scholarly journals Interleukin-33/ Suppression of Tumorigenicity 2 in Renal Fibrosis: Emerging Roles in Prognosis and Treatment

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Yang Tan ◽  
Hao-Yue Jing ◽  
Yue-Rong Ma

Chronic kidney disease (CKD) is a major public health problem that affects more than 10% of the population worldwide and has a high mortality rate. Therefore, it is necessary to identify novel treatment strategies for CKD. Incidentally, renal fibrosis plays a central role in the progression of CKD to end-stage renal disease (ESRD). The activation of inflammatory pathways leads to the development of renal fibrosis. In fact, interleukin-33 (IL-33), a newly discovered member of the interleukin 1 (IL-1) cytokine family, is a crucial regulator of the inflammatory process. It exerts pro-inflammatory and pro-fibrotic effects via the suppression of tumorigenicity 2 (ST2) receptor, which, in turn, activates other inflammatory pathways. Although the role of this pathway in cardiac, pulmonary, and hepatic fibrotic diseases has been extensively studied, its precise role in renal fibrosis has not yet been completely elucidated. Recent studies have shown that a sustained activation of IL-33/ST2 pathway promotes the development of renal fibrosis. However, with prolonged research in this field, it is expected that the IL-33/ST2 pathway will be used as a diagnostic and prognostic tool for renal diseases. In addition, the IL-33/ST2 pathway seems to be a new target for the future treatment of CKD. Here, we review the mechanisms and potential applications of the IL-33/ST2 pathway in renal fibrosis; such that it can help clinicians and researchers to explore effective treatment options and develop novel medicines for CKD patients.

Author(s):  
Antonio Munafò ◽  
Stefano Frara ◽  
Norberto Perico ◽  
Rosaria Di Mauro ◽  
Monica Cortinovis ◽  
...  

AbstractObesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with β3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree.


Author(s):  
Md. Mahmudul Amin

Diabetes is a major public health problem which has been increasing day by day throughout the world with an alarming rate. In recent years, several plant extracts have been examined for their anti-diabetic properties to identify alternative treatment strategies that pose less risk for diabetes. It has been shown that different parts of these plants are collected from diverse regions and administered in different pharmaceutical preparations. The aim of the present review is to provide an overview of the phytochemicals present in S. cumini plants and their potent anti-diabetic activity, toxicological and biological effects of these plant extracts, their current state, limitation and future prospects in developing countries that are not included in the European Pharmacopoeia. In addition, a prospective research result of synergistic use of this plant with other plant (Ficus racemosa) done presently in our laboratory has been included. Based on the available evidence, we highlight the ways in which their therapeutic potential can be properly harnessed and provide scientific evidence for the discovery of novel leads for herbal drug development.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Perditer Okyere ◽  
Isaac Okyere ◽  
Richard Kobina Dadzie Ephraim ◽  
Joseph Attakorah ◽  
Charlotte Osafo ◽  
...  

Background. Renal diseases over the years have become one of the leading causes of morbidity and mortality worldwide. In this study, we assessed the spectrum and clinical characteristics of Ghanaians with renal diseases at the nephrology unit of Komfo Anokye Teaching Hospital (KATH), Kumasi. Methods. This was a retrospective hospital-based study conducted at Komfo Anokye Teaching Hospital (KATH) from the years 2005 to 2017. A non-randomized sampling approach was used to include 1426 participants who were diagnosed with AKI, CKD, ESRD, and nephrotic syndrome at the nephrology unit of KATH during the years under review. All the 1426 patients were eligible for the study. Demographic characteristics as well as clinical data such as the kind of renal disease presentation, causes of the renal disease, and the treatment options were also obtained from their records. Results. Overall, 1009 of the total participants had CKD (70.76%), 295 participants had ESRD (20.69%), 72 participants had AKI (5.05%), and 50 participants had nephrotic syndrome (3.51%). Furthermore, 69 (23.4%) participants with ESRD were on dialysis whiles 6 (8.3) and 17 (1.7) participants with only AKI and CKD superimposed AKI, respectively, were on dialysis. 226 (76.6%) participants with ESRD were on conservative therapy. Hypertension emerged as the major cause of renal disease presentation (53.93%) with bilateral leg edema (13.46%) being the major complaint. There was a significant association between CKD and age (p≤0.001). Nephrotic syndrome also showed a significant association with age (p≤0.001). Conclusion. This study revealed that patients at the nephrology unit of KATH, Ghana, are mainly adults between ages 46–55. The clinical pattern of renal diseases is dominated by CKD and ESRD. We conclude that hypertension, chronic glomerulonephritis, diabetic nephropathy, and sepsis are the most common causes of renal diseases. The commonest clinical presentations are bilateral leg edema, palpitations, headache, breathlessness, dizziness, and vomiting. Early diagnosis and management of these conditions may prevent or delay the progress to end-stage renal disease.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Md Sayed Ali Sheikh ◽  
Umme Salma ◽  
Baohai Zhang ◽  
Jimei Chen ◽  
Jian Zhuang ◽  
...  

