Growing evidence of the microbiome's role in human health and disease has emerged since the creation of the Human Microbiome Project. Recent studies suggest that alterations in microbiota composition (dysbiosis) may play an essential role in the occurrence, development, and prognosis of prostate cancer (PCa), which remains the second most frequent male malignancy worldwide. Current advances in biological technologies, such as high-throughput sequencing, transcriptomics, and metabolomics, have enabled research on the gut, urinary, and intra-prostate microbiome signature and the correlation with local and systemic inflammation, host immunity response, and PCa progression.
View Article and Find Full Text PDFThe main hypothesis of this study is that gene expression profiles (GEPs) integrating both tumor antigenicity and a pre-existing adaptive immune response can be used to generate distinct immune-related signatures of BRAF mutant colorectal cancers (BRAF-CRCs) to identify actionable biomarkers predicting response to immunotherapy. GEPs of 89 immunotherapy-naïve BRAF-CRCs were generated using the Pan-Cancer IO 360 gene expression panel and the NanoString nCounter platform and were correlated with microsatellite instability (MSI) status and with CD8+ tumor-infiltrating lymphocyte (TIL) content. Hot/inflamed profiles were found in 52% of all cases, and high scores of Tumor Inflammation Signature were observed in 42% of the metastatic BRAF-CRCs.
View Article and Find Full Text PDFHomologous Recombination Deficiency (HRD) is a frequent feature of high-grade epithelial ovarian carcinoma (EOC), associated with sensitivity to PARP-inhibitors (PARPi). The best characterized causes of HRD in EOCs are germline or somatic mutations in and genes. Although promoter methylation is a well-known mechanism of gene transcriptional repression, few data have been published about gene methylation in EOCs.
View Article and Find Full Text PDFRed clover (Trifolium pratense L., Fabaceae; RCL), a perennial plant rich in isoflavones, is a natural alternative for menopausal symptoms, as well as antiaging and antioxidant. Isoflavone preparations usually contain aglycones and β-glycosides.
View Article and Find Full Text PDFBackground: Parkinson's disease (PD) affects an estimated 7 to 10 million people worldwide, and only symptomatic treatments are presently available to relieve the consequences of brain dopaminergic neurons loss. Neuronal degeneration in PD is the consequence of neuroinflammation in turn influenced by peripheral adaptive immunity, with CD4+ T lymphocytes playing a key role. CD4+ T cells may however acquire proinflammatory phenotypes, such as T helper (Th) 1 and Th17, as well as anti-inflammatory phenotypes, such as Th2 and the T regulatory (Treg) one, and to what extent the different CD4+ T cell subsets are imbalanced and their functions dysregulated in PD remains largely an unresolved issue.
View Article and Find Full Text PDFThis study tests the hypothesis that in isolated human polymorphonuclear leukocytes (PMN) adrenergic ligands can affect neutrophil extracellular trap (NET) formation. We have previously shown that, in PMN, adrenaline (A), through the activation of adrenergic receptors (AR), reduces stimulus-dependent cell activation; we have, therefore, planned to investigate if AR are involved in NET production. PMN were obtained from venous blood of healthy subject.
View Article and Find Full Text PDFThis data article presents a dataset of mRNA levels for dopaminergic receptors, adrenoceptors and for tyrosine hydoxylase, the rate-limiting enzyme in the synthesis of catecholamines, in peripheral blood mononuclear cells as well as in CD4+ T effector and regulatory cells from subjects with clinically isolated syndromes (CIS), which is a first episode of neurological disturbance(s) suggestive of multiple sclerosis. CIS subjects are divided into two groups according to their eventual progression, after 12 months from CIS, to clinically established multiple sclerosis. The data reported are related to the article entitled "Dopaminergic receptors and adrenoceptors in circulating lymphocytes as putative biomarkers for the early onset and progression of multiple sclerosis" (M.
View Article and Find Full Text PDFParkinson's disease (PD) is characterized by loss of dopaminergic neurons in substantia nigra pars compacta, α-synuclein (α-syn)-rich intraneuronal inclusions (Lewy bodies), and microglial activation. Emerging evidence suggests that CD4+ T lymphocytes contribute to neuroinflammation in PD. Since the mainstay of PD treatment is dopaminergic substitution therapy and dopamine is an established transmitter connecting nervous and immune systems, we examined CD4+ T naive and memory lymphocytes in PD patients and in healthy subjects (HS), with specific regard to dopaminergic receptor (DR) expression.
View Article and Find Full Text PDFClinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β.
View Article and Find Full Text PDFObjectives: Adrenergic modulation of immunity has been extensively characterized, however, few information exist regarding polymorphonuclear leukocytes (PMN), despite their key role in immunity and inflammation. We investigated the effect of adrenergic agents on human PMN migration, CD11b and CD18 expression, reactive oxygen species (ROS) and interleukin (IL)-8 production, and on adrenoceptor (AR) expression.
