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Cells Feb 2021The signal transducer and activator of transcription 6 (STAT6) transcription factor promotes activation of the peroxisome proliferator-activated receptor gamma (PPARγ)...
The signal transducer and activator of transcription 6 (STAT6) transcription factor promotes activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway in macrophages. Little is known about the effect of proximal signal transduction leading to PPARγ activation for the resolution of acute inflammation. Here, we studied the role of STAT6 signaling in PPARγ activation and the resolution of acute sterile inflammation in a murine model of zymosan-induced peritonitis. First, we showed that STAT6 is aberrantly activated in peritoneal macrophages after zymosan injection. Utilizing and wild-type (WT) mice, we found that STAT6 deficiency further enhanced zymosan-induced proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-6, and macrophage inflammatory protein-2 in peritoneal lavage fluid (PLF) and serum, neutrophil numbers and total protein amount in PLF, but reduced proresolving molecules, such as IL-10 and hepatocyte growth factor, in PLF. The peritoneal macrophages and spleens of mice exhibited lower mRNA and protein levels of PPARγ and its target molecules over the course of inflammation than those of WT mice. The deficiency of STAT6 was shown to impair efferocytosis by peritoneal macrophages. Taken together, these results suggest that enhanced STAT6 signaling results in PPARγ-mediated macrophage programming, contributing to increased efferocytosis and inflammation resolution.
Topics: Acute Disease; Animals; Inflammation; Mice; PPAR gamma; STAT6 Transcription Factor; Signal Transduction
PubMed: 33652833
DOI: 10.3390/cells10030501 -
Journal of Inflammation Research 2023Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or...
PURPOSE
Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30-50%. Therefore, novel strategies to treat sepsis are urgently needed.
METHODS
Andrographolide (AD), the main active ingredient of , reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Hence, this study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms.
RESULTS
Results showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity.
CONCLUSION
These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis.
PubMed: 37822531
DOI: 10.2147/JIR.S422342 -
BMJ Open Jul 2020Intra-abdominal infections (IAIs) are common surgical emergencies and cause a significant worldwide burden per year. Since the concept of intraoperative peritoneal...
INTRODUCTION
Intra-abdominal infections (IAIs) are common surgical emergencies and cause a significant worldwide burden per year. Since the concept of intraoperative peritoneal lavage (IOPL) was proposed in 1905, it has been widely used in the surgery practice. However, the effectiveness of IOPL in patients with IAIs has always been controversial. Our objective is to identify whether it is beneficial to flush the abdominal cavity with saline in IAIs surgery through a comprehensive systematic review and meta-analysis.
METHODS AND ANALYSIS
This protocol is reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Electronic databases (including the Cochrane library, MEDLINE, EMBASE, Web of Science, etc) and clinical trial registry platforms will be searched from inception to 8 September 2019. Randomised controlled trials, quasi-randomised clinical trials and cohort studies comparing IOPL and suction alone in IAIs will be included. The primary outcomes are mortality and abscess rate. Two independent reviewers will screen literature, collect data and assess risk of bias of included studies. Discussion or a third reviewer will be referred for any disagreements. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. We will perform meta-analysis using random-effects model. Subgroup analysis, sensitivity analysis and publication bias will be conducted if data are enough.
ETHICS AND DISSEMINATION
Ethical approval is not required for this systematic review and meta-analysis protocol. Results of this study will be published in a peer-reviewed journal, presented at relevant conferences and disseminated to local and international policy makers.
PROSPERO REGISTRATION NUMBER
CRD42019145109.
Topics: Humans; Intraabdominal Infections; Peritoneal Lavage; Publication Bias; Research Design; Meta-Analysis as Topic; Systematic Reviews as Topic
PubMed: 32690517
DOI: 10.1136/bmjopen-2019-036273 -
Pakistan Journal of Medical Sciences 2022To identify the percentage of ovarian cancers with positive peritoneal cytology and to correlate the positive cytology with the prognostic factors.
OBJECTIVES
To identify the percentage of ovarian cancers with positive peritoneal cytology and to correlate the positive cytology with the prognostic factors.
METHODS
This retrospective, cross-sectional study, evaluated the data of surgical specimens of malignant ovarian tumors, received in the Department of Pathology, Dow University of Health Sciences over a period of three years. The peritoneal cytology was correlated with these prognostic parameters: the size of the tumor, stage, capsular invasion, omental, and lymph node metastasis.
