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Neurology(R) Neuroimmunology &... Sep 2024Neutrophils, underestimated in multiple sclerosis (MS), are gaining increased attention for their significant functions in patients with MS and the experimental...
BACKGROUND AND OBJECTIVES
Neutrophils, underestimated in multiple sclerosis (MS), are gaining increased attention for their significant functions in patients with MS and the experimental autoimmune encephalomyelitis (EAE) animal model. However, the precise role of neutrophils in cervical lymph nodes (CLNs), the primary CNS-draining lymph nodes where the autoimmune response is initiated during the progression of EAE, remains poorly understood.
METHODS
Applying single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive immune cell atlas of CLNs during development of EAE. Through this atlas, we concentrated on and uncovered the transcriptional landscape, phenotypic and functional heterogeneity of neutrophils, and their crosstalk with immune cells within CLNs in the neuroinflammatory processes in EAE.
RESULTS
Notably, we observed a substantial increase in the neutrophil population in EAE mice, with a particular emphasis on the significant rise within the CLNs. Neutrophils in CLNs were categorized into 3 subtypes, and we explored the specific roles and developmental trajectories of each distinct neutrophil subtype. Neutrophils were found to engage in extensive interactions with other immune cells, playing crucial roles in T-cell activation. Moreover, our findings highlighted the strong migratory ability of neutrophils to CLNs, partly regulated by triggering the receptor expressed on myeloid cells 1 (TREM-1). Inhibiting TREM1 with LR12 prevents neutrophil migration both in vivo and in vitro. In addition, in patients with MS, we confirmed an increase in peripheral neutrophils with an upregulation of TREM-1.
DISCUSSION
Our research provides a comprehensive and precise single-cell atlas of CLNs in EAE, highlighting the role of neutrophils in regulating the periphery immune response. In addition, TREM-1 emerged as an essential regulator of neutrophil migration to CLNs, holding promise as a potential therapeutic target in MS.
Topics: Encephalomyelitis, Autoimmune, Experimental; Neutrophils; Animals; Triggering Receptor Expressed on Myeloid Cells-1; Mice; Single-Cell Analysis; Mice, Inbred C57BL; Female; Sequence Analysis, RNA; Lymph Nodes
PubMed: 38954781
DOI: 10.1212/NXI.0000000000200278 -
PloS One 2024Autoimmune diseases affect 5-10% of the global population and cause chronic pain and impaired functionality. Chronic pain management involves pharmacological and...
BACKGROUND
Autoimmune diseases affect 5-10% of the global population and cause chronic pain and impaired functionality. Chronic pain management involves pharmacological and non-pharmacological interventions, with non-pharmacological options gaining attention as safe, effective, and cost-effective alternatives. However, further research is needed to determine the effectiveness of these therapies in African patients with autoimmune diseases, as existing evidence varies.
METHODS
This review protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023449896). Electronic databases (PubMed, Africa Index Medicus, Cochrane Library, CINAHL, PsycINFO, and Web of Science) will be used for searching published articles. The study will use R for data synthesis, employing a random-effects meta-analysis approach to calculate pooled effect sizes, assess heterogeneity using the I2 statistic, and evaluate publication bias. In conclusion, this protocol aims to fill the knowledge gap on non-pharmacological therapies for chronic pain in patients with autoimmune diseases in Africa. It will potentially enhance evidence-based decision-making to improve pain management and, hence, the quality of life of people with autoimmune diseases in Africa.
Topics: Humans; Systematic Reviews as Topic; Chronic Pain; Autoimmune Diseases; Meta-Analysis as Topic; Africa; Pain Management; Quality of Life
PubMed: 38954682
DOI: 10.1371/journal.pone.0306564 -
Genetics and Molecular Biology 2024Despite their global prevalence, the mechanisms for mood disorders like bipolar disorder and major depressive disorder remain largely misunderstood. Mood stabilizers and...
