Extracellular vesicles (EVs) are evaginations of the cytoplasmic membrane, containing nucleic acids, proteins, lipids, enzymes, and toxins. EVs participate in various bacterial physiological ...processes.
interacts and communicates with the host skin.
EVs may have an essential role in this communication mechanism, modulating the immunological environment. This work aimed to evaluate if
EVs can modulate cytokine production by keratinocytes in vitro and in vivo using the imiquimod-induced psoriasis murine model.
EVs were obtained from a commensal strain (ATC12228EVs) and a clinical isolated strain (983EVs). EVs from both origins induced IL-6 expression in HaCaT keratinocyte cultures; nevertheless, 983EVs promoted a higher expression of the pro-inflammatory cytokines VEGF-A, LL37, IL-8, and IL-17F than ATCC12228EVs. Moreover, in vivo imiquimod-induced psoriatic skin treated with ATCC12228EVs reduced the characteristic psoriatic skin features, such as acanthosis and cellular infiltrate, as well as VEGF-A, IL-6, KC, IL-23, IL-17F, IL-36γ, and IL-36R expression in a more efficient manner than 983EVs; however, in contrast, Foxp3 expression did not significantly change, and IL-36 receptor antagonist (IL-36Ra) was found to be increased. Our findings showed a distinctive immunological profile induction that is dependent on the clinical or commensal EV origin in a mice model of skin-like psoriasis. Characteristically, proteomics analysis showed differences in the EVs protein content, dependent on origin of the isolated EVs. Specifically, in ATCC12228EVs, we found the proteins glutamate dehydrogenase, ornithine carbamoyltransferase, arginine deiminase, carbamate kinase, catalase, superoxide dismutase, phenol-soluble β1/β2 modulin, and polyglycerol phosphate α-glucosyltransferase, which could be involved in the reduction of lesions in the murine imiquimod-induced psoriasis skin. Our results show that the commensal ATCC12228EVs have a greater protective/attenuating effect on the murine imiquimod-induced psoriasis by inducing IL-36Ra expression in comparison with EVs from a clinical isolate of
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Psoriasis is a chronic inflammatory disease distinguished by an excessive proliferation and abnormal differentiation of keratinocytes. Immune cells, such as T lymphocytes and neutrophils, and ...inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and interleukin 17 (IL-17), are essential for maintaining psoriatic lesions. Additionally, a hypoxic milieu present in the skin promotes the expression of transcriptional factor hypoxia-inducible factor-1 alpha (HIF-1α). This protein regulates the expression of angiogenic and glycolytic factors, such as vascular endothelial grown factor and lactate dehydrogenase (LDH), both relevant in chronic inflammation. The von Hippel-Lindau protein (pVHL) is a negative regulator of HIF-1α. Previously, we found that pVHL was almost absent in the lesions of psoriasis patients; therefore, we investigated the impact of rescue pVHL expression in lesional skin. We used the imiquimod-induced psoriasis-like mouse model as an adenoviral vector that allowed us to express pVHL in the skin. Our data show that, in lesional skin, pVHL expression was reduced, whereas HIF-1α was increased. Remarkably, the retrieval of pVHL prevented psoriatic lesions, diminishing erythema, scale, and epidermal and vascular thickness. Furthermore, pVHL expression was capable of reducing HIF-1α, LDH, TNF-α and immune cell infiltration (mainly IL-17
neutrophils). In conclusion, our results demonstrate that pVHL has a protective role to play in the pathophysiology of psoriasis.
Psoriasis is a chronic inflammatory skin disease where the altered regulation in angiogenesis, inflammation, and proliferation of keratinocytes are the possible causes of the disease, and the ...transcription factor “hypoxia-inducible factor 1-alpha” (HIF-1α) is involved in the homeostasis of these three biological phenomena. In this review, the role of HIF-1α in the cross talk between the cytokines and cells of the immunological system involved in the pathogenesis of psoriasis is discussed.
