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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 -
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 -
Biochimica Et Biophysica Acta.... Dec 2023ATP synthase inhibitory factor 1 (ATPIF1) is a mitochondrial protein that regulates the activity of FF-ATP synthase. Mice lacking ATPIF1 throughout their bodies (Atpif1)...
ATP synthase inhibitory factor 1 (ATPIF1) is a mitochondrial protein that regulates the activity of FF-ATP synthase. Mice lacking ATPIF1 throughout their bodies (Atpif1) exhibit a reduction in the number of neutrophils. However, it remains unclear whether the inactivation of ATPIF1 impairs the antibacterial function of mice, this study aimed to evaluate it using a mouse peritonitis model. Mice were intraperitoneally injected with E. coli to induce peritonitis, and after 24 h, the colonies of E. coli were counted in agarose plates containing mice peritoneal lavage fluids (PLF) or extract from the liver. Neutrophils were analyzed for glucose metabolism in glycolysis following LPS stimulation. Reactive oxygen species (ROS) and lactic acid (LA) levels in neutrophils were measured using flow cytometry and Seahorse analysis, respectively. N-Acetylcysteine (NAC) and 2-Deoxy-d-glucose (2-DG) were employed to assess the role of ROS and LA in neutrophil bactericidal activity. RNA-seq analysis was conducted in neutrophils to investigate potential mechanisms. In ATPIF1 neutrophils, bactericidal activity was enhanced, accompanied by increased levels of ROS and LA compared to wildtype neutrophils. The augmented bactericidal activity of ATPIF1 neutrophils was reversed by pretreatment with NAC or 2-DG. RNA-seq analysis revealed downregulation of multiple genes involved in glutathione metabolism, pyruvate oxidation, and heme synthesis, along with increased expression of inflammatory and apoptotic genes. This study suggests that the inactivation of the Atpif1 gene enhances glucose metabolism in neutrophils, resulting in increased bactericidal activity mediated by elevated levels of ROS and LA. Inhibiting ATPIF1 may be a potential approach to enhance antibacterial immunity.
Topics: Adenosine Triphosphate; Escherichia coli; Gene Silencing; Glycolysis; Neutrophils; Nitric Oxide Synthase; Peritonitis; Reactive Oxygen Species; Animals; Mice; ATPase Inhibitory Protein
PubMed: 37558010
DOI: 10.1016/j.bbadis.2023.166820 -
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 -
Scientific Reports Feb 2024Extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) are pivotal bioactive structures involved in various processes including inflammation. Herein we...
Extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) are pivotal bioactive structures involved in various processes including inflammation. Herein we report the interactions between EVs and NETs during murine endotoxemia studied in situ directly in the vasculature (cremaster muscle, liver sinusoids) using intravital microscopy (IVM). We captured NETs and EV release in real time by both non- and polarized neutrophils in liver but not in cremaster vasculature. When comparing numbers of circulating EVs of various origin (nanoparticle tracking analysis-NTA, flow cytometry) with those interacting with endothelium and NETs (IVM) we observed that whereas platelet and monocyte/macrophage-derived EVs dominate in blood and peritoneal lavage, respectively, mostly neutrophil-derived EVs interact with the vascular lining, NETs and leukocytes. Despite the interaction, NETs do not affect EV formation as NET release inhibition did not alter EV release. However, EVs inhibit NETs formation and in particular, erythrocyte-derived EVs downregulate NET release and this effect is mediated via Siglec-E-dependent interactions with neutrophils. Overall, we report that EVs are present in NETs in vivo and they do modulate their release but the process in not bidirectional. Moreover, EVs isolated from body fluids might not reflect their importance in direct endothelial- and leukocyte-related interactions.
Topics: Mice; Animals; Extracellular Traps; Neutrophils; Inflammation; Leukocytes; Extracellular Vesicles
PubMed: 38409254
DOI: 10.1038/s41598-024-55081-x -
Revista Da Associacao Medica Brasileira... 2023In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian...
OBJECTIVE
In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian hyperstimulation syndrome in a rat model.
