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International Journal of Molecular... Nov 2021Peritonitis caused by LPS is a severe clinical challenge, which causes organ damage and death. However, the mechanism of LPS-induced peritonitis has not been fully...
Peritonitis caused by LPS is a severe clinical challenge, which causes organ damage and death. However, the mechanism of LPS-induced peritonitis has not been fully revealed yet. Here, we investigated the transcriptome profile of the peritoneal tissue of LPS-induced peritonitis in mice. A model of LPS-induced peritonitis in mice was established (LPS 10 mg/kg, i.p.), and the influence of TAK 242 (TLR4 inhibitor) on the level of inflammatory cytokines in mouse peritoneal lavage fluid was investigated by using an ELISA test. Next, the peritoneal tissues of the three groups of mice (Control, LPS, and LPS+TAK 242) ( = 6) were isolated and subjected to RNA-seq, followed by a series of bioinformatics analyses, including differentially expressed genes (DEGs), enrichment pathway, protein-protein interaction, and transcription factor pathway. Then, qPCR verified-hub genes that may interact with TAK 242 were obtained. Subsequently, the three-dimensional structure of hub proteins was obtained by using homology modeling and molecular dynamics optimization (300 ns). Finally, the virtual docking between TAK 242 and hub proteins was analyzed. Our results showed that TAK 242 significantly inhibited the production of inflammatory cytokines in the peritoneal lavage fluid of mice with peritonitis, including IL-6, IFN-γ, IL-1β, NO, and TNF-α. Compared with the Control group, LPS treatment induced 4201 DEGs (2442 down-regulated DEGs and 1759 up-regulated DEGs). Compared with the LPS group, 30 DEGs were affected by TAK 242 (8 down-regulated DEGs and 22 up-regulated DEGs). A total of 10 TAK 242-triggered hub genes were obtained, and the possible docking modes between TAK 242 and hub proteins were acquired. Overall, our data demonstrated that a large number of DEGs were affected in LPS-triggered peritonitis mice. Moreover, the TLR4 inhibitor TAK 242 is capable of suppressing the inflammatory response of LPS-induced peritonitis. Our work provides clues for understanding the pathogenesis of LPS-induced peritonitis in mice.
Topics: Animals; Cytokines; Gene Expression Profiling; Gene Expression Regulation; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Peritoneal Lavage; Peritoneum; Peritonitis; Signal Transduction; Sulfonamides; Toll-Like Receptor 4; Transcriptome
PubMed: 34884814
DOI: 10.3390/ijms222313008 -
World Journal of Gastrointestinal... Mar 2023Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free... (Clinical Trial)
Clinical Trial
BACKGROUND
Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free cancer cells may still exist after resection. In addition, the surgery itself may lead to the dissemination of tumor cells. Therefore, it is necessary to remove residual tumor cells. Recently, some researchers found that extensive intraoperative peritoneal lavage (EIPL) plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients. However, few studies explored the safety and long-term outcome of EIPL after curative gastrectomy.
AIM
To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL.
METHODS
According to the inclusion and exclusion criteria, a total of 150 patients with advanced GC were enrolled in this study. The patients were randomly allocated to two groups. All patients received laparotomy. For the non-EIPL group, peritoneal lavage was washed using no more than 3 L of warm saline. In the EIPL group, patients received 10 L or more of saline (1 L at a time) before the closure of the abdomen. The surviving rate analysis was compared by the Kaplan-Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern.
RESULTS
The basic information in the EIPL group and the non-EIPL group had no significant difference. The median follow-up time was 30 mo (range: 0-45 mo). The 1- and 3-year overall survival (OS) rates were 71.0% and 26.5%, respectively. The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group ( < 0.05). For the OS of patients, the EIPL, Borrmann classification, tumor size, N stage, T stage and vascular invasion were significant indicators. Then multivariate analysis revealed that EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors. The prognosis of the EIPL group was better than the non-EIPL group ( < 0.001). The 3-year survival rate of the EIPL group (38.4%) was higher than the non-EIPL group (21.7%). For the recurrence-free survival (RFS) of patients, the risk factor of RFS included EIPL, N stage, vascular invasion, type of surgery, tumor location, Borrmann classification, and tumor size. EIPL and tumor size were independent risk factors. The RFS curve of the EIPL group was better than the non-EIPL group ( = 0.004), and the recurrence rate of the EIPL group (24.7%) was lower than the non-EIPL group (46.4%). The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group ( < 0.05).
CONCLUSION
EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. In addition, the overall survival curve and RFS curve were better in the EIPL group.
