scholarly journals Sexual Dimorphism of Corticosteroid Signaling during Kidney Development

2021 ◽  
Vol 22 (10) ◽  
pp. 5275
Author(s):  
Margaux Laulhé ◽  
Laurence Dumeige ◽  
Thi An Vu ◽  
Imene Hani ◽  
Eric Pussard ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Signaling Pathways ◽  
Kidney Development ◽  
Dependent Manner ◽  
Specific Expression ◽  
Glucocorticoid Signaling ◽  
Sexual Characteristics ◽  
Gender Differential ◽  
Fetus And Neonate

Sexual dimorphism involves differences between biological sexes that go beyond sexual characteristics. In mammals, differences between sexes have been demonstrated regarding various biological processes, including blood pressure and predisposition to develop hypertension early in adulthood, which may rely on early events during development and in the neonatal period. Recent studies suggest that corticosteroid signaling pathways (comprising glucocorticoid and mineralocorticoid signaling pathways) have distinct tissue-specific expression and regulation during this specific temporal window in a sex-dependent manner, most notably in the kidney. This review outlines the evidence for a gender differential expression and activation of renal corticosteroid signaling pathways in the mammalian fetus and neonate, from mouse to human, that may favor mineralocorticoid signaling in females and glucocorticoid signaling in males. Determining the effects of such differences may shed light on short term and long term pathophysiological consequences, markedly for males.

scholarly journals Maintenance of Hematopoietic Stem Cells Through Regulation of Wnt and mTOR Pathways.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2309-2309
Author(s):  
Jian Huang ◽  
Peter S. Klein
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Signaling Pathways ◽  
Glycogen Synthase ◽  
Dependent Manner ◽  
Mtor Inhibition ◽  
Self Renewal ◽  
Hematopoietic Stem

Abstract Abstract 2309 Hematopoietic stem cells (HSCs) maintain the ability to self-renew and to differentiate into all lineages of the blood. The signaling pathways regulating hematopoietic stem cell (HSCs) self-renewal and differentiation are not well understood. We are very interested in understanding the roles of glycogen synthase kinase-3 (Gsk3) and the signaling pathways regulated by Gsk3 in HSCs. In our previous study (Journal of Clinical Investigation, December 2009) using loss of function approaches (inhibitors, RNAi, and knockout) in mice, we found that Gsk3 plays a pivotal role in controlling the decision between self-renewal and differentiation of HSCs. Disruption of Gsk3 in bone marrow transiently expands HSCs in a b-catenin dependent manner, consistent with a role for Wnt signaling. However, in long-term repopulation assays, disruption of Gsk3 progressively depletes HSCs through activation of mTOR. This long-term HSC depletion is prevented by mTOR inhibition and exacerbated by b-catenin knockout. Thus GSK3 regulates both Wnt and mTOR signaling in HSCs, with opposing effects on HSC self-renewal such that inhibition of Gsk3 in the presence of rapamycin expands the HSC pool in vivo. In the current study, we found that suppression of the mammalian target of rapamycin (mTOR) pathway, an established nutrient sensor, combined with activation of canonical Wnt/ß-catenin signaling, allows the ex vivo maintenance of human and mouse long-term HSCs under cytokine-free conditions. We also show that combining two clinically approved medications that activate Wnt/ß-catenin signaling and inhibit mTOR increases the number of long-term HSCs in vivo. Disclosures: No relevant conflicts of interest to declare.

Morphometric studies of artemia males from different populations of the Altai region

2020 ◽  
pp. 28-38
Author(s):  
L. Vesnina ◽  
G. Lukerina ◽  
T. Ronzhina ◽  
A. Savos’kin ◽  
D. Surkov
Keyword(s):  
Sexual Dimorphism ◽  
Hydrogen Index ◽  
Morphometric Parameters ◽  
Altai Region ◽  
Sexual Structure ◽  
Different Populations ◽  
Artemia Population ◽  
Term Data ◽  
Brine Salinity

The long-term data from morphometric studies of Artemia males from bisexual and parthenogenetic populations from hyperhaline reservoirs of the Altai region (Bolshoe Yarovoe Lake, Maloe Shklo Lake, and the Tanatar Lakes system) is analyzed in this paper. The description of signs of sexual dimorphism and sexual structure in different populations is given. The influence of brine salinity and hydrogen index on morphometric parameters of males was analyzed. There are differences in the sexual structure of the Artemia population: in the lakes Maloe Shklo and the thanatar system, the populations are bisexual (the share of males is 28.5 — 75.0 %), in the lake Bolshoe yarovoe — parthenogenetic (the share of males on average does not exceed 3 %). At the same time, sexual dimorphism is typical for both types of populations: females are larger than males, males have a larger head (the distance between the eyes is greater by 15.5 %, the diameter of the eye is 26.1 %, the length of the antenna is 22.3 %) and a larger number of bristles (36.1 %). The greatest variability is observed in the parameters of the Furka structure associated with the salinity of water by feedback and the pH — line indicator. Significant differences between the samples of males were revealed. The largest number of significant differences in morphometric indicators was found between samples of males from bisexual populations (lake thanatar and lake Maloe Shklo), the smallest — between males from the parthenogenetic population of lake Bolshoe yarovoe and males from lake Maloe Shklo.

