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Journal of Ethnopharmacology Jan 2024Carthami flos is a dried flower of the Asteraceae plant Carthamus tinctorius (L.). Danhong injection, composed of Carthami flos and Danshen can prevent the formation of...
ETHNOPHARMACOLOGICAL RELEVANCE
Carthami flos is a dried flower of the Asteraceae plant Carthamus tinctorius (L.). Danhong injection, composed of Carthami flos and Danshen can prevent the formation of postoperative peritoneal adhesions. Quercetin (QUE), an active compound of Carthami flos, has also been proved to prevent postoperative abdominal and uterine cavity adhesions. However, whether QUE is the key component in Carthami flos and the mechanism in preventing postoperative peritoneal adhesions has not been studied.
AIM OF THE STUDY
To predict whether QUE is the key molecule in Carthami flos and explore the effect and mechanism of QUE in preventing postoperative peritoneal adhesions.
MATERIALS AND METHODS
Drug composition and target analysis was used to predict the key component in Carthami flos. The method of cecum-sidewall abrasion was used to establish adhesion models, and the antiadhesion effect of QUE was evaluated with the adhesion scoring system. Network pharmacology was used to predict the targets and potential mechanism of QUE in preventing adhesion. The mechanism was further verified by immunofluorescence, Western blot, wound healing experiment, and molecular docking.
RESULTS
Quercetin was predicted to be the key to preventing postoperative peritoneal adhesions in Carthami flos. Animal experiments revealed that QUE effectively ameliorated adhesions and reduced the expression of mesothelial-mesenchymal transition (MMT) related markers and TGF-β1. Moreover, the TGF-β1/PI3K/AKT pathway was predicted via protein-protein interaction and Kyoto encyclopedia of Genes and Genomes enrichment analysis to play a crucial part in preventing adhesion by QUE. Furthermore, in vitro experiments and molecular docking demonstrated that QUE could block the TGF-β1/PI3K/AKT pathway through forming a stable combination with TβR-II, thereby inhibiting MMT and ameliorating peritoneal adhesion.
CONCLUSIONS
QUE can not only reduce postoperative TGF-β1 but also block the TGF-β1/PI3K/AKT pathway to inhibit MMT of mesothelial cells, and finally alleviate postoperative peritoneal adhesions. These findings may provide insights towards development of a safe and effective anti-adhesive drug for prevention of postoperative peritoneal adhesions.
Topics: Animals; Peritoneum; Transforming Growth Factor beta1; Quercetin; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Molecular Docking Simulation
PubMed: 37777024
DOI: 10.1016/j.jep.2023.117242 -
Peritoneal Dialysis International :... Jul 2022Transport of serum proteins from the circulation to peritoneal dialysate in peritoneal dialysis patients mainly focused on total protein. Individual proteins have hardly... (Review)
Review
Transport of serum proteins from the circulation to peritoneal dialysate in peritoneal dialysis patients mainly focused on total protein. Individual proteins have hardly been studied. We determined serum and effluent concentrations of four individual proteins with a wide molecular weight range routinely in the standardised peritoneal permeability analysis performed yearly in all participating patients. These include β-microglobulin, albumin, immunoglobulin G and α-macroglobulin. The dependency of transport of these proteins on their molecular weight and diffusion coefficient led to the development of the peritoneal protein restriction coefficient (PPRC), which is the slope of the relation between the peritoneal clearances of these proteins and their free diffusion coefficients in water, when plotted on a double logarithmic scale. The higher the PPRC, the more size restriction to transport. In this review, we discuss the results obtained on the PPRC under various conditions, such as effects of various osmotic agents, vasoactive drugs, peritonitis and the hydrostatic pressure gradient. Long-term follow-up of patients shows an increase of the PPRC, the possible causes of which are discussed. Venous vasculopathy of the peritoneal microcirculation is the most likely explanation.
