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Aug 2017 DOI 10.14302/issn.2576-2818.jfb-14-553
Bernardini LCorresponding author
Lunicare Medical Center-SISMER Satellite, Sarzana, Italy
All independent experimental data on epithelial and glandular cells lines of human endometrium support the evidence for a rapid production of eicosanoids from the LH/hCG receptors when exposed to the hCG hormone. Prostaglandins rapidly act on the surrounding endometrial stromal cells throughout the adenylyl cyclase enzyme leading to very large amounts of cAMP and angiogenic factors (VEGF) production. The cAMP is the most important intracellular second messenger and along with progesterone accomplishes the full process of decidualization and acquisition of receptivity after estrogenic priming of the endometrium. The status of uterine receptivity lasts few days only and timing for successful embryo-signal transduction system activation by the endometrium is probably short. In absence of in vivo embryonic signals it is impossible to predict, on individual bases, how the intensity of all the complex interlinked molecular changes of decidualization might ever be in case of exposure to native hCG. In other terms, amount of prostaglandins and cAMP produced in response to variably glycosylated hCG are all, in vivo, not measurable variables and should be viewed as a “wave” of biochemical chain reactions. Embryonic hCG is secreted in form of multiple isomers having an unpredictable variable level of glycosylation and control of this variable remains elusive. During cycles of ovarian stimulation many drugs (FSH, LH, HCG) interact with different G-protein coupled receptors (GPCRs) making it possible to alter the prostaglandins-mediated decidualization process ready to be elicited only by hCG of pregnancy. Since the molecules (cAMP and progesterone) controlling endometrial stromal cells differentiation into decidual cells are critical for successful implantation and placenta formation, the evidence of fast eicosanoids production associated with endometrial LH/hCG receptors exposure to hCG and the potential by human endometrium to produce, in response, very large amounts of cAMP has biological and clinical relevance.
Nov 2025 DOI 10.14302/issn.3070-5657.je-24-5327
Khanday ShifanCorresponding author
Human embryonic development is a highly coordinated and complex process that transforms a single fertilized cell into a fully formed human organism. This process is governed by intricate molecular mechanisms involving genetic regulation, signal transduction pathways, and intercellular communication. This study explores key molecular pathways controlling human embryonic development, focusing on the roles of morphogens, transcription factors, signaling molecules, and epigenetic modifications. By reviewing the most recent literature and experimental studies, we aim to highlight the molecular orchestration that directs cell fate decisions, tissue patterning, and organogenesis in humans.
Mar 2023 DOI 10.14302/issn.2474-7785.jarh-22-4381
Tariku Belay YilkalCorresponding author
Background Ageing is a life process in which progressive molecular, cellular, physiological and anatomical changes manifesting in humans and animals including other organisms lead to the decline of biological functions. Immunoglobulins (Igs) are glycoprotein molecules produced by white blood cells mainly B lymphocytes following signal transduction as a result of their interaction with pathogenic microbes or poisonous substances introduced into the body systems. They elicit responses against the side effects of pathogens and poisons in which their response efficiency usually declines as we are ageing. Objective Thus, the similarities between Igs’ immune response against the different amounts of xenobiotics and the biological changes associated with ageing have been systematically assessed using the reports of different study results on humans and animals. Methods First, a literature search was carried out in google, PubMed and google scholar using planned search terms related to the title of this study. Review and original articles were retrieved, downloaded and saved on a computer. And then the effects of different factors i.e. xenobiotics, age, sex and lifestyle-based practices on the levels of serum Igs (IgG, IgA and IgM) in animals and humans have been studied using a systematic review of different literature sources. Finally, the relationship between the findings of various studies has been assessed and judgment on the possible cause of ageing has been made. Results The findings of different research have demonstrated that the signaling efficiency of immunoglobulin M (IgM) has been limited by the amount of test compounds administered to study Balb c mice in the oral route. The response efficiency of IgM immune response against the lower doses of test compounds were high compared to the higher doses of test compounds which was low. The results of different other studies also demonstrated that the decline of serum IgM levels was associated with ageing. The relationship between alcohol consumption and the concentration of serum Igs was also described in the report of different studies. These studies have shown that there was lower level of IgG in the blood serum of alcohol consumers compared to non-consumers. The study has also demonstrated a lower level of serum IgM with higher alcohol consumption and higher serum concentration with moderate beer consumption. Conclusion The trajectory of Igs’ immune response against different amounts of xenobiotics was highly associated with the trajectory of biological changes during ageing. These research findings might be the possible evidence to conclude that ageing is caused by the foodstuffs and non-foodstuffs we usually consume, the lifestyles we usually experience and the way of life we usually live in the environment which gradually defiling the natural processes of the body.
Jan 2014 DOI 10.14302/issn.2326-0793.jpgr-13-355
Tarassishin LeonidCorresponding author
Department of Microbiology and Immunology
FIP-2 is a multifunctional protein which is involved in various cellular processes. Using different approaches we investigated its regulatory activity. The microarray analysis has shown that FIP-2 substantially altered the expression of 75 genes (35+/40-) from different functional groups with maximal presentation in “Signal transduction” and “Transcription regulation”. Real time RT-PCR indicated significant elevation in the transcription of chemokines, particularly IL-8 (CXCL8). Production of IL-8 in HEK293 cells dramatically increased with FIP-2 overexpression. We also demonstrated that FIP-2 induced activation of IL-8 promoter activity through NF-kB binding site. Additionally, we showed that FIP-2 could interact with PAK3 and increase its kinase activity. Overall, we demonstrated the role of FIP-2 in the regulation of chemokines (IL-8, MPIF-1, MCP-1) and kinases (PAK3, ALK).
Dec 2012 DOI 10.14302/issn.2326-0793.jpgr-12-100
Li ShitaoCorresponding author
Department of Microbiology & Immunobiology, Harvard Medical School, Boston, Massachusetts, 02115, USA.
Defining protein-protein interactions is essential for understanding the mechanisms by which cells regulate basic functions, such as metabolism, transcription, and signal transduction. Affinity purification followed by tandem mass spectrometry (AP-MS) has application for discovery of new interactors regulating various cellular processes. Here we optimize the purification method for AP-MS and develop a simplified unbiased analytical tool, Z-score plus prey occurrence and reproducibility (ZSPORE) for data analysis. Using this pipeline we achieve a higher efficiency of AP-MS and enhanced identification of high confidence interacting proteins (HCIP) in mammalian cells. When applied to analysis of the innate immune interactome, these methods enhanced HCIP identification. In addition, we investigated the GRB2 complex, which is associated with signal transduction and cell growth. Twenty-four known GRB2 interacting proteins were identified plus 26 new GRB2 binding partners. Thus, these straightforward methods recapitulate known protein interactions, discover novel complexes, and allow mapping of protein interaction networks.