•Low expression of IL-6 and TNF-α correlates with IκBNS and BCL-3 in uterus.•IκBNS and BCL-3 are expressed in uterus.•IκBNS and BCL-3 control the expression of IL-6 and TNF-α in murine uterus.
The ...dynamic regulation of NF-κB activity in the uterus maintains a favorable environment of cytokines necessary to prepare for pregnancy throughout the estrous cycle. Recently, the mechanisms that directly regulate the NF-κB transcriptional activity in different tissues are of growing interest. IκBNS and BCL-3 are negative nuclear regulators of NF-κB activity that regulate IL-6 and TNF-α transcription, respectively. Both cytokines have been described as important factors in the remodeling of uterus for blastocyst implantation. In this work we analyzed in ICR mice the mRNA expression and protein production profile of IL-6, TNF-α, and their correspondent negative transcription regulators IκBNS or BCL-3 using real-time PCR, western blot and immunochemistry. We found that the expression of TNF-α and IL-6 was oscillatory along the estrous cycle, and its low expression coincided with the presence of BCL-3 and IκBNS, and vice versa, when the presence of the regulators was subtle, the expression of TNF-α and IL-6 was exacerbated. When we compared the production of TNF-α and IL-6 in the different estrous stages relating with diestrus we found that at estrus there is an important increase of the cytokines (p<0.05) decreasing at metestrus to reach the basal expression at diestrus. In the immunochemistry analysis we found that at diestrus BCL-3 is distributed all over the tissue with a barely detected TNF-α, but on the contrary, at estrus the expression of BCL-3 is not detected with TNF-α clearly observable along the tissue; the same phenomenon occur in the analysis of IκBNS and IL-6. With that evidence we suggest that the expression of TNF-α and IL-6 might be regulated through NF-κB nuclear regulators BCL-3 and IκBNS in the uterus of mice as has been demonstrated in other systems.
Psoriasis is a chronic inflammatory skin disease where the altered regulation in angiogenesis, inflammation, and proliferation of keratinocytes are the possible causes of the disease, and the ...transcription factor "hypoxia-inducible factor 1-alpha" (HIF-1α) is involved in the homeostasis of these three biological phenomena. In this review, the role of HIF-1α in the cross talk between the cytokines and cells of the immunological system involved in the pathogenesis of psoriasis is discussed.
This research presents an experimental study focused on measuring temperature at the tool flank during the up-milling process at high cutting speed. The proposed system deals with emissivity ...compensation through a two-photodetector system and during calibration. A ratio pyrometer composed of two photodetectors and a multimode fiber-optic coupler is employed to capture the radiation emitted by the cutting insert. The pyrometer is calibrated using an innovative calibration system that addresses theoretical discrepancies arising from various factors affecting the measurement of cutting temperature. This calibration system replicates the milling process to generate a calibration curve. Experimentally, AISI 4140 steel is machined with coated tungsten carbide inserts, using cutting speeds of 300 and 400 m/min, and feed rates of 0.08 and 0.16 mm/tooth. The results reveal a maximum recorded cutting temperature of 518 °C and a minimum of 304 °C. The cutting temperature tends to increase with higher cutting speeds and feed rates, with cutting speed being the more influential factor in this increase. Both the pyrometer calibration and experimental outcomes yield satisfactory results. Finally, the results showed that the process and the device prove to be a convenient, effective, and precise method of measuring cutting temperature in machine processes.