Topics: Biological Transport; Dialysis Solutions; Humans; Peritoneal Dialysis; Peritoneum; Permeability; Protein Transport
PubMed: 35102776
DOI: 10.1177/08968608221075102 -
BMC Cancer Jun 2023Peritoneal metastasis is one of the main causes of death in patients with gastric cancer (GC). Galectin-1 regulates various undesirable biological behaviors in GC and...
BACKGROUND
Peritoneal metastasis is one of the main causes of death in patients with gastric cancer (GC). Galectin-1 regulates various undesirable biological behaviors in GC and may be key in GC peritoneal metastasis.
METHODS
In this study, we elucidated the regulatory role of galectin-1 in GC cell peritoneal metastasis. GC and peritoneal tissues underwent hematoxylin-eosin (HE), immunohistochemical (IHC), and Masson trichrome staining to analyze the difference in galectin-1 expression and peritoneal collagen deposition in different GC clinical stages. The regulatory role of galectin-1 in GC cell adhesion to mesenchymal cells and in collagen expression was determined using HMrSV5 human peritoneal mesothelial cells (HPMCs). Collagen and corresponding mRNA expression were detected with western blotting and reverse transcription PCR, respectively. The promoting effect of galectin-1 on GC peritoneal metastasis was verified in vivo. Collagen deposition and collagen I, collagen III, and fibronectin 1 (FN1) expression in the peritoneum of the animal models were detected by Masson trichrome and IHC staining.
RESULTS
Galectin-1 and collagen deposition in the peritoneal tissues was correlated with GC clinical staging and were positively correlated. Galectin-1 enhanced the ability of GC cells to adhere to the HMrSV5 cells by promoting collagen I, collagen III, and FN1 expression. The in vivo experiments confirmed that galectin-1 promoted GC peritoneal metastasis by promoting peritoneal collagen deposition.
CONCLUSION
Galectin-1-induced peritoneal fibrosis may create a favorable environment for GC cell peritoneal metastasis.
Topics: Animals; Humans; Galectin 1; Peritoneal Fibrosis; Peritoneal Neoplasms; Peritoneum; Stomach Neoplasms
PubMed: 37328752
DOI: 10.1186/s12885-023-11047-2 -
International Journal of Molecular... Nov 2019Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of long-term peritoneal dialysis (PD), which may even occur after patients have switched to... (Review)
Review
Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of long-term peritoneal dialysis (PD), which may even occur after patients have switched to hemodialysis (HD) or undergone kidney transplantation. The incidence of EPS varies across the globe and increases with PD vintage. Causative factors are the chronic exposure to bioincompatible PD solutions, which cause long-term modifications of the peritoneum, a high peritoneal transporter status involving high glucose concentrations, peritonitis episodes, and smoldering peritoneal inflammation. Additional potential causes are predisposing genetic factors and some medications. Clinical symptoms comprise signs of intestinal obstruction and a high peritoneal transporter status with incipient ultrafiltration failure. In radiological, macro-, and microscopic studies, a massively fibrotic and calcified peritoneum enclosed the intestine and parietal wall in such cases. Empirical treatments commonly used are corticosteroids and tamoxifen, which has fibrinolytic properties. Immunosuppressants like azathioprine, mycophenolate mofetil, or mTOR inhibitors may also help with reducing inflammation, fibrin deposition, and collagen synthesis and maturation. In animal studies, N-acetylcysteine, colchicine, rosiglitazone, thalidomide, and renin-angiotensin system (RAS) inhibitors yielded promising results. Surgical treatment has mainly been performed in severe cases of intestinal obstruction, with varying results. Mortality rates are still 25-55% in adults and about 14% in children. To reduce the incidence of EPS and improve the outcome of this devastating complication of chronic PD, vigorous consideration of the risk factors, early diagnosis, and timely discontinuation of PD and therapeutic interventions are mandatory, even though these are merely based on empirical evidence.
