scholarly journals An Evidence-Based Update on the Molecular Mechanisms Underlying Periodontal Diseases

2020 ◽  
Vol 21 (11) ◽  
pp. 3829 ◽  
Author(s):  
Syed Saad B. Qasim ◽  
Dalal Al-Otaibi ◽  
Reham Al-Jasser ◽  
Sarhang S. Gul ◽  
Muhammad Sohail Zafar
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Periodontal Diseases ◽  
Evidence Based ◽  
Oral Diseases ◽  
Cellular Mechanisms ◽  
Ongoing Research ◽  
Physiological Processes ◽  
Recent Developments ◽  
Small Parts

Several investigators have reported about the intricate molecular mechanism underlying periodontal diseases (PD). Nevertheless, the role of specific genes, cells, or cellular mechanisms involved in the pathogenesis of periodontitis are still unclear. Although periodontitis is one of the most prevalent oral diseases globally, there are no pre-diagnostic markers or therapeutic targets available for such inflammatory lesions. A pivotal role is played by pro- and anti-inflammatory markers in modulating pathophysiological and physiological processes in repairing damaged tissues. In addition, effects on osteoimmunology is ever evolving due to the ongoing research in understanding the molecular mechanism lying beneath periodontal diseases. The aim of the current review is to deliver an evidence-based update on the molecular mechanism of periodontitis with a particular focus on recent developments. Reports regarding the molecular mechanism of these diseases have revealed unforeseen results indicative of the fact that significant advances have been made to the periodontal medicine over the past decade. There is integrated hypothesis-driven research going on. Although a wide picture of association of periodontal diseases with immune response has been further clarified with present ongoing research, small parts of the puzzle remain a mystery and require further investigations.

Extracellular domains play different roles in gap junction formation and docking compatibility

2014 ◽  
Vol 458 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Donglin Bai ◽  
Ao Hong Wang
Keyword(s):  
Gap Junction ◽  
Molecular Mechanisms ◽  
Bond Forming ◽  
Functional Studies ◽  
Extracellular Domains ◽  
Physiological Processes ◽  
Recent Developments ◽  
Non Covalent Interactions ◽  
Alignment Analysis ◽  
Heterotypic Channels

GJ (gap junction) channels mediate direct intercellular communication and play an important role in many physiological processes. Six connexins oligomerize to form a hemichannel and two hemichannels dock together end-to-end to form a GJ channel. Connexin extracellular domains (E1 and E2) have been shown to be important for the docking, but the molecular mechanisms behind the docking and formation of GJ channels are not clear. Recent developments in atomic GJ structure and functional studies on a series of connexin mutants revealed that E1 and E2 are likely to play different roles in the docking. Non-covalent interactions at the docking interface, including hydrogen bonds, are predicted to form between interdocked extracellular domains. Protein sequence alignment analysis on the docking compatible/incompatible connexins indicate that the E1 domain is important for the formation of the GJ channel and the E2 domain is important in the docking compatibility in heterotypic channels. Interestingly, the hydrogen-bond forming or equivalent residues in both E1 and E2 domains are mutational hot spots for connexin-linked human diseases. Understanding the molecular mechanisms of GJ docking can assist us to develop novel strategies in rescuing the disease-linked connexin mutants.

scholarly journals Precision Therapy of Pancreatic Cancer: From Bench to Bedside

2020 ◽  
Vol 36 (5) ◽  
pp. 373-380
Author(s):  
Katrin Jana Ciecielski ◽  
Alexandra Berninger ◽  
Hana Algül
Keyword(s):  
Pancreatic Cancer ◽  
Targeted Therapy ◽  
Molecular Mechanisms ◽  
Diagnostic Methods ◽  
Ductal Adenocarcinoma ◽  
Ongoing Research ◽  
Precision Therapy ◽  
Recent Developments ◽  
Palliative Setting ◽  
Insight Into

<b><i>Background:</i></b> Pancreatic ductal adenocarcinoma (PDAC), with a mortality rate of 94% and a 5-year-survival rate of only 8%, is one of the deadliest cancer entities worldwide, and early diagnostic methods as well as effective therapies are urgently needed. <b><i>Summary:</i></b> This review summarizes current clinical procedure and recent developments of oncological therapy in the palliative setting of metastatic PDAC. It further gives examples of successful, as well as failed, targeted therapy approaches and finally discusses promising ongoing research into the decade-old question of the “undruggability” of KRAS. <b><i>Key Messages:</i></b> Bench-driven concepts change the clinical landscape from “one size fits all” towards precision medicine. With growing insight into the molecular mechanisms of pancreatic cancer the era of targeted therapy in PDAC is gaining a new momentum.

scholarly journals Modulation of MicroRNAs as a Potential Molecular Mechanism Involved in the Beneficial Actions of Physical Exercise in Alzheimer Disease

