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Frontiers in Veterinary Science 2022Coinfection with Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) causes synergistic pathogenic effects and serious losses to the poultry industry....
Coinfection with Marek's disease virus (MDV) and reticuloendotheliosis virus (REV) causes synergistic pathogenic effects and serious losses to the poultry industry. However, whether there is a synergism between the two viruses in viral replication and the roles of host factors in regulating MDV and REV coinfection remains elusive. In this study, we found that MDV and REV coinfection increased viral replication in coinfected cells as compared to a single infection in a limited period. Further, we explore the host cell responses to MDV and REV coinfection using tandem mass tag (TMT) peptide labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Compared with MDV/REV-infected cells, 38 proteins increased (fold change > 1.2) and 60 decreased (fold change < 0.83) their abundance in MDV and REV coinfected cells. Differentially accumulated proteins (DAPs) were involved in important biological processes involved in the immune system process, cell adhesion and migration, cellular processes, and multicellular organismal systems. STRING analysis found that IRF7, MX1, TIMP3, and AKT1 may be associated with MDV and REV synergistic replication in chicken embryo fibroblasts (CEFs). Western blotting analysis showed that the selected DAPs were identical to the quantitative proteomics data. Taken together, we verified that MDV and REV can synergistically replicate in coinfected cells and revealed the host molecules involved in it. However, the synergistic pathogenesis of MDV and REV needs to be further studied.
PubMed: 35392111
DOI: 10.3389/fvets.2022.854007 -
PloS One 2021Several pathophysiological processes are involved in Parkinson's disease (PD) and could inform in vivo biomarkers. We assessed an established biomarker panel, validated... (Clinical Trial)
Clinical Trial Observational Study
AIM
Several pathophysiological processes are involved in Parkinson's disease (PD) and could inform in vivo biomarkers. We assessed an established biomarker panel, validated in Alzheimer's Disease, in a PD cohort.
METHODS
Longitudinal cerebrospinal fluid (CSF) samples from PPMI (252 PD, 115 healthy controls, HC) were analyzed at six timepoints (baseline, 6, 12, 24, 36, and 48 months follow-up) using Elecsys® electrochemiluminescence immunoassays to quantify neurofilament light chain (NfL), soluble TREM2 receptor (sTREM2), chitinase-3-like protein 1 (YKL40), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), S100, and total α-synuclein (αSyn).
RESULTS
αSyn was significantly lower in PD (mean 103 pg/ml vs. HC: 127 pg/ml, p<0.01; area under the curve [AUC]: 0.64), while all other biomarkers were not significantly different (AUC NfL: 0.49, sTREM2: 0.54, YKL40: 0.57, GFAP: 0.55, IL-6: 0.53, S100: 0.54, p>0.05) and none showed a significant difference longitudinally. We found significantly higher levels of all these markers between PD patients who developed cognitive decline during follow-up, except for αSyn and IL-6.
CONCLUSION
Except for αSyn, the additional biomarkers did not differentiate PD and HC, and none showed longitudinal differences, but most markers predict cognitive decline in PD during follow-up.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Female; Humans; Longitudinal Studies; Male; Middle Aged; Neuroglia; Parkinson Disease; alpha-Synuclein
PubMed: 34618817
DOI: 10.1371/journal.pone.0257372 -
NPJ Parkinson's Disease Oct 2022We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the...
We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson's Progression Markers Initiative (PPMI). We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging, and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as <65% of age/sex-expected lowest putamen SBR) and 11% had hyposmia (defined as ≤15th percentile for age and sex). Only 5 of 176 LRRK2 NMCs developed PD during follow-up. Although NMCs scored significantly worse on numerous clinical scales at baseline than HCs, there was no longitudinal change in any clinical measures over 2 years or in DAT binding. There were no longitudinal differences in CSF and serum biomarkers between NMCs and HCs. Urinary BMP was significantly elevated in NMCs at all time points but did not change longitudinally. Neither baseline biofluid biomarkers nor the presence of DAT deficit correlated with 2-year change in clinical outcomes. We observed no significant 2-year longitudinal change in clinical or biomarker measures in LRRK2 G2019S NMCs in this large, well-characterized cohort even in the participants with baseline DAT deficit. These findings highlight the essential need for further enrichment biomarker discovery in addition to DAT deficit and longer follow-up to enable the selection of NMCs at the highest risk for conversion to enable future prevention clinical trials.