Topics: Adrenal Cortex Hormones; Humans; Immunosuppressive Agents; Peritoneal Dialysis; Peritoneal Fibrosis; Peritoneum; Renin-Angiotensin System; Risk Factors
PubMed: 31744097
DOI: 10.3390/ijms20225765 -
Biomolecules Dec 2021Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer... (Review)
Review
Formation of peritoneal adhesions (PA) is one of the major complications following intra-abdominal surgery. It is primarily caused by activation of the mesothelial layer and underlying tissues in the peritoneal membrane resulting in the transition of mesothelial cells (MCs) and fibroblasts to a pro-fibrotic phenotype. Pro-fibrotic transition of MCs-mesothelial-to-mesenchymal transition (MMT), and fibroblasts activation to myofibroblasts are interconnected to changes in cellular metabolism and culminate in the deposition of extracellular matrix (ECM) in the form of fibrotic tissue between injured sides in the abdominal cavity. However, ECM is not only a mechanical scaffold of the newly synthetized tissue but reciprocally affects fibrosis development. Hyaluronan (HA), an important component of ECM, is a non-sulfated glycosaminoglycan consisting of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA) that can affect the majority of processes involved in PA formation. This review considers the role of endogenously produced HA in the context of different fibrosis-related pathologies and its overlap in the development of PA.
Topics: Epithelium; Fibroblasts; Hyaluronic Acid; Myofibroblasts; Peritoneum
PubMed: 35053193
DOI: 10.3390/biom12010045 -
BJS Open Sep 2023The open abdomen is an innovation that greatly improved surgical understanding of damage control, temporary abdominal closure, staged abdominal reconstruction, viscera... (Review)
Review
BACKGROUND
The open abdomen is an innovation that greatly improved surgical understanding of damage control, temporary abdominal closure, staged abdominal reconstruction, viscera and enteric fistula care, and abdominal wall reconstruction. This article provides an evidence-informed, expert, comprehensive narrative review of the open abdomen in trauma, acute care, and vascular and endovascular surgery.
METHODS
A group of 12 international trauma, acute care, and vascular and endovascular surgery experts were invited to review current literature and important concepts surrounding the open abdomen.
RESULTS
The open abdomen may be classified using validated systems developed by a working group in 2009 and modified by the World Society of the Abdominal Compartment Syndrome-The Abdominal Compartment Society in 2013. It may be indicated in major trauma, intra-abdominal sepsis, vascular surgical emergencies, and severe acute pancreatitis; to facilitate second look laparotomy or avoid or treat abdominal compartment syndrome; and when the abdominal wall cannot be safely closed. Temporary abdominal closure and staged abdominal reconstruction methods include a mesh/sheet, transabdominal wall dynamic fascial traction, negative pressure wound therapy, and hybrid negative pressure wound therapy and dynamic fascial traction. This last method likely has the highest primary fascial closure rates. Direct peritoneal resuscitation is currently an experimental strategy developed to improve primary fascial closure rates and reduce complications in those with an open abdomen. Primary fascial closure rates may be improved by early return to the operating room; limiting use of crystalloid fluids during the surgical interval; and preventing and/or treating intra-abdominal hypertension, enteric fistulae, and intra-abdominal collections after surgery. The majority of failures of primary fascial closure and enteroatmospheric fistula formation may be prevented using effective temporary abdominal closure techniques, providing appropriate resuscitation fluids and nutritional support, and closing the abdomen as early as possible.
CONCLUSION
Subsequent stages of the innovation of the open abdomen will likely involve the design and conduct of prospective studies to evaluate appropriate indications for its use and effectiveness and safety of the above components of open abdomen management.
Topics: Humans; Acute Disease; Intra-Abdominal Hypertension; Prospective Studies; Pancreatitis; Peritoneum; Fistula
PubMed: 37882630
DOI: 10.1093/bjsopen/zrad084 -
The Journal of Maternal-fetal &... Dec 2023To demonstrate the surgical and morbidity differences between upper and lower parametrial placenta invasion (PPI).
OBJECTIVE
To demonstrate the surgical and morbidity differences between upper and lower parametrial placenta invasion (PPI).
