Molecular mechanisms of Chinese herb formula free and easy wanderer in the treatment of mental disorders

Background: Posttraumatic stress disorder (PTSD) is a mental disorder after traumatic events and is characterized by repeated experience of a trauma with disturbing recurring reflections, avoidance or numbing of memories of the event and hyper-arousal. Due to the high prevalence it has attracted much attention in the past years. The etiology is unclear and new treatment methods are urgently required. Various recipes of Chinese herbs are successfully used in Asian countries against mental disorders. For example, Free and Easy Wanderer (FAEW) has been a complex herbal mixture for treating mental disorders in China for centuries, but its mode of action is still unclear. Method: We conducted the following studies to elucidate the mechanisms of FAEW: (1) we have chosen a "reverse pharmacology" approach and initially used clinical data to verify identified potential PTSD mechanisms in subsequent in vitro and in silico studies. For this purpose, microarray-based transcriptome-wide mRNA expression profiles of PTSD patients were analyzed, the effect of FAEW and the clinically established antidepressant fluoxetine on the transcription factor NF-κB using reporter cell assays and Western blotting was investigated. (2) We investigated the neuroprotective effect of FAEW under oxidative stress and the underlying mechanism by microarray and Western blot experiments. (3) We identified various potential drugs by molecular docking and literature research based on the phytochemical components of FAEW. Results: FAEW showed high anti-inflammatory activity by inhibiting NF-κB. PTSD-associated oxidative stress was induced by hydrogen peroxide in the experiment. Here it was shown that FAEW counteracts oxidative stress through KEAP1-NRF2/HO-1 pathway. Paeoniflorin, albiflorin, baicalin, isoliquiritin and liquiritin in silico bound with high affinity to the proteins IκK, p65 and KEAP1. Conclusion: FAEW has a variety of drugs and is active against inflammation by inhibition of NF-κB and against oxidative stress by activation of KEAP1-NRF2/HO-1 signaling pathway, which could be relevant mechanisms of Free and Easy Wanderer in the treatment of mental disorders. Key words: Free and Easy Wanderer, posttraumatic stress disorder, inflammation, oxidative stress, NF-κB, KEAP1-NRF2/HO-1X, 108 Seite

Laser-Matter Interaction in the Bulk of Semiconductor and Dielectric

The research in the field of laser-induced materials processing is evolving continuously with new inventions in laser technology. This chapter mainly discusses the relevant physical mechanisms of laser ablation based on laser-matter interaction. Femtosecond laser excitation provides suitable conditions for studying the basic processes in irradiated materials, as compared to the duration of these processes, femtosecond laser pulses are sufficiently short. In the process of laser action on the matter, the thermal mechanism, charge carrier removal, thermal and structural effects, and other processes are extremely complex. The ultrashort laser pulse instantly puts the material in a strong nonequilibrium state characterized by hot electrons and cold ions. After the pulse ends, the electron transfers its energy to the ion through electron phonon coupling in sub-picoseconds. This heats up the phonon bath before the slow thermal effect can reconstruct the material. The electron effect plays an important and possibly dominant role in the laser ablation of nonmetallic solid surfaces. This review first describes the mechanism of laser-matter interaction from the perspective of energy, summarizes the electronic excitation and energy relaxation paths of light on semiconductors and dielectric materials, focuses on the electronic excitation and relaxation mechanisms in laser-induced ionization, desorption, and ablation, and finally analyzes the above-mentioned related processes from the perspective of material structure relaxation

Microsatellites reveal a strong subdivision of genetic structure in Chinese populations of the mite Tetranychus urticae Koch (Acari: Tetranychidae)

Contact: [email protected] audienceBACKGROUND: Two colour forms of the two-spotted spider mite (Tetranychus urticae Koch) coexist in China: a red (carmine) form, which is considered to be native and a green form which is considered to be invasive. The population genetic diversity and population genetic structure of this organism were unclear in China, and there is a controversy over whether they constitute distinct species. To address these issues, we genotyped a total of 1,055 individuals from 18 red populations and 7 green populations in China using eight microsatellite loci. RESULTS: We identified 109 alleles. We found a highly significant genetic differentiation among the 25 populations (global F-ST = 0.506, global F-ST({ENA}) = 0.473) and a low genetic diversity in each population. In addition, genetic diversity of the red form mites was found to be higher than the green form. Pearson correlations between statistics of variation (AR and H-E) and geographic coordinates (latitude and longitude) showed that the genetic diversity of the red form was correlated with latitude. Using Bayesian clustering, we divided the Chinese mite populations into five clades which were well congruent with their geographic distributions. CONCLUSIONS: Spider mites possess low levels of genetic diversity, limit gene flow between populations and significant and IBD (isolation by distance) effect. These factors in turn contribute to the strong subdivision of genetic structure. In addition, population genetic structure results don't support the separation of the two forms of spider mite into two species. The morphological differences between the two forms of mites may be a result of epigenetic effects

