Hormone-like Molecules Research Articles

Molecular and biochemical characterizations of a Fasciola gigantica retinoid X receptor-α isoform A (FgRXRα-A)

Fascioliasis is a parasitic infection in animals and humans caused by the parasitic flatworm genus Fasciola, which has two major species, F. hepatica and F. gigantica. A major concern regarding this disease is drug resistance, which is increasingly reported worldwide. Hence, the discovery of a novel drug as well as drug targets is crucially required. Therefore, this study aims to characterize the novel drug target in the adult F. gigantica. In the beginning, we hypothesized that the parasite might interact with some host molecules when it lives inside the liver parenchyma or bile ducts, specifically hormones and hormone-like molecules, through the specific receptors, primarily nuclear receptors (NRs), which are recognized as a major drug target in various diseases. The retinoid X receptor (RXR) is a member of subfamily 2 NRs that plays multitudinous roles in organisms by forming homodimers or heterodimers with other NRs. We obtained the full-length amino acid sequences of F. gigantica retinoid X receptor-alpha (FgRXRα-A) from the transcriptome of F. gigantica that existed in the NCBI database. The FgRXRα-A were computationally predicted for the basic properties, multiple aligned, phylogeny analyzed, and generated of 2D and 3D models. Moreover, FgRXRα-A was molecular cloned and expressed as a recombinant protein (rFgRXRα-A), then used for immunization for specific polyclonal antibodies. The native FgRXRα-A was detected in the parasite extracts and tissues, and the function was investigated by in vitro binding assay. The results demonstrated the conservation of FgRXRα-A to the other RXRs, especially RXRs from the trematodes. Interestingly, the native FgRXRα-A could be detected in the testes of the parasite, where the sex hormones are accumulated. Moreover, the binding assay revealed the interaction of 9-cis retinoic acid and FgRXRα-A, suggesting the function of FgRXRα-A. Our findings suggested that FgRXRα-A will be involved with the sexual reproduction of the parasite by forming heterodimers with other NRs, and it could be the potential target for further drug development of fascioliasis.

Application of nanomaterials as potential quorum quenchers for disease: Recent advances and challenges

Chemical signal molecules are used by bacteria to interact with one another. Small hormone-like molecules known as autoinducers are produced, released, detected, and responded to during chemical communication. Quorum Sensing (QS) is the word for this procedure; it allows bacterial populations to communicate and coordinate group behavior. Several research has been conducted on using inhibitors to prevent QS and minimize the detrimental consequences. Through the enzymatic breakdown of the autoinducer component, by preventing the formation of autoinducers, or by blocking their reception by adding some compounds (inhibitors) that can mimic the autoinducers, a technique known as “quorum quenching” (QQ) disrupts microbial communication. Numerous techniques, including colorimetry, electrochemistry, bioluminescence, chemiluminescence, fluorescence, chromatography-mass spectroscopy, and many more, can be used to test QS/QQ. They all permit quantitative and qualitative measurements of QS/QQ molecules. The mechanism of QS and QQ, as well as the use of QQ in the prevention of biofilms, are all elaborated upon in this writing, along with the fundamental study of nanoparticle (NP)in QQ. Q.

225-LB: Reciprocal Regulatory Interactions of Adipocytes and B Lymphocytes

Obesity, a global health problem, leads to chronic inflammation of adipose tissue (AT), an immune-mediated process linked to metabolic dysfunction and disease, including type II diabetes mellitus. Adipocytes, the most abundant cellular constituent of AT, store lipids and secrete adipokines, a group of hormone-like molecules such as adiponectin and adipsin that regulate metabolism and immune cell functions. In mouse models of diet-induced obesity, distinct subsets of B lymphocytes have been implicated in both exacerbating and mitigating AT inflammation and insulin resistance, but the immunoregulatory mechanisms underlying these effects are incompletely understood. Similarly, whether B lymphocytes and adipocytes engage in regulatory interactions with each other is not known. To investigate this question, we performed in vitro co-culture studies using murine 3T3-L1 adipocytes and I.29µ+ B cells, a murine B cell lymphoma that initiates robust secretion of IgM antibodies and the anti-inflammatory cytokine interleukin (IL)-10 upon activation by lipopolysaccharide (LPS). The induction of IgM and IL-10 secretion was markedly attenuated when I.29µ+ B cells were stimulated with LPS while co-cultured in direct contact with 3T3-L1 adipocytes. This inhibitory effect was also observed, albeit to a lesser degree, when the two cell types were co-cultured but separated by a semipermeable membrane. Conversely, secretion of adiponectin and adipsin by 3T3-L1 adipocytes was reduced when the adipocytes were co-cultured with I.29µ+ B cells, both in direct contact and when separated by a semipermeable membrane. This reduction of adipokine output was observed in both the absence and presence of LPS to activate the B cells. These data support the hypothesis that B lymphocytes and adipocytes can engage in reciprocal interactions that modulate the functions of these two secretory cell types and, in turn, may influence AT homeostasis and inflammation in healthy and obese states. Disclosure J. W. Brewer: None. R. L. Judd: None. M. K. Allman: None. S. R. Carroll: None. S. Granger: None. A. Hall: None. K. Pownall: None. J. Quintana: None. N. Arellano rangel: None. J. Thomas: None. Funding Edward Via College of Osteopathic Medicine Center for One Health

