-
Asian Pacific Journal of Cancer... Jun 2024Presently, ovarian cancer remains the leading cause of death in gynecological malignancies. The survival rate of these patients is low, which might be caused by early... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Presently, ovarian cancer remains the leading cause of death in gynecological malignancies. The survival rate of these patients is low, which might be caused by early metastases and delayed diagnosis. Therefore, it is crucial to investigate novel practical markers that provide early prognostic value which helps construct individualized treatment.
METHODS
A thorough investigation of the neutrophil-lymphocyte ratio (NLR) and lymphocyte ratio (PLR) in ovarian cancer patients was conducted using article selection from PubMed, Cochrane, Science Direct, and Google Scholar databases. The outcomes and hazard ratio (HR) were obtained using Review Manager 5.4, and the 95% Confidence Interval (CI) result was calculated. The chief endpoints of interest in this study include overall survival (OS) and progression-free survival (PFS).
RESULTS
Sixteen studies with 3,862 patients were included with a mean age of 50.6 years and a mean follow-up of 45.84 months. Multivariate studies demonstrated that a higher NLR is associated with worse PFS and OS, HR 1.35;95% CI [1.05-1.74] and HR 1.46; 95% CI [1.16-1.83] respectively. Similar results are observed with PLR and poorer PFS and OS, HR 1.62; 95% CI [1.09-2.43] and HR 1.66; 95% CI [1.12-2.46].
CONCLUSION
Pre-treatment PLR and NLR were found to be prognostic factors in determining PFS and OS in ovarian cancer. High values in pre-treatment PLR and NLR may indicate worse clinical outcomes.
Topics: Humans; Female; Ovarian Neoplasms; Neutrophils; Prognosis; Lymphocytes; Biomarkers, Tumor; Blood Platelets; Lymphocyte Count; Survival Rate; Platelet Count
PubMed: 38918652
DOI: 10.31557/APJCP.2024.25.6.1921 -
Nature Communications Jun 2024Adipose tissue macrophages (ATMs) influence obesity-associated metabolic dysfunction, but the mechanisms by which they do so are not well understood. We show that...
Adipose tissue macrophages (ATMs) influence obesity-associated metabolic dysfunction, but the mechanisms by which they do so are not well understood. We show that miR-6236 is a bona fide miRNA that is secreted by ATMs during obesity. Global or myeloid cell-specific deletion of miR-6236 aggravates obesity-associated adipose tissue insulin resistance, hyperglycemia, hyperinsulinemia, and hyperlipidemia. miR-6236 augments adipocyte insulin sensitivity by inhibiting translation of negative regulators of insulin signaling, including PTEN. The human genome harbors a miR-6236 homolog that is highly expressed in the serum and adipose tissue of obese people. hsa-MIR-6236 expression negatively correlates with hyperglycemia and glucose intolerance, and positively correlates with insulin sensitivity. Together, our findings establish miR-6236 as an ATM-secreted miRNA that potentiates adipocyte insulin signaling and protects against metabolic dysfunction during obesity.
Topics: MicroRNAs; Obesity; Animals; Adipocytes; Hyperglycemia; Humans; Signal Transduction; Insulin; Insulin Resistance; Mice; Male; PTEN Phosphohydrolase; Mice, Inbred C57BL; Macrophages; Adipose Tissue; Myeloid Cells; Mice, Knockout; Hyperinsulinism
PubMed: 38918428
DOI: 10.1038/s41467-024-49632-z -
Signal Transduction and Targeted Therapy Jun 2024
Topics: Tuberculosis; Macrophages; Humans; Nanoparticles; Cell Membrane; Animals; Mycobacterium tuberculosis; Macrophage Activation; Mice
PubMed: 38918362
DOI: 10.1038/s41392-024-01855-8 -
PloS One 2024The Neutrophil-to-Lymphocyte Ratio (NLR) is a clinical indicator of peripheral inflammation that is easily accessible. It is worth noting that the formation of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Neutrophil-to-Lymphocyte Ratio (NLR) is a clinical indicator of peripheral inflammation that is easily accessible. It is worth noting that the formation of amyloid-β (Aβ) plaques and neurofibrillary tangles has been linked to inflammation and immune dysregulation. The main objective of this systematic review and meta-analysis is to comprehensively evaluate the existing body of research concerning the NLR in the context of Alzheimer's disease (AD) and mild cognitive impairment (MCI).
