scholarly journals The Interface between Cell Signaling Pathways and Pregnane X Receptor

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3262
Author(s):  
Robert S. Rogers ◽  
Annemarie Parker ◽  
Phill D. Vainer ◽  
Elijah Elliott ◽  
Dakota Sudbeck ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Pregnane X Receptor ◽  
The Body ◽  
Post Translational Modifications ◽  
Significant Drug Interaction ◽  
Drug Biotransformation ◽  
Expression Of Genes ◽  
Gene Environment ◽  
Nutrient Signaling ◽  
Clinically Significant

Highly expressed in the enterohepatic system, pregnane X receptor (PXR, NR1I2) is a well-characterized nuclear receptor (NR) that regulates the expression of genes in the liver and intestines that encode key drug metabolizing enzymes and drug transporter proteins in mammals. The net effect of PXR activation is to increase metabolism and clear drugs and xenobiotics from the body, producing a protective effect and mediating clinically significant drug interaction in patients on combination therapy. The complete understanding of PXR biology is thus important for the development of safe and effective therapeutic strategies. Furthermore, PXR activation is now known to specifically transrepress the inflammatory- and nutrient-signaling pathways of gene expression, thereby providing a mechanism for linking these signaling pathways together with enzymatic drug biotransformation pathways in the liver and intestines. Recent research efforts highlight numerous post-translational modifications (PTMs) which significantly influence the biological function of PXR. However, this thrust of research is still in its infancy. In the context of gene-environment interactions, we present a review of the recent literature that implicates PXR PTMs in regulating its clinically relevant biology. We also provide a discussion of how these PTMs likely interface with each other to respond to extracellular cues to appropriately modify PXR activity.

Acute exudative paraneoplastic polymorphous vitelliform maculopathy in a patient with thymoma, myasthenia gravis, and polymyositis

2021 ◽  
pp. 112067212199404
Author(s):  
He Yu ◽  
Xinyu Ma ◽  
Nianting Tong ◽  
Zhanyu Zhou ◽  
Yu Zhang
Keyword(s):  
Myasthenia Gravis ◽  
Medical Center ◽  
Postoperative Radiotherapy ◽  
Clinical Manifestations ◽  
Subretinal Fluid ◽  
Metastatic Tumor ◽  
The Body ◽  
Pleural Thickening ◽  
History Of ◽  
Clinically Significant

Importance: This is the first reported case of acute exudative paraneoplastic polymorphous vitelliform maculopathy (AEPPVM) in a patient with thymoma, accompanied by myasthenia gravis (MG) and polymyositis. Objective: To examine the pathogenesis of ocular disease in a patient with yolk-like fundus lesions and thymoma, MG, and polymyositis throughout the body based on clinical manifestations, diagnosis, differential diagnosis, and genetic testing to determine the appropriate treatment course. Design, setting, and participants: We describe a 63-year-old woman who presented to our tertiary medical center with a 3-month history of reduced visual acuity in both eyes. Concurrent fundoscopy revealed a 2.0 × 1.7-mm, unifocal, yellow, round vitelliform lesion in the macular region, surrounded by multifocal, shallow, yellow-white pockets of subretinal fluid. The patient’s medical history included thymoma with thymectomy treatment, combined with pericardiectomy and postoperative radiotherapy (20 years prior), followed by a diagnosis of MG with suspect thymic association (15 years prior). Three years prior, the patient had been diagnosed with polymyositis related to paraneoplastic syndrome; 1 year prior, she had been examined for pleural thickening due to suspected metastatic tumor. Results: On her most recent follow-up visit at 3 months after initial diagnosis, the patient was stable with no clinically significant progression in ocular or systemic conditions.

scholarly journals Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 287
Author(s):  
Yew Rong Kong ◽  
Yong Xin Jong ◽  
Manisha Balakrishnan ◽  
Zhui Ken Bok ◽  
Janice Kwan Kah Weng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Chronic Diseases ◽  
Carica Papaya ◽  
Antioxidant Properties ◽  
Natural Antioxidants ◽  
The Body ◽  
Health Conditions ◽  
Chemical Components ◽  
Impaired Wound Healing

