381 research outputs found
Low Grade Inflammation as a Common Pathogenetic Denominator in Age-Related Diseases: Novel Drug Targets for Anti-Ageing Strategies and Successful Ageing Achievement
Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable
intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis
and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased
predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a
common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show
that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old
humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and agerelated
diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the
ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively
discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling agerelated
low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing
Genotyping of Sex Hormone-Related Pathways in Benign and Malignant Human Prostate Tissues: Data of a Preliminary Study
Prostate cancer (PCa) is a major health issue in Westernized countries, representing a common cause of morbidity
and mortality in the elderly male population. Endogenous sex steroids, along with environmental factors (notably
diet) and host immune and inflammatory responses, are likely to cooperate in the pathogenesis of the disease.
Based on the assumption that a complex endocrine–inflammatory-immune interaction is primarily implicated in
human PCa, we have investigated the interplay between sex steroids and inflammation in development and
growth of human PCa. To this end, we have assessed nine functional single nucleotide polymorphisms (SNP)s of
five genes involved in sex hormone-related pathways in both hyperplastic and malignant human prostate tissues,
as well as in matched controls and in a ‘‘supercontrol’’ group composed of male Sicilian centenarians. In particular,
the following genes were investigated: AR-OMIM313700, SRD5A2-NM-000348, CYP19-NM-031226,
ERS1-NM-001122742, ERS2-NM-001040276. A significant association with prostate cancer was found in seven out
of the nine SNPs considered. Although this is a preliminary study and larger investigations are needed to confirm
the role of these genes in PCa development and/or progression, our data might provide an experimental basis to
develop additional or alternative strategies for prevention and treatment of PCa
Pro-inflammatory genetic markers of atherosclerosis
Atherosclerosis (AS) is a chronic, progressive, multifactorial disease mostly affecting large and medium-sized elastic and muscular arteries. It has formerly been considered a bland lipid storage disease. Currently, multiple independent pathways of evidence suggest this pathological condition is a peculiar form of inflammation, triggered by cholesterol-rich lipoproteins and influenced both by environmental and genetic factors. The Human Genome Project opened up the opportunity to dissect complex human traits and to understand basic pathways of multifactorial diseases such as AS. Population-based association studies have emerged as powerful tools for examining genes with a role in common multifactorial diseases that have a strong environmental component. These association studies often estimate the risk of developing a certain disease in carriers and non-carriers of a particular genetic polymorphism. Dissecting out the influence of pro-inflammatory genes within the complex pathophysiology of AS and its complications will help to provide a more complete risk assessment and complement known classical cardiovascular risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug or lifestyle modification; i.e. it will open the door to personalized medicine
Changes of Inflammatory Mediators in Obese Patients After Laparoscopic Cholecystectomy
Background Obesity is associated with the impairment of
immunological functions. The aim of this study was to
analyze some inflammatory mediators in obese subjects
who underwent laparoscopic cholecystectomy.
Methods Seventeen consecutive female patients with a
BMI ranging from 35 to 45 kg/m2 (obese) and 17 consecutive
female patients with BMI ranging from 20 to
25 kg/m2 (nonobese) were included in the study. All
patients were affected by symptomatic gallbladder stone
disease and underwent laparoscopic cholecystectomy.
Changes in levels of leukocytes, neutrophils, IL-6, IL-10,
leptin, and adiponectin were evaluated.
Results We observed a significant increase in leukocyte
and neutrophil levels in the obese subjects compared to the
nonobese subjects. The serum levels of leptin and IL-6
were higher in the postoperative period (compared to the
baseline values in both groups), and always higher in the
obese. Both adiponectin and IL-10 increased in the postoperative
period in nonobese subjects and was always
higher than in the obese.
Conclusions Obese patients have a stronger acute
inflammatory response than do nonobese subjects in reaction
to surgical stress
Serum levels of total IgE and soluble CD23 in bronchial asthma
The aim of the present study was to compare, during the pollen season, serum levels of total IgE and soluble CD23 (sCD23) from patients with allergic bronchial asthma, with those from healthy subjects. Significantly higher levels of total IgE and sCD23 were found in patients with asthma compared to the control group. Both in normal controls and in asthmatic patients, a significant correlation was shown between the levels of these two molecules. In asthmatic patients, significant correlations were found for both total IgE and sCD23, with lung function measured as bronchial responsiveness to inhaled methacholine. These results suggest that in asthmatic patients, in addition to the study of total serum IgE levels, the assessment of sCD23 serum levels may be helpful in the evaluation of disease activity
Low Grade Inflammation as a Common Pathogenetic Denominator in Age-Related Diseases: Novel Drug Targets for Anti-Ageing Strategies and Successful Ageing Achievement
Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable
intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis
and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased
predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a
common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show
that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old
humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and agerelated
diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the
ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively
discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling agerelated
low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing
NF-κB pathway activators as potential ageing biomarkers: targets for new therapeutic strategies.
