1,226 research outputs found

    The antagonism of the prokineticin system counteracts bortezomib induced side effects: Focus on mood alterations

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    The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation. We also verify if the therapeutic treatment with the antagonist of the prokineticin (PK) system PC1, which is known to contrast pain and neuroinflammation, can prevent mood alterations. Mice were treated with BTZ (0.4 mg/kg three times/week for 4 weeks); mechanical allodynia and locomotor activity were evaluated over time while anxiety (dark light and marble burying test), depression (sucrose preference and swimming test) and supraspinal neuroinflammation were checked at the end of the protocol. BTZ treated neuropathic mice develop anxiety and depression. The presence of mood alterations is related to the presence of neuroinflammation and PK system activation in prefrontal cortex, hippocampus and hypothalamus with high levels of PK2 and PKR2 receptor, IL‐6 and TNF‐α, TLR4 and an upregulation of glial markers. PC1 treatment, counteracting pain, prevented the development of supraspinal inflammation and depression‐like behavior in BTZ mice

    Small non-coding RNA profiling in plasma extracellular vesicles of bladder cancer patients by next-generation sequencing: Expression levels of miR-126-3p and piR-5936 increase with higher histologic grades

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    Bladder cancer (BC) is the tenth most frequent cancer worldwide. Due to the need for recurrent cystoscopies and the lack of non-invasive biomarkers, BC is associated with a high management burden. In this respect, small non-coding RNAs (sncRNAs) have been investigated in urine as possible biomarkers for BC, but in plasma their potential has not yet been defined. The expression levels of sncRNAs contained in plasma extracellular vesicles (EVs) from 47 men with BC and 46 healthy controls were assessed by next-generation sequencing. The sncRNA profiles were compared with urinary profiles from the same subjects. miR-4508 resulted downregulated in plasma EVs of muscle-invasive BC patients, compared to controls (adj-p = 0.04). In World Health Organization (WHO) grade 3 (G3) BC, miR-126-3p was upregulated both in plasma EVs and urine, when compared to controls (for both, adj-p < 0.05). Interestingly, two sncRNAs were associated with the risk class: miR-4508 with a downward trend going from controls to high risk BC, and piR-hsa-5936 with an upward trend (adj-p = 0.04 and adj-p = 0.05, respectively). Additionally, BC cases with low expression of miR-185-5p and miR-106a-5p or high expression of miR-10b-5p showed shorter survival (adj-p = 0.0013, adj-p = 0.039 and adj-p = 0.047, respectively). SncRNAs from plasma EVs could be diagnostic biomarkers for BC, especially in advanced grade

    Preliminary study on the effect of size of individual stall on the behavioural and immune reactions of dairy calves

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    Ten Italian Friesian female calves were housed in individual stalls of two different dimensions (0.73 m x 1.21 m vs 1.00 m x 1.50 m) during the Ist month of life in order to evaluate the effect of space on the welfare of dairy calves. Behavioural observations were made on d 2 to 3 (period 1) and on d 28 to 29 (period 2) during daylight using a time-lapse video recording system. At 10, 20, and 30 d, blood samples were taken and analysed with phytohemagglutinin stimulation to determine lymphocyte proliferation. During the second period, the calves in large stall spent more time lying (P<0.05) and grooming (P<0.001), and the calves in small stalls exhibited more time searching for feed (P<0.001). Lymphocyte proliferation was statistically lower in calves housed in smaller stalls (P<0.01). Moreover, lymphocyte proliferation was negatively correlated with time spent searching for feed (P<0.01)

    Dietary total antioxidant capacity and colorectal cancer in the Italian EPIC cohort

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    Background Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed. Methods We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center. Results Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44\u20130.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19\u20133.66; 3rd tertile 2.48 95%CI: 1.32\u20134.66; P trend 0.007). Intakes of vitamin C, vitamin E, and f-carotene were not significantly associated with colorectal cancer risk. Conclusions Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers

    Lymphocyte subsets and the role of Th1/Th2 balance in stressed chronic pain patients

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    Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients. Copyright (c) 2008 S. Karger AG, Basel

    Type 1 plasminogen activator inhibitor as a common risk factor for cancer and ischaemic vascular disease: the EPICOR study

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    OBJECTIVES: We examined the association of plasminogen activator inhibitor-1 (PAI-1) levels with colorectal cancer, breast cancer, acute coronary syndrome (ACS) and ischaemic stroke. DESIGN: Nested case-cohort study. SETTING: The European Prospective Investigation into Cancer and Nutrition-Italy cohort. PARTICIPANTS: A centre-stratified random sample of 850 participants (286 men, 564 women) was selected as subcohort and compared with 303 colorectal cancers, 617 breast cancers, 688 ACS and 158 ischaemic strokes, in a mean follow-up of 9.11 years. MAIN OUTCOMES AND MEASURES: Primary incident cases of colon cancer, breast cancer, ACS and ischaemic stroke. PAI-1 levels were measured in citrated plasma by ELISA. HR and 95% CI, adjusted by relevant confounders and stratified by centre, were estimated by a Cox regression model using Prentice method. RESULTS: Individuals in the highest compared with the lowest quartile of PAI-1 had significantly increased risk of colorectal cancer (RR=2.28; 95% CI 1.46 to 3.55; P for trend<0.0012), breast cancer (HR=1.70; 95% CI 1.21 to 2.39; p<0.0055), ACS (HR=2.57; 95% CI 1.75 to 3.77; p<0.001) and ischaemic stroke (HR=2.27; 95% CI 1.28 to 4.03; p<0.0017), after adjustment for sex and age. Additional adjustment for disease-specific confounders, insulin or other metabolic variables did not modify the associations. Risk of colon cancer was stronger for men and for whole and distal colon localisation. Risk for breast cancer was stronger in postmenopausal women. CONCLUSIONS: Our data provide the first evidence that elevated levels of PAI-1 are potential risk factors for colorectal and breast cancer and a common pathway for cancer and cardiovascular disease
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