Anti-swelling and Analgesic Mechanism of Jianpi Tongluo Prescription from MAPKs Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the anti-swelling and analgesic effects of Jianpi Tongluo prescription （JPTL） and to explore its mechanism initially. MethodA total of 120 ICR mice were divided into normal group， model group， JPTL low-， medium- and high-dose groups （5， 10， 20 g·kg-1） and positive drug （celecoxib， 0.03 g·kg-1） group， with 10 in each group （po，once a day）. Complete freund's adjuvant （CFA） was used to induce the model of chronic inflammatory pain， and xylene-induced ear swelling test， hot plate test and acetic acid writhing test were performed to observe the anti-swelling and analgesic effects of different doses of JPTL in these four acute and chronic models. Further， enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of prostaglandin E2 （PGE2）， interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum and inflammatory paw of mice with chronic inflammatory pain， and the expressions of aquaporin 1 （AQP1）， aquaporin 3 （AQP3）， cyclooxygenase 1 （COX1）， cyclooxygenase 2 （COX2） and mitogen-activated protein kinases （MAPKs） in inflammatory paw were detected by Western blot， to explore the preliminary mechanism of JPTL. ResultCompared with the conditions in the normal group， there was a significant increase in the ear swelling of xylene-induced model mice， a shortened paw withdrawal latency in the hot plate test （P<0.01）. Compared with the model group， JPTL remarkably increased the inhibition rate of xylene-induced ear swelling （P<0.05， P<0.01）， prolonged the latency period of writhing caused by acetic acid and reduced the number of writhing （P<0.05， P<0.01）. Compared with normal group, the degree of feet swelling in chronic inflammatory pain mice was significantly increased， the threshold of mechanical pain was decreased and the threshold of cold pain was increased （P<0.05， P<0.01）， the protein contents of AQP1 and AQP3 in inflammatory feet were increased， and the contents of IL-1β， IL-6， TNF-α， PGE2 and COX2 in inflammatory feet were increased in serum and/or inflammatory feet. The protein expression levels of p-p38 MAPK， p-JNK and p-ERK in inflammatory feet were increased （P<0.01）. Compared with the model group， JPTL relieved paw swelling of mice with chronic inflammatory pain， elevated mechanical withdrawal threshold while decreased cold withdrawal threshold， with analgesia lasting for 4 h and the optimal time point for analgesia being 2 h after administration （P<0.05， P<0.01）. Moreover， JPTL down-regulated AQP1， AQP3， COX2， p-p38 MAPK， p-JNK and p-ERK in inflammatory paw of mice with chronic inflammatory pain and reduced IL-1β， IL-6， TNF-α， and PGE2 in serum and/or inflammatory paw， but it had no significant effect on COX1 （P<0.05， P<0.01）. ConclusionJPTL has anti-swelling and analgesic effects， and its mechanism is related to inhibiting the production of cytokines and inflammatory mediators via the down-regulation of MAPKs signaling pathway， which provides an experimental basis for the clinical application of JPTL.

Mediator Complex Subunit 8:Expression in Gastric Cancer, Prognostic Significance,and Impact on Cell Cycle / 中国医学科学院学报

Objective To investigate the expression and prognostic significance of mediator complex subunit 8 (MED8) in gastric cancer and its impact on the cell cycle.Methods The expression of MED8 in gastric cancer and adjacent tissues and its correlation with patients' prognosis were analyzed using public databases.A validation cohort of 104 patients who underwent radical resection for gastric cancer in the First Affiliated Hospital of Bengbu Medical College from June 2012 to July 2017 was included.The receiver operating characteristic curve was established to evaluate the predictive value of MED8 for postoperative 5-year survival.Bioinformatics tools were used to predict the biological roles of MED8 in gastric cancer.The effect of the MED8 level on the G1/S phase transition of gastric cancer cells (MGC-803) was analyzed via lentivirus transduction and flow cytometry.Western blotting was carried out to assess the impact of MED8 expression on the protein levels of cyclin-dependent kinase 4(Cdk4) and G1/S-specific cyclin-D1(CyclinD1) in MGC-803 cells.Results The high expression of MED8 in the gastric cancer tissue was associated with poor prognosis (P<0.001) and had prognostic significance (area under curve=0.733,P<0.001).Gene enrichment analysis suggested that MED8 may participate in the cell cycle process.Flow cytometry results revealed that the upregulation of MED8 expression promoted the transition of MGC-803 cells from the G1 phase to the S phase (P<0.001),while the downregulation of MED8 had the opposite effect (P<0.001).Western blotting showed increases in the protein levels of Cdk4 and CyclinD1 in MGC-803 cells with upregulated MED8 expression (all P<0.001),and decreases in the cells with downregulated MED8 expression (all P<0.001).Conclusion MED8 is highly expressed in gastric cancer and may affect its progression and prognosis by regulating the G1/S phase transition of gastric cancer cells.

