ABSTRACT
BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, which promotes a sustained inflammatory environment in the central nervous system. Regulatory T cells (Tregs) play an important role in the control of inflammation and might play a neuroprotective role. Indeed, a decrease in Treg number and function has been reported in PD. In this context, pramipexole, a dopaminergic receptor agonist used to treat PD symptoms, has been shown to increase peripheral levels of Treg cells and improve their suppressive function. The aim of this work was to determine the effect of pramipexole on immunoregulatory Treg cells and its possible neuroprotective effect on human dopaminergic neurons differentiated from human embryonic stem cells. METHODS: Treg cells were sorted from white blood cells of healthy human donors. Assays were performed with CD3/CD28-activated and non-activated Treg cells treated with pramipexole at concentrations of 2 or 200 ng/mL. These regulatory cells were co-cultured with in vitro-differentiated human dopaminergic neurons in a cytotoxicity assay with 6-hydroxydopamine (6-OHDA). The role of interleukin-10 (IL-10) was investigated by co-culturing activated IL-10-producing Treg cells with neurons. To further investigate the effect of treatment on Tregs, gene expression in pramipexole-treated, CD3/CD28-activated Treg cells was determined by Fluidigm analysis. RESULTS: Pramipexole-treated CD3/CD28-activated Treg cells showed significant protective effects on dopaminergic neurons when challenged with 6-OHDA. Pramipexole-treated activated Treg cells showed neuroprotective capacity through mechanisms involving IL-10 release and the activation of genes associated with regulation and neuroprotection. CONCLUSION: Anti-CD3/CD28-activated Treg cells protect dopaminergic neurons against 6-OHDA-induced damage. In addition, activated, IL-10-producing, pramipexole-treated Tregs also induced a neuroprotective effect, and the supernatants of these co-cultures promoted axonal growth. Pramipexole-treated, activated Tregs altered their gene expression in a concentration-dependent manner, and enhanced TGFß-related dopamine receptor regulation and immune-related pathways. These findings open new perspectives for the development of immunomodulatory therapies for the treatment of PD.
Subject(s)
Benzothiazoles , Dopaminergic Neurons , Oxidopamine , Pramipexole , T-Lymphocytes, Regulatory , Humans , Pramipexole/pharmacology , T-Lymphocytes, Regulatory/drug effects , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Oxidopamine/toxicity , Benzothiazoles/pharmacology , Coculture Techniques , Interleukin-10/metabolism , Cells, Cultured , Neuroprotective Agents/pharmacology , Dopamine Agonists/pharmacologyABSTRACT
Background: Immunomodulatory drugs and immunotherapies are being evaluated in clinical trials for the treatment of neuroinflammation, as the latter is an essential mechanism for the development and progression of Parkinson's disease. Objective: The objective of the study is to review recent evidence on the evaluation of immunomodulators in randomized controlled clinical trials measuring improvement of motor symptoms. Methods: A meta-analysis of Movement Disorder Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS III) scores extracted from seven articles selected after an online search of PubMed, Cochrane Library, and Clarivate's Web of Science for randomized controlled clinical trials published between 2000 and July 2023 was performed. The selected articles reported clinical trials evaluating the effects of specific immunomodulators or treatments with known effects on the immune system and inflammation. MDS-UPDRS III scores were reported in these studies, and the results of the placebo groups were compared with those of the treatment groups. Results: A total of 590 patients treated with immunomodulators and 622 patients treated with placebo were included. A test for heterogeneity yielded an I2 value > 50%. The mean standard difference for change in MDS-UPDR III score was -0.46 (CI [95%] = -0.90 - -0.02, p < 0.01). No significant differences were found in the change in mean MDS-UPDR III score between the treatment and placebo groups; however, two studies showed a trend toward separation from the mean. Conclusion: The immunomodulatory treatments included in this study showed no efficacy in improving motor symptoms in Parkinson's disease patients. Further clinical trials with larger patient populations are needed.
