scholarly journals Eukaryotic Initiation Factor 4A-3: A Review of Its Physiological Role and Involvement in Oncogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiazhou Ye ◽  
Xiaomin She ◽  
Ziyu Liu ◽  
Ziqin He ◽  
Xing Gao ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Physiological Role ◽  
Thioredoxin Reductase ◽  
Initiation Factor ◽  
Future Research ◽  
Exon Junction Complex ◽  
Phospholipid Hydroperoxide Glutathione Peroxidase ◽  
Potential Association ◽  
Transcriptional Gene Regulation ◽  
Underlying Mechanisms

EIF4A3, a member of the DEAD-box protein family, is a nuclear matrix protein and a core component of the exon junction complex (EJC). Under physiological conditions, EIF4A3 participates in post-transcriptional gene regulation by promoting EJC control of precursor mRNA splicing, thus influencing nonsense-mediated mRNA decay. In addition, EIF4A3 maintains the expression of significant selenoproteins, including phospholipid hydroperoxide glutathione peroxidase and thioredoxin reductase 1. Several recent studies have shown that EIF4A3 promotes tumor growth in multiple human cancers such as glioblastoma, hepatocellular carcinoma, pancreatic cancer, and ovarian cancer. Molecular biology studies also showed that EIF4A3 is recruited by long non-coding RNAs to regulate the expression of certain proteins in tumors. However, its tumor-related functions and underlying mechanisms are not well understood. Here, we review the physiological role of EIF4A3 and the potential association between EIF4A3 overexpression and tumorigenesis. We also evaluate the protein’s potential utility as a diagnosis biomarker, therapeutic target, and prognosis indicator, hoping to provide new ideas for future research.

scholarly journals Structural and Functional Remodeling of Mitochondria in Cardiac Diseases

2021 ◽  
Vol 22 (8) ◽  
pp. 4167
Author(s):  
Xiaonan Sun ◽  
Jalen Alford ◽  
Hongyu Qiu
Keyword(s):  
Regulatory Network ◽  
Molecular Basis ◽  
Therapeutic Potential ◽  
Research Direction ◽  
Future Research ◽  
Cardiac Diseases ◽  
Functional Remodeling ◽  
Underlying Mechanisms ◽  
Mitochondrial Remodeling ◽  
Normal Cellular Function

Mitochondria undergo structural and functional remodeling to meet the cell demand in response to the intracellular and extracellular stimulations, playing an essential role in maintaining normal cellular function. Merging evidence demonstrated that dysregulation of mitochondrial remodeling is a fundamental driving force of complex human diseases, highlighting its crucial pathophysiological roles and therapeutic potential. In this review, we outlined the progress of the molecular basis of mitochondrial structural and functional remodeling and their regulatory network. In particular, we summarized the latest evidence of the fundamental association of impaired mitochondrial remodeling in developing diverse cardiac diseases and the underlying mechanisms. We also explored the therapeutic potential related to mitochondrial remodeling and future research direction. This updated information would improve our knowledge of mitochondrial biology and cardiac diseases’ pathogenesis, which would inspire new potential strategies for treating these diseases by targeting mitochondria remodeling.

scholarly journals PHYSIOLOGY OF SUCCESSFUL AGING: IMPLICATIONS FOR HEALTH AND WELL-BEING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S434-S434
Author(s):  
Konstantinos Mantantzis ◽  
Denis Gerstorf ◽  
Thomas M Hess
Keyword(s):  
Older Adults ◽  
Successful Aging ◽  
Well Being ◽  
Empathic Accuracy ◽  
Future Research ◽  
Subjective Well Being ◽  
Use Of Data ◽  
Aging Study ◽  
Underlying Mechanisms ◽  
Relationship Factors

