Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Le traumatisme psychique constitue une blessure du langage par atteinte des réseaux de significations

ObjectivesTrauma appears within the discourse of mentally injured people, materializing what we have recently defined as “post traumatic psycholinguistic syndrome” (SPLIT). Translating unspeakability, revival, and dissociation, this clinical entity associates three significant disturbances : traumatic anomia (missing words, reduction of the elocutionary flow, deictic gestures, etc.); linguistic repetitions (of words and phrases, verbal intrusions, echophrasias, etc.); and phrasal and discursive disorganization (incomplete sentences, tense discordance, dysfluence, lack of logical connectors, etc.). What are the causes of these semiological and psycholinguistic expressions? What are their psychological and/or neuropsychological processes? It is time to come up with a new concept intended to go beyond the previous models in order to better identify people suffering from post-traumatic mental disorders, to better organize and evaluate psychotherapeutic care, and also to help practitioners collaborate more effectively on these first two goals. But how to evoke, affirm, or speak out about the consequences of unspeakability? Nothing is more apparently contradictory than wanting to define the language void. How to account for the fractures of psychic trauma in discourse? Nothing is more uncertain than to try to organize the upheavals, the disorders caused by dissociation in language. Finally, how to specify the reiteration of the trauma using words and sentences without this modeling being dissociative or repetitive? Today, thanks to a psycholinguistic reading, essential dimensions of post-traumatic suffering, hitherto hidden, can be clarified. Why exactly does an event cause trauma in the life of a subject at a given moment in her/his existence? Why is a latency phase structured between the traumatic event and the return of reviviscences under the influence of a re-triggering factor? How to differentiate the notion of dissociation as a normal phenomenon from the so-called traumatic dissociation? How to explain the multiple clinical forms of post-traumatic psychological disorders?MethodsFrom Pierre's clinical history, we chronologically detail the structuring and the consequences of the signified reflection that are constitutive of the psychic trauma: the psycholinguistic tools here help to formulate a new etiopathogenic conception of trauma and its psychological consequences. Then, thanks to Jean's testimony, taking up the retrospective meaning of the clinical analysis from chronic repetition syndrome, we discover the phases of tension regarding signified knowledge, up to the network prior to the traumatic confrontation. Finally, illustrated by Karima's disorder, beyond depersonalization, we explain that the analysis of the disturbances of a singular signified network, and also of an attack on its familial and societal bases, testifies to individual and collective subjectivities.ResultsComing from the real world, and therefore also from the body, the stimuli made up of signals picked up by our senses combine to compose an event that can be objectified by its temporal, spatial, biological, and physico-chemical coordinates. These elements combine into a unit, which is then interpreted by the mind, which attributes meaning to this event, which has become subjective reality. But when the subject is not sufficiently prepared to be confronted with this meaning that appears to be in extreme contradiction with her/his previous cardinal networks of significations, it makes “too much sense:” this irreconcilable hyper-signified (that we call the traumatic signified) results in post-traumatic dissociation. In other words, it is an impossibility of concordance of a signified with certain systems of prior significations that constitutes the pathogenesis of the trauma; and a situation runs a greater risk of being traumatic when it contradicts, or, moreso, endangers some or all of the subject's cardinal meanings. This unbearable signified reflexively blocks the capacities of significations immediately pre- and post-trauma, then dissociates the psychic functions to varying degrees and intensities. The traumatic signified, rejected, becomes unattainable: the stimuli that led to its formation find themselves confined to the state of reviviscences, each replication of which attempts to cross the barrier of inconceivability. Limiting sensory compounds to their raw states without the possibility of representational integration, associative pathways remain blocked. The signifier is referred to a hypo-signifier confined to the infra-linguistic by its