Inflammatory status in human hepatic cirrhosis María Martínez-Esparza María Tristán-Manzano Antonio J Ruiz-Alcaraz Pilar García-Pe?arrubia
World journal of gastroenterology,
11/2015, Letnik:
21, Številka:
41
Journal Article
Odprti dostop
This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus(HCV) infection and chronic ...alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcoholinduced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis(HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared withHCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gutmesenteric lymph nodes-peritoneal-systemic axis.
CD33 (siglec-3), a well-known target in leukemia therapy, is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including NK cells. It may ...constitute a control mechanism of the innate immune system; nevertheless, its role as an inhibitory receptor remains elusive. Using human NK cells as a cellular model, we analyzed CD33 inhibitory function upon different activating receptors. In high-cytotoxicity NKL cells, CD33 displayed a prominent inhibition on cytotoxicity triggered by the activating receptors NKG2D and, in a lower extent, 2B4, whereas it did not inhibit NKp46-induced cytotoxicity. NKp46 was partially inhibited by CD33 only when low-cytotoxicity NKL cells were tested. CD33 triggering did not inhibit IFN-γ secretion, contrasting with ILT-2 and CD94/NKG2A inhibitory receptors that inhibited cytotoxicity and IFN-γ secretion induced by all activating receptors tested. CD33-mediated inhibition of NKG2D-induced triggering involved Vav1 dephosphorylation. Our results support the role of CD33 as an inhibitory receptor preferentially regulating the NKG2D/DAP10 cytotoxic signaling pathway, which could be involved in self-tolerance and tumor and infected cell recognition.
Summary Background & aims Maternal–fetal transfer of docosahexaenoic acid (DHA) is impaired by gestational diabetes mellitus (GDM), but the underlying mechanisms are still unknown. MFSD2a was ...recently recognized as a lyso-phospholipid (lyso-PL) transporter that facilitates DHA accretion in brain. The role of this transporter in placenta is uncertain. We evaluated effects of GDM and its treatment (diet or insulin) on phospholipid species, fatty acid profile in women, cord blood and placental fatty acid carriers. Methods Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 GDM-diet, 20 GDM-insulin). Fetal ultrasound was performed at gestational week 38. At delivery, maternal and neonatal anthropometry was performed, and fatty acids in total lipids and phospholipid species were analyzed in placenta, maternal and venous cord blood. Western-blot analyses were performed for placental fatty acid carriers. Results Fetal abdominal circumference z -score at 38 weeks tended to higher values in GDM ( P = 0.071), pointing toward higher fetal fat accretion in these babies. DHA percentage in cord serum total lipids ( P = 0.029) and lyso-PL ( P = 0.169) were reduced in GDM. Placental MFSD2a was reduced in both GDM groups and was positively correlated to DHA values in cord serum total lipids ( r = 0.388, P = 0.003). Among established placental lipid carriers, only FATP4 was correlated to DHA concentration in placental lyso-PL. In all compartments, DHA percentage was inversely correlated to fetal abdominal circumference. Conclusions In offspring of women with GDM treated either with diet or insulin, higher fetal fat accretion and lower placental MFSD2a contribute to reduce DHA availability. Lyso-PL appear to contribute to materno-fetal DHA transport.
The influence of aerobic training on cardiovascular disorders has already been demonstrated. However, the effect of resistance training is less well known. Arterial stiffness is an increasingly ...important measure in cardiovascular health. Therefore, this review attempted to study the results of resistance training-based interventions on arterial stiffness in healthy people, for both acute and chronic interventions. A literature search was conducted for randomized controlled trials on the acute and chronic effects of strength training. Studies published in PubMed and SportDiscus databases between 1999 and April 2019 were analyzed. In chronic strength training effects, the majority of groups showed large (d = -1.49 to -1.20) and moderate (d = -1.07) decreases, and small and trivial changes in arterial stiffness. In acute effects interventions, a very large decrease (d = -3.92) was observed, while large (d = 1.24-1.48) and very large (d = 3.88) increases were also found. A resistance training-based intervention of more than four weeks' duration with a frequency of two days per week seems not to compromise cardiovascular health, due to decreases in arterial stiffness. However, there is a general trend towards both increasing and maintaining arterial stiffness after isolated strength training sessions.
Gestational diabetes mellitus (GDM) is associated with increased fetal adiposity, which may increase the risk of obesity in adulthood. The placenta has insulin receptors and maternal insulin can ...activate its signaling pathways, affecting the transport of nutrients to the fetus. However, the effects of diet or insulin treatment on the placental pathophysiology of GDM are unknown.
