Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 85
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-34769816

RESUMO

Multiple chemical sensitivity (MCS) is a multisystem, recurrent, environmental disorder that flares in response to different exposures (i.e., pesticides, solvents, toxic metals and molds) under the threshold limit value (TLV) calculated for age and gender in the general population. MCS is a syndrome characterized by cutaneous, allergic, gastrointestinal, rheumatological, endocrinological, cardiological and neurological signs and symptoms. We performed a systematic review of the literature to summarize the current clinical and therapeutic evidence and then oriented an eDelphi consensus. Four main research domains were identified (diagnosis, treatment, hospitalization and emergency) and discussed by 10 experts and an MCS patient. Thus, the first Italian MCS consensus had the double aim: (a) to improve MCS knowledge among healthcare workers and patients by standardizing the clinical and therapeutic management to MCS patients; and (b) to improve and shed light on MCS misconceptions not supported by evidence-based medicine (EBM).


Assuntos
Hipersensibilidade , Sensibilidade Química Múltipla , Consenso , Humanos , Itália/epidemiologia , Sensibilidade Química Múltipla/diagnóstico , Sensibilidade Química Múltipla/epidemiologia , Sensibilidade Química Múltipla/terapia , Solventes
2.
Medicine (Baltimore) ; 100(46): e27847, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797320

RESUMO

ABSTRACT: Excessively increased training volume and/or intensity and competition can lead to development of overtraining syndrome, causing a performance decrement in athletes. Tracking individual response to exercise intensity is crucial for establishing recovery strategies.We assessed the exercise intensity-dependent variability of stress response biomarkers, namely cortisol (C), testosterone (T), s-IgA, and advanced oxidation protein products (AOPP), in saliva samples of teenage elite water polo players. Saliva was collected on a day of training match (T1) and a day of competitive match (T2), at morning, before and after match.Cortisol/proteins and testosterone/proteins concentrations decreased throughout day T1, whereas increased throughout day T2. The highest values were measured after match on day T2 (2.5 ±â€Š0.5 vs 14.6 ±â€Š6.3 ng/mg; 0.061 ±â€Š0.024 vs 0.371 ±â€Š0.15 ng/mg, respectively). sIgA/proteins and AOPP/proteins concentrations increased throughout both days, and were higher after T2 match than T1 one (respectively, 1073.0 ±â€Š438.2 vs 71.0 ±â€Š17.3 µg/mg; 78.05 ±â€Š24.2 vs 15.98 ±â€Š3.16 nmol/mg, P = .003). Significant differences between concentrations of different biomarkers recorded on T1 and T2 were found only for AOPP, suggesting an increased oxidative stress on day T2. Free testosterone/cortisol ratio on day T2 was lower than that at morning (0.053 ±â€Š0.021 vs 0.107 ±â€Š0.031), indicating an increased catabolic response after competitive match.A highly significant positive correlation was found between Cortisol/Proteins and Testosterone as well as s-IgA/Proteins on day T1, and between Cortisol/Proteins and AOPP on day T2.In conclusion, we found that different types of activities, such a training or competitive session can affect the hormonal response, immunity, and oxidative stress, thereby modulating athletic performance.Our findings also confirm the usefulness of saliva testing as noninvasive way for monitoring the individual response to changes in exercise intensity in teenage elite water polo players.

