Advances in research on pharmacotherapy of sarcopenia.
Ontology highlight
ABSTRACT:
SUBMITTER: Feike Y
PROVIDER: S-EPMC8444957 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease mostly seen in middle-aged women characterized by progressive nonsuppurative destruction of small bile ducts resulting in intrahepatic cholestasis, parenchymal injury and ultimately end-stage liver disease. Despite major breakthroughs in our understanding of PBC, there remains only one FDA-approved agent for treatment: ursodeoxycholic acid (UDCA) to which one-third of patients are unresponsive.Biochemical response to treatment with UDCA is associated with excellent survival rates in PBC patients. However, there is a need for alternative treatments for nonresponders. Results from human epidemiological and genetic studies as well as preclinical studies in PBC animal models have provided a strong impetus for the development of new therapeutic agents. In this review, we discuss the recent advances in translational research in PBC focusing on promising therapeutic approaches, namely immune-based targeted therapies and agents targeting the synthesis and circulation of bile acids.We are in a new era for the development of novel therapies for PBC. Data on fibrates, budesonide and obeticholic acid offer encouragement for nonresponders to UDCA.
| S-EPMC4591873 | biostudies-literature
Project description:Abstract The coronavirus infectious disease-2019 (COVID-19) has overwhelmed like a shock wave in a completely unprepared world. Despite coronavirus infections were involved in previous epidemic outbreaks, no antiviral agent was developed for specific treatment. As a consequence, since the beginning of this pandemic, both repositioned and experimental drugs were used to treat the infected patients without evidence of clinical efficacy. Just based on experience coming from the use of antiviral agents to treat other viruses (eg, lopinavir/ritonavir, remdesivir) and supposed antiviral or immunomodulatory activities of drugs with no approved antiviral indications (eg hydroxychloroquine, tocilizumab), clinicians have faced the ongoing pandemic. Currently, after about 9 months from the COVID-19 spread, there is still no antiviral agent capable of ensuring the cure of this syndrome. Clinical trials are beginning to confirm the benefits of some drugs, while for other compounds, efficacy and safety have not yet been confirmed. Randomized clinical trials (RCT) have denied or downsized the beneficial effects attributed to certain molecules, such as aminoquinolines, largely used in clinical practice at the beginning of COVID-19 spread. Conversely, at the same time, they have provided evidence for unexpected effectiveness of other agents that have been underutilized, such as steroids, which were not used in SARS treatment because of the threatened effect on viral replication. Evidence deriving from pathologic studies have demonstrated that the prothrombotic effects of SARS-CoV-2 can be prevented by heparin prophylaxis, underlining the need for personalized treatment for patients with severe disease. The main aim of this review is to synthesize the available information and evidence on both repositioned and experimental drugs for the treatment of COVID-19, focusing on the need to exercise caution on the use of unproven medical therapies.
| S-EPMC7800714 | biostudies-literature
Project description:BackgroundPatients with 21-hydroxylase deficiency congenital adrenal hyperplasia (21OHD-CAH) have poor health outcomes with increased mortality, short stature, impaired fertility, and increased cardiovascular risk factors such as obesity. To address this, there are therapies in development that target the clinical goal of treatment, which is to control excess androgens with an adrenal replacement dose of glucocorticoid.MethodsNarrative review of publications on recent clinical developments in the pharmacotherapy of congenital adrenal hyperplasia.SummaryTherapies in clinical development target different levels of the hypothalamo-pituitary-adrenal axis. Two corticotrophin-releasing factor type 1 (CRF1) receptor antagonists, Crinecerfont and Tildacerfont, have been trialled in poorly controlled 21OHD-CAH patients, and both reduced ACTH and androgen biomarkers while patients were on stable glucocorticoid replacement. Improvements in glucocorticoid replacement include replacing the circadian rhythm of cortisol that has been trialled with continuous s.c. infusion of hydrocortisone and Chronocort, a delayed-release hydrocortisone formulation. Chronocort optimally controlled 21OHD-CAH in 80% of patients on an adrenal replacement dose of hydrocortisone, which was associated with patient-reported benefits including restoration of menses and pregnancies. Adrenal-targeted therapies include the steroidogenesis-blocking drug Abiraterone acetate, which reduced adrenal androgen biomarkers in poorly controlled patients.ConclusionsCRF1 receptor antagonists hold promise to avoid excess glucocorticoid replacement in patients not controlled on standard or circadian glucocorticoid replacement such as Chronocort. Gene and cell therapies are the only therapeutic approaches that could potentially correct both cortisol deficiency and androgen excess.