NEDD4L facilitates granulosa cell ferroptosis by promoting GPX4 ubiquitination and degradation

Background: Polycystic ovary syndrome (PCOS) is an androgen disorder and ovarian dysfunction disease in women of reproductive age. The cell death of granulosa cells (GCs) plays an important role in the development of PCOS. However, the mechanism of GC death is still unclear. Methods: In the current study, NEDD4L was found to be elevated in PCOS GEO (Gene Expression Omnibus) databases and mouse models. The cell viability was analyzed by CCK-8 and FDA staining. The expression of ferroptosis markers was assessed by ELISA and immunofluorescence. The direct interaction of GPX4 and NEDD4L was verified by co-immunoprecipitation assay. Result: Functionally, results from CCK-8 and FDA staining demonstrated that NEDD4L inhibited the cell viability of KGN cells and NEDD4L increased the levels of iron, malonyldialdehyde, and reactive oxygen species and decreased glutathione levels. Moreover, the cell death of KGN induced by NEDD4L was blocked by ferroptosis inhibitor, suggesting that NEDD4L regulates KGN cell ferroptosis. Mechanistically, NEDD4L directly interacts with GPX4 and promotes GPX4 ubiquitination and degradation. Conclusion: Taken together, our study indicated that NEDD4L facilitates GC ferroptosis by promoting GPX4 ubiquitination and degradation and contributes to the development of PCOS

Biopiracy <i>versus </i>one-world medicine – from colonial relicts to global collaborative concepts

Background: Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neocolonialism.Hypothesis: : The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe.Study design: Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only fragmentary solutions at best. Conventional medicine from industrialized countries cannot be afforded by the impoverished population in the Third World. Confronted with exploding costs, even health systems in Western countries are endangered to burst. Complementary and alternative medicine (CAM) is popular among the general public in industrialized countries, although the efficacy is not sufficiently proven according to the standards of evidence-based medicine. CAM is often available without prescription as over-the-counter products with non-calculated risks concerning erroneous self-medication and safety/toxicity issues. The concept of integrative medicine attempts to combine holistic CAM approaches with evidence-based principles of conventional medicine.Conclusion: To realize the concept of One-World Medicine, a number of standards have to be set to assure safety, efficacy and applicability of traditional medicine, e.g. sustainable production and quality control of herbal products, performance of placebo-controlled, double-blind, randomized clinical trials, phytovigilance, as well as education of health professionals and patients

Solar Ring Mission: Building a Panorama of the Sun and Inner-heliosphere

Solar Ring (SOR) is a proposed space science mission to monitor and study the Sun and inner heliosphere from a full 360{\deg} perspective in the ecliptic plane. It will deploy three 120{\deg}-separated spacecraft on the 1-AU orbit. The first spacecraft, S1, locates 30{\deg} upstream of the Earth, the second, S2, 90{\deg} downstream, and the third, S3, completes the configuration. This design with necessary science instruments, e.g., the Doppler-velocity and vector magnetic field imager, wide-angle coronagraph, and in-situ instruments, will allow us to establish many unprecedented capabilities: (1) provide simultaneous Doppler-velocity observations of the whole solar surface to understand the deep interior, (2) provide vector magnetograms of the whole photosphere - the inner boundary of the solar atmosphere and heliosphere, (3) provide the information of the whole lifetime evolution of solar featured structures, and (4) provide the whole view of solar transients and space weather in the inner heliosphere. With these capabilities, Solar Ring mission aims to address outstanding questions about the origin of solar cycle, the origin of solar eruptions and the origin of extreme space weather events. The successful accomplishment of the mission will construct a panorama of the Sun and inner-heliosphere, and therefore advance our understanding of the star and the space environment that holds our life.Comment: 41 pages, 6 figures, 1 table, to be published in Advances in Space Researc

Molecular mechanisms of Chinese herb formula free and easy wanderer in the treatment of mental disorders

Background: Posttraumatic stress disorder (PTSD) is a mental disorder after traumatic events and is characterized by repeated experience of a trauma with disturbing recurring reflections, avoidance or numbing of memories of the event and hyper-arousal. Due to the high prevalence it has attracted much attention in the past years. The etiology is unclear and new treatment methods are urgently required. Various recipes of Chinese herbs are successfully used in Asian countries against mental disorders. For example, Free and Easy Wanderer (FAEW) has been a complex herbal mixture for treating mental disorders in China for centuries, but its mode of action is still unclear. Method: We conducted the following studies to elucidate the mechanisms of FAEW: (1) we have chosen a "reverse pharmacology" approach and initially used clinical data to verify identified potential PTSD mechanisms in subsequent in vitro and in silico studies. For this purpose, microarray-based transcriptome-wide mRNA expression profiles of PTSD patients were analyzed, the effect of FAEW and the clinically established antidepressant fluoxetine on the transcription factor NF-κB using reporter cell assays and Western blotting was investigated. (2) We investigated the neuroprotective effect of FAEW under oxidative stress and the underlying mechanism by microarray and Western blot experiments. (3) We identified various potential drugs by molecular docking and literature research based on the phytochemical components of FAEW. Results: FAEW showed high anti-inflammatory activity by inhibiting NF-κB. PTSD-associated oxidative stress was induced by hydrogen peroxide in the experiment. Here it was shown that FAEW counteracts oxidative stress through KEAP1-NRF2/HO-1 pathway. Paeoniflorin, albiflorin, baicalin, isoliquiritin and liquiritin in silico bound with high affinity to the proteins IκK, p65 and KEAP1. Conclusion: FAEW has a variety of drugs and is active against inflammation by inhibition of NF-κB and against oxidative stress by activation of KEAP1-NRF2/HO-1 signaling pathway, which could be relevant mechanisms of Free and Easy Wanderer in the treatment of mental disorders. Key words: Free and Easy Wanderer, posttraumatic stress disorder, inflammation, oxidative stress, NF-κB, KEAP1-NRF2/HO-

