scholarly journals Busulfan administration produces toxic effects on epididymal morphology and inhibits the expression of ZO-1 and vimentin in the mouse epididymis

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Fang Fang ◽  
Ke Ni ◽  
Yiting Cai ◽  
Qian Zhao ◽  
Jin Shang ◽  
...  
Keyword(s):  
Single Injection ◽  
Morphological Structure ◽  
Estrogen Receptor Α ◽  
Structure And Function ◽  
Testicular Damage ◽  
Protein Levels ◽  
Zonula Occludens ◽  
Zonula Occludens 1 ◽  
And Function ◽  
Mouse Epididymis

Busulfan is an alkane sulphonate currently used as an anticancer drug and to prepare azoospermic animal models, because it selectively destroys differentiated spermatogonia in the testes. However, few studies have focussed on the exact effects of busulfan treatment on the epididymis currently. The present study assessed the effect of busulfan on epididymal morphology and the blood–epididymis barrier in mice. We treated mice with a single injection of busulfan and detected the effect at different time points. We showed that busulfan was toxic to the morphological structure and function of the epididymis. Furthermore, busulfan treatment down-regulated the epididymal expression of vimentin and zonula occludens-1 (ZO-1) at the mRNA and protein levels. In addition, there was an increase in total androgen receptor (AR) levels, whereas the estrogen receptor-α (ER-α) levels were reduced, both in the caput and cauda regions after busulfan treatment, which may be secondary to the testicular damage. In conclusion, our study describes the effects of busulfan administration on the mouse epididymis and also provides a potential understanding of male infertility arising from chemotherapy-related defects in the epididymis.

scholarly journals Decreased ZO1 expression causes loss of time-dependent tight junction function in the liver of ob/ob mice

2021 ◽  
Author(s):  
Yuya Tsurudome ◽  
Nao Morita ◽  
Michiko Horiguchi ◽  
Kentaro Ushijima
Keyword(s):  
Tight Junction ◽  
Dark Period ◽  
Vital Role ◽  
Time Dependent ◽  
Signal Transduction System ◽  
Binding Ability ◽  
Protein Levels ◽  
Multiple Organs ◽  
Zonula Occludens ◽  
Zonula Occludens 1

Abstract Diabetes patients are at a high risk of developing complications related to angiopathy and disruption of the signal transduction system. The liver is one of the multiple organs damaged during diabetes. Few studies have evaluated the morphological effects of adhesion factors in diabetic liver. The influence of diurnal variation has been observed in the expression and functioning of adhesion molecules to maintain tissue homeostasis associated with nutrient uptake. The present study demonstrated that the rhythm-influenced functioning of tight junction was impaired in the liver of ob/ob mice. The tight junctions of hepatocytes were loosened during the dark period in normal mice compared to those in ob/ob mice, where the hepatocyte gaps remained open throughout the day. The time-dependent expression of zonula occludens 1 (ZO1) in the liver plays a vital role in the functioning of the tight junction. The time-dependent expression of ZO1 was nullified and its expression was attenuated in the liver of ob/ob mice. ZO1 expression was inhibited at the mRNA and protein levels. The expression rhythm of ZO1 was found to be regulated by heat shock factor (HSF)1/2, the expression of which was reduced in the liver of ob/ob mice. The DNA-binding ability of HSF1/2 was decreased in the liver of ob/ob mice compared to that in normal mice. These findings suggest the involvement of impaired expression and functioning of adhesion factors in diabetic liver complications.

scholarly journals Foxl2, a Forkhead Transcription Factor, Modulates Nonclassical Activity of the Estrogen Receptor-α

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5085-5093 ◽  
Author(s):  
So-Youn Kim ◽  
Jeffrey Weiss ◽  
Minghan Tong ◽  
Monica M. Laronda ◽  
Eun-Jig Lee ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Transcription Factor ◽  
Direct Action ◽  
Ovarian Follicle ◽  
Estrogen Receptor Α ◽  
Ovary Development ◽  
Activator Protein 1 ◽  
Forkhead Transcription Factor ◽  
Protein Levels ◽  
And Function