Chronic inflammation is a major biological mechanism underpinning biological ageing process and age-related
diseases. Inflammation is also the key response of host defense against pathogens and tissue injury. Current opinion
sustains that during evolution the host defense and ageing process have become linked together. Thus, the large
array of defense factors and mechanisms linked to the NF-κB system seem to be involved in ageing process. This
concept leads us in proposing inductors of NF-κB signaling pathway as potential ageing biomarkers. On the other
hand, ageing biomarkers, represented by biological indicators and selected through apposite criteria, should help to
characterize biological age and, since age is a major risk factor in many degenerative diseases, could be
subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. In this
report, some inflammatory biomarkers will be discussed for a better understanding of the concept of biological
ageing, providing ideas on eventual working hypothesis about potential targets for the development of new
therapeutic strategies and improving, as consequence, the quality of life of elderly populatio
Serum levels of soluble IL-2R, CD4 and CD8 in bronChial asthma
The aim of the present study was to compare serum levels of soluble forms of interleukin-2 receptor, CD4 and CD8, released by lymphocytes during activation of the immune system, in patients with allergic bronchial asthma, with those in healthy subjects. Significantly higher levels of soluble IL-2R and soluble CD4 were found in patients with asthma compared with the control group. In contrast, lower levels of soluble CD8 values were found in patients with asthma compared to the control group. Significant correlations were found for both sIL-2R and sCD4 and these two molecules, with lung function measured as bronchial responsiveness to inhaled methacholine. These results strengthen previous suggestions that in allergic bronchial asthma, activation of T cells plays a significant role in the disease pathogenesis
Serum Levels of Soluble IL-2R, CD4 and CD8 in Chronic Active HCV Positive Hepatitis
The aim of the present study was to compare serum levels of soluble
forms of interleukin-2 receptor, CD4 and CD8, released by
lymphocytes during activation ofthe immune system, in patients with
histologically verified chronic active hepatitis associated to
hepatitis C virus infection, with those in healthy subjects.
Significantly higher levels of soluble IL-2R and soluble CD8 were
found in patients with chronic active hepatitis compared with
controls. In contrast no difference was found for soluble CD4 values
in the two groups. No correlations were found for both sIL-2R and
sCD8 and these two molecules with other parameters of liver
function. These results indicate that in these patients there is a
general activation of the immune system, but the lack of correlation
with parameters of liver function strengthens the suggestion that
this activation does not play a role in the pathogenesis of chronic
type C hepatitis
A Pilot Study on Prostate Cancer Risk and Pro-Inflammatory Genotypes: Pathophysiology and Therapeutic Implications
Host genetic factors are crucial risk determinants for many human cancers. In this framework, an interesting model is
represented by prostate cancer (PC), which is featured by a complex pathophysiology with a strong genetic component. Multiple genes
seem to influence PC risk and several single nucleotide polymorphisms (SNPs) of candidate genes modifying PC susceptibility have been
identified. It is noteworthy the potential association of common SNPs in pro-inflammatory genes with PC risk, since chronic
inflammation is assumed to play a key role in prostate carcinogenesis. With the aim to identify candidate genes as an experimental basis
to develop new strategies for both prevention and treatment of PC, we have investigated the potential role of common SNPs of a gene
cluster (TLR4, TLR2, PTGS2 and 5-Lo), involved in innate and inflammatory response, in PC cases, age-matched controls and
centenarians from Sicily. Six SNPs were genotyped and their association with PC risk determined. Statistical analysis evidenced a
significant association of some pro-inflammatory gene SNPs with an increased risk of PC. Furthermore, significant differences were
observed comparing the three groups in the combined presence of a \u201chigh responder\u201d pro-inflammatory profile. Overall, the present
results suggest the likely association of these SNPs and PC risk, clearly motivating the need of larger studies to confirm the role of these
genes in PC development and/or progression
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