Research progress on berberine in the prevention and treatment for periodontitis / 口腔疾病防治

@#Berberine is a natural isoquinoline alkaloid extracted from Rhizoma Coptidis and other Chinese herbal medicines. Since berberine has a variety of biological effects, such as bacteriostasis, anti-inflammatory, anti-bone resorption and blood sugar-lowering effects, and is associated with few side effects, studies are increasingly discovering its potential application in the prevention and treatment of periodontitis. This review summarizes the relevant research progress of berberine in the prevention and treatment of periodontitis in recent years, aiming to provide a new strategy for the clinical prevention and treatment of periodontitis. The results of the literature review showed that berberine could prevent the occurrence and development of periodontitis by inhibiting periodontal pathogens, reducing periodontal tissue inflammation and inhibiting alveolar bone resorption. However, the mechanism of periodontitis is complicated, and current research remains limited. In the future, more in vivo and in vitro studies are needed to further explore the mechanism of berberine in inhibiting the occurrence and development of periodontitis, and more large-sample prospective clinical studies should be conducted to confirm the effect of berberine on the prevention and treatment of periodontitis.

Regulatory role of the transcriptional coactivator Mediator 1 in skin hair regeneration and its mechanisms / 中华皮肤科杂志

Objective:To investigate the effect of the transcriptional coactivator Mediator 1 (Med1) on mouse hair regeneration, and to explore potential mechanisms.Methods:Med1 flox/flox C57BL/6J mice were mated with K14-Cre mice, and the mice with epidermis-specific knockout of Med1 gene, namely K14-Cre-expressing Med1 flox/flox mice (knockout group) , were obtained by using the Cre-Loxp system, while Med1 flox/flox mice without K14-Cre expression served as control group. Mice in the two groups (3 mice in each group) were raised together for 8 weeks followed by dorsal hair removal. Hair regeneration was observed for 12 consecutive days after hair removal. After 12 days, all mice in the two groups were sacrificed, their depilated and non-depilated dorsal skin tissues were resected, and total RNA was extracted from the tissues. Real-time quantitative PCR was performed to determine the mRNA expression of hair keratin genes, vitamin D receptor/β-catenin pathway-related genes, and genes associated with maintenance of hair follicle stem cell proliferation and quiescence. Paraffin-embedded sections of depilated and non-depilated mouse skin tissues were prepared, and immunofluorescence staining was conducted to determine the number of stem cells in the hair follicle bulge. Two-independent-sample t test was used for comparisons between two groups. Results:From days 0 to 12 after depilation, hair regeneration was delayed in the depilated skin area in the knockout group compared with the control group. Real-time quantitative PCR showed significantly decreased mRNA relative expression levels of hair keratin genes Ha1 and Krt2-16, vitamin D receptor/β-catenin pathway-related genes S100a3, Dlx3 and Tubb3, and genes associated with maintenance of hair follicle stem cell proliferation and quiescence including Lhx2, Sox9 and Nfatc1 in the depilated skin tissues in the knockout group (22.09 ± 12.32, 2.07 ± 0.20, 0.02 ± 0.01, 12.36 ± 2.12, 1.75 ± 0.46, 0.39 ± 0.02, 4.42 ± 0.76, 0.44 ± 0.07, respectively) compared with the control group (70.53 ± 9.46, 7.76 ± 0.49, 0.05 ± 0.01, 26.16 ± 2.96, 2.60 ± 0.14, 0.71 ± 0.09, 11.93 ± 0.42, 0.75 ± 0.04, respectively; t = 5.40, 18.64, 3.89, 6.57, 3.04, 6.10, 15.03, 6.18, respectively, all P < 0.05) . Immunofluorescence staining showed that the number of CD34 +K15 + hair follicle stem cells in the hair follicle bulge in both depilated and non-depilated skin tissues was significantly lower in the knockout group than in the control group. Conclusion:Med1 gene knockout may down-regulate the expression of downstream genes of the vitamin D receptor/β-catenin pathway and genes associated with maintenance of hair follicle stem cell proliferation and quiescence (Sox9, Nfatc1 and Lhx2) , and reduce the number of hair follicle stem cells, leading to hair follicle differentiation disorder and hair regeneration delay.

Correlations between psoriasis and obesity / 中华皮肤科杂志

It has become a consensus that there is a correlation between psoriasis and obesity, but the exact mechanism is not yet clear. Studies demonstrate that common inflammatory pathways and insulin resistance may contribute to the association between psoriasis and obesity. Understanding the impact of obesity on the occurrence and treatment of psoriasis will be beneficial to the treatment of psoriasis.

