scholarly journals Effects of GnRH immunization on the reproductive axis and thymulin

2015 ◽  
Vol 226 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Shiping Su ◽  
Xiaoxia Sun ◽  
Xiuhong Zhou ◽  
Fuigui Fang ◽  
Yunsheng Li
Keyword(s):  
Early Stage ◽  
Feedback Regulation ◽  
Reproductive Hormones ◽  
The Self ◽  
Endocrine Function ◽  
Dependent Manner ◽  
Hpg Axis ◽  
Bidirectional Regulation ◽  
Repressive Effect

The bidirectional regulation of thymulin in the reproductive-endocrine function of the hypothalamic–pituitary–gonadal (HPG) axis of rats immunized againstGnRHremains largely unclear. We explored the alterations in hormones in the HPG axis in immunized rats to dissect the repressive effect of immunization on thymulin, and to clarify the interrelation of reproductive hormones and thymulinin vivo. The results showed that, in the first 2 weeks of booster immunization, thymulin was repressed when reproductive hormones were severely reduced. The self-feedback regulation of thymulin was then stimulated in later immune stages: the rising circulating thymulin upregulated LH and FSH, including GnRH in the hypothalamus, although the levels of those hormones were still significantly lower than in the control groups. In astrocytes, thymulin produced a feedback effect in regulated GnRH neurons. However, in the arcuate nucleus (Arc) and the median eminence (ME), the mediator of astrocytes and other glial cells were also directly affected by reproductive hormones. Thus, in immunized rats, the expression of glial fibrillary acidic protein was distinctly stimulated in the Arc and ME. This study demonstrated that thymulin was downregulated by immunization againstGnRHin early stage. Subsequently, the self-feedback regulation was provoked by low circulating thymulin. Thereafter, rising thymulin levels promoted pituitary gonadotropins levels, while acting directly onGnRHneurons, which was mediated by astrocytes in a region-dependent manner in the hypothalamus.

scholarly journals Prolactin and Male Fertility: The Long and Short Feedback Regulation

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
M. K. Gill-Sharma
Keyword(s):  
Chromatin Condensation ◽  
Feedback Regulation ◽  
Pituitary Hormones ◽  
Feedback Mechanism ◽  
Reproductive Hormones ◽  
Male Rats ◽  
Normal Men

In the last 20 years, a pituitary-hypothalamus tissue culture system with intact neural and portal connections has been developed in our lab and used to understand the feedback mechanisms that regulate the secretions of adenohypophyseal hormones and fertility of male rats. In the last decade, several in vivo rat models have also been developed in our lab with a view to substantiate the in vitro findings, in order to delineate the role of pituitary hormones in the regulation of fertility of male rats. These studies have relied on both surgical and pharmacological interventions to modulate the secretions of gonadotropins and testosterone. The interrelationship between the circadian release of reproductive hormones has also been ascertained in normal men. Our studies suggest that testosterone regulates the secretion of prolactin through a long feedback mechanism, which appears to have been conserved from rats to humans. These studies have filled in a major lacuna pertaining to the role of prolactin in male reproductive physiology by demonstrating the interdependence between testosterone and prolactin. Systemic levels of prolactin play a deterministic role in the mechanism of chromatin condensation during spermiogenesis.

scholarly journals The E3 ubiquitin ligase RNF216/TRIAD3 is a central regulator of the hypothalamic-pituitary-gonadal axis

2021 ◽  
Author(s):  
Arlene J. George ◽  
Yarely C. Hoffiz ◽  
Christopher Ware ◽  
Bin Dong ◽  
Ning Fang ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Cell Activity ◽  
Calcium Transient ◽  
Therapeutic Interventions ◽  
List Type ◽  
Dependent Manner ◽  
Hpg Axis ◽  
Knock Out ◽  
Soma Size