Insight into Mechanistic Action of Thymoquinone Induced Melanogenesis in Cultured Melanocytes

2019 ◽  
Vol 26 (12) ◽  
pp. 910-918
Author(s):  
Kamal U. Zaidi ◽  
Firoz N. Khan ◽  
Sharique A. Ali ◽  
Kausar P. Khan
Keyword(s):  
Western Blot ◽  
Signaling Pathways ◽  
Cell Line ◽  
Melanoma Cell ◽  
Melanoma Cell Line ◽  
Protein Kinase Inhibitors ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
B16f10 Melanoma ◽  
B16f10 Melanoma Cell

Background: Melanin plays a crucial role in camouflage, social communication and protection against harmful ultraviolet radiations. Melanin is synthesized by melanocytes through melanogenesis and several intrinsic and extrinsic factors are involved during the process. Any change occuring in the normal melanogenesis process can cause severe pigmentation problems of hypopigmentation or hyperpigmentation. Objective: The present study is based on the evaluation of the effect of thymoquinone on melanogenesis and their possible mechanism of action using the B16F10 melanoma cell line for the production via blocking signaling pathways. Methods: Phase contrast microscopy, cell viability, tyrosinase activity, melanin content and western blot analysis were used in the present study. Results: In the present investigation, cultured melanocytes exhibit that the stimulation of melanin synthesis when treated with thymoquinone. Tyrosinase activity and melanin production in B16F10 melanoma cell line was increased in doze-dependent manner. In western blot, we investigated the involvement of the cAMP/PKA pathway in thymoquinone induced melanogenesis. It was observed protein kinase inhibitors PKA, PKC, PKB and MEK1 decreased the stimulatory effects of thymoquinone from 11.45- fold value to 8.312, 6.631, 4.51, and 7.211-fold value, respectively. However, the results also prove that thymoquinone may partially induce tyrosinase expression via PKA, PKB, PKC and MEK1 signaling pathways. Conclusion: The present finding proposed that thymoquinone is a protective challenger for melanogenesis and it might be useful for the treatment of hypopigmentary disorders.

scholarly journals HYBID (alias KIAA1199/CEMIP) and hyaluronan synthase coordinately regulate hyaluronan metabolism in histamine-stimulated skin fibroblasts

2020 ◽  
Vol 295 (8) ◽  
pp. 2483-2494
Author(s):  
Hiroyuki Yoshida ◽  
Mika Aoki ◽  
Aya Komiya ◽  
Yoko Endo ◽  
Keigo Kawabata ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Fold Increase ◽  
Histamine Receptor ◽  
Skin Fibroblasts ◽  
Dependent Manner ◽  
Skin Damage ◽  
Photoaged Skin ◽  
Molecular Sizes ◽  
Ha Synthase ◽  
Hyaluronan Binding

The immune-regulatory compound histamine is involved in the metabolism of the essential skin component hyaluronan (HA). We previously reported that histamine up-regulates the expression of HYBID (hyaluronan-binding protein involved in hyaluronan depolymerization, also called CEMIP or KIAA1199), which plays a key role in HA degradation. However, no information is available about histamine's effects on HA synthase (HAS) expression, the molecular sizes of HA species produced, and histamine receptors and their signaling pathways in skin fibroblasts. Moreover, histamine's effects on photoaged skin remain elusive. Here, we show that histamine increases HA degradation by up-regulating HYBID and down-regulating HAS2 in human skin fibroblasts in a dose- and time-dependent manner and thereby decreases the total amounts and sizes of newly produced HA. Histamine H1 blocker abrogated the histamine effects on HYBID up-regulation, HAS2 suppression, and HA degradation. Histamine H1 agonist exhibited effects on HA levels, composition, and breakdown similar to those of histamine. Of note, blockade of protein kinase Cδ or PI3K–Akt signaling abolished histamine-mediated HYBID stimulation and HAS2 suppression, respectively. Immunohistochemical experiments revealed a significant ∼2-fold increase in tryptase-positive mast cells in photoaged skin, where HYBID and HAS2 expression levels were increased and decreased, respectively, compared with photoprotected skin. These results indicate that histamine controls HA metabolism by up-regulating HYBID and down-regulating HAS2 via distinct signaling pathways downstream of histamine receptor H1. They further suggest that histamine may contribute to photoaged skin damage by skewing HA metabolism toward degradation.

