scholarly journals Role of apoptosis and autophagy in tuberculosis

2017 ◽  
Vol 313 (2) ◽  
pp. L218-L229 ◽  
Author(s):  
Adam Lam ◽  
Rohan Prabhu ◽  
Christine M. Gross ◽  
Lee Ann Riesenberg ◽  
Vinodkumar Singh ◽  
...  
Keyword(s):  
Vital Role ◽  
Host Responses ◽  
First Line ◽  
Active Infection ◽  
Primary Host ◽  
Treatment Regimens ◽  
Cellular Processes ◽  
Systemic Symptoms ◽  
Rich History

Tuberculosis (TB) is one of the oldest known human diseases and is transmitted by the bacteria Mycobacterium tuberculosis (Mtb). TB has a rich history with evidence of TB infections dating back to 5,800 b.c. TB is unique in its ability to remain latent in an individual for decades, with the possibility of later reactivation, causing widespread systemic symptoms. Currently, it is estimated that more than one-third of the world’s population (~2 billion people) are infected with Mtb. Prolonged periods of therapy and complexity of treatment regimens, especially in active infection, have led to poor compliance in patients being treated for TB. Therefore, it is vitally important to have a thorough knowledge of the pathophysiology of Mtb to understand the disease progression, as well as to develop novel diagnostic tests and treatments. Alveolar macrophages represent both the primary host cell and the first line of defense against the Mtb infection. Apoptosis and autophagy of macrophages play a vital role in the pathogenesis and also in the host defense against Mtb. This review will outline the role of these two cellular processes in defense against Mtb with particular emphasis on innate immunity and explore developing therapies aimed at altering host responses to the disease.

MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target

2020 ◽  
Vol 26 ◽  
Author(s):  
Yini Ma ◽  
Xiu Cao ◽  
Guojuan Shi ◽  
Tianlu Shi
Keyword(s):  
Digestive System ◽  
Target Genes ◽  
Malignant Neoplasm ◽  
Vital Role ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Promising Therapeutic Target ◽  
Direct Target ◽  
Potential Strategy

: MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles for cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as valuable biomarkers for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

scholarly journals The Role of Non-Coding RNAs in the Sorafenib Resistance of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinyao Hu ◽  
Hua Zhu ◽  
Yang Shen ◽  
Xiaoyu Zhang ◽  
Xiaoqin He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Circular Rnas ◽  
First Line ◽  
Advanced Hcc ◽  
Chemotherapy Agent ◽  
Development Of Resistance ◽  
Non Coding Rnas

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Sorafenib is approved by the U.S. Food and Drug Administration to be a first-line chemotherapy agent for patients with advanced HCC. A portion of advanced HCC patients can benefit from the treatment with sorafenib, but many patients ultimately develop sorafenib resistance, leading to a poor prognosis. The molecular mechanisms of sorafenib resistance are sophisticated and indefinite. Notably, non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are critically participated in the occurrence and progression of tumors. Moreover, growing evidence has suggested that ncRNAs are crucial regulators in the development of resistance to sorafenib. Herein, we integrally and systematically summarized the molecular mechanisms and vital role of ncRNAs impact sorafenib resistance of HCC, and ultimately explored the potential clinical administrations of ncRNAs as new prognostic biomarkers and therapeutic targets for HCC.

Regulation of hemidesmosome dynamics and cell signaling by integrin α6β4

2021 ◽  
Vol 134 (18) ◽  
Author(s):  
Lisa te Molder ◽  
Jose M. de Pereda ◽  
Arnoud Sonnenberg
Keyword(s):  
Signal Transduction ◽  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Cellular Processes ◽  
Integrin Α6β4

ABSTRACT Hemidesmosomes (HDs) are specialized multiprotein complexes that connect the keratin cytoskeleton of epithelial cells to the extracellular matrix (ECM). In the skin, these complexes provide stable adhesion of basal keratinocytes to the underlying basement membrane. Integrin α6β4 is a receptor for laminins and plays a vital role in mediating cell adhesion by initiating the assembly of HDs. In addition, α6β4 has been implicated in signal transduction events that regulate diverse cellular processes, including proliferation and survival. In this Review, we detail the role of α6β4 in HD assembly and beyond, and we discuss the molecular mechanisms that regulate its function.