PubMed: 37032799
DOI: 10.4240/wjgs.v15.i3.430 -
Revista Do Colegio Brasileiro de... 2020to assess whether laparoscopy with peritoneal lavage is superior to computed tomography for staging gastric adenocarcinoma and whether it can modify the surgical... (Comparative Study)
Comparative Study
OBJECTIVE
to assess whether laparoscopy with peritoneal lavage is superior to computed tomography for staging gastric adenocarcinoma and whether it can modify the surgical approach.
METHODS
we conducted a retrospective study of 46 patients with gastric adenocarcinoma treated by the digestive surgery team of the Passo Fundo Clinics Hospital (RS), from January 2015 to December 2018, and submitted to laparoscopy with preoperative peritoneal lavage. All patients underwent preoperative clinical staging with computed tomography.
RESULTS
of the 46 patients analyzed, the majority had tumors located in the cardia (34.8%), poorly differentiated (69.6%), and subtype signet ring cells (65.2%). In 91.3%, the computed tomography scan did not identify peritoneal carcinomatosis or distant metastasis. Among these patients with negative computed tomography for distant disease, 21.8% had positive peritoneal lavage for neoplastic cells and had their therapeutic approaches modified.
CONCLUSION
laparoscopy and peritoneal lavage altered the surgical decision in 21.8% of patients, providing a more reliable preoperative staging in gastric adenocarcinoma.
Topics: Adenocarcinoma; Aged; Digestive System Surgical Procedures; Female; Gastrectomy; Humans; Laparoscopy; Male; Middle Aged; Neoplasm Staging; Peritoneal Lavage; Preoperative Care; Retrospective Studies; Stomach Neoplasms; Tomography, X-Ray Computed
PubMed: 32022110
DOI: 10.1590/0100-6991e-20192314 -
Journal of Gastric Cancer Jan 2024Liquid biopsy, a minimally invasive procedure that causes minimal pain and complication risks to patients, has been extensively studied for cancer diagnosis and... (Review)
Review
Liquid biopsy, a minimally invasive procedure that causes minimal pain and complication risks to patients, has been extensively studied for cancer diagnosis and treatment. Moreover, it facilitates comprehensive quantification and serial assessment of the whole-body tumor burden. Several biosources obtained through liquid biopsy have been studied as important biomarkers for establishing early diagnosis, monitoring minimal residual disease, and predicting the prognosis and response to treatment in patients with cancer. Although the clinical application of liquid biopsy in gastric cancer is not as robust as that in other cancers, biomarker studies using liquid biopsy are being actively conducted in patients with gastric cancer. Herein, we aimed to review the role of various biosources that can be obtained from patients with gastric cancer through liquid biopsies, such as blood, saliva, gastric juice, urine, stool, peritoneal lavage fluid, and ascites, by dividing them into cellular and acellular components. In addition, we reviewed previous studies on the diagnostic, prognostic, and predictive biomarkers for gastric cancer using liquid biopsy and discussed the limitations of liquid biopsy and the challenges to overcome these limitations in patients with gastric cancer.
PubMed: 38225764
DOI: 10.5230/jgc.2024.24.e5 -
Critical Care (London, England) Nov 2023Extracellular histones have been associated with severity and outcome in sepsis. The aim of the present study was to assess the effects of sodium-β-O-Methyl...
BACKGROUND
Extracellular histones have been associated with severity and outcome in sepsis. The aim of the present study was to assess the effects of sodium-β-O-Methyl cellobioside sulfate (mCBS), a histone-neutralizing polyanion, on the severity and outcome of sepsis in an experimental model.
METHODS
This randomized placebo-controlled experimental study was performed in 24 mechanically ventilated female sheep. Sepsis was induced by fecal peritonitis. Animals were randomized to three groups: control, early treatment, and late treatment (n = 8 each). mCBS was given as a bolus (1 mg/kg) followed by a continuous infusion (1 mg/kg/h) just after sepsis induction in the early treatment group, and 4 h later in the late treatment group. Fluid administration and antimicrobial therapy were initiated 4 h T4 after feces injection, peritoneal lavage performed, and a norepinephrine infusion titrated to maintain mean arterial pressure (MAP) between 65-75 mmHg. The experiment was blinded and lasted maximum 24 h.
RESULTS
During the first 4 h, MAP remained > 65 mmHg in the early treatment group but decreased significantly in the others (p < 0.01 for interaction, median value at T4: (79 [70-90] mmHg for early treatment, 57 [70-90] mmHg for late treatment, and 55 [49-60] mmHg for the control group). mCBS-treated animals required significantly less norepinephrine to maintain MAP than controls (p < 0.01 for interaction) and had lower creatinine (p < 0.01), lactate (p < 0.01), and interleukin-6 (p < 0.01) levels, associated with reduced changes in H3.1 nucleosome levels (p = 0.02). Early treatment was associated with lower norepinephrine requirements than later treatment. Two control animals died; all the mCBS-treated animals survived.
