Markers Of Response Research Articles

Dexmedetomidine leads to the amelioration of stress response to surgery.

To determine the impact of intravenous Dexmedetomidine (Dex) administered perioperatively on stress response markers in patients undergoing ENT surgeries. This randomized interventional study was conducted at POFs Hospital and NUMS affiliated WMC, Wah Cantt, in collaboration with IIMC Rawalpindi, Pakistan, from October 2021 to April 2022. One hundred patients aged between 15-60 years, after satisfying the inclusion standards were randomly divided into two groups C and D. Group-C (n=50) received normal saline in addition to the standard anesthesia protocol. The intervention Group-D (n=50) was administered 1µg/kg dexmedetomidine hydrochloride intravenously over 10 minutes just before the induction followed 0.5μg/kg/hr as maintenance dose till the end of surgery. Serum inflammatory biomarkers (interleukins-6, TNF-α and cortisol) were measured in blood samples in both groups, taken at 0 (T0), 30 minutes(T1), and two hours (T2) time intervals and analyzed by using Enzyme-linked immunosorbent assay (ELISA). Data was statistically analyzed using SPSS 23. The patients receiving Dex showed marked decrease in serum levels of cortisol, TNF- α and interleukins-6, from 139.73 to10.18, 99.51 to 0.96 and 85.09 to 0.96 respectively. Comparison between C and D groups revealed significant differences (p≤0.05) in these serum biomarkers. In the present study, intravenous Dex suppressed the intraoperative rise in levels of cytokine secretion and enhanced smooth recovery with no incidence of nausea and vomiting. These effects could be attributed to the anti-inflammatory effects of dexmedetomidine.

Regional use of extracellular microvesicles of mesenchymal stromal cells in acute necrotizing pancreatitis in an experiment

Background. The significance of the problem of treatment of acute pancreatitis is due to an increase in the incidence with an increase in the number of necrotizing forms, accompanied by a high incidence of severe complications and high mortality.Objective. To identify the impact of regionally used extracellular microvesicles of mesenchymal stromal cells on the endogenous intoxication markers in acute necrotizing pancreatitis in the experiment.Material and methods. Acute pancreatitis was induced by the introduction of a 0.3 ml of 5% solution of non-ionic polyethylene glycol octylphenol ether detergent into the caudal part of the rat pancreas. The study was conducted on 42 adult Wistar rats, which were randomly divided into 4 groups. Group I (n=6) included intact animals, Group II (control group) (n=12) included rats with pancreatitis without treatment, Group III (n=12) consisted of rats with pancreatitis treated with analgesia + infusions of 0.9% sodium chloride solution (saline), Group IV (n=12) included rats with pancreatitis treated with analgesia+ saline infusions + regional application of extracellular microvesicles of mesenchymal stromal cells. Cells were obtained from the bone marrow of healthy animals. Microvesicles were obtained by differential centrifugation under sterile conditions. Microvesicles were administered one day after the pancreatitis induction through the catheter installed into the pathologically altered part of the pancreas. The dose of microvesicles was calculated as equivalent to (derived from) 1 million mesenchymal stromal cells. The hematological parameters, markers of the systemic manifestation of the pathological process (alpha-amylase, aspartate aminotransferase, alanine aminotransferase), the endogenous intoxication markers (lipid peroxidation activity, nitric oxide level), the systemic inflammatory response markers (tumor necrosis factor-alpha, interleukin-6) were studied on the 3rd and 7th day from the start of disease modeling.Results. Regional use of extracellular microvesicles of mesenchymal stromal cells in the treatment of acute experimental necrotizing pancreatitis at an early stage helped to normalize the level of blood platelets, reduce enzymeemia, elements of endogenous intoxication (interleukin-6, tumor necrosis factor-alpha), and the nitric oxide level.Conclusion. The early application of extracellular microvesicles of mesenchymal stromal cells in the treatment of acute necrotizing pancreatitis in an experiment has a positive effect on parameters, which are key links of pathogenesis and leading markers of this disease severity.

