Progress in molecular biology and translational science最新文献

Researchers are interested in drug repurposing or drug repositioning of existing pharmaceuticals because of rising costs and slower rates of new medication development. Other investigations that authorized these treatments used data from experimental research and off-label drug use. More research into the causes of depression could lead to more effective pharmaceutical repurposing efforts. In addition to the loss of neurotransmitters like serotonin and adrenaline, inflammation, inadequate blood flow, and neurotoxins are now thought to be plausible mechanisms. Because of these other mechanisms, repurposing drugs has resulted for treatment-resistant depression. This chapter focuses on therapeutic alternatives and their effectiveness in drug repositioning. Atypical antipsychotics, central nervous system stimulants, and neurotransmitter antagonists have investigated for possible repurposing. Nonetheless, extensive research is required to ensure their formulation, effectiveness, and regulatory compliance.

Many diseases are caused by misfolded and denatured proteins, leading to neurodegenerative diseases. In recent decades researchers have developed a variety of compounds, including polymeric inhibitors and natural compounds, antibodies, and chaperones, to inhibit protein aggregation, decrease the toxic effects of amyloid fibrils, and facilitate refolding proteins. The causes and mechanisms of amyloid formation are still unclear, and there are no effective treatments for Amyloid diseases. This section describes research and achievements in the field of inhibiting amyloid accumulation and also discusses the importance of various strategies in facilitating the removal of aggregates species (refolding) in the treatment of neurological diseases such as chemical methods like as, small molecules, metal chelators, polymeric inhibitors, and nanomaterials, as well as the use of biomolecules (peptide and, protein, nucleic acid, and saccharide) as amyloid inhibitors, are also highlighted.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system possess a broad range of applications for genetic modification, diagnosis and treatment of infectious as well as non-infectious disease. The CRISPR-Cas system is found in bacteria and archaea that possess the Cas protein and guide RNA (gRNA). Cas9 and gRNA forms a complex to target and cleave the desired gene, providing defense against viral infections. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), herpesviruses, human papillomavirus (HPV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cause major life threatening diseases which cannot cure completely by drugs. This chapter describes the present strategy of CRISPR-Cas systems for altering the genomes of viruses, mostly human ones, in order to control infections.

Protozoan parasitic diseases pose a substantial global health burden. Understanding the pathogenesis of these diseases is crucial for developing intervention strategies in the form of vaccine and drugs. Manipulating the parasite's genome is essential for gaining insights into its fundamental biology. Traditional genomic manipulation methods rely on stochastic homologous recombination events, which necessitates months of maintaining the cultured parasites under drug pressure to generate desired transgenics. The introduction of mega-nucleases (MNs), zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs) greatly reduced the time required for obtaining a desired modification. However, there is a complexity associated with the design of these nucleases. CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated proteins) is the latest gene editing tool that provides an efficient and convenient method for precise genomic manipulations in protozoan parasites. In this chapter, we have elaborated various strategies that have been adopted for the use of CRISPR-Cas9 system in Plasmodium, Leishmania and Trypanosoma. We have also discussed various applications of CRISPR-Cas9 pertaining to understanding of the parasite biology, development of drug resistance mechanism, gene drive and diagnosis of the infection.

Chimeric antigen receptors (CAR) are synthetic receptors engineered to target a user-defined antigen. They comprise an extracellular single-chain variable fragment for target recognition and intracellular signalling domains commonly derived from immune cells. CAR-T cells have proven to be successful in therapy of some cancers. CAR-T cells are activated upon antigen-priming and subsequent intracellular signalling. However, tonic signalling in CAR-T cells remains a challenge in developing CAR-T therapeutics of high efficacy as it causes early T-cell exhaustion, limiting therapeutic persistence. Moreover, a poor choice of target antigen leads to off-target cytotoxicity, often hampering the host's survival. In addition, conventional methods of delivering CAR gene circuits utilise viral vectors, such as lentiviruses and retroviruses, which insert the CAR gene circuits into transcriptionally active sites in the genome. This increases the risks of malignant transformation due to improper genome integration. Optimisation in CAR-T engineering, from the architecture of CAR gene circuits to the structure of CAR and the behaviour of CAR-T cells, is paramount to ensure high efficacy, persistence, and precision in CAR-T therapy. This review provides insights into engineering CAR-T cells for precision in cancer therapy by highlighting the key strategies recently developed to optimise the function and efficiency of CARs. The delivery method of CAR gene circuits, circuit and structural modification of CAR, T-cell phenotype manipulation and T-cell arming will be discussed to accentuate their interplay in regulating CAR-T therapy's safety, precision, and efficacy.