CONCLUSIONS
Neutralization of extracellular histones with mCBS was associated with reduced norepinephrine requirements, improved tissue perfusion, less renal dysfunction, and lower circulating IL-6 in experimental septic shock and may represent a new therapeutic approach to be tested in clinical trials.
Topics: Animals; Female; Hemodynamics; Histones; Interleukin-6; Lactic Acid; Norepinephrine; Sepsis; Sheep; Shock, Septic; Sodium; Sulfates
PubMed: 38001494
DOI: 10.1186/s13054-023-04741-x -
Frontiers in Medicine 2022Excessive inflammation and increased apoptosis of macrophages contribute to organ damage and poor prognosis of sepsis. Ginkgolic acid (GA) is a natural constituent...
BACKGROUND
Excessive inflammation and increased apoptosis of macrophages contribute to organ damage and poor prognosis of sepsis. Ginkgolic acid (GA) is a natural constituent extracted from the leaves of , that can regulate inflammation and apoptosis. The present study aims to investigate the potential effect of GA in treating sepsis and its possible mechanisms.
MATERIALS AND METHODS
Here, a classic septic mice model and a lipopolysaccharide (LPS)-induced RAW 264.7 inflammation model were established. Cytokines in serum and culture supernatant were detected by ELISA, and the mRNA levels of them were examined by PCR. Hematoxylin and eosin (H&E) staining was performed to determine histopathological changes in liver, lung and kidney. Bacterial burden in the blood, peritoneal lavage fluids (PLFs) and organs were observed on Luria-Bertani agar medium. Flow cytometry and western blotting was used to detect apoptosis and the expression level of apoptosis related molecules, respectively. Moreover, the levels of SUMOylation were detected by western blotting. The activity of NF-κB p65 was assessed by immunofluorescence staining and western blotting.
RESULTS
The result showed that GA promoted inflammatory responses, reduced bacterial clearance, aggravated organ damage, and increased mortality in septic mice. GA increased apoptosis in peritoneal macrophages (PMs) and RAW 264.7 cells. Meanwhile, GA inhibited SUMOylation and increased the nuclear translocation of NF-κB p65 as well as its phosphorylation level.
CONCLUSION
Collectively, GA promotes inflammation and macrophage apoptosis in sepsis, which may be mediated by inhibiting the SUMOylation process and increasing NF-κB p65 activity.
PubMed: 36743669
DOI: 10.3389/fmed.2022.1108882 -
Respiratory Research Jan 2023Pulmonary inflammation involves complex changes of the immune cells, in which macrophages play important roles and their function might be influenced by metabolism....
Pulmonary inflammation involves complex changes of the immune cells, in which macrophages play important roles and their function might be influenced by metabolism. Slc38a6 acts as a carrier of nutrient for macrophages (Mφ) to exert the function. In this study, pneumonia patient blood was found up-regulated SLC38A6 expression, which correlated with monocytes number and white blood cell number. The similar result was also shown in LPS induced sepsis mice. To reveal the key role of Slc38a6, we used systemic and conditional knock-out mice. Either systemic or Lyz specific knock-out could alleviate the severity of sepsis mice, reduce the proinflammatory cytokine TNF-α and IL-1β expression in serum and decrease the monocytes number in bronchial alveolar lavage and peritoneal lavage via flow cytometry. In order to reveal the signal of up-regulated Slc38a6, the Tlr4 signal inhibitor TAK242 and TLR4 knock-out mice were used. By blocking Tlr4 signal in macrophages via TAK242, the expression of Slc38a6 was down-regulated synchronously, and the same results were also found in Tlr4 knock-out macrophages. However, in the overexpressed Slc38a6 macrophages, blocking Tlr4 signal via TAK242, 20% of the mRNA expression of IL-1β still could be expressed, indicating that up-regulated Slc38a6 participates in IL-1β expression process. Collectively, it is the first time showed that an amino acid transporter SLC38A6 up-regulated in monocytes/macrophages promotes activation in pulmonary inflammation. SLC38A6 might be a promising target molecule for pulmonary inflammation treatment.
