COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to ...promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment of SARS-CoV2-infected apoptotic cells exacerbates inflammatory cytokine production, inhibits the expression of efferocytic receptors, and impairs continual efferocytosis by macrophages. We also provide evidence supporting that lung monocytes and macrophages from severe COVID-19 patients have compromised efferocytic capacity. Our findings reveal that dysfunctional efferocytosis of SARS-CoV-2-infected cell corpses suppress macrophage anti-inflammation and efficient tissue repair programs and provide mechanistic insights for the excessive production of pro-inflammatory cytokines and accumulation of tissue damage associated with COVID-19 immunopathogenesis.
Recent studies have demonstrated the intimate relationship between depression and immune disturbances. Aware of the efficacy limits of existing antidepressant drugs and the potential ...anti-inflammatory properties of propentofylline, we sought to evaluate the use of propentofylline as a depression treatment. We used a rat model of depression induced by repetitive lipopolysaccharide (LPS) administrations. We have studied sickness behavior, by assessing daily body weight, open field behavior, and TNF-α plasmatic levels. Anxiety-like behavior (light-dark test), depressive-like behavior (forced swim test), plasmatic levels of the brain-derived neurotrophic factor (BDNF, depression biomarker), and central glial fibrillary acidic protein (GFAP) expression (an astrocyte biomarker) were also evaluated. LPS induced body weight loss, open field behavior impairments (decreased locomotion and rearing, and increased immobility), and increased TNF-α levels in rats, compared with control group. Thus, LPS induced sickness behavior. LPS also increased the immobility and reduced climbing in the forced swim test, when compared with the control group, i.e., LPS induced depressive-like behavior in rats. Propentofylline prevented sickness behavior after four days of consecutive treatment, as well as prevented the depressive-like behavior after five days of consecutive treatments. Propentofylline also prevented the increase in GFAP expression induced by LPS. Neither LPS nor propentofylline has influenced the anxiety and BDNF levels of rats. In conclusion, repetitive LPS administrations induced sickness behavior and depressive-like behavior in rats. Propentofylline prevented both sickness behavior and depressive-like behavior via neuroinflammatory pathway. The present findings may contribute to a better understanding and treatment of depression and associated diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of this study was to prepare various 4-substituted N-phenyl-1,2,3-triazole derivatives using click chemistry. The derivatives were screened in vitro for antimicrobial activity against ...Mycobacterium tuberculosis strain H37Rv (ATCC 27294) using the Alamar Blue susceptibility test. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM). Derivatives of isoniazid (INH), (E)-N′-(1-aryl)-1H-1,2,3-triazole-4-yl)methylene isonicotinoyl hydrazides, exhibited significant activity with MIC values ranging from 2.5 to 0.62 μg/mL. In addition, they displayed low cytotoxicity against liver cells (hepatoma HepG2) and kidney cells (BGM), thereby providing a high therapeutic index. The results demonstrated the potential and importance of developing new INH derivatives to treat mycobacterial infections.
There has been a rapid increase in the number of cases of COVID-19 in Latin America, Africa, Asia and many countries that have an insufficient number of physicians and other health care personnel, ...and the need for the inclusion of medical students on health teams is a very important issue. It has been recommended that medical students work as volunteers, undergo appropriate training, not undertake any activity beyond their level of competence, and receive continuous supervision and adequate personal protective equipment. However, the motivation of medical students must be evaluated to make volunteering a more evidence-based initiative. The aim of our study was to evaluate the motivation of medical students to be part of health teams to aid in the COVID-19 pandemic.
We developed a questionnaire specifically to evaluate medical students' perceptions about participating in the care of patients with suspected infection with coronavirus during the COVID-19 pandemic. The questionnaire had two parts: a) one part with questions on individual characteristics, year in medical school and geographic location of the medical school and b) a second part with twenty-eight statements assessed on a 5-point Likert scale (totally agree, agree, neither agree nor disagree, disagree and totally disagree). To develop the questionnaire, we performed consensus meetings with a group of faculty and medical students. The questionnaire was sent to student organizations of 257 medical schools in Brazil and answered by 10,433 students. We used multinomial logistic regression models to analyze the data. Statements associated with greater odds ratios for participation of medical students in the COVID-19 pandemic were related to a sense of purpose or duty ("It is the duty of the medical student to put himself or herself at the service of the population in the pandemic"), altruism ("I am willing to take risks by participating in practice in the context of the pandemic"), and perception of good performance and professional identity ("I will be a better health professional for having experienced the pandemic"). Males were more prone than females to believe that only interns should participate in the care of patients with COVID-19 (odds ratio 1.36 coefficient interval 95%:1.24-1.49) and that all students should participate (OR 1.68 CI:1.4-1.91).