Foxl2 is a forkhead transcription factor required for ovary development and ovarian follicle maturation. In this report, we identified and characterized a functional relationship between Foxl2 expression and estrogen receptor (ER)-α signaling. We show that Foxl2 has no effect on classical ERα-mediated transcription, which occurs through canonical estrogen response elements. However, Foxl2 suppresses ERα signaling through nonclassical tethered transcriptional pathways. Specifically, the selective ER modulator tamoxifen stimulates activator protein-1 (AP1)-dependent transcription via the ERα, and this enhancement is blocked by Foxl2. Two lines of evidence suggest that Foxl2 suppression is mediated by physical interactions with ERα rather than direct action at AP1 binding sites. First, ERα is coimmunoprecipitated with Foxl2. Second, activation of a upstream activating sequence (UAS) reporter by Gal4-cJun in the presence of ERα and tamoxifen was blocked by Foxl2, demonstrating suppression in the absence of an AP1 site. Cyclooxygenase-2 (COX2), which is required for ovulation, was identified through expression profiling as a candidate physiological target for nonclassical ERα signaling and thus modulation by ERα/Foxl2 interactions. This possibility was confirmed by two sets of experiments. COX2 protein levels were induced by ERα in the presence of tamoxifen, and protein expression was suppressed by Foxl2. In addition, ERα stimulation of the COX2 promoter was repressed by Foxl2. We conclude that ERα and Foxl2 interact and that Foxl2 selectively suppresses ERα-mediated transcription of AP1-regulated genes. These data provide a potential point of convergence for ERα and Foxl2 to regulate ovarian development and function.

scholarly journals Вплив «Хоріоцену» на деякі біохімічні показники крові у підсисних свиноматок

2016 ◽  
pp. 102-105
Author(s):  
П. П. Шатохін ◽  
К. В. Супруненко ◽  
Л. П. Каришева
Keyword(s):  
Research Group ◽  
Environmentally Friendly ◽  
Inorganic Phosphorus ◽  
Structure And Function ◽  
Control Group ◽  
Metabolic Processes ◽  
Protein Levels ◽  
Multiple Input ◽  
And Function

У роботі представлені результати наукових досліджень щодо розробки та впровадження у ветеринарну практику екологічно чистих препаратів, а саме плацентарних, здатних нормалізувати метаболічні процеси у тканинах, та відновлювати структуру та функції органів і систем організму. Встановлено, що двократне введення хоріоцену збільшує вміст білка в крові на 1,5 % у порівнянні з показником першої доби після опоросу та на 5,3 % – показника тварин контрольної групи на 28-му добу. Вміст глюкози після введення препарату збільшився у всіх групах р<0,001, але у дослідних групах цей показник був вищим, ніж у контрольній на 8,7, 7,0 та 6,1 %. На фоні гіперфосфатемії вміст неорганічного фосфору в крові свиноматок 3-ї дослідної групи на 28-му добу був на 17 % нижчим, ніж у свиноматок групи контролю. The paper presents the results of research on the development and implementation of environmentally friendly practices of veterinary preparations, namely placental able to normalize metabolic processes in tissues and restore the structure and function of organs and body systems. We established that the yard at multiple input of «Horiotsen» increased protein levels on 1,5 % compared to the index of the first days after farrowing and 5,3 % – rate of animals in the control group at 28th day. Glucose increase after the injection in all groups – p<0,001, but in the experimental groups the figure was higher than in the control one by 8,7, 7,0 and 6,1 %. Against the background of hyperphosphatemia content of inorganic phosphorus in the blood sows of 3rd research group at the 28th day was 17 Im% lower than in the control group of sows.

scholarly journals High glucose reduces expression of podocin in cultured human podocytes by stimulating TRPC6

2019 ◽  
Vol 317 (6) ◽  
pp. F1605-F1611 ◽  
Author(s):  
Xiao-Yu Lu ◽  
Bing-Chen Liu ◽  
Yu-Ze Cao ◽  
Chang Song ◽  
Hua Su ◽  
...  
Keyword(s):  
High Glucose ◽  
Transient Receptor Potential ◽  
Morphological Changes ◽  
Receptor Potential ◽  
Diabetic Rat ◽  
Protein Levels ◽  
Zonula Occludens ◽  
Junction Protein ◽  
Zonula Occludens 1 ◽  
Transient Receptor

