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Journal of Cancer 2022Rho-GTPases control a variety of cellular functions mainly by regulating microtubule and actin dynamics, affecting the cytoskeleton, and are important regulators of the... (Review)
Review
Rho-GTPases control a variety of cellular functions mainly by regulating microtubule and actin dynamics, affecting the cytoskeleton, and are important regulators of the structural plasticity of dendrites and spines. Members of the Rho-GTPase family include Ras-related C3 botulinum toxin substrate 1 (Rac1), RhoA (Ras homologous), and cell division control protein 42 (Cdc42). Cdc42 is involved in the regulation of a variety of tumor and non-tumor diseases through a cascade of multiple signaling pathways. Active Cdc42 can regulate intercellular adhesion, cytoskeleton formation, and cell cycle, thus affecting cell proliferation, transformation, and dynamic balance as well as migration and invasion of tumor cells by regulating the expression of effector proteins. Here we discuss the role of Cdc42 in promoting metastasis, invasion, epithelial-mesenchymal transformation and angiogenesis in malignant tumors. The significant role of Cdc42 in non-tumor diseases is also discussed. Since Cdc42 plays a central role in the development of various diseases, small molecule inhibitors targeting Cdc42 have important clinical significance in the prevention and treatment of these diseases.
PubMed: 35154449
DOI: 10.7150/jca.65415 -
Biomedical and Environmental Sciences :... Aug 2010Age-related increment of the prevalence of CD4(+)CD25(+) regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in... (Review)
Review
OBJECTIVE
Age-related increment of the prevalence of CD4(+)CD25(+) regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence.
METHODS
Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells.
RESULTS
It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8(+) T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4(+)CD25(+) T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4(+) T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years.
CONCLUSIONS
Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.
Topics: Aging; Animals; CD4 Antigens; Humans; Interleukin-2 Receptor alpha Subunit; T-Lymphocytes, Regulatory
PubMed: 20934123
DOI: 10.1016/S0895-3988(10)60072-4 -
Frontiers in Medicine 2023To evaluate the subclinical changes in corneal dendritic cell density (CDCD) and corneal subbasal nerve density (CSND) in asymptomatic contact lens (CL) wearers. (Review)
Review
PURPOSE
To evaluate the subclinical changes in corneal dendritic cell density (CDCD) and corneal subbasal nerve density (CSND) in asymptomatic contact lens (CL) wearers.
METHODS
Databases including PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for trials and studies reporting the changes of corneal CDCD and CSND in contact lens wearers published until 25 June 2022. PRISMA guidelines as well as recommended meta-analysis practices were followed. Meta-analysis was conducted using RevMan V.5.3 software.
RESULTS
After the screening, 10 studies with 587 eyes of 459 participants were included. Seven studies reported the data of CDCD. Compared with the control group, CDCD in the CL wearers was higher (18.19, 95% CI 18.8-27.57, = 0.0001). Type of confocal microscopy (IVCM), wear duration, and frequency of lens change were sources of heterogeneity. The difference in CSND between CL wearers and the control group was insignificant, and subgroup analysis did not reveal a source of heterogeneity.
CONCLUSION
Overall, CDCD increased in CL wears, while CSND did not show significant differences. IVCM is a feasible tool to assess subclinical changes in CL wearers.
PubMed: 36993811
DOI: 10.3389/fmed.2023.1149803 -
PLoS Neglected Tropical Diseases Jan 2012Burkholderia pseudomallei is a Category B select agent and the cause of melioidosis. Research funding for vaccine development has largely considered protection within... (Review)
Review
BACKGROUND
Burkholderia pseudomallei is a Category B select agent and the cause of melioidosis. Research funding for vaccine development has largely considered protection within the biothreat context, but the resulting vaccines could be applicable to populations who are at risk of naturally acquired melioidosis. Here, we discuss target populations for vaccination, consider the cost-benefit of different vaccination strategies and review potential vaccine candidates.
