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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 -
Alternative Therapies in Health and... Feb 2024Intraperitoneal chemotherapy is an effective way to kill free tumor cells in the abdominal cavity. The safety and efficacy of raltitrexed perfusion during radical...
BACKGROUND
Intraperitoneal chemotherapy is an effective way to kill free tumor cells in the abdominal cavity. The safety and efficacy of raltitrexed perfusion during radical surgery for elderly patients with colorectal cancer are still unclear.
METHODS
In accordance with computer-generated random allocation sequences, 116 elderly patients with colorectal cancer who received radical surgery were randomly grouped into the raltitrexed intraperitoneal perfusion group or the saline intraperitoneal perfusion group from January 2020 to December 2021 in the First Affiliated Hospital of Bengbu Medical University. t tests and χ2 tests were used to analyze the difference between the two groups of the clinical characteristics, pathological features, perioperative parameters, and carcinoembryonic antigen mRNA in the peritoneal lavage fluid.
RESULTS
No statistically significant differences in postoperative complications after radical surgery were observed between the two groups. No statistically significant differences in peripheral blood indexes were observed between the two groups before surgery or on the first and third days after surgery. One day after radical surgery, the alanine transaminase (54.33 ± 4.93 vs 51.01 ± 5.56) and aspartate transaminase (49.28 ± 4.30 vs 50.99 ± 3.88) in the peripheral blood were higher in the raltitrexed intraperitoneal perfusion group than in the saline intraperitoneal perfusion group. At the same time, no significant difference was found on the third day after surgery. No significant differences in side effects of chemotherapy were observed between the two groups. The positive rate of carcinoembryonic antigen mRNA in the raltitrexed intraperitoneal perfusion group (8.47%) was significantly lower than that in the saline intraperitoneal perfusion group (22.81%) after surgery.
CONCLUSION
Raltitrexed perfusion during radical surgery is safe and feasible for elderly patients with CRC and can reduce the positive rate of carcinoembryonic antigen mRNA in peritoneal lavage fluid, so it can be explored as a treatment option.
PubMed: 38401095
DOI: No ID Found -
Pancreatology : Official Journal of the... May 2024/Objective: Preoperative treatment of resectable pancreatic ductal adenocarcinoma (PDAC) is gaining popularity worldwide. However, the characteristics of tumors located...
Tumor location, clinicopathological features, and perioperative and prognostic outcomes in patients who underwent pancreatic resection following neoadjuvant chemoradiotherapy for resectable pancreatic cancer: A retrospective study.
BACKGROUND
/Objective: Preoperative treatment of resectable pancreatic ductal adenocarcinoma (PDAC) is gaining popularity worldwide. However, the characteristics of tumors located in the pancreatic head (Ph), or those in the body or tail (Pbt), after surgery following neoadjuvant chemoradiotherapy (NACRT) remain unclear. This study aimed to evaluate and compare the clinicopathological features, perioperative outcomes, and prognosis of patients with resectable PDAC who underwent NACRT followed by curative pancreatic resection, focusing on distinguishing between Ph and Pbt PDACs.
METHODS
We included 107 patients with resectable PDAC who underwent curative resection following NACRT between 2009 and 2023. Clinicopathological features, perioperative and prognostic outcomes, recurrence patterns, and prognoses were compared between Ph and Pbt PDAC groups.
RESULTS
Tumors were found in the Ph and Pbt in 64 and 43 patients, respectively. Albumin levels and lymphocyte-to-monocyte ratios after NACRT were significantly lower in the Ph group than in the Pbt group. The Pbt group showed significantly higher rates of positive peritoneal lavage cytology and serosal, arterial, and portal vein invasion than the Ph group did. Overall and recurrence-free survival were similar between the two groups. The most common site of initial postoperative recurrence was the lung only in both groups; however, the rate of peritoneal dissemination only was significantly higher in the Pbt group than in the Ph group.
CONCLUSIONS
The prognoses based on tumor locations in the Ph and Pbt after surgery following NACRT are similar. Following the resection of resectable Pbt PDAC, the possibility of peritoneal dissemination recurrence should be considered.
Topics: Humans; Prognosis; Neoadjuvant Therapy; Retrospective Studies; Chemoradiotherapy; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Pancreatectomy; Adenocarcinoma
PubMed: 38383175
DOI: 10.1016/j.pan.2024.02.007 -
ACS Nano Feb 2024Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective peritoneal models has hindered the exploration of the potential mechanisms...
Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective peritoneal models has hindered the exploration of the potential mechanisms behind gastric cancer's peritoneal metastasis. An accumulating body of research indicates that small extracellular vesicles (sEVs) play an indispensable role in peritoneal metastasis of gastric cancer cells. In this study, a biomimetic peritoneum was constructed. The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, and it enables the recurrence of peritoneal metastasis process . Based on this model, the association between the mechanical properties of sEVs and the invasiveness of gastric cancer was identified. By performing nanomechanical analysis on sEVs, we found that the Young's modulus of sEVs can be utilized to differentiate between malignant clinical samples (ascites) and nonmalignant clinical samples (peritoneal lavage). Furthermore, patients' ascites-derived sEVs were verified to stimulate the mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis. In summary, nanomechanical analysis of living sEVs could be utilized for the noninvasive diagnosis of malignant degree and peritoneal metastasis of gastric cancer. This finding is expected to contribute future treatments.
Topics: Humans; Peritoneum; Stomach Neoplasms; Peritoneal Neoplasms; Ascites; Biomimetics; Extracellular Vesicles
PubMed: 38349890
DOI: 10.1021/acsnano.3c02285 -
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 -
World Journal of Surgery Feb 2024The recurrence of acute diverticulitis (AD) of the colon is frequent and leads to hospital readmissions and the need for elective surgery in selected cases. It is... (Observational Study)
Observational Study
INTRODUCTION
The recurrence of acute diverticulitis (AD) of the colon is frequent and leads to hospital readmissions and the need for elective surgery in selected cases. It is important to individualize risk factors and develop predictive tools for their identification.
MATERIALS AND METHODS
This prospective observational study included 368 patients who were diagnosed with AD between 2016 and 2021 in a tertiary general university hospital during their first episode and who had a good response to antibiotic, percutaneous, or peritoneal lavage treatment. Univariate and multivariate Cox regression analyses of the variables associated with recurrence were performed. Subsequently, a predictive risk score was developed and validated through survival studies.
RESULTS
After a median follow-up of 50 months, there were 71 (19.3%) cases of recurrence out of a total of 368 patients. The mean time of recurrence was 15 months, and 73.3% of cases of recurrence occurred before 2 years of follow-up. Recurrence was independently associated with presentation with colonic perforation in the antimesenteric location (HR 3.67 95% CI [1.59-8.4]) and a CRP level greater than 100 mg/dl (HR 1.69 95% CI [1.04-2.77). A score with 5 variables was created that differentiated two risk groups: intermediate risk (0-3 points), with 19% recurrence and high risk (more than 3 points), with 42% recurrence.
CONCLUSIONS
The risk of recurrence after the first episode of diverticulitis can be estimated using predictive scores. The detection of high-risk patients facilitates the individualization of follow-up and treatment.
Topics: Humans; Diverticulitis, Colonic; Recurrence; Diverticulitis; Risk Factors; Prospective Studies; Retrospective Studies
PubMed: 38310307
DOI: 10.1002/wjs.12045 -
International Journal of Surgery Case... Feb 2024Although abdominal computed tomography angiography (CTA) may be a gold standard for early diagnosis of small intestinal microperforation, early missed and delayed...
INTRODUCTION AND IMPORTANCE
Although abdominal computed tomography angiography (CTA) may be a gold standard for early diagnosis of small intestinal microperforation, early missed and delayed diagnosis are often important factors leading to poor prognosis. The cellular morphology diagnosis of abdominal puncture fluid (DAPF) or diagnostic peritoneal lavage (DPL) may have unexpected clinical outcomes.
CASE PRESENTATION
We report a case of small bowel microperforation which dues to BAT. A 39-year-old male with a chief complaint of "multiple injuries to the whole body from a car accident within 7 hours" was admitted to the trauma center. The first abdominal CTA ruled out perforation of abdominal parenchymatous organs and gastrointestinal tract. Subsequently, the patient underwent emergency surgery for traumatic shock, followed by clinical manifestations of persistent fever and septic shock. After diagnostic abdominal puncture fluid cell morphology examination, intestinal perforation was first considered.
CLINICAL DISCUSSION
Routine examination of abdominal puncture fluid can usually roughly determine the condition of visceral trauma, especially quickly and conveniently determine whether there is intra-peritoneal bleeding. However specific diagnostic components which were found in the cell images of abdominal puncture fluid also showed the clinical value of cellular morphology of DAPF.
CONCLUSION
The cellular morphology examination of DAPF/DPL may be the simplest, fastest, and most effective method for diagnosing small intestinal perforation due to blunt abdominal trauma(BAT). The value of DAPF /DPL in traumatic gastrointestinal injury cannot be ignored, especially for patients with BAT.
PubMed: 38306870
DOI: 10.1016/j.ijscr.2024.109316 -
Gan To Kagaku Ryoho. Cancer &... Dec 2023A woman in her 70s underwent distal pancreatectomy(D2 dissection)for a pancreatic tail carcinoma after a close examination of the cause of her poorly controlled diabetes...