6-PPD quinone at environmentally relevant concentrations induced damage on longevity in C. elegans: Mechanistic insight from inhibition in mitochondrial UPR response

6-PPD quinone (6-PPDQ) exists widely in water environment media, causing acute lethality to some aquatic species. Long-term exposure to 6-PPDQ reduced the lifespan of Caenorhabditis elegans. However, the molecular basis for mitochondrial control of 6-PPDQ toxicity remains largely unclear. Using HSP-6 as marker of mitochondrial unfolded protein response (mt UPR), we observed activation of mt UPR by 0.1 and 1 μg/L 6-PPDQ and inhibition in mt UPR by 10 μg/L 6-PPDQ. Additionally, increased atfs-1, ubl-5, and dve-1 expressions were caused by 0.1 and 1 μg/L 6-PPDQ and decreased expressions of these genes were induced by 10 μg/L 6-PPDQ. Neuronal and intestinal RNA interference (RNAi) of hsp-6 caused susceptibility to 6-PPDQ toxicity on longevity, and atfs-1, ubl-5, and dve-1 acted in neurons and intestine to modulate mt UPR and 6-PPDQ toxicity on longevity. Meanwhile, 6-PPDQ (1 and 10 μg/L) increased expressions of histone methyltransferase genes met-2 and set-6, and decreased expressions of histone demethylase genes jmjd-1.2 and jmjd-3.1. Neuronal RNAi of set-6 and intestinal RNAi of met-2 accelerated hsp-6, atfs-1, ubl-5, and dve-1 expressions and extended lifespan of 6-PPDQ exposed nematodes. In contrast, neuronal RNAi of jmjd-1.2 and jmjd-3.1 and intestinal RNAi of jmjd-1.2 suppressed these 4 gene expressions and reduced lifespan of 6-PPDQ exposed nematodes o. In nematodes, RNAi of hsp-6 could also enhance mitochondrial dysfunction and mitochondrial reactive oxygen species (ROS) induced by 6-PPDQ. Therefore, 6-PPDQ caused damage on longevity was associated with suppression in mt UPR, which was under regulation of certain histone methylation related signals.

Overexpression of StERECTA enhances drought tolerance in Arabidopsis thaliana

Drought is a major abiotic stresses that severely hinder plant growth and agricultural productivity. The receptor-like kinase gene, ERECTA, has been proved to play important role in promoting the response to abiotic stress in crops. However, the specific molecular mechanisms underlying the drought resistance mediated by ERECTA in potato (Solanum tuberosum L.) are not well understood. In this study, sequence analysis confirmed that the StERECTA gene contains eight leucine-rich repeat (LRR) domains and an S_TKc domain, and these domains were highly conserved in Solanaceae family. Under drought stress, Arabidopsis thaliana strains overexpressing StERECTA showed increased biomass, proline (PRO) content, and antioxidant enzyme activities compared to the wild-type strains while the mutant ERECTA strain (er105) exhibited opposite phenotype. Additionally, StERECTA overexpression upregulated the expression of drought response marker genes (LEA3, DREB2A and P5CS1), improved levels of ABA and auxin, reduced stomatal density and relative expression level of stomatal development related genes (SPCH, FAMA and MUTE). Furthermore, Co-immunoprecipitation (Co-IP) assays demonstrated that StERECTA physically interacted with the YODA protein. In conclusion, our study provides new insights into the role and regulatory mechanism of StERECTA in response to drought stress. These findings may serve as a basis for genetic improvement of potato to enhance their tolerance to abiotic stress.

Multi-Omics Exploration of ABA Involvement in Identifying Unique Molecular Markers for Single and Combined Stresses in tomato plants.

