scholarly journals The Role of the UPR Pathway in the Pathophysiology and Treatment of Bipolar Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
Mahmoud Suliman ◽  
Michael W. Schmidtke ◽  
Miriam L. Greenberg
Keyword(s):  
Bipolar Disorder ◽  
Target Genes ◽  
New Drugs ◽  
Mood Stabilizers ◽  
Future Research ◽  
Therapeutic Mechanism ◽  
New Perspective ◽  
Human Neuronal Cells ◽  
The Unfolded Protein Response ◽  
Upr Pathway

Bipolar disorder (BD) is a mood disorder that affects millions worldwide and is associated with severe mood swings between mania and depression. The mood stabilizers valproate (VPA) and lithium (Li) are among the main drugs that are used to treat BD patients. However, these drugs are not effective for all patients and cause serious side effects. Therefore, better drugs are needed to treat BD patients. The main barrier to developing new drugs is the lack of knowledge about the therapeutic mechanism of currently available drugs. Several hypotheses have been proposed for the mechanism of action of mood stabilizers. However, it is still not known how they act to alleviate both mania and depression. The pathology of BD is characterized by mitochondrial dysfunction, oxidative stress, and abnormalities in calcium signaling. A deficiency in the unfolded protein response (UPR) pathway may be a shared mechanism that leads to these cellular dysfunctions. This is supported by reported abnormalities in the UPR pathway in lymphoblasts from BD patients. Additionally, studies have demonstrated that mood stabilizers alter the expression of several UPR target genes in mouse and human neuronal cells. In this review, we outline a new perspective wherein mood stabilizers exert their therapeutic mechanism by activating the UPR. Furthermore, we discuss UPR abnormalities in BD patients and suggest future research directions to resolve discrepancies in the literature.

Epidemiological and Clinical Variables Related with the Predominant Polarity on Bipolar Disorder: A Systematic Review

2017 ◽  
Vol 41 (S1) ◽  
pp. S115-S116
Author(s):  
J. García-Jiménez ◽  
A. Porras-Segovia ◽  
J.M. Gota-Garcés ◽  
J.E. Muñoz-Negro ◽  
L. Gutiérrez-Rojas
Keyword(s):  
Bipolar Disorder ◽  
Atypical Antipsychotics ◽  
Mood Stabilizers ◽  
Future Research ◽  
Type I ◽  
Inclusion Criteria ◽  
Clinical Correlates ◽  
History Of ◽  
Competing Interest

IntroductionType I and type II classification of bipolar disorder (BD) may not provide useful information to the clinician regarding epidemiological and clinical correlates.New classifications have recently been proposed, such as the Predominant Polarity (PP) classification, which is based on the tendency of the patient to relapse in the manic (Manic Predominant Polarity [MPP]) or the depressive (Depressive Predominant Polarity [DPP]) poles along the course of the disease.ObjectivesTo explore the epidemiological and clinical correlates of PP.MethodsWe performed a search of the PubMed and Web of Science databases up to June 1st 2016, using the keywords “bipolar disorder”, “polarity” and “predominant polarity”.ResultsThe initial search identified 1598 articles. Only 17 articles met inclusion criteria. Factors associated with MPP are manic onset, history of drug abuse and a better response to atypical antipsychotics and mood stabilizers. Meanwhile DPP is associated with depressive onset, more relapses, longer acute episodes, and a higher risk of suicide. Moreover, delay until diagnosis, mixed episodes and comorbid anxiety disorders are more prevalent in DPP patients, whose treatment often involves quetiapine and lamotrigine.LimitationsFew prospective studies. Variability of results.ConclusionsPP classification may be useful for the clinical management of BD. Further research in this field is needed. Future research should use standardized definitions and more comparable methods.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Hamlet’s augury: how to manage discontinuation of mood stabilizers in bipolar disorder

2021 ◽  
Vol 11 ◽  
pp. 204512532110006
Author(s):  
Mutahira M. Qureshi ◽  
Allan H. Young
Keyword(s):  
Bipolar Disorder ◽  
Treatment Guidelines ◽  
Term Treatment ◽  
Mood Stabilizers ◽  
High Rate ◽  
Future Research ◽  
High Quality Research ◽  
Medication Discontinuation ◽  
Long Term Treatment

Research has generated good quality evidence about the treatment and management of bipolar disorder in acute and, to some degree, sub-acute/continuation phases. This has informed various guidelines about the treatment and management of bipolar disorder (BD). However, for the long-term or maintenance phase of illness, most guidelines peter out and, in the absence of sufficiently high-quality research evidence, remain vague. This is particularly evident for the important clinical question of discontinuing mood stabilizing pharmacological agents after a period of remission has been achieved. The aim of this review is to put together current existing evidence about discontinuing mood stabilizers after a period of remission in order to come up with a structured and coherent strategy for managing such discontinuation and to make recommendations for future research. To this end, we reviewed the main relevant treatment guidelines and subsequent evidence following the publication of these guidelines. The current recommended long-term treatment of BD is usually considered within the same principles applicable to any chronic health condition (e.g. hypertension or diabetes) where the focus is on continuing treatment at minimum effective medication dose often life-long, switching to alternative choice of medication due to side-effects and very few, if any, indications for complete cessation. However, in the absence of strong evidence on long-term treatment and the high rate of non-concordance in BD, medication discontinuation is a very important aspect of the treatment that should be given due consideration at every aspect of the treatment.

