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The ductus arteriosus is an important lifeline for fetal circulation.Prostaglandins（PG）are involved in the dilatation of the ductus arteriosus during fetal life as well as the anatomical remodeling of the ductus arteriosus after birth. Patent ductus arteriosus（PDA）is a common congenital heart disease in preterm infants.The treatment by inhibiting local PG synthesis is currently the principal means of clinical practice，with indomethacin and ibuprofen being the most commonly applied drugs，but the prevalence of adverse effects has led scholars to focus on other targets of the PG synthesis pathway. This paper reviews relevant medications and combines the physiological effects of PG on ductus arteriosus in different stages to summarize the current drugs of treating PDA and their related research advances，with the aim to provide new strategies for the treatment and future research of this condition.
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Objective To investigate the correlation between serum levels of prostaglandin-endoperoxide synthase 2(PTGS2),chitinase-3-like protein 1(CHI3L1)and cognitive impairment caused by cerebrovascular disease.Methods From October 2020 to October 2022,96 inpatients with cerebrovascular diseases admitted to the Third People's Hospital of Chengdu were regarded as the study subjects.The basic clinical data of the patients were recorded,the serum levels of PTGS2 and CHI3L1 were detected by enzyme-linked immunosorbent assay,and these patients were grouped into normal group(n=60)and impaired group(n=36)based on the presence or absence of cognitive impairment.The correlation between serum PTGS2 and CHI3L1 levels and fasting blood glucose(FBG)and homocysteine(Hcy)was analyzed by Pearson method.Logistic regression model was used to determine whether serum PTGS2 and CHI3L1 were independent risk factors for predicting cognitive impairment.Receiver operating characteristic(ROC)curve was drawn,and the predictive value of CHI3L1 and serum PTGS2 expression level in cognitive impairment in patients with cerebrovascular disease was analyzed according to the area under the curve(AUC).Results Compared with the normal group,the levels of serum PTGS2(29.30±9.46 pg/ml vs 17.86±5.40 pg/ml)and CHI3L1(13.04±4.06 pg/ml vs 7.51±2.66 pg/ml)in the disorder group were increased,and the differences were statistically significant(t=7.553,8.065,all P＜0.05).Multivariate Logistic regression analysis showed that FBG(OR=3.612,95%CI:2.324～5.614),Hcy(OR=2.584,95%CI:1.351～4.944),PTGS2(OR=1.964,95%CI:1.194～3.231)and CHI3L1(OR= 1.556,95%CI:1.023～2.367)were independent risk factors of cognitive impairment(all P＜0.05).PTGS2 was positively correlated with FBG and Hcy(r=0.368,0.551,all P＜0.05),and CHI3L1 was positively correlated with FBG and Hcy(r=0.510,0.376,all P＜0.05).The ROC curve showed that the area under curve(AUC)of PTGS2 and CHI3L1 in predicting cognitive impairment was 0.819 and 0.829,respectively.The AUC of the combined prediction of cognitive impairment was 0.902,which was obviously higher than that of the independent prediction of the two(Z =2.089,2.293;P=0.037,0.021),with sensitivity and specificity of 77.78%and 98.33%,respectively.Conclusion PTGS2 and CHI3L1 were highly expressed in the serum of patients with cognitive impairment of cerebrovascular disease,indicating that both were related to cognitive impairment of patients with cerebrovascular disease.
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BACKGROUND:Ginseng extracts have been found to significantly improve osteoarthritis,but the therapeutic effects of ginseng polysaccharide extracts on osteoarthritis have not been reported. OBJECTIVE:To investigate the effect of ginseng polysaccharide on the expression of prostaglandin E2/6-keto-prostaglandin F1α in traumatic osteoarthritis model rats. METHODS:Sixty male Sprague-Dawley rats were selected and randomly divided into healthy group,model group,ginseng polysaccharide low-dose group,ginseng polysaccharide medium-dose group,ginseng polysaccharide high-dose group and dexamethasone group.Except for 10 rats in the healthy group,the other rats were taken to establish traumatic osteoarthritis models.The healthy group and model group were given 0.2 mL of normal saline intraperitoneally.The low-,medium-,and high-dose groups were intraperitoneally injected with 0.1,0.25,0.5 μg/mL ginseng polysaccharide,respectively.In the dexamethasone group,0.2mg/kg dexamethasone(0.2 mL)was injected intraperitoneally.Injections were given once every 3 days,for 4 consecutive weeks.Serum prostaglandin E2 and 6-keto-prostaglandin F1α levels were detected by ELISA.The bone and joint function of rats were assessed by the Mankin's score.Hematoxylin-eosin staining was used to observe the pathologic morphology of the knee joints of rats.Western blot and PCR were used to detect the protein and mRNA expression of tumor necrosis factor α and interleukin-1β,interleukin-10 in articular cartilage tissue,respectively. RESULTS AND CONCLUSION:Compared with the model group,serum prostaglandin E2 levels were decreased in the medium-dose group and dexamethasone group,while serum 6-keto-prostaglandin F1α levels were increased(P<0.05).Compared with the medium-dose group and dexamethasone group,the above-mentioned indicators were significantly improved in the high-dose group,and there was no significant difference between the medium-dose group and dexamethasone group(P>0.05).Compared with the model group,the Mankin's score was reduced in the medium-dose group and dexamethasone group(P<0.05),but there was no significant difference between the medium-dose group and dexamethasone group(P>0.05).Compared with the medium-dose group and dexamethasone group,the Mankin's score was significantly reduced in the high-dose group(P<0.05).The cartilage tissue layer of rats in the model and low-dose groups was significantly thinned,the cracks and chondrocytes deep into the bone layer were largely lost,the tide line was seriously broken and blurred,the collagen fibers in the synovial layer were increased and thickened,and a large number of chondrocytes were destroyed and arranged irregularly.These pathological changes were improved in the medium-dose group and dexamethasone group compared with the model group as well as improved in the high-dose group compared with the medium-dose group.Compared with the model group,the expression of tumor necrosis factor-α and interleukin-1β was reduced,while the expression of interleukin-10 was increased in the medium-dose group and dexamethasone group(P<0.05).These indicators in the joint were significantly improved in the high-dose group compared with the medium-dose group and dexamethasone group(P<0.05),but there was no significant difference between the medium-dose group and dexamethasone group(P>0.05).To conclude,ginseng polysaccharide can improve the inflammatory level and pathological morphology of traumatic osteoarthritis rats and reduce the Mankin's score.Its mechanism may be related to the regulation of prostaglandin E2/6-keto-prostaglandin F1α levels.