Over the past decade, our research group has found that plant responses to combined abiotic stresses are unique and cannot be inferred from studying plants exposed to individual stresses. Understanding how adaptative plant mechanisms integrate from stress perception to biochemical and physiological adjustments is a major challenge in abiotic stress signaling studies. Considering abscisic acid (ABA) as a key regulator in plant abiotic stress responses, in our study, ABA-deficient plants (flc) exposed to single or combined salinity and heat stresses were evaluated and different -omics analyses were conducted. Significant changes in biomass, photosynthesis, ions, transcripts, and metabolites occurred in mutant plants under single or combined stresses. Exogenous ABA application in flc mutants did not fully recover plant phenotypes or metabolic levels but induced cellular reprogramming with changes in specific markers. Multi-omics analysis aimed to identify ABA-dependent, ABA-independent, or stress-dependent markers in plant responses to single or combined stresses. We demonstrated that studying different -omics as a whole led to the identification of specific markers for each stress condition that were not detectable when each -omic was studied individually. This resource article provides an important and novel reference for scientists working in the field of plant abiotic stress. Future exploration of the transcriptomic, ionomic and metabolomic data presented in this study could lead to the identification of new pathways and genes associated with ABA signaling processes. These findings may be utilized to enhance crop resilience to heat waves, salinity, and their combination, contributing to addressing food security challenges in a climate change scenario.

The interaction of ambient ozone and personal temperature variability on blood markers of inflammation, oxidative stress, coagulation, endothelial function, and stress hormones

The interaction between ozone and temperature on cardiovascular biomarkers has not been thoroughly examined. A panel study was conducted among 40 college students with four equal interval follow-ups in Hefei, Anhui Province, China between August and October 2021. Real-time concentrations of ozone were collected from a nearby monitoring device. Temperature variability parameters included diurnal temperature range (DTR), the standard-deviation of temperature (SDT), and temperature variability (TV). A set of cardiovascular biomarkers were measured, including markers of inflammation (Granulocyte-macrophage colony-stimulating factor, GM-CSF and serum amyloid A, SAA), coagulation (D-dimer and ADAMTS13), oxidative stress (Myeloperoxidase, MPO and Growth differentiation factor-15, GDF-15), endothelial function (vascular endothelial growth factor A, VEGFA), and stress hormone (5-hydroxytryptamine, 5-HT). Linear mixed-effect models were conducted to analyze the associations between ozone, temperature variability, and all blood markers. The results showed significant associations among ozone, DTR, SDT, TV, and blood markers, suggesting harmful effects on markers. For instance, a 10-μg/m3 increase in ozone at lag 2d was associated with higher levels of SAA by 19.65% (95%CI: 13.70, 25.60), VEGFA by 10.90% (95%CI: 4.57, 17.22), GDF-15 by 5.33% (95%CI: 0.59, 10.06), and GM-CSF by 2.52% (95%CI: 1.70, 3.34), but 13.09% lower D-dimer (95%CI: 6.99, 19.19). We also found statistically significant interaction between ozone and TV exposures for GM-CSF and SAA. This study shows that ambient ozone and personal TV exposures may independently have acute effects on markers of inflammation, oxidative stress, coagulation, endothelial function, and neuroendocrine stress response. Simultaneous exposure to these factors may also lead to interactive effects on inflammation markers. These findings offer valuable insights for developing comprehensive strategies in cardiovascular disease control and prevention.

Detection of the BRAFV600E Mutation in Circulating Free Nucleic Acids as a Biomarker of Thyroid Cancer: A Review.