Subject(s)
Immunomodulating Agents , Parkinson Disease , Randomized Controlled Trials as Topic , Parkinson Disease/drug therapy , Parkinson Disease/therapy , Humans , Immunomodulating Agents/administration & dosage , Immunomodulating Agents/therapeutic use , Immunomodulating Agents/pharmacology , Immunomodulation , Immunologic Factors/therapeutic use , Immunologic Factors/administration & dosage , Immunotherapy/methodsABSTRACT
Whilst the contribution of peripheral and central inflammation to neurodegeneration in Parkinson's disease and the role of the immune response in this disorder are well known, the effects of the anti-inflammatory response on the disease have not been described in depth. This study is aimed to assess the changes in the regulatory/inflammatory immune response in recently diagnosed, untreated PD patients and a year after. Twenty-one PD patients and 19 healthy controls were included and followed-up for 1 year. The levels of immunoregulatory cells (CD4+ Tregs, Bregs, and CD8+ Tregs); classical, nonclassical, and intermediate monocytes, and proinflammatory cells (Th1, Th2, and Th17) were measured by flow cytometry. Cytokine levels were determined by ELISA. Clinical follow-up was based on the Hoehn & Yahr and UDPRS scales. Our results indicate that the regulatory response in PD patients on follow-up was characterized by increased levels of active Tregs, functional Tregs, TR1, IL-10-producing functional Bregs, and IL-10-producing classical monocytes, along with decreased counts of Bregs and plasma cells. With respect to the proinflammatory immune response, peripheral levels of Th1 IFN-γ+ cells were decreased in treated PD patients, whilst the levels of CD4+ TBET+ cells, HLA-DR+ intermediate monocytes, IL-6, and IL-4 were increased after a 1-year follow-up. Our main finding was an increased regulatory T cell response after a 1-year follow-up and its link with clinical improvement in PD patients. In conclusion, after a 1-year follow-up, PD patients exhibited increased levels of regulatory populations, which correlated with clinical improvement. However, a persistent inflammatory environment and active immune response were observed.
ABSTRACT
Progressive supranuclear palsy (PSP) is a neurodegenerative disease, commonly observed as a movement disorder in the group of parkinsonian diseases. The term PSP usually refers to PSP-Richardson's syndrome (PSP-RS), the most typical clinical presentation. However, the broad concept of progressive supranuclear palsy syndrome (PSP-S) applies to a set of clinical entities that share a pathophysiological origin and some symptoms. According to its clinical predominance, PSP-S is divided into subtypes. PSP-S has clinical similarities with Parkinson's disease, and both pathologies are classified in the group of parkinsonisms, but they do not share pathophysiological traits. By contrast, the pathophysiology of corticobasal syndrome (CBS) depends on tau expression and shares similarities with PSP-S in both pathophysiology and clinical picture. An involvement of the immune system has been proposed as a cause of neurodegeneration. The role of neuroinflammation in PSP-S has been studied by neuroimaging, among other methods. As it is the case in other neurodegenerative pathologies, microglial cells have been attributed a major role in PSP-S. While various studies have explored the detection and use of possible inflammatory biomarkers in PSP-S, no significant advances have been made in this regard. This review is aimed at highlighting the most relevant information on neuroinflammation and peripheral inflammation in the development and progression of PSP-S, to lay the groundwork for further research on the pathophysiology, potential biomarkers, and therapeutic strategies for PSP-S.
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Treatment options are limited for patients with non-clear cell renal cell carcinoma (nccRCC). Patients with nccRCC experienced a favorable objective response rate (ORR) in a phase 2 trial of cabozantinib plus nivolumab. We now report updated efficacy and safety results at median follow-up of 34 mo for patients with papillary, unclassified, or translocation-associated RCC. Cabozantinib and nivolumab were administered at standard doses to patients with metastatic nccRCC that had progressed on zero or one line of systemic therapy. The primary endpoint was the ORR according to Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Forty patients were treated. At median follow-up of 34 mo for survivors, the ORR was 48% (95% confidence interval [CI] 31.5-63.9%). Median PFS was 13 mo (95% CI 7-16); the 12-mo and 24-mo PFS rates were 51% (95% CI 34-65%) and 23% (95% CI 11-37%), respectively. Median OS was 28 mo (95% CI 23-43); the 18-mo and 36-mo OS rates were 70% (95% CI 53-82%) and 44% (95% CI 28-60%), respectively. No new safety signals were seen with cabozantinib and nivolumab. This extended follow-up analysis demonstrates promising efficacy, and highlights the potential for sustained responses with cabozantinib plus nivolumab in patients with metastatic nccRCC.
