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Scientific Reports May 2024In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study...
In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study sought to determine whether positive peritoneal lavage cytology (CY+) precludes pancreatectomy. Furthermore, we propose a novel liquid biopsy using peritoneal lavage fluid to detect viable peritoneal tumor cells (v-PTCs) with TelomeScan F35, a telomerase-specific replication-selective adenovirus engineered to express green fluorescent protein. Resectable cytologically or histologically proven PDAC patients (n = 53) were enrolled. CY was conducted immediately following laparotomy. The resulting fluid was examined by conventional cytology (conv-CY; Papanicolaou staining and MOC-31 immunostaining) and by the novel technique (Telo-CY; using TelomeScan F35). Of them, 5 and 12 were conv-CY+ and Telo-CY+, respectively. All underwent pancreatectomy. The two double-CY+ (conv-CY+ and Telo-CY+) patients showed early peritoneal recurrence (P-rec) postoperatively, despite adjuvant chemotherapy. None of the three conv-CY+ Telo-CY- patients exhibited P-rec. Six of the 10 Telo-CY+ conv-CY- patients (60%) relapsed with P-rec. Of the remaining 38 double-CY- [conv-CY-, Telo-CY-, conv-CY± (Class III)] patients, 3 (8.3%) exhibited P-rec. Although conv-CY+ status predicted poor prognosis and a higher risk of P-rec, Telo-CY was more sensitive for detecting v-PTC. Staging laparoscopy and performing conv-CY and Telo-CY are needed to confirm the indication for pancreatectomy.
Topics: Humans; Peritoneal Lavage; Pancreatic Neoplasms; Male; Female; Aged; Middle Aged; Pancreatectomy; Carcinoma, Pancreatic Ductal; Cytodiagnosis; Aged, 80 and over; Neoplasm Recurrence, Local; Liquid Biopsy; Peritoneal Neoplasms; Adult; Cytology
PubMed: 38702437
DOI: 10.1038/s41598-024-60936-4 -
Mediators of Inflammation 2023Sepsis is a life-threatening clinical condition caused by infection and transposition of pathogens and pathogen-associated molecular patterns (PAMPs) into the host...
Sepsis is a life-threatening clinical condition caused by infection and transposition of pathogens and pathogen-associated molecular patterns (PAMPs) into the host bloodstream. During sepsis, activation of toll-like receptors (TLRs) on immune cells triggers the release of pro-inflammatory cytokines and overstimulates the production of vasodilatory mediators such as nitric oxide (NO). These vascular changes lead to widespread inflammation, tissue damage, multiple organ failure, and often death. New therapeutic options are urgently needed. To this end, thiostrepton (TST) has emerged as a candidate for sepsis treatment due to its action as an antibiotic and anti-inflammatory molecule (TLR7-9 inhibitor). Reports in the literature suggest that TLR9 inhibition substantially suppresses the excessive host inflammatory response and attenuates sepsis-induced mortality in the cecal ligation and puncture (CLP) murine model of sepsis. However, to the best of our knowledge, TST has never been directly tested as a therapeutic option for the management of sepsis, possibly due to its low water solubility and drug delivery issues. These facts prompted us to test the central hypothesis that TST encapsulated in phospholipid sterically stabilized micelles (TST-SSM) could be developed into a novel treatment for sepsis. Thus, using our published method of encapsulating the hydrophobic antibiotic TST-SSM, we evaluated the efficacy of TST-SSM nanomedicine in the murine model of polymicrobial sepsis. We found that TST-SSM increased the median survival of CLP-induced septic mice from 31 to 44 hr by reducing the bacterial burden in the blood and peritoneal lavage. Moreover, plasma levels of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor-alpha) and NO derivatives were also reduced, whereas renal and hepatic function biomarkers creatinine and aspartate transferase were significantly improved. In conclusion, we identified that TST-SSM nanomedicine has significant potential as a therapeutic agent for sepsis management, primarily due to its anti-inflammatory and antibiotic properties.
Topics: Animals; Mice; Thiostrepton; Toll-Like Receptor 9; Disease Models, Animal; Nanomedicine; Sepsis; Inflammation; Anti-Bacterial Agents; Cytokines
PubMed: 37662481
DOI: 10.1155/2023/4035516 -
Saudi Pharmaceutical Journal : SPJ :... Jun 2024Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol...