Oxidative stress is a result of disruption in the balance between antioxidants and pro-oxidants in which subsequently impacting on redox signaling, causing cell and tissue damages. It leads to a range of medical conditions including inflammation, skin aging, impaired wound healing, chronic diseases and cancers but these conditions can be managed properly with the aid of antioxidants. This review features various studies to provide an overview on how Carica papaya help counteract oxidative stress via various mechanisms of action closely related to its antioxidant properties and eventually improving the management of various oxidative stress-related health conditions. Carica papaya is a topical plant species discovered to contain high amounts of natural antioxidants that can usually be found in their leaves, fruits and seeds. It contains various chemical compounds demonstrate significant antioxidant properties including caffeic acid, myricetin, rutin, quercetin, α-tocopherol, papain, benzyl isothiocyanate (BiTC), and kaempferol. Therefore, it can counteract pro-oxidants via a number of signaling pathways that either promote the expression of antioxidant enzymes or reduce ROS production. These signaling pathways activate the antioxidant defense mechanisms that protect the body against both intrinsic and extrinsic oxidative stress. To conclude, Carica papaya can be incorporated into medications or supplements to help manage the health conditions driven by oxidative stress and further studies are needed to investigate the potential of its chemical components to manage various chronic diseases.

Inhibition of Hepatic Microsomal Drug Metabolism by the Hydrazines Ro 4-4602, MK 486, and Procarbazine Hydrochloride

1972 ◽  
Vol 50 (7) ◽  
pp. 721-724 ◽  
Author(s):  
Norman R. Bade ◽  
Stuart M. MacLeod ◽  
Kenneth W. Renton
Keyword(s):  
Drug Interaction ◽  
Drug Metabolism ◽  
Sleeping Time ◽  
Hydrazine Derivatives ◽  
Significant Drug Interaction ◽  
Microsomal Drug Metabolism ◽  
Clinically Significant ◽  
Hepatic Biotransformation

Preliminary experiments were undertaken to examine the effect of three hydrazine derivatives, viz. Ro 4-4602, MK 486, and procarbazine hydrochloride, on hepatic microsomal drug metabolism in rats. All three compounds when given as pretreatment significantly prolonged pentobarbital sleeping time. In vitro, the hepatic microsomal N-demethylation of aminopyrine was inhibited. It is concluded that all three drugs are possible sources of clinically significant drug interaction when administered in combination with other agents which undergo hepatic biotransformation.

scholarly journals Immediate and Long-Term Results of the Spleen-Preserved Operations in the Surgical Treatment of Gastric Cancer

2020 ◽  
Vol 13 (3) ◽  
pp. 227-232
Author(s):  
Marina I. Rogozianskaia ◽  
Alexander Nikolayevich Redkin ◽  
Ivan Petrovich Moshurov
Keyword(s):  
Gastric Cancer ◽  
Surgical Treatment ◽  
Total Gastrectomy ◽  
The Body ◽  
Long Term Results ◽  
D2 Lymphadenectomy ◽  
Spleen Preserving ◽  
Cardiac Region ◽  
Clinically Significant

ntroduction. Currently, total gastrectomy with D2 lymphadenectomy is the standard surgical treatment for proximal gastric cancer at the resectable stages (I-III). The issue of advisability of splenectomy as a component of lymphadenectomy remains a controversial one, especially when the tumor is localized in the region of the body or cardiac region of the stomach.The aim of the study was to compare immediate and long-term outcomes, including the quality of life, between spleen preserving and spleen removing surgeries.Methods. The study included 363 patients with gastric cancer II-III stages, localized in the upper and/or the middle third of the stomach, who underwent surgery at the Voronezh Regional Clinical Oncology Hospital and the Voronezh Clinical Hospital of the Russian Railway-Medicine in 2015-2017. All patients were conditionally divided into 2 groups for comparative retrospective analysis. All patients of the first (experimental or spleen-preserved) group (144 patients) were performed R0 total gastrectomy with D2 lymphadenectomy, including splenic hilar nodes (№ 10,11) removal without splenectomy. Patients of the second (control or splenectomy) group (219 patients) were performed R0 total gastrectomy with D2 lymphadenectomy and prophylactic splenectomy (for splenic hilar nodes removal).Results. The average duration of the operation and the volume of blood loss did not differ in both groups. The incidence of early postoperative surgical complications was lower in the spleen-preserved group. Splenectomy was associated with more severe complications of class 4 and 5 according to the Clavien-Dindo classification. Conclusion. Parameters of the 1- and 3-year overall survival rate did not differ in both groups. The results of the GSRS questionnaire were similar in both groups, excluding reflux-esophageal symptoms scale. The reflux scale demonstrated a statistically and clinically significant advantage of spleen preservation.