Subject(s)
Anilides , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Renal Cell , Kidney Neoplasms , Nivolumab , Pyridines , Humans , Anilides/therapeutic use , Nivolumab/therapeutic use , Nivolumab/adverse effects , Pyridines/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/mortality , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/mortality , Male , Female , Middle Aged , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Progression-Free Survival , Treatment OutcomeABSTRACT
The association of silver nanoparticles (AgNps) to sealant agent Palaseal® can be a promising alternative for complete denture wearers who may develop denture stomatitis (DS). The study aimed to evaluate the anti-Candida and biocompatible potential of silver nanoparticles synthesized by three routes associated with denture glaze to prevent and/or treat oral candidiasis. Surface acrylic resin specimens were treated with different associations of glaze with AgNps (VER+AgUV, VER+AgTurk and VER+AgGm). As controls, specimens were treated with glaze+nystatin (VER+Nyst), glaze only (VER) or submerged in PBS (PBS). Afterwards, Candida albicans biofilm was developed for 24 h, 15 d and 30 d. Subsequently, the biofilm was quantified by CFU/mL, XTT assay and confocal laser scanning microscopy. Fibroblasts were submitted to conditioned medium with the same associations for 24, 48 and 72 h and LIVE/DEAD® viability test was carried out. Regardless of the period, there was a significant reduction (p < 0.01) of viable fungal cells load, as well as inhibition of fungal metabolic activity, in specimens treated with glaze+AgNps associations, compared to VER and PBS. The anti-Candida effects of the associations were similar to the VER+Nyst group, with emphasis on VER+AgGm, which showed the highest percentage values of non-viable fungal cells maintained over time. The associations did not prove toxicity to fibroblasts. The AgNps exerted antimicrobial activity against C. albicans biofilms and are biocompatible. The most effective results were achieved with the association of glaze+silver nanoparticles synthesized by the green chemistry method (AgGm), proving to be an innovative alternative in the management of DS.
ABSTRACT
The neurovascular unit, composed of vascular endothelium, vascular smooth muscle, extracellular matrix components, pericytes, astrocytes, microglia, and neurons, allows the highly regulated exchange of molecules and the limited trafficking of cells to the brain through coordinated signaling activity. The passage of peripheral immune cells to the brain parenchyma is observed when there is clear damage to the barriers of this neurovascular unit, as occurs in traumatic brain injury. The possibility of leukocyte infiltration to the brain in neurodegenerative conditions has been proposed. In this review, we focus on describing the evidence for peripheral immune cell infiltration to the brain in the two most frequent neurodegenerative diseases: Alzheimer's and Parkinson's diseases. In particular, we address the mechanisms that promote the passage of these cells into the brain under such pathological conditions. We also discuss the relevance of the resulting cellular interactions, which provide evidence that the presence of peripheral immune cells in the brain is a key point in these neurodegenerative diseases.
ABSTRACT
Parkinson's disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, and aging as its biggest risk factors. Mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) are biological aging markers with inconclusive results regarding their association with PD. A case-control study was used to measure TL and mtDNA-CN using qPCR in PBMCs. PD patients were naive at baseline (T0) and followed-up at one (T1) and two (T2) years after the dopaminergic treatment (DRT). Plasmatic cytokines were determined by ELISA in all participants, along with clinical parameters of patients at T0. While TL was shorter in patients vs. controls at all time points evaluated (p < 0.01), mtDNA-CN showed no differences. An increase in mtDNA-CN and TL was observed in treated patients vs. naive ones (p < 0.001). Our statistical model analyzed both aging markers with covariates, showing a strong correlation between them (r = 0.57, p < 0.01), and IL-17A levels positively correlating with mtDNA-CN only in untreated patients (r = 0.45, p < 0.05). TL and mtDNA-CN could be useful markers for monitoring inflammation progression or treatment response in PD. DRT might modulate TL and mtDNA-CN, reflecting a compensatory mechanism to counteract mitochondrial dysfunction in PD, but this needs further investigation.