Intra-peritoneal lavage of rhizome and its active constituent gingerol impede inflammation, angiogenesis, and fibrosis following post-operative peritoneal adhesion in male rats.
Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol compounds on surgical-induced peritoneal adhesion, and their strategies that disrupted the PA formation pathways to suppress their incidence. First, liquid chromatography-mass spectrometry (LC-MS) was established to separate and identify several chemical groups of ginger rhizome extract. In the next steps, male Wistar albino rats were randomly selected and divided into various groups, namely sham, control, ginger extract (0.6, 1.8, 5 %w/v), and gingerol (0.05, 0.1, 0.3, and 1 %w/v). Finally, we investigated the macroscopic parameters such as wound healing, body weight as well as spleen height and weight. In addition, visual peritoneal adhesion assessment was performed via Nair et al and Adhesion Scoring Scheme. Moreover, the microscopic parameters and biological assessment was performed via and immunoassays. The present findings revealed significant improvement in wound healing and reduction of the adhesion range, as Nair et al. and Adhesion Scoring Scheme scoring, in both the ginger and gingerol groups compared to the PA group (). Whereas, gingerol (0.3 % w/v) was able to increase the body weight in rats () at end stage of experiment. Also, inflammation, angiogenesis, and fibrosis were significantly decreased due to the downregulation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF), respectively, in the ginger and gingerol groups compared to the PA group (). In contrast, the levels of IL-10 were increased in the ginger and gingerol groups compared to the control group (). Our results proved that ginger rhizome and gingerol, as novel therapeutic compounds, could be used to prevent PA for their beneficial anti-inflammatory as well as anti-fibrosis properties in clinical trials. However, further clinical studies are required to approve the effectiveness of ginger and gingerol.
PubMed: 38737808
DOI: 10.1016/j.jsps.2024.102092 -
MSystems Aug 2023Bacteriophages, viruses that parasitize bacteria, are known to be abundant at sites of bacterial colonization, but the relationship between phages and bacteria at sites...
Bacteriophages, viruses that parasitize bacteria, are known to be abundant at sites of bacterial colonization, but the relationship between phages and bacteria at sites of infection is unclear. Bacteriophages are highly specific to their bacterial host species, and so we hypothesize that phage populations would mirror those of bacterial pathogens within infected tissues. To test this, here we study publicly available cell-free DNA (cfDNA) generated using next-generation sequencing of infected bodily fluids, including urine, joint fluid, peritoneal fluid, bronchoalveolar lavage fluid, cerebrospinal fluid, and abscess fluid, as well as uninfected control samples. These were analyzed using a computational pipeline for identifying bacteriophage sequences in cfDNA. We find that bacteriophage sequences are present in both infected and uninfected bodily fluids and represent a variety of bacteriophage morphologies and bacterial hosts. Additionally, phages from , , and are overrepresented both in terms of proportion and diversity in fluids infected with these same pathogens. These data indicate that phages reflect the relative abundance of their bacterial hosts at sites of infection. Bacteriophage sequences may help inform future investigative and diagnostic approaches that utilize cell-free DNA to study the microbiome within infected tissues. IMPORTANCE Bacteriophages are an active area of investigation in microbiome research, but most studies have focused on phage populations at sites of bacterial colonization. Little is known about bacteriophage ecology at sites of active infection. To address this gap in knowledge, we utilized a publicly available data set to study bacteriophage populations in cell-free DNA collected from sites of infection. We find that phages reflect the relative abundance of their bacterial hosts at sites of infection. These studies may lead to future investigative and diagnostic approaches that incorporate phages as well as bacterial cell-free DNA.
Topics: Bacteriophages; Bacteria; Ecology; Host Specificity; Microbiota
PubMed: 37526425
DOI: 10.1128/msystems.00497-23 -
Frontiers in Immunology 2024Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous...