Observation and analysis on clinical efficacy of Dachengqi decoction for acute pancreatitis / 中华危重病急救医学

Objective:To observe the clinical efficacy of Dachengqi decoction combined with octreotide in the treatment of patients with acute pancreatitis (AP).Methods:From March 2018 to February 2021, a total of 68 patients with mild acute pancreatitis (MAP) and moderately severe acute pancreatitis (MSAP) admitted to Shanghai Traditional Chinese Medicine-Integrated Hospital were included, and they were randomly divided into western medicine treatment group and Dachengqi decoction group. The patients in the western medicine treatment group received conventional western medicine (octreotide+symptomatic treatment); in the Dachengqi decoction group, 100 mL of Dachengqi decoction was taken orally on the basis of conventional western medicine, twice a day; the observation time for both groups was 7 days. The levels of inflammation parameters [white blood cell count (WBC), interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP)] and serum amylase (Amy) before and after treatment of patients between the two groups, as well as the occurrence of clinical efficacy indicators and adverse reactions were compared.Results:Among the 68 included patients, 4 were excluded because the specimen was not obtained or the patient gave up the treatment. A total of 64 patients were finally enrolled in the analysis, including 32 cases in the Dachengqi decoction group and 32 cases in the western medicine treatment group respectively. There was no statistically significant difference in inflammation parameters or serum Amy levels before treatment between the two groups. At 7 days of treatment, the inflammatory parameters and serum Amy levels of the two groups were significantly lower than those before treatment [western medicine treatment group: WBC (×10 9/L) was 5.94±2.08 vs. 11.81±3.66, IL-6 (ng/L) was 7.22 (5.72, 14.23) vs. 30.13 (15.77, 85.37), PCT (μg/L) was 0.068 (0.052, 0.128) vs. 0.290 (0.231, 0.428), CRP (mg/L) was 26.0 (18.3, 35.8) vs. 112.0 (62.0, 126.0), Amy (U/L) was 77 (57, 116) vs. 352 (162, 1 576); Dachengqi decoction group: WBC (×10 9/L) was 5.56±2.04 vs. 12.22±2.85, IL-6 (ng/L) was 5.70 (3.26, 11.06) was 50.30 (23.99, 88.32), PCT (μg/L) was 0.038 (0.028, 0.808) vs. 0.308 (0.129, 0.462), CRP (mg/L) was 11.0 (3.5, 24.0) vs. 150.0 (75.0. 193.0), Amy (U/L) was 78 (57, 104) vs. 447 (336, 718); all P < 0.05], and the levels of IL-6, PCT, and CRP decreased more significantly after treatment in the Dachengqi decoction group (all P < 0.05). The total clinical effective rate of patients in the Dachengqi decoction group was significantly higher than that of the western medicine treatment group [93.75% (30/32) vs. 71.88% (23/32), P < 0.05]. There was no obvious adverse event during the treatment and observation period in the two groups. Conclusion:Dachengqi decoction combined with octreotide therapy could improve the clinical efficacy of AP patients, and its mechanism might be related to reducing the level of inflammatory factors, thereby inhibiting the inflammatory response, and regulating the level of serum Amy.

Coactivator p300-induced H3K27 acetylation mediates lipopolysaccharide-induced inflammatory mediator synthesis / 南方医科大学学报

OBJECTIVE@#To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism.@*METHODS@#Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq).@*RESULTS@#Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level.@*CONCLUSION@#LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.

"Cada um é um": constituição de saberes em uma experiência de formação na perspectiva inclusiva / "Cada uno es uno": constitución e saberes en una experiencia de formación inclusiva / "Each one is one": constitution of knowledge in a training experience from the inclusive perspective / «Chacun est un¼: constitution de savoirs dans une expérience de formation inclusive

Este artigo discute os resultados de uma pesquisa que investigou uma experiência de formação inicial na qual licenciandos de diferentes cursos de Graduação atuavam como mediadores de estudantes com deficiência em uma escola comum. A partir do conceito psicanalítico de saber, buscou-se compreender como se dá a mobilização de saberes pelos mediadores e quais efeitos emergiram para a sua formação profissional como professores. Por meio de rodas de conversa e entrevistas individuais, os depoimentos dos participantes apontaram saberes em construção no percurso de cada mediador, o que os possibilitava encontrar saídas para os impasses presentes na relação com o outro no contexto escolar. Os mediadores reconheceram a importância dessa vivência para a formação, elencaram aproximações e paradoxos na articulação teoria-prática, além de expressarem suas próprias elaborações acerca desta experiência

Este artículo discute resultados de una investigación que estudió una experiencia de formación inicial donde licenciandos de diferentes cursos actuaban como mediadores de estudiantes com deficiência en una escuela común. A partir del concepto psicoanalítico del saber,se buscó compreender como se realiza la movilización de saberes por mediadores y qué efectos surgieron para su formación profesional. A través de círculos de charlas y entrevistas individuales, los testimonios de los participantes indicaron saberes en construcción en la trayectoria de cada mediador, posibilitándolos a encontrar salidas para obstáculos presentes en la relación con el outro en el contexto escolar. Los mediadores reconocieron la importancia de esa vivencia para la formación, mencionaron aproximaciones y contradicciones en la articulación teoría-práctica, además de expressar sus propias elaboraciones acerca de esta experiencia

