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International Journal of Gynaecology... Mar 2024To evaluate vaginal delivery in obese women who underwent cervical ripening at term using a dinoprostone vaginal insert or a cervical ripening balloon (CRB), and to...
OBJECTIVE
To evaluate vaginal delivery in obese women who underwent cervical ripening at term using a dinoprostone vaginal insert or a cervical ripening balloon (CRB), and to assess maternal and neonatal morbidity according to the method.
METHODS
A prospective cohort study including obese women with a live singleton fetus in cephalic presentation who required cervical ripening at term (≥37 weeks) for maternal and/or fetal disease using a dinoprostone vaginal insert or a CRB. The primary outcome was vaginal delivery. Secondary outcomes were a favorable cervix (Bishop score >6) after 24 h, the time from device insertion to delivery, and composite maternal and neonatal morbidity.
RESULTS
In total, 135 consecutive women were analyzed (107 CRB, 79.3%; 28 dinoprostone vaginal insert, 20.7%). Vaginal delivery (86 [80.4%] after CRB vs 19 [67.9%] after dinoprostone vaginal insert; P = 0.248), favorable cervix within 24 h after device placement (52 [48.6%] vs 17 [60.7%]; P = 0.264), and maternal morbidity (12 [11.2%] vs 4 [14.3%]; P = 0.646) were similar between the groups. The time from device insertion to delivery also did not differ between the groups. Neonatal morbidity was significantly higher after the dinoprostone vaginal insert (11 [39.3%] vs 20 [18.7%]; P = 0.030). Cervical ripening using the dinoprostone vaginal insert, compared with the CRB, was significantly associated with neonatal morbidity (adjusted odds ratio 4.00, 95% confidence interval 1.34-12.5), but not with maternal morbidity (adjusted odds ratio 1.23, 95% confidence interval 0.30-4.38).
CONCLUSIONS
Vaginal delivery, a favorable cervix after 24 h, the time from device insertion to delivery, and maternal morbidity did not significantly differ between the CRB and the dinoprostone vaginal insert for cervical ripening in obese women at term. Nevertheless, neonatal morbidity was significantly associated with the dinoprostone vaginal insert, compared with the CRB, among obese women who required cervical ripening at term.
PubMed: 38520064
DOI: 10.1002/ijgo.15480 -
European Journal of Immunology Jun 2024Metastatic colorectal cancer (CRC) is highly resistant to therapy and prone to recur. The tumor-induced local and systemic immunosuppression allows cancer cells to evade...
Metastatic colorectal cancer (CRC) is highly resistant to therapy and prone to recur. The tumor-induced local and systemic immunosuppression allows cancer cells to evade immunosurveillance, facilitating their proliferation and dissemination. Dendritic cells (DCs) are required for the detection, processing, and presentation of tumor antigens, and subsequently for the activation of antigen-specific T cells to orchestrate an effective antitumor response. Notably, successful tumors have evolved mechanisms to disrupt and impair DC functions, underlining the key role of tumor-induced DC dysfunction in promoting tumor growth, metastasis initiation, and treatment resistance. Conventional DC type 2 (cDC2) are highly prevalent in tumors and have been shown to present high phenotypic and functional plasticity in response to tumor-released environmental cues. This plasticity reverberates on both the development of antitumor responses and on the efficacy of immunotherapies in cancer patients. Uncovering the processes, mechanisms, and mediators by which CRC shapes and disrupts cDC2 functions is crucial to restoring their full antitumor potential. In this study, we use our recently developed 3D DC-tumor co-culture system to investigate how patient-derived primary and metastatic CRC organoids modulate cDC2 phenotype and function. We first demonstrate that our collagen-based system displays extensive interaction between cDC2 and tumor organoids. Interestingly, we show that tumor-corrupted cDC2 shift toward a CD14+ population with defective expression of maturation markers, an intermediate phenotype positioned between cDC2 and monocytes, and impaired T-cell activating abilities. This phenotype aligns with the newly defined DC3 (CD14 CD1c CD163) subset. Remarkably, a comparable population was found to be present in tumor lesions and enriched in the peripheral blood of metastatic CRC patients. Moreover, using EP2 and EP4 receptor antagonists and an anti-IL-6 neutralizing antibody, we determined that the observed phenotype shift is partially mediated by PGE2 and IL-6. Importantly, our system holds promise as a platform for testing therapies aimed at preventing or mitigating tumor-induced DC dysfunction. Overall, our study offers novel and relevant insights into cDC2 (dys)function in CRC that hold relevance for the design of therapeutic approaches.
