organization has acknowledged coronavirus disease 2019 (COVID-19) disease as a pandemic. Efforts are being made all over the world to raise awareness to prevent the spread of the disease. The goal of this study was to assess the attitude, perception, and knowledge of Pakistani people toward COVID-19 disease. We conducted a cross-sectional survey in which a questionnaire of 17 questions was transformed online on Google forms and was sent to random individuals online. A total of 1,000 questionnaires from individuals throughout Pakistan were evaluated. The results revealed that 42.9% of the participants knew about COVID-19 through social media, the largest source of information. Most of the participants (48.3%) started working from home amid the lockdown; 39.9% of the participants reported that they wash their hands every hour, and 56.9% participants are using a surgical mask. About thermal scanners, 30.5% of the people answered they may be effective, and 46.0% of the people think COVID-19 is a bioweapon; 59% of the participants think everyone is susceptible, whereas 83.9% of the people recognize fever as a primary symptom; 65.2% of the people are practicing social distancing, whereas 85.1% of the people think social gatherings causes spread of the disease. In general, participants had a good knowledge about the disease and a positive attitude toward protective measures. The effective measures are being taken by the government and the public; still, there remains a need for further awareness campaigns and knowledge of safe interventions to combat the spread of disease.


Assuntos
COVID-19 , Conhecimentos, Atitudes e Prática em Saúde , Percepção , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Paquistão , SARS-CoV-2 , Mídias Sociais/tendências , Inquéritos e Questionários
10.
Pharmaceutics ; 12(9)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32961942

RESUMO

As the ingestion of drug products with alcohol could have adverse effects on the release of drugs from dosage forms, it is important to understand the mechanisms underpinning the influence on drug release by evaluating the effect of alcohol-containing media on the behaviour of pharmaceutical excipients. In this work, the effect of hydroalcoholic media containing up to 40% v/v absolute ethanol was evaluated, employing both the regular (CR) and direct compression grades (DC) of hypromellose. X-ray microtomography (XµT) and magnetic resonance imaging (MRI) were used as complementary techniques in determining the influence of the media composition on the ability of the CR and DC polymers to form and evolve the gel layer that controls drug release. Particle and powder properties of the polymer were characterised to determine any relationship to performance in hydroalcoholic media. Triboelectrification results showed the CR grade formulation to charge electropositively whereas the DC grade charged electronegatively. The flow properties also showed the DC grade to have a superior flow as compared to its CR counterpart. Differences in particle morphology between the grades influenced charging and flow behaviour of the powders; however, it did not seem to impact significantly either on the mechanical strength or the drug release properties of the compacted formulation using the model drug propranolol HCl. XµT and MRI imaging were successfully used as complementary techniques in determining the gel layer/hydration layer thickness measurements as the layer developed, as well as following ingress of hydroalcoholic media and its impact on the dry core. The result showed that although differences were present in the gel layer thickness potentially due to differences in particle morphology, this also did not impact significantly on the dissolution process, especially in acidic and hydroalcoholic media.

13.
Environ Sci Pollut Res Int ; 27(26): 32944-32953, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32524406

RESUMO

With the rapid development in nanoscience and nanotechnology, rare earth oxide nanomaterials (REO-NMs) have been increasingly used due to their unique physical and chemical characteristics. Despite the increasing applications of REO NPs, scarce information is available on their detrimental effects. In the current study, we investigate the toxic effect of ytterbium oxide nanoparticles (Yb2O3 NPs) in mouse model by using various techniques including inductively coupled plasma mass spectrometry (ICP-MS) analysis over 30 days of exposure. Furthermore, we elucidated lung lavage fluid of mice for biochemical and cytological analysis, and lung tissues for histopathology to interpret the NP side effects. We observed a significant concentration of Yb2O3 NPs accumulated in the lung, liver, kidney, and heart tissues. Similarly, increased bioaccumulation of Yb content was found in the olfactory bulb compared to other reigns of brain. The cytological analysis of bronchoalveolar lavage fluid (BALF) revealed a significant elevation in the percentage of neutrophils and lymphocytes. Biochemical analysis showed an instilled Yb2O3 NPs, showing signs of oxidative damage through up-regulation of 60-87% of MDA while down-regulation of 20-40% of GSH-PX and GSH content. The toxicity pattern was more evident from histopathological observations. These interpretations provide enough evidence of bioaccumulation of Yb2O3 NPs in mice tissues. Overall, our findings reveal that acute exposure of Yb2O3 NPs through intranasal inhalation may cause toxicity via oxidative stress, which leads to a chronic inflammatory response. Graphical abstract Graphical illustrations of experimental findings.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Animais , Bioacumulação , Líquido da Lavagem Broncoalveolar , Pulmão , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo , Óxidos , Itérbio
14.
Chemosphere ; 259: 127369, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32593814