Heart failure is a major public health problem especially in the aging population (≥65 years old), affecting nearly 5 million Americans and 15 million European people. Effective management of heart failure (HF) depends on a correct and rapid diagnosis. Presently, BNP (brain natriuretic peptide) or N-terminal pro-brain natriuretic peptide (NT-proBNP) assay is generally accepted by the international community for diagnostic evaluation and risk stratification of patients with HF. However, regardless of its widespread clinical use, BNP is still encumbered by reduced specificity. As a result, diagnosis of heart failure remains challenging. Although significant improvement happened in the clinical management of HF over the last 2 decades, traditional treatments are ultimately ineffective in many patients who progress to advanced HF. Therefore, a novel diagnostic, prognostic biomarker and new therapeutic approach are required for clinical management of HF patients. Circulating miRNAs seem to be the right choice for novel noninvasive biomarkers as well as new treatment strategies for HF. In this review, we briefly discuss the diagnostic, prognostic, and therapeutic role of circulating miRNAs in heart failure patients. We also mentioned our own technique of extraction of RNA and detection of circulating miRNAs from human plasma and oxidative stress associated miRNAs with HF.


F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 367 ◽  
Author(s):  
Raoel Maan ◽  
Adriaan J. van der Meer

Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population.


2019 ◽  
Vol 8 ◽  
pp. 216495611985803 ◽  
Author(s):  
Deanna R Befus ◽  
Sharon Hull ◽  
Justine Strand de Oliveira ◽  
Gillian Sanders Schmidler ◽  
Morris Weinberger ◽  
...  

Background Migraine is a disabling neurological disorder and the sixth biggest cause of disability worldwide. The World Health Organization has declared migraine a major public health problem due to a paucity of knowledge about cause and effective treatment options. Both in incidence and severity, migraine disproportionately affects people occupying marginalized social locations (SL). Managed pharmacologically, migraine is treated with daily preventive and as-needed abortive medications. Both come with high literal and figurative costs: intolerable side effects, medication interactions, and prohibitive prices. Cost prohibitive, ineffective, and unsustainable pharmacological treatment options have contributed to high levels of interest in complementary approaches by people with migraine, but little is known about their motivations, patterns of use or access, or how these may vary by SL. Method We conducted focus groups with 30 people with migraine to explore their desires and recommendations for migraine clinicians and researchers. We used qualitative content analysis to identify themes. Outcomes: We identified 4 themes: a more holistic, collaborative, long-term treatment approach; medication as a short-term solution; high personal and economic costs of medication; and desire for more information and access to natural approaches. Across SL, participants expressed keen interest in integrative approaches and wanted better access to complementary modalities. Participants in marginalized SL described reliance on traditional/folk remedies, including engagement with family and community healers, who they described as more affordable and culturally accessible. Conclusions Holistic and integrative approaches were preferred over medication as long-term migraine management strategies. However, people in marginalized SL, while disproportionately disabled by migraine, did not feel as comfortable accessing integrative approaches through currently available channels. Engaging with these communities and using a critical lens to explore barriers to access can develop options to make complementary modalities more approachable, while also attending to systemic blind spots that may unintentionally alienate socially marginalized groups.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Xingyong Wan ◽  
Chengfu Xu ◽  
Chaohui Yu ◽  
Youming Li

Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major public health problem worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD that may progress to cirrhosis and hepatocellular carcinoma. The pathogenesis of disease progression from NAFLD to NASH has not been fully understood. Immunological mechanisms that have been increasingly recognized in the disease progression include defects in innate immunity, adaptive immunity, Toll-like receptor (TLR) signaling, and gut-liver axis. The NLRP3 inflammasome is an intracellular multiprotein complex involved in the production of mature interleukin 1-beta (IL-1β) and induces metabolic inflammation. NLRP3 inflammasome has been recently demonstrated to play a crucial role in the progression of NASH. This review highlights the recent findings linking NLRP3 inflammasome to the progression of NASH.


2019 ◽  
Vol 67 (9) ◽  
pp. 701-715 ◽  
Author(s):  
Niki Prakoura ◽  
Juliette Hadchouel ◽  
Christos Chatziantoniou

Renal fibrosis is an important component of chronic kidney disease, an incurable pathology with increasing prevalence worldwide. With a lack of available therapeutic options, end-stage renal disease is currently treated with renal replacement therapy through dialysis or transplantation. In recent years, many efforts have been made to identify novel targets for therapy of renal diseases, with special focus on the characterization of unknown mediators and pathways participating in renal fibrosis development. Using experimental models of renal disease and patient biopsies, we identified four novel mediators of renal fibrosis with potential to constitute future therapeutic targets against kidney disease: discoidin domain receptor 1, periostin, connexin 43, and cannabinoid receptor 1. The four candidates were highly upregulated in different models of renal disease and were localized at the sites of injury. Subsequent studies showed that they are centrally involved in the underlying mechanisms of renal fibrosis progression. Interestingly, inhibition of either of these proteins by different strategies, including gene deletion, antisense administration, or specific blockers, delayed the progression of renal disease and preserved renal structure and function, even when the inhibition started after initiation of the disease. This review will summarize the current findings on these candidates emphasizing on their potential to constitute future targets of therapy:


2012 ◽  
Vol 8 (3) ◽  
pp. 313-321 ◽  
Author(s):  
Nadi K Gupta ◽  
Christine A Bowman

Sexually transmitted infections (STIs) constitute a major public health problem in the UK and may result in very costly complications. Many STIs pose the risk of a number of adverse pregnancy outcomes including miscarriage, still birth, preterm delivery, low birth weight and ophthalmia neonatorum. National guidelines for the management of STIs are produced and regularly revised by the British Association of Sexual Heath and HIV. This review outlines the latest recommended treatment options during pregnancy for the commonly encountered STIs.


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