This Special Issue of the International Journal of Molecular Sciences (IJMS) focuses on ‘Genetic ... more This Special Issue of the International Journal of Molecular Sciences (IJMS) focuses on ‘Genetic and Molecular Regulations of Neuronal Activity’ [...]
Background The diffuse distribution of nicotinic cholinergic receptors (nAChRs) in both brain and... more Background The diffuse distribution of nicotinic cholinergic receptors (nAChRs) in both brain and peripheral immune cells points out their involvement in several pathological conditions. Indeed, the deregulated function of the nAChR was previously correlated with cognitive decline and neuropsychiatric symptoms in Alzheimer’s disease (AD) and Dementia with Lewy bodies (DLB). The evaluation in peripheral immune cells of nAChR subtypes, which could reflect their expression in brain regions, is a prominent investigation area. Objectives This study aims to evaluate the expression levels of both the nAChR subunits and the main known inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of patients with DLB and AD to better characterize their involvement in these two diseases. Results Higher gene expression levels of TNFα, IL6 and IL1β were observed in DLB and AD patients in comparison with healthy controls (HC). In our cohort, a reduction of nAChRα4, nAChRβ2 and nAChRβ4 was...
Periodontitis is one of the main frequent intraoral diseases. Pathogenesis triggers are the immun... more Periodontitis is one of the main frequent intraoral diseases. Pathogenesis triggers are the immune responses with pro-inflammatory cytokines production and non-coding RNAs expression. The purpose of the present study was to evaluate the involvement of selected miRNAs in various stages of periodontitis and their relationship with the levels of inflammatory mediators in gingival crevicular fluid (GCF). For this study, 36 subjects (21 with periodontal disease, 15 healthy controls) were selected with an age mean of 59.1 ± 3.7 years. Clinical parameters included plaque index, gingival index, sulcus bleeding index, pocket depth, and clinical attachment level. The GCF samples were taken using capillary paper. The levels of miRNAs in GCF were estimated using a Real-Time PCR and TNFα and IL-6 levels were assessed by enzyme-linked immunosorbent assay (ELISA). The results indicated that the miRNA-103a-3p, miRNA-23a-3p, miRNA-15a-5p, and miRNA-223-3p were significantly upregulated with respect ...
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss o... more Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss of the central nervous system (CNS). Despite its spread throughout the world, the mechanisms that determine its onset are still to be defined. Immunological, genetic, viral, and environmental factors and exposure to chemicals may trigger MS. Many studies have highlighted the anti-inflammatory and anti-oxidant effects of medicinal herbs, which make them a natural and complementary treatment for neurodegenerative diseases. A severe reduction of several MS symptoms occurs with herbal therapy. Thus, the request for medicinal plants with potential beneficial effects, for MS patients, is constantly increasing. Consequently, a production increase needs. Unfortunately, many medicinal herbs were untested and their action mechanism, possible adverse effects, contraindications, or interactions with other drugs, are poorly or not investigated. Keeping in mind the pathological mechanisms of MS and the...
Background. Wound healing (WH) is a complex process involving several stages, such as hemostasis,... more Background. Wound healing (WH) is a complex process involving several stages, such as hemostasis, inflammation, re-epithelialization, and remodeling. Many factors can impair WH, and different pharmacological approaches were studied to date, but the increase in antibiotic resistance, invasiveness, treatment duration, and high cost, have often hampered the resolution of the wound. In this study, we investigated the possible application of water-soluble carvacrol prodrugs (WSCPs) and hyaluronic acid (HA) and their formulations (WSCPs/HA) to improve WH and regulate the inflammatory response. Materials and methods. Firstly, the cytotoxicity of 0.1, 1 and 10 µg/mL of HA, WSCPs and WSCPs/HA formulations were evaluated on HaCaT cells and THP-1 cell lines. The ability of WSCPs/HA formulations to modulate wound repair was evaluated in an in vitro model of WH, using HaCaT cells at 6, 18, and 24 h. The expression of WH mediators, after wound closure was determined by qRT-PCR. Following, we pola...
