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Frontiers in Immunology 2024
Topics: Biomarkers; Animals; Humans; Host-Parasite Interactions; Trypanosomiasis; Trypanosomatina; Trypanosoma
PubMed: 38938579
DOI: 10.3389/fimmu.2024.1422067 -
Frontiers in Immunology 2024The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms...
BACKGROUND
The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date.
METHODS
We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY).
RESULTS
We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the well-documented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment.
CONCLUSION
In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles.
Topics: Humans; Female; Male; Adult; Middle Aged; Multiple Sclerosis; Fingolimod Hydrochloride; Immunity, Innate; Methylprednisolone; Immunophenotyping; Leukocytes, Mononuclear; Adrenal Cortex Hormones; Immunosuppressive Agents; Glucocorticoids
PubMed: 38938576
DOI: 10.3389/fimmu.2024.1404316 -
Frontiers in Immunology 2024Human respiratory viruses are the most prevalent cause of disease in humans, with the highly infectious RSV being the leading cause of infant bronchiolitis and viral...
Human respiratory viruses are the most prevalent cause of disease in humans, with the highly infectious RSV being the leading cause of infant bronchiolitis and viral pneumonia. Responses to type I IFNs are the primary defense against viral infection. However, RSV proteins have been shown to antagonize type I IFN-mediated antiviral innate immunity, specifically dampening intracellular IFN signaling. Respiratory epithelial cells are the main target for RSV infection. In this study, we found RSV-NS1 interfered with the IFN-α JAK/STAT signaling pathway of epithelial cells. RSV-NS1 expression significantly enhanced IFN-α-mediated phosphorylation of STAT1, but not pSTAT2; and neither STAT1 nor STAT2 total protein levels were affected by RSV-NS1. However, expression of RSV-NS1 significantly reduced ISRE and GAS promoter activity and anti-viral IRG expression. Further mechanistic studies demonstrated RSV-NS1 bound STAT1, with protein modeling indicating a possible interaction site between STAT1 and RSV-NS1. Nuclear translocation of STAT1 was reduced in the presence of RSV-NS1. Additionally, STAT1's interaction with the nuclear transport adapter protein, KPNA1, was also reduced, suggesting a mechanism by which RSV blocks STAT1 nuclear translocation. Indeed, reducing STAT1's access to the nucleus may explain RSV's suppression of IFN JAK/STAT promoter activation and antiviral gene induction. Taken together these results describe a novel mechanism by which RSV controls antiviral IFN-α JAK/STAT responses, which enhances our understanding of RSV's respiratory disease progression.
Topics: STAT1 Transcription Factor; Humans; Signal Transduction; Interferon-alpha; Respiratory Syncytial Virus, Human; Viral Nonstructural Proteins; Respiratory Syncytial Virus Infections; Janus Kinases; Cell Nucleus; Phosphorylation; Active Transport, Cell Nucleus; Cell Line
PubMed: 38938568
DOI: 10.3389/fimmu.2024.1395809 -
Frontiers in Psychiatry 2024This study aims to evaluate the efficacy of repeated transcranial magnetic stimulation (rTMS) combined with fluoxetine in enhancing the early antidepressant response in...
OBJECTIVES
This study aims to evaluate the efficacy of repeated transcranial magnetic stimulation (rTMS) combined with fluoxetine in enhancing the early antidepressant response in first-episode adolescent depression cases, providing insights for patient diagnosis and treatment.
METHODS
One hundred and thirty-five adolescents experiencing their first depressive episode were randomly assigned to either a sham group treated with fluoxetine or to low or high repetitive transcranial magnetic stimulation (rTMS) groups receiving both rTMS and fluoxetine. Therapeutic effects were assessed by comparing changes in Hamilton Depression Scale (HAMD-17) scores, cognitive function scores from the Wisconsin Card Sorting Test (WCST), and Clinical Global Impression-improvement (CGI-I) scores, along with recording adverse reactions.