SummaryRNF216/TRIAD3 is an E3 ligase that ubiquitinates substrates in the nervous system. Recessive mutations in RNF216/TRIAD3 cause Gordon Holmes syndrome (GHS), where hypogonadotropic hypogonadism is a core phenotype. However, the functions of RNF216/TRIAD3 within the neuroendocrine system are not well-understood. Here, we used the CRISPR-Cas9 system to knock out Rnf216/Triad3 in GT1-7 cells, a GnRH immortalized cell line derived from mouse hypothalamus. Rnf216/Triad3 knockout cells had decreased steady state Gnrh and reduced calcium transient frequency. To address functions of RNF216/TRIAD3 in vivo, we generated a Rnf216/Triad3 constitutive knockout (KO) mouse. KO mice of both sexes showed reductions in GnRH and soma size. Furthermore, KO mice exhibited sex-specific phenotypes with males showing gonadal impairment and derangements in gonadotropin release compared to KO females, which only had irregular estrous cyclicity. Our work shows that dysfunction of RNF216/TRIAD3 affects the HPG axis in a sex-dependent manner, implicating sex-specific therapeutic interventions for GHS.HighlightsRnf216/Triad3 controls Gnrh and intrinsic hypothalamic cell activityRnf216/Triad3 knockout male mice have greater reproductive impairments than femalesRnf216/Triad3 controls the HPG axis at multiple levels

scholarly journals In-Vivo Toxicity Studies and In-Vitro Inactivation of SARS-CoV-2 by Povidone-iodine In-situ Gel Forming Formulations

2020 ◽  
Author(s):  
Bo Liang ◽  
Xudong Yuan ◽  
Gang Wei ◽  
Wei Wang ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Povidone Iodine ◽  
Early Stage ◽  
Etiologic Agent ◽  
Dependent Manner ◽  
Forming Technology ◽  
Long Acting ◽  
Dose Dependent

AbstractTo curb the spread of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, we characterize the virucidal activity of long-acting Povidone Iodine (PVP-I) compositions developed using an in-situ gel forming technology. The PVP-I gel forming nasal spray (IVIEW-1503) and PVP-I gel forming ophthalmic eye drop (IVIEW-1201) rapidly inactivated SARS-CoV-2, inhibiting the viral infection of VERO76 cells. No toxicity was observed for the PVP-I formulations. Significant inactivation was noted with preincubation of the virus with these PVP-I formulations at the lowest concentrations tested. It has been demonstrated that both PVP-I formulations can inactivate SARS-CoV-2 virus efficiently in both a dose-dependent and a time-dependent manner. These results suggest IVIEW-1503 and IVIEW-1201 could be potential agents to reduce or prevent the transmission of the virus through the nasal cavity and the eye, respectively. Further studies are needed to clinically evaluate these formulations in early-stage COVID-19 patients.

scholarly journals Fraxinellone Has Anticancer Activity by Inducing Osteosarcoma Cell Apoptosis via Promoting Excessive Autophagy Flux

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin He ◽  
Wenkan Zhang ◽  
Jiaming He
Keyword(s):  
Cell Apoptosis ◽  
Early Stage ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Orthotopic Model ◽  
Autophagy Flux ◽  
Neuroprotective Effects ◽  
Anti Cancer ◽  
And Migration

Osteosarcoma is a malignant bone tumor that is easy to metastasize in the early stage and has a very poor prognosis. Fraxinellone (FRA) is one of the main components isolated from the D. dasycarpus plant. Its anti-inflammatory and neuroprotective effects have been confirmed, but the research on the anti-cancer effect of FRA and its potential mechanism is relatively scarce. In this study, we found that FRA inhibited the proliferation and migration of osteosarcoma cells HOS and MG63 in a dose-dependent manner. Immunofluorescence, fluorescence staining and western blotting analysis showed that FRA could simultaneously induce osteosarcoma cell apoptosis and increase autophagy flux. Subsequent turnaround experiments suggested that the pro-apoptotic effect of FRA was achieved through excessive autophagy flux. The results of the xenograft orthotopic model further supported the anti-cancer effects of FRA, indicating that FRA treatment inhibited the growth of osteosarcoma, and the pro-apoptotic and autophagy effects of FRA were also proved in vivo. These studies provide new ideas for the future treatment of osteosarcoma and offer theoretical support for the anti-cancer mechanism of FRA.