Topics: Animals; Mice; Inflammation; Interleukin-1beta; Lipopolysaccharides; Macrophages; Mice, Knockout; Pneumonia; Signal Transduction; Toll-Like Receptor 4; Nerve Tissue Proteins; Amino Acid Transport Systems, Neutral
PubMed: 36707853
DOI: 10.1186/s12931-023-02330-8 -
African Journal of Paediatric Surgery :... 2022Appendicitis is one of the most common paediatric surgical pathologies seen by paediatric surgeons worldwide. Laparoscopic appendectomy is undertaken for all cases of...
AIM
Appendicitis is one of the most common paediatric surgical pathologies seen by paediatric surgeons worldwide. Laparoscopic appendectomy is undertaken for all cases of appendicitis in our institute. Intraperitoneal lavage following appendectomy is the conventional way of managing complicated appendicitis; however, some surgeons debate the efficacy of this practice. The aim of this study was to compare outcomes of intraperitoneal lavage versus suction only in children with complicated appendicitis.
METHODS
Data were collected retrospectively between January 2018 and January 2019. All patients undergoing laparoscopic appendectomy for complex appendicitis were included and divided into two groups, patients who had suction only and those who had lavage and suction. Outcome parameters studied were the length of stay (LOS), number of temperature spikes > 37.7 (TS), operative times (OT) and readmission for intra-abdominal collections. Comparison between the two groups was performed using two sample t-test with unequal variance, significance was set at P < 0.05.
RESULTS
A total of 115 patients were included (lavage n = 52, Suction n = 63). The LOS (P = 0.0054), TS (0.0109), OT (P < 0.0001) were significantly higher in the lavage group compared to the suction-only group. Overall rates of readmission were similar between groups, however, readmission for the confirmed intra-abdominal collection was more common in the lavage group.
CONCLUSION
Based on our study, it appears that there is no advantage in performing an intraperitoneal lavage for complex appendicitis. It resulted in a prolonged stay, more post-operative TS and longer operative duration. The likelihood of being readmitted with an intra-abdominal collection following a lavage was higher compared to suction only.
Topics: Appendectomy; Appendicitis; Child; Humans; Laparoscopy; Length of Stay; Morbidity; Peritoneal Lavage; Postoperative Complications; Retrospective Studies; Treatment Outcome
PubMed: 36018206
DOI: 10.4103/ajps.ajps_146_21 -
Science Advances Aug 2020Detection of free gastric cancer cells in peritoneal lavages and ascites plays a vital role in gastric cancer. However, due to the low content of cancer cells in...
Detection of free gastric cancer cells in peritoneal lavages and ascites plays a vital role in gastric cancer. However, due to the low content of cancer cells in patients' peritoneal lavages, traditional detection methods lack sensitivity and cannot satisfy clinical demand. In this study, we used an optically induced electrokinetics (OEK) microfluidic method for label-free separation and characterization of patient gastric cancer cells. This method showed high effectiveness and sensitivity. We successfully separated cancer cells from a simulated peritoneal lavage mixture of gastric cancer cell lines and peritoneal lavage cells in a ratio of 1:1000. We further separated gastric cancer cells from six patients' ascites with purity up to 71%. In addition, we measured the cell membrane capacitances, which may be used as a biomarker for gastric cancer cells. Thus, our method can be used to effectively and rapidly detect peritoneal metastasis and to acquire cellular electrical information.
PubMed: 32821829
DOI: 10.1126/sciadv.aba9628 -
World Journal of Surgical Oncology May 2023This is a letter to the editor on a study by Jambor et al. on the role of staging laparoscopy in identifying occult and distant metastases in pancreatic adenocarcinoma...
This is a letter to the editor on a study by Jambor et al. on the role of staging laparoscopy in identifying occult and distant metastases in pancreatic adenocarcinoma patients. In this study, inclusion of staging laparoscopy as an adjunct to computed tomography resulted in an absolute risk reduction of 12.5% for non-therapeutic laparotomy. The study found no correlation between the presence of occult and distant metastases, and serum CA 19-9 level, tumour size or location, which was in significant contrast to a number of other studies. This was likely due to the smaller sample size of the study and restriction to a single high-volume referral centre. It is also noted that staging laparoscopy cannot detect vascular invasion, lymph node involvement and deep hepatic metastases. The sensitivity of peritoneal lavage cytology in detecting occult metastases is low as well. Inclusion of biomarkers like peritoneal lavage tumour DNA may improve sensitivity. Hence, even as this study adds to the evidence supporting staging laparoscopy, further studies on improving the sensitivity of staging laparoscopy are warranted.
Topics: Humans; Pancreatic Neoplasms; Adenocarcinoma; Neoplasm Staging; Laparoscopy
PubMed: 37198653
DOI: 10.1186/s12957-023-02975-1