scholarly journals Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 190 ◽  
Author(s):  
Xiaojiaoyang Li ◽  
Runping Liu ◽  
Yanyan Wang ◽  
Weiwei Zhu ◽  
Derrick Zhao ◽  
...  
Keyword(s):  
Kupffer Cells ◽  
Noncoding Rna ◽  
Macrophage Activation ◽  
Critical Role ◽  
Vital Role ◽  
Primary Biliary Cholangitis ◽  
M1 Polarization ◽  
Hepatic Macrophages ◽  
Duct Ligation ◽  
Almost All

Activation of hepatic macrophages represents the critical driving force to promote cholestatic liver injury. Exosomes, as important small extracellular vesicles released by almost all types of cells, contribute to intercellular communication. We previously reported that cholangiocyte-derived exosomal long noncoding RNA (lncRNA) H19 plays a vital role in disrupting bile acid homeostasis in hepatocytes and promoting the activation of hepatic stellate cells (HSCs). Exosomal H19 derived from cholangiocytes was rapidly taken up by Kupffer cells. However, the mechanistic links between exosomal lncRNA H19 and macrophage-driven inflammation in cholestasis remain unclear. Here, we reported that the hepatic H19 level was closely correlated with macrophage activation and hepatic fibrosis in both Mdr2-/- and bile duct ligation (BDL) cholestatic mouse models, as well as in human primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) patients. Exosomal H19 significantly induced the expression and secretion of chemokine (C–C motif) ligand 2 (CCL-2) and interleukin 6 (IL-6) in Kupffer cells. H19-enriched exosomes enhanced the activation M1 polarization of Kupffer cells and promoted the recruitment and differentiation of bone marrow-derived macrophages, which were inhibited by a CCL-2 pharmacological inhibitor. In conclusion, Cholangiocyte-derived exosomal H19 played a critical role in macrophage activation, differentiation, and chemotaxis through CCL-2/CCR-2 signaling pathways, which represent a therapeutic target for cholestatic liver diseases.

scholarly journals Cholangiocyte-Derived Exosomal Long Noncoding RNA PICALM-AU1 Promotes Pulmonary Endothelial Cell EndMT in Hepatopulmonary Syndrome

2021 ◽  
Author(s):  
Congwen Yang ◽  
Yihui Yang ◽  
Yang Chen ◽  
Jian Huang ◽  
Caiyi Li ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Critical Role ◽  
Cell Communication ◽  
Hepatopulmonary Syndrome ◽  
Clinical Problem ◽  
Luciferase Reporter ◽  
Target Cells ◽  
Common Bile Duct Ligation ◽  
Mesenchymal Transition ◽  
Duct Ligation

Abstract Background: Hepatopulmonary syndrome (HPS) is an important clinical problem with limited understanding of disease pathologies. Exosome mediated cell-cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. A new lncRNA PICALM-AU1 was found and upregulated in the liver of subjects with HPS. However, the expression and biological functions of the lncRNA PICALM-AU1 are still unknown. Methods: HPS rat model was constructed by common bile duct ligation (CBDL). RNA macroarray was used to analyze the expression differential lncRNAs in HPS rat liver. PICALM-AU1 expression in the serum exosome was measured in 56 HPS patients and in 73 patients with liver cirrhosis but not HPS. qPCR, Fluorescence in situ hybridization were used to analyze PICALM-AU1 expression and location. Virus derived PICALM-AU1 upregulation and down regulation were applied in rats and PMVECs cells. The effects of PICALM-AU1 on PMVECs was determined via CCK8 assay and transwell assay. PICALM-AU1 and miR144-3p relationship was analysis by Dual-luciferase reporter assay.Results: In this study, we found lncRNA PICALM-AU1 expressed in the cholangiocyte of liver, secreted as exosome into the serum. PICALM-AU1 carrying serum exosomes induced endothelial-mesenchymal transition (EndMT) of PMVECs and promoted lung injury. Furthermore, overexpression of PICALM-AU1 significantly suppressed miR144-3p and subsequently induced ZEB1 expression.Conclusions: Taken together, our findings present a road map of targeting the newly identified cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the pathologic angiogenesis of HPS by promoting EndMT and represents a potential therapeutic target for HPS.

scholarly journals Musings about the Importance of Comparative Psychology: Reflections from Undergraduate Students

2020 ◽  
Vol 33 ◽  
Author(s):  
Heather M. Hill
Keyword(s):  
Undergraduate Students ◽  
Critical Role ◽  
Comparative Psychology ◽  
The United States ◽  
Vital Role ◽  
Hispanic Serving Institution ◽  
Psychology Today ◽  
Hispanic Serving ◽  
Psychology Course ◽  
Almost All