This article discusses the results of a survey that investigated an initial training experience in which undergraduates from different undergraduate courses acted as mediators for students with disabilities in a regular school. Based on the psychoanalytical concept of knowledge, we sought to understand how knowledge is mobilized by these mediators and what effects have emerged for their professional development as teachers. Through round tables and individual interviews, the participants testimonies pointed to knowledge under construction in each mediator's path, which enabled them to find solutions to the impasses present in the relationship with the other in the school context.The mediators recognized the importance of this experience for training, listed approaches and paradoxes in the theory-practice articulation, in addition to expressing their own elaborations about this experience

Cet article discute les résultats d'une recherche qui a été menée sur une expérience de formation initiale dans laquelle des étudiants en licence de premier cycle sont intervenus comme des médiateurs des élèves handicapés. A partir du concept psychanalytique de savoir, nous cherchons à comprendre comment s'effectue la mobilisation de savoirs par les médiateurs et quels sont les effets qui en ont émergé pour leur formation professionnelle. Les témoignages des participants ont indiqué des savoirs en construction dans le parcours de chaque médiateur, ce qui leur permettait de trouver des solutions aux impasses présentes dans la relation avec l'autre en contexte scolaire. Les médiateurs ont reconnu l'importance de cette expérience pour leur formation, ils ont énuméré des approches et des paradoxes dans l'articulation théorie-pratique

MEDIATOR COMPLEX OR EMPATHY SICKNESS AND JUDGE COMPLEX

We put ourselves in others shoes. How often? Does it bring pain? Does it affect our mood? Mediator is defined as a person who attempts to make people involved in a conflict come to an agreement; a go-between while complex is an abnormality, most often a serious one. Judge on the other hand, decides cases. This is an introduction to a proposed complex wherein the author is admitted to have some symptoms of which may be considered. That we often derive sorrow from the sorrow of others, is a matter of fact too obvious to require any instances to prove it. – Adam Smith

Effect of recombinant human growth hormone on corneal epithelial wound healing / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To explore the effects of recombinant human growth hormone(rHGH)on early rehabilitation in rabbit corneal epithelial wound. <p>METHODS:Thirty-two New Zealand rabbits were selected to establish the corneal epithelial defects models. One eye was treated with normal saline(NC group)and the other eye was treated with 20nmol/L rHGH(rHGH group)in a randomized double-blinded way. The corneal healing process was monitored by the corneal fluorescein staining scores at 0h, 24h, 48h, and 72h after the surgery. The central corneal sensitivity was detected by Cochet-Bonnet corneal esthesiometer and the concentrations of inflammatory mediators interlecukin-1α(IL-1α), interlecukin-17(IL-17), interlecukin-21(IL-21), Leptin, matrix metalloproteinase-9(MMP-9)and tumor necrosis factor-α(TNF-α)in collected tears were measured by multiplex antibody microarray. <p>RESULTS: The corneal epithelial healing rates of the NC group and rHGH group were(62.52±6.73)% and(79.62±10.62)%(<i>P</i><0.05),(90.56±9.57)% and(98.43±3.65)%(<i>P</i><0.05)at 48h and 72h postoperatively. The central corneal sensitivity of rHGH group(4.22±0.26)cm was better than that in NC group(3.22±0.42)cm at 48h after surgery(<i>P</i><0.05). The expressions of TNF-α and IL-1α increased in both groups at each time point after operation, and the expressions in NC group were higher than those in the rHGH group. Both groups had higher MMP-9 concentrations in the tear fluid at 24 and 48h postoperation in comparison with the point before the operation. The MMP-9 expression in NC group was higher than that in the rHGH group at 48h postoperatively. The expressions of IL-21 in NC group were higher than those in the rHGH group at 24 and 48h postoperation in comparison with the point before the operation(<i>P</i><0.05). No significant differences in tearIL-17 and Leptin were observed between groups before and after surgery(<i>P</i>>0.05).<p>CONCLUSION: Topical application of rHGH can accelerate the early stage of rabbit corneal epithelial wound healing <i>in vivo</i>.

Amphetamine causing damage of dopamine cells via inhibiting of protein kinase B / glycogen synthase kinase-3β/ collapsin response mediator protein-2 signal pathway / 解剖学报

Objective To explore the damage mechanism of dopamine cells induced by amphetamine (AMPH). Methods The damage model of dopaminergic cells in mice was established by intraperitoneal injection of AMPH. The mice were randomly grouped into control, saline, amphetamine treatment for 1 day, 7 days, 14 days and 28 days. Each group contained 10 mice. The model of cell injury was established by use of AMPH in PC12 cells. The dopaminergic fibers of corpus striatum and PC12 cells were observed by the immunohistochemistry and immunofluorescence method, and changes of proteins in the protein kinase B (Akt) / glycogen synthase kinase 3β(GSK-3β) / collapsin response mediator protein 2 (CRMP-2) signal pathway were detected by Western blotting. Results AMPH caused the damage of dopaminergic fibers in the mouse corpus striatum and PC12 cells. Meanwhile, AMPH inhibited Akt and GSK-3β phosphorylation levels, and increased phosphorylated CRMP-2 level. Nerve growth factor(NGF), an agonist of Akt, or SB216763, an inhibitor of GSK-3β protected PC12 cells against AMPH-induced toxicity through upregulation of Aat and GSK-3β phosphorylation and downregulated of phosphorylation CRMP-2. Conclusion AMPH causes damage of dopamine cells via inhibition of Akt/ GSK-3β/ CRMP-2 signal pathway.