3.
Biomed Rep ; 15(6): 101, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34667598

RESUMO

Chronically increased oxidative stress has been reported in patients with multiple chemical sensitivity (MCS). Recently, a single nucleotide polymorphism of the gene coding for mitochondrial superoxide dismutase (SOD2), namely the missense substitution A16V (C47>T) resulting in alteration of SOD2 enzyme activity, has been reported to be associated with MCS. However, the influence of SOD2 A16V genetic background on redox status of patients with MCS has not yet been investigated. Here, the results of a retrospective analysis aimed to evaluate the role of the SOD2 A16V polymorphism in the alterations of antioxidant defense markers as well as fatty acid (FA) composition of erythrocyte membranes in 67 patients with MCS matched with 55 healthy controls is reported. The mutated SOD2 V16 variant was observed more frequently in the MCS group compared with the control group, and this difference was statistically significant. The most common genotype in both groups was the heterozygous SOD2 AV16 variant, whereas the mutated SOD2 VV16 variant was more frequently observed in the MCS group, although the difference was not significant. The MCS cohort showed significantly depleted levels of plasma total antioxidant activity, ubiquinol, erythrocyte reduced glutathione and membrane polyunsaturated FA levels, coupled with significant increases in glutathione peroxidase activity, likely accounting for sustained detoxification from lipoperoxides. Notably, the highest levels of oxidative stress were found in patients with MCS bearing the genotype SOD2 AA16, whereas intermediate levels were found in patients bearing the heterozygous AV16 genotype. Healthy subjects bearing the SOD2 AA16 genotype also showed increased oxidative stress compared with carriers of other SOD2 genotypes. Despite the need for further confirmations in larger cohorts, due to MCS population genetic heterogeneity, these preliminary findings suggest that SOD2 defective activity makes certain patients with MCS more susceptible to developing oxidative stress following a chronic daily exposure to pro-oxidant insults.

4.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298941

RESUMO

Clinical research aiming at objectively identifying and characterizing diseases via clinical observations and biological and radiological findings is a critical initial research step when establishing objective diagnostic criteria and treatments. Failure to first define such diagnostic criteria may lead research on pathogenesis and etiology to serious confounding biases and erroneous medical interpretations. This is particularly the case for electrohypersensitivity (EHS) and more particularly for the so-called "provocation tests", which do not investigate the causal origin of EHS but rather the EHS-associated particular environmental intolerance state with hypersensitivity to man-made electromagnetic fields (EMF). However, because those tests depend on multiple EMF-associated physical and biological parameters and have been conducted in patients without having first defined EHS objectively and/or endpoints adequately, they cannot presently be considered to be valid pathogenesis research methodologies. Consequently, the negative results obtained by these tests do not preclude a role of EMF exposure as a symptomatic trigger in EHS patients. Moreover, there is no proof that EHS symptoms or EHS itself are caused by psychosomatic or nocebo effects. This international consensus report pleads for the acknowledgement of EHS as a distinct neuropathological disorder and for its inclusion in the WHO International Classification of Diseases.


Assuntos
Biomarcadores/metabolismo , Hipersensibilidade/metabolismo , Sensibilidade Química Múltipla/metabolismo , Animais , Consenso , Diagnóstico por Imagem/métodos , Testes Diagnósticos de Rotina/métodos , Campos Eletromagnéticos , Humanos , Doenças do Sistema Nervoso/metabolismo
5.
Curr Issues Mol Biol ; 43(2): 704-715, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34287264

RESUMO

Patients with cardiovascular disease (CVD) and periodontitis (PT) show shared risk factors as result of the altered molecular mechanisms associated with pathological conditions. The aim of our study was to evaluate if the plasma biomarkers associated with endothelial dysfunction may also be related to alterations in the inflammatory status in peripheral blood mononuclear cells (PBMC). Patients with PT, coronary heart disease (CHD), or both diseases as well as controls were enrolled. Plasma levels of coenzyme Q10 (CoQ10), 3-nitrotyrosine (NT), and asymmetric dimethylarginine (ADMA) were assessed using HPLC. mRNA levels of caspase-1 (CASP1), NLR family pyrin domain containing 3 (NLRP3), and tumor necrosis factor-α (TNF-α) in PBMC from the recruited subjects were quantified using real-time PCR. Patients with PT + CHD showed lower CoQ10 plasma levels and increased concentrations of NT in comparison to healthy subjects. ADMA levels were higher in CHD and PT + CHD patients compared to controls. Transcript levels of CASP1, NLRP3, and TNF-α were up-regulated in PBMC from all patient groups when compared to healthy subjects. Our results suggest a possible causal link between oxidative stress, high levels of NT and ADMA, and inflammasome activation, which may be involved in the endothelial inflammatory dysfunction leading to the pathogenesis and progression of CHD in PT patients.

