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Immunity, Inflammation and Disease Jun 2024To explore the efficacy and potential mechanism of Fengshi Gutong capsule (FSGTC) in osteoarthritis (OA) inflammation.
OBJECTIVE
To explore the efficacy and potential mechanism of Fengshi Gutong capsule (FSGTC) in osteoarthritis (OA) inflammation.
METHODS
The impact of FSGTC on laboratory indicators of OA patients was explored using data mining technology and association rule analysis. Then, the OA cell model was constructed by inducing chondrocytes (CHs) with interleukin-1β (IL-1β). In the presence of FSGTC intervention, the regulatory mechanism of PACER/COX2/PGE2 in OA-CH viability and inflammatory responses was evaluated.
RESULTS
Retrospective data mining showed that FSGTC effectively reduced inflammation indexes (ESR, HCRP) of OA patients. Cell experiments showed that LncRNA PACER (PACER) silencing inhibited the proliferation activity of OA-CHs, increased the level of COX2 protein, elevated the levels of PGE2, TNF-α, and IL-1β, and decreased the levels of IL-4 and IL-10 (p < .01). On the contrary, FSGTC-containing serum reversed the effect of PACER silencing on OA-CHs (p < .01). After the addition of COX2 pathway inhibitor, the proliferation activity of OA-CHs was enhanced; the levels of PGE2, TNF-α, and IL-1β were decreased while the levels of IL-4 and IL-10 were increased (p < .01).
CONCLUSION
FSGTC inhibits IL-1β-induced inflammation in CHs and ameliorates OA by upregulating PACER and downregulating COX2/PGE2.
Topics: Chondrocytes; RNA, Long Noncoding; Humans; Interleukin-1beta; Cyclooxygenase 2; Dinoprostone; Osteoarthritis; Inflammation; Drugs, Chinese Herbal; Down-Regulation; Male; Female; Up-Regulation; Middle Aged
PubMed: 38938021
DOI: 10.1002/iid3.1334 -
Journal of Biosciences 2024Noradrenaline (NA) and serotonin (5-HT) induce nociception and antinociception. This antagonistic effect can be explained by the dose and type of activated receptors. We...
Noradrenaline (NA) and serotonin (5-HT) induce nociception and antinociception. This antagonistic effect can be explained by the dose and type of activated receptors. We investigated the existence of synergism between the noradrenergic and serotonergic systems during peripheral antinociception. The paw pressure test was performed in mice that had increased sensitivity by intraplantar injection of prostaglandin E (PGE). Noradrenaline (80 ng) administered intraplantarly induced an antinociceptive effect, that was reversed by the administration of selective antagonists of serotoninergic receptors 5-HT isamoltan, 5-HT BRL15572, 5-HT ketanserin, 5-HT ondansetron, but not by selective receptor antagonist 5-HT SB-269970. The administration of escitalopram, a serotonin reuptake inhibitor, potentiated the antinociceptive effect at a submaximal dose of NA. These results, indicate the existence of synergism between the noradrenergic and serotonergic systems in peripheral antinociception in mice.
Topics: Animals; Mice; Norepinephrine; Serotonin; Serotonin Antagonists; Male; Receptors, Serotonin; Dinoprostone; Citalopram; Nociception; Analgesics; Ondansetron; Ketanserin; Pain; Selective Serotonin Reuptake Inhibitors
PubMed: 38920106
DOI: No ID Found -
International Journal of Women's Health 2024To evaluate factors predictive of the success of a slow-release dinoprostone vaginal insert for cervical ripening.
OBJECTIVE
To evaluate factors predictive of the success of a slow-release dinoprostone vaginal insert for cervical ripening.
METHODS
This retrospective study included 187 women who received dinoprostone vaginal inserts for cervical ripening. The participants were divided into two groups: the transvaginal delivery group (n = 87) and cesarean section termination group (n = 100). The correlation between the parameters present before cervical ripening with dinoprostone slow release and its success, as well as complications and adverse outcomes, was analyzed. Cesarean section predictors and area under the curve (AUC) were compared between the two Groups.
