Research progress of manganese exposure on abnormal GnRH release in hypothalamus affecting reproductive function / 环境与职业医学

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.

The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy

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.

An in vitro anti-inflammatory effect of Thai propolis in human dental pulp cells

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.

Efectos antirresortivos y antimicrobianos de los antiinflamatorios no esteroideos en lesiones periapicales / Antiresorptive and antimicrobial effects of nonsteroidal anti-inflammatory drugs in periapical lesion

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)

Metabolomics study of rat tail vibration model / 环境与职业医学

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.

Chemical Constituents and Biological Activities of Mitrella Kentii (Blume) Miq. Leaf Oil (Komponen Kimia dan Aktiviti Biologi Minyak Daun Mitrella Kentii (Blume) Miq.) / Jurnal Sains Kesihatan Malaysia

@#Chemical constituents and biological activities of the Mitrella kentii leaf oil were investigated in this study. Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were used to determine the chemical constituents of the oil. The oil was evaluated for its ability to inhibit prostaglandin E2 (PGE2 ) and thromboxane B2 (TXB2 ) productions in human whole blood using a radioimmunoassay technique. Its inhibitory effect on plateletactivating factor (PAF) receptor binding with rabbit platelets using 3 H-PAF as a ligand and its free radical scavenging effect on DPPH were also investigated. Caryophyllene oxide (33.8%w/w), E,Z-farnesol (6.9%), benzyl benzoate (6.5%w/w) and viridiflorol (6.5%w/w) were among the major components of the oil. Even though weak inhibitory activities were observed in both PGE2 and TXB2 assays, significant results were obtained in both PAF receptor binding inhibition and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging effect with IC50 value of 6.6 µg/mL and 155.6 µg/mL respectively. These promising activities warrant the development of the oil as an anti-inflammatory agent.

The effect of ultrasound-guided stellate ganglion block on serum immune inflammatory response, PGE 2, SP, 5-HT expression and brain protection in patients undergoing radical mastectomy for breast cancer / 中国医师杂志

Objective:To investigate the effect of ultrasound-guided stellate ganglion block (SGB) in patients undergoing radical mastectomy, and to provide an effective reference for the selection of clinical anesthesia.Methods:A total of 86 patients undergoing radical mastectomy for breast cancer in the First Affiliated Hospital of Hunan Traditional Chinese Medicine College from January 2018 to December 2019 were selected as the research objects and randomly divided into two groups, with 43 cases in each group. On the basis of conventional general anesthesia, the observation group was treated with ultrasound-guided SGB intervention at the level of the sixth cervical vertebra on the left, and 0.5% ropivacaine was injected with 7 ml. The control group was treated with ultrasound-guided injection of equal volume normal saline at the same site. The hemodynamics and serum inflammatory factors, cellular immunity, prostaglandin E 2 (PGE 2), substance P (SP), serotonin (5-HT) expression, cerebral oxygen metabolism indexes before anesthesia induction (T 1), before intubation (T 2), immediately after intubation (T 3), during skin incision (T 4) and extubation (T 5), and cognitive function score before and after surgery of the two groups were measured respectively. Results:⑴ Hemodynamics: the heart rate (HR) and mean arterial pressure (MAP) of the observation group at T 2, T 3, T 4 were lower than those of the control group ( P<0.05), and there was no significant difference between the two groups at T 1, T 5 ( P>0.05). ⑵ Inflammation and immune status: there was no significant difference in interleukin (IL)-2, IL-18, tumor necrosis factor-α (TNF-α), CD3 + , CD4 + and CD8 + between the two groups at T 1, T 5 ( P>0.05); the IL-2, IL-18, TNF-α and CD8 + at T 2, T 3 and T 4 in the observation group were lower than those in the control group, while the CD3 + and CD4 + were higher than that in the control group ( P<0.05). ⑶ Pain mediators and cerebral oxygen metabolism indexes: there was no significant difference in the levels of PGE 2, SP, 5-HT, SjvO 2, Da-jvO 2 and CEO 2 between the two groups at T 1 and T 5 ( P>0.05); The levels of PGE 2, SP, 5-HT, Da-jvO 2 and CEO 2 in the observation group at T 2, T 3 and T 4 were lower than those in the control group, and the SjvO 2 was higher than those in the control group ( P<0.05). ⑷ Cognitive function: there was no significant difference in Mini Mental State Examination (MMSE) scores between the two groups at 1 day before and 5 days after operation ( P>0.05). At 1 and 3 days after operation, the MMSE score of the observation group was higher than that of the control group ( P<0.05). Conclusions:Ultrasound-guided SGB has a good application effect in patients undergoing radical mastectomy and can reduce the fluctuation of intraoperative hemodynamics, intraoperative inflammatory stress and immunosuppressive effects of the body, reduce the release of pain mediators, and at the same time improve cerebral oxygen metabolism, and promote postoperative cognitive function recovery.

