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Molecular Therapy. Oncology Jun 2024Cell surface molecules transiently upregulated on activated T cells can play a counter-regulatory role by inhibiting T cell function. Deletion or blockade of such...
Cell surface molecules transiently upregulated on activated T cells can play a counter-regulatory role by inhibiting T cell function. Deletion or blockade of such immune checkpoint receptors has been investigated to improve the function of engineered immune effector cells. CD38 is upregulated on activated T cells, and although there have been studies showing that CD38 can play an inhibitory role in T cells, how it does so has not fully been elucidated. In comparison with molecules such as PD1, CTLA4, LAG3, and TIM3, we found that CD38 displays more sustained and intense expression following acute activation. After deleting CD38 from human chimeric antigen receptor (CAR) T cells, we showed relative resistance to exhaustion and improved anti-tumor function . CD38 is a multifunctional ectoenzyme with hydrolase and cyclase activities. Reintroduction of CD38 mutants into T cells lacking CD38 provided further evidence supporting the understanding that CD38 plays a crucial role in producing the immunosuppressive metabolite adenosine and utilizing nicotinamide adenine dinucleotide (NAD) in human T cells. Taken together, these results highlight a role for CD38 as an immunometabolic checkpoint in T cells and lead us to propose CD38 deletion as an additional avenue for boosting CAR T cell function.
PubMed: 38912091
DOI: 10.1016/j.omton.2024.200819 -
Frontiers in Immunology 2024Bilateral facial palsy with paresthesia (FDP) is a rare variant of GBS, characterized by simultaneous bilateral facial palsy and paresthesia of the distal limbs....
Bilateral facial palsy with paresthesia (FDP) is a rare variant of GBS, characterized by simultaneous bilateral facial palsy and paresthesia of the distal limbs. Mounting evidence indicates that the presence of anti-GT1a IgG has a pathogenic role as an effector molecule in the development of cranial nerve palsies in certain patients with GBS, whereas anti-GT1a antibody is rarely presented positive in FDP. Here, we report the case of a 33-year-old male diagnosed with FDP presented with acute onset of bilateral facial palsy and slight paresthesias at the feet as the only neurological manifestation. An antecedent infection with no identifiable reason for the fever or skin eruptions was noted in the patient. He also exhibited cerebrospinal fluid albuminocytologic dissociation and abnormal nerve conduction studies. Notably, the testing of specific serum anti-gangliosides showed positive anti-GT1a IgG/IgM Ab. The patient responded well to intravenous immunoglobulin therapy. This case brings awareness to a rare variant of GBS, and provides the first indication that anti-GT1a antibodies play a causative role in the development of FDP. The case also suggests that prompt management with IVIG should be implemented if FDP is diagnosed.
Topics: Humans; Male; Adult; Paresthesia; Facial Paralysis; Autoantibodies; Gangliosides; Immunoglobulins, Intravenous; Immunoglobulin G; Guillain-Barre Syndrome
PubMed: 38911860
DOI: 10.3389/fimmu.2024.1410634 -
Frontiers in Immunology 2024IgG4-related disease (IgG4-RD) is a recently described autoimmune disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4 plasma cells in... (Review)
Review
IgG4-related disease (IgG4-RD) is a recently described autoimmune disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4 plasma cells in multiple organ systems. Recent advancements have significantly enhanced our understanding of the pathological mechanism underlying this immune-mediated disease. T cell immunity plays a crucial role in the pathogenesis of IgG4-RD, and follicular helper T cells (Tfh) are particularly important in germinal center (GC) formation, plasmablast differentiation, and IgG4 class-switching. Apart from serum IgG4 concentrations, the expansion of circulating Tfh2 cells and plasmablasts may also serve as novel biomarkers for disease diagnosis and activity monitoring in IgG4-RD. Further exploration into the pathogenic roles of Tfh in IgG4-RD could potentially lead to identifying new therapeutic targets that offer more effective alternatives for treating this condition. In this review, we will focus on the current knowledge regarding the pathogenic roles Tfh cells play in IgG4-RD and outline potential therapeutic targets for future clinical intervention.