6.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652555

RESUMO

Several studies have demonstrated a relevant role of intestinal epithelial cells in the immune response and in chronic inflammatory conditions, including ulcers, colitis, and Crohn's disease. Baicalin (BA), extracted from the root of Scutellaria baicalensis, has various beneficial healthy effects, including anti-inflammatory activity. However, few studies have evaluated BA effects on autophagic signaling in epithelial cell response to inflammatory stimuli. To explore possible beneficial effects of BA, HT-29 cells were exposed to lipopolysaccharide (LPS), in presence or absence of BA, for 4 h. We evaluated mRNA levels of autophagy-related genes and cytokines, triggering inflammatory response. Furthermore, the expression of claudin 1, involved in the regulation of paracellular permeability was analyzed. BA treatment repressed LPS-induced expression of TNF-α and IL-1ß. The down-regulation of autophagy-related genes induced by LPS was counteracted by cell pretreatment with BA. Under these conditions, BA reduced the NF-κB activation caused by LPS. Also, BA restored mRNA and protein levels of claudin 1, which were reduced by LPS. In conclusion, in intestinal epithelial cells BA regulates the NF-κB activation and modulates both autophagic and inflammatory processes, leading to an improvement of paracellular permeability. These results suggest that the anti-inflammatory effects of BA can be associated to the regulation of autophagic flux.


Assuntos
Autofagia/efeitos dos fármacos , Células Epiteliais/metabolismo , Flavonoides/farmacologia , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Células HT29 , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Permeabilidade/efeitos dos fármacos
7.
Antioxidants (Basel) ; 9(11)2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33167396

RESUMO

Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes and extra-pineal cells, plays an important role in timing circadian rhythms (24-h internal clock) and regulating the sleep/wake cycle in humans. However, in recent years melatonin has gained much attention mainly because of its demonstrated powerful lipophilic antioxidant and free radical scavenging action. Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant. Melatonin-induced signal transduction through melatonin receptors promotes the expression of antioxidant enzymes as well as inflammation-related genes. Melatonin also exerts an immunomodulatory action through the stimulation of high-affinity receptors expressed in immunocompetent cells. Here, we reviewed the efficacy, safety and side effects of melatonin supplementation in treating oxidative stress- and/or inflammation-related disorders, such as obesity, cardiovascular diseases, immune disorders, infectious diseases, cancer, neurodegenerative diseases, as well as osteoporosis and infertility.

8.
PLoS One ; 15(11): e0239407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33186385

RESUMO

BACKGROUND: Recent literature data have highlighted the important role of hypovitaminosis D in pregnancy complications and prenatal/perinatal health. Vitamin D action takes place through vitamin D receptor (VDR) activation. Two single nucleotide polymorphisms of VDR gene, FokI and BsmI, have been reported to affect VDR molecular signaling and be associated with several disorders, including hypertension. METHODS: We carried out a case-control study aimed to assess vitamin D serum levels together with the distribution of VDR FokI and BsmI in a population of 116 pregnant women with gestational hypertension (GH) and 69 normotensive pregnant women (CTR). RESULTS: Hypovitaminosis D was largely prevalent both in GH (81%) and CTR (69%) pregnant women. Vitamin D insufficiency (10-30 ng/ml) had a similar frequency in both cohorts (GH 60% vs CTR 58%), while vitamin D deficiency (<10 ng/ml) was more frequent in GH cohort than in CTR one (21% vs 11%). Regression analysis showed that GH was significantly (p = 0.031) linked to vitamin D status. Vitamin D deficiency was associated with a threefold-increased risk of developing GH, while a normal vitamin D status was protective against this pregnancy disorder. The VDR FF/bB haplotype was the most frequent in GH cohort, and resulted to increase by two folds the risk for GH. Notably, hypovitaminosis D was found in 92% of FF/bB GH pregnant women, 27% of which had deficient vitamin D levels compared with 11% of their normotensive counterparts. CONCLUSIONS: Despite being preliminary, these findings suggest that genotyping of pregnant women for VDR polymorphisms may be useful for a tailored vitamin D supplementation strategy.