A woman in her 70s underwent distal pancreatectomy(D2 dissection)for a pancreatic tail carcinoma after a close examination of the cause of her poorly controlled diabetes mellitus. Intraoperative rapid peritoneal washing cytology showed no malignant findings, but histopathological examination revealed Ptb, TS2, tub2, pT3, ly1, v3, ne3, mpd0, pS0, pRP1, pOO0, pPCM0, pDPM0, pN0, pM0, pCY1, pStage ⅡA, R0(Pancreatic Cancer Treatment Protocol 7th Edition). The patient was treated with S-1 therapy for 6 months postoperatively and is alive 1 year and 9 months without recurrence. The prognosis after resection of pancreatic cancer with positive peritoneal washing cytology is said to be worse than that of patients with negative, because of the high recurrence rate of peritoneal metastasis. We report a case of pancreatic tail carcinoma with positive peritoneal washing cytology with recurrence-free survival after surgery and chemotherapy.
Topics: Female; Humans; Carcinoma; Pancreatectomy; Pancreatic Neoplasms; Peritoneal Lavage; Peritoneum; Prognosis; Aged
PubMed: 38303272
DOI: No ID Found -
Gan To Kagaku Ryoho. Cancer &... Dec 2023A case is a female of 61-year-old. She visited her local doctor with a chief complaint of frequent burping. She was hospitalized for gastric cancer with pyloric...
A case is a female of 61-year-old. She visited her local doctor with a chief complaint of frequent burping. She was hospitalized for gastric cancer with pyloric stenosis. Although open gastrectomy was planned the gastric cancer was unresectable due to pancreatic invasion and peritoneal dissemination. Cytology with abdominal lavage was CY0. She underwent gastrojejunostomy. She was treated by 19 courses of chemotherapy with SOX therapy for 2 years. The tumor reduced, and she underwent distal gastrectomy as conversion surgery. Pathological findings were por2>muc>tub2>tub1, ypT2(ypMP), INF c, int, Ly1a, V0, pPM0, pDM0, pN0(0/43), ypStage ⅠB, R0, Grade 2b. Adjuvant chemotherapy(S-1 and docetaxel)was administered after conversion surgery. She is alive without recurrence for 1 year and 6 months after gastrectomy. We report a case of Stage Ⅳ gastric cancer treated with conversion surgery after chemotherapy.
Topics: Humans; Female; Middle Aged; Stomach Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Gastrectomy; Docetaxel; Chemotherapy, Adjuvant
PubMed: 38303169
DOI: No ID Found -
Molecular Biology Reports Jan 2024Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic...
BACKGROUND
Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic potential was aimed.
METHODS AND RESULTS
Three extracts of A. aspera [aqueous (AaAq), hydroalcoholic (AaHA), ethanolic (AaEt)] were evaluated for their potency against C48/80-induced anaphylaxis in mice at 200 mg/kg BW oral dose. The effective dose of the most potent extract was determined through its effect on C48/80-induced anaphylaxis, and was further analyzed through its effect on mast cell degranulation, histamine-induced bronchospasm and ovalbumin (OVA)-induced asthma in a murine model. Among the three extracts, AaAq was found to be most potent at 200 mg/kg BW. AaAq 400 (400 mg/kg BW) was found to be the most effective dose in terms of inhibition of mortality and histamine level. AaAq 400 prevented the peritoneal and mesenteric mast cells from undergoing morphological changes due to degranulation induced by C48/80. Further, AaAq 400 delayed pre-convulsive time in histamine-induced bronchospasm. In the OVA-induced asthma model, AaAq 400 inhibited the level of inflammatory cell count in blood, bronchoalveolar lavage fluid and peritoneal fluid of mice. The Th2 cytokines (IL-4, IL-5, IL-13), TGF-β and OVA-specific IgE were also reduced as evaluated by ELISA. Also, significant reduction in IL-5 (an eosinophilia indicator) transcript abundance and lung inflammatory score was observed. AaAq was safe up to 4000 mg/kg BW.
CONCLUSIONS
Thus AaAq 400 possesses significant antiallergic potential and acts via attenuation of C48/80-induced anaphylaxis and inhibition of mast cell degranulation. It reduces pre-convulsive dyspnea in histamine-induced bronchospasm and Th2 cytokines in asthmatic mice.
Topics: Animals; Mice; Ovalbumin; Achyranthes; Histamine; Anaphylaxis; p-Methoxy-N-methylphenethylamine; Bronchial Spasm; Disease Models, Animal; Interleukin-5; Asthma; Anti-Allergic Agents; Cytokines
PubMed: 38270668
DOI: 10.1007/s11033-023-09137-2