Excessive salt intake is a widespread health issue observed in almost every country around the world. A high salt diet (HSD) has a strong correlation with numerous diseases, including hypertension, chronic kidney disease, and autoimmune disorders. However, the mechanisms underlying HSD-promotion of inflammation and exacerbation of these diseases are not fully understood. In this study, we observed that HSD consumption reduced the abundance of the gut microbial metabolite L-fucose, leading to a more substantial inflammatory response in mice. A HSD led to increased peritonitis incidence in mice, as evidenced by the increased accumulation of inflammatory cells and elevated levels of inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1, also known as C-C motif chemokine ligand 2 or CCL2), in peritoneal lavage fluid. Following the administration of broad-spectrum antibiotics, HSD-induced inflammation was abolished, indicating that the proinflammatory effects of HSD were not due to the direct effect of sodium, but rather to HSD-induced alterations in the composition of the gut microbiota. By using untargeted metabolomics techniques, we determined that the levels of the gut microbial metabolite L-fucose were reduced by a HSD. Moreover, the administration of L-fucose or fucoidan, a compound derived from brown that is rich in L-fucose, normalized the level of inflammation in mice following HSD induction. In addition, both L-fucose and fucoidan inhibited LPS-induced macrophage activation . In summary, our research showed that reduced L-fucose levels in the gut contributed to HSD-exacerbated acute inflammation in mice; these results indicate that L-fucose and fucoidan could interfere with HSD-promotion of the inflammatory response.
Topics: Mice; Animals; Sodium Chloride, Dietary; Fucose; Inflammation; Diet; Polysaccharides
PubMed: 38596683
DOI: 10.3389/fimmu.2024.1333848 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Sep 2023To investigate the effect of Isodopharicin C (Iso C), a traditional Chinese herbal medicine extract, on NLRP3 inflammasome activation and lipopolysaccharide...
OBJECTIVE
To investigate the effect of Isodopharicin C (Iso C), a traditional Chinese herbal medicine extract, on NLRP3 inflammasome activation and lipopolysaccharide (LPS)-induced septic shock in mice.
METHODS
Murine bone marrow-derived macrophages (BMDM) and human monocytic THP-1 cells were stimulated with LPS before treatment with different NLRP3 inflammasome agonists to activate canonical NLRP3 inflammasomes. The non-canonical NLRP3 inflammasomes were activated by intracellular LPS transfection, and AIM2 inflammasomes were activated with poly A: T. The cleavage of caspase-1 induced by NLRP3 activation was measured using Western blotting. The levels of NLRP3-dependent and -independent pro-inflammatory cytokines in the cell culture supernatant were detected using ELISA, and the intracellular potassium ion concentration was measured using ICP-OES. In the animal experiment, C57BL/6J mouse models of septic shock (induced by intraperitoneal LPS injection) were treated with Iso C, and the levels of IL-1β, TNF-α and IL-6 in the serum and peritoneal lavage fluid were detected using ELISA. The survival time of the mice was observed within 48 h after LPS injection and a survival curve was plotted.
RESULTS
In BMDM cells, Iso C dose-dependently inhibited the activation of canonical NLRP3 inflammasomes and non-canonical NLRP3 inflammasomes (<0.05) without obviously affecting the secretion levels of TNF-α and IL-6 (>0.05), the activation of AIM2 inflammasomes (>0.05), or K + efflux, the upstream signaling of NLRP3 activation (>0.05). Iso C inhibited the activation of canonical NLRP3 inflammasomes in human THP-1 cells. In septic C57BL/6J mice, Iso C treatment significantly reduced IL-1β levels in the serum and peritoneal lavage fluid, and prolonged the survival time of the mice (<0.05).
CONCLUSION
Iso C specifically inhibits NLRP3 inflammasome activation and alleviates septic shock in mice, and can serve as a potential small molecule compound for treatment of inflammatory diseases.
Topics: Animals; Humans; Mice; Inflammasomes; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Shock, Septic; Tumor Necrosis Factor-alpha
PubMed: 37814861
DOI: 10.12122/j.issn.1673-4254.2023.09.04 -
Heliyon Nov 2023The treatment of sepsis remains challenging and the liver is a non-neglectful target of sepsis-induced injury. Uncontrolled inflammatory responses exert a central role...
AIMS
The treatment of sepsis remains challenging and the liver is a non-neglectful target of sepsis-induced injury. Uncontrolled inflammatory responses exert a central role in the pathophysiological process of sepsis-induced acute liver injury (SI-ALI). Maresin1 (MaR1) is a derivative of omega-3 docosahexaenoic acid (DHA), which has been shown to have anti-inflammatory effects and is effective in a variety of sepsis-related diseases. This study aimed to determine the effect of MaR1 on cecal ligation and puncture (CLP)-caused SI-ALI and explore its possible mechanisms.