Human periodontal ligament mesenchymal stem cells (hPDLSCs) are a promising cell type model for r... more Human periodontal ligament mesenchymal stem cells (hPDLSCs) are a promising cell type model for regenerative medicine applications due to their anti-inflammatory, immunomodulatory and non-tumorigenic potentials. Extremely low-frequency electromagnetic fields (ELF-EMF) are reported to affect biological properties such as cell proliferation and differentiation and modulate gene expression profile. In this study, we investigated the effects of an intermittent ELF-EMF exposure (6 h/day) for the standard differentiation period (28 days) and for 10 days in hPDLSCs in the presence or not of osteogenic differentiation medium (OM). We evaluated cell proliferation, de novo calcium deposition and osteogenic differentiation marker expression in sham and ELF-EMF-exposed cells. After ELF-EMF exposure, compared with sham-exposed, an increase in cell proliferation rate (p < 0.001) and de novo calcium deposition (p < 0.001) was observed after 10 days of exposure. Real-time PCR and Western blot...
Recently, mineral healing clays have gained much attention for wound-dressing applications. Here,... more Recently, mineral healing clays have gained much attention for wound-dressing applications. Here, we selected halloysite (HAL) clay as a biocompatible, non-toxic material that is useful as a drug delivery system to enhance the healing properties of water-soluble terpenoids 1-3 (T1-3). Terpenoids-loaded HAL clay (TH1-3) was prepared and characterized by adsorption equilibrium studies, X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and release studies. The results reveal that T1-3 were adsorbed at the HAL surface with good efficiency. The prevalent mechanism of drug retention is due to the adsorption via electrostatic interactions between the cationic groups of the T1-3 and the HAL’s external surface. Release studies demonstrated that T3 was released in a higher percentage (>60%) compared to T1-2 (≈50%). Additionally, TH1-3 were assessed for their antimicrobial activity and ...
Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation... more Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation, and remodeling. Impaired WH may be the consequence of the alteration of one of these phases and represents a significant health and economic burden to millions of individuals. Thus, new therapeutic strategies are the topics of intense research worldwide. Although radiofrequency electromagnetic field (RF-EMF) has many medical applications in rehabilitation, pain associated with musculoskeletal disorders, and degenerative joint disorders, its impact on WH is not fully understood. The process of WH begins just after injury and continues during the inflammatory and proliferative phases. A thorough understanding of the mechanisms by which RF-EMF can improve WH is required before it can be used as a non-invasive, inexpensive, and easily self-applicable therapeutic strategy. Thus, the aim of this study is to explore the therapeutic potential of different exposure setups of RF-EMF to drive fas...
Background: The improvements in HIV infection therapy and the large availability of antiretrovira... more Background: The improvements in HIV infection therapy and the large availability of antiretroviral drugs have led to an increased survival among HIV infected people, and simultaneously to a raised morbidity and mortality due to not-AIDS-related events in this group compared to the general population. An increased systemic inflammation and a persistent immune activation play a pivotal role in determining high rates of non-AIDS comorbidities. In the last years, many natural or synthetic immunomodulatory molecules acting by different mechanisms have been conceived. Pidotimod is a synthetic dipeptide molecule showing immunomodulatory properties. The aim of this pilot study was to evaluate the effects of Pidotimod supplementation on residual inflammation in HIV infected population. Methods: Forty HIV positive individuals under cART were enrolled: 30 were treated with Pidotimod supplementation (study group) and 10 served as control group (without Pidotimod supplementation). For all partic...
Several clinical studies have suggested the impact of sinusoidal and pulsed electromagnetic field... more Several clinical studies have suggested the impact of sinusoidal and pulsed electromagnetic fields in quickening wound repair processes and tissue regeneration. The clinical use of extremely low-frequency electromagnetic fields could represent a novel frontier in tissue repair and oral health, with an interesting clinical perspective. The present study aimed to evaluate the effect of an extremely low-frequency sinusoidal electromagnetic field (SEMF) and an extremely low-frequency pulsed electromagnetic field (PEMF) with flux densities of 1 mT on a model of oral healing process using gingival fibroblasts. An in vitro mechanical injury was produced to evaluate wound healing, migration, viability, metabolism, and the expression of selected cytokines and protease genes in fibroblasts exposed to or not exposed to the SEMF and the PEMF. Interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β), metalloproteinase 2 (MMP-2), monocyte chemoattractant protein 1 (MCP-1), inducible nitric...
Periodontal disease (PD) is an inflammatory condition of the tissues supporting the teeth, which ... more Periodontal disease (PD) is an inflammatory condition of the tissues supporting the teeth, which is widespread among the adult population. Evidence shows a relationship between PD and vitamin D levels, which is involved in the regulation of bone metabolism, mineral homeostasis, and inflammatory response. This study aimed to perform a simultaneous evaluation of inflammatory mediators and vitamin D levels in saliva in periodontopathic patients to better understand their role in periodontal disease. In this observational study, clinical periodontal parameter examination was performed for each patient. Moreover, the saliva levels of 25(OH)D3, TGFβ, IL-35, IL-17A, and MMP9 were evaluated using an ELISA assay. An increase in TGFβ, IL-35, MMP9, and IL-17A salivary levels and a reduction in 25(OH)D3 levels were observed in periodontopathic patients with respect to the healthy controls. The present study revealed significant positive correlation between cytokines and highly negative correlat...