The protective effect of Medicoscab Tincture on deep partial thickness burn rats and its mechanism / 中国药理学通报

Aim To investigate the effect of Medi- coscab Tincture could increase the healing rate of burn coscab Tincture on the wound repair of deep partial thickness burn in rats and its possible mechanism. Methods SD100 rats were used to make a rat model of deep partial thickness burn. The rats were randomly divided into five groups; normal, model control, positive control, Medicoscab Tincture high-dose, and Medicoscab Tincture low-dose. The dosing group was changed daily for 14 consecutive days. The healing rate and water content of wound were measured at 3 d, 7 d and 14 d after burn. The activities of superoxide dismutase (SOD) and catalase (CAT) and the content of malondialdehyde ( MDA) were determined by bio-chemical analysis. Serum levels of tumor necrosis fac- tor-a (TNF-a), interleukin-1 (3 (IL-1(3) and interleu- kin-6 (IL-6) in rats were determined. Results Medi- wound and decrease the water content of burn wound tissue in rats ( P < 0. 05 ). The activity of SOD significantly increased, the content of MDA decreased (P < 0. 05), and the contents of TNF-a, IL-1 (3 and IL-6 in serum of burned rats decreased ( P < 0. 05, P < 0.01). Conclusions Medicoscab Tincture can improve the wound healing rate, reduce the wound water content, increase SOD activity, reduce the content of MDA in the wound, and reduce the serum levels of inflammatory factors TNF-a, IL-1 (3 and IL-6. Therefore, Medicoscab Tincture has a protective effect on deep partial thickness burn in rats.

Effect of aluminum-maltolate on primary hippocampal neuron neurite damage by regulating CRMP2 through GSK-3β in mice / 环境与职业医学

Background Aluminum can induce irreversible structural and synaptic functional damage, and the associated mechanism may be related to the neurite damage regulated by glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP2). Objective This experiment is conducted to investigate the effect of aluminum-maltolate [Al(mal)3] on primary hippocampal neuron neurites in mice, and reveal the role of GSK-3β-CRMP2 in this process. Methods The hippocampus of newborn ICR mice (≤ 24 h old) was used for primary neuronal cultures. On the 5th day in vitro (DIV5), neuron purity detection were performed by confocal laser scanning microscopy. On DIV7, the neurons were transfected with lentiviral vector-mediated mNeonGreen. On DIV10, the neurons with mNeonGreen fluorescence in good growth state were treated with Al(mal)3. The stage I experimental groups were blank control group, maltol group, 10 µmol·L−1 Al group, 20 µmol·L−1 Al group, and 40 µmol·L−1 Al group. Then 20 µmol·L−1 Al was used to establish a model of neurite injury and for the intervention. The stage II experimental groups were blank control group, dimethyl sulfoxide (DMSO) group, Al (20 µmol·L−1) group, SB (GSK-3β inhibitor, 1 µmol·L−1), and SB (1 µmol·L−1)+Al (20 µmol·L−1) group. CCK-8 method was used to detect the viability of neurons. The primary hippocampal neurons of mice were scanned with high content analysis system at 0 h and 48 h after Al or SB treatment, and the density and length of neurites were analyzed. Western blotting was used to detect the expression and phosphorylation levels of CRMP2 and GSK-3β in primary hippocampal neurons of mice. Results The immunofluorescence results showed that the purity of primary neurons was more than 90%. Compared with the blank control group in stage I, the cell viability rates of the 10, 20, and 40 µmol·L−1 Al groups were decreased after 48h of Al(mal)3 treatment (P<0.05), while the cell viability rate of the maltol group had no significant change. There was no significant difference in cell viability rate among the DMSO group, the SB group, and the control group after 48h of SB treatment, and the viability rate of neurons in the SB+Al group was higher than that in the Al group (P<0.05) in stage II. The 48 h/0 h ratios of average number and length of neurites in the control group were 90.13%±11.70% and 113.24%±8.34%, respectively. The 48 h/0 h ratios in the Al group were 56.47%±16.36% and 62.06%±6.75%, respectively, which were lower than those in the control group (P<0.05). The 48 h/0 h ratios of average number of neurites in the SB group (99.03%±21.83%) was not significantly different from that in the control group, but the 48 h/0 h ratio of average length of neurites in the SB group (128.72%±15.39%) was higher than that in the control group (P<0.05). The 48 h/0 h ratios of average number (72.59%±10.89%) and length of neurites (93.84%±14.65%) in the SB+Al group were significantly increased compared with those in the Al group (P<0.05). Western blotting results showed that: There was no significant difference in GSK-3β protein level among all groups; compared with the control group (1.00±0.18), the protein level of p-GSK-3β in the Al group (0.45±0.05) was significantly decreased, and that in the SB group (1.32±0.23) was significantly increased; the protein level of p-GSK-3β in the SB+Al group (0.80±0.05) was significantly higher than that in the Al group (P<0.05). Compared with the control group (1.00±0.07), the CRMP2 protein level in the Al group (0.66±0.11) was significantly decreased (P<0.05), while that in the SB group (1.01±0.02) was not significantly changed. Compared with the control group (1.00±0.13), the p-CRMP2 protein level in the Al group (1.50±2.18) was significantly increased, and that in the SB group (0.62±0.09) was significantly decreased (P<0.05); the protein level of p-CRMP2 in the SB+Al group (1.28±0.24) was lower than that in the Al group (P<0.05). Conclusion Aluminum may activate GSK-3β, increase CRMP2 phosphorylation level, and damage neurite growth.