Topics: Humans; Immunoglobulin G4-Related Disease; T Follicular Helper Cells; Animals; Immunoglobulin G; Germinal Center; Plasma Cells; T-Lymphocytes, Helper-Inducer; Biomarkers
PubMed: 38911857
DOI: 10.3389/fimmu.2024.1413860 -
ACS Omega Jun 2024Increasing evidence indicates that peripheral blood vessels play a pivotal role in regulating tumor growth with the presence of new blood vessels facilitating tumor...
Increasing evidence indicates that peripheral blood vessels play a pivotal role in regulating tumor growth with the presence of new blood vessels facilitating tumor growth and metastasis. Nevertheless, the impact of specific molecule-mediated angiogenesis on the tumor immune microenvironment (TIME) and individual prognosis of uterine corpus endometrial carcinoma (UCEC) remains uncertain. The transcriptome information on 217 prognostic angiogenesis-related genes was integrated, and the angiogenesis patterns of 506 UCEC patients in The Cancer Genome Atlas (TCGA) cohort were comprehensively evaluated. We identified five angiogenic subtypes, namely, EC1, EC2, EC3, EC4, and EC5, which differed significantly in terms of prognosis, clinicopathological features, cancer hallmarks, genomic mutations, TIME patterns, and immunotherapy responses. Additionally, an angiogenesis-related prognostic risk score (APRS) was constructed to enable an individualized comprehensive evaluation. In multiple cohorts, APRS demonstrated a powerful predictive ability for the prognosis of UCEC patients. Likewise, APRS was confirmed to be associated with clinicopathological features, genomic mutations, cancer hallmarks, and TIME patterns in UCEC patients. The predictability of APRS for immune checkpoint inhibitor (ICI) therapy was also salient. Subsequently, the expression levels of four angiogenesis-related hub genes were verified by qRT-PCR, immunohistochemistry, and single-cell sequencing data analysis. The effects of four representative genes on angiogenesis were validated by Wound-Healing and Transwell assays, tube formation assay in vitro, and tumor xenograft model in vivo. This study proffered a new classification of UCEC patients based on angiogenesis. The established APRS may contribute to individualized prognosis prediction and immunotherapy selections that are better suited for UCEC patients.
PubMed: 38911819
DOI: 10.1021/acsomega.4c03034 -
MedComm Jul 2024Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD is controversial. Alternatively activated...
Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney diseases. Here, we aim to investigate whether and how macrophage integrin αM (ITGAM) contributes to hyperuricemia-related CKD. In vivo, we explored dynamic characteristics of renal tissue in hyperuricemia-related CKD mice. By incorporating transcriptomics and phosphoproteomics data, we analyzed gene expression profile, hub genes and potential pathways. In vitro, we validated bioinformatic findings under different conditions with interventions corresponding to core nodes. We found that hyperuricemia-related CKD was characterized by elevated serum uric acid levels, impaired renal function, activation of macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed as the potential core gene, which was associated with focal adhesion signaling. Notably, we confirmed the upregulated expression of macrophage ITGAM, activated pathway, and macrophage M2 polarization in injured kidneys. In vitro, through silencing , inhibiting p-FAK or p-AKT1 phosphorylation, and concurrent inhibiting of p-FAK while activating p-AKT1 all contributed to the modulation of macrophage M2 polarization. Our results indicated targeting macrophage ITGAM might be a promising therapeutic approach for preventing CKD.
