Exploring the potential of drug repurposing for liver diseases: A comprehensive study.

Drug repurposing involves the investigation of existing drugs for new indications. It offers a great opportunity to quickly identify a new drug candidate at a lower cost than novel discovery and development. Despite the importance and potential role of drug repurposing, there is no specific definition that healthcare providers and the World Health Organization credit. Unfortunately, many similar and interchangeable concepts are being used in the literature, making it difficult to collect and analyze uniform data on repurposed drugs. This research was conducted based on understanding general criteria for drug repurposing, concentrating on liver diseases. Many drugs have been investigated for their effect on liver diseases even though they were originally approved (or on their way to being approved) for other diseases. Some of the hypotheses for drug repurposing were first captured from the literature and then processed further to test the hypothesis. Recently, with the revolution in bioinformatics techniques, scientists have started to use drug libraries and computer systems that can analyze hundreds of drugs to give a short list of candidates to be analyzed pharmacologically. However, this study revealed that drug repurposing is a potential aid that may help deal with liver diseases. It provides available or under-investigated drugs that could help treat hepatitis, liver cirrhosis, Wilson disease, liver cancer, and fatty liver. However, many further studies are needed to ensure the efficacy of these drugs on a large scale.

Stem Cells Reprogramming in Diabetes Mellitus and Diabetic Complications: Recent Advances.

BACKGROUND: The incidence of diabetes mellitus (DM) is dramatically increasing worldwide, and it is expected to affect 700 million cases by 2045. Diabetes influences health care economics, human quality of life, morbidity, and mortality, which were primarily seen extensively in developing countries. Uncontrolled DM, which results in consistent hyperglycemia, may lead to severe life-threatening complications such as nephropathy, retinopathy, neuropathy, and cardiovascular complications. METHODOLOGY: In addition to traditional therapies with insulin and oral anti-diabetics, researchers have developed new approaches for treatment, including stem cell (SC) therapy, which exhibits promising outcomes. Besides its significant role in treating type one DM (T1DM) and type two DM (T2DM), it can also attenuate diabetic complications. Furthermore, the development of insulin-producing cells can be achieved by using the different types of SCs, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and multiple types of adult stem cells, such as pancreatic, hepatic, and mesenchymal stem cells (MSC). All these types have been extensively studied and proved their ability to develop insulin-producing cells, but every type has limitations. CONCLUSION: This review aims to enlighten researchers about recent advances in stem cell research and their potential benefits in DM and diabetic complications.

Targeting necroptosis in fibrosis.

Necroptosis, a type of programmed cell death that resembles necrosis, is now known to depend on a different molecular mechanism from apoptosis, according to several recent studies. Many efforts have reported the possible influence of necroptosis in human disorders and concluded the crucial role in the pathophysiology of various diseases, including liver diseases, renal injuries, cancers, and others. Fibrosis is the most common end-stage pathological cascade of several chronic inflammatory disorders. In this review, we explain the impact of necroptosis and fibrosis, for which necroptosis has been demonstrated to be a contributing factor. We also go over the inhibitors of necroptosis and how they have been applied to fibrosis models. This review helps to clarify the role of necroptosis in fibrosis and will encourage clinical efforts to target this pathway of programmed cell death.

The melatonin receptor agonist agomelatine protects against acute pancreatitis induced by cadmium by attenuating inflammation and oxidative stress and modulating Nrf2/HO-1 pathway.

Pancreatitis is a serious effect of the heavy metal cadmium (Cd) and inflammation and oxidative stress (OS) are implicated in Cd-induced pancreatic injury. This study evaluated the effect of the melatonin receptor agonist agomelatine (AGM) on Cd-induced acute pancreatitis (AP), pointing to its modulatory effect on inflammation, OS, and Nrf2/HO-1 pathway. Rats were supplemented with AGM orally for 14 days and a single injection of cadmium chloride (CdCl2) on day 7. Cd increased serum amylase and lipase and caused pancreatic endocrine and exocrine tissue injury. Malondialdehyde (MDA), nitric oxide (NO) and myeloperoxidase (MPO) were elevated, nuclear factor (NF)-kB p65, inducible NO synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF)-α and CD40 were upregulated, and antioxidants were decreased in the pancreas of Cd-administered rats. AGM ameliorated serum amylase and lipase and pancreatic OS, NF-kB p65, CD40, pro-inflammatory mediators and caspase-3, prevented tissue injury and enhanced antioxidants. AGM downregulated Keap1 and enhanced Nrf2 and HO-1 in the pancreas of Cd-administered rats. In silico findings revealed the binding affinity of AGM with Keap1, HO-1, CD40L and caspase-3. In conclusion, AGM protected against AP induced by Cd by preventing inflammation, OS and apoptosis and modulating Nrf2/HO-1 pathway.

What's your cup of tea? The role of herbal compounds in the management of multiple sclerosis.