confusion with the referent, the “objective and material” components of the traumatic event. Dissociation is therefore only a symptomatic reaction, secondary to the trauma, which it reinforces once again by limiting any possibility of representing the trauma. This dissociation does not involve forgetting the traumatic signified but “protects” the adjacent networks of meanings from it as much as it “keeps” this hypersignified intact, therefore ultimately “protecting” it as well. The traumatic signified persists somewhere, and even ends up being found everywhere: when the networks of meanings turn out to be globally disturbed, the tightest links remain those of the traumatic hypersignified that ultimately governs all the networks of meanings.DiscussionOur insufficient knowledge prevents us from precisely qualifying the architecture of the signified idiosyncratic networks and their evolutionary capacities; we cannot predict, beforehand, the reaction of an individual confronted with a potentially psychotraumatic situation. For most clinical situations, we affirm that the psychological trauma occurs in a psychically healthy subject, that is, not suffering from any psychiatric illness or any obvious psychopathological conflict. Psychotherapy will make it possible to discover the signified, sometimes ancient, origins of a trauma occurring in a singular subject. How was this subjectivity constructed? Beyond individual subjectivity, the intensity of certain confrontations such as serious attacks or macrosocial catastrophes such as genocide, would seem to lead to psychological wounds in any individual, even at the scale of a population. While, throughout existence, each subject produces a system of significations in connection with a unique psychic construction, the latter persists – resulting from, and often remaining overseen by, the community essence of a base of signifying networks, which we call “societal subjectivity.” Here, the psychological trauma can correspond to an individual and “common” injury as a failure of a sharing, or of ancestral beliefs anchored in the collective memory, defining the culture. By the collapse of acquired certainties, the cognitive patterns transmitted by education, language, and everything that establishes one's belonging to a society, trauma shakes the networks of individual and group meanings. Horror has a higher traumatogenic risk, because it defeats the fundamentals of humankind, the foundations of a signified network common to a culture, or even to all cultures, to the human condition. This is the case with murder, rape, torture, wars, genocides. Testifying to an instinct for survival stemming from the biological foundations of every living being, the impossibility of “living death” appears to be anchored in our networks of meanings and is manifested by indescribability, traumatic as such: being deserted by the language collides with the condition of speaking. And yet, it remains possible to say something about it... As a path of progressive desocialization, the occasional loss of the community of language, followed by its lasting traumatic ravages, can be appeased by the reestablishment of a speech link, either within the mind of the subject alone, or promoted by the exchange with others, in a psychotherapeutic setting, for example.ConclusionWhere theoretical discourses have sometimes proved divisive, going beyond the symptoms of indescribability and dissociation, psychodynamic practice today offers to unite. Thanks to psycholinguistic listening, phenomena that have never been explained take on meaning: the singularity of traumatic perception, the chronology of disorders including the latency phase, factors that trigger reviviscences, and the diversity of chronic clinical forms. All these post-traumatic symptoms are consequential to a linguistic wound, a difficulty in accessing meaning, the undermining of two dimensions characterizing and constructing the human being. As much as it integrates extralinguistic determinants, if the traumatic signified is undoubtedly not only speech, language appears the optimal way to identify it as such, while in the same movement appeasing it. The traumatic hypersignified is discovered through clinical analysis and psychotherapy, through deferred action, through the attribution of meaning, through the retrospective reconstruction of an unstable “real,” through a changing narration eternally distancing itself from reviviscences. But what precisely are the mechanisms of effective therapies ? What are the intersubjective links called for in the discussion between patient and practitioner? Could the operations that we call “psychotherapy” be made up of mobilizations of the networks of meanings by speech acts?     