MAIN METHODS
Mice were subjected to CLP, and then intravenously injected via tail vein with low-dose MaR1 (0.5 ng, 200 μL) or high-dose MaR1 (1 ng, 200 μL) or sterile normal saline (NS) (200 μL) 1 h later. Then, the survival rate, body weight change, liver function, bacterial load, neutrophil infiltration, and inflammatory cytokines were detected.
RESULTS
MaR1 significantly increased the 7-day survival rate and reduced the bacterial load in peritoneal lavage fluid and blood in a dose-dependent manner in mice with SI-ALI. Treatment with MaR1 could also restore the function of the liver in septic mice. Besides, MaR1 exerted anti-inflammatory effects by decreasing the expression of pro-inflammatory molecules (TNF-α, IL-6 and IL-1β), bacterial load, and neutrophil infiltration and increasing the expression of anti-inflammatory molecules (IL-10).
SIGNIFICANCE
Our experimental results showed that MaR1 alleviated liver injury induced by sepsis. This work highlighted a potential clinic use of MaR1 in treating acute inflammation of SI-ALI, but also provided new insight into the underlying molecular mechanism.
PubMed: 38027581
DOI: 10.1016/j.heliyon.2023.e21883 -
European Journal of Surgical Oncology :... Apr 2024Diagnostic laparoscopy (DL) with peritoneal lavage has been adopted as a standard staging procedure for patients with gastric cancer (GC). Evaluation of the value of DL...
INTRODUCTION
Diagnostic laparoscopy (DL) with peritoneal lavage has been adopted as a standard staging procedure for patients with gastric cancer (GC). Evaluation of the value of DL is important given ongoing improvements in diagnostic imaging and treatment. As contemporary data from European centres are sparse, this retrospective cohort study aimed to assess the yield of DL in patients with potentially curable gastric cancer, and to identify predictive factors for peritoneal metastases.
METHODS
Patients with adenocarcinoma of the stomach, treated between January 2016 and December 2018, were identified from institutional databases of two high volume European Upper-GI centres. Patients who underwent a DL with peritoneal lavage for potentially curable disease after clinical staging with imaging (cT1-4N0-3M0) were included. The primary outcome was the proportion of patients with a positive DL, defined as macroscopic metastatic disease, positive peritoneal cytology washings (PC+) or locally irresectable disease.
RESULTS
Some 80 of 327 included patients (24.5%) had a positive DL, excluding these patients from neoadjuvant treatment (66 of 327; 20.2%) and/or surgical resection (76 of 327; 23.2%). In 34 of 327 patients (10.3%), macroscopic metastatic disease was seen, with peritoneal deposits in 30 of these patients. Only 16 of 30 patients with peritoneal disease had positive cytology. Some 41 of 327 patients (12.5%) that underwent DL had PC+ in the absence of macroscopic metastases and five patients (1.5%) had an irresectable primary tumour. Diffuse type carcinoma had the highest risk of peritoneal dissemination, irrespective of cT and cN categories.
CONCLUSION
The diagnostic yield of staging laparoscopy is high, changing the management in approximately one quarter of patients. DL should be considered in patients with diffuse type carcinoma irrespective of cT and cN categories.
Topics: Humans; Peritoneal Lavage; Stomach Neoplasms; Retrospective Studies; Peritoneal Neoplasms; Neoplasm Staging; Laparoscopy; Adenocarcinoma
PubMed: 38428107
DOI: 10.1016/j.ejso.2024.108233 -
World Journal of Gastrointestinal... Oct 2023Our previous study found that the telomerase-associated protein 1 (, rs938886 and rs1713449) and homo sapiens RecQ like helicase 5 (, rs820196) single nucleotide...
BACKGROUND
Our previous study found that the telomerase-associated protein 1 (, rs938886 and rs1713449) and homo sapiens RecQ like helicase 5 (, rs820196) single nucleotide polymorphisms (SNPs) were associated with changes in heart rate (HR) ≥ 30% during peritoneal lavage with distilled water after gastrectomy. This study established a single tube method for detecting these three SNPs using two-dimensional (2D) polymerase chain reaction (PCR), and investigated whether SNP-SNP and SNP-environment interactions increase the risk of high HR variability (HRV).
