Human bocavirus(HBoV) is a parvovirus isolated about a decade ago and found worldwide in both respiratory samples, mainly from early life and children of 6-24 mo of age with acute respiratory infection, and in stool s...Human bocavirus(HBoV) is a parvovirus isolated about a decade ago and found worldwide in both respiratory samples, mainly from early life and children of 6-24 mo of age with acute respiratory infection, and in stool samples, from patients with gastroenteritis. Since then, other viruses related to the first HBoV isolate(HBoV 1), namely HBoV 2, HBoV 3 and HBoV 4, have been detected principally in human faeces. HBo Vs are small nonenveloped single-stranded DNA viruses of about 5300 nucleotides, consisting of three open reading frames encoding the first two the non-structural protein 1(NS1) and nuclear phosphoprotein(NP1) and the third the viral capsid proteins 1 and 2(VP1 and VP2). HBoV pathogenicity remains to be fully clarified mainly due to the lack of animal models for the difficulties in replicating the virus in in vitro cell cultures, and the fact that HBo V infection is frequently accompanied by at least another viral and/or bacterial respiratory and/or gastroenteric pathogen infection. Current diagnostic methods to support HBoV detection include polymerase chain reaction, real-time PCR, enzymelinked immunosorbent assay and enzyme immunoassay using recombinant VP2 or virus-like particle capsid proteins, although sequence-independent amplification techniques combined with next-generation sequencing platforms promise rapid and simultaneous detection of the pathogens in the future. This review presents the current knowledge on HBoV genotypes with emphasis on taxonomy, phylogenetic relationship and genomic analysis, biology, epidemiology, pathogenesis and diagnostic methods. The emerging discussion on HBoV s as true pathogen or innocent bystander is also emphasized.展开更多
Motor neuron disease includes a heterogeneous group of relentless progressive neurological disorders defined and characterized by the degeneration of motor neurons.Amyotrophic lateral sclerosis is the most common and ...Motor neuron disease includes a heterogeneous group of relentless progressive neurological disorders defined and characterized by the degeneration of motor neurons.Amyotrophic lateral sclerosis is the most common and aggressive form of motor neuron disease with no effective treatment so far.Unfortunately,diagnostic and prognostic biomarkers are lacking in clinical practice.Neurofilaments are fundamental structural components of the axons and neurofilament light chain and phosphorylated neurofilament heavy chain can be measured in both cerebrospinal fluid and serum.Neurofilament light chain and phosphorylated neurofilament heavy chain levels are elevated in amyotrophic lateral sclerosis,reflecting the extensive damage of motor neurons and axons.Hence,neurofilaments are now increasingly recognized as the most promising candidate biomarker in amyotrophic lateral sclerosis.The potential usefulness of neurofilaments regards various aspects,including diagnosis,prognosis,patient stratification in clinical trials and evaluation of treatment response.In this review paper,we review the body of literature about neurofilaments measurement in amyotrophic lateral sclerosis.We also discuss the open issues concerning the use of neurofilaments clinical practice,as no overall guideline exists to date;finally,we address the most recent evidence and future perspectives.展开更多
The subgenual cingulate cortex has been found to be different in structure and function in mood and affective disorders compared to healthy individuals. Imaging studies have shown a decrease in function of the subgenu...The subgenual cingulate cortex has been found to be different in structure and function in mood and affective disorders compared to healthy individuals. Imaging studies have shown a decrease in function of the subgenual region in bipolar disorder and depression, with overall glial number shown to be decreased in these disorders. Decreases in subgenual grey matter in SZ have been observed also. In this neuropathological study upon formalin-fixed coronal brain sections we describe the morphological finding of de- creased frequency of subgenual cingulate crown bifurcation (p = 0.02) as compared to control, bipolar and depression cases. This suggests that the cingulate cortex in schizophrenia may be morphologically distinct in utero formation, potentially enabling an early identification of high-risk individuals.展开更多