Medical students are more motivated by a sense of purpose or duty, altruism, perception of good performance and values of professionalism than by their interest in learning. These results have implications for the development of volunteering programs and the design of health force policies in the present pandemic and in future health emergencies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lead halide perovskite materials have attracted significant attention in the context of photovoltaics and other optoelectronic applications, and recently, research efforts have been directed to ...nanostructured lead halide perovskites. Collodial nanocrystals (NCs) of cesium lead halides (CsPbX3, X = Cl, Br, I) exhibit bright photoluminescence, with emission tunable over the entire visible spectral region. However, previous studies on CsPbX3 NCs did not address key aspects of their chemistry and photophysics such as surface chemistry and quantitative light absorption. Here, we elaborate on the synthesis of CsPbBr3 NCs and their surface chemistry. In addition, the intrinsic absorption coefficient was determined experimentally by combining elemental analysis with accurate optical absorption measurements. 1H solution nuclear magnetic resonance spectroscopy was used to characterize sample purity, elucidate the surface chemistry, and evaluate the influence of purification methods on the surface composition. We find that ligand binding to the NC surface is highly dynamic, and therefore, ligands are easily lost during the isolation and purification procedures. However, when a small amount of both oleic acid and oleylamine is added, the NCs can be purified, maintaining optical, colloidal, and material integrity. In addition, we find that a high amine content in the ligand shell increases the quantum yield due to the improved binding of the carboxylic acid.
The factors that influence biodiversity and productivity of hydrothermal ecosystems are not well understood. Here we investigate the relationship between fluid mixing, biodiversity, and ...chemosynthetic primary productivity in three co‐localized hot springs (RSW, RSN, and RSE) in Yellowstone National Park that have different geochemistry. All three springs are sourced by reduced hydrothermal fluid, but RSE and RSN receive input of vapour phase gas and oxidized groundwaters, with input of both being substantially higher in RSN. Metagenomic sequencing revealed that communities in RSN were more biodiverse than those of RSE and RSW in all dimensions evaluated. Microcosm activity assays indicate that rates of dissolved inorganic carbon (DIC) uptake were also higher in RSN than in RSE and RSW. Together, these results suggest that increased mixing of reduced volcanic fluid with oxidized fluids generates additional niche space capable of supporting increasingly biodiverse communities that are more productive. These results provide insight into the factors that generate and maintain chemosynthetic biodiversity in hydrothermal systems and that influence the distribution, abundance, and diversity of microbial life in communities supported by chemosynthesis. These factors may also extend to other ecosystems not supported by photosynthesis, including the vast subterranean biosphere and biospheres beneath ice sheets and glaciers.
The potato cyst nematode (PCN), Globodera pallida, has acquired significant importance throughout Europe due to its widespread prevalence and negative effects on potato production. Thus, rapid and ...reliable diagnosis of PCN is critical during surveillance programs and for the implementation of control measures. The development of innovative technologies to overcome the limitations of current methodologies in achieving early detection is needed. Lab-on-a-chip devices can swiftly and accurately detect the presence of certain nucleotide sequences with high sensitivity and convert the presence of biological components into an understandable electrical signal by combining biosensors with microfluidics-based biochemical analysis. In this study, a specific DNA-probe sequence and PCR primers were designed to be used in a magnetoresistive biosensing platform to amplify the internal transcribed spacer region of the ribosomal DNA of G. pallida. Magnetic nanoparticles were used as the labelling agents of asymmetric PCR product through biotin−streptavidin interaction. Upon target hybridization to sensor immobilized oligo probes, the fringe field created by the magnetic nanoparticles produces a variation in the sensor’s electrical resistance. The detection signal corresponds to the concentration of target molecules present in the sample. The results demonstrate the suitability of the magnetic biosensor to detect PCR target product and the specificity of the probe, which consistently distinguishes G. pallida (DV/V > 1%) from other cyst nematodes (DV/V < 1%), even when DNA mixtures were tested at different concentrations. This shows the magnetic biosensor’s potential as a bioanalytical device for field applications and border phytosanitary inspections.