Malaria placentaria submicroscópica: histopatología y expresión de mediadores de procesos fisiológicos / Submicroscopic placental malaria: histopathology and expression of physiological process mediators

RESUMEN Objetivos: Relacionar entre sí los eventos histopatológicos de malaria placentaria (MP), el comportamiento de células inmunitarias y la expresión de genes asociados a citoquinas, hipoxia, inflamación y angiogénesis en placentas con o sin infección plasmodial. Materiales y métodos: Diseño transversal, con tres grupos independientes. Las mujeres y sus placentas fueron captadas en 2009-2016, en los hospitales de Puerto Libertador y Tierralta, noroccidente de Colombia. El tamaño muestral se definió por conveniencia. El diagnóstico malárico se basó en PCR cuantitativa en tiempo real. Resultados: Se estudiaron 20 casos con MP por P. vivax (MP-V), 20 casos de MP por P. falciparum (MP-F) y 19 sin MP; 95% de los casos de MP son infección plasmodial placentaria submicroscópica (IPPS). Los tres grupos difieren en frecuencia y cantidad de eventos histopatológicos. Los mediadores de procesos fisiológicos presentaron diferencia significativa entre grupos, excepto IL-2, VEGF, VEGFR-1 y C5a. Conclusiones: Las placentas con infección difieren claramente de las no infectadas. P. vivax se comporta tan patógeno como P. falciparum. Se resalta la aproximación al abordaje integral del problema de MP. La infección plasmodial placentaria submicroscópica causa alteraciones tisulares y en mediadores fisiológicos como lo hace la infección microscópica, aunque probablemente en menor grado.

ABSTRACT Objetives: To relate histopathological events of placental malaria (PM), immune cell behavior and gene expression associated with cytokines, hypoxia, inflammation and angiogenesis in placentas with or without plasmodial infection. Materials and methods: Transversal design, with three independent groups. Women were recruited, and their placentas were collected in 2009-2016, in the hospitals of Puerto Libertador and Tierralta, northwestern Colombia. The sample size was defined by convenience. The malaria diagnosis was based on real-time quantitative PCR. Results: We studied 20 cases of PM by P. vivax (PM-V), 20 cases of PM by P. falciparum (PM-F) and 19 without PM; 95% of the cases of PM are submicroscopic placental plasmodial infection (SPPI). The three groups differ in frequency and number of histopathological events. Physiological process mediators showed significant difference between groups, except IL-2, VEGF, VEGFR-1 and C5a. Conclusions: Infected placentas are clearly different from uninfected ones. P. vivax behaves as pathogenic as P. falciparum. The approximation to the integral approach of the problem of PM is underlined. Submicroscopic placental plasmodial infection causes tissue and physiological mediator alterations as does microscopic infection, although probably to a lesser degree.

O conto como objeto mediador: uma experiência com grupos com universitários / The short story as a mediator object: a group experience with university students / El cuento como objeto mediador: una experiencia de grupos con estudiantes universitarios

O objetivo geral deste trabalho é relatar a experiência de um grupo operativo temático com universitários que utilizou uma peça literária (conto) como objeto mediador, problematizando o uso deste dispositivo como um meio de cuidado em saúde mental na universidade. Realiza-se a análise de uma sessão do grupo operativo com o tema "família" à luz do referencial teórico da psicanálise vincular e do trabalho com grupos em instituições. Resultados: a constituição dos grupos levou em consideração as especificidades do público universitário e o vínculo com a instituição; o conto é um objeto cultural pré-constituído que mobiliza o pré-consciente e favorece os processos de simbolização; a escolha do conto como objeto mediador nos grupos relatados está em consonância com a tarefa primária da instituição universitária; o dispositivo apresentado constituiu-se como espaço de simbolização das experiências vividas na universidade e nas relações interpessoais, com potencial para a elaboração do sofrimento psíquico do jovem universitário. O grupo mediado por contos mostrou-se como um dispositivo de cuidado em saúde mental dos universitários a ser investigado e sistematizado, tendo em vista a ampliação da preocupação com os agravos à saúde mental na instituição universitária.

