REDIMEH Project:Ibero-American Integrative Network for Clinical Research in Homeopathy

If there were one lacking or insufficient issue which conscious medical orientated homeopaths could regret, it would be probably high quality clinical research. A big part of the homeopathic community still insists in the traditional ways of building knowledge, leading us nowhere. There is now an agreement between clinical researchers that there have been done enough efforts with Randomized Control Trials (RCT). But what we need today is good quality scientific research that could improve our daily practice. This article introduce the REDIMEH, an Ibero-American Integrative Network for Clinical Research in Homeopathy, horizontal in structure, with no political objectives, with the only intention of joining efforts in order to obtain enough clinical data to draw out valid conclusions. Keywords: REDIMED, atopic dermatitis, clinical research.  Projeto REDIMED: Red Integrada Ibero-Americana para Pesquisa Clínica em Homeopatia ResumoSe pudermos apontar uma questão, a qual os verdadeiros médicos homeopatas podem se lamentar, esta deveria ser a falta ou insuficiéncia de pesquisas clínicas de alta qualidade. Uma grande parte da comunidade homeopática ainda insiste nas formas tradicionais de construção de conhecimento, levando-nos a lugar algum. Existem pontos bem estabelecidos pelos pesquisadores clínicos que tem se esforçado muito com a realização de Ensaios Controlados Randomizados (RCT). O que mais precisamos hoje é de investigação científica de boa qualidade, que possa melhorar a nossa prática diária. Este artigo apresenta o projeto REDIMEH, uma Rede Integrada Ibero-Americana para Pesquisa Clínica em Homeopatia, de estrutura horizontal, sem objetivos políticos, com a intenção de unir esforços no sentido de obter dados clínicos suficientes para chegarmos a conclusões válidas para a prática clínica diária. Palavras-chave: REDIMED, dermatite atópica, investigação clínica.  Proyecto REDIMEH: Red Iberoamericana Integrativa de Investigación Clínica en Homeopatía ResumenSi hubiera uma cuestión de la cual los médicos homeopatas podrían pesar, sería probablemente la investigación clínica de alta calidad. Una gran parte de la comunidad homeopática sigue insistiendo en las formas tradicionales de construcción del conocimiento, que nos conduce a ninguna parte. En la actualidad, existe un acuerdo entre los investigadores clínicos, que ya se han hecho lo suficiente con los esfuerzos de control de ensayos aleatorios (RCT). Pero lo que necesitamos hoy es la investigación científica de buena calidad que pueda mejorar nuestra práctica diaria. Este artículo presentará el REDIMEH, uma Red Iberoamericana Integrativa de Investigación Clínica en Homeopatía, con una estructura horizontal, sin objetivos políticos, con la única intención de unir esfuerzos con el propósito de obtener datos clínicos suficientes para sacar conclusiones válidas. Palabras-clave: REDIMED, dermatitis atópica, investigación clínica  Correspondence author: Jose Eizayaga, [email protected], www.maimonides.edu How to cite this article: Eizayaga J. REDIMEH Project: Ibero-American Integrative Network for Clinical Research in Homeopathy. Int J High Dilution Res [online]. 2009 [cited YYYY Month dd]; 8(27): 50-52. Available from: http://journal.giri-society.org/index.php/ijhdr/article/view/340/392. ÂÂÂ

Systematic Characterization of Heterogeneity caused by Neuroinflammation in Alzheimer’s Disease based on Integrative Network Analysis

Background: Alzheimer's disease (AD) is the most common cause of dementia. As a heterogenous disease, there are several clinically and pathobiological defined subtypes with different molecular signatures. Neuroinflammation contributed to AD pathogenesis, however, the roles it played in the heterogeneity of AD was unclear. Objective: We aimed to illustrate the roles neuroinflammation played in the heterogeneity of AD. Method: An integrative network analysis based on transcriptomics, miRNOmics, and proteomics was performed to illustrate the heterogeneous characters of AD. Combined-functional-networks and hypothesis-network were constructed and analyzed to explore the roles neuroinflammation played in AD heterogeneity. Results: Astrocytes, microglia, ‘M2 macrophage-Neuron’, and ‘Microglia- Neuron’ were shown to be enriched in neuroinflammation related functional terms in a cell- and spatial-specific way. The microglia and neurons could interact with each other in three different ways including indirect interactions via intermediate cells, indirect interactions via soluble factors, and direct interactions established localized and functionally distinct signaling, all of which were used to control different biological processes. The combined network analyses exhibited the key roles neuroinflammation plays in the 'AD hypothesis network’. Conclusion : The AD heterogeneity may be caused by the heterogeneous cells involved in neuroinflammation and the crosstalks between spatial-specific molecular signatures.

Integrated omics networks reveal the temporal signaling events of brassinosteroid response in Arabidopsis

Brassinosteroids (BRs) are plant steroid hormones that regulate cell division and stress response. Here we use a systems biology approach to integrate multi-omic datasets and unravel the molecular signaling events of BR response in Arabidopsis. We profile the levels of 26,669 transcripts, 9,533 protein groups, and 26,617 phosphorylation sites from Arabidopsis seedlings treated with brassinolide (BL) for six different lengths of time. We then construct a network inference pipeline called Spatiotemporal Clustering and Inference of Omics Networks (SC-ION) to integrate these data. We use our network predictions to identify putative phosphorylation sites on BES1 and experimentally validate their importance. Additionally, we identify BRONTOSAURUS (BRON) as a transcription factor that regulates cell division, and we show that BRON expression is modulated by BR-responsive kinases and transcription factors. This work demonstrates the power of integrative network analysis applied to multi-omic data and provides fundamental insights into the molecular signaling events occurring during BR response.