Nutritional and metabolic signalling through GPCRs.

Deregulated metabolism is a well-known feature of several challenging diseases, including diabetes, obesity and cancer. Besides their important role as intracellular bioenergetic molecules, dietary nutrients and metabolic intermediates are released in the extracellular environment. As such, they may achieve unconventional roles as hormone-like molecules by activating cell surface G-protein-coupled receptors (GPCRs) that regulate several pathophysiological processes. In this review, we provide an insight into the role of lactate, succinate, fatty acids, amino acids as well as ketogenesis-derived and β-oxidation-derived intermediates as extracellular signalling molecules. Moreover, the mechanisms by which their cognate metabolite-sensing GPCRs integrate nutritional and metabolic signals with specific intracellular pathways will be described. A better comprehension of these aspects is of fundamental importance to identify GPCRs as novel druggable targets.

Recovery using “float” from high intensity stress on growth hormone-like molecules in resistance trained men

ObjectiveThe purpose of this study was to examine the influence of a novel “floatation-restricted environmental stimulation therapy” (floatation-REST) on growth hormone responses to an intense resistance exercise stress. DesignNine resistance trained men (age: 23.4 ± 2.5 yrs.; height: 175.3 ± 5.4 cm; body mass: 85.3 ± 7.9 kg) completed a balanced, crossover-controlled study design with two identical exercise trials, differing only in post-exercise recovery intervention (i.e., control or floatation-REST). A two-week washout period was used between experimental conditions. Plasma lactate was measured pre-exercise, immediately post-exercise and after the 1 h. recovery interventions. Plasma iGH was measured pre-exercise, immediately-post exercise, and after the recovery intervention, as well as 24 h and 48 h after the exercise test. The bGH-L was measured only at pre-exercise and following each recovery intervention. ResultsFor both experimental conditions, a significant (P ≤ 0.05) increase in lactate concentrations were observed immediately post-exercise (~14 mmol • L-1) and remained slightly elevated after the recovery condition. The same pattern of responses was observed for iGH with no differences from resting values at 24 and 48 h of recovery. The bGH-L showed no exercise-induced changes following recovery with either treatment condition, however concentration values were dramatically lower than ever reported. ConclusionThe use of floatation-REST therapy immediately following intense resistance exercise does not appear to influence anterior pituitary function in highly resistance trained men. However, the lower values of bGH suggest dramatically different molecular processing mechanisms at work in this highly trained population.

High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity, systemic metabolism, and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here, we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced invitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences to murine EECs, including hormones, sensory receptors, and transcription factors. Notably, several hormone-like molecules were identified. Inter-EEC communication is exemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.

DOHaD: a disease-oriented, epoch-making, British-originated theory with Hungarian roots