The sub-field of comparative psychology has ebbed and flowed since the establishment of the field of psychology. Today, comparative psychology is taught rarely as an elective, much less as a required course within psychology departments around the United States. Based on responses on a beginning of semester reflection assignment about the field of psychology, when first or second year undergraduate students are asked about their knowledge of psychology and the various fields within, most have never heard of comparative psychology. Those that have heard of comparative psychology from a high school course, the students rarely mention it freely. The purpose of this essay is to share the reflections of students who have completed an upper division elective comparative psychology course at a primarily undergraduate, Hispanic-serving institution. In this course, the students were asked to reflect on what they know about comparative psychology at the beginning of the course and to return to those early reflections at the end of the course. One major finding is that the majority of the students state that this course should be a required course or a capstone for psychology as it integrates all of their required coursework together into a common experience. This synthesis enabled the students to see the importance of comparative analysis and the role understanding animals plays in understanding humans. Comparative psychology should not simply be a historical facet of the field of psychology, but should continue to play a critical role in shaping the experiences of students of psychology. Whether it is simply to make students of psychology aware of the role animal research has in understanding almost all aspects of psychology (clinical, learning, health, development, personality, social, biopsychology, neuroscience, behavioral economics, cognition) or to highlight the need that investigating the same question in different subjects is valuable, comparative psychology has a vital role in our field today.

scholarly journals The Role of Vitamin K in Cholestatic Liver Disease

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2515
Author(s):  
Halima Sultana ◽  
Michio Komai ◽  
Hitoshi Shirakawa
Keyword(s):  
Liver Disease ◽  
Vitamin K ◽  
Animal Studies ◽  
Critical Role ◽  
Pregnane X Receptor ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Risk Of Death ◽  
Duct Ligation ◽  
Related Liver Disease

Vitamin K (VK) is a ligand of the pregnane X receptor (PXR), which plays a critical role in the detoxification of xenobiotics and metabolism of bile acids. VK1 may reduce the risk of death in patients with chronic liver failure. VK deficiency is associated with intrahepatic cholestasis, and is already being used as a drug for cholestasis-induced liver fibrosis in China. In Japan, to treat osteoporosis in patients with primary biliary cholangitis, VK2 formulations are prescribed, along with vitamin D3. Animal studies have revealed that after bile duct ligation-induced cholestasis, PXR knockout mice manifested more hepatic damage than wild-type mice. Ligand-mediated activation of PXR improves biochemical parameters. Rifampicin is a well-known human PXR ligand that has been used to treat intractable pruritus in severe cholestasis. In addition to its anti-cholestatic properties, PXR has anti-fibrotic and anti-inflammatory effects. However, because of the scarcity of animal studies, the mechanism of the effect of VK on cholestasis-related liver disease has not yet been revealed. Moreover, the application of VK in cholestasis-related diseases is controversial. Considering this background, the present review focuses on the effect of VK in cholestasis-related diseases, emphasizing its function as a modulator of PXR.

XIST: A Meaningful Long Noncoding RNA in NSCLC Process

2020 ◽  
Vol 26 ◽  
Author(s):  
Yujie Shen ◽  
Yexiang Lin ◽  
Kai Liu ◽  
Jinlan Chen ◽  
Juanjuan Zhong ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Critical Role ◽  
Biological Functions ◽  
Potential Therapeutic Target ◽  
Considerable Evidence ◽  
Lncrna Xist ◽  
Nsclc Patients ◽  
The Relationship

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.

Azim Azimzada’s attitude towards poetry of Mirza Alakbar Sabir

2021 ◽  
Vol 66 (05) ◽  
pp. 140-144
Author(s):  
Nəzrin Novruz qızı Məmmədova ◽  
Keyword(s):  
Key Words ◽  
World Literature ◽  
Strong Influence ◽  
Fine Art ◽  
Vital Role ◽  
Creative People ◽  
Graphic Art ◽  
Book Illustrations ◽  
Almost All ◽  
As If

The heritage that Mirza Alakbar Sabir left for us has always been a source of inspiration for creative people throughout ages. People who are engaged in fine art have always highly appreciated this work too. It requires too much responsibility to address Mirza Alakbar Sabir’s poetry, one of the most famous literary figures in world literature. As if the artists who addressed this patriotic writer’s poetry, feel the poet and created unique works with an inspiration that they got from him. It is undeniable that Azim Azimzada played a vital role in publicity of Mirza Alakbar Sabir’s poetry. Azim Azimzada’s all illustrations are engraved in people’s memory. Average spectators can perceive artist’s illustrations too. By looking through illustrations, it is possible to guess almost all poems that they are dedicated to. Educating people who are indifferent to education and waking them up from this ignorance was Azim Azimzada’s main goal. Artist’s illustrations differentiate with its harsh ironic spirit which is the main peculiarity of Sabir’s poetry. We can definitely see the strong influence of Sabir’s poetry in Azim Azimzada’s works. This is the reason why Azim Azimzada is usually called as Sabir of fine art. Literary approach of artists towards Sabir’s poetry has still been ongoing so far. Addressing Sabir’s poetry by most artists is the sign of love, respect and curiosity to Sabir’s works and life. Key words: Mirza Alakbar Sabir, book illustrations, Azim Azimzade, “Hophopname”, Azerbaijani graphic art, master of caricature

