Mechanisms that prevent inappropriate or excessive interleukin-17-producing T helper (Th17) cell responses after microbial infection may be necessary to avoid autoimmunity. Here, we define a pathway ...initiated by engagement of type I IFN receptor (IFNAR) expressed by dendritic cells (DC) that culminated in suppression of Th17 cell differentiation. IFNAR-dependent inhibition of an intracellular translational isoform of Osteopontin, termed Opn-i, derepressed interleukin-27 (IL-27) secretion and prevented efficient Th17 responses. Moreover, Opn-i expression in DC and microglia regulated the type and intensity of experimental autoimmune encephalomyelitis (EAE). Mice containing DC deficient in Opn-i produced excessive amounts of IL-27 and developed a delayed disease characterized by an enhanced Th1 response compared with the dominant Th17 response of Opn-sufficient mice. Definition of the IFNAR-Opn-i axis that controls Th17 development provides insight into regulation of Th cell sublineage development and the molecular basis of type I interferon therapy for MS and other autoimmune diseases.
Highlights • Whether frailty is a potential cardiovascular risk factor is currently poorly understood. • In this meta-analysis frailty was associated with a higher prevalence and incidence of CVD. • ...Interventional studies are needed to test if improving frail and prefrail status can reduce CV risk and outcomes.
Osteopontin (Opn) contributes to diverse biological processes that include immune responses, vascularization, and bone formation. Until recently, studies describing the activities of Opn have focused ...on the cytokine-like properties of the secreted protein. Here, we show that alternative translation of a single Opn mRNA species generates a secreted and intracellular isoform. Utilization of a 5' canonical translation start site generates a protein that includes an N-terminal signal sequence allowing targeting to secretory vesicles and cytokine secretion, whereas usage of a downstream start site generates a shortened protein that lacks the N-terminal signal sequence and localizes mainly to cytoplasm. The coordinated action of these Opn gene products regulates the functional phenotype of subsets of dendritic cells.
species are multi-resistant bacteria with ability to cause opportunistic infections.
We isolated 45
species from soil, sewage and the clinic with the aim of investigating their susceptibility to ...commonly used antimicrobial agents.
The identities of isolates were confirmed with 16S rRNA gene sequence and MALDI-TOF analysis. Anti-microbial resistance, biofilm production and clonal diversity were also evaluated. The minimum inhibitory concentration technique as described by Clinical & Laboratory Standards Institute: CLSI Guidelines (CLSI) was employed for the evaluation of isolate susceptibility to antibiotics.
Forty-five
species which include 36 environmental strains and 9 clinical strains of
were considered in this study. 32 (88.9 %) environmental strains were identified to be
, 2 (5.6 %) were
, and 2 (5.6 %) cluster as
spp.
isolates were resistant to at least six of the antibiotics tested, including
/
(
).
Environmental isolates from this study were resistant to SXT which is commonly used for the treatment of
infections. This informs the need for good public hygiene as the environment could be a reservoir of multi-resistant bacteria. It also buttresses the importance of surveillance study in the management of bacterial resistance.
Infections caused by Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., Entamoeba histolytica, Giardia lamblia, Plasmodium spp., and Trichomonas vaginalis, are part of a large list of human ...parasitic diseases. Together, they cause more than 500 million infections per year. These protozoa parasites affect both low- and high-income countries and their pharmacological treatments are limited. Therefore, new and more effective drugs in preclinical development could improve overall therapy for parasitic infections even when their mechanisms of action are unknown. In this review, a number of heterocyclic compounds (diamidine, guanidine, quinoline, benzimidazole, thiazole, diazanaphthalene, and their derivatives) reported as antiprotozoal agents are discussed as options for developing new pharmacological treatments for parasitic diseases.
The strategies for controlling the insect pest Spodoptera frugiperda have been developing over the past four decades; however, the insecticide resistance and the remarkable adaptability of this ...insect have hindered its success. This review first analyzes the different chemical compounds currently available and the most promising options to control S. frugiperda. Then, we analyze the metabolites obtained from plant extracts with antifeedant, repellent, insecticide, or ovicide effects that could be environmentally friendly options for developing botanical S. frugiperda insecticides. Subsequently, we analyze the biological control based on the use of bacteria, viruses, fungi, and parasitoids against this pest. Finally, the use of sex pheromones to monitor this pest is analyzed. The advances reviewed could provide a wide panorama to guide the search for new pesticidal strategies but focused on environmental sustainability against S. frugiperda.
Electrostatic precipitators (ESPs) are commonly the most used filtration technology at industrial environments considering that ESPs allow to have a high dedusting efficiency. ESP insulators are key ...components in a precipitator inasmuch as if they do not work properly, the efficiency decreases quickly, and even having an inadequate insulation can end up in a serious accident. Therefore, there are several recommendations given about the adequate material for each insulator type and also about how to maintain an ESP insulator in good working conditions.