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Primary hypertrophic osteoarthropathy(PHO) is a rare disease also known as pachydermoperiostosis. We reported a painless case whose diagnosis was confirmed by genetic test. A 24-year-old male presented a series of symptoms that first began at 14. He suffered from progressive clubbed-fingers accompanied by swelling of the wrist and ankle joints. Facial skin concentric thickening and alar nose broadening appeared simultaneously and increased progressively. He was also prone to acne and hyperhidrosis. X-rays showed thickening of the metacarpal and phalangeal bones, as well as symmetrical periosteal ossification of both the tibia and fibula. Clinical diagnosis of PHO is difficult because of the variable features. With acromegaly excluded, the diagnosis was confirmed by a genetic test. Whole exome sequencing revealed a heterozygous SLCO2A1 c.611C > T(p.Ser204Lue) and SLCO2A1 c.1602C > A(p.Asn534Lys) mutation from each parent. It suggests that primary hypertrophic osteoarthropathy should be considered for young limb hypertrophic patients especially when periosteal thickening signs were showed in X-ray. A confirmatory diagnosis can be made through the genetic test.
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ObjectiveTo investigate the expression levels of serum high-mobility group box 1 （HMGB1）， soluble CD163 （sCD163）， and prostaglandin E2 （PGE2） in patients with hepatitis B virus-related chronic-on-acute liver failure （HBV-ACLF）， and to evaluate the value of the three indicators used alone or in combination in predicting prognosis. MethodsA total of 76 patients with HBV-ACLF who were hospitalized in Department of Infectious Diseases， The First Affiliated Hospital of Xinxiang Medical University， from July 1， 2022 to September 30， 2023 were enrolled， and according to the 28-day prognosis， they were divided into survival group with 48 patients and death group with 28 patients. General data were collected， Model for End-Stage Liver Disease （MELD） score was calculated， and ELISA was used to measure the serum levels of HMGB1， sCD163， and PGE2. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Spearman rank correlation test was used to analyze the correlation of HMGB1， sCD163， and PGE2 with MELD score； the receiver operating characteristic （ROC） curve was used to analyze the value of HMGB1， sCD163， and PGE2 used alone or in combination in predicting the prognosis of HBV-ACLF patients. ResultsThere were significant differences between the two groups in total bilirubin， white blood cell count， the percentage of neutrophils， procalcitonin， serum amyloid A， interleukin-6， serum sodium， and serum creatinine （all P<0.05）. Compared with the survival group， the death group had significantly higher serum levels of HMGB1 （Z=-2.997， P=0.003） and sCD163 （Z=-2.972， P=0.003）， a significantly higher MELD score （t=-6.997， P<0.001）， and a significantly lower serum level of PGE2 （Z=-4.909， P<0.001）. The Spearman rank correlation test showed that HMGB1 and sCD163 were positively correlated with MELD score （r=0.431 and 0.319， both P<0.05）， while PGE2 was negatively correlated with MELD score （r=-0.412， P<0.05）. The ROC curve analysis showed that HMGB1， sCD163， and PGE2 used alone had an area under the ROC curve （AUC） of 0.717， 0.716， and 0.856， respectively， while the combination of the three indicators had the highest predictive value， with an AUC of 0.930， a sensitivity of 0.778， and a specificity of 0.920. ConclusionSerum HMGB1， sCD163， and PGE2 used alone or in combination have a good reference value in predicting the prognosis of HBV-ACLF patients， and the combination of the three indicators has the highest predictive value， which holds promise for further observation and research.