METHODS
A total of 36 female Wistar rats were randomly allocated to one of the five groups, including disease-free and ovarian hyperstimulation syndrome controls: Group no OHSS (control, n=6) received saline only intraperitoneally (i.p.); group just OHSS (ovarian hyperstimulation syndrome only, n=6) received 10 IU pregnant mare serum gonadotropin and 30 IU human chorionic gonadotropin subcutaneously to produce ovarian hyperstimulation syndrome; group cabergoline+OHSS (cabergoline+ovarian hyperstimulation syndrome, n=8) received 100 μg/kg oral cabergoline; group aflibercept (12.5 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 12.5 mg/kg i.p. aflibercept; and group aflibercept (25 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 25 mg/kg i.p. aflibercept. The groups were compared for ovarian weight, immunohistochemical vascular endothelial growth factor expression, spectrophotometric vascular permeability evaluated with methylene blue solution in peritoneal lavage, and body weight growth.
RESULTS
Vascular endothelial growth factor immunoexpression was substantially greater in the just OHSS group (22.00±10.20%) than in the aflibercept (12.5 mg/kg)+OHSS (7.87±6.13%) and aflibercept (25 mg/kg)+OHSS (5.63±4.53%) groups (p=0.008 and p=0.005, respectively). Post-hoc tests indicated that cabergoline, 12.5 mg/kg aflibercept, and 25 mg/kg aflibercept decreased vascular permeability compared to the untreated ovarian hyperstimulation syndrome group (p=0.003, p=0.003, and p=0.001, respectively). JOH group had the heaviest ovaries, whereas aflibercept (25 mg/kg)+OHSS group had the lightest. In terms of body weight gain, cabergoline+OHSS group was substantially greater than the aflibercept (12.5 mg/kg)+OHSS and aflibercept (25 mg/kg)+OHSS groups (p=0.006 and p=0.007, respectively).
CONCLUSION
Aflibercept, an antiangiogenic medication, decreased ovarian hyperstimulation syndrome by lowering the vascular permeability and vascular endothelial growth factor expression.
Topics: Humans; Pregnancy; Horses; Rats; Female; Animals; Ovarian Hyperstimulation Syndrome; Cabergoline; Rats, Wistar; Vascular Endothelial Growth Factor A; Body Weight
PubMed: 37909622
DOI: 10.1590/1806-9282.20230789 -
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 -
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 -
The British Journal of Surgery May 2024Laparoscopic lavage (LPL) has been suggested for treatment of non-feculent perforated diverticulitis. In this observational study, the surgical treatment of diverticular... (Observational Study)
Observational Study
BACKGROUND
Laparoscopic lavage (LPL) has been suggested for treatment of non-feculent perforated diverticulitis. In this observational study, the surgical treatment of diverticular disease in Sweden outside prospective trials was investigated.
METHODS
This population-based study used the National Patient Register to identify all patients in Sweden with emergency admissions for diverticular disease, as defined by ICD codes from July 2014 to December 2020. Demographics, surgical procedures and outcomes were assessed. In addition, register data since 1997 were retrieved to assess co-morbidities, previous abdominal surgeries, and previous admissions for diverticular disease.
RESULTS
Among 47 294 patients with emergency hospital admission, 2035 underwent LPL (427 patients) or sigmoid resection (SR, 1608 patients) for diverticular disease. The mean follow-up was 30.8 months. Patients selected for LPL were younger, healthier and with less previous abdominal surgery for diverticular disease than those in the SR group (P < 0.01). LPL was associated with shorter postoperative hospital stay (mean 9.4 versus 14.9 days, P < 0.001) and lower 30-day mortality (3.5% versus 8.7%, P < 0.001). Diverticular disease-associated subsequent surgery was more common in the SR group than the LPL group except during the first year (P < 0.001). LPL had a lower mortality rate during the study period (stratified HR 0.70, 95% c.i. 0.53-0.92, P = 0.023).
CONCLUSION
Laparoscopic lavage constitutes a safe alternative to sigmoid resection for selected patients judged clinically to require surgery.
Topics: Humans; Male; Female; Laparoscopy; Aged; Sweden; Peritoneal Lavage; Middle Aged; Registries; Intestinal Perforation; Diverticulitis, Colonic; Length of Stay; Treatment Outcome; Aged, 80 and over
PubMed: 38713610
DOI: 10.1093/bjs/znae109