Subject(s)
DNA, Mitochondrial , Parkinson Disease , Humans , DNA, Mitochondrial/genetics , Case-Control Studies , DNA Copy Number Variations/genetics , Parkinson Disease/genetics , Telomere/genetics , Mitochondria/genetics , BiomarkersABSTRACT
PURPOSE: To evaluate the published literature on tooth-tissue supported removable partial dentures (RPDs) and determine the attachment system that provides the best clinical outcome. MATERIALS AND METHODS: A comprehensive search of studies published up to November 2021 was performed in the PubMed/MEDLINE, Web of Science, and Cochrane Library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The study protocol was approved and was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42021268449). The PICO question was, "What is the best attachment system used in Kennedy class I and II removable partial dentures?" RESULTS: The search identified 871 articles, of which 21 met the inclusion criteria. The evaluation period in the studies ranged from 3 to 282 months. A total of 1,357 patients were included, of which 526 used prostheses with attachments. The mini SG attachment (extracoronal) was the most commonly used attachment, and the survival rate ranged from 37% to 98.1% in 10 studies, with no significant differences between the systems. Among the 10 studies selected for quantitative analysis, the meta-analysis revealed an overall failure rate of 16.6% (95% confidence interval: 10.4-25.4%), and heterogeneity of I²=65.725 (Q-value: 26.258, P=.002). CONCLUSION: Clinical studies comparing different attachment systems for rehabilitation are lacking. Our findings suggest that attachment-retained RPDs have good retention and better esthetics than conventional RPDs and that the extracoronal attachment system is the most viable choice for treatment at the free end.
ABSTRACT
Background: In Parkinson's disease (PD), exosomes carry α-synuclein (α-syn), a fibrillar protein aggregates with potential value as a biomarker. Objective: Evidence on blood levels of exosomal α-syn in PD patients and controls was reviewed for their consistency. Methods: Thirty-six studies on exosomal α-syn concentrations in PD were identified in a systematic literature search and meta-analysis. Results: Both raw and ratio-adjusted blood exosomal α-syn levels were consistently higher in PD patients than in controls. The standardized mean difference (SMD) was 1.54 (0.18-2.90, CI95%, p < 0.01) and 1.53 (0.23-2.83, CI95%, p < 0.01), respectively. Conclusion: Our results suggest that exosomal α-syn concentrations could be a useful biomarker for PD.
Subject(s)
Extracellular Vesicles , Parkinson Disease , Humans , alpha-Synuclein , Biomarkers , Parkinson Disease/diagnosisABSTRACT
ABSTRACT Background: In Parkinson's disease (PD), exosomes carry α-synuclein (α-syn), a fibrillar protein aggregates with potential value as a biomarker. Objective: Evidence on blood levels of exosomal α-syn in PD patients and controls was reviewed for their consistency. Methods: Thirty-six studies on exosomal α-syn concentrations in PD were identified in a systematic literature search and meta-analysis. Results: Both raw and ratio-adjusted blood exosomal α-syn levels were consistently higher in PD patients than in controls. The standardized mean difference (SMD) was 1.54 (0.18-2.90, CI95%, p < 0.01) and 1.53 (0.23-2.83, CI95%, p < 0.01), respectively. Conclusion: Our results suggest that exosomal α-syn concentrations could be a useful biomarker for PD.
ABSTRACT
Coherent multi-transducer ultrasound (CoMTUS) creates an extended effective aperture through the coherent combination of multiple arrays, which results in images with enhanced resolution, extended field-of-view, and higher sensitivity. The subwavelength localization accuracy of the multiple transducers required to coherently beamform the data is achieved by using the echoes backscattered from targeted points. In this study, CoMTUS is implemented and demonstrated for the first time in 3-D imaging using a pair of 256-element 2-D sparse spiral arrays, which keep the channel count low and limit the amount of data to be processed. The imaging performance of the method was investigated using both simulations and phantom tests. The feasibility of free-hand operation is also experimentally demonstrated. Results show that, in comparison to a single dense array system using the same total number of active elements, the proposed CoMTUS system improves spatial resolution (up to 10 times) in the direction where both arrays are aligned, contrast-to-noise-ratio (CNR, up to 46%), and generalized CNR (up to 15%). Overall, CoMTUS shows a narrower main lobe and higher contrast-to-noise ratio, which results in an increased dynamic range and better target detectability.