The transient receptor potential canonical 6 (TRPC6) channel and podocin are colocalized in the glomerular slit diaphragm as an important complex to maintain podocyte function. Gain of TRPC6 function and loss of podocin function induce podocyte injury. We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown. Western blot analysis and confocal microscopy were used to examine both expression levels of TRPC6, podocin, and nephrin and morphological changes of podocytes in response to high glucose. High glucose increased the expression of TRPC6 but reduced the expression of podocin and nephrin, in both cultured human podocytes and type 1 diabetic rat kidneys. The decreased podocin was diminished in TRPC6 knockdown podocytes. High glucose elevated intracellular Ca2+ in control podocytes but not in TRPC6 knockdown podocytes. High glucose also elevated the expression of a tight junction protein, zonula occludens-1, and induced the redistribution of zonula occludens-1 and loss of podocyte processes. These data together suggest that high glucose reduces protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.

scholarly journals Maternal vitamin B12 in mice positively regulates bone, but not muscle mass and strength in post-weaning and mature offspring

2021 ◽  
Author(s):  
Parminder Singh ◽  
Svetalana Telnova ◽  
Bin Zhou ◽  
Abdalla D Mohamed ◽  
Vanessa De Mello ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Muscle Mass ◽  
Genetic Model ◽  
Single Injection ◽  
Structure And Function ◽  
Wild Type ◽  
And Function ◽  
Mouse Genetic Model ◽  
Mouse Genetic

Vitamin B12 deficiency has been shown to affect bone mass in rodents and negatively impact bone formation in humans. In this study using mouse models we define the effect of B12 supplementation in the wild-type mother and B12 deficiency in a mouse genetic model (Gif-/- mice) during gestation on the bone and muscle architecture, and mechanical properties in the offspring. Analysis of bones from 4 weeks-old offspring of the wild-type mother following vehicle or B12 supplementation during gestation (From embryonic day 0.5-20.5) showed an increase in bone mass caused by an isolated increase in bone formation in the B12 supplemented group compared to vehicle controls. Analysis of effect of B12 deficiency in the mother in a mouse genetic model (Gif-/- mice) on long bone architecture of the offspring showed a compromised cortical and trabecular bone mass, which was completely prevented by a single injection of B12 in the B12-deficient Gif-/- mothers.Biomechanical analysis of long bones of the offspring born from B12 supplemented wild-type mothers showed an increase in bone strength, and conversely offspring born from B12-deficient Gif-/- mothers revealed a compromised bone strength, which could be rescued by a single injection of B12 in the B12-deficient Gif-/- mother. Muscle structure and function analysis however revealed no significant effect on muscle mass, structure and grip strength of B12 deficiency or supplementation in Gif-/- mice compared to littermate controls. Together, these results demonstrate the beneficial effect of maternally-derived B12 in the regulation of bone structure and function in the offspring.

P5998The Phosphodiesterase 4D interacting protein averts volume overload - but not pressure overload-induced pathological myocardial remodeling

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B A Mohamed ◽  
M Elkenani ◽  
J Jakubiczka-Smorag ◽  
M Bader ◽  
G Hasenfuss ◽  
...  
Keyword(s):  
Pressure Overload ◽  
Mortality Rates ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Myocardial Remodeling ◽  
Interacting Protein ◽  
Protein Levels ◽  
Cardiac Structure And Function ◽  
And Function ◽  
Phosphodiesterase 4D

Abstract Background Although volume- and pressure-overload (VO and PO, respectively) are hemodynamic stress, each results in distinct phenotypes. The Phosphodiesterase 4D interacting protein (PDE4DIP) is a protein involved in cardiac muscle contraction and suggested to play a role in cardiomyopathy. We previously identified Pde4dip transcript as being downregulated in VO but upregulated in PO. Objective We wanted to address whether Pde4dip deletion would alter the progression of pathological myocardial remodeling and heart failure (HF) following hemodynamic stress. Methods Pde4dip knockout (Pde4dip-KO) and age- and sex-matched wild-type (WT) mice were exposed to aortocaval shunt-triggered VO or transthoracic aortic constriction (TAC)-induced PO. Mortality rates were assessed and the cardiac structure and function were determined by serial echocardiography. Results The PDE4DIP protein levels decreased significantly in volume-overloaded hearts. However, pressure-overloaded hearts did not alter PDE4DIP protein levels, suggesting different posttranscriptional modifications that might affect the PDE4DIP protein expression in VO versus PO. The Pde4dip-KO Hearts were structurally and functionally normal in echocardiographic and morphometric analyses. However, Pde4dip deletion mildly attenuated the mortality rates in shunt-, but not in TAC-operated mice. A significant deterioration of left ventricle geometry and function was observed in volume-overloaded WT hearts at 12 weeks after shunt, but preserved cardiac function were noticed in shunt-operated Pde4dip-KO mice. On the other hand, TAC-operated WT and Pde4dip-KO mice exhibited a significant, but comparable deterioration of cardiac structure and function compared to sham mice. Conclusion Here we identified the PDE4DIP as an essential regulator of pathological myocardial remodeling following VO, but irrelevant to the development of cardiac dysfunction after TAC. Further investigations are warranted to dissect the possible mechanisms underlying the protective role of PDE4DIP deletion in the setting of VO. Acknowledgement/Funding This work was supported by DFG (SFB1002 project D04 to KT and D01 to GH; IRTG1816 to ME); BAM was funded by DSHF