The general objective of this paper is to report the experience of a thematic operative group with university students who used a literary piece (short story) as a mediator object, problematizing the use of this device as a means of mental health care in the university. It is performed the analysis of a session of the operative group with the theme "family" in the light of the theoretical framework of psychoanalysis linkage and the work with groups in institutions. Results: the constitution of the groups took into account the specificities of the university public and the bond with the institution; the short story is a pre-constituted cultural object that mobilizes the preconscious and favors the processes of symbolization; the choice of the short story as a mediator object in the reported groups is in line with the primary task of the university institution; the presented device was constituted as a space of symbolization of the experiences lived in the university and in the interpersonal relations, with potential for the elaboration of the psychic suffering of the young university student. The group mediated by short stories proved to be a mental health care device for university students to be investigated and systematized, with a view to increasing concern about mental health problems in the university institution.

El objetivo general de este trabajo es informar la experiencia de un grupo operativo temático con estudiantes universitarios que utilizaron una pieza literaria (cuento) como objeto mediador, problematizando el uso de este dispositivo como un medio de atención de salud mental en la universidad. El análisis de una sesión del grupo operativo con el tema "familia" se realiza a la luz del marco teórico del psicoanálisis vincular y del trabajo con grupos en instituciones. Resultados: la constitución de los grupos tuvo en cuenta las especificidades del público universitario y el vínculo con la institución; el cuento es un objeto cultural preconstituido que estimula el preconsciente y favorece los procesos de simbolización; la elección del cuento como objeto mediador en los grupos informados está en línea con la tarea principal de la institución universitaria; el dispositivo presentado se constituyó como un espacio de simbolización de las experiencias vividas en la universidad y en las relaciones interpersonales, con potencial para la elaboración del sufrimiento psíquico del joven universitario. El grupo mediado por cuentos demostró ser un dispositivo de cuidado en la salud mental para estudiantes universitarios para ser investigado y sistematizado, tiendo en cuenta el aumento de la preocupación por los problemas de salud mental en la institución universitaria.

Mediator complexes regulate skeletal muscle metabolic function: a review / 药学学报

Mediator complexes involved in skeletal muscle metabolic processes have become a hot research topic in recent years. The mediator complex is a multi-protein complex which participates in transcription by bridging specific transcription factors and basal transcriptional machinery (RNA polymerase II). Mediator complexes are involved in regulating the expression of transcription factors related to skeletal muscle metabolism and muscle fiber transformation, such as PPARs and PGC1α. These mediators participate in skeletal muscle glucose metabolism by regulating glucose transporter GLUT4 and key transcription factors of metabolic pathways. In addition, they regulate metabolic diseases by regulating the expression of PPARγ, UCP-1 and other genes involved in skeletal muscle lipid metabolism and mitochondrial functions. This article reviews the mechanism and effects of mediator complexes on skeletal muscle metabolism.

Emotion regulation as the mediator of reductions in anxiety and depression in the Unified Protocol (UP) for transdiagnostic treatment of emotional disorders: double-blind randomized clinical trial / Regulação emocional como mediadora de reduções em ansiedade e depressão no Protocolo Unificado para o tratamento transdiagnóstico de transtornos psicológicos: ensaio clínico randomizado duplo-cego

Abstract Objective: An important subject in evaluation of the efficacy of treatments is to examine how the intervention is effective and to identify the consequences of that treatment. In this regard, the current study investigates the role of emotion regulation as the mediator of the treatment outcomes of therapy using the Unified Protocol (UP) for transdiagnostic treatment of emotional disorders. Method: This article describes a double-blind randomized clinical trial. A sample of 26 individuals was selected based on cut-off scores for the Beck Depression Inventory and Beck Anxiety Inventory and their final diagnoses were confirmed with the Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV). The sample was randomly divided into two groups: control and treatment (13 patients each). The treatment group received 20 one-hour UP sessions. The Beck Depression Inventory, the Beck Anxiety Inventory, and the Difficulties in Emotion Regulation Scale were administered at two stages, pre-treatment and post-treatment. Results: The UP reduced anxiety and depression in patients through improvement in emotion regulation. Furthermore, the results showed that the difficulty engaging in goal-directed behavior and non-acceptance of emotional response subscales were capable of predicting 62% of variance in anxiety scores. In turn, two subscales, difficulty engaging in goal-directed behavior and lack of emotional clarity, predicted 72% of variance in depression scores. Conclusion: Emotion regulation can be considered as a potential mediating factor and as predictive of outcomes of transdiagnostic treatment based on the UP. Clinical trial registration: Iranian Registry of Clinical Trials, IRCT2017072335245N1.