Background: Liquid biopsy is a method that could potentially improve the management of thyroid cancer (TC) by enabling the detection of circulating tumor DNA and RNA (ctDNA, ctRNA). The BRAFV600E mutation appears to be the most representative example of a biomarker in liquid biopsy, as it is the most specific mutation for TC and a target for molecular therapeutics. The aim of this review is to summarize the available data on the detection of the BRAFV600E mutation in liquid biopsy in patients with TC. Methods: A comprehensive analysis of the available literature on the detection of the BRAFV600E mutation in liquid biopsy in TC was performed. Thirty-three papers meeting the inclusion criteria were selected after full-text evaluation. Results: Eleven papers discussed correlations between BRAF mutation and clinicopathological characteristics. Nine studies tested the utility of BRAFV600E detection in the assessment of residual or recurrent disease. Seven studies investigated BRAF-mutated circulating tumor nucleic acids (ctNA) as a marker of response to targeted therapy. In seven studies the method did not detect the BRAFV600E mutation. Conclusions: This review shows the potential of BRAFV600E-mutated ctNA detection in monitoring disease progression, particularly in advanced TC. The diagnostic value of BRAFV600E-mutated ctNA detection appears to be limited to advanced TC. The choice of the molecular method (quantitative PCR [qPCR], droplet digital polymerase chain reaction [ddPCR], and next-generation sequencing [NGS]) should be made based on the turnaround time, sensitivity of the test, and the clinical indications. Despite the promising outcomes of some studies, there is a need to verify these results on larger cohorts and to unify the molecular methods.

The dual nature of DNA damage response in obesity and bariatric surgery-induced weight loss

This novel study applies targeted functional proteomics to examine tissues and cells obtained from a cohort of individuals with severe obesity who underwent bariatric surgery (BS), using a Reverse-Phase Protein Array (RPPA). In obese individuals, visceral adipose tissue (VAT), but not subcutaneous adipose tissue (SAT), shows activation of DNA damage response (DDR) markers including ATM, ATR, histone H2AX, KAP1, Chk1, and Chk2, alongside senescence markers p16 and p21. Additionally, stress-responsive metabolic markers, such as survivin, mTOR, and PFKFB3, are specifically elevated in VAT, suggesting both cellular stress and metabolic dysregulation. Conversely, peripheral blood mononuclear cells (PBMCs), while exhibiting elevated mTOR and JNK levels, did not present significant changes in DDR or senescence markers. Following BS, unexpected increases in phosphorylated ATM, ATR, and KAP1 levels, but not in Chk1 and Chk2 nor in senescence markers, were observed. This was accompanied by heightened levels of survivin and mTOR, along with improvement in markers of mitochondrial quality and health. This suggests that, following BS, pro-survival pathways involved in cellular adaptation to various stressors and metabolic alterations are activated in circulating PBMCs. Moreover, our findings demonstrate that the DDR has a dual nature. In the case of VAT from individuals with obesity, chronic DDR proves to be harmful, as it is associated with senescence and chronic inflammation. Conversely, after BS, the activation of DDR proteins in PBMCs is associated with a beneficial survival response. This response is characterized by metabolic redesign and improved mitochondrial biogenesis and functionality. This study reveals physiological changes associated with obesity and BS that may aid theragnostic approaches.

Neuroimaging markers of aberrant brain activity and treatment response in schizophrenia patients based on brain complexity

The complexity of brain activity reflects its ability to process information, adapt to environmental changes, and transition between states. However, it remains unclear how schizophrenia (SZ) affects brain activity complexity, particularly its dynamic changes. This study aimed to investigate the abnormal patterns of brain activity complexity in SZ, their relationship with cognitive deficits, and the impact of antipsychotic medication. Forty-four drug-naive first-episode (DNFE) SZ patients and thirty demographically matched healthy controls (HC) were included. Functional MRI-based sliding window analysis was utilized for the first time to calculate weighted permutation entropy to characterize complex patterns of brain activity in SZ patients before and after 12 weeks of risperidone treatment. Results revealed reduced complexity in the caudate, putamen, and pallidum at baseline in SZ patients compared to HC, with reduced complexity in the left caudate positively correlated with Continuous Performance Test (CPT) and Category Fluency Test scores. After treatment, the complexity of the left caudate increased. Regions with abnormal complexity showed decreased functional connectivity, with complexity positively correlated with connectivity strength. We observed that the dynamic complexity of the brain exhibited the characteristic of spontaneous, recurring “complexity drop”, potentially reflecting transient state transitions in the resting brain. Compared to HC, patients exhibited reduced scope, intensity, and duration of complexity drop, all of which improved after treatment. Reduced duration was negatively correlated with CPT scores and positively with clinical symptoms. The results suggest that abnormalities in brain activity complexity and its dynamic changes may underlie cognitive deficits and clinical symptoms in SZ patients. Antipsychotic treatment partially restores these abnormalities, highlighting their potential as indicators of treatment efficacy and biomarkers for personalized therapy.

