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Neurological Sciences : Official... Jun 2024High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years,... (Review)
Review
High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years, immunotherapy has changed the prognosis of many cancers, increasing the hope for HGG therapy. We conducted a comprehensive search on PubMed, Scopus, Embase, and Web of Science databases to include relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Fifty-two papers were finally included (44 phase II and eight phase III clinical trials) and further divided into four different subgroups: 14 peptide vaccine trials, 15 dendritic cell vaccination (DCV) trials, six immune checkpoint inhibitor (ICI) trials, and 17 miscellaneous group trials that included both "active" and "passive" immunotherapies. In the last decade, immunotherapy created great hope to increase the survival of patients affected by HGGs; however, it has yielded mostly dismal results in the setting of phase III clinical trials. An in-depth analysis of these clinical results provides clues about common patterns that have led to failures at the clinical level and helps shape the perspective for the next generation of immunotherapies in neuro-oncology.
Topics: Humans; Glioma; Immunotherapy; Brain Neoplasms; Immune Checkpoint Inhibitors
PubMed: 38308708
DOI: 10.1007/s10072-024-07350-w -
Frontiers in Pharmacology 2024Photodynamic therapy (PDT) is a minimally invasive treatment approach for precancerous and cancerous lesions, known for its ability to activate the host immune...
Photodynamic therapy (PDT) is a minimally invasive treatment approach for precancerous and cancerous lesions, known for its ability to activate the host immune response. This study conducted a bibliometric analysis to identify the research trends and hotspots related to the immune response in PDT. We analyzed articles and reviews published from 1989 to 2023, retrieved from the Web of Science database. Using Citespace and VOSviewer, we visualized the distribution patterns of these studies in time and space. The analysis revealed a substantial increase in the number of publications on PDT-related immune response since 1989. A total of 1,688 articles from 1,701 institutions were included in this analysis. Among thei nstitutions, the Chinese Academy of Sciences demonstrated exceptional productivity and a willingness to collaborate with others. Additionally, 8,567 authors contributed to the field, with Mladen Korbelik, Michael R. Hamblin, and Wei R. Chen being the most prolific contributors. The current research focus revolves around novel strategies to enhance antitumor immunity in PDT, including PDT-based dendritic cell vaccines, combination therapies with immune checkpoint inhibitors (ICIs), and the use of nanoparticles for photosensitizer delivery. Furthermore, genes such as CD8A, TNF, CD4, IFNG, CD274, IL6, IL10, CALR, HMGB1, and CTLA4 have been evaluated in the context of PDT-related immunity. PDT not only achieves tumor ablation but also stimulates the immune response, bolstering antitumor immunity. This study highlights the emerging hotspots in PDT-related immune response research and provides valuable insights for future investigations aimed at further enhancing antitumor immunity.
PubMed: 38288443
DOI: 10.3389/fphar.2024.1299253 -
Biomolecules Nov 2023Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular... (Review)
Review
Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.
Topics: Humans; Proteome; Neurodegenerative Diseases; Proteomics; Mitochondria; Neurons; Mitochondrial Proteins
PubMed: 38002320
DOI: 10.3390/biom13111638 -
Gastric Cancer : Official Journal of... Nov 2023The status of regional tumour draining lymph nodes (LN) is crucial for prognostic evaluation in gastric cancer (GaC) patients. Changes in lymph node microarchitecture,... (Meta-Analysis)
Meta-Analysis Review
The clinical importance of the host anti-tumour reaction patterns in regional tumour draining lymph nodes in patients with locally advanced resectable gastric cancer: a systematic review and meta-analysis.
BACKGROUND
The status of regional tumour draining lymph nodes (LN) is crucial for prognostic evaluation in gastric cancer (GaC) patients. Changes in lymph node microarchitecture, such as follicular hyperplasia (FH), sinus histiocytosis (SH), or paracortical hyperplasia (PH), may be triggered by the anti-tumour immune response. However, the prognostic value of these changes in GaC patients is unclear.
METHODS
A systematic search in multiple databases was conducted to identify studies on the prognostic value of microarchitecture changes in regional tumour-negative and tumour-positive LNs measured on histopathological slides. Since the number of GaC publications was very limited, the search was subsequently expanded to include junctional and oesophageal cancer (OeC).
RESULTS
A total of 28 articles (17 gastric cancer, 11 oesophageal cancer) met the inclusion criteria, analyzing 26,503 lymph nodes from 3711 GaC and 1912 OeC patients. The studies described eight different types of lymph node microarchitecture changes, categorized into three patterns: hyperplasia (SH, FH, PH), cell-specific infiltration (dendritic cells, T cells, neutrophils, macrophages), and differential gene expression. Meta-analysis of five GaC studies showed a positive association between SH in tumour-negative lymph nodes and better 5-year overall survival. Pooled risk ratios for all LNs showed increased 5-year overall survival for the presence of SH and PH.