Surface roughness is affected by the tool geometry, feed rate, overcutting by built-up edge, and tool vibration in the depth of the cut direction. However, dividing the roughness value into each ...component is difficult. Therefore, a new prediction method for the position of the tool contour on the roughness curve is proposed to divide the measured roughness value into components. This proposed method consists of two processes. In one, the roughness curve is divided into the roughness curve formed during each revolution of the work material regardless of the clarity of the feed marks. The other is the process that predicts the vertical position of the tool contour. If the vertical position of the tool contour can be predicted, the vibration and overcutting components of roughness can also be predicted. In this study, the transition of roughness components such as the theoretical roughness, vibration width, and overcutting is studied with the increase in the cutting distance in the turning of chromium molybdenum steel, JIS SCM435. When supplying a 10% emulsion mist, the measured R z is smaller than that of the dry condition. In both the dry and mist supply conditions, the measured R z increases from the beginning of cutting then decreases and then increases again with the increase in the cutting distance. The largest component of the total roughness in both the dry and mist supply conditions is the theoretical roughness R th . The ratio ranges between 50.3% and 78.7%. Regardless of the cutting conditions, the vibration width in the depth of the cut direction is relatively constant. The overcutting slightly increases after the start of cutting, then decreases when the maximum contact length exceeds approximately 0.1 mm. The proposed method verifies the ratio of the surface roughness components and is an effective method for improving the surface roughness.
The study sought to correlate fear, stress, knowledge regarding COVID-19 in Nursing students and recent graduates in Mexico.
Correlational design, sample comprising 912 nursing students and graduates ...during the last 18 months from public and private universities of Mexico. To measure the variables, the study applied the instrument Fear of COVID-19 Scale, knowledge subscale of the scale Knowledge, attitudes, and practices towards COVID-19, and the instrument COVID Stress Scale.
Relationship was found of the age variable with fear, danger of contamination, traumatic stress, knowledge and minor socioeconomic consequences (p<0.05). Likewise, relationship was observed of fear with stress regarding COVID-19, danger of contamination, socioeconomic consequences, xenophobia, traumatic stress, and compulsive checking (p<0.05). Stress and knowledge explain the presence of fear regarding COVID-19 in 50.3%, and fear and knowledge explain stress regarding COVID-19 in 50.4%.
Nursing students and recent graduates have high levels of stress and fear, besides low level of knowledge. The presence of high stress and low knowledge predict fear regarding COVID-19. Interventions are required on knowledge, stress, and fear regarding COVID-19 in the population studied.
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•Gobiesox adustus individuals is a monophyletic group.•Gobiesox adustus populations conform four genetically divergent, allopatric groups restricted to biogeographic ...province.•Analyses confirm the existence of four independent evolutionary units.•Habitat discontinuities, oceanographic processes and ecological characteristics seems to be causes population structure.
The Panamic Clingfish Gobiesox adustus is widely distributed in the Tropical Eastern Pacific (TEP), from the central Gulf of California, Mexico to Ecuador, including the oceanic Revillagigedo Archipelago, and Isla del Coco. This cryptobenthic species is restricted to very shallow rocky-reef habitats. Here, we used one mitochondrial and three nuclear DNA markers from 155 individuals collected across the distribution range of the species in order to evaluate if geographically structured populations exist and to elucidate its evolutionary history. Phylogenetic analyses recovered a monophyletic group, with four well-supported, allopatric subgroups. Each subgroup corresponded to one of the following well-known biogeographic regions/provinces: 1) the Revillagigedo Archipelago, 2) the Cortez + Mexican provinces (Mexico), 3) the Panamic province (from El Salvador to Ecuador), and 4) Isla del Coco. A molecular-clock analysis showed a mean date for the divergence between clade I (the Revillagigedos and Cortez + Mexican provinces) and clade II (Panamic province and Isla del Coco) in the Pliocene, at ca. 5.33 Mya. Within clade I, the segregation between the Revillagigedos and Cortez + Mexican province populations was dated at ca. 1.18 Mya, during the Pleistocene. Within clade II, the segregation between samples of Isla del Coco and the Panamic province samples was dated at ca. 0.77 Mya, during the Pleistocene. The species tree, Bayesian species delimitation tests (BPP and STACEY), the ΦST, AMOVA, and the substantial genetic distances that exist between those four subgroups, indicate that they are independent evolutionary units. These cladogenetic events seem to be related to habitat discontinuities, and oceanographic and geological processes that produce barriers to gene flow for G. adustus, effects of which are enhanced by the intrinsic ecological characteristics of this species.