Posttraumatic stress disorder among earthquake survivors of the Wenchuan area (Sichuan, China)

Background: On May 12, 2008, an earthquake with a power of 8.0 M on the Richter scale occurred in the Wenchuan County of Sichuan Province in southwest China, which was unprecedented in magnitude and aftermath. Approximately 70,000 people were killed and nearly 20,000 went missing. The earthquake caused a wide number of mental and physical health outcomes among survivors, and posttraumatic stress disorder (PTSD) was one of the most commonly studied. Methods: We conducted a systematic overview to assess research achievements about PTSD in the past 6 years after the Wenchuan earthquake, including symptoms and risk factors about PTSD among Wenchuan earthquake survivors, as well as research developments in genetics, molecular biology, and treatment of PTSD. Results: The large body of research conducted after the Wenchuan earthquake suggests that the burden of PTSD among persons with high exposure was substantial. Adolescents and adults were among the most studied populations with high prevalence rates. Phytotherapy with Chinese herbs as well as acupuncture were rarely studied as of yet, although published data indicated promising therapy effects. Genome-wide microarray technologies are widely used in experimental mice and rat models to study PTSD mechanisms as well as in patients suffering from PTSD and other psychosomatic disorders to search for novel biomarkers and to monitor the effectiveness of treatment interventions. Conclusion: Using genomic and transcriptomic technologies, our future research will focus on the efficacy and safety of Chinese medicine to find potential interventions and effective treatments of PTSD

Unraveling the link between heavy metals, perfluoroalkyl substances and depression: Insights from epidemiological and bioinformatics strategies

Heavy metals and per- and polyfluoroalkyl substances (PFASs) have become particularly important when studying the development of depression, a common illness that severely restricts psychosocial functioning and diminishes quality of life. Therefore, the potential joint effects of heavy metal and PFAS exposure on depression, as well as the underlying mechanisms involved, were investigated by using integrated epidemiological and bioinformatic approaches in the present study. A thorough analysis of 7301 samples from the National Health and Nutrition Examination Survey (NHANES) cycles that occurred between 2005 and 2018 was performed. Single-exposure studies have shown that cadmium exposure is positively associated with depression, whereas perfluorooctanesulfonic acid (PFOS) exposure and perfluorodecanoic acid (PFDE) exposure are negatively associated with depression. Furthermore, the Bayesian kernel machine regression (BKMR) and quantile g-computation (QGcomp) models were employed to investigate the collective impact of exposure to mixed metals on depression. Cadmium emerged as the principal contributor to depression. Moreover, the addition of PFAS to the metal mixture had an antagonistic effect on depression, with PFOS having the most prominent influence. Analysis of the effects of co-exposure to cadmium and PFOS confirmed the presence of an antagonistic effect. The inflection points of cadmium and PFOS were determined to be −1.11 and 2.27, respectively. Additionally, exposure to cadmium and PFOS had the opposite effects on two crucial pathways, namely, the rap1 and calcium signaling pathways, which involve core genes related to depression such as ADORA2A, FGF2, and FGFR1. These findings have significant implications for future studies and provide new strategies for exploring the mechanisms underlying co-exposure effects

Microbial colonization induces histone acetylation critical for inherited gut-germline-neural signaling.

The gut-neural axis plays a critical role in the control of several physiological processes, including the communication of signals from the microbiome to the nervous system, which affects learning, memory, and behavior. However, the pathways involved in gut-neural signaling of gut-governed behaviors remain unclear. We found that the intestinal distension caused by the bacterium Pseudomonas aeruginosa induces histone H4 Lys8 acetylation (H4K8ac) in the germline of Caenorhabditis elegans, which is required for both a bacterial aversion behavior and its transmission to the next generation. We show that induction of H4K8ac in the germline is essential for bacterial aversion and that a 14-3-3 chaperone protein family member, PAR-5, is required for H4K8ac. Our findings highlight a role for H4K8ac in the germline not only in the intergenerational transmission of pathogen avoidance but also in the transmission of pathogenic cues that travel through the gut-neural axis to control the aversive behavior