Anti-adhesion decreases negative tissue changes in a murine model of vasectomy.
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ABSTRACT:
SUBMITTER: Kavoussi PK
PROVIDER: S-EPMC9732707 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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Anti-adhesion decreases negative tissue changes in a murine model of vasectomy.
Translational andrology and urology 20221101 11
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Project description:BackgroundPost-vasectomy pain syndrome (PVPS) is difficult to treat. Direct damage to the vas deferens, inflammation, compression of nerves through fibrotic adhesions, and congestion of the epididymis are known to cause PVPS. The purpose of this study was to evaluate whether the application of anti-adhesion agents after vasectomy can reduce the degree of adhesion and fibrosis in a rat model.MethodsIn the study, 11 Sprague-Dawley rats (22 vas deferens) from each group were evaluated. In the experimental group, surgery was terminated after applying the anti-adhesion agent; this was not applied in the control group. After 14 days of vasectomy, the scrotum was dissected to evaluate the degree of gross adhesion at the vasectomy site. Histological examination of the surrounding tissues, including the vas deferens and the spermatic cord, was also performed.ResultsAdhesions were not observed in 72.73% (16/22) rats from the experimental group, in which the anti-adhesion agent was applied; in contrast, the incidence of adhesions in the control group was 100%. There was a statistically significant relationship between the distribution of grades for adhesion and anti-adhesion agent (chi-square, P<0.001). On classification of fibrosis and inflammation, application of the anti-adhesion agent was significantly associated with lower grade inflammation and fibrosis compared to that of the control group (chi-square, P=0.001). The rate of intact muscle structure was 90.91% (20/22) in the experimental group, and 36.36% (8/22) in the control group, and the application of the anti-adhesion agent demonstrated significant association with preservation of intact muscle structure (chi-square, P<0.001).ConclusionsThe application of an anti-adhesion agent after vasectomy prevented the development of adhesion, fibrosis, and inflammation reaction and further reduced structural destruction.
| S-EPMC9547164 | biostudies-literature
Project description:BackgroundFree radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction. We therefore assessed the efficacy of the mitochondria-targeted anti-oxidant MitoQ in reducing IR injury in a murine heterotopic cardiac transplant model.MethodsHearts from C57BL/6 donor mice were flushed with storage solution alone, solution containing the anti-oxidant MitoQ, or solution containing the non-anti-oxidant decyltriphenylphosphonium control and exposed to short (30 minutes) or prolonged (4 hour) cold preservation before transplantation. Grafts were transplanted into C57BL/6 recipients and analyzed for mitochondrial reactive oxygen species production, oxidative damage, serum troponin, beating score, and inflammatory markers 120 minutes or 24 hours post-transplant.ResultsMitoQ was taken up by the heart during cold storage. Prolonged cold preservation of donor hearts before IR increased IR injury (troponin I, beating score) and mitochondrial reactive oxygen species, mitochondrial DNA damage, protein carbonyls, and pro-inflammatory cytokine release 24 hours after transplant. Administration of MitoQ to the donor heart in the storage solution protected against this IR injury by blocking graft oxidative damage and dampening the early pro-inflammatory response in the recipient.ConclusionsIR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury.
| S-EPMC4626443 | biostudies-literature
Project description: Not available
| S-BSST942 | biostudies-other
Project description:Ovarian cancer is the fifth leading cause of cancer deaths in U.S. women and the deadliest gynecologic malignancy. This lethality is largely due to the fact that most cases are diagnosed at metastatic stages of the disease when the prognosis is poor. Epidemiologic studies consistently demonstrate that parous women have a reduced risk of developing ovarian cancer, with a greater number of births affording greater protection; however little is known about the impact of parity on ovarian cancer metastasis. Here we report that multiparous mice are less susceptible to ovarian cancer metastasis in an age-matched syngeneic murine allograft model. Interferon pathways were found to be upregulated in healthy adipose tissue of multiparous mice, suggesting a possible mechanism for the multiparous-related protective effect against metastasis. This protective effect was found to be lost with age. Based on this work, future studies exploring therapeutic strategies which harness the multiparity-associated protective effect demonstrated here are warranted.