ABSTRACT
The ability to modulate the host immune response has allowed some parasites to establish themselves in the tissues of an immunocompetent organism. While some parasite excretion/secretion products (ESPs) were recently reported to induce differentiation of regulatory T cells (Tregs), their identity is not known. This work is aimed to identify and characterize ESPs of Taenia crassiceps cysticerci linked with Treg induction in vivo. ESPs were obtained from cultures of T. crassiceps cysticerci and inoculated in mice, measuring Treg levels by flow cytometry. Proteins in ESPs were analyzed by electrophoresis; then, ESPs were classified as either differential or conserved. Differentially included proteins were MS-sequenced and functionally characterized. Only 4 of 10 ESPs induced Tregs. Proteins with catalytic activity and those involved in immunological processes predominated, supporting the idea that these molecules could play an important role in the induction of Tregs.
Subject(s)
Parasites , Taenia , Animals , Mice , Cysticercus , T-Lymphocytes, Regulatory , Flow Cytometry , Mice, Inbred BALB CABSTRACT
OBJECTIVE: To evaluate the antimicrobial potential of silver nanoparticles (Ag NPs) synthesized using three different routes (ultraviolet light, Turkevich, and green chemistry method using Glycine max extract) associated with COREGA® denture powder adhesive. METHODS: Heat-cured acrylic resin specimens were treated with different Ag NPs associated with the adhesive (AD + Ag UV, AD + Ag Turk, and AD + Ag Gm groups). As controls, the specimens were treated with a combination of adhesive and nystatin (AD + Nyst group), only adhesive (AD group), or submerged on the surface of the specimens (PBS group). After the treatments, biofilms of C. albicans developed for 3, 6, and 12 h on the specimen surfaces. The biofilm was quantified using colony-forming units per milliliter, colorimetric assay, and confocal laser scanning microscopy. RESULTS: Regardless of the period, we observed an inhibition of fungal load and a reduction in metabolic activity and biofilm mass in the resin specimens treated with the combinations AD/Ag NPs, compared to AD and PBS. The antimicrobial action of the AD + Turk and AD + Ag Gm groups was similar than that for the AD + Nyst group in all periods and viability tests, except for the biofilm mass (12 h). CONCLUSIONS: The COREGA® adhesive with Ag NPs, mainly those synthesized using the Turkevich and Glycine max methods, showed excellent antimicrobial activity against C. albicans biofilms, maintained for up to 12 h. CLINICAL SIGNIFICANCE: The association of Ag NPs to the adhesive can add preventive or therapeutic effects against denture stomatitis, to this prosthetic material.
Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Candida albicans/physiology , Silver/pharmacology , Dental Cements/pharmacology , Anti-Infective Agents/pharmacology , Biofilms , Dentures , Denture Bases/microbiologyABSTRACT
Purpose: To describe clinical characteristics and effectiveness of health care in patients with rheumatoid arthritis (RA) as part of a multidisciplinary care model (MCM) in a specialized rheumatology center, compared with the results of a national registry of RA (NARRA) as evidence of real-world management. Patients and Methods: We conducted a real-world study (July 1, 2018 to June 30, 2019) based on an analysis of electronic health records of a cohort of RA patients managed with the "Treat-to-Target" strategy in a specialized rheumatology center in Colombia with an MCM, compared with the NARRA that includes different models of usual care. Results: We have analyzed 7053 subjects with RA treated at a specialized rheumatology center and 81,492 patients from the NARRA. Cohorts were similar in their baseline characteristics, with women in predominance and diagnosis age close to 50 years. At the time of diagnosis, a higher proportion of clinical diagnostic test use and rheumatology consultation access was observed in the specialized rheumatology center than in the national registry (4-6 per year versus three or less). In addition, higher proportions of patients in remission and low disease activity were reported for the specialized rheumatology center, with a >40% amount of data lost in the national registry. Pharmacological management was similar regarding the analgesic use. In the specialized center, Certolizumab was more frequently used than in the NARRA registry; also, there were significant differences in methotrexate, leflunomide, and sulfasalazine use, being higher in the specialized rheumatology center. Conclusion: The MCM of a specialized center in RA can guarantee comprehensive care, with better access to all the services required to manage the disease. It ensures specialist management and evidence-based care that facilitates the achievement of therapeutic objectives. In addition, better patient records and follow-ups are available to evaluate health outcomes.
