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1.
Mol Oncol ; 18(5): 1123-1142, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38514909

RESUMO

Store-operated Ca2+ entry (SOCE) is a major mechanism for Ca2+ influx in colorectal cancer (CRC) cells. This mechanism, regulated by the filling state of the intracellular Ca2+ stores, is mediated by the endoplasmic reticulum Ca2+ sensors of the stromal interaction molecules (STIM) family [stromal interaction molecule 1 (STIM1) and STIM2] and the Ca2+-release-activated Ca2+ channels constituted by Orai family members, with predominance of calcium release-activated calcium channel protein 1 (Orai1). CRC cells exhibit enhanced SOCE due to remodeling of the expression of the key SOCE molecular components. The enhanced SOCE supports a variety of cancer hallmarks. Here, we show that treatment of the colorectal adenocarcinoma cell lines HT-29 and Caco-2 with inanimate Lacticaseibacillus paracasei (CECT9610) and Lactiplantibacillus plantarum (CECT9608) attenuates SOCE, although no detectable effect is seen on SOCE in normal colon mucosa cells. The effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics was mediated by downregulation of Orai1 and STIM1, while the expression levels of Orai3 and STIM2 remained unaltered. Treatment of HT-29 and Caco-2 cells with inanimate Lacticaseibacillus paracasei and Lactiplantibacillus plantarum impairs in vitro migration by a mechanism likely involving attenuation of focal adhesion kinase (FAK) tyrosine phosphorylation. Cell treatment with the Orai1 inhibitor synta-66 attenuates SOCE and prevents any further effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics. Together, our results indicate for the first time that Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics selectively exert negative effects on Ca2+ influx through SOCE in colorectal adenocarcinoma cell lines, providing evidence for an attractive strategy against CRC.


Assuntos
Cálcio , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Cálcio/metabolismo , Fosforilação , Células HT29 , Células CACO-2 , Quinase 1 de Adesão Focal/metabolismo , Probióticos/farmacologia , Molécula 1 de Interação Estromal/metabolismo
2.
Vet Rec ; 185(20): 629, 2019 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-31515441

RESUMO

BACKGROUND: Wild boar is an important reservoir of Mycobacterium tuberculosis variant bovis, the main causative agent of bovine tuberculosis (bTB). A proportion of tuberculosis (TB)-affected wild boars shed M tuberculosis by nasal route, favouring the maintenance of bTB in a multihost scenario. The aim of this work was to assess if M tuberculosis nasal excretion is influenced by factors commonly associated with high TB prevalence in wild boar. METHODS: TB diagnosis and M tuberculosis isolation were carried out in 112 hunted wild boars from mid-western Spain. The association between the presence of M tuberculosis DNA in nasal secretions and explanatory factors was explored using partial least squares regression (PLSR) approaches. RESULTS: DNA from M tuberculosis was detected in 40.8 per cent nasal secretions of the TB-affected animals. Explanatory factors provided a first significant PLSR X's component, explaining 25.70 per cent of the variability observed in M tuberculosis nasal shedding. The presence of M tuberculosis in nasal secretions is more probable in animals suffering from generalised TB and mainly coinfected with Metastrongylus species and porcine circovirus type 2, explaining nearly 90 per cent of the total variance of this model. CONCLUSION: Measures aiming to control these factors could be useful to reduce M tuberculosis shedding in wild boar.


Assuntos
Mycobacterium bovis/isolamento & purificação , Nariz/microbiologia , Sus scrofa/microbiologia , Doenças dos Suínos/epidemiologia , Tuberculose/veterinária , Animais , Coinfecção/epidemiologia , Reservatórios de Doenças , Feminino , Masculino , Espanha/epidemiologia , Suínos , Tuberculose/epidemiologia
3.
Int J Exp Pathol ; 98(6): 347-355, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29315931

RESUMO

Organ tissue damage is a key contributor to host morbidity and mortality following infection with microbial agents. Severe immune responses, excessive cellular recruitment and necrosis of cells all play a role in disease pathology. Understanding the pathogenesis of disease can aid in identifying potential new therapeutic targets or simply act as a diagnostic tool. Burkholderia pseudomallei is a Gram-negative bacterium that can cause acute and chronic diseases. The BALB/c mouse has been shown to be highly susceptible to aerosol challenge with B. pseudomallei and hence acts as a good model to study the acute and potentially lethal form of the disease melioidosis. In our study, BALB/c mice were challenged and culled at predetermined time points to generate a pathological time course of infection. Lung, liver and spleen were subjected to pathological and immunohistochemical analysis. The number and type of microscopic lesions within each organ, as well as the location and the mean percentage of neutrophils, B cells, T cells and Burkholderia capsule antigen within the lesions, were all characterized during the time course. Neutrophils were determined as the key player in tissue pathology and generation of lesions, with B cells playing an insignificant role. This detailed pathological assessment increases our understanding of B. pseudomallei disease.


Assuntos
Linfócitos B/patologia , Burkholderia pseudomallei/patogenicidade , Neutrófilos/patologia , Baço/microbiologia , Animais , Linfócitos B/microbiologia , Burkholderia pseudomallei/imunologia , Modelos Animais de Doenças , Fígado/microbiologia , Fígado/patologia , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Neutrófilos/microbiologia , Baço/patologia , Linfócitos T/microbiologia , Linfócitos T/patologia
4.
Trop Anim Health Prod ; 46(2): 305-11, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24158359

RESUMO

This work is an approach to the molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) bovine infections in Tunisia. A total of 35 MTBC isolates from both lateral retropharyngeal lymph node samples of cattle slaughtered in different Tunisian regions were genotyped by spoligotyping and variable number tandem repeat typing (VNTR)-typing. Spoligotyping allowed to identify two profiles not previously registered, namely SB2024, a Mycobacterium caprae isolate from Nabeul Region (North East Tunisia), the first description of this species in the country, and SB2025 (Mycobacterium bovis) from Sfax Region (Southern Tunisia). A second M. caprae isolate with a spoligotyping profile previously described in Europe mainland, SB0418, was also isolated from a bovine of Sfax region. Both isolates suggest the possibility of a widespread distribution of this species in the country. The predominant spoligotype was SB0120, present in all Tunisian regions selected for the study but Nabeul. Molecular typing also allowed to describe a mixed infection caused by two different M. bovis isolates (SB0120 and SB0848) in the same animal. VNTR typing was highly discriminant by testing a panel of six loci. Loci QUB3232 and QUB11b were the most discriminant, whereas ETR-D and QUB11a had the lower diversity index. The value of allelic diversity can significantly vary among countries; thus, it is important to standardize a panel of loci for future inter-laboratory comparisons. Although VNTR typing proved to be useful for an efficient discrimination among MTBC isolates, especially in combination with spoligotyping, further studies are needed in order to assess the genetic diversity of the MTBC in Tunisia.


Assuntos
Genótipo , Repetições Minissatélites/genética , Mycobacterium bovis/isolamento & purificação , Tuberculose Bovina/microbiologia , Animais , Bovinos , Variação Genética , Epidemiologia Molecular , Tipagem Molecular , Tuberculose Bovina/epidemiologia , Tunísia/epidemiologia
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