An inverse relationship between meal frequency and body weight has been observed in several studies: however, little information is available on the effects of a snack consumption on energy and nutrient intakes in adu...An inverse relationship between meal frequency and body weight has been observed in several studies: however, little information is available on the effects of a snack consumption on energy and nutrient intakes in adults. In this study, 19 healthy volunteers consumed daily for 3 weeks, in a cross-over design, one of two isocaloric snacks (bread with salmon spread or bread with salami). Diet composition, anthropometrics, blood pressure, lipid and fatty acid profiles, fasting plasma glucose levels and high sensitivity C reactive protein (hs-CRP) were assessed at the beginning of the study and before and after each dietary period. The inclusion of a mid afternoon snack in the standard meal pattern (breakfast, lunch, dinner) was associated with a significant reduction in energy intake at dinner (the reduction being larger after the snack prepared with the salmon spread);the total daily caloric intake, however, was not changed by the snack consumption, since the snack caloric intake was fully compensated by the lower dinner energy intake. No significant change has been observed in any of the measured biochemical or anthropometric parameters, even if a trend toward a plasma hs-CRP reduction and toward a more favourable HUFA index was observed after the salmon spread snack consumption. These observations indicate that the regular consumption of a balanced mid afternoon snack has no adverse effects on energy intake and biochemical parameters of healthy adults with a moderately active lifestyle;the snack consumption results, however, in different distributions of the energy intake among meals. The snack composition (salmon or salami) may further influence these effects.展开更多
Chronic diseases are often accompanied by inflammatory and degenerative processes. Estrogens have repeatedly been found to be involved in these processes. Testosterone (T) is the main precursor of estrogen in the brai...Chronic diseases are often accompanied by inflammatory and degenerative processes. Estrogens have repeatedly been found to be involved in these processes. Testosterone (T) is the main precursor of estrogen in the brain and T replacement in chronic diseases has become important in recent years, prompting research on new T-conjugated molecules. We recently synthesized three new molecules including unsaturated fatty acid esters: T-linoleate (TL), T-oleate (TO) and T-eicosapentanoate (TEPA). These substances were s.c. administered for 7 days to intact male rats subjected to the formalin test (FT). Three other groups were included as comparisons: NAIVE, receiving no substance, OIL, treated with almond oil (vehicle), and TN, treated with T-undecanoate, a?saturated?fatty acid. Spontaneous behaviors and pain-induced responses were determined during the FT, hormones (T and dihydrotestosterone, DHT) were determined in blood, while estrogen receptors (ERα?and?β) were detected at the genomic and proteomic levels in the hippocampus, hypothalamus and spinal cord. In the hippocampus, ERα?and ERβ?mRNA levels were increased respectively by TN and TL treatments with respect to OIL, whereas the hypothalamus TO and TL caused a decrease of ERα?mRNA levels. At the proteomic level, TO, TL and TEPA decreased the levels of ERα?in the hypothalamus, whereas TEPA decreased ERβ?in the spinal cord, hippocampus and hypothalamus. There was no effect of treatment on the spontaneous behaviors, while the TO and TL groups showed lower pain-induced behaviors (paw jerk frequency and licking duration) than the OIL group. TN increased paw jerk frequency and decreased licking duration with respect to OIL. The treatments had no effect on T and DHT plasma levels. These results clearly indicate the possibility of pain and ER modulation by T-esters.展开更多
Brain synapses play a key role in neuronal communication:this“conversation”is at the basis of all brain activities and synaptic dysfunction leads to brain disorders.We study the modulators of this crucial synaptic f...Brain synapses play a key role in neuronal communication:this“conversation”is at the basis of all brain activities and synaptic dysfunction leads to brain disorders.We study the modulators of this crucial synaptic function and we here present the evidence supporting the c-Jun N-terminal kinase(JNK)pathway as a pivotal actor in this scenario.展开更多
Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, ce...Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, cell death and nociception, and highlights how alterations in their gene expression within the dorsal root ganglia can affect functional recovery. The majority of studies used polymerase chain reaction within animal models to analyse the dynamic changes following peripheral nerve injuries. This review aims to highlight the factors at the gene expression level that impede functional recovery and are hence are potential targets for therapeutic approaches. Where possible the experimental model, specific time-points and cellular location of expression levels are reported.展开更多
Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulati...Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulation and the saltatory conduction of nerve impulses.The formation of myelin is a complex process during which the OL precursor cells(OPCs,also known as NG2-glia)become mature OLs through a highly regulated program of differentiation.In addition,OPCs persist in the adult grey and white matter parenchyma,representing approximately 6%of the total number of CNS cells.Beyond their role in myelin generation and turn-over,it is now clear that OPCs have the capability to control tissue homeostasis and to sense and react to inflammation which characterizes many neurological diseases.展开更多
Schwann cells and neuroregeneration:Peripheral nerve injury is a common cause of morbidity,which affects millions of people worldwide.The peripheral nervous system,differently from the central nervous system,has an in...Schwann cells and neuroregeneration:Peripheral nerve injury is a common cause of morbidity,which affects millions of people worldwide.The peripheral nervous system,differently from the central nervous system,has an intrinsic ability to regenerate after injury.However,in most cases the regenerative outcome is not completely satisfactory,in particular for long-gap peripheral nerve injuries in which the microsurgical approach is not possible.In these cases。展开更多
In the last years,axonal conductance of action potential trains became a novel subject of study,changing the view of axons,from a static cable-like compartment to a more complex and dynamic system(Debanne et al.,2011)...In the last years,axonal conductance of action potential trains became a novel subject of study,changing the view of axons,from a static cable-like compartment to a more complex and dynamic system(Debanne et al.,2011).Axonal computation,indeed,is canonically constituted by the action of voltage-gated ion channels,such as the classic Na+and K+channels,but recent studies demonstrated that it can be modulated by the action of other ion channel pumps,and metabolic factors(Byczkowicz et al.,2019;Zang and Marder.展开更多
Obesity represents a major public health problem,as it leads to metabolic disorders involved in the development of type 2 diabetes,fatty liver diseases,cardiovascular diseases and cancer(1).The Western lifestyle,inclu...Obesity represents a major public health problem,as it leads to metabolic disorders involved in the development of type 2 diabetes,fatty liver diseases,cardiovascular diseases and cancer(1).The Western lifestyle,including over-feeding of highly refined diets and sedentary behavior,is associated with systemic low-grade inflammation,responsible for chronic degenerative disease.Moreover,animal and human data have demonstrated the impact of high-fat diet feeding on the onset of metabolic endotoxemia.This latter,being characterized by increase blood lipopolysaccharide(LPS)levels,triggers low-grade inflammation and contributes to the development of obesity.The gut microbiota are a candidate sources of plasma LPS.Indeed,LPS is a major component of the outer membrane in Gram-negative bacteria and its plasma levels are correlated with changes in intestinal microbiota where the Gram-negative to Gram-positive ratio is increased by high fat feeding(1).Not surprising that in humans,obesity is characterized by dysbiosis,i.e.imbalances in the composition and function of the intestinal microbes.Currently,many studies are being conducted to assess the contribution of intestinal microflora metabolites[mainly short-chain fatty acids(SCFAs)]to the organism’s homeostasis.Dietary fibers have been promoted for their health benefits and high-fiber intake has been reported as beneficial in numerous chronic diseases(2).However,we have to keep in mind that consumption of dietary fiber significantly alters the composition of the gut microbiota.展开更多
Nonalcoholic fatty liver disease(NAFLD)is the major contributor to the global burden of chronic liver diseases and ranges from simple and reversible steatosis to nonalcoholic steatohepatitis(NASH),which may progress i...Nonalcoholic fatty liver disease(NAFLD)is the major contributor to the global burden of chronic liver diseases and ranges from simple and reversible steatosis to nonalcoholic steatohepatitis(NASH),which may progress into cirrhosis and hepatocellular carcinoma(HCC).HCC represents the most common liver cancer,and it is a leading cause of death worldwide with an increasing trend for the future.Due to late diagnosis,non-responsiveness to systemic therapy,and high cancer heterogeneity,the treatment of this malignancy is challenging.To date,liver biopsy and ultrasound(US)are the gold standard procedures for HCC diagnosis and surveillance,although they are not suitable for mass screening.Therefore,it is impelling to find new,less invasive diagnostic strategies able to detect HCC at an early stage as well as monitor tumor progression and recurrence.Common and rare inherited variations that boost the switching from NASH to liver cancer may help to predict tumor onset.Furthermore,epigenetic changes which reflect intertumoral heterogeneity occur early in tumorigenesis and are highly stable under pathologic conditions.The severity of hepatic injuries can be detected through the analysis of cell circulating tumor DNAs(ctDNAs),microRNAs(miRNAs),and noncoding RNAs(ncRNAs),which are involved in several pathological processes that feature cancer,including cell growth,survival,and differentiation,thus representing appealing biomarkers for HCC.Therefore,this review discusses the current options for HCC surveillance,focusing on the role of genetic and epigenetic biomarkers as new strategies to refine HCC management.展开更多