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Background: The intentional commencement of cervical ripening and uterine contraction for the purpose of achieving delivery prior to the onset of spontaneous parturition is known as induction of labour. When the benefits to the mother or the foetus surpass the benefits of extending the pregnancy, it is indicated. The purpose of this study was to assess the efficacy of a transcervical foley's catheter with extra amniotic saline infusion against intra cervical prostaglandin E2 gel for inducing labour in term pregnant women.Methods: From January 2020 to June 2021, a comparative study was undertaken at R.L. Jalappa Hospital and Research Centre. The study enrolled a total of 72 individuals. After obtaining informed consent from the patients who were admitted, and meeting the inclusion criteria, detailed history was collected, baseline investigations were done. After clinical examination of the patient, by using the simple lottery method, patients were divided into group A (Extra amniotic saline infusion group with Foley’s catheter) and group B (Dinoprostone (PGE2 gel) group).Results: Prolonged gestational age, hypertensive disorders in pregnancy, and oligohydramnios were the most frequent causes for induction in the EASI group, accounting for 38.89%, 38.89%, and 22.22%, respectively. The dinoprostone group has 36.11%, 33.33%, and 25%, respectively. After induction, the majority of patients in the EASI group had a modified Bishop's score of 2.Conclusions: Our research found that PGE2 and EASI were equally effective in inducing labour.
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Total radical prostatectomy for advanced prostate cancer may lead to sexual impotence, since it is associated with severe erectile dysfunction. A widely recommended treatment for this disabling condition is intracavernous penile injection of a mixture of prostaglandin E1, papaverine, and phentolamine. To our knowledge, we present the first case of anaphylaxis associated with intracavernous penile injection of prostaglandin E1 in combination with papaverine and phentolamine.
A prostatectomia radical total para câncer de próstata avançado pode levar à impotência sexual, associada a uma disfunção erétil grave. Um tratamento amplamente recomendado para esta condição incapacitante é a injeção intracavernosa no pênis de uma mistura de prostaglandina E1, papaverina e fentolamina. Até onde sabemos, estamos apresentando o primeiro caso de anafilaxia associada à injeção intracavernosa peniana de prostaglandina E1 em combinação com papaverina e fentolamina.
الموضوعات
Humans , Male , Middle Agedالملخص
Introducción: El glaucoma es la principal causa de ceguera irreversible en el mundo. La prevalencia mundial de glaucoma en personas de 40 a 80 años se estima en un 3,5 %. Objetivo: Comparar el efecto reductor de la PIO de Latanoprostene bunod (LBN) al 0,024% con Latanoprost al 0,005 % en sujetos con glaucoma de ángulo abierto (GAA) o hipertensión ocular (HTO). Metodología: Ensayo observacional de estudio de cohorte prospectivo. Resultados: Fue realizado en 28 pacientes (56 ojos) quienes fueron aleatorizados en 2 grupos paralelos (28 ojos por grupo), el grupo Latanoprost y el grupo LBN. En el grupo LBN la media de la PIO antes del tratamiento fue de 25,3 ± 6,6 mmHg y la media de la PIO luego de 1 mes de tratamiento fue de 16,5 ± 4,9 mmHg (p<0,05). En el grupo Latanoprost la media de la PIO antes del tratamiento fue de 23,6 ± 3,6 mmHg y la media de la PIO luego de 1 mes de tratamiento con Latanoprost al 0,005% fue de 15,3 ± 2,4 mmHg (p<0,05). Sin embargo, al comparar las PIOs luego de 1 mes de tratamiento con LBN 0,024% y Latanoprost 0,005% se objetiva que la diferencia en reducción de la presión intraocular entre estos dos fármacos no fue significativa (p= 0,238). Discusión: Las prostaglandinas tópicas, con su potente efecto hipotensor ocular son una importante opción de tratamiento para el glaucoma. La reducción de la PIO es la esperada con ambos medicamentos, sin embargo, no existen diferencias significativas entre ambas luego de 1 mes de uso. Con respecto a los efectos secundarios, en el grupo LBN se encontró más efectos adversos oculares.
Introduction: Glaucoma is the main cause of irreversible blindness worldwide. The global prevalence of glaucoma in people aged 40 to 80 years is estimated at 3.5%. Objective: To compare the intraocular pressure (IOP) lowering effect of 0.024% Latanoprostene bunod (LBN) with 0.005% Latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: Observational trial of prospective cohort study. Results: It was performed in 28 patients (56 eyes) who were randomized into 2 parallel groups (28 eyes per group), the Latanoprost group and the Latanoprostene bunod (LBN) group. In the LBN group, the mean intraocular pressure before treatment was 25.3 ± 6.6 mmHg and the mean intraocular pressure after 1 month of treatment was 16.5 ± 4.9 mmHg (p<0,05). In the Latanoprost group, the mean intraocular pressure before treatment was 23.6 ± 3.6 mmHg and the mean intraocular pressure after 1 month of treatment with 0.005% Latanoprost was 15.3 ± 2.4 mmHg (p<0,05). However, when comparing the IOPs to the 1-month treatment with Latanoprostene bunod 0.024% and Latanoprost 0.005%, it is observed, through ANOVA, that the difference in intraocular pressure reduction between these two drugs is not significant (p= 0,238). Discussion: Topical prostaglandins, with their potent ocular hypotensive effect (resulting from increased uveoscleral outflow), are an important treatment option for glaucoma. The IOP reduction is as expected with both drugs, however, there are no significant differences between the two. In the LBN group, more drug-related ocular adverse effects were found after 1 month of use.