Topics: Colorectal Neoplasms; Humans; Dendritic Cells; Organoids; Dinoprostone; Interleukin-6; Coculture Techniques; Phenotype; Cell Plasticity
PubMed: 38509863
DOI: 10.1002/eji.202350891 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Mar 2024To explore the molecular mechanism of miR-515-5p in inhibiting chondrocyte apoptosis and alleviating inflammatory response in osteoarthritis (OA).
[miR-515-5p targeting Toll-like receptor 4 regulates myeloid differentiation primary response gene 88/nuclear factor-kappa B pathway to inhibit apoptosis and inflammatory response of osteoarthritis chondrocytes].
OBJECTIVE
To explore the molecular mechanism of miR-515-5p in inhibiting chondrocyte apoptosis and alleviating inflammatory response in osteoarthritis (OA).
METHODS
Human cartilage cell line C28/I2 was cultured and treated with 10 ng/mL interleukin 1β (IL-1β) for 24 hours to construct an OA model. C28/I2 cells were transfected with miR mimics, mimics negative control (NC), over expression (oe)-NC, and oe-Toll-like receptor 4 (TLR4), respectively, and then treated with 10 ng/mL IL-1β for 24 hours to establish OA model. Cell proliferation capacity was detected by cell counting kit 8 and 5-Ethynyl-2'-deoxyuridine, cell apoptosis and cell cycle were detected by flow cytometry, and B-cell lymphoma 2 protion (Bcl-2), Bcl-2-associated X protein (Bax), cleaved-Caspase-3, TLR4, myeloid differentiation primary response gene 88 (MyD88), p65 and phosphorylated p65 (p-p65) protein expression levels were detected by Western blot. Real-time fluorescence quantitative PCR was used to detect mRNA expression levels of miR-515-5p and TLR4, and ELISA was used to detect pro-inflammatory factor prostaglandin E2 (PGE2), tumor necrosis factor α (TNF -α), and IL-6 levels in cell supernatant. The potential binding sites between miR-515-5p and TLR4 were predicted by BiBiServ2 database, and the targeting relationship between miR-515-5p and TLR4 was verified by dual luciferase reporting assay.
RESULTS
After the treatment of C28/I2 cells with IL-1β, the expressions of miR-515-5p and Bcl-2 protein and the proliferation ability of C28/I2 cells significantly reduced. The expression levels of Bax and cleaved-Caspase-3 protein, the levels of pro-inflammatory factors (PGE2, TNF-α, IL-6) in the supernatant of C28/I2 cells, and the apoptosis of C28/I2 cells significantly increased. In addition, the proportion of the cells at S phase and G phase decreased significantly, and the proportion of cells at G phase increased significantly, suggesting that the cell cycle was blocked after IL-1β treatment. After transfection with miR mimics, the expression level of miR-515-5p in the cells significantly up-regulated, partially reversing the apoptosis of OA chondrocytes induced by IL-1β, and alleviating the cycle arrest and inflammatory response of OA chondrocytes. After treating C28/I2 cells with IL-1β, the mRNA and protein levels of TLR4 significantly increased. Overexpression of miR-515-5p targeted inhibition of TLR4 expression and blocked activation of MyD88/nuclear factor κB (NF-κB) pathway. Overexpression of TLR4 could partially reverse the effect of miR mimics on IL-1β-induced apoptosis and inflammation of OA chondrocytes.