MATERIALS AND METHODS
Forty patients with placenta accreta spectrum (PAS) into the parametrium underwent surgery between 2015 and 2020. Based on the peritoneal reflection, the study compared two types of parametrial placental invasion (PPI), upper or lower. Surgical approach to PAS follows a conservative-resective method. Before delivery, surgical staging by pelvic fascia dissection established a final diagnosis of placental invasion. In upper PPI cases, the team attempted to repair the uterus after resecting all invaded tissues or performing a hysterectomy. In cases of lower PPI, experts performed a hysterectomy in all cases. The team only used proximal vascular (aortic occlusion) control in cases of lower PPI. Surgical dissection for lower PPI started finding the ureter in the pararectal space, ligating all the tissues (placenta and newly formed vessels) to create a tunnel to release the ureter from the placenta and placenta suppletory vessels. Overall, at least three pieces of the invaded area were sent for histological analysis.
RESULTS
Forty patients with PPI were included, 13 in the upper parametrium and 27 in the lower parametrium. MRI indicated PPI in 33/40 patients; in three, the diagnosis was presumed by ultrasound or medical background. The intrasurgical staging categorizes 13 cases of PPI performed and finds diagnosis in seven undetected cases. The expertise team completed a total hysterectomy in 2/13 upper PPI cases and all lower PPI cases (27/27). Hysterectomies in the upper PPI group were performed by extensive damage of the lateral uterine wall or with a tube compromise. Ureteral injury ensued in six cases, corresponding to cases without catheterization or incomplete ureteral identification. All aortic vascular proximal control (aortic balloon, internal aortic compression, or aortic loop) was efficient for controlling bleeding; in contrast, ligature of the internal iliac artery resulted in a useless procedure, resulting in uncontrollable bleeding and maternal death (2/27). All patients had antecedents of placental removal, abortion, curettage after a cesarean section, or repeated D&C.
CONCLUSIONS
Lower PAS parametrial involvement is uncommon but associated with elevated maternal morbidity. Upper and lower PPI has different surgical risks and technical approaches; consequently, an accurate diagnosis is needed. The clinical background of manual placental removal, abortion, and curettage after a cesarean or repeated D&C could be ideally studied to diagnose a possible PPI. For patients with high-risk antecedents or unsure ultrasound, a T2 weight MRI is always recommended. Performing comprehensive surgical staging in PAS allows the efficient diagnosis of PPI before using some procedures.
Topics: Pregnancy; Humans; Female; Placenta Accreta; Cesarean Section; Peritoneum; Placenta; Hysterectomy; Retrospective Studies; Morbidity
PubMed: 36966802
DOI: 10.1080/14767058.2023.2183764 -
Korean Journal of Radiology May 2023Diagnosing bowel and mesenteric trauma poses a significant challenge to radiologists. Although these injuries are relatively rare, immediate laparotomy may be indicated... (Review)
Review
Diagnosing bowel and mesenteric trauma poses a significant challenge to radiologists. Although these injuries are relatively rare, immediate laparotomy may be indicated when they occur. Delayed diagnosis and treatment are associated with increased morbidity and mortality; therefore, timely and accurate management is essential. Additionally, employing strategies to differentiate between major injuries requiring surgical intervention and minor injuries considered manageable via non-operative management is important. Bowel and mesenteric injuries are among the most frequently overlooked injuries on trauma abdominal computed tomography (CT), with up to 40% of confirmed surgical bowel and mesenteric injuries not reported prior to operative treatment. This high percentage of falsely negative preoperative diagnoses may be due to several factors, including the relative rarity of these injuries, subtle and non-specific appearances on CT, and limited awareness of the injuries among radiologists. To improve the awareness and diagnosis of bowel and mesenteric injuries, this article provides an overview of the injuries most often encountered, imaging evaluation, CT appearances, and diagnostic pearls and pitfalls. Enhanced diagnostic imaging awareness will improve the preoperative diagnostic yield, which will save time, money, and lives.
Topics: Humans; Wounds, Nonpenetrating; Abdominal Injuries; Intestines; Mesentery; Tomography, X-Ray Computed; Retrospective Studies
PubMed: 37133211
DOI: 10.3348/kjr.2022.0998 -
Journal For Immunotherapy of Cancer Apr 2023Gastric cancer (GC) that metastasizes to the peritoneum is fatal. CF33 and its genetically modified derivatives show cancer selectivity and oncolytic potency against...