Screening of prostaglandin E2 receptor 4 antagonist from active compounds of Baeckea frutescens L. and its anti-rheumatoid arthritis effect in vivo / 中国药科大学学报

@#The objectives of the study were to screen prostaglandin E2 receptor 4 antagonist from active compounds of Baeckea frutescens L. and to explore its anti-rheumatoid arthritis effect.The HEK293T-EP4 cell antagonist screening model was established in vitro. Homogeneous time-resolved fluorescence (HTRF) technique was used to screen the active compounds of Baeckea frutescens L..SPF grade ICR male mice were randomly divided into control group, model group, methotrexate group, and Baeckea frutescens L.compound BF-2 (100, 50 and 25 mg/kg) groups. The collagen-induced arthritis (CIA) mouse model was established in vivo. The swelling volume of the toes of mice was measured, and the pathological examination was analyzed by staining with hematoxylin and eosin.SPF grade ICR mice, male, were randomly divided into control group, BF-2 (100, 50 and 25 mg/kg) group, and aspirin group.The acetic acid-induced body writhing test was observed.The EP4 in vitro antagonist screening model was successfully established.The preliminary screening results found that BF-2, BF-20, BF-11 and BF-12 had strong EP4 antagonistic activity [(102.11 ± 3.45)%, (90.31 ± 3.59)%, (75.72 ± 1.79)% and (76.84 ± 1.64)%], and BF-2 had the strongest antagonistic activity (IC50 = 0.99 ± 0.08 μg/mL).BF-2 could significantly inhibit the toe swelling of CIA mice, and relieve the degradation of articular cartilage matrix and inflammatory cell infiltration.At the same time, compared with the control group, the writhing times of the mice in each dose of BF-2 were significantly reduced.In this study, BF-2 of Baeckea frutescens L.was selected as an EP4 antagonist, which has potential anti-rheumatoid arthritis activity.

Comparative study on cervical ripening and labour induction with dinoprostone versus foley’s catheter with extra amniotic saline infusion

Background: Induction of labour is defined as initiation of uterine contractions before spontaneous onset of labour. This observational study compares the effect of prostaglandin E2 (PGE2) and extra amniotic saline infusion (EASI) for pre-labour ripening of unfavourable uterine cervix.Methods: This was a prospective study conducted on 100 pregnant women with gestational age ≥37 weeks during a year period in the department of obstetrics and gynaecology of government TD medical college, Alappuzha, Kerala. The period of study was for one year from June 2002 to July 2003. All patients were divided into two groups. Group-1 contains 47 patients who received intracervical PGE2, (Dinoprostone gel, 0.5 mg). Group-2 contains 53 patients who were induced with EASI. The main outcome variables were the number of subjects with favourable Bishop's score, mode of delivery, maternal complications and neonatal outcomes.Results: Majority of the patients in both the groups were in the age of 21-30 years. There was significant difference in age, parity and gestational age of both groups. In this study it was found significant difference in the occurrence of hyper stimulation among PGE2 and EASI; whereas, there was no significant difference in the occurrence of maternal pyrexia among two groups. High incidence of caesarean section was found in EASI. APGAR score of new born babies was high in labour induced with PGE2.Conclusions: PGE2 and EASI have similar efficacy in induction of labour, but EASI is associated with more side effects. Cost wise EASI is more cost effective than PGE2.