METHODS AND FINDINGS
Melioidosis is highly endemic in Thailand and northern Australia, where a biodefense vaccine might be adopted for public health purposes. A cost-effectiveness analysis model was developed, which showed that a vaccine could be a cost-effective intervention in Thailand, particularly if used in high-risk populations such as diabetics. Cost-effectiveness was observed in a model in which only partial immunity was assumed. The review systematically summarized all melioidosis vaccine candidates and studies in animal models that had evaluated their protectiveness. Possible candidates included live attenuated, whole cell killed, sub-unit, plasmid DNA and dendritic cell vaccines. Live attenuated vaccines were not considered favorably because of possible reversion to virulence and hypothetical risk of latent infection, while the other candidates need further development and evaluation. Melioidosis is acquired by skin inoculation, inhalation and ingestion, but routes of animal inoculation in most published studies to date do not reflect all of this. We found a lack of studies using diabetic models, which will be central to any evaluation of a melioidosis vaccine for natural infection since diabetes is the most important risk factor.
CONCLUSION
Vaccines could represent one strand of a public health initiative to reduce the global incidence of melioidosis.
Topics: Animals; Australia; Bacterial Vaccines; Biological Warfare Agents; Bioterrorism; Burkholderia pseudomallei; Cost-Benefit Analysis; Disease Models, Animal; Humans; Melioidosis; Public Health; Thailand
PubMed: 22303489
DOI: 10.1371/journal.pntd.0001488 -
Journal of Psychiatry & Neuroscience :... Jul 2018Scaffolding proteins represent an evolutionary solution to controlling the specificity of information transfer in intracellular networks. They are highly concentrated in...
Scaffolding proteins represent an evolutionary solution to controlling the specificity of information transfer in intracellular networks. They are highly concentrated in complexes located in specific subcellular locations. One of these complexes is the postsynaptic density of the excitatory synapses. There, scaffolding proteins regulate various processes related to synaptic plasticity, such as glutamate receptor trafficking and signalling, and dendritic structure and function. Most scaffolding proteins can be grouped into 4 main families: discs large (DLG), discs-large-associated protein (DLGAP), Shank and Homer. Owing to the importance of scaffolding proteins in postsynaptic density architecture, it is not surprising that variants in the genes that code for these proteins have been associated with neuropsychiatric diagnoses, including schizophrenia and autism-spectrum disorders. Such evidence, together with the clinical, neurobiological and genetic overlap described between schizophrenia and autism-spectrum disorders, suggest that alteration of scaffolding protein dynamics could be part of the pathophysiology of both. However, despite the potential importance of scaffolding proteins in these psychiatric conditions, no systematic review has integrated the genetic and molecular data from studies conducted in the last decade. This review has the following goals: to systematically analyze the literature in which common and/or rare genetic variants (single nucleotide polymorphisms, single nucleotide variants and copy number variants) in the scaffolding family genes are associated with the risk for either schizophrenia or autism-spectrum disorders; to explore the implications of the reported genetic variants for gene expression and/or protein function; and to discuss the relationship of these genetic variants to the shared genetic, clinical and cognitive traits of schizophrenia and autism-spectrum disorders.
Topics: Autism Spectrum Disorder; Genetic Predisposition to Disease; Genetic Variation; Humans; Nerve Tissue Proteins; Schizophrenia
PubMed: 29947605
DOI: 10.1503/jpn.170066 -
Translational Stroke Research Feb 2015Aerobic exercise may be a catalyst to promote neuroplasticity and recovery following stroke; however, the optimal methods to measure neuroplasticity and the effects of... (Review)
Review
Aerobic exercise may be a catalyst to promote neuroplasticity and recovery following stroke; however, the optimal methods to measure neuroplasticity and the effects of training parameters have not been fully elucidated. We conducted a systematic review and synthesis of clinical trials and studies in animal models to determine (1) the extent to which aerobic exercise influences poststroke markers of neuroplasticity, (2) the optimal parameters of exercise required to induce beneficial effects, and (3) consistent outcomes in animal models that could help inform the design of future trials. Synthesized findings show that forced exercise at moderate to high intensity increases brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I), nerve growth factor (NGF), and synaptogenesis in multiple brain regions. Dendritic branching was most responsive to moderate rather than intense training. Disparity between clinical stroke and stroke models (timing of initiation of exercise, age, gender) and clinically viable methods to measure neuroplasticity are some of the areas that should be addressed in future research.