RESULTS
Eighty malignant ovarian tumors were diagnosed. Serous carcinoma was the most common ovarian tumor, diagnosed in 24(30.0%) cases, followed by endometrioid carcinoma in 17(21.25%) and Granulosa cell tumor in 11 (13.75%) cases. The mean age of the patients was 41.91 years (range 7-71 years). The mean size of the tumors was 10.03 cm (SD 5.62 cm). The ovarian capsular invasion was present in 27(33.75%) tumors. Peritoneal cytology was positive in 10/24 cases, with a detection rate of 41.66%. Omentum was involved in 12/34(35.29%) cases. Lymph node dissection was performed in three cases, two were reported as positive for metastasis. Peritoneal cytology significantly correlated with the tumor size (p=0.045), and with ovarian capsular invasion (p=0.054) and omental metastasis (p=0.052). Most of the tumors were staged as FIGO stage IA.
CONCLUSION
Peritoneal cytology correlates with the tumor size, stage, and omental metastasis of the malignant ovarian tumors. It should be routinely performed at the time of surgery for the optimal staging of the patients.
PubMed: 35035413
DOI: 10.12669/pjms.38.1.4393 -
Frontiers in Immunology 2024Various immune cell types play critical roles in sepsis with numerous distinct subsets exhibiting unique phenotypes even within the same cell population. Single-cell RNA...
INTRODUCTION
Various immune cell types play critical roles in sepsis with numerous distinct subsets exhibiting unique phenotypes even within the same cell population. Single-cell RNA sequencing (scRNA-seq) enables comprehensive transcriptome profiling and unbiased cell classification. In this study, we have unveiled the transcriptomic landscape of immune cells in sepsis through scRNA-seq analysis.
METHODS
We induced sepsis in mice by cecal ligation and puncture. 20 h after the surgery, the spleen and peritoneal lavage were collected. Single-cell suspensions were processed using a 10× Genomics pipeline and sequenced on an Illumina platform. Count matrices were generated using the Cell Ranger pipeline, which maps reads to the mouse reference transcriptome, GRCm38/mm10. Subsequent scRNA-seq analysis was performed using the R package Seurat.
RESULTS
After quality control, we subjected the entire data set to unsupervised classification. Four major clusters were identified as neutrophils, macrophages, B cells, and T cells according to their putative markers. Based on the differentially expressed genes, we identified activated pathways in sepsis for each cell type. In neutrophils, pathways related to inflammatory signaling, such as NF-κB and responses to pathogen-associated molecular patterns (PAMPs), cytokines, and hypoxia were activated. In macrophages, activated pathways were the ones related to cell aging, inflammatory signaling, and responses to PAMPs. In B cells, pathways related to endoplasmic reticulum stress were activated. In T cells, activated pathways were the ones related to inflammatory signaling, responses to PAMPs, and acute lung injury. Next, we further classified each cell type into subsets. Neutrophils consisted of four clusters. Some subsets were activated in inflammatory signaling or cell metabolism, whereas others possessed immunoregulatory or aging properties. Macrophages consisted of four clusters, namely, the ones with enhanced aging, lymphocyte activation, extracellular matrix organization, or cytokine activity. B cells consisted of four clusters, including the ones possessing the phenotype of cell maturation or aging. T cells consisted of six clusters, whose phenotypes include molecular translocation or cell activation.
CONCLUSIONS
Transcriptomic analysis by scRNA-seq has unveiled a comprehensive spectrum of immune cell responses and distinct subsets in the context of sepsis. These findings are poised to enhance our understanding of sepsis pathophysiology, offering avenues for targeting novel molecules, cells, and pathways to combat infectious diseases.
Topics: Mice; Animals; Pathogen-Associated Molecular Pattern Molecules; Gene Expression Profiling; Transcriptome; Cytokines; Sepsis
PubMed: 38343542
DOI: 10.3389/fimmu.2024.1347453 -
Chinese Journal of Cancer Research =... Feb 2024Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence...
OBJECTIVE
Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.
METHODS
In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.
RESULTS
Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. and were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0).
CONCLUSIONS
There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.
PubMed: 38455368
DOI: 10.21147/j.issn.1000-9604.2024.01.07 -
Cureus Aug 2023Peritonitis is inflammation of the peritoneum that can arise from a number of complications affecting the lining of the abdominal wall and organs. Acute abdomen and...
Peritonitis is inflammation of the peritoneum that can arise from a number of complications affecting the lining of the abdominal wall and organs. Acute abdomen and peritonitis is a rare complication in a previously healthy woman following a seemingly uncomplicated normal full-term vaginal delivery. We report such a case in a 20-year-old gravida 2 para 2 (G2P2) woman of Guatemalan descent, who presented nine days postpartum following an uncomplicated delivery, to the emergency room with acute abdomen and associated systemic inflammatory reaction. Interventional radiology paracentesis was performed, yielding a milky, purulent peritoneal fluid with no visible organisms and negative cultures. Antibiotics and paracentesis were insufficient in managing her condition, which continued to worsen over the course of several days. Given her continued deterioration despite clinical intervention, she underwent an exploratory laparotomy and peritoneal lavage along with continued broad-spectrum antibiotics. Cultures continued to be negative but operative findings included diffuse fibrinous peritonitis with no obvious abscess or perforated abdominal viscus. Following surgical laparotomy, she recovered fully without any complications. We review the available literature regarding peritonitis, discuss its management, and speculate as to its cause in this case.