METHOD
We conducted a comprehensive online search and included studies that evaluated the NLR in 1) patients with AD or MCI and 2) healthy control (HC) participants. We also pooled mean and standard deviation (SD) data for each group.
RESULTS
Ultimately, 12 studies encompassed 1,309 individuals diagnosed with AD with mean NLR levels of 2.68, 1,929 individuals with MCI with mean NLR levels of 2.42, and 2,064 HC with mean NLR levels of 2.06 were included in this systematic review and meta-analysis. The mean NLR was 0.59 higher in AD patients compared to HC participants (mean difference (MD) = 0.59 [0.38; 0.80]). Similarly, the mean NLR was higher in AD than MCI patients (MD = 0.23 [0.13; 0.33]). Additionally, the mean NLR was higher in individuals with MCI compared to HC participants (MD = 0.37 [0.22; 0.52]). In the subgroup meta-analysis based on the Mini-Mental State Examination (MMSE), AD patients with lower MMSE scores (using a cut-off of 20) exhibited significantly higher mean NLR (3.10 vs. 2.70, with a p-value for subgroup differences < 0.01).
CONCLUSION
The NLR, which serves as a marker of peripheral inflammation, shows increased levels in individuals with AD and MCI compared to HC participants. Furthermore, our study indicates that NLR levels are significantly higher in AD than MCI. Additionally, our novel finding suggests significantly higher NLR levels among AD patients with more severe cognitive decline compared to AD patients with less severe cognitive decline. So, it can be concluded that the higher cognitive decline in humans is accompanied by higher NLR levels. Further longitudinal researches are needed to explore more details about the relationship between inflammation and dementia.
Topics: Alzheimer Disease; Humans; Neutrophils; Lymphocytes; Cognitive Dysfunction; Lymphocyte Count
PubMed: 38917167
DOI: 10.1371/journal.pone.0305322 -
ImmunoHorizons Jun 2024Malaria is a serious vector-borne disease characterized by periodic episodes of high fever and strong immune responses that are coordinated with the daily synchronized...
Malaria is a serious vector-borne disease characterized by periodic episodes of high fever and strong immune responses that are coordinated with the daily synchronized parasite replication cycle inside RBCs. As immune cells harbor an autonomous circadian clock that controls various aspects of the immune response, we sought to determine whether the intensity of the immune response to Plasmodium spp., the parasite causing malaria, depends on time of infection. To do this, we developed a culture model in which mouse bone marrow-derived macrophages are stimulated with RBCs infected with Plasmodium berghei ANKA (iRBCs). Lysed iRBCs, but not intact iRBCs or uninfected RBCs, triggered an inflammatory immune response in bone marrow-derived macrophages. By stimulating at four different circadian time points (16, 22, 28, or 34 h postsynchronization of the cells' clock), 24-h rhythms in reactive oxygen species and cytokines/chemokines were found. Furthermore, the analysis of the macrophage proteome and phosphoproteome revealed global changes in response to iRBCs that varied according to circadian time. This included many proteins and signaling pathways known to be involved in the response to Plasmodium infection. In summary, our findings show that the circadian clock within macrophages determines the magnitude of the inflammatory response upon stimulation with ruptured iRBCs, along with changes of the cell proteome and phosphoproteome.