To test whether gas and oil field work is accompanied by stress and altered immune function, the ... more To test whether gas and oil field work is accompanied by stress and altered immune function, the perception of workplace stress, levels of salivary cortisol, plasma levels, and mononuclear cell production of cytokines were examined in 80 healthy workers recruited among a population of operators on gas and oilfields. Specific questionnaires for determining the perception of anxiety, occupational stress, and subjective symptoms were administered. Salivary cortisol and cytokines plasma levels were evaluated by Elisa and to investigate immune function, both spontaneous and PHA-or LPS-induced expression and production of cytokines were assessed by qRT-PCR. Workers showed medium stress levels at work, with growth and increased motivation for work, and based on salivary cortisol concentrations, were divided into two groups of ≤10 ng/mL (n = 31) or >10 ng/mL (n = 49). Statistically significant higher plasma levels of IL-6, while lower TNFα, were detected in workers with cortisol >10 ng/mL. Also, BMI, DL, JD and Job strain were significantly higher in workers with cortisol >10 ng/mL. Thus, even modest variations of cortisol might have a role in the modulation of immune response and worker's vulnerability to health imbalance.Thus, the evaluation of immune status, in addition to cortisol levels, could be useful to prevent illnesses; exacerbation of pre-existing conditions; morbidity; and consequent absences from work, with economic repercussions.
Background: Alzheimer’s disease (AD), the most threatening neurodegenerative diseases, is charact... more Background: Alzheimer’s disease (AD), the most threatening neurodegenerative diseases, is characterized by the loss of memory and language function, an unbalanced perception of space and other cognitive and physical manifestations. Pathology of the AD is characterized by neuronal loss, and the extensive distribution of senile plaques and neurofibrillary tangles (NFTs). The role of environment and the diet in the AD is being studied actively, and nutrition is certainly one of the main factors playing a prominent role in the prevention of neurodegenerative diseases. In this context, the relationship between dementia and wine use/abuse has received increased research interest in recent times, with varying and often conflicting results. Scope and approach: This review aims to critically summarize the most recent studies conducted to clarify the relationship between wine drinking and AD, as well as whether effects are influenced by quantity and/or frequency of drinking. Key findings and ...
RANTES and related molecules, constitute the C-C class of chemokine supergene family and a group ... more RANTES and related molecules, constitute the C-C class of chemokine supergene family and a group of cytokines produced by hematopoietic cells constitute the MCP-1 or C-X-C class. The roles of most of these chemokines are not well known, although members of the C-X-C family are inflammatory agents. Here, we report that intradermal injection of RANTES 10 ng/50 μL subcutaneously in the abdominal skin produced a strong inflammatory reaction, as evidenced by Evans blue dye, greater than FMLP (10−6 mol/L) (∼57%); while MCP-1, 10 ng/50 μL was less effective than FMLP (10−6 mol/L) (∼54%). Moreover, the histologic analysis of the cells stained with Toluidine blue (0.1%) were analyzed at a magnification of ×40). RANTES 10 ng/50 μL and LPS produced higher numbers (142 ± 11 and 193 ± 21 of cells/200 mm2, respectively) of basophilic cell accumulation in the skin injection sites compared with FMLP (10−6 mol/L) (127 ± 14/200 mm2), while MCP-1 10 ng/50 μL was less effective (88 ± 10/200 mm2). Elect...
Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis, pregnancy mor... more Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis, pregnancy morbidity and fetal loss caused by pathogenic autoantibodies directed against phospholipids (PL) and PL-cofactors. Isolated neurological APS may represent a significant diagnostic challenge, as epidemiological, clinical and neuroimaging features may overlap with those of multiple sclerosis (MS). In an open view, MS could be considered as an organ-specific anti-lipid (phospholipid and glycosphingolipid associated proteins) disease, in which autoreactive B cells and CD8+ T cells play a dominant role in its pathophysiology. In MS, diverse autoantibodies against the lipidprotein cofactors of the myelin sheath have been described, whose pathophysiologic role has not been fully elucidated. We carried out a review to select clinical studies addressing the prevalence of antiphospholipid (aPL) autoantibodies in the so-called MS-like syndrome. The reported prevalence ranged between 2% and 88%, particularly aCL and aβ2GPI, with predominant IgM isotype and suggesting worse MS prognosis. Secondarily, an updated summary of current knowledge on the pathophysiological mechanisms and events responsible for these conditions is presented. We draw attention to the clinical relevance of diagnosing isolated neurological APS. Prompt and accurate diagnosis and antiaggregant and anticoagulant treatment of APS could be vital to prevent or at least reduce APS-related morbidity and mortality.