ABSTRACT
BACKGROUND: Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin (IVIg) and plasmapheresis, have shown mixed results in patient improvement. OBJECTIVE: To compare the efficacy of IVIg administration with that of corticosteroids, plasmapheresis, and placebo in autoimmune neurological diseases like Guillain-Barré syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, optic neuritis, and multiple sclerosis. METHODS: A systematic review was performed on the databases PubMed, MEDLINE, Embase, and Cochrane. Controlled, randomized studies comparing the efficacy of IVIg with placebo, plasmapheresis, and/or glucocorticoid administration were selected. Only studies reporting the number of patients who improved after treatment were included, irrespective of language or publication year. In total, 23 reports were included in the meta-analysis study. RESULTS: Our meta-analysis showed a beneficial effect of IVIg administration on patient improvement over placebo (OR = 2.79, CI [95%] = 1.40-5.55, P = 0.01). Meanwhile, IVIg administration showed virtually identical effects to plasmapheresis (OR = 0.83, CI [95%] = 0.45-1.55, P < 0.01). Finally, no significant differences were found in the efficacy of IVIg and glucocorticoid administration (OR = 0.98, Cl [95%] = 0.58-1.68, P = 0.13). CONCLUSION: IVIg can be regarded as a viable therapeutic approach, either as a first- or second-line therapy, and as an adjuvant therapy for autoimmune neurological diseases.
Subject(s)
Guillain-Barre Syndrome , Myasthenia Gravis , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Humans , Immunoglobulins, Intravenous/therapeutic use , Myasthenia Gravis/drug therapy , Plasma Exchange , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/drug therapyABSTRACT
Food Loss and Waste (FLW) reduction and prevention can be crucial entry points to achieve sustainable food systems. However, the complexity of this problem poses the need for multistakeholder and multidimensional approaches. The Costa Rican FLW Reduction Network has been working since 2014 as a collaborative platform that brings together different sectors and disciplines to promote a change through communication and awareness, alliances, and research and innovation. The purpose of our study was to share the experience of Costa Rica in regards to the applied FLW actions and its catalytic effect on FLW innovation. The study was developed through a multimethod approach that included case studies, stakeholder analysis and literacy analysis to provide an overall assessment of the strategy as input for further efforts in this matter. The main findings indicate that collaborative actions among institutions and sectors are vital in promoting FLW reduction; however, FLW innovation is still at an inception phase where financial resources and policy barriers remain as aspects to address. In conclusion, the Costa Rica FLW Network represents an asset to trigger ongoing and future actions, and approaches like an integrated innovation ecosystem must be promoted.
ABSTRACT
BACKGROUND: Neuroinflammation has been proved to play a role in dopaminergic neuronal death in Parkinson's disease (PD). This link highlights the relevance of the immune response in the progression of the disease. However, little is known about the impact of peripheral immune response on the disease. This study is aimed to evaluate how immune cell populations change in untreated PD patients followed-up for 2 years. METHODS: Thirty-two patients with no previous treatment (PD-0 yr) and twenty-two healthy subjects (controls) were included in the study. PD patients were sampled 1 and 2 years after the start of the treatment. CD4 T cells (naïve/central memory, effector, and activated), CD8 T cells (activated, central memory, effector memory, NKT, Tc1, Tc2, and Tc17), and B cells (activated, plasma, and Lip-AP) were characterized by flow cytometry. RESULTS: We observed decreased levels of naïve/central memory CD4 and CD8 T cells, Tc1, Tc2, NKT, and plasma cells, and increased levels of effector T cells, activated T cells, and Tc17. CONCLUSIONS: PD patients treated for 2 years showed an imbalance in the naive/effector immune response. Naïve and effector cell levels were associated with clinical deterioration. These populations are also correlated to aging. On the other hand, higher Tc17 levels suggest an increased inflammatory response, which may impact the progression of the disease. Our results highlight the relevant effect of treatment on the immune response, which could improve our management of the disease.