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Manganese plays an important physiological role in the organism, and excessive manganese exposure can cause impairment of neurological and reproductive functions. Gonadotropin-releasing hormone secreted by the hypothalamus acts as an initiator to regulate reproductive functions, such as gonadal development, onset of puberty, and gonadal hormone release. But the mechanism by which manganese damages the hypothalamus leading to abnormal gonadotropin-releasing hormone release is still unclear yet. Kisspeptin, prostaglandin E2, and nitric oxide may act as stimulators to increase the release of gonadotropin-releasing hormone, while the stimulatory or inhibitory effect of γ-aminobutyric acid on the release of gonadotropin-releasing hormone is controversial. Based on current research, manganese has been less studied with Kisspeptin, and studies with prostaglandin E2, nitric oxide, and γ-aminobutyric acid mainly focused on inflammation, oxidative stress, and neurotransmitter transmission. Therefore, taking Kisspeptin, prostaglandin E2, γ-aminobutyric acid, and nitric oxide as the breakthrough points, this paper introduced the mechanism of manganese affecting the release of gonadotropin-releasing hormone in the hypothalamus through the above four pathways, and proposed that the abnormal release of gonadotropin-releasing hormone in the hypothalamus may be one of the mechanisms by which manganese regulates reproductive function, providing a new direction for the prevention and treatment of manganese-induced reproductive damage in the future.
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Objective To investigate the effects of aerosolized inhalation of different doses of pros-taglandin E1(PGE1)on pulmonary shunt and oxygenation during one-lung ventilation(OLV)when the fraction of inspiration O2 was 40％.Methods A total of 156 patients undergoing radical operation of esophageal cancer,121 males and 35 females,aged 18-64 years and BMI 18-30 kg/m2,ASA physical status Ⅱ or Ⅲ were included in the study.The patients were randomly assigned into 4 groups using a random number table:PGE1 0.1 μg/kg group(group L,n=39),PGE1 0.2 μg/kg group(group M,n=38),PGE 0.3 μg/kg group(group H,n=39),and a saline control group(group C,n=40).Patients re-ceived different therapy before OLV,namely inhaling either PGE1 0.1,0.2,0.3 μg/kg,and saline into right lung for a duration of 10 minutes.Venous blood and arterial blood were drawn from right internal jugu-lar vein catheter and radial artery catheter for blood gas analysis at pre-anesthesia(T0),pre-nebulization(T1),OLV 10 minutes(T2),OLV 15 minutes(T3),OLV 30 minutes(T4),OLV 60 minutes(T5),and OLV 120 minutes(T6).HR,MAP,PaO2,oxygenation index(OI),pulmonary shunt fraction(Qs/Qt),PaCO2,and peak airway pressure(Ppeak)were also recorded at above time points.Intraoperative hypox-emia,intraoperative hypotension,clinical pulmonary infection score(CPIS)on the second postoperative day and postoperative pulmonary complications(PPCs)within 7 days were recorded.Results Compared with group C,groups L,M,and H showed a lower incidence of hypoxemia(P＜0.05),group H demon-strated lower MAP at T2 and T3(P＜0.05),groups L,M,and H displayed lower Qs/Qt and higher PaO2 and OI at T2-T4(P＜0.05),group H had a lower CPIS on the second postoperative day(P＜0.05).Compared with group L,group H exhibited lower Qs/Qt at T2-T4,and higher PaO2 and OI at T3 and T4.There were no significant differences in the incidence of hypotension,HR,PaCO2,Ppeak,and the occur-rence of PPCs within 7 days among the four groups.Conclusion Nebulized inhalation of PGE,0.1,0.2 and 0.3 μg/kg under FiO2 40％before OLV can effectively reduce Qs/Qt,improve oxygenation and de-crease the incidence of hypoxemia.However,it has no significant impact on PPCs.PGE,0.3 μg/kg exhibits the best improvement in oxygenation and can also reduce CPIS on the second postoperative day,close monitoring of circulatory fluctuations is still required.
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Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.
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Objective:To investigate the efficacy of modified surgery in the treatment of breast abscess and its effects on inflammatory reaction and pain-related factors.Methods:A total of 100 patients with breast abscess who were treated in Zhoushan Women and Children's Hospital from December 2019 to October 2022 were included in this study. They were divided into an observation group and a control group ( n = 50 per group) using the random number table. The control group received vacuum assisted rotary resection, while the observation group underwent modified surgery. Operation conditions, postoperative complications, and postoperative conditions were recorded in each group. Before and 24 hours after surgery, inflammatory reaction and pain-related factors were compared between the two groups. Results:There was no significant difference in operative time between the two groups ( P > 0.05). The intraoperative bleeding volume in the observation group was (23.14 ± 4.53) mL, which was significantly lower than (36.52 ± 7.18) mL in the control group ( t = 11.14, P < 0.001). The incidence of complications in the observation group was 6.00% (3/50), which was significantly lower than 20% (10/50) in the control group ( χ2 = 4.33, P < 0.05). The observation group had significantly lower postoperative visual analogue scale score [(2.42 ± 0.78) points], fewer dressing changes [(5.26 ± 1.34) times], and lower scar degree [(6.82 ± 1.27) mm] compared with the control group [(3.56 ± 0.89) points, (7.43 ± 1.62) times, (9.12 ± 1.54) mm, t = 6.81, 7.30, 8.15, all P < 0.001]. At 24 hours after surgery, high-sensitivity C-reactive protein, interleukin-1 β, and tumor necrosis factor-α in the observation group were (14.52 ± 3.37) mg/L, (182.13 ± 23.32) ng/L, and (20.08 ± 2.89) ng/L, respectively, which were significantly lower than (29.94 ± 5.45) mg/L, (231.24 ± 16.56) ng/L, and (29.98 ± 4.36) ng/L in the control group ( t = 17.02, 12.14, 13.38, all P < 0.001). At 24 hours after surgery, prostaglandin E 2 and substance P in the observation group were (97.14 ± 18.78) ng/L and (175.18 ± 24.37) μg/L respectively, which were significantly lower than (148.65 ± 20.06) ng/L and (265.41 ± 27.86) μg/L in the control group ( t = 13.26, 17.24, both P < 0.001). Conclusion:The modified surgical treatment for breast abscess shows significant effects with fewer complications and minimal impact on inflammatory response, effectively inhibiting the release of pain-related factors.