International journal of molecular sciences, Jan 30, 2016
Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (... more Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of AC...
In vitro immune effects of Pt compounds of occupational and/or environmental importance, or those... more In vitro immune effects of Pt compounds of occupational and/or environmental importance, or those used in cancer treatment were studied. Spontaneous and PHA-stimulated proliferation of peripheral blood mononuclear cells (PBMC) and in vitro release of TNF-alpha, IFN-gamma, and IL-5 were assessed in presence of high and very low concentrations of Pt salts: 10(-4) and 10(-7) M (NH4)2[PtCl6], (NH4)2[PtCl4], PtCl4, PtCl2, Na2PtI6, and cis-diaminedichloroPt (CisPt). Spontaneous and PHA-stimulated PBMC proliferation were both inhibited by 10(-4) M (NH4)2[PtCl6] and (NH4)2[PtCl4], while only PHA-stimulated proliferation was inhibited by 10(-4) M CisPt, without significant effects of the other Pt salts. TNF-alpha release from PBMC was reduced by 10(-4) M (NH4)2[PtCl6] and INF-gamma release was reduced by 10(-4) and 10(-7) M hexa- and tetrachloroplatinate and 10(-4) M Na2PtI6, but not by other Pt salts. IL-5 release (related to the Th2 immune response) was inhibited by 10(-4) M (NH4)2[PtCl6],...
The effects of graded concentrations of Pt, Pd, and Rh salts on spontaneous and PHA-stimulated pe... more The effects of graded concentrations of Pt, Pd, and Rh salts on spontaneous and PHA-stimulated peripheral blood mononuclear cell (PBMC) proliferation and IFN-gamma, TNF-alpha, and IL-5 release were the focus of this study. Spontaneous PBMC proliferation was inhibited by all 10(-4) M salts (with the exception of PtCl2), while it was enhanced by 10(-5) M PtCl2 as well as by 10(-5) and 10(-6) M (NH4)2[RhCl6] and RhCl3 (but not by 10(-7) M salts). Pt, Pd, and Rh compounds showed similar effects on PHA-stimulated PBMC proliferation and cytokine release; however, the effects on IFN-gamma release were stronger. Thus, 10(-4) and 10(-5) M (NH4)2[PtCl6] and 10(-4) M (NH4)2[PtCl4] inhibited the PHA-stimulated immune activity; 10(-4) M PtCl2 did not exert activity, while 10(-6) M (NH4)2[PtCl6] and 10(-5) and 10(-6) M (NH4)2[PtCl4] and PtCl2 enhanced PBMC proliferation and/or cytokine release. (NH4)2[PdCl6] showed stronger dose-related inhibitory effects (present also at 10(-7) M concentration) ...
Zinc (Zn) and selenium (Se) exert regulatory activities on immune functions, while cadmium (Cd) i... more Zinc (Zn) and selenium (Se) exert regulatory activities on immune functions, while cadmium (Cd) is an immunotoxic agent. The object of this study was to detect effects of 10(-4), 10(-5), and 10(-6) M Cd sulphate, Zn sulphate, and sodium selenite, and their combinations on human peripheral blood mononuclear cell (PBMC) proliferation and IFN-gamma and TNF-alpha production. Only 10(-5) M Zn sulphate significantly enhanced spontaneous PBMC proliferation, which was unaffected by the other salts. At 10(-4) and 10(-5) M, Cd sulphate exerted a dose-response inhibitory action on phytohemagglutinin- (PHA-) stimulated PBMC proliferation and cytokine release, while 10(-4) M and 10(-5) M Zn sulphate and 10(-5) M sodium selenite induced a stimulatory effect on both proliferation and cytokine release; 10(-4) M sodium selenite enhanced only the PBMC proliferation; at 10(-6) M, none of the salts changed the PHA-stimulated immune activity. Moreover, 10(-4) and 10(-5) M Zn and 10(-5) M Se strongly upr...