Methods: Migration was measured by the Boyden chamber assay, CD11b/CD18 expression was assessed by flow cytometry, intracellular ROS were detected by spectrofluorimetry, and IL-8 was quantitated by standard ELISA assay.
Objective: Observations in both animal models of arthritis and patients with rheumatoid arthritis (RA) suggest a role for dopamine and its receptors in RA. Because synovial fibroblasts (SFs) contribute to inflammation and joint destruction in RA, the aim of this study was to investigate dopaminergic pathways in SFs obtained from patients with RA and, for comparison, in SFs from patients with osteoarthritis (OA) undergoing knee joint replacement surgery.
Methods: The expression of all dopamine receptors (D1 -D5 ) and dopamine transporter was assessed by immunofluorescence and immunohistochemical staining.
Bergamot (Citrus aurantium L. subsp. bergamia) essential oil (BEO) is used in folk medicine as an antiseptic and anthelminthic and to facilitate wound healing.
View Article and Find Full Text PDFObjective: We investigated dopaminergic inhibition of CD4+CD25(high) regulatory T lymphocytes (Treg) in relapsing-remitting multiple sclerosis (MS) patients treated with interferon (IFN)-β.
Methods: MS patients were prospectively studied at baseline and during 1 year of IFN-β, and compared with healthy controls (HCs). Treg were separated by immunomagnetic sorting and the effect of dopamine (DA) on Treg was assessed in coculture experiments with homologous effector T lymphocytes (Teff).
Plants are the main source of molecules with antioxidant and radical scavenging properties that aid the natural defence systems of cells and may be involved in the preservation of human health, particularly preventing all the physiopathological conditions where oxidative damage is a hallmark. Achillea collina Becker ex Rchb. is a medicinal plant of the Achillea millefolium aggregate (yarrow) traditionally used, particularly in mountain areas, as an infusion or alcohol extract for its digestive, antiinflammatory, analgesic, antipyretic and wound healing properties.
View Article and Find Full Text PDFObjective: To investigate the endogenous dopaminergic/adrenergic system of lymphocytes in multiple sclerosis (MS) patients during treatment with interferon (IFN)-beta.
Methods: Patients with relapsing-remitting MS undergoing IFN-beta treatment were prospectively studied during the first year of treatment. Circulating lymphocytes were obtained at baseline and after 1, 3, 6 and 12 months of treatment and assayed for catecholamine (CA) production and mRNA expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in the synthesis of CA), beta(2)-adrenoceptors (AR) and D2, D3 and D5 dopaminergic receptors (DR).
Lignans are plant polyphenols which may possess anticancer, antioxidant, antimicrobial, anti-inflammatory and immunomodulatory activities. In particular, the lignan 7-hydroxymatairesinol (HMR/lignan, HMR) is a novel precursor of the mammalian lignan enterolactone (EL). In the present study, we investigated the estrogenicity of HMR and of EL in comparison to estradiol (E2), by measuring their effects on growth and apoptotic markers in the human estrogen-sensitive cell line MCF-7.
View Article and Find Full Text PDFBackground: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial.
Methods: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2).
Results: The RR interval value (p < 0.
CD4+CD25+ regulatory T lymphocytes (Tregs) are specialized T cells playing a key role in the control of immune homeostasis. Here, we show that human Tregs constitutively express tyrosine hydroxylase (TH, EC 1.14.
View Article and Find Full Text PDFInterferon (IFN)-gamma plays a pivotal role in the pathogenesis of multiple sclerosis (MS), while IFN-beta may be able to modify the clinical course of the disease, eventually also by counterbalancing IFN-gamma-mediated effects. Catecholamines (CA) exert important effects on the immune response, both as transmitters between the nervous and the immune system, as well as autocrine/paracrine mediators in immune cells, and several lines of evidence support their involvement in MS. In particular, dysregulated production of CA seems to occur in peripheral blood mononuclear cells (PBMCs) of MS patients.
View Article and Find Full Text PDFActivation of human peripheral blood mononuclear cells (PBMC) triggers endogenous production of catecholamines (CA) through protein kinase (PK) C-dependent induction of tyrosine hydroxylase (TH; EC 1.14.16.
View Article and Find Full Text PDFDopamine (DA) modulates apoptosis in neuronal and non-neuronal cells, and dopaminergic pathways contribute to neurodegenerative disease. Human lymphocytes express dopaminergic receptors and DA transporters, and synthesize endogenous catecholamines, which may modulate apoptosis in these cells. In the present study, dopaminergic modulation of apoptosis was investigated in human peripheral blood mononuclear cells (PBMCs) obtained from healthy donors.
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