AIM
To investigate whether genotypes, genetic patterns, SNP-SNP and SNP-environment interactions were associated with HRV.
METHODS
2D PCR was used to establish a single-tube method to detect rs938886 and rs1713449 and rs820196, and the results were compared with those of sanger sequencing. After adjusting for confounders such as age, sex, smoking, hypertension, and thyroid dysfunction, a nonconditional logistic regression model was used to assess the associations between the genotypes and the genetic patterns (codominant, dominant, overdominant, recessive, and additive) of the three SNPs and a risk ≥ 15% or ≥ 30% of a sudden drop in HR during postoperative peritoneal lavage in patients with gastric cancer. Gene-gene and gene-environment interactions were analyzed using generalized multifactor dimensionality reduction.
RESULTS
The coincidence rate between the 2D PCR and sequencing was 100%. When the HRV cutoff value was 15%, the patients with the (rs820196) TC genotype had a higher risk of high HRV than those who had the TT genotype (odds ratio = 1.97; 95%CI: 1.05-3.70; = 0.045). Under the codominant and overdominant models, the TC genotype of (rs820196) was associated with a higher risk of HR decrease relative to the TT and TT + CC genotypes ( = 0.031 and 0.016, respectively). When the HRV cutoff value was 30%, patients carrying the GC-TC genotypes of rs938886 and rs820196 showed a higher HRV risk when compared with the GG-TT genotype carriers ( = 0.01). In the three-factor model of rs938886, rs820196, and rs1713449, patients carrying the GC-TC-CT genotype had a higher risk of HRV compared with the wild-type GG-TT-CC carriers ( = 0.01). For rs820196, nonsmokers with the TC genotype had a higher HRV risk compared with nonsmokers carrying the TT genotype ( = 0.04). When the HRV cutoff value was 15%, patients carrying the TT-TT and the TC-CT genotypes of rs820196 and rs1713449 showed a higher HRV risk when compared with TT-CC genotype carriers ( = 0.04 and 0.01, respectively). Patients carrying the GC-CT-TC genotypes of rs938886, rs1713449, and rs820196 showed a higher HRV risk compared with GG-CC-TT genotype carriers ( = 0.02). When the HRV cutoff value was 15%, the best-fitting models for the interactions between the SNPs and the environment were the rs820196-smoking ( = 0.022) and rs820196-hypertension ( = 0.043) models. Consistent with the results of the previous grouping, for rs820196, the TC genotype nonsmokers had a higher HRV risk compared with nonsmokers carrying the TT genotype ( = 0.01).
CONCLUSION
The polymorphism of the and genes were associated with HRV during peritoneal lavage with distilled water after gastrectomy.
PubMed: 37969699
DOI: 10.4240/wjgs.v15.i10.2154 -
Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response.Cell Reports Mar 2024Neutrophil-derived bactericidal/permeability-increasing protein (BPI) is known for its bactericidal activity against gram-negative bacteria and neutralization of...
Neutrophil-derived bactericidal/permeability-increasing protein (BPI) is known for its bactericidal activity against gram-negative bacteria and neutralization of lipopolysaccharide. Here, we define BPI as a potent activator of murine dendritic cells (DCs). As shown in GM-CSF-cultured, bone-marrow-derived cells (BMDCs), BPI induces a distinct stimulation profile including IL-2, IL-6, and tumor necrosis factor expression. Conventional DCs also respond to BPI, while M-CSF-cultivated or peritoneal lavage macrophages do not. Subsequent to BPI stimulation of BMDCs, CD4 T cells predominantly secrete IL-22 and, when naive, preferentially differentiate into T helper 22 (Th22) cells. Congruent with the tissue-protective properties of IL-22 and along with impaired IL-22 induction, disease severity is significantly increased during dextran sodium sulfate-induced colitis in BPI-deficient mice. Importantly, physiological diversification of intestinal microbiota fosters BPI-dependent IL-22 induction in CD4 T cells derived from mesenteric lymph nodes. In conclusion, BPI is a potent activator of DCs and consecutive Th22 cell differentiation with substantial relevance in intestinal homeostasis.
Topics: Animals; Mice; Tumor Necrosis Factor-alpha; Cells, Cultured; T-Lymphocytes, Helper-Inducer; Dendritic Cells; Permeability
PubMed: 38457343
DOI: 10.1016/j.celrep.2024.113929