Progress in molecular biology and translational science最新文献

Ribonucleic acids (RNAs), including the messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), play important roles in living organisms and viruses. In recent years, the RNA-based technologies including the RNAs inhibiting other RNA activities, the RNAs targeting proteins, the RNAs reprograming genetic information, and the RNAs encoding therapeutical proteins, are useful methods to apply in prophylactic and therapeutic vaccines. In this review, we summarize and highlight the current application of the RNA therapeutics, especially on mRNA vaccines which have potential for prevention and treatment against human and animal infectious diseases.

Designing and predicting novel drug targets to accelerate drug discovery for treating metabolic dysfunction-associated steatohepatitis (MASH)-cirrhosis is a challenging task. The presence of superimposed (nested) and co-occurring clinical and histological phenotypes, namely MASH and cirrhosis, may partly explain this. Thus, in this scenario, each sub-phenotype has its own set of pathophysiological mechanisms, triggers, and processes. Here, we used gene/protein and set enrichment analysis to predict druggable pathways for the treatment of MASH-cirrhosis. Our findings indicate that the pathogenesis of MASH-cirrhosis can be explained by perturbations in multiple, simultaneous, and overlapping molecular processes. In this scenario, each sub-phenotype has its own set of pathophysiological mechanisms, triggers, and processes. Therefore, we used systems biology modeling to provide evidence that MASH and cirrhosis paradoxically present unique and distinct as well as common disease mechanisms, including a network of molecular targets. More importantly, pathway analysis revealed straightforward results consistent with modulation of the immune response, cell cycle control, and epigenetic regulation. In conclusion, the selection of potential therapies for MASH-cirrhosis should be guided by a better understanding of the underlying biological processes and molecular perturbations that progressively damage liver tissue and its underlying structure. Therapeutic options for patients with MASH may not necessarily be of choice for MASH cirrhosis. Therefore, the biology of the disease and the processes associated with its natural history must be at the forefront of the decision-making process.

Obesity, diabetes, and other metabolic disorders place a huge burden on both the physical health and financial well-being of the community. While the need for effective treatment of metabolic disorders remains urgent and the reality is that traditional drug development involves high costs and a very long time with many pre-clinical and clinical trials, the need for drug repurposing has emerged as a potential alternative. Scientific evidence has shown the anti-diabetic and anti-obesity effects of old drugs, which were initially utilized for the treatment of inflammation, depression, infections, and even cancers. The drug library used modern technological methods to conduct drug screening. Computational molecular docking, genome-wide association studies, or omics data mining are advantageous and unavoidable methods for drug repurposing. Drug repurposing offers a promising avenue for economic efficiency in healthcare, especially for less common metabolic diseases, despite the need for rigorous research and validation. In this chapter, we aim to explore the scientific, technological, and economic issues surrounding drug repurposing for metabolic disorders. We hope to shed light on the potential of this approach and the challenges that need to be addressed to make it a viable option in the treatment of metabolic disorders, especially in the future fight against metabolic disorders.

Personalized medicine has emerged as a revolutionary approach to healthcare in the 21st century. By understanding a patient's unique genetic and biological characteristics, it aims to tailor treatments specifically to the individual. This approach takes into account factors such as an individual's lifestyle, genetic makeup, and environmental factors to provide targeted therapies that have the potential to be more effective and lower the risk of side reactions or ineffective treatments. It is a paradigm shift from the traditional "one size fits all" approach in medicine, where patients with similar symptoms or diagnoses receive the same standard treatments regardless of their differences. It leads to improved clinical outcomes and more efficient use of healthcare resources. Drug repurposing is a strategy that uses existing drugs for new indications and aims to take advantage of the known safety profiles, pharmacokinetics, and mechanisms of action of these drugs to accelerate the development process. Precision medicine may undergo a revolutionary change as a result, enabling the rapid development of novel treatment plans utilizing drugs that traditional methods would not otherwise link to. In this chapter, we have focused on a few strategies wherein drug repurposing has shown great success for precision medicine. The approach is particularly useful in oncology as there are many variations induced in the genetic material of cancer patients, so tailored treatment approaches go a long way. We have discussed the cases of breast cancer, glioblastoma and hepatocellular carcinoma. Other than that, we have also looked at drug repurposing approaches in anxiety disorders and COVID-19.

Female cancers, which include breast and gynaecological cancers, represent a significant global health burden for women. Despite advancements in research pertinent to unearthing crucial pathological characteristics of these cancers, challenges persist in discovering potential therapeutic strategies. This is further exacerbated by economic burdens associated with de novo drug discovery and clinical intricacies such as development of drug resistance and metastasis. Drug repurposing, an innovative approach leveraging existing FDA-approved drugs for new indications, presents a promising avenue to expedite therapeutic development. Computational techniques, including virtual screening and analysis of drug-target-disease relationships, enable the identification of potential candidate drugs. Integration of diverse data types, such as omics and clinical information, enhances the precision and efficacy of drug repurposing strategies. Experimental approaches, including high-throughput screening assays, in vitro, and in vivo models, complement computational methods, facilitating the validation of repurposed drugs. This review highlights various target mining strategies based on analysis of differential gene expression, weighted gene co-expression, protein-protein interaction network, and host-pathogen interaction, among others. To unearth drug candidates, the technicalities of leveraging information from databases such as DrugBank, STITCH, LINCS, and ChEMBL, among others are discussed. Further in silico validation techniques encompassing molecular docking, pharmacophore modelling, molecular dynamic simulations, and ADMET analysis are elaborated. Overall, this review delves into the exploration of individual case studies to offer a wide perspective of the ever-evolving field of drug repurposing, emphasizing the multifaceted approaches and methodologies employed for the same to confront female cancers.