Topics: Animals; Macrophages; Mice; Erythrocytes; Malaria; Plasmodium berghei; Circadian Rhythm; Mice, Inbred C57BL; Reactive Oxygen Species; Cytokines; Circadian Clocks; Cells, Cultured; Proteome
PubMed: 38916585
DOI: 10.4049/immunohorizons.2400021 -
The ISME Journal Jun 2024As unicellular predators, ciliates engage in close associations with diverse microbes, laying the foundation for the establishment of endosymbiosis. Originally...
As unicellular predators, ciliates engage in close associations with diverse microbes, laying the foundation for the establishment of endosymbiosis. Originally heterotrophic, ciliates demonstrate the ability to acquire phototrophy by phagocytizing unicellular algae or by sequestering algal plastids. This adaptation enables them to gain photosynthate and develop resistance to unfavorable environmental conditions. The integration of acquired phototrophy with intrinsic phagotrophy results in a trophic mode known as mixotrophy. Additionally, ciliates can harbor thousands of bacteria in various intracellular regions, including the cytoplasm and nucleus, exhibiting species specificity. Under prolonged and specific selective pressure within hosts, bacterial endosymbionts evolve unique lifestyles and undergo particular reductions in metabolic activities. Investigating the research advancements in various endosymbiotic cases within ciliates will contribute to elucidate patterns in cellular interaction and unravel the evolutionary origins of complex traits.
PubMed: 38916437
DOI: 10.1093/ismejo/wrae117 -
Microbiology (Reading, England) Jun 2024Bacterial infection is a dynamic process resulting in a heterogenous population of infected and uninfected cells. These cells respond differently based on their...
Bacterial infection is a dynamic process resulting in a heterogenous population of infected and uninfected cells. These cells respond differently based on their bacterial load and duration of infection. In the case of infection of macrophages with Crohn's disease (CD) associated adherent-invasive (AIEC), understanding the drivers of pathogen success may allow targeting of cells where AIEC replicate to high levels. Here we show that stratifying immune cells based on their bacterial load identifies novel pathways and therapeutic targets not previously associated with AIEC when using a traditional homogeneous infected population approach. Using flow cytometry-based cell sorting we stratified cells into those with low or high intracellular pathogen loads, or those which were bystanders to infection. Immune cells transcriptomics revealed a diverse response to the varying levels of infection while pathway analysis identified novel intervention targets that were directly related to increasing intracellular AIEC numbers. Chemical inhibition of identified targets reduced AIEC intracellular replication or inhibited secretion of tumour necrosis factor alpha (TNFα), a key cytokine associated with AIEC infection. Our results have identified new avenues of intervention in AIEC infection that may also be applicable to CD through the repurposing of already available inhibitors. Additionally, they highlight the applicability of immune cell stratification post-infection as an effective approach for the study of microbial pathogens.
Topics: Crohn Disease; Macrophages; Humans; Escherichia coli Infections; Escherichia coli; Tumor Necrosis Factor-alpha; Bacterial Load; Bacterial Adhesion; Host-Pathogen Interactions
PubMed: 38916198
DOI: 10.1099/mic.0.001470 -
BioRxiv : the Preprint Server For... Jun 2024To investigate ultra-high-dose rate helium ion irradiation and its potential FLASH sparing effect with the endpoint acute brain injury in preclinical in vivo settings.
PURPOSE
To investigate ultra-high-dose rate helium ion irradiation and its potential FLASH sparing effect with the endpoint acute brain injury in preclinical in vivo settings.
MATERIAL AND METHODS
Raster-scanned helium ion beams were administered to explore and compare the impact of dose rate variations between standard dose rate (SDR at 0.2 Gy/s) and FLASH (at 141 Gy/s) radiotherapy (RT). Irradiation-induced brain injury was investigated in healthy C57BL/6 mice via DNA damage response kinetic studies using nuclear γH2AX as a surrogate for double-strand breaks (DSB). The integrity of the neurovascular and immune compartments was assessed via CD31+ microvascular density and microglia/macrophages activation. Iba1+ ramified and CD68+ phagocytic microglia/macrophages were quantified, together with the expression of inducible nitric oxide synthetase (iNOS).