Despite their global prevalence, the mechanisms for mood disorders like bipolar disorder and major depressive disorder remain largely misunderstood. Mood stabilizers and antidepressants, although useful and effective for some, do not have a high responsiveness rate across those with these conditions. One reason for low responsiveness to these drugs is patient heterogeneity, meaning there is diversity in patient characteristics relating to genetics, etiology, and environment affecting treatment. In the past two decades, novel induced pluripotent stem cell (iPSC) research and technology have enabled the use of human-derived brain cells as a new model to study human disease that can help account for patient variance. Human iPSC technology is an emerging tool to better understand the molecular mechanisms of these disorders as well as a platform to test novel treatments and existing pharmaceuticals. This literature review describes the use of iPSC technology to model bipolar and major depressive disorder, common medications used to treat these disorders, and novel patient-derived alternative treatment methods for non-responders stemming from past publications, as well as presenting new data derived from these models.
PubMed: 38954533
DOI: 10.1590/1678-4685-GMB-2023-0305 -
Indian Journal of Public Health Apr 2024There are several leadership training programs for health researchers in India. However, there is a need to develop context-tailored leadership and mentoring approaches.
BACKGROUND
There are several leadership training programs for health researchers in India. However, there is a need to develop context-tailored leadership and mentoring approaches.
OBJECTIVE
The objective of the study is to critically analyze the available leadership training programs in India for health researchers and service providers, for the leadership domains incorporated and overall training approaches.
MATERIALS AND METHODS
We used an exploratory-descriptive design to identify and review leadership training programs for health researchers and service providers/managers that had been offered by Indian institutions between 2013 and 2018. Our analytic approach was based on "transformational leadership" and "leader-member exchange" theories of leadership, curricula of popular leadership training programs worldwide, and the International Clinical Epidemiology Network model for leadership in health research in India based on a nationwide primary study.
RESULTS
We identified and reviewed 20 leadership training programs. These were heterogeneous in aim, scope (broad-based/thematic), course content, design, target participants and class profile, mode of delivery and training method, duration, frequency, and fund arrangements. The programs infrequently included topics on soft skills, mentoring, risk mitigation, collaboration for research, funding dynamics, institutional transformation, self-view and peer perception, and personal well-being. The programs insufficiently addressed contextual challenges of career exploration and risk mitigation, project management, strategic planning, and decision-making, ethics and integrity, negotiations, networking and collaboration, understanding funding dynamics, and mentoring. Only three programs linked to the training to the participants' ecosystem.
CONCLUSIONS
There is a need to develop customized course contents and training strategies that address the requirements of the local context vis-à-vis globally connected research ecosystems.
Topics: Leadership; India; Humans; Curriculum; Research Personnel; Health Services Research; Mentoring
PubMed: 38953813
DOI: 10.4103/ijph.ijph_762_23 -
Frontiers in Immunology 2024Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of...
BACKGROUND
Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs.
METHODS
We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the and efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods.
RESULTS
The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model.
CONCLUSIONS
This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.
Topics: Receptors, IgG; Humans; Animals; Mice; Neoplasms; T-Lymphocytes; Tumor Microenvironment; Antibodies, Monoclonal; Cell Line, Tumor; Xenograft Model Antitumor Assays; Immunotherapy, Adoptive; Receptor, ErbB-2; Antineoplastic Agents, Immunological; Receptors, Chimeric Antigen; Female; Antigens, CD20
PubMed: 38953027
DOI: 10.3389/fimmu.2024.1400177 -
Frontiers in Immunology 2024The immune system plays an important role in the development and treatment of thyroid cancer(THCA).However, the correlation between immune cells and THCA has not been...
BACKGROUND
The immune system plays an important role in the development and treatment of thyroid cancer(THCA).However, the correlation between immune cells and THCA has not been systematically studied.
METHODS
This study used a two-sample Mendelian randomization (MR) study to determine the causal relationship between immune cell characteristics and THCA. Based on a large sample of publicly available genetic data, we explored the causal relationship between 731 immune cell characteristics and THCA risk. The 731 immunophenotypes were divided into 7 groups, including B cell panel(n=190),cDC panel(n=64),Maturation stages of T cell panel(n=79),Monocyte panel(n=43),Myeloid cell panel(n=64),TBNK panel(n=124),and Treg panel(n=167). The sensitivity of the results was analyzed, and heterogeneity and horizontal pleiotropy were excluded.
