scholarly journals Potential role of Zinc supplement in CVD and COVID-19 co-morbidity

2020 ◽  
Author(s):  
Muhammad Karim ◽  
Shahnaz Sultana ◽  
Rokaia Sultana ◽  
Mohammad Tariqur Rahman
Keyword(s):  
Viral Replication ◽  
Potential Role ◽  
Treatment Plan ◽  
Functional Expression ◽  
Therapeutic Interventions ◽  
Selective Treatment ◽  
Zinc Supplement ◽  
Co Morbidity ◽  
The Given

As far as the comorbidity is concerned, cardiovascular diseases (CVD) appear to be accounted for the highest prevalence, severity, and fatality among COVID 19 patients. A wide array of causal links connecting CVD and COVID-19 baffle the overall prognosis as well as the efficacy of the given therapeutic interventions. At the centre of this puzzle lies ACE2 that works as a receptor for the SARS-CoV-2 and functional expression of which is also needed to minimize vasoconstriction otherwise would lead to high blood pressure. Furthermore, SARS-CoV-2 infection seems to reduce the functional expression of ACE2. Given these circumstances, it might be advisable to consider a treatment plan for COVID-19 patients with CVD in an approach that would neither aggravate the vasodeleterious arm of RAAS nor compromise the vasoprotective arm of RAAS but is effective to minimize or if possible, inhibit the viral replication. A zinc supplement to the selective treatment plan, to be decided by the clinicians depending on the cardiovascular conditions of the patients, is hereafter proposed that might greatly enhance the therapeutic outcome. Notably, ACE2 is a zinc metalloenzyme and zinc is also known to inhibit viral replication.

scholarly journals The role of rumination in illness trajectories in youth: linking trans-diagnostic processes with clinical staging models

2016 ◽  
Vol 46 (12) ◽  
pp. 2467-2484 ◽  
Author(s):  
A. B. Grierson ◽  
I. B. Hickie ◽  
S. L. Naismith ◽  
J. Scott
Keyword(s):  
Mental Disorders ◽  
Emotional Regulation ◽  
Potential Role ◽  
Psychotic Disorders ◽  
Developmental Trajectory ◽  
Clinical Staging ◽  
Neurocognitive Deficits ◽  
Illness Onset ◽  
Co Morbidity

Research in developmental psychopathology and clinical staging models has increasingly sought to identify trans-diagnostic biomarkers or neurocognitive deficits that may play a role in the onset and trajectory of mental disorders and could represent modifiable treatment targets. Less attention has been directed at the potential role of cognitive-emotional regulation processes such as ruminative response style. Maladaptive rumination (toxic brooding) is a known mediator of the association between gender and internalizing disorders in adolescents and is increased in individuals with a history of early adversity. Furthermore, rumination shows moderate levels of genetic heritability and is linked to abnormalities in neural networks associated with emotional regulation and executive functioning. This review explores the potential role of rumination in exacerbating the symptoms of alcohol and substance misuse, and bipolar and psychotic disorders during the peak age range for illness onset. Evidence shows that rumination not only amplifies levels of distress and suicidal ideation, but also extends physiological responses to stress, which may partly explain the high prevalence of physical and mental co-morbidity in youth presenting to mental health services. In summary, the normative developmental trajectory of rumination and its role in the evolution of mental disorders and physical illness demonstrates that rumination presents a detectable, modifiable trans-diagnostic risk factor in youth.

scholarly journals Effect of alpha-1 antitrypsin Portland variant (α1-PDX) on HIV-1 replication

2000 ◽  
Vol 352 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Bouchaib BAHBOUHI ◽  
Mourad BENDJENNAT ◽  
Denise GUÉTARD ◽  
Nabil Georges SEIDAH ◽  
Elmostafa BAHRAOUI
Keyword(s):  
Viral Replication ◽  
Potential Role ◽  
Serine Proteinase ◽  
Recombinant Vaccinia Virus ◽  
Jurkat Cells ◽  
Serine Proteinase Inhibitor ◽  
Cdna Insert ◽  
Alpha 1 Antitrypsin ◽  
Hiv 1