| S-EPMC6317723 | biostudies-literature
Project description:BackgroundIntra-abdominal adhesions develop after nearly every abdominal surgery, commonly causing female infertility, chronic pelvic pain, and small bowel obstruction. Pentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The aim of this study was to investigate whether PTX can reduce post-operative intra-abdominal adhesion formation via collagen deposition, tissue plasminogen activator (tPA) level, inflammation, angiogenesis, and fibrosis.MethodsSeventy male BALB/c mice were randomized into one of three groups: (1) sham group without peritoneal adhesion model; (2) peritoneal adhesion model (PA group); (3) peritoneal adhesion model with PTX (100 mg/kg/day i.p.) administration was started on preoperative day 2 and continued daily (PA + PTX group). On postoperative day 3 and day 7, adhesions were assessed using the Lauder scoring system. Parietal peritoneum was obtained for histological evaluation with hematoxylin and eosin (HE) and picrosirius red staining. Fibrinolysis was analyzed by tPA protein levels in the peritoneum by ELISA. Immunohistological analysis was also conducted using markers for angiogenesis (ki67+/CD31+), inflammation (F4/80+) and fibrosis (FSP-1+ and α-SMA+). All the comparisons were made by comparing the PA group with the PTX treated PA group, and p < 0.05 was considered statistically significant.ResultsIntra-abdominal adhesions were markedly reduced by PTX treatment. Compared with the PA group, PTX treatment had lower adhesion scores than the PA group on both day 3 and day 7 (p < 0.05). Histological evaluations found that PTX treatment reduced collagen deposition and adhesion thickening. ELISA analysis showed that PTX treatment significantly increased the level of tPA in the peritoneum. In addition, in the immunohistological analysis, PTX treatment was found to significantly decrease the number of ki67+/CD31+ cells at the site of adhesion. Finally, we also observed that in the PTX treated group, there was a reduction in the expression of F4/80+, FSP-1+, and α-SMA+ cells at the site of adhesion.ConclusionPTX may decrease intra-abdominal adhesion formation via increasing peritoneal fibrinolytic activity, suppressing angiogenesis, decreasing collagen synthesis, and reducing peritoneal fibrosis. Our findings suggest that PTX can be used to decrease post-operative intra-abdominal adhesion formation.
| S-EPMC6110259 | biostudies-literature
Project description:Cannabidiol (CBD) (25 mg/kg peroral) treatment was shown to improve metabolic outcomes in ovariectomized (OVX) mice deficient in 17β-estradiol (E2). Herein, CBD effects on intestinal and hepatic bile acids (BAs) and inflammation were investigated. Following RNA sequencing of colon tissues from vehicle (VEH)- or CBD-treated sham surgery (SS) or OVX mice (n = 4 per group), differentially expressed genes (DEGs) were sorted in ShinyGO. Inflammatory response and bile secretion pathways were further analyzed. Colon content and hepatic BAs were quantified by LC-MS (n = 8-10 samples/group). Gut organoids were treated with CBD (100, 250, 500 µM) with or without TNFα and lipopolysaccharide (LPS) followed by mRNA extraction and qPCR to assess CBD-induced changes to inflammatory markers. The expression of 78 out of 114 inflammatory response pathway genes were reduced in CBD-treated OVX mice relative to vehicle (VEH)-treated OVX mice. In contrast, 63 of 111 inflammatory response pathway genes were increased in CBD-treated sham surgery (SS) mice compared to VEH-treated SS group and 71 of 121 genes were increased due to ovariectomy. CBD did not alter BA profiles in colon content or liver. CBD repressed Tnf and Nos2 expression in intestinal organoids in a dose-dependent manner. In conclusion, CBD suppressed colonic inflammatory gene expression in E2-deficient mice but was pro-inflammatory in E2-sufficient mice suggesting CBD activity in the intestine is E2-dependent.
| S-EPMC9855871 | biostudies-literature
Project description:Cancer immunotherapy employing checkpoint inhibitors holds great promise across diverse cancers; nonetheless, a substantial proportion of patients (ranging from 55 to 87%) remain unresponsive to this treatment. To amplify therapeutic efficiency, we propose a synergistic therapeutic strategy that entails the deployment of targeted nano-sized particles carrying Toll-like receptor (TLR) agonists to the tumor site. This innovative approach seeks to activate intratumoral antigen-presenting cells using bioengineered outer membrane vesicles (OMVs) derived from gram-negative bacteria. These OMVs possess inherent attributes of surface-exposed immune stimulators and TLR-activating components, rendering them intriguing candidates for investigation. These OMVs were meticulously designed to selectively target cancer cells exhibiting an overexpression of epidermal growth factor receptor (EGFR). To gauge the precision of this targeting, the conducted affinity-based assays aimed at determining the equilibrium dissociation constant of the single-chain variable fragment employed for this purpose. In vitro experiments confirmed the OMVs' proficiency in adhering to EGFR-overexpressed cancer cells. Moreover, the evaluation extended to an in vivo context, where the therapeutic effect of nanovesicles was appraised within the tumor microenvironment of the triple-negative breast cancer mouse model. Notably, both intraperitoneal and intratumoral administrations of nanovesicles exhibited the ability to activate natural killer cells and skew M2 macrophage towards an M1 phenotype. The combined scrutiny of in vitro and in vivo findings underscores the potential efficiency of OMVs as a promising strategy for future anti-tumor endeavors.