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Objective @#To investigate the effect of adeno⁃associated virus ( AAV) delivery of short hairpin RNA ( shRNA) against the Ptger3 gene in the lateral parabrachial nucleus (LPB) on the fever induced by microinjection of prostaglandin E2 (PGE2 ) into the LPB and the intraperitoneal injection of lipopolysaccharide (LPS) .@*Methods@#AAV2⁃shRNA⁃Ptger3(EP3) ⅣEGFP ( shRNA⁃EP3) and AAV2⁃ CMV⁃ EGFP ( shRNA⁃control) viruses were constructed and transfected the rat LPB by stereotaxic injection. Four weeks later, the transfection efficiency of AAV viruses was observed by fluorescence microscopy , and the knockdown efficiency was determined by real⁃time PCR of EP3 receptor mRNA on the LPB. The effects of microinjection of saline or PGE2 in the LPB or intraperitoneal injection of LPS on body temperature (Tcore ) and energy expenditure (EE) of shRNA⁃control group and shRNA⁃EP3 group were monitored using an animal monitoring system with temperature telemetry.@*Results @# AAV virus transfecnificant difference in basal body temperature between shRNA⁃control group and shRNA⁃EP3 group. Tcore and EE were briefly and slightly increased after microinjection of saline in the LPB , but there was no significant difference between the two groups. Compared with the shRNA⁃control group , the febrile response induced by LPB PGE2 was attenuated in the shRNA⁃EP3 group (P < 0. 05) . Furthermore , the knockdown of EP3 receptor of LPB also attenuated the LPS⁃induced fever, and the Tcore 5. 5 h post⁃LPS in the shRNA⁃EP3 rats increased compared with the baseline (P < 0. 05) , which was lower than that in the shRNA⁃control rats ( P < 0. 01) . @*Conclusion @#EP3 receptor knockdown in LPB attenuates the febrile response induced by microinjection of PGE2 in the LPB and intraperitoneal injection of LPS , suggesting that EP3 receptors of LPB mediate the pyrogenic action of LPB PGE2 and partly participate in LPS⁃induced fever.
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Abstract Objective To explore the potential for development of Thai propolis extract as a pulp capping agent to suppress pulpal inflammation from dental pulp infections. This study aimed to examine the anti-inflammatory effect of the propolis extract on the arachidonic acid pathway, activated by interleukin (IL)-1β, in cultured human dental pulp cells. Methodology Dental pulp cells, isolated from three freshly extracted third molars, were first characterized for their mesenchymal origin and treated with 10 ng/ml of IL-1β in the presence or absence of non-toxic concentrations of the extract from 0.08 to 1.25 mg/ml, as determined by the PrestoBlue cytotoxic assay. Total RNA was harvested and analyzed for mRNA expressions of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2). Western blot hybridization was performed to investigate COX-2 protein expression. Culture supernatants were assayed for released prostaglandin E2 levels. Immunofluorescence was conducted to determine involvement of nuclear factor-kappaB (NF-kB) in the inhibitory effect of the extract. Results Stimulation of the pulp cells with IL-1β resulted in the activation of arachidonic acid metabolism via COX-2, but not 5-LOX. Incubation with various non-toxic concentrations of the propolis extract significantly inhibited upregulated COX-2 mRNA and protein expressions upon treatment with IL-1β (p<0.05), resulting in a significant decrease in elevated PGE2 levels (p<0.05). Nuclear translocation of the p50 and the p65 subunits of NF-kB upon treatment with IL-1β was also blocked by incubation with the extract. Conclusions Upregulated COX-2 expression and enhanced PGE2 synthesis upon treatment with IL-1β in human dental pulp cells were suppressed by incubation with non-toxic doses of Thai propolis extract via involvement of the NF-kB activation. This extract could be therapeutically used as a pulp capping material due to its anti-inflammatory properties.