On the basis of comparative epidemiological statistical studies, the ’developmental origin of health and disease’ (DOHaD) theory was published in 1986, testifying the interrelation between certain perinatal events, like under- and overfeeding as well as infant mortality with cardiovascular lethality in adults (Barker DJ, Osmond C, Lancet, 1986; 137: 1077–1081) – and at present it is widely extended. The theory is rather similar to the hormonal imprinting concept, which had been published 6 years earlier (Csaba G, Biol Rev Cambr Philos Soc. 1980; 55: 47–63 and Horm Metab Res. 1984; 16: 329–335). This demonstrated the role of perinatal encounter with hormones or hormone-like molecules with adult’s endocrino-pathological events based on animal experiments. Barker hypothesized the role of hormonal imprinting in DOHaD (Phillips DI, Barker DJ, Osmond C, Acta Endocrinol (Copenh). 1993; 129: 134–138: „A possible explanation is that thyroid hormones present in the breast milk and absorbed by the suckling infant could, by the process of hormonal imprinting, permanently down-regulate the set point of thyroid homeostasis”, and this could have encouraged him to create the theory. Both theories suggest the relationship between the perinatal events and adult-age disease manifestation, however, in the case of faulty imprinting, perinatal disease does not have a role in the provocation by imprinters (only the encounter between the imprinter and the hormone receptor), but in the case of DOHaD, this seems to be involved in the process. The whole process points to the disturbance of epigenetic programming. On the basis of the present standpoint, DOHaD is valid in non-communicative diseases, however, considering the impact of faulty hormonal imprinting to the immune system, the extension to communicative diseases is expected and likely also the involvement of lifespan. Further critical developmental period is the adolescence (puberty), when similar reprogramming could be possible and also in certain cases (e.g., in the immune system) disease-causing reprogramming could occur during the whole life. The two concepts are not racing, but using different methods for verification supplement and support each other, by building up identical conclusions (faulty reprogramming) giving epigenetical explanation for numerous diseases. DOHaD and its antecedent, hormonal imprinting are not only theories, but realities, which are commendable to consider in diagnosis and therapy. Studying the tendencies of human creativeness, in all probability, the importance of DOHaD (and faulty imprinting) will be growing in the near and far future. Orv Hetil. 2020; 161(16): 603–609.

Late manifested sequelae of medications in the critical periods of development. The widening of the faulty hormonal imprinting conception

Hormonal imprinting is a physiological process, which is a part of the receptor-hormone complex development. It determines the binding capacity of the receptors across the lifespan. It takes place perinatally in the critical period of hormone receptor development, when the developmental window for imprinting is open and permits the binding of hormone-like molecules (related or synthetic hormones, endocrine disruptors etc.) causing disturbances of the endocrine system, and the systems- influenced organs by it, for life. This is the faulty hormonal imprinting. However, studying the medical database, PubMed, a lot of data can be found on the harmful late (adult age) effects of medication in the critical period of development with non-hormonal molecules, which are manifested later in functional alterations or diseases. This could mean that in the process of faulty imprinting, the openness of the developmental window could be more important than the structural similarity of a molecule to hormones. As developmentally critical period for faulty imprinting by hormone-like molecules is not exclusively the perinatal one (this is justified in the case of faulty hormonal imprinting), the pubertal period was also studied from this aspect and similarities to the impact of perinatal use have been found (this could be called "Pubertal Origin of Health and Disease = POHaD). While in the case of hormonal faulty imprinting, the mechanism seems to be clear (considering the role of receptors), the mechanism of drug-provoked imprinting is presently uncleared (considering the variety of medications which cause late-manifested alterations). The medicaments-caused faulty imprinting conception calls attention to the dangers of medication in the perinatal as well as the pubertal periods. Orv Hetil. 2020; 161(2): 43-49.

Regulation of Antibiotic Production by Signaling Molecules in Streptomyces.

The genus Streptomyces is a unique subgroup of actinomycetes bacteria that are well-known as prolific producers of antibiotics and many other bioactive secondary metabolites. Various environmental and physiological signals affect the onset and level of production of each antibiotic. Here we highlight recent findings on the regulation of antibiotic biosynthesis in Streptomyces by signaling molecules, with special focus on autoregulators such as hormone-like signaling molecules and antibiotics themselves. Hormone-like signaling molecules are a group of small diffusible signaling molecules that interact with specific receptor proteins to initiate complex regulatory cascades of antibiotic biosynthesis. Antibiotics and their biosynthetic intermediates can also serve as autoregulators to fine-tune their own biosynthesis or cross-regulators of disparate biosynthetic pathways. Advances in understanding of signaling molecules-mediated regulation of antibiotic production in Streptomyces may aid the discovery of new signaling molecules and their use in eliciting silent antibiotic biosynthetic pathways in a wide range of actinomycetes.