CONCLUSION
miR-515-5p negatively regulates the expression of TLR4, inhibits the activation of MyD88/NF-κB pathway and apoptosis of OA chondrocytes, and effectively alleviates the inflammatory response of the cells.
Topics: Humans; Adaptor Proteins, Signal Transducing; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Chondrocytes; Dinoprostone; Interleukin-1beta; Interleukin-6; MicroRNAs; Myeloid Differentiation Factor 88; NF-kappa B; Osteoarthritis; RNA, Messenger; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha
PubMed: 38500425
DOI: 10.7507/1002-1892.202312091 -
Respiratory Physiology & Neurobiology Jun 2024Extracellular acidification is a major component of tissue inflammation, including airway inflammation in asthmatics. However, its physiological/pathophysiological...
PURPOSE
Extracellular acidification is a major component of tissue inflammation, including airway inflammation in asthmatics. However, its physiological/pathophysiological significance in bronchial function is not fully understood. Currently, the functional role of extracellular acidification on bronchial contraction was explored.
METHODS
Left main bronchi were isolated from male BALB/c mice. Epithelium-removed tissues were exposed to acidic pH under submaximal contraction induced by 10 M acetylcholine in the presence or absence of a COX inhibitor indomethacin (10 M). Effects of AH6809 (10 M, an EP receptor antagonist), BW A868C (10 M, a DP receptor antagonist) and CAY10441 (3×10 M, an IP receptor antagonist) on the acidification-induced change in tension were determined. The release of prostaglandin E (PGE) from epithelium-denuded tissues in response to acidic pH was assessed using an ELISA.
RESULTS
In the bronchi stimulated with acetylcholine, change in the extracellular pH from 7.4 to 6.8 caused a transient augmentation of contraction followed by a sustained relaxing response. The latter inhibitory response was abolished by indomethacin and AH6809 but not by BW A868C or CAY10441. Both indomethacin and AH6809 significantly increased potency and efficacy of acetylcholine at pH 6.8. Stimulation with low pH caused an increase in PGE release from epithelium-denuded bronchi. Interestingly, the acidic pH-induced bronchial relaxation was significantly reduced in a murine asthma model that had a bronchial hyperresponsiveness to acetylcholine.
CONCLUSION
Taken together, extracellular acidification could inhibit the bronchial contraction via autocrine activation of EP receptors. The diminished acidic pH-mediated inhibition of bronchial tone may contribute to excessive bronchoconstriction in inflamed airways such as asthma.
Topics: Animals; Male; Mice; Acetylcholine; Asthma; Benzyl Compounds; Bronchi; Dinoprostone; Hydrogen-Ion Concentration; Imidazoles; Indomethacin; Inflammation; Muscle Contraction; Mice, Inbred BALB C
PubMed: 38492830
DOI: 10.1016/j.resp.2024.104251 -
Journal of Family Medicine and Primary... Jan 2024Vaginal pH has been suggested to be one of the causative factors, responsible for variation in prostaglandin efficacy for induction of labour. The purpose of this study...
OBJECTIVE
Vaginal pH has been suggested to be one of the causative factors, responsible for variation in prostaglandin efficacy for induction of labour. The purpose of this study was to analyse the effect of vaginal douching with normal saline before insertion of dinoprostone vaginal insert for induction of labour.
METHODS
This randomised controlled study was done in the Department of Obstetrics and Gynaecology for a period of 1 year. Using a computer-generated random number table, subjects were allocated in two groups. In group A (study group), vaginal douching was done with 20 cc of sterile 0.9% NaCl and vaginal pH was again measured with pH paper strips just before inserting dinoprostone pessary. Dinoprostone pessary was inserted without douching in group B (control group).
RESULTS
There was a significant increase in the vaginal pH after douching with normal saline (4.91 vs 5.52, < 0.001). Mean intrinsic vaginal pH (pH before inserting dinoprostone insert) in women who delivered vaginally was significantly higher than that of the women who had a caesarean section (5.10 vs 4.63, < 0.001). Time interval between dinoprostone insertion to active phase of labour, duration of active phase of labour, time interval between dinoprostone insertion, and complete cervical dilatation and mode of delivery were not significantly different between the two groups.