RESULTS
The total effectiveness rate in the rTMS groups (Low, 95.56%; High, 97.78%) was significantly higher than in the Sham rTMS group (80%) (F = 11.15, P<0.0001). Post-treatment, not only the Low but also the High rTMS group exhibited more significant reductions in HAMD-17 (Low, 21.05; High, 21.45) and CGI-I scores (Low, 3.44; High, 3.60) compared to the Sham rTMS group (HAMD-17, 16.05; CGI-I, 2.57) (two weeks: F = 7.889, P = 0.0006; four weeks: F = 15.900, P<0.0001). Additionally, the two rTMS groups exhibited fewer erroneous responses and persistent errors in the WCST and completed more WCST categorizations than the Sham rTMS group. There was no significant difference in adverse reaction rates between the groups (F=4.421, P=0.0794).
CONCLUSIONS
The combination of fluoxetine with rTMS demonstrates enhanced therapeutic effectiveness in treating adolescent depression, effectively controlling disease progression, reducing depressive symptoms, and improving cognitive function, making it a valuable clinical approach.
PubMed: 38938464
DOI: 10.3389/fpsyt.2024.1397706 -
Frontiers in Psychiatry 2024Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can... (Review)
Review
Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called "therapy-resistant depression". The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics. The integration of the flow of multi-omic information into molecular pathways may produce better outcomes than the current psychopharmacological approach, which targets singular molecular factors mainly related to the monoamine systems, disregarding the complex network of our organism. The concept of system biomedicine involves the integration and analysis of enormous datasets generated with different technologies, creating a "patient fingerprint", which defines the underlying biological mechanisms of every patient. This review, centered on precision medicine, explores the integration of multi-omic approaches as clinical tools for prediction in MDD at a single-patient level. It investigates how combining the existing technologies used for diagnostic, stratification, prognostic, and treatment-response biomarkers discovery with artificial intelligence can improve the assessment and treatment of MDD.
PubMed: 38938457
DOI: 10.3389/fpsyt.2024.1422939 -
Epidemiology and Health Jun 2024Tea consumption has been considered beneficial to human health because tea contains phytochemicals such as polyphenols and theaflavins. We conducted a systematic review...
OBJECTIVES
Tea consumption has been considered beneficial to human health because tea contains phytochemicals such as polyphenols and theaflavins. We conducted a systematic review and meta-analysis on the association between tea consumption and mortality from all causes, cardiovascular disease (CVD), and cancer to provide a quantitative assessment of current evidence.
METHODS
The PubMed, Web of Science, and Scopus databases were searched through April 2024 to identify eligible studies. Random effects models were used to combine study-specific effect estimates (ESs).
RESULTS
A total of 38 prospective cohort data sets (from 27 papers) with 1,956,549 participants were included in this meta-analysis. The pooled ESs of the highest versus lowest categories of tea consumption were 0.90 (95% CI, 0.86-0.95) for all-cause mortality, 0.86 (95% CI, 0.79-0.94) for CVD mortality, and 0.90 (95% CI, 0.78-1.03) for cancer mortality. In the dose-response analysis, a nonlinear association was observed. The greatest risk reductions were observed for the consumption of 2 cups/day for all-cause mortality (ES, 0.91; 95% CI, 0.88-0.94) and 1.5 cups/day for cancer mortality (ES, 0.92; 95% CI, 0.89-0.96), whereas additional consumption did not show a further reduction in the risk of death. A plateau was observed for CVD mortality at moderate consumption levels (1.5-3 cups/day), but a sustained reduction in mortality risk was observed at higher intake levels.
CONCLUSION
Moderate tea consumption (e.g., 1.5-2 cups/day) was associated with lower all-cause, CVD, and cancer mortality compared to no tea consumption. Further well-designed prospective studies are needed for a definitive Conclusion.
PubMed: 38938012
DOI: 10.4178/epih.e2024056 -
Journal of Cachexia, Sarcopenia and... Jun 2024The effects of post-coronavirus disease 2019 (COVID-19) syndrome on the cardiorespiratory and muscular fitness in older people are of utmost relevance. This study aimed...
BACKGROUND
The effects of post-coronavirus disease 2019 (COVID-19) syndrome on the cardiorespiratory and muscular fitness in older people are of utmost relevance. This study aimed to evaluate the effects of a 12-week telerehabilitation programme on cardiorespiratory and muscular fitness and body composition in older patients with post-COVID-19 syndrome.