This Special Issue of the International Journal of Molecular Sciences (IJMS) focuses on ‘Genetic ... more This Special Issue of the International Journal of Molecular Sciences (IJMS) focuses on ‘Genetic and Molecular Regulations of Neuronal Activity’ [...]
Background The diffuse distribution of nicotinic cholinergic receptors (nAChRs) in both brain and... more Background The diffuse distribution of nicotinic cholinergic receptors (nAChRs) in both brain and peripheral immune cells points out their involvement in several pathological conditions. Indeed, the deregulated function of the nAChR was previously correlated with cognitive decline and neuropsychiatric symptoms in Alzheimer’s disease (AD) and Dementia with Lewy bodies (DLB). The evaluation in peripheral immune cells of nAChR subtypes, which could reflect their expression in brain regions, is a prominent investigation area. Objectives This study aims to evaluate the expression levels of both the nAChR subunits and the main known inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of patients with DLB and AD to better characterize their involvement in these two diseases. Results Higher gene expression levels of TNFα, IL6 and IL1β were observed in DLB and AD patients in comparison with healthy controls (HC). In our cohort, a reduction of nAChRα4, nAChRβ2 and nAChRβ4 was...
Periodontitis is one of the main frequent intraoral diseases. Pathogenesis triggers are the immun... more Periodontitis is one of the main frequent intraoral diseases. Pathogenesis triggers are the immune responses with pro-inflammatory cytokines production and non-coding RNAs expression. The purpose of the present study was to evaluate the involvement of selected miRNAs in various stages of periodontitis and their relationship with the levels of inflammatory mediators in gingival crevicular fluid (GCF). For this study, 36 subjects (21 with periodontal disease, 15 healthy controls) were selected with an age mean of 59.1 ± 3.7 years. Clinical parameters included plaque index, gingival index, sulcus bleeding index, pocket depth, and clinical attachment level. The GCF samples were taken using capillary paper. The levels of miRNAs in GCF were estimated using a Real-Time PCR and TNFα and IL-6 levels were assessed by enzyme-linked immunosorbent assay (ELISA). The results indicated that the miRNA-103a-3p, miRNA-23a-3p, miRNA-15a-5p, and miRNA-223-3p were significantly upregulated with respect ...
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss o... more Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss of the central nervous system (CNS). Despite its spread throughout the world, the mechanisms that determine its onset are still to be defined. Immunological, genetic, viral, and environmental factors and exposure to chemicals may trigger MS. Many studies have highlighted the anti-inflammatory and anti-oxidant effects of medicinal herbs, which make them a natural and complementary treatment for neurodegenerative diseases. A severe reduction of several MS symptoms occurs with herbal therapy. Thus, the request for medicinal plants with potential beneficial effects, for MS patients, is constantly increasing. Consequently, a production increase needs. Unfortunately, many medicinal herbs were untested and their action mechanism, possible adverse effects, contraindications, or interactions with other drugs, are poorly or not investigated. Keeping in mind the pathological mechanisms of MS and the...
Background. Wound healing (WH) is a complex process involving several stages, such as hemostasis,... more Background. Wound healing (WH) is a complex process involving several stages, such as hemostasis, inflammation, re-epithelialization, and remodeling. Many factors can impair WH, and different pharmacological approaches were studied to date, but the increase in antibiotic resistance, invasiveness, treatment duration, and high cost, have often hampered the resolution of the wound. In this study, we investigated the possible application of water-soluble carvacrol prodrugs (WSCPs) and hyaluronic acid (HA) and their formulations (WSCPs/HA) to improve WH and regulate the inflammatory response. Materials and methods. Firstly, the cytotoxicity of 0.1, 1 and 10 µg/mL of HA, WSCPs and WSCPs/HA formulations were evaluated on HaCaT cells and THP-1 cell lines. The ability of WSCPs/HA formulations to modulate wound repair was evaluated in an in vitro model of WH, using HaCaT cells at 6, 18, and 24 h. The expression of WH mediators, after wound closure was determined by qRT-PCR. Following, we pola...
