scholarly journals The Relevance of MicroRNAs in the Pathogenesis and Prognosis of HCV-Disease: The Emergent Role of miR-17-92 in Cryoglobulinemic Vasculitis

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1364
Author(s):  
Serena Lorini ◽  
Laura Gragnani ◽  
Anna Linda Zignego

Hepatitis C virus (HCV) is a major public health problem. HCV is a hepatotropic and lymphotropic virus that leads to hepatocellular carcinoma (HCC) and lymphoproliferative disorders such as cryoglobulinemic vasculitis (CV) and non-Hodgkin’s lymphoma (NHL). The molecular mechanisms by which HCV induces these diseases are not fully understood. MicroRNAs (miRNAs) are small non-coding molecules that negatively regulate post-transcriptional gene expression by decreasing their target gene expression. We will attempt to summarize the current knowledge on the role of miRNAs in the HCV life cycle, HCV-related HCC, and lymphoproliferative disorders, focusing on both the functional effects of their deregulation as well as on their putative role as biomarkers, based on association analyses. We will also provide original new data regarding the miR 17-92 cluster in chronically infected HCV patients with and without lymphoproliferative disorders who underwent antiviral therapy. All of the cluster members were significantly upregulated in CV patients compared to patients without CV and significantly decreased in those who achieved vasculitis clinical remission after viral eradication. To conclude, miRNAs play an important role in HCV infection and related oncogenic processes, but their molecular pathways are not completely clear. In some cases, they may be potential therapeutic targets or non-invasive biomarkers of tumor progression.

Author(s):  
Shaha Pramod ◽  
Ragi Skanda ◽  
Bhoite Amol ◽  
Tamboli Asif ◽  
Gautama Amol

Introduction: Pulmonary embolism (PE) is the third most common acute heart disease after myocardial infarction and stroke and is a major public health problem. PE is a disease that has high morbidity and mortality, yet it is challenging to obtain a diagnosis. Objective: The study aims to assess the role of MDCT-PA in the diagnosis of pulmonary embolism, and it's associated conditions in suspected cases of pulmonary embolism. Materials and Methods: The study was conducted in the department of radiology in KRISHNA INSTITUTE OF MEDICAL SCIENCES DEEMED TO BE UNIVERSITY situated in KARAD equipped with a 16 slice MDCT scanner (EMOTION) manufactured by Siemens. Results: Through the study period of one and half year and have met the inclusion criteria, a total of 90 consecutive patients who presented with suspicion of PE were referred for MDCT-PA in the department of radio-diagnosis, Krishna Hospital, Karad. A review of all the cases was done, and the results were presented in the form of tables. Conclusion: Multidetector computed tomography pulmonary angiography can be used to confidently diagnose pulmonary embolism in which it is not contraindicated. MDCT-PA is the investigation of choice because it is a rapid, non-invasive study, highly sensitive and specific.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Anna Linda Zignego ◽  
Carlo Giannini ◽  
Laura Gragnani

Hepatitis C virus (HCV) infection is a serious public health problem because of its worldwide diffusion and sequelae. It is not only a hepatotropic but also a lymphotropic agent and is responsible not only for liver injury—potentially evolving to cirrhosis and hepatocellular carcinoma—but also for a series of sometimes severely disabling extrahepatic diseases and, in particular, B-cell lymphoproliferative disorders. These latter range from benign, but prelymphomatous conditions, like mixed cryoglobulinemia, to frank lymphomas. Analogously withHelicobacter pylorirelated lymphomagenesis, the study of the effects of viral eradication confirmed the etiopathogenetic role of HCV and showed it is an ideal model for better understanding of the molecular mechanisms involved. Concerning these latter, several hypotheses have been proposed over the past two decades which are not mutually exclusive. These hypotheses have variously emphasized the important role played by sustained stimulation of the immune system by HCV, infection of the lymphatic cells, viral proteins, chromosomal aberrations, cytokines, or microRNA molecules. In this paper we describe the main hypotheses that have been proposed with the corresponding principal supporting data.


Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 594 ◽  
Author(s):  
Daniela Pellegrino ◽  
Daniele La Russa ◽  
Alessandro Marrone