Correlation between neutrophil to lymphocyte ratio and C-reactive protein in diverse disease states in hospitalized patients.

This study aims to find if any significant correlation exists between C-reactive protein and Neutrophil to Lymphocyte Ratio as an indirect measure of inflammation. We selected 983 patients with any inflammatory condition who presented to a tertiary care hospital and were admitted in medical wards or Intensive Care Units (ICUs) of KRL Hospital Islamabad from December 2021 to December 2022. The study was a cross sectional study and convenience sampling was done. The patients were categorized into five groups depending upon their pathophysiology. Kolmogorov Smirnov test was used to assess the normality of the data, and Spearman's coefficient was used to calculate the correlation between NLR and CRP. A total of 983 patients were included. Mean CRP and NLR levels were 89.9±3.2 and 7.06±0.24, respectively. There was a significant positive correlation between CRP-NLR in the infectious, non-infectious non-inflammatory, and malignancy groups (0.420, 0.381, 0.642, p <0.01), and inflammatory group (0.322, p <0.05), and no correlation with chronic diseases. A significant correlation was shown to exist between CRP and NLR in patients with malignancies, non-infective non-inflammatory, inflammatory, and infective conditions and can therefore be used interchangeably to detect the presence of inflammation. Further exploration of these associations may contribute to a more nuanced understanding of the intricate relationships between different markers of inflammation and response to treatment.

Pan-immune-inflammation value as a prognostic biomarker for colon cancer and its variation by primary tumor location.

A growing body of research indicates significant differences between left-sided colon cancers (LCC) and right-sided colon cancers (RCC). Pan-immune-inflammation value (PIV) is a systemic immune response marker that can predict the prognosis of patients with colon cancer. However, the specific distinction between PIV of LCC and RCC remains unclear. To investigate the prognostic and clinical significance of PIV in LCC and RCC patients. This multicenter retrospective cohort study included 1510 patients with colon cancer, comprising 801 with LCC and 709 with RCC. We used generalized lifting regression analysis to evaluate the relative impact of PIV on disease-free survival (DFS) in these patients. Kaplan-Meier analysis, as well as univariate and multivariate analyses, were used to examine the risk factors for DFS. The correlation between PIV and the clinical characteristics was statistically analyzed in these patients. A total of 1510 patients {872 female patients (58%); median age 63 years [interquartile ranges (IQR): 54-71]; patients with LCC 801 (53%); median follow-up 44.17 months (IQR 29.67-62.32)} were identified. PIV was significantly higher in patients with RCC [median (IQR): 214.34 (121.78-386.72) vs 175.87 (111.92-286.84), P < 0.001]. After propensity score matching, no difference in PIV was observed between patients with LCC and RCC [median (IQR): 182.42 (111.88-297.65) vs 189.45 (109.44-316.02); P = 0.987]. PIV thresholds for DFS were 227.84 in LCC and 145.99 in RCC. High PIV (> 227.84) was associated with worse DFS in LCC [PIV-high: Adjusted hazard ratio (aHR) = 2.39; 95% confidence interval: 1.70-3.38; P < 0.001] but not in RCC (PIV-high: aHR = 0.72; 95% confidence interval: 0.48-1.08; P = 0.114). These findings suggest that PIV may predict recurrence in patients with LCC but not RCC, underscoring the importance of tumor location when using PIV as a colon cancer biomarker.

Cellular responses following ex vivo lung exposure to the nerve agent VX – Potential for additional treatment targets?