scholarly journals Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Flurina Boehi ◽  
Patrick Manetsch ◽  
Michael O. Hottiger
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Cellular Responses ◽  
Dynamic Regulation ◽  
Post Translational Modifications ◽  
Adp Ribosylation ◽  
Cellular Processes ◽  
Adp Ribosyltransferase ◽  
Cell Signaling Pathways

AbstractSignaling cascades provide integrative and interactive frameworks that allow the cell to respond to signals from its environment and/or from within the cell itself. The dynamic regulation of mammalian cell signaling pathways is often modulated by cascades of protein post-translational modifications (PTMs). ADP-ribosylation is a PTM that is catalyzed by ADP-ribosyltransferases and manifests as mono- (MARylation) or poly- (PARylation) ADP-ribosylation depending on the addition of one or multiple ADP-ribose units to protein substrates. ADP-ribosylation has recently emerged as an important cell regulator that impacts a plethora of cellular processes, including many intracellular signaling events. Here, we provide an overview of the interplay between the intracellular diphtheria toxin-like ADP-ribosyltransferase (ARTD) family members and five selected signaling pathways (including NF-κB, JAK/STAT, Wnt-β-catenin, MAPK, PI3K/AKT), which are frequently described to control or to be controlled by ADP-ribosyltransferases and how these interactions impact the cellular responses.

scholarly journals Comprehensive Review of Cardiovascular Involvement in COVID-19

2021 ◽  
pp. e1-e19
Author(s):  
Ruff Joseph Macale Cajanding
Keyword(s):  
Cardiac Involvement ◽  
Health Care Systems ◽  
The Body ◽  
Cardiac Pathology ◽  
Current State ◽  
Global Pandemic ◽  
Cardiovascular Involvement ◽  
Disease Causation ◽  
Care Systems ◽  
Clinically Significant

COVID-19 has emerged as one of the most devastating and clinically significant infectious diseases of the last decade. It has reached global pandemic status at an unprecedented pace and has placed significant demands on health care systems worldwide. Although COVID-19 primarily affects the lungs, epidemiologic reports have shown that the disease affects other vital organs of the body, including the heart, vasculature, kidneys, brain, and the hematopoietic system. Of importance is the emerging awareness of the effects of COVID-19 on the cardiovascular system. The current state of knowledge regarding cardiac involvement in COVID-19 is presented in this article, with particular focus on the cardiovascular manifestations and complications of COVID-19 infection. The mechanistic insights of disease causation and the relevant pathophysiology involved in COVID-19 as they affect the heart are explored and described. Relevant practice essentials and clinical management implications for patients with COVID-19 with a cardiac pathology are presented in light of recent evidence.

scholarly journals Primary vulvar squamous cell carcinomas with high T cell infiltration and active immune signaling are potential candidates for neoadjuvant PD-1/PD-L1 immunotherapy

2021 ◽  
Vol 9 (10) ◽  
pp. e003671
Author(s):  
Kim E Kortekaas ◽  
Saskia J Santegoets ◽  
Liselotte Tas ◽  
Ilina Ehsan ◽  
Pornpimol Charoentong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Signaling Pathways ◽  
T Cell Activation ◽  
Squamous Cell ◽  
Molecular Subtype ◽  
Cell Infiltration ◽  
Immune Signaling ◽  
T Cell Infiltration ◽  
Expression Of Genes

BackgroundA profound insight into the immune landscape of vulvar squamous cell carcinoma (VSCC) is lacking. Here, an in-depth interrogation of T cell infiltration, local immune contexture, signaling pathways and checkpoint molecule expression was performed in early-stage and late-stage VSCC.MethodsThe type, location, and infiltration pattern of T cells were studied in 109 patients with primary VSCC FIGO stage I–III. RNA expression of genes involved in immune oncology and oncogenic signaling pathways was analyzed in 40 VSCC, matched for prognostic clinicopathological variables, analyzed for HPV and p53 status, and selected based on T cell infiltration.ResultsHigh intraepithelial infiltration with CD4 or CD8 T cells was associated with longer overall and recurrence-free survival and formed an independent prognostic factor, outperforming molecular subtype and stage of the disease. Strong T cell infiltrated VSCC displayed a coordinated immune response reflected by a positive association between T cells and different lymphocyte and myeloid cell subsets. The expression of genes involved in the migration of T cells and myeloid cells, T cell activation and costimulation, interferon (IFN)-γ signaling, cytotoxicity and apoptosis was higher than in low infiltrated tumors. An active immune signaling profile was observed in all inflamed, part of the altered-excluded and not in altered-immunosuppressed or deserted VSCC. While several checkpoint molecules were overexpressed, only PD-L1 expression displayed discriminatory ability and clinical usefulness. High PD-L1 expression was detected in all inflamed and ~60% of the altered-excluded VSCC.ConclusionAn active immune signaling profile is present in 35% of primary FIGO I–III VSCCs, suggesting potential responsiveness to neoadjuvant PD-1/PD-L1 immunotherapy.