Human periodontal ligament mesenchymal stem cells (hPDLSCs) are a promising cell type model for r... more Human periodontal ligament mesenchymal stem cells (hPDLSCs) are a promising cell type model for regenerative medicine applications due to their anti-inflammatory, immunomodulatory and non-tumorigenic potentials. Extremely low-frequency electromagnetic fields (ELF-EMF) are reported to affect biological properties such as cell proliferation and differentiation and modulate gene expression profile. In this study, we investigated the effects of an intermittent ELF-EMF exposure (6 h/day) for the standard differentiation period (28 days) and for 10 days in hPDLSCs in the presence or not of osteogenic differentiation medium (OM). We evaluated cell proliferation, de novo calcium deposition and osteogenic differentiation marker expression in sham and ELF-EMF-exposed cells. After ELF-EMF exposure, compared with sham-exposed, an increase in cell proliferation rate (p < 0.001) and de novo calcium deposition (p < 0.001) was observed after 10 days of exposure. Real-time PCR and Western blot...
Recently, mineral healing clays have gained much attention for wound-dressing applications. Here,... more Recently, mineral healing clays have gained much attention for wound-dressing applications. Here, we selected halloysite (HAL) clay as a biocompatible, non-toxic material that is useful as a drug delivery system to enhance the healing properties of water-soluble terpenoids 1-3 (T1-3). Terpenoids-loaded HAL clay (TH1-3) was prepared and characterized by adsorption equilibrium studies, X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and release studies. The results reveal that T1-3 were adsorbed at the HAL surface with good efficiency. The prevalent mechanism of drug retention is due to the adsorption via electrostatic interactions between the cationic groups of the T1-3 and the HAL’s external surface. Release studies demonstrated that T3 was released in a higher percentage (>60%) compared to T1-2 (≈50%). Additionally, TH1-3 were assessed for their antimicrobial activity and ...
Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation... more Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation, and remodeling. Impaired WH may be the consequence of the alteration of one of these phases and represents a significant health and economic burden to millions of individuals. Thus, new therapeutic strategies are the topics of intense research worldwide. Although radiofrequency electromagnetic field (RF-EMF) has many medical applications in rehabilitation, pain associated with musculoskeletal disorders, and degenerative joint disorders, its impact on WH is not fully understood. The process of WH begins just after injury and continues during the inflammatory and proliferative phases. A thorough understanding of the mechanisms by which RF-EMF can improve WH is required before it can be used as a non-invasive, inexpensive, and easily self-applicable therapeutic strategy. Thus, the aim of this study is to explore the therapeutic potential of different exposure setups of RF-EMF to drive fas...
Background: The improvements in HIV infection therapy and the large availability of antiretrovira... more Background: The improvements in HIV infection therapy and the large availability of antiretroviral drugs have led to an increased survival among HIV infected people, and simultaneously to a raised morbidity and mortality due to not-AIDS-related events in this group compared to the general population. An increased systemic inflammation and a persistent immune activation play a pivotal role in determining high rates of non-AIDS comorbidities. In the last years, many natural or synthetic immunomodulatory molecules acting by different mechanisms have been conceived. Pidotimod is a synthetic dipeptide molecule showing immunomodulatory properties. The aim of this pilot study was to evaluate the effects of Pidotimod supplementation on residual inflammation in HIV infected population. Methods: Forty HIV positive individuals under cART were enrolled: 30 were treated with Pidotimod supplementation (study group) and 10 served as control group (without Pidotimod supplementation). For all partic...
Several clinical studies have suggested the impact of sinusoidal and pulsed electromagnetic field... more Several clinical studies have suggested the impact of sinusoidal and pulsed electromagnetic fields in quickening wound repair processes and tissue regeneration. The clinical use of extremely low-frequency electromagnetic fields could represent a novel frontier in tissue repair and oral health, with an interesting clinical perspective. The present study aimed to evaluate the effect of an extremely low-frequency sinusoidal electromagnetic field (SEMF) and an extremely low-frequency pulsed electromagnetic field (PEMF) with flux densities of 1 mT on a model of oral healing process using gingival fibroblasts. An in vitro mechanical injury was produced to evaluate wound healing, migration, viability, metabolism, and the expression of selected cytokines and protease genes in fibroblasts exposed to or not exposed to the SEMF and the PEMF. Interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β), metalloproteinase 2 (MMP-2), monocyte chemoattractant protein 1 (MCP-1), inducible nitric...
Periodontal disease (PD) is an inflammatory condition of the tissues supporting the teeth, which ... more Periodontal disease (PD) is an inflammatory condition of the tissues supporting the teeth, which is widespread among the adult population. Evidence shows a relationship between PD and vitamin D levels, which is involved in the regulation of bone metabolism, mineral homeostasis, and inflammatory response. This study aimed to perform a simultaneous evaluation of inflammatory mediators and vitamin D levels in saliva in periodontopathic patients to better understand their role in periodontal disease. In this observational study, clinical periodontal parameter examination was performed for each patient. Moreover, the saliva levels of 25(OH)D3, TGFβ, IL-35, IL-17A, and MMP9 were evaluated using an ELISA assay. An increase in TGFβ, IL-35, MMP9, and IL-17A salivary levels and a reduction in 25(OH)D3 levels were observed in periodontopathic patients with respect to the healthy controls. The present study revealed significant positive correlation between cytokines and highly negative correlat...