Subject(s)
Parkinson Disease , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Case-Control Studies , Humans , ImmunityABSTRACT
PURPOSE: Several frameworks coincide in the importance of addressing social impacts to ensure sustainability. However, the agri-food sector, regarded as key in sustainable production, still neglects to identify potential social impacts when applying life cycle approaches. This work contributes to understanding the social performance of three agricultural products from a Latin American and Caribbean developing country as Costa Rica while recognising the challenges of Social-Life Cycle Assessment (S-LCA) application in this context. METHODS: S-LCA represents a powerful technique to evaluate the potential social impacts of a product. Three case studies were analysed through S-LCA, using the subcategory assessment method (SAM) to characterise the social impacts and detect hotspots in the production of green coffee, raw milk and leafy vegetables. Primary data was collected through questionnaires to relevant informants and observations. In addition to secondary information, these data and information were used to assess eight impact subcategories for the farmer and worker stakeholder groups and nine subcategories for the local community. RESULTS AND DISCUSSION: The main results suggest that the Costa Rican institutional and market frameworks provide an enabling environment for a generally positive social performance in the studied cases. The assessed stakeholders can fulfil basic needs through access to inputs and services and achieve fair-trading conditions. Child labour, forced labour and evidence of environmental or health risks for the surrounding communities were absent. Important efforts to address the delocalisation, migration and child labour were observed, suggesting the potential development of social handprints in further studies. However, the farm production phase, related to farmers and workers, entails hotspots regarding social security and women's empowerment. Moreover, farmers appear as the most vulnerable group because of their overall social performance. CONCLUSIONS: S-LCA helped identify relevant areas of intervention in the context of these particular case studies; however, further research and capacity building are recommended to tackle the detected challenges, both in the agri-food chains and in the use of S-LCA. Furthermore, these findings can aid in future decision and policy-making to improve and safeguard the positive social performance observed in the studied products. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11367-021-01964-4.
ABSTRACT
Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex etiology. Various genetic factors are associated with susceptibility to developing SLE and contribute to its onset and progression. Different single-nucleotide polymorphisms (SNPs) have been associated with SLE in several populations. The rs12979860 SNP in interferon lambda 3/4 (IFNλ3/4) is significantly associated with SLE susceptibility in patients negative for nephritis in Taiwanese people, and interferon-stimulated genes (ISGs) are differentially expressed in normal liver by the rs12979860 genotype. This study aimed to investigate whether rs12979860 is associated with the presence of SLE and lupus nephritis in Mexican individuals as well as with the expression of several ISGs in SLE patients. In total, 439 SLE patients and 358 healthy donors were genotyped for rs12979860 using real-time PCR, and allelic discrimination plots were constructed. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated from the venous blood of SLE patients by centrifugation (n = 78). The mRNA levels of 2'-5'-oligoadenylate synthetase like (OASL), myxovirus resistance 1 (MX1), 2'5'-oligoadenylate synthetase 1 (OAS1), interferon-stimulated gene 15 (ISG15) and lymphocyte antigen 6 complex, locus E (LY6E) were determined using real-time PCR. The distributions of rs12979860 genotypes and allele frequencies were compared between SLE patients and healthy donors; case-control analysis revealed that rs12979860 was not associated with SLE susceptibility (OR 1.18, 95% CI 0.97-1.45, p = 0.08) or with the risk for lupus nephritis (OR 0.913, 95% CI 0.590-1.411, p = 0.682). However, OASL expression levels in PBMCs were significantly different between rs12979860 genotypes in SLE patients: median OASL mRNA levels were significantly higher in patients carrying the CC genotype (197.10, IQR 71.10-411.17) than in those with CT/TT genotypes (173.75, IQR 58.80-278.75, p = 0.016). Our results suggest that the SNP rs12979860 does not play a relevant role in susceptibility to SLE in Mexican individuals. However, IFNλ3/4 genotypes appear to be associated with OASL expression in PBMCs from patients with SLE.