Genes, Cells, and MiRNAs

Novel methods to treat HF include gene, cell and microRNA delivery. There have been few gene therapy trials in HF. The CUPID I and II trials with AAV1.SERCA2a showed unconvincing results. The STOP-HF trial using direct intra-myocardial injection of a non-integrating plasmid vector carrying stromal cell-derived factor-1 showed no clinical effects and the AC6 gene transfer trial used IC infusion of escalating doses of Ad5.hAC6 was similarly negative. Despite high hopes stem cell trials to date in HF have not shown convincing clinical benefits. More recent clinical trials in this area have investigated the injection of cell stimulating paracrine factors (peptides, small molecules, hormone-like molecules) without actual cell delivery. Micro-RNA’s (miRNAs) are small non-coding RNA strands, comprising 19-25 nucleotides, that have a distinct signalling role and a various patterns of expression in ischaemic myocardium, hypertrophy, cardiomyopathies, and overt HF. They act at the post-transcriptional regulation level. Numerous novel miRNAs have been discovered, and their in-depth role has been characterised. miRNAs can serve as therapeutic substances or therapeutic targets in a range of cardiovascular diseases. Clinical trials are likely in the near future.

Inactivation of Prostaglandin E2 as a Mechanism for UGT2B17-Mediated Adverse Effects in Chronic Lymphocytic Leukemia

High expression of the metabolic enzyme UDP-glucuronosyltransferase UGT2B17 in chronic lymphocytic leukemia (CLL) cells was associated with poor prognosis in two independent studies. However, the underlying mechanism remains unknown. We hypothesized that UGT2B17 impacts intracellular levels of hormone-like signaling molecules involved in the regulation of gene expression in leukemic cells. We initially confirmed in a third cohort of 291 CLL patients that those with high UGT2B17 displayed poor prognosis (hazard ratio of 2.31, P = 0.015). Consistent with the unfavorable prognostic significance of elevated UGT2B17 expression in CLL patients, high UGT2B17 expression was associated with enhanced proliferation of MEC1 and JVM2 malignant B-cell models. Transcriptomic analyses revealed that high UGT2B17 was linked to a significant alteration of genes related to prostaglandin E2 (PGE2) and to its precursor arachidonic acid, both in cell models and a cohort of 448 CLL patients. In functional assays, PGE2 emerged as a negative regulator of apoptosis in CLL patients and proliferation in cells models, whereas its effect was partially abrogated by high UGT2B17 expression in MEC1 and JVM2 cells. Enzymatic assays and mass-spectrometry analyses established that the UGT2B17 enzyme inactivates PGE2 by its conjugation to glucuronic acid (GlcA) leading to the formation of two glucuronide (G) derivatives. High UGT2B17 expression was further associated with a proficient inactivation of PGE2 to PGE2-G in CLL patient cells and cell models. We conclude that UGT2B17-dependent PGE2 glucuronidation impairs anti-oncogenic PGE2 effects in leukemic cells, thereby partially contributing to disease progression in high UGT2B17 CLL patients.

Comparative Evaluation of Hormones and Hormone-Like Molecule in Lineage Specification of Human Induced Pluripotent Stem Cells.

Background and ObjectivesProficient differentiation of human pluripotent stem cells (hPSCs) into specific lineages is required for applications in regenerative medicine. A growing amount of evidences had implicated hormones and hormone-like molecules as critical regulators of proliferation and lineage specification during in vivo development. Therefore, a deeper understanding of the hormones and hormone-like molecules involved in cell fate decisions is critical for efficient and controlled differentiation of hPSCs into specific lineages. Thus, we functionally and quantitatively compared the effects of diverse hormones (estradiol 17-β (E2), progesterone (P4), and dexamethasone (DM)) and a hormone-like molecule (retinoic acid (RA)) on the regulation of hematopoietic and neural lineage specification.Methods and ResultsWe used 10 nM E2, 3 μM P4, 10 nM DM, and 10 nM RA based on their functional in vivo developmental potential. The sex hormone E2 enhanced functional activity of hematopoietic progenitors compared to P4 and DM, whereas RA impaired hematopoietic differentiation. In addition, E2 increased CD34+CD45+ cells with progenitor functions, even in the CD43− population, a well-known hemogenic marker. RA exhibited lineage-biased potential, preferentially committing hPSCs toward the neural lineage while restricting the hematopoietic fate decision.ConclusionsOur findings reveal unique cell fate potentials of E2 and RA treatment and provide valuable differentiation information that is essential for hPSC applications.