文摘An inverse relationship between meal frequency and body weight has been observed in several studies: however, little information is available on the effects of a snack consumption on energy and nutrient intakes in adults. In this study, 19 healthy volunteers consumed daily for 3 weeks, in a cross-over design, one of two isocaloric snacks (bread with salmon spread or bread with salami). Diet composition, anthropometrics, blood pressure, lipid and fatty acid profiles, fasting plasma glucose levels and high sensitivity C reactive protein (hs-CRP) were assessed at the beginning of the study and before and after each dietary period. The inclusion of a mid afternoon snack in the standard meal pattern (breakfast, lunch, dinner) was associated with a significant reduction in energy intake at dinner (the reduction being larger after the snack prepared with the salmon spread);the total daily caloric intake, however, was not changed by the snack consumption, since the snack caloric intake was fully compensated by the lower dinner energy intake. No significant change has been observed in any of the measured biochemical or anthropometric parameters, even if a trend toward a plasma hs-CRP reduction and toward a more favourable HUFA index was observed after the salmon spread snack consumption. These observations indicate that the regular consumption of a balanced mid afternoon snack has no adverse effects on energy intake and biochemical parameters of healthy adults with a moderately active lifestyle;the snack consumption results, however, in different distributions of the energy intake among meals. The snack composition (salmon or salami) may further influence these effects.
文摘Chronic diseases are often accompanied by inflammatory and degenerative processes. Estrogens have repeatedly been found to be involved in these processes. Testosterone (T) is the main precursor of estrogen in the brain and T replacement in chronic diseases has become important in recent years, prompting research on new T-conjugated molecules. We recently synthesized three new molecules including unsaturated fatty acid esters: T-linoleate (TL), T-oleate (TO) and T-eicosapentanoate (TEPA). These substances were s.c. administered for 7 days to intact male rats subjected to the formalin test (FT). Three other groups were included as comparisons: NAIVE, receiving no substance, OIL, treated with almond oil (vehicle), and TN, treated with T-undecanoate, a?saturated?fatty acid. Spontaneous behaviors and pain-induced responses were determined during the FT, hormones (T and dihydrotestosterone, DHT) were determined in blood, while estrogen receptors (ERα?and?β) were detected at the genomic and proteomic levels in the hippocampus, hypothalamus and spinal cord. In the hippocampus, ERα?and ERβ?mRNA levels were increased respectively by TN and TL treatments with respect to OIL, whereas the hypothalamus TO and TL caused a decrease of ERα?mRNA levels. At the proteomic level, TO, TL and TEPA decreased the levels of ERα?in the hypothalamus, whereas TEPA decreased ERβ?in the spinal cord, hippocampus and hypothalamus. There was no effect of treatment on the spontaneous behaviors, while the TO and TL groups showed lower pain-induced behaviors (paw jerk frequency and licking duration) than the OIL group. TN increased paw jerk frequency and decreased licking duration with respect to OIL. The treatments had no effect on T and DHT plasma levels. These results clearly indicate the possibility of pain and ER modulation by T-esters.
基金funded by Ricerca Finalizzata 2016 RF-2016-02361941MIUR,-PON“Ricerca e Innovazione”PerMedNet id project ARS01_01226-PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE Prot.2017MYJ5TH312 European Commission’s Horizon 2020 research and innovation program,No.847749。
文摘Brain synapses play a key role in neuronal communication:this“conversation”is at the basis of all brain activities and synaptic dysfunction leads to brain disorders.We study the modulators of this crucial synaptic function and we here present the evidence supporting the c-Jun N-terminal kinase(JNK)pathway as a pivotal actor in this scenario.
基金supported by the Hargreaves and Ball Trust,the National Institute for Health Research(II-LA-0313-20003)(to AJR)the Rosetrees Trust,the Academy of Medical Sciences,and the Manchester Regenerative Medicine Network(MaRMN)(to AF and AJR)Progetto Eccellenza from the Italian Ministry of Research(to VM)
文摘Subsequent to a peripheral nerve injury, there are changes in gene expression within the dorsal root ganglia in response to the damage. This review selects factors which are well-known to be vital for inflammation, cell death and nociception, and highlights how alterations in their gene expression within the dorsal root ganglia can affect functional recovery. The majority of studies used polymerase chain reaction within animal models to analyse the dynamic changes following peripheral nerve injuries. This review aims to highlight the factors at the gene expression level that impede functional recovery and are hence are potential targets for therapeutic approaches. Where possible the experimental model, specific time-points and cellular location of expression levels are reported.