RESULTS
There were statistical differences between the two groups in body mass index (BMI), height, cervical Bishop score, cephalic position, time of medication use, and fetal head position at the time of medication use (<0.05). The optimal thresholds for identifying cesarean section in dinoprostone vaginal insert for cervical ripening were 162.5 for height (AUC = 0.61), 10.65 cm for amniotic fluid index (AUC = 0.6), S-2.5 for cephalic position (AUC = 0.61), 5.5 for bishop score of cervix (AUC = 0.65). The height, amniotic fluid index, cephalic position, and Bishop score of the cervix were included in the same model. The AUC value of the combined model was higher than the AUC value of the single factor.
CONCLUSION
The combined model was a better predictor of cesarean section in dinoprostone vaginal inserts for cervical ripening and labor induction. The success of cervical ripening with a dinoprostone slow-release vaginal insert can be predicted by the factors that can be recognized at admission.
PubMed: 38887592
DOI: 10.2147/IJWH.S461094 -
Immunity Jun 2024Mast cells (MCs) are effectors in type 2 immunity, well known for their detrimental roles in allergy. In this issue of Immunity, Alhallak et al. now identify a...
Mast cells (MCs) are effectors in type 2 immunity, well known for their detrimental roles in allergy. In this issue of Immunity, Alhallak et al. now identify a protective role of MCs against exacerbated immune responses mediated by prostaglandin E (PGE)-driven soluble ST2.
Topics: Mast Cells; Animals; Humans; Inflammation; Dinoprostone; Interleukin-1 Receptor-Like 1 Protein; Mice; Receptors, Cell Surface
PubMed: 38865961
DOI: 10.1016/j.immuni.2024.05.011 -
Reproductive Sciences (Thousand Oaks,... Jun 2024To compare effectiveness and safety of the Cook's balloon with vaginal dinoprostone to induce labor in patients with previous cesarean section. Observational, and...
To compare effectiveness and safety of the Cook's balloon with vaginal dinoprostone to induce labor in patients with previous cesarean section. Observational, and retrospective study that included pregnant women at ≥ 37 weeks' gestation, with unfavorable cervix, singleton pregnancy, intact membranes, and a previous cesarean section, who had undergone labor induction in the period 2014-2019. 170 patients (86 balloon-84 dinoprostone) were analyzed. The proportion of women achieving vaginal delivery within 24 h was higher in the dinoprostone than in double-balloon group (RR, 3.24; 95% CI, 1.36-7.72). No significant differences were detected in the first 48 h in vaginal deliveries (P = .749) or in cesarean section rates (P = .634). Nor were there differences in maternal or fetal safety profiles. A body mass index > 35 increased the risk of cesarean section by 1.53 times (P = .017) and a Bishop's test score < 3 by 1.91 times (P = .009). A vaginal delivery following a cesarean section decreased the probability of another cesarean section by 0.46 times (P = .039). Labor induction with vaginal dinoprostone achieves better vaginal delivery rates in the first 24 h vs Cook's balloon. While the difference in uterine rupture rate did not reach significance, this was higher in women receiving prostaglandin.
PubMed: 38862859
DOI: 10.1007/s43032-024-01617-5 -
BMC Urology Jun 2024This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development.
BACKGROUND
This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development.
METHODS
By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes.
RESULTS
The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P < 0.01). Smooth muscle cells treated with PGE2 displayed increased cAMP and phosphorylated PKA.
CONCLUSIONS
PGE2 binding to EP2 induces ureteral relaxation through the cAMP-PKA pathway. This will provide a new theoretical basis for the development of new therapeutic approaches for the use of PGE2 in the treatment of ureteral stones.
Topics: Receptors, Prostaglandin E, EP2 Subtype; Cyclic AMP; Dinoprostone; Cyclic AMP-Dependent Protein Kinases; Ureteral Calculi; Animals; Ureter; Signal Transduction; Male; Muscle Relaxation
PubMed: 38851678
DOI: 10.1186/s12894-024-01504-w -
Molecular Pain 2024Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked...
Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked prolongation of prostaglandin E (PGE)-induced mechanical hyperalgesia, in vivo. In vitro, priming in nociceptors is characterized by a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. In the present in vitro study we tested the hypothesis that a mu-opioid receptor (MOR) agonist opioid analgesic, morphine, can produce priming by its direct action on nociceptors. We report that treatment of nociceptors with morphine, in vitro, produces a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. Our findings support the suggestion that opioids act directly on nociceptors to induce priming.
Topics: Morphine; Animals; Nociceptors; Dinoprostone; Receptors, Opioid, mu; Analgesics, Opioid; Male; Rats; Ganglia, Spinal; Hyperalgesia; Rats, Sprague-Dawley; Dose-Response Relationship, Drug
PubMed: 38828868
DOI: 10.1177/17448069241260348 -
Journal of Musculoskeletal & Neuronal... Jun 2024To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y...
Effects of Combined Application of Percutaneous Vertebroplasty and Zoledronic Acid on Bone Mineral Density, Bone Metabolism, NPY and PGE2 in Elderly Patients with Osteoporotic Lumbar Vertebral Compression Fracture.
OBJECTIVE
To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y (NPY) and prostaglandin E2 (PGE2) in elderly patients with osteoporotic lumbar vertebral compression fracture (OVCF).
METHODS
The medical records of 118 elderly patients with OVCF who received treatment at our hospital from March 2018 to March 2020 were collected and analyzed retrospectively. Vertebral body height, spinal function, pain degree, and lumbar BMD were compared between the two groups upon admission and three years after the operation. Additionally, the levels of bone-specific alkaline phosphatase (BALP), 25-hydroxyvitamin D (25-(OH)D), beta collagen degradation fragments (β-CTx), neuropeptide Y (NPY), and prostaglandin E2 (PGE2) in the two groups were measured at admission and three years after the operation. Furthermore, complications in the two groups within three years after the operation were documented.
RESULTS
After three years post-operation, the combination group showed a significantly greater improvement in vertebral body height compared to the control group (P<0.05). Moreover, the combination group exhibited a significantly lower Oswestry Disability Index (ODI) score compared to the control group (P<0.05).
CONCLUSION
In elderly patients with OVCF, the combined use of zoledronic acid and percutaneous vertebroplasty is effective in improving lumbar function, BMD, and bone metabolism indices, while reducing pain and the levels of NPY and PGE2.
Topics: Humans; Aged; Female; Fractures, Compression; Zoledronic Acid; Male; Vertebroplasty; Lumbar Vertebrae; Dinoprostone; Bone Density; Spinal Fractures; Neuropeptide Y; Osteoporotic Fractures; Aged, 80 and over; Bone Density Conservation Agents; Retrospective Studies; Combined Modality Therapy
PubMed: 38826002
DOI: No ID Found -
Immunity Jun 2024Severe asthma and sinus disease are consequences of type 2 inflammation (T2I), mediated by interleukin (IL)-33 signaling through its membrane-bound receptor, ST2....
Severe asthma and sinus disease are consequences of type 2 inflammation (T2I), mediated by interleukin (IL)-33 signaling through its membrane-bound receptor, ST2. Soluble (s)ST2 reduces available IL-33 and limits T2I, but little is known about its regulation. We demonstrate that prostaglandin E (PGE) drives production of sST2 to limit features of lung T2I. PGE-deficient mice display diminished sST2. In humans with severe respiratory T2I, urinary PGE metabolites correlate with serum sST2. In mice, PGE enhanced sST2 secretion by mast cells (MCs). Mice lacking MCs, ST2 expression by MCs, or E prostanoid (EP) receptors by MCs showed reduced sST2 lung concentrations and strong T2I. Recombinant sST2 reduced T2I in mice lacking PGE or ST2 expression by MCs back to control levels. PGE deficiency also reversed the hyperinflammatory phenotype in mice lacking ST2 expression by MCs. PGE thus suppresses T2I through MC-derived sST2, explaining the severe T2I observed in low PGE states.