Chronic kidney disease (CKD) is a major public health problem worldwide and affects both elderly and young subjects. Its main consequences include the loss of renal function, leading to end-stage renal disease, an increased risk of cardiovascular disease, a significant increase in morbidity and mortality, and a decrease in health-related quality of life. This review arose in significant part from work in the authors’ laboratory, complemented by literature data, and was based on a translational approach: we studied the role of many CKD risk factors, such as hypertension, obesity, and oxidative stress/inflammation. The aim was to identify new molecular mechanisms of kidney damage to prevent it through successful behavior modifications. For this purpose, in our studies, both human and animal models were used. In the animal models, we analyzed the mechanisms of renal damage induced by hypertension (spontaneously hypertensive rats) and obesity (cafeteria diet-fed rats), showing that redox disequilibrium in plasma and tissue is extremely important in renal alteration in terms of both oxidative damage (lipid peroxidation, altered expression antioxidant enzymes) and apoptotic pathway (intrinsic/extrinsic) activation. In hemodialysis patients, we explored the correlation between the global oxidative balance and both inflammatory markers and cardiovascular risk, showing a strong correlation between the oxidative index and the blood levels of C-reactive protein and previous cardiovascular events. This multilevel approach allowed us to individually and synergistically analyze some aspects of the complex pathogenic mechanisms of CKD in order to clarify the role of the new amplified risk factors for CKD and to prepare an effective personalized prevention plan by acting on both modifiable and nonmodifiable risk factors.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
D. Calzada ◽  
S. Baos ◽  
L. Cremades-Jimeno ◽  
B. Cárdaba

The immune system regulates itself to establish an appropriate immune response to potentially harmful pathogens while tolerating harmless environmental antigens and self-antigens. A central role in this balance is played by regulatory T cells (Tregs) through various ways of actions. By means of molecule secretion and cell-cell contact mechanisms, Tregs may have the capacity to modulate effector T cells and suppress the action of proinflammatory cytokines across a broad range of cell types. As a result, abnormal regulatory T cell function has been pointed as a main cause in the development of allergic diseases, a major public health problem in industrialized countries, with a high socioeconomic impact. This prevalence and impact have created an international interest in improving the allergy diagnosis and therapy. Additionally, research has sought to gain a better understanding of the molecular mechanisms underlining this kind of disease, in order to a better management. At this respect, the role of Treg cells is one of the most promising areas of research, mainly because of their potential use as new immunotherapeutical approaches. Therefore, the aim of this review is to update the existing knowledge of the role of Tregs in this pathology deepening in their implication in allergen-specific therapy (AIT).


2016 ◽  
Vol 64 (6) ◽  
pp. 1078-1081 ◽  
Author(s):  
Suthat Liangpunsakul ◽  
Bin Gao

Alcoholic liver disease (ALD) is a major public health problem worldwide and is the leading cause of end-stage liver disease. While the ultimate control of ALD will require the prevention of alcohol abuse, better understanding of the mechanisms of alcohol-induced liver injury may lead to treatments of fatty liver, alcoholic hepatitis, and prevention or delay of occurrence of cirrhosis. The elucidation and the discovery of several new concepts in ALD pathogenesis have raised our understanding on the complex mechanisms and the potential in developing the new strategies for therapeutic benefits. In this review, we provide the most up-to-date information on the basic molecular mechanisms focusing on the role of fat-specific protein 27/CIDEC in the pathogenesis of ALD.


2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 967-971
Author(s):  
Poonam Thakre ◽  
Waqar M. Naqvi ◽  
Trupti Deshmukh ◽  
Nikhil Ingole ◽  
Sourabh Deshmukh

The emergence in China of 2019 of severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) previously provisionally names 2019-nCoV disease (COVID19) caused major global outbreak and is a major public health problem. On 30 January 2020, the WHO declared COVID19 to be the sixth international public health emergency. This present pandemic has engrossed the globe with a high rate of mortality. As a front line practitioner, physiotherapists are expected to be getting in direct contact with patients infected with the virus. That’s why it is necessary for understanding the many aspects of their role in the identification, contains, reduces and treats the symptoms of this disease. The main presentation is the involvement of respiratory system with symptoms like fever, cough, sore throat, sneezing and characteristics of pneumonia leads to ARDS(Acute respiratory distress syndrome) also land up in multiorgan dysfunction syndrome. This text describes and suggests physiotherapy management of acute COVID-19 patients. It also includes recommendations and guidelines for physiotherapy planning and management. It also covers the guidelines regarding personal care and equipment used for treatment which can be used in the treatment of acute adult patients with suspected or confirmed COVID-19.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Godfrey Grech ◽  
Marieke von Lindern

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.


2021 ◽  
Vol 17 (7) ◽  
pp. 141-152
Author(s):  
Tamoud Modak, MD, DM ◽  
Siddharth Sarkar, MD, MRCPsych ◽  
Yatan Pal Singh Balhara, MD

Opioid use disorder is a major public health problem, and opioid replacement therapy with buprenorphine (BPN) is a clinically effective and evidence-based treatment for it. To deter misuse of the tablet through the injecting route, BPN coformulated with naloxone (BNX) in 4:1 ratio is available in many countries. Despite this, significant diversion and injecting use of the BNX combination has been reported from across the world. In this article, the pharmacological properties of BPN and BNX and the evidence for their diversion are reviewed. Also, a critical examination is made of the evidence supporting the role of naloxone in reducing the agonist effects of BPN when used through the injecting route. Based on this evidence, a hypothesis explaining the continued diversion of BNX has been proposed.


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