RESULTS
Helium FLASH RT significantly prevented acute brain tissue injury compared with SDR. This was demonstrated by reduced levels of DSB and structural preservation of the neurovascular endothelium after FLASH RT. Moreover, FLASH RT exhibited reduced activation of neuroinflammatory signals compared with SDR, as detected by quantification of CD68+ iNOS+ microglia/macrophages.
CONCLUSION
To our knowledge, this is the first report on the FLASH-sparing neuroprotective effect of raster scanning helium ion radiotherapy in vivo.
PubMed: 38915610
DOI: 10.1101/2024.06.13.598785 -
BioRxiv : the Preprint Server For... Jun 2024Immune cells elicit a continuum of transcriptional and functional states after spinal cord injury (SCI). In mammals, inefficient debris clearance and chronic...
Immune cells elicit a continuum of transcriptional and functional states after spinal cord injury (SCI). In mammals, inefficient debris clearance and chronic inflammation impede recovery and overshadow pro-regenerative immune functions. We found that, unlike mammals, zebrafish SCI elicits transient immune activation and efficient debris clearance, without causing chronic inflammation. Single-cell transcriptomics and inducible genetic ablation showed zebrafish macrophages are highly phagocytic and required for regeneration. Cross-species comparisons between zebrafish and mammalian macrophages identified ( ) as a macrophage-enriched zebrafish gene. Genetic deletion of zebrafish impairs phagocytosis and regeneration, causes aberrant and chronic immune activation, and can be rescued by transplanting wild-type immune precursors into mutants. Conversely, genetic expression of human accelerates debris clearance and regeneration by reprogramming myeloid precursors into activated phagocytes. This study establishes a central requirement for elevated phagocytic capacity to achieve innate spinal cord repair.
PubMed: 38915507
DOI: 10.1101/2024.06.11.598515 -
Virology Journal Jun 2024Omicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high...
BACKGROUND
Omicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high transmissibility and immune evasion. Early identification of Omicron cases in clinical settings is crucial for controlling its spread. Previous studies have indicated that changes in hematological parameters can be used to predict the severity of coronavirus disease 2019 (COVID-19). However, the role of hematological parameters in non-severe and asymptomatic cases remains unknown. This study aimed to investigate the role of hematological parameters in non-severe and asymptomatic Omicron variant infections.
METHODS
Hematological parameters and results were analyzed and compared in symptomatic (n = 356) and asymptomatic (n = 171) groups respectively, and between these two groups with positive COVID-19 tests. The utility of hematological parameters for predicting positive COVID-19 tests was analyzed using receiver operating characteristic curves.
RESULTS
Individuals with non-severe cases exhibited decreased levels of platelets, lymphocytes, eosinophils, basophils, lymphocytes (%), eosinophils (%), and basophils (%), while exhibiting elevated counts of monocytes, neutrophils (%), monocytes (%), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) when compared to suspected cases or asymptomatic carriers. In asymptomatic patients, positive carriers had lower leukocyte, neutrophil, and lymphocyte counts but higher monocyte, monocyte (%), PLR, and CRP levels than negative carriers. Basophil counts combined with lymphocytes or the PLR demonstrated a more significant predictive value in screening non-severe cases earlier compared to other parameters. The combined assessment of the monocyte (%) and the PLR had the highest area under the curve for diagnosing asymptomatic carriers.
CONCLUSIONS
Circulating basophils, alone or in combination with other hematological parameters, may be used as efficient biomarkers for early screening of non-severe Omicron cases.
Topics: Humans; COVID-19; Male; Female; SARS-CoV-2; Middle Aged; Adult; Asymptomatic Infections; Aged; Young Adult; Severity of Illness Index; Neutrophils; C-Reactive Protein; Biomarkers; Basophils; ROC Curve; Adolescent
PubMed: 38915037
DOI: 10.1186/s12985-024-02414-x