To test whether gas and oil field work is accompanied by stress and altered immune function, the ... more To test whether gas and oil field work is accompanied by stress and altered immune function, the perception of workplace stress, levels of salivary cortisol, plasma levels, and mononuclear cell production of cytokines were examined in 80 healthy workers recruited among a population of operators on gas and oilfields. Specific questionnaires for determining the perception of anxiety, occupational stress, and subjective symptoms were administered. Salivary cortisol and cytokines plasma levels were evaluated by Elisa and to investigate immune function, both spontaneous and PHA-or LPS-induced expression and production of cytokines were assessed by qRT-PCR. Workers showed medium stress levels at work, with growth and increased motivation for work, and based on salivary cortisol concentrations, were divided into two groups of ≤10 ng/mL (n = 31) or >10 ng/mL (n = 49). Statistically significant higher plasma levels of IL-6, while lower TNFα, were detected in workers with cortisol >10 ng/mL. Also, BMI, DL, JD and Job strain were significantly higher in workers with cortisol >10 ng/mL. Thus, even modest variations of cortisol might have a role in the modulation of immune response and worker's vulnerability to health imbalance.Thus, the evaluation of immune status, in addition to cortisol levels, could be useful to prevent illnesses; exacerbation of pre-existing conditions; morbidity; and consequent absences from work, with economic repercussions.
Background: Alzheimer’s disease (AD), the most threatening neurodegenerative diseases, is charact... more Background: Alzheimer’s disease (AD), the most threatening neurodegenerative diseases, is characterized by the loss of memory and language function, an unbalanced perception of space and other cognitive and physical manifestations. Pathology of the AD is characterized by neuronal loss, and the extensive distribution of senile plaques and neurofibrillary tangles (NFTs). The role of environment and the diet in the AD is being studied actively, and nutrition is certainly one of the main factors playing a prominent role in the prevention of neurodegenerative diseases. In this context, the relationship between dementia and wine use/abuse has received increased research interest in recent times, with varying and often conflicting results. Scope and approach: This review aims to critically summarize the most recent studies conducted to clarify the relationship between wine drinking and AD, as well as whether effects are influenced by quantity and/or frequency of drinking. Key findings and ...
RANTES and related molecules, constitute the C-C class of chemokine supergene family and a group ... more RANTES and related molecules, constitute the C-C class of chemokine supergene family and a group of cytokines produced by hematopoietic cells constitute the MCP-1 or C-X-C class. The roles of most of these chemokines are not well known, although members of the C-X-C family are inflammatory agents. Here, we report that intradermal injection of RANTES 10 ng/50 μL subcutaneously in the abdominal skin produced a strong inflammatory reaction, as evidenced by Evans blue dye, greater than FMLP (10−6 mol/L) (∼57%); while MCP-1, 10 ng/50 μL was less effective than FMLP (10−6 mol/L) (∼54%). Moreover, the histologic analysis of the cells stained with Toluidine blue (0.1%) were analyzed at a magnification of ×40). RANTES 10 ng/50 μL and LPS produced higher numbers (142 ± 11 and 193 ± 21 of cells/200 mm2, respectively) of basophilic cell accumulation in the skin injection sites compared with FMLP (10−6 mol/L) (127 ± 14/200 mm2), while MCP-1 10 ng/50 μL was less effective (88 ± 10/200 mm2). Elect...
Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis, pregnancy mor... more Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis, pregnancy morbidity and fetal loss caused by pathogenic autoantibodies directed against phospholipids (PL) and PL-cofactors. Isolated neurological APS may represent a significant diagnostic challenge, as epidemiological, clinical and neuroimaging features may overlap with those of multiple sclerosis (MS). In an open view, MS could be considered as an organ-specific anti-lipid (phospholipid and glycosphingolipid associated proteins) disease, in which autoreactive B cells and CD8+ T cells play a dominant role in its pathophysiology. In MS, diverse autoantibodies against the lipidprotein cofactors of the myelin sheath have been described, whose pathophysiologic role has not been fully elucidated. We carried out a review to select clinical studies addressing the prevalence of antiphospholipid (aPL) autoantibodies in the so-called MS-like syndrome. The reported prevalence ranged between 2% and 88%, particularly aCL and aβ2GPI, with predominant IgM isotype and suggesting worse MS prognosis. Secondarily, an updated summary of current knowledge on the pathophysiological mechanisms and events responsible for these conditions is presented. We draw attention to the clinical relevance of diagnosing isolated neurological APS. Prompt and accurate diagnosis and antiaggregant and anticoagulant treatment of APS could be vital to prevent or at least reduce APS-related morbidity and mortality.