PubMed: 38911067
DOI: 10.1002/mco2.580 -
Cureus May 2024The purpose of the present review is the investigation of healthy dietary patterns and diet quality in relation to depression risk. Nutritional psychiatry is to develop... (Review)
Review
The purpose of the present review is the investigation of healthy dietary patterns and diet quality in relation to depression risk. Nutritional psychiatry is to develop scientifically based research that defines the role of nutrition and nutrients in various aspects of mental health. Growing evidence from the field suggests that diet may play an important role in the prevention and/or treatment of depression. In contrast, there is evidence that unhealthy diets may increase the risk of depression. This emerging research suggests that dietary interventions could help prevent depression or be an alternative or adjunctive therapy for depression. The Mediterranean diet (MedDiet), the Dietary Approaches to Stop Hypertension (DASH) diet, and the vegetarian diet are examined in this review. The electronic databases PubMed, Scopus, and Google Scholar were searched for relevant studies published during the last five years. We found many results that support that healthy eating patterns (high in vegetables, fruits, whole grains, nuts, seeds, and fish, low in processed foods) are related to a reduction in the risk of depression. The most robust findings are related to MedDiet, where we also found several positive results for the DASH diet. Regarding the vegetarian diet, there are inconsistent reports. Furthermore, a consistent finding refers to a lower Dietary Inflammatory Index (DII) as associated with a lower depression risk. It has been observed that people suffering from depression have poorer nutritional quality, with lower fruit and vegetable intake. This observation may strengthen the argument that nutritional interventions should be incorporated as an important "pillar" in the multifactorial treatment of patients. However, more well-designed studies are needed to establish the relationship between dietary patterns and mental health. In particular, interventional, longitudinal studies could be more enlightening.
PubMed: 38910729
DOI: 10.7759/cureus.60920 -
Cureus May 2024Primitive neuroectodermal tumors (PNETs) are unprecedented threatening neoplasms beginning from primitive neuroectodermal cells. PNETs are reported as the predominant...
Primitive neuroectodermal tumors (PNETs) are unprecedented threatening neoplasms beginning from primitive neuroectodermal cells. PNETs are reported as the predominant incidence observed in children and young adults with a high mortality rate. These neuroectodermal tumors are quite aggressive with a life expectancy of eight months on average. PNETs belong to the family of small round cell tumors majorly affecting bones and soft tissues in different body parts such as the brain, lungs, spine, and pelvic region. Computed tomography (CT) and magnetic resonance imaging (MRI) play a major role in giving the size, extent, and resectability of the tumors. A confirmed diagnosis is then made by histopathology and immunohistochemistry markers. This report depicts a case of PNET found within the right lung of a 13-year-old female, enumerating the clinical introduction, demonstrative handle, treatment modalities, and results. The case underscores the significance of precise conclusions and multidisciplinary approaches in pediatric PNET cases. Once the provisional diagnosis of pleuropulmonary blastoma or PNET was given on CT, a conformational histopathological examination was carried out. Histopathological analysis confirmed the final diagnosis of PNET, and the patient underwent neoadjuvant therapy as the tumor was non-resectable due to its massive size.
PubMed: 38910629
DOI: 10.7759/cureus.60820 -
BMC Infectious Diseases Jun 2024Respiratory infections have long been recognized as a primary cause of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Additionally, the emergence...
BACKGROUND
Respiratory infections have long been recognized as a primary cause of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Additionally, the emergence of antimicrobial resistance has led to an urgent and critical situation in developing countries, including Vietnam. This study aimed to investigate the distribution and antimicrobial resistance of bacteria in patients with AE-COPD using both conventional culture and multiplex real-time PCR. Additionally, associations between clinical characteristics and indicators of pneumonia in these patients were examined.
METHODS
This cross-sectional prospective study included 92 AE-COPD patients with pneumonia and 46 without pneumonia. Sputum specimens were cultured and examined for bacterial identification, and antimicrobial susceptibility was determined for each isolate. Multiplex real-time PCR was also performed to detect ten bacteria and seven viruses.