Mood Stabilizers, Oxidative Stress and Antioxidative Defense in Euthymia of Bipolar Disorder

2016 ◽  
Vol 15 (4) ◽  
pp. 381-389 ◽  
Author(s):  
Susanne A. Bengesser ◽  
Nina Lackner ◽  
Armin Birner ◽  
Martina Platzer ◽  
Frederike T. Fellendorf ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bipolar Disorder ◽  
Mood Stabilizers ◽  
Antioxidative Defense

scholarly journals Research and application progress of lignin-based composite membrane

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Youjing Li ◽  
Fen Li ◽  
Ying Yang ◽  
Baocai Ge ◽  
Fanzhu Meng
Keyword(s):  
Environmental Pollution ◽  
Raw Materials ◽  
Waste Product ◽  
Functional Materials ◽  
Polymeric Materials ◽  
Composite Membranes ◽  
Organic Polymer ◽  
Future Research ◽  
Sustainable Resources ◽  
New Perspective

Abstract In view of the serious environmental pollution, which is the greatest problem the world is facing, and the continuous consumption of raw materials, it is imminent to search for green and sustainable resources. Lignin is an organic polymer that exists widely in nature, and if it can be transformed from traditional low-value waste product with low range of applications to functional materials with high application prospects, it can be of great significance to alleviate environmental pollution and shortage of fossil resources. One of the functional applications of lignin involves its use to fabricate composite with other polymeric materials, which can then be used to prepare membrane materials. This review summarizes the recent research and application progress of combining lignin with polypropylene, polyvinyl alcohol, starch, cellulose, chitosan, and other polymeric materials to prepare composite membranes; and summarizes the future development direction of lignin-based composite membranes. We hope this review may provide a new perspective to the understanding of lignin-based composite membranes and a useful reference for future research.

scholarly journals Thermoplastic Pultrusion: A Review

Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 180
Author(s):  
Kirill Minchenkov ◽  
Alexander Vedernikov ◽  
Alexander Safonov ◽  
Iskander Akhatov
Keyword(s):  
Composite Structures ◽  
Raw Materials ◽  
Thermoplastic Composites ◽  
Future Research ◽  
Transportation Industry ◽  
Architectural Engineering ◽  
Simulation Techniques ◽  
New Perspective ◽  
The Many ◽  
Lower Production

Pultrusion is one of the most efficient methods of producing polymer composite structures with a constant cross-section. Pultruded profiles are widely used in bridge construction, transportation industry, energy sector, and civil and architectural engineering. However, in spite of the many advantages thermoplastic composites have over the thermoset ones, the thermoplastic pultrusion market demonstrates significantly lower production volumes as compared to those of the thermoset one. Examining the thermoplastic pultrusion processes, raw materials, mechanical properties of thermoplastic composites, process simulation techniques, patents, and applications of thermoplastic pultrusion, this overview aims to analyze the existing gap between thermoset and thermoplastic pultrusions in order to promote the development of the latter one. Therefore, observing thermoplastic pultrusion from a new perspective, we intend to identify current shortcomings and issues, and to propose future research and application directions.

scholarly journals Sulforaphane Inhibits the Expression of Long Noncoding RNA H19 and Its Target APOBEC3G and Thereby Pancreatic Cancer Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 827
Author(s):  
Yiqiao Luo ◽  
Bin Yan ◽  
Li Liu ◽  
Libo Yin ◽  
Huihui Ji ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Colony Formation ◽  
Noncoding Rna ◽  
Target Genes ◽  
Gene Array ◽  
New Drugs ◽  
Tumor Promoter ◽  
Ductal Adenocarcinoma ◽  
Pilot Studies

Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and the therapeutic options available usually have little impact on survival. Great hope is placed on new therapeutic targets, including long noncoding RNAs (lncRNAs), and on the development of new drugs, based on e.g., broccoli-derived sulforaphane, which meanwhile has shown promise in pilot studies in patients. We examined whether sulforaphane interferes with lncRNA signaling and analyzed five PDAC and two nonmalignant cell lines, patient tissues (n = 30), and online patient data (n = 350). RT-qPCR, Western blotting, MTT, colony formation, transwell and wound healing assays; gene array analysis; bioinformatics; in situ hybridization; immunohistochemistry and xenotransplantation were used. Sulforaphane regulated the expression of all of five examined lncRNAs, but basal expression, biological function and inhibition of H19 were of highest significance. H19 siRNA prevented colony formation, migration, invasion and Smad2 phosphorylation. We identified 103 common sulforaphane- and H19-related target genes and focused to the virus-induced tumor promoter APOBEC3G. APOBEC3G siRNA mimicked the previously observed H19 and sulforaphane effects. In vivo, sulforaphane- or H19 or APOBEC3G siRNAs led to significantly smaller tumor xenografts with reduced expression of Ki67, APOBEC3G and phospho-Smad2. Together, we identified APOBEC3G as H19 target, and both are inhibited by sulforaphane in prevention of PDAC progression.