Revising the Assumption that Ḥadīṯ Studies Flourished in the 11th/17th-Century Ḥiǧāz: Ibrāhīm al-Kūrānī’s (d. 1101/1690) Contribution

Arabica ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 1-35
Author(s):  
Naser Dumairieh
Keyword(s):  
General Framework ◽  
18Th Century ◽  
Critical Role ◽  
17Th Century ◽  
Main Interest ◽  
Islamic World ◽  
The Core ◽  
Revival Movement ◽  
Almost All

Abstract The Ḥiǧāz in the 11th/17th century has long been considered the center of a “revival” movement in ḥadīṯ studies. This assumption has spread widely among scholars of the 11th-/17th- and 12th-/18th-century Islamic world based on the fact that the isnāds of many major ḥadīṯ scholars from almost all parts of the Islamic world from the 11th/17th century onward return to a group of scholars in the Ḥiǧāz. The scholarly group that is assumed to have played a critical role in the flourishing of ḥadīṯ studies in the 11th/17th-century Ḥiǧāz is called the al-Ḥaramayn circle or network. However, to date, there have been no studies that investigate what was actually happening in that century concerning ḥadīṯ studies. Examining the actual ḥadīṯ studies of one of the scholars at the core of al-Ḥaramayn circle, i.e. Ibrāhīm b. Ḥasan al-Kūrānī, will unpack the main interest of Ḥiǧāzī scholars in ḥadīṯ literature, reveal previously unstudied aspects of ḥadīṯ studies in the 11th/17th-century Ḥiǧāz, correct some unexamined assumptions, and situate the ḥadīṯ efforts of scholars of the 11th/17th-century Ḥiǧāz within a general framework of developments within ḥadīṯ studies.

scholarly journals E2F activity is regulated by cell cycle-dependent changes in subcellular localization.

1997 ◽  
Vol 17 (12) ◽  
pp. 7268-7282 ◽  
Author(s):  
R Verona ◽  
K Moberg ◽  
S Estes ◽  
M Starz ◽  
J P Vernon ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Nuclear Localization ◽  
Mammalian Cells ◽  
Critical Role ◽  
Biological Properties ◽  
Dependent Manner ◽  
Restriction Point ◽  
Cycle Dependent ◽  
Almost All

E2F directs the cell cycle-dependent expression of genes that induce or regulate the cell division process. In mammalian cells, this transcriptional activity arises from the combined properties of multiple E2F-DP heterodimers. In this study, we show that the transcriptional potential of individual E2F species is dependent upon their nuclear localization. This is a constitutive property of E2F-1, -2, and -3, whereas the nuclear localization of E2F-4 is dependent upon its association with other nuclear factors. We previously showed that E2F-4 accounts for the majority of endogenous E2F species. We now show that the subcellular localization of E2F-4 is regulated in a cell cycle-dependent manner that results in the differential compartmentalization of the various E2F complexes. Consequently, in cycling cells, the majority of the p107-E2F, p130-E2F, and free E2F complexes remain in the cytoplasm. In contrast, almost all of the nuclear E2F activity is generated by pRB-E2F. This complex is present at high levels during G1 but disappears once the cells have passed the restriction point. Surprisingly, dissociation of this complex causes little increase in the levels of nuclear free E2F activity. This observation suggests that the repressive properties of the pRB-E2F complex play a critical role in establishing the temporal regulation of E2F-responsive genes. How the differential subcellular localization of pRB, p107, and p130 contributes to their different biological properties is also discussed.

scholarly journals Drosophila Gut—A Nexus Between Dietary Restriction and Lifespan

2018 ◽  
Vol 19 (12) ◽  
pp. 3810 ◽  
Author(s):  
Ting Lian ◽  
Qi Wu ◽  
Brian Hodge ◽  
Kenneth Wilson ◽  
Guixiang Yu ◽  
...  
Keyword(s):  
Digestive Tract ◽  
Dietary Restriction ◽  
Healthy Aging ◽  
Fat Body ◽  
Critical Role ◽  
Vital Role ◽  
Intestinal Epithelial ◽  
Beneficial Effects ◽  
Accumulation Of Damage