Multiple Sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease that is characterized by a complex etiology. Efforts towards the management of MS have long been directed towards symptomatic relief, as well as the use of immune-modulatory, disease modifying therapies; however, inconsistent treatment responses still prevail, increasing the risk for disease progression. While a great deal of research attempted to unravel the complexity of treatment responses in light of epigenetic variability, parallel efforts in the direction of alternative medicine may be as paramount. Herbal compounds have long been regarded as safe and versatile options for aiding in various disorders, including neurodegenerative conditions like MS. Numerous studies have taken interest in a myriad of herbal plants for their potential benefit in alleviating some of the most common MS symptoms such as spasticity and fatigue, delaying the progression of the disease, as well as influencing the overall quality of life for MS patients. This review aims to provide a comprehensive overview of recent clinical studies examining the effects of various herbal plants on different aspects of MS, in an attempt to shed light on an important tool for aiding in the management of this complex and multifactorial disease.

Rs205764 and rs547311 in linc00513 may influence treatment responses in multiple sclerosis patients: A pharmacogenomics Egyptian study.

Background: Multiple sclerosis (MS) is characterized by a complex etiology that is reflected in the lack of consistently predictable treatment responses across patients of seemingly similar characteristics. Approaches to demystify the underlying predictors of aberrant treatment responses have made use of genome-wide association studies (GWAS), with imminent progress made in identifying single nucleotide polymorphisms (SNPs) associated with MS risk, disease progression, and treatment response. Ultimately, such pharmacogenomic studies aim to utilize the approach of personalized medicine to maximize patient benefit and minimize rate of disease progression. Objective: Very limited research is available around the long intergenic non-coding RNA (linc)00513, recently being reported as a novel positive regulator of the type-1 interferon (IFN) pathway, following its overexpression in the presence of two polymorphisms: rs205764 and rs547311 in the promoter region of this gene. We attempt to provide data on the prevalence of genetic variations at rs205764 and rs547311 in Egyptian MS patients, and correlate these polymorphisms with the patients' responses to disease-modifying treatments. Methods: Genomic DNA from 144 RRMS patients was isolated and analyzed for genotypes at the positions of interest on linc00513 using RT-qPCR. Genotype groups were compared with regards to their response to treatment; additional secondary clinical parameters including the estimated disability status score (EDSS), and onset of the disease were examined in relation to these polymorphisms. Results: Polymorphisms at rs205764 were associated with a significantly higher response to fingolimod and a significantly lower response to dimethylfumarate. Moreover, the average EDSS of patients carrying polymorphisms at rs547311 was significantly higher, whereas no correlation appeared to exist with the onset of MS. Conclusion: Understanding the complex interplay of factors influencing treatment response is pivotal in MS. One of the factors contributing to a patient's response to treatment, as well as disease disability, may be polymorphisms on non-coding genetic material, such as rs205764 and rs547311 on linc00513. Through this work, we propose that genetic polymorphisms may partially drive disease disability and inconsistent responses to treatment in MS; we also aim to draw attention towards genetic approaches, such as screening for specific polymorphisms, to possibly direct treatment choices in such a complex disease.

Therapeutic interventions of acute and chronic liver disorders: A comprehensive review.

Liver disorders are one of the most common pathological problems worldwide. It affects more than 1.5 billion worldwide. Many types of hepatic cells have been reported to be involved in the initiation and propagation of both acute and chronic liver diseases, including hepatocytes, Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells (HSCs). In addition, oxidative stress, cytokines, fibrogenic factors, microRNAs, and autophagy are also involved. Understanding the molecular mechanisms of liver diseases leads to discovering new therapeutic interventions that can be used in clinics. Recently, antioxidant, anti-inflammatory, anti-HSCs therapy, gene therapy, cell therapy, gut microbiota, and nanoparticles have great potential for preventing and treating liver diseases. Here, we explored the recent possible molecular mechanisms involved in the pathogenesis of acute and chronic liver diseases. Besides, we overviewed the recent therapeutic interventions that targeted liver diseases and summarized the recent studies concerning liver disorders therapy.

COVID-19 and hepatic injury: cellular and molecular mechanisms in diverse liver cells.

The coronavirus disease 2019 (COVID-19) represents a global health and economic challenge. Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases. Besides, other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2, including cytokine storm, hypoxia, endothelial cells, and even some treatments for COVID-19. On the other hand, several groups of people could be at risk of hepatic COVID-19 complications, such as pregnant women and neonates. The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury, hepatic illness comorbidity, and risk factors. Besides, it is focused on the vaccination process and the role of developed vaccines in preventing hepatic injuries due to SARS-CoV-2 infection.

Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.

According to data provided by World Health Organization, hepatocellular carcinoma (HCC) is the sixth most common cause of deaths due to cancer worldwide. Tremendous progress has been achieved over the last 10 years developing novel agents for HCC treatment, including small-molecule kinase inhibitors. Several small molecule inhibitors currently form the core of HCC treatment due to their versatility since they would be more easily absorbed and have higher oral bioavailability, thus easier to formulate and administer to patients. In addition, they can be altered structurally to have greater volumes of distribution, allowing them to block extravascular molecular targets and to accumulate in a high concentration in the tumor microenvironment. Moreover, they can be designed to have shortened half-lives to control for immune-related adverse events. Most importantly, they would spare patients, healthcare institutions, and society as a whole from the burden of high drug costs. The present review provides an overview of the pharmaceutical compounds that are licensed for HCC treatment and other emerging compounds that are still investigated in preclinical and clinical trials. These molecules are targeting different molecular targets and pathways that are proven to be involved in the pathogenesis of the disease.