A Comprehensive Survey of Neural Architecture Search

2021 ◽  
Vol 54 (4) ◽  
pp. 1-34
Author(s):  
Pengzhen Ren ◽  
Yun Xiao ◽  
Xiaojun Chang ◽  
Po-yao Huang ◽  
Zhihui Li ◽  
...  
Keyword(s):  
Research Work ◽  
Search Space ◽  
Feature Representation ◽  
Future Research ◽  
Related Research ◽  
Neural Architecture ◽  
Comprehensive Survey ◽  
Future Research Directions ◽  
Intuitive Idea ◽  
New Perspective

Deep learning has made substantial breakthroughs in many fields due to its powerful automatic representation capabilities. It has been proven that neural architecture design is crucial to the feature representation of data and the final performance. However, the design of the neural architecture heavily relies on the researchers’ prior knowledge and experience. And due to the limitations of humans’ inherent knowledge, it is difficult for people to jump out of their original thinking paradigm and design an optimal model. Therefore, an intuitive idea would be to reduce human intervention as much as possible and let the algorithm automatically design the neural architecture. Neural Architecture Search ( NAS ) is just such a revolutionary algorithm, and the related research work is complicated and rich. Therefore, a comprehensive and systematic survey on the NAS is essential. Previously related surveys have begun to classify existing work mainly based on the key components of NAS: search space, search strategy, and evaluation strategy. While this classification method is more intuitive, it is difficult for readers to grasp the challenges and the landmark work involved. Therefore, in this survey, we provide a new perspective: beginning with an overview of the characteristics of the earliest NAS algorithms, summarizing the problems in these early NAS algorithms, and then providing solutions for subsequent related research work. In addition, we conduct a detailed and comprehensive analysis, comparison, and summary of these works. Finally, we provide some possible future research directions.

scholarly journals Exercise is medicine: a new perspective for health promotion in bipolar disorder

2020 ◽  
Vol 20 (11) ◽  
pp. 1099-1107
Author(s):  
Alberto Souza Sá Filho ◽  
Elie Cheniaux ◽  
Carolina Cavalcante de Paula ◽  
Eric Murillo-Rodriguez ◽  
Diogo Teixeira ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Health Promotion ◽  
New Perspective

Prescribing practices of Indian psychiatrists in the treatment of bipolar disorder

2019 ◽  
Vol 53 (5) ◽  
pp. 458-469 ◽  
Author(s):  
YC Janardhan Reddy ◽  
Venugopal Jhanwar ◽  
Rajesh Nagpal ◽  
MS Reddy ◽  
Nilesh Shah ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Maintenance Treatment ◽  
Bipolar Depression ◽  
Mood Stabilizer ◽  
Self Report ◽  
Mood Stabilizers ◽  
Prescribing Practices ◽  
Term Outcome ◽  
Cross Sectional ◽  
Long Term Outcome

Objective: The treatment of bipolar disorder is challenging because of its clinical complexity and availability of multiple treatment options, none of which are ideal mood stabilizers. This survey studies prescription practices of psychiatrists in India and their adherence to guidelines. Method: In total, 500 psychiatrists randomly selected from the Indian Psychiatric Society membership directory were administered a face-to-face 22-item questionnaire pertaining to the management of bipolar disorder. Results: For acute mania, most practitioners preferred a combination of a mood stabilizer and an atypical antipsychotic to monotherapy. For acute depression, there was a preference for a combination of an antidepressant and a mood stabilizer over other alternatives. Electroconvulsive therapy was preferred in the treatment of severe episodes and to hasten the process of recovery. Approximately, 50% of psychiatrists prescribe maintenance treatment after the first bipolar episode, but maintenance therapy was rarely offered lifelong. While the majority (85%) of psychiatrists acknowledged referring to various clinical guidelines, their ultimate choice of treatment was also significantly determined by personal experience and reference to textbooks. Limitations: The study did not study actual prescriptions. Hence, the responses to queries in the survey are indirect measures from which we have tried to understand the actual practices, and of course, these are susceptible to self-report and social-desirability biases. This was a cross-sectional study; therefore, temporal changes in responses could not be considered. Conclusion: Overall, Indian psychiatrists seemed to broadly adhere to recommendations of clinical practice guidelines, but with some notable exceptions. The preference for antidepressants in treating depression is contrary to general restraint recommended by most guidelines. Therefore, the efficacy of antidepressants in treating bipolar depression in the context of Indian psychiatrists’ practice needs to be studied systematically. Not initiating maintenance treatment early in the course of illness may have serious implications on the long-term outcome of bipolar disorder.

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