| S-EPMC8679847 | biostudies-literature
Project description:Mercury (Hg) is a highly toxic, non-essential, naturally occurring metal with a variety of uses. Mercury is not required for any known biological process and its presence in the human body may be detrimental, especially to the nervous system. Both genetic and behavioral studies suggest that mercury levels, age (both of exposure and at testing), and genetic background determine disease processes and outcome. The metal receptors and genes responsible for mercury metabolism also appear to play a pivotal role in the etiology of mercury-induced pathology. This review presents information about the latest advances in mercury research, with particular focus on low-level exposures and the contribution of genetics to toxic outcome. Future studies should address the contribution of genetics and low-level mercury exposure to disease, namely gene x environment interactions, taking into consideration age of exposure as developing animals are exquisitely more sensitive to this metal. In addition to recent advances in understanding the pathology associated with mercury exposure, the review highlights transport mechanisms, cellular distribution and detoxification of mercury species in the body.
| S-EPMC5181110 | biostudies-literature
Project description: Not available
| S-EPMC8419847 | biostudies-literature
Project description:Background:Hepatocellular carcinoma (HCC) is the cancer with the second highest mortality in the world due to its late presentation and limited treatment options. As such, there is an urgent need to identify novel biomarkers for early diagnosis and to develop novel therapies. The availability of next-generation sequencing (NGS) data from tumors of liver cancer patients has provided us with invaluable resources to better understand HCC through the integration of data from different sources to facilitate the identification of promising biomarkers or therapeutic targets. Findings:Here, we review key insights gleaned from more than 20 NGS studies of HCC tumor samples, comprising approximately 582 whole genomes and 1,211 whole exomes mainly from the East Asian population. Through consolidation of reported somatic mutations from multiple studies, we identified genes with different types of somatic mutations, including single nucleotide variations, insertion/deletions, structural variations, and copy number alterations as well as genes with multiple frequent viral integration. Pathway analysis showed that this curated list of somatic mutations is critically involved in cancer-related pathways, viral carcinogenesis, and signaling pathways. Lastly, we addressed the future directions of HCC research as more NGS datasets become available. Conclusions:Our review is a comprehensive resource for the current NGS research in HCC, consolidating published articles, potential gene candidates, and their related biological pathways.
| S-EPMC6335342 | biostudies-literature
Project description:Diffuse gliomas are the most frequent brain tumours, representing 75% of all primary malignant brain tumours in adults. Because of their locally aggressive behaviour and the fact that they cannot be cured by current therapies, they represent one of the most devastating cancers. The present review summarises recent advances in our understanding of glioma development and progression by use of various in vitro and in vivo models, as well as more complex techniques including cultures of 3D organoids and organotypic slices. We discuss the progress that has been made in understanding glioma heterogeneity, alteration in gene expression and DNA methylation, as well as advances in various in silico models. Lastly current treatment options and future clinical trials, which aim to improve early diagnosis and disease monitoring, are also discussed.
| S-EPMC7831916 | biostudies-literature
Project description: Not available
| S-EPMC8647618 | biostudies-literature
Project description:The pathophysiology of atrial fibrillation (AF) is broad, with components related to the unique and diverse cellular electrophysiology of atrial myocytes, structural complexity, and heterogeneity of atrial tissue, and pronounced disease-associated remodeling of both cells and tissue. A major challenge for rational design of AF therapy, particularly pharmacotherapy, is integrating these multiscale characteristics to identify approaches that are both efficacious and independent of ventricular contraindications. Computational modeling has long been touted as a basis for achieving such integration in a rapid, economical, and scalable manner. However, computational pipelines for AF-specific drug screening are in their infancy, and while the field is progressing quite rapidly, major challenges remain before computational approaches can fill the role of workhorse in rational design of AF pharmacotherapies. In this review, we briefly detail the unique aspects of AF pathophysiology that determine requirements for compounds targeting AF rhythm control, with emphasis on delimiting mechanisms that promote AF triggers from those providing substrate or supporting reentry. We then describe modeling approaches that have been used to assess the outcomes of drugs acting on established AF targets, as well as on novel promising targets including the ultra-rapidly activating delayed rectifier potassium current, the acetylcholine-activated potassium current and the small conductance calcium-activated potassium channel. Finally, we describe how heterogeneity and variability are being incorporated into AF-specific models, and how these approaches are yielding novel insights into the basic physiology of disease, as well as aiding identification of the important molecular players in the complex AF etiology.
| S-EPMC6131668 | biostudies-other
Project description:Recent advances in optical mapping have allowed the construction of improved genome assemblies with greater contiguity. Optical mapping also enables genome comparison and identification of large-scale structural variations. Association of these large-scale genomic features with biological functions is an important goal in plant and animal breeding and in medical research. Optical mapping has also been used in microbiology and still plays an important role in strain typing and epidemiological studies. Here, we review the development of optical mapping in recent decades to illustrate its importance in genomic research. We detail its applications and algorithms to show its specific advantages. Finally, we discuss the challenges required to facilitate the optimization of optical mapping and improve its future development and application.
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