There are very few studies on possible defects in the insulin signaling pathway in the GDM placenta. Such defects could influence the placental transport of nutrients to the fetus. In this review we discuss the state of insulin signaling pathways in placentas of women with GDM, as well as the role of exogenous insulin in placental nutrient transport to the fetus, and fetal adiposity. Key Messages: Maternal insulin in the third trimester is correlated with fetal abdominal circumference at that time, suggesting the important role of insulin in this process. Since treatment with insulin at the end of pregnancy may activate placental nutrient transport to the fetus and promote placental fatty acid transfer, it would be interesting to improve maternal hyperlipidemia control in GDM subjects treated with this hormone. More research in this area with high number of subjects is necessary.
Core stability has a strong relationship with dynamic balance stability (DBS). The purpose of this review with meta-analysis was to analyse the effects of core training programmes from different ...studies on DBS. A literature search was performed using different databases. Subgroups analyses on duration, training frequency, total sessions, chronological age, training status, equipment and movements were performed. A random-effects model for meta-analyses was used. Thirteen studies were selected for the systematic review and 10 for the meta-analysis, comprising 226 participants. A moderate effect was noted for core training on DBS (p < 0.001; ES = 0.634). Greater DBS improvements were found in core training interventions with ≤6 weeks (ES = 0.714), after high volume (ES = 0.787) and more frequent interventions (ES = 0.787), as well as in younger participants (ES = 0.832). In addition, body weight exercises may be better than med ball, swiss ball or band resisted exercises. Core training improves DBS among athletes and a non-trained population, creating a more solid stable base that allows better lower extremity movements. This could be more effective considering different modulators ≤6 weeks intervention, >2 sessions per week, >17 total sessions, body weight core programmes and applied to ≤18.0 years old.
Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact ...that an estimated 176 million women are affected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not efficient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework,
crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates. Several inflammation-related signaling pathways have been included among the known targets of isothiocyanates, but those involving aquaporin water channels have an important role in endometriosis. Therefore, the aim of this review is to highlight the promising effects of the phytochemicals present in
spp. as major candidates for inclusion in a dietary approach aiming to improve the inflammatory condition of women affected with endometriosis. This review points out the potential roles of glucosinolates and isothiocyanates from
as anti-inflammatory compounds, which might contribute to a reduction in endometriosis symptoms. In view of these promising results, further investigation of the effect of glucosinolates on chronic inflammatory diseases, either as diet coadjuvants or as therapeutic molecules, should be performed. In addition, we highlight the involvement of aquaporins in the maintenance of immune homeostasis. In brief, glucosinolates and the modulation of cellular water by aquaporins could shed light on new approaches to improve the quality of life for women with endometriosis.
Macrophages are a diverse myeloid cell population involved in innate and adaptive immune responses, embryonic development, wound repair, and regulation of tissue homeostasis. These cells link the ...innate and adaptive immunities and are crucial in the development and sustainment of various inflammatory diseases. Macrophages are tissue-resident cells in steady-state conditions; however, they are also recruited from blood monocytes after local pathogen invasion or tissue injury. Peritoneal macrophages vary based on their cell complexity, phenotype, and functional capabilities. These cells regulate inflammation and control bacterial infections in the ascites of decompensated cirrhotic patients. Our recent work reported several phenotypic and functional characteristics of these cells under both healthy and pathological conditions. A direct association between cell size, CD14/CD16 expression, intracellular level of GATA-6, and expression of CD206 and HLA-DR activation/maturation markers, indicate that the large peritoneal macrophage CD14
high
CD16
high
subset constitutes the mature phenotype of human resident peritoneal macrophages during homeostasis. Moreover, elevated expression of CD14/CD16 is related to the phagocytic capacity. The novel large CD14
high
CD16
high
peritoneal subpopulation is increased in the ascites of cirrhotic patients and is highly sensitive to lipopolysaccharide (LPS)-induced activation, thereby exhibiting features of inflammatory priming. Thus, phosphorylation of ERK1/2, PKB/Akt, and c-Jun is remarkably increased in response to LPS
in vitro
, whereas that of p38 MAPK is reduced compared with the monocyte-derived macrophages from the blood of healthy controls. Furthermore,
in vitro
activated monocyte-derived macrophages from ascites of cirrhotic patients secreted significantly higher levels of IL-6, IL-10, and TNF-α and lower amounts of IL-1β and IL-12 than the corresponding cells from healthy donor’s blood. Based on these results, other authors have recently reported that the surface expression level of CD206 can be used to identify mature, resident, inflammatory peritoneal macrophages in patients with cirrhosis. Soluble CD206 is released from activated large peritoneal macrophages, and increased concentrations in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) indicate reduced odds of survival for 90 d. Hence, the level of soluble CD206 in ascites might be used to identify patients with SBP at risk of death. In conclusion, peritoneal macrophages present in ascites of cirrhotic patients display multiple phenotypic modifications characterized by reduced ratio of cells expressing several membrane markers, together with an increase in the ratios of complex and intermediate subpopulations and a decrease in the classic-like subset. These modifications may lead to the identification of novel pharmaceutical targets for prevention and treatment of hepatic damage.