scholarly journals The Potential of Telomeric G-Quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophils

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 249 ◽  
Author(s):  
Ekaterina A. Golenkina ◽  
Galina M. Viryasova ◽  
Nina G. Dolinnaya ◽  
Valeria A. Bannikova ◽  
Tatjana V. Gaponova ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Viral Infections ◽  
Uv Spectroscopy ◽  
Human Neutrophils ◽  
First Line ◽  
Cellular Effects ◽  
Cellular Processes ◽  
G Quadruplex ◽  
New Generation

Human neutrophils are the first line of defense against bacterial and viral infections. They eliminate pathogens through phagocytosis, which activate the 5-lipoxygenase (5-LOX) pathway resulting in synthesis of leukotrienes. Using HPLC analysis, flow cytometry, and other biochemical methods, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs) able to fold into G-quadruplex structures on the main functions of neutrophils. Designed ODNs contained four human telomere TTAGGG repeats (G4) including those with phosphorothioate oligoguanosines attached to the end(s) of G-quadruplex core. Just modified analogues of G4 was shown to more actively than parent ODN penetrate into cells, improve phagocytosis of Salmonella typhimurium bacteria, affect 5-LOX activation, the cytosol calcium ion level, and the oxidative status of neutrophils. As evident from CD and UV spectroscopy data, the presence of oligoguanosines flanking G4 sequence leads to dramatic changes in G-quadruplex topology. While G4 folds into a single antiparallel structure, two main folded forms have been identified in solutions of modified ODNs: antiparallel and dominant, more stable parallel. Thus, both the secondary structure of ODNs and their ability to penetrate into the cytoplasm of cells are important for the activation of neutrophil cellular effects. Our results offer new clues for understanding the role of G-quadruplex ligands in regulation of integral cellular processes and for creating the antimicrobial agents of a new generation.

scholarly journals Pathobiology of pulmonary arterial hypertension: understanding the roads less travelled

2017 ◽  
Vol 26 (146) ◽  
pp. 170093 ◽  
Author(s):  
Anna R. Hemnes ◽  
Marc Humbert
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Critical Role ◽  
Fatal Disease ◽  
Treatment Regimens ◽  
Cellular Processes ◽  
Considerable Research ◽  
Pulmonary Arterial ◽  
Target Alternative

The pathobiology of pulmonary arterial hypertension (PAH) is complex and incompletely understood. Although three pathogenic pathways have been relatively well characterised, it is widely accepted that dysfunction in a multitude of other cellular processes is likely to play a critical role in driving the development of PAH. Currently available therapies, which all target one of the three well-characterised pathways, provide significant benefits for patients; however, PAH remains a progressive and ultimately fatal disease. The development of drugs to target alternative pathogenic pathways is, therefore, an attractive proposition and one that may complement existing treatment regimens to improve outcomes for patients. Considerable research has been undertaken to identify the role of the less well-understood pathways and in this review we will highlight some of the key discoveries and the potential for utility as therapeutic targets.

scholarly journals The role of the cardiac lymphatic system in the development and progression of heart failure and novel therapeutic approaches for its management in post-infarction cardiac remodeling

2020 ◽  
Vol 19 (3) ◽  
pp. 2281
Author(s):  
Yu. S. Korneva ◽  
R. V. Ukrainets
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Remodeling ◽  
Lymphatic Vessels ◽  
Myocardial Damage ◽  
Myocardial Edema ◽  
Experimental Models ◽  
Vital Role ◽  
Treatment Regimens