Signs of alveolar bone damage in early stages of periodontitis and its prevention by stimulation of cannabinoid receptor 2. Model in rats / Signos de daño óseo alveolar en estadios tempranos de periodontitis y su prevención por estimulación del receptor cannabinoide 2. Modelo en ratas microcisalhamento do cimento resinoso

ABSTRACT The aims of the present study were, first, to identify signs of alveolar bone damage in early stages of experimental periodontitis (EP) and, second, to assess its possible prevention by treatment with cannabinoid receptor 2 agonist HU 308. Experimental periodontitis was induced by injections of lipopolysaccharide (LPS) (1mg/ml) in gums surrounding maxillary and mandibular first molar, 3 days per week, and untreated controls were kept for comparison. Then, a 3-week study was conducted including eighteen new rats (six rats per group): 1) controls; 2) experimental periodontitis rats; and 3) experimental periodontitis rats treated daily with HU 308 (500 ng/ml). After euthanasia, alveolar bone loss was assessed by morphometric and histomorphometric techniques, and the content of prostaglandin E2 (PGE2) in gingival tissue was evaluated by radioimmunoassay. The first signs of alveolar bone loss were apparent at 3 weeks of experimental periodontitis (ρ<0.05) in the mandibular first molar, but there was no detectable change at 1 week, leading us to establish 3 weeks as an early stage of experimental periodontitis. Rats subjected to 3-week experimental periodontitis showed less interradicular bone volume, less whole bone perimeter and fewer bone formation areas, and higher periodontal space height, bone resorption areas, number of osteoclasts and gingival content of prostaglandin E2 than controls, while HU 308 prevented, at least partially, the deleterious effects (ρ<0.001). We can conclude that a 3-week term of lipopolysaccharide-induced periodontitis in rats provides a valid model of the early stage of the disease, as emerging damage is observed in bone tissue. Furthermore, harmful effects at 3 weeks could be prevented by local stimulation of cannabinoid receptor 2, before greater damage is produced.

RESUMEN El objetivo del presente trabajo fue, en primer lugar, identificar signos de daño óseo alveolar en estadios tempranos de periodontitis experimental y, en segundo lugar, evaluar su posible prevención mediante el tratamiento con el agonista del receptor cannabinoide 2, HU 308. La periodontitis experimental fue inducida por inyecciones de lipopolisacárido (1mg/ml) en la encía circundante al primer molar maxilar y mandibular, 3 días por semana, en tanto que controles no tratados fueron mantenidos para la comparación. Posteriormente, un estudio de 3 semanas con dieciocho nuevas ratas (seis por grupo) fue desarrollado: 1) controles; 2) ratas con periodontitis experimental, y 3) ratas con periodontitis experimental tratadas diariamente con HU 308 (500ng/ml). Luego de la euthanasia, la pérdida ósea alveolar fue evaluada por técnicas morfométricas e histomorfométricas, y el contenido de prostaglandina E2 en el tejido gingival fue determinado por radioinmunoensayo. Los primeros signos de pérdida ósea alveolar fueron evidentes a las 3 semanas de inducción de periodontitis experimental (ρ<0.05) en el primer molar mandibular, mientras que no hubo cambios detectables luego de 1 semana de inducción, hecho que nos condujo a establecer a las 3 semanas como un estadio temprano de periodontitis experimental, Las ratas sometidas a perdiodontitis experimental de 3 semanas mostraron menor volumen óseo interradicular, menor perímetro óseo y menos áreas de formación ósea, y mayor altura del espacio periodontal, más áreas de reabsorción ósea, mayor número de osteoclastos y mayor contenido gingival de prostaglandina E2, en comparación a los controles, mientras que el tratamiento con HU 308 previno, al menos parcialmente, los efectos deletéreos (ρ<0.001). Podemos concluir que el término de 3 semanas de periodontitis inducida por lipopolisacárido es un modelo válido de estadio inicial de la enfermedad experimental, dado que se evidencia daño emergente en el tejido óseo. Asimismo, los efectos deletéreos de 3 semanas podrían ser prevenidos por la estimulación local del receptor cannabinoide 2, antes que un daño mayor sea producido.

A prospective randomized comparison of mifepristone with misoprostol and prostaglandin E2 gel with misoprostol for medical termination of pregnancy between 13-20 week of gestation