Topics: Animals; Interleukin-1 Receptor-Like 1 Protein; Mast Cells; Dinoprostone; Mice; Interleukin-33; Humans; Mice, Knockout; Lung; Asthma; Receptors, Prostaglandin E, EP2 Subtype; Mice, Inbred C57BL; Inflammation; Female; Male; Signal Transduction; Pneumonia
PubMed: 38821053
DOI: 10.1016/j.immuni.2024.05.003 -
PloS One 2024The Maternal and Perinatal Death Surveillance and Response (MPDSR) was introduced in Kenya in 2016 and implemented at Kiambu Level 5 Hospital (KL5H) three years later in... (Comparative Study)
Comparative Study
BACKGROUND
The Maternal and Perinatal Death Surveillance and Response (MPDSR) was introduced in Kenya in 2016 and implemented at Kiambu Level 5 Hospital (KL5H) three years later in 2019. During a routine MPDSR meeting at KL5H, committee members identified a possible link between the off-label use of 200mcg misoprostol tablets divided eight times to achieve the necessary dose for labour induction (25mcg) and maternal deaths. Following this, an administrative decision was made to switch from misoprostol to dinoprostone for the induction of labour in June of 2019. This study aimed to assess the overall impact of MPDSR as well as the effect of replacing misoprostol with dinoprostone on uterine rupture, maternal and neonatal deaths at KL5H.
METHODS
We conducted a retrospective cohort study of women who gave birth at KL5H between January 2018 and December 2020. We defined the pre-intervention period as January 2018-June 2019, and the intervention period as July 2019-December 2020. We randomly selected the records of 411 mothers, 167 from the pre-intervention period and 208 from the intervention period, all of whom were induced. We used Bayes-Poisson Generalised Linear Models to fit the risk of uterine rupture, maternal and perinatal death. 12 semi-structured key person questionnaires was used to describe staff perspectives regarding the switch from misoprostol to dinoprostone. Inductive and deductive data analysis was done to capture the salient emerging themes.
RESULTS
We reviewed 411 patient records and carried out 12 key informant interviews. Mothers induced with misoprostol (IRR = 3.89; CI = 0.21-71.6) had an increased risk of death while mothers were less likely to die if they were induced with dinoprostone (IRR = 0.23; CI = 0.01-7.12) or had uterine rupture (IRR = 0.56; CI = 0.02-18.2). The risk of dying during childbearing increased during Jul 2019-Dec 2020 (IRR = 5.43, CI = 0.68-43.2) when the MPDSR activities were strengthened. Induction of labour (IRR = 1.01; CI = 0.06-17.1) had no effect on the risk of dying from childbirth in our setting. The qualitative results exposed that maternity unit staff preferred dinoprostone to misoprostol as it was thought to be more effective (fewer failed inductions) and safer, regardless of being more expensive compared to misoprostol.
CONCLUSION
While the period immediately following the implementation of MPDSR at KL5H was associated with an increased risk of death, the switch to dinoprostone for labour induction was associated with a lower risk of maternal and perinatal death. The use of dinoprostone, however, was linked to an increased risk of uterine rupture, possibly attributed to reduced labour monitoring given that staff held the belief that it is inherently safer than misoprostol. Consequently, even though the changeover was warranted, further investigation is needed to determine the reasons behind the rise in maternal mortalities, even though the MPDSR framework appeared to have been put in place to quell such an increase.
Topics: Humans; Misoprostol; Female; Labor, Induced; Pregnancy; Retrospective Studies; Adult; Dinoprostone; Oxytocics; Uterine Rupture; Infant, Newborn; Young Adult; Perinatal Death; Maternal Mortality
PubMed: 38820427
DOI: 10.1371/journal.pone.0304631