While amyloid has traditionally been viewed as a harmful formation, emerging evidence suggests that amyloids may also play a functional role in cell biology, contributing to normal physiological processes that have been conserved throughout evolution. Functional amyloids have been discovered in several creatures, spanning from bacteria to mammals. These amyloids serve a multitude of purposes, including but not limited to, forming biofilms, melanin synthesis, storage, information transfer, and memory. The functional role of amyloids has been consistently validated by the discovery of more functional amyloids, indicating a conceptual convergence. The biology of amyloids is well-represented by non-pathogenic amyloids, given the numerous ones already identified and the ongoing rate of new discoveries. In this chapter, functional amyloids in microorganisms, animals, and plants are described.

Regenerative medicine and cosmetics are currently two outstanding fields for drug discovery. Although many pharmaceutical products for regenerative medicine and cosmetics have received approval by official agencies, several challenges are still needed to overcome, especially financial and time issues. As a result, drug repositioning, which is the usage of previously approved drugs for new treatment, stands out as a promising approach to tackle these problems. Recently, increasing scientific evidence is collected to demonstrate the applicability of this novel method in the field of regenerative medicine and cosmetics. Experts in drug development have also taken advantage of novel technologies to discover new candidates for repositioning purposes following computational approach, one of two main approaches of drug repositioning. Therefore, numerous repurposed candidates have obtained approval to enter the market and have witnessed financial success such as minoxidil and fingolimod. The benefits of drug repositioning are undeniable for regenerative medicine and cosmetics. However, some aspects still need to be carefully considered regarding this method including actual effectiveness during clinical trials, patent regulations, data integration and analysis, publicly unavailable databases as well as environmental concerns and more effort are required to overcome these obstacles.

CRISPR-Cas systems have revolutionised precision medicine by enabling personalised treatments tailored to an individual's genetic profile. Various CRISPR technologies have been developed to target specific disease-causing genes in blood cancers, and some have advanced to clinical trials. Although some studies have explored the in vivo applications of CRISPR-Cas systems, several challenges continue to impede their widespread use. Furthermore, CRISPR-Cas technology has shown promise in improving the response of immunotherapies to blood cancers. The emergence of CAR-T cell therapy has shown considerable success in the targeting and correcting of disease-causing genes in blood cancers. Despite the promising potential of CRISPR-Cas in the treatment of blood cancers, issues related to safety, ethics, and regulatory approval remain significant hurdles. This comprehensive review highlights the transformative potential of CRISPR-Cas technology to revolutionise blood cancer therapy.

Misfolded proteins assemble into fibril structures that are called amyloids. Unlike usually folded proteins, misfolded fibrils are insoluble and deposit extracellularly or intracellularly. Misfolded proteins interrupt the function and structure of cells and cause amyloid disease. There is increasing evidence that the most pernicious species are oligomers. Misfolded proteins disrupt cell function and cause cytotoxicity by calcium imbalance, mitochondrial dysfunction, and intracellular reactive oxygen species. Despite profound impacts on health, social, and economic factors, amyloid diseases remain untreatable. To develop new therapeutics and to understand the pathological manifestations of amyloidosis, research into the origin and pathology of amyloidosis is urgently needed. This chapter describes the basic concept of amyloid disease and the function of atypical amyloid deposits in them.

Respiratory infections such as Coronavirus disease 2019 are a substantial worldwide health challenge, frequently resulting in severe sickness and death, especially in susceptible groups. Conventional drug development for respiratory infections faces obstacles such as extended timescales, substantial expenses, and the rise of resistance to current treatments. Drug repurposing is a potential method that has evolved to quickly find and reuse existing medications for treating respiratory infections. Drug repurposing utilizes medications previously approved for different purposes, providing a cost-effective and time-efficient method to tackle pressing medical needs. This chapter summarizes current progress and obstacles in repurposing medications for respiratory infections, focusing on notable examples of repurposed pharmaceuticals and their probable modes of action. The text also explores the significance of computational approaches, high-throughput screening, and preclinical investigations in identifying potential candidates for repurposing. The text delves into the significance of regulatory factors, clinical trial structure, and actual data in confirming the effectiveness and safety of repurposed medications for respiratory infections. Drug repurposing is a valuable technique for quickly increasing the range of treatments for respiratory infections, leading to better patient outcomes and decreasing the worldwide disease burden.