Background: Worldwide mid-trimester abortion constitutes 10-15% of all induced abortions. Similar trend is seen in India where mid-trimester abortion accounts for 12.9% of all abortions. Prostaglandins have been used for therapeutic termination of pregnancy from 9-22 weeks of gestation since 1970s. The ideal method for mid-trimester abortion with best efficacy and acceptability and least side effects are still to be found. Objective of this study was to compare two drug regimens for mid trimester abortion using mifepristone with intra-vaginal misoprostol and prostaglandin E2 (PGE2) gel with intra-vaginal misoprostol for efficacy and side effects.Methods: This prospective randomized comparative clinical study was conducted on 50 women seeking mid trimester abortion, in two groups. One group received PGE2 gel and misoprostol, second group received mifepristone and misoprostol. Induction abortion interval, side effects were compared between two groups.Results: The mean induction-abortion interval in Group 1 was 6.50±3.54 hours and in Group 2 was 7.33±2.5 hours. In Group 1, success rate at 15 hours was 88%. In Group 2, success rate was 92% both at 15 and 24 hours. Surgical evacuation was required in 8% women in both groups.Conclusions: Both regimens are safe and has a few minor side effects. There was no major side effect and blood loss was within acceptable limits in both groups. The cost of abortifacients and hospital stay was lessor in group1 (prostaglandin gel and misoprostol) making it more economical.

A comparative study of the effect of induction of labour with vaginal misoprostol versus prostaglandin E2 gel on the incidence of pathological cardiotocography tracing

Background: The objective of the present study was to compare the two most commonly used agents for induction of labor-vaginal misoprostol and intracervical dinoprostone gel in terms of the incidence of cardiotocography (CTG) abnormalities and its correlation with fetal distress and fetomaternal outcome.Methods: This is prospective case-control study conducted in department of obstetrics and gynecology, RIMS, Ranchi over a period of 15 months. 112 women requiring induction were randomly assigned to two groups of 56 each, Group M received vaginal misoprostol and Group D received intracervical dinoprostone E2 gel. 56 women with spontaneous labor served as control group. Groups were compared in terms of the incidence of suspicious or pathological CTG tracings, fetal distress, induction to vaginal delivery time, vaginal delivery rates, dose requirements, rate of emergency cesarean.Results: Misoprostol was associated with shorter induction to delivery time (9.54 hours) than dinoprostone gel (13.54 hours), higher vaginal delivery rates (80.35% versus 62.5%), higher delivery rates (73.9%) with single dose itself unlike Group D, where 47.22% required more than one dose. Incidence of suspicious CTG was higher in group M (15.68%) versus 10.25% in Group D. Incidence of pathological CTG was also highest in Group M (7.8%) followed by Group D (2.56%) and Group C (7.8%). Dinoprostone gel lead to failed induction in 25% women, and hence higher caesarean rates.Conclusions: While misoprostol is a better agent for induction when compared with dinoprostone E2 gel in terms of induction-delivery time, higher vaginal delivery rates, less dose requirement, it is associated with greater incidence of non-reassuring/pathological CTG. There was justified improvement in perinatal outcome due to preparedness beforehand with use of CTG.

Maternal and fetal outcomes with the use of prostaglandins E2 as a cervical ripening agent for induction of labour

Background: In modern medicine induction of labour is required in patients for a good feto-maternal outcome. PGE2 is a prostaglandin analogue which has been used as a cervical ripening agent to improve bishops score. Objective of this study was to evaluate the efficacy of intravaginal PGE2 gel as a cervical ripening agent in unfavourable cervix for induction of labor and any complications associated with its use.Methods: This study comprised of 90 women who required labor induction. Singleton pregnancy above 37 weeks, live intrauterine fetus, Cephalic presentation, Bishop score of 1-6, reactive FHR pattern were included. Women who required only single induction were categorized as Group 1. Those requiring more than one dose after reassessment of bishops scoring at 6, 12 and 18 hours belonged to Group 2.Results: Group1 had more of younger population below 30 years consisting more primigravidas with > 80% women having gestational age of > 39 weeks. Most common indication for induction of labour in both groups was post-dated pregnancy. 65 patients received one dose of cerviprime gel forming Group 1. In Group 2, 72% received 2 doses and 28%, 3 doses of gel. Initial bishops score mean was 4.2 in Group 1 and 4.1 in Group 2. Mean change in bishop score was analysed after 6, 12, and 18 hours of instillations of PGE2 gel. Significant p value was obtained in all groups requiring one, two and three doses of gel. In Group 1, 12.3% and in Group 2, 16% had LSCS. Maternal side effects were minimal and neonatal outcome was good.Conclusions: The study showed that intravaginal application of PGE2 is effective, safe and acceptable method as a cervical ripening agent for labor induction in women with poor bishops score. It reduces caesarean delivery rate without increasing maternal and neonatal morbidity.