RESULTS
The detection rates of pathogens in AE-COPD patients with pneumonia were 92.39%, compared to 86.96% in those without pneumonia. A total of 26 pathogenic species were identified, showing no significant difference in distribution between the two groups. The predominant bacteria included Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, followed by Acinetobacter baumannii and Streptococcus mitis. There was a slight difference in antibiotic resistance between bacteria isolated from two groups. The frequency of H. influenzae was notably greater in AE-COPD patients who experienced respiratory failure (21.92%) than in those who did not (9.23%). S. pneumoniae was more common in patients with stage I (44.44%) or IV (36.36%) COPD than in patients with stage II (17.39%) or III (9.72%) disease. ROC curve analysis revealed that C-reactive protein (CRP) levels could distinguish patients with AE-COPD with and without pneumonia (AUC = 0.78).
CONCLUSION
Gram-negative bacteria still play a key role in the etiology of AE-COPD patients, regardless of the presence of pneumonia. This study provides updated evidence for the epidemiology of AE-COPD pathogens and the appropriate selection of antimicrobial agents in Vietnam.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Cross-Sectional Studies; Vietnam; Prospective Studies; Male; Female; Aged; Middle Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Bacteria; Pneumonia, Bacterial; Microbial Sensitivity Tests; Sputum; Aged, 80 and over; Pneumonia
PubMed: 38910264
DOI: 10.1186/s12879-024-09515-6 -
Respiratory Research Jun 2024Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver...
Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.
Topics: Humans; Antitubercular Agents; Male; Metabolomics; Female; Chemical and Drug Induced Liver Injury; Longitudinal Studies; Adult; Middle Aged; Biomarkers; Prospective Studies; Predictive Value of Tests; Tuberculosis; Bile Acids and Salts
PubMed: 38907347
DOI: 10.1186/s12931-024-02837-8 -
BMC Oral Health Jun 2024Dental pathogens play a crucial role in oral health issues, including tooth decay, gum disease, and oral infections, and recent research suggests a link between these...
BACKGROUND
Dental pathogens play a crucial role in oral health issues, including tooth decay, gum disease, and oral infections, and recent research suggests a link between these pathogens and oral cancer initiation and progression. Innovative therapeutic approaches are needed due to antibiotic resistance concerns and treatment limitations.
METHODS
We synthesized and analyzed piperine-coated zinc oxide nanoparticles (ZnO-PIP NPs) using UV spectroscopy, SEM, XRD, FTIR, and EDAX. Antioxidant and antimicrobial effectiveness were evaluated through DPPH, ABTS, and MIC assays, while the anticancer properties were assessed on KB oral squamous carcinoma cells.
RESULTS
ZnO-PIP NPs exhibited significant antioxidant activity and a MIC of 50 µg/mL against dental pathogens, indicating strong antimicrobial properties. Interaction analysis revealed high binding affinity with dental pathogens. ZnO-PIP NPs showed dose-dependent anticancer activity on KB cells, upregulating apoptotic genes BCL2, BAX, and P53.
CONCLUSIONS
This approach offers a multifaceted solution to combatting both oral infections and cancer, showcasing their potential for significant advancement in oral healthcare. It is essential to acknowledge potential limitations and challenges associated with the use of ZnO NPs in clinical applications. These may include concerns regarding nanoparticle toxicity, biocompatibility, and long-term safety. Further research and rigorous testing are warranted to address these issues and ensure the safe and effective translation of ZnO-PIP NPs into clinical practice.
Topics: Zinc Oxide; Humans; Piperidines; Apoptosis; Alkaloids; Benzodioxoles; Mouth Neoplasms; bcl-2-Associated X Protein; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53; Biofilms; Polyunsaturated Alkamides; Nanoparticles; Antioxidants; Microbial Sensitivity Tests; Metal Nanoparticles; Antineoplastic Agents; Microscopy, Electron, Scanning; X-Ray Diffraction; Cell Line, Tumor; KB Cells
PubMed: 38907185
DOI: 10.1186/s12903-024-04399-z