International journal of molecular sciences, Jan 30, 2016
Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (... more Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of AC...
In vitro immune effects of Pt compounds of occupational and/or environmental importance, or those... more In vitro immune effects of Pt compounds of occupational and/or environmental importance, or those used in cancer treatment were studied. Spontaneous and PHA-stimulated proliferation of peripheral blood mononuclear cells (PBMC) and in vitro release of TNF-alpha, IFN-gamma, and IL-5 were assessed in presence of high and very low concentrations of Pt salts: 10(-4) and 10(-7) M (NH4)2[PtCl6], (NH4)2[PtCl4], PtCl4, PtCl2, Na2PtI6, and cis-diaminedichloroPt (CisPt). Spontaneous and PHA-stimulated PBMC proliferation were both inhibited by 10(-4) M (NH4)2[PtCl6] and (NH4)2[PtCl4], while only PHA-stimulated proliferation was inhibited by 10(-4) M CisPt, without significant effects of the other Pt salts. TNF-alpha release from PBMC was reduced by 10(-4) M (NH4)2[PtCl6] and INF-gamma release was reduced by 10(-4) and 10(-7) M hexa- and tetrachloroplatinate and 10(-4) M Na2PtI6, but not by other Pt salts. IL-5 release (related to the Th2 immune response) was inhibited by 10(-4) M (NH4)2[PtCl6],...
The effects of graded concentrations of Pt, Pd, and Rh salts on spontaneous and PHA-stimulated pe... more The effects of graded concentrations of Pt, Pd, and Rh salts on spontaneous and PHA-stimulated peripheral blood mononuclear cell (PBMC) proliferation and IFN-gamma, TNF-alpha, and IL-5 release were the focus of this study. Spontaneous PBMC proliferation was inhibited by all 10(-4) M salts (with the exception of PtCl2), while it was enhanced by 10(-5) M PtCl2 as well as by 10(-5) and 10(-6) M (NH4)2[RhCl6] and RhCl3 (but not by 10(-7) M salts). Pt, Pd, and Rh compounds showed similar effects on PHA-stimulated PBMC proliferation and cytokine release; however, the effects on IFN-gamma release were stronger. Thus, 10(-4) and 10(-5) M (NH4)2[PtCl6] and 10(-4) M (NH4)2[PtCl4] inhibited the PHA-stimulated immune activity; 10(-4) M PtCl2 did not exert activity, while 10(-6) M (NH4)2[PtCl6] and 10(-5) and 10(-6) M (NH4)2[PtCl4] and PtCl2 enhanced PBMC proliferation and/or cytokine release. (NH4)2[PdCl6] showed stronger dose-related inhibitory effects (present also at 10(-7) M concentration) ...
Zinc (Zn) and selenium (Se) exert regulatory activities on immune functions, while cadmium (Cd) i... more Zinc (Zn) and selenium (Se) exert regulatory activities on immune functions, while cadmium (Cd) is an immunotoxic agent. The object of this study was to detect effects of 10(-4), 10(-5), and 10(-6) M Cd sulphate, Zn sulphate, and sodium selenite, and their combinations on human peripheral blood mononuclear cell (PBMC) proliferation and IFN-gamma and TNF-alpha production. Only 10(-5) M Zn sulphate significantly enhanced spontaneous PBMC proliferation, which was unaffected by the other salts. At 10(-4) and 10(-5) M, Cd sulphate exerted a dose-response inhibitory action on phytohemagglutinin- (PHA-) stimulated PBMC proliferation and cytokine release, while 10(-4) M and 10(-5) M Zn sulphate and 10(-5) M sodium selenite induced a stimulatory effect on both proliferation and cytokine release; 10(-4) M sodium selenite enhanced only the PBMC proliferation; at 10(-6) M, none of the salts changed the PHA-stimulated immune activity. Moreover, 10(-4) and 10(-5) M Zn and 10(-5) M Se strongly upr...
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Papers by Marcella Reale