Aging is often defined as the accumulation of damage at the molecular and cellular levels which, over time, results in marked physiological impairments throughout the organism. Dietary restriction (DR) has been recognized as one of the strongest lifespan extending therapies observed in a wide array of organisms. Recent studies aimed at elucidating how DR promotes healthy aging have demonstrated a vital role of the digestive tract in mediating the beneficial effects of DR. Here, we review how dietary restriction influences gut metabolic homeostasis and immune function. Our discussion is focused on studies of the Drosophila digestive tract, where we describe in detail the potential mechanisms in which DR enhances maintenance of the intestinal epithelial barrier, up-regulates lipid metabolic processes, and improves the ability of the gut to deal with damage or stress. We also examine evidence of a tissue-tissue crosstalk between gut and neighboring organs including brain and fat body. Taken together, we argue that the Drosophila gut plays a critical role in DR-mediated lifespan extension.

scholarly journals Cul4-Ddb1 ubiquitin ligases facilitate DNA replication-coupled sister chromatid cohesion through regulation of cohesin acetyltransferase Esco2

2018 ◽  
Author(s):  
Haitao Sun ◽  
Jiaxin Zhang ◽  
Jingjing Zhang ◽  
Zhen Li ◽  
Qinhong Cao ◽  
...  
Keyword(s):  
Dna Replication ◽  
Ubiquitin Ligase ◽  
Sister Chromatid ◽  
Critical Role ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligases ◽  
Sister Chromatid Cohesion ◽  
Vital Role ◽  
Chromatid Cohesion ◽  
Evolutionarily Conserved

AbstractCohesin acetyltransferases Esco1 and Esco2 play a vital role in establishing sister chromatid cohesion. How Esco1 and Esco2 are controlled to achieve this in a DNA replication-coupled manner remains unclear in higher eukaryotes. Here we show that Cul4-RING ligases (CRL4s) play a critical role in sister chromatid cohesion in human cells. Depletion of Cul4A, Cul4B or Ddb1 subunits substantially reduces normal cohesion efficiency. We also show that Mms22L, a vertebrate ortholog of yeast Mms22, is one of Ddb1 and Cul4-associated factors (DCAFs) involved in cohesion. Several lines of evidence suggest a selective interaction of CRL4s with Esco2, but not Esco1. Depletion of either CRL4s or Esco2 causes a defect in Smc3 acetylation which can be rescued by HDAC8 inhibition. More importantly, both CRL4s and PCNA act as mediators for efficiently stabilizing Esco2 on chromatin and catalyzing Smc3 acetylation. Taken together, we propose an evolutionarily conserved mechanism in which CRL4s and PCNA regulate Esco2-dependent establishment of sister chromatid cohesion.Author summaryWe identified human Mms22L as a substrate specific adaptor of Cul4-Ddb1 E3 ubiquitin ligase. Downregulation of Cul4A, Cul4B or Ddb1 subunit causes reduction of acetylated Smc3, via interaction with Esco2 acetyltransferase, and then impairs sister chromatid cohesion in 293T cells. We found functional complementation between Cul4-Ddb1-Mms22L E3 ligase and Esco2 in Smc3 acetylation and sister chromatid cohesion. Interestingly, both Cul4-Ddb1 E3 ubiquitin ligase and PCNA contribute to Esco2 mediated Smc3 acetylation. To summarise, we demonstrated an evolutionarily conserved mechanism in which Cul4-Ddb1 E3 ubiquitin ligases and PCNA regulate Esco2-dependent establishment of sister chromatid cohesion.

scholarly journals The potential function of forehead gland secretions in conflict resolution of the male Great Himalayan leaf-nosed bats

2020 ◽  
Author(s):  
Chunmian Zhang ◽  
Congnan Sun ◽  
Jeffrey R. Lucas ◽  
Hao Gu ◽  
Jiang Feng ◽  
...  
Keyword(s):  
Conflict Resolution ◽  
Potential Function ◽  
Chemical Communication ◽  
Vital Role ◽  
Physical Contact ◽  
Gas Chromatography Mass Spectrometry ◽  
Behavioral Studies ◽  
Individual Discrimination ◽  
Behavioral Evidence ◽  
Almost All

AbstractChemical communication is an important aspect of social behavior in almost all animals. Here, we used gas chromatography-mass spectrometry (GC-MS) to detect the chemical composition, and behavioral tests to evaluate the potential function of forehead gland secretions between adult male Great Himalayan leaf-nosed bats, Hipposideros armiger. Our results showed that the concentrations of compounds and their categories differed significantly among individuals, and behavioral studies indicated that males are capable of utilizing the secretions for individual discrimination. Moreover, paired males that were incapable of gland protrusion showed more physical contact and longer contest duration compared to pairs in which both males could protrude the gland. In trials where only one male could protrude the gland, males with gland protrusion were more likely to win in contests. These findings provide the first behavioral evidence that chemical communication plays a vital role in conflict resolution in non-human mammals.

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