The
6k (X
=
H, Y
=
NO
2, pIC
50
=
4.55
M) and
6l (X
=
F, Y
=
CN, pIC
50
=
4.27
M) are the most potent trypanocidal agents. However,
6l showed the most promising overall profile, with low toxicity (0% ...of cell death).
Chagas disease (American trypanosomiasis) is one of the most important parasitic diseases with serious social and economic impacts mainly on Latin America. This work reports the synthesis, in vitro trypanocidal evaluation, cytotoxicity assays, and molecular modeling and SAR/QSAR studies of a new series of
N-phenylpyrazole benzylidene-carbohydrazides. The results pointed
6k (X
=
H, Y
=
p-NO
2, pIC
50
=
4.55
M) and
6l (X
=
F, Y
=
p-CN, pIC
50
=
4.27
M) as the most potent derivatives compared to crystal violet (pIC
50
=
3.77
M). The halogen-benzylidene-carbohydrazide presented the lowest potency whereas
6l showed the most promising profile with low toxicity (0% of cell death). The best equation from the 4D-QSAR analysis (Model 1) was able to explain 85% of the activity variability. The QSAR graphical representation revealed that bulky X-substituents decreased the potency whereas hydrophobic and hydrogen bond acceptor Y-substituents increased it.
•Phenolic acids are representative molecules in the diet.•After absorption, they are extensively metabolized in the organism.•Glucuronidation, methylation and sulfation reactions occur in their ...metabolism.•Glucuronated metabolites exert antioxidant action in vivo.•Methylated and glucuronated derivatives increase antimicrobial and antitumor activities.
Phenolic acids are present in our diet in different foods, for example mushrooms. Due to their bioactive properties, phenolic acids are extensively studied and there is evidence of their role in disease prevention. Nevertheless, in vivo, these compounds are metabolized and circulate in the organism as glucuronated, sulphated and methylated metabolites, displaying higher or lower bioactivities. To clarify the importance of the metabolism of phenolic acids, knowledge about the bioactivity of metabolites is extremely important.
In this review, chemical features, biosynthesis and bioavailability of phenolic acids are discussed, as well as the chemical and enzymatic synthesis of their metabolites. Finally, metabolite bioactive properties are compared with that of the corresponding parental compounds.
Brazilian spotted fever (BSF), caused by the bacterium Rickettsia rickettsii, has been associated with the transmission by the tick Amblyomma sculptum, and one of its main hosts, the capybara ...(Hydrochoerus hydrochaeris).
During 2015-2019, we captured capybaras and ticks in seven highly anthropic areas of São Paulo state (three endemic and four nonendemic for BSF) and in two natural areas of the Pantanal biome, all with established populations of capybaras.
The BSF-endemic areas were characterized by much higher tick burdens on both capybaras and in the environment, when compared to the BSF-nonendemic areas. Only two tick species (A. sculptum and Amblyomma dubitatum) were found in the anthropic areas; however, with a great predominance of A. sculptum (≈90% of all ticks) in the endemic areas, in contrast to a slight predominance of A. dubitatum (≈60%) in the nonendemic areas. Tick species richness was higher in the natural areas, where six species were found, albeit with a predominance of A. sculptum (≈95% of all ticks) and environmental tick burdens much lower than in the anthropic areas. The BSF-endemic areas were characterized by overgrowth populations of A. sculptum that were sustained chiefly by capybaras, and decreased populations of A. dubitatum. In contrast, the BSF-nonendemic areas with landscape similar to the endemic areas differed by having lower tick burdens and a slight predominance of A. dubitatum over A.sculptum, both sustained chiefly by capybaras. While multiple medium- to large-sized mammals have been incriminated as important hosts for A. sculptum in the natural areas, the capybara was the only important host for this tick in the anthropic areas.
The uneven distribution of R. rickettsii infection among A. sculptum populations in highly anthropic areas of São Paulo state could be related to the tick population size and its proportion to sympatric A. dubitatum populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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