Abstract Research into peripheral physiology and its association with cognition, emotionality, and social/physical functioning has received considerable attention over the years. However, many of the underlying mechanisms are not well understood. In this symposium, we have compiled a set of four empirical projects that showcase current and future endeavors to address some of the long-standing questions about when, how, and why physiology shapes and is shaped by key psychosocial resources. Hawkley et al. make use of data from the NSHAP and HRS longitudinal studies to investigate whether social relationships such as number of friends predicts risk of diabetes among older adults. Wilson et al. use dyadic data from young and middle-aged couples to examine cardiometabolic similarity among spouses, and how such concordance is shaped by key relationship factors such as emotional closeness. Pauly et al. use data from two daily-life studies of older couples to investigate how physiological synchrony in cortisol is modulated by partner interactions, empathy, and empathic accuracy. Finally, Mantantzis et al. make use of multi-year longitudinal data from the Berlin Aging Study II to examine the role of glucose regulation capacity for trajectories of subjective well-being among older adults. Thomas Hess will discuss the importance of these papers, discuss strengths and weaknesses of the approaches chosen, and consider implications for future research.

scholarly journals Dual modulation of Ras-Mnk and PI3K-AKT-mTOR pathways: A Novel c-FLIP inhibitory mechanism of 3-AWA mediated translational attenuation through dephosphorylation of eIF4E

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Reyaz ur Rasool ◽  
Bilal Rah ◽  
Hina Amin ◽  
Debasis Nayak ◽  
Souneek Chakraborty ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Cell Cycle Progression ◽  
De Novo ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Apoptosis Resistance ◽  
Nih3t3 Cells ◽  
Eukaryotic Translation ◽  
Underlying Mechanisms

Abstract The eukaryotic translation initiation factor 4E (eIF4E) is considered as a key survival protein involved in cell cycle progression, transformation and apoptosis resistance. Herein, we demonstrate that medicinal plant derivative 3-AWA (from Withaferin A) suppressed the proliferation and metastasis of CaP cells through abrogation of eIF4E activation and expression via c-FLIP dependent mechanism. This translational attenuation prevents the de novo synthesis of major players of metastatic cascades viz. c-FLIP, c-Myc and cyclin D1. Moreover, the suppression of c-FLIP due to inhibition of translation initiation complex by 3-AWA enhanced FAS trafficking, BID and caspase 8 cleavage. Further ectopically restored c-Myc and GFP-HRas mediated activation of eIF4E was reduced by 3-AWA in transformed NIH3T3 cells. Detailed underlying mechanisms revealed that 3-AWA inhibited Ras-Mnk and PI3-AKT-mTOR, two major pathways through which eIF4E converges upon eIF4F hub. In addition to in vitro studies, we confirmed that 3-AWA efficiently suppressed tumor growth and metastasis in different mouse models. Given that 3-AWA inhibits c-FLIP through abrogation of translation initiation by co-targeting mTOR and Mnk-eIF4E, it (3-AWA) can be exploited as a lead pharmacophore for promising anti-cancer therapeutic development.

scholarly journals Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients

Reproduction ◽  
2014 ◽  
Vol 148 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Fulu Dong ◽  
Yuan Zhang ◽  
Fei Xia ◽  
Yi Yang ◽  
Sidong Xiong ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Normal Pregnancy ◽  
Recurrent Spontaneous Abortion ◽  
Future Research ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Transcriptional Gene Regulation

MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that involved in post-transcriptional gene regulation. Evidence indicates that miRNAs play essential roles in endometriosis, pre-eclampsia, infertility and other reproductive system diseases. However, whether miRNAs are involved in recurrent spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA expression profiles in six pairs of villus or decidua from RSA patients and normal pregnancy (NP) women using a human miRNA microarray. Some of the chip results were confirmed by RT-qPCR. In the villi of RSA patients, expression of hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly lower, comparing with those of NP control. As well, a total of five miRNAs (hsa-miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were upregulated in the decidua of RSA patients. The target genes of these differentially expressed miRNAs were predicted by miRWalk, and we speculate a network of miRNA regulating RSA by target genes function on adhesion, apoptosis and angiogenesis. Our study may help clarify the molecular mechanisms which are involved in the progression of RSA, and provide a reference for future research.

scholarly journals Intestinal Absorption Profile of Three Polygala Oligosaccharide Esters in Polygalae Radix and the Effects of Other Components in Polygalae Radix on Their Absorption