scholarly journals Effects of emodin on intestinal mucosal barrier by the upregulation of miR-218a-5p expression in rats with acute necrotizing pancreatitis

2020 ◽  
Vol 34 ◽  
pp. 205873842094176
Author(s):  
Yang Tan ◽  
Wei Zhang ◽  
Hai-ying Wu ◽  
Jing Xia ◽  
Huang-bo Zhang ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Intestinal Tract ◽  
Caspase 3 ◽  
Intestinal Cell ◽  
Caspase 9 ◽  
Acute Severe Pancreatitis ◽  
Protein Levels ◽  
Zonula Occludens ◽  
Severe Pancreatitis ◽  
Zonula Occludens 1

Emodin is an effective component in rhubarb to cure intestinal dysfunction, but the specific mechanism remains unknown. This study aimed to evaluate the protective effects of emodin on intestinal dysfunction caused by acute severe pancreatitis and reveal the functional mechanism of emodin in the treatment of this condition. An acute severe pancreatitis model was prepared using taurocholate. In the treatment group, 50 mg/kg emodin was injected intravenously 2 h before the induction of acute severe pancreatitis at an interval of 8 h. After 24 h, the gene expression and protein levels of miR-218a-5p, RhoA, ROCK1, Akt, Notch1, Bax, Bcl-2, Fas, FasL, caspase-3, and caspase-9 were determined through reverse transcription polymerase chain reaction and Western blot analysis. The protein levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract were also determined through Western blot analysis. The effects of miR-218a-5p on the apoptosis of rat intestinal epithelial cell-18 were observed through flow cytometry. The effects of emodin on intestinal cell apoptosis induced by acute severe pancreatitis were observed via TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Pathological changes in the pancreas and intestine of rats in each group were observed through hematoxylin and eosin staining. After 24 h of acute severe pancreatitis induced by taurocholate, emodin reduced the expression of miR-218a-5p in the intestinal tract; increased the expression of Notch1 and Bcl-2; decreased the expression levels of RhoA, ROCK1, Akt, Bax, Fas, FasL, caspase-3, and caspase-9; inhibited the intestinal cell apoptosis caused by acute severe pancreatitis; increased the protein expression levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract; and alleviated intestinal dysfunction caused by acute severe pancreatitis. Emodin could regulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the intestine. It could also inhibit intestinal cell apoptosis induced by acute severe pancreatitis and improve the intestinal dysfunction caused by severe acute pancreatitis.

Paradigms in Morphology

2020 ◽  
Author(s):  
Petar Milin ◽  
James P. Blevins
Keyword(s):  
Morphological Structure ◽  
Structure And Function ◽  
Morphological Processing ◽  
Behavioral Correlates ◽  
Linguistic Structure ◽  
And Function ◽  
Traditional Approaches ◽  
Grammatical Tradition

Studies of the structure and function of paradigms are as old as the Western grammatical tradition. The central role accorded to paradigms in traditional approaches largely reflects the fact that paradigms exhibit systematic patterns of interdependence that facilitate processes of analogical generalization. The recent resurgence of interest in word-based models of morphological processing and morphological structure more generally has provoked a renewed interest in paradigmatic dimensions of linguistic structure. Current methods for operationalizing paradigmatic relations and determining the behavioral correlates of these relations extend paradigmatic models beyond their traditional boundaries. The integrated perspective that emerges from this work is one in which variation at the level of individual words is not meaningful in isolation, but rather guides the association of words to paradigmatic contexts that play a role in their interpretation.

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