Cardiotonic steroid ouabain stimulates steroidogenesis in Leydig cells via the α3 isoform of the sodium pump

Cardiotonic steroids such as ouabain are potent inhibitors of the sodium pump and have been widely used for centuries in the treatment of congestive heart failure. In recent decades, however, they have also been identified as hormone-like molecules that trigger signaling cascades of physiological relevance by using the various sodium pump α subunit isoforms as receptors. The murine Leydig cell line MLTC-1 expresses both the ubiquitous, relatively ouabain-insensitive α1 isoform of the sodium pump and the ouabain-sensitive α3 isoform that is normally found in neuronal cells. The physiological relevance of the simultaneous presence of the two isoforms in Leydig cells has not been previously addressed.MLTC-1 Leydig cells contain lipid droplets (LDs) and are capable of progesterone biosynthesis when stimulated by luteinizing hormone (LH). When exposed to low nanomolar concentrations of ouabain, they respond with stimulation of Erk1/2, CREB, and ATF-1 phosphorylation, LD enlargement, and perilipin2 mobilization to the LDs. As a result, progesterone biosynthesis is augmented. Abrogation of α3 isoform expression by siRNA prevents all of the above responses, indicating that it is the hormone/receptor-like interaction of ouabain exclusively with this isoform that triggers the signaling events that normally occur when LH binds to its receptor.Considering that ouabain is produced endogenously and is found in seminal fluid, one can speculate that effects of this substance on germ and somatic cells of the testis might play a role in male reproductive physiology.

Irisin Mediates Effects on Bone via αV Integrin Receptors

Exercise is crucial to prevent obesity, diabetes, fatty liver disease, and osteoporosis. These beneficial effects are partially mediated by myokines, hormone‐like molecules produced by skeletal muscle. Irisin is a myokine which is a cleaved product from fibronectin type III domain‐containing protein 5 (FNDC5) and is shed into the intracellular milieu and blood circulation to reach other organs. Particularly irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the αV class of integrins and biophysical studies identify interacting surfaces between irisin and αV/β5 integrin. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. In vivo, injection of recombinant irisin protein increases the expression of sclerostin in osteocyte‐enriched bone as well as the levels of plasma sclerostin, and chemical inhibition of the αV integrins blocks the irisin‐induced effects. Genetic ablation of FNDC5/irisin completely blocks osteocytic osteolysis and bone resorption induced by ovariectomy, preventing bone loss and supporting an important role for irisin in skeletal remodeling. The identification of the irisin receptor and its roles in bone biology should greatly facilitate our understanding of irisin's function in exercise and human health.Support or Funding InformationHyeonwoo (Chad) Kim was supported by a cardiovascular T32 grant (5T32HL007374‐38). Bruce M. Spiegelman was supported by NIH grants (4 R01DK54477‐19, DK61502, B.M.S.) and the JPB Foundation (629803). Lynda F. Bonewald was supported by NIH grant (PO1AG039335). Clifford J. Rosen was supported by NIH grant (NIDDK RC2 092759).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hormonal Imprinting: The First Cellular-level Evidence of Epigenetic Inheritance and its Present State.

Hormonal imprinting takes place perinatally at the first encounter between the developing hormone receptor and its target hormone. This process is needed for the normal function of the receptor-hormone pair and its effect is life-long. However, in this critical period, when the developmental window is open, related molecules (members of the same hormone family, synthetic hormones and hormone-like molecules, endocrine disruptors) also can be bound by the receptor, causing life-long faulty imprinting. In this case, the receptors’ binding capacity changes and alterations are caused at adult age in the sexual and behavioral sphere, in the brain and bones, inclination to diseases and manifestation of diseases, etc. Hereby, faulty hormonal imprinting is the basis of metabolic and immunological imprinting as well as the developmental origin of health and disease (DOHaD). Although the perinatal period is the most critical for faulty imprinting, there are other critical periods as weaning and adolescence, when the original imprinting can be modified or new imprintings develop. Hormonal imprinting is an epigenetic process, without changing the base sequence of DNA, it is inherited in the cell line of the imprinted cells and also transgenerationally (up to 1000 generations in unicellulars and up to the 3rd generation in mammals are justified). Considering the enormously growing number and amount of faulty imprinters (endocrine disruptors) and the hereditary character of faulty imprinting, this latter is threatening the whole human endocrine system.