The present work investigated the potential role of alpha-1 antitrypsin Portland variant (α1-PDX), a bioengineered serine proteinase inhibitor (serpin), in the interference with the viral replication of HIV-1, induction of syncytia and maturation of envelope glycoprotein gp160 to gp120 and gp41. A Jurkat lymphoid cell line transfected with a plasmid containing the α1-PDX cDNA (J-PDX) and expressing the protein in a stable manner was infected with HIV-1Lai. Controls were Jurkat cells transfected with the same vector pcDNA3 without the cDNA insert (J-pcDNA3). The results showed that viral replication of HIV-1 was significantly inhibited with a delay in replication kinetics in J-PDX cells as compared with J-pcDNA3 cells. In addition, a comparison of the infectious capacity of viruses produced in the presence and absence of α1-PDX revealed that this capacity differed. It was found that α1-PDX exerts its effect by interfering with the formation of syncytia between J-PDX cells infected with gp160 recombinant vaccinia virus, or after infection by HIV-1 and co-culture with uninfected Molt-4 cells. In contrast, when the same experiments were performed with J-pcDNA3 cells, a large number of syncytia was obtained. Analysis of viral proteins by Western blotting and densitometry showed that the inhibition of the cytopathic effect of HIV-1 and viral replication was correlated with the capacity of α1-PDX to interfere with the maturation of gp160 to gp120 and gp41.

scholarly journals GRP78 in lung cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shengkai Xia ◽  
Wenzhe Duan ◽  
Wenwen Liu ◽  
Xinri Zhang ◽  
Qi Wang
Keyword(s):  
Lung Cancer ◽  
Er Stress ◽  
Potential Role ◽  
Prognostic Biomarker ◽  
Therapeutic Interventions ◽  
Comprehensive Understanding ◽  
Protein Response ◽  
First Time

AbstractGlucose-regulating protein 78 (GRP78) is a molecular chaperone in the endoplasmic reticulum (ER) that promotes folding and assembly of proteins, controls the quality of proteins, and regulates ER stress signaling through Ca2+ binding to the ER. In tumors, GRP78 is often upregulated, acting as a central stress sensor that senses and adapts to changes in the tumor microenvironment, mediating ER stress of cancer cells under various stimulations of the microenvironment to trigger the folding protein response. Increasing evidence has shown that GRP78 is closely associated with the progression and poor prognosis of lung cancer, and plays an important role in the treatment of lung cancer. Herein, we reviewed for the first time the functions and mechanisms of GRP78 in the pathological processes of lung cancer, including tumorigenesis, apoptosis, autophagy, progression, and drug resistance, giving a comprehensive understanding of the function of GRP78 in lung cancer. In addition, we also discussed the potential role of GRP78 as a prognostic biomarker and therapeutic target for lung cancer, which is conducive to improving the assessment of lung cancer and the development of new therapeutic interventions.

scholarly journals SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein

2022 ◽  
Author(s):  
Marius Walter ◽  
Irene P Chen ◽  
Albert Vallejo-Gracia ◽  
Ik-Jung Kim ◽  
Olga Bielska ◽  
...  
Keyword(s):  
Viral Replication ◽  
Catalytic Domain ◽  
Therapeutic Interventions ◽  
Stable Complex ◽  
Structural Protein ◽  
Knock Out ◽  
Protein Interactome ◽  
Lysine Residues ◽  
Dependent Protein

SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD-dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 stably interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions.

scholarly journals Inflammation and autoimmunity in pulmonary hypertension: is there a role for endothelial adhesion molecules? (2017 Grover Conference Series)

2018 ◽  
Vol 8 (2) ◽  
pp. 204589321875759 ◽  
Author(s):  
Wolfgang M. Kuebler ◽  
Sébastien Bonnet ◽  
Arata Tabuchi
Keyword(s):  
Pulmonary Hypertension ◽  
Potential Role ◽  
Disease Process ◽  
Experimental Models ◽  
Therapeutic Interventions ◽  
Pulmonary Resistance ◽  
Resistance Vessels ◽  
Endothelial Adhesion Molecules ◽  
Inflammatory Component