scholarly journals Immunological detection of fructated proteins in vitro and in vivo

1998 ◽  
Vol 336 (1) ◽  
pp. 101-107 ◽  
Author(s):  
Nobuko MIYAZAWA ◽  
Yoshimi KAWASAKI ◽  
Junichi FUJII ◽  
Myint THEINGI ◽  
Ayumu HOSHI ◽  
...  
Keyword(s):  
Reducing Sugars ◽  
Early Stage ◽  
Polyol Pathway ◽  
Diabetic Rat ◽  
Dependent Manner ◽  
Glycation End Products ◽  
Lysine Residues ◽  
Activity Of Enzymes

An antibody has been raised against fructated lysine in proteins by immunizing fructated lysine-conjugated ovalbumin in rabbits. The affinity-purified antibody specifically recognized proteins incubated with fructose but not with other reducing sugars such as glucose, galactose or ribose, as judged by immunoblotting and ELISA techniques. Competitive binding to this antibody was observed specifically by fructated lysine but not by glucated lysine, glucose, fructose or lysine. The antibody binds specifically to fructated lysine residues in the protein but not to borohydride-reduced material or advanced glycation end products, indicating that the antibody recognizes only the reducing, carbonyl-containing forms produced in the early stage of the fructation reaction. When BSA was incubated with various concentrations of fructose, the reactivity of the antibody increased in a dose- and time-dependent manner. When soluble proteins prepared from either normal or streptozotocin-induced diabetic rat eyes were analysed by ELISA with this antibody, an increase in the reactive components was observed as a function of aging as well as under diabetic conditions. Western blotting analysis showed that lens crystallin reacted highly with this antibody. Because fructose is biosynthesized largely through the polyol pathway, which is enhanced under diabetic conditions, and lens is known to have a high activity of enzymes in this pathway, this antibody is capable of recognizing fructated proteins in vivo. Thus it is a potentially useful tool for investigating two major issues that seem to be involved in diabetic complications, namely the glycation reaction and the polyol pathway.

CircMETTL3, Upregulated in a m6A-dependent Manner, Promotes Breast Cancer Progression through circMETTL3/miR-31-5p/CDK1 axis

2020 ◽  
Author(s):  
Zhi Li ◽  
HaiYan Yang ◽  
XinYuan Dai ◽  
Xu Zhang ◽  
YuZhou Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Biological Function ◽  
Breast Cancer Progression ◽  
Host Gene ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Repressive Effect ◽  
Rna Immunoprecipitation

Abstract Background: Growing evidence indicates N6-methyladenosine (m6A) has biological function in oncogenesis. METTL3, the catalytic component, is the most important part of methyltransferase complex and plays a crucial role in cancers. However, the biological function of circRNAs derived from METTL3 and the underlying molecular mechanism remains unclear.Methods: Quantitative real-time PCR was used to determine the circMETTL3 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circMETTL3 on tumor growth and metastasis in breast cancer. Mechanistically, fluorescent in situ hybridization, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between circMETTL3 and miR-31-5p in breast cancer. Furthermore, we explored regulatory effects of m6A modification on circMETTL3 expression with m6A RNA immunoprecipitation.Results: We found that circMETTL3 was significantly upregulated in breast cancer. The results indicated that circMETTL3 could promote breast cancer cell proliferation, migration and invasion as well as tumorigenesis in vivo. Mechanistic analysis showed that circMETTL3 might act as a ceRNA (competing endogenous RNA) of miR-31-5p to relieve the repressive effect of miR-31-5p on its target cyclin-dependent kinases (CDK1). Moreover, m6A modification of circMETTL3 might affect its expression.Conclusion: Our findings suggest that circMETTL3 promotes breast cancer progression through circMETTL3/miR-31-5p/CDK1 axis. Moreover, METTL3, the host gene of circMETTL3, may regulates circMETTL3 expression in a m6A-dependent manner, while circMETTL3 has no effect on METTL3 expression, providing a new relationship between the circRNA and the corresponding host gene. Thus, it may serve as a new diagnostic marker or therapeutic target for breast cancer patients.