Evidence of functional bile acid signaling pathways in adipocytes

Background and aimBile acids (BA) are increasingly recognized as pleiotropic and hormone-like signaling molecules with metabolic and endocrine functions. However, the role of BA in white adipocyte physiology remains somewhat obscure. It was the aim to investigate the BA receptors (FXR, TGR5) and FGFR1 (Fibroblast growth factor receptor 1) as well as Bsep (bile salt export pump) in white adipocytes and in murine and human adipose tissue (AT) and to investigate effects of different BA species in adipocyte physiology. Patients, material and methodsReceptor mRNA expression was quantified by real-time PCR in mice, humans and during 3T3-L1 pre-adipocyte differentiation. Adipokines were measured by ELISA upon stimulation by several BA. Effects of BA on TNF- and LPS-induced MCP-1 secretion and lipolysis were analyzed. TNF-induced lipolysis was investigated by glycerol assay. ResultsThe present data provide for the first time a detailed expression profile of FXR, TGR5, FGFR1, and Bsep during adipocyte differentiation and in murine and human AT. FGFR1 expression is upregulated in adipose tissue of LPS-injected animals. Several BA regulate secretion of adipokines such as adiponectin and resistin differentially. Importantly, TNF- and LPS-induced MCP-1 release from adipocytes as well as TNF-induced lipolysis can be antagonized by cholic acid (CA) and deoxycholic acid (DCA). ConclusionsThe present data provide evidence of functional BA signaling pathways in adipocytes and argue for certain MCP-1 related anti-inflammatory effects of BA in TNF- and LPS-induced inflammation, whereas pro-inflammatory resistin is induced by CA and glycocholic acid (GCA). Systemic bile acids might represent a hormonal network regulating white adipocyte physiology including lipolysis.

Endocrinologia e controle da vitelogênese em carrapatos

Background : : : : Ticks are distributed worldwide, with impacts on human and animal health. The cattle tick Rhipicephalus (Boophilus) microplus is the main parasite that affects livestock in tropical and subtropical regions of the world, causing large economical losses. Tick control methods are based on the application of chemical acaricides, which has resulted in selection of resistant ticks and a potential risk of environmental pollution and food contamination. Vaccines have showed to be a feasible tick control method that offers a cost-effective, environmental friendly alternative to chemical control. However, more than ten years after the commercialization of the first vaccine against ticks, the identification of tick-protective antigens remains a limiting step in the development of an efficient formulation that would avoid the use of chemical acaricides. So, the study of parasite biology and understanding physiological mechanisms could be a good strategy to find new targets for an efficient vaccine. Review : It was reviewed the main insights about the reproductive process in ticks, emphasizing the hormonal control of vitellogenesis and enzymes involved in vitellin processing during embryogenesis. The processes of vitellogenesis and embryogenesis have been studied in various organisms, particularly in cockroaches, flies and ticks. Although the roles of 20-hydroxyecdysone (20E) and juvenile hormone have been well characterized for vitellogenesis in insects, we know much less about the hormonal control of vitellogenesis in ticks. Initially, it was hypothesized that juvenile hormone was involved in tick vitellogenin-synthesis. However, more critical studies uncovered no evidence for the occurrence of juvenile hormone or juvenile hormone-like molecules in several tick species. Current research shows that in ticks, it appears that ecdysteroids, and not juvenile hormone, regulate the expression of the vitellogenin gene and the synthesis and release of vitellogenin protein into the hemolymph. In general, the carbohydrate, lipid and amino acid composition of tick vitellogenin is similar to that of insect vitellogenin. Once in the hemolymph, oocytes uptake vitellogenin through receptor-mediated endocytosys. However, there are different strategies to control vitellogenin synthesis and uptake by ovary in ixodide ticks. In the oocytes, vitellogenin is partially processed in the endosomal compartment and then stored as vitellin, the main reserve of protein for embryo development, in specialized organelles, the yolk granules. Embryo development depends on the availability of yolk material stored into oocytes. So, the characterization of molecules involved in vitellogenesis and embryo development contribute to a better understanding of the tick parasite physiology. During embryogesesis, acidic enzymes are responsible for the availability of this material and embryo nutrition. The Vitellin-Degrading Cysteine Endopeptidase (VTDCE), Boophilus Yolk Pro-Cathepsin (BYC) and Tick Heme Binding Aspartic Proteinase (THAP) are enzymes involved in vitellin hydrolysis in R. microplus eggs. These enzymes are produced by gut and fat body and transported through the hemolymph to be internalized into the oocytes and then play their role in tick embryo nutrition. As VTDCE, BYC and THAP are involved in an important physiological process, their potential as targets in an anti-tick vaccine is an attractive research topic. With this objective, various enzymes have been tested in native or recombinant forms as candidate immunogens to a multiantigenic anti-tick vaccine. Conclusion : Significant advancements have been made in recent years on understanding the tick reproductive process, and some molecules that can be possible targets for development of new tick control strategies have been characterized.