Root canal contamination or exposure to lipopolysaccharide differentially modulate prostaglandin E 2 and leukotriene B 4 signaling in apical periodontitis

Abstract Purpose To evaluate the kinetics of apical periodontitis development in vivo , induced either by contamination of the root canals by microorganisms from the oral cavity or by inoculation of bacterial lipopolysaccharide (LPS) and the regulation of major enzymes and receptors involved in the arachidonic acid metabolism. Methodology Apical periodontitis was induced in C57BL6 mice (n=96), by root canal exposure to oral cavity (n=48 teeth) or inoculation of LPS (10 µL of a suspension of 0.1 µg/µL) from E. coli into the root canals (n= 48 teeth). Healthy teeth were used as control (n=48 teeth). After 7, 14, 21 and 28 days the animals were euthanized and tissues removed for histopathological and qRT-PCR analyses. Histological analysis data were analyzed using two-way ANOVA followed by Sidak's test, and qRT-PCR data using two-way ANOVA followed by Tukey's test (α=0.05). Results Contamination by microorganisms led to the development of apical periodontitis, characterized by the recruitment of inflammatory cells and bone tissue resorption, whereas inoculation of LPS induced inflammatory cells recruitment without bone resorption. Both stimuli induced mRNA expression for cyclooxygenase-2 and 5-lipoxygenase enzymes. Expression of prostaglandin E 2 and leukotriene B 4 cell surface receptors were more stimulated by LPS. Regarding nuclear peroxisome proliferator-activated receptors (PPAR), oral contamination induced the synthesis of mRNA for PPARδ, differently from inoculation of LPS, that induced PPARα and PPARγ expression. Conclusions Contamination of the root canals by microorganisms from oral cavity induced the development of apical periodontitis differently than by inoculation with LPS, characterized by less bone loss than the first model. Regardless of the model used, it was found a local increase in the synthesis of mRNA for the enzymes 5-lipoxygenase and cyclooxygenase-2 of the arachidonic acid metabolism, as well as in the surface and nuclear receptors for the lipid mediators prostaglandin E2 and leukotriene B4.

Immunomodulatory characteristics of mesenchymal stem cells mediated by inflammatory factors / 中国组织工程研究

BACKGROUND: Mesenchymal stem cells possess strong immunomodulatory capacity, mainly involved in the proliferation, differentiation and functional status of immune cells, and the secretion of inflammatory factors. The immunomodulatory capacity of mesenchymal stem cells is regulated by inflammatory factors. As the type and level of inflammatory factors in the microenvironment change, the immune regulation function of mesenchymal stem cells also changes. OBJECTIVE: To review the research progress of inflammatory factor intervention in the immune regulation of mesenchymal stem cells. METHODS: A computer-based retrieval of PubMed, Elsevier and CNKI databases was performed. The keywords were “mesenchymal stem cells, immune regulation, plasticity, interferon gamma, transforming growth factor beta, interleukin-17, interleukin-35, prostaglandins E2” in Chinese and English, respectively. The articles concerning the effects of inflammatory factor intervention on the immune regulation of mesenchymal stem cells were included. RESULTS AND CONCLUSION: After intervention and pre-treatment of interferon-γ, transforming growth factor-β, interleukin-17, interleukin-35 and prostaglandin E2, the biological characteristics of mesenchymal stem cells have also changed. The interventions cannot only reshape the tissue microenvironment and affect the inflammatory response, but also reconstruct the immune balance, which further treats or alleviates the disease progression. Reasonable individualized and differentiated treatments will be performed at different disease stages according to inflammatory and immunological reaction of the disease. All of them are expected to further improve the therapeutic effect of mesenchymal stem cells on immuno-inflammatory diseases.

Prostaglandin e2 induces expression of mineralization genes by undifferentiated dental pulp cells

Abstract Prostaglandin E2 (PGE2) is a lipid mediator usually released during inflammation. This study aimed to investigate the potential of soluble or microsphere-loaded PGE2 on inducing differentiation of dental pulp stem cells. PGE2-loaded microspheres (MS) were prepared using an oil-in-water emulsion solvent extraction-evaporation process and were characterized. Mouse dental pulp stem cells (OD-21) were stimulated with soluble or PGE2-loaded MS (0.01 and 0.1 µM). Cell viability was determined by MTT colorimetric assay. Ibsp, Bmp2 and Runx2 expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) after 3, 6, and 24 h. The results showed that the soluble PGE2 reduced dental pulp stem cells viability after 24 h of stimulation whereas PGE2-loaded MS did not. Soluble PGE2 up-regulated Ibsp and Bmp2 at 3 h, differently from PGE2-loaded MS. On the other hand, PGE2-MS induced Bmp2 and Runx2 at 6 h and Ibsp at 24 h. In conclusion, our in vitro results show that PGE2, soluble or loaded in MS are not cytotoxic and modulateIbsp,Bmp2, andRunx2gene expression in cultured OD-21 cells.