CONCLUSIONS
This systematic review suggests that sinus histiocytosis and paracortical hyperplasia in regional tumour-negative lymph nodes may provide additional prognostic information for gastric and oesophageal cancer patients. Further studies are needed to better understand the lymph node reaction patterns and explore their impact of chemotherapy treatment and immunotherapy efficacy.
Topics: Humans; Stomach Neoplasms; Hyperplasia; Histiocytosis, Sinus; Clinical Relevance; Lymph Nodes; Prognosis; Esophageal Neoplasms; Neoplasm Staging
PubMed: 37776394
DOI: 10.1007/s10120-023-01426-w -
Magnetic Resonance Imaging Dec 2023Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and... (Review)
Review
Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and inflammation, which lead to neurodegeneration and cognitive decline. Its diagnosis and monitoring are performed through conventional structural MRI, in which T2-hyperintense lesions can be identified, but this technique lacks sensitivity and specificity, mainly in detecting damage to normal appearing tissues. Models of diffusion-weighted MRI such as diffusion-tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) allow to uncover microstructural abnormalities that occur in MS, mainly in normal appearing tissues such as the normal appearing white matter (NAWM), which allows to overcome limitations of conventional MRI. DTI is the standard method used for modelling this kind of data, but it has limitations, which can be tackled by using more complex diffusion models, such as NODDI, which provides additional information on morphological properties of tissues. Although there are several studies in MS using both diffusion models, there is no formal assessment that summarizes the findings of both methods in lesioned and normal appearing tissues, and whether one is more advantageous than the other. Hence, this systematic review aims to identify what microstructural abnormalities are seen in lesions and/or NAWM in relapsing-remitting MS while using two different approaches to modelling diffusion data, namely DTI and NODDI, and if one of them is more appropriate than the other or if they are complementary to each other. The search was performed using PubMed, which was last searched on November 2022, and aimed at finding studies that either utilized both DTI and NODDI in the same dataset, or only one of the methods. Eleven articles were included in this review, which included cohorts with a relatively low sample size (total number of patients = 254, total number of healthy controls = 240), and patients with a moderate disease duration, all with relapsing-remitting MS. Overall, studies found decreased fractional anisotropy (FA), neurite density index (NDI) and orientation dispersion index (ODI), and increased mean, axial and radial diffusivities (MD, AD and RD, respectively) in lesions, when compared to contralateral NAWM and healthy controls' white matter. Compared to healthy controls' white matter, NAWM showed lower FA and NDI and higher MD, AD, RD, and ODI. Results from the included articles confirm that there is active demyelination and inflammation in both lesions and NAWM, as well as loss in neurites, and that structural damage is not confined to focal lesions, which is in concordance with histological findings and results from other imaging techniques. Furthermore, NODDI is suggested to have higher sensitivity and specificity, as seen by inspecting imaging results, compared to DTI, while still being clinically feasible. The use of biomarkers derived from such advanced diffusion models in clinical practice could imply a better understanding of treatment efficacy and disease progression, without relying on the manifestation of clinical symptoms, such as relapses.
Topics: Humans; Multiple Sclerosis; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; White Matter; Brain; Neurites; Image Processing, Computer-Assisted
PubMed: 37775062
DOI: 10.1016/j.mri.2023.09.010 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal... (Review)
Review
INTRODUCTION
Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed.
MATERIALS AND METHODS
Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed.
RESULTS
From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias.
CONCLUSIONS
This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays.
Topics: Adult; Humans; Kidney Transplantation; Living Donors; Immune Tolerance; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Transplantation Tolerance
PubMed: 37709652
DOI: 10.1016/j.trre.2023.100792 -
Behavioural Brain Research Oct 2023SARS-CoV-2 infection produces a wide range of symptoms. Some of the structural changes caused by the virus in the nervous system are found in the medial temporal lobe,... (Review)
Review
SARS-CoV-2 infection produces a wide range of symptoms. Some of the structural changes caused by the virus in the nervous system are found in the medial temporal lobe, and several neuropsychological sequelae of COVID-19 are related to the function of the hippocampus. The main objective of the systematic review is to update and further analyze the existing evidence of hippocampal and related cortices' structural and functional alterations due to SARS-CoV-2 infection. Both clinical and preclinical studies that used different methodologies to explore the effects of this disease at different stages and grades of severity were considered, besides exploring related cognitive and emotional symptomatology. A total of 24 studies were identified by searching in SCOPUS, Web Of Science (WOS), PubMed, and PsycInfo databases up to October 3rd, 2022. Thirteen studies were performed in clinical human samples, 9 included preclinical animal models, 3 were performed post-mortem, and 1 included both post-mortem and preclinical samples. Alterations in the hippocampus were detected in the acute stage and after several months of infection. Clinical studies revealed alterations in hippocampal connectivity and metabolism. Memory alterations correlated with altered metabolic profiles or changes in grey matter volumes. Hippocampal human postmortem and animal studies observed alterations in neurogenesis, dendrites, and immune response, besides high apoptosis and neuroinflammation. Preclinical studies reported the viral load in the hippocampus. Olfactory dysfunction was associated with alterations in brain functionality. Several clinical studies revealed cognitive complaints, neuropsychological alterations, and depressive and anxious symptomatology.