2020 ◽  
Vol 21 (14) ◽  
pp. 4977 ◽  
Author(s):  
Alex Cleber Improta-Caria ◽  
Carolina Kymie Vasques Nonaka ◽  
Bruno Raphael Ribeiro Cavalcante ◽  
Ricardo Augusto Leoni De Sousa ◽  
Roque Aras Júnior ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Physical Exercise ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Normal Brain ◽  
Physiological Processes ◽  
Normal Brain Function ◽  
Post Transcriptional Regulation

Alzheimer disease (AD) is one of the most common neurodegenerative diseases, affecting middle-aged and elderly individuals worldwide. AD pathophysiology involves the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain, along with chronic neuroinflammation and neurodegeneration. Physical exercise (PE) is a beneficial non-pharmacological strategy and has been described as an ally to combat cognitive decline in individuals with AD. However, the molecular mechanisms that govern the beneficial adaptations induced by PE in AD are not fully elucidated. MicroRNAs are small non-coding RNAs involved in the post-transcriptional regulation of gene expression, inhibiting or degrading their target mRNAs. MicroRNAs are involved in physiological processes that govern normal brain function and deregulated microRNA profiles are associated with the development and progression of AD. It is also known that PE changes microRNA expression profile in the circulation and in target tissues and organs. Thus, this review aimed to identify the role of deregulated microRNAs in the pathophysiology of AD and explore the possible role of the modulation of microRNAs as a molecular mechanism involved in the beneficial actions of PE in AD.

scholarly journals GRAPPA Treatment Recommendations: An Update from the GRAPPA 2013 Annual Meeting

2014 ◽  
Vol 41 (6) ◽  
pp. 1237-1239 ◽  
Author(s):  
Laura C. Coates ◽  
Christopher T. Ritchlin ◽  
Arthur F. Kavanaugh
Keyword(s):  
Psoriatic Arthritis ◽  
Clinical Course ◽  
Scientific Evidence ◽  
Current Evidence ◽  
Evidence Based ◽  
Inflammatory Disorder ◽  
Ongoing Research ◽  
Diarthrodial Joints ◽  
Recent Developments ◽  
New Guidelines

Psoriatic arthritis (PsA) is a chronic systemic inflammatory disorder characterized by the association of arthritis and periarticular inflammation in patients with psoriasis. In addition to a heterogeneous and variable clinical course, PsA is complex and multifaceted and may include prominent involvement in the peripheral and axial diarthrodial joints, the skin and nails, and in periarticular structures such as entheses. A central mission of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is to develop guidelines, based upon the best scientific evidence, for the optimal treatment of patients with PsA. Guidelines were previously published in 2009 based on an evidence-based systematic review. Given important recent developments and robust ongoing research into the treatment of PsA, GRAPPA undertook to update the guidelines. Herein we outline the specific methods and procedures used both in the initial and the current evidence-based, systematic reviews of treatments for PsA. We also review the numerous discussions regarding how best to finalize and publish these new guidelines in 2014.

scholarly journals Scraping through the ice: uncovering the role of TRPM8 in cold transduction

2011 ◽  
Vol 300 (6) ◽  
pp. R1278-R1287 ◽  
Author(s):  
Daniel D. McCoy ◽  
Wendy M. Knowlton ◽  
David D. McKemy
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Temperature Sensitive ◽  
Cellular Mechanisms ◽  
Ongoing Research ◽  
Peripheral Tissues

The proper detection of environmental temperatures is essential for the optimal growth and survival of organisms of all shapes and phyla, yet only recently have the molecular mechanisms for temperature sensing been elucidated. The discovery of temperature-sensitive ion channels of the transient receptor potential (TRP) superfamily has been pivotal in explaining how temperatures are sensed in vivo, and here we will focus on the lone member of this cohort, TRPM8, which has been unequivocally shown to be cold sensitive. TRPM8 is expressed in somatosensory neurons that innervate peripheral tissues such as the skin and oral cavity, and recent genetic evidence has shown it to be the principal transducer of cool and cold stimuli. It is remarkable that this one channel, unlike other thermosensitive TRP channels, is associated with both innocuous and noxious temperature transduction, as well as cold hypersensitivity during injury and, paradoxically, cold-mediated analgesia. With ongoing research, the field is getting closer to answering a number of fundamental questions regarding this channel, including the cellular mechanisms of TRPM8 modulation, the molecular context of TRPM8 expression, as well as the full extent of the role of TRPM8 in cold signaling in vivo. These findings will further our understanding of basic thermotransduction and sensory coding, and may have important implications for treatments for acute and chronic pain.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Natural Products for Regulating Macrophages M2 Polarization