Atrial fibrillation (AF) is common and increases the risk of stroke and mortality. Previous studies have suggested that air pollution is an important risk factor for new-onset AF. Herein, we review ...the evidence regarding: 1) the association between exposure to particulate matter (PM) and new-onset AF, and 2) the risk of worse clinical outcomes in patients with pre-existent AF and their relation to PM exposure.
A selection of studies between 2000 and 2023 linking PM exposure and AF was performed through searches in PubMed, Scopus, Web of Science, and Google Scholar.
17 studies from different geographical areas demonstrated that exposure to PM was associated with an increased risk of new-onset AF, although the results were heterogeneous regarding the temporal pattern (short- or long-term) ultimately related to AF. Most of the studies concluded that the risk of new-onset AF increased between 2 %–18 % per 10 μg/m3 increment in PM2.5 or PM10 concentrations, whereas the incidence (percentage of change of incidence) increased between 0.29 %–2.95 % per 10 μg/m3 increment in PM2.5 or PM10. Evidence about the association between PM and adverse events in patients with pre-existent AF was scarce but 4 studies showed a higher risk of mortality and stroke (between 8 %–64 % in terms of hazard ratio) in patients with pre-existent AF when PM exposure was higher.
Exposure to PM (both PM2.5 and PM10) is a risk factor for AF, and a risk factor for mortality and stroke in patients who already suffer from AF. Since the relationship between PM and AF is independent of the region of the world, PM should be considered as a global risk factor for both AF and worse clinical outcomes in AF patients. Specific measures to prevent air pollution exposure need to be adopted.
Upper panel = Association between particulate matter exposure and new-onset atrial fibrillation.
Lower panel = Risk of mortality and stroke in patients with pre-existent atrial fibrillation in relation to particulate matter exposure. Display omitted
•Previous evidence showed that air pollution increases atrial fibrillation (AF) risk.•Short and long-term exposure to PM2.5 or PM10 leads to a higher risk of new-onset AF.•In patients with previous AF, exposure to high PM2.5 or PM10 concentrations raises mortality and stroke risks.•Air pollution should be considered as a risk factor for both AF and adverse events.
Acute myeloid leukemia (AML) is a cancer of the myeloid blood cells mainly treated with chemotherapy for cancer remission, but this non-selective treatment also induces numerous side effects. ...Investigations with bioactive compounds from plant-derived foods against cancer have increased in the last years because there is an urgent need to search for new anti-leukemic agents possessing higher efficacy and selectivity for AML cells and fewer negative side effects. In this study, we analyzed the anti-leukemic activity of several phytochemicals that are representative of the major classes of compounds present in cruciferous foods (glucosinolates, isothiocyanates, hydroxycinnamic acids, flavonols, and anthocyanins) in the human acute myeloid leukemia cell line HL-60. Our results revealed that among the different Brassica-derived compounds assayed, sulforaphane (SFN) (an aliphatic isothiocyanate) showed the most potent anti-leukemic activity with an IC50 value of 6 µM in dose-response MTT assays after 48 h of treatment. On the other hand, chlorogenic acid (a hydroxycinnamic acid) and cyanidin-3-glucoside (an anthocyanin) also displayed anti-leukemic potential, with IC50 values of 7 µM and 17 µM after 48 h of incubation, respectively. Importantly, these compounds did not show significant cell toxicity in macrophages-like differentiated cells at 10 and 25 µM, indicating that their cytotoxic effects were specific to AML cancer cells. Finally, we found that these three compounds were able to induce the NRF2/KEAP1 signaling pathway in a dose-dependent manner, highlighting SFN as the most potent NRF2 activator. Overall, the present evidence shed light on the potential for using foods and ingredients rich in anticancer bioactive phytochemicals from Brassica spp.
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