RESUMO

Rapidly increasing water contamination has turned into a major threat globally. The pollutants such as organic and inorganic compounds, heavy metals, and biological organisms are among the major contributor to water pollution. Therefore, the removal of these contaminants has attracted the researchers a lot. Various methodologies are being carried out for the purpose. Among them, the metal-organic frameworks (MOFs) with several active sites and tailorable porous architectures as adsorbents or photocatalytic removal agents is a fast-growing class of coordination chemistry to remove these agents from water. To date, numerous approaches dealing with water treatment including conservative and advanced technologies have been presented. This article thoroughly reviews the application of MOFs toward how to remove the toxic agents from water. The leading objective is to present up-to-date information and references regarding MOFs based materials toward wastewater treatment applications.


Assuntos
Estruturas Metalorgânicas , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Adsorção , Poluentes Ambientais/química , Metais Pesados/química , Porosidade , Águas Residuárias , Poluentes Químicos da Água/análise , Poluição da Água , Purificação da Água/métodos
15.
Front Microbiol ; 11: 433, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32265874

RESUMO

Mycobacterium bovis is the causative agent of bovine tuberculosis, has been identified a serious threat to human population. It has been found that sodium butyrate (NaB), the inhibitor of histone deacetylase, can promote the expression of cathelicidin (LL37) and help the body to resist a variety of injuries. In the current study, we investigate the therapeutic effect of NaB on the regulation of host defense mechanism against M. bovis infection. We found an increased expression of LL37 in M. bovis infected THP-1 cells after NaB treatment. In contrast, NaB treatment significantly down-regulated the expression of Class I HDAC in THP-1 cells infected with M. bovis. Additionally, NaB reduced the expression of phosphorylated P65 (p-P65) and p-IκBα, indicating the inhibition of nuclear factor-κB (NF-κB) signaling. Furthermore, we found that NaB treatment reduced the production of inflammatory cytokines (IL-1ß, TNF-α, and IL-10) and a key anti-apoptotic marker protein Bcl-2 in THP-1 cell infected with M. bovis. Notably, mice showed high resistance to M. bovis infection after NaB treatment. The reduction of viable M. bovis bacilli indicates that NaB-induced inhibition of M. bovis infection mediated by upregulation of LL37 and inhibition of NF-κB signaling pathway. These observations illustrate that NaB mediate protective immune responses against M. bovis infection. Overall, these results suggest that NaB can be exploited as a therapeutic strategy for the control of M. bovis in animals and human beings.

16.
J Infect Dis ; 221(3): 438-448, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31495880

RESUMO

BACKGROUND: Mycobacterium bovis persistently survives in macrophages by developing multiple strategies to evade host immune responses, and the early induction of interferon-ß (IFN-ß) is one of these critical strategies. The mitochondrial transcription factor A (TFAM) plays a vital role in mitochondrial DNA (mtDNA) metabolism and has been suggested to influence IFN-ß production in response to viral infection. However, its role in the production of IFN-ß by M. bovis has not been elucidated. METHODS: In the current study, we investigated the role of TFAM in the production of IFN-ß in M. bovis-infected macrophages. RESULTS: We found that knockdown of TFAM expression significantly reduced M. bovis-induced IFN-ß production, mtDNA copy numbers and cytosolic mtDNA were increased in murine macrophages with M. bovis infection, cytosolic mtDNA contributed to IFN-ß production, and TFAM was required for the increase in mtDNA copy numbers induced by M. bovis. We also observed that TFAM affected the intracellular survival of M. bovis. CONCLUSIONS: Our results suggest that TFAM plays an essential role in M. bovis-induced IFN-ß production by regulating mtDNA copy numbers. This might be a new strategy adopted by M. bovis for its intracellular survival.