Assuntos
Calcifediol/sangue , Predisposição Genética para Doença/genética , Hipertensão Induzida pela Gravidez/genética , Receptores de Calcitriol/genética , Deficiência de Vitamina D/genética , Estudos de Casos e Controles , Feminino , Humanos , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Transdução de Sinais/genética
9.
Int J Mol Sci ; 21(20)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066266

RESUMO

Conflicting results on the involvement of vitamin D deficiency in inflammatory and immune response in HIV+ subjects are reported. We aimed to characterize the possible influence of vitamin D status on changes in expression of tissue transglutaminase gene (TGM2) and other genes involved in inflammatory response and autophagy in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. HIV+ subjects (n = 57) under antiretroviral therapy (ART) and healthy controls (n = 40) were enrolled. mRNA levels of 1-alpha-hydroxylase (CYP27B1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), TGM2, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 homolog (ATG5), and Beclin 1 (BECN1) were quantified by real-time PCR. In HIV+ subjects, 25(OH)D3 plasma levels were negatively correlated with time since HIV diagnosis. In PBMC from HIV+ subjects, increases in gene expression of TNF-α and IFN-γ in comparison to controls were observed. The highest increase in TNF-α transcripts was observed in HIV+ subjects with deficient 25(OH)D3 levels. Autophagy-related genes LC3, ATG5, and BECN1 were down-regulated in HIV+ subjects. Moreover, TGM2 transcripts were up-regulated in PBMC from HIV+ subjects with 25(OH)D3 deficiency. Changes observed in PBMC from HIV+ subjects appeared to be dependent on vitamin D status. The present results suggest that vitamin D deficiency is associated with changes in the expression of markers of inflammation and autophagy, resulting in immune cell dysfunction.


Assuntos
Autofagia , Proteínas de Ligação ao GTP/genética , Infecções por HIV/metabolismo , Monócitos/metabolismo , Transglutaminases/genética , Vitamina D/sangue , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Adulto , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Feminino , Proteínas de Ligação ao GTP/metabolismo , Infecções por HIV/sangue , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Transglutaminases/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Int J Mol Sci ; 21(14)2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664456

RESUMO

The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field.


Assuntos
Ciclodextrinas/metabolismo , Doxorrubicina/metabolismo , Expressão Gênica/efeitos dos fármacos , Grafite/metabolismo , Nanoestruturas/administração & dosagem , Neoplasias/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Ciclodextrinas/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes , Humanos , Camundongos , Neoplasias/tratamento farmacológico
11.
Clin Chim Acta ; 507: 219-223, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32371216

RESUMO

Vitamin D status is involved in the risk of many chronic diseases including cancer, inflammatory and autoimmune disease. The RANK/RANKL/OPG system is also implicated in the orchestration of immune functions. We aimed to investigate the expression of RANKL, OPG and markers of inflammation and immune activation in peripheral blood mononuclear cells (PBMC) from healthy subjects with different 25(OH)D3 plasma levels. The 25(OH)D3 plasma concentrations were assessed by HPLC. The gene expression was evaluated by qRT-PCR. The expression of CYP27B1 was lower in subjects with 25(OH)D3 levels below 50 nmol/L (deficiency) than subjects with both insufficient and sufficient levels of 25(OH)D3. In subjects with deficiency, we observed the up-regulation of RANKL, TNF-α, IFN-γ, ICAM and LFA-1, and a reduction of the anti-inflammatory cytokines IL-13 and IL-4 in comparison to other subjects. Finally, we found a negative correlation between RANKL mRNA levels and 25(OH)D3 and between 25(OH)D3 and ICAM mRNA levels. A positive correlation between ICAM and RANKL was observed. Our results give evidence of the modulatory effects of circulating 25(OH)D3 levels on gene expression of biomarkers of immune activation in PBMC, suggesting the possible use of PBMC as ex-vivo model to characterize molecular mechanisms of immune/inflammatory response in hypovitaminosis conditions.