Resumo A Prostaglandina E2 (PGE2) é um mediador lipídico comumente liberado durante a inflamação. Este estudo teve como objetivo investigar o potencial da PGE2, solúvel ou na forma de microesferas, na diferenciação de células-tronco de polpa dentária. Microesferas de PGE2 (MS) foram preparadas por meio do processo de extração/evaporação de solvente em emulsão óleo-em-água e foram caracterizadas. Células-tronco de linhagem derivadas da polpa dentária de camundongos (OD-21) foram estimuladas com PGE2 solúvel ou na forma de MS (0,01 e 0,1 µM). A citotoxicidade foi determinada por ensaio colorimétrico MTT. A expressão gênica de Ibsp, Bmp2 e Runx2 foi avaliada por meio de reação em cadeia da polimerase em tempo real (qRT-PCR) após 3, 6 e 24 h. Os resultados mostraram que as MS contendo PGE2 não foram citotóxicas para células-tronco da polpa dentária, enquanto MS vazias ou PGE2 solúvel reduziram a viabilidade celular após 24 h de estimulação. PGE2 solúvel aumentou a expressão de Ibsp e Bmp2 após 3 h, diferentemente da PGE2 em MS. Por outro lado, PGE2-MS induziram a expressão de Bmp2 e Runx2 após 6h de estímulo e Ibsp após 24h. Em conclusão, nossos resultados in vitro demonstram que a PGE2, solúvel ou em microesferas não são citotóxicas e modulam a expressão gênica deIbsp,Bmp2 eRunx2em células OD-21.

Roles of Mesenchymal Stem Cells in Tissue Regeneration and Immunomodulation

Mesenchymal stem cells are classified as multipotent stem cells, due to their capability to transdifferentiate into various lineages that develop from mesoderm. Their popular appeal as cell-based therapy was initially based on the idea of their ability to restore tissue because of their differentiation potential in vitro; however, the lack of evidence of their differentiation to target cells in vivo led researchers to focus on their secreted trophic factors and their role as potential powerhouses on regulation of factors under different immunological environments and recover homeostasis. To date there are more than 800 clinical trials on humans related to MSCs as therapy, not to mention that in animals is actively being applied as therapeutic resource, though it has not been officially approved as one. But just as how results from clinical trials are important, so is to reveal the biological mechanisms involved on how these cells exert their healing properties to further enhance the application of MSCs on potential patients. In this review, we describe characteristics of MSCs, evaluate their benefits as tissue regenerative therapy and combination therapy, as well as their immunological properties, activation of MSCs that dictate their secreted factors, interactions with other immune cells, such as T cells and possible mechanisms and pathways involved in these interactions.

Applicability of membrane separation technique for concentrating anti-inflammatory compounds of Cornus officinalis Decoction based on anti-rheumatoid arthritis activity / 中草药