Electrolipolysis associated with aerobic activity does not reduce subcutaneous adipose tissue of the abdominal region of young women: A randomized clinical trial

ObjectiveTo analyze the effects of electrolysis, through a medium frequency current, associated to aerobic physical activity in the body composition of young women.MethodsThe study was composed of 34 sedentary women (24.35 ± 4.43 years, 71.30 ± 7.08 kg, 1.61 ± 0.06 m, 27.31 ± 1.67 kg/m2) which were evaluated for their anthropometric measures and body composition. The volunteers were randomly assigned to two group: Electrolyphysis plus Aerobic Exercise (gEEA): 17 volunteers were submitted to the application, for 60 min , of the Aussie current, followed by aerobic physical activity (77% of HRmax) on the trampoline for 40 min, through video-lessons of Jump; and Aerobic Exercise group (gEA): 17 volunteers performed only physical activity following the same parameters mentioned above. Each group performed its protocols twice weekly, for 5 weeks, totaling 10 sessions. For the data analysis, measures repeated ANOVA was performed to compare the means of the variables analyzed before and after the treatment protocols using the SPSS - 21.0 software, adopting a p ≤ 0.05.ResultsAlthough gEEA decreased suprailiac skinfold (p = 0.04), abdominal skinfold (p = 0.03) and circumference at umbilical scar (p = 0.02) in an intragroup analysis, these means differences in anthropometric measures were not important between-groups (p > 0.05). Furthermore, there were no effect of treatment on body composition (p > 0.05).ConclusionTo this studied condition, our results suggested that application of medium frequency electrolysis did not enhance the losses on anthropometric measures and body composition.     

The longitudinal associations between mental health indicators and digital media use and physical activity during adolescence: A latent class approach

IntroductionEvidence for the relationship between movement behaviors and mental health among adolescents is inconclusive. We aimed to identify profiles of digital media use (including related bedtime delay) and leisure-time physical activity (LTPA) in adolescence, and to examine whether preadolescent mental health predicted later behavior profiles.MethodsThis study included 1285 participants assessed at 11 years of age, and followed-up four years later. Participants completed the Self-Perception Profile for Children (SPPC), Center for Epidemiological Studies Depression Scale for Children (CES-DC) and Screen for Child Anxiety-Related Emotional Disorders (SCARED) at baseline, and reported digital media use (active and passive use, gaming, and related bedtime delays) and LTPA at follow-up. A latent class approach was employed to identify behavior profiles, membership of which was then predicted with mental health and covariates, including baseline digital media use and LTPA.ResultsWe identified four behavior profiles: 1) high digital media use/moderate LTPA (20% of adolescents; 78% boys), 2) moderate digital media use/high LTPA (31%; 28%), 3) high digital media use/high LTPA (26%; 15%), 4) high passive digital media use and gaming/low LTPA (23%; 89%). After adjusting for covariates, higher LTPA and better perception of athletic competence at baseline associated with higher odds of belonging to any other profile than to the unhealthiest profile (4) at follow-up. Symptoms of depression or anxiety did not associate with later behavior profiles.ConclusionsLTPA and related self-esteem seem to be stronger predictors of future digital media use and LTPA behavior during adolescence than mental health symptoms alone.     

Case Report: Transient Stress Hyperglycemia in the Patient With ST-Elevation Myocardial Infarction

Transient stress hyperglycemia in the setting of acute myocardial infarction is a frequent phenomenon. Its transient nature should not dissuade the clinician from management of elevated blood glucose in a patient after an ST-elevation myocardial infarction. This case presents an adult patient after an ST-elevation myocardial infarction with transient stress hyperglycemia and the evidence used to identify optimal pharmacologic management and secondary prevention.     

北京市某社区15例恢复期精神疾病患者生存压力调查

目的 了解生活在社区的恢复期精神疾病患者在疾病康复过程中的生存压力。方法 2017年8月至2018年1月,选取北京市某社区15例恢复期精神疾病患者,通过半结构式访谈的方式收集资料,以Colaizzi 7步分析法分析资料。结果 得出4个主题:精神疾病症状和药物不良反应等引起的生理性压力;因疾病转归和日常生活角色冲突产生的精神心理性压力;社会歧视、缺乏工作机会和难以获取社会福利资源等带来的社会环境压力;贬低歧视和家庭亲属关系恶化导致的人际交往压力。结论 恢复期精神疾病患者重返家庭和社会后存在明显的生存压力,压力源包括疾病症状、社会歧视、人际关系等多个方面,因此,应注重消除精神疾病患者的自我歧视,完善社会支持与社会福利体系,增加个性化的社区精神康复活动,以减轻患者生存压力,促进其康复。