BACKGROUND
Gastric cancer (GC) that metastasizes to the peritoneum is fatal. CF33 and its genetically modified derivatives show cancer selectivity and oncolytic potency against various solid tumors. CF33-hNIS and CF33-hNIS-antiPDL1 have entered phase I trials for intratumoral and intravenous treatments of unresectable solid tumors (NCT05346484) and triple-negative breast cancer (NCT05081492). Here, we investigated the antitumor activity of CF33-oncolytic viruses (OVs) against GC and CF33-hNIS-antiPDL1 in the intraperitoneal (IP) treatment of GC peritoneal metastases (GCPM).
METHODS
We infected six human GC cell lines AGS, MKN-45, MKN-74, KATO III, SNU-1, and SNU-16 with CF33, CF33-GFP, or CF33-hNIS-antiPDL1 at various multiplicities of infection (0.01, 0.1, 1.0, and 10.0), and performed viral proliferation and cytotoxicity assays. We used immunofluorescence imaging and flow cytometric analysis to verify virus-encoded gene expression. We evaluated the antitumor activity of CF33-hNIS-antiPDL1 following IP treatment (3×10 pfu × 3 doses) in an SNU-16 human tumor xenograft model using non-invasive bioluminescence imaging.
RESULTS
CF33-OVs showed dose-dependent infection, replication, and killing of both diffuse and intestinal subtypes of human GC cell lines. Immunofluorescence imaging showed virus-encoded GFP, hNIS, and anti-PD-L1 antibody scFv expression in CF33-OV-infected GC cells. We confirmed GC cell surface PD-L1 blockade by virus-encoded anti-PD-L1 scFv using flow cytometry. In the xenograft model, CF33-hNIS-antiPDL1 (IP; 3×10 pfu × 3 doses) treatment significantly reduced peritoneal tumors (p<0.0001), decreased amount of ascites (62.5% PBS vs 25% CF33-hNIS-antiPDL1) and prolonged animal survival. At day 91, seven out of eight mice were alive in the virus-treated group versus one out of eight in the control group (p<0.01).
CONCLUSIONS
Our results show that CF33-OVs can deliver functional proteins and demonstrate effective antitumor activity in GCPM models when delivered intraperitoneally. These preclinical results will inform the design of future peritoneal-directed therapy in GCPM patients.
Topics: Humans; Mice; Animals; Oncolytic Viruses; Peritoneal Neoplasms; Oncolytic Virotherapy; Peritoneum; Stomach Neoplasms
PubMed: 37019471
DOI: 10.1136/jitc-2022-006280 -
Journal of Leukocyte Biology Apr 2021The peritoneal cavity is a fluid filled space that holds most of the abdominal organs, including the omentum, a visceral adipose tissue that contains milky spots or... (Review)
Review
The peritoneal cavity is a fluid filled space that holds most of the abdominal organs, including the omentum, a visceral adipose tissue that contains milky spots or clusters of leukocytes that are organized similar to those in conventional lymphoid tissues. A unique assortment of leukocytes patrol the peritoneal cavity and migrate in and out of the milky spots, where they encounter Ags or pathogens from the peritoneal fluid and respond accordingly. The principal role of leukocytes in the peritoneal cavity is to preserve tissue homeostasis and secure tissue repair. However, when peritoneal homeostasis is disturbed by inflammation, infection, obesity, or tumor metastasis, specialized fibroblastic stromal cells and mesothelial cells in the omentum regulate the recruitment of peritoneal leukocytes and steer their activation in unique ways. In this review, the types of cells that reside in the peritoneal cavity, the role of the omentum in their maintenance and activation, and how these processes function in response to pathogens and malignancy will be discussed.
Topics: Adaptive Immunity; Animals; Humans; Immunity; Immunity, Innate; Omentum; Peritoneal Cavity
PubMed: 32881077
DOI: 10.1002/JLB.5MIR0720-271RR