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Los antiinflamatorios no esteroideos (AINE) son un grupo de fármacos que han sido comúnmente prescritos por sus propiedades antiinflamato- rias, antipiréticas y analgésicas, mismas que se deben a la inhibición de la formación de prostaglandinas. Este mecanismo ha sido ampliamente respaldado en la literatura; sin embargo, en la actualidad poco se co- noce sobre las propiedades adicionales de estos medicamentos como el efecto antirresortivo y antimicrobiano. La función antirresortiva se debe principalmente al bloqueo de la producción de prostaglandinas en específico la PGE2, que posee gran potencial osteoclastogénico, esencial para la aparición de lesiones periapicales; asimismo, la acción antimicrobiana de los AINE está relacionada con la afectación directa de la perpetuación de biopelícula, potencian la acción de los antibióticos, entre otros. Dichos efectos combinados podrían contribuir en la cura- ción de lesiones periapicales. El objetivo de este estudio es recopilar información actualizada sobre estas funciones agregadas de los AINE, con el fin de dar a conocer a los profesionales estos beneficios en la terapéutica de las lesiones periapicales (AU)
Non-steroidal anti-inflammatory (NSAIDs) are a group of drugs that have been commonly prescribed for their anti-inflammatory, antipyretic and analgesic properties, which are due to the inhibition of prostaglandin formation. This mechanism has been widely supported in the literature; however, currently little is known about the additional properties of these drugs such as the antiresorptive and antimicrobial effect. The antiresorptive function is mainly due to the blockage of prostaglandin production, specifically PGE2, which has great osteoclastogenic potential, and is essential for the appearance of periapical lesions; likewise, the antimicrobial action of NSAIDs is related to the fact that they directly affect the perpetuation of biofilms, enhance the action of antibiotics, among others. These combined effects could contribute to the healing of periapical lesions. The aim of this study is to gather updated information on these added functions of NSAIDs, in order to inform professionals about these benefits in the therapy of periapical lesion (AU)
الموضوعات
Periapical Diseases/drug therapy , Anti-Inflammatory Agents, Non-Steroidal , Bacterial Infections/drug therapy , Tooth Resorption/drug therapyالملخص
Background Previous studies have confirmed that nicotine exposure is an independent risk factor for miscarriage, but it is not clear whether nicotine causes unexplained recurrent spontaneous abortion (URSA) through oxidative stress. Objective To explore potential mediating effect of oxidative stress on the relationship between nicotine exposure and URSA. Methods Using a 1∶1 matched case-control study, 88 patients with URSA visiting Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University from April to October in 2018 were selected as the case group, and 88 pregnant women without adverse pregnancy outcomes and seeking induced abortion in the outpatient clinic of the same hospital were selected as the control group. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in urine were determined by enzyme-linked immunosorbent assay, and the level of urinary nicotine was determined by gas chromatography-mass spectrometry. Conditional logistic regression was used to analyze the associations of nicotine, 8-OHdG, and 8-iso-PGF2α with the risk of URSA. Multiple linear regression was used to analyze the association of nicotine with 8-OHdG and 8-iso-PGF2α. The potential mediating effect of oxidative stress on URSA after nicotine exposure was explored by dichotomous mediating model. Results The median concentrations (creatinine corrected) of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were 7.78, 4.84, and 44.10 μg·g−1, respectively, while those of the control group were 6.48, 3.34, and 29.39 μg·g−1, respectively. The concentrations of nicotine, 8-OHdG, and 8-iso-PGF2α in urine of the case group were all higher than those of the control group (P < 0.05). The results of conditional logistic regression model showed that after adjusting selected confounding factors, compared with the Q1 groups of nicotine and 8-iso-PGF2α, the OR (95%CI) values of URSA in the Q4 groups were 4.20 (1.33-13.29) and 6.25 (1.66-23.59), respectively. Compared with the Q1 group of 8-OHdG, the OR (95%CI) values of URSA in the Q1, Q2, and Q3 groups were 5.47 (1.43-20.93), 4.24 (1.28-14.07), and 6.36 (1.82-22.28), respectively. The results of multiple linear regression showed that after adjusting confounding factors, there was a positive correlation between urinary nicotine and 8-OHdG in both the case group and the control group, and the b (95%CI) values were 0.76 (0.67-0.86) and 0.81 (0.67-0.95) respectively; there was a positive correlation between urinary nicotine and 8-iso-PGF2α in both the case group and the control group, and the b (95%CI) values were 0.65 (0.55-0.75) and 0.76 (0.64-0.87), respectively. The results of dichotomous mediating analysis showed that the mediating effect of 8-iso-PGF2α and its 95%CI on the relationship between nicotine exposure and URSA was 1.518 (0.749-2.311). Conclusion Internal nicotine exposure is a risk factor for URSA and is positively correlated with oxidative stress, and it may lead to URSA through lipid peroxidation damage.
الملخص
Background The metabolites and metabolic pathways of hand-arm vibration syndrome have not yet been elucidated. Objective To investigate the effect of local vibration on endogenous metabolites in rat serum by metabolomic analysis, to preliminarily explore the potential metabolic pathway of endogenous metabolites, so as to provide evidence for further research on the mechanism of hand-arm vibration syndrome. Methods Thirty-two SPF male SD rats, (211.3±11.1) g, 7−8 weeks of age, were selected and randomly divided into three groups: control group (14 rats, without vibration), 7 d vibration group (9 rats, continuously vibration for 7 d), and 14 d vibration group (9 rats, continuous vibration for 14 d). The vibration rats were vibrated every day for 4 h, the frequency weighted acceleration was 4.9 m·s−2, the vibration frequency was 125 Hz, and the vibration direction was one-way vertical vibration. The control group had the same conditions except not contacting vibration. After the vibration exposure, the blood samples taken from the abnormal aorta of rats were collected, and the changes of rat serum metabolome were analyzed by ultra-performance liquid chromatography-tandem time-of-flight mass spectrometry. Principal components analysis (PCA) was used to explore changes in rat serum metabolic profile, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to screen out differential metabolites. Combined with online databases, a metabolic pathway enrichment analysis of differential metabolites was performed. Results The PCA analysis showed that compared with the control group, the rat serum metabolic profiles in the 7 d group and the 14 d group were clearly differentiated, and the rat serum metabolic profiles in the 7 d group and the 14 d group partially overlapped. The OPLS-DA analysis showed significant differences between groups. The main parameters were: model interpretation rate R2Y=0.914, model predictive ability Q2=0.58. The OPLS-DA analysis screened out 26 and 119 differential metabolites from the 7 d group and the 14 d group respectively, and there were 24 common differential metabolites between the 7 d group and the 14 d group. The metabolomic pathway analysis showed that local vibration-induced changes in rat serum metabolism were mainly related to arachidonic acid metabolism in the 14 d group, among which the metabolites with significant effects were arachidonic acid, prostaglandin E2, and prostaglandin D2. Conclusion Local vibration could affect the normal metabolism in rats, and the metabolic pathway with significant influence is arachidonic acid metabolism after a 14 d exposure and the involved metabolites are arachidonic acid, prostaglandin E2, and prostaglandin D2.