Topics: Animals; Humans; COVID-19; SARS-CoV-2; Hippocampus; Temporal Lobe
PubMed: 37703951
DOI: 10.1016/j.bbr.2023.114662 -
Frontiers in Physiology 2023Studies have shown that exercise increases angiogenesis and perfusion in the hippocampus, activates neurogenesis in the dentate gyrus and increases synaptic plasticity,...
Studies have shown that exercise increases angiogenesis and perfusion in the hippocampus, activates neurogenesis in the dentate gyrus and increases synaptic plasticity, as well as increases the complexity and number of dendritic spines, all of which promote memory function and protect against cognitive decline. Flavonoids are gaining attention as antioxidants in health promotion due to their rich phenolic content, particularly for their modulating role in the treatment of neurodegenerative diseases. Despite this, there has been no comprehensive review of cognitive improvement supplemented with flavonoid and prescribed with exercise or a combination of the two interventions has been conducted. The purpose of this review is to determine whether a combined intervention produces better results when given together than when given separately. Relevant articles assessing the effect of physical exercise, flavonoid or in combination on cognitive related biomarkers and neurobehavioral assessments within the timeline of January 2011 until June 2023 were searched using three databases; PubMed, PROQUEST and SCOPUS. A total of 705 articles were retrieved and screened, resulting in 108 studies which are in line with the objective of the current study were included in the analysis. The selected studies have shown significant desired effect on the chosen biomarkers and neurobehavioral assessments. identifier: [CRD42021271001].
PubMed: 37664425
DOI: 10.3389/fphys.2023.1216948 -
Cureus Aug 2023Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis.... (Review)
Review
Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Meanwhile, more recently, clinical practice and research efforts have uncovered increasing cases of psoriatic lesion development tied to initiating treatment with a TNF-α inhibitor. The underlying mechanisms associated with this occurrence have yet to be fully elucidated. A review and analysis of cases of paradoxical psoriasis currently published in the literature is warranted. In addition, exploring possible mechanisms of action and potential treatment options associated with favorable outcomes is much needed. A systematic literature review was performed utilizing PubMed and Google Scholar databases (1992-present), in which 106 cases of paradoxical psoriasis were reviewed. The most common morphology developed was plaque psoriasis vulgaris. There was a female predominance (61.3%), and the most common underlying autoimmune disease was rheumatoid arthritis (45.3%). In addition, the most commonly associated drug with the onset of psoriatic lesions was infliximab (62.3%). Furthermore, the findings suggest that the most well-supported mechanism of action involves the uncontrolled release of interferon-alpha (IFN-α) from plasmacytoid dendritic cells (pDCs) after TNF-α inhibition. While TNF-α inhibitors have been shown to have great benefits to patients with rheumatologic diseases, cases of paradoxical psoriasis demonstrate the importance of close monitoring of patients on TNF-α inhibitors to allow for early recognition, treatment, and potentially change to a different mechanism of action of the medication used to prevent further progression of the inflammatory lesions.
PubMed: 37664349
DOI: 10.7759/cureus.42791 -
Survey of Ophthalmology 2024Although there have been numerous innovations in the management of retinal detachment (RD) over the past decades, there is still limited understanding of the... (Review)
Review
Although there have been numerous innovations in the management of retinal detachment (RD) over the past decades, there is still limited understanding of the pathophysiological processes that take place before and after repair. Summarizing key concepts using animal studies may allow for a better assessment of common pre- and postoperative microstructural abnormalities in RD. We performed a systematic literature review on Ovid MEDLINE, EMBASE, and Cochrane Controlled Register of Trials from January 1968 to January 2022, searching animal or human studies reporting retinal histologic changes following primary or induced RD. Thirty-two studies were included. Main cellular events were summarized: photoceptor apoptosis occurs as early as 12 hours after RD and, although most cells survive, there is extensive remodeling. Outer segments progressively degenerate, while inner segments are reorganized. Rod and cone opsins are redistributed, and rod axons retract while cones undergo changes in shape. Second- and third-order neurons rearrange their dendritic processes, and Müller cells become hypertrophic, growing into the subretinal space. Finally, retinal pigment epithelium cells undergo a change in their morphology. Acknowledging critical morphologic changes following RD is crucial in understanding why anatomical and functional outcomes can vary. Insights from histological studies, together with high-resolution imaging, may be key in identifying novel biomarkers in RD.
Topics: Animals; Humans; Retinal Detachment; Retina; Retinal Cone Photoreceptor Cells; Retinal Degeneration
PubMed: 37652188
DOI: 10.1016/j.survophthal.2023.08.001