Assuntos
Inflamação/sangue , Leucócitos Mononucleares/metabolismo , Ligante RANK/sangue , Vitamina D/análogos & derivados , Biomarcadores/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Ligante RANK/genética , RNA Mensageiro/sangue , RNA Mensageiro/genética , Vitamina D/sangue
12.
Int J Mol Sci ; 21(5)2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32182774

RESUMO

Systemic inflammation and immune activation are striking features of multiple chemical sensitivity (MCS). The rs2298383 SNP of ADORA2A gene, coding for adenosine receptor type 2A (A2AR), has been involved in aberrant immune activation. Here we aimed to assess the prevalence of this SNP in 279 MCS patients and 238 healthy subjects, and its influence on ADORA2A, IFNG and IL4 transcript amounts in peripheral blood mononuclear cells of randomly selected patients (n = 70) and controls (n = 66) having different ADORA2A genotypes. The ADORA2A rs2298383 TT mutated genotype, significantly more frequent in MCS patients than in controls, was associated with a three-fold increased risk for MCS (O.R. = 2.86; C.I. 95% 1.99-4.12, p < 0.0001), while the CT genotype, highly prevalent among controls, resulted to be protective (O.R. = 0.33; C.I. 95% 0.224-0.475, p < 0.0001). Notably, ADORA2A mRNA levels were significantly lower, while IFNG, but not IL4, mRNA levels were significantly higher in TT MCS patients compared with controls. A significant negative correlation was found between ADORA2A and both IFNG and IL4, while a significant positive correlation was found between IFNG and IL4. These findings suggest that A2AR defective signaling may play a relevant role in PBMC shift towards a pro-inflammatory phenotype in MCS patients.


Assuntos
Citocinas/genética , Leucócitos Mononucleares/fisiologia , Sensibilidade Química Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor A2A de Adenosina/genética , Transcrição Genética/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Interferon gama/genética , Interleucina-4/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética
13.
Int J Mol Med ; 45(6): 1951-1959, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32186757

RESUMO

Low levels of pesticides persist in the environment and can affect the health of exposed subjects. Oxidative stress is considered as one of the mechanisms responsible for the adverse effects on human health and some molecules may represent useful biomarkers for the evaluation of this physiological balance. This study investigated the role of these biomarkers, such as advanced oxidation protein products (AOPP), advanced glycation end­products (AGE) and reactive oxygen metabolites (ROMs) in relation to genetic polymorphisms of paraoxonase (PON)1, PON2, glutathione S­transferase pi 1 (GSTP1), glutathione S­transferase theta 1 (GSTT1) and glutathione S­transferase mu 1 (GSTM1). An increase in the levels of these biomarkers is usually inversely associated with the depletion of the biological antioxidant potential (BAP). The results revealed a statistically significant difference in the sex­dependent variation of AGE, BAP, AOPP and ROM protein levels. Furthermore, an association between the PON2 S331C gene polymorphism and the serum levels of AOPP, ROMs and BAP was found. Thus, compared with AGE, the levels of AOPP and ROMs provided a more sensitive biomarker, with an improved association with the PON2 genotype. Such an association strengthen the importance of PON in the occurrence of oxidative stress. According to these results, an individual's genetic background may be taken into account for the health surveillance of individuals occupationally exposed to pesticides, in order to define a cluster of highly susceptible workers so as to guarantee greater protection.