Assuntos
Replicação do DNA , DNA Mitocondrial/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Grupo de Alta Mobilidade/metabolismo , Interferon beta/biossíntese , Macrófagos/imunologia , Mycobacterium bovis/imunologia , Tuberculose/imunologia , Tuberculose/veterinária , Animais , Linhagem Celular Tumoral , Citosol/metabolismo , DNA Mitocondrial/metabolismo , Proteínas de Ligação a DNA/genética , Técnicas de Silenciamento de Genes , Proteínas de Grupo de Alta Mobilidade/genética , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mycobacterium bovis/metabolismo , Transdução de Sinais/genética , Tuberculose/microbiologia
17.
BMC Infect Dis ; 19(1): 1031, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801478

RESUMO

BACKGROUND: Mycobacterium bovis (M. bovis) is the principal causative agent of bovine tuberculosis; however, it may also cause serious infection in human being. Type I IFN is a key factor in reducing viral multiplication and modulating host immune response against viral infection. However, the regulatory pathways of Type I IFN signaling during M. bovis infection are not yet fully explored. Here, we investigate the role of Type I IFN signaling in the pathogenesis of M. bovis infection in mice. METHODS: C57BL/6 mice were treated with IFNAR1-blocking antibody or Isotype control 24 h before M. bovis infection. After 21 and 84 days of infection, mice were sacrificed and the role of Type I IFN signaling in the pathogenesis of M. bovis was investigated. ELISA and qRT-PCR were performed to detect the expression of Type I IFNs and related genes. Lung lesions induced by M. bovis were assessed by histopathological examination. Viable bacterial count was determined by CFU assay. RESULTS: We observed an abundant expression of Type I IFNs in the serum and lung tissues of M. bovis infected mice. In vivo blockade of Type I IFN signaling reduced the recruitment of neutrophils to the lung tissue, mediated the activation of macrophages leading to an increased pro-inflammatory profile and regulated the inflammatory cytokine production. However, no impact was observed on T cell activation and recruitment in the early acute phase of infection. Additionally, blocking of type I IFN signaling reduced bacterial burden in the infected mice as compared to untreated infected mice. CONCLUSIONS: Altogether, our results reveal that Type I IFN mediates a balance between M. bovis-mediated inflammatory reaction and host defense mechanism. Thus, modulating Type I IFN signaling could be exploited as a therapeutic strategy against a large repertoire of inflammatory disorders including tuberculosis.


Assuntos
Interferon Tipo I/metabolismo , Mycobacterium bovis/patogenicidade , Tuberculose/tratamento farmacológico , Tuberculose/metabolismo , Animais , Anticorpos/farmacologia , Citocinas/metabolismo , Feminino , Humanos , Interferon Tipo I/antagonistas & inibidores , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos Endogâmicos C57BL , Mycobacterium bovis/imunologia , Receptor de Interferon alfa e beta/antagonistas & inibidores , Receptor de Interferon alfa e beta/imunologia , Transdução de Sinais/efeitos dos fármacos
18.
Int J Mol Sci ; 20(23)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31795474