scholarly journals Fungal cryptochrome with DNA repair activity reveals an early stage in cryptochrome evolution

2015 ◽  
Vol 112 (49) ◽  
pp. 15130-15135 ◽  
Author(s):  
Victor G. Tagua ◽  
Marcell Pausch ◽  
Maike Eckel ◽  
Gabriel Gutiérrez ◽  
Alejandro Miralles-Durán ◽  
...  
Keyword(s):  
Dna Repair ◽  
Blue Light ◽  
Early Stage ◽  
Single Gene ◽  
Dna Lesions ◽  
Pyrimidine Dimer ◽  
Dependent Manner ◽  
Phycomyces Blakesleeanus

DASH (Drosophila, Arabidopsis, Synechocystis, Human)-type cryptochromes (cry-DASH) belong to a family of flavoproteins acting as repair enzymes for UV-B–induced DNA lesions (photolyases) or as UV-A/blue light photoreceptors (cryptochromes). They are present in plants, bacteria, various vertebrates, and fungi and were originally considered as sensory photoreceptors because of their incapability to repair cyclobutane pyrimidine dimer (CPD) lesions in duplex DNA. However, cry-DASH can repair CPDs in single-stranded DNA, but their role in DNA repair in vivo remains to be clarified. The genome of the fungus Phycomyces blakesleeanus contains a single gene for a protein of the cryptochrome/photolyase family (CPF) encoding a cry-DASH, cryA, despite its ability to photoreactivate. Here, we show that cryA expression is induced by blue light in a Mad complex-dependent manner. Moreover, we demonstrate that CryA is capable of binding flavin (FAD) and methenyltetrahydrofolate (MTHF), fully complements the Escherichia coli photolyase mutant and repairs in vitro CPD lesions in single-stranded and double-stranded DNA with the same efficiency. These results support a role for Phycomyces cry-DASH as a photolyase and suggest a similar role for cry-DASH in mucoromycotina fungi.

scholarly journals Bisphenol A and Its Analogues Deteriorate the Hormones Physiological Function of the Male Reproductive System: A Mini-Review

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1744
Author(s):  
Asma’ ‘Afifah Shamhari ◽  
Zariyantey Abd Hamid ◽  
Siti Balkis Budin ◽  
Nurul Jehan Shamsudin ◽  
Izatus Shima Taib
Keyword(s):  
Adverse Effects ◽  
Reproductive System ◽  
Physiological Function ◽  
Human Biomonitoring ◽  
Reproductive Hormones ◽  
Male Reproductive System ◽  
Hpg Axis ◽  
Physiological Functions

BPA is identified as an endocrine-disrupting chemical that deteriorates the physiological function of the hormones of the male reproductive system. Bisphenol F (BPF), bisphenol S (BPS), and bisphenol AF (BPAF) are actively explored as substitutes for BPA and are known as BPA analogues in most manufacturing industries. These analogues may demonstrate the same adverse effects as BPA on the male reproductive system; however, toxicological data explaining the male reproductive hormones’ physiological functions are still limited. Hence, this mini-review discusses the effects of BPA and its analogues on the physiological functions of hormones in the male reproductive system, focusing on the hypothalamus-pituitary-gonad (HPG) axis, steroidogenesis, and spermatogenesis outcomes. The BPA analogues mainly show a similar negative effect on the hormones’ physiological functions, proven by alterations in the HPG axis and steroidogenesis via activation of the aromatase activity and reduction of spermatogenesis outcomes when compared to BPA in in vitro and in vivo studies. Human biomonitoring studies also provide significant adverse effects on the physiological functions of hormones in the male reproductive system. In conclusion, BPA and its analogues deteriorate the physiological functions of hormones in the male reproductive system as per in vitro , in vivo , and human biomonitoring studies.

