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Proceedings of the National Academy of... May 2024Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment...
Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment in sialyltransferase mice. We found a marked decrease in eosinophil extravasation into CCL11-stimulated cremaster muscles and into the inflamed peritoneal cavity of mice. Ex vivo flow chamber assays uncovered reduced adhesion of compared to wild type eosinophils. Using flow cytometry, we show reduced binding of CCL11 to eosinophils. Further, we noted reduced binding of CCL11 to its chemokine receptor CCR3 isolated from eosinophils. This was accompanied by almost absent CCR3 internalization of CCL11-stimulated eosinophils. Applying an ovalbumin-induced allergic airway disease model, we found a dramatic reduction in eosinophil numbers in bronchoalveolar lavage fluid following intratracheal challenge with ovalbumin in -deficient mice. Finally, we also investigated tissue-resident eosinophils under homeostatic conditions and found reduced resident eosinophil numbers in the thymus and adipose tissue in the absence of ST3Gal-IV. Taken together, our results demonstrate an important role of ST3Gal-IV in CCR3-induced eosinophil recruitment in vivo rendering this enzyme an attractive target in reducing unwanted eosinophil infiltration in various disorders including allergic diseases.
Topics: Animals; Receptors, CCR3; Sialyltransferases; Eosinophils; Mice; beta-Galactoside alpha-2,3-Sialyltransferase; Mice, Knockout; Chemokine CCL11; Mice, Inbred C57BL; Ovalbumin; Bronchoalveolar Lavage Fluid
PubMed: 38687790
DOI: 10.1073/pnas.2319057121 -
Annali Italiani Di Chirurgia 2024Laparoscopic appendectomy followed by postoperative intravenous (IV) antibiotics is the standard of care for acute appendicitis and postoperative prevention of...
BACKGROUND
Laparoscopic appendectomy followed by postoperative intravenous (IV) antibiotics is the standard of care for acute appendicitis and postoperative prevention of intra-abdominal abscesses. The aim of or study was to determine if intraperitoneal irrigation with antibiotics could help prevent intra-abdominal abscess formation after laparoscopic appendectomy for complicated appendicitis in pediatric patients.
METHODS
A retrospective study was conducted on consecutive pediatric patients with acute appendicitis who had appendectomy in our Pediatric Surgery Department between August 2020 and February 2022. We compared two groups with similar age and symptoms. The first group (A) was treated with the normal standard of care, i.e., laparoscopic appendectomy and postoperative IV antibiotic therapy. For the second group (B) intraperitoneal cefazoline irrigation was added at the end of the laparoscopic procedure. Postoperative intra-abdominal abscess was diagnosed with ultrasound examination, performed after clinical suspicion/abnormal blood test results.
RESULTS
One hundred sixty patients (males:females 109:51; median age 10.5 years [range 3-17 years]) who had laparosopic appendectomy for complicated appendicitis were included, 82 in group A and 78 in group B. In the first 7 days after surgery, 18 patients in group and 5 in group B developed an intra-abdominal abscess (p < 0.005). Drains were positioned in 38 patients in group A vs. 9 in group B. One patient in group A had a different complication which was infection of the surgical incision.
CONCLUSIONS
Intraperitoneal cefazoline irrigation at the end of the laparoscopic appendectomy in pediatric patients significantly reduces the formation of intra-abdominal abscesses.
Topics: Humans; Appendectomy; Child; Laparoscopy; Retrospective Studies; Abdominal Abscess; Male; Female; Child, Preschool; Adolescent; Appendicitis; Postoperative Complications; Anti-Bacterial Agents; Cefazolin; Peritoneal Lavage
PubMed: 38684488
DOI: 10.62713/aic.3381 -
Cellular & Molecular Biology Letters Apr 2024Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased...
Mitochondrial (mt)DNA-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling promotes pyroptosis of macrophages via interferon regulatory factor (IRF)7/IRF3 activation to aggravate lung injury during severe acute pancreatitis.
BACKGROUND
Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate the cellular immune suppression during the process of SAP, where cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) plays an important role. However, the function and mechanism of cGAS-STING in SAP-induced lung injury (LI) remains unknown.
METHODS
Lipopolysaccharide (LPS) was combined with caerulein-induced SAP in wild type, cGAS and sting mice. Primary macrophages were extracted via bronchoalveolar lavage and peritoneal lavage. Ana-1 cells were pretreated with LPS and stimulated with nigericin sodium salt to induce pyroptosis in vitro.