In the last few years, immune checkpoint inhibitors (ICIs) improved treatment strategies for advanced non-small cell lung cancer (NSCLC) with no targetable driver mutations. Empirical evidence strongly suggests that males and females differ in outcomes following the use of ICIs for treatments of solid cancers. Women in fact exhibit greater humoral and cell-mediated immune responses and an even more advanced immune editing which plays an important role in controlling cancer rising and evolution. However, at present, no conclusive studies have addressed differences in response to ICIs regarding sex and, to note, reproductive status in women or autoimmune diseases in both sexes are often not recorded in clinical trials. Consequently, it can be argued that to assess cancer responses and study cancer spread, results of published studies in men may not unconditionally be applied on female patients treated with ICIs, and vice versa. In this chapter have been discussed recent data about gender differences in the immune system and in NSCLC patients treated with ICIs, highlighting sex as a key factor in evaluating different responses in the two sexes.

Over the past decades, drug discovery utilizing small pharmacological compounds, fragment-based therapeutics, and antibody therapy have significantly advanced treatment options for many human diseases. However, a major bottleneck has been that>70% of human proteins/genomic regions are 'undruggable' by the above-mentioned approaches. Many of these proteins constitute essential drug targets against complex multifactorial diseases like cancer, immunological disorders, and neurological diseases. Therefore, alternative approaches are required to target these proteins or genomic regions in human cells. RNA therapeutics is a promising approach for many of the traditionally 'undruggable' targets by utilizing methods such as antisense oligonucleotides, RNA interference, CRISPR/Cas-based genome editing, aptamers, and the development of mRNA therapeutics. In the following chapter, we will put emphasis on recent advancements utilizing these approaches against challenging drug targets, such as intranuclear proteins, intrinsically disordered proteins, untranslated genomic regions, and targets expressed in inaccessible tissues.

It is estimated that millions of people around the world experience various types of tissue injuries every year. Regenerative medicine was born and developed for understanding and application with the aim of replacing affected organs or some cells. The research, manufacture, production, and distribution of RNA in cells have acted as a basic foundation for the development and testing of therapies and treatments that are widely applied in different fields of medicine. Vaccines against COVID-19 are considered one of the brilliant and outstanding successes of RNA therapeutics research. With the characteristics of bio-derived RNA therapeutics, the mechanism of rapid implementation, safe production, and flexibility to create proteins depending on actual requirements. Based on the advantages above in this review, we discuss RNA therapeutics for regenerative medicine, and the types of RNA therapies currently being used for regenerative medicine. The relationship between disease and regenerative medicine is currently being studied or tested in RNA therapeutics. We have also covered the mechanisms of action of RNA therapy for regenerative medicine and some of the limitations in our current understanding of the effects of RNA therapy in this area. Additionally, we have also covered developing RNA therapeutics for regenerative medicine, focusing on RNA therapeutics for regenerative medicine. As a final point, we discuss potential applications for therapeutics for regenerative medicine in the future, as well as their mechanisms.

This chapter explores two significant aspects of the ongoing COVID-19 pandemic: the realistic prediction of its end and the status of long-term COVID in 2023. While the World Health Organization (WHO) declared an end to COVID-19 as a public health emergency, the possibility of future waves caused by variants remains. Widespread vaccination and prior infections provide substantial protection, but the virus is expected to persist, necessitating continued monitoring and potential reimplementation of control measures. Long-term COVID, characterized by persistent or new symptoms after the acute phase, remains a concern. Recent findings suggest a reduced risk of prolonged COVID with initial Omicron variants. However, targeted treatments are lacking, and current approaches rely on symptomatic and supportive care. Psychological support and multidisciplinary interventions are essential. Comprehensive studies, standardized criteria, and international registries are needed to advance research and develop effective therapies. Understanding these uncertainties will guide us towards effectively managing the pandemic and providing optimal care for long COVID patients.

This book chapter presents a concise overview of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. It explores viral classification based on morphology and nucleic acid composition with a focus on DNA and RNA viruses, the SARS-CoV-2 structure including the structural as well as nonstructural proteins in detail, and the viral replication mechanisms. The chapter then delves into the characteristics and diversity of coronaviruses, particularly SARS-CoV-2, highlighting its similarities with other beta-coronaviruses. The replication and transcription complex, RNA elongation, and capping, as well as the role of accessory proteins in viral replication and modulation of the host immune response is discussed extensively.