PubMed: 37701003
DOI: 10.7759/cureus.43339 -
Cancer Cytopathology Jul 2021
Topics: Cytodiagnosis; Endometrial Neoplasms; Female; Humans; Pelvis; Peritoneal Lavage
PubMed: 33481350
DOI: 10.1002/cncy.22407 -
The American Surgeon Oct 2023Some reports suggest Diagnostic peritoneal aspiration (DPA) or lavage (DPL) may better select which hypotensive blunt trauma patients (BTPs) require operation, compared...
BACKGROUND
Some reports suggest Diagnostic peritoneal aspiration (DPA) or lavage (DPL) may better select which hypotensive blunt trauma patients (BTPs) require operation, compared to ultrasonography. However, whether both moderately hypotensive (systolic blood pressure [SBP] < 90 mmHg) and severely hypotensive (SBP < 70 mmHg) patients benefit from DPA/DPL is unclear. We hypothesized DPA/DPL used within the first hour increases risk of death for severely vs moderately hypotensive BTPs.
METHODS
The 2017-2019 Trauma Quality Improvement Program database was queried for BTPs ≥ 18 years old with hypotension upon arrival. We compared moderately and severely hypotensive groups. A multivariable logistic regression analysis was performed controlling for age, comorbidities, emergent operation, blood transfusions, and injury profile.
RESULTS
From 134 hypotensive patients undergoing DPA/DPL, 66 (49.3%) had severe hypotension. Patients in both groups underwent an emergent operation (43.9% vs 58.8%, = .09) in a similar amount of time (median, 42-min vs 54-min, = .11). Compared to the moderately hypotensive group, severely hypotensive patients had a higher rate and associated risk of death (84.8% vs 50.0%, < .001) (OR 5.40, CI 2.07-14.11, < .001). The strongest independent risk factor for death was age ≥ 65 (OR 24.81, CI 4.06-151.62, < .001).
DISCUSSION
Among all BTPs undergoing DPA/DPL within the first hour of arrival, an over 5-fold increased risk of death for patients with severe hypotension was demonstrated. As such, DPA/DPL within this group should be used with caution, particularly for older patients, as they may be better served by immediate surgeries. Future prospective research is needed to confirm these findings and elucidate the ideal DPA/DPL population in the modern era of ultrasonography.
Topics: Humans; Adolescent; Abdominal Injuries; Peritoneal Lavage; Peritoneum; Wounds, Nonpenetrating; Hypotension
PubMed: 37154296
DOI: 10.1177/00031348231175132 -
Updates in Surgery Aug 2023The aim of this study is to define the importance of peritoneal CEA (pCEA) as a prognostic factor of overall survival (OS) and disease-free survival (DFS) in gastric...
The aim of this study is to define the importance of peritoneal CEA (pCEA) as a prognostic factor of overall survival (OS) and disease-free survival (DFS) in gastric cancer (GC) patients surgically treated with a curative intent In our department. A total of 64 patients affected by gastric cancer with intraoperatively measurement of CEA on peritoneal lavage were enrolled in the study. Patients were divided into two groups: (A) the peritoneal lavage CEA ( -) with CEA < 0.5 ng/ml and (B) the peritoneal lavage CEA ( +) with CEA ≥ 0.5 ng/ml. Then we analyzed OS and DFS of the two groups correlating them to others clinico-pathological features. Furthermore, we investigated the correlation between pCEA and peritoneal cytology. We demonstrated a strong significant difference in OS and in DFS in CEA ( +) patients. We emphasized that pCEA had a strong survival impact, in both OS and DFS, in selected patients affected by diffuse histotype GC (p = 0.0048 and p = 0.0030 respectively), stage III (p = 0.015 and p = 0.021, respectively) and distal gastric cancer (p = 0.0036 and p = 0.0017, respectively). There is a strong need to recognize prognostic factors that can help clinicians to stratify patients at high risk to develop post-surgical recurrences and moreover to recognize who could benefit from an aggressive surgical treatment of cytoreductive surgery and intra-peritoneal chemotherapy.pCEA is a good predictor of survival in advanced gastric cancer and could discriminate which patients need a more accurate follow-up program and an intensive therapeutic strategy.
Topics: Humans; Carcinoembryonic Antigen; Prognosis; Stomach Neoplasms; Peritoneal Lavage; Peritoneum
PubMed: 37347355
DOI: 10.1007/s13304-023-01542-3