Resumo Objetivo: É importante, na avaliação da eficácia de tratamentos, examinar como a intervenção tem efeito e identificar suas consequências. O presente estudo investiga o papel da regulação emocional enquanto mediadora de desfechos do tratamento que emprega o Protocolo Unificado (PU) para o tratamento transdiagnóstico de transtornos psicológicos. Método: Este artigo descreve um ensaio clínico randomizado duplo-cego. Uma amostra de 26 indivíduos foi selecionada com base em escores pré-estabelecidos para o Inventário de Depressão de Beck e o Inventário de Ansiedade de Beck, e seus diagnósticos finais foram confirmados utilizando o instrumento Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV). A amostra foi dividida aleatoriamente em dois grupos: controle e tratamento (13 pacientes em cada). O grupo tratamento recebeu 20 sessões de PU de 1 hora cada. O Inventário de Depressão de Beck, Inventário de Ansiedade de Beck Beck e Escala de Dificuldades de Regulação Emocional foram administrados em duas etapas, antes e depois do tratamento. Resultados: O PU reduziu a ansiedade e a depressão em pacientes, ao melhorar a regulação emocional. Além disso, os resultados mostraram que as subescalas dificuldade de se engajar em comportamentos orientados por objetivos e não aceitação de resposta emocional responderam por 62% da variância nos escores de ansiedade. Nos escores de depressão, duas subescalas, dificuldade de se engajar em comportamentos orientados por objetivos e falta de claridade emocional, explicaram 72% da variância. Conclusão: A regulação emocional pode ser considerada o principal fator mediador e também preditora de desfechos do tratamento transdiagnóstico baseado no PU. Registro do ensaio clínico: Iranian Registry of Clinical Trials, IRCT2017072335245N1.

Estrogen receptor coactivator Mediator Subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Breast cancer, one of the most frequent cancer types, is a leading cause of death in women worldwide. Estrogen receptor (ER) a is a nuclear hormone receptor that plays key roles in mammary gland development and breast cancer. About 75% of breast cancer cases are diagnosed as ER-positive; however, nearly half of these cancers are either intrinsically or inherently resistant to the current anti-estrogen therapies. Recent studies have identified an ER coactivator, Mediator Subunit 1 (MED1), as a unique, tissue-specific cofactor that mediates breast cancer metastasis and treatment resistance. MED1 is overexpressed in over 50% of human breast cancer cases and co-amplifies with another important breast cancer gene, receptor tyrosine kinase HER2. Clinically, MED1 expression highly correlates with poor disease-free survival of breast cancer patients, and recent studies have reported an increased frequency of MED1 mutations in the circulating tumor cells of patients after treatment. In this review, we discuss the biochemical characterization of MED1 and its associated MED1/Mediator complex, its crosstalk with HER2 in anti-estrogen resistance, breast cancer stem cell formation, and metastasis both in vitro and in vivo. Furthermore, we elaborate on the current advancements in targeting MED1 using state-of-the-art RNA nanotechnology and discuss the future perspectives as well.

Nogo-A in the rat dorsal root ganglion promotes the polymerization of tubulin and inflammatory heat hyperalgesia / 解剖学报

Objective To investigate the regulation of microtubules by Nogo-A in the dorsal root ganglia during the inflammatory pain. Methods The ipsilateral paw withdrawal latency (PWL) was measured in wild type rats(WT, n = 12) and Nogo-A konck-out (Nogo-A KO) rats (n = 14) after complete Freunds adjuvant (CFA) injection. Western blotting and immunofluorescent staining were used to study the expression of microtubules and phosphorylated collapsin response mediator protein 2(p-CRMP2)in the dorsal root ganglion (DRG) of both groups. Results Knock out of Nogo-A in rats had'attenuated the CFA-induced inflammatory hyperalgesia. The acetylated tubulin was reduced, and the expression of p-CRMP2 was increased in the DRG of the Nogo-A KO rats. Conclusion Nogo-A is involved in the regulation of inflammatory heat hyperalgesia by promoting the microtubule polymerization via CRMP2 pathway.

Effect of procyanidin B2 on inflammatory mediators of human periodontal ligament cells / 上海交通大学学报（医学版）

Objective: To investigate the effects of procyanidin B2 on the expression of inflammatory mediators in human periodontal ligament cells (hPDLCs) induced by Porphyromonas gingivalis lipopolysaccharide (LPS). Methods: hPDLCs were cultured using tissue explant method in vitro. The effect of procyanidin B2 on the cell viability of hPDLCs was detected by MTT assay. hPDLCs were stimulated by P. gingivalis LPS after treatment with procyanidin B2 for 1 h. The expressions of IL-1β, IL-6, and IL-8 mRNA and proteins were detected by real-time PCR and ELISA assay. Reactive oxygen species (ROS) in the cytoplasm was observed under fluorescence microscope. Nitric oxide (NO) in the supernatant was detected by Griess assay. Results: 100.00 µg/mL procyanidin B2 could enhance the cell viability of hPDLCs. Procyanidin B2 could inhibit the expressions of IL-1β, IL-6, and IL-8 mRNA and proteins in hPDLCs. It could also downregulate ROS and NO in hPDLCs induced by P. gingivalis LPS. Conclusion: Procyanidin B2 can play an anti-inflammatory role by inhibiting inflammatory mediators in hPDLCs induced by P. gingivalis LPS.