Topics: Aged; Animals; Brain; Brain-Derived Neurotrophic Factor; Clinical Trials as Topic; Dendrites; Exercise Therapy; Female; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Nerve Growth Factor; Neuronal Plasticity; Recovery of Function; Stroke; Stroke Rehabilitation; Synapses
PubMed: 25023134
DOI: 10.1007/s12975-014-0357-7 -
Critical Reviews in Toxicology Aug 2021Endocrine-disrupting chemicals (EDCs) refer to a group of chemicals that cause adverse effects in human health, impairing hormone production and regulation, resulting in...
Endocrine-disrupting chemicals (EDCs) refer to a group of chemicals that cause adverse effects in human health, impairing hormone production and regulation, resulting in alteration of homeostasis, reproductive, and developmental, and immune system impairments. The immunotoxicity of EDCs involves many mechanisms altering gene expression that depend on the activation of nuclear receptors such as the aryl hydrocarbon receptor (AHR), the estrogen receptor (ER), and the peroxisome proliferator-activated receptor (PPAR), which also results in skin and intestinal disorders, microbiota alterations and inflammatory diseases. This systematic review aims to review different mechanisms of immunotoxicity and immunomodulation of T cells, focusing on T regulatory (Treg) and Th17 subsets, B cells, and dendritic cells (DCs) caused by specific EDCs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), bisphenols (BPs) and polyfluoroalkyl substances (PFASs). To achieve this objective, a systematic study was conducted searching various databases including PubMed and Scopus to find , , and biomonitoring studies that examine EDC-dependent mechanisms of immunotoxicity. While doing the systematic review, we found species- and cell-specific outcomes and a translational gap between and experiments. Finally, an adverse outcome pathway (AOP) framework is proposed, which explains mechanistically toxicity endpoints emerging from different EDCs having similar key events and can help to improve our understanding of EDCs mechanisms of immunotoxicity. In conclusion, this review provides insights into the mechanisms of immunotoxicity mediated by EDCs and will help to improve human health risk assessment.
Topics: Endocrine Disruptors; Humans; Immune System; Polychlorinated Dibenzodioxins; Receptors, Estrogen
PubMed: 35015608
DOI: 10.1080/10408444.2021.2009438 -
PloS One 2014Lung cancer, particularly non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality. Chemotherapy combined dendritic cells co-cultured with... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and safety of chemotherapy combined with dendritic cells co-cultured with cytokine-induced killer cells in the treatment of advanced non-small-cell lung cancer: a systematic review and meta-analysis.
BACKGROUND
Lung cancer, particularly non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality. Chemotherapy combined dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) immunotherapy has been applied in advanced NSCLC patients' treatment, but couldn't provide consistent beneficial results. Therefore, it is necessary to evaluate the efficiency and safety of combination therapy to promote the application.
METHODS
A literature search for randomized controlled trials of NSCLC was conducted in PubMed database. Before meta-analysis was performed, studies were evaluated heterogeneity. Pooled risk ratios (RRs) were estimated and 95% confidence intervals (CIs) were calculated using a fixed-effect model. Sensitivity analysis was also performed.
RESULTS
Six eligible trials were enrolled. Efficiency and safety of chemotherapy followed by DC-CIK immunotherapy (experimental group) and chemotherapy alone (control group) were compared. 1-year overall survival (OS) (P = 0.02) and progression free survival (PFS) (P = 0.005) in the experimental group were significantly increased compared with the control. Disease control rate (DCR) (P = 0.006) rose significantly in experimental group. However, no significant differences between the two groups were observed in 2-year OS (P = 0.21), 2-year PFS (P = 0.10), overall response rate (ORR) (P = 0.76) and partial response (PR) (P = 0.22). Temporary fever, anemia, leukopenia and nausea were the four major adverse events (AEs) treated by chemotherapy. The incidence of anemia, leukopenia and nausea in the experimental group was obviously lower than the control group. Temporary fever rate was higher in experimental group than that in the control, but could be alleviated by taking sufficient rest.