scholarly journals Elucidation of Melanogenesis-Associated Signaling Pathways Regulated by Argan Press Cake in B16 Melanoma Cells

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2697
Author(s):  
Thouria Bourhim ◽  
Myra O. Villareal ◽  
Chemseddoha Gadhi ◽  
Hiroko Isoda
Keyword(s):  
Signaling Pathways ◽  
Press Cake ◽  
Global Gene Expression ◽  
Melanoma Cells ◽  
B16 Melanoma ◽  
Dependent Manner ◽  
Melanin Biosynthesis ◽  
B16 Melanoma Cells ◽  
Pigmentary Disorders ◽  
Argan Oil

The beneficial effect on health of argan oil is recognized worldwide. We have previously reported that the cake that remains after argan oil extraction (argan press-cake or APC) inhibits melanogenesis in B16 melanoma cells in a time-dependent manner without cytotoxicity. In this study, the global gene expression profile of B16 melanoma cells treated with APC extract was determined in order to gain an understanding of the possible mechanisms of action of APC. The results suggest that APC extract inhibits melanin biosynthesis by down-regulating microphthalmia-associated transcription factor (Mitf) and its downstream signaling pathway through JNK signaling activation, and the inhibition of Wnt/β-catenin and cAMP/PKA signaling pathways. APC extract also prevented the transport of melanosomes by down-regulating Rab27a expression. These results suggest that APC may be an important natural skin whitening product and pharmacological agent used for clinical treatment of pigmentary disorders.

scholarly journals Sexual dimorphism in the long-term stability (10 years) of skeletal Class III treatment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Natalia Tejedor ◽  
Conchita Martín ◽  
José Antonio Alarcón ◽  
María Dolores Oteo-Calatayud ◽  
Juan Carlos Palma-Fernández
Keyword(s):  
Sexual Dimorphism ◽  
Class Iii ◽  
Class Iii Malocclusion ◽  
Skeletal Class ◽  
Term Stability ◽  
Long Term Stability ◽  
Fixed Appliances ◽  
Males And Females ◽  
Class Iii Treatment

Abstract Background Class III malocclusion is associated with high sexual dimorphism, especially in individuals older than 13 years of age, with significant differences in growth between males and females during the pubertal and postpubertal stages, and in adulthood. The aim of this research was to examine differences between males and females in long-term stability (10 years) of treatment for skeletal Class III malocclusion. Methods Thirty patients (15 males and 15 females) with skeletal Class III malocclusion, who had been treated with rapid maxillary expansion (RME) combined with face mask protraction followed by fixed appliances, were selected sequentially. Thirty patients (15 males and 15 females) with skeletal Class I and mesofacial patterns treated only with fixed appliances for dental problems served as the control group. Differences between groups and sexes were evaluated using lateral cephalograms taken at the start of treatment (T0), immediately after the end of treatment (T1), and after 10 years (T2). The long-term treatment success rate was calculated. Results Ten years after Class III treatment, overjet and overbite relapse occurred similarly in females (− 0.68 ± 0.7 mm; − 0.38 ± 0.75 mm, respectively) and males (− 1.09 ± 1.47 mm; − 0.64 ± 0.9 mm, respectively); the ANB angle and Wits appraisal became significantly more negative in males (− 1.37 ± 1.06°; − 2.7 ± 2.53 mm) than in females (− 0.18 ± 1.26°; − 0.46 ± 1.94 mm). The success rate was 73.3% in males and 80% in females. Conclusions Significant differences in the long-term stability of Class III treatment outcomes have been found between males and females, with a larger skeletal Class III relapse and lower long-term success rates in males.

Epigenetic mechanisms involved in intrauterine growth restriction and aberrant kidney development and function

2020 ◽  
pp. 1-11
Author(s):  
Thu N. A. Doan ◽  
Jessica F. Briffa ◽  
Aaron L. Phillips ◽  
Shalem Y. Leemaqz ◽  
Rachel A. Burton ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Intrauterine Growth Restriction ◽  
Kidney Development ◽  
Dna Methyltransferases ◽  
Growth Restriction ◽  
Epigenetic Mechanisms ◽  
Specific Expression ◽  
Maternal Line ◽  
Intrauterine Growth ◽  
Increased Risk

Abstract Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6–13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

scholarly journals Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 307
Author(s):  
Yong Bok Seo ◽  
You Suk Suh ◽  
Ji In Ryu ◽  
Hwanhee Jang ◽  
Hanseul Oh ◽  
...  
Keyword(s):  
T Cell ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Dependent Manner ◽  
Viral Loads ◽  
Cell Responses ◽  
Rapid Spread

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

Sign in / Sign up

Export Citation Format

Share Document