RESULTS
After FDR correction, the effect of immunophenotype on THCA was not statistically significant. It is worth mentioning, however, that there are some unadjusted low P-values phenotypes. The odds ratio (OR) of CD62L on monocyte on THCA risk was estimated to be 0.953 (95% CI=0.930~0.976, =1.005×10),and which was estimated to be 0.975(95% CI=0.961-0.989, =7.984×10) for Resting Treg%CD4 on THCA risk. Furthermore, THCA was associated with a reduced risk of 5 immunophenotype:CD25 on CD39+ CD4 on Treg (OR=0.871, 95% CI=0.812~0.935, =1.274×10), activated Treg AC (OR=0.884, 95% CI=0.820~0.953, =0.001), activated & resting Treg % CD4 Treg (OR=0.872, 95%CI=0.811~0.937,=2.109×10),CD28- CD25++ CD8br AC(OR=0.867,95% CI=0.809~0.930,=6.09×10),CD28-CD127-CD25++CD8brAC(OR=0.875,95%CI=0.814~0.942,=3.619×10).THCA was associated with an increased risk of Secreting Treg % CD4 Treg (OR=1.143, 95% CI=1.064~1.229, =2.779×10) and CD19 on IgD+ CD24+ (OR=1.118, 95% CI=1.041~1.120, =0.002).
CONCLUSIONS
These findings suggest the causal associations between immune cells and THCA by genetic means. Our results may have the potential to provide guidance for future clinical research.
Topics: Humans; Mendelian Randomization Analysis; Thyroid Neoplasms; Immunophenotyping; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Monocytes
PubMed: 38953025
DOI: 10.3389/fimmu.2024.1425873 -
Sexual Medicine Jun 2024Cardiovascular diseases (CVDs) and erectile dysfunction (ED) frequently co-occur, significantly affecting the quality of life of individuals. (Review)
Review
BACKGROUND
Cardiovascular diseases (CVDs) and erectile dysfunction (ED) frequently co-occur, significantly affecting the quality of life of individuals.
AIM
To assess the impact of cardiac rehabilitation (CR) on ED in patients with CVD through a systematic review and meta-analysis.
METHODS
This study analyzed randomized controlled trials and other studies comparing CR with usual care for adult males (≥18 years) with any cardiac disease. Literature searches were extensive, and the risk of bias was evaluated by the Cochrane Collaboration tool. Data from 6 studies involving 668 participants were included in the meta-analysis.
OUTCOMES
The primary outcome was the improvement in ED, as measured with the International Index of Erectile Function.
RESULTS
A statistically significant improvement in erectile function was observed across 6 studies, with a Morris dppc2 effect size of 0.38 (95% CI, 0.17-0.59). Despite initial high heterogeneity ( = 95.7%), identification and correction for selective outcome reporting bias mitigated this issue.
CLINICAL TRANSLATION
CR has a modest but statistically significant impact on improving ED in patients with CVD, indicating its potential positive contribution to the quality of life of this group.
STRENGTHS AND LIMITATIONS
The study's strengths include a comprehensive literature search and a rigorous methodological approach. Limitations involve high heterogeneity among studies and a low level of evidence due to small sample sizes and study quality; however, the source of heterogeneity was identified and mitigated following risk-of-bias assessment.
CONCLUSION
The results suggest that CR has a statistically significant but modest impact on improving ED in patients with CVD. Clinicians should consider the integration of CR into the clinical management of these individuals. This study underscores the potential for CR to contribute positively to the quality of life for patients with CVD by addressing associated ED (PROSPERO: CRD42022374625).
PubMed: 38953013
DOI: 10.1093/sexmed/qfae043 -
PeerJ 2024The volcano rabbit () is a lagomorph endemic to the central mountains of the Trans-Mexican Volcanic Belt and is classified as threatened at extinction risk. It is a...