| S-EPMC10541432 | biostudies-literature
Project description:Background and purposeCerebral cavernous malformations (CCMs) are characterized by grossly dilated capillaries, associated with vascular leak and hemorrhage, and occur in sporadic or inherited (autosomal-dominant) forms with mutations in 1 of 3 gene loci (CCM 1, 2 or 3). We previously reported that the CCM1 protein (KRIT1) localizes to endothelial cell-cell junctions and loss of KRIT1 leads to junctional instability associated with activation of RhoA and its effector Rho kinase. Although Rho kinase inhibition has been proposed as potential therapy for CCM, there has been no demonstration of a therapeutic effect on CCM lesion genesis in vivo.MethodsOur recently generated a model of CCM1 disease (Ccm1(+/-)Msh2(-/-)) was treated with the Rho kinase inhibitor fasudil (100 mg/kg/day administered in drinking water from weaning to 5 months of age), or placebo, and blindly assessed CCM lesion burden by systematic survey of animals' brains. For comparison, we also assessed therapeutic effect in previously described Ccm2(+/-)Trp53(-/-) mice treated with the same dose and duration of fasudil and placebo.ResultsFasudil-treated Ccm1(+/-)Msh2(-/-) mice had a significantly decreased prevalence of CCM lesions compared with placebo controls. Lesions in treated animals were smaller and less likely associated with hemorrhage, inflammation, and endothelial proliferation and exhibited decreased expression of Rho kinase activation biomarkers. A therapeutic effect was also documented in Ccm2(+/-)Trp53(-/-) mice.ConclusionsThis represents the first report of therapeutic benefit of pharmacological therapy in development and progression of CCMs and indicates that Rho kinase activation is a critical step in CCM lesion genesis and maturation.
| S-EPMC3265629 | biostudies-literature
Project description:BackgroundSevere acute muscle injury results in massive cell damage, causing the release of actin into extracellular fluids where it complexes with the vitamin D-binding protein (DBP). We hypothesized that a systemic DBP deficiency would result in a less proinflammatory phenotype.MethodsC57BL/6 wild-type (WT) and DBP-deficient (DBP-/-) mice received intramuscular injections of either 50% glycerol or phosphate-buffered saline into thigh muscles. Muscle injury was assessed by histology. Cytokine levels were measured in plasma, muscle, kidney, and lung.ResultsAll animals survived the procedure, but glycerol injection in both strains of mice showed lysis of skeletal myocytes and inflammatory cell infiltrate. The muscle inflammatory cell infiltrate in DBP-deficient mice had remarkably few neutrophils as compared with WT mice. The neutrophil chemoattractant CXCL1 was significantly reduced in muscle tissue from DBP-/- mice. However, there were no other significant differences in muscle cytokine levels. In contrast, plasma obtained 48 hours after glycerol injection revealed that DBP-deficient mice had significantly lower levels of systemic cytokines interleukin 6, CCL2, CXCL1, and granulocyte colony-stimulating factor. Lung tissue from DBP-/- mice showed significantly decreased amounts of CCL2 and CXCL1 as compared with glycerol-treated WT mice. Several chemokines in kidney homogenates following glycerol-induced injury were significantly reduced in DBP-/- mice: CCL2, CCL5, CXCL1, and CXCL2.ConclusionsAcute muscle injury triggered a systemic proinflammatory response as noted by elevated plasma cytokine levels. However, mice with a systemic DBP deficiency demonstrated a change in their cytokine profile 48 hours after muscle injury to a less proinflammatory phenotype.
| S-EPMC5970036 | biostudies-literature
Project description:Osteosarcoma (OS) is a primary malignant bone tumor with a high propensity for local recurrence and distant metastasis. We previously showed a secreted, dominant-negative LRP5 receptor (DNLRP5) suppressed in vitro migration and invasion of the OS cell line SaOS-2. Therefore, we hypothesized DNLRP5 also has in vivo antitumor activity against OS. We used the 143B cell line as a model to study the effect of DNLRP5 by stable transfection. Inhibition of Wnt signaling by DNLRP5 was verified by a reduction in TOPFLASH luciferase activity. In soft agar, DNLRP5-transfected 143B cells formed fewer and smaller colonies than control transfected cells. DNLRP5 transfection reduced in vivo tumor growth of 143B cells in nude mice. DNLRP5 also decreased in vitro cellular motility in a scratch wound assay. In a spontaneous pulmonary metastasis model, DNLRP5 reduced both the size and number of lung metastatic nodules. The reduction in cellular invasiveness by DNLRP5 was associated with decreased expression of matrix metalloproteinase-2, N-cadherin, and Snail. Our data suggest canonical Wnt/LRP5 signaling reflects an important underlying mechanism of OS progression. Therefore, strategies to suppress LRP5-mediated signaling in OS cells may lead to a reduction in local or systemic disease burden.
| S-EPMC2493003 | biostudies-other