Effects of CD4+CD25+Foxp3+regulatory T cells on earlyPlasmodium yoelii17XL infection in BALB/c mice

Parasitology ◽  
2009 ◽  
Vol 136 (10) ◽  
pp. 1107-1120 ◽  
Author(s):  
GUANG CHEN ◽  
JUN LIU ◽  
QING-HUI WANG ◽  
YI WU ◽  
HUI FENG ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Early Stage ◽  
Plasmodium Yoelii ◽  
Dependent Manner ◽  
T Cell Apoptosis

SUMMARYThe outcome ofPlasmodium yoelii17XL-infected BALB/c and DBA/2 mice, ranging from death to spontaneous cure, respectively, depends largely on the establishment of effective pro-inflammatory type 1 responses during the early stages of infection and associates with CD4+CD25+Foxp3+regulatory T cells (Tregs). Here, effects of Tregs were analysed on earlyP. yoelii17XL infection in BALB/c and DBA/2 mice.In vivodepletion of Tregs significantly reversed the inhibited establishment of effective pro-inflammatory type 1 responses in BALB/c mice, indicating that this cell population contributed to the suppression of T-cell function in malaria. Moreover, the proportion and absolute numbers of IL-10-secreting Tregs in BALB/c mice were significantly higher than that found in DBA/2 mice by intracytoplasmic staining, and IL-10 production was correlated with the Tregs population. In addition,in vivoTregs depletion decreased the production of IL-10 and the apoptosis of CD4+T cells. Consistently, IL-10R blockade also had the same effect as that of Tregs depletion inP. yoelii17XL-infected BALB/c mice. Our data demonstrate that Tregs perhaps have an important role in regulating pro-inflammatory type 1 responses in an IL-10-dependent manner and induce CD4+T cell apoptosis during the early stage ofP. yoelii17XL infection.

scholarly journals Neurotransmitters Affect Larval Development by Regulating the Activity of Prothoracicotropic Hormone-Releasing Neurons in Drosophila melanogaster

2021 ◽  
Vol 15 ◽  
Author(s):  
Shun Hao ◽  
Julia Yvonne Gestrich ◽  
Xin Zhang ◽  
Mengbo Xu ◽  
Xinwei Wang ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Larval Development ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Larval Metamorphosis ◽  
Prothoracicotropic Hormone ◽  
Bidirectional Regulation ◽  
And Control ◽  
Ach Receptors

Ecdysone, an essential insect steroid hormone, promotes larval metamorphosis by coordinating growth and maturation. In Drosophila melanogaster, prothoracicotropic hormone (PTTH)-releasing neurons are considered to be the primary promoting factor in ecdysone biosynthesis. Recently, studies have reported that the regulatory mechanisms of PTTH release in Drosophila larvae are controlled by different neuropeptides, including allatostatin A and corazonin. However, it remains unclear whether neurotransmitters provide input to PTTH neurons and control the metamorphosis in Drosophila larvae. Here, we report that the neurotransmitters acetylcholine (ACh) affect larval development by modulating the activity of PTTH neurons. By downregulating the expression of different subunits of nicotinic ACh receptors in PTTH neurons, pupal volume was significantly increased, whereas pupariation timing was relatively unchanged. We also identified that PTTH neurons were excited by ACh application ex vivo in a dose-dependent manner via ionotropic nicotinic ACh receptors. Moreover, in our Ca2+ imaging experiments, relatively low doses of OA caused increased Ca2+ levels in PTTH neurons, whereas higher doses led to decreased Ca2+ levels. We also demonstrated that a low dose of OA was conveyed through OA β-type receptors. Additionally, our electrophysiological experiments revealed that PTTH neurons produced spontaneous activity in vivo, which provides the possibility of the bidirectional regulation, coming from neurons upstream of PTTH cells in Drosophila larvae. In summary, our findings indicate that several different neurotransmitters are involved in the regulation of larval metamorphosis by altering the activity of PTTH neurons in Drosophila.

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