The volcano rabbit () is a lagomorph endemic to the central mountains of the Trans-Mexican Volcanic Belt and is classified as threatened at extinction risk. It is a habitat specialist in bunchgrass communities. The annual wildfires that occur throughout its distribution range are a vulnerability factor for the species. However, the effects of wildfires on volcano rabbit populations are not fully understood. We evaluated the occupancy and change in the volcano rabbit relative abundance index in the burned bunchgrass communities of the Ajusco-Chichinautzin Mountain Range during an annual cycle of wildfire events. Additionally, we assessed the factors that favor and limit occupation and reoccupation by the volcano rabbit using the relative abundance index in burned plots as an indicator of these processes. The explanatory factors for the response of the volcano rabbit were its presence in the nearby unburned bunchgrasses, the height of three species of bunchgrass communities, the proportion of different types of vegetation cover within a 500 m radius around the burned plots, heterogeneity of the vegetation cover, and the extent of the wildfire. Statistical analyses indicated possible reoccupation in less than a year in burned bunchgrass communities adjacent to unburned bunchgrass communities with volcano rabbits. The relative abundance index of volcano rabbits was not favored when the maximum height of the bunchgrass community was less than 0.77 m. When the vegetation around the burned plots was dominated by forest (cover >30% of the buffer) and the fire was extensive, the number of latrines decreased per month but increased when the bunchgrass and shrub cover was greater around the burned plots. While the statistical results are not conclusive, our findings indicate a direction for future projects, considering extensive monitoring to obtain a greater number of samples that contribute to consolidating the models presented.
Topics: Animals; Wildfires; Mexico; Ecosystem; Lagomorpha; Rabbits; Poaceae
PubMed: 38952973
DOI: 10.7717/peerj.17510 -
Data in Brief Aug 2024The large-fruited fresh-market tomato cultivated in the U.S. represents a unique fruit market class of contemporary (modern) tomatoes for direct consumption. The genomes...
The large-fruited fresh-market tomato cultivated in the U.S. represents a unique fruit market class of contemporary (modern) tomatoes for direct consumption. The genomes of F plants from crosses between inbred contemporary U.S. large-fruited fresh-market tomatoes were sequenced. 516 F individual plants randomly selected from five different biparental segregating populations were used for DNA extraction. The polymerase chain reaction (PCR)-free, paired-end (2 × 150 bp) sequencing libraries (350 bp DNA fragment length) were prepared, and sequenced on average 5 Gb for each plant using the Illumina next-generation sequencing technologies [1,2]. Raw Illumina reads with adapter contamination and/or uncertain nucleotides constitute (Ns, >10 % of either read; Q-score 5 or lower, >50 % of either read) were removed. This data article will contribute to improving our knowledge of the genetic recombination and variation in tomato.
PubMed: 38952950
DOI: 10.1016/j.dib.2024.110567 -
Leukemia Research Reports 2024Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy associated with various combinations of gene mutations, epigenetic abnormalities, and chromosome...
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy associated with various combinations of gene mutations, epigenetic abnormalities, and chromosome rearrangement-related gene fusions. Despite the significant degree of heterogeneity in its pathogenesis, many gene fusions and point mutations are recurrent in AML and have been employed in risk stratification over the last several decades. Gene fusions have long been recognized for understanding tumorigenesis and their proven roles in clinical diagnosis and targeted therapies. Advances in DNA sequencing technologies and computational biology have contributed significantly to the detection of known fusion genes as well as for the discovery of novel ones. Several recurring gene fusions in AML have been linked to prognosis, treatment response, and disease progression. In this report, we present a case with a long history of essential thrombocythemia and hallmark mutation transforming to AML characterized by a previously unreported fusion gene. We propose mechanisms by which this fusion may contribute to the pathogenesis of AML and its potential as a molecular target for tyrosine kinase inhibitors.
PubMed: 38952949
DOI: 10.1016/j.lrr.2024.100465