Assuntos
Arildialquilfosfatase/genética , Biomarcadores/metabolismo , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Estresse Oxidativo/genética , Praguicidas/efeitos adversos , Polimorfismo Genético/genética , Antioxidantes/metabolismo , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos
14.
Int J Mol Sci ; 21(4)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085516

RESUMO

Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, p16, cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non-MYCN-amplified) and IMR-32 (MYCN-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of HIF-1α in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of MYCN amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.


Assuntos
Proteínas de Ligação ao GTP/genética , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/enzimologia , Neuroblastoma/genética , Transglutaminases/genética , Ciclo Celular/genética , Morte Celular/genética , Hipóxia Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Fragmentação do DNA , Humanos , Proteína Proto-Oncogênica N-Myc/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
Eur J Pediatr Surg ; 30(6): 524-528, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707727

RESUMO

INTRODUCTION: CO2 pneumoperitoneum can influence the biological behavior of neuroblastoma (NB). Angiogenesis and genetic features are responsible for malignant phenotype of this tumor. We examined the CO2 effects on N-Myc, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) expression as critical biomarkers of tumor invasiveness, in NB cells without N-Myc amplification. MATERIALS AND METHODS: SH-SY5Y cells were exposed to CO2 (100%) at 15 mm Hg pressure for 4 hours and then moved to normal condition for 24 hours. Control cells were incubated with 5% CO2 for the same time. In control and CO2-exposed cells, the messenger ribonucleic acid (mRNA) levels of hypoxia-inducible factor (HIF)-1α, HIF-2α, VEGF-A, and MMP-2 were quantified by real-time polymerase chain reaction. N-Myc expression was evaluated by Western blot analysis. RESULTS: The exposure to 15 mm Hg CO2 (100%) for 4 hours induced an increase in HIF-1α, but not in HIF-2α, mRNA levels. No differences were observed in N-Myc expression between exposed and control cells at each incubation time. Similarly, no significant differences were found for VEGF-A and MMP-2 transcript levels. In CO2 exposed cells, we observed only a slight increase in both VEGF-A and MMP-2 mRNA levels after 4 and 24 hours in comparison to controls. CONCLUSION: In our study, the hypoxic environment induced by CO2 exposure does not affect the expression of critical biomarkers of NB aggressiveness, such as N-Myc, VEGF, and MMP-2, in human SH-SY5Y NB cells without N-Myc amplification. These data suggest that CO2 pneumoperitoneum might not adversely impact NB cell invasiveness; however, it is necessary to evaluate these effects in others in vitro and in vivo models.


Assuntos
Dióxido de Carbono/farmacologia , Neuroblastoma/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Procedimentos Cirúrgicos Minimamente Invasivos , Invasividade Neoplásica , Neuroblastoma/cirurgia , Pneumoperitônio , RNA Mensageiro/efeitos dos fármacos , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos
16.
Amino Acids ; 52(2): 171-179, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31292720

RESUMO

Agmatine, a metabolite generated by arginine decarboxylation, has been reported as neuromodulator and neuroactive substance. Several findings suggest that agmatine displays neuroprotective effects in several models of neurodegenerative disorders, such as Parkinson's disease (PD). It has been hypothesized that biogenic amines may be involved in neuroprotection by scavenging oxygen radicals, thus preventing the generation of oxidative stress. Mitochondrial dysfunction, that leads to a reduction of oxygen consumption, followed by activation of prolyl hydroxylase and decrease of hypoxia-inducible factor 1 alpha (HIF-1α) levels, has been demonstrated to play a role in PD pathogenesis. Using rotenone-treated differentiated SH-SY5Y cells as the in vitro PD model, we here investigated the molecular mechanisms underlying agmatine neuroprotective effects. Our results showed that the preliminary addition of agmatine induces HIF-1α activation, and prevents the rotenone-induced production of free radical species, and the activation of apoptotic pathways by inhibiting mitochondrial membrane potential decrease and caspase 3 as well as cytochrome c increase. Notably, these effects are mediated by HIF-1α, as indicated by experiments using a HIF-1α inhibitor. The present findings suggest that the treatment with agmatine is able to counteract the neuronal cell injury evoked by mitochondrial toxins.