RESULTS
SAP triggered NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated pyroptosis of alveolar and peritoneal macrophages in mouse model. Knockout of cGAS/STING could ameliorate NLRP3 activation and macrophage pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria further induced macrophage STING activation in a cGAS- and dose-dependent manner. Upregulated STING signal can promote NLRP3 inflammasome-mediated macrophage pyroptosis and increase serum interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α levels and, thus, exacerbate SAP-associated LI (SAP-ALI). Downstream molecules of STING, IRF7, and IRF3 connect the mtDNA-cGAS-STING axis and the NLRP3-pyroptosis axis.
CONCLUSIONS
Negative regulation of any molecule in the mtDNA-cGAS-STING-IRF7/IRF3 pathway can affect the activation of NLRP3 inflammasomes, thereby reducing macrophage pyroptosis and improving SAP-ALI in mouse model.
Topics: Animals; Pyroptosis; Interferon Regulatory Factor-3; Mice; Signal Transduction; DNA, Mitochondrial; Membrane Proteins; Nucleotidyltransferases; Pancreatitis; Macrophages; Lung Injury; Interferon Regulatory Factor-7; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Lipopolysaccharides; Male; Disease Models, Animal
PubMed: 38671352
DOI: 10.1186/s11658-024-00575-9 -
Probiotics and Antimicrobial Proteins Apr 2024Curdlan, a β-1,3/1,6-glucan found in Alcaligenes faecalis (A. faecalis) wall, activates innate and humoral immunity. The aim of this study is to evaluate whether...
Curdlan, a β-1,3/1,6-glucan found in Alcaligenes faecalis (A. faecalis) wall, activates innate and humoral immunity. The aim of this study is to evaluate whether pretreated rats with A. faecalis A12C could prevent sepsis disturbances and identify the immunomodulatory mechanisms involved. Experiments occurred in two stages: a survival study with 16 rats randomly divided into septic (SC) (n = 8) and septic pretreated (SA) (n = 8) groups and 45 rats divided into four groups: healthy (AGUSAN) (n = 9), septic (AGUIC) (n = 13), septic pretreated (AGUIA) (n = 14), and healthy pretreated (AGUSTO) (n = 9). Sepsis was induced by cecal ligation and puncture after 30 days of A. faecalis A12C pretreatment or without. SA group had a higher survival rate of 58% vs. 16% for SC group (P < 0.05). Overall, AGUIA showed better status than AGUIC (P < 0.01). Higher monocytosis was found in AGUIA and AGUSTO vs. AGUIC and AGUSAN, respectively (P < 0.05). A gradual increase in curdlan fecal concentration was observed in AGUIA during pretreatment. Fecal concentrations of Escherichia coli significantly decreased in AGUIA and AGUSTO. Bacterial load in urine, peritoneal lavage fluid (PLF), and bronchoalveolar lavage fluid (BALF) decreased (P < 0.05) in AGUIA vs. AGUIC. Finally, lower inflammation was observed in serum, BALF, and PLF, with reduced IL-6, IL-10, IL-1β, and TNF-α, along with less damage in lungs and peritoneum in AGUIA vs. AGUIC. These findings suggest the connection between curdlan-produced by A. faecalis A12C-with the immune system and the reduction in severity of experimental sepsis.
PubMed: 38668821
DOI: 10.1007/s12602-024-10252-0 -
Case Reports in Gastroenterology 2024Crohn's disease (CD) is complicated by intestinal strictures and fistula formation; however, intestinal perforation is relatively rare.
INTRODUCTION
Crohn's disease (CD) is complicated by intestinal strictures and fistula formation; however, intestinal perforation is relatively rare.
CASE PRESENTATION
Following a traffic accident in the evening, a 39-year-old woman experienced abdominal pain that worsened the following morning and was taken to the emergency department. She had a 17-year history of CD and eight endoscopic balloon dilations for descending colonic strictures. She presented with a high fever of 40.0°C, along with tenderness and rebound pain throughout her abdomen, with the most substantial point being in the lower left abdomen. Computed tomography showed thickening of the descending colon wall, increased fat concentration around the wall, and a slight presence of air in the mesentery near the intestinal wall. We diagnosed the patient with generalized peritonitis due to traumatic penetration of the mesentery of the descending colon and performed emergency surgery. Intraoperative observation of the abdominal cavity with a laparoscope revealed purulent ascites but no apparent perforation or edematous mesentery, with white moss and redness in the descending colon. This prompted the decision to perform peritoneal lavage drainage and a transverse colonic double colostomy. The postoperative course was favorable, and the patient was discharged from the hospital on the postoperative day 14. Four months after discharge, colostomy closure was performed.
CONCLUSION
Relatively minor trauma in patients with CD can result in colon injury. An injured bowel is usually accompanied by active lesions due to CD; however, caution is required, as endoscopic balloon dilatation without accompaniment may be a background factor.