Objective:a-Synuclein has been studied as a potential biomarker for Parkinson's disease(PD)with no concluding results.Accordingly,there is an urgent need to find out reliable specific biomarkers for PD.GPR37 is an...Objective:a-Synuclein has been studied as a potential biomarker for Parkinson's disease(PD)with no concluding results.Accordingly,there is an urgent need to find out reliable specific biomarkers for PD.GPR37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile parkinsonism.Here,we investigated whether GPR37 is upregulated in sporadic PD,and thus a suitable potential biomarker for PD.Methods:GPR37 protein density and mRNA expression in postmortem substantia nigra(SN)from PD patients were analysed by immunoblot and RT-qPCR,respectively.The presence of peptides from the N-terminus-cleaved domain of GPR37(i.e.ecto-GPR37)in human cerebrospinal fluid(CSF)was determined by liquid chromatography-mass spectrometric analysis.An engineered in-house nanoluciferase-based immunoassay was used to quantify ecto-GPR37 in CSF samples from neurological control(NC)subjects,PD patients and Alzheimer's disease(AD)patients.Results:GPR37 protein density and mRNA expression were significantly augmented in sporadic PD.Increased amounts of ecto-GPR37 peptides in the CSF samples from PD patients were identified by mass spectrometry and quantified by the in-house ELISA method.However,the CSF total a-synuclein level in PD patients did not differ from that in NC subjects.Similarly,the cortical GPR37 mRNA expression and CSF ecto-GPR37 levels in AD patients were also unaltered.Conclusion:GPR37 expression is increased in SN of sporadic PD patients.The ecto-GPR37 peptides are significantly increased in the CSF of PD patients,but not in AD patients.These results open perspectives and encourage further clinical studies to confirm the validity and utility of ecto-GPR37 as a potential PD biomarker.展开更多
In this study, the effects of Radio Electric Asymmetric Conveyer(REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with1-methyl-4-phenyl-...In this study, the effects of Radio Electric Asymmetric Conveyer(REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP),were investigated in vivo. We found that the REAC tissue optimization treatment specific for neuro-regenerative purposes(REAC TO-RGN-N) attenuated the inflammatory picture evoked by MPTP-induced nigro-striatal damage inmice, decreasing the levels of pro-inflammatory molecules and increasing anti-inflammatory mediators. Besides, there was a significant reduction of both astrocyte and microglial activation in MPTP-treated mice exposed to REAC TORGN-N. These results indicated that REAC TO-RGN-N treatment modulates the pro-inflammatory responses and reduces neuronal damage in MPTP-induced parkinsonism.展开更多
文摘Human bocavirus(HBoV) is a parvovirus isolated about a decade ago and found worldwide in both respiratory samples, mainly from early life and children of 6-24 mo of age with acute respiratory infection, and in stool samples, from patients with gastroenteritis. Since then, other viruses related to the first HBoV isolate(HBoV 1), namely HBoV 2, HBoV 3 and HBoV 4, have been detected principally in human faeces. HBo Vs are small nonenveloped single-stranded DNA viruses of about 5300 nucleotides, consisting of three open reading frames encoding the first two the non-structural protein 1(NS1) and nuclear phosphoprotein(NP1) and the third the viral capsid proteins 1 and 2(VP1 and VP2). HBoV pathogenicity remains to be fully clarified mainly due to the lack of animal models for the difficulties in replicating the virus in in vitro cell cultures, and the fact that HBo V infection is frequently accompanied by at least another viral and/or bacterial respiratory and/or gastroenteric pathogen infection. Current diagnostic methods to support HBoV detection include polymerase chain reaction, real-time PCR, enzymelinked immunosorbent assay and enzyme immunoassay using recombinant VP2 or virus-like particle capsid proteins, although sequence-independent amplification techniques combined with next-generation sequencing platforms promise rapid and simultaneous detection of the pathogens in the future. This review presents the current knowledge on HBoV genotypes with emphasis on taxonomy, phylogenetic relationship and genomic analysis, biology, epidemiology, pathogenesis and diagnostic methods. The emerging discussion on HBoV s as true pathogen or innocent bystander is also emphasized.
文摘Motor neuron disease includes a heterogeneous group of relentless progressive neurological disorders defined and characterized by the degeneration of motor neurons.Amyotrophic lateral sclerosis is the most common and aggressive form of motor neuron disease with no effective treatment so far.Unfortunately,diagnostic and prognostic biomarkers are lacking in clinical practice.Neurofilaments are fundamental structural components of the axons and neurofilament light chain and phosphorylated neurofilament heavy chain can be measured in both cerebrospinal fluid and serum.Neurofilament light chain and phosphorylated neurofilament heavy chain levels are elevated in amyotrophic lateral sclerosis,reflecting the extensive damage of motor neurons and axons.Hence,neurofilaments are now increasingly recognized as the most promising candidate biomarker in amyotrophic lateral sclerosis.The potential usefulness of neurofilaments regards various aspects,including diagnosis,prognosis,patient stratification in clinical trials and evaluation of treatment response.In this review paper,we review the body of literature about neurofilaments measurement in amyotrophic lateral sclerosis.We also discuss the open issues concerning the use of neurofilaments clinical practice,as no overall guideline exists to date;finally,we address the most recent evidence and future perspectives.