METHODS
One hundred twenty older patients with post-COVID-19 syndrome were randomly assigned to one of two groups: patients who carried out the telerehabilitation programme (n = 60; age: 65.0 ± 5.2; female: 14.2%) and a control group (n = 60; age: 64.3 ± 5.0; female: 24.5%). An incremental cardiopulmonary exercise testing, isokinetic strength test, and bioelectrical impedance analysis were performed to compare cardiorespiratory and muscle strength responses and body composition between telerehabilitation and control groups.
RESULTS
A significant increase in the cardiopulmonary exercise testing duration was found in the telerehabilitation group compared to the control group (mean difference = 88.9 s, P = 0.001). Peak oxygen uptake increased in the telerehabilitation group (mean difference = 3.0 mL·kg·min, P < 0.001) and control group (mean difference = 1.9 mL·kg·min, P < 0.001). Power output in cycle ergometer (mean difference = 25.9 watts, P < 0.001), fat free mass (mean difference = 2.1 kg, P = 0.004), soft lean mass (mean difference = 2.1 kg, P = 0.003), and skeletal muscle mass (mean difference = 1.4 kg, P = 0.003) only increased in the telerehabilitation group. A significant increase in the power output was observed in the telerehabilitation group compared with the control group in both lower limbs after isokinetic strength test of the leg extension at a speed of 60° (right: mean difference = 18.7 watts, P = 0.012; left: mean difference = 15.3 watts, P = 0.010). The peak torque of right leg extension increased only in the telerehabilitation group after isokinetic strength test at a speed of 60° (mean difference = 13.1 N·m, P < 0.001). A significant increase in the power output was observed in the telerehabilitation group compared with the control group in the left leg extension after isokinetic strength test at a speed of 180° (mean difference = 30.2 watts, P = 0.003).
CONCLUSIONS
The telerehabilitation programme improved cardiorespiratory and muscular fitness, and body composition in older patients with post-COVID-19 syndrome to a greater extent than a control group. The telerehabilitation programmes may be an alternative to improve the sequelae of post-COVID-19 syndrome in older patients.
PubMed: 38937986
DOI: 10.1002/jcsm.13530 -
Alzheimer's Research & Therapy Jun 2024Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's... (Meta-Analysis)
Meta-Analysis Review
The cognitive effect of non-invasive brain stimulation combined with cognitive training in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.
BACKGROUND
Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, data from clinical trials or meta-analysis involving NIBS combined with CT have shown controversial results. The aim of this systematic review and meta-analysis was to evaluate short-term and long-term effects of NIBS combined with CT on improving global cognition and other specific cognitive domains in patients with AD and MCI.
METHODS
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases including PubMed, Web of Science, EBSCO, Cochrane Library and Embase were searched up from inception to 20 November 2023. The PEDro scale and the Cochrane's risk of bias assessment were used to evaluate risk of bias and methodological quality of included studies. All statistical analyses were conducted with Review Manager 5.3.
RESULTS
We included 15 studies with 685 patients. The PEDro scale was used to assess methodological quality with a mean score of 7.9. The results of meta-analysis showed that NIBS combined with CT was effective on improving global cognition in AD and MCI (SMD = 0.52, 95% CI (0.18, 0.87), p = 0.003), especially for patients accepting repetitive transcranial magnetic stimulation (rTMS) combined with CT (SMD = 0.46, 95% CI (0.14, 0.78), p = 0.005). AD could achieve global cognition improvement from NIBS combined with CT group (SMD = 0.77, 95% CI (0.19, 1.35), p = 0.01). Transcranial direct current stimulation (tDCS) combined with CT could improve language function in AD and MCI (SMD = 0.29, 95% CI (0.03, 0.55), p = 0.03). At evaluation follow-up, rTMS combined with CT exhibited larger therapeutic responses to AD and MCI in global cognition (SMD = 0.55, 95% CI (0.09, 1.02), p = 0.02). AD could achieve global cognition (SMD = 0.40, 95% CI (0.03, 0.77), p = 0.03) and attention/working memory (SMD = 0.72, 95% CI (0.23, 1.20), p = 0.004) improvement after evaluation follow-up from NIBS combined with CT group.
CONCLUSIONS
Overall, NIBS combined with CT, particularly rTMS combined with CT, has both short-term and follow-up effects on improving global cognition, mainly in patients with AD. tDCS combined with CT has advantages on improving language function in AD and MCI. Future more studies need evaluate cognitive effects of NIBS combined with CT on other specific cognitive domain in patients with cognitive deterioration.