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
YinYing Ba ◽  
MengLin Wang ◽  
KunFeng Zhang ◽  
QiJun Chen ◽  
JiaJia Wang ◽  
...  
Keyword(s):  
Future Research ◽  
Active Components ◽  
Sodium Caprate ◽  
P Glycoprotein ◽  
Paracellular Absorption ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
Rat Gut ◽  
Human Nervous System

Oligosaccharide esters, which are among the main active components of Polygalae Radix (PR), demonstrate significant pharmacological activities in the human nervous system. In our previous research, some other constituents in PR were able to improve the bioavailability of oligosaccharide esters such as sibiricose A5 (SA5), sibiricose A6 (SA6), and 3,6′-disinapoyl sucrose (DISS), but the related components and their underlying mechanisms remain unknown. The present study aimed to investigate the intestinal absorptive profile of SA5, SA6, and DISS and the absorptive behavior influenced by the coadministration of polygalaxanthone III and total saponins of PR (TS) using an in vitro everted rat gut sac model, along with the possible mechanisms that may influence absorption. The results showed that TS could significantly enhance the absorption of SA5, SA6, and DISS monomers. Verapamil, a P-glycoprotein inhibitor, was able to elevate the absorption of SA5 and SA6, and an absorption experiment using Rho123 led us to conclude that TS influenced the absorption of SA5 and SA6 in a manner similar to that of a P-glycoprotein inhibitor. Sodium caprate, a paracellular absorption enhancer, was found to increase the absorption of SA5, SA6, and DISS. Results showed that the absorption mechanisms of SA5 and SA6 may combine active transport with paracellular passive penetration, while DISS’s absorption was dominated by paracellular passive penetration. However, the relationship between polygala saponins and the absorption of SA5, SA6, and DISS by paracellular passive penetration remain to be examined. This is the direction of our future research.

scholarly journals CSF1R-related leukoencephalopathy

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. 1092-1104 ◽  
Author(s):  
Takuya Konno ◽  
Koji Kasanuki ◽  
Takeshi Ikeuchi ◽  
Dennis W. Dickson ◽  
Zbigniew K. Wszolek
Keyword(s):  
White Matter ◽  
Cultured Cells ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Future Research ◽  
Primary Role ◽  
Extrapyramidal Signs ◽  
Underlying Mechanisms

Since the discovery of CSF1R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids in 2012, more than 70 different mutations have been identified around the world. Through the analyses of mutation carriers, CSF1R-related leukoencephalopathy has been distinctly characterized clinically, radiologically, and pathologically. Typically, patients present with frontotemporal dementia-like phenotype in their 40s–50s, accompanied by motor symptoms, including pyramidal and extrapyramidal signs. Women tend to develop the clinical symptoms at a younger age than men. On brain imaging, in addition to white matter abnormalities, thinning of the corpus callosum, diffusion-restricted lesions in the white matter, and brain calcifications are hallmarks. Primary axonopathy followed by demyelination was suggested by pathology. Haploinsufficiency of colony-stimulating factor-1 receptor (CSF1R) is evident in a patient with a frameshift mutation, facilitating the establishment of Csf1r haploinsufficient mouse model. These mice develop clinical, radiologic, and pathologic phenotypes consistent with those of human patients with CSF1R mutations. In vitro, perturbation of CSF1R signaling is shown in cultured cells expressing mutant CSF1R. However, the underlying mechanisms by which CSF1R mutations selectively lead to white matter degeneration remains to be elucidated. Given that CSF1R mainly expresses in microglia, CSF1R-related leukoencephalopathy is representative of primary microgliopathies, of which microglia have a pivotal and primary role in pathogenesis. In this review, we address the current knowledge of CSF1R-related leukoencephalopathy and discuss the putative pathophysiology, with a focus on microglia, as well as future research directions.

scholarly journals The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Sanchez ◽  
Maria D. Ganfornina
Keyword(s):  
Systematic Review ◽  
Physiological Function ◽  
Physiological Role ◽  
Future Research ◽  
Lipid Management ◽  
Health And Disease ◽  
Apolipoprotein D ◽  
Extracellular Structures ◽  
Cellular Compartments