Objective To investigate the anti-inflammatory effect of Cornus officinalis (CO) Decotion and its refined solutions from membrane separation by using 0.05 μm inorganic ceramic membrane (CO-0.05) and 10K polysulfone hollow fiber membrane (CO-10K), and evaluate the applicability of the membrane separation technique for concentrating the anti-inflammatory compounds of C. officinalis Decotion. Methods Inflammatory model of interleukin (IL)-1β and tumor necrosis factor (TNF)-α stimulated human fibroblast-like synoviocytes (HFLS) was prepared. The CCK-8 assay and ELISA were applied to detect the effects of C. officinalis Decotion and its refined solutions on the viability of HFLS and the secretion of inflammatory cytokines, respectively. Moreover, the animal model of adjuvant arthritis (AA) was used. The SD rats were divided into six groups: control group, model (AA) group and AA groups intragastrically receiving CO (120 mg/kg), CO-0.05 (120 mg/kg), CO-10K (120 mg/kg) and TGP (0.125 mg/kg) with daily treatments for 23 days. The weight and paw swelling of rats in different groups were detected. The ELISA was used to detect secretion levels of prostaglandin E2 (PGE2), IL-1, IL-6, and TNF-α in serum. Results The production of vascular endothelial growth factor (VEGF) induced by IL-1β/TNF-α were significantly inhibited with C. officinalis Decotion and its refined solutions by membrane separation treatment (P < 0.05, 0.01, 0.001). C. officinalis Decoction and the refined solutions significantly ameliorated paw swelling and increased weight gain of AA rats (P < 0.05, 0.01, 0.001), and reduced the secretion of TNF-α, PGE2, IL-1, IL-6 in serum (P < 0.001). By comparing the inhibition efficiency of inflammatory cytokines by inorganic ceramic membrane refined solution and polysulfone hollow fiber membrane refined solution, the polysulfone hollow fiber membrane refined solution exhibited better anti-inflammatory activity. Conclusion Both of refined solutions of C. officinalis Decotion from inorganic ceramic membrane and polysulfone hollow fiber membrane separation exhibited dramatically anti-inflammtory activity. Moreover, the polysulfone hollow fiber membrane was more applicable for concentrating the anti-inflammatory compounds of C. officinalis Decotion.

Pharmacodynamic Evaluation of Tanreqing Inhalation Solution / 中国实验方剂学杂志

Objective: To clarify the antitussive, expectorant, antipyretic and anti-inflammatory effects of Tanreqing inhalation solution, and provide basis and data support for further research and development of this preparation. Method: The methods of cough induced by ammonia and tracheal phenol red excretion were used to observe the antitussive and expectorant effects of Tanreqing inhalation solution in mice. The fever model of rats was established by intraperitoneal injection of bacterial lipopolysaccharide(LPS) to observe the antipyretic effect of the Tanreqing inhalation solution, the acute pneumonia model of rats was established by atomizing LPS inhalation, and the anti-inflammatory effect of Tanreqing inhalation solution was observed. Result: Tanreqing inhalation solution could reduce the number of coughs in mice induced by ammonia water, increase the amount of phenol red excretion in mouse trachea, decrease the levels of body temperature and its related regulatory factors of prostaglandin E2(PGE2) and cyclic adenosine monophosphate(cAMP) of rats induced by LPS, decrease the white blood cell(WBC) count and the neutrophil ratio(NEUT) in bronchoalveolar lavage fluid(BALF) of rats with LPS-induced acute pneumonia, and reduce the levels of nuclear transcription factor-κB(NF-κB) and interleukin-1β(IL-1β) in lung tissue. Conclusion: Tanreqing inhalation solution has obvious antitussive, expectorant, antipyretic and anti-inflammatory effects, which is worthy of further development and promotion.

Effect of electroacupunture on supplementary analgesia and the levels of serum β-endorphin and prostaglandin E in patients with total knee arthroplasty / 中国针灸

OBJECTIVE@#To observe the effect on supplementary analgesia after total knee arthroplasty (TKA) treated with electroacupunture, and explore it's mechanism.@*METHODS@#A total of 40 patients with severe knee osteoarthritis were randomized into an observation group and a control group, 20 cases in each one. During the operation, patients were given epidural anesthesia in the two groups, conventional patient controlled epidural analgesia and oral celecoxib were applied after the operation. In the observation group, electroacupunture was used at Liangqiu (ST 34), Xuehai (SP 10), Yinlingquan (SP 9), Zusanli (ST 36), Fenglong (ST 40) and Qiuxu (GB 40) on the operation side from the 1st to 7th day after the operation to support analgesia, 30 min for each time, once a day. The visual analogue scale (VAS) was used to record postoperative pain of resting state and active state. The levels of serum prostaglandin E and β-endorphin were measured on the 1st and 7th day after surgery in the two groups.@*RESULTS@#In the observation group, the VAS scores of resting state and active state were superior to the control group on the 3rd, 5th and 7th day after the operaton (all <0.05); after the treatment, the level of serum β-endorphin was increased and the level of serum prostaglandin E was reduced in the two groups (all <0.05), and the change of the observation group was larger than that of the control group (both <0.05).@*CONCLUSION@#Electroacupunture has the effect of supplementary analgesia for patients after TKA, the mechanism may be related to promote the synthesis of β-endorphin and inhibit the synthesis of prostaglandin E.