CONCLUSION
Although douching with normal saline increases vaginal pH, douching does not help in increasing the chances of vaginal delivery because it gives a transient effect. Rather, it is intrinsic vaginal pH, which is a better decisive factor for successful vaginal delivery.
PubMed: 38482325
DOI: 10.4103/jfmpc.jfmpc_1108_23 -
Cells Mar 2024NAD boosting via nicotinamide riboside (NR) confers anti-inflammatory effects. However, its underlying mechanisms and therapeutic potential remain incompletely defined....
NAD boosting via nicotinamide riboside (NR) confers anti-inflammatory effects. However, its underlying mechanisms and therapeutic potential remain incompletely defined. Here, we showed that NR increased the expression of CC-chemokine receptor 7 (CCR7) in human M1 macrophages by flow cytometric analysis of cell surface receptors. Consequently, chemokine ligand 19 (CCL19, ligand for CCR7)-induced macrophage migration was enhanced following NR administration. Metabolomics analysis revealed that prostaglandin E2 (PGE2) was increased by NR in human monocytes and in human serum following in vivo NR supplementation. Furthermore, NR-mediated upregulation of macrophage migration through CCL19/CCR7 was dependent on PGE2 synthesis. We also demonstrated that NR upregulated PGE2 synthesis through SIRT3-dependent post-transcriptional regulation of cyclooxygenase 2 (COX-2). The NR/SIRT3/migration axis was further validated using the scratch-test model where NR and SIRT3 promoted more robust migration across a uniformly disrupted macrophage monolayer. Thus, NR-mediated metabolic regulation of macrophage migration and wound healing may have therapeutic potential for the topical management of chronic wound healing.
Topics: Humans; Dinoprostone; Sirtuin 3; Ligands; Receptors, CCR7; Macrophages; Niacinamide; Pyridinium Compounds
PubMed: 38474420
DOI: 10.3390/cells13050455 -
Prostaglandins, Leukotrienes, and... Feb 2024Prostaglandin E2 (PGE2) signals differently through 4 receptor subtypes (EP1-EP4) to elicit diverse physiologic/pathologic effects. We previously reported that PGE2 via...
Prostaglandin E2 (PGE2) signals differently through 4 receptor subtypes (EP1-EP4) to elicit diverse physiologic/pathologic effects. We previously reported that PGE2 via its EP3 receptor reduces cardiac contractility and male mice with cardiomyocyte-specific deletion of the EP4 receptor (EP4 KO) develop dilated cardiomyopathy. The aim of this study was to identify pathways responsible for this phenotype. We performed ingenuity pathway analysis (IPA) and found that genes differentiating WT mice and EP4 KO mice were significantly overrepresented in mitochondrial (adj. p value = 6.28 × 10) and oxidative phosphorylation (adj. p value = 1.58 × 10) pathways. Electron microscopy from the EP4 KO hearts show substantial mitochondrial disarray and disordered cristae. Not surprisingly, isolated adult mouse cardiomyocytes (AVM) from these mice have reduced ATP levels compared to their WT littermates and reduced expression of key genes involved in the electron transport chain (ETC) in older mice. Moreover, treatment of AVM from C57Bl/6 mice with PGE2 or the EP3 agonist sulprostone resulted in changes of various genes involved in the ETC, measured by the Mitochondrial Energy Metabolism RT-profiler assay. Lastly, the EP4 KO mice have reduced expression of superoxide dismuatse-2 (SOD2), whereas treatment of AVM with PGE2 or sulprostone increase superoxide production, suggesting increased oxidative stress levels in these EP4 KO mice. Altogether the current study supports the premise that PGE2 acting via its EP4 receptor is protective, while signaling through its other receptors, likely EP3, is deleterious.