Role of MicroRNAs and Long Non-Coding RNAs in Regulating Angiogenesis in Human Breast Cancer- A Molecular Medicine Perspective

2021 ◽  
Vol 22 ◽  
Author(s):  
Vandana Golhani ◽  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Signaling Pathways ◽  
Cancer Therapeutics ◽  
Molecular Medicine ◽  
Dependent Manner ◽  
Protein Coding ◽  
Controlled Systems ◽  
Expression Of Genes ◽  
Non Coding Rnas

: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are proficient in regulating gene expression post-transcriptionally. Considering the recent trend in exploiting non-coding RNAs (ncRNAs) as cancer therapeutics, the potential use of miRNAs and lncRNAs as biomarkers and novel therapeutic agents against angiogenesis is an important scientific aspect. An estimated 70% of the genome is actively transcribed, only 2% of which codes for known protein-coding genes. Long noncoding RNAs (lncRNAs) are a large and diverse class of RNAs > 200 nucleotides in length, and not translated into protein, and are of utmost importance and it governs the expression of genes in a temporal, spatial, and cell context-dependent manner. Angiogenesis is an essential process for organ morphogenesis and growth during development, and it is relevant during the repair of wounded tissue in adults. It is coordinated by an equilibrium of pro-and anti-angiogenic factors; nevertheless, when affected, it promotes several diseases, including breast cancer. Signaling pathways involved here are tightly controlled systems that regulate the appropriate timing of gene expression required for the differentiation of cells down a particular lineage essential for proper tissue development. Lately, scientific reports are indicating that ncRNAs, such as miRNAs, and lncRNAs, play critical roles in angiogenesis related to breast cancer. The specific roles of various miRNAs and lncRNAs in regulating angiogenesis in breast cancer, with particular focus on the downstream targets and signaling pathways regulated by these ncRNAs with molecular medicine perspective, are highlighted in this write-up.

scholarly journals Arrdc2 and Arrdc3 elicit divergent changes in gene expression in skeletal muscle following anabolic and catabolic stimuli

2019 ◽  
Vol 51 (6) ◽  
pp. 208-217 ◽  
Author(s):  
Bradley S. Gordon ◽  
Michael L. Rossetti ◽  
Alexey M. Eroshkin
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Tibialis Anterior ◽  
Gene Networks ◽  
Tibialis Anterior Muscle ◽  
The Body ◽  
Molecular Networks ◽  
Expression Of Genes ◽  
Consistent Change ◽  
Mechanical Overload

Skeletal muscle is a highly plastic organ regulating various processes in the body. As such, loss of skeletal muscle underlies the increased morbidity and mortality risk that is associated with numerous conditions. However, no therapies are available to combat the loss of muscle mass during atrophic conditions, which is due in part to the incomplete understanding of the molecular networks altered by anabolic and catabolic stimuli. Thus, the current objective was to identify novel gene networks modulated by such stimuli. For this, total RNA from the tibialis anterior muscle of mice that were fasted overnight or fasted overnight and refed the next morning was subjected to microarray analysis. The refeeding stimulus altered the expression of genes associated with signal transduction. Specifically, expression of alpha arrestin domain containing 2 (Arrdc2) and alpha arrestin domain containing 3 (Arrdc3) was significantly lowered 70–85% by refeeding. Subsequent analysis showed that expression of these genes was also lowered 50–75% by mechanical overload, with the combination of nutrients and mechanical overload acting synergistically to lower Arrdc2 and Arrdc3 expression. On the converse, stimuli that suppress growth such as testosterone depletion or acute aerobic exercise increased Arrdc2 and Arrdc3 expression in skeletal muscle. While Arrdc2 and Arrdc3 exhibited divergent changes in expression following anabolic or catabolic stimuli, no other member of the Arrdc family of genes exhibited the consistent change in expression across the analyzed conditions. Thus, Arrdc2 and Arrdc3 are a novel set of genes that may be implicated in the regulation of skeletal muscle mass.

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