While pulmonary hypertension (PH) has traditionally not been considered as a disease that is directly linked to or, potentially, even caused by inflammation, a rapidly growing body of evidence has demonstrated the accumulation of a variety of inflammatory and immune cells in PH lungs, in and around the wall of remodeled pulmonary resistance vessels and in the vicinity of plexiform lesions, respectively. Concomitantly, abundant production and release of various inflammatory mediators has been documented in both PH patients and experimental models of PH. While these findings unequivocally demonstrate an inflammatory component in PH, they have fueled an intense and presently ongoing debate as to the nature of this inflammatory aspect: is it a mere bystander of or response to the actual disease process, or is it a pathomechanistic contributor or potentially even a trigger of endothelial injury, smooth muscle hypertrophy and hyperplasia, and the resulting lung vascular remodeling? In this review, we will discuss the present evidence for an inflammatory component in PH disease with a specific focus on the potential role of the endothelium in this scenario and highlight future avenues of experimental investigation which may lead to novel therapeutic interventions.

scholarly journals Immunophilin Ligands Modulate Phagocytosis and Viral 2 Replication in HIV-Infected Macrophages

2021 ◽  
Author(s):  
Anish Sathe ◽  
Ana Sanchez ◽  
Benchawanna Soontornniyomkij ◽  
Mary Swinton ◽  
Shibangi Pal ◽  
...  
Keyword(s):  
Viral Replication ◽  
Blood Donors ◽  
Potential Role ◽  
People Living With Hiv ◽  
Protective Effects ◽  
Macrophage Phenotype ◽  
Brain Macrophages ◽  
Infected Cells ◽  
Living With Hiv

Abstract (1) Background: HIV-associated neurocognitive disorders (HAND) can occur as a result of HIV-mediated neuroinflammation and affect people living with HIV (PWH) despite advances in combination antiretroviral therapy (cART). Brain macrophages have been implicated as a source of virus and neurotoxic factors. In this study, we examined the potential role of the immunophilin ligands rapamycin and FK506 in modulating neuroinflammation caused by infected macrophages. (2) Methods: Monocytes were isolated from blood samples from three different blood donors and were differentiated into macrophages (MDMs). These cells were subsequently infected with HIV and treated with combinations of an antiretroviral (ARV) cocktail (raltegravir, emtricitabine, and tenofovir), FK506, and rapamycin. Immunocytochemistry and RT-qPCR were used to analyze the phagocytosis of amyloid beta and the expression of macrophage phenotype-associated markers such as Iba1, TREM2, and IL-6. Viral replication was measured using p24 ELISA. (3) Results: Viral replication among infected MDMs as indicated by p24 levels was positively correlated with Iba1 levels and negatively correlated with IL-6 expression. However, infected MDMs showed lower Iba1 levels than non-infected cells. Rapamycin treatment appeared to lower p24 levels across all donors. Phagocytosis was associated with higher Iba1 levels and was impaired in rapamycin-treated MDMs. (4) Conclusions: Rapamycin seemed to protect against viral replication. However, decreased replication was correlated with a decrease in phagocytic activity. Iba1 may be involved in phagocytosis and HIV infection while IL-6 appeared to indicate protective effects against replication.

scholarly journals R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde

2021 ◽  
Vol 22 (16) ◽  
pp. 8850
Author(s):  
Sidrit Uruci ◽  
Calvin Shun Yu Lo ◽  
David Wheeler ◽  
Nitika Taneja
Keyword(s):  
Replication Fork ◽  
Potential Role ◽  
Genome Instability ◽  
Chromatin Modification ◽  
Therapeutic Interventions ◽  
Epigenetic Landscape ◽  
Physiological Processes ◽  
Stalled Fork ◽  
Chromatin Modifiers

Since their discovery, R-loops have been associated with both physiological and pathological functions that are conserved across species. R-loops are a source of replication stress and genome instability, as seen in neurodegenerative disorders and cancer. In response, cells have evolved pathways to prevent R-loop accumulation as well as to resolve them. A growing body of evidence correlates R-loop accumulation with changes in the epigenetic landscape. However, the role of chromatin modification and remodeling in R-loops homeostasis remains unclear. This review covers various mechanisms precluding R-loop accumulation and highlights the role of chromatin modifiers and remodelers in facilitating timely R-loop resolution. We also discuss the enigmatic role of RNA:DNA hybrids in facilitating DNA repair, epigenetic landscape and the potential role of replication fork preservation pathways, active fork stability and stalled fork protection pathways, in avoiding replication-transcription conflicts. Finally, we discuss the potential role of several Chro-Mates (chromatin modifiers and remodelers) in the likely differentiation between persistent/detrimental R-loops and transient/benign R-loops that assist in various physiological processes relevant for therapeutic interventions.