2020 ◽  
Vol 15 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Zhen Chang ◽  
Youhan Wang ◽  
Chang Liu ◽  
Wanli Smith ◽  
Lingbo Kong
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Research Progress ◽  
Cellular Mechanisms ◽  
Pharmacological Activities ◽  
Current Review ◽  
M2 Polarization ◽  
Macrophages Polarization ◽  
Herbal Plants

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.

scholarly journals The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses

2021 ◽  
Vol 22 (15) ◽  
pp. 8338
Author(s):  
Asad Jan ◽  
Nádia Pereira Gonçalves ◽  
Christian Bjerggaard Vaegter ◽  
Poul Henning Jensen ◽  
Nelson Ferreira
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Alpha Synuclein ◽  
Experimental Models ◽  
Cellular Factors ◽  
Recent Developments ◽  
Novel Targets ◽  
Presynaptic Protein

The pathological aggregation of the presynaptic protein α-synuclein (α-syn) and propagation through synaptically coupled neuroanatomical tracts is increasingly thought to underlie the pathophysiological progression of Parkinson’s disease (PD) and related synucleinopathies. Although the precise molecular mechanisms responsible for the spreading of pathological α-syn accumulation in the CNS are not fully understood, growing evidence suggests that de novo α-syn misfolding and/or neuronal internalization of aggregated α-syn facilitates conformational templating of endogenous α-syn monomers in a mechanism reminiscent of prions. A refined understanding of the biochemical and cellular factors mediating the pathological neuron-to-neuron propagation of misfolded α-syn will potentially elucidate the etiology of PD and unravel novel targets for therapeutic intervention. Here, we discuss recent developments on the hypothesis regarding trans-synaptic propagation of α-syn pathology in the context of neuronal vulnerability and highlight the potential utility of novel experimental models of synucleinopathies.

scholarly journals Assessing the Potential of Catch-Only Models to Inform on the State of Global Fisheries and the UN’s SDGs

2021 ◽  
Vol 13 (11) ◽  
pp. 6101
Author(s):  
Rishi Sharma ◽  
Henning Winker ◽  
Polina Levontin ◽  
Laurence Kell ◽  
Dan Ovando ◽  
...  
Keyword(s):  
Stock Assessment ◽  
Fishing Effort ◽  
The State ◽  
Sources Of Information ◽  
Ongoing Research ◽  
Traditional Assessment ◽  
Stock Status ◽  
Stock Assessments ◽  
Recent Developments ◽  
Measure Of Performance

Catch-only models (COMs) have been the focus of ongoing research into data-poor stock assessment methods. Two of the most recent models that are especially promising are (i) CMSY+, the latest refined version of CMSY that has progressed from Catch-MSY, and (ii) SRA+ (Stock Reduction Analysis Plus) a recent developments in field. Comparing COMs and evaluating their relative performance is essential for determining the state of regional and global fisheries that may be lacking necessary data that would be required to run traditional assessment models. In this paper we interrogate how performance of COMs can be improved by incorporating additional sources of information. We evaluate the performance of COMs on a dataset of 48 data-rich ICES (International Council for the Exploration of Seas) stock assessments. As one measure of performance, we consider the ability of the model to correctly classify stock status using FAO’s 3-tier classification that is also used for reporting on sustainable development goals to the UN. Both COMs showed notable bias when run with their inbuilt default heuristics, but as the quality of prior information increased, classification rates for the terminal year improved substantially. We conclude that although further COM refinements show some potential, most promising is the ongoing research into developing biomass or fishing effort priors for COMs in order to be able to reliably track stock status for the majority of the world’s fisheries currently lacking stock assessments.

New horizons in mitochondrial contact site research

2020 ◽  
Vol 401 (6-7) ◽  
pp. 793-809
Author(s):  
Naama Zung ◽  
Maya Schuldiner
Keyword(s):  
Endoplasmic Reticulum ◽  
Molecular Mechanisms ◽  
Contact Site ◽  
New Horizons ◽  
Contact Sites ◽  
Future Goals ◽  
Close Proximity ◽  
Recent Developments ◽  
Site Field ◽  
First Contact

AbstractContact sites, areas where two organelles are held in close proximity through the action of molecular tethers, enable non-vesicular communication between compartments. Mitochondria have been center stage in the contact site field since the discovery of the first contact between mitochondria and the endoplasmic reticulum (ER) over 60 years ago. However, only now, in the last decade, has there been a burst of discoveries regarding contact site biology in general and mitochondrial contacts specifically. The number and types of characterized contacts increased dramatically, new molecular mechanisms enabling contact formation were discovered, additional unexpected functions for contacts were shown, and their roles in cellular and organismal physiology were emphasized. Here, we focus on mitochondria as we highlight the most recent developments, future goals and unresolved questions in the field.

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