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Abstract Background: At present, parathyroid hormone is the only existing anabolic bone therapy but produces hypercalcemia. Prostaglandin E1 (PGE1) has been suggested as a bone anabolic agent that allows bone modeling formation without producing hypercalcemia. This study aimed to corroborate these PGE1 properties. Methods: For 22 days, rabbits (n = 30) were divided into three groups (n = 10 each group) and received intravenous solutions: vehicle (control group), palate disjunction + vehicle (sham group), and palate disjunction + 50 mg of PGE1 (PGE1 group). On days 1, 3, and 22, palatine suture X-rays were taken. On day 22, bone formation markers were analyzed, and the rabbits were sacrificed. Bone palate undecalcified samples were processed. Histomorphometry software was used to analyze bone parameters, and the mineralization front was stained with toluidine blue. Scalloped lines reflect remodeling-based bone formation (RBF), and smooth lines reflect modeling-based formation (MBF). Results: X-rays showed more significant palatal disjunction in the PGE1 group; this group exhibited significant calcitriol serum increments. Hypercalciuria was observed in the PGE1 group, and resorption markers (N-telopeptides) remained stable. Sutural bones in the PGE1 group exhibited significant anabolism in structural parameters. RBF was 20%, and MBF was 6% in the sham group; in the PGE1 group, RBF was 8.6%, and MBF was 17%. In the PGE1 group, mineralization was significantly accelerated, but resorption remained stable. Conclusions: This model suggests that PGE1 favors palate disjunction, calcitriol synthesis, and shortens the mineralization. Therefore, PGE1 is an important bone anabolic molecule predominantly of modeling-based form and no hypercalcemia.
Resumen Introducción: La hormona paratiroidea es la única molécula anabólica ósea, pero ocasiona hipercalcemia. La prostaglandina E1 (PGE1) sugiere ser un anabólico óseo con formación por modelación predominante y generalmente no ocasiona hipercalcemia. El objetivo de este estudio fue corroborar estas propiedades de la PGE1. Métodos: Por 22 días, 30 conejos divididos en tres grupos (n = 10 cada grupo) recibieron una solución por vía intravenosa: vehículo (grupo control), disyunción palatina más vehículo (grupo sham) y disyunción palatina más 50 mg de PGE1 (grupo PGE1). A los días 1, 3 y 22 se obtuvieron radiografías de la sutura palatina. En el día 22 se analizaron los marcadores bioquímicos de formación ósea y se sacrificó a los conejos. Las suturas y los huesos suturales se procesaron sin descalcificar. La evaluación histomorfométrica fue digitalizada y el frente de mineralización ósea se tiñó con azul de toluidina. Las líneas irregulares reflejan resorción (remodelación) y las líneas rectas no resorción (modelación). Resultados: Radiográficamente, la disyunción palatina fue mayor en el grupo PGE1. Este grupo mostró una hipercalcitonemia significativa, pero la calcemia y los marcadores resortivos (N-telopéptidos) se mantuvieron estables. Por histomorfometría, los huesos suturales del grupo PGE1 mostraron anabolismo significativo en parámetros estructurales. En el grupo sham, la remodelación ósea fue del 20% y la modelación fue del 6%; en el grupo PGE1, la remodelación fue del 8.6% y la modelación fue del 17%. En este mismo grupo, la mineralización fue significativamente acelerada, pero la resorción se mantuvo igual. Conclusiones: Este modelo sugiere que la PGE1 favorece la disyunción palatina y el aumento del calcitriol, y acelera la mineralización y el anabolismo óseo por modelación predominante sin hipercalcemia.