PubMed: 38665146
DOI: 10.1159/000537973 -
Oncogene Jun 2024Detection of peritoneal dissemination (PD) in gastric cancer (GC) patients remains challenging. The feasibility of tumor-guided cell-free DNA (cfDNA) detection in...
Detection of peritoneal dissemination (PD) in gastric cancer (GC) patients remains challenging. The feasibility of tumor-guided cell-free DNA (cfDNA) detection in prospectively collected peritoneal fluid (ascites and peritoneal lavage) was investigated and compared to conventional cytology in 28 patients. Besides conventional cytology, next generation sequencing was performed on primary tumor DNA and cell-free DNA from peritoneal fluid. Patients were retrospectively grouped into: a positive group (with PD) and a negative group (without PD). Detectable mutations were found in the primary tumor of 68% (n = 19). Sensitivity of PD detection by tumor-guided cfDNA analysis was 91%, compared to 64% by conventional cytology. Within the positive group (n = 11), tumor-guided cfDNA was detected in all patients with ascites samples (4/4, 100%) and in 86% (6/7) of the lavage samples, opposed to 4/4 (100%) patients with ascites and 43% (3/7) with lavage by conventional cytology. Within the negative group (n = 8), conventional cytology was negative for all samples. In two patients, tumor-guided cfDNA was detected in peritoneal lavage fluid. Interestingly, these 2 patients developed PD within 6 months, suggesting a prognostic value of tumor-guided cfDNA detection. This study showed that tumor-guided cfDNA detection in peritoneal fluids of GC patients is feasible and superior to conventional cytology in detecting PD.
Topics: Humans; Stomach Neoplasms; Peritoneal Neoplasms; Female; Ascitic Fluid; Male; Middle Aged; Aged; Cell-Free Nucleic Acids; Retrospective Studies; Circulating Tumor DNA; Adult; High-Throughput Nucleotide Sequencing; Biomarkers, Tumor; Ascites; Mutation; Aged, 80 and over; Peritoneal Lavage; DNA, Neoplasm
PubMed: 38654110
DOI: 10.1038/s41388-024-03034-z -
Theranostics 2024A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured...
Lipid nanoparticle encapsulated large peritoneal macrophages migrate to the lungs via the systemic circulation in a model of clodronate-mediated lung-resident macrophage depletion.
A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured tissues and impart wound healing properties. Here, we sought to expand on this unique ability of large peritoneal macrophages (LPMs) by investigating whether these GATA6+ LPMs could also intravasate into systemic circulation and migrate to extra-peritoneally located lungs upon ablating lung-resident alveolar macrophages (AMs) by intranasally administered clodronate liposomes in mice. C12-200 cationic lipidoid-based nanoparticles were employed to selectively deliver a small interfering RNA (siRNA)-targeting CD-45 labeled with a cyanine 5.5 (Cy5.5) dye to LPMs via intraperitoneal injection. We utilized a non-invasive optical technique called Diffuse Flow Cytometry (DiFC) to then systemically track these LPMs in real time and paired it with more conventional techniques like flow cytometry and immunocytochemistry to initially confirm uptake of C12-200 encapsulated siRNA-Cy5.5 (siRNA-Cy5.5 (C12-200)) into LPMs, and further track them from the peritoneal cavity to the lungs in a mouse model of AM depletion incited by intranasally administered clodronate liposomes. Also, we stained for LPM-specific marker zinc-finger transcription factor GATA6 in harvested cells from biofluids like broncho-alveolar lavage as well as whole blood to probe for Cy5.5-labeled LPMs in the lungs as well as in systemic circulation. siRNA-Cy5.5 (C12-200) was robustly taken up by LPMs. Upon depletion of lung-resident AMs, these siRNA-Cy5.5 (C12-200) labeled LPMs rapidly migrated to the lungs via systemic circulation within 12-24 h. DiFC results showed that these LPMs intravasated from the peritoneal cavity and utilized a systemic route of migration. Moreover, immunocytochemical staining of zinc-finger transcription factor GATA6 further confirmed results from DiFC and flow cytometry, confirming the presence of siRNA-Cy5.5 (C12-200)-labeled LPMs in the peritoneum, whole blood and BALF only upon clodronate-administration. Our results indicate for the very first time that selective tropism, migration, and infiltration of LPMs into extra-peritoneally located lungs was dependent on clodronate-mediated AM depletion. These results further open the possibility of therapeutically utilizing LPMs as delivery vehicles to carry nanoparticle-encapsulated oligonucleotide modalities to potentially address inflammatory diseases, infectious diseases and even cancer.