Topics: Animals; Myocytes, Cardiac; Dinoprostone; Mice; Receptors, Prostaglandin E, EP4 Subtype; Mice, Knockout; Male; Mice, Inbred C57BL; Mitochondria, Heart; Oxidative Phosphorylation; Mitochondria
PubMed: 38471265
DOI: 10.1016/j.plefa.2024.102614 -
American Journal of Obstetrics and... Mar 2024This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical... (Review)
Review
This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 μg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings.
Topics: Female; Humans; Pregnancy; Abortifacient Agents, Nonsteroidal; Cervical Ripening; Dinoprostone; Hyaluronoglucosaminidase; Labor, Induced; Mifepristone; Misoprostol; Nitric Oxide Donors; Oxytocics; Oxytocin
PubMed: 38462252
DOI: 10.1016/j.ajog.2023.02.009 -
Molecular Biology Reports Mar 2024Early embryonic mortality is one of the major intriguing factors of reproductive failure that causes considerable challenge to the mammalian cell biologists. Heat stress...
Effect of heat exposure on prostaglandin production and expression of COX-2, PGES, PGFS, ITGAV and LGALS15 mRNAs in endometrial epithelial cells of buffalo (Bubalus bubalis).
BACKGROUND
Early embryonic mortality is one of the major intriguing factors of reproductive failure that causes considerable challenge to the mammalian cell biologists. Heat stress is the major factor responsible for reduced fertility in farm animals. The present study aimed to investigate the influence of heat stress on prostaglandin production and the expression of key genes, including COX-2, PGES, PGFS, ITGAV and LGALS15, in buffalo endometrial epithelial cells.
METHODS AND RESULTS
Buffalo genitalia containing ovaries with corpus luteum (CL) were collected immediately post-slaughter. The stages of the estrous cycle were determined based on macroscopic observations of the ovaries. Uterine lumens of the mid-luteal phase (days 6-10 of the estrous cycle) were washed and treated with trypsin to isolate epithelial cells, which were then cultured at control temperature (38.5 °C for 24 h) or exposed to elevated temperatures [38.5 °C for 6 h, 40.5 °C for 18 h; Heat Stressed (HS)]. The supernatant and endometrial epithelial cells were collected at various time points (0, 3, 6, 12, and 24 h) from both the control and treatment groups. Although heat stress (40.5 °C) significantly (P < 0.05) increased COX-2, PGES, and PGFS transcripts in epithelial cells but it did not affect the in vitro production of PGF and PGE. The expression of ITGAV and LGALS15 mRNAs in endometrial epithelial cells remained unaltered under elevated temperature conditions.
CONCLUSION
It can be concluded that elevated temperature did not directly modulate prostaglandin production but, it promoted the expression of COX-2, PGES and PGFS mRNA in buffalo endometrial epithelial cells.
Topics: Animals; Female; Cyclooxygenase 2; Buffaloes; RNA, Messenger; Dinoprostone; Epithelial Cells
PubMed: 38457014
DOI: 10.1007/s11033-024-09361-4 -
Sheng Li Xue Bao : [Acta Physiologica... Feb 2024Prostaglandin E (PGE2) is an important lipid molecule derived from arachidonic acid, which regulates a variety of physiological and pathological activities. Based on the... (Review)
Review
Prostaglandin E (PGE2) is an important lipid molecule derived from arachidonic acid, which regulates a variety of physiological and pathological activities. Based on the inhibition of inflammatory PGE production, non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the most commonly used drugs to treat inflammatory diseases and to relieve fever and pain symptoms. PGE mediates its functions via four different G protein-coupled receptors, named EP1-EP4. Though the limited distribution and low PGE affinity of EP1, it plays important roles in the maintenance of many physiological functions and homeostasis. Moreover, EP1 is widely involved in the inflammatory response, pain perception and multisystem pathological function regulation. In this review, we will briefly summarize the recent advances on the physiological and pathophysiological function of EP1 and its targeted drugs development.
Topics: Humans; Arachidonic Acid; Dinoprostone; Homeostasis; Pain
PubMed: 38444136
DOI: No ID Found