Apolipoprotein D is a chordate gene early originated in the Lipocalin protein family. Among other features, regulation of its expression in a wide variety of disease conditions in humans, as apparently unrelated as neurodegeneration or breast cancer, have called for attention on this gene. Also, its presence in different tissues, from blood to brain, and different subcellular locations, from HDL lipoparticles to the interior of lysosomes or the surface of extracellular vesicles, poses an interesting challenge in deciphering its physiological function: Is ApoD a moonlighting protein, serving different roles in different cellular compartments, tissues, or organisms? Or does it have a unique biochemical mechanism of action that accounts for such apparently diverse roles in different physiological situations? To answer these questions, we have performed a systematic review of all primary publications where ApoD properties have been investigated in chordates. We conclude that ApoD ligand binding in the Lipocalin pocket, combined with an antioxidant activity performed at the rim of the pocket are properties sufficient to explain ApoD association with different lipid-based structures, where its physiological function is better described as lipid-management than by long-range lipid-transport. Controlling the redox state of these lipid structures in particular subcellular locations or extracellular structures, ApoD is able to modulate an enormous array of apparently diverse processes in the organism, both in health and disease. The new picture emerging from these data should help to put the physiological role of ApoD in new contexts and to inspire well-focused future research.

scholarly journals High-frequency oscillations and the neurobiology of schizophrenia

2013 ◽  
Vol 15 (3) ◽  
pp. 301-313 ◽  
Keyword(s):  
High Frequency ◽  
Large Scale ◽  
Oscillatory Activity ◽  
Current Evidence ◽  
Neural Oscillations ◽  
Future Research ◽  
Normal Brain ◽  
Brain Functions ◽  
Critical Issues ◽  
Underlying Mechanisms

Neural oscillations at low- and high-frequency ranges are a fundamental feature of large-scale networks. Recent evidence has indicated that schizophrenia is associated with abnormal amplitude and synchrony of oscillatory activity, in particular, at high (beta/gamma) frequencies. These abnormalities are observed during task-related and spontaneous neuronal activity which may be important for understanding the pathophysiology of the syndrome. In this paper, we shall review the current evidence for impaired beta/gamma-band oscillations and their involvement in cognitive functions and certain symptoms of the disorder. In the first part, we will provide an update on neural oscillations during normal brain functions and discuss underlying mechanisms. This will be followed by a review of studies that have examined high-frequency oscillatory activity in schizophrenia and discuss evidence that relates abnormalities of oscillatory activity to disturbed excitatory/inhibitory (E/I) balance. Finally, we shall identify critical issues for future research in this area.

scholarly journals Obsessive healthy eating and orthorexic eating tendencies in sport and exercise contexts: A systematic review and meta-analysis

2021 ◽  
Author(s):  
Jana Strahler ◽  
Hanna Wachten ◽  
Anett Mueller-Alcazar
Keyword(s):  
Systematic Review ◽  
Gender Differences ◽  
Healthy Eating ◽  
Meta Analysis ◽  
Group Analysis ◽  
Future Research ◽  
Exercise Behaviors ◽  
Sport And Exercise ◽  
Underlying Mechanisms ◽  
Meta Analyses

AbstractBackgroundOrthorexia Nervosa (ON) and exercise addiction (ExAdd) are two phenomena believed to overlap. We conducted a meta-analysis exploring the link between ON and (addictive) exercise behaviors.MethodsA systematic review of major databases and gray literature was carried out for studies reporting on ON and (addictive) exercise behaviors. Random effects meta-analyses were undertaken calculating correlations between ON and (addictive) exercise behaviors. A sub-group analysis investigated gender differences.ResultsTwenty-five studies with 10,134 participants (mean age = 25.21; 56.4% female) were included. Analyses showed a small overall correlation between ON and exercise (21 studies, r = 0.12, 95% CI |0.06–0.18|) and a medium overall correlation between ON and ExAdd (7 studies, r = 0.29, 95% CI |0.13–0.45|). Gender differences were negligible.ConclusionsOrthorexic eating correlated slightly and moderately with exercise and ExAdd, respectively, expressing some unique and shared variance of these behaviors. While this does not suggest ON and addictive exercising to be independent, it does not indicate substantial comorbidity. Future research should focus on clinical relevance, underlying mechanisms, vulnerability, and risk factors.

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