Assuntos
Agmatina/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inseticidas/toxicidade , Fármacos Neuroprotetores/metabolismo , Rotenona/toxicidade , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Regulação para Cima/efeitos dos fármacos
17.
Int J Mol Sci ; 21(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881664

RESUMO

Genetic polymorphisms as well as environmental exposures to chemical compounds, iatrogenic, psychological, and physical trauma may play a pathophysiological role in multiple chemical sensitivity (MCS) olfactory complaints, given that xenobiotic metabolism is influenced by sequence variations in genes of metabolizing enzymes. Thus, the aim of the present study was to depict-by means of multiple regression analysis-how different genetic conditions, grouped according to their function as well as clinical background and environmental exposure may interfere with those olfactory complaints referred by MCS patients. Therefore, MCS patients after gene polymorphism sequencing, the olfactory-related quality of life score-calculated by means of the Questionnaire of Olfactory Disorder in forty-six MCS patients-have been found to significantly rely on the phase I and II enzymes score and exposure to previous compounds and surgical treatments. The present work-implementing for the first time a genetic-acquired factors model on a regression analysis-further reinforces those theories, positing MCS as a complex, multifactorial, disease in which the genetic risk related to phase I and II enzymes involved in xenobiotic detoxification, olfactory, and neurodegenerative diseases play a necessary, but probably not sufficient role, along the pathophysiological route of the disease.


Assuntos
Sensibilidade Química Múltipla/patologia , Qualidade de Vida , Adulto , Alelos , Sistema Enzimático do Citocromo P-450/genética , Exposição Ambiental , Feminino , Frequência do Gene , Genótipo , Glutationa Transferase/genética , Humanos , Inativação Metabólica , Masculino , Pessoa de Meia-Idade , Sensibilidade Química Múltipla/genética , Polimorfismo Genético , Análise de Regressão , Superóxido Dismutase/genética
18.
Medicina (Kaunas) ; 55(10)2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591338

RESUMO

Background and Objectives: Diabetes mellitus (DM) and hypertension (HT) are characterized by cell damage caused by inflammatory and metabolic mechanisms induced by alteration in reduction-oxidative status. Serum advanced oxidation protein products (AOPP) are new markers of protein damage induced by oxidative stress. We evaluated serum levels of AOPP in a cohort of patients with DM and HT, with or without renal complications, compared with a control healthy population. Materials and Methods: The study group comprised of 62 patients with type 2 DM and 56 with HT. The 62 patients affected by DM were further distinguished in 24 subjects without renal impairment, 18 with diabetic nephropathy (DN), 20 with chronic kidney disease (CKD) stage 2-3 secondary to DN. The subgroup of 56 patients with primary HT comprised 26 subjects without renal complications and 30 with CKD (stage 2-3) secondary to HT. Thirty healthy controls, matched for age and sex, were recruited among blood donors. Results: Increased AOPP levels were found in DM patients compared with healthy subjects, although not significantly. This index was higher and more significant in patients with DN and CKD secondary to DN than in DM patients without nephropathy (p < 0.05) or controls (p < 0.0001). Patients with HT and with kidney impairment secondary to HT also had significantly higher AOPP serum levels than controls (p < 0.01 and p < 0.0001, respectively). There were no significant differences in mean AOPP levels among DM and HT patients. Conclusion: Our study showed that oxidative stress was higher in diabetic or hypertensive subjects than in healthy controls and, in particular, it appeared to be more severe in patients with renal complications. We suggest that the assessment of AOPP in diabetic and hypertensive patients may be important to predict the onset of renal failure and to open a new perspective on the adoption of antioxidant molecules to prevent CKD in those settings.