CONCLUSIONS
Chemotherapy combined with DC-CIK immunotherapy showed superiority in DCR, 1-year OS and PFS, and no more AEs appeared, however, there was no significant improvement in ORR, PR, 2-year OS and PFS. As a whole, the combination therapy is safer but modest in efficacy for advanced NSCLC patients.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Coculture Techniques; Cytokine-Induced Killer Cells; Databases, Factual; Dendritic Cells; Disease-Free Survival; Humans; Immunotherapy; Lung Neoplasms; Remission Induction; Survival Rate
PubMed: 25268709
DOI: 10.1371/journal.pone.0108958 -
Neuroscience and Biobehavioral Reviews May 2022Once considered only scaffolding proteins at glutamatergic postsynaptic density (PSD), Homer1 proteins are increasingly emerging as multimodal adaptors that integrate... (Review)
Review
The Homer1 family of proteins at the crossroad of dopamine-glutamate signaling: An emerging molecular "Lego" in the pathophysiology of psychiatric disorders. A systematic review and translational insight.
Once considered only scaffolding proteins at glutamatergic postsynaptic density (PSD), Homer1 proteins are increasingly emerging as multimodal adaptors that integrate different signal transduction pathways within PSD, involved in motor and cognitive functions, with putative implications in psychiatric disorders. Regulation of type I metabotropic glutamate receptor trafficking, modulation of calcium signaling, tuning of long-term potentiation, organization of dendritic spines' growth, as well as meta- and homeostatic plasticity control are only a few of the multiple endocellular and synaptic functions that have been linked to Homer1. Findings from preclinical studies, as well as genetic studies conducted in humans, suggest that both constitutive (Homer1b/c) and inducible (Homer1a) isoforms of Homer1 play a role in the neurobiology of several psychiatric disorders, including psychosis, mood disorders, neurodevelopmental disorders, and addiction. On this background, Homer1 has been proposed as a putative novel target in psychopharmacological treatments. The aim of this review is to summarize and systematize the growing body of evidence on Homer proteins, highlighting the role of Homer1 in the pathophysiology and therapy of mental diseases.
Topics: Carrier Proteins; Dopamine; Glutamates; Homer Scaffolding Proteins; Humans; Mental Disorders; Signal Transduction
PubMed: 35248676
DOI: 10.1016/j.neubiorev.2022.104596 -
PloS One 2019TIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
TIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to contribute to the various intracellular signals and immune responses, importantly the regulation of Th1 and Th17 cell differentiation, which plays a remarked role in fight against inflammatory and autoimmune diseases. Association of TIM family gene polymorphisms with rheumatoid arthritis (RA) has been frequently investigated. The findings however are not entirely consistent. Therefore, we carried out the present meta-analysis to examine the association between RA and the following TIM family gene polymorphisms: rs41297579, rs1036199, rs10515746, and rs7700944.
METHODS
A systematic search of Scopus, PubMed, and Web of Science databases was conducted through December 2018. Combined odds ratios (OR) with their corresponding 95% confidence intervals (CI) were calculated under different possible genetic models.
RESULTS
A total of eight case-control studies were included in the present meta-analysis. The results demonstrated significant association of RA with TIM-3 rs1036199 polymorphism under dominant (OR, 1.93, 95% CI, 1.43-2.61) and allelic models (OR, 1.74, 95% CI, 1.31-2.30). None of the other examined polymorphisms indicated significant association with RA.
CONCLUSIONS
The present meta-analysis revealed that the TIM-3 rs1036199 polymorphism might confer susceptibility to RA. Further studies are required to reassert our findings.
Topics: Arthritis, Rheumatoid; Genetic Association Studies; Genetic Predisposition to Disease; Hepatitis A Virus Cellular Receptor 1; Hepatitis A Virus Cellular Receptor 2; Humans; Membrane Proteins; Polymorphism, Single Nucleotide
PubMed: 30730912
DOI: 10.1371/journal.pone.0211146