The Haywain: Anti-synthetase Antibodies in Patients with Inflammatory Diseases: Targeting Monocytes or Neutrophils?

2020 ◽  
Vol 27 (17) ◽  
pp. 2863-2871
Author(s):  
Bob Meek ◽  
Ger T. Rijkers
Keyword(s):  
Diagnostic Tool ◽  
Potential Role ◽  
Splice Variants ◽  
Inflammatory Diseases ◽  
Therapeutic Interventions ◽  
Inflammatory Disorders ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Wide Range

Autoantibiodies against aminoacyl-tRNA synthetases are found in patients suffering from a wide range of autoimmune and inflammatory disorders. Recent data indicate that these antibodies are directed against splice-variants of synthetase genes, the so-called catalytic nulls. Latter molecules have cytokine-like functions and are involved in the regulation of the activation of lymphocytes, monocytes and granulocytes. The potential role of anti-synthetase antibodies as a diagnostic tool and a target for therapeutic interventions is discussed.

Emerging evidence for potential role of Ca2+-ATPase-mediated calcium accumulation in symbiosomes of infected root nodule cells

2017 ◽  
Vol 44 (10) ◽  
pp. 955 ◽  
Author(s):  
Igor M. Andreev
Keyword(s):  
Soil Bacteria ◽  
Potential Role ◽  
Root Nodule ◽  
Plant Root ◽  
Symbiotic Association ◽  
Root Cells ◽  
Infected Root ◽  
Living Organisms ◽  
The Given

Symbiosomes are organelle-like compartments responsible for nitrogen fixation in infected nodule cells of legumes, which are formed as a result of symbiotic association of soil bacteria rhizobia with certain plant root cells. They are virtually the only source of reduced nitrogen in the Earth’s biosphere, and consequently, are of great importance. It has been proven that the functioning of symbiosomes depends to a large extent on the transport of various metabolites and ions – most likely including Ca2+ – across the symbiosome membrane (SM). Although it has been well established that this cation is involved in the regulation of a broad spectrum of processes in cells of living organisms, its role in the functioning of symbiosomes remains obscure. This is despite available data indicating both its transport through the SM and accumulation within these compartments. This review summarises the results obtained in the course of studies on the given aspects of calcium behaviour in symbiosomes, and on this basis gives a possible explanation of the proper functional role in them of Ca2+.

Understanding novel mechanisms of microbial pathogenesis in chronic lung disease: implications for new therapeutic targets

2018 ◽  
Vol 132 (3) ◽  
pp. 375-379 ◽  
Author(s):  
Mathew Suji Eapen ◽  
Sukhwinder Singh Sohal
Keyword(s):  
Lung Disease ◽  
Chronic Lung Disease ◽  
Potential Role ◽  
Therapeutic Interventions ◽  
Airflow Limitation ◽  
Microbial Pathogenesis ◽  
Disease Trajectory ◽  
Airway Infections ◽  
Clinical Conditions

Airway infections are considered as one of the vital factors driving the pathophysiology of chronic lung disease with significant influences on disease trajectory. Opportunistic lung microbes in diseased conditions induce excessive exacerbations and contribute to airflow limitation. Though there has been considerable amount of information that ascertains their links with airway inflammation, the intricate interaction in clinical conditions are poorly understood and requires further deciphering. Current therapeutic interventions for such pathologies are few and lack the ability to modulate underlying dysfunctional immunity as well as suppress the excessive infectious conditions. Thus, in this Commentary we provide a focused outlook on the mechanisms involved in microbial infestation in lung diseases and provides important information on new therapeutic interventions including the potential role of Resolvins and their derivatives as alternative therapeutic agents in combating such multifaceted pathological mechanisms.

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