Estrogen Hormone Is an Essential Sex Factor Inhibiting Inflammation and Immune Response in COVID-19

Although vaccines have been evaluated and approved for SARS-CoV-2 infection prevention, there remains a lack of effective treatments to reduce the mortality of COVID-19 patients already infected with SARS-CoV-2. The global data of COVID-19 showed that men have a higher mortality rate than women. We further observed that the proportion of mortality of female increases starting from around the age of 55 significantly. Thus, sex is an essential factor associated with COVID-19 mortality, and sex related genetic factors could be interesting mechanisms and targets for COVID-19 treatment. However, the associated sex factors and signaling pathways remain unclear. Here, we propose to uncover the potential sex associated factors using systematic and integrative network analysis. The unique results indicated that estrogen hormones (ER), e.g., estrone and estriol, 1) interacting with ESR1/2 receptors, 2) can inhibit SARS-CoV-2 caused inflammation and immune response signaling in host cells; and 3) estrogen hormone is associated with the distinct fatality rates between male and female COVID-19 patients. Specifically, a high level of estradiol protecting young female COVID-19 patients, and estrogen loss to an extremely low level in females after about 55 years of age causing the increased fatality rate of women. In conclusion, estrogen hormone, interacting with ESR1/2 receptors, is an essential sex factor that protects COVID-19 patients by inhibiting inflammation and immune response caused by SARS-CoV-2 infection. Medications perturb the down-stream of ESR1/ESR2 to inhibit the inflammation and immune response can be effective or synergistic combined with other existing drugs for COVID-19 treatment.

Identification of consistent post-translational regulatory triplets related to oncogenic and tumour suppressive modulators in childhood acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. It can be caused by mutations that turn on oncogenes or turn off tumour suppressor genes. For instance, changes in certain genes including Rb and p53 are common in ALL cells. Oncogenes and TSGs may serve as a modulator gene to regulate the gene expression level via their respective target genes. To investigate the regulatory relationship between oncogenes, tumour suppressor genes and transcription factors at the post translational level in childhood ALL, we performed an integrative network analysis on the gene regulation in the post-translational level for childhood ALL based on many publicly available cancer gene expression data including TARGET and GEO database. Methods We collected 259 childhood ALL-related genes from the latest online leukemia database, Leukemia Gene Literature Database. These 259 genes were selected from a comprehensive systematic literature with experimental evidences. The identified and curated genes were also associated with patient survival cases and we incorporated this pediatric ALL-related gene list into our analysis. We extracted the known human TFs from the TRRUST database. Among 259 childhood ALL-related genes, 101 unique regulators were mapped to the list of oncogene and tumour suppressor genes (TSGs) from the ONGene and the TSGene databases, and these included 74 TSGs, 62 oncogenes and 46 TF genes. Results The resulted regulation was presented as a hierarchical regulatory network with transcription factors (TFs) as intermediate regulators connecting the top modulators (oncogene and TSGs) to the common target genes. Cross-validation was applied to the results from the TARGET dataset by identifying the consistent regulatory motifs based on three independent ALL expression datasets. A three-layer regulatory network of consistent positive modulators in childhood ALL was constructed in which 74 modulators (40 oncogenes, 34 TSGs) are considered as the most important regulators. The middle layer and the bottom layer contain 34 TFs and 176 target genes, respectively. Oncogenes mostly participated in positive regulation of gene expression and the transcription process of RNA II polymerase, while TSGs were mainly involved in the negative regulation of gene expression. In addition, the oncogene-specific targets were enriched with regulators of the MAPK cascade while tumour suppressor-specific targets were associated with cell death. Conclusion The results revealed that oncogenes and TSGs possess a different functional regulatory pattern with regard to not only their biological functions but also their specific target genes in childhood ALL cancer progression. Taken together, our findings could contribute to a better understanding of the important regulatory mechanisms and this method could be used to analyse the targeted genes at the post-translational level in childhood ALL through integrative network analysis.

Dynamic behavioral and molecular changes induced by chronic stress exposure in mice

Depression is a leading cause of disabilities around the world, and the underlying mechanisms involved in its pathophysiology are broad and complex. Exposure to chronic stress is a risk factor for developing depressive-symptoms and contributes to cellular and molecular changes precipitating the emergence of symptoms. In the brain, excitatory neurons, inhibitory interneurons and supporting astroglial cells are all sensitive to chronic stress exposure and are known to be impaired in depression. Using an animal model of chronic stress, we assessed the impact of variable durations of chronic stress on the emergence of behavioral deficits and associated molecular changes in the prefrontal cortex (PFC), brain region highly sensitive to stress and impaired in depression. Mice were exposed to up to 35 days of chronic restraint stress and were assessed weekly on behavioral tests measuring anxiety and anhedonia. PFC Protein and RNA levels of specific markers of excitatory, inhibitory synapses and astroglia were quantified using western blot and qPCR, respectively. Correlation and integrative network analyses were used to investigated the impact of chronic stress on the different compartments. Results showed that chronic stress induces anxiety-like behaviors within 7 days, while anhedonia-like behaviors were observed only after 35 days. At the molecular level, alterations of many markers were observed, in particular with longer exposure to chronic stress. Finally, correlation analyses and integrative network analyses revealed that male and female mice react differently to chronic stress exposure and that some markers seem to be more correlated to behaviors deficits in males than in females. Our study demonstrate that chronic induces a dynamic changes that can be observed at the behavioral and molecular levels, and that male and female mice, while exhibiting similar symptoms, have different underlying pathologies.