文摘The subgenual cingulate cortex has been found to be different in structure and function in mood and affective disorders compared to healthy individuals. Imaging studies have shown a decrease in function of the subgenual region in bipolar disorder and depression, with overall glial number shown to be decreased in these disorders. Decreases in subgenual grey matter in SZ have been observed also. In this neuropathological study upon formalin-fixed coronal brain sections we describe the morphological finding of de- creased frequency of subgenual cingulate crown bifurcation (p = 0.02) as compared to control, bipolar and depression cases. This suggests that the cingulate cortex in schizophrenia may be morphologically distinct in utero formation, potentially enabling an early identification of high-risk individuals.
基金supported by Ministerio de Ciencia,Innovacion y Universidades-Agencia Estatal de Investigacion/FEDER(SAF2017-87349-R and MDM-2017-0729)ISCIII/FEDER(PIE14/00034 and PI19/00144)+5 种基金Generalitat de Catalunya(2017SGR1604,2017SGR595)Fundacio la Marato de TV3(Grant 20152031)FWO(SBO-140028)ERC consolidator grant(Progsy 649116)Stiftelsen for Strategisk Forskning and a Wallenberg Clinical Scholarship to PS.The CRG/UPF Proteomics Unit is part of the Spanish Infrastruaure for Omics Technologies(ICTS OmicsTech)is a member of the ProteoRed PRB3 consortium which is supported by grant PT17/0019 of the PEI+D+i 2013-2016 from the Instituto de Salud Carlos Ⅲ(ISCⅢ)and ERDF.
文摘Objective:a-Synuclein has been studied as a potential biomarker for Parkinson's disease(PD)with no concluding results.Accordingly,there is an urgent need to find out reliable specific biomarkers for PD.GPR37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile parkinsonism.Here,we investigated whether GPR37 is upregulated in sporadic PD,and thus a suitable potential biomarker for PD.Methods:GPR37 protein density and mRNA expression in postmortem substantia nigra(SN)from PD patients were analysed by immunoblot and RT-qPCR,respectively.The presence of peptides from the N-terminus-cleaved domain of GPR37(i.e.ecto-GPR37)in human cerebrospinal fluid(CSF)was determined by liquid chromatography-mass spectrometric analysis.An engineered in-house nanoluciferase-based immunoassay was used to quantify ecto-GPR37 in CSF samples from neurological control(NC)subjects,PD patients and Alzheimer's disease(AD)patients.Results:GPR37 protein density and mRNA expression were significantly augmented in sporadic PD.Increased amounts of ecto-GPR37 peptides in the CSF samples from PD patients were identified by mass spectrometry and quantified by the in-house ELISA method.However,the CSF total a-synuclein level in PD patients did not differ from that in NC subjects.Similarly,the cortical GPR37 mRNA expression and CSF ecto-GPR37 levels in AD patients were also unaltered.Conclusion:GPR37 expression is increased in SN of sporadic PD patients.The ecto-GPR37 peptides are significantly increased in the CSF of PD patients,but not in AD patients.These results open perspectives and encourage further clinical studies to confirm the validity and utility of ecto-GPR37 as a potential PD biomarker.
基金supported by a Fondazione Umberto Veronesi 2011 grant to RRa grant from the University of Bari(Fondi di Ateneo 2014)a grant from the University of Salento(Fondi di Ateneo 2014)
文摘In this study, the effects of Radio Electric Asymmetric Conveyer(REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP),were investigated in vivo. We found that the REAC tissue optimization treatment specific for neuro-regenerative purposes(REAC TO-RGN-N) attenuated the inflammatory picture evoked by MPTP-induced nigro-striatal damage inmice, decreasing the levels of pro-inflammatory molecules and increasing anti-inflammatory mediators. Besides, there was a significant reduction of both astrocyte and microglial activation in MPTP-treated mice exposed to REAC TORGN-N. These results indicated that REAC TO-RGN-N treatment modulates the pro-inflammatory responses and reduces neuronal damage in MPTP-induced parkinsonism.