Cardiac lymphatic vessels play a vital role in maintaining homeostasis in both physiological and pathological conditions, providing outflow of metabolites. It has been shown that myocardial infarction and postinfarction cardiac remodeling is accompanied by the lymphatic remodeling, which entails functional disorders and is of great importance in heart failure pathogenesis. As a result of progressive myocardial edema, hypoxia and fibrosis of the interstitial space increase, aggravating edema. Other pathways of additional myocardial damage and contractility reduction are triggered. Lymphatic efflux is associated with arrhythmias. Experimental models showed the positive effect of exogenous activation of lymphangiogenesis in relation to the prevention and treatment of heart failure, which can be further used to improve treatment regimens. This review discusses cardiac lymphatic remodeling after myocardial infarction, as well as the pathogenesis of related complications.

scholarly journals Role of noncoding RNA in drug resistance of prostate cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Lifeng Ding ◽  
Ruyue Wang ◽  
Danyang Shen ◽  
Sheng Cheng ◽  
Huan Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Vital Role ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Remarkable Progress ◽  
Made In

AbstractProstate cancer is one of the most prevalent forms of cancer around the world. Androgen-deprivation treatment and chemotherapy are the curative approaches used to suppress prostate cancer progression. However, drug resistance is extensively and hard to overcome even though remarkable progress has been made in recent decades. Noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, are a group of cellular RNAs which participate in various cellular processes and diseases. Recently, accumulating evidence has highlighted the vital role of non-coding RNA in the development of drug resistance in prostate cancer. In this review, we summarize the important roles of these three classes of noncoding RNA in drug resistance and the potential therapeutic applications in this disease.

scholarly journals The Role of mTOR Inhibitors in Hematologic Disease: From Bench to Bedside

2021 ◽  
Vol 10 ◽  
Author(s):  
Yimei Feng ◽  
Xiaoli Chen ◽  
Kaniel Cassady ◽  
Zhongmin Zou ◽  
Shijie Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Hematological Malignancies ◽  
Mtor Inhibitors ◽  
Cellular Growth ◽  
Hematologic Disease ◽  
Graft Versus Host ◽  
Treatment Regimens ◽  
Cellular Processes ◽  
Glucose And Lipid Metabolism

The mTOR pathway plays a central role in many cellular processes, such as cellular growth, protein synthesis, glucose, and lipid metabolism. Aberrant regulation of mTOR is a hallmark of many cancers, including hematological malignancies. mTOR inhibitors, such as Rapamycin and Rapamycin analogs (Rapalogs), have become a promising class of agents to treat malignant blood diseases—either alone or in combination with other treatment regimens. This review highlights experimental evidence underlying the molecular mechanisms of mTOR inhibitors and summarizes their evolving role in the treatment of hematologic disease, including leukemia, lymphoma, myeloma, immune hemocytopenia, and graft-versus-host disease (GVHD). Based on data presented in this review, we believe that mTOR inhibitors are becoming a trusted therapeutic in the clinical hematologist’s toolbelt and should be considered more routinely in combination therapy for the management of hematologic disease.

Mass Spectrometry Investigation of Glycosylation Aberration via De-N-Glycopeptide Analysis

2013 ◽  
Vol 66 (7) ◽  
pp. 770 ◽  
Author(s):  
Vivekananda Shetty ◽  
Ramila Philip
Keyword(s):  
Mass Spectrometry ◽  
Vital Role ◽  
Cellular Processes ◽  
Challenging Tasks ◽  
Proteomics Research ◽  
Disease Initiation ◽  
Branched Structures ◽  
Glycopeptide Analysis

Proteomics research on glycan alterations has received great attention owing to their implications in disease initiation and progression. Determination of the glycoprotein expression remains one of the most challenging tasks as the glycan residues in a given glycoprotein exist in complex branched structures and differ in linkage. In view of the vital role of glycan changes in cellular processes and disease progression, there has been an increased interest in developing methodologies for the detection of these changes. A subset of proteomics methods are discussed here that demonstrate the utility of the glycan-free de-N-glycopeptide analysis for the screening of complex glycoproteome as well as discovery of glycopeptide/glycoprotein biomarkers.

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