Topics: Humans; Cognitive Dysfunction; Alzheimer Disease; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation; Cognitive Behavioral Therapy; Cognition; Combined Modality Therapy; Cognitive Training
PubMed: 38937842
DOI: 10.1186/s13195-024-01505-9 -
Veterinary Research Jun 2024Respiratory diseases constitute a major health problem for ruminants, resulting in considerable economic losses throughout the world. Parainfluenza type 3 virus (PIV3)...
Respiratory diseases constitute a major health problem for ruminants, resulting in considerable economic losses throughout the world. Parainfluenza type 3 virus (PIV3) is one of the most important respiratory pathogens of ruminants. The pathogenicity and phylogenetic analyses of PIV3 virus have been reported in sheep and goats. However, there are no recent studies of the vaccination of sheep or goats against PIV3. Here, we developed a purified inactivated ovine parainfluenza virus type 3 (OPIV3) vaccine candidate. In addition, we immunized sheep with the inactivated OPIV3 vaccine and evaluated the immune response and pathological outcomes associated with OPIV3 TX01 infection. The vaccinated sheep demonstrated no obvious symptoms of respiratory tract infection, and there were no gross lesions or pathological changes in the lungs. The average body weight gain significantly differed between the vaccinated group and the control group (P < 0.01). The serum neutralization antibody levels rapidly increased in sheep post-vaccination and post-challenge with OPIV3. Furthermore, viral shedding in nasal swabs and viral loads in the lungs were reduced. The results of this study suggest that vaccination with this candidate vaccine induces the production of neutralizing antibodies and provides significant protection against OPIV3 infection. These results may be helpful for further studies on prevention and control strategies for OPIV3 infections.
Topics: Animals; Sheep; Respirovirus Infections; Vaccines, Inactivated; Sheep Diseases; Viral Vaccines; Respirovirus; Immunogenicity, Vaccine; Vaccination
PubMed: 38937820
DOI: 10.1186/s13567-024-01339-1 -
Slit2-Robo4 signal pathway and tight junction in intestine mediate LPS-induced inflammation in mice.European Journal of Medical Research Jun 2024Sepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical...
BACKGROUND
Sepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical pathological event in sepsis, but the underlying mechanism has not yet been fully elucidated.
METHODS
The animal model was established for two batches. In the first batch of experiments, Adult C57BL/6J mice were randomly divided into control group and LPS (5 mg/kg, i.p.)group . In the second batch of experiments, mice were randomly divided into control group, LPS group, and LPS+VX765(10 mg/kg, i.p., an inhibitor of NLRP3 inflammasome) group. After 24 hours, mice were anesthetized with isoflurane, blood and intestinal tissue were collected for tissue immunohistochemistry, Western blot analysis and ELISA assays.
RESULTS
The C57BL/6J mice injected with LPS for twenty-four hours could exhibit severe inflammatory reaction including an increased IL-1β, IL-18 in serum and activation of NLRP3 inflammasome in intestine. The injection of VX765 could reverse these effects induced by LPS. These results indicated that the increased level of IL-1β and IL-18 in serum induced by LPS is related to the increased intestinal permeability and activation of NLRP3 inflammasome. In the second batch of experiments, results of western blot and immunohistochemistry showed that Slit2 and Robo4 were significant decreased in intestine of LPS group, while the expression of VEGF was significant increased. Meanwhile, the protein level of tight junction protein ZO-1, occludin, and claudin-5 were significantly lower than in control group, which could also be reversed by VX765 injection.
CONCLUSIONS
In this study, we revealed that Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice, which may account for the molecular mechanism of sepsis.
Topics: Animals; Lipopolysaccharides; Mice; Signal Transduction; Nerve Tissue Proteins; Inflammation; Intercellular Signaling Peptides and Proteins; Tight Junctions; Mice, Inbred C57BL; Male; Receptors, Cell Surface; Receptors, Immunologic; Intestinal Mucosa; NLR Family, Pyrin Domain-Containing 3 Protein; Intestines; Disease Models, Animal; Inflammasomes
PubMed: 38937814
DOI: 10.1186/s40001-024-01894-5