Topics: Animals; Clodronic Acid; Nanoparticles; Mice; Lung; Macrophages, Peritoneal; Macrophages, Alveolar; RNA, Small Interfering; GATA6 Transcription Factor; Liposomes; Mice, Inbred C57BL; Carbocyanines; Cell Movement; Flow Cytometry
PubMed: 38646640
DOI: 10.7150/thno.91062 -
Zhonghua Yi Xue Za Zhi Apr 2024Peritoneal metastasis is the common route of metastasis in gastric cancer and is a major cause of death in advanced gastric cancer. Early intervention with comprehensive... (Review)
Review
Peritoneal metastasis is the common route of metastasis in gastric cancer and is a major cause of death in advanced gastric cancer. Early intervention with comprehensive treatment can effectively improve the prognosis of some patients with peritoneal metastasis. However, early peritoneal metastasis in gastric cancer is predominantly micro-metastasis, which cannot be effectively evaluated by imaging studies. Moreover, the detection of disseminated cancer cells in peritoneal lavage suffers from a low detection rate and significant heterogeneity. In recent years, the development and application of new liquid biopsy technologies such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have provided new means to assess potential peritoneal metastasis at the cellular and molecular levels, gradually becoming research hotspots in this field. This review will summarize the relevant progress of liquid biopsy in peritoneal metastasis, which holds significant importance for improving the prognosis of gastric cancer patients in China.
Topics: Stomach Neoplasms; Humans; Liquid Biopsy; Peritoneal Neoplasms; Neoplastic Cells, Circulating; Prognosis; Circulating Tumor DNA
PubMed: 38644279
DOI: 10.3760/cma.j.cn112137-20230823-00292 -
BMJ Open Apr 2024Accurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form...
Ga-FAPI-04 positron emission tomography/CT and laparoscopy for the diagnosis of occult peritoneal metastasis in newly diagnosed locally advanced gastric cancer: study protocol of a single-centre prospective cohort study.
INTRODUCTION
Accurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer and mainly diagnosed by diagnostic laparoscopy and peritoneal lavage evaluation. However, diagnostic laparoscopy is invasive and less cost-effective. It is urgent to develop a safe, fast and non-invasive functional imaging method to verify the peritoneal metastasis of gastric cancer. The aim of our study was to evaluate the proportion of patients in whom Ga-FAPI-04 positron emission tomography/CT (PET/CT) led to a change in treatment strategy and to assess the diagnostic accuracy of Ga-FAPI-04 PET/CT for the detection of occult peritoneal metastasis compared with laparoscopic exploration.
METHODS AND ANALYSIS
In this single-centre, prospective diagnostic test accuracy study, a total of 48 patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma (cT4a-b, N0-3, M0, based on CT images) who are considering radical tumour surgery will be recruited. All participants will undergo Ga-FAPI-04 PET/CT before the initiation of laparoscopic exploration. The primary outcome is the proportion of patients with occult peritoneal metastatic lesions detected by Ga-FAPI-04 PET/CT, leading to a change in therapy strategy. The secondary outcomes include the diagnostic performance of Ga-FAPI-04 PET/CT for occult peritoneal metastasis, including sensitivity, specificity, accuracy, positive predictive value and negative predictive value.
ETHICS AND DISSEMINATION
The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (2022-1484). Study results will be presented at public and scientific conferences and in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
ChiCTR2300067591.
Topics: Humans; Stomach Neoplasms; Gallium Radioisotopes; Prospective Studies; Peritoneal Neoplasms; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Laparoscopy; Fluorodeoxyglucose F18; Quinolines
PubMed: 38643004
DOI: 10.1136/bmjopen-2023-075680 -
Urology Case Reports May 2024Fournier's gangrene, a rare and life-threatening soft tissue infection affecting the genitalia and perineum, results from various microorganisms. This rapidly...
Fournier's gangrene, a rare and life-threatening soft tissue infection affecting the genitalia and perineum, results from various microorganisms. This rapidly progressing necrotizing fasciitis yields higher mortality and morbidity rates. We report a case of a 1-month-old male infant with Fournier's gangrene due to perforation transverse colon complicated with septic shock and pneumonia also accompanied by patent processus vaginalis. Radiological findings of pneumonia and pneumoperitoneum were exhibited. Early diagnosis and management are demanded to mitigate life-threatening and improve the prognosis. The patient underwent incision drainage, peritoneal lavage, exploratory laparotomy, colostomy, necrotomy debridement, and patent processus vaginalis ligation after hemodynamic status stabilization.
PubMed: 38601087
DOI: 10.1016/j.eucr.2024.102721