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•We have clarify the main working conditions of an ESP.•The main used porcelains are presented.•We have proposed porcelain with high alumina content.•The main reasons of a breakage and their solutions are mentioned.•Maintenance good practises and systems to avoid dust-layer are suggested.
Chagas disease (CD) is a neglected disease caused by the parasite
, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse ...effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn) as cruzain (Cz) inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal effect of four selected compounds. Among these drugs, one fibrate antilipemic (etofyllin clofibrate) and three β-lactam antibiotics (piperacillin, cefoperazone, and flucloxacillin) showed better trypanocidal effects (LC
range 15.8-26.1 μg/mL) in comparison with benznidazole and nifurtimox (LC
range 33.1-46.7 μg/mL). A short-term in vivo evaluation of these compounds showed a reduction of parasitemia in infected mice (range 90-60%) at 6 h, but this was low compared to benznidazole (50%). This work suggests that four known FDA drugs could be used to design and obtain new trypanocidal agents.
Recent advances in antitubercular natural products García, Abraham; Bocanegra-García, Virgilio; Palma-Nicolás, Jose Prisco ...
European journal of medicinal chemistry,
03/2012, Letnik:
49
Journal Article
Recenzirano
Currently, one third of the world’s population is infected with Mycobacterium tuberculosis and 8.9–9.9 million new and relapse cases of tuberculosis are reported every year. The emergence of new ...cases, the increased incidence of multi-drug resistant strains of M. tuberculosis, and the adverse effects of first- and second-line antituberculosis drugs have led to renewed research interest in natural products in the hope of discovering new antitubercular leads. Interestingly, hundreds of natural products, possessing novel, uncommon, and known structural architectures, have been reported to exhibit activity towards non-resistant and multi-drug resistant strains of M. tuberculosis. The present review covers literature published during the last five years about those naturally occurring compounds with reported growth inhibitory activity in vitro towards sensitive and resistant M. tuberculosis strains. Compounds with antitubercular properties at minimal inhibitory concentrations (MICs) of less than 50 μg/mL or 60 μM were selected and grouped according to their source of origin (plants, bacteria, fungi, marine organisms, etc) and chemical type (terpenes, steroids, alkaloids, flavonoids, poliketides, peptides, etc). In some cases, the selection covers those structurally relevant natural products with low bioactivity (MICs of ≤128 μg/mL), and also those semisynthetic derivatives with remarkable antitubercular activity (MICs of ≤10 μg/mL). Additionally, this review includes a special section for those natural products that specifically target genes or enzymes of M. tuberculosis.
The present review covers literature published during the last five years about those naturally occurring compounds with reported growth inhibitory activity in vitro towards sensitive and resistant Mycobacterium tuberculosis strains. Compounds with antitubercular properties at minimal inhibitory concentrations (MICs) of less than 50 μg/mL or 60 μM and antitubercular selectivity indexes higher than 10 were selected and grouped according to their source of origin (plants, bacteria, fungi, marine organisms, etc) and chemical type (terpenes, steroids, alkaloids, flavonoids, poliketides, peptides, etc). In some cases, the selection covers those structurally relevant natural products with low bioactivity (MICs of ≤128 μg/mL), and also those semisynthetic derivatives with remarkable antitubercular activity (MICs of ≤10 μg/mL). Additionally, this review includes a special section for those natural products that specifically target genes or enzymes of M. tuberculosis. Display omitted
► Revision of the reported antitubercular natural products from 2006 to 2011. ► Natural products against sensitive & multidrug resistant strains of M. tuberculosis. ► Some semisynthetic compounds exhibited potent activity against these bacteria. ► Promising molecules exhibited antitubercular selectivity indexes higher than 10. ►New and known compounds inhibited specific enzymes in M. tuberculosis.
Objective: To assess the prevalence of fecal incontinence and its association with clinical, functional, and cognitive-behavioral variables, medication use, frailty, falls, and quality of life in ...community-dwelling older adults (aged 65 years or older). Methods: Cross-sectional, multicenter study carried out across 16 Brazilian cities. The question “In the last 12 months, did you experience fecal incontinence or involuntary passage of stool?” was defined as the indicator variable for fecal incontinence. Bivariate analyses were carried out to assess the prevalence of fecal incontinence and sociodemographic characteristics, comorbidities, cognition, functional capacity, depression, frailty, quality of life, and falls. Logistic regression analysis was also performed, with fecal incontinence as the dependent variable. Results: Overall, 6855 subjects were evaluated; 66.56% were female, 52.93% white, and the mean age was 73.51 years. The prevalence of fecal incontinence was 5.93%. It was associated with worse self-care (OR 1.78 1.08–2.96), dependence for basic activities of daily living (OR 1.29 1.01–1.95), and urinary incontinence (OR 4.22 3.28–5.41). Furthermore, the absence of polypharmacy was identified as a protective factor (OR 0.61 0.44–0.85). Conclusion: The overall prevalence of fecal incontinence was 5.93%. On logistic regression, one quality of life variable, dependence for basic activities of daily living, and polypharmacy were significantly associated with fecal incontinence.
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