PubMed: 36273008
DOI: 10.1038/s41531-022-00404-w -
NPJ Parkinson's Disease Feb 2023We quantified concentrations of three isoforms of the endolysosomal lipid, bis(monoacylglycerol) phosphate (BMP) in the urine of deeply phenotyped cohorts in the...
We quantified concentrations of three isoforms of the endolysosomal lipid, bis(monoacylglycerol) phosphate (BMP) in the urine of deeply phenotyped cohorts in the Parkinson's Progression Markers Initiative: LRRK2 G2019S PD (N = 134) and non-manifesting carriers (NMC) (G2019S+ NMC; N = 182), LRRK2 R1441G PD (N = 15) and R1441G+ NMC (N = 15), GBA1 N409S PD (N = 76) and N409S+ NMC (N = 178), sporadic PD (sPD, N = 379) and healthy controls (HC) (N = 190). The effects of each mutation and disease status were analyzed using nonparametric methods. Longitudinal changes in BMP levels were analyzed using linear mixed models. At baseline, all LRRK2 carriers had 3-7× higher BMP levels compared to HC, irrespective of the disease status. GBA1 N409S carriers also showed significant, albeit smaller, elevation (~30-40%) in BMP levels compared to HC. In LRRK2 G2019S PD, urinary BMP levels remained stable over two years. Furthermore, baseline BMP levels did not predict disease progression as measured by striatal DaT imaging, MDS-UPDRS III Off, or MoCA in any of the cohorts. These data support the utility of BMP as a target modulation biomarker in therapeutic trials of genetic and sPD but not as a prognostic or disease progression biomarker.
PubMed: 36854767
DOI: 10.1038/s41531-023-00468-2 -
Frontiers in Veterinary Science 2023
PubMed: 38026625
DOI: 10.3389/fvets.2023.1326282 -
Journal of Gastrointestinal Surgery :... Jul 2023Autologous fat grafting (AFG) has shown promise in the treatment of complex wounds, with trials reporting good healing rates and safety profile. We aim to investigate...
BACKGROUND
Autologous fat grafting (AFG) has shown promise in the treatment of complex wounds, with trials reporting good healing rates and safety profile. We aim to investigate the role of AFG in managing complex anorectal fistulas.
METHODS
This was a retrospective review of a prospectively maintained IRB-approved database. We examined the rates of symptom improvement, clinical closure of fistula tracts, recurrence, complications, and worsening fecal incontinence. Perianal disease activity index (PDAI) was obtained for patients undergoing combination of AFG and fistula plug treatment.
RESULTS
In total, 52 unique patients underwent 81 procedures, of which Crohn's was present in 34 (65.4%) patients. The majority of patients previously underwent more common treatments such as endorectal advancement flap or ligation of intersphincteric fistula tract. Fat-harvesting sites and processing technique were selected by the plastic surgeons based on availability of trunk fat deposits. When analyzing patients by their last procedure, 41 (80.4%) experienced symptom improvement, and 29 (64.4%) experienced clinical closure of all fistula tracts. Recurrence rate was 40.4%, and complication rate was 15.4% (7 postoperative abscesses requiring I&D and 1 bleeding episode ligated at bedside). The abdomen was the most common site of lipoaspirate harvest at 63%, but extremities were occasionally used. There were no statistically significant differences in outcomes when comparing single graft treatment to multiple treatments, Crohn's and non-Crohn's, different methods of fat preparation, and diversion.
CONCLUSION
AFG is a versatile procedure that can be done in conjunction with other therapies and does not interfere with future treatments if recurrence occurs. It is a promising and affordable method to safely address complex fistulas.
Topics: Humans; Treatment Outcome; Rectal Fistula; Surgical Flaps; Fecal Incontinence; Ligation; Crohn Disease; Inflammation; Adipose Tissue; Anal Canal; Recurrence
PubMed: 37268827
DOI: 10.1007/s11605-023-05719-4 -
JAMA Neurology Nov 2020Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future...
IMPORTANCE
Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis.
OBJECTIVE
To investigate the potential of the novel tau radiotracer 18F-PI-2620 as a biomarker in patients with clinically diagnosed PSP.
DESIGN, SETTING, AND PARTICIPANTS
In this cross-sectional study, participants underwent dynamic 18F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019.
MAIN OUTCOMES AND MEASURES
Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, 18F-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex.
RESULTS
Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP-non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable 18F-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with 18F-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP-non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region.