RESUMO

Mycobacterium bovis (M. bovis) is the causative agent of bovine tuberculosis in cattle population across the world. Human beings are at equal risk of developing tuberculosis beside a wide range of M. bovis infections in animal species. Autophagic sequestration and degradation of intracellular pathogens is a major innate immune defense mechanism adopted by host cells for the control of intracellular infections. It has been reported previously that the catalytic subunit of protein phosphatase 2A (PP2Ac) is crucial for regulating AMP-activated protein kinase (AMPK)-mediated autophagic signaling pathways, yet its role in tuberculosis is still unclear. Here, we demonstrated that M. bovis infection increased PP2Ac expression in murine macrophages, while nilotinib a tyrosine kinase inhibitor (TKI) significantly suppressed PP2Ac expression. In addition, we observed that TKI-induced AMPK activation was dependent on PP2Ac regulation, indicating the contributory role of PP2Ac towards autophagy induction. Furthermore, we found that the activation of AMPK signaling is vital for the regulating autophagy during M. bovis infection. Finally, the transient inhibition of PP2Ac expression enhanced the inhibitory effect of TKI-nilotinib on intracellular survival and multiplication of M. bovis in macrophages by regulating the host's immune responses. Based on these observations, we suggest that PP2Ac should be exploited as a promising molecular target to intervene in host-pathogen interactions for the development of new therapeutic strategies towards the control of M. bovis infections in humans and animals.


Assuntos
Proteínas Quinases Ativadas por AMP/imunologia , Macrófagos/imunologia , Mycobacterium bovis/imunologia , Proteína Fosfatase 2/imunologia , Tuberculose/veterinária , Animais , Autofagia , Bovinos , Interações Hospedeiro-Patógeno , Humanos , Macrófagos/microbiologia , Camundongos , Mycobacterium bovis/fisiologia , Fagocitose , Células RAW 264.7 , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose Bovina/imunologia , Tuberculose Bovina/microbiologia
19.
Int J Biol Macromol ; 140: 871-876, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31437503

RESUMO

This study focusses on antibacterial properties and wound healing potential of curcumin cross-linked with chitosan-PVA membranes. The crude curcumin was extracted from the rhizome of (Curcumin longa) and chitosan-PVA 80 was also prepared separately. The synergistic potential 10, 20 and 30 mg of curcumin alone and in combination with chitosan-PVA was determined. The antibacterial, scavenging potential of free radical, total phenolic and total flavonoids contents were documented through spectrophotometric methods. Finally, the wound healing potential was tested on experimental animal (rabbits). Rabbits were divided into different groups; untreated (control), treated with 10, 20 and 30 mg of curcumin and its combination with chitosan-PVA80. Chitosan-PVA exhibited significant antibacterial property against bacterial pathogens. Wound healing trials on 2nd degree burns showed chitosan as substantial wound healing agent for wound bandages. Results have shown that chitosan wound gauzes augmented the granule and fibrous connective tissues formation.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Quitosana/química , Curcumina/química , Curcumina/farmacologia , Álcool de Polivinil/química , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Masculino , Coelhos
20.
Polymers (Basel) ; 11(7)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261678

RESUMO

Hydroxypropyl methyl cellulose, HPMC, a hydrophilic polymer, is widely used for the development of extended release hydrophilic matrices and it is also considered as a good contender for the fabrication of 3D printing of matrix tablets. It is often combined with plasticisers to enable extrusion. The aim of the current project was to develop plasticizer-free 3D printed hydrophilic matrices using drug loaded filaments prepared via HME to achieve an in vitro (swelling, erosion and drug release) and in vivo (drug absorption) performance which is analogous to hydrophilic matrix tablets developed through conventional approaches. Additionally, the morphology of the printed tablets was studied using quantitative 3D surface texture studies and the porosity calculated. Filaments were produced successfully and used to produce matrix tablets with acceptable drug loading (95-105%), mechanical and surface texture properties regardless of the employed HPMC grade. The viscosity of HPMC had a discernible impact on the swelling, erosion, HPMC dissolution, drug release and pharmacokinetic findings. The highest viscosity grade (K100M) results in higher degree of swelling, decreased HPMC dissolution, low matrix erosion, decreased drug release and extended drug absorption profile. Overall, this study demonstrated that the drug loaded (glipizide) filaments and matrix tablets of medium to high viscosity grades of HPMC, without the aid of plasticisers, can be successfully prepared. Furthermore, the in vitro and in vivo studies have revealed the successful fabrication of extended release matrices.

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