Assuntos
Produtos da Oxidação Avançada de Proteínas/análise , Nefropatias Diabéticas/classificação , Hipertensão Renal/classificação , Nefrite/classificação , Adulto , Produtos da Oxidação Avançada de Proteínas/sangue , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/fisiopatologia , Feminino , Humanos , Hipertensão Renal/sangue , Hipertensão Renal/fisiopatologia , Itália , Masculino , Pessoa de Meia-Idade , Nefrite/sangue , Nefrite/fisiopatologia , Estresse Oxidativo
19.
Mediators Inflamm ; 2019: 7894017, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360119

RESUMO

Investigations on prostate inflammation-related disorders, including acute and chronic prostatitis, chronic pelvic pain syndrome, benign prostate hyperplasia (BPH), and prostate cancer (PCa), are still ongoing to find new, accurate, and noninvasive biomarkers for a differential diagnosis of those pathological conditions sharing some common macroscopic features. Moreover, an ideal biomarker should be useful for risk assessment of prostate inflammation progression to more severe disorders, like BPH or PCa, as well as for monitoring of treatment response and prognosis establishment in carcinoma cases. Recent literature evidence highlighted that changes in the expression of transglutaminases, enzymes that catalyze transamidation reactions leading to posttranslational modifications of soluble proteins, occur in prostate inflammation-related disorders. This review focuses on the role specifically played by transglutaminases 4 (TG4) and 2 (TG2) and suggests that both isoenzymes hold a potential to be included in the list of candidates as novel diagnostic biomarkers for the above-cited prostate pathological conditions.


Assuntos
Biomarcadores Tumorais/metabolismo , Isoenzimas/metabolismo , Transglutaminases/metabolismo , Biomarcadores Tumorais/genética , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Humanos , Isoenzimas/genética , Masculino , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Processamento de Proteína Pós-Traducional , Transglutaminases/genética
20.
Urol Int ; 103(4): 459-465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30991399

RESUMO

BACKGROUND: Lichen sclerosus (LS) is a disease of the skin of unclear etiology that can occur in the foreskin. Topical therapy with corticosteroids is recommended, but they can have side effects. OBJECTIVES: We aimed to compare the effects of ozonides with vitamin E acetate (OZOILE) versus topical corticosteroid in children undergoing circumcision. METHOD: Twenty children undergoing circumcision were treated before surgery: 10 children with OZOILE cream and 10 with 0.1% mometasone furoate once a day for 7 days. Ten age-matched patients with LS of the foreskin without any treatment were recruited as controls. Transcript levels of proinflammatory and anti-inflammatory cytokines and e-cadherin were evaluated in removed foreskins by qRT-PCR. RESULTS: OZOILE and steroid topical treatment produced a similar reduction of TNF-α and IL-1ß mRNA levels in foreskins from patients with LS when compared to untreated patients (p < 0.001). OZOILE and steroid treatment caused an increase in the transcript levels of IL-13 and e-cadherin in the foreskin of patients affected by LS in comparison to untreated foreskin (p < 0.001). CONCLUSIONS: On the basis of our biochemical data, a randomized clinical trial might be useful to verify the actual clinical effect of OZOILE as alternative treatment to corticosteroids in children affected by LS of the foreskin.


Assuntos
Corticosteroides/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Prepúcio do Pênis , Doenças dos Genitais Masculinos/tratamento farmacológico , Líquen Escleroso e Atrófico/tratamento farmacológico , Furoato de Mometasona/uso terapêutico , Azeite de Oliva/uso terapêutico , Ozônio/uso terapêutico , Vitamina E/uso terapêutico , Administração Tópica , Adolescente , Criança , Pré-Escolar , Humanos , Inflamação/tratamento farmacológico , Masculino , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...