Intrinsic Hormone-Like Molecules and External Root Resorption During Orthodontic Tooth Movement. A Systematic Review and Meta-Analysis in Preclinical in-Vivo Research.

Background: External root resorption constitutes an adverse effect of orthodontic treatment. The aim of the present meta-analysis was to identify the effect of induced intrinsic/ hormone-like molecules such as prostaglandins, interleukins and others on external root resorption after orthodontic tooth movement in experimental animalsMethods: An electronic database search of the literature was performed (Medline via PubMed, EMBASE, LILACS, and Open Gray). Search terms included root resorption, tooth movement and animal type. Risk of bias assessment was made using the SYRCLE guidelines for animal studies and reporting quality was assessed through ARRIVE. Random effects meta-analysis was performed for the outcome root resorption after orthodontic tooth movement.Results: Of the 124 articles initially retrieved, 13 were eligible for inclusion in the systematic review, while only 2 were included in the quantitative synthesis. Five studies investigated the effect of Prostaglandin E2, four studies the effect of Thyroxine, two the effect of Calcium ions (Ca++), while the rest investigated Misoprostol, Interleukin-12 and Interleukin-4. Risk of Bias in all studies was judged to be high overall, while reporting quality was suboptimal. According to the quantitative synthesis, there was no difference in root resorption after orthodontic tooth movement when Prostaglandin E2 coupled with Ca++ was administered in comparison to no substance administration (SMD: 0.48 mm2; 95% CI: −0.22, 1.19; p = 0.18).Conclusions: Overall, there was no evidence to suggest a variation in root resorption when Prostaglandin E2 and Ca++ were administered, while there is an overriding need for further high quality experimental studies to inform available evidence on the effect of intrinsic substances on external root resorption.

Cell biology of fat storage.

The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion. Brown fat, on the other hand, dissipates chemical energy in the form of heat, thereby defending against hypothermia, obesity, and diabetes. It is now appreciated that there are two distinct types of thermogenic fat cells, termed brown and beige adipocytes. In addition to these distinct properties of fat cells, adipocytes exist within adipose tissue, where they are in dynamic communication with immune cells and closely influenced by innervation and blood supply. This review is intended to serve as an introduction to adipose cell biology and to familiarize the reader with how these cell types play a role in metabolic disease and, perhaps, as targets for therapeutic development.

Death and survival in Streptococcus mutans: differing outcomes of a quorum-sensing signaling peptide.

Bacteria are considered “social” organisms able to communicate with one another using small hormone-like molecules (pheromones) in a process called quorum-sensing (QS). These signaling molecules increase in concentration as a function of bacterial cell density. For most human pathogens, QS is critical for virulence and biofilm formation, and the opportunity to interfere with bacterial QS could provide a sophisticated means for manipulating the composition of pathogenic biofilms, and possibly eradicating the infection. Streptococcus mutans is a well-characterized resident of the dental plaque biofilm, and is the major pathogen of dental caries (cavities). In S. mutans, its CSP QS signaling peptide does not act as a classical QS signal by accumulating passively in proportion to cell density. In fact, particular stresses such as those encountered in the oral cavity, induce the production of the CSP pheromone, suggesting that the pheromone most probably functions as a stress-inducible alarmone by triggering the signaling to the bacterial population to initiate an adaptive response that results in different phenotypic outcomes. This mini-review discusses two different CSP-induced phenotypes, bacterial “suicide” and dormancy, and the underlying mechanisms by which S. mutans utilizes the same QS signaling peptide to regulate two opposite phenotypes.