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ABSTRACT Chitosan is a biopolymer with bactericidal/bacteriostatic effect, biocompatible and biodegradable. It has been used in tissue engineering to replace tissues partially or completely by releasing bioactive materials or influencing cell growth, usually in regenerative medicine and dentistry. The aim of this study was to evaluate the cytotoxic and anti-inflammatory effect of chitosan alone or with hemostatic gelatin (Spongostand®) in cultures of human pulp cells (HPC), human gingival fibroblasts (HGF) and mouse pre-osteoblasts (MC3T3-E1, ATCC). HPC and HGF were isolated from patients. Cells were subcultured in DMEM. Chitosan was inoculated at different concentrations (0-0.5%) and hemostatic gelatins impregnated with chitosan (0.19%) were placed directly in the presence of cells and incubated for 24 hours. Cell viability was determined by MTT method and mean cytotoxic concentration (CC50) was calculated from the dose-response curve. Anti-inflammatory effect was calculated from the in vitro gingivitis model induced with interleukin 1beta (IL-1β) in HGF and protein detection. The data were subjected to Shapiro-Wilk, Kruskal-Wallis and Mann-Whitney tests. Experiments were performed in triplicate of three independent assays. Cell viability of HPC, HGF and MC3T3-E1 in contact with chitosan decreased significantly (p<0.05). The HPC were the most sensitive (CC50= 0.18%), followed by HGF (CC50= 0.18%) and MC3T3-E1 (CC50= 0.19%). The cytotoxicity of gelatins impregnated with chitosan decreased cell viability of HGF and HPC by 11% and 5%, respectively. The proinflammatory effect was reduced significantly in the gingivitis model. To conclude, chitosan induces moderate cytotoxic effects alone or with hemostatic gelatin at 0.19%, in dose-dependent manner, with anti-inflammatory effects on human gingival fibroblasts. The use of chitosan as a biomaterial can be an excellent choice for use in regenerative dentistry.
RESUMEN El quitosano es un biopolímero con efecto bactericida/bacteriostático, biocompatible y biodegradable. Se ha utilizado en ingeniería de tejidos con el fin de reemplazar parcial o completamente los tejidos como material bioactivo o influyendo en el crecimiento celular, comúnmente, para medicina y odontología regenerativa. Evaluar el efecto citotóxico y antiinflamatorio del quitosano solo o con gelatina hemostática (Spongostand®) en cultivos con células pulpares humanas (HPC), fibroblastos gingivales humanos (HGF) y preosteoblastos de ratón (MC3T3-E1, ATCC). HPC, HGF se aislaron de pacientes. Las células se subcultivaron en DMEM. Se inoculó quitosano a diferentes concentraciones (0-0,5%) y se colocaron gelatinas hemostáticas impregnadas con quitosano (0,19%) directamente en presencia de células y se incubaron durante 24 horas. La viabilidad celular se determinó mediante el método MTT y se calculó la concentración citotóxica media (CC50) a partir de la curva dosis-respuesta. El efecto antiinflamatorio se calculó a partir del modelo de gingivitis in vitro inducido con interleucina 1β (IL-1β) en HGF. Los datos se sometieron a las pruebas de Shapiro-Wilk, Kruskal-Wallis y Mann-Whitney. Los experimentos se realizaron por triplicado de tres ensayos independientes. La viabilidad celular de HPC, HGF y MC3T3-E1 en contacto con el quitosano disminuyó significativamente la viabilidad celular (p <0.05). Las HPC fueron las más sensibles (CC50= 0,18%) seguido de HGF (CC50= 0,18%) y MC3T3-E1 (CC50= 0,19%). Las gelatinas impregnadas con quitosano mostraron una disminución en la viabilidad celular para HGF, HPC de 11% y 5% respectivamente y se redujo significativamente el efecto pro-inflamatorio en el modelo de gingivitis humano. El quitosano induce efectos citotóxicos moderados solo o con gelatina hemostática a 0,19% de forma dosis-dependiente con efectos antiinflamatorios en fibroblastos gingivales humanos. El uso de quitosano como biomaterial puede ser una excelente opción para su uso en odontología regenerativa.
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Objective:To investigate the effect of long-term application of prostaglandin analog drops on bulbar conjunctival thickness in rabbits.Methods:Twenty-four healthy New Zealand white rabbits were randomly divided into latanoprost group, carteolol group and blank control group using the random number table method, with 8 rabbits in each group.The left eyes of rabbits were taken as experimental eyes.The rabbits in the latanoprost group and carteolol group were given latanoprost eye drops or carteolol eye drops once a day for 2 months according to grouping.The bulbar conjunctival thickness of left eyes of the latanoprost group and carteolol group were measured by optical coherence tomography (OCT) at baseline and two months after administration, respectively.The conjunctival tissue of the three groups were extracted to investigate the protein and mRNA expression level of matrix metalloproteinases-1 (MMP-1) and MMP-3 by Western blot and real-time fluorescence quantitative polymerase chain reaction (PCR). The study protocol was approved by an Ethics Committee of Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (No.2017-0014). The use and care of the experimental animals complied with the ARVO Statement.Results:In the latanoprost group, the conjunctival thickness was significantly reduced from baseline (178.88±5.23)μm to (124.19±11.29)μm at 2 months after administration ( P<0.01). In the carteolol group, there existed no significant difference in the conjunctival thickness between baseline (184.94±11.85)μm and (183.31±8.71)μm at 2 months after administration ( P>0.05). The conjunctival thickness at 2 months after administration of the latanoprost group was significantly thinner than that of the carteolol group ( P<0.01). The protein and mRNA expression levels of MMP-1 and MMP-3 in conjunctival tissue of the latanoprost group were significantly higher than those of the blank control group and carteolol group (all at P<0.01). Conclusions:The long-term topical use of prostaglandin analog drops can significantly reduce the bulbar conjunctival thickness in rabbits.The mechanism may be related to the elevated expression levels of MMP-1 and MMP-3 in the bulbar conjunctival tissue.