CONCLUSIONS AND RELEVANCE
This multicenter evaluation indicates a value of 18F-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP.
Topics: Aged; Biomarkers; Cross-Sectional Studies; Diagnosis; Female; Fluorine Radioisotopes; Gray Matter; Humans; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Positron-Emission Tomography; Pyridines; Sensitivity and Specificity; Severity of Illness Index; Supranuclear Palsy, Progressive; tau Proteins
PubMed: 33165511
DOI: 10.1001/jamaneurol.2020.2526 -
Viruses Jul 2021Due to the emergence of antibiotic resistance and new and more complex diseases that affect livestock animal health and food security, the control of epidemics has... (Review)
Review
Due to the emergence of antibiotic resistance and new and more complex diseases that affect livestock animal health and food security, the control of epidemics has become a top priority worldwide. Vaccination represents the most important and cost-effective measure to control infectious diseases in animal health, but it represents only 23% of the total global animal health market, highlighting the need to develop new vaccines. A recent strategy in animal health vaccination is the use of extracellular vesicles (EVs), lipid bilayer nanovesicles produced by almost all living cells, including both prokaryotes and eukaryotes. EVs have been evaluated as a prominent source of viral antigens to elicit specific immune responses and to develop new vaccination platforms as viruses and EVs share biogenesis pathways. Preliminary trials with lymphocytic choriomeningitis virus infection (LCMV), porcine reproductive and respiratory syndrome virus (PRRSV), and Marek's disease virus (MDV) have demonstrated that EVs have a role in the activation of cellular and antibody immune responses. Moreover, in parasitic diseases such as (chickens) and (mice) protection has been achieved. Research into EVs is therefore opening an opportunity for new strategies to overcome old problems affecting food security, animal health, and emerging diseases. Here, we review different conventional approaches for vaccine design and compare them with examples of EV-based vaccines that have already been tested in relation to animal health.
Topics: Animals; Chickens; Exosomes; Herpesvirus 2, Gallid; Poultry Diseases; Swine; Swine Diseases; Vaccination; Viral Vaccines; Virus Diseases
PubMed: 34452364
DOI: 10.3390/v13081499 -
Biological Trace Element Research Feb 2023The rapid spread of new pathogens (SARS-CoV-2 virus) that negatively affect the human body has huge consequences for the global public health system and the development... (Review)
Review
The rapid spread of new pathogens (SARS-CoV-2 virus) that negatively affect the human body has huge consequences for the global public health system and the development of the global economy. Appropriate implementation of new safety regulations will improve the functioning of the current model supervising the inhibition of the spread of COVID-19 disease. Compliance with all these standards will have a key impact on the health behavior of individual social groups. There have been demonstrably effective treatments that proved to be effective but were rapidly dismissed for unknown reasons, such as ivermectin and hydroxychloroquine. Various measures are used in the world to help inhibit its development. The properties of this element provide hope in preventing the development of the SARS-CoV-2 virus. The aim of this review is to synthesize the latest literature data and to present the effect of sodium selenite in reducing the incidence of COVID-19 disease.
Topics: Humans; SARS-CoV-2; COVID-19; Selenium; Hydroxychloroquine; Ivermectin
PubMed: 35305539
DOI: 10.1007/s12011-022-03208-4 -
Journal of Clinical Medicine Nov 2019Multiple myeloma (MM) is a malignancy of clonal plasma cells accounting for approximately 10% of haematological malignancies. MM mainly affects older patients, more... (Review)
Review
Multiple myeloma (MM) is a malignancy of clonal plasma cells accounting for approximately 10% of haematological malignancies. MM mainly affects older patients, more often males and is more frequently seen in African Americans. The most frequent manifestations of MM are anaemia, osteolytic bone lesions, kidney failure and hypercalcemia. The anaemia develops secondary to suppression of erythropoiesis by cytokine networks, similarly to the mechanism of anaemia of chronic disease. The concomitant presence of kidney failure, especially chronic kidney disease (CKD) and MM per se, leading to anaemia of chronic disease (ACD) in combination, provoked us to pose the question about their reciprocal dependence and relationship with specific biomarkers; namely, soluble transferrin receptor (sTfR), growth differentiation factor 15 (GDF15), hepcidin 25 and zonulin. One or more of these are new biomarkers of ferric management may be utilized in the near future as prognostic predictors for patients with MM and kidney failure.
PubMed: 31683939
DOI: 10.3390/jcm8111828