文摘Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulation and the saltatory conduction of nerve impulses.The formation of myelin is a complex process during which the OL precursor cells(OPCs,also known as NG2-glia)become mature OLs through a highly regulated program of differentiation.In addition,OPCs persist in the adult grey and white matter parenchyma,representing approximately 6%of the total number of CNS cells.Beyond their role in myelin generation and turn-over,it is now clear that OPCs have the capability to control tissue homeostasis and to sense and react to inflammation which characterizes many neurological diseases.
文摘Schwann cells and neuroregeneration:Peripheral nerve injury is a common cause of morbidity,which affects millions of people worldwide.The peripheral nervous system,differently from the central nervous system,has an intrinsic ability to regenerate after injury.However,in most cases the regenerative outcome is not completely satisfactory,in particular for long-gap peripheral nerve injuries in which the microsurgical approach is not possible.In these cases。
文摘In the last years,axonal conductance of action potential trains became a novel subject of study,changing the view of axons,from a static cable-like compartment to a more complex and dynamic system(Debanne et al.,2011).Axonal computation,indeed,is canonically constituted by the action of voltage-gated ion channels,such as the classic Na+and K+channels,but recent studies demonstrated that it can be modulated by the action of other ion channel pumps,and metabolic factors(Byczkowicz et al.,2019;Zang and Marder.
文摘Obesity represents a major public health problem,as it leads to metabolic disorders involved in the development of type 2 diabetes,fatty liver diseases,cardiovascular diseases and cancer(1).The Western lifestyle,including over-feeding of highly refined diets and sedentary behavior,is associated with systemic low-grade inflammation,responsible for chronic degenerative disease.Moreover,animal and human data have demonstrated the impact of high-fat diet feeding on the onset of metabolic endotoxemia.This latter,being characterized by increase blood lipopolysaccharide(LPS)levels,triggers low-grade inflammation and contributes to the development of obesity.The gut microbiota are a candidate sources of plasma LPS.Indeed,LPS is a major component of the outer membrane in Gram-negative bacteria and its plasma levels are correlated with changes in intestinal microbiota where the Gram-negative to Gram-positive ratio is increased by high fat feeding(1).Not surprising that in humans,obesity is characterized by dysbiosis,i.e.imbalances in the composition and function of the intestinal microbes.Currently,many studies are being conducted to assess the contribution of intestinal microflora metabolites[mainly short-chain fatty acids(SCFAs)]to the organism’s homeostasis.Dietary fibers have been promoted for their health benefits and high-fiber intake has been reported as beneficial in numerous chronic diseases(2).However,we have to keep in mind that consumption of dietary fiber significantly alters the composition of the gut microbiota.
基金supported by Italian Ministry of Health(Ricerca Corrente 2022,Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico,Milano)Ricerca Finalizzata Ministero della Salute GR-2019-12370172.
文摘Nonalcoholic fatty liver disease(NAFLD)is the major contributor to the global burden of chronic liver diseases and ranges from simple and reversible steatosis to nonalcoholic steatohepatitis(NASH),which may progress into cirrhosis and hepatocellular carcinoma(HCC).HCC represents the most common liver cancer,and it is a leading cause of death worldwide with an increasing trend for the future.Due to late diagnosis,non-responsiveness to systemic therapy,and high cancer heterogeneity,the treatment of this malignancy is challenging.To date,liver biopsy and ultrasound(US)are the gold standard procedures for HCC diagnosis and surveillance,although they are not suitable for mass screening.Therefore,it is impelling to find new,less invasive diagnostic strategies able to detect HCC at an early stage as well as monitor tumor progression and recurrence.Common and rare inherited variations that boost the switching from NASH to liver cancer may help to predict tumor onset.Furthermore,epigenetic changes which reflect intertumoral heterogeneity occur early in tumorigenesis and are highly stable under pathologic conditions.The severity of hepatic injuries can be detected through the analysis of cell circulating tumor DNAs(ctDNAs),microRNAs(miRNAs),and noncoding RNAs(ncRNAs),which are involved in several pathological processes that feature cancer,including cell growth,survival,and differentiation,thus representing appealing biomarkers for HCC.Therefore,this review discusses the current options for HCC surveillance,focusing on the role of genetic and epigenetic biomarkers as new strategies to refine HCC management.