Following inhalation exposure to organophosphorus nerve agents, symptoms rapidly develop and severe respiratory symptoms, such as bronchorrhea and bronchoconstriction are the leading causes of lethality. Nerve agent-induced lung injury is little investigated and the standard treatment for symptomatic relief targets the enzyme acetylcholinesterase and muscarinic acetylcholine and GABAergic receptors. In the present study, cellular responses in lung tissue during the acute (40 min) and extended phase (24 h) following severe exposure to the nerve agent VX have been investigated using an ex vivo rat precision-cut lung slice model including electrostimulation to induce a cholinergic response. Changes in protein amount, cell viability, together with, inflammatory and oxidative stress markers have been determined in both the lung tissue and incubation medium.During the acute phase, VX caused significantly increased airway contraction and decreased airway relaxation. Five micromolar of VX did not affect the sample protein levels and cell viability in lung tissue. Among seven markers of cellular responses investigated in the lung tissue, increased levels of heme oxygenase-1 and matrix metalloproteinase-9 together with decreased levels of glutathione in the incubation medium were observed in the acute phase following VX-exposure compared to electrostimulation only. No difference in cellular response was observed following VX-exposure for 24 h compared to the air control. In comparison, LPS-exposure resulted in time-dependent changes in all markers of inflammation and oxidative response.In conclusion, the present study demonstrated VX-specific patterns of oxidative responses in the lung, as well as, signs of inflammatory response and remodelling of extracellular matrix. These potential mechanisms of tissue injury should be further investigated for their potential as additional therapeutic targets during the acute phase of intoxication.

Bladder sparing options for muscle-invasive bladder cancer.

This review critically evaluates the current state of bladder-sparing options in muscle-invasive bladder cancer (MIBC) and provides an overview of future directions in the field. Bladder-sparing treatments have emerged as viable alternatives to radical cystectomy (RC) for selected patients with MIBC, especially in those who are unfit for RC or elect bladder preservation. Numerous studies have assessed the efficacy of trimodal therapy (TMT), with outcomes comparable to RC in a subgroup of well selected patients. Combining immunotherapy with conventional treatments in bladder-sparing approaches can yield promising outcomes. Current research is making significant progress in optimizing treatment protocols by exploring new combinations of systemic therapy agents, innovative drug delivery methods, and biomarker-based approaches. Furthermore, clinical markers of response are being tested to ensure adequate response assessment. Bladder preservation promise to offer a viable alternative to RC for selected patients with MIBC with the potential to improve patient quality of life. Careful patient selection and ongoing research are essential to optimize patient selection, response assessment, and salvage strategies. As evidence continues to evolve, the role of bladder preservation in MIBC is likely to expand, providing patients with more treatment options tailored to their needs and preferences.

Analysis of Inflammatory Markers in Response to Induction of Reprometabolic Syndrome by a Eucaloric High Fat Diet in Normal Weight Women.

Obesity is associated with chronic low-level inflammation and is known to contribute to metabolic dysfunction and hypogonadotropic hypogonadism, which we have previously termed the 'Reprometabolic Syndrome.' To investigate potential factors involved in obesity-related reproductive endocrine dysfunction, we conducted a secondary analysis of inflammatory markers in a sample of normal weight women exposed to a one-month eucaloric high-fat diet (HFD), which, as reported earlier, induced the relative hypogonadotropic hypogonadism characteristic of Reprometabolic Syndrome. Eighteen healthy women with a BMI between 18.0-24.9kg/m2 and regular menstrual cycles participated in the study. Frequent blood sampling was performed during the early follicular phase before and after the one-month eucaloric HFD intervention (48% of calories from fat). Serum samples pooled from each participant were analyzed using immunoassay to measure levels of 30 cytokines, interleukins, and chemokines. Differences between pre- and post-HFD intervention measures were examined by one-sample t-tests. Exposure to the eucaloric HFD did not result in changes in body weight. HFD-induction of Reprometabolic Syndrome in normal weight women was associated with a significant elevation only in the anti- inflammatory cytokine IL-10 (p = 0.04). Eotaxin, IL-6 and MIP-1β also increased in response to the HFD, but not statistically significantly (p = 0.07). Results suggest that the increase in multiple inflammatory markers, typically associated with obesity, are not primary mediators of the relative hypogonadotropic hypogonadism of Reprometabolic Syndrome. Clinical Trials Registration Number: NCT02653092; Date of Registration: January 6, 2016.

Role of Circular RNAs in Prostate Cancer.

This study aims to summarize the current literature to demonstrate the importance of circular RNAs (circRNAs) in multiple aspects of prostate cancer (PCa) occurrence, progression, and treatment resistance and explore the potential role in therapeutic strategies aimed at targeting this molecule in PCa. The relevant literature from PubMed and Medline databases is reviewed in this article. Non-coding RNA has been proven to play a vital role in regulating tumor progression. Among them, circular RNA plays a more unique role due to its nonlinear structure. Lots of circRNAs were found to be differentially expressed in PCa and regulate cell signaling pathways by regulating particular gene expressions. Recent studies have demonstrated that circRNAs are associated with the chemoresistance of urinary tumors, suggesting that circRNAs might be a novel therapeutic target and a marker for therapeutic response and prognosis assessment. The potential crosstalk of circRNAs modifications in PCa development, therapy, and regulation of tumor metabolism is portrayed in this review. However, more preclinical and clinical trials of this targeted strategy are necessary for the treatment of urinary tumors.

Serum albumin nadir as marker of inflammatory response in abdominal trauma

Serum albumin nadir as marker of inflammatory response in abdominal trauma

144P Analysis of a novel predictive marker of immune checkpoint response in head and neck cancer, calculated from histopathological slides through inferred transcriptomics

144P Analysis of a novel predictive marker of immune checkpoint response in head and neck cancer, calculated from histopathological slides through inferred transcriptomics

A loss of tuning of both pro-coagulant and inflammatory responses in monocytes in patients with preeclampsia

An imbalance between pro- and anti-angiogenesis is one of the leading causes of preeclampsia (PE). Monocytes, known as regulators of angiogenesis during immune responses, cooperate with platelets, but the specifics of these responses during pregnancy remain unclear. In this study, we investigated the relationship between pro-coagulant responses on monocytes [platelet activation marker CD61 as a monocyte-platelet aggregate (MPA), tissue factor (CD142), etc.], inflammatory responses [soluble CD40 ligand (sCD40L), soluble suppression of tumorigenesis-2 (sST2), etc.], and the balance of angiogenesis [soluble Fms-related receptor tyrosine kinase 1/placental growth factor (sFlt-1/PLGF) ratio]. In PE, markers of pro-coagulant and inflammatory responses were higher than those in normal pregnancy (NP). Interestingly, in NP, these markers harmonized with the sFlt-1/PLGF ratio, but not in PE. Furthermore, ex vivo examinations showed that upregulation of CD142 induced by additional platelet activation with adenosine diphosphate was diminished in PE. Conversely, low-dose aspirin, which is used as a preventive treatment for PE, could inhibit the increase of CD61 and sST2 under inflammatory stimuli and platelet activation in NP but not in PE. These results indicate that monocytes in PE upregulate basal activity and lose responsiveness to stimulation. The elevation of pro-coagulant and inflammatory responses may be mitigated by prophylaxis with low-dose aspirin. Therefore, the findings suggesting a loss of tuning of both pro-coagulant and inflammatory responses on monocytes help in understanding the pathology of PE. The harmonization between pro-coagulant responses, inflammatory responses, and angiogenesis may serve as useful indicators for the prediction and preventive treatment of PE.

Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the desmoid tumors

BackgroundDual inhibition using anti-programmed death-1 (PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors has proven effective in many cancers. However, its efficacy in rare solid cancers remains unclear. Desmoid tumors...

Circulating monocytes as a marker of response to adalimumab in patients with hidradenitis suppurativa: A single institution, real-world cohort study

